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. Person living in temperate region Age – 18 to 40 years Association with HLA DR2 gene ENVIRONMENTAL HEREDITARY

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). MRI: Abnormal increased signal in the periventricular white matter Gross

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 B 12, 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. eakness 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 Alzheimer's disease Alzheimer's disease Idiopathic Parkinson's disease Idiopathic Parkinson's disease Huntington's Disease Amyotrophic lateral sclerosis Floppy baby syndrome Guillain Barré Syndrome

d/d of dementia Degenerative disorders Degenerative disorders Multi-infarct Dementia Multi-infarct Dementia Dementia with lewy body Dementia with lewy body Parkinson disease Parkinson disease Huntington disease Huntington disease Nurosyphilis, Nurosyphilis, AIDS-associated dementia AIDS-associated dementia Creutzfeldt-Jakob disease Creutzfeldt-Jakob disease Chronic subdural hematoma Chronic subdural hematoma Demyelinating disease Demyelinating disease and toxic-metabolic disorders. 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). 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 A. *Neurofibrillary Tangle : composed of Hyper phosphorylated of Protein tau. B. Aß B. *Neuritic (senile) plaques with amyloid core(Aß) C. C. Amyloid angiopathy D. 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 beta- amyloid (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 DefinitionGenesMorphology 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. 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 the Peripheral nerve. 2. Caused by Viral, Mycoplasmal Infection 3. 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