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Demyelinating Disease
Dr. Basu
Multiple sclerosis (MS)
Sporadic chronic relapsing-remitting
disease.
Demyelation of brain, optic nerve and
spinal cord.
Pathogenesis: Multifactorial ?
Autoimmune disease.
Caused by CD4+ T cells mediated injury to
the oligodendrocytes.
ENVIRONMENTAL
HEREDITARY
Person living in temperate region
Age – 18 to 40 years
Association with HLA DR2 gene
Morphology
Demyelinated plaque in a patient with
multiple sclerosis in white matter.
Acute lesion: well demarcated plaque,
inflammatory cells +.
Chronic lesion: no inflammatory cells.
Here is a (MS).
Gross
MRI: Abnormal increased signal in the
periventricular white matter
Laboratory
1.
CSF of increased protein [ IgG ] that
demonstrates oligoclonal bands on
electrophoresis.
2.
Presence of Myelin Basic Protein [ indicate the
presence of active myelin breakdown]
Clinical Features
Waxing and waning of neurological sings over
few years.
Visual disturbance ( diplopia, blurred vision).
Emotional disturbance.Gait abnormality, Speech
disturbance.
Treatment:
Acute: steroid
Others: interferon beta.
Nutritional Disorder
Wernicke's disease.
Korsakoff psychosis
Subacute combined degeneration of
spinal cord.
Wernicke's disease.
Etiology: chronic alcoholism
with thiamine deficiency.
Present with ataxia.
Peripheral neuropathy
Morphology: small petechial
hemorrhages in the
mammillary bodies.
Korsakoff psychosis
If the Wernicke's encephalopathy is not
treated the patient may develop Korsakoff
psychosis.
Cannot remember new memories , or
retrieve old memories.
Sub acute combined degeneration of spinal cord.
Cause: Deficiency of Vitamin B12, OCCUR IN A
PATIENT OF PERNICIOUS ANAEMIA.
Morphology: Spongy ( vacuolar) degeneration of
posterior and lateral columns ( combined ) of spinal
cord.
Special stain
reveal no
myelin ( pale
areas)
Clinical Features
Weakness, Abnormal sensation on the limbs (insect
crawling, pin pricking ) , Mental problems.
Loss of vibration sense is the most
consistent sign and is more pronounced
in legs than in the arms.
Late stage: increased deep tendon
reflexes, clonus and Babinski sign.
Next topics
d/d of dementia
Degenerative disorders
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Alzheimer's disease
Idiopathic Parkinson's disease
Huntington's Disease
Amyotrophic lateral sclerosis
Floppy baby syndrome
Guillain Barré Syndrome
d/d of dementia
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Degenerative disorders
Multi-infarct Dementia
Dementia with lewy body
Parkinson disease
Huntington disease
Nurosyphilis,
AIDS-associated dementia
Creutzfeldt-Jakob disease
Chronic subdural hematoma
Demyelinating disease
and toxic-metabolic disorders.
Degenerating disorder
Degenerative disease of the CNS
characterized clinically by progressive
cognitive impairment and memory loss.
Disease of the grey matter.
Examples: Alzheimer's
disease
Alzheimer's disease
Dementia with
preservation of normal
level of conscious
ness.
Age : 30% past age
85 years.
Mostly sporadic
15% family history of
Dementia.
Pathogenesis: 15% case are familial
Genetic factor ? Trisomy 21
Perivascular deposition of A beta amyloid
Hyper phosphorylation of Protein tau
Expression of specific alleles of apoprotein E (E2, E3,
E4: E4 increased risk)
In familial case: Mutations in genes endoding the
cellular proteins presenilin-1 and presenilin-2
PATHOGENESIS of early onset
Early onset:


Persons with trisomy 21 living to age of
40y invariably develop Alzheimer's disease
(earlier than normal).
Mutations in genes endoding the cellular
proteins presenilin-1 and presenilin-2
Morphology
Gross
A. Cerebral cortical atrophy
B. Dilatation of ventricle (hydrocephalus ex vacuo)
Micro:
A. *Neurofibrillary Tangle : composed of Hyper
phosphorylated of Protein tau.
B. *Neuritic (senile) plaques with amyloid core(Aß)
C. Amyloid angiopathy
D. Lewy body
Atrophy
Compensatory dilation of the cerebral ventricles
hydrocephalus ex vacuo
Microscopy
All microscopic
changes are commonly
seen in hippocampus:
CA1 region
Neurofibrillary Tangles
Neuritic (senile)
plaque stained for
tau protein(
brown) and betaamyloid (red)
Clinical features
Insidious onset in very old age
Progressive memory loss (Dementia)
Change in mood and behavior
Aphasia – become mute
No specific treatment yet.
Multi-infarct Dementia
The cumulative effect of multiple small areas of
infarction result in neuronal loss equivalent to
Alzheimer's disease.
Multiple focal atrophy of cortex.
Dementia : other
Dementia with lewy
body:
Clinical: memory
loss, visual
hallucination,
parkinsonism.
Presence of lewy body.
Involve limbic system and
cingulate gyrus, substantia
nigra, neocortex.
Try: cholinesterase inhibitor.
Parkinson's Disease
Definition
Genes
Morphology
Clinical features
Idiopathic Parkinson's disease
It is a degenerative disease commonly
begins in late middle age and the course
is slowly progressive.
Also know as: paralysis agitans.
Pathogenesis
1. An autosomal dominant form with
mutations in the alpha-synuclein gene
2. And, an autosomal recessive form with
mutations in the ubiquitin-protein
ligase (Parkin) gene.
Morphology:
Loss of dopaminergic neurons (neuromelanin) in
the pars compacta of the substantia nigra.
NORMAL
A rounded pink cytoplasmic Lewy body is seen ( cortical neuron)
microscopically with H and E stain at the left.
Immunostain for alpha-synuclein on right.
Clinical Features
Festinating gait, cogwheel
rigidity of the limbs.
Pill rolling type of tremor at
rest.
In time the patient's facies will
become mask-like.
Treatment: Levodopa with
other drug combination.
Huntington's Disease : Pathogenesis
Autosomal dominant disorder.
Age: 20 and 50 years, with a course that
averages 15 years to death.
Involve extrapyramidal system.
Huntington's Disease : Pathogenesis
Increased trinucleotide CAG repeat
sequences occur in of HD gene that encodes
for a protein, called huntingtin.
Loss of GABA nergic neurons… produce
chorea.
Effect of mutant gene
Severe atrophy of the caudate nuclei and
compensatory dilation of ventricles.
Clinical Features
Involuntary movements ; choreiform
movements. Hyperkinetic with rigidity /
seizures
Depression and mood swings
Huntington's Chorea
It is a also known as motor neuron
disease.
Definition
 Amyotrophic lateral sclerosis (ALS) or
Lou Gehrig disease, is a degenerative
disorder characterized by a
spontaneous, progressive loss of both
1. Upper motor neurons in the cerebral
cortex and
2. Lower motor neurons in the anterior
horns of the spinal cord.
Morphology
loss of anterior horn
cells of spinal cord: lead
to atrophy of the
skeletal muscle.
This is called “grouped
atrophy”.
Trichrome stain.
Clinical signs- ALS
Develop bulbar signs ( difficulty in
deglutition) and symptoms.
Spasticity.
Abnormally brisk deep tendon reflexes,
and a Babinski sign.
Friedreich ataxia
Autosomal recessive: early onset
Triplet Nucleotide repeat of frataxin gene
Involve: dorsal coloum, Cranial nerve: VII,
X, XII
Clinical: Gait ataxia, dysarthria, become
wheel chair bound at age 5.
DISEASE OF THE PERIPHERAL
NERVOUS SYSTEM.
Guillain Barré Syndrome
1. Most common life threatening disease of
2.
3.
the Peripheral nerve.
Caused by Viral , Mycoplasmal Infection
Or, May develop spontaneously.
acute ascending polyneuritis
C/F
Rapid ascending motor weakness
May lead to death leading to respiratory
failure and Death.
Morphology
Peripheral Nerves are infiltrated by
macrophage and Reactive lymphocytes.
CSF will show increase Protein
segmental myelin loss
Remember !!!!
Since laboratory tests can not specifically
diagnose GBS, doctors must recognize
the disease form its pattern of symptoms
George Charles Guillain : Jean-Alexander Barré
Thank you