Demyelinating Disease

Demyelinating Disease

·        = Selective, primary destruction of myelin

·        Diseases of CNS and PNS myelin do not affect the other

·        CNS Demyelinating disease:

o   Multiple Sclerosis

o   Acute Disseminated Encephalomyelitis

o   Progressive Multifocal Leucoencephalopathy (PML)

o   Toxins

o   Leucodystrophies

·        PNS Demyelinating Diseases:

o   Guillain-Barre Syndrome

o   Diphtheria

o   Diabetes Mellitus

o   IgM Paraproteinaemia

o   Leucodystrophies

o   Hypertrophic neuropathies (eg Charcot-Marie Tooth Disease)

·        Secondary Demyelination:

o   Infarction

o   Abscess

o   Contusion/Compression

Multiple Sclerosis

·        Chronic autoimmune demyelination of CNS neurons

·        Epidemiology:

o   Female to male = 2: 1

·        Peak age of onset 20 to 40 years

o  Marked racial difference in susceptibility.  Caucasian most common.  Africans/Asians rare

o  Genetic risk modified by environmental risks up to age 15 (from studies of immigrants)

o  Risk 15 times higher if first degree relative with MS.  Associated with HLA-DR2 haplotype

·        Can be sensory or motor

·        Diagnosis: Two lesions in different places at different times.  Lesions normally visible on MRI 

·        One spinal chord lesion may account for diffuse symptoms. As it grows through a spinal chord column a single lesion may progressively affect other areas

·        Highly variable course.  Relapsing and remitting

·        Worse after exercise

·        Pathology:

o  Autoimmune destruction of oligodendrocytes, ?triggered by a viral infection in a genetically susceptible host

o  Multiple plaques distributed throughout the cerebral hemispheres (especially periventricular white matter), optic fibres, brain stem, cerebellum and spinal chord

o  Active plaques: are soft yellow or pink and granular. Myelin breakdown ® foamy macrophages, T-suppressor cytotoxic cells, T-helper cells, and plasma cell infiltrate. Also reactive astrocytes

o  Chronic plaques: well defined, sclerotic and grey. Sharply defined areas of demyelination with compacted astrocytes processes (Þ gliosis)

o  Lesions expand by concentric outward growth. Poor correlation between number of plaques and symptoms

·        Tx: b-interferons

Progressive Multifocal Leukoencephalopathy (PML)

·        Like MS: multiple discrete foci of myelin destruction with relative preservation of axons

·        Caused by JC virus (DNA papovavirus common in the community) in immunodeficient patients

·        Relentlessly progressive 

·        Pathology: multiple lipid laden macrophages, oligodendrocytes with ground-glass nuclei (viral inclusions)