Demyelinating Diseases

1. Demyelinating Diseases Done by: Moh’d Sulaiman Al-Houqani Moh’d Ali Al-Ali

2. Introduction Demyelinating disorders of the CNS affect myelin and/or oligodendroglia with relative sparing of axons. Oligodendrocytes, like Schwann cells in the peripheral nervous system, are responsible for the formation of myelin around CNS axons. One Schwann cell myelinates one axons but one oligodendrocyte may myelinate several contiguous axons, and the close proximity of cell to axon may not be obvious by light microscopy. Oligodendrocyte are present in gray matter near neural cell bodies and in white matter near axons. Myelin is composed of protein 20% & lipids.

3. Classification of the Demyelinating diseases: Multiple sclerosis: A-  Chronic relapsing encephalomyelopathic form. B-   Acute multiple sclerosis. C-  Neuromyelitis optica. Diffuse cerebral sclerosis (encephalitis periaxalis diffuse) or Schilder and concentric sclerosis of Balo. Acute disseminated encephalomyelitis. A-  Following measles, rubella & influenza. B-   Following rabies or smallpox vaccination. Acute and subacute necrotizing hemorrhagic encephalitis. A-  Acute encephalopathic form (hemorrhagic leukoencephalitis of Hurst) B-   Subacute necrotic myelopathy C-  Acute brain purpura(acute pericapillary encephalorrhagia)

4. Multiple Sclerosis MS referred by the British as disseminated sclerosis & by French as Sclerose en plaques. MS is a common demyelinating disease, characterized by focal disturbance of function and a relapsing and remitting course. Higher incidence of the disease found in the northern most latitude of the northern & southern hemispheres compared to southernmost latitudes. MS usually occur in young adults with a peak age incidence of 20-40 years. more female than males are affected. The risk of MS in relative patients increases 20 folds.

5. Pathology • Scattered lesions with a greyish color. • 1mm to several cm in size. • Are present in the white matter of the brain and spinal cord and are referred to as plaques. • perivenous distribution.

6. RECENT LESIONS LATER OLD LESION • Myelin destruction • Relative axon sparing • Perivenous infiltration with MNP • Breakdown of BBB Astrocyte proliferation • Relatively acellular • More clearly demarcated. • Bare axons are surrounded by astrocytes.

7. Pathology These lesions have a predilection for the following sites within the brain & SC.: • Optic nerves • Periventricular region • Brainstem • Cervical SC. (CS. Tract & PC.)

8. Pathogenesis Genetic predisposition Environmental Exposure (Virus) Autoimmune attack by CD4 T-cell Demyelination Multiple Sclerosis

9. Clinical Features • Sensory Symptoms • Numbness & Paraesthesia • Impaired vibration & Joint position sensation • Lhermitte’s Sign ( Shock-like sensation in the limb) • Dysaesthesia + Sensory loss to pain & Temp.

10. Clinical Features • Motor Symptoms • Monoparesis • Paraparesis • Signs • Increased tone • Hyperactive tendon reflexes • Absent abdominal reflexes • Pyramidal distribution weakness

11. Clinical Features Optic Neuritis • Inflammatory demyelination of one or both optic nerves • Pain around one eye • Blurred vision • Loss of color vision • Swollen optic disc( Papillitis) • Visual field defect • Diplopia & Vertigo Uhthoff phenomenon

12. Clinical Course: 1- Acute MS • Explosive onset • Death may occur in months • Dramatic recovery and prolonged remission may occur

13. 2- Slowly Progressive MS: • Common in older age group • No relapse/remission • Takes the form of a Progressive myelopathy Disability Time

14. 3- Relapsing MS: • Accumulating disability Disability Time

15. 4- Benign form • Abrupt onset • Good remission • Long latent period Disability Time

16. Investigation No diagnostic test. Only support the clinical suspicion. Neuropsychological measurement of conduction within the CNS to detect second a symptomatic lesion.: • Visual evoked potential(VEP): in optic nerve the latency of the large positive wave is delayed . the amplitude may also be reduced. • Somatosensory evoked response (SSEP) may detect central sensory pathway lesion. • Brain stem auditory evoked potential (BAEP) may detect brain stem lesion.

17. CSF examination by lumbar puncture normal • Mild pleocytosis mainly lymphocytes. • Total protein maybe elevated • gammaglobuline in 50% • Electrophoresis of CSF using agar shows discrete bands which are not present in serum. Oligoclonalband

18. MRI MRI is more sensitive showing white matter disease. On T-2 weighted images, patchy area of abnormal white matter are found most commonly in cerebral hemisphere in paraventicular areas; often lesions can be present in the cerebellum , brain stem, cervical and or thoracic spinal cord Area of demyelination in cerebral hemisphere

19. Demyelination in the Cervical Spinal Cord MRI finding are not necessarily diagnostic

20. Management Anti-inflammatory & immunpsuppressive therapy: • ACTH my shortnes the duration of relapses but won’t influence the outcome. • Immunosuppressive- cyclophosphamide, azothiaprine- no evidence of value & potential dangerous; marrow toxicity, etc. occasionally used in acute MS. Enhancement of cell mediated immunity • Interferon has been suggested but not evaluated. Physical treatment • Body cooling has been applied in acute situation…. Dietary measures • Low glutein or polyunsaturated fat supplemented diets. In summary • No available specific therapy proven value.