YEAR 2 HNS BLOCK

CONTENT

As of 2020-2021 M25 Year 2 Teaching Schedule…

Code Lesson Name Professor Notes Teacher’s

page note
number available?
HNS01 Overview of the central nervous system YS Chan 4 Yes
HNS02 Brainstem RCC Chang 8
HNS03 Thalamus and cerebral cortex RCC Chang 27
HNS04 Meninges and blood supply GKK Leung 32
HNS05 Infection of the CNS I: bacterial and fungal KY Yuen / Yes
infection
HNS06 Chemical neurotransmission I DKY Shum 55
HNS07 Chemical neurotransmission II DKY Shum 57
HNS08 Cranial nerves CSW Lai 59
HNS09 Pathology of CNS infection SY Leung / Yes
HNS10 Infections of the CNS II: Viral and prion JFW Chan 64
infections of the CNS
HNS11 Infections of the CNS III: Principles of KKW To 67
antiviral therapy
HNS12 Somaesthetic pathway and Somatic CSW Lai 70
sensation
HNS13 Pain pathway and mechanisms of pain KO Lai 75
HNS14 Narcotic analgesics JKF Ng 78
HNS15 Sedatives and hypnotics JCW Mak 81
HNS16 Pathology of raised intracranial pressure SY Leung / Yes
and cerebrovascular disease
HNS17 Motor system GKK Leung 82
HNS18 Structure and function of head and neck GL Tipoe / Yes
HNS19 Cerebellum YS Chan 89 Yes
HNS20 Control of movement KO Lai 93
HNS21 Vasculature and lymphatic of head and CC Cheung /
neck
HNS22 Face and scalp TS Cecot 97
HNS23 Nerves of head and neck TS Cecot 102
HNS24 Nasal cavity GL Tipoe / Yes
HNS25 Oral cavity, submandibular and sublingual J Yang 104
glands
HNS26 Smell and taste & Salivary and nasal JYS Chu 108
secretion
HNS27 Pharynx GL Tipoe 112 Yes
HNS28 Parotid and infratemporal regions J Yang / Yes
HNS29 Larynx GL Tipoe 114 Yes
HNS30 Swallowing and speech RKY Tsang 116
HNS31 NPC and other head and neck tumours JM Nicholls / Yes
HNS32 Infectious causes of upper airway SKP Lau / Yes
obstruction
HNS33 Common ENT inflammatory diseases: VSH To 118
anatomic and physiological appraisal
 HNS34 Common ENT cancers: anatomic and RKY Tsang 121
physiologic appraisal
HNS35 Ear GL Tipoe 125 Yes
HNS36 Pathology of intracranial tumors SY Leung / Yes
HNS37 Audition YS Chan 129 Yes
HNS38 Vestibular system YS Chan 132 Yes
HNS39 Orbit GL Tipoe 136 Yes
HNS40 Vision YS Chan 140 Yes
HNS41 Eye movement LW Lim 144
HNS42 High cortical function CSW Lai 149
HNS43 Limbic system and central autonomic LW Lim 153
function and Learning and memory
HNS44 Anti-depressants RLC Hoo 157
HNS45 Anti-psychotics RLC Hoo 161
HNS46 Drugs used for neurodegenerative diseases JCW Mak 165
HNS47 Molecular basis of neurological diseases YQ Song 169
HNS48 Behavioral neuroscience PC Sham 173
HNS49 When we all become Methuselah DKM Ip 177
HNS50 To CT or not to CT in traumatic head DKM Ip 179
injury
HNS Exam focus 182
Comments:
 Before using notes, you can check whether the same teacher is still teaching that lecture.
Often there are substantial differences in teaching content when a different professor is
teaching.
 Some teachers published notes. Suggest reading Teacher’s notes whenever available.
 Sorry I haven’t written notes for all the lectures. Do check out seniors’ notes from other
years.
o Note that practicals were not listed in the table above
 ‘Exam focus’ provides additional resources for revision.

Total pages: 206

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INTRODUCTION

Set of notes on Head, Neck and Nervous System block lectures (based on M25 Year 2 2020-2021
curriculum)

SYMBOLS AND ABBREVIATIONS

: Important / Needs memorize

: Special point to note
 Italianized / in Grey: Likely not important / Reference reading
 Bold / Underlined / Highlighted: Important
 > is equivalent to an arrow pointing towards right, not ‘more than’
 D, M, Y: Day, Month, Year

CONTACT

If you would like to annotate, a Microsoft Word format is available for download here
(https://drive.google.com/drive/folders/12jK5yUcUtghrGv5YkDMtmZRHr-wVVi7Q?usp=sharing)

Despite efforts to minimize errors, it is likely there are mistakes somewhere. If you spot a mistake,
you can write to me at u3569884@connect.hku.hk. Thanks!

Feel free to reach me for any feedbacks, or if you have any questions! Add oil, add triglycerides!
ʕ•́ᴥ•̀ʔ っ♡

THANK YOU!

Many teachers made good PowerPoint slides and even prepared lecture notes for us, of which this
set of notes is largely based on. I’m very grateful for their teaching. Thanks to my classmates and
PBL groupmates for their support towards the production of this set of notes. They provided much
valuable feedback, spotted errors, and made suggestions. The notes published by my seniors kept
me afloat. Finally, thanks to the admins for keeping all these resources tidy and accessible to all.

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HNS01 OVERVIEW OF THE CENTRAL NERVOUS SYSTEM

OVERVIEW

1. Basic neuroanatomy
2. Synapse: Excitation and Inhibitory
3. Sensory systems: Basics, Sensory transduction, Topographical organization, Bilateral inputs
to cortex
4. Motor system
5. Cognition: Association cortex, Limbic system, Autonomic control
6. Pathological overview (Bridging physiology and pathology): Epilepsy, Parkinson’s disease,
Alzheimer’s disease, Psychosis e.g. Schizophrenia, Drug addiction

1. BASIC NEUROANATOMY
 Cerebral cortex: for Cognition, Perception (of sensation), Voluntary movement
 Limbic system (for Emotion, Cognition): consist of Hippocampus, Amygdala
 Brainstem (Housekeeping, connects higher center to spinal cord): Midbrain, Pons, Medulla
 Cerebellum: Motor coordination
 3 cardinal neuromotor regions: Motor cortex, Cerebellum, Basal ganglia (Substantia nigra,
nucleus accumbens)

2. SYNAPSE

STIMULATORY VS. INHIBITORY

Stimulatory Inhibitory
Examples E.g. Glutamatergic synapse E.g. GABAergic synapse (activated by
(activated by glutamate) GABA)
Role Accelerator Inhibitor (breaking effect)
Neurotransmitte Releases excitatory Release inhibitory neurotransmitter e.g.
r neurotransmitter e.g. Glutamate GABA
Process Activates cell > Release Activates cell > Release
neurotransmitter > neurotransmitter > Hyperpolarization
Depolarization
Ion responsible Na, Ca Cl (getting out of neurons)
Potential Stimulatory postsynaptic Inhibitory postsynaptic potential
potential

3. SENSORY SYSTEM

PROCESS OF SENSATION PERCEPTION

 2 parts: Sensation; Perception
 Sensation:
o Sensatory transducer: Converting stimulus to neural signals (via receptors)
o Receptive field: From receptor to neuron (‘Territory of receptor’)
o Central processing
 Perception (At the higher centers)
o At association cortex
o Subjected to past experiences, reasoning and personality

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SENSORY TRANSDUCERS
Types of sense (and notable sensory transducers)

Somatic senses Special Senses

 Touch (Free nerve ending: Pain,  Taste
temperature; Meissner corpuscle: Touch /  Smell
Pressure)  Hearing
 Body position  Balance
 Temperature  Vision
 Pain

There are various sensors in various parts of the body. Their characteristics:
 Division of labor (e.g. some for touch / pressure, pain, temperature, etc.)
 Stimuli activates several receptors at the same time, but to different degree

SENSORY PATHWAY
Important characteristic: Crossed ascending projection
 See diagram: 2 different pathways (Blue vs. Red) [But will learn systematically
in later lectures, so can ignore this for now]
o Blue: Left finger’s mechanoreceptor > Spinal cord > Dorsal column
nuclei > Midbrain > Thalamus > Cortex ]
o Red: Not passing through Dorsal column nuclei
 Characteristics of Sensory Pathway:
1. There is ‘Crossed ascending projection (i.e. left stimulus crosses and
is processed by the right cortex)
2. There is fine division of labor (even if all these are just mechanoreceptors)
 Via Dorsal Column nuclei: Discriminative touch, Vibration, Position sense
 Not via Dorsal Column nuclei: Temperature, Pain
 Another example is Taste sensation
o By taste cells (Chemoreceptors, i.e. Taste buds)
o Basic sensation: Bitter, Salt, Sour, Sweet, Umami
o Some are Ion channels: Salty, Sour, Bitter, Chili
o Some are GPCR: Sweet, Bitter

SENSORY CORTEX
Special characteristics:
 Narrow vertical columns of submodalities in Cortex (i.e. they are further divided into small
compartments for processing sensory signals originating from different body locations)
 Topographic body map (‘Little man’): Shows distorted body surfaces based on tactile
sensibility (hence, magnified areas e.g. fingers, lips, tongue has highest acuity

4. MOTOR SYSTEM
 Types of motor control
o Reflexive (e.g. Stretch reflex, Pain withdraw reflex)
o Voluntary
 The 3 Cardinal neuromotor regions:
1. Motor cortex

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  then via the cortico-spinal tract > Spinal cord
 There are other relay stations (e.g. Red nucleus, Reticular nuclei, Superior
colliculus, etc.)
2. Cerebellum
3. Basal Ganglia
 2 important characteristics of Motor control
o Topography: Most are allocated at: Fingers, Facial region (hence, dexterity)
o Cross descending projection

5. COGNITION
ASSOCIATION AREA
 For cognition and consciousness
 Important characteristic: Lateralization of the cerebral cortex:
Right hemisphere Left hemisphere
Musical & Artistic abilities Logical thinking
Imagination, Fantasization Science and Math
Perception of space, Body control, Awareness Language & Writing

LIMBIC SYSTEM
 Comprises of: Hippocampus, Amygdala.
 So important for cognition! E.g. Learning and Memory, Sleep and Wakefulness, Emotions
 Example: Fear response
 Pathway: Visual thalamus > Visual cortex > Amygdala
o Amygdala then signals 2 pathways: to Motor system, to Autonomic nervous system
(e.g. increase heart rate)

6. PATHOLOGICAL OVERVIEW: BRIDGING PHYSIOLOGY AND PATHOLOGY

Disease Brief discussion
Epilepsy Abnormal neurons that leads to spread of abnormal synchronized cortical
discharge  Motor problems
Parkinson’s disease Degeneration of Dopamine Neurons > Disappearance of Substantia nigra
(Part of the basal ganglia, which is part of the 3 cardinal areas for motor
control  Movement disorders)
Alzheimer’s disease Degeneration of Hippocampus (‘Extreme shrinkage’) > Lost memory and
ability to learn (Recall: Hippocampus is part of the limbic system i.e.
cognitively very important)
Hence: Dementia is an important symptom of Alzheimer’s
Microbiological pathogenesis: Tangled Tau fragments + Accumulation of
amyloid plague  Damaged neuron
Psychosis e.g. (This part isn’t really about the disease, but the use of drug: PCP, aka
Schizophrenia ‘Angel dust’, recreational drug). PCP blocks Glutamate binding sites
(Recall: The accelerating synaptic channels), which leads to behaviors
mimicking Schizophrenia
Drug addiction Neurons in the nucleus accumbens (part of basal ganglia): Binding of
Cocaine / Heroin reduces dopamine uptake / increases dopamine release
 Increase post-synaptic neuron’s cAMP  Activate some other neurons
 Addiction

FURTHER DISCUSSION: FMRI (STATE OF THE ART IMAGING TECHNIQUES)

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 Measures O2 usage in blood flow associated with neural activities
GALLERY

Sensory little man Tomography (but little man ≠

tomography)

Alzheimer’s: Massive
hippocampus shrink

LEARNING OBJECTIVES

 Understand that neurons, connected by excitatory / inhibitory synapses, are functional units
of neural networks.
 Recognize that information processing of sensory systems involves similar organizational
and physiological principles.
 Recognize different levels of neural control as exemplified in movement, cognition and
autonomic function.
 Appreciate the neuropathological impacts of dysfunction of neurons and their excitatory /
inhibitory connections.

Note: This lecture an overview the HNS block, so almost all content taught here will be taught again
in later lectures, hence no panics if you don’t understand something here. Maybe pay some special
notice to the underlined content, otherwise you’re all good to go on :)

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HNS02 BRAINSTEM

OUTLINE

1. Introduction to Brainstem
2. Functions of the Brainstem
3. Anatomy Highlights
a. Surface
b. Internal
4. Disorders of Brainstem
5. Learning Objectives
6. Anatomy images and Practice

INTRODUCTION TO BRAINSTEM

Components: Midbrain, Pons, Medulla oblongata

(2) FUNCTIONS OF BRAINSTEM

1. Passage: all ascending and descending pathways pass through (Decussation at Medulla)
2. Location: Nuclei of most cranial nerve
3. Life center: Heart rate, breath, BP, ascending activating system (Reticular formation)

Cranial nucleus Important structures & functions

Midbrain III – V (3-5)  Red nuclei (Motor coordination)
 Tetum: Superior (Visual reflex); Inferior (Hearing)
 Substantia Nigra (Melanin)
Pons X – IX (5 – 9)  Pontine
 Sleep center
 Respiratory center
Medulla V, IX-XII (5, 9-12)  Life processes (e.g. Heart rate) + Reflex (e.g. Vomiting)
 Pyramids (Descending decussation)
 Olive: Balance, Coordination; Hearing

RETICULAR FORMATION (ARAS)

 Function:
o Integration of functions (e.g. Sensory, Visceral, Limbic, Motor)
o Behaviors (e.g. Wakefulness & alertness, sleep cycles)
 Examples (they contain different structures and systems)
o Locus coeruleus-norepinephrine system: Fight & Flight
o Raphe nucleus-serotonin system
o Pontine-acetylcholine system: Sleep-awakeness
o Substantial nigra-Ventral Tegmental Area (VTA): Motor & Incentive behavior

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ANATOMY HIGHLIGHTS

(This only serves as a checklist. You still need to know the locations of the structures in Dr. Cheung’s
slides because it will be examined, e.g. Labelling question in SAQ!! TAT)

SURFACE ANATOMY
Midbrain
 Anterior: Oculomotor nerve,
Interpeduncular fossa
 Lateral: Cerebral peduncle
 Posterior: Superior, Inferior
colliculus; trochlear nerve
Pons
 Anterior: Basilar sulcus
 Lateral: Trigeminal nerve
 Posterior: Superior, Middle,
Inferior cerebellar peduncle;
Sulcus limitans, Stria
medullary, Median sulcus.
Medulla oblongata
 Anterior: Anterior median
fissure; Decussation at pyramids
 Lateral: Olive
 Posterior: Cuneate, Gracile
tubercle; 4th ventricle, posterior
median fissure

INTERNAL ANATOMY
Medulla Oblongata
Lower Middle Upper
 Posterior: Nucleus gracilis,  Posterior: +Hypoglossal (XII)  Posterior: +Opening of 4th
Nucleus cuneatus  Middle: -Internal arcuate ventricle (wide)
 Middle: Internal arcuate fiber,  Lateral: Same Line of nucleus: Vestibular (VIII),
Reticular formations  Anterior: Same Vagus (X), Trigeminal (V), Ambiguus
 Lateral: Nucleus of trigeminal (IX, X, XI), Spinothalamic
nerve  Middle: +Medial lemniscus
 Anterior: Medullary pyramids  Lateral: +Inferior olive
 Anterior: +Corticospinal tract
Pons
Midbrain
Lower Upper
 Posterior: Abducens nucleus  Posterior: +Superior Tectum (Posterior):
(VII), facial nerve (VII), Middle cerebellar peduncle Superior colliculus
cerebellar peduncle, Reticular  Middle: Pontine nucleus & Tegmentum:
formation, medial lemniscus Pontocerebellar fibers (moved  Posterior: Cerebral aqueduct &
(horizontal) up), +Reticular formation (two periaqueductal gray; Oculomotor
 Middle: Corticospinal tract locations). +trochlear nucleus nucleus
(patchy) (IV)  Middle: Red nucleus, Reticular
 Lateral: /  Lateral: Same formation, Substantia nigra
 Anterior: Pontine nucleus &  Anterior: Same (Important)
pontocerebellar fibers  Lateral: Cerebral peduncle/crus,
Corticospinal tract
 Anterior: Interpeduncular fossa
Diagrams please see PowerPoint / Last session of this note.
Recommended usage: Print this out and view side-by-side with PowerPoint
Note on PowerPoint Images: Black for fibers, white for cell body

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(4) DISORDERS OF BRAINSTEM

Syndrome Occlusion / Symptoms

Pathology
Wallenberg Posterior Inferior Ipsilateral analgesia (face); Contralateral analgesia (below
Cerebellar artery neck; Spinothalamic tract), etc.
Medial Medullary Vertebral artery Contralateral impaired sensation (Medial lemniscus),
Contralateral hemiparesis (Corticospinal tract), etc.
Hydrocephalus Cerebral aqueduct (Not discussed in this lecture)
Parkinsonism Degeneration of (Not discussed in this lecture)
neurons
Damaged reticular formation Lesion  Sleep / Coma (∵interrupted ascending activating
system)
NB: Refer to PowerPoint slides for more detailed discussion on Symptoms

(5) LEARNING OBJECTIVES

1. To learn the components of brainstem

2. To recognize the external morphology of the brainstem
3. To identify the major internal organization of the brainstem
4. To know the major functions of the brainstem
5. To appreciate its relationship with the cranial nerves

10
 This is a Page Break
The content: 1000 pages detailing the
anatomy on every single artery, vein, nerve
and lymph

My anatomical knowledge: Head & Shoulders

Knees and Toes

Continue next page:

Diagrams of HNS02

11
(6) ANATOMY PRACTICE

ANATOMY OUTLINE
1. Surface anatomy
a. Posterio(lateral)
b. Anterior
c. Midbrain
d. Pons
e. Medulla oblongata
2. Internal structures
a. Midbrain
b. Pons
c. Medulla Oblongata

ANATOMY OF BRAINSTEM (ANSWERS)

SURFACE ANATOMY –POSTEROLATERAL

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13
SURFACE ANATOMY –ANTERIOR

14
SURFACE ANATOMY –MIDBRAIN

SURFACE ANATOMY –PONS

SURFACE ANATOMY –MEDULLA OBLONGATA

15
INTERNAL STRUCTURES –MIDBRAIN

Internal structure of Brainstem: Axon in black, Cell body in white

INTERNAL STRUCTURES –PONS

16
INTERNAL STRUCTURES --MEDULLA OBLONGATA

17
18
1A. SURFACE ANATOMY –POSTEROLATERAL

19
1B. SURFACE ANATOMY –ANTERIOR

20
1C. SURFACE ANATOMY –MIDBRAIN

1D. SURFACE ANATOMY –PONS

21
1E. SURFACE ANATOMY –MEDULLA OBLONGATA

2A. INTERNAL STRUCTURES –MIDBRAIN

In case you are wondering: yes these will be examined. See

M25 Summative SAQ, there was a question asking to label
a schematic diagram. (I did not study these diagrams well,
so I messed up that question, *REGRET* don’t be like me.
[But of course prioritize, since technically anything can be examined, and
probability matters.])

22
2B. INTERNAL STRUCTURES –PONS

23
2C. INTERNAL STRUCTURES --MEDULLA OBLONGATA

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26
HNS03 THALAMUS AND CEREBRAL CORTEX

OUTLINE

1. Thalamus
2. Cerebral cortex

THALAMUS

Anatomy & Locations

 Anatomy: A smol round button-like ovoid boi.
2 halves joined by interthalamic adhesions.
 Locations
o Anterior: Interventricular foramen
o Posterior: Pulvinar
o Superior: Stratum zonale, Striata terminalis
o Inferior: Hypothalamus
o Medial: Lateral wall of 3rd ventricle
o Lateral: Nerve fibers of internal capsule

Thalamus is part of Diencephalon. Structures at Diencephalon & Functions

1. Epithalamus (Smallest region): (Pineal gland) Secretes melatonin
2. Thalamus (Largest region): Modulate sensation (Relays sensory input to cortex).
a. Note: All Sensory pathways pass through thalamus, but motor pathways DON’T
3. Subthalamus (Connects subthalamus nuclei & basal ganglia): Control motor & emotions
4. Hypothalamus: Control Body temperature, circadian rhythm, wake / sleep cycle, eating &
drinking, emotions; Regulates pituitary glands (headquarter of hormones)

Nuclei of thalamus (See PowerPoint / Diagram on next page)

 Midline (interthalamic adhesions), Medial, Internal medullar lamina (Diffused nucleus),
Anterior.
 Lateral dorsal, Lateral Posterior
 Ventral anterior, ventral lateral, ventral posterior (Medial, Lateral)
 Pulvinar, Lateral geniculate body, Medial geniculate body

Notable relays of Thalamus

From Through To
Substantial nigra, ventral pallidum, Medial dorsal Thalamus Prefrontal cortex
Olfactory cortex, Amygdala
Mammillothalamic tract & Fornix Anterior thalamus Cingulate gyrus
Basal ganglia Ventral anterior Premotor cortex
thalamus
Cerebellum Ventral lateral thalamus Motor cortex
Spinothalamic tract, Medial & Ventral Posterior Somatosensory cortex
Trigeminal lemniscus
Optic tract, Lateral lemniscus, Lateral & Medial Visual & Auditory cortex
Inferior colliculus Geniculate

27
 Note corresponding locations by colors.
Important: Ventral posterior lateral for trunk and limbs, Ventral
posterior medial for head and neck.

CEREBRAL CORTEX

Neuroanatomy components
 Lobes (Frontal, Parietal, Occipital, Temporal)
 Sulcus (e.g. Central sulcus –separates Frontal vs. Parietal) vs. Gyrus
 Grey matter (Outside, Cell body; Including insula) vs. White matter (Inside, Fibers)
 Named structures:
o Cortex: Cortex; Insula
o Out  In: Cortex  Radiata (e.g. Corona, Optic)  Internal capsule  Cerebral
peduncle
o Association fibers: [1] Superior longitudinal fasciculus (Connect front & Back &
temporal lobe); [2] Arcuate fibers (between adjacent gyrus)
Functions (Selected): Language, Learning (Memory), Motion
 Language: Broca's (creation), Wernicke’s (comprehension) + Primary auditory cortex
(listen). Arcuate fasciculus.
o Easy to remember: Broca sounds like ‘Broadcast’, so it is for creation of language.
 Learning (memory):
o Limbic system (Cingulate gyrus + cortex of all lobes)
o Septal nuclei & Nucleus basalis (Basal Nucleus of Meynert): For working memory
(visual attention, habitual learning)
 All cholinergic neuron at cortex stems connected to it (green)

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Learning Pathway (Papez circuit):

Mammillothalamic
Hippocampus Fimbria Fornix Mamillary body
tract

Posterior
Anterior thalamic Repeat
Cingulate Gyrus Parahippocampus Entorhinal cortex
nucleus ( Hippocampus)
(Cingulum)

Note the locations of each structures.

Location of Septal Nuclei & Nucleus Basalis (Basal nucleus of Meynert):

PATHOLOGICAL EXAMPLES OF CEREBRAL CORTEX

Disease Description
Alzheimer’s disease Global brain atrophy (but firstly hippocampus)  Poor memory and
language
Frontotemporal lobe Local degeneration of Frontotemporal lobe (Clinically similar to
dementia Alzheimer’s; PET to differentiate: Red for active metabolic rate, Blue for
inactive)
Creutzfeldt-Jakob Formation of Beta-sheets prions  Kill neurons, spongiform appearances
disease in brain. Teenage onset, initial symptoms: Poor learning, memory  Die
in a few months

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LARGE AND IMPORTANT IMAGES

DIENCEPHALON: THALAMUS
LOCATION

CEREBRAL CORTEX

Basic Anatomy:

🧠Lobes (Frontal, Parietal,

Occipital, Temporal);

🧠Sulcus (e.g. Central sulcus –

separates Frontal vs. Parietal);
Gyrus

Le temporal lobe guy:

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 ↑Anatomy by Cortex / Function

↑Grey and White Matter of Brain

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HNS04 MENINGES AND BLOOD SUPPLY

OUTLINE

1. Meninges: Dura, Arachnoid, Pia

2. CSF circulation
3. Cerebral arterial supply
4. Cerebral venous drainage

1. MENINGES

Meninges: Dura (Periosteal, Meningeal), Arachnoid, Pia

DURA
 Important structures
o Dural folds (4): Falx cerebri (with superior & inferior sagittal sinus), Tentorium
cerebelli, Falx cerebelli, Diaphragma sellae
o Tentorium hiatus: Important place where brainstem passes
 Blood & Nerve supply
o Blood supply: Middle meningeal artery (and others)
o Nerve: Trigeminal (Supratentorial), C1-3 (Infratentorial)
 Very pain sensitive
 Pathological:
o Epidural hematoma (Skull fracture)
o Brain herniation: Cerebrum herniated alone tentorium hiatus and compresses
brainstem

ARACHNOID MATER
 Transparent spider-web
 Function: CSF circulation, support vessels & nerves, cushion brain
 Pathological:
o Intracranial hypertension: Papilledema (CSF space extends to eye) > Retina
engorgement
o Subarachnoid hemorrhage (by aneurysm in artery)

PIA MATER
 Adheres to brain, invagination at artery forms choroid plexus (secretes CSF)

Point to note: Spine

 Brain: Brain; Dura (Periosteal, Meningeal), Arachnoid, Pia
 Spine till L1: - Periosteal (Periosteum layer doesn't go to spine, everything else does)
 Spine at L1: Conus medullaris
 Spine L1-S2: Filum terminale.
 Spine S2 Below: Cauda equina (Meninges forms epineurium, stronger nerve roots)
 Pathological: Lumbar puncture (L345)

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2. CEREBRALSPINAL FLUID CIRCULATION

CSF Introduction
 ~130ml (2.3ml in spine); Pressure 8-15mmHg
 Production: from Plasma at choroid plexus (at ventricles)
 Functions: Buoyance, shock absorber, regulate intracranial pressure, homeostasis, clear
metabolic waste (Glymphatic system)
 Composition: No RBC, Little protein & WBC (<5/mm3), Less glucose, Less Ca K, More Cl
 Pathological:
o Subarachnoid haemorrhage: heavily blood stained CSF
o Xanthochromia: there was blood but broken down, yellow looking CSF
o Infection: Turbid CSF
Cerebral ventricles
 Cerebral ventricles: Lateral ventricles, Interventricular foramen, Third ventricle, cerebral
aqueduct, fourth ventricle, central canal
 Imaging (Please reference with PowerPoint / diagrams starting from Page 35 in this set of notes)
o Axial: Frontal horn, Body, Occipital horn, Temporal horn
o Coronal: Interventricular foramen, third ventricle
o Sagittal: Third ventricle, (Thalamus, midbrain), Cerebral aqueduct, Fourth ventricle,
(pons and medulla), Median aperture
o Other structures on imaging
 Small gaps = Sulcus
 Big gaps, Fissures; Interhemispheric, Lateral / Sylvian (Frontal | temporal)
 Spaces: Suprasellar cistern, Pre-pontine cistern, Cisterna magna, Basal cistern
Pathway of CSF Circulation: Choroid plexus secretes CSF  L & R lateral ventricle  Foramen Monroe
 3rd ventricle  Aqueduct  4th Ventricle (+Choroid plexus at 4th ventricle secrete additional CSF) +
Foramen of Luschka + Foramen of Magendie  Subarachnoid space (in brain and spinal cord)

Pathological:
 Hydrocephalus (Less blood flow, Brain fiber stretch.) Caused by increased production (tumor of
choroid plexus), Flow obstruction, Impaired absorption (e.g. arachnoid inflammation /
haemorrhage > Fibrosis). Treatment:
o (Risky) Brain herniation if you tap Raised ICP (depending on what's the cause of the high
ICP & when CSF space and ventricles good communication, brain herniation is very
dangerous)
o Endoscopic third ventriculostomy (if tumor obstructs 4th ventricle). Allow CSF drained
to arachnoid

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3. CEREBRAL ARTERY SUPPLY

Major divisions:
 Anterior: LR Internal Carotid  Gives Anterior CA, Middle CA
 Posterior: LR Vertebral artery
 Connected via: Circle of Willis, Surface anastomosis

Descriptions of Major Cerebral Artery:

Artery Travels where Supplies Points to note

Anterior CA Within Front & Coursing of Internal Carotid Artery: Cervical part >
interhemispheric Superior [Petrous part] Enters (Petrous temporal bone) >
fissure part of [Cavernous part] Anterior (Cavernous sinus) >
cerebrum [Cerebral part] Superior (Pierce dura &
subarachnoid) > Branches
Middle CA Within lateral Lateral Has Lenticulostriate arteries (Smol perforators;
(Sylvian) fissure Stroke). MCA is an end artery that doesn’t has
anastomoses (no collaterals, not part of Willis
circle!), so once occluded, damage is certain.
Vertebro- Around brainstem Cerebellum, Course: Subclavian > Foramen transversarium C1-6 >
basilar artery and cerebellum brainstem Around C1, enters foramen magnum (Easily injured
complex in neck)
Notable structures: Basilar artery, Posterior CA,
Posterior communicating artery
Notable branches: Superior, Anterior & Posterior
inferior cerebellar artery.
 Pathology: Cerebral infarction. Circle of Willis is a collateral (Tie up one, others can supply).
However, these are not perfect collaterals. The extent of injury depends on the anatomical
variations of Circle of wills (e.g. whether there is hypoplasia at anterior communicating artery).
Angiogram to determine.
 Other blood supply
o Blood supply at Spinal cord: Artery of Adamkiewicz (Great radiculomedullary), Anterior
& posterior spinal artery, (Intercostal artery)
o Microcirculation: Neurovascular unit (Microcirculation & Glial cell forms BBB) for
material exchange

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4. CEREBRAL VENOUS DRAINAGE

Sigmoid

Pathological: Subdural haemorrhage (Dura & Brain) [vs. Epidural haemorrhage]

Epidural Subdural
Cause Fractured skull (Brain not injured) Torn vein
Location Between skull and dura Between dura and brain
Prognosis Good Bad
Other venous channels: Basilar plexus (Some drainage at base), Cavernous sinus (Drains orbit, near
important structures Cranial nerve & ICA. Thrombosis danger: Infection within Danger triangle of face)

LEARNING OBJECTIVES

 Understand the anatomy of the meninges and its clinical relevance

 Describe and identify key structures of the cerebral ventricular system and abnormalities
affecting cerebrospinal fluid dynamics
 Understand and describe the vascular anatomy of the brain and spinal cord and appreciate its
application in the diagnosis of stroke

CONTINUE: DIAGRAMS OF HNS04 & FILL IN THE BLANKS EXERCISE

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Continue: Diagrams
of HNS04

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PICTURES

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 Ultimately: Drains into Internal Jugular Veins

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PRACTICE (FILL IN THE BLANKS)

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 Superficial

Deep

Ultimately: Drains into

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CONTINUE HNS04: (MORE DETAILED / EXTRA CONTENT) NOTES

MENINGES

Functions
 Protection
 Supports blood vessels supplying the brain
 Spaces for CSF flow

Comprises of: Dura mater, Arachnoid, Pia

DURA MATER
Tough barriers for protection. 2 layers, containing:
 Outer endosteal (/ periosteal) layer:
o Inner surface adhering to skull
o Ending at foramen magnum (∴Head only, not in spine)
 Inner meningeal layer:
o Adheres to endosteal layer most of the time, except at dura folds
o Ends at filum terminale (S2 level), Covering brain and spinal cord

Dural folds:
 Where inner meningeal layer separates from outer endosteal layer. The locations:
o Falx cerebri, Tentorium cerebelli
o Falx cerebelli, Diaphragma sellae
 Divides brains in several compartments:
o Left vs. Right
o Supratentorial vs. Infratentorial

Dura’s Nerve & Blood supply

 Nerve: Trigeminal nerve (supratentorial) + C1-3 (Infratentorial)  [These are very sensitive to
pain; hence Dura is very sensitive to pain and a cause of headache]
 Blood supply: Middle meningeal artery

Dura: Clinical relevance: Meningiomas (Tumor arising from tumor, usually benign but can be big)

ARACHNOID LAYER
Basic information
 Loose spider-web like layer: Arachnoid trabeculae linking arachnoid membrane to pia mater
 CSF running in subarachnoid space (Between arachnoid and pia)

Functions:
 CSF circulation
 Support Cerebral vessels
 Space for cranial nerve
 Cushion the brain

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Arachnoid granulations
 Projections into venous sinus
 For CSF circulation back to venous blood

PIA MATER
 Soft tender innermost membrane
 Covers brain and spinal cord, following cerebral sulci and gyri
 Forms Choroid plexus (in ventricles, which produces CSF)

Clinical relevance: Epidural vs. Subdural hematoma

Epidural hematoma Subdural hematoma

Cause Fractured skull (Brain not injured) Torn vein
Location Between skull and dura Between dura and brain
Prognosis Good Bad
Clinical relevance: Subarachnoid haemorrhage: Blood within subarachnoid space

Epidural Haemorrhage Subdural Haemorrhage Subarachnoid Haemorrhage

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HNS06 CHEMICAL NEUROTRANSMISSION I

OUTLINE

1. Electrical vs. Chemical synapse

2. Quantal nature of neurotransmitter release
3. Molecular machinery of vesicles & neurotransmitter release
4. Toxins that mediate neurotransmitter release
5. Presynaptic targets of neurotransmitter release

ELECTRICAL VS. CHEMICAL SYNAPSE

Electrical Chemical
Mechanism Physically joined by gap Neurotransmitters released & diffused across
junctions synapse
Abundance Less Most
Communication Ions flow directly Neurotransmitter
Nature All-or-none Signal modulation / adjustable magnitude (by
amount of neurotransmitters released)
Effect Excitatory only Excitatory or inhibitory (depending on
neurotransmitters)
Speed Quicker Slower

QUANTAL NATURE OF NEUROTRANSMITTER RELEASE

 Nature: Fixed size, spontaneous without stimulation but increases frequency with
stimulation.
 5000Ach molecules required to produce 0.5mV mini-end plate potential
 Quanta: Synaptic potentials are integral multiples of unit response (Vesicles)
 ACh release is Ca dependent

MOLECULAR MACHINERY OF VESICLES & NEUROTRANSMITTER RELEASE

 Mediating proteins: Synpatotagmin, Synaptobrevin, Syntaxin, , SNAP-25

 The proteins are not all there at the same time. In general, those for Ca channel tethering 
Ca triggering  Fusion

TOXINS THAT MEDIATE NEUROTRANSMITTER RELEASE

 Tetanus: Cleaves Synaptobrevin (on Inhibitory neurons)

 Botulinum toxin (BoTX): different type cleaves Synaptobrevin, Syntaxin, SNAP 25 (on
Motor /excitatory neurons)
 Alpha-latrotoxin: binds to neurexin to cause vesicle release even without Ca

PRESYNAPTIC TARGETS OF NEUROLOGICAL DISEASES

 Congenital myasthenic syndromes

o Cause: Defective ChAT  Poor ACh resynthesis  Inadequate release
o Inheritance: Autosomal recessive: inadequate ACh resynthesis
o Presentation: Episodic apnea, weak eye muscles (double vision), mouth and throat
muscles (chewing & swallowing difficulty)

55
 o Treatment: AChE inhibitors
 Lambert-Eaton myasthenic syndrome
o Cause: Serum antibodies attack voltage gated Ca channels  not enough Ca
dependent ACh release
o Treatment: Plasma exchange to remove antibodies, Use immuno-suppressants

LEARNING OBJECTIVE

 Characteristics of chemical synapse.

 Mechanics of neurotransmitter release.
 Vesicular vs calcium hypothesis.

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HNS07 CHEMICAL NEUROTRANSMISSION II

OUTLINE

1. Neurotransmitters
2. Receptors: nACh, Glutamate, GABA
3. Others

NEUROTRANSMITTERS

 Criteria of neurotransmitter: is stored at presynaptic terminal, can be released, can be

removed
o Can be produced / stored at presynaptic terminal: Synaptic vesicles have substance
and enzyme), Exogenous substance to inhibit degradation
o Can be released: In response to presynaptic depolarization
o Can produce response: Specific receptors on post-synaptic side ( Can be mimicked
by exogenous neurotransmitters)
 Properties of some neurotransmitters
o Excitatory: ACh, Glutamate, Epinephrine & Norepinephrine, Histamine, ATP
o Inhibitory: GABA, Glycine, Serotonin
o Both: Dopamine, Neuropeptides
 Classification by size:
o Large molecules: Neuropeptides
o Small molecules: the rest
 Way of synthesis (differs by size)
o Small: Slow transport, meet precursors at axon terminal
o Large: Fast transport, prepacked with precursor at cell body
o Both transported from cell body (ER / Nucleus for transcription & translation) to
axon terminal by microtubules

RECEPTORS
 Features:
o Partly extracellular, Partly intramembranous, Partly intracellular
o Commonly several subunits, although binding site may not be shared by all subunits
 Examples of receptors:
o Glutamate (Excitatory): AMPA, NMDA, Kainate
o Inhibitory: GABA, Glycine
o Serotonin: 5HT3
 Summary: Synaptic receptors vs. Ionotropic receptors
Ionotropic Metabotropic
Type Ligand-gated ion channel G protein coupled receptors
Example nACh, GABA, AMPA, NMDA mACh, mGluRs
Response Change in conformation leads Activates secondary messengers > AP
to ion flux > AP generation generation and other cellular effects
Speed Fast Slow
Duration of Short Long
response

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NICOTINIC ACH RECEPTORS
 ACh cycle (important but already learnt)
 nAChR blockers: e.g. alpha bungarotoxin, alpha neurotoxin, Erabutoxin, Curare, Arecoline

GLUTAMATE RECEPTORS
 2 receptors: AMPA, NMDA receptor
o AMPA: Na ion channels
o NMDA: Mg routinely blocks the channel even when glutamate binds. When
depolarization is big, the Mg will be kicked away, and channel is opened for Ca and
Na influx. Na generates new potential. Ca activates changes in the cell (e.g. vesicle
transport and fusion at post-synaptic).
Hence, the sequence: AMPA first, then NMDA
 Special feature: NMDAR-dependent Long Term Potentiation
o Meaning: High frequency stimulation of axons can cause long-lasting increase in
sensitivity of post-synaptic neuron to that stimulation.
o Cause: Influx in Ca > Activate enzymes e.g. CaMKII > Phosphorylates scaffolding
proteins e.g. PSD > More AMPAR insertion from perisynaptic to synaptic region >
Faster depolarization (i.e. positive feedback) [i.e. Influx of Ca triggers a number of
steps that leads to long term potentiation]
 Regulating Glutamate and metabotropic glutamate receptors (mGluRs)
o G protein coupled receptor: Binding > ATP replace GDP on alpha subunit > Direct or
indirect (i.e. as secondary messenger) of ion channel
o Changes ‘plasticity’ of NMDARs (i.e. similar to regulating sensitivity / amount of
NMDARs expressed… I guess)

GABA RECEPTOR (OPTIONAL)

 Different types of receptors, e.g. A and C. A Receptor: 2 alpha, 2 beta, 1 gamma.
 GABA allows Cl- to flux in > hyperpolarization (Inhibitory post-synaptic potential IPSP)
 Benzodiazepine increases GABA binding > Prolonged effect > Sleep / Anti-anxiety

OTHERS
 Spatial summation vs. Temporal summation
o Spatial: potential from different synapse > summation at hillock
o Temporal: same synapse create a quick potential ('in rapid succession') >
Summation at hillock
 Glutamate-glutamine-GABA cycle
o Glutamate: Recycle via EAAT, mainly by astrocytes (converted to glutamine > give
to neuron via SNAT) or by neuron directly (repacked in vesicles)
o GABA: derived from glutamate, GABA taken up by GAT-3 > Broken down to
glutamate and reproduced again
 Or Metabolized: Converted to succinate > Tricarboxylic acid cycle (mediates
cellular ATP synthesis) Enzymes: GABA aminotransferase, succinic
semialdehyde dehydrogenase

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HNS08 CRANIAL NERVES

(1) SUMMARY
Note: Faculty has their own notes (Dr. Cora Lai, Dr. Cecot) which are in greater detail. Strongly recommend you refer to that one instead, it is more
useful.
Name Typ Origin Synapse location Supplies Function Signs of damage
e
I Olfactory SS Bipolar cells of Olfactory bulb Superior nasal concha, Upper 1/3 of Smell Anosmia
olfactory epithelium nasal septum
II Optic SS Retinal ganglion Lateral geniculate Retinal bipolar cells Vision Blindness
cells nuclei
-- Superior colliculus, -- -- Pupillary No consensual
Pretectal nuclei light reflex pupillary constriction
III Oculomotor SM Oculomotor nucleus Recti: Superior, Inferior, Medial; Eye Ophthalmoplegia
Inferior oblique movement, Severe ptosis
Levator palpebrae superioris Upper eyelid
elevation
VM Edinger-Westphal nucleus Ciliary ganglion (to pupillary Pupillary Mydriasis, No
sphincters) contraction, consensual pupillary
accommodat constriction
ion of lens
IV Trochlear SM Trochlea nucleus Superior oblique muscle Intorsion Diplopia, tilted head
V Trigeminal S Trigeminal ganglion Spinal trigeminal Ophthalmic, Maxillary, Mandibular Sensation No facial sensation, no
nucleus, Principal divisions ipsilateral corneal
trigeminal nucleus  To skin of face reflex
S Mesencephalic trigeminal nucleus Mastication muscles, Periodontal Propriocepti Insignificant
membrane, temporomandibular ve reflex
joint, external ocular muscle
BM Trigeminal motor nucleus Temporalis, masseter, lateral and
medial pterygoids, tensor veli
palatini, tensor tympani, anterior
belly of digastric muscle
VI Abducens SM Abducens nucleus Lateral rectus muscle Abduction of Diplopia, cannot
eye abduct eye
VII Facial BM Facial nerve Facial muscle: Buccinator, Facial Paralysis of facial
Stapedius, Stylohyoid, posterior expression muscle (Ipsilateral)
belly of digastric, Platysma, articulation,
occipitalis ingestion
VM Superior salivatory nucleus Major petrosal nerve Pterygoid Nasal, No lacrimation
canal & ganglion  Maxillary nerve Lacrimal
 Lacrimal gland, mucous glands secretion
of nasal cavity
Chorda tympani  Lingual nerve  Salivary Little saliva / dry mouth
Submandibular ganglion and secretion
sublingual glands
SS Geniculate ganglion Solitary nucleus Taste buds of anterior 2/3 of tongue Taste Loss of taste at
(Rostral) corresponding parts
GS Geniculate ganglion Spinal trigeminal Posterior auricular region, external Sensory (?) Insignificant
nucleus (caudal) auditory meatus, tympanic
membrane (ear things)
VIII Vestibulo- SS Vestibular ganglion Vestibular nuclei Hair cells of ampullary crest in Balance Vertigo (spinning),
cochlear and cerebellum semicircular ducts and maculae of Disequilibrium,
saccule and utricle nystagmus
SS Spiral ganglion Cochlear nucleus Hair cells of spiral organ of Corti Hearing Neural deafness
IX Glosso- BM Nucleus ambiguus -- Stylopharyngeus, superior Elevates Slight dysphagia
pharyngeal pharyngeal constrictor pharynx
VM Inferior salivatory -- Tympanic plexus  Minor petrosal Salivary Little saliva / dry mouth
nucleus nerve  Otic ganglion  secretion
Auriculotemporal nerve  Parotid
gland
SS Inferior (Petrosal) Solitary nucleus Taste buds in posterior 1/3 of Taste Loss of taste at
ganglion (Rostral) tongue corresponding parts
GS Inferior, Superior Spinal trigeminal Anterior epiglottis, root of tongue, Sensory Tonsillar anesthesia.
ganglion nucleus soft palate border, uvula, tonsil, Loss of gag reflex from
pharynx, auditory tube, middle ear ipsilateral stimulus

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 VS Inferior ganglion Solitary nucleus Carotid sinus & bulb Reflex Insignificant
X Vagus BM Nucleus ambiguus Palate, Pharyngeal constrictors, Deglutition, Dysphagia,
larynx Phonation Hoarseness, paralysis
of soft palate,
deviation of velum and
uvula to contralateral
side
VM Dorsal motor nucleus Cardiac, Pulmonary, Esophageal, (Those Insignificant
celiac, mesenteric plexus, etc. effects about
vagus supply
last year)
VS Inferior (nodose) Solitary nucleus Epiglottis: taste bud
ganglion Posterior epiglottis, pharynx, Visceral Anesthesia of pharynx
larynx, trachea, bronchi, sensation, and larynx ipsilaterally
esophagus, stomach, small reflex
intestine, colon
Aortic sinus and bulb Reflex --
S Superior (jugular) Spinal trigeminal External ear and meatus Sensory Anesthesia of
ganglion nucleus (caudal) ipsilateral external
auditory meatus
XI Accessory BM Nucleus ambiguous Communicates with vagal branches Swallowing, Insignificant
cranial (Pharynx, Larynx) Vocalization
Spinal BM Motoneurons of spinal assessor nucleus Sternocleidomastoid, Trapezius Movements Weakness in turning
muscle of head and head towards opposite
shoulder side and shrugging
shoulder
XII Hypoglossal SM Hypoglossal nucleus Styloglossus, hyoglossus, Tongue Tongue wasting
genioglossus, tongue movement (Ipsilateral), ipsilateral
deviation upon
protrusion
Note: S=General Sensory (e.g. touch, pain, temperature), somatic / visceral; SS=Special sensory: Smell, vision, taste, hearing, balance; SM=Somatic
Sensory; BM=Brachial motor (pharyngeal muscles)

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ANATOMY

Location of nucleus:

🧠 Sensory: (1) Principle, (2) Mesencephalic, (3) Spinal trigeminal, (4) Vestibular, (5) Cochlear, (6) Solitary

🧠 Motor: (1) Oculomotor, (2) Edinger-Westphal preganglionic, (3) Spinal trigeminal, (4) Vestibular, (5) Facial, (6) Abducens, (7) Superior salivatory, (8)
Inferior salivatory, (9) Hypoglossal, (10) Dorsal motor vagal. (11) Ambiguus

62
 More on Trigeminal nerve
 The 3 Branches / Divisions: Ophthalmic; Maxillary, Mandibular
 Nucleus: Trigeminal motor, Mesencephalic, Pontine trigeminal,
Spinal trigeminal, Trigeminal nerve (V) ganglion

Locations of the Cranial nerves

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HNS10 INFECTIONS OF THE CNS II: VIRAL AND PRION INFECTIONS OF THE CNS

OUTLINE

1. Background
a. Clinical conditions: Meningitis, Encephalitis Meningoencephalitis, Myelitis
b. Pathogenesis
c. Etiologies
d. Laboratory diagnosis
2. Specific virus: Enterovirus, Herpesvirus (HSV, VZV), Arbovirus (JEV), Rabies virus
3. Prions

BACKGROUND

 Clinical conditions. … is the inflammation of

o Meningitis: Meninges (Infectious or Non-infectious)
o Encephalitis: Brain parenchyma
o Myelitis (Myeloradiculitis): Spinal cord (& Nerve roots). Commonly together.
 Symptoms:
o Fever
o Meningeal irritation: Neck stiffness, Kernig's sign
o Increase intracranial pressure: Headache, vomiting
o Brain parenchyma involvement: Altered consciousness, seizure, neurological signs
o Specific to cause: Parotitis in mumps, Rash in enterovirus
 Pathogenesis:
1. Cytolytic effects of direct invasion: Breaching of host immunity (e.g. mucosa) >
Hematogenous dissemination > Cross BBB to CNS > Inflammatory responses (e.g.
Altered BBB to allow Ig leakage into CSF, Local CNS Ig synthesis)
2. Post-infectious syndromes, E.g. Rubella (Usually biphasic). Replicate outside > Cross
reacting immune response > Demyelination
 Etiologies (Selected):
o Meningitis: Enterovirus (Echovirus, Coxsackievirus), Herpesvirus (esp. HSV2)
o Encephalitis: HSV1, Enterovirus, Arbovirus (JEV)
o Myelitis:
 Acute: Enterovirus, Arbovirus, herpesvirus, mumps
 Chronic: HTLV-1, etc.
 Laboratory diagnosis
o Specimens:
 CSF (Lumbar puncture): All.
 Viral typical: Less WBC than bacterial, Predominantly lymphocytes,
normal protein, gram stain negative, CSF normal
 Throat swab: Adenovirus, Parainfluenza, Influenza
 Skin vesicular: VZV, HSV, EV
 Serology: Arbovirus
  Rectal swab
 Brain biopsy seldom but necessary in unexplained progressive neurological
deterioration
(Note: May not directly indicate CNS involvement, but could aid diagnosis)
o Other investigations:
 PCR/RT-PCR
 Antibody test: IgM indicates intrathecal synthesis but is a late finding, Paired
sera (measure antibody index), Single serum IgM (JEV, EBV, CMV)
 Viral culture seldom

SPECIFIC VIRUS

Enterovirus
 Background: Small RNA virus in Picornaviridae. Lots of types (Polio, CoxAB, Echovirus, EV70,
EV71, EVD68
 Clinical: Commonest cause of aseptic meningitis. Cause Hand, Foot & Mouth disease
(characteristic lesions). Most mild and self-limiting, occasionally severe (brainstem encephalitis,
flaccid paralysis [esp. polio])
 Susceptibility: Marked summer seasonality, children most susceptible, school outbreak
 Treatment: No specific antivirals (rely on immunomodulation)

HSV
 Pathology: Primary invasion via olfactory nerve (to frontal lobe), Reactivation from trigeminal
ganglion to infect pia mater & brain. Both HSV meningitis (self-limiting, HSV2; Recurrent
benign lymphocytic meningitis) and encephalitis (fatal, common permanent brain damage)
possible / medical emergency
 Clinical: Pertained to brain (Altered consciousness, headache, Seizures, vomiting, various
neurological dysfunctions e.g. memory loss, personality change).
 Diagnosis: PCR with lesion. Encephalitis: Empirical antiviral (acyclovir) with long course (2-3W)
saves lives & prevents relapse.

VZV (Very common, quite important)

 Background: Herpesviridae. Latency at dorsal root ganglion (reactivated in immunodeficiency
e.g. AIDs)
 Clinical: Skin lesions. Primary (chicken pox) vs. Secondary (Shingles). May or may not have CNS
manifestation, may be during or after episode (Commonly myelitis/ Myeloradiculitis with
characteristic segmental paresis pattern, acute cerebella ataxia, Encephalitis (seldom
meningitis))

JEV (Quite common in Asia, much less common overseas)

 Background: RNA Flaviviridae / Arbovirus, transmitted by mosquitoes (Zoonosis). Asia.
 Clinical: <2W incubation, mostly (95%) asymptomatic, but severe symptoms possible: Fever,
seizures (subtle e.g. eyebrow twitch), permanent neurological damage) [Subclinical]
 Diagnosis: IgM, PCR

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Rabies virus (Dr Chan: ‘No need to worry so much because it is rare’)
 Background: RNA Rhabdoviridae. Zoonosis (Dogs, transmit by bites), HK eradicated (imported
case possible). Replication at bite, travels to brain via spinal cord to cause encephalitis.
 Clinical: Incubate could be to years. Always fatal. Prodromal: mild symptoms e.g. itch on
wound. 2 types of manifestations: Furious (Meningoencephalitis) vs. Paralytic (Flaccid paralysis
starting from bite)
 Diagnosis: Brain / Skin biopsy > RT-PCR
 Treatment: No treatment, though post-exposure prophylaxis needed (Active/Passive
immunization). Control stray dogs & vaccinate them.

PRIONS
Dr Chan: ‘No need to worry too much about Prion because it is very rare’
 Background: Infectious proteins from misfolded isoform (Protease insensitive; could be genetic
or acquired. Accumulation of PrPc). Resistant to heat and UV as no DNA or RNA.
 Clinical: Rapid neurological decline. Rare. Spongiform encephalopathy. Lack of inflammatory
response (normal CSF). Rapid dementia and neurological deficits.
 Diagnosis: MRI brain, CSF to check specific proteins for CJD
 Treatment: None.
 Prevention: Special precaution for neurological procedures, blood transfusion, transplantation.
Avoid dietary exposure.
CJD
 Types: Sporadic (most), Genetic (few)
 Most common prion but still rare.
 Clinical: Psychiatric then neurological. Quick neurological progression with whole brain
involvement, death <1Y.
 Other types: Variant CJD reported in recent years: from Bovine. Iatrogenic in transplants
(extremely rare). Kuru (now eradicated). Animal: Scrapie in sheep, Bovine spongiform
encephalopathy in Cattle (mad cow diseases; zoonotic).
 Transmission: No person to person (except iatrogenic). Open ward with standard precautions,
but dispose all instruments (+Labelling all samples, perform as last case). Special disinfectant if
must reuse (Cl, NaOH, some enzymes)

LEARNING OUTCOMES

 Relate the pathogenesis of viral meningitis, encephalitis and myelitis to the clinical features
seen in these diseases.
 List the common viral aetiological agents causing meningitis, encephalitis and myelitis.
 Describe the epidemiology and pathogenesis of common viral infections of the CNS.
 Describe the laboratory diagnosis of viral infections.
 Describe the pathogenesis, epidemiology, clinical presentations, diagnosis and prevention of
prion diseases

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HNS11 INFECTIONS OF THE CNS III: PRINCIPLES OF ANTIVIRAL THERAPY

OUTLINE

1. Background
2. Herpesviridae (HSV, VZV, CMV)
3. Influenza
4. SARS-CoV-2
5. HIV antiretroviral
6. Hepatitis
7. Broad spectrum antivirals

BACKGROUND

 Lifecycle of virus: Attachment, penetration, uncoating, gene expression and replication, protein
synthesis processing & assembly, and release (by exocytosis) ± Maturation
o Extra steps for HIV (Retrovirus): [1] RNA to DNA; [2] Integrate gene into host genome
 (Classification of antivirals by Mechanism of action: Entry, Uncoating, Polymerase, Protease,
Release inhibitor)
 Classification of antivirals by antiviral activity: See below
 Considerations in choosing antivirals: [1] Antiviral activity, [2] antiviral resistance (though
antiviral-susceptibility seldom checked because not cost-effective; rely on trial-and-error), [3]
Pharmacodynamics & pharmacokinetics (e.g. avoid oral drug in diarrheic patients), [4] Side
effects (avoid inhaled Cidofovir in asthmatic patients)

ANTIVIRALS FOR HERPESVIRIDAE (HSV, VZV, CMV)

 DNA Polymerase inhibitor: Acyclovir & Cidofovir (for HSV, VZV); Ganciclovir, Foscarnet (CMV)
o Acyclovir: Deoxyguanosine analogue. Prodrug (Triphosphorylated by viral thymidine
kinase, then by cellular enzyme). Side effect: Neurotoxicity, Renal
o Valacyclovir: Prodrug of Acyclovir (Ester hydrolyzed by liver) for better oral
absorption / higher bioavailability
o Ganciclovir: Same as Acyclovir. Side effect +bone marrow suppression & teratogenic
(pregnant women contraindicated)
o Valganciclovir: Prodrug of Ganciclovir (similar to Valacyclovir)
o Cidofovir: Deoxycytidine analogue; for acyclovir resistant. Side effect: Nephrotoxicity
o Foscarnet: Pyrophosphate analogue targeting DNA polymerase. For ganciclovir
resistant CMV. Side effect: Nephrotoxicity, neurotoxicity, electronic imbalance, etc.
(Quite toxic, second line)
 (New) Inhibit DNA terminase complex (for DNA processing & packaging): UL56/Letermovir. For
resistant.

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INFLUENZA DRUGS

 Influenza drugs: M2 inhibitors (Amantadine, Rimantadine), Neuraminidase inhibitors

(oseltamivir, zanamivir), Acid polymerase inhibitor (Baloxavir)
o M2 inhibitors (Amantadine, Rimantadine): Seldom used now due to resistance. Inhibits
acid-mediated dissociation & alteration of hemagglutinin. Side effect: CNS symptoms
o Neuraminidase inhibitors (oseltamivir, zanamivir): Inhibit release. Oseltamivir (well
tolerated but some resistance); Zanamivir (inhaled, cause bronchospasm, but effective
for some resistant strains)
o Acid polymerase inhibitor (Baloxavir): Inhibit endonuclease (cannot acquire host pre-
mRNA as PA subunit of viral polymerase blocked).

SARS-COV-2 DRUGS

 SARS-CoV-2: Remdesivir, Dexamethasone, IFN beta-1b. Triple therapy (Interferon, Lopinavir-

ritonavir, Ribavirin)
o Remdesivir: Adenosine analogue. Prodrug. Inhibit viral polymerase.
o Dexamethasone: A steroid (not an antiviral) to suppress inflammation. Consistently
reduces mortality.
o IFN beta-1b: Induce host antiviral proteins
o Triple therapy: Interferon (induces host antiviral proteins), Lopinavir-ritonavir
(Protease inhibitor), Ribavirin (Guanosine analogue)

HIV ANTIRETROVIRAL DRUGS

 Antivirals for HIV (Antiretroviral therapy): Reverse transcriptase inhibitors, Protease inhibitors,
Entry inhibitors
o Entry inhibitors (Receptors: coreceptor CCR5): CCR5 antagonist Maraviroc; Fusion
inhibitor Enfuvirtide
o Reverse transcriptase inhibitors (Receptor: Reverse transcriptase): First line, 2 types: [1]
Nucleoside analogue reverse transcriptase inhibitor (NRTI) e.g. Zidovudine; [2] Non-
NRTI (NNRTI) e.g. Efavirenz
o Integrase inhibitor
o Protease inhibitors (for post-translational processing): Lopinavir-Ritonavir
 General side effects: Cardiac (e.g. Long QT interval), GIT (can be very severe), Endocrine &
Metabolic (Lactic acidosis, Dyslipidemia, Lipodystrophy), Bone marrow suppression,
Hypersensitivity (e.g. Steven Johnson Syndrome), etc.

HEPATITIS DRUGS (REFER TO OTHER LECTURES)

 HBV: Nucleoside analogues e.g. Entecavir

 HCV: Protease inhibitors, (Interferons, Ribavirin)

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BROAD SPECTRUM ANTIVIRALS

 Ribavirin:
o Guanosine analogue, with various MoA: inhibit viral polymerase, cause lethal
mutagens, alters nucleotide pool.
o Effective against many virus (hence broad spectrum) but not very effective. Specialty:
Hepatitis E, respiratory virus, Hantavirus, for immunocompromised patients.
o Major side effects: Hemolysis, bone marrow suppression.
 Cidofovir: Acyclovir-resistant HSV, Adenovirus, BK virus, Poxvirus, papillomavirus. Side effect:
Nephrotoxicity
 Lopinavir-Ritonavir: Protease inhibitor, originally for HIV, now proven useful for various
coronavirus (MERs, COVID-19)

LEARNING OBJECTIVES

 Describe the biology, transmission and pathogenesis of prion diseases and contrast this with
those of viruses and bacteria.
 Describe the infection control risks posed by prion infections.
 Describe the mechanisms of action of commonly used antiviral agents and compare them with
antibiotics.
 Describe the use of antivirals in herpes simplex virus, varicella zoster virus, cytomegalovirus,
HIV and influenza disease.

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HNS12 SOMAESTHETIC PATHWAY AND SOMATIC SENSATION

OUTLINE

1. Somesthetic receptors –Basics

2. Somesthetic Pathways
3. Clinical Relevance

INTRODUCTION

Classifications
 By consciousness
o Conscious (Cerebral cortex)
o Unconscious (Cerebellum, etc.)
 By type of stimulus
o Exteroception: external e.g. pressure, touch)
o Proprioception: internal e.g. muscles, joints
o Interoception: internal functioning e.g. pH, O2
Note: Sensation and perception are not the same.
Perception (conscious interpretation, e.g. awareness of pain & discomfort)
Not all sensation turns into perception. It depends on whether it enters the cerebral
cortex (sensation may not be processed, or may be processed by cerebellum
unconsciously)

General organization of somatosensory system: Receptors + Circuit

 Receptor: Sensory Receptors
 Circuit: Ascending pathway (by Pseudo unipolar neurons)
o Myelinated: Aα (Proprioceptor, thickest and quickest), Aβ (Mechanoreceptor), Aδ
(Temperature)
o Non-myelinated: C
 Perceptual: Processing in cortical sensory area

SOMESTHETIC RECEPTORS

 Types of sensation: General vs. Special

o General: e.g. Touch, temperature, pain, vibration
o Special: Light, odour, taste, balance, sound

Receptors names:
 Mechanoreceptors:
o 3 qualities to detect: Pressure, vibration, touch
o Types of receptors:
 In Epidermis: Free nerve endings (Social touch, injurious force)
 In Superficial dermis: Hair follicles (skin movement), Meissner corpuscle (skin
motion), Merkel cell (Fine tactile / discriminative touch, temperature)
 In Deep dermis: Ruffini corpuscle (stretch), Pacinian corpuscle (vibration)

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  Proprioceptors
o 3 qualities: Position (limb, body), movement (direction, velocity), force (of contraction)
o Proprioceptors: Muscle spindle, Golgi tendon organ, joints
 Thermoreceptors:
o 2 qualities: Cold, Warm
o Receptors: Transient receptor potential receptors (Detects cold & heat pain; gated by
both temperatures and chemical ligands e.g. menthol, mint, capsaicin)
 Pain receptors (Nociceptors / free nerve endings; detects chemicals ligands from damaged cell)
 Glossary
o Receptive field: Area monitored by single receptor cell (Larger = less sensitive). Tested
by 2-point discriminative test
o Lateral inhibition: Suppressed sensatory signals at neighboring receptors

2. SOMESTHETIC PATHWAYS

INTRODUCTION

The types:
1. Spinothalamic / Anterolateral (at A&Lateral spinothalamic tract)
2. Dorsal column-medial lemniscus (at cuneate fasciculus & gracile fasciculus)
3. Spinocerebellar (at A&P spinocerebellar tract

Other Information
 Peripheral signal to sensory cortex: through 2-3 successive neurons (+ some other interneurons
along the path)
 Anterolateral (1) and Posterior (2): Thalamus  Sensory cortex
 Spinocerebellar: Terminates at cerebellum (Does not contribute to sensory perception)

ORDERS OF NEURONS
Order First order neurons Second order neurons Third order neurons
From Skin (e.g. cutaneous 1st order neuron (spinal 2nd order neuron
receptors, cord/ brainstem)
proprioceptors)
To CNS (e.g. Spinal cord, Thalamus, Cerebellum Cerebral cortex (Primary
brainstem) sensory cortex)
Cell body locations Dorsal root / Cranial Dorsal horn of spinal Thalamus
cord
Synapse with 2nd order, Interneurons 3rd order Primary sensory cortex
in CNS (if reflex) neurons
Others -- Axon: Decussation Present in spinothalamic
and DCML pathway

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DETAILS OF THE 3 PATHWAYS
Pathway (1) Spinothalamic (2) DCML (3) Spinocerebellar
Nature Conscious perception Conscious perception Unconscious perception
Function Light non- Discriminative fine touch Coordinate skeletal muscle
discriminative touch, (Merkle cell), vibration activity (Unconscious
pressure and itch (Pacinian corpuscle), proprioception; Muscle /
(anterior pathway), proprioception (Muscle tendon stretch 
pain and temperature spindles, tendon organs) Cerebellum).
(lateral pathway)
Fiber type Small myelinated (Aδ) Large Myelinated (Aα, Aβ, --
and unmyelinated (c) Aγ)
Receptor Free nerve endings Merkel cell, Pacinian Proprioceptors
corpuscle, muscle spindles,
tendon organs, etc.
1st order Dorsal root ganglion Dorsal root ganglion 3 types pathways:
( Gracile fasciculus (below a. Dorsal spinocerebellar:
T6), Cuneate fasciculus from lower trunk; synapse
(above T6)) at nucleus dorsalis (Clarke)
2nd order Dorsal horn of grey Gracile nucleus, Cuneate b. Cuneocerebellar: from
matter (in spinal cord) nucleus (in medulla) upper trunk and neck
3rd order Ventral posterolateral VPM (Face), VPL (Body) c. Ventral spinocerebellar:
nucleus (in thalamus) thalamus from lower limb spinal
Anatomy: Lateral + Anterior Medial lemniscus (Cuneate motor neurons
the tracts / spinothalamic tract fasciculus [lateral∵upper],
fibers gracile fasciculus [medial∵
lower]
Decussation Anterior white Medulla oblongata No (a, b)
commissure (spinal Undone ∵Cross twice (c)
cord)
Summary of Terminates at dorsal 2nd order fibers from dorsal Unconscious proprioception
highlights horn  Decussation column nuclei  rather than conscious
in spinal cord Decussation in medulla  sensation. 2 neurons only.
Ascend in medial lemniscus Ipsilateral.
 Thalamus
Important They will branch cranially to the posterior horn across Always ipsilateral ∵none
midline, and caudally to 3-5 spinal cord levels (hence /undone decussation
damage at one section may affect function a few
levels below –contralaterally)
Diagram See PowerPoint –very good
diagrams!

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(Personal suggestion: Remember to go to HNS Anatomy Practicals! It really helped with my
understanding since these are so hard to visualize.)

ADDITIONAL UNIT: CRANIAL NERVES –TRIGEMINOTHALAMIC TRACT

 Some cranial nerves also have somatosensory functions: Trigeminal (V), Facial (VII),
Glossopharyngeal (IX), Vagus (X)
 They follow the typical 3-order neuron system to relay sensation:
o 1st: Enters cranial nerve
o 2nd: ± Decussation  Ascends to thalamus
o 3rd: Ascends to somatosensory cortex (at VPM)

3. CLINICAL RELEVANCE: LOSS OF SOMAESTHETIC SENSATION

LOSS OF SOMAETHETIC SENSATION

Damage to: “Damage to the thalamic projection

neurons in the spinal cord or brainstem or
 Primary sensory neuron (i.e. Peripheral nerve injury): No sensation in regionto the third order neurons in the cerebral
hemisphere will cause loss of sensation
supplied from the body below the level of the lesion”
o Dermatome: Area of skin supplied by the right and left dorsal
roots of the single spinal segment
 Single spinal segment: Usually sensation from a skin
location is relayed by neurons of a few spinal segments.
It takes 3 damaged nerves for a skin region to lose
sensory function totally.
 Thalamic projection neurons in spinal cord / brainstem / Third order neurons in cerebral
hemispheres: No sensation from body below the level
 Cause of damage: Lesions, injury, infarct, etc.

Processing of information
 Most somatic sensory information is relayed to thalamus for processing
 Adaptation: Reduce information to cerebral cortex (1%)

LOSS OF FUNCTION AT PICA AND AICA

 PICA (Lateral medullary syndrome); AICA (Lateral pontine syndrome): Various common
symptoms:
o Spinal trigeminal tract (Loss of pain & temperature at ipsilateral face)
o Spinothalamic tract (Loss of pain & temperature at contralateral body)
o Vestibular nuclei (vertigo, nausea, vomiting); Inferior cerebellar peduncle (Ataxia,
Dysmetria)
o Sympathetic fibers (Ipsilateral Horner syndrome)
 Specific symptoms to differentiate between

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 o PICA only:
 Nucleus ambiguus (Dysphagia, hoarseness, decreased gag reflex)
 Solitary tract (Ipsilateral taste loss)
o AICA only:
 Cochlear nucleus (Ipsilateral hearing loss),
 Facial nerve (Ipsilateral facial paralysis, taste loss at anterior 2/3 of tongue,
decreased lacrimation & salivation

BROWN-SEQUARD SYNDROME
 Hemisection of spinal cord. E.g. at T10, effects:
o Ipsilateral loss of proprioceptive sensation & 2-point discrimination
o Ipsilateral motor paralysis below the level
o Contralateral loss of pain and temperature sensation a few levels below lesion (∵ spinal
thalamic vs. DC tract & Dermatome)

LEARNING OBJECTIVES

 To distinguish the modalities of

somatic sensation
 To state the qualities and receptors of
each somatosensory modality
 To understand the anatomy of major
ascending sensory pathways

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HNS13 PAIN PATHWAY AND MECHANISMS OF PAIN

OUTLINE

1. Background
2. Receptors of pain: Nociceptors
3. Pathway of Pain
4. Pain sensitization
5. Perceptions of pain (Referred pain, Pain modulations)

BACKGROUND (NOT IMPORTANT)

 Features of pain: Unpleasant, Emotional, Tissue damage (actual or potential)

 Classification:
o Somatic vs. Visceral
 Somatic: Superficial (initial vs. delay) vs. Deep (Bons, joints, muscle)
 Double pain sensation: Fast & Rapid (for initial pain) vs. Slow & dull

RECEPTORS OF PAIN: NOCICEPTORS

 Free nerve endings / not encapsulated

 Widely distributed around body but NOT in some places, e.g. notably brain / neural tissue
 2 types of afferent nerve fibers: Alpha-delta; C fibers

Types of pain detected
Description
Quality of fibers
Types of stimulus detected
Alpha-delta C-fibers
Initial pain (Sharp & rapid) Delay pain, Deep pain (Dull & slow)
Sharp, Pricking Burning, dull
Myelinated & Thicker Unmyelinated & Thinner
Mechanical Chemicals (e.g. pH, hypoxia, lactic
Extreme temperature acid, prostaglandin, etc.)

PAIN PATHWAY (SIGNAL TRANSDUCTION)

Pain sensation has 2 aspects: Discrimination (localization, intensity, quality) vs. Affective
1. Discriminative aspect of pain
 Neurotransmitter: Glutamate (both), Substance P (C fibers only)
a) Pathway at body: Spinothalamic tract (Decussate at anterior white commissure to
contralateral; > thalamus (VPL) nucleus > Cortex S1, S2
b) Pathway at H&N: Trigeminothalamic tract (Trigeminal nucleus > (2nd order)
descend to Medulla > Decussation > Thalamus (VPM) > Cortex S1, S2)
2. Affective aspect of pain (Affect-motivational pain pathway: to various locations)
 Limbic system: Thalamus, cingulate cortex, amygdala, hypothalamus
 Reticular formation: Cannot sleep well

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PAIN SENSITIZATION

 Hypersensitivity. Key points:

o Injury=more sensitive (lower threshold to induce pain)
o Will spread to remote site
o 2 types of hypersensitivity: Allodynia (normally non-painful stimulus becomes painful)
vs. Hyperalgesia (painful stimulus becomes even more painful)
 Mechanism of pain sensitization: Peripheral vs. Central sensitization
a) Peripheral sensitization (at site of injury). Causes of pain: Mechanical, Chemical from
damaged cells (Bradykinin, Prostaglandin, Substance P (stimulates histamine release),
Calcitonin-gene-related peptide: Stimulates nociceptor directly + inflammation for
hyperalgesia; Chemicals spread to neighboring sites to cause secondary pain
b) Central sensitization (at central pathway, increased excitability of second order neuron
at dorsal horn of spinal cord). Mechanisms: Inflammation > Mast cells release NGF
taken up and transported to cell body to increase transcription of BDNF > released to
synaptic cleft to increase excitability of 2nd order neuron
 Abnormal pain: Damages in pain pathways
o Neuropathic pain (at peripheral / central pathways): Burning / electrical sensation, e.g.
shingles
o Thalamic pain syndrome (Dejerine-Roussy) severe burning pain e.g. stroke
o Example: Phantom limb. Increased excitability of the second order neuron
o (Main point here is that damages in pain pathways leads to spontaneous pain)

PERCEPTIONS OF PAIN

 Pain is a feeling involving subjective perceptions

 Interpretations on: Quality of pain (e.g. sharp, pricking, tearing, crushing, etc. from A-delta & C
fibers), Intensity, Temporal (time), localization (where)

REFERRED PAIN

 Defn.: Pain at a site other than actual source; visceral nociceptors can be sensed as superficial
pain at areas sharing same dorsal root e.g. Myocardial infarction, gall stone colic, etc.
 Pain is not well-localized because:
1. Low innervation density & wide receptive field (compared to other receptors)
2. Coarse topographic representation (going to a lot of regions e.g. limbic system poor
topography)
3. Convergence-Projection (esp. referred pain): Branching & convergent ascending fibers
(2 sources converge at same 2nd order neuron).

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MODULATION OF PAIN

2 types of modulation: Central vs. Local

1. Central modulation: (2 pathways) Descending pain modulatory
pathway (from brainstem to spinal cord)
a) Pathway 1: Descending pain modulatory pathway:
Periaqueductal gray (PAG) at midbrain > descends to
medulla (Nucleus raphe magnus) >Serotonin to dorsal horn
enkephalin interneuron
b) Pathway 2: Upper pons (Noradrenergic locus coeruleus) >
descends to medulla > Norepinephrine to dorsal horn
enkephalin interneuron
c) Then: Enkephalin interneuron release enkephalin
d) Effects:
1. Inhibit release of neurotransmitters (glutamate, Substance P) from nociceptor
to 2ndary neuron
2. Hyperpolarize postsynaptic 2nd order neuron
2. Local modulation (local spinal circuit): Gate control theory
o Activate A-beta mechanoreceptors (e.g. skin rubbing) > Activates interneuron to
suppress activation of secondary neuron by nociceptors

LEARNING OBJECTIVES

 Define nociception and different types of pain

 Describe how pain is relayed from nociceptors to the spinal cord
 Describe the ascending pain pathways to the brain

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HNS14 NARCOTIC ANALGESICS

OVERVIEW

1. Background
2. Details (Classification, Mechanism, Pharmacology, Metabolism, Side effects, special drugs)

BACKGROUND

 Narcotic (common name) = Opioids (scientific). For pain relief.

 Analgesic (vs. Anesthetics): General pain e.g. headache (vs. pain from tooth extraction), Pain
sensation only (vs. all sensations), Pain modulation (vs. blocks pain conduction)
 There are endogenous opioids: Enkephalins, Endorphins
 2 issues: Dependence (they want more and more), Overusing causes dangerous respiratory
issues. Derivatives of morphine aim to tackle these 2 issues, but still haven't found a safe opioid
completely devoid of these 2 issues.

DETAILS

Clinical classification: Strong vs. Mild

 Strong: Morphine, Pethidine, Fentanyl family
 Mild: Partial agonist (Pentazocine, Buprenorphine, Butorphanol, Tramadol),
dextropropoxyphene (not available in market now because side effects)
 Special: Methadone/Physeptone (Mainly used for opioid detoxification; Slow onset=slow
high=less addictive. Also used for chronic pain)

Mechanism of action: Mu receptors

 Mu receptors: Which Morphine binds. Major effects: Pain + relief, respiratory depression
 Found in CNS: drug needs to cross BBB (many opioids have either lipid solubility, or nonionized
fraction at blood pH)
 Common administration route: Intravenous, Oral

Pharmacology
1. Agonist and partial agonist
a. Agonist: Dose increase = response increase till 100%
b. Partial agonist: Doesn't increase to 100%, e.g. only 50% max.
c. Agonist antagonist: Give mild opioids to a patient on strong opioids, paradoxically the
pain relief is worse because mild opioids will displace full agonist.
2. Addictive potential depends on speed of onset (Fast onset = bigger high = more addictive).
a. Cross-over point indicates equilibrium between bloodstream and effect site (blood
concentration=CNS concentration). Alfentanil quickest onset & more addictive, but
quick onset also have advantages (no time lag between effect & drowsiness > plasma
concentration representative of CNS concentration & clinical effects)
b. Of course, how addictive is also related to how high it came make you feel (Euphoria):
Pethidine > Morphine > Methadone

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 3. Duration of effect related to contact sensitive half time
a. Contact sensitive half time: Half time is contact time sensitive (Higher contact sensitive
half time: Longer you administer, later it takes for effect to wear off after ministration)
b. Contact sensitive half time depends on how much the drug accumulates in the body
c. Most sensitive: Fentanyl; Not contact sensitive at all: Remifentanil
4. Other uncommon routes if IV / oral not possible: Indwelling subcutaneous cannula,
Transmucosal (not preferred, too accessible for addiction), direct injection to CNS (epidural
injection; smaller dose required)
5. Opioid is considered a dangerous drug because it has narrow therapeutic window
a. Narrow therapeutic window (ED95, LD5): This dose produce desirable effect in 95% of
subjects, but kills 5%.
b. Hence, Patient controlled analgesia: Repeated self-administered dose

Metabolism for excretion:

 Morphine > Morphine-6-glucuronide is an active metabolite (Water soluble but still active)
 Pethidine > Norpethidine (a minor metabolite but is neurotoxic > Seizure.) Vulnerable: Normal
liver + Weak kidneys + Repeated pethidine (i.e. can metabolize + cannot excrete=accumulation)

Side effects on opioids (by severity / common):

 Acute: Sedation, Nausea & vomiting, Respiratory depression (dangerous), Euphoria, Miosis
(useful clinical sign)
 Chronic: all acute side effects, constipation, tolerance/dependence
o Tolerance: Decreased effect of a drug
o Dependence: Physical dependence (from withdrawal symptoms), Psychological
addiction (=addiction) [not a lot of patients develop addiction, hence opioid is a
reasonable drug choice, but should discontinue if spotted patients start having
addiction]

Special mentions of drugs

1. Tramadol (very common mild opioid)
o Doesn’t cause much sedation & respiratory depression, no euphoria (no addiction)
o Drug-drug interaction: antidepressants
2. Naloxone (Narcan): Opioid antagonist, antidote for opioid overdose
o Treatment of opioid overdose: Maintain Ventilation to prevent respiratory distress +
Naloxone with continuous monitoring (Naloxone half-time is short, continuously
observe to avoid kick-back after Naloxone effect is over)

Choosing an opioid: Efficacy (strong vs. mild pain), side effects, onset & duration, route of
administration (only fentanyl has transdermal), Safety (avoid respiratory distress), addictive potential

LEARNING OBJECTIVES

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  Understand basic pharmacology of opioids
 Know the common routes of administration of opioids
 Administer opioid analgesics safely.
 Recognize and manage opioids related side effects.

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HNS15 SEDATIVES AND HYPNOTICS

SHORT SUMMARY

 Sedatives vs. Hypnotics. Sedative similar to Anxiolytics, they focus on limbic system and
regulates thoughts. Sedatives works on RAS (reticular activating system) to cause sleep.
 Examples of anxiety disorder: GAD, OCD, Panic, Phobia, PTSD
 Insomnia: >30 minutes to sleep / wake at 3+ nights / week
 Common causes of insomnia:
o Psychological: Stress, Grief, Anxiety, depression, mania
o Medical: CV problems, Apnea, asthma, shift work
o Pharmacological: Caffeine
 Barbiturates can cause coma; Benzodiazepines don't. It also has no drug interactions, and
antagonists are available, so much safer.

BENZODIAZEPINES

 MoA of Benzodiazepines: Binds to BZ1 and BZ2 receptors in GABA-chloride receptor >
Potentiate GABA's action on Cl channels > More FREQUENT opening and more Cl and
hyperpolarization > Reduce neural activity which keeps a person awake.
 Indications: Panic disorder (Alprazolam), Spasms (Diazepam), Amnesia (Midazolam), Sleep
(Triazolam)
 Side effects: Drowsiness, Confusion...
 Flumazenil, the antidote: Binds GABA receptor (Competitive blocker)

BARBITUATES

 MoA: That of Benzodiazepine (but longer DURATION, not frequency) + Blocking AMPA
receptors (less glutamate excitation) + Block Na channels (Pentobarbital only)
 Adverse: CYP450 interactions.

OTHER DRUGS

 Buspirone: Binds Serotonin 1A receptor > inhibit serotonin release

 Hydroxyzine: Antihistamine with antiemetic powers (overcome anxiety)
 Antidepressants: See other chapters
 Propranolol: Beta blockers. Reduces sympathetic response symptoms of anxiety

 Zolpidem / Zaleplon: Selective BZ1 biding

 Eszopiclone: Interacts with GABA receptor complex
 Ramelteon: Melatonin receptor agonists.
 Chloral hydrate: Converts to trichloroethane.

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HNS17 MOTOR SYSTEM

OUTLINE
1. Overview & Motor cortex
2. Pyramidal system Note: Recommend viewing lecture again for revision,
3. Extrapyramidal system because this note isn’t very good, and the topic is very
4. Spinal cord complicated. Also because Gilberto made it interesting.
5. Case study

OVERVIEW & MOTOR CORTEX

 Overview:
o Upper motor neuron: Cerebrum to brainstem / spinal cord > Commands Lower motor
neuron (LMN)
o Lower motor neuron: Either cranial nerves or anterior horn cells of spinal cord > Muscles
to execute muscle movement
 Two parallel subsystem
o Pyramidal system: Direct voluntary control
o Extrapyramidal system: Indirect involuntary control
 Areas involved in movement at cerebral cortex
o Primary motor area (M1): Generate signals of
movement [Precentral gyrus of frontal lobe (Brodmann
4)]
o Premotor area (PMA): Integrates sensory & motor
information [Immediately anterior to M1 (Brodmann 6)]
o Supplementary motor area (SMA): Planning and
sequence of movement [Brodmann 6 but more medial
(buried within longitudinal fissure)]
o Primary Sensory area (S1): role in movement Control.
Sensory feedback is very important esp. for fine movements (think about dissection
class)
Note the locations of these areas (See right, identify Central sulcus first to orientate)
Import
-ance Question Answer
A Cortical motor area and “M1 encodes parameters to define individual movements or simple
function (as seen from movement sequences to provide minute-to-minute precise
past paper answers) conscious control. PMC is responsible for controlling proximal and
axial muscles via direct descending projections, selection and
execution of motor programs based on visual and somatosensory
cues. M2 is responsible for motor programming of complex
movement and coordination of bilateral movement.” (Answer quite
hard to understand, sad.)
B Where do these 3 M1 (Brodmann 4, Precental gyrus of frontal lobe), PMC (Brodmann
cortical motor control 6 lateral, immediately anterior to M1), M2 (Brodmann 6 medial,
centers locate buried within longitudinal fissure)

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  Clinical relevance. In reality when you:
o Simple motion e.g. finger contraction: Primary motor area activated
o Repetitive motion: Sensory area activated
o Complex sequence movement e.g. violin: Supplementary motor area (lots of planning)
o Thinking about movement: Supplementary motor area
General rule: Greater complexity = more involvement beyond M1
Supplementary motor area syndrome (i.e. injured): Not actually paralyzed, but cannot
movement muscle (problem with initiating movement)
 Motor homunculus
o More medial (Big muscles/gross movement, limbs) vs. More lateral (large area for hand,
face. Fine movements, lots of neurons because lots of motor units)

SECTION SUMMARY
 UMN commands LMN in brainstem or spinal cord to execute motor movement
 Parallel arrangement of the pyramidal system & extrapyramidal system Primary Motor cortex
(M1) executes voluntary movement via the pyramidal system
 Extrapyramidal system controls involuntary movement & modulates voluntary movement
 Sensory & association cortexes play important roles in complex movement executed by M1

PYRAMIDAL SYSTEM

 Pyramidal system
o Gross anatomy: Cortex > Cerebral peduncle (midbrain) > Pyramids (Medulla) & “ > ” means 
Decussation > Lateral corticospinal tract
o Layers of the pyramidal tract: Pyramidal tract cells (Betz cells) originate from Layer V of
M1 (total 6 layers of cerebral cortex).
o Consists of Corticobulbar tract (to cranial nerves) and Corticospinal tract (to spinal
motor neurons)
o Internal capsule & Corona radiata:
 Internal capsule: Where the fibers twist. V-shaped, consists of anterior limb,
Genu (knee), Posterior limb). Allocation e.g. face at anterior, limbs at posterior
 Corona radiata: A 'radiating crown'. Fibers from corona radiata converge to
form internal capsule.
 Corticobulbar tract (Bulbar means medulla oblongata, so this one for face only / cranial nerves):
o Originate mostly lateral (Head and Neck)>Corticobulbar tract (to cerebral
peduncle>Decussation and exit via cranial nerves (eye movement by separate system)
o LMN also supplied by ipsilateral UMN (i.e. if the contralateral cranial nerve
malfunction, it may still function because of ipsilateral UMN). Except: CN VII for lower
face, CN XII for genioglossus muscle (tongue motor)
o Clinical relation: Facial nerve palsy. DDx:
 Right brain stroke (i.e. no right UMN but still have left UMN > preserved
forehead movements) [Central palsy]
 Left facial nerve injury (no LMN to entire left face) [Peripheral palsy]
 Corticospinal tract:

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 o More medial (limbs)>Cerebral peduncle>Pyramids>
 Most would decussate at Pyramids>Lateral corticospinal tract (supply distal
muscles, i.e. fine motor)
 Few would not decussate>Forms anterior corticospinal tract (supplies axial &
proximal muscles, i.e. gross motor)
o Clinical relevance: Stroke (at lenticulostriate arteries, from MCA). Affects corticospinal
tract>UMN paralysis of contralateral limbs & lower face (upper face preserved because
of ipsilateral UMN supply)
 Other causes of UMN lesion: Cerebral infarction, Tumor, Pontine haemorrhage
(before decussation). Pathology medulla and down would lead to ipsilateral
loss.

SUMMARY
 Disease of the pyramidal tract (from the cortex to the spinal cord) can cause:
o UMN (not LMN) lesion: Loss of cranial nerve motor functions (corticobulbar tract). e.g.,
contralateral lower facial weakness
o Loss of spinal nerve motor function (corticospinal tract). e.g., contralateral limb
weakness
 These presentations enable clinical localization of the disease

EXTRAPYRAMIDAL SYSTEM
 Extrapyramidal system key structures: Basal ganglia (C shaped, from embryology
development). Includes (See diagram below):
o Caudate nucleus (head, body, tail)
o Putamen
o Striatum: Descending fibers from cortex transverse through internal capsule breaks the
connection between caudate nucleus & putamen, forming a striated pattern
o Globus pallidus (Pale globe), medial to putamen
o Subthalamic nucleus (not shown), Substantia nigra (not shown)

Illustrative diagram Axial (MARS clearer) Coronal

Rmb to go to anatomy practical to see the structures!!

EXTRAPYRAMIDAL SYSTEM: BASAL GANGLIA

 Main function of basal ganglia: Modulate movement, many other functions beyond motor
control. Disease causes abnormal movement initiation, pattern, speed, etc.

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  Brief outlining / keypoints of its complex motor modulation
pathway:
o Caudate nucleus & Putamen receives signals from cortex.
They will interact with substantia nigra and globus pallidus
to communicate with subthalamic nucleus.
o Globus pallidus signals thalamus back to cortex
o The signal is now modified, so primary motor neuron can
execute the signal
 Clinical Relevance: Parkinson’s disease
o Cause: Loss of Substantia nigra (black substance)'s dopaminergic neurons > movement
disorder.
o One way of treatment: Deep brain stimulator to correct abnormal circuitry
(neurostimulator to subthalamic nucleus) [Mainstay is still drugs, see future lectures]

EXTRAPYRAMIDAL SYSTEM: BRAINSTEM

 Extrapyramidal system: Brainstem (involved in both pyramidal & extrapyramidal), esp. the
Reticular formation (collection of brainstem nuclei). Functions:
o Reticular activating system (keeps cortex awake)
o Integrates higher motor centers & sensory information
o Brainstem motor nuclei: Red nucleus, Reticular nuclei, Vestibular nuclei
 Red nucleus (in midbrain): Cerebral cortex & Cerebellum > Rubrospinal tract
(decussated). Predominantly flexion.
 Reticular nuclei (in pons & medulla): Forms medial & lateral reticulospinal
tracts. For extensor & flexor balance
 Vestibular nuclei (in medulla):
 Communicate with inner ear, forms vestibulospinal tract. For
equilibrium & balance. Predominantly extension.
 Lateral vestibulospinal tract: Cerebellum, & vestibular apparatus >
Lateral vestibular nucleus & tract > Decussation in spinal cord>
Contralateral trunk muscles >maintains posture & balance
o Babies: Labyrinthine righting reflex (baby self-corrects it's head
position when tilted)
 Functions of extrapyramidal activities:
o Innervates axial muscle, posture, muscle tone: Balance
o Balances flexion and extension
o Clinical relevance: Disease at different level of brainstem leads to different extents of
loss of descending motor function > different posturing, e.g. decorticate posturing
(Lesion above red nucleus but rubrospinal tract intact > Flexion), Decerebrate
posturing (lesion below red nucleus and rubrospinal tract cut out>extensor
unopposed; worse prognosis)
o Post stroke recovery: e.g. internal capsule infarction
 Lateral CST affected: Poor fine motor function (distal muscle)

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  Extrapyramidal tracts retained: Good recovery at gross movement (Proximal muscles & gross
movements)
 Imbalance between flexion & extension (lower motor neuron damaged): Upper limb (incl.
fingers) flexed; lower limb extended

SUMMARY
 The basal ganglion generates & modulates motor movement by communicating with the
motor cortex & thalamus via the caudate nucleus, putamen & globus pallidus
o Substantia nigra is involved in Parkinson’s disease
o Brainstem extrapyramidal system exerts involuntary motor control to axial muscles &
maintains posture
 Diseases affecting different levels of the brainstem may manifest with decorticate or
decerebrate posturing
 Cerebellum – see another WCS

SPINAL CORD
 Topographic: Dorsal (Sensory), Ventral (Motor); Columns of fibers
o Pyramidal system in spinal cord:
 General rule: Advanced vs. Primitive system
 Advanced: Crossed fibers at Lateral CST (pyramidal) and Rubrospinal
tract (extrapyramidal), in lateral descending system, for more complex
movements
 Primitive: Uncrossed fibers at other extrapyramidal tracts, in ventral
descending system, innervating axial muscles (for Posture & Reflex)
o Cross section of spinal tract:
 Lateral: Lateral reticulospinal tract, Corticospinal tract, Rubrospinal tract
 Medial: Medial reticulospinal tract, Ventral corticospinal tract, Vestibulospinal
tract, tectospinal tract
 This arrangements facilitates communication in spinal grey matter (Anterior
horns for distal muscle more lateral, Anterior horns for proximal muscle more
anterior)

 UMN vs. LMN lesions:

o UMN lesion: e.g. Spinal cord injury
o LMN lesion: e.g. anterior horn cells (CNS), Spinal nerve (PNS)
o UMN usually suppresses reflex so that it is more tempered. UMN injury leads to
hyperreflexia.
o This is probably ONE OF THE MOST IMPORTANT CONCEPTS OF MBBS: UMN vs. LMN

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 o Both paralyzed, but in UMN: Spastic (good muscle tone) vs. in LMN: Flaccid (poor
muscle tone)
 More elaborations on the same idea: Myelopathy vs. Radiculopathy
o Myelo= Spinal cord, affects LMN lesion at that level & UMN lesion below that level. e.g.
ventral intervertebral disc herniation
o Radiculo=nerve root, only LMN injured but cord is unaffected. e/g/ lateral intervertebral
disc herniation
 Spinal cord injury. Examples
o Brachial plexus: C5-T1 to Upper limb
o C4 injury: Entire brachial plexus affect>Quadriplegic
o C6 injury (C5 spared): Shoulder can move, which can be very important, because
patient may be able to push himself up, still quadriplegic
o Brachial plexus spared: Paraplegic (UL can move)
 Conus medullaris & Cauda equina
o Conus medullaris (L1). Above this is UMN, Lower down is Cauda equina, has no spinal
cord so all LMN, Conus medullaris is mixed LMN & UMN
o Cauda equina syndrome (a LMN problem)

CASE STUDY

CASE 1
 Presentation (& Implication):
o Patient: My right leg is weak
o You find that upper limb is also weak (so something higher up)
o Patient also has speech deficit (so something in cortex)
o Facial weakness on right, only at lower face (Central type of left upper motor neuron)
 Diagnosis: E.g. Left cerebral hemisphere stroke, UMN lesion

CASE 2
 Presentation:
o Patient: My right leg is weak!

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 o You find that the RUL and LUL is normal (Brachial plexus spared)
o LLL weak (affects thoracic and lumbar spine)
o Both LL hypertonic & Hyper-reflexic (UMN issue affecting both limb)
o Babinski's response (loss of descending control)
 Diagnosis: E.g. thoracic spinal cord tumor

CASE 3
 Presentation
o Patient: My right leg is weak
o RUL, LLL, LUL problem (Isolated right leg problem)
o RLL: Flaccid, absent of reflex
 Diagnosis: E.g. Lower motor neuron problem, e.g. herniated lumbar disc radiculopathy

SUMMARY
 The spina cord is the final common pathway for limb & trunk motor function
o Lateral CST: fine & complex movement
o Extrapyramidal tracts: trunk & proximal movement
o UMN vs. LMN lesions are clinically distinct
 Myelopathy vs. Radiculopathy
 Neuroanatomy is essential for making clinical diagnosis

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HNS19 CEREBELLUM

OUTLINE

1. Cerebellum: Introduction
2. Cerebellum: Cortex circuitry & cell types
3. Pathways of Cerebellum

CEREBELLUM: INTRODUCTION

 Function: Integrate sensorimotor

 Topographical Anatomical subdivisions of cerebellum
o Horizontal: Primary fissure: Anterior / Posterior lobe;
Flocculonodular lobe; 10 lobes (no need this stage)
o Vertical (AP lobe only): Vermis, Intermediate hemisphere
(Grey matter only), Lateral hemisphere
 Linked to cerebrum by 3 peduncles: Superior, Middle (biggest),
Inferior (lots of fibers inside)
o Superior: Output path from Cerebellum (Dentate, Interposed,
Fastigial), to cerebrum cortex & vestibular nucleus, etc.
o Middle: Input from corticopontine fibers to pons, mossy fibers
o Inferior: Input from Climbing fiber (from olive), Mossy fiber
 Internal anatomy:
o Cerebellar cortex (Grey matter)
o 4 subcortical cerebellar nuclei (Lateral to medial): Dentate,
Emboliform, Globose, Fastigial nucleus
o Median: Vermis

SECTION SUMMARY

 Cerebellum as a motor center: Coordinates upper & lower limb

 Subdivisions: Cerebellar cortex & subnuclei
 Cerebellar peduncles: Input & output projections (ESP. Input)

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CEREBELLUM: CORTEX CIRCUITRY & CELL TYPES

 Cerebellar cortex circuitry

o 2 types of input: Climbing fiber, Mossy fiber
 Climbing fiber (Direct): From inferior olive
 Mossy fiber (Indirect): To granule cell
o Both converge on Purkinje cell > Either inhibit deep cerebellar nuclei, then vestibular
nuclei, or directly inhibit vestibular nuclei (i.e. both inhibit)
 Cell types: Purkinje, Basket, Stellate, Granule
o Purkinje cell axons do not cross into adjacent zone, it is very longitudinal.
o Purkinje cell has huge dendritic tree. Purkinje cell is often excited (either by climbing
fiber or mossy fiber) to make Inhibitory output (e.g. vestibular nuclei)
o Basket cell is another inhibitor cell. At the axon hillock, it inhibits P cell activity.
Additionally, secondary control by transverse fiber. I.e. basket cell can control
excitatory output of P cell
o Stellate cell also inhibits Dendritic tree of Purkinje cell.
o Granule cell: Parallel fibers interact with dendritic tree of P cell (Stimulatory), or stellate
cell & basket cell
 I think I missed something... maybe review later
 Basket & Satellite cell inhibits the off-site area (??)
 Should also try to ORIENTATE yourself where the Purkinje fiber is, otherwise,
very hard to understand
 Cerebellar cortex circuitry
o Activate parallel fiber > Activate on-beam spread (Bidirectional spread) > Activate
dendritic tree of Purkinje cell.
o Dendritic tree activated > Spreads inwards to excite stellate & basket cells
 I.e. stimulating parallel fibers activates Purkinje cell, stellate cell, basket cell
o Then, basket cell activates neighboring P cells (i.e. INHIBITION)
o Consequence: 2 different fashion of activation
 Activation of P cell inhibits subcortical cell & brainstem cell
 Disinhibition of neighboring subcortical cells & brainstem cells
o This slide is said to help with revision, please refer to color and number coding:

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SECTION SUMMARY

 Circuitry within cerebellar cortex

 Spread of mossy input to (1) Excite P cells that inhibit VN and subcortical cells. (2) Excite basket
cells that inhibit adjacent P cells (disinhibition)

PATHWAYS OF CEREBELLUM

 Cerebellar sensory inputs

o Vermis & Flocculonodular area for vestibular inputs, Central part
of vermis for visual & auditory inputs
 Cerebellar output: note the anatomical positions
o 3 components: Vermis, Intermediate hemisphere, Lateral
hemisphere
o 3 Nuclei: Fastigial nuclei, Inter-posted nuclei, Dentate nucleus
o 3 Pathways: vestibulocerellum, Spinocerebellum,
Cerebralcerebellum
 Cerebellar homunculus (nothing too special)

Functional units of cerebellum

 Vestibulocerebellum (at Flocculonodular lobe)
o Vestibulospinal reflex (Tilty table): Vestibular end organ & Spinal
cord > Vestibular nucleus (modulated by Vermal cerebellum & vestibulocerebellum) >
Vestibulospinal tract & reticulospinal tract
o Perturbation of cerebellum leads to malfunctioning of the tracts
 Spinocerebellum: Vermis, Intermediate hemisphere
o Medial corticonulcear zone: Controls postural (reflexive) movements, Coordinate
vestibulo-ocular reflex
o Vestibulo-ocular reflex (Rotatory nystagmus): Similar pathway but to vestibulo-ocular
tract
o Medial corticonulcear zone: postural / voluntary control of axial & proximal body parts
(missed the pathway, maybe check out video later)
o Intermediate corticonulcear zone: for error detection & moment-to-moment correction
(missed the pathway, maybe check out video later)
 Cerebrocerebellum (Lateral corticonulcear zone)
o Association cortex > movement design > pontine relay nuclei > Mossy fiber >
hemisphere > Dentate >movement program > Thalamus > motor cortex > Corticospinal
tract > Spinal cord > muscle (Voluntary movement)
o In short: Association cortex (initiates movements) > Hemisphere (adjusted) > motor
cortex (signals execution) > Muscles

Clinical correlation: Ataxia

 Meaning: Errors in rate, range, force, direction

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  E.g.: Lack coordination, gait abnormality, slurred speech, tremors, etc.
 Ataxia gait: Swinging side to side
 Other presentations: Intention tremor (i.e. no shake when no move; vs. unintentional e.g.
Parkinson’s), Hypotonus, Nystagmus
 Clinical test:
o Upper limb test: Dysdiadochokinesia test (Flippy hands), Finger-nose-finger / Past-
pointing test (Dysmetria, Intention tremor)
o Lower limb test: Heel-to-shin test, Gait control: Tandem walking test / Heel-to-toe test
(Usually automatic, but under descending control). Cerebellar dysfunction no straight
line

SECTION SUMMARY 3

 Sensory input distribution vs. Motor output projections

 Functional units: vestibulocerebellum, Spinocerebellum, Cerebralcerebellum
 Clinical relevance

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HNS20 CONTROL OF MOVEMENT

OUTLINE

1. Background
2. Brainstem
3. Basal ganglia

BACKGROUND

 Types of movements: Reflex, Rhythmic motor pattern, Voluntary movement

o Reflex: Simple, Rapid, Stereotyped, involuntary, protective
o Rhythmic motor pattern: Only initiation is voluntary, afterwards its stereotyped,
repetitive, and automatic
o Voluntary: Complex, goal oriented & voluntary, can improve with practice
 Control of movement: Introduction
o Aspects to control: Time, postural, sensorimotor integration & error detection (e.g.
feed forward & backward)
o 3 hierarchical levels of motor control (see Gilberto's Lecture): Cerebral cortex (UMN),
Brainstem (UMN, LMN/Cranial nerves), Spinal cord (LMN)
 Additionally: Basal ganglia, Cerebellum (modulates movement via thalamus &
brainstem > Regulates UMN)
o Need sensory information to modulate movement control (mostly by vestibular
system, joint afferent, muscle spindles)
o Somatotopic arrangement:
 Lower motor neurons are all on ventral /
anterior side (Anterior grey horn cells):
Medial (axial muscle) vs. Lateral (limb
muscles & fine motor) [The 'final common
pathway']. See Gilberto's lecture for more
o Interneuron in the intermediate zone
 Spinal cord, without the brain, can perform a few functions:
Stereotyped response e.g. stretch reflex, stereotyped motor coordination e.g. flexion,
Rhythmic locomotor pattern e.g. walking
o Stretch Reflex
 Triggered by muscle stretch (proprioceptor)
 Monosynaptic reflex innervated on same muscle being stretched
 Inhibitory effect on antagonistic muscle
o Flexion reflex
 Triggered by nociceptor > Interneuron (polysynaptic) > Excitatory (Flex knee)
 Inhibitory effect on antagonistic muscle (Cross extension reflex on contralateral
limb)
 Postural regulation to maintain balance
 Descending control from brain affects strength of spinal reflex (damaged UMN
leads to hyperreflexity)

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 For more comprehensive discussion on Reflex, see Reflex lecture
o Rhythmic locomotor pattern: Initiated by mesencephalic locomotor region (MLR) in
brainstem, but spinal cord can maintain the rhythmic pattern itself when disconnected
from brain

SECTION LEARNING OBJECTIVE

 Describe the three types of movement: reflexes, rhythmic motor patterns and voluntary
movement
 Describe the hierarchical organization of motor control
 Describe the functional organization of the spinal motor system: final common pathway and
spinal reflex in stereotyped response, motor coordination and rhythmic locomotor pattern

BRAINSTEM

 Brainstem. Contains both UMN and LMN (Cranial nerves)

o UMN: Maintains posture (to LMN), controls head and eyes
o LMN: Directly controls H&N motor (e.g. chewing, swallowing)
 4 descending pathways from brainstem to spinal cord
1. Vestibulospinal tract (originates from vestibular nuclei, in response to inner ear)
2. Reticulospinal tract (originates from reticular formation, in response to ongoing
movements)
3. Tectospinal tract (originates from tectum, coordinates head orientation)
4. Rubrospinal tract (originates from red nucleus, manipulating objects)
o Pathways:
 1, 2, 3 > Medial anterior grey horn > Axial & proximal muscles (posture &
balance)
 > Lateral anterior grey horn > distal muscle (limbs & fine motor)
 4 outputs of motor cortex
1. Corticospinal tract (Cortex to spinal cord, bypasses brainstems)
2. Corticobulbar tract (> brainstem >Innervates facial muscles)
3. Cortex > Brainstem (Reticular formation) > Axial & Proximal muscles)
4. Complicated loop involving basal ganglia and cerebellum for movement modulation
 Corticospinal tracts: 2 different types
o Cortex > Medulla oblongata > Pyramids >Decussation > Lateral motor neurons (Distal
muscles, esp. fingers)
o Cortex > Medulla oblongata > Pyramids >No decussation until spinal cord > Medial
motor neurons (axial muscles for posture)
 Premotor cortex (PMA, SMA)
o They connect with M1, but can also directly project to brainstem & spinal cord
o Receives inputs via sensory area (posterior parietal cortex) and prefrontal cortex
(initiates / decides movement / intention)
o PMA, SMA: Mostly for intention (PMA: external stimulus; SMA: Self-initiated, also
bilateral control e.g. both hands)

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SECTION LEARNING OBJECTIVE

 Recognize the role of brainstem in the control of posture and coordination.

 Describe the cortical motor areas and their functions.

BASAL GANGLIA

 Basal ganglia, Overview:

o Consist of 5 nuclei: Stratum (Caudate nucleus, putamen), Globus pallidus, Subthalamic
nucleus, substantial nigra [See Gilberto’s Lecture]
o Important for control with movement. Disease: e.g. Parkinson's. Huntington's chorea
 Role of basal ganglia and pathways (complicated)
o Direct: Cerebral cortex > Caudate / Putamen > Globus pallidus internal segment >
VA/VL of thalamus > Frontal cortex (Inhibits an inhibitory network = exaggerates
movement)
o Indirect: Cerebral cortex > Caudate / Putamen > Globus pallidus External segment >
Subthalamic nucleus > Globus pallidus internal segment > VA/VL of thalamus > Frontal
cortex (Inhibits movement)
o Direct & Indirect pathways usually in balance.

Clinical Relevance:
 In Parkinson’s: Degeneration of substantia nigra
o Substantia nigra activates direct pathway via D1 (Dopamine receptors for direct
pathway) and D2 (Dopamine inhibitory receptors for indirect pathway) at caudate /
putamen
o Loss substantia nigra ('loss of dopaminergic input') = loss activation of direct pathway &
loss inhibition of indirect pathway = Less activation, more inhibition on movement =
low thalamic activity, reduced & slow movement
o Treatment: L-DOPA (Prodrug that becomes Dopamine)
 In Huntington's chorea (hyperkinetic disorder)

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 o Selective depletion of nucleus in indirect pathway between caudate / putamen > Less
indirect pathway to suppress thalamic activity
 In Hemiballismus (hyperkinetic disorder)
o Stroke in subthalamic nucleus
o Subthalamic nucleus usually enhances indirect pathway to suppress thalamic activity
o Injury at subthalamic nucleus > Less indirect pathway > more thalamic activity >
exaggerated movement

SECTION LEARNING OBJECTIVE

 Recognize the role of basal ganglia in movement control and related movement disorders

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HNS22 FACE AND SCALP

OVERVIEW

1. Face and scalp: Introduction

2. Scalp
3. Muscles of Face and Scalp
4. Innervation
5. Blood supply and Lymphatics: Arteries, Veins, Lymph

FACE AND SCALP: INTRODUCTION

 Borders of Head and Neck: Occipital protuberance > Superior nuchal line > Lower edge of
mandible > back
 Borders of face and scalp: Supraciliary arches (Below: Face; Behind: Scalp. So forehead is scalp)
 Surface of face are demarked by: Bones and Cartilage, Fatty tissue, effects of aging, hair and
placement
 Features of face:
o Eye: Suprapalpebral sulcus, Infrapalpebral sulcus, Epicanthal, Glabella (between ciliary
arches)
o Nose: Apex, Dorsum, Ala, Naris, Nasal septum
o Oral: Fissure, superior and inferior lip, Vermillion border, Labial commissure, Nasolabial
sulcus, Philtrum, Mentolabial sulcus, Mental protuberance, Tubercle of upper lip
 Clinical relevance: Plastic surgery: Flowing scar of wrinkle (attachment point of muscle).
Wrinkles are attachments of muscles when skin lose elasticity wrinkles would show.
 Section summary
o The face provides our identity as an individual human. Thus, birth or acquired
defects have consequences beyond their physical effects.
o The individuality of the face results primarily from anatomical variation.
o The way in which the facial muscles alter the basic features is critical to
communication.
o Lips and the shape and degree of opening of the mouth are important components
of speech, but emphasis and subtleties of meaning are provided by our facial
expressions.

SCALP

 Layers of scalp: (from bone) Skin, Connective tissue (vasculature and nerves), Aponeurosis
(=gala aponeurotica), Loose connective tissue (with emissary veins, spread of infection
internally), Pericranium (periosteum of skull)
 Clinical relevance: Laceration of arteries in dense subcutaneous tissue. Muscles (Occipitalis
and frontalis) pulls blood vessels in that area hence they cannot constrict, hence profuse
bleeding.
 Section summary

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 o Structure of scalp: The scalp is a somewhat mobile soft tissue mantle covering the
calvaria.
o The primary subcutaneous component of the scalp is the musculoaponeurotic as to
which the overlying skin is firmly attached, but it is separated from the outer
periosteum (pericranium) of the cranium by loose areolar tissue.
o The areolar layer enables the mobility of the scalp over the calvaria and permits
traumatic separation of the scalp from the cranium.
o Attachment of the skin to the epicranial aponeurosis keeps the edges of superficial
wounds together, but a wound that also penetrates the epicranial aponeurosis gaps
widely.
o Blood may collect in the areolar space deep to the aponeurosis after a head injury .

MUSCLES OF FACE AND SCALP

Note: Black (Need to know) vs. Grey (Good to know)

Additional features: 1. Occipitofrontal is: Raise eyebrow. 2. Orbital group. Eyelids (Prevent eyeballs
from injury and extensive light; spread tears). 3. Nasal group (Unimportant in humans). 4. Oral group.
Also, please check diagrams.

 Features: Small & Thin, located in subcutaneous tissue (superficial fascia, directly attached to
skin and WITHOUT fascia, a distinctive features). They're there because they need to pull the
skin and change expression. All developed from second pharyngeal arch. ALL innervated by
Facial nerve (CNVII)
 Main functions: Movement of fascial orifices, Protection, Facial expression, Food ingestion (e.g.
close mouth for swallowing), Speaking
 Section summary
o Muscles of face and scalp: The facial muscles play important roles as the dilators
and sphincters of the portals of the alimentary (digestive), respiratory, and visual
systems (oral and palpebral fissures and nostrils), controlling what enters and some
of what exits from our bodies.

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 o Other facial muscles assist the muscles of mastication by keeping food between the
teeth during chewing.
o Fleshy portions of the face (eyelids and cheeks) form dynamic containing walls for
the orbits and oral cavity.
o Facial muscles are all derived from the second pharyngeal arch and are therefore
supplied by the nerve of this arch, the facial nerve (CN VII).
o Facial muscles are subcutaneous, most having a skeletal origin and a cutaneous
insertion.
o The face lacks the deep fascia present elsewhere in the body.

INNERVATION OF FACE AND SCALP

 Sensory
o Sensory of face: Trigeminal nerve (V1, 2, 3)
o Sensory of Scalp: C2, C3, C4; Anterior & Posterior ramus
o Cutaneous distribution of scalp: Scalp: Greater occipital, Third occipital, Lesser occipital,
Great auricular
 Motor: CN7. With 6 divisions (Superior to Inferior) Temporal, Zygomatic, Buccal, Marginal
mandibular, Cervical, Posterior auricular
o Clinical relevance: Bell's palsy. Normal on one side, but paralysis on the other. Cannot
close eye, dribbling saliva, drinking difficulty, etc.
 Section summary
o The face is highly sensitive. It receives sensory innervation from the three divisions
of the trigeminal nerve (CN V).
o The major terminal branches of each division reach the subcutaneous tissue of each
side of the face via three foramina that are aligned vertically. (More in upcoming
lectures)
o Each division supplies a distinct sensory zone, similar to a dermatome, but without
the overlapping of adjacent nerves; therefore, injuries result in distinct and defined
areas of paresthesia.
o The divisions of CN V supply sensation not only to the superficial skin of the face
but also to deep mucosal surfaces of the conjunctival sacs, cornea, nasal cavity, and
paranasal sinuses and to the oral cavity and vestibule.
o The skin covering the angle of the mandible is innervated by the great auricular
nerve, a branch of the cervical plexus.
o Eight nerves supply sensation to the scalp via branches arising from all three
divisions of CN V, anterior to the auricle of the external ear and branches of cervical
spinal nerves posterior to the auricle.
o The facial nerve (CN VII) is the motor nerve of the face, supplying all the muscles of
facial expression, including the platysma, occipital belly of occipitofrontalis, and
auricular muscles that are not part of the face per se.
o These muscles receive innervation from CN VII primarily via five branches of the
parotid (nerve) plexus.

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BLOOD SUPPLY & LYMPHATICS

ARTERY

 Origins: Region supplied by ICA (smaller anterosuperior part) vs. ECA (the rest)
 External carotid artery (many branches):
o Facial artery (to superior and inferior labial artery) > Angular artery
o Superficial temporal artery: Transverse facial, Frontal & Parietal branches
o Maxillary artery, Posterior auricular artery, Occipital artery
o Clinical relevance: Arterial anastomoses between ECA and ICA. E.g. Angular artery and
External nasal artery
 Arterial pulses: Carotid pulse, Facial pulse (midpoint of mandible), Temporal pulse
(Immediately anterior to external acoustic meatus), Superficial temporal pulse
 Section summary
o Vasculature of face and scalp: The face and scalp are highly vascular. The terminal
branches of the arteries of the face anastomose freely (including anastomoses
across the midline with their contralateral partners). Thus, bleeding from facial
lacerations may be diffuse, with the lacerated vessel bleeding from both ends.
o Most arteries of the face are branches or derivatives of branches of the external
carotid artery; the arteries arising from the internal carotid that supply the
forehead are exceptions.
o The main artery to the face is the facial artery.
o The arteries of the scalp are firmly embedded in the dense connective tissue
overlying the epicranial aponeurosis. Thus, when lacerated, these arteries bleed
from both ends, like those of the face, but are less able to constrict or retract than
other superficial vessels; therefore, profuse bleeding results.

VEINS

 Internal jugular vein: Vein names similar to artery. Notable ones: Supraorbital vein,
Supratrochlear, Angular, deep facial, superficial temporal, Retromandibular vein. Then can flow
to entire internal or external jugular vein
 Importantly the pterygoid plexus: direct connection by emissary veins to cavernous sinus.
Valveless, hence infection risk Danger area of face (drained by facial nerve), blood could go
back to cavernous sinus. If septicemia could lead to meningitis and cavernous sinus
 Section summary
o The veins of the face and scalp generally accompany arteries, providing a primarily
superficial venous drainage.
o However, they also anastomose with the pterygoid venous plexus and with dural
venous sinuses via emissary veins, which provide a potentially dangerous route for
the spread of infection.
o Most nerves and vessels of the scalp run vertically toward the vertex; thus, a
horizontal laceration may produce more neurovascular damage than a vertical one.

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LYMPHATICS

 Nodes: Parotid, Submandibular, Submental > Superficial lymph nodes > Deep cervical lymph
nodes > LR jugular trunks
 Clinical aspect: Potential sites of metastasis. Nodes are easy to palpate but the drainage is
deeper.
 Section summary
o The lymphatic drainage of most of the face follows the venous drainage to lymph
nodes around the base of the anterior part of the head (submandibular, parotid,
submental) next drain into the superficial cervical nodes.
o All nodes of the face drain in turn to the deep cervical lymph nodes.

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HNS23 NERVES OF HEAD AND NECK

OUTLINE

1. Revision
2. Ganglia
3. Nerve
a. Spinal nerve at HN region
b. Cranial nerve at HN region
4. Others

REVISION

 Neuron vs. Nerve: Individual cells vs. Bundle

o Nerve: Many axon wrapped by Endoneurium to form a Fascicle; many fascicle wrapped
by Perineurium. The entire nerve wrapped by epineurium
 Sensory vs. Motor (autonomic) ganglia
o Sensory: Cell bodies outside CNS > ganglion (because Pseudounipolar neurons)
o Motor (autonomic) ganglia: Forms synapse

GANGLIA

 Ganglia: collection of cell bodies outside CNS

 Types: Motor vs. Sensory
o Motor (autonomic only): Sympathetic or Parasympathetic
 Sympathetic: all at sympathetic chain. In HN area (x3): Superior, Middle,
Inferior cervical ganglia
 Parasympathetic ganglia (x4): Ciliary, Pterygopalatine, Otic, Submandibular
o Sensory: General vs. Special
 Special (conveys information from 5 special senses: Vision, Smell, Taste,
Balance, Hearing): Vestibular (balance), Spiral (hearing), Inferior vagal + Inferior
glossopharyngeal + Geniculate (taste)
 General: Dorsal root (spinal) + Trigeminal (information from skin & mucous
membrane), Superior vagal, Superior glossopharyngeal, Inferior
glossopharyngeal (Internal receptors e.g. baroreceptors)

NERVE

SPINAL NERVES AT THE HN REGION

 Spinal nerve contains: Ventral root, Dorsal root, Autonomic nerves (only Great rami
communicants at this level)
 Total of 8 cervical nerves
 Dermatome: No C1 (only C2-5 on HN region), but the cervical plexus allows a nerve to originate
from more than one nerve roots
 Cervical plexus: forms Ansa cervicalis (nerve loop, around subclavian artery)

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CRANIAL NERVE AT THE HN REGION

 12 pairs of Cranial nerve (numbering by order of exit superior to inferior), CN II is a protrusion of

diencephalon
 Recognizing the origin of the nerve (see other chapters)
 Classification by function: Sensory (1, 2, 8); Motor (3, 4, 6, 11, 12), Mixed (5, 7, 9, 10) (see other
chapters)
 Autonomic innervation
o Sympathetic: Thoracolumbar (T1-L2), ganglia i.e. synapse at sympathetic chain
o Parasympathetic: Craniosacral, ganglia i.e. synapse at supplying organ, but named
ganglia at HN region (see above: for Oculomotor, Facial, Glossopharyngeal nerve)
 Random facts
o Neurotransmitter at synapse: both Acetylcholine
o Sympathetic neurons cell body at lateral horn
o ONLY GREY RAMI COMMUNICANTS at cervical region!
 Clinical classification of Cranial Nerves

AUTONOMIC RESPONSES IN HN
Type Effector Response
Muscle Dilator pupillae Pupillary dilation
Superior tarsal Upper eyelid elevation
Arrector pili Piloerection
Smooth muscles of blood vessel wall Vasodilation & constriction
Glands Salivary Produce saliva
Sweat Sweating

OTHERS

Excellent summary tables from Cecot and Dr. Khong Mei Li. See their Moodle uploads.

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HNS25 ORAL CAVITY, SUBMANDIBULAR AND SUBLINGUAL GLANDS

OVERVIEW

1. Oral cavity
2. Palate
3. Tongue
4. Glands of mouth: Submandibular, Sublingual
5. Teeth

ORAL CAVITY

 Divisions of oral cavity:

o Oral cavity proper: surrounded by teeth
o Vestibule: between gum and teeth
 Anatomical landmarks:
o Roof: Hard palate
o Floor: Mylohyoid muscle (CNV3)
o Sides: Buccinator (by facial nerve)
o Anterior: Oral fissure
o Posterior: Oropharynx (separated by palatoglossal arch)
Note: Attachment of buccinator muscle (C shaped): Maxilla > Pterygomaxillary
ligament > Pterygomandibular raphe > External oblique line of mandible
Note: Greater = Anterior palatine nerve; Lesser = Posterior palatine nerves
 Bones:
o Upper: Maxilla (palatal process), Palatine (horizontal plate)
o Lower: Mandible
 Nerve of oral cavity (here gingiva only, all parasympathetic)
o CNV2 (maxillary of trigeminal) for roof: Anterior palatine nerve (posterior; from
pterygopalatine ganglion. Same course as anterior palatine artery), Nasopalatine nerve
(anterior, enters via Incisive foramen)
o CNV3 (mandibular of trigeminal) for lower: Lingual nerve for floor, Buccal and mental
nerve for cheek
 Anatomical landmarks:
o Roof: Hard palate
o Floor: Mylohyoid muscle (CNV3)
o Sides: Buccinator (by facial nerve)
o Anterior: Oral fissure
o Posterior: Oropharynx (separated by palatoglossal arch)
 Clinical relevance: Cleft palate. Before birth, the premaxilla and maxilla are not yet fused.
Failure in fusion of maxilla (and rarely the premaxilla) leads to cleft palate
 Anatomy focus of mouth
o Floor of mouth: Hyoid muscles
 Hyoid bone: Slung between mandible and styloid process

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  Elevators of hyoid bone: Mylohyoid muscle (Sheet like, forms base of mouth),
Geniohyoid muscle (finger like, C1 via CNXII), Stylohyoid
 Depressors of hyoid bone: Thyrohyoid, Omohyoid, Sternohyoid
o Landmarks of mouth (using hyoglossus as landmark)
 Lateral to hyoglossus: Lingual nerve, Submandibular duct, Hypoglossal nerve
(CNXII), Stylohyoid muscle
 Medial to hyoglossus: Glossopharyngeal nerve (CNIX), Stylohyoid ligament,
Lingual artery

PALATE

 Divisions: Hard vs. Soft palate

 Hard palate anatomy: Foramina (1+2+2)
o Incisive foramen (for Nasopalatine nerve)
o Greater palatine foramen (for greater palatine artery and anterior palatine nerve)
o Lesser palatine foramen (for middle and posterior palatine nerves)
 Soft palate anatomy: muscles
o Soft palate is the aponeurosis of Tensor Veli Palatini. It is act upon by 5 pairs of muscles:
1. Tensor veli palatini: the only one supplied by medial pterygoid V3 (the rest by vagus:
pharyngeal plexus). Function: tense up aponeurosis so that other muscles can act on it,
opens the eustachian tube
2. Levator veli palatini (V shaped sling): Pulls soft palates upwards / outwards (close off
nasopharynx when swallowing)
3. Palatopharyngeal (inverted V, slings inferiorly to form palatopharyngeal arch).
Depresses soft palate, elevates larynx
4. Palatoglossus (Sphincter of oropharyngeal isthmus in swallowing)
5. Musculus uvulae (Gives shape of uvula)
 Blood supply
o Hard: Greater palatine artery
 Course: Maxillary artery > Greater palatine canal >* Greater palatine foramen
> GREATER PALATINE ARTERY > Incisive foramen (to nasal cavity)>
Anastomosis with sphenopalatine artery
 Accompanies Greater palatine nerve
o Soft: Lesser palatine artery (*> lesser palatine foramen)

TONGUE

 Division: Anterior 2/3 (in oral cavity), Posterior 1/3 (in oropharynx) [separated by vallate
papillae]
o Anterior division: Think mucosa, Papillae (Filiform, Fungiform, Foliate), mostly for
mastication and digestion
o Vallate papillae: V shaped (V=Vallate), Tip called foramen caecum (remnant of
thyroglossal duct). No more papillae behind this, becomes lingual tonsil (more nodular
rather than papillate); followed by sulcus terminalis

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 o Posterior: Not discussed much, lol.
 Muscles of tongue
o Muscles: 4 intrinsic, 4 extrinsic (outside to inside)
 Intrinsic: Superior longitudinal fibers, Inferior longitudinal fibers, Transverse
(originates from fibrous septum), Vertical fibers (from mucous membrane to
downwards)
 Extrinsic: Genioglossus (drags ROOT, not tip, of tongue forward), Hyoglossus,
Styloglossus, Palatoglossus
o All by Hypoglossal nerve (CN12), Except for PALATOGLOSSUS since it links soft palate
(Vagus)
 Blood supply to tongue
o Lingual artery (from hyoglossus to tip, branch of external carotid artery)
o Ranine veins (from tongue undersurface, to common facial vein)
o Lingual vein (branch of internal jugular vein)
 Innervation of tongue
o Sensory
 Anterior division:
 General sensory: Lingual nerve (branch of V3)
 Special sensory: Chorda tympani (VII, via lingual nerve)
 Posterior division (both General and Special): Glossopharyngeal nerve (IX)
[including Vallate papillae]
o Secretomotor (Parasympathetic): Chorda tympani (VII, via lingual nerve)
 Anatomical focus
o Lingual papillae (anterior division)
 3 + 1 types:
 Filiform (conical, shape only but no taste buds). Fungiform (mushroom
like, red, taste buds), Foliate (serous glands + taste buds)
 Special: Vallate papillae. The posterior part's 'invasion' to anterior parts
at terminal sulcus, contains taste buds
 Distribution: Filiform and Fungiform in anteriorly, Foliate posterolateral
o Other structures: Frenulum of tongue (mucous membrane fold, 脷筋): opening of
submucosal gland
 Swallowing act (nothing new)
1. Chewing food: Mastication to form bolus
2. Conscious decision to swallow, tongue push bolus backwards
3. Reflex by CNS. Receptors in pharynx triggers: Soft palate raised to close off
nasopharynx, larynx pulled upwards, peristalsis / movement in pharynx and esophagus
propels food down
 Clinical relevance (important):
o Damage of hypoglossal nerve. Tongue points to AFFECTED sides (Right
hypoglossal nerve cut = points to right) because right genioglossus cannot contract
o Damage to Vagus nerve. Uvula points to UNaffected side (e.g. left vagus cut, uvula
points left because only left uvulae is contracted)

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GLANDS OF MOUTH

SUBMANDIBULAR GLAND

 Acinar divisions: Superficial (under mylohyoid) vs. Deep (curved around mylohyoid and lies
above mylohyoid)
 Duct travels between sublingual and genioglossus muscle, opens at frenulum
 Anatomy focus / relationships:
o Facial artery: Grooves around mandible between superficial glands
o Common fascial vein: below the superficial glands
o Mandibular branch of facial nerve: lateral to superficial glands

SUBLINGUAL GLAND

 Acinar: Between mylohyoid and genioglossus

 Lots of ducts (15), half opens into submandibular duct, half to sublingual fold / papilla

TEETH

 Primary (deciduous) teeth (x20), Permanent teeth (3+2+1+2)x4=32

 Nerve supply:
o Upper: Maxillary CNV2 > Anterior, Middle, Posterior superior alveolar nerve
o Lower: Mandibular CNV3 > Main, Incisive branch of inferior alveolar nerve
 Clinical relation: Dental occlusion, affects appearance, digestion, other problems (e.g. pain at
Temporal mandibular joint). Class 1 normal, Class 2 maxillary protrusion. Class 3 mesiocclusion
i.e. mandibular protrusion.

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HNS26 SMELL AND TASTE & SALIVARY AND NASAL SECRETION

OVERVIEW

1. Salivary glands
2. Salivary secretion: Mechanism and Regulation
3. Taste and smell
4. Nasal secretion: Mechanism and Regulation

SALIVARY GLANDS

 Types of Salivary glands: Parotid (largest, secrets at upper molars), Submandibular (secrets the
most, release beneath tongue), Sublingual (release beneath tongue). Plus ~100-1000 smaller ones
(mostly for lubrication)
 Types of Salivary secretion: Parotid (serous), Submandibular (mixed), Sublingual (mucous). Serous
acinar: Darkly stained, Round nucleus + Apex of protein granule. Mucous: Light stained, Flat nucleus
 Function: Serous (enzymes, isotonic), Mucous (lubrication & trap microbes)
 Other cell types in secretory units (Quick revision):
o Myoepithelial cells for contracting gland to enhance secretion (+prevent distension of
glands when filled)
o Intercalated duct: By cuboidal epithelium. Also secrets lysozyme and lactoferrin.
o Intercalated duct becomes Striated duct: with basal membrane (with mitochondria). Energy
needed for electrolyte changes (reabsorption & secretion)
 Composition saliva:
o Mostly (99.5%) water
o Solids: Organic (Enzymes, Mucin, Lactoferrin), Inorganic (minerals: basically most things we
know e.g. Na, K, Cl, HCO3-; Ca2+ and PO43- for teeth mineralization, F- to prevent caries)
 pH: 6.2-7.4
 Functions of saliva
1. Hydration and lubrication of oral tissue
2. Help mastication and swallowing (mucin)
3. Dissolve food for taste (saliva is hypotonic)
4. Initiate digestion (amylase: alpha 1-4 bonds, lipase)
5. Antibacterial effects to promote oral hygiene (lysozyme, mucin, lactoferrin (prevent
bacteria from getting iron), IgGAM)
 Salivary secretion: 2 stages
1. Stage 1: Production of isotonic primary saliva
 Ca2+ dependent Chloride outflux: Ca stimulates Cl channel opening > Cl leaves cell
and enters lumen
 Accompanied by paracellular Na outflux, and paracellular and apical Aquaporin 5
(AQP5) water transport (Easy to remember: Na always follows Cl, then water
always follows NaCl)
 How to get the Cl in the first place? NaKATPase coupled with NKCC1 channel
(influx of Na, Cl, and K).
 Balance of K: outflux by basal Ca activated K channels
2. Stage 2 (in striated duct): Electrolyte reabsorption to form hypotonic secondary saliva

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  Na reabsorption: Basal NaKATPase coupled with apical ENaC or basal NaHCO3-
cotransporter
 Bicarbonate secretion: basal NaHCO3- cotransporter coupled with apical HCO3-/Cl-
exchanger
 Cl reabsorption: apical HCO3-/Cl- exchanger coupled with basal Cl- channels
o Ducts here are impermeable to water, hence water cannot follow NaCl and hypotonicity is
achieved
o Tonicity related to flow rate: Slow = complete ion exchange = highly hypotonic. Fast = less
hypotonic
 Protein secretion in salivary gland. 3 modes of protein secretion:
1. Regulated secretion (secrets most): Exocytosis
2. Constitutive secretion: new proteins enter Golgi network, then secreted
3. Transcytosis: secretes immunoglobin only (because they are synthesized by plasma cells
and NOT acinar, so they need to enter cell and be ejected to lumen). Steps: Dimeric IgA
released into interstitial matrix > bind to polymeric immunoglobin receptor (a), entire thing
plus receptor transported in vesicles & pIgR slightly cleaved (Receptor coils around IgA and
prevents it being digested by proteases during secretion). This is nervous system regulated.

SALIVARY SECRETION: MECHANSIM AND REGULATION

 Afferent signals to Salivary Center. 3 triggers: Mechanical (i.e. chewing), gustatory, olfactory
1. Mechanical (Masticatory salivary reflex): CNV > Trigeminal nucleus > Superior salivatory
nucleus
2. Gustatory (Gustatory salivary reflex): CN7 facial (for anterior tongue), CN9
Glossopharyngeal (for posterior tongue). Both > Nucleus solitary tract > Inferior solitary
nucleus
3. Olfactory (olfactory-salivary reflex): Olfactory nerve (CN1) > Medial olfactory area
 Others: Fear and Anxiety > Descending pathways of cortical center (higher center) >
Salivatory nucleus
o These > Descending pathways of salivatory center > Superior cervical ganglion > Glands.
See below
 Molecular signals of Salivary Secretion
o Under autonomic (both sympathetic & parasympathetic) > controls Type and Amount of
saliva secreted. Process:
 Sympathetic: NE binds to Beta1 adrenergic receptor (GPCR) > Increase ATP,
increase cAMP > PKA > Exocytosis and protein vesicles > More protein secretion
 Parasympathetic: ACh binds to M3 (GPCR) > PLC activation and increase IP3 >
increase Ca > Increase production of primary saliva
 Both causes myoepithelial cell contraction > Release of stored products
o Note special point: Salivary vesicles respond to increase cAMP level (vs. other cells are Ca
dependent vesicle exocytosis)
 Efferent signals of Salivary gland
o Parasympathetic: CN7, CN9, CN10. Superior & Inferior salivatory nucleus located in Medulla
Oblongata:
 Sublingual, Submandibular: Superior salivatory nucleus > CN7 > Chorda tympani >
Lingual > Submandibular ganglion & synapse

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  Parotid gland: Inferior salivatory nucleus > CN9 > Tympanic nerve > CN 7 Lesser /
superficial petrosal nerve > Otic ganglion & synapse > Auriculotemporal nerve
(CN5)
o Sympathetic: T1-4 > Superior cervical ganglion > External carotid arterial plexus
 Summary of products:
o Sympathetic: (Parotid, Submandibular) High protein serous secretion (slow / no flow) +
Ductal contraction
o Parasympathetic: (Sublingual, Submandibular) Mucous, (Parotid) Low protein serous +
Ductal contraction

TASTE AND SMELL

 Chemoreceptors for Taste:

o 5 basic taste qualities: Sweet, Umami, Bitter, Salty, Sour
o More on the Papillae (by location): Circumvallate (CN9 Glossopharyngeal) at posterior,
Foliate at anterolateral, Fungiform anteriorly
o Taste receptor form bundles at papilla. Different receptors for different tastes, e.g. Salt
(ENaC), Sour (HCN, ASICs, PKD2L1), Bitter (T2Rs), Umami (T1R1, T1R3), Sweat (T1R2,
T1R3)
 Olfactory receptors:
o Functional receptors about 100-200 (poor sense of smell), but combined effects are still
reasonable. One odorants can stimulate 1+ receptors.
o Same type of receptors are geographically dispersed, but their stimulations are grouped by
glomerulus (hence enormous number of odorants are detected). Second order olfactory
neurons (mitral cell) relays signals from glomerulus to higher neurons
o Signal transduction: Binding opens ion channels > signal generation / depolarization
 Nasal cavity
o Epithelium: Squamous, Respiratory epithelium, Olfactory epithelium
o Types of cells in olfactory mucosa: Olfactory sensory neurons, Supporting cells, Basal cells
 Olfactory sensory neurons: Bipolar neuron, cilia at one end (catch odorants). Axons
penetrate cribriform plate.
 Supporting cells: Supports epithelium (metabolic, physical), secrete mucous, etc.
 Basal cells: Progenitors
 Nasal secretion
o Mostly secreted from respiratory epithelium ("Ciliated pseudostratified columnar
epithelium with goblet cells").
 Cell types: Ciliated columnar cells (Microvilli), Goblet cells, Basal cells (Progenitors
and cell adhesion)
 Semi-permeable membrane: allergens and drugs can pass, so drugs can make use
of this to administer to CNS
o Glands: Sero/submucosal gland. Contains serous + mucous, i.e. Lactoferrin & lysozyme +
mucoglycoprotein. Glands work with goblet cells
o Lamina propria contains dense blood vessel & nerve. Increase in vascular permeability >
Swell & more secretion of nasal fluid
o i.e. 2 types of structures for secretion: Goblet cells, Seromucosal glands (although they
work together)

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 o Nasal blanket (layer of mucous formed by secretion)
 Slightly acidic, majority is water, similar to saliva; similar functions to saliva too
 2 layers: Outer mucosal (gel, viscous and maintained by submucosal and goblet
cells), Inner periciliary (aqueous, containing ions. Allows ciliary movement)
 Maintenance of Thickness is important: too thick you can't beat it away, too thin
there's nothing to beat. Maintaining clearance is important too.

NASAL SECRETION: MECHANISM AND REGULATION

 Nasal Secretion mechanism (Briefly mentioned):

o Na reabsorption: basal NaKATPase coupled with apical ENaC
o Cl secretion: basal NaKCl- cotransporter coupled with CFTR, ECl-C
o Secretion of H ion: NaHCO3- cotransporter, coupled with NHE (Slightly acidic secretion)
 Regulation of nasal secretion
o Both chemosensory and mechanoreceptors + nociceptors. Both myelinated, and non-
myelinated.
o [Afferent] Sensory: CNV1 (Ophthalmic) for anterior nasal mucosa, CNV2 (maxillary) for
posterior nasal mucosa
o [Efferent] The following 3 nerve pathways mediates nasal secretion:
 Reflex stimulates nasal secretion. Neurotransmitter: Substance P, Calcitonin gene
related peptide
 Parasympathetic: CNVII (Facial) > Sphenopalatine = Pterygopalatine ganglion |
Synapse. Neurotransmitters: ACh, VIP (Vasoactive intestinal polypeptide). Effects:
VD, sinusoidal engorgement, glandular discharge
 Sympathetic: Innervates vessels. Neurotransmitters: NE, Neuropeptide Y. Effects:
VC, decrease secretion

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HNS27 PHARYNX

OUTLINE

1. At the pharynx
2. Summary

This is just a short summary. Please see Dr. Tipoe’s diagrams and also his notes for more details.

AT THE PHARYNX

 Auditory:
o Opening of pharyngotympanic / auditory tube
o Tubal elevation (by cartilage), Salphingopharyngeal fold (with Salphingopharyngeus
muscle), Pharyngeal recess (fossa of Rosenmuller, prone to nasopharyngeal cancer)
 Pharyngeal lymphoids (tonsils): Adenoids, Tonsils (between arches), Lingual tonsils (posterior
to tongue)
o Clinical relevance: Tonsillectomy. May lead to extensive bleeding because tonsillar
artery and vein (also CN9, and Internal carotid artery) lateral to tonsils.
 Arches (fold containing muscle): Palatoglossal, Palatopharyngeal. Elevates larynx.
 Vallecula: often location foreign body lodging
 Layers of pharyngeal fascia (in to out)
o Pharyngeal fascias (Pharyngobasilar, Buccopharyngeal)
o Prevertebral (Alar part, Prevertebral part)
o Forms space between 2 layers: Retropharyngeal space (extends to form posterior
mediastinum)
 Pharyngeus muscle:
o Salphingopharyngeus, Palatopharyngeus,
o Superior pharyngeal constrictor, middle PC, Inferior PC (Thyropharyngeal,
Cricopharyngeal: Connects to esophagus, CNX). Constrictors attach to skull at
pharyngeal tubercle.
 Important palate muscles: Levator veli palatini, Tensor veli palatini. Elevates soft palate, opens
auditory tube
 Muscles attaching to Styloid process
o Stylohyoid (CN3), Digastric (CN5), Stylopharyngeus (CN9, coursing immediately
superior to the muscle)

SUMMARY

 All muscles of the soft palate and pharynx are supplied by pharyngeal plexus (C9-11) except
o Tensor veli palatini: V3
o Stylopharyngeus: IX
o Cricopharyngeus: X
 All muscles of tongue supplied by hypoglossal nerve, except Palatoglossus muscle (by
pharyngeal plexus)

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  Supplies
o Arterial: Ascending pharyngeal artery (branch of External Carotid Artery)
o Venous: Pharyngeal venous plexus
o Lymph: Retropharyngeal Lymph node > Jugulodigastric node > internal jugular vein

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HNS29 LARYNX

OVERVIEW

1. Larynx
2. Summary
Check out Dr. Tipoe’s nice schematics!

LARYNX

 Cartilage: Thyroid, Cricoid, Corniculate, Arytenoid (All hyaline, because they ossify)
o Thyroid: Lamina, Arch
o Cricoid: Laryngeal prominence (Adam's apple), Superior & Inferior horn, Oblique line
(attachment of inferior pharyngeal constrictor), Lamina
o Arytenoids: 'fidget-shaped', Superior (Apex), Anterior (Vocal process, for attachment of
vocal cord), Lateral (Muscular process, attachment of intrinsic muscles)
o Corniculate: a small one at Arytenoid apex
 Joints: Cricothyroid (allows AP movement), Cricoarytenoid (allows Medial-Lateral movement)
 Fibrous membranes:
o Thyrohyoid membrane (with hiatus for superior laryngeal vessel & internal laryngeal
nerve),
o Quadrangular membrane (with vestibular ligament at inferior border. Vestibular
ligament + mucosa = vestibular fold = false vocal cord),
o Conus elasticus (=cricoid thyroid membrane. Superior end forms focal cord)
Clinical relevance of Cricothyroid ligament (anterior portion): Cricothyrotomy to allow
access to airway. (Alternatively, one can do tracheostomy for long term airway access)
 Other important structures:
o Thyroepiglottic muscle (Middle of Quadrangular membrane), Aryepiglottic muscle
(Posterior border of Quadrangular membrane). Both controls laryngeal inlet.
o Cricothyroid muscle (tenses vocal cord), (Lateral) cricoarytenoid muscle (adducts vocal
cord)
o Epiglottis: a Yellow cartilage (they don't ossify)
o Saccule: Divides the larynx into supraglottic (vestibule) area, and infraglottic area (with
different blood and nerve supplies). Has a sinus.
 Supraglottic: Superior laryngeal AV (from external carotid artery > Superior
thyroid artery). Internal laryngeal nerve (CNX > Superior laryngeal nerve).
Superior cervical deep nodes
 Infraglottic: Inferior laryngeal AV (Subclavian > Thyrocervical trunk). Recurrent
laryngeal (CNX). Inferior deep cervical nodes.
 Muscle:
o Extrinsic (moves whole larynx)
 Elevation:
 Suprahyoid: Stylohyoid (CN7), geniohyoid (C1), mylohyoid(CNV3)
 Digastric (CNV3, CN7)

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  Pharyngeus (by pharyngeal plexus C9-11): stylopharyngeus,
Salphingopharyngeus, Palatopharyngeus, thyrohyoid (C1)
 Depression (strep muscles / infrahyoids, innervated by Ansa cervicalis C1-3):
Sternohyoid, Sternothyroid, omohyoid, thyroid muscle
 Intrinsic (moves parts of larynx):
a) Those controlling laryngeal inlet (Prevent foreign bodies from entering trachea)
b) Those controlling vocal cord (phonation, sneezing, coughing, increase abdominal
pressure by Valsalva's maneuver)
a) Those controlling laryngeal inlet
o Epiglottis
o Aryepiglottic muscle, Thyroepiglottic muscle: Controls laryngeal inlet
b) Those controlling vocal cord
o Thyroarytenoid (relaxes vocal cord), Vocalis (tenses vocal cord + lift the thyroid
cartilage during abduction)
o Rima glottidis: Space between the 2 vocal cord
o Lateral cricoarytenoid (adductor), Posterior cricoarytenoid (abductor)
 Other muscles of arytenoids & esophagus
o Aryepiglottic muscle (surrounds esophagus), Oblique arytenoid (extension of
aryepiglottic muscles at arytenoid bone). Transverse arytenoid (covers transversely,
forms posterior arytenoid)

SUMMARY

 All intrinsic muscles of larynx are innervated by Recurrent Laryngeal nerve, Except the
Cricothyroid muscle (innervated by External laryngeal nerve)
 Superior laryngeal nerve > Internal and External Laryngeal nerve.
o Internal: Sensory to Vestibule
o External Motor to Cricothyroid

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HNS30 SWALLOWING AND SPEECH

OVERVIEW

1. Swallowing
2. Speech: Phonation, Articulation

SWALLOWING

 Phases: Oral, oropharyngeal, esophageal phases (refer to GIS)

 Neural control of swallowing:
o Oral: Mastication (CNV), Tongue movement (CNXII), Sensation CNV2, CNV3, CNIX
o Oropharyngeal phase: Tongue movement (XII), Sensation (CNIX), Soft palate
movement (CNV, CNIX)
o Pharyngeal phase: Sensation (CNIX, Superior laryngeal nerve CNX), Laryngeal
elevation (CNV, CNVII, CNXII, ansa cervicalis of cervical plexus). Closure of glottis
(Recurrent laryngeal nerve of CNX), Opening of upper esophageal sphincter /
Cricopharyngeus (CNX of Pharyngeal plexus)
 Preventing aspiration: Closure of laryngeal inlet (Elevate larynx and closure by epiglottis),
Closure of false cord & glottis (most important), Generation of positive pressure in trachea
 Clinical: Swallowing problems
o Symptoms: Globus (lump in 'throat'), dysphagia, choking, cough, aspiration,
pneumonia
o Cause: Intraluminal, Intramural, Extraluminal; CNS Pathology (Sensory / Motor /
Coordination)
o Investigations: Endoscopy, VFSS (Videofluroscopic swallowing study), Manometry
(evaluate muscle power), CT/MRI for neural problem

SPEECH

 2 components: Phonation (generating the sound, e.g. aah..), Articulation (say the words)
 4 types of muscles needed. Intrinsic muscles of larynx:
1. Adductors (close glottis): Lateral cricoarytenoid, transverse and oblique arytenoid
muscle
2. Shortening vocal cord: Thyroarytenoid, vocalis
3. Lengthening vocal cord: Cricothyroid muscle (supplied by Superior laryngeal nerve
and NOT recurrent laryngeal)
4. Posterior cricoarytenoid (most important muscle: responsible for opening vocal fold. If
not open, no inspiration. Abductor.)
 Histology of vocal cord:
o Mucosa: Non-keratinize squamous epithelium in true vocal cord, Pseudostratified
squamous epithelium in other places
o Subepithelial tissue: (3 layers of lamina propria) Superficial (Reinke's space),
Intermediate, Deep. Superficial lamina propria with loose connective tissue to allow

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 vocal cord epithelium to vibrate freely (fibrosis in this area generates hoarseness).
Intermediate & deep layers make up vocal ligament. Vocalis & thyroarytenoid muscle.

PHONATION

 Mechanism
1. Closure of vocal cord & generation of subglottic pressure (increase in pressure in the
subglottic airway, about 3-5cm H2O)
2. Vocal folds forced open > Immediate fall in subglottic pressure > subglottic pressure
builds up again
3. Vibration generates sound (Male 120Hz, Female 230 Hz)
 Controls:
o Loudness: depends on force of expiration (depends on lung function & respiratory
muscle)
o Pitch: depends on size of larynx (e.g. male, larger larynx, so vocal cord longer), tension
& length of vocal folds, intrinsic laryngeal muscle's action
 Clinical: Phonation problems
o Symptoms: Hoarseness
o Causes: Lung disease, Recurrent laryngeal nerve palsy (surgical complication),
Neurological problem, vocal fold pathologies (polyps, tumors)
o Investigations: Laryngoscopy, esophagoscopy, CXR, CT, etc. (no need now, clinical
years revisit)

ARTICULATION

 Articulation: Generation of sound

 Muscles: Mandible (CNV), Lips (CNVII), Larynx (CNX), Soft palate (CNXI), Tongue (CNXII)
 Clinicians should differentiate between Dysarthria vs. Dysphonia: Articulation problem vs.
Phonation problem (e.g. hoarseness)
 Clinical: Articulation problems:
o Symptoms: Dysarthria, Expressive aphasia
o Cause (Seems not important): Tongue tie, oral pathologies, CNS pathologies
 E.g. Neurological:
 Cerebellar problem can lead to poor coordination of muscles.
 Expressive aphasia (slightly different): Broca's problem (can write, can
understand, cannot speak out or read)
o Investigations: Endoscopy, CT/MRI brain (Clinical years revisit)

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HNS33 COMMON ENT INFLAMMATORY DISEASES: ANATOMIC AND
PHYSIOLOGICAL APPRAISAL

OVERVIEW

1. Background
2. Nose infections
3. Ear infections
4. Mouth infections
5. Deep neck space infections
6. Summary

BACKGROUND

 Common ENT inflammatory disease

 Inflammation of sinuses: Rhinosinusitis
 Causes: [1]Infectious, [2]Allergic, [3]Others e.g. drug induced (e.g. aspirin), hormonal, etc.

NOSE INFECTIONS

 Allergic rhinitis:
o Pathophysiology: Type 1 Hypersensitivity (IgE). Allergen pass through epithelium >
Mast cells > release Cytokines (e.g. Histamine, IL)> Symptoms.
o Phases: (Early phase): Sneeze & Itch. (Late phase e.g. Months / Year) Thickening of
mucosa > Chronic nasal obstructions
o Investigations: Anterior rhinoscopy with speculum. Swollen mucous membrane
(Inferior turbinate) obstructing aperture
 Infective Rhinitis
o Common URT infections: H influenzae, Streptococcus pneumoniae, Staphylococcus
o Investigations: Anterior rhinoscopy with speculum. Colored nasal discharge, rather
sticky.
 Sinusitis
o Recall nasal sinuses + 8 Paranasal sinuses, 4 on each side
o Normal pathway of drainage: all to ostiomeatal complex
o Pathophysiology: Disturbed mucociliary pathway (e.g. polyp) > Mucous retention
o Investigation: X-ray shows air fluid level (Air white, fluid hazy; Normally there shouldn't
be any fluid, so presence already indicates sinusitis). CT to better define involvement.
Endoscopy shows draining pus.
o Complications: Spreads to neighboring e.g. eye (progression: orbital cellulitis > orbital
abscess > blind) and brain > danger!

EAR INFECTIONS

 Recall anatomy: Outer, Middle, Inner ear (inner ear usually don't have infections)
 Otitis externa

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 o Pathophysiology: Disturbance to earwax removal cycle > accumulation of dead skin >
breeding ground for bacteria > Inflammation (more cell turn over) > Vicious cycle
 Contents of Earwax: Desquamated cell, Cerumen, Sebum. Function: protection
(impermeable to water + acidic). However, there should only be a thin layer
(Regulation by the way cells are multiplied: Pars tensa [located around
eardrum] multiple inwards to outwards, skin is shed outward). I.e. it is self-
cleaning.
o Presentation: Eryseptalis (red around pinna), Furuncle of external ear canal.
o Treatment: Stop the cycle i.e. removing that earwax. Drain the pus, give anti-
inflammatory drugs.
 Otitis media
o Types: Acute vs. Chronic (from unresolved acute. Involves ear drum e.g. hole. Subtypes:
Active i.e. discharging vs. Inactive / dry)
o Common causative: Streptococcus pneumoniae, Hemophilus influenzae; or Viral
o Investigations: Endoscopy. Very red, very engorged / bulged, with hints of pus behind
eardrum .
o Complications:
 Discharge (ear drum burst due to pus accumulation and going out. This could
cause permanent damage to eardrum if not treated.) Or, if the eardrum doesn't
burst, the pus escapes to mastoid cavity (posterior) mastoiditis (area behind
year, bone infection)
 Nerve palsy (Facial nerve e.g. palsy and loss of wrinkles), Abducens never palsy
(affecting the entire temporal bone). (MRI sees hypertense ring on hypodense
lesion)
o Note: Chronic suppurative otitis media burst eardrum may not heal up, so could be
permanent. Although, eardrum broke leads to conductive ‘deafness’ (but patient
wouldn’t be totally deaf, because even if entire conductive pathway loss would only
lead to ~40% hearing loss.) So in a minor perforation patient may not notice it at all.

MOUTH INFECTIONS

 Tonsillitis
o Causative agent: Bacterial (Streptococcus pyogenes, staphylococci, pneumococci, H.
influenzae), Viral (Rhinovirus adenovirus, EBV), Others (Syphilis, diphtheria, M. TB)
o Clinical feature: Fever, Sore throat, Otalgia (referred pain to ears), Trismus (cannot
open caw wide), Odynophagia. At the tonsils, viral vs. bacterial cause differentiated.
Important part, see CPRS (Dr. Samson Wong's lecture)
o Local complication (pus in peritonsillar abscess = quinsy). Asymmetric palate, deviated
uvula. Investigation: needle aspiration, CT (Hypodense)
o Note: Tonsillar stones are not actually stones (not calcified), but is actually soft particles
of pus accumulates

 Pharyngitis

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 o Presentation: General redness in pharyngeal area (Viral) vs. Pus and abscess (bacterial)
o Clinical features: Airway & Swallowing problem (Supraglottic), Voice (Glottis), Croup
(Subglottic)
 Epiglottitis: Cherry red in laryngoscopy, thumb sign on imaging. AIRWAY most important, must
maintain AIRWAY at all times.
 Sialadenitis (Salivary gland infection)
o Cause: usually Blockage of gland e.g. stone, inflammation, trauma > buildup of saliva /
stagnant. Submandibular gland most likely obstructed (commonly stone because more
viscous secretion. Stones: CT can see / externally can see).
o Clinical signs: Swelling in gland area.
o Treatment: Drain pus.

[If you have time, you can also revisit Dr. SSY Wong’s good CPRS lecture on Upper Respiratory Tract.
Notes for this lecture is included in the last section of this notes (“Additional resources”), additionally
Dr. SSY Wong also publish very good notes which you can find on Goddisk.]

DEEP NECK SPACE INFECTIONS

 More dangerous because close of airway

 Locations: Parapharyngeal, Retropharyngeal
o Parapharyngeal: Complications of untreated infections at that area. Usually unilateral
and doesn't look like quinsy.
o Retropharyngeal: commonly in children (because they have more lymph nodes there).
Systemically unwell and may complicate airway. Imaging investigation (loss cervical
lordosis)

SUMMARY (FROM LECTURER)

 Not all inflammatory conditions are infectious e.g. allergic rhinitis

 Knowing anatomy of HN is important.
 Knowing pathophysiology can help understand risk factors and treatment.

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HNS34 COMMON ENT CANCERS ANATOMIC AND PHYSIOLOGIC APPRAISAL

OVERVIEW

1. Chapter introduction
2. Ear
3. Nose
4. Oral cavity, oropharynx
5. Neck
6. Thyroid & Parathyroid
7. Larynx, pharynx, esophagus
8. Skin, fascia, muscle

CHAPTER INTRODUCTION

 Recall anatomical structures / potential cancer locations: Ear & Skull base; Nasal cavity &
Paranasal sinuses, Oral cavity, Neck & Thyroid gland, Larynx & Pharynx, Esophagus, Skin &
muscle
 Function: Vital sensory (Hearing, vision, smell, taste), Breathing, Swallowing, Speech, Facial
expression
 Treatment:
o Surgery (Resection & Reconstruction of defect), Radiotherapy, Chemotherapy
(Induction, Concurrent, adjuvant, Palliative). Usually combined
 Note: Treatment can affect 'form' i.e. external appearance (psychosocial
effect). It looks less important but NO it is important! See ppt images and you
will understand.

EAR

 Function: Hearing & Balance

 Compartments: External, Middle (ear drum, Ossicles), Inner (Cochlea & balance organs)
 Clinical pearls: Cancer in nasopharynx
o Cancer in nasopharynx can block eustachian tube opening > Fluid accumulated in
middle ear > Conductive deafness
o Symptoms: Unilateral hearing loss, Unilateral tinnitus (i.e. ringing, this caused by
hearing loss)
 Random points
o Ear also has form problem.
o Radiation therapy near inner year can damage cochlear > hearing loss

NOSE

 Function: Smell & Air passage

 Compartments: Nasal cavity, Paranasal, Eustachian tube
 Clinical pearls: Cancer in nose
o Sinuses are deep in skull, so it is hard to detect. Early symptoms only nasal bleeding.

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 o Spread of cancer: Lamina paperacea (lateral nasal bone) is the thinnest bone in the
body, cancer can easily spread from nasal cavity through this bone to eye, so eye needs
removal too (much debilitation)
o Spread of cancer: Actually, bones separating nasal sinuses in skull are all quite thin, e.g.
ethmoid plate easily allows tumors to spread from nasal space to brain :(

ORAL CAVITY, OROPHARYNX

 Function: Food passage & defense, Taste, Speech

 Compartments:
o Lip, Tongue, Mandible, teeth, palate, floor of mouth, buccal mucosa
o Salivary glands
o Tonsils, Posterior pharyngeal wall
 Clinical pearls: Removal of tongue.
o This affects speech and swallowing. Reconstruction only provides lining but no
muscular function. Functional outcome depends on how much tongue muscles left.
(Usually remove less than half  tongue still okay)

NECK


Common place for benign lesion, lots of lymph nodes, many important structures (Cranial
nerves, important blood vessels)
 Lymphatic drainage of neck:
o Deep lymphatics lie in fascia spaces, which are created by externally investing fascia,
prevertebral fascia, carotid and pretracheal fascia internally, but they do not run within
carotid sheath or other fascial wrappings.
o Yet, the nodes may be in close association with the fascia. Cancer spread to lymph node
may also spread to fascia, so may need to remove what's inside the fascia e.g. muscles,
veins
 Important: Anatomical 6 regions of neck (divided by levels of lymph nodes). Why important?
o Cancers spread in a predictable pattern. Cancer from different locations spread to
different levels first (See important table below) (Indicates anatomical boundaries)
o Also, teacher say ‘commonly examined’. SIKES!
Node groups, Boundaries, and Drainage / Metastasis route
 Group 1: Submental (A) and Submandibular (B) (divided by accessory nerve)
o 1a: Submental (Ant digastric - Hyoid): Lower lip, Tongue tip, Anterior mouth floor,
Mandibular incisors
o 1b: Submandibular (Ant & Post digastric - Stylohyoid - mandible): Submandibular
gland, Oral cavity, Tongue, Anterior nasal cavity
 Group 2: Upper jugular (Base of skull – Hyoid – Stylohyoid – SCM)
o Nasal cavities, Oral cavity, Pharynx, Larynx; Parotid and Submandibular glands
 Group 3: Mid jugular (Hyoid – Cricoid – Sternohyoid – SCM)
o Oral cavity, Pharynx, Larynx, Thyroid
 Group 4: Lower jugular (Cricoid – Clavicle – Sternohyoid- SCM)
o Pharynx, Larynx, Thyroid, Cervical esophagus

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  Group 5: Posterior triangle (SCM, Clavicle, Trapezius)
o NASOPHARYNGEAL CANCER (Otherwise not a lot of cancers go here)
 Group 6: Pretracheal (Hyoid - Suprasternal notch - Strap muscles)
 SUPRACLAVICULAR fossa (SCF)
o Left side drains most of body via THORACIC DUCT  Drains to Virchow's node (left
supraclavicular node)
o Enlargement of Virchow’s node hence can indicate metastatic cancers around the
body, e.g. pancreatic cancers
 Radical neck dissection
o Classically:
 Remove lymphatics involved in metastasis (Level 1-5 lymphatics)
 Plus: Sternocleidomastoid, Internal jugular vein
 Plus: Accessory nerve (CNXI), Cervical plexus [These pass through lymphatic
layer]
o Modified: Preserving one or more of the 'plus' above (nonetheless, Cervical plexus still
usually sacrificed)
o Selective: not all lymphatics, only those with highest chance of metastasis. E.g. Level VI
for thyroid cancer; Level 1-3 for tongue cancer. These reserved for patients with no
obvious nodal metastasis, but has high chance of occult nodal metastasis.

THYROID & PARATHYROID

 Function: Metabolism (Thyroxine), Ca level (Parathyroid)

 Close proximity to: Recurrent laryngeal nerve, trachea, esophagus
 Presentation: Mass, or Endocrine disturbance (Hyperthyroidism,
Hypercalcemia in Adenomas of thyroid and parathyroid respective).
 Investigation: Special isotopic scans to detect physiological abnormalities.
Images:
o e.g. Tc99 MIBI scan for Parathyroid, showing increase uptake of
Tc99 in affected parathyroid adenoma. There are 4 parathyroid
glands, so need to know which one affected
o e.g. Radioactive iodine for thyroid (Lateral picture)
 Surgical pearls: knowing anatomy of region around thyroid. Easily damage things:
o Parathyroid: but there's 4 of them so some should still be functional.
o Recurrent laryngeal nerve in thyroid surgery. Damage cause voice hoarseness
(similarly, if tumor grows big and press on recurrent laryngeal nerve also cause
hoarseness). Patient also choke in drinking fluids. Bilateral damage leads to bilateral
vocal cord palsy > Airway obstruction.
o Superior laryngeal nerve: it lies just superior to thyroid, and external branch lies on
cricothyroid muscle, so quite easily damage. Damage should be tolerable in normal
people, but can't sing high pitch.

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LARYNX, PHARYNX, ESOPHAGUS

 Function: Phonation, Air passage, swallowing

 Intervention: Surgical may or may not preserve function (depending on whether removal
involves true vocal fold). Alternatively Chemotherapy + radiotherapy ('organ preservation', i.e.
doesn't damage the structure and may preserve vocal functions.
 Laryngectomy (for more advance cancer): Loss speech, loss filter function of nose (e.g. breath
in dirt or even fly), loss nasal cavity humidification, ineffective cough (no true cord to build up
pressure, mucous may coat)

SKIN, FASCIA, MUSCLE

 Not exactly functionally a problem since can borrow flaps from other areas, e.g. skin graft, local
flaps / Reconstruction
 E.g. Deltopectoral flap (Skin+Cutaneous+Blood supply from internal mammary artery) to cover
neck defect

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HNS35 EAR

DIAGRAMS

Sorry, I don’t have new notes, I only drew some of the diagrams from Dr. Tipoe and annotated a bit.
Dr. Tipoe has his own notes, recommend reading those.

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HNS37 AUDITION

OVERVIEW

1. Introduction and Basic sound conductance

2. Signal transduction
3. Nervous pathway, reflex, and other important points

INTRODUCTION AND BASIC SOUND CONDUCTANCE

 Sound cues: Frequency (Tone), Intensity, Location

 Types of sound conduction: Air (Outer ear > Middle > Inner) vs. Bone (Temporal > Inner ear)
 Hearing examination: Auroscope (look at tympanic membrane), Weber test (Bone and Air
conduction), Pure tone test, Newborn hearing test (BAER: Brainstem Auditory Evoked
Response)
 Features:
o Area ratio enlarges sound (Tympanic membrane vs. Oval membrane)
o Middle ear muscle reflex: Attenuates low frequency, improve speech discrimination,
protects inner ear
 Process of sound detection:
o [Conduction (=Impedance matching i.e. air to fluid): Air vibration > Ear bones >
Perilymph]
o Conduction pathway: Air vibration > Ear drum > Ear bones (Malleus, Incus, Stapes) >
Oval window > Perilymph vibration > Endolymph (sandwiched layer) > Basilar
membrane > Hair cells > Sensory transduction
o Sensory transduction: High K in endolymph, bending opens K channels, K enters hair
cell > depolarization > open Ca2+ (voltage gated Ca channel) > Increase Ca2+ >
Neurotransmitter (glutamate) released > generates action potential at VIII
 Functions by compartments: Outer ear for air conductance, middle ear for impedance matching
(i.e. air vibration to liquid), inner ear for sensory transduction (via movement of peri and
endolymph)
 Common hearing disorders:
o Tinnitus (ringing / hissing sound e.g. in noisy environment)
o Hearing loss (2 types: conductive at middle ear vs. Sensorineural hearing loss at
cochlear nerve, due to e.g. temporal bone fracture)

SIGNAL TRANSDUCTION

 Processing of Sound Frequency: How to determine the tone / frequency of sound?

o Characteristics of Basilar membrane: Base / Proximal (narrow & stiff) vs. Apex / Distal
(wide & floppy).
o Low frequency vs. High frequency: Entire membrane vibrate vs. Only basal part. The
locations of the basilar membrane vibrating allows Topotonic distribution.
  How to determine Sound intensity: Depends on the vibration magnitude of basilar membrane
 Features of Auditory pathways:
o Ascending: Tonotopic, Bilateral (similar to vision), Crossed
o Descending: Modulates outer hair cell activity
 Descending pathway: Cocktail party phenomenon (hearing what your neighbor saying in loud
background voice)
o Selective filtering: active control of hair cell to selectively hear sounds.
o Pathway: CNS activate superior olive > Organ of Corti > Shorten the hair cell
 Outer vs. Inner hair cell: 3 rows vs. 1 row. Also, less signals vs. most signals
 Clinical relevance: Cochlear implant / Bionic ear: Make use of tonotopic arrangement of 8th
nerve. Microphone to collect sound > sound processor > wire in cochlear > stimulate electrodes
at specific sites in cochlea > patient’s own VIII
 Importance of tonotopic difference:
o V-shaped tuning curve at cochlear level: Receptive field (when the intensity and
frequency is responsive. When sound intensity is low, the receptive field is narrow.
When the sound intensity is high, the receptive field is wide.
o Sharpening of V-shaped to nerve level: Receptive field
o to enhance frequency discrimination of sound [Frequency selectivity]

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SECTION 3 (MOST IMPORTANT)

 7 relay station of ascending auditory pathway: Cochlear nerve > Cochlear nucleus > Superior
olive > Lateral lemniscus > Inferior colliculus > Thalamus (Medial Geniculate body)> Auditory
cortex.
 Features:
o Tonotopic pattern (in Cochlea, In auditory cortex. High>Low)
o Crossed connection: allow sound to be compared for location
 Analysis of 'temporal pattern':
o Different cell types in cochlear nucleus extracts different features of sounds e.g. onset,
late phase, regular intervals
o However, there is always a backup copy that is exactly the same as the input signal.
 Spatial localization of sound: First crudely at the superior olivary nucleus (comparing time and
intensity of signals in 2 ears), then more accurately at higher centers
 Reflex response: Head orientation to novel sound, Startle response to loud sound (Related to
inferior colliculus)
o Thalamus (Medial Geniculate body): Relay station (not discussed this lecture)
 Primary auditory cortex
o Arrangement: Topographical. 6 layers of cells that interprets different part of auditory
pathway and different frequencies. Biaural band arrangement (Left Right LRLR
'columnar arrangement')
o Wernicke for Language recognition, Broca's for language perception. Arcuate fasciculus
to communicate between the 2 areas.

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HNS38 VESTIBULAR SYSTEM

OVERVIEW

1. Introduction to vestibular system

2. Signal transduction: Arrangement of semicircular canal and otolith organs
3. Central processing and Reflex
4. Involvement of other organs: Cerebellum, Cerebral cortex
5. Others: Clinical correlations

INTRODUCTION TO VESTIBULAR SYSTEM

 Vestibular system: Perception of Balance

 Organs: Semicircular canal, Otolith organ. Signal conducted by CN8
 Function of Vestibular system:
o By organ:
 Semicircular canal: Detects head rotation (=Angular acceleration)
 Otolith organ (Utricle, Saccule): Detects gravity, Linear acceleration.
o By pathway:
 Vestibulo-thalamo-cortical projection: for Head motion, Spatial orientation
 Vestibulo-ocular pathway: for stabilizing eye during head movement
 Vestibulo-spinal pathway: Postural adjustment
 Clinical: Abnormalities in vestibular system. Dizziness (Altered orientation ins space),
Disequilibrium. One needs to differentiate where the cause of the complains are, because not
necessarily vestibular system (e.g. light headedness) [See more in final section]

SIGNAL TRANSDUCTION: SEMICIRCULAR CANAL AND OTOLITH ORGANS

SEMICIRCULAR CANALS

 Allows rotations 3D: 3 sets of Semicircular canal: Horizontal (LR), Anterior and Posterior canal.
o Note: Horizontal is actually not horizontal and is inclined. Take special note on clinical
test.
 Operates as Complementary pairs: Acceleration and Deceleration. One side accelerates, the
other side decelerates. Synchronous increase or decrease enhances excitability.
 Signal transduction:
o Basic principles: Many stereocilia, one kinocilium. Movement in direction along
kinocilium, other directions ineffective. Positive direction cause depolarization and
increased firing. Negative direction causes hyperpolarization and decreased firing.
o Process and microstructures: Stereocilia sitting on cupula, surrounded by endolymph.
In movement, endolymph move, bends cupula. Bending towards kinocilium causes
depolarization and fires CN8, bending against kinocilium causes hyperpolarization.
When movement stop, inertia causes cupula to bend in opposite directions (hence
hyperpolarizes the CN8). In other words, acceleration towards one direction causes

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 increased firing in one side of CN8, and decreased firing in the other side. (\hence
Structural and Functional Polarization / Push & Pull arrangement > Sharpens signals)

OTOLITH ORGAN

 Otolith organs: Utricle, Saccule. Detects linear acceleration & Head tilt.
o Utricle: Horizonal, Saccules: Vertical. Hence sideways movement activates utricle,
whereas vertical movement (e.g. jumping up and down) stimulates saccules.
 Otolith organ's hair cells. Embedded in epithelium with hair embedded in jelly-like substance
(acts like a uniform unit). The tip of hair contains otoconia crystals (anchors the hair into the
jelly-like substance) [in pathological conditions these crystals may dislodge].
 Signal transduction in otolith organ:
o Similar to semicircular canals: In translational head movement (i.e. moving forward or
backward) or head tilt: moves otoconia, activates stereocilium to tilt towards
kinocilium.
o Utricle located in horizontal plane. Middle in striola, on either sides, hairs are oriented
in opposite directions. This means movements in one direction would activate different
subsets of hair cells. Because of their different direction of hair cells, they can detect
head movement in a 360 degrees fashion in a horizontal pain.
o Meanwhile Saccule only activated when there is vertical plane movement (i.e. up-down
movement). Like utricle, they have striola and the hair cells oriented in opposite
directions on the 2 sides of striola.
 Summary of Main ideas
o Push and Pull achievable because there are hair cells aligned in opposite directions at
the two sides of striola > Enhance excitability.
o Recruit specific subgroup of hair cells that is in the right orientation.
 [Section 1] Take home message
o 3 main vestibular functions. Disruption of these functions produces clinical symptoms,
namely dizziness and disequilibrium.
o Hair cells: Kinocilium vs. Stereocilia.
o Semicircular canals for 3D angular acceleration: Complementary pairs. Endolymph,
Cupula, Crista ampullaris
o Otolith organs for linear acceleration and head tilt. Multidirectional orientation of hair
cells allows

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CENTRAL PROCESSING AND REFLEX

 Pathways: Vestibulo-spinal pathway (for neck, trunk, limbs / Extensors). Vestibulo-ocular

pathways (for Extraocular muscles). Reflexes:
o Postural reflex. Tilting of the substratum: extension of limb to avoid fall during tilt
o Vestibulo-ocular reflex: Triggered by otolith or canal related signals.
 Lateral tilt of 50 degrees lead to 5 degree counter rolling of eye (Doll's eye
reflex, basically non-detectable).
 Forward pitch (前傾) leads to eye elevation, again non-detectable due to small
magnitude.
 Anterior posterior linear acceleration: shows significant deviation (Upwards).
e.g. pilot helmet is compensated by moving 40 degrees up.
o Canal induced vestibular nystagmus:
 Per-rotatory nystagmus: Slow (2 secs) initial eye movement to focus on moving
object. However, eye socket has boundary, it is followed by fast phase
anticipatory eye movement, to the opposite direction. Slow and Fast phases
repeat, producing ‘Per rotatory nystagmus’.
 End of rotation: Post rotatory nystagmus. (Opposite direction of firing)
o Trineuronal arc of vestibulo-ocular reflex. 8th nerve detects movement by hair cells.
Right vestibular nucleus directs to CN responsible for eye movement. 3rd neuron is the
CN neuron innervating extraocular muscles.
 [Section 2] Take home message
o Compensatory reflexes: Vestibulo-spinal, vestibulocochlear
 Vestibulo-spinal: for neck, trunk and limb (in antigravity response, involves
extensors e.g. tilting table). Also for postural reflex.
 Vestibulocochlear: Otolith related reflex causes eye counter-roll or elevation.
Canal related reflex causes Nystagmus (Fast + Slow phase: Per-rotatory, Post-
rotatory)

INVOLVEMENT OF OTHER ORGANS: CEREBELLUM, CEREBRAL CORTEX

 Cerebellum / Vestibulocerebellum (Esp. Flocculonodular part).

o Canal sends afferent fiber to vestibulocerebellum, output of purkinje cells (inhibitory
cells), to inhibit the vestibular nucleus. Adjust magnitude of movement e.g. reflex of
eye.
o Vestibular nucleus also involved in vestibulospinal and reticulospinal tract, hence
cerebellum dysfunction also leads to abnormal eye movement and postural reflex.
o Vestibular system also innervates autonomic nervous system > motion sickness.
 Cerebral cortex
o Cerebral cortex: Subjective orientation and motion in space.
o Ascending pathway: vestibular nucleus > Thalamus > Entorhinal cortex <> Parietal
cortex. (Disrupted labyrinth signals in canals is found to make subjects unable to
recognize their way home)

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 o Vestibular nucleus and somatic signals leads to conscious awareness of body
orientation.
o Visual vestibular conflict highlights the interaction between vestibular system and
ocular system (HK science museum, lol)

OTHERS: CLINICAL CORRELATION

 Dizziness: a sensation of altered orientation in space. Cause could be vestibular vs. non-
vestibular. Vestibular, patient may complain spinning, nausea, vomiting. Non-vestibular
complains e.g. lightheadedness, symptoms e.g. pallor.
o Vertigo: different causes.
 [Seconds] Benign paroxysmal positional vertigo: Short duration but severe,
complains of room spinning. But this is benign.
 [Minutes] Meniere's disease: Fluctuating pressure of endolymph, hence
membrane becomes dilated (hydrops) and is dysfunctional. This is due to
abnormal secretion of endolymph.
 [Days] Neuritis, Trauma, Infarct produces vertigo lasting days.
o Cupulolithiasis. The otoconia dislodge and plucks a canal, hence endolymph flow is
disrupted > abnormal signal of CN8
 Disequilibrium: again could be due to vestibular problem, but also problems in cerebellum,
proprioception.
 Physiological dizziness (due to visual-vestibular conflict e.g. reading on the bus)

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HNS39 ORBIT

DIAGRAMS

Sorry, I don’t have new notes, I only drew some of the diagrams from Dr. Tipoe and annotated a bit.
Dr. Tipoe has his own notes, recommend reading those.

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HNS40 VISION

OVERVIEW

1. Introduction to Vision
2. Color perception and visual acuity
3. Binocular vision: Perception of depth, Motion perception
4. Form recognition
5. Others: Signal integration, Scientific development

INTRODUCTION TO VISION

 Vision. Features to extract: Visual acuity, Binocular vision, Form recognition, Motion perception
 Abnormality of eyeball:
o Lens: Cataract
o Retina: Retinal detachment, Macular degeneration
 Pupillary reflex: a Clinical reflex. Pupil constriction pathway (involves parasympathetic
pathway) vs. Pupil dilation (involves sympathetic)
 Sensory transduction: In dark, Na channel opens due to cGMP activation > depolarization >
transmitter release > depolarizing by bipolar cell > retinal ganglion cell > CN2 > CNS. In light,
cGMP process stop, Na channel closed. Cell hyperpolarized and doesn't release transmitter >
Bipolar cell doesn't depolarize. Hence, can detect light or dark .

COLOR PERCEPTION AND VISUAL ACUITY

 Visual acuity: Near / Far accommodation. Ciliary muscle contraction and relaxation controls lens
thickness
 Cones vs. Rods
o Cones for color, 3 types to detect blue, green, red.
o Different distribution across eccentricity. Fovea having all cones. Rods more towards
center (except at fovea), decreases along periphery.
o Small receptive field allows high acuity. In fovea, each cone is supplied by one ganglion
cell for small receptive field and high acuity. At peripheral retina, several cones are
supplied by one ganglion cell, hence larger receptive field and lower acuity.
o Rhodopsin is a photopigment, reversible reaction to opsin + retinal. In light becomes
opsin and retinal. In dark opsin and retinal becomes rhodopsin.
 Disorders:
o Macular degeneration (due to genetics, age, nutrition, smoking). Amsler grid to detect
any distorted image. Ophthalmoscope shows early dry. Optical coherence tomography
shows undulated fovea.
o Retinal detachment: Curtain obstructing visual, light flashes.
o Glaucoma: Pressure build up causes damage to optic nerve.
 [Section 1] Take home message:
o Common eye disease: those concerning lens, retina, eye pressure.
o Pupillary reflex pathway

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 o Visual acuity and accommodation
o Sensory transduction. Photoreceptor (cones or rods) to bipolar and retinal cells.

BINOCULAR VISION: PERCEPTION OF DEPTH, MOTION PERCEPTION

 Binocular vision. How images are registered in the 2 eyes converged in the brain?
o Crossed projection: Left visual field projects to right visual cortex. Partial projection
achieved in the optic chiasma. Crossed projection and binocular vision allows depth
perception.
o Visual pathway: Light in retina > ipsilateral LGB > Visual cortex. Arrangement of
thalamus is highly layered and organized: information received at different sections of
the retina is segregated in the thalamus. Again, the arrangement in visual field is also
layered (further segregation) and different columns (e.g. into 6 layers), in an alternative
manner (LRLR) [More on modular organization of primary visual cortex: Ocular
dominance column (Alternate columns, e.g. LRLR)]
 Retina cell types (5): Light needs to pass through several layers of cells before they can be
projected at rods or cones, which leads to information processing. Retinal ganglion cells have
different classifications:
o by Receptive field: Concentric. On-center vs. off-center cells. On center ganglion cell is
located in the center of receptive field, when light is projected to the receptive field, the
on center cell fires but the off surround cells becomes silent.
 Off center ganglion cell is directly the opposite: when light delivered to center,
they do not fire (i.e. off-center), but fires in surrounding cells (on-surrounding).
What is the function of this cell type? To detect shadows and darkness (Light in
center leads to no signals, shading of center leads to many signals, shading of
enter cells including surrounding area leads to moderate signals)
o by color e.g. red-green vs. blue-yellow.
o by M vs. P cell (Magnocellular cells vs. Parvocellular cells. Magnocellular for large
receptive field, stimulus movement and objects with high contrast (Layers 1 and 2 in
thalamus). Parvocellular cells: for small receptive fields, fine details, color
discrimination. (Layers 3-6 in thalamus, the main point is that different elements of
vision are being extracted.)
In summary, they have good division of labor.
 [Section 2] Section summary:
o Binocular vision that allows for depth perception. Retinotopic projection to primary
visual cortex. Ocular dominance columns / modular organization.
o Retinal processing: Concentric-surrounding receptive field, On vs. Off-centers, M vs. P
cells.

FORM RECOGNITION

 Visual pathway: Retino-genicular-cortical pathway.

o The primary visual cortex has differentiated recognition of forms e.g. one column only
detects one forms. Neighboring columns are responsible to detect forms of slightly

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 altered orientation (called orientation column). [Modular organization of primary visual
cortex]
o Complex cells (e.g. T) would be broken down into simpler components (e.g. - and | ) to
be processed. Higher visual cortex (e.g. in tertiary visual cortex) would be able to detect
more complex forms (Called grandmother cells / complex cells)
 Primary visual cortex is arranged in a modular pattern, 2D-ly. In one dimension, the location
e.g. LR. On the other dimension, vertical column cells (Orientation columns) responsible to
vertical and horizontal inputs.
 Parallel pathways: Distinct MP pathways, separate functional paths.

OTHERS: SIGNAL INTEGRATION, SCIENTIFIC ADVANCEMENT

 How to integrate all these information / components of vision?

o Higher visual cortex. Pathway: V1 (Visual cortex 1 /primary) > Ventral or Dorsal
pathway. Ventral for motion, Dorsal for form recognition.
 Scientific advancement
o Cortical implant: implant to cortical implant. Camera in front, can register external
image and direct it to electrodes in cortical region. This technology isn’t mature,
because the primary visual cortex because V1 is only for extracted very basic
information. One needs the ventral and dorsal pathway too.
o Artificial retina. Retinal electrode array for stimulation, stimulate the intact CN2 then
interpret.
 [Section 3] Take home message
o Form recognition
o Receptive field change. In retina as concentric circles, but then changed into
rectangular fields or columns in primary visual cortex.
o Orientation column (Modular organization)
o Higher visual cortex (via ventral pathway)
o Motion perception: Magnocellular pathway projected to higher visual cortexes (via
dorsal pathway)

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HNS40 VISION SUMMARY PAGE
1. Light reflex:
o Name: Papillary light reflex, Definitions of Direct (Ipsilateral pupillary constriction when
light shown) and consensual reflex (Contralateral pupillary constriction when light
shown)
o Sphincter papillae (Parasympathetic, Edinger Westphal, midbrain), Dilator papillae
(Sympathetic). Not to mix up with ciliary muscles!!
o Pathway: CN2 > Lateral geniculate body > CN3
2. Various eye diseases: Cataract (lens, reduced Red reflex), Macular degeneration, Retinal
detachment, Glaucoma (Pressure build up presses on optic nerves (Close angle more common
in Chinese).
3. Visual pathway:
o Features: Crossed projection, Binocular vision for depth perception
o Pathway: Draw diagram + Practice: predict outcome when you cut at different locations
4. Receptive field:
o RF description: Convergence of LGB cell signals (concentric) on one linear axis (NOT
multiple axis)
o RF among simple cells in striate cortex: Parallel on-off zones (with receptive field along
one linear axis)
o Cell divisions by Magnocellular (Large RF) vs. Parvocellular cells (Small RF). Separate
parallel pathways (Ventral for motion, Dorsal for form recognition) and features are
integrated in higher visual cortex.

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HNS41 EYE MOVEMENT

OVERVIEW

1. Eye: Background Information

2. 5 basic types of eye movement
3. Neural control of eye
4. Clinical relevance: Vision pathway lesion, Gaze pathway lesion

EYE: BACKGROUND INFORMATION

 3 layers: Outer, Middle, Inner

o Outer: sclera, Cornea
o Middle: Choroid, Ciliary body, Iris
o Inner: Retina
 2 chambers: Anterior, Posterior. Anterior for aqueous chamber. Posterior for vitreous humor.
 Functions of eye movement: for visual acuity (such that it focus on fovea). For directing fovea to
object of interest (fovea vision = foveation)
 Sympathetic stimulation leads to dilation, Parasympathetic stimulation leads to constriction of
pupil.
 Extraocular muscles. 3 different axis: Horizontal (by medial and lateral rectus muscle). Vertical
(Superior and inferior rectus + Superior and inferior oblique). Torsion (Intorsion, Extorsion,
involving all the muscles)
o Note: both superior and inferior oblique's insertion is medial to eyeball .
 Innervation of extraocular muscle. Abducens (for lateral rectus). Trochlear for superior oblique
muscles (contralateral innervation, i.e. left nerve to right. The rest are ipsilateral). Oculomotor
(everyone else, plus parasympathetic from Edinger Westphal)
 Complete oculomotor palsy: Ptosis (paralysis of Levator palpebrae), Mydriasis (Dilation due to
unopposed sympathetic fibers). Dedicated eye laterally and downwards (unopposed superior
oblique and lateral rectus action). Lower accommodation to light (paralysis of constrictor
papillae)

5 BASIC TYPES OF EYE MOVEMENTS

 Saccade, Smooth pursuit, Vergence, vestibulo-ocular, Optokinetic.

 Classification:
o Gaze-shifting (voluntary / attention): Saccade, Smooth pursuit, Vergence,
o Gaze-stabilizing (Reflexive): vestibulo-ocular, Optokinetic.
 Important Note: Vestibulo-ocular and optokinetic system acts in
complementary and frequency dependent fashion > Stabilize gaze over a broad
range of stimulation frequencies.

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 Name Main point Others
1 Saccade Rapid and ballistic Small or large movements alike.
movement. Modified by Very small microsaccades involuntary to prevent fading
visual feedback. Burst of on retina.
signals initiates. Normal short delay of 200ms between target and eye
position for computation of target position and
conversion to motor commands to extraocular muscles
2 Smooth ASSURES FOVEAL 2 phases: Pursuit initiation (Eye starts tracking, 100ms
pursuit FIXATION, triggered by open-loop as there is no time for visual feedback),
moving image. Used to Pursuit maintenance (Catchup saccade made so that
track moving objects. eye movement catches up with object)
Slow and quasi-voluntary.
3 Vergenc Align fovea of each eye Conjugate vs. Deconjugate movement (Conjugate = 2
e with targets located at eyes moving in same direction, Deconjugate /
different distance from Disjunctive movements = moving in different direction
observer (?). Near reflex triad are accommodation of lens to
adjust focus when far object moves close: (1) Increase
curvature of lens, (2) Pupillary constriction. (3) Sharpens
image on retina
4 Vestibulo Gaze stabilization brought 2 forms: Rotational VOR (Semi-circular canal sensing
-ocular by eye moves in a head rotation) vs. Translational VOR (Otolith organs
reflex direction opposite to head sensing linear head acceleration).
movement. Involves VIII (The vestibular system detects brief, transient changes
Abducens and PPRF in head position. Again, towards kinocilium is activate,
(Paramedian pontine against kinocilium is deactivate. Pathway:
reticular formation) Vestibular ganglion > Medial vestibular nucleus > Right
abducent nucleus >
 > Medial longitudinal fasciculus > Oculomotor
nucleus > Medial rectus; OR
 > Pons > Lateral rectus.
VOR suppression test: Rotating chair, Caloric reflex test
(Irrigation of duct with hot vs. cold water > Eye move
towards cold water and opposite to hot water.)

5 Optokine Gaze stabilization driven Tracking until end of excursion (train > Quick saccade /
tic by retina slip > Image optokinetic nystagmus. Both reflexive and involuntary.
steady on retina
See summary (3 pages behind) for simplified version for easier memory.

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NEURAL CONTROL OF EYE MOVEMENT

 Main point 1: Synaptic circuitry is responsible for horizontal eye movement.

o Burst neuron firing pattern: Lots of firing initially, gradually maintained throughout
contraction
o The direction of eye is determined by activity of different nucleus. Horizontal gaze
center: Paramedial pontine reticular formation. Vertical gaze center: Rostral Interstitial
nucleus.
o Sensory information received can in turns influence the horizontal gaze center by:
 Direct route: Frontal eye field > Contralateral PPRF
 Indirect: Frontal eye field > Ipsilateral superior colliculus > Contralateral PPRF
 After PPRF: (1) Ipsilateral activation of right abducent nucleus > Lateral rectus
in ipsilateral eye + (2) Contralateral activation of oculomotor nucleus > Medial
rectus in contralateral eye
 Main point 2: Sensory-Motor Structures and the connections that govern saccadic &smooth
pursuit eye movements.
o There is complicated interaction between the cortical and subcortical structures. Visual
signals are processed by dorsal spatial vision pathway, which guide motor planning in
frontal eye fields.
o Brain structures involved in selecting visual targets for saccade and planning
movements: Superior colliculus, Frontal eye fields, Lateral intraparietal area.
 Main point 3 (Important): Neurons in all these 3 areas have both (1) Visual receptive field, and
(2) movement field, which is spatially overlapping.
1. Visual receptive field: Visual stimuli activates cell?
2. Movement field: neurons in this field respond prior to execution of saccadic eye
movement
o 3 types of neurons: Visual, Visual/Movement, Movement. Place code for saccade
vector.
o 3 types of responses generated from different layers in superior colliculus: Superficial,
Intermediate, Deep. Superficial (mostly visual information), Intermediate (from visual
or movement cells), Deep (movement information)
o Both Superior colliculi and frontal eye field contributes to saccade planning and
generation. Lesions in Superior colliculi or Frontal eye field leads to deficits in saccade,
whereas lesions in both areas leads to saccade abolishment.
 Superior colliculi: Sensori-motor integration, responsible for planning metrics
(e.g. amplitude, direction) of saccade
 Frontal Eye Field: Target selection of saccade

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CLINICAL RELEVANCE

OPTIC PATHWAY LESION

GAZE CENTER LESION

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HELPFUL DIAGRAM
 Vestibular ganglion > Medial vestibular nucleus > Right abducent nucleus >
o >'Medial longitudinal fasciculus > Oculomotor nucleus > Medial rectus; OR
o >"Pons > Lateral rectus.
SUMMARY (FROM PAST PAPER)
Question
A Characteristic of smooth pursuit system
C What is the trigger for smooth pursuit
system
C Gaze stabilization is brought about by
which eye movements
B How is saccade generated?
B Characteristic of saccade
C Guess the eye movement: holds image
steady on retina
B Conjugate eye movement requires
PPRF. What does that stand for?
B Vestibulo-ocular reflex involves which
nucleus
B Recite: 5 basic eye movements
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Answer
Assures foveal fixation
Moving image
Optokinetic, Vestibulo-ocular
Burst of output from moving eye to new object
Can be modified by visual feedback
Optokinetic
Paramedian pontine reticular formation
VIII Abducens
(1) Saccade: Rapid and ballistic movement. Modified
by visual feedback. Burst of signals initiates. (2) Slow
pursuit: ASSURES FOVEAL FIXATION, triggered by
moving image. Used to track moving objects, slow
and quasi-voluntary. (3) Vergence: Align fovea of
each eye with targets located at different distance
from observer. (4) Vestibulo-ocular reflex: Gaze
stabilization brought by eye moves in a direction
opposite to head movement. Involves VIII Abducens
and PPRF (Paramedian pontine reticular formation).
(5) Optokinetic: Gaze stabilization driven by retina
slip > Image steady on retina
HNS42 HIGH CORTICAL FUNCTION

OUTLINE

 Neocortex / Cerebral cortex. Embryology:

Prosencephalon (Forebrain) > Telencephalon > Cerebral
hemisphere
 Rostral vs. Caudal in brain vs. Spinal cord (note other
directions in brain too e.g. dorsal, ventral).
 Controls nearly all aspects of behavior e.g. perception,
language, decision making
 Cerebral hemisphere superficial landmarks (see notebook
drawings)
 Laminar organization of Brodmann's area: Based on histology (6 layers n brain). Functional
areas. Still used today.
 Thalamocortical relationship. Thalamocortical projections quite correlate with the locations of
cerebellum. e.g. Anterior nucleus receives from mamillary bodies and projects to cingulate
gyrus. Dorsal medial nucleus from amygdala and olfactory cortex and projects to prefrontal
cortex. Ventral lateral nucleus from cerebellum and basal ganglia, projects to primary motor
cortex. VPM from spinothalamic tract and DCLM projects to primary somatosensory cortex.
LGN receives from retina to primary visual cortex. MGN projects to auditory cortex. Review
diagram on ppt.
 (Broad) functional categories of cerebral cortex. Primary motor, Primary sensory, Unimodal
association cortex (secondary), multimodal association area
o Unimodal association area: Adjacent to primary cortex, for higher level association
o Multimodal association area: receive info from different sensory modalities, to produce
unified perception, and representation of percept in memory. Also other cognitive
functions e.g. language, planning, imagination, spatial appreciation.

CEREBRAL CORTEX: LOBES AND AREAS

 Functional areas of cerebral lobes (by lobes)

o Frontal (Prefrontal, Premotor, Primary motor): Emotion, Personality, Executive
function, control movement
o Parietal (Primary somatosensory, Somatosensory association): Shape, Texture,
Forming and understanding speech
o Occipital (Primary visual, visual association): Process visual information
o Temporal (Primary auditory, Auditory association): Speech and Hearing, remember
auditory experience
 Cerebral cortex: Motor area
o Cortexes: Primary motor {4}, Premotor {6}, Frontal eye field {8}, Broca's area {44, 45}
o Primary motor cortex: Mapped upside down, more neurons for face and hand (delicate
movement). There is continuous stream of sensory information (e.g. tactile, sensory)
that modulates motor, also other structures e.g. cerebellum, basal ganglia.

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  Sensory areas: Conscious awareness of sensation
o Primary somatosensory cortex {1, 2, 3}, Visual cortex {17}, Auditory cortex {41, 42},
Vestibular cortex, Gustatory cortex, Olfactory
o Primary somatosensory cortex: mapped upside down, more neurons for head and face
[disproportionate representation]
 Primary visual cortex
o Recall visual fields and light projections: Upside down and LR reversed in retina >
Medial part of retina projects contralaterally, Lateral part of retina projects ipsilaterally
via Optic chiasm > Lateral geniculate body of thalamus > Cerebral cortex (i.e. left and
right parts of image and processed by DIFFERENT parts of brain!)
o 2 visual pathways to primary visual cortex: Superior lobe ('Parietal optic radiation') for
lower retinal fields. temporal optical radiation (=Meyer's loop, inferiorly) for higher
retinal fields. Projection to calcarine fissure (Occipital lobe fissure located in primary
visual cortex, dividing it into superior and inferior portions. See diagram below.
o Macula projects to caudal visual cortex
 Important and useful diagrams:

Typical visual field defects and corresponding lesion sites

1. Optic nerve lesion (e.g. optic neuritis): Monocular amaurosis
2. Optic chiasma lesion (e.g. pituitary macroadenoma):
bitemporal hemianopia
3. Optic tract lesion (e.g. craniopharyngioma): homonymous
hemianopia
4. Temporal optic radiation lesion (e.g. post-temporal
lobectomy): homonymous upper
quadratic hemianopia
5. Parietal optic radiation lesion (e.g. parietal glioma): lower
quadratic hemianopia
6. Visual cortical lesion (e.g. occipital lobe infarct): dense

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 homonymous hemianopia with macular sparing
 Auditory cortex: Tonotopic map
o Proximal for high frequency, Distal for lower frequency.
o Pathway: Cochlear nucleus > Superior olivary nucleus > Inferior colliculus > MGN >
Primary auditory cortex. Frequency map maintained throughout pathway
 Vestibular cortex: Dispersed at different regions e.g. some regions of motor cortex, some
regions of somatosensory
 Gustatory cortex. Pathway: CN7, 9, 10 > Solitary nucleus (medulla oblongata) > Central
tegmental tract > VPM > Gustatory cortex (partly in insula, partly in frontal operum)
 Olfactory cortex. Pathway: Olfactory mucosa > olfactory bulb > olfactory cortex (e.g. anterior
olfactory nucleus, olfactory tubercle, etc.) > Various other locations e.g. hypothalamus,
hippocampus, amygdala (Projections to these locations regulate feeding behaviors, odor
discrimination and identification)
 Association area
o for Higher cognitive functions e.g. learning, memory (Experiments: Increase in
association area size correlates with complexity of behaviors, comparison between
animals vs. humans)
o Different association areas: Frontal, Parietal, Temporal, Limbic
 Frontal: behavior, working memory
 Parietal: Sensory modulation to motor, Spatial awareness
 Temporal: Recognize sensory stimuli, Factual knowledge
 Limbic: Emotions, Episodic memory
o Prefrontal cortex: Higher cognitive functions, executive functions (e.g. decision
making), Socializing, planning, but not for movements (although they are connected
with many regions of brain, including motor region). Region receives mediodorsal
nucleus of thalamus. Dysfunction associated with PSYCHIATRIC disorders.

CEREBRAL DOMINANCE

 Interesting:
o Corpus callosotomy, Split brain experiment
o Neurological pathway of seeing a word and saying it out: Visual cortex > Wernicke's
area > Broca's area > Primary motor cortex
o Cerebral dominance shown in: Language, Space and attention
 Cerebral dominance: Language
o Left hemisphere: Broca's area (Motor of speech and writing; Expressive speech),
Wernicke's area (Sensory or Comprehension of written or spoken language / Receptive
speech)
o Types of aphasia: Broca, Wernicke, Global, Conduction (damaged arcuate fasciculus,
the linkage between Broca and Wernicke's area)
 Cerebral dominance: Space and attention
o Parietal association on Right hemisphere

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 o Contralateral neglect (Defects in non-dominant cortex > Defects in attention, Defects in
spatial surrounding)

OTHER CORTICAL DYSFUNCTION (UNRELATED TO CEREBRAL DOMINANCE)

 Apraxia: disordered motor control after parietal association cortex / premotor / supplementary
motor cortex. Construction apraxia: unable to internalize or duplicate spatial relationships of
individualized parts)
 Ataxia. Optic ataxia: damage to dorsomedial parietal cortex > difficult grasping, visual
guidance, reaching
 Agnosia (not knowing): general term to describe large higher level disorder of sensory
perception. Subclassified into different types of sensory problems e.g. tactile agnosia,
prosopagnosia
 Other concepts. Neuroplasticity: brain isn't fixed, has ability to change. Implication: Can learn;
after injury have phantom limb sensation (change in sensation > spread of connections to the
amputated area / Cortical remapping of referred sensation)

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HNS43 LIMBIC SYSTEM AND CENTRAL AUTONOMIC FUNCTION AND LEARNING
AND MEMORY

OUTLINE

1. Definition of Emotions
2. Development of understanding of emotions: Historical, Components
3. Modern concepts of limbic system, Autonomic nervous system’s role, Reward system and
pleasure

DEFINITION OF EMOTIONS

 Emotion: 3 parts. Physiological response, Feelings, Behavior

 Involves autonomic system e.g. increase HR, cutaneous blood flow
e.g. blushing
 2 psychophysiological indices for evaluating emotional reactions:
skin conductance, startling response

DEVELOPMENT OF UNDERSTANDING OF EMOTIONS

HISTORICAL DEVELOPMENT OF UNDERSTANDING OF

EMOTIONS

(For leisure reading only)

1934: Bard and Cannon. When cerebral hemisphere (disconnects

hypothalamus) removed, angry behavior shown spontaneously with usual
A proposed neural circuit for
autonomic physiological response e.g. increase heart rate and BP, arching of
emotion. The circuit originally
back (Called 'sham rage' because there is no obvious target)
proposed by James Papez is
indicated by thick lines; more
1937: Papez. Proposes Papez circuit primitive version, thinking it include
recently described connections
cingulate gyrus, parahippocampal gyrus, hippocampal formation. At this
are shown by fine lines. The
stage it is quite primitive and consists only Internal feelings, behavior hippocampal formation
patterns, autonomic control. James Papez proposed for primary ones, includes the hippocampus
emotional involves more cortex. proper and surrounding
structures, e.g. entorhinal
1939: Keidrich Kluver and Paul Busy. When temporal lobe removed, monkey cortex
have little emotion, increase oral activity. Later, Kluver-Busy syndrome refers
to amygdala damage reduces fear in patients. Commonly found in autisms. Further evidence: electrical
stimulation of amygdala produces fear and anxiety. Sight of fearful stimuli also shows amygdala
hyperactivity. Temporal
lobe ablation shows: Loss of fear, less aggression, hyperoral, forgetful.

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COMPONENTS OF NERVOUS SYSTEM THAT PROVIDES EMOTIONS

 Duchene's photography to study human facial expression

o Genuine smile: Zygomaticus major + Orbicularis oculi
o Neural system damage of emotional expression: Duchenne smile

MODERN CONCEPTION OF LIMBIC SYSTEM

 Components: Central + Peripheral

o Central: Evaluative components of emotions cerebral cortex
o Peripheral: autonomic, via hypothalamus
 Hippocampus and mamillary bodies not important for emotion
 Amygdala participates in triangular circuit, which links to thalamus directly or indirectly (via
ventral basal ganglia, or orbital and medial prefrontal cortex)

ROLE OF AUTONOMIC SYSTEM IN EMOTIONS

 Autonomic system has important role in emotions

o Comprehensive list of sympathetic and parasympathetic activity e.g. pupil dilation (see
PowerPoint)
o Autonomic control: trigger hypothalamus to generate response, via visceral reflex
circuitry. Hypothalamus plays a role in internal homeostasis and motivation, in addition
to autonomic control.

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  Flow of information controlling autonomic function: Sensory information from visceral
afference > Solitary nucleus > project to brainstem and hypothalamus. Brainstem plays a role in
autonomic responses. Amygdala's central nucleus mediates brainstem and hypothalamus
responses.

REWARD SYSTEM AND EUPHORIA, FOOD INTAKE, AND OTHERS

 Hypothalamus on food intake drive. Lesion in lateral hypothalamus causes reduced food intake.
 Septal region is the 'pleasure center' via dopaminergic pathway: projected to nucleus
accumbens. VTA (Ventral tegmental area) neurons increase activity when animals presented
with reward, so VTA provides a learning signal that reflects reward expectation > use to
guide behavior and modulate emotional responses.
o Drugs: Cocaine and amphetamines increase dopamine released in brain > Mediates
emotional responses projected to hypothalamus and limbic system (Both drugs block
dopamine reuptake transporter). They enhances pleasure produced by self-stimulation
 Another pathway for reward system: Medial forebrain bundle. Activation of MFB activates
Ventral tegmental area.
 Monoamine and emotions:
o Dopamine: From ventral tegmental area and Substantia nigra: for reward, pleasure and
euphoria, fine tuning of motor functions, compulsion, preservation
o Serotonin From Raphe Nucleus: for mood, memory processing, sleep and cognition
o NE: from locus coeruleus
o Acetylcholine: from basal forebrain

LEARNING OBJECTIVES

1. Define emotion
2. Describe structure of limbic system (Development to modern conception)
3. Components of nervous system in emotion experience
4. Autonomic function in fight or flight situations

LEARNING AND MEMORY

 Learning: new information acquired; Memory: Can recall

 Classification of memory: Declarative vs. Non-declarative
o Declarative (Explicit) [Conscious]: Daily episodes, Words and their meaning, History
 Episodic (events) vs. Semantic (Facts learnt)
o Nondeclarative (Implicit) [Unconscious]: Motor skills, association, priming cues,
Puzzle solving skills
 Brain area involved:
o Explicit: mostly medial temporal lobe
o Implicit: Priming (Neocortex), Procedures (Stratum), Associative learning (Amygdala
for emotions, Cerebellum for skeletal), Habitual (Reflex)
 Priming: Change in processing of stimulus due to previous encounter

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  Temporal categories of human memory: Immediate (quickly remember then forget), Short
term, Long term. Yet all these memories can be forgotten
 4 distinct process of memory: Encoding (acquire new information), Storage (in cortical layers),
Consolidation (Labile information > Stable information), Retrieval (recall)
 Memory & Aging: PEC shows people with good recall have more diverse area activated e.g. L and
R.
 Amnesia. Types: Retrograde (memory loss due to trauma /lesion, forgets previous events) vs.
Anterograde (Cannot form new memories)
 Key points
o 3 types of temporal memory
o Explicit vs. implicit memory
o (Comment: said to be important during lecture, but actually seldom examined?)

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HNS44 ANTI-DEPRESSANTS

OVERVIEW

1. Depression: Signs, Categories, Cause

2. Depression: Medications
3. Depression: Notes on Prescription

DEPRESSION: SIGNS, CATEGORIES, CAUSE

 Signs & Symptoms: Feeling sad empty and hopeless, Change in sleeping pattern (shorten,
lengthen, insomnia), change in dietary habits (more / less), apathy towards pleasurable life
activities, increase in anger or irritability, Fatigue or loss of energy, Suicidal ideations.
o Note: Man and Women may have different, even opposite symptoms. Men vs. Women
symptoms: Blame others vs. Self-blame. Create conflict vs. avoid conflict. Insomnia vs.
Oversleeping. (Potential reason: Testosterone mediates stress response; Women more
vulnerable)
 Categories (Diagnostic and Statistical Manual of Mental Disorders) based on Number of
symptoms and Duration: Major (5+ symptoms, >2W), Dysthymic (2+ symptoms, 2+ years),
Minor (2+ symptoms, ~2W)
 Cause of depression
o A Multifactorial disease: Genetics (Slc6a15, an AA transporter), Personality, Brain
chemistry, brain hormones, Environmental factors (e.g. loss of loved ones).
o Hypothesis for cause of depression (please know this, good for PBL):
1. Monoamine hypothesis: Low level / deficit in function of neurotransmitter e.g.
Serotonin (=5-HT, =5-hydroxytryptamine), Norepinephrine, Dopamine (controls mood,
anxiety, mental and motor activities)
 Limitations: Many depressed patients do not have alternations in monoamines.
Monoamines tend to increase immediately with antidepressant usage, but
benefits would not be seen until many weeks later (commonly patients feel
worse for first week of treatment). Removal of tryptophan (serotonin precursor)
does not lead to depressive responses. [Regardless, the treatment approach of
increasing monoamines still used because it is the most accessible anti-
depression treatment]
2. Neurotrophic (Neurogenesis) Hypothesis: Depression is due to impaired growth of
neurons.
 Evidence: Anti-depressants increases neuronal growth and synaptic
conductivity. Depression associated with 5-10% loss of volume in hippocampus.
Depression causes decrease in brain-derived neurotropic factor (BNDF). BNDP
regulates neuroplasticity, neurogenesis, and emotions. Animal models show
anti-depressant enhances BDNF levels.
 Limitations: BDNF knockout mice does not show have depression. Social
stressed animal shows increased BDNF level rather than a decrease.
1.

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DEPRESSION: MEDICATIONS

Type Examples Mechanism Note Adverse effects / Contraindications

1 Selective Fluoxetine Serotonin selective reuptake First line CYP interactions. Fluoxetine, Paroxetine: inhibits
serotonin (Prozac), blocker > Presynaptic uptake because CYP2D6, contraindication e.g. Tricyclic
reuptake Paroxetine, of 5-HT > Increase 5HT level least side antidepressants, since they are 2D6 substrates).
inhibitor Citalopram, effect (less, Fluvoxamine: a CYP3A4 inhibitor (Contraindicated with
(SSRI) Escitalopram, mild, and Diltiazem, a 3A4 substrate).
Sertraline, transient), Citalopram, Escitalopram, Sertraline: CYP interactions.
Fluvoxamine Safe, Cheap Others: [1]Nausea, GI disturbance, Diarrhea
(increased serotonergic activity in gut). [2]Diminished
sexual function and interest (increased serotonergic
activity in spinal cord). [3]Reduced coagulation and
bleeding risk (inhibits serotonin uptake in platelets,
reduces serotonin-mediated platelet activation).
[4]Vasoconstriction (Inhibits nitric oxide synthase, less
NO).
(Paroxetine: notable severe weight gain / sexual
dysfunction)
2 Norepinephri Atomoxetine, Block norepinephrine reuptake transporter > Increase BP, alter heart rate, CNS effects e.g. insomnia
ne reuptake Maprotiline, Increase NE
inhibitor Reboxetine

3 Serotonin Venlafaxine, Blocks both serotonin and NE Little Those from 1 and 2 (since inhibit both serotonin and
norepinephri Desvenlafaxine transporter > Reduce affinity to NE reuptake transporters)
ne reuptake , Duloxetine, reuptake. other
inhibitor Bupropion, receptors
Mirtazapine
4 Tricyclic antidepressants Prevents reuptake with all 3 monoamines Much (Side effects of 1+2+those from Dopamine
associated with mood (Serotonin, NE, increase and Dopamine receptor blocking). Unsafe
Dopamine) (Lethal if overdosed and serious drug interactions).
Only prescribed if SSRI non-responsive).
5 Serotonin Trazodone [1]Blocks 5-HT(2a) receptor > Unable to release 5-HT(2a) neurotransmitters;
antagonistic ([2]less effect on blocking reuptake transporter).
 reuptake [3]Metabolized to meta-chloro-phenyl piperazine (mCPP) activates 5HT(1a)
inhibitor
(SARI)

6 Alpha 2 Mianserin Block alpha-2 presynaptic autoreceptor (not Adverse effects: Sedation, Dry mouth, Dizziness,
Adrenergic a transporter) > suppress negative feedback Vertigo
receptor (Normally: too much NE > bind to
antagonist autoreceptor > reduce release, i.e. maintain
proper level of NE) > enhance NE release
7 Monoamine Phenelzine, Block monoamine oxidase > less decrease Rarely used because not safe: e.g. [1]Potentially lethal
oxidase Tranylcypromi monoamines > Increased level food-drug interactions: e.g. food high with tyramine
inhibitor ne (non- like meat, avocados, bananas, pineapple, eggplants >
selective), MAOI prevents breakdown of tyramine in blood >
Moclobemide blood tyramine increase > Tyramine can cause release
(Selective) of stroked monoamines [Serotonin syndrome] >
uncontrolled monoamine level > Side effects e.g.
hypertensive crisis, stroke, even death. Very strict low
tyramine diet required but sometimes it is hard to tell
which food). [2]Other adverse effects e.g. orthostatic
hypotension, weight gain, CNS e.g. insomnia.
[3]Serotonin syndrome renders discontinuation of
other types of anti-depressants few weeks before
starting MAOI (and conversely i.e. stopping MAOI and
starting other drugs)
8 Melatonin Agomelatine [1]Binds melatonin receptor > (Unapprove Adverse effects: Deranged liver function (monitoring
receptor Regulates circadian rhythm, d for required)
agonist better sleeping pattern > depression
unknown mechanism to treatment
decrease depression. but easily
[2] Binds to 5HT2c > available as
Dopamine, Norepinephrine supplement
s)

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DEPRESSION: ISSUES ON PRESCRIPTION

 Common side effects of antidepressants:

o Dry mouth
o CNS disturbance: e.g. insomnia, nausea, nervousness
o Increase suicidality in patients <25 years (but no association 65+ years). Blackbox
warning as serious risk to some especially children, teens, young adults.
o Withdrawal symptoms (Mnemonic ABCDE): Agitation & Anxiety, Balance problem
& Bad dreams, Concentration problem, Dizziness Diarrhea (+Nausea, Vomiting),
Electric shock-like sensation, Flu-like symptoms. Extreme symptoms: Psychosis,
Confusion, Excitement. Dose tapering (gradually reduce dose) over 4 weeks.
 Antidepressants also used to treat other disorders e.g. panic disorders
 Antidepressant is a common drug, lots of people take antidepressants e.g. in USA, 1 in 10.
The most commonly prescribed drugs among young adults.
 Not everyone respond to antidepressants (reportedly 25%, although most still respond
well). Also, both depression and effects of medicines are still not well understood.
o For mild-moderate depression, antidepressant drugs are ineffective ('nonexistent to
negligible effects' compared to placebo), although it is significantly effective in
severe depression.
o Antidepressants should only be prescribed when the risk of undertreatment far
outweigh those of antidepressant mediations. 'Talk therapies' e.g. Cognitive-
behavioral therapy / interpersonal therapy (i.e. teaching ways of thinking / changing
habits contributive to depression) should be opted for patients where risks are
moderate.
 An issue with talk therapy is cost (time consuming, hence doctors may not
take patients) and the lack of coverage by insurance companies.
HNS45 ANTI-PSYCHOTICS

OUTLINE

1. Psychosis: Introduction
2. Typical antipsychotics
3. Atypical antipsychotics
4. Other uses of antipsychotics and problems

PSYCHOSIS: INTRODUCTION

 What is psychosis: Mental health problem that stops someone from thinking clearly, telling the
difference between reality and imagination, and preventing them from acting normally.
 It is not a disease, but a spectrum of symptoms. Symptoms: Hallucination, Delusion, Confused
and disturbed thoughts, Lack of insight and self-awareness
o Hallucination (a key symptom). Can be any of the 5 senses: Seeing something that
doesn't exist, sound, smell, touch e.g. insect crawling, taste e.g. something unpleasant.
smelling)
o Delusion: believing something that when examined rationally is not true (esp. based on
their suspicion) e.g. neighbor is going to kill him, cell phone is a mind controlling device,
that a medical student had done enough revision.
o Confused and disturbed thoughts: Speech is rapid and constant, speech may be
random, train of thought may suddenly stop leading to abrupted pause in conversing or
activity
o Lack of insight and self-awareness: They don't know they're acting strange, have
hallucination. They however can recognize behaviors of others, hence they think
everyone is psychiatric whereas they are normal (i.e. lack of insight). Hence they don't
seek help early (Delay of 1.5 years in HK)
 It is hence important for their family and friends to seek help for them. It is
important to seek health early, since they can remit if seeking early.
o Catatonia: Unable to focus and concentrate
 Causes of psychosis
o Main causes: Psychological condition (e.g. mental illness), General medical conditions,
Substances (e.g. alcohol and drugs)
o Others: Genetics, brain structural changes, hormone / sleep pattern.
o Psychological conditions: Schizophrenia (repeated psychosis, but only presents when
the person have psychotic syndromes), Bipolar (Swinging between manic / energetic to
depression). Severe stress or anxiety, Lack of sleep, and severe depression can also
breed psychotic behaviors.
o General medical conditions: Many e.g. VitB deficiency, Stroke. VitB deficiency lead to
sudden psychotic symptoms and treating VitB deficiency markedly alleviates psychosis,
yet mechanism unknown (said to regulate neural tube formation in embryonic stage but
unsure if the effect extends to adulthood). Stroke: affects 1% (considered rare), neuron
apoptosis and local damage.
o Substances e.g. alcohol and drug abuse. e.g. Cannabis increases dopamine in brain and
changes brain chemistry (40% more likely to get psychosis)
 Epidemiology: More common that perceived (1% have at least one episode of psychosis at some
point in life, 6 times the people with Type 1 diabetes). Most develop during older teens or during
adulthood (rarely children under 15). In HK: 200,000 psychotic patients, 1300 new cases
annually.

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  Treatment options: Antipsychotic medications, Psychological therapies (address underlying
cause / talk therapy), Social support, family therapy, Self-help group. Severe cases need to be
admitted to psychiatric unit.
o Antidepressants are used to treat depressive disorders (main aim is to lift someone's
mood), hence it is different from antipsychotic drugs. They also have different MOA:
e.g. Antidepressant by enhancing monoamines, antipsychotics by blocking dopamine
and inhibiting reward driven learning.
o Early diagnosis can improve outcome and avoid complications. If left untreated: likely
to have drug and alcohol problem, higher risk of suicide (1 in 25 kill themselves), may kill
others too.
 Antipsychotics and Dopamine hypothesis
 Formulations:
o Oral (Pills and syrups)
o Slow-release antipsychotics: every 2-6W
o Rapid-disintegrating formation: for patients who like to cheek (含住粒藥扮食咗). This
dissolves quickly upon contact with saliva making cheeking impossible
Both doesn't cure schizophrenia and bipolar disorder, but ameliorate symptoms
 Classification and Examples
o Typical (Classic): D2 receptor blocker. E.g. Chlorpromazine, Fluphenazine, Haloperidol,
Pericyazine, Perphenazine, Pimozide, Sulpiride, Trifluoperazine, Zuclopenthixol.
o Atypical (newer drug): Serotonin receptor blocker. E.g. Aripiprazole, Ziprasidone,
Clozapine, Olanzapine, Quetiapine, Risperidone,. Paliperidone, Lurasidone, Iloperidone,
, Asenapine maleate.

TYPICAL ANTIPSYCHOTICS

 History: First generation, available since 1950, price much less than newer drugs (since old),
effect against positive signs (e.g. Hallucination, Delusion, Disorganized thinking, agitation) but
NOT the negative signs (Lack of drive, Social withdrawal, Apathy, Lack emotional response).
 Dopamine's role in Psychosis
o Excessive amount of dopamine causes psychosis symptom development
o Role of Dopamine: Dopamine associated with how we feel something is significant,
important, or interesting. Also responsible for some normal functions e.g. memory,
emotions, social behavior and self-awareness.
 This is based on several clinical observations: 1. Drugs blocking D2 receptors
alleviates psychosis symptoms. 2. Dopamine agonist exacerbates psychosis. 3.
Increased dopamine receptors are found in untreated schizophrenics.
 *Hypothesis is not perfect because: 1. Antipsychotic drugs are only effective in
most patients but not all. 2. Some drugs (e.g. atypical drugs) are effective, but
they bind to other receptors and not specifically to D2. So Dopamine is not the
sole cause.
 Dopamine receptor binding mechanism for symptom alleviation:
o 5 subtypes of dopamine receptors (D1-5). They are located in different regions and have
different role.
o D2 is most concentrated in Cortex, Corpus Stratum Limbic system and Basal ganglia,
Pituitary gland, Hypothalamus.
o Hence, blocking of D2 receptor in Mesolimbic and mesocortical region can help
antipsychosis. These area responsible for memory, motivation and emotional response,
addiction, etc.

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 o However, blocking of dopamine receptors in neighboring regions e.g. Nigrostriatal
pathway, Tuberoinfundibular pathway would cause lots of problems / side effects,
because these areas are responsible for hormonal regulation, pregnancy, sensory
process, etc.
 Side effects of Antipsychotics. Blocking D2 in other regions not controlling mood,
o e.g. Nigrostriatal regions (in basal ganglia, responsible for extrapyramidal function):
Dystonic (involuntary contractions of muscles), Akathisia (motor restlessness),
Parkinsonism (muscle rigidity, cognitive impairment. Can appear immediately or after
prolonged use), Tardive dyskinesia (repetitive movement of orofacial structures e.g.
tongue protrusion).
o e.g. Tuberoinfundibular region (associated with hypothalamus and pituitary). Greatly
affects hormonal functions e.g. Increased prolactin / Prolactinaemia (Dopamine binds to
anterior pituitary > Remove natural suppression on prolactin production) > Milk
discharge (Galactorrhea) in both men and women and Gynecomastia + Act on thalamus
to inhibit gonadotropin stimulating hormone > Less FSH, LH > Sexual dysfunction and
libido loss
Summary of side effects: Extrapyramidal symptoms, Hyperprolactinemia, Drowsiness.
Nevertheless still commonly used because much cheaper.
o Rare (1/500) and severe side effects: neuroleptic malignant syndrome. Antipsychotics
cause thermoregulatory center to fail. Patient 's temperature may >40C, a medical
emergency. Symptoms: e.g. rigidity, immobility, muscle breakdown, mutism, fever,
tachycardia, diaphoresis, pupil dilation, elevated BP. Seen in 1-3D after treatment.

ATYPICAL ANTIPSYCHOTICS

 Special Characteristic:
o Binds to 5HT2 receptor (higher affinity with this than D2.). Because it quickly unbinds
D2 receptor, also less side effect.
o Treat both Negative and Positive sign of psychosis.
 Side effects of atypical antipsychotics.
o Serotonin regulates energy expenditure and caloric intake. May lead to severe obesity
(due to combined actions of H1 and H2 receptors), hypercholesterolemia and
hyperlipidemia, High BGL and Increased DM risk.
o Those of traditional antipsychotics' dopamine receptor blocking and neuroleptic
malignant syndrome. (Newer generation binds less affinity to it but not completely
none)
o Others: Block
 α-1 adrenergic receptor: Reflexive tachycardia, Postural hypotension
 Muscarinic receptor: Hyperthermia, Tachycardia, Mydriasis, dry mouth,
constipation, Urinary retention.
 Histaminergic receptor: Sedation, Slowness
 Comparing side effects between typical vs. New drugs
o Extrapyramidal syndrome: Much less in new drugs. This is the main difference and a key
reason for why people would choose new drugs despite expansive.
o Aripiprazole has best performance in avoiding sedation and weight gain.
 Other points to note:
o Withdrawal problem and dose tapering needed. Mechanism of withdrawal problem:
Blocked D2 receptor > Increase D2 receptor (Compensatory). If D2 blocker suddenly
removed, will lead to sudden binding of D2 to D2 receptor > Super-sensitivity psychosis.

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 Hence dose tapering required, and 2-3W for switching drugs. This can cause rebound of
psychosis.

OTHER USES OF ANTIPSYCHOTICS AND PROBLEMS

 Commonly prescribed also for: Mild mood disorders, Everyday anxiety, Insomnia, Mild
emotional discomfort / severe depression (used in combination with antidepressants)
 Off label ‘use’: agitation, headache condition, anxiety, suppressing hiccups, autism irritability in
children (Risperidone).
 Other points to note:
o Use in anxiety disorder: Clinical trials show no benefits and no FDA approval. Yet, 20%
anxiety patients prescribed with antipsychotics. This is not good.
o Many children in foster care are taking antipsychotics. It is found that they are typically
neglected or abused. Yet, recall that children under 15 are extremely rare to suffer from
schizophrenic (which is the main condition antipsychotics are approved to treat) (2/1M
children, <1% in older teens), they are more likely to have psychiatric and behavior
problems rather than psychosis. Moreover, 99% are prescribed with atypical
antipsychotics because they are more expensive and heavily advertised, despite these
drugs not approved for youth usage. So, this is bad.
 Why is it bad for children? Their brain is developing, can cause severe weight
gain and increase DM risk (2-4 times). Worse is that many evidence based non-
pharmacological interventions proves to be effective and no adverse effects
(e.g. talk therapy), yet no one is willing to spend money to push them, and
rather they push drugs.
o Everyone can do a better job in this: Better benefits vs. risk evaluation in FDA, provider,
and patient.
o Bottom line:
 Atypical antipsychotics can be lifesaving for schizophrenia, bipolar, severe
depression.
 But these drugs should not be given to treat low-grade unhappiness,
anxiety, and insomnia that comes with modern life.

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HNS46 DRUGS USED FOR NEURODEGENERATIVE DISEASES

OVERVIEW

1. Introduction to Neurodegenerative disease

2. Parkinson’s Disease
3. Huntington’s disease
4. Alzheimer’s disease

INTRODUCTION TO NEURODEGENERATIVE DISEASES

 What are neurodegenerative disease? Affects brain function, control of movement,

executive functions, etc. Usually from deterioration of neurons in brain and spinal cord.
o Brain region involved: Basal ganglia (movement, reward), Hippocampus (memory),
Hypothalamus (controls most body function e.g. breathing, movement,
hemostasis).
 2 notable types: Parkinson’s (movement), Alzheimer’s (memory)

PARKINSON’S DISEASE

 Epidemiology: Most common movement disorder, 2% of 65Y+ (epidemiology related to

aging population). 2nd most common neurodegenerative disease (1st: Alzheimer’s). Sharp
increase in 60Y+
 Parkinson’s' 4 characteristics: Resting tremor in limb, Muscle rigidity, Bradykinesia,
Abnormal posture and gait (everything very slow). Progression can vary, but often starting
on one side before moving contralaterally. Eventually most patient confined to wheelchair
in later stages.
 Cause: Reduced dopamine release in basal ganglia (affects nigrostriatal: basal ganglia to
substantia nigra).
 Root cause: Mostly idiopathic. Drug induced (e.g. antipsychotics: Reserpine depletes
dopamine store, Haloperidol blocks dopaminergic blocker), Toxin that damages
dopaminergic neuron, Viral infection / encephalitis, Trauma-repeated head injury (e.g.
boxer)

TREATMENT STRATEGIES

 Treatment strategies in PD: re-establish balance between dopamine and acetylcholine in

brain.
o Increase dopamine activity in nigrostriatal system: Refer to YS Chan's lecture
o Reduce muscarinic cholinergic activity in striatum: Reduce muscle contraction and
tremor as a result of Dopamine ACh imbalance.
 Issue: blood brain barrier. However, the precursor of dopamine, Levodopa, can pass
through. However, DOPA decarboxylase is required. Large doses are required for this drug
because peripheral DOPA decarboxylase could break down drug before it produce effect +
well absorption from GIT. The drug has high therapeutic value and is the drug of choice in
elderly. This has short half-level so may have 'on-off effect'
 Drugs to avoid:

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 1. Nonselective MAO inhibitors (Leading to excessive dopamine in periphery.
Dopamine can be converted to epinephrine and norepinephrine, may cause life-
threatening hypertensive crisis).
2. Pyridoxine (VitB6): will increase peripheral breakdown of L-dopa
3. Antipsychotics: will block dopamine receptors > it itself already causes Parkinson
like symptoms
 General Adverse effects
o Due to conversion of L-dopa to dopamine in periphery: Nausea, vomiting,
Arrhythmia, Postural hypotension
o Due to overstimulation of central dopamine receptor: Dyskinesia, Hallucination,
Restlessness, Confusion
 Treatment of drug-induced parkinsonism: Lower drug level, change drug, use
anticholinergic agent
 General Mechanism of Actions:
o Agonize dopamine receptors. Two types:
 D1-like (Gs coupled) receptors: D1, D5
 D2-like (Gi coupled) receptors: D2, D3, D4
 3 trade names to remember:
o Sinemet: L-dopa+Carbidopa
o Madopar: L-dopa+Benserazide
o Stalevo (Triple therapy): L-dopa, Carbidopa, Entacapone

Group (Name) Mechanism Prescription note Adverse effect

Bromocriptine D2-like receptor agonist Delay L-dopa usage in Erythromelalgia (Red painful
younger patients. swollen hands, hence it is not
Combined in late stage. commonly used nowadays).
Hallucination and Delirium,
Nausea and vomiting,
Cardiac arrhythmia, Postural
hypotension.
Pramipexole, First-line therapy in Less because it's new. Some:
Ropinirole younger patients. Dyskinesia, Dizziness,
Combined in late stage. Insomnia or Somnolence,
Postural hypotension
Rotigotine Transdermal (Good for Application site reaction,
patient with swallowing Dizziness, Headache, Nausea
difficulty e.g. elderly).
Pergolide Agonize D1 and D2 Combined in late stage. UTI, Hallucination,
receptor Confusion, Postural
hypotension
Selective inhibiting MAO-B to Initially alone esp. in Hypertensive crisis (when
monoamine metabolize dopamine younger patients (if this dose too high, Dopamine is
oxidase B helps and dopamine level peripheral concentration too
inhibitor is high enough then we high, would become
(Selegiline, don't need to use L-dopa); epinephrine)
Rasagiline) combined in later stages.
Catechol-O- Block COMT for Must be combined (only Diarrhea, Hepatic necrosis
methyl peripheral conversion of an add-on, it only blocks (for tolcapone) Sleep
transferase L-dopa to 3-O- peripheral conversion of disorder, dyskinesia,

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 inhibitor methydopa > More L-dopa to 3-O- Hallucination, Postural
(Entacapone, levodopa to CNS > methydopa.) hypotension.
Tolcapone) Convert to dopamine
Dopamine Enhance dopamine Originally an antiviral, but Restlessness, agitation,
Facilitator release from surviving found to have this effect. confusion, Peripheral edema,
(Amantadine) nigral neurons + Inhibit More effective than Skin rash, postural
reuptake of dopamine at Anticholinergic agent in hypotension.
synapse. reducing bradykinesia and
rigidity. Combined use in
later stages.
Central Reduce cholinergic ALWAYS an add-on. Sedation, Urinary retention,
anticholinergi output of striatum by Dry mouth, Constipation,
c agent blocking the receptor > Mental confusion
(Benztropine, Reduce primary
Benzhexol, symptoms e.g. tremor,
Biperidine) rigidity, akinesia (but not
bradykinesia) as well as
secondary symptoms
(e.g. drooling)
Peripheral In periphery, doesn't cross BBB > Less conversion of peripheral L-dopa to Dopamine >
DOPA Increase L-dopa concentration in brain. SINEMET (with Carbidopa) OR MADOPAR
decarboxylase (with Benserazide) is a combined drug form of L-dopa and Carbidopa in 4:1.
inhibitor
(Carbidopa,
Benserazide)

HUNTINGTON'S DISEASE

 Pathogenesis: Genetic disorder due to single defective dominant gene in Chromosome 4 >
Hyper-reactivity of Dopaminergic pathway due to diminished GABA function in basal
ganglia > Involuntary movement > Dementia
 Symptoms: Depression, Cognitive decline
 Treatment: Symptomatic and only partially successful
 Medications
1. For movement disorder:
a. Tetrabenazine. Mechanism: MOA: Depletes dopamine > Suppress
involuntary jerking and writhing movement (Chorea)
b. Antipsychotic (Haloperidol, Risperidone the newer drug). Use
antipsychotics side effect to suppress movement.
2. For psychiatric disorder:
a. Antidepressants (SSRI e.g. Fluoxetine)
b. Mood-stabilizing drug (Carbamazepine) to treat irritability

ALZHEIMER'S DISEASE

 Epidemiology: Commonly diagnosed in 65Y+, affecting 1 in 85 people in the future.

 Severe cortical shrinkage, severely enlarged ventricle, hippocampus shrinking. Amyloid
plaques and Neurofibrillary tangles.
 Symptoms: Forgetfulness, Lose interest in family, Deterioration of work performance,
Behavior changes, Slow walking and falls (Will be wheelchair confined)

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  Stages:
1. Pre-dementia (Mild cognitive impairment),
2. Mild (early dementia) difficulty remembering newly learnt information (but they
could recall something they learnt long time ago)
3. Moderate: Disorientation, Mood, Behavior changes, deepening confusion about
events, time and place (e.g. forgot they ate already so they keep eating)
4. Sever (advanced): Difficulty speaking, swallowing, walking (Wheelchair bound)
 Treatment: limited (No cure, can only stop progression.).
1. Improve cholinergic transmission within CNS (e.g. reduce ACh breakdown).
2. Prevent excitotoxicity actions of NMDA glutamate receptors in selected brain areas
(In Alzheimer’s, patients' NMDA keep firing)
 Drugs used:
o Acetylcholinesterase inhibitor (/Anticholinesterase)
 Examples: Donepezil (in all stages), Rivastigmine (transdermal, all stages),
Galantamine (mild to moderate stages).
 Adverse: Anorexia, Urine incontinence, Dizziness, Nausea, vomiting,
Diarrhea, Abdominal cramps, agitation
o NMDA receptor antagonist
 Example: Memantine (Moderate to severe)
 Mechanism: Uncompetitive binding to NMDA receptor antagonist > Protect
neurons from excitotoxic effects of glutamate
 Adverse: Constipation, Headache, Dizziness, Confusion

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HNS47 MOLECULAR BASIS OF NEUROLOGICAL DISEASES

OVERVIEW

1. Introduction: Neurological disease

2. Parkinson’s disease
3. Alzheimer’s disease

INTRODUCTION: NEUROLOGICAL DISEASE

 Many forms of neurological diseases:

o Genetics: Huntington's disease
o Infection: HIV, meningitis, prion
o Autoimmune: Myasthenia gravis
o Inflammation: Multiple sclerosis
o Neurodegeneration: Alzheimer's disease
o Motor neuron disease: Parkinson's

PARKINSON'S DISEASE

 Unintended and uncontrollable movement

 Exact cause unknown, genetic and environmental factors. Mostly sporadic, few (10-20%)
genetic
 Incidence: (China): 44 / million (3.4% in nursing home have probable PD)
 Diagnosis: all 4 aspects needs to be satisfied: Clinical, Pathological, Biochemical, Imaging
e.g. PET
 Clinical
o 6 cardinal feature of Parkinson:
1. Tremor at rest (Unintentional tremor),
2. Bradykinesia/Hypokinesia/Akinesia (Loss of movement or reduced scale
e.g. facial expression),
3. Rigidity (of muscles. Cogwheel: stiff muscle but with tremor in same
muscle),
4. Loss of postural reflex (impaired balance that leads to fall),
5. Flexed posture of neck, trunk and limbs,
6. Freezing phenomenon
o Other clinical signs
 Personality & Behavior: Depression, fearful, anxiety, passive, dependent,
Loss of motivation, apathy
 Cognition & Mental: Braphrenia (slow thoughts), Tip of the tongue
phenomenon (can't recall familiar words, but can recall words of similar
meaning), Dementia
 Sensory: Abnormal sensation e.g. Pain, Paresthesia, Numbness
 Sleep problems: Sleep fragmentation, REM sleep behavior disorder
 Autonomic: Incontinence, Sexual dysfunction, Hypotension
 Fatigue
 Cause: Substantia nigra pars compacta and Locus coeruleus lose monoamine neurons (See
Motor Control lecture)

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  Pathological feature: Lewy body (Hallmark), increased glial cell. Lewy body: inclusion body
made up of alpha synuclein, ubiquitin, and others; eosinophilic.
 Genetics: PARK 1 (Alpha-synuclein, autosomal dominant), PARK 2 (Parkin, autosomal
recessive)
 Pathogenesis (Not sure about details):
o Most sporadic, some genetic
1. Alpha synuclein type:
 PARK 1 controls alpha-synuclein, autosomal dominant. Faster but later
presentation.
 Alpha synuclein has 2 forms: In cytosol they unfold, but in membranes they
form helical structure. These 2 states are usually in equilibrium.
 However, in PD, alpha synuclein aggregate via small oligomeric
intermediates (e.g. ubiquitin) to form large fibrillar forms > Lewy body
2. Parkin type Parkinson disease:
 PARK 2 controls Parkin (Ubiquitin ligase), autosomal recessive. Slower but
earlier presentation.
 In normal conditions: E1, E2 and E3 (Parkin mediated ring box) all carries
ubiquitin, which will be docked in target protein to form ubiquitin chains.
Via interaction of ubiquitin ligase, ubiquitin chain is broken down by
proteasome.
 In pathological condition: Parkin mutation > Ubiquitin ligase unable to
cause proteasomic degradation of ubiquitin chain. Ubiquitin (and parkin
substrates?) accumulates and intoxicate neurons to death.
 Summary of PD
o Neurodegenerative disease with movement disorder + neuropsychiatric clinical
features
o Majority sporadic, some genetic forms
o Six cardinal features of Parkinson
o Progressive, chronic, incurable
o Pathology: depigmentation (loss of neuromelanin) and neuronal loss particularly in
SNpc, LC
o Pathogenesis:
 Alpha-synuclein mutation leading to formation of Lewy body
 Parkin mutation inhibiting E3 ubiquitin ligase, ubiquitin chain fails to
degrade, toxic to neurons

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ALZHEIMER'S DISEASE

 Age developed neurological disorder leading to progressive loss of cognitive function

 Presentation: Memory loss, unusual behaviors, personality changes, declined ability to
think, eventually death (4th leading cause of death)
 Prevalence: 24 million worldwide (mostly people 85Y+, a problem with aging society)
 Burden:
o Cost: USD25-30,000/year
o Family members: emotional, physical, financial stress
o Predictably more severe in Asian countries.
o HK: 8th leading cause of death, dramatic increase in mortality since 2007
 Classification:
o By age of onset: Early (<=65Y) vs. Late (>65Y)
o By family history: Sporadic (90%) vs. Familial (10%)
 Risk factors: Aging, family history, head injury, vascular risk factors, genetic factors,
lifestyle, etc.
o Cool lancet paper diagrams: Non modifiable e.g. genetic = 65%, modifiable (e.g.
hypertension, DM, physical activity, social life lol) = 35%
 Diagnosis: by NINCDS-ADRDA (Only probable diagnosis, no clinical hallmarks). Summary.
Diagnosed by:
o Cognitive deficits in 2+/4 areas;
o Mini-mental state examination score <24
o Progressive worsening cognitive function
o Neuropsychological evaluations
o Imaging: Structural (MRI) and Functional imaging (PET, SPECT Single photon
emission computed tomography)
o Biological markers: CSF /Blood Amyloid, CSF Tau
 Evaluation of cognitive features of AD:
o Memory: Episodic memory, delayed recall of stories, word list learning test
(remembering a loss of 12 word after reading 3 times), Paired association (visual
memory) and Working memory
o Attention and executive deficits: Poor concentration, poor selective attention (focus
on particular object for some time) problem in conducting complex task
o Language and knowledge: Impaired semantic (knowing meaning of word),
Category fluency test (e.g. cow is an animal, train is a transport), word definition
problem, deficit in word finding e.g. names, Later phonological and syntactic
deficits (hearing and reading defects)
o Visuospatial and Perceptual abilities: Cannot draw 3D, Apraxia
o Neuropsychiatric feature (as a sign of progression): Apathy (e.g. lack of feeling,
interest and concern, present in all patients), Anxiety (50%), Depression (25%)
 Macroscopic: Brain atrophy (broadened sulci), especially in hippocampus and many lobes
 Pathological hallmarks of AD in brain
1. Extracellular amyloid plaques
2. Intracellular neurofibrillary tangles (Abnormal form of microtubules associated with
Tau protein)
3. +Innate immunity and Inflammation

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 3 pathological features of AD: (1)APP mutation. (2)Tau tangles. (3)Innate immunity
and Inflammation
 Genetics: Autosomal dominant. APP mutation (Amyloid plaque proteins), PSEN 1 and 2
 Pathogenesis
1. APP mutation
o In normal situations: APP is processed by cleavage of secretase into AICD
and Alpha-Beta40 or 42, which will be degraded by neprilysin / IDE / APOE.
o Pathogenic: Mutation in APP or PSEN 1 alters degradation > Increased
Alpha-Beta40 or 42 > Cumulation forms Alpha-beta plaques and intoxicates
neurons
2. Tau tangles
o In normal neurons: Microtubule stability maintained by Tau protein
o Pathological: Hyperphosphorylation leads to Tau protein loss in microtube
> Microtube instability and Tau Tangles formation
3. Apolipoprotein E is an important risk factor for AD
o Function of ApoE: transport plasma lipids
o Mechanisms associated with alpha-beta clearance and neuronal repair.
Studies found that E4 allele has increased frequency and earlier onset of AD
cases (3 times higher risk)

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HNS48 BEHAVIORAL NEUROSCIENCE

OUTLINE

1. Introduction
2. Motivation: Internal drives and eating disorders
3. Associative learning: Rewards and drug abuse
4. Emotions: Monoamines and mood disorders
5. Cognition: Dopamine and psychosis

LECTURE SUMMARY (SINCE THIS LECTURE IS VERY INFREQUENTLY ASKED)

 Drive theory ("Homeostasis") includes Need (Deviation), Drive, Behavior (action that
restores normal)
 High Ghrelin or Low leptin can cause hyperphagia.
 Associative learning (Classical conditioning / pairs stimulus to reward vs. Instrumental
conditioning / positive reinforcement by reward)
 Mesolimbic / Ventral stratum drives reward circuit by Dopamine. Vs. Aversive stimuli
activates amygdala
 Prefrontal cortex problem causes psychological diseases e.g. depression

INTRODUCTION

Behavior neuroscience is a combination of 3 disciplines: Behaviorism (studying observable

behavior), Cognitive science (studying mental process), Neuroscience (studying nervous system)

MOTIVATION

 Definition: what initiates, maintains, and directs behavior

 Motivator examples
o Internal states as motivator: e.g. thirst, hunger, pain
o External stimuli as motivator: e.g. water, food, predator
o Mostly instinctive (i.e. inborn and does not require learning. For example: infants’
attachment to parents, and vice versa. 3F (Fight flight freeze) in response to danger.
Feeding in response to food and hunger
 Drive theory
o Drive is a mechanism for maintaining homeostasis
o Components: Need, Drive, Behavior.
 Need: Deviation from normal range e.g. low BGL
 Drive: Tension induced by need e.g. hunger
 Behavior: Action that reduces drive so that it returns to normal range e.g.
eating
 Hypothalamus:
o An important structure to maintain homeostasis.
o Adaptations: Lacks BBB to receive chemical signals from bloodstream
o Also activates orexin neurons to increase arousal and food seeking in response to
energy deficiency
 Eating disorders
o Hypophagia: Can result from lateral hypothalamic lesions

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 o Hyperphagia. Can result from: ventromedial hypothalamic lesions, Raised ghrelin
e.g. Prader-Willi Syndrome (Chromosome 15 microdeletion > Raised ghrelin), or
Leptin deficiency
o Anorexia nervosa: Hypophagia despite raised ghrelin and low leptin. Cause: Top-
down control by cortical regions
 Limitations of drive theory:
o Cannot explain all behavior, e.g. eating when not hungry, eating more food when
there is greater variety. (i.e. certain stimuli e.g. food have incentive / rewarding
properties which can motivate behavior even when there is an absence of internal
drive)

ASSOCIATIVE LEARNING

 Behaviorism considers all animal behaviors as a result of both Instincts and Simple
associated learning
 2 Types: Classical conditioning vs. Instrumental conditioning
o Classical conditioning
 Example: (Pavlov's dog) Doggo repeatedly exposed to pairing of sound with
food eventually developed a salivating response to sound alone.
Terminologies:
 Unconditional stimulus (US): Food
 Unconditional response: Food-induced salivation
 Conditioned stimulus (CS): Sound
 Conditioned response: Sound-induced salivation
 Points to note:
 Response is automatic
 When conditioned stimulus disassociated with unconditional
stimulus, eventually will cease to elicit conditioned response, i.e.
extinction (undoing the effect / association)
o Instrumental conditioning: Action consistently followed by a reward tends to
increase in frequency (Positive reinforcement)
 Goal directed activity
o When reward cease to pair with action, action gradually becomes less frequent
(extinction)
o Positive reinforcement slowed down in patients with Parkinson’s (i.e. dopamine’s
involvement)
 Incentive salience: Reward elicits internal state of focused attention and eagerness. This is
mediated by dopamine, via the mesolimbic (ventral stratum) and mesocortical pathways,
and partially through the release of endogenous opioid peptides.
o Food is a natural reward. Food increases dopamine as shown in scans
o Direct stimulation of some brain regions (Electrical / Chemical) can trigger reward
circuit. Self-stimulation becomes intensive and takes on compulsive quality, even at
the expense of other behaviors.
o Reward circuit is associated with reinforcement learning. Dopamine plays a crucial
role in these circuit.

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 o Drugs that increases dopamine: initially activates ventral striatum > reward circuit
(Reinforces drug usage). Eventually drug use becomes less of a pleasure and more
compulsive, activity is driven more by dorsal stratum than ventral stratum
o Aversive stimuli: Punishment leads to negative reinforcement. Amygdala
responsible.

EMOTIONS

 Associative learning can only generate rather rigid behavioral response. Emotion can drive
rapid, flexible and effective behavior responses.
 Anxiety: during anticipation of averse stimuli.
o Somatic features e.g. increased HR.
o Psychologically, worry, agitation, apprehension.
o Anxiety is evolved to prepare animal for danger, although excessive anxiety can be
disabling e.g. anxiety disorders.
Phobia: Extreme and irrational anxiety response. Leads to avoid feared object or
situation. Exposure therapy attempts to dissociate feared object from fear
(exposing until the subject calms down)
 Depression: Developed (in animals) when they are repeated exposed to averse stimuli that
they cannot influence or avoid > inactive (learned helplessness). Depressive mood may be
an evolved adaptation to hopeless situations (allowing us to accept defeat, conserve
resources, reflect, plan), yet excessive intensity or time is disabling (mood disorders).
 Measures of mood disorders. Questionnaire and test. Examples: Beck Depression Inventory
(Self-reported), Hamilton Depression Scale (Expert administered), Stroop task (Naming
color of neutral vs. emotional word e.g. sad; Patient with depression / mania be slow in
naming)
 Arousal and monoamines: contains adrenaline, serotonin, dopamine. Projections of NE and
serotonin widespread throughout brain (more transient), for dopamine concentrated in
frontal lobe region (more sustained).
 Brain centers of emotions: emotions controlled by complex interaction between prefrontal
cortex (ventromedial prefrontal and anterior cingulate) and subcortical nuclei (amygdala
and ventral striatum). System is regulated by input from dorsolateral prefrontal cortex
(mediates interaction between cognition and emotions)
 Negative cognitive bias. Patients with depression exhibit biased thoughts and beliefs e.g.
Selective attention to negative events, negative appraisal to trivial social cues, selective
activation of negative memories, internal attribution of failures > Negative rumination.
Cognitive therapy addresses this bias, synergistic with monoamine drug treatment.

COGNITION

 Allows flexibility and sophistication in behaviors

 Include: Working memory, Verbal fluency, Abstract reasoning and planning (executive
function), Social perception (Empathy), Inhibiting instinctive impulse.
 Main areas: Basal ganglia, thalamus, cortex
 Various areas of testing: Tower test (abstract planning), Wisconsin card sorting test.
 Cognition and emotion interface: Prefrontal cortex with working memory interacts with
basal ganglia to formulate goal directed behaviors.

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 o Prefrontal cortex has limited capacity, so they only focus on the task at hand and
filter off other stimulus
o When there is reward, dopamine would cause opening of attention gate,
hence shift to the rewarding task
 Psychosis
o Symptoms: Delusions (Firmly held bizarre ideas), Hallucination (sensory perception
in absence of external stimulus), thought disorders (disorganized speech)
o Disorders: Schizophrenia (with cognitive deficits), affective psychosis (mood
symptoms)
o Cause: over-active dopamine system (e.g. amphetamine abuse)
o Treatment: Antipsychotic (blocks D2 receptors)

SUMMARY

Theories of motivation (instincts, drives and incentives), involving dopamine as the

neurotransmitter for incentive salience, are particularly relevant for understanding eating disorders
• Classical and operant conditioning provide explanations for simple learned behaviors and a
model for drug addiction. They form the basis of behavior therapy for fears and phobias
(exposure)
• Anxiety and depression are abnormal mood states caused by dysfunction of
neurotransmitter systems (serotonin and noradrenaline) and brain centers (amygdala,
anterior cingulate cortex).
• Dopamine hyper-reactivity leads to psychotic symptoms through inappropriate incentive
salience and impaired sensory gating

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HNS49 WHEN WE ALL BECOME METHUSELAH

OVERVIEW

1. Population aging as a global problem

2. Health issues in elderly population
3. Dementia: Public Health

POPULATION AGING AS A GLOBAL PROBLEM

 Factors leading to global ageing

1. Increasing longevity, as reflected by increased life expectancy (average number of
years an individual is expected to live) e.g. Life expectancy at birth (Life expectancy
given the mortality patterns at time of birth remains constant)
i. Generally life expectancy increases with average annual income. When it
increases to certain GDP it plateaus (i.e. Exponential / Greatly helps if you're
poor, but you don't need to get very rich)
ii. HK: One of the area of highest life expectancy
2. Decreasing newborns. Reduced fertility rates (average number of children that a
woman would bear over her lifetime)
i. 2.1 was estimated to be the minimum number required for the next
generation to replace their parents
ii. HK: One of the places with lowest fertility rate
 Projections:
o World aged 60+ doubles (to 22%),
o In all parts of the world (most serious in low- or middle- income countries, because
most rapid demographic change, double burden, poor accessibility to affordable
health care)
 Hong Kong aging population and implications
o Most people in age group of 50 years (Diamond shape).
o Government often encourages people to give more birth, at the same time coping
with more elderly (e.g. silver economy)
o 85+ is the fastest growing age group
o Healthcare service consumption is highest among those very young neonates, and
those ~65+. Long term care in hospitals.

HEALTH ISSUES IN ELDERLY POPULATION

 Health issues of aging population / elderly

1. Physiological changes and comorbidities.
2. Vulnerability e.g. maltreatment, most vulnerable in crisis e.g. disaster, economic
downturns
3. Widened definition of normality in elderly. (There is increased physiological
heterogeneity e.g. CV endurance, lung capacity). Common findings are not normal,
e.g. hypertension, osteoarthritis, dementia. These should not be ignored.
Understanding patient's perspective (their understanding on life may not be the
same as those of other age groups). [NB: One needs to lead a healthy lifestyle when
young, not just starting when they are old.]

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 4. Geriatric medicine has different presentation (just like pediatric is different). E.g.
Pneumonia in 90Y may present with delirium. Not text-book symptoms
Note: Disability threshold could be lowered if there is more support from the
society
 Tools to evaluate disability
1. Activities of Daily Living: Dressing, Eating, Walking, Going to bathroom, Bathing
(Failing indicates severe functional disabilities)
2. Instrumental activities of Daily Living: Shopping, Housekeeping, Bill paying, Food
preparation, Travel (Failing indicates dysfunction, less severe than ADL)
o Note (for own reference)
 65-69: <10% need help with either
 85+: 60% need help with IADL, 40% need help with ADL

DEMENTIA: PUBLIC HEALTH

 Commonest cause: Alzheimer's (65%), Vascular dementia (from minor strokes, 30%)
 Epidemiology: Increasing with aging population. Mostly in developing countries (greatest
aging population)
 Prevalence of dementia in HK: 10% of community elderly, higher incidence in female.
 Difficulty: Difficult and late diagnosis. Most people living with dementia have not received
formal diagnosis (especially serious in low/middle income countries).
o Difficult in early diagnosis because signs can be subtle, e.g. Impaired ability to
remember new things, impaired reasoning in handling complex functional tasks,
language impairment, decline in emotional control and motivation, change in
personality and behavior, impaired visual spatial abilities.
 Screening: There is no program of routine screening (no reliable biomarkers). Instead,
opportunistic screening in primary health care is used. Screening tools: e.g. Mini-mental
state examination (MMSE), Abbreviated Mental Test (AMT)
 Management: Early intervention, yet no cure. Medications (improve memory, cognitive
functions, symptoms e.g. depression, psychosis) and behavioral therapy. Education,
counselling, support groups.
 Implications
o Burden to caregivers (mostly informal caregivers e.g. spouse, adult children, other
family members). They are also prone to mental disorders and may imply have
implication on work flexibility / economic impact
o Stigmatization due to lack of awareness
 Healthcare costs
o Types: Informal (e.g. unpaid care from family), Direct cost of medical care, Direct
cost of social care (provided by e.g. residential homes)
 Low and middle income: Mostly from informal care (There wasn't enough
service from medical and social care)
 High income countries: Mostly informal and social care. (Lower medical
care costs)
o Overall economic impact of dementia: about 1% of GDP
 What to do: make dementia a public health priority (Investment, Improve attitudes,
promote dementia friendly society, increase research)

HNS50 TO CT OR NOT TO CT IN TRAUMATIC HEAD INJURY

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OUTLINE

1. TBI background
2. Role of neuroimaging in TBI
3. Defensive medical practices
4. Clinical decision rules
5. Summary (Provided by teacher, quite comprehensive)

TBI BACKGROUND

 Epidemiology of TBI: Very frequent, with huge healthcare burden (high mortality,
permanent neurological damage. In US: 10% total healthcare budget)
 At risk group: Young children, Elderly
 Age and sex: Male >> Female (Male: Bimodal distribution: decrease in late childhood, later
uptake in teenage years, Female: Positively skewed distribution)
 Causes. Largely preventable: Falls at home, traffic accidents, assaults. Sports injuries.
 HK: 1.7 per 1000 in paediatric. population. Due to fall at home, traffic accidents.

ROLE OF NEUROIMAGING IN TBI, DEFENSIVE MEDICAL PRACTICES

 Pathophysiology. 2 damages: primary (directly due to damage) vs. Secondary (Late

changes from cerebral blood flow changes and raised ICP)
 Sequelae: highly variable. Mostly mild, 2% with lifelong disability.
 Treatment: Prevent secondary injury and complications.
 Role of neuroimaging:
o Acute: Determine presence and extent of injury, severity and operability, inform
surgical planning / guide procedures e.g. burr holes, extracranial landmarks
o Chronic: Identify chronic sequelae, prognosis, guide rehabilitation, determine
aggressiveness of management
 Types of imaging
o Plane XR: Low diagnostic value, generally not very useful. It can indicate skull
fracture, but even if skull fracture (5%) usually doesn't mean need of surgery in most
(97%) patients. Although, potential abnormalities could be found it e.g. Contusion,
hematoma, diffuse axonal injury, subdural hematoma, other lesions. Still generally
not useful.
o CT (Compared to MRI):
 +ve: Generally imaging modality of choice in <24H injury. More readily
available, easier on patients with ventilator support / traction. Superior in
evaluating bone lesions and acute hemorrhage.
 -ve: Underestimates injury in <3hrs. Misses abnormalities (10-20%, esp.
small lesions, those close to metal, bones, calcifications)
o MRI (Compared to CT)
 +ve: Generally the imaging modality of choice in 48-72 hrs after injury.
Better sensitivity (in both acute and chronic) esp. in hematoma, axonal
injury, contusions, subtle neuronal damages, brainstem, basal ganglia,
thalamus.
 Problems in routine neuroimaging in TB:
o Not all require neuroimaging. e.g. very mild cases (<10% have positive findings)

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 o Costly (Money and Time)
Hence: Important to identify patients who have needs to do imaging

DEFENSIVE MEDICAL PRACTICES

 Meaning: Tests and procedures driven by the fear of malpractice liability rather than
medical indications.
 Consequences: Cost (to patient, to healthcare system), Additional health risk in invasive
procedure, Emotions
 Solutions: Evidence based medicine to inform hospital policies and procedures.

CLINICAL DECISION RULES

 Purpose: Reduce cost, avoid unnecessary radiation risk, prioritize.

 Similar to screening test TP FP FN TN. Slight modification in Clinical Decision Rules :
o CDR: Clinical decision rule (+ve vs. -ve)
o SII: Severe intracranial injury on CT (Sick vs. Healthy)
o Calculations: Sensitivity, Specificity. PPV, NPV. Likelihood ratio.
 Likelihood ratio good:
o Can assess how good a diagnostic test is
o Can select appropriate diagnostic test
o Can calculate post-test probability for a target disorder
 Two common clinical decision rules of TBI: New Orleans Criteria, Canadian Head CT rules
1. New Orleans Criteria (For GCS 15/15, predicts need for CT)
 Identify symptoms: Short-term memory deficit, drug or alcohol
intoxication, 60Y+, Seizure, Headache, vomiting, trauma above clavicle >
Recursing partitioning analysis. Likelihood ratio of each of this criteria
evaluated. Then, test the criteria with new set of data.
2. Canadian CT head rule (GCS 13-15. predicts need for neurological intervention and
CT)
 Symptoms identified: GSF<15 within 2 hrs after head injury. Suspected
open / depressed skull fracture. Signs of basal skull fracture, >2 episodes of
vomiting. Patients >65Y.
 4 important signs suggestive of basal skull fracture: Hemotympanum, CSF
otorrhea / rhinorrhea, Racoon eye (vs. cosmetic effect!), Battle sign (blood
at periauricular area)
 Medium signs: Amnesia >30 mins, Dangerous mechanism of head impact,
e.g. struck / ejected by vehicle, >1M fall.
o Limitations on generalizability: Only included patients with certain GCS score and
inclusion criteria
 Cranial CT for mild TBI in China
o Background: No existing criteria for selecting mild TBI for CT, so almost all TBI
patients undergo CT in emergency department

SUMMARY

 Most TBI are mild and not associated with chronic sequelae.

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  Indiscriminate use of CT are costly and associated with harm, so careful identification of
patients for CT is important
 Validated decision tools e.g. New Orleans Criteria, Canadian CT head rule. They are highly
sensitive.

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HNS EXAM FOCUS

EXAM FOCUS DESCRIPTION

 Revision notes in Question-and-Answer format

 What it includes:
o Highlights of important points from most lecture contents
o Highlights of important points from past paper
 However, there are some limitations:
 Areas where table may be incomplete:
o Anatomy, Histology, Embryology: Often not fully included; recommend studying
elsewhere with images.
o Pharmacology
 MoA: All MoAs are assumed to be in Importance Class A (See explanatory
table below) and they could easily be found in lecture notes. So it is not
documented below.
 Side effects: Key side effects might be missing from the table.
o It doesn’t include all lectures. Some lectures are still missing (If you can’t find it

below, then that lecture is missing☹ )

 Suggested use: Study first  Test: find paper to cover up right hand side  Recite  Then
check the answer
 Note:
o Some lectures have been combined during documentation, because they teach very
similar things. E.g. MSS030415 means it already included key points from both
MSS03, MSS04, and MSS15.
 Importance rating (Third column ‘I’ in table):

Meaning
A Very important
B Quite important
C Important
D Good to know
E Not important, Quick read-
through is good enough
Comments
Often because they frequently appear in Past Paper while
carrying a lot of marks, or lecturer placed special emphasis
on this, or it is crucial to the overall understanding the
lecture.
Likely appeared in past paper, or lecturer placed some
emphasis. These should be memorized.
Although less important, it may still appear in exam.
Suggest memorizing these too.
These are unlikely to appear in exam because they are
relatively trivial knowledge.
It is still good to know them, after all ‘no knowledge is
useless.’ But maybe prioritize, study after A, B, and C.

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 Lecture I Question Answer
1 HNS01 C Stimulatory neurotransmitters & Ions involved Glutamate, Na Ca
2 HNS01 C Inhibitory neurotransmitters & Ions involved GABA, Cl
3 HNS01 C 5 Special senses Taste, Smell, Hearing, Balance, Vision
4 HNS01 D 2 Characteristics of Sensory Pathway Crossed ascending projection (Left stimulus to right cortex). Fine
division of labour (Dorsal column nuclei for Discriminative touch,
vibration, position; Non-dorsal column nuclei for Temperature & pain)
5 HNS01 C 3 neuromotor regions Motor cortex (via Corticospinal tract to spinal cord), Cerebellum, Basal
ganglia
6 HNS01 D 2 characteristics of Motor control Topography (most at fingers for dexterity / motor homunculus), Cross
descending projection
7 HNS01 C Left vs. Right hemisphere responsibilities [Logics & Language] vs. [Arts & Spatial] (Easy to remember: L for Left,
Logic, Language)
8 HNS01 B Responsibilities of Limbic system Learning, Emotions
9 HNS01 C Parkinson's disease: degeneration of what neurons, at where? Dopaminergic, Substantia nigra pars compacta (part of basal ganglia,
which is part of motor control > Parkinson gait)
10 HNS01 C Alzheimer's disease: degeneration at where & briefly the cause? Hippocampus, Amyloid plague (Tangled Tau fragments)
11 HNS02 A 5 divisions of brain and function Telencephalon (Cerebral hemispheres + basal ganglia), Diencephalon
(Thalamus & hypothalamus + Corpus callosum), Mesencephalon
(midbrain), Metencephalon (Pons, Cerebellum), Myelencephalon
(Medulla oblongata)
12 HNS02 A 3 parts of brainstem Midbrain, Pons, Medulla oblongata
13 HNS02 B Function of brainstem [1] Life center (Heart rate, breathing, etc.) and reflex (e.g. vomiting); [2]
Passage of all ascending and descending pathways (for integration). [3]
Origin of most cranial nerves
14 HNS02 B Which area use serotonin as neurotransmitter Raphe nucleus
15 HNS02 B Vomiting center location Medulla
16 HNS02 B Vestibular nucleus location Medulla
17 HNS02 B Nerve mediates pain signal of teeth Trigeminal nerve
18 HNS02 B Red nucleus location Midbrain
19 HNS02 B Superior colliculus location Midbrain
20 HNS02 B Reticular formation location Pons
21 HNS02 C Micturition center location Brainstem (although the reflex center is in spinal cord)
22 HNS02 C Embryological origin of neural tissues Ectoderm
23 HNS02 D Notable structures in midbrain Red nuclei, aqueduct, Tectum & Tegmentum, Substantia nigra
 (melanin)
24 HNS02 D Notable structures in pons Pontine, Sleep center, Respiratory center
25 HNS02 D Notable structures in medulla Heart rate center, Vomiting reflex, olive for balance and hearing
(Vestibular nucleus location), pyramids for decussation
26 HNS02 D Function of reticular formation Integrate information, Regulate behaviors
27 HNS02 D Examples of reticular formation Locus coeruleus-norepinephrine; Raphe nucleus-serotonin; Pontine-
acetylcholine, Substantial nigra-Ventral Tegmental Area
28 HNS03 B Thalamus is located at which division of brain? Diencephalon
29 HNS03 B Function of thalamus Relay sensory information to cortex
30 HNS03 C Corpus callosum is grey or white matter? White
31 HNS03 D Anatomical relationships with reference to Thalamus Anteriorly Interventricular foramen. Posteriorly pulvinar. Superiorly s
zonale & stria terminalis. Inferiorly hypothalamus. Medially 3rd
ventricle. Laterally internal capsule.
32 HNS03 D 4 -thalamus and functions Epithalamus secretes melatonin. Thalamus relays sensory input to
cortex. Subthalamus controls motor and emotions. Hypothalamus
controls homeostasis and regulates pituitary (hormone headquarters)
33 HNS03 B Ventral posterior lateral vs. ventral posterior medial part of VPL for body, VPM for Head (Easy to remember: L for Lower, M for
thalamus responsible for body parts Mouth)
34 HNS03 B Sulcus vs. Gyrus Sulcus goes in, Gyrus goes out (Easy to remember: 'Central sulcus',
hence sulcus should go in)
35 HNS03 D How does the fibers go from cortex to peduncle? Cortex or Insula > Radiata (corona, optic) > internal capsule > cerebral
peduncle
36 HNS03 C 2 special fibers Superior longitudinal fasciculus (front and back), Arcuate fibers
(between adjacent gyrus)
37 HNS03 C Function of Broca's and Wernicke’s area Language. Broca for creation, Wernicke for comprehension. (Easy to
remember: Broca = broadcast, i.e. cannot create words. W=What?=
cannot understand)
38 HNS03 B Limbic system includes (Crudely) amygdala, hippocampus, cingulate gyrus (Nb: many
structures from Papez circuit are also part of limbic system).
39 HNS03 D Meynert nucleus for what? Working memory (all cholinergic neurons)
40 HNS03 C Learning pathway of Papez (Paper = Learning) Hippocampus, Fimbria, Fornix, Mamillary body, Mammillothalamic
tract, Anterior thalamic nucleus, Posterior cingulate gyrus,
Parahippocampus, Entorhinal cortex, repeat
41 HNS03 B Alzheimer's disease first affects neurons of which part? Hippocampus
42 HNS03 C Draw the cortex of brain See: https://ibb.co/4Ws92Dh (But you can find similar diagrams online)

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 43 HNS04 A Which meningeal space does artery and vein flow? Subarachnoid
44 HNS04 B What is found in subarachnoid space? CSF, Artery & vein
45 HNS04 B Function of dura mater in brain? Form dura septa to limit brain movement
46 HNS04 B Function of pia mater? Forms choroid plexus, invagination in ventricles (CSF circulation)
47 HNS04 B Midline shift in CT indicates High intracranial pressure
48 HNS04 A Draw a diagram showing arterial supply at brain (cranial) See: https://ibb.co/VSx3JNw (Credits TeachMeAnatomy, can also find
other images online)
49 HNS04 A 4 dural folds Falx cerebri, Tentorium cerebelli, Falx cerebelli, Diaphragma sellae
50 HNS04 A 3 layers of meninges Dura (Periosteal, Meningeal), Arachnoid, Pia
51 HNS04 C Periosteal vs. Meningeal layer of Dura Periosteal layer is the only layer that doesn't go into spine. Every else
layer does
52 HNS04 C Subarachnoid space terminates at which spinal level S2 [Easy to remember: Subarachnoid S for S2]
53 HNS04 C What terminates at L2 level Conus medullaris
54 HNS04 B CSF composition compared to blood No RBC, Less: protein, WBC, glucose, Ca, K. More: Cl
55 HNS04 B Where is CSF? Subarachnoid space, Pia (in ventricles)
56 HNS04 A CSF circulation pathway Choroid plexus for secretion > Lateral ventricles (sylvius) > Foramen
Monro (interventricular) > 3rd ventricle > Aqueduct > 4th ventricle >
Luschka & Magendie > Subarachnoid
57 HNS04 A Draw a diagram showing venous drainage at brain See: https://ibb.co/542q4wX (Credits online image)
58 HNS04 B Middle Cerebral Artery is or is not Circle of Willis Nope
59 HNS05 C 4 types of brain infections [1] Meningitis, Encephalitis, Meningoencephalitis, Ventriculitis. [2] Brain
abscess. [3] Parameningeal infections (Epidural & Subdural abscess). [4]
Suppurative venous sinus thrombosis.
60 HNS05 D Pathogenesis of bacterial meningitis Nasopharyngeal mucosa > Phagocytic vacuole > Bacteraemia > Release
endotoxin > Pro-inflammatory cytokines
61 HNS05 C 2 Pathological changes of bacterial meningitis [1] Brain: Increase BBB permeability, Cerebral and subarachnoid
edema. [2]Venous thrombosis > Cerebral ischemia
62 HNS05 A CSF findings of: Bacterial meningitis Neutrophil predominant, LOW GLUCOSE, high protein, turbid
63 HNS05 A CSF findings of: viral meningitis Lymphocyte predominant, NORMAL GLUCOSE, high protein
64 HNS05 A CSF finding of: Fungi & Tuberculosis Lymphocyte predominant, LOW GLUCOSE, high protein
65 HNS05 C Can Viral and Fungi/Tuberculosis meningitis be slightly turbid Yes
66 HNS05 A Reference CSF open pressure 15-25 cm/H2O
67 HNS05 B Time cut-off for acute vs. subacute meningitis 1W
68 HNS05 B 3 common acute meningitis pathogens among 3M-18Y Streptococcus pneumoniae, Neisseria meningitides, Hemophilus
influenzae B (These 3 not so common in HK due to vaccination)

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 69 HNS05 B 2 common acute meningitis pathogens among adults (18-50Y) Streptococcus pneumoniae, Neisseria meningitidis
70 HNS05 A HIV associated strongly to which pathogenic cause of meningitis? Cryptococcal meningitis
71 HNS05 A Empirical IV antibiotics (+- drugs) while waiting for lumbar puncture Vancomycin + Ceftriaxone (+- Dexamethasone)
72 HNS05 B Common pathogens of subacute meningitis Mycobacterium tuberculosis, Cryptococcus neoformans (most
immunocompromised)
73 HNS05 B Anti-tuberculosis agents for tuberculosis meningitis Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (Don't use
streptomycin because poor BBB penetrance)
74 HNS05 C Guess the pathogen: Brain abscess predisposed by otitis media Streptococcus viridans (Oral bacteria, probably because middle ear
connected to Auditory tube)
75 HNS05 C Guess the pathogen: Brain abscess predisposed by endocarditis or Staphylococcus aureus
pulmonary suppuration
76 HNS05 B Guess the pathogen: Brain abscess in immunocompromised Toxoplasma gondii
77 HNS05 B How to tell between meningoencephalitis vs. only meningitis Physical examination (Neurological deficits), Imaging (brain
(important to know encephalitis involvement because different involvement)
treatment & prognosis)
78 HNS05 B Meningoencephalitis commonly caused by which group of Viral (Bacterial meningoencephalitis not common at all, except for
pathogens? predisposition e.g. bacteraemia, spiral bacteria, chronic pathogens e.g.
tuberculosis)]
79 HNS05 A The full name of the 2 common fungal / tuberculosis pathogens of Mycobacterium tuberculosis (Positive ZN stain), Cryptococcus
subacute meningitis; and what further test could tell them apart neoformans (Positive Indian ink stain: Halo) [Note: Microbiologically
microbiologically because clinically Indian ink stain only present in 50% of Cryptococcus
neoformans CSF culture. Also, please make sure know how to spell the 2
pathogens]
80 HNS05 B Guess the pathogen: Meningitis associated with pigs *oink* Streptococcus suis
81 HNS05 B Guess the pathogen: Meningitis associated with cattle *moo* / soil / Listeria monocytogenes
farmer / fresh water
82 HNS05 B Guess the pathogen: Meningitis associated with cats *meow* and Toxoplasma gondii
immunocompromised
83 HNS05 C Guess the pathogen: Meningitis associated with hemolysis (dark Plasmodium falciparum
urine & anaemia), Africa visit
84 HNS05 C Guess the pathogen: Meningitis associated with birds *chirp chirp* Cryptococcus neoformans [Easy to remember: bird 'Chirp' sounds like
and immunocompromised 'Cryp', no? {Ignore me plz})
85 HNS05 B Common meningitis pathogens among <3M Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes (vs.
Hemophilus influenza B in 3M-18Y)
86 HNS05 A The 1 most commonest cause of meningitis in Cryptococcus neoformans
immunocompromised

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 87 HNS05 A The most important predisposition to cryptococcus neoformans HIV
88 HNS05 A Tips for MCQ: Viral meningitis presents which unique CSF content NORMAL glucose (vs. others: reduced) [Not sure if this is a clinically
change compared to other pathogens definite sign but seems useful for MCQ choosing between options]
89 HNS05 A Meningitis: Neisseria meningitidis or gonorrhoeae Neisseria meningitidis (gonorrhoeae isn't even mentioned in the
chapter, don't mix up!)
90 HNS05 C Property differences between Neisseria meningitidis vs. [1] Polysaccharide capsule vs. none. [2] Ferments glucose & maltose vs.
gonorrhoeae glucose only (although both oxidase positive). [3] Vaccines to some
serotypes vs. none
91 HNS0607 B Precursors of acetylcholine; Enzyme that produces acetylcholine Acetyl CoA, Choline; Choline acetyltransferase.
92 HNS0607 B Enzyme that breaks down acetylcholine, products Acetylcholinesterase, Choline, Acetate.
93 HNS0607 C Match: nACh, mACh, Ligand gated (Ionotropic), G-protein coupled Nicotinic is ligand gated (Ionotropic), Muscarinic is G-protein coupled
(Metabolotropic) (Metabolotropic). Ionotropic faster and shorter duration;
Metabolotropic the reverse.
94 HNS0607 D Alpha motorneurons release which kind of neurotransmitter Ach
95 HNS0607 D Lambert-Eaton myasthenic syndrome. What it attack? Serum antibodies attack voltage gated Ca channels > not enough Ca
dependent ACh release
96 HNS0607 B Levodopa synthesis reaction Hydroxylation of Tyrosine to L-dopa
97 HNS0607 B Dopamine synthesis reaction & Vitamin required Decarboxylation of Levodopa to dopamine (B6 Pyridoxine)
98 HNS0607 B NE synthesis reaction and Vitamin required β-hydroxylation from dopamine to noradrenaline (Vitamin C)
99 HNS0607 B Who takes up: Dopamine, GABA, Glutamate Pre-synaptic, Glial cells, Perisynaptic astroglial cells (via transporters) ,
respectively
100 HNS0607 C Class: Dopamine receptors, Glutamate receptors G protein coupled receptor; (Transiently Ligand gated NaK channel,
followed by) Ligand-gated Ca channel
101 HNS0607 C Neurotransmitter associated with reward pathway. Which area of Dopamine, Nucleus accumbens
brain is most responsible for addiction?
102 HNS0607 C Hallucinations likely due to hyperactivation of Hyper-reactive dopaminergic
103 HNS0607 C Name the 2 types of glutamic receptor. Which is responsible for Ionotropic (NMDA), Metabotropic Glutamate receptor. Ionotropic
producing NOS? (NMDA) [Metabotropic glutamate receptors are muscarinic receptors
and regulates plasticity]
104 HNS0607 C Glutamate causes influx of cation to postsynaptic neurone. T/F? T
105 HNS0607 A Stroke: Glutamate and NO, Pathogenesis and Treatment. Answer Answers: https://ibb.co/17WxQ4T
the questions: https://ibb.co/7kF3FCY [But some people say this
question is old and lecturer changed, so not sure]
106 HNS0607 C Identify A and B: https://ibb.co/VpT0TGn A: γ-aminobutyric acid (GABA), B: Glutamate
107 HNS0607 B Write an equation showing the formation of Glutamate α-ketoglutarate + Aspartate --Glutamate-oxaloacetate transaminase->

187
 Oxaloacetic acid + Glutamate
108 HNS0607 B Write an equation showing the formation of GABA Glutamate --Glutamate decarboxylase---> GABA + CO2
109 HNS0607 C GABA hyperpolarizes by allowing influx of which ion Cl
110 HNS0607 C Neurotoxin that could alter neurotransmitter exocytosis Botulinum toxin
111 HNS0607 B How does Botox limit neurotransmitter release at motor nerve Target SYNAPTOBREVIN / Syntaxin / (SNAP) (depending on which one
endings, what does it target appears as option) > Cleave SNARE protein, which is involved in vesicle
appositioning at pre-synaptic membrane
112 HNS0607 B MoA of SARIN the nerve poison? Cholinesterase inhibitor > Continuously depolarizes Ach receptors
113 HNS0607 C What does clostridium toxins do? Cleave SNARE proteins
114 HNS0607 D State the target of: Clostridium, Alpha Latrotoxin Synaptobrevin, Neurexin (>Vesicle release)
115 HNS0607 C Inhibitory or Excitatory: ACh, ATP, Dopamine, Epinephrine & NE, Excitatory: ACh, Glutamate, Epinephrine & Norepinephrine, Histamine,
GABA, Glutamine, Glycine, Neuropeptides Serotonin ATP. Inhibitory: GABA, Glycine, Serotonin. Both: Dopamine,
Neuropeptides
116 HNS0607 A The 3 criteria for Neurotransmitter (condensed version, details Can be produced: Synaptic vesicles have substrates and enzyme),
please see Dr. Shum's powerpoint) Exogenous substance to inhibit degradation. Can be released: In
response to presynaptic depolarization. Can produce response: Specific
receptors on post-synaptic side ( Can be mimicked by exogenous
neurotransmitters)
117 HNS0607 D ?? (Old PP LQ, skip if can't understand) List 4 molecular biochemical Activation of Adenyl cyclase which is mediated by G protein,
mechanisms that may lead to defective dopamine-mediated signal Mobilization of intracellular calcium store as a result of Phospholipase C
transduction. stimulation, Activation of K current by G protein, NaK exchange by
NaKATPase by dopamine receptor
118 HNS0607 D Name an AA that could serve as a precursor for NT Many could (e.g. Remember Glycine), Valine couldn't
(neurotransmitter), and one that couldn't
119 HNS0607 C Increased permeability of which ion allows hyperpolarization K
120 HNS0607 C (For MCQ) Oxidation of neurotransmitter is not a known Okay
mechanism of neurotransmitter termination. Some possible ways
are: Degradation of neurotransmitter, Receptor mediated
endocytosis, Reuptake by glial cells and pre-synaptic terminals.
121 HNS0607 C Stimulation usually leads to increase in nerve cell excitability. T/F? T (This is called NMDAR-dependent Long-Term Potentiation)
122 HNS0607 D Briefly explain the Quantal nature of neurotransmitters Synaptic potentials are integral multiples of unit, neurotransmitter
amount released in fixed size (due to vesicles)
123 HNS0607 B A mechanism that blocks release of neurotransmitter in chemical Absence of extracellular Ca (Unimportant note: Influx of Ca into
synapse presynaptic axon stimulates vesicular fusion with axon membrane)
124 HNS0607 A Recite this page about glutamic receptors: https://ibb.co/RpYr9Cy Okay!
125 HNS08 B Cranial nerve: Gustatory sensation of the Anterior 2/3 of tongue CN7

188
 126 HNS08 B Cranial nerve: Motor function of masticatory muscle CN5
127 HNS08 B Cranial nerve: Superior rectus CN3
128 HNS08 B CN: Autonomic supply to major salivary gland CN9
129 HNS08 B CN: Supply to cardiac plexus CN10
130 HNS08 B CN: Motor function of muscles of tongue CN12
131 HNS08 B Cranial nerve classifications: Purely sensory, Purely motor, Mixed, Pure sensory (1, 2, 8), Pure motor (4, 6, 11, 12), Mixed (3, 5, 7, 9, 10),
Special sensory Special (3, 7, 9, 10)
132 HNS08 C What allows Pacinian corpuscle (Vibration) and Ruffini corpuscle Rate of adaptation.
(Stretch) to detect different stimuli?
133 HNS08 B Recite table: Embryological divisions of brain and Cranial nerve https://ibb.co/qCtxBsw
nucleus locations
134 HNS08 A Draw the diagram for nerve root outlet at the brain base https://ibb.co/JrF0Rr0
135 HNS08 A Nerve root levels: Sympathetic, Parasympathetic Parasympathetic: Cranial sacral output; Sympathetic: Thoracolumbar
(T1-L2)
136 HNS09 A Gross pathological presentation of Mycobacterium tuberculosis Meninges fibrosis (White nodules and exudates), due to granulomatous
meningitis, cause inflammation
137 HNS09 A Pathogenesis of granuloma (Mycobacterium tuberculosis [1]Epithelioid cell join to form Langerhan giant cell with horseshoe
meningitis) [x2] nucleus alignment. [2]Granulation tissue with fibrosis.
138 HNS09 C Glial scars are formed by which glial cell Astrocytes
139 HNS09 B Most important histological feature of viral encephalitis Neuronophagia by microglia
140 HNS09 C Venous thrombosis is a late complication of which disease? Bacterial meningitis (vs. Endarteritis obliterans in Tuberculosis
meningitis vs. Neuronophagia by microglia in viral meningitis)
141 HNS09 D Which direction does bacterial meningitis spread to (with reference Posterior to spinal cord
to spinal cord)
142 HNS09 C Mycobacterium tuberculosis related to which kind of necrosis Caseous
143 HNS09 B List the sequelae of tuberculous meningitis Fibrosis is the most important sequelae of MTB. [1]Fibrosis in
subarachnoid space (due to inflammation exudate) leads to obstructive
hydrocephalus (most common / important complication), increased ICP
and herniation. [2]Fibrosis of artery forms Endarteritis obliterans,
Stroke. [3]Fibrosis of brain base leads to cranial nerve palsy and
neurological deficits. [4] Epilepsy
144 HNS09 D Does cryptococcus neoformans form granuloma too? Yes, but less common than MTB.
145 HNS09 C 2 pathogenesis of viral encephalitis Cytopathic effects, Immunological responses (post-viral encephalitis)
146 HNS09 D Common brain location involved in HSV Temporal lobe
147 HNS09 D Viral meningitis: Histological features Neuronophagia by microglia (most important). Others: Perivascular

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 cuffing, microglial stars (grouped proliferated microglia)
148 HNS09 C Pathogens associated with post-infectious encephalitis Measles, Varicella, Influenza
149 HNS09 D Histological feature of post-infectious encephalitis Myelin destroyed more than axon; Perivascular cuffing, destruction,
gliosis
150 HNS10 A Virus causing Hand Food Mouth Enterovirus (71, Echovirus, Coxsachie A or B) OR Herpes simplex virus
151 HNS10 A Most likely pathogen (specifically) for Hand Foot Mouth Disease Enterovirus 71
152 HNS10 B Enterovirus 71 group Picornavirus -> Enterovirus A
153 HNS10 B 5 Diagnostic methods of Enterovirus 71 RT-PCR, Cell culture of faeces / vesicle fluid, Serology of antibody
(double titre), ELIZA of antigen, Direct microscopy of vesicular fluid
154 HNS10 C Clinical sign of Hand Foot Mouth Hand and Mouth vesicles (lol)
155 HNS10 C Clinical sign: Meningoencephalitis vs. Encephalitis Check neck stiffness (Neck soft = encephalitis). [Note: Although this
differentiation wouldn't be clinically important (vs. differentiating
between meningitidis and meningoencephalitis is clinically important),
just know which answer to put in SAQ]
156 HNS10 C Enterovirus 71 Encephalitis: Diagnosis vs. Disease vs. Pathogens Encephalitis vs. Hand food mouth OR Flaccid paralysis (if symptoms
(know what these terms mean) demonstrate) vs. Enterovirus 71
157 HNS10 B Enterovirus flaccid paralysis: pathogen live in where? Anterior horn cell
158 HNS10 A 3 Routes of HSV entrance to CNS Hematogenous (from viraemia), Primary (Olfactory to CNS),
Reactivation (Live in ganglion > gingivostomatitis via trigeminal nerve)
159 HNS10 A Treatment for HSV encephalitis IV Acyclovir, 2-3W
160 HNS10 B Diagnostic method of HSV encephalitis PCR (DNA virus) of CSF
161 HNS10 B Draw the diagram for CNS viral infection classification See: https://ibb.co/s9fB1JP
162 HNS10 C State 4 virus associated with flaccid paralysis Enterovirus, Poliovirus, West Nile, Dengue
163 HNS10 C Is HTLV1 associated with flaccid paralysis? No
164 HNS10 C High mortality HSV encephalitis: Type 1 or 2? Type 1 (Type 2 HSV encephalitis happens only in immunocompromised,
and when it does it is recurrent but benign.)
165 HNS10 B Guess the pathogen: meningitis associated with rapid circulatory Neisseria meningitidis
collapse
166 HNS10 C Guess the pathogen: acute viral meningitis with lower motor neuron Poliovirus (or other virus causing flaccid paralysis)
paralysis
167 HNS10 C Guess the pathogen: Negri bodies, doesn't respond to empirical Rabies
antibiotics
168 HNS10 B Group of virus with notable seasonality Enterovirus
169 HNS10 C Where does VZV vs. HSV remain latent? Dorsal root ganglion vs. dk
170 HNS10 A 5 groups of symptoms of meningoencephalitis [1]Meningeal irritation: Headache (CNV1, C2), Neck stiffness (Kernig,

190
 Brudzinski), Photophobia (Basal meninges at diaphragma sellae).
[2]Encephalopathic (Altered conscious, neurological signs sense /
motor, epilepsy). [3]Increased ICP: Vomiting, Cushing's triad (Increased
BP, Irregular breathing, Bradycardia). [4]Systemic e.g. fever,
leucocytosis. [5]Peripheral signs: e.g. Parotitis in mumps, Rash
(petechiae, purpura) in enterovirus [Everyone go read KY Yuen's good
notes: HNS05!]
171 HNS12 A Recite: DCML Pathway. DCML Pathway is for general somatosensation, including sensations by
Merkle cell for discriminative fine touch, Pacinian corpuscle for
vibration, and muscle spindles and tendon organ for proprioception.
The axons are large myelinated A (alpha, beta, and gamma). Signals
from lower limb, that is below T6, enters as the nucleus of their first
order neuron locates at the dorsal root ganglion, to the gracile
fasciculus. Above T6, neurons from upper trunk joins, with their first
order neuron located at the dorsal root ganglion, to the cuneate
fasciculus. Although mostly they ascend, some fibers may descend a
few dermatomes. At the lower medulla oblongata level, they meet the
second order neuron, their nucleus namely the gracile nucleus and
cuneate nucleus, and decussate at the same level, via the arcuate fibers,
to the medial lemniscus. They are then projected to the thalamus, with
the Ventral posterior lateral VPL responsible for the rest of the body,
and the ventral posterior medial VPM responsible for face. They are
then projected to the cortex according to their thalamic locations:
Laterally the face, upper limb, and medially the lower limb. [Easy to
remember: Thalamic nucleus VPM M for Mouth, so face. VPL L for
lower, so body]
172 HNS12 A Recite: Spinothalamic pathway. The spinothalamic pathway. the second pathway for general
somatosensation, subdivides into the lateral and anterior spinothalamic
pathway. The anterior spinothalamic pathway is responsible for light
non-discriminative touch, pressure and itch; whereas the lateral
spinothalamic pathway for pain and temperature. Both are by free
nerve endings and contains mainly small myelinated fibers like A-delta
and C fibers. The lateral spinothalamic pathway is topographical with
the cervical region most medial; whereas the anterior is non-
topographical. Sensory neurons with their nucleus located in the dorsal
root ganglion enters and immediately synapses, then decussates via
anterior white commissure to contralateral side. Like DCML, a few fibers

191
 descends to a few dermatomes below. These second order neurons
ascend to the ventral posterolateral nucleus of thalamus, more medially
the upper trunk and more laterally the lower trunk (but both upper and
lower trunk still posterolateral, because the posterior medial is reserved
for head which is not in this pathway), then to the cerebral cortex (lower
trunk more medial)
173 HNS12 B Recite briefly the pathway for spinothalamic. CN5, 7, 9, 10 > Enters pons > Descends to synapse in medulla >
Decussate > Ascend VPM Thalamus.
174 HNS12 A Location of decussation of: DCML, Spinothalamic, Corticospinal DCML is lower medulla (Internal arcuate fibers). Spinothalamic is 一入
就 decussate. Corticospinal is at pyramids.
175 HNS12 B Ventral spinothalamic tract detects what? Light touch, pressure, itch
176 HNS12 B Spinotrigeminal tract project to which part of thalamus Ventral posteromedial nucleus
177 HNS12 A Brown Sequard syndrome presentation Loss of: Ipsilateral fine tough, Vibration, Proprioception (DCML),
Ipsilateral spastic paralysis (for UMN lesion, Corticospinal), Contralateral
loss of light pain and temperature (lateral spinothalamic), Total loss in
motor (flaccid paralysis) and sensory innervation at level of lesion (LMN
injury)
178 HNS1719 A UMN vs. LMN damage difference See Dr. Leung’s slide: https://ibb.co/HNT8m0s
179 HNS1719 B Decerebrate position Limbs hyperextended, feet plantarflexed, hand flexed and pronated,
arms adducted.
180 HNS1719 B Decerebrate position cause Damage to rubrospinal tract (below nucleus) leads to inability to
generate signals favouring flexion. Unopposed extensor activities of
reticular and vestibular nucleus cases limb extension.
181 HNS1719 C Decorticate posturing cause Lesion above red nucleus, higher center cannot inhibit the intact
rubrospinal tract. Decorticate posturing produces flexion in arms and
supination of hand, otherwise similar to decerebrate.
182 HNS1719 B 3+1 extrapyramidal tract, general and specific functions Trunk and proximal muscle movement (Rubrospinal [red nucleus]:
flexion, Reticulospinal [reticular nucleus]: Flexion balance extension,
Vestibulospinal tract [Vestibular nucleus]: extension and balance.
Tectospinal tract [Tectum]: head orientation)
183 HNS1719 A Cortical motor area and brief functions (should also know what M1 Primary motor (Generates motor signals, precision e.g. dexterity),
lesion in area causes) PMC Premotor (Integrates sensory and motor esp. visual feedback,
Control proximal and axial muscles), M2 Supplementary motor (Motor
programming: Planning and sequence of movements, Bilateral
movement)
184 HNS1719 A Cortical motor area and function (Past paper answer version, very M1 encodes parameters to define individual movements or simple

192
 annoying) movement sequences to provide minute-to-minute precise conscious
control. PMC is responsible for controlling proximal and axial muscles
via direct descending projections, selection and execution of motor
programmes based on visual and somatosensory cues. M2 is responsible
for motor programming of complex movement and coordination of
bilateral movement.
185 HNS1719 B Where do these 3 cortical motor control centers locate M1 (Brodmann 4, Precental gyrus of frontal lobe), PMC (Brodmann 6
lateral, immediately anterior to M1), M2 (Brodmann 6 medial, buried
within longitudinal fissure)
186 HNS1719 B Name 2 SUBCORTICAL structures of motor control Cerebellum, Basal ganglia
187 HNS1719 B Cerebellum's role in motor [1]Error-correction: Actions requiring real-time sensory feedback e.g.
visual, tactile, proprioceptive (Threading a needle). [2]Ballistic
movement too fast to benefit from sensory guide and requires previous
experience (e.g. swing golf). [3]Vestibulocerebellum for posture and
balance maintenance
188 HNS1719 C Basal ganglia role in motor Action selection (e.g. select motor commands to produce complex
pattern e.g. writing) and motivation (with limbic system)
189 HNS1719 B Brainstem's role in motor control Posture adjustment
190 HNS1719 B Spinal cord's role in motor control Locomotion and reflex, Final common pathway of movement
191 HNS1719 B An additional cortical area in motor control + brief function Posterior parietal cortex, use sensory inputs to construct a map of
extrapersonal space to guide motor
192 HNS1719 B Summarize the neural structures controlling motor 3 cortical structures (M1, PMC, M2), 2 subcortical (Cerebellum, Basal
nucleus), 2 additional (Brainstem, Spinal cord), 1 additional cortical
(Posterior parietal)
193 HNS1719 B Recite: Corticospinal tract Originates from medial M1, descends along cerebral peduncle then
pyramids. Most would decussate at pyramid to form lateral
corticospinal tract to supple distal muscles for fine motor. Few would
not decussate and descend along ipsilateral anterior funiculus to form
anterior corticospinal tract to supply proximal muscles for gross motor.
194 HNS1719 B Summarize the functions of Lateral vs. Anterior corticospinal tract Lateral for contralateral fine motor, Anterior for ipsilateral gross motor.
195 HNS1719 B Type of neurons: Sensory Pseudounipolar
196 HNS1719 B What is in the ventral spinal root? Motor axons
197 HNS1719 B What is in the sympathetic ganglion? Postganglionic sympathetic neurons
198 HNS1719 C Where are the preganglionic sympathetic neurons located? Thoracic spinal cord
199 HNS1719 B Neural structure releasing dopamine? Basal ganglia
200 HNS1719 C Intention tremor is a sign of damage in? Cerebellum (NOT basal ganglia!)

193
 201 HNS1719 B M1 distribution: from lateral to medial (Draw motor homunculus)
202 HNS1719 B Where does the pyramids locate Medulla (Lateral corticospinal tract decussate at the pyramids, so it
decussate at medulla level)
203 HNS1719 C Friend of anterior corticospinal tract Rubrospinal tract (Nani what are you asking)
204 HNS1719 C 2 components of lateral motor system (Lateral motor = 'advanced') Rubrospinal tract, Lateral corticospinal tract
205 HNS1719 B Which section of the spinal cord does corticospinal tract terminate? Ventral horn
206 HNS1719 B Internal capsule arrangements Draw the diagram
207 HNS1719 B Which limb of internal capsule does corticospinal tract pass Posterior limb
through?
208 HNS1719 B Output locations of sympathetic and parasympathetic nerve Sympathetic (Thoracolumbar: T1-L2), Parasympathetic (Craniosacral:
CN 3 7 9 10, S1-2)
209 HNS1719 A Lacunar infarct of left basal ganglia. What the patient experience? Right side hemiplegia
210 HNS1719 B Describe the course of corticobulbar tract. What does it supply? Lateral M1 > Cerebellar peduncle > DECUSSATE (yes it will decussate
like Corticospinal) > Cranial nerves
211 HNS1719 B Which region of face receives dual innervation from corticobulbar Upper portion of face. In brain stroke, upper face motor function
tract? Hence, compare symptoms of brain stroke vs. nerve palsy. preserved as they receive dual innervation, only lower face that does not
receive dual innervation is paralysed. In facial nerve palsy the entire side
of face is paralysed.
212 HNS1719 B 'Voluntary complex motor function' impairment associated with Substantia nigra
damage in
213 HNS1719 D Reticular activating system is responsible for what? Wakefulness
214 HNS1719 C Where is nucleus accumbens located Ventral striatum
215 HNS1719 C Functions of pyramidal vs. Extrapyramidal system Voluntary vs. Involuntary motor
216 HNS1719 C Where is primary sensory cortex located Parietal lobe, immediately behind central sulcus
217 HNS1719 D 5 nucleus of basal ganglia Caudate nucleus, Putamen / Lentiform nucleus, Striatum (from internal
capsule), Globus pallidus (Pale globe), Subthalamic nucleus and
substantia nigra
218 HNS1719 D Outline the complex motor modulation pathway at basal ganglia Direct pathway: Cerebral cortex > Caudate / Putamen > [-]Internal
segment of globus pallidus > [-] VA/VL in thalamus > Frontal cortex
(Inhibit an inhibitory network = exaggerates movement). Indirect
pathway: Cerebral cortex > Caudate / Putamen > [-] External segment of
globus pallidus > [-]Subthalamic nucleus > Globus pallidus of internal
segment > [-] VA/VL in thalamus > Frontal cortex (Triple inhibition leads
to inhibiting movement). Direct and indirect pathways usually in
balance. [Memory corner: Direct exaggerates, indirect inhibits. Indirect
additionally go to subthalamic nucleus, otherwise the same]

194
 219 HNS1719 B Parkinson's disease: loss of which substances? Substantia nigra's dopaminergic neurons. As a result there is less direct
pathway and movement is slow / inhibited.
220 HNS1719 D Cauda equina is a LMN or UMN? LMN
221 HNS1719 D Where is conus medullaris? L1. Below L2 is cauda equina.
222 HNS1719 D Compare involvements of Myelopathy vs. Radiculopathy Myelopathy affects spinal cord (LMN at that level + UMN below level),
Radiculopathy affects nerve (LMN only)
223 HNS32 A Suspected acute epiglottitis, what would you do? Call ENT surgeon for laryngoscopy to protect airway.
224 HNS32 B Guess the pathogen: Factor X and V for growth H. influenzae
225 HNS32 B Guess the pathogen: Chocolate agar H. influenzae
226 HNS32 C Guess the pathogen: 8 RMA segments Influenza virus
227 HNS32 B Guess the pathogen: Monospot test positive Epstein Barr virus
228 HNS32 C Guess the pathogen: IV drug user with vertebral osteomyelitis and S. aureas (S. aureus already associated with IV and osteomyelitis too)
retropharyngeal abscess
229 HNS32 B Guess the pathogen: Pseudomembrane formation in throat, Elek Corynebacterium diphtheria
test positive, visit Bangladesh
230 HNS32 B Etiologies of croup E.g. Parainfluenza and Influenza virus, Mycoplasma, Rhinovirus (But
NOT Coronavirus and NOT bacteria!)
231 HNS32 B Guess pathogen: Subconjunctival hemorrhage and lymphocytosis Bordetella pertussis
suggestive of which condition
232 HNS32 C Pertussis use which medium Bordet-Gengou medium
233 HNS32 A Someone have breathing difficulty, any breathing difficulty not just Protect airway (Laryngoscopy)!
acute epiglottitis. What you do?
234 HNS32 C Which 2 pathogen have toxoid vaccine Diphtheria, Tetanus
235 HNS32 C Guess the condition: Trismus and Asymmetry of tonsils Parapharyngeal abscess
236 HNS32 C Uncomplicated acute bacterial sinusitis should be treated by Empirical antibiotics without need for microbiological investigations
237 HNS32 B Croup cause: Bacterial or Viral Viral! No antibiotics needed
238 HNS32 A Mediastinitis associated with which condition? Retropharyngeal abscess
239 HNS32 C Acute epiglottitis vs. Croup Bacterial vs. Viral cause. More severe vs. Less severe (in terms of onset,
fever, stridor, speech and swallowing). Barking seen in croup but no
cough in acute epiglottitis [Generalized answer for easier memory,
standard answer please see Dr. Lau's notes: https://ibb.co/pzhsf22)
240 HNS32 A Parapharyngeal space infection causes notable complications like Jugular vein thrombophlebitis, Carotid artery erosion
241 HNS32 C Notable clinical feature of submandibular space infection Board like swelling
242 HNS32 B Name the 3 deep fascia space infection. Why are these places Submandibular & Sublingual, Parapharyngeal, Retropharyngeal. They
infected? are infected due to primary infection in other locations (submandibular

195
 and sublingual from dental problem, Retropharyngeal from oral or
vertebral osteomyelitis / s. aureus)
243 HNS32 B Quinsy is also known as what and the causative agent is Peritonsillar abscess, often oropharyngeal organisms / streptococcus
pyogenes
244 HNS32 B Laryngoscopic finding of acute epiglottitis Cherry red epiglottis
245 HNS32 C Last Year CPRS Dr. Samson Wong has good lecture on upper See reference / additional resources at the bottom of the notes. Dr.
respiratory tract infection. Revisit his lecture / read notes again Samson Wong also has his own notes.
maybe?
246 HNS32 A Dictate the bacteria classifications https://ibb.co/F3h37tw
247 HNS33 B Functions of paranasal sinus Voice resonance, Reduce weight of skull
248 HNS33 A Name 4 paranasal sinus Maxillary, Frontal, ethmoid, sphenoid (Point that on yourself to make
sure you know where they are)
249 HNS33 A 3 important bacteria for upper airway problems (e.g. sinusitis, otitis Streptococcus pneumoniae, Hemophilus influenzae, Moraxella
media infection) catarrhalis
250 HNS33 A Drainage of paranasal sinus: pathway? Ostiomeatal complex (Frontonasal meatus > Semilunar hiatus > Middle
meatus)
251 HNS33 C Frontal sinus: Innervation and blood supply Supraorbital nerve (from CNV1), Anterior ethmoidal artery (from
internal carotid)
252 HNS33 C Sphenoid sinus: Innervation and blood supply Posterior ethmoidal nerve (From CNV1), Pharyngeal branch of maxillary
artery
253 HNS33 C Ethmoid sinus: Innervation and blood supply Ethmoidal branch of nasociliary nerve AND maxillary nerve. Anterior
and posterior ethmoidal arteries.
254 HNS33 B Maxillary sinus: Innervation and blood supply Anterior, middle, and posterior superior alveolar nerve (CNV2),
posterior superior alveolar A, infraorbital A, posterior lateral nasal
arteries
255 HNS33 C Common allergens for rhinitis in HK House dust mite faecal pellets, Pollen, Pet hair
256 HNS33 B Symptoms of allergic rhinitis: Immediate vs. late Immediate: Itch and sneeze. Late: Thickening of mucosa leading to
chronic nasal obstructions
257 HNS33 B Briefly outline the pathogenesis of allergic rhinitis Type 1 hypersensitivity: Allergen pass through epithelium > IgE and
Mast cells > Histamines and cytokines > Symptoms
258 HNS33 B Enlargement of which sinus leads to significant nasal obstruction Inferior turbinate (Chronic edematous inferior turbinate)
259 HNS33 C Which sinus is the largest? Maxillary sinus
260 HNS33 B Commonest cause of nasal obstruction Viral infection (not allergy)
261 HNS33 B Complications of sinusitis affecting the orbit Orbital cellulitis, Orbital abscess. Damage optic nerve
262 HNS33 B Symptoms of acute otitis media Hearing loss and deafness, tinnitus, tugging of ear

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 263 HNS33 A Guess the condition: long-standing infection at perforated tympanic Chronic suppurative otitis media
membrane
264 HNS33 B Spread of middle ear infection: where? Middle cranial fossa forming brain abscess (they only separated by thin
tegmen tympani, this is a notable point.) Mastoid antrum. Inner ear.
May also cause nerve palsy: CN5, 6)
265 HNS33 B Infections of ear causes which 2 types of hearing loss? Conductive, Sensorineural. (Conductive due to perforation of tympanic
membrane; Sensorineural loss because otitis media can cause lesion in
auditory division of vestibulocochlear nerve)
266 HNS33 B Swelling behind pinna after otitis media hints on which Mastoid antrum infection, Facial nerve palsy (since stylomastoid
complication? What problem would that cause neurologically? foramen, the exit of facial nerve, is quite near to mastoid antrum).
267 HNS33 B Route of administration for otitis media Oral, Ototopical (ear drop)
268 HNS33 A Causes of oral ulceration Aphthous (immune issue), Traumatic, Carcinoma
269 HNS33 A Risk factors for oral squamous cell carcinoma Smoking, Alcohol, HPV
270 HNS33 B Which 2 locations does the fish bone commonly lodge Vallecula, Pyriform fossa
271 HNS33 B Histological features of inflammatory nasal polyp Eosinophils, edematous stroma
272 HNS33 C Symptoms: Otitis externa vs. Otitis media (Otitis externa) External auditory canal shows swelling / erysipelas with
furuncles. Although both complains otalgia and otorrhea
273 HNS33 B How to diagnose chronic suppurative otitis media Chronic infection symptoms + Perforated tympanic membrane
274 HNS33 C Sinusitis: briefly the pathophysiology Disrupted mucociliary pathway e.g. polyp > Mucous retention
275 HNS33 C X-ray features of sinusitis Air fluid level (normally shouldn't have any fluid levels)
276 HNS33 C Otitis externa: briefly the pathophysiology Disturbed earwax removal cycle > accumulate dead skin > breeding of
bacteria and inflammation
277 HNS33 D Earwax removal cycle (brief) Pars tensa multiply outwards, skin shed out (i.e. self-cleaning)
278 HNS33 C Contents of earwax Desquamated cell, cerumen, sebum
279 HNS33 D Function of earwax Protection (impermeable to water and acid)
280 HNS33 B Causative agents of tonsillitis Bacterial (Streptococcus pyogenes, Streptococcus pneumoniae, H
influenzae); Viral (Rhinovirus adenovirus EBV), Others (Syphilis
diphtheria MTB)
281 HNS33 C Complications of tonsillitis Peritonsillar abscess (Quinsy)
282 HNS33 C Cause of sialadenitis Blockages of gland by e.g. stone > Saliva build-up
283 HNS33 C Commonest gland for sialadenitis Parotid
284 HNS33 A How to differentiate between viral vs. streptococcal things? (See: Dr. SSY Wong CPRS62 Upper Respiratory Tract Infections:
https://ibb.co/18sx1fS)
285 HNS36 B Convulsion in middle-aged patients is suggestive of Neoplasia
286 HNS36 B Where does secondary brain tumor usually affect Junction of white and grey matter of brain and rarely involves meninges

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 287 HNS36 A Histological pattern of meningioma 1. Whorled pattern of meningothelial cells. 2. Psammoma body
formation. 3. Small calcospherites. 4. Fibroblastic proliferation.
288 HNS36 A Secondary brain tumor from stomach: 3 histological signs Signet ring (gastric adenocarcinoma), Glandular differentiation,
Cytological malignant features e.g. pleomorphism, increased mitotic
figure, disorganized architecture)
289 HNS36 A Where is adenocarcinoma commonly found (i.e. where to inspect if Lung, Stomach, Breast
patient shows metastatic adenocarcinoma)
290 HNS36 B Intracranial tumors of neuroectodermal origin (x 4) and others (x 2): Glioblastoma multiforme, Astrocytoma, Oligodendroglioma,
name them Ependymomas (These 4: Neuroectodermal origin). Schwannoma,
Meningioma, medulloblastoma.
291 HNS36 C Guess the brain tumor: Child tumor although not the commonest. Astrocytoma
Occurs at brainstem and cerebellum. Diffuse and aggressive,
recurrence very common.
292 HNS36 C Guess the brain tumor: Commonest tumors in childhood, sensitive Medulloblastoma
to radiotherapy. Occurs at vermis of cerebellum, densely stained
nucleus, rosette
293 HNS36 C For your memory: the 2 types of childhood tumor and where they Medulloblastoma, Astrocytoma. Affects cerebellum (Vermis, and
affect? cerebellum/brainstem respectively)
294 HNS36 C Guess the brain tumor: Middle age, aggressive, varied histology Glioblastoma multiforme
295 HNS36 B Histological feature of glioblastoma multiforme Pseudopallisade formation
296 HNS36 C Guess the brain tumor: Good prognosis, calcification, purple brown, Oligodendrogliomas
box-like
297 HNS36 C Guess the brain tumor: At brainstem or cerebellum, leads to Ependymomas
increased ICP, forms rosette and pseudorosette
298 HNS36 C Guess the brain tumor: Occurs at acoustic nerve or CN5, 2 types. Schwannoma
Type A palisading, type B forms patches
299 HNS36 C Guess the brain tumor: occurs in old women, good prognosis Meningioma
300 HNS36 A Guess the brain tumor: found in children Medulloblastoma (The other possible one is Astrocytoma, but really
medulloblastoma is far more common)
301 HNS36 B Guess the brain tumor: histologically most malignant Glioblastoma multiforme
302 HNS36 A Guess the brain tumor: (middle-aged lady) complaining hearing Schwannoma (The fact that it is middle aged women might point to
loss, mass at cerebellopontine angle meningioma, but hearing loss and cerebellopontine angle is too much a
sign to miss, both suggesting schwannoma)
303 HNS36 A Guess the brain tumor: Mass at falx cerebri, psammoma bodies Meningioma
304 HNS39_F A CN problem: Ptosis III (Innervates Levator palpebrae superioris)
305 HNS39_F C (For PBL) Venous vs. artery occlusion: How to differentiate Gradual vs. Immediate effects

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 306 HNS39_F C Where does danger triangle of face include Nose + Upper lip
307 HNS39_F A What is special about the cavernous sinus? VALVELESS
308 HNS39_F A Clinical importance of danger triangle of face Much anastomosis VALVELESS allows extracranial infection to spread
intracranially.
309 HNS43 A Characteristic of smooth pursuit system Assures foveal fixation
310 HNS43 C What is the trigger for smooth pursuit system Moving image
311 HNS43 C Gaze stabilization is brought about by which eye movements Optokinetic, Vestibulo-ocular
312 HNS43 B How is saccade generated? Burst of output from moving eye to new object
313 HNS43 B Characteristic of saccade Can be modified by visual feedback
314 HNS43 C Guess the eye movement: holds image steady on retina Optokinetic
315 HNS43 B Conjugate eye movement requires PPRF. What does that stand for? Paramedian pontine reticular formation
316 HNS43 B Vestibulo-ocular reflex involves which nucleus VIII Vestibular
317 HNS43 B Recite: 5 basic eye movements (1) Saccade: Rapid and ballistic movement. Modified by visual feedback.
Initiated by burst of signals. (2) Slow pursuit: ASSURES FOVEAL
FIXATION, triggered by moving image. Used to track moving objects,
slow and quasi-voluntary. (3) Vergence: Align fovea of each eye with
targets located at different distance from observer. (4) Vestibulo-ocular
reflex: Gaze stabilization brought by eye moves in a direction opposite
to head movement. Involves VIII Vestibular and PPRF (Paramedian
pontine reticular formation). (5) Optokinetic: Gaze stabilization driven
by retina slip > Image steady on retina
318 HNS43 B Classification of memory Declarative (Explicit, Conscious) for Daily episodes, word meanings,
history. Nondeclarative (Implicit, Unconscious) Motor procedures /
procedural, Associative conditioning, Priming, Habitual / non-
associative learning (Details see Dr Lim's powerpoint:
https://ibb.co/vzJRD0v)
319 HNS43 B 3 types of temporal memories Immediate, Short, Long term
320 HNS43 D Priming meaning Change in processing of stimulus due to previous encounter
321 HNS43 C 4 distinct process of memory Encoding (acquire new information), Storage (in cortical layers),
Consolidation (Labile information > Stable information), Retrieval
(recall)
322 HNS43 C 2 types of Amnesia. Retrograde (Forgets previous events) vs. Anterograde (Cannot form
new memories)

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200
REFERENCE AND SUPPLEMENTARY MATERIALS

SOME OTHER DIAGRAMS

UMN vs. LMN (Alternative version):

202
MICROBIOLOGY PRACTICAL II: THE MICROBIOLOGY INVESTIGATION OF CNS
INFECTIONS II
Note: Faculty has their own notes which are in greater detail for this practical. Strongly
recommend you refer to that one instead, it is more useful.

OVERVIEW

1. Demonstration
2. Cases

DEMONSTRATION

 Inverted microscope of cytopathic effects: illustrate virus's cytopathic effect on monolayers

of cells. Rabies and enterovirus also can be cultured because of their characteristic patterns
of cytopathy. However, virus culture is now seldom used because it is slow (several days).
 Viral transport medium often with base balanced salt, ingredients to maintain viral activity,
some antibiotics and antifungals to keep them sterile, with pH indicator (to tell if they are
optimal for use. Orange indicates neutral pH and these are ready for use. Purple means it is
alkaline and shouldn't be used. Yellow shows its acidic and shouldn't be used. Viral transport
medium. Should refrigerate if delayed transport (but don't freeze, virus will be killed).
 PCR. Recall stages: Denaturation, Primer annealing, Elongation, Repeat. Different types of
probes, fluorescence, etc. Some more advanced stuff.
 Antibody response: Recall typical IgM (Immediate and short-lived / few months) and IgG
(Later and long-lived / life-long)
 Cryptococcus neoformans: Indian Ink doesn't enter capsule, hence white halo / clear zone.

CASES

CASE 4

History: 2 YO, Flu-like illness and fever. To GP in morning, vomited 3 times, 39C, neck stiffness.
Refer to hospital.

Investigations: Lumbar puncture. Clear, WBC elevated, 90% lymphocytes. Protein increase, glucose
normal. Gram stain -ve, Acid fast -ve, Indian ink stain -ve. Inoculate in blood and chocolate agar, -ve.
Compliment fixation test for virus, acute serum non conclusive. Further inoculate in monkey kidney
cell line, enterovirus infected.

Diagnosis: by performing neutralization test. Persist cytopathy in anti-cox b. Anti-echovirus shows

non-cytopathy, hence anti-echovirus can neutralize pathogen. Diagnosed as echovirus. Further
confirm with PCR + Electrophoresis.

CASE 5

History: 35/F, 5 days fever, abnormal behavior, seizure, confuse, febrile 38.5C

CSF: Clear, Elevated WBC slightly, lymphocytes predominant. Protein elevated, glucose normal.
Gram stain WBC with none identified bacteria, ZN-ve, Indian ink -ve. Blood and chocolate agar -ve.
Inoculation to lung fibroblast cell yields non-significant cytopathy, although this doesn't completely
exclude virus (low sensitivity esp. in low viral load). PCR shows HSV+. Paired serum in acute &

203
Convalescence, 4-fold rise in HSV, hence a recent infection. Recall route of virus in herpes simplex
encephalitis, direct infection of olfactory bulb could go to frontal, then spread to parietal. Small
sensory fibers from trigeminal ganglion projects to dura mater in anterior dura fossa. Recall HSV
encephalitis is an emergency with high mortality rate. Gross anatomy of brain shows marked
hemorrhages.

CASE 6

History: 40/M, Recurrent headache, progressive confusion, forgetfulness. PE confused otherwise

stable, mild neck rigidity.

CSF: Turbid, WBC elevated, lymphocyte predominant, Protein elevated, glucose decrease. Indian
ink positive, encapsulated yeast. Gram smear saw yeast, ZN saw yeast, Indian ink shows
encapsulated yeast with thick halo, characteristic of cryptococcus neoformans (CN). Blood culture
and isolated form culture yields fungus. Urea slant tests + (changes yellow to red/pink, since CN is
urease positive). Other tests: cryptococcal antigen lateral flow assay, this is fast and easy, just enter
strip and see double strip (Control + test band).

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AIRWAY MICROBIOLOGY (TAKEN FROM CPRS 62 UPPER RESPIRATORY TRACT
INFECTIONS)

UPPER RESPIRATORY TRACT INFECTION

Upper respiratory tract infection
Diphtheria
Causative Corynebacterium diphtheriae
Agent’s special Chinese character palisades
things Metachromatic granules
Pathogenesis Toxin mediated
Swab Throat swab
Epidemiology Droplet transmission, Asymptomatic carrier
Related conditions Cutaneous diphtheria (On skin)
Management Treatment: Antitoxin, Penicillin, Erythromycin
Prophylaxis: TOXOID Vaccination
Pharyngitis
Causative Mostly viral
Group A streptococcus (Streptococcus pyogenes)
Transmission (Group A streptococcus) Aerosol
Presentation and For Group A streptococcus: Suppurative (e.g. pneumonia, bacteraemia), Non-
complications suppurative (Rheumatic heart disease, glomerulonephritis)
Treatment For Group A streptococcus: Penicillin
Acute Epiglottis
Epidemiology Usually children, sometimes adults
Causative Hemophilus influenza, etc.
Management Be ready to intube (Laryngoscopy)
Investigations Laryngoscopy, lateral neck X-ray
Treatment 3rd generation cephalosporin
Acute sinusitis
Causative Allergy
Bacteria: Streptococcus pneumonia, Haemophilus influenza, Moraxella catarrhalis
Viral: Rhinovirus, parainfluenza, etc.
Diagnosis Sinus X ray, sinus puncture (not for routine)
Management Empirical antibiotics (amoxicillin-clavulanate: Covers Streptococcus
pneumonia + Haemophilus influenza) [No need microbiological investigation in
healthy children]
Acute otitis media
Epidemiology Childhood disease
At risk population Anatomical defects that inhibit middle ear drainage (e.g. Cleft palate),
Immunodeficiency
Causative Mainly bacterial: Streptococcal pneumonia, Haemophilus influenzae, Moraxella
catarrhalis
Clinical signs Ear drainage, hearing loss
Diagnosis Clinical, tympanocentesis
Management Empirical antibodies (e.g. amoxicillin-clavulanate)
Otitis externa
Causative Staphylococcus aureus, etc.

LOWER RESPIRATORY TRACT INFECTION I

Lower respiratory tract infection I
CROUP
Aetiology of croup Viral (Parainfluenza, Influenza, Rhinovirus BUT NOT

205

Clinical manifestations of croup.
Methods for aetiological diagnosis of
croup.
Principles of management of croup.
PERTUSSIS
Microbiological characteristics of
Bordetella pertussis.
Current epidemiology of pertussis.
Key clinical manifestations of
pertussis.
(A bit of pathology)
Methods for aetiological diagnosis
of pertussis.
Clinical presentation
Principles of management of
pertussis.
Vaccines against pertussis.
PNEUMONIA
Important pathogens of community-
acquired pneumonia.
Clinical approach to community-
acquired pneumonia.
Laboratory diagnosis of community-
acquired pneumonia.
Principles of treatment for
community-acquired pneumonia.
ATYPICAL PNEUMONIA, LUNG ABSCESS, EMPYEMA THORACIS
Clinical characteristics.
Common pathogens involved.
Tests of choice for aetiological
diagnosis.
NOSOCOMIAL
At risk population
Common pathogens
Empirical treatment
Others
Aspiration pneumonia: Causative
Lung abscess
Empyema thoracis
206
coronavirus), children
Seal’s bark, Steeper sign, inspiratory stridor
Antigen detection
Ventilatory support
Gram negative coccobacillus
Mainly children, sometimes adults. Droplet transmission.
Whoop, post-tussive vomiting
Toxin mediated
Virulent factors (for attachment): Fimbriae, Filamentous
haemagglutinin
Culture: Bordet Gengou medium
Infants with severe cough, Subconjunctival haemorrhage
Macrolides
Killed whole cell, Acellular vaccines
Streptococcus pneumoniae
Haemophilus influenzae, Staphylococcus aureus, Klebsiella
pneumoniae
Lung disease (e.g. COPD): Pseudomonas aeruginosa
Children: Virus
Others: TB
Evaluation: Aetiology (Acute vs. Chronic), History (Community
acquired vs. Nosocomial; exposure history), Patient characteristic
(Immunodeficient?), Physical examination, inspections (e.g. blood
count)
Culture, viral antigen detection, PCR
SPUTUM collection!
Antibiotic (Beta lactam + macrolide)
Atypical: Long course, not responding to empirical antibiotics, no
findings on normal agar
Mycoplasma pneumonia, Chlamydia, Chlamydophila, legionella
Antigen test, PCR, special medium culture
Intubed (bypass physical barriers)
Resistant (e.g. MRSA)
Piperacillin, Tazobactam
Immediate: Chemical (e.g. Reflux), Foreign body
Subsequently: Bacterial pneumonia (Common causative:
Anaerobes in oropharynx)
Cavitating pus, shows air fluid level
Pus in pleural space