Demyelinating Disease

1. Demyelinating Disease Dr. Basu

2. Multiple sclerosis (MS) • Sporadic chronic relapsing-remitting disease. • Demyelation of brain, optic nerve and spinal cord.

3. 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

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

5. Here is a (MS). Gross MRI: Abnormal increased signal in the periventricular whitematter

6. Laboratory • CSF of increased protein [ IgG ] that demonstrates oligoclonal bands on electrophoresis. • Presence of Myelin Basic Protein [ indicate the presence of active myelin breakdown]

7. 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.

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

9. Wernicke's disease. • Etiology: chronic alcoholism with thiamine deficiency. • Present with ataxia. Peripheral neuropathy • Morphology: small petechial hemorrhages in the mammillary bodies.

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

11. 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)

12. 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.

13. 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

14. 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.

15. 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

16. 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.

17. 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

18. 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

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

20. Atrophy Compensatory dilation of the cerebral ventricles hydrocephalus ex vacuo

21. 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

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

23. 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.

24. Dementia : other

25. Parkinson's Disease • Definition • Genes • Morphology • Clinical features

26. 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.

27. Pathogenesis • An autosomal dominant form with mutations in the alpha-synuclein gene • And, an autosomal recessive form with mutations in the ubiquitin-protein ligase (Parkin) gene.

28. Morphology: • Loss of dopaminergic neurons (neuromelanin) in the pars compacta of the substantia nigra. NORMAL

29. 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.

30. 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.

31. Huntington's Disease : Pathogenesis • Autosomal dominant disorder. • Age: 20 and 50 years, with a course that averages 15 years to death. • Involve extrapyramidal system.

32. 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.

33. Effect of mutant gene Severe atrophy of the caudate nuclei and compensatory dilation of ventricles.

34. Clinical Features • Involuntary movements ; choreiform movements. Hyperkinetic with rigidity / seizures • Depression and mood swings Huntington's Chorea

35. It is a also known as motor neuron disease.

36. 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.

37. Morphology • loss of anterior horn cells of spinal cord: lead to atrophy of the skeletal muscle. • This is called “grouped atrophy”. Trichrome stain.

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

39. 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.

40. DISEASE OF THE PERIPHERAL NERVOUS SYSTEM.

41. Guillain Barré Syndrome • Most common life threatening disease of the Peripheral nerve. • Caused by Viral , Mycoplasmal Infection • Or, May develop spontaneously. acute ascending polyneuritis

42. C/F • Rapid ascending motor weakness • May lead to death leading to respiratory failure and Death.

43. Morphology • Peripheral Nerves are infiltrated by macrophage and Reactive lymphocytes. • CSF will show increase Protein segmental myelin loss

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

45. George Charles Guillain : Jean-Alexander Barré Thank you