Pathology of the

Nervous System
Prof Madya Dr Zariyantey Abd Hamid
OVERVIEW
HYDROCEPHALUS
CSF FORMATION
 CSF
FLOW
6
HYDROCEPHALUS
 TYPES OF HYDROCEPHALUS
• Non-communicating or obstructive
(Obstruction within ventricular system)

• Communicating or non-obstructive
(Malfunction of arachnoid villi)
 CAUSES OF HYDROCEPHALUS
§ Lesions or malformations of the posterior
fossa:
a) Chiari malformations : structural
defects in the cerebellum
b) Dandy-walker syndrome

§ Tumors
§ Meningitis
§ Hemorrhage
 Dandy – Walker
Malformation

• Rare congenital malformation

that involves the cerebellum
and fourth ventricle.

• Characterized by:
i. agenesis or hypoplasia of
the cerebellar vermis,
ii. cystic dilatation of the
fourth ventricle,
iii. and enlargement of the
posterior fossa.
 Chiari
Malformation

• Structural defects in the base of the

skull and cerebellum, the part of the
brain that controls balance.

• Normally the cerebellum and parts of

the brain stem sit above an opening in
the skull that allows the spinal cord to
pass through it (called the foramen
magnum).

• When part of the cerebellum extends

below the foramen magnum and into
the upper spinal canal, it is called a
Chiari malformation (CM).
CLINICAL MANIFESTATIONS

§ NEUROLOGICAL SYMPTOMS:
1. POOR FEED
2. LETHARGY
3. VOMITING
4. HEADACHE
 COMPLICATIONS
• Can cause serious illness leading to coma and eventually death.

• Increased Risk For Developmental Disabilities

• Mean IQ Is Reduced Compared To General Population

• Abnormalities In Memory

• Visual Problems

• Patients Require Long Term Follow Up (Multidisciplinary) For Symptom

Managements

• Some Patients Show Aggressive Behavior.

 THERAPY
§ MEDICAL:
a) ACETAZOLAMIDE
b) FUROSEMIDE

§ SURGICAL:
a) V-P (Ventriculoperitoneal) SHUNT PLACEMENT
VP - SHUNT

SHUNT SYSTEMS
 Vascular and
Circulatory Disorders

STROKE
 DEFINITIONS
Transient Ischemic Attack (TIA)
• A stroke in which symptoms resolve within 24 hours
• also known as a ministroke,
• a temporary decrease in blood supply to part of brain causes TIA,
• TIA occurs when a clot or debris blocks blood flow to part of
brain and the blockage is temporary.

Stroke
• A stroke in which symptoms resolve within more than 24 hours

Progressive stroke
• A stroke that are still evolving and the patient’s condition continues
to worsen.
• This condition is usually the result of severe hemorrhage
 MAJOR CLASSIFICATION OF STROKE
• known as a Cerebral Vascular Attack (CVA),
• defined as when blood flow is interrupted or reduced to the brain.
• When blood flow is not present in the brain, brain cells die rather quickly which
can result in permanent damage.
• two major classification of stroke : Ischemic and hemorrhagic strokes

ISCHEMIC STROKE HEMORRHAGIC STROKE

• Defined as when arteries are narrowed or
blocked causing decreased blood flow to the
brain.
• 85% of strokes are categorized as ischemic.
• Two subcategories of Ischemic Stroke:
Thrombotic and Embolic Stroke
• Defined as when a blood vessel in the
brain leaks or ruptures.
• Also known as red infarct
• Brain hemorrhages can result from
many conditions such as uncontrolled
high blood pressure (hypertension),
over usage of anticoagulants and weak
spots in blood vessel walls (aneurysms)
• two subcategories of hemorrhagic
stroke: Subarachnoid Hemorrhage and
Intracerebral Hemorrhage.
 MAJOR CLASSIFICATION OF STROKE
Classified based on the mechanism of stroke:

Ischemic (Infarction)
• Thrombosis : occurs when a blood clot (thrombus) forms in one of the arteries that
supply blood to brain
• Embolism : occurs when a blood clot or other debris forms away from brain is
circulated through bloodstream to lodge in narrower brain arteries
• Hypotensive stroke – cerebral hypoperfusion commonly associated with shock.

Hemorrhagic Stroke
• Intracerebral hemorrhage: a blood vessel in the brain bursts and spills into the
surrounding brain tissue, damaging brain cells. Brain cells nearby are also deprived of
blood and damaged
• Subarachnoid hemorrhage: an artery on or near the surface of brain bursts and spills
into the space between the surface of brain and skull, further limiting the blood flow.

Cryptogenic Stroke
- unknown origin , the cause can’t be determined.
Conditions influencing progression and
extent of ischemic injury
 Major Categories
of Ischemic Stroke

■ Thrombosis

■ Embolism

■ Hypotensive Stroke
 Thrombotic Stroke
Large blood vessel infarct
• Atherosclerosis in patients with hypertension, hypercholesterolemia
and diabetes mellitus
• Cause blood vessel prone to injury and subsequent clot formation
• Lead to occlusive blood vessel – reduced cerebral blood flow and
cerebral perfusion – ischemia – infarct.

Small blood vessel infarct

• Microatheroma – small atheroma due to plaque formation on the
interior wall of blood vessel
• Lipohyalinosis due to untreated diabetes mellitus and hypertension.
A degenerative disease marked by lipids that accumulate within the
walls of blood vessels:
• Embolism
• Micro-anuerysms – further complication can lead to bleeding
 Thrombotic Stroke

Other pathological causes:

i. Fibro muscular dysplasia
ii. Arteritis
iii. Hypercoagulability – abnormality of blood
coagulation – increases the risk of
thrombosis
 Embolic Stroke
• Embolism originate from detachment of a
thrombus from the site of a plaque or from other
sources of embolus eg: cancer cells, fat cells, air

• Generally “smaller” strokes than thrombotic

strokes
Hypotensive Stroke
 Hemorrhagic Stroke
■ Traumatic causes

■ Non-traumatic causes
i. Chronic hypertension
ii. Vascular malfunction ; fibromuscular dysplasia, aneurysm
iii. Bleeding disorders
iv. Anticoagulation therapy
v. Amyloid angiopathy – amyloid deposition weaken the blood
vessel , increase risk of bleeding
Fibromuscular dysplasia : Abnormal growth Aneursym: a weakening and bulging
within the wall of an artery of an artery wall
 SIGNS OF STROKE
Slurred speech, Droppy face Headache, Sound worsens

Leaning to one side when walking; Lost balancing

Total or partial loss of vision, Blurred vision

Arm weakness or numbness on one side

 Risk Factors for Stroke

1. Diabetes mellitus
2. Abnormality of systemic blood circulation ; eg hypertension
and hypotension
3. Vascular abnormality ; eg Anuerysm
4. Family history of MI and Stroke
5. Obesity
6. Hypercholestrolemia
INFECTIONS OF CNS:

MENINGITIS
 DEFINITIONS

1. Meningitis:
a. inflammation of the protective membrane lining
the brain and spinal cord.
b. Two types: Leptomeningitis (inflammation of
Pia mater, sub arachnoid space and
cerebrospinal fluid (CSF) and Pachymeningitis
(inflammation of dura mater; rare condition)
2. Encephalitis
a. Inflammation of brain tissue
 Causes of Meningitis

1. Infections
a. Bacterial (common is S. Pneumoniae)
b. Viral (most common type of meningitis)

c. Fungal , Protozoa, Parasite (Opportunistic infections

which most commonly affecting
immunocompromised patients eg: AIDS, cancer)

2. Non-infections
a. Malignancy
b. Autoimmune eg: SLE

c. Chemical – irritation to meninges

 Routes of Infections

1. Direct implantation
i. traumatic injury
2. Neighbouring structures
i. sinusitis
ii. otitis media
iii. osteomylitis
iv. nasopharyngeal infections
3. Hematogenous (most common route of infections)
4. Iatrogenic ( increased risk in chronic meningitis patients)
i. Lumbar puncture
ii. VP-shunt
 Types of Meningitis
1. Acute Pyogenic Meningitis
i. can also present with sepsis and septic shock –leading to death
ii. cause by anti-phagocytic microorganism (encapsulated
microorganism) which are not phagocytosis by macrophages
in blood circulations.
iii. reach the brain and they release cytokines and cellular
mediators stimulating inflammatory response

2. Aseptic meningitis (viral and non-infection causes)

3. Chronic meningitis ; eg caused by chronic infection such as

TB
 Types of Meningitis

• Caused by virus.
• Caused by bacteria
• Less severe
• Quite severe and may result in
• Resolves without specific
a) brain damage
treatment within a week or two
b) hearing loss
• Also called as aseptic meningitis
c) learning disability
• It would also causes death!
 Clinical Presentation Of
Meningitis
1. Fever
2. Neck stiffness
3. Poor feed (neonates)
4. Lethargy
5. Nuchal Rigidity
6. Headache due to cerebral edema which increase the intracranial
pressure.
7. Photophobia due to vasodilatation which increase blood vessel
permeability, hence increase intracranial pressure causing optic
nerve compression. Manifested by pain and discomfort of light
exposure.
 Laboratory Investigations
1. History and physical examinations
2. Complete blood counts – measure WBC for infections
3. Blood culture
4. CSF analysis – gold standard
 CSF Findings
Types of
CSF Color WBCs counts Protein levels Glucose levels
Meningitis

High
Bacterial Turbid Very High Very Low
(neutrophils)

Normal/
High Moderately
Viral Clear Moderately
(lymphocytes) increase
decrease
High
TB Turbid (lymphocytes) Very High Very Low
 Management of Meningitis
1. Reduce ICP
2. ANTIBIOTICS
3. Anti-tuberculosis
4. Anti-viral
5. Anti-fungal
DISEASES OF MYELIN
AND PERIPHERAL
NERVE
Multiple
Sclerosis
 What is Multiple Sclerosis?
1) It is a Chronic and Progressive Autoimmune Disease

2) In MS, the body attacks and destroys the fatty tissue called myelin that
insulates an axon/nerve and oligodendrocytes.

3) Also known as demyelination disease.

4) If damage is severe it can also destroy the nerve/axon itself.

5) MS affects the central nervous system, spinal cord, optic nerves which
results in sensory, motor, cognitive and visual problems.

6) Inflames the white matter in the brain which creates plaques.

7) Plaques block neurotransmission and thus inhibit communications between

neuronal cells.
 Pathogenesis of Multiple Sclerosis
1) In MS, abnormal clone of T cytotoxic cells expressing a receptor which allow their entry to
the brain through BBB.

2) The T-cells bind to myelin and oligodendrocytes and become activated

3) The activation of these abnormal clone of T-cells secrete cytokines and cellular mediators
which further attract migration of B-cells producing autoantibodies targeting myelin sheath and
migration of macrophages into brain.

4) These lead to worsen inflammation, myelin injury and phagocytosis of oligodendrocytes by

macrophages.

5) These immunological injury activates the activity of T-regulator cells to suppress immune
system, which improve re-mylienation of the axon.

6) However, long-term conditions lead to failure re-myelination which lead to permanent

demyelination and scar formation : MULTIPLE SCLEROSIS

7) Producing plaques in white matter which inhibit neurotransmission – lead to MOTOR,

SENSORY, COGNITIVE and VISUAL problems
Pathogenesis of Multiple Sclerosis
 SYMPTOMS OF MULTIPLE SCLEROSIS
Symptoms depends on the LOCATION of THE PLAQUES

1) CHARCOT’S NEUROLOGICAL TRIAD

• Dysarthria : slurred or slow speech that difficult to understand

Interfere with conscious movement (eg; eating & talking) and unconscious
movements (eg; swallowing)

• Nystagmus : involuntary rapid eye movements due to plaques on nerves

eyes.
Affect optic nerves : manifested by loss of visions, optic neuritis (blurring or
dark spots)
Affect eyes movement causing pain and double visions

• Intention tremor : Plaques along motor pathways that can lead to muscle
weakness, spasms, tremor, ataxia and paralysis.
 SYMPTOMS OF MULTIPLE SCLEROSIS
Symptoms depends on the LOCATION of THE PLAQUES

2) Plaques on sensory pathways from skin

• Numbness, paresthesia (tingling, itching, burning)

3) Plaques in autonomic nervous systems

• Bladder and bowel symptoms

• Sexual dysfunction

4. Higher order activities

• Poor concentrations & critical thinking

• Depression and anxiety

 ETIOLOGY OF MULTIPLE SCLEROSIS
1. Genetic factors
• Female > male
• Mutation of T-cells receptor; eg: overexpression of HLA-DR2
• Family history of MS

2. Environmental factors
• Infections EBV

• Vitamin D Deficiency
 Role of Vitamin D in MS

• Vitamin D deficiency
– Vitamin D3 receptor important in immune
function
– Present on T regulator cell

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 Role of Vitamin D in MS
1. US cohort study found that 3.5 times more women residing in northern states
were diagnosed with MS than southern states.

2. MS more prominent in areas reporting less than 2000 hours of sunshine

annually

3. A Finnish study found lower serum vitamin D levels in in MS patients .

4. A line between dietary intake of vitamin D and the incidence of MS has been
suggested in Norway along the coastal areas where intake of vitamin D -
enriched diets such as fatty fish, dairy products, and cereals lowered the
incidence of MS.

5. Dietary information from the Nurse’s Health Study of 187,000 women showed
those with a history of vitamin D supplementation as low as 400 units daily had
a 40% less chance of developing MS.

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 Laboratory Investigation &
Treatments
1. MRI- detect white matter plaques
2. CSF analysis – increased level of Antibodies
3. Treatments :
• Plasmapheresis – remove autoantibodies
• Immunosuppressant
• Vitamin D supplementation
• Cognitive rehabilitation
• Physical therapy
TAMAT