Demyelinating Disease

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Demyelinating Disease

• Dr. Basu

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Multiple sclerosis (MS)

• Sporadic chronic relapsing-remitting disease.
• Demyelation of brain, optic nerve and spinal cord.

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Pathogenesis Multifactorial ?

• Autoimmune disease.
• Caused by CD4 T cells mediated injury to the
  oligodendrocytes.
• Person living in temperate region
• Age 18 to 40 years
• Association with HLA DR2 gene

ENVIRONMENTAL
HEREDITARY
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Morphology

• Demyelinated plaque in a patient with multiple
  sclerosis in white matter.
• Acute lesion well demarcated plaque,
  inflammatory cells .
• Chronic lesion no inflammatory cells.

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Here is a (MS).
Gross
MRI Abnormal increased signal in the
periventricular white matter
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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

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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.

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Nutritional Disorder

• Wernicke's disease.
• Korsakoff psychosis
• Subacute combined degeneration of spinal cord.

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Wernicke's disease.

• Etiology chronic alcoholism with thiamine
  deficiency.
• Present with ataxia. Peripheral neuropathy
• Morphology small petechial hemorrhages in the
  mammillary bodies.

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Korsakoff psychosis

• If the Wernicke's encephalopathy is not treated
  the patient may develop Korsakoff psychosis.
• Cannot remember new memories , or retrieve old
  memories.

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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)
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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.

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Next topics

• d/d of dementia
• Degenerative disorders
• Alzheimer's disease
• Idiopathic Parkinson's disease
• Huntington's Disease
• Amyotrophic lateral sclerosis
• Floppy baby syndrome
• Guillain Barré Syndrome

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d/d of dementia

• 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.

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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

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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.

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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
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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

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Morphology

• Gross
• Cerebral cortical atrophy
• Dilatation of ventricle (hydrocephalus ex vacuo)
• Micro
• Neurofibrillary Tangle composed of Hyper
  phosphorylated of Protein tau.
• Neuritic (senile) plaques with amyloid core(Aß)
• Amyloid angiopathy
• Lewy body

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Atrophy
Compensatory dilation of the cerebral ventricles
hydrocephalus ex vacuo
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Microscopy
All microscopic changes are commonly seen in
hippocampus CA1 region
Neuritic (senile) plaque stained for tau protein(
brown) and beta-amyloid (red)
Neurofibrillary Tangles
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Clinical features

• Insidious onset in very old age
• Progressive memory loss (Dementia)
• Change in mood and behavior
• Aphasia become mute
• No specific treatment yet.

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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.

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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.
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Parkinson's Disease

• Definition
• Genes
• Morphology
• Clinical features

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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.

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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.

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Morphology

• Loss of dopaminergic neurons (neuromelanin) in
  the pars compacta of the substantia nigra.

NORMAL
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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.
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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.

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Huntington's Disease Pathogenesis

• Autosomal dominant disorder.
• Age 20 and 50 years, with a course that
  averages 15 years to death.
• Involve extrapyramidal system.

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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.

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Effect of mutant gene

• Severe atrophy of the caudate nuclei and
  compensatory dilation of ventricles.

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Clinical Features

• Involuntary movements choreiform movements.
  Hyperkinetic with rigidity / seizures
• Depression and mood swings

Huntington's Chorea
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It is a also known as motor neuron disease.
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Definition

• Amyotrophic lateral sclerosis (ALS) or Lou Gehrig
  disease, is a degenerative disorder characterized
  by a spontaneous, progressive loss of both
• Upper motor neurons in the cerebral cortex and
• Lower motor neurons in the anterior horns of the
  spinal cord.

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Morphology

• loss of anterior horn cells of spinal cord lead
  to atrophy of the skeletal muscle.
• This is called grouped atrophy.

Trichrome stain.
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Clinical signs- ALS

• Develop bulbar signs ( difficulty in deglutition)
  and symptoms.
• Spasticity.
• Abnormally brisk deep tendon reflexes, and a
  Babinski sign.

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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.

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• DISEASE OF THE PERIPHERAL NERVOUS SYSTEM.

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Guillain Barré Syndrome

1. Most common life threatening disease of the
   Peripheral nerve.
2. Caused by Viral , Mycoplasmal Infection
3. Or, May develop spontaneously.

acute ascending polyneuritis
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C/F

• Rapid ascending motor weakness
• May lead to death leading to respiratory failure
  and Death.

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Morphology

• Peripheral Nerves are infiltrated by macrophage
  and Reactive lymphocytes.
• CSF will show increase Protein

segmental myelin loss
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Remember !!!!

• Since laboratory tests can not specifically
  diagnose GBS, doctors must recognize the disease
  form its pattern of symptoms

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George Charles Guillain Jean-Alexander Barré
Thank you