Selected lecture materials

(for systematic approach and details

refer to seminars and listed literature,
video materials attached)
Course in Neurology
Medical University of Gdansk
Faculty of Medicine
Department of Neurology
(Head: Prof. Bartosz Karaszewski)

Dept Team work

(to be updated each year)
Neurological examination : A I M S

1. identify symptoms / cluster symptoms

(history, physical examination)
2. localize within the nervous system (take into account
that lesions might be multiple, diffuse or pathology
might concern complex pathways)
(history, physical examination, neuroimaging,
electrophysiology, other)
3. etiology
(history, physical examination, neuroimaging,
electrophysiology, lab, other)
4. prevention and treatment
(evidence-based medicine: clinical trials, metaanalyses,
rare diseases)
source: Daroff RB, Fenichel GM, Jankovic J, Mazziotta JC: Bradley's
Neurology in Clinical Practice, Elsevier Medical Books,
Philadelphia, PA, 2012
Extreme attention to localisation
(functional anatomy)

Is your patient’s disorder focal, multifocal or

system ?
source:http://quizlet.com/11292074/chapter-11-fundamentals-of-the-nervous-system-and-nervous-tissue-flash-cards/
A patient with feet numbness:
1) Peripheral neuropathy ?
2) Combined with backache and loss of
sphincter control – spinal cord / cauda
equina lesion
A patient complaing of progressive weakness in
right limbs
1) Combined with ataxia and unilateral deafness
– acoustic neuroma ?
2) Combined with aphasia – acute stroke, left
hemisphere ?
A patient with paraparesis
1) Combined with back pain – spinal cord
lesion ?
2) Combined with headache – parasagital
meningioma ?
 Cerebrovascular disorders
- selection, mainly acute stroke
Cerebral arteries
 Circle of Willis
• Circle of Willis
• Carotid and vertebrobasilar
arteries

– anterior cerebral artery (ACA)

– middle cerebral artery (MCA)
– posterior cerebral artery (PCA)
 WHO 1976 (historical)

 a clinical syndrome characterized by rapidly

developing clinical symptoms and/or signs of
focal and global loss of cerebral function

 with symptoms lasting more than 24 hours or

leading to death

 with no apparent cause other than that of

vascular origin
Ischemic stroke 85% Intracerebral
hemorrhage 10%

Subarachnoidal bleeding 5%
 Epidemiology (stroke)

• Second / third / fourth / fifth (depending on

methodology / disease classification) cause of
mortality in humans

• Main (first) cause of complex persistent disability

in adults

• General mortality after stroke – about 30% within

a year from onset
 Ischemic Stroke – basic terms

- Ischemic stroke vs brain infarction

- Penumbra and (vs) tissue at risk
- Large vessel occlusion (large vesse disease) vs small
vessel occlusion (small vessel disease)
- Acute ischemia vs hypoxia, asphyxia
 Ischemic Stroke – etiology
• Large-artery local disease
• Arterio-arterial embolism (resulting in large or/and
small vessel occlusion)
• Cardioembolism (resulting in large or/and small vessel
occlusion)
• Small-artery occlusive disease
• ’Venous strokes’
• Hemodynamic strokes: watershed and internal-zone
(local or/and systemic hemodynamics)
• Blood disorders

Varius background causes in each category

eg, coagulopathies, hemoglobinopathies, hyperviscosity (eg due to polycythemia

or thrombocytosis), arterial wall pathology (arteritis – rheumatoid vasculitis, SLE,
polyarteritis nodosa, giant cell arteritis, Takayasu’s arteritis, granulomatous
arteritis – ”Wegener’s granulomatosis”), fibromuscular dysplasia, sarcoidosis,
post-radiotherapy, etc.
 Ischemic Stroke – etiology
Location, „shape” (area involved) and distribution of lesions in
the brain help to conclude on etiology

• Occlusion
– Large vessel ( teritorial infarction)
– Branch vessel (subteritorial infarction)
– Perforating vessel (lacunar infarction)
• No occlusion
– Watershed / internal zone
• Venous characteristics
Thrombogenesis of ICA
Localisation of atherosclerotic stenoses
 ICA stenosis

• Asymptomatic : sufficient Willis circulstion

(sometimes even with bilateral occlusion)
• Symptomatic : cause of 20 % of ischemic
strokes ( 1.hemodynamic compromise,
2. cerebral embolism )
Carotid endarterectomy or stenting
in stroke prevention
 Dissection of ICA

source: Uncommon Causes of Stroke; W: Practical Neuroimaging in Stroke: A Case-

Based Approach; Autorzy: Alejandro A. Rabinstein, Steven J. Resnick; Wydawnictwo
Saunders, 2010
 CTA (VA dissection)

dzięki uprzejmości: II Zakład Radiologii Gdańskiego Uniwersytetu

Medycznego
TOF (VA dissection)
Thromboembolism
 Cardioembolism
- Atrial fibrillation
- Recent myocardial infarction
- Prosthetic valves
- Rheumatoid heart disease
- Ischemic heart disease
- Bacterial endocarditis
- Atrial myxoma
- Patent foramen ovale (paradoxical embolism)
– Fat / air/ tumor emboli
– Other
 CADASIL (FLAIR, axial)

anterior-temporal external capsule semiovale

 CADASIL (T2, SE, sagittal)

occipital-sparing pons
 CADASIL

(T2, TSE, SPAIR /turbo spin

echo sequence with fat
saturation/ coronal)

orbitofrontal-sparing
Low-flow infarcts 5-10%

Watershed infarcts
-MCA/ ACA
- MCA/PCA

Eg, acute heart failure

Low flow strokes: a- internal zone
b- watershed
 Hemodynamic stroke – example causes

• Acute hypotonia
• Severe anemia
• Carotid artery stenosis/occlusion

Potential triggers : exercise, cough, large dinner, emotions, hot bath,

excess heat, high mountaineering
 Lenticulostriate arteries
perforating arteries

• Lacunar stroke (d<1,5cm)

• Poorly controlled
hypertension
• Lipohialinosis – occlusion
• Embolism
• Other
Lacunar syndromes
 Differential diagnosis, masks
• Hypo- and hyperglycemia
• Electrolyte imbalances (esp. re sodium)
• Toxcity of various origin
• Epidural or subdural hematoma
• Brain tumors
• Post-seizure
• Migraine
• Other (plenty)
 Early CT changes (examples)
early CT (top)
24h CT (bottom)

Obscuration Loss of
of basal insular
ganglia ribbon
 Early CT changes (examples)
early CT (top)
24h CT (bottom)

Effacement
of sulci
Hyperdensive MCA
Hemorrhagic transformation
Intracerebral hemorrhage (ICH)
• 15% of all strokes
• Severe acute headache much more common
than in acute brain ischemia
• Basic classification:
– Intracerebral hemorrhage
– Subarachnoid hemorrhage
– Mixed
• Primary (hemorrhagic stroke – various
reasons) vs secondary (into another brain
structural pathology eg, tumor or ischemic
transformation)
 ICH – hypertensive
arteriopathy
• micro-aneurysms (Charcot-Bouchard)
• typical localisation:
Subarachnoidal hemorrhage
(SAH)
Circle of Willis
Cerebral aneurysms

Symptoms due to:

1. Mass efect
(”tumour”)

2. Bleeding
(”stroke” and
”meningismus”)
 Aneurysm - shape

Saccular Fusiform
(sac-like) (spindle-shaped)
 Fusiform aneurysm-
often basilar and vertebral arteries
• Acute – dissection
• Chronic – non-
atheromatous
vasculopathy, e.g.
autoimmunologic and
connective tissue
disease
 SAH
• Endovascular coiling (closure)
• Neurosurgical clipping
• Neuro-Intensive care (complex, various problems)
Chronic neurological disorders
- selection
 Global burden of neurological disorders

Disability-adjusted life-years (DALY)

DALY: combination of 2 components:

 years lost due to premature mortality
 years lived with disability

One DALY is the equivalent of one healthy life-year lost

Contribution of specific causes to the combined burden of neurological
and cerebrovascular diseases

The global burden of neurologic diseases.

Chin, Jerome; MD, PhD; Vora, Nirali

Neurology. 83(4):349-351, July 22, 2014.

DOI: 10.1212/WNL.0000000000000610

Source: GBD 2010 Results by Cause 1990-2010. Available at:

http://ghdx.healthmetricsandevaluation.org/global-burden-
disease-study-2010-gbd-2010-data-downloads.

© 2014 American Academy of Neurology. Published by American Academy of Neurology. 2

 Table DALY

The global burden of neurologic diseases.

Chin, Jerome; MD, PhD; Vora, Nirali

Neurology. 83(4):349-351, July 22, 2014.

DOI: 10.1212/WNL.0000000000000610

Table DALY for all causes and for neurologic disorders and cerebrovascular disease, stratified by region and income

© 2014 American Academy of Neurology. Published by American Academy of Neurology. 2

Dementia
 Dementia - epidemiology

Dementia by type in Canadian

population (Feldman et al. Neuroepidemiology, 2003)

latin demens - ‘without mind’

Dementia - “a global deterioration of

mental functioning in its cognitive,
emotional and conative aspects”
(Fratiglioni L, et al. Lancet Neurol 2004)
 Epidemiology
Approximately 5% of the over 65-year-olds and more than 50%
●

of 90-year-olds have a dementia disorder

●More than 25 million people worldwide suffered from dementia

in 2000. By 2030, that number is expected to rise up to 63
million, 65% of whom in less developed countries
(Launer LJ. Aging 2005)

According to the European Collaboration on Dementia in

●

Europe, there are currently 8.45 million patients with AD

Dementia causes a significant financial burden to the society,

●

which is estimated at 141 billion Euros annualy

 Alzheimer’s disease (AD)
- described in 1906 by a German psychiatrist and
neuropathologist, Alois Alzheimer
- initially named ”presenile dementia"
- Alzheimer’s disease used for the first time by Emil
Kraepelin in 1910
 Alzheimer Disease:
"What is your name?“ "Auguste.“
"Family name?“ "Auguste.“
"What is your husband's name?“ - she
hesitates, finally answers: "I believe ...
Auguste.“
"Your husband?“ "Oh, so!“
"How old are you?“ "Fifty-one.“
"Where do you live?“
"Oh, you have been to our place“
"Are you married?“ "Oh, I am so
confused.“
"Where are you right now?“ "Here and
Auguste Deter
everywhere, here and now, you must not
think badly of me.“
"Where are you at the moment?“ "This is
where I will live.“
"Where is your bed?“ "Where should it
be?“
AD - neuropathology
AD - pathology
AD-pathology
Stages of Alzheimer Disease
 Diagnosis of AD

- Neuropsychological assessment of
cognitive functions (episodic memory
impairement is the first deviation in most
patients)

- Neuroimaging (preferably MRI);

hypocampal atrophy – sensitivity and
specificity 80-90%

- CSF (decreased concentration of beta-

amyloid 42 (Ab42) and increased
Florida Alzheimer’s disease Reaserch Center
concentration of total-tau or phospho-tau);
combined assessment of the two results
in sensitivitity of 85–94% and specificity of
83–100%
 AD - treatment

Cholinesterase Inhibitors (ChEIs) – donepezil, rivastigmine and

●

galantamine; Efficacy on cognitive function; shown in the RCTs in patients

with mild to moderate AD

Memantine (a non-competitive N-methyl-D-aspartate receptor antagonist) -

●

moderate to severe AD (RCTs)

● The benefits of combining memantine and ChEIs not clear

●Cognitive stimulation or rehabilitation may be considered in patients with

mild to moderate AD (good practice point). Occupational therapy can
improve patients functioning and reduce needs for informal care

● Antipsychotics – in special situations (not routinely)

Movement disorders
Parkinson disease (PD)
 Parkinson disease

- Neurodegenerative
- Age of onset 20-80yrs, mean at diagnosis – 55
- Morbidity 160/100 000 in general population, 550/100
000 in elderly >70yrs
- Necrosis of the dopaminergic cells of the ventral part
of substantia nigra pars compacta: motor symptoms
start when ~ 60% are necrotic / striatum concentraion
of dopamine is reduced by ~ 80%
 Parkinson disease
Step 1 Check towards the Parkinsonian syndrome (combination
of specific signs and symptoms)

Bradykinesia (slowness of initiation of voluntary movements with

progressive reduction in speed and amplitude or repetitive actions)
PLUS at least one of the following:
 Muscular rigidity
 4- to 6-Hz rest tremor
 Postural instability that is not caused by primary visual, vestibular,
cerebellar or proprioceptive dysfunction
 Parkinson disease (PD)
Step 2 Exclusion criteria for Parkinson's disease
- Stroke / reccurent strokes with stepwise
progression of parkinsonian characteristics - Strictly unilateral features after 3 years

- Head injury / repeated head injuries - Supranuclear gaze palsy

- History of encephalitis - Cerebellar signs

- Oculogyric crises - Early severe autonomic involvement

- Neuroleptic treatment at onset of symptoms - Early severe dementia with disturbances of

memory, language and praxis
- More than one affected relative (*)
- Babinski’s sign
- Sustained remission
- Presence of a cerebral tumour or
communicating hydrocephalus on CT
- Negative response to large doses of L-dopa
(exclude malabsorption)
- MPTP exposure
- Other
 Parkinson disease (PD)
Step 3 Supportive prospective positive criteria of Parkinson's disease

Three or more required (definite diagnosis):

 Unilateral onset
 Rest tremor
 Progressive disorder
 Persistent asymmetry (*)
 Excellent response (70–100%) to L-dopa
 Severe L-dopa-induced chorea
 Responding to L-dopa for 5 or more years (*)
 Clinical course of 10 years or more (*)
 Hyposmia
 Visual hallucinations
Parkinson disease (PD)

Smith et al. 2012

Parkinson disease
 Parkinson disease
- treatment options (general approach)
Pharmacotherapy Nonpharmacological

 Levodopa  Education
 Dopamine agonsts  Nutrition
 MAO-B inhibitors  Excercise
 COMT inhibitors  Support services
 Amantadine
 Anticholinergics Surgery

 Deep brain stimulation

 Other / epeimental
Parkinson disease - progression
Parkinson disease - DBS
Parkinson disease - DBS
 Dystonia
 sustained or intermittent muscle contractions causing abnormal, often repetitive
movements, postures, or both
 dystonic movements are typically patterned, twisting, and may be tremulous
 often initiated or worsened by voluntary action, and associated with overflow
muscle activation

Albanese A et al., Mov Disord, 2013

 Classification of dystonia
1. Age at onset
• Infancy (birth to 2 years)
• Childhood (3–12 years)
• Adolescence (13–20 years)
• Early adulthood (21–40 years)
• Late adulthood (>40 years)
2. Distribution
• Focal
• Segmental
• Multifocal
• Generalized (with or without leg involvement)
• Hemidystonia

Albanese A et al., Mov Disord, 2013

Cervical dystonia
Writers cramp
Meige syndrome
 Dystonia: treatment

 Botulinum toxin
 Pallidal DBS
 Dopaminergic therapy
 Anidopaminergic therapy (tetrabenazine)
 Anicholinergic drugs
 Baclofen
 Other/supportive
Huntington's Disease
 Huntington's disease

 Autosomal dominant (AD), neurodegenerative disease leading

to motor, cognitive and behavioural impairement
 Mutation of huntingtin gene (HTT, 4 chromosome);
expansion of CAG triplets (<35 – normal: not affected, 36-39 –
reduced penetrance; >40 – full penetrance), dynamic
mutation, amplification
 Onset of symptoms 35-44yrs
 <10% starts before the age of 20 (juvenile, Westphal variant),
akinetic-rigid syndrome
Huntington disease
Friedreich's ataxia
 Friedreich's ataxia
 Autosomal recessive, neurodegenerative disease
 Amplification of GAA triplets in the FXN gene (chromosome 9)
(<34 – normal, 34-65 – permutation, 66-1700 – disease)
reduced level of frataxin (iron-binding proteins), 96%
homozygotic
 Onset at 8-15yrs (rarely >50)
 Morbidity 1/30 000-50 000 (Europe, USA), most common
cause of inherited ataxia
 atactic gait is the firs symptom in most patients
Friedreich's ataxia
Multiple sclerosis
 Multiple slerosis
clinical course in the early phase
Multiple sclerosis – patients complaints

www.mutiplesclerosis.net
 Multiple sclerosis
– general clinical course
Multiple sclerosis – natural history
Multiple sclerosis - diagosis
Multiple sclerosis - diagnosis
Motor unit
 Neuromuscular disaeses
- general classification
Spinal Muscular atrophy (SMA) and otherdisorders of motor neuron
a) Spinal muscular atrophies (Type 1-4)
b) Motor neuron disaese (eg, ALS)
c) Viral disorders (eg, Poliomyelitis)

Disorders of motor nerve roots (eg. disc prolapse, tumor)

Disorders of peripheral nerves

a) Genetically determined polyneuropathies (eg, CMT)
b) Acquired polyneuropathies (eg, GBS, CIDP, paraproteinemias)
c) Mononeuropathies (eg, posttraumatic, vasulitis)
 Neuromuscular disaeses
- general classification (contin.)

Disorders of neuromuscular transmission

a) Myasthenia gravis
b) Lambert-Eaton syndrome

Muscular disorders
a) Genetically determined myopaties (eg, DMD, BMD)
b) Acquired myopathies (eg, drug induced, inflammatory)
c) Metabolic myopathies (eg, glycogen storage errors,
endocrine mypathies)
 Amyotophic Lateral Sclerosis (ALS)

 Prevalence 3.9/100 000 in general population (USA)

 Mean age at onset 60-69yrs
 More common among white males
 90-95% - sporadic, 5-10% - familial (1/3: mutation in
“chromosome 9 open reading frame 72” gene, 1/5:
mutation in SOD1 gene)
Amyotrophic Lateral Sclerosis (ALS)
 RILUZOL

EDARAVONE