Transcript of Primary Diseases of Myelin Demyelinating diseases: Damage to previously normal myelin...
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- Primary Diseases of Myelin Demyelinating diseases: Damage to
previously normal myelin Immune-mediated injury: multiple sclerosis
Viral infection of oligodendrocytes Drugs and other toxic agents
Dysmyelinating diseases (Leukodystrophy): Abnormal myelin synthesis
/ turnover
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- Multiple Sclerosis Relapsing/remitting episodes of neurologic
deficits, separated in time, white matter lesions separated in
space Women affected twice as often (20 40 years)
Environmental/genetic: loss of tolerance to myelin antigens (CD4 T
cells react against self antigens in myelin sheath) 15-fold risk if
disease present in first-degree relative
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- Morphology Plaques: multiple, well-circumscribed, gray-tan
lesions Microscopic: Active plaque - myelin breakdown, macrophages
containing myelin debris, perivascular lymphocytes Small lesions on
small veins, axons relatively preserved Quiescent /inactive plaques
- Gliosis, no inflammation, little to no myelin left
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- Multiple Sclerosis
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- Clinical Features Relapses followed by remissions Sensory
dysfunction: paresthesias, loss of pain/ temperature / vibratory
sensations UMN dysfunction: spasticity, DTRs, muscle spasm,
Babinski, weakness Autonomic dysfunction: urge incontinence; sexual
dysfunction; bowel motility dysfunction Optic neuritis, Bilateral
internuclear ophthalmoplegia Cerebellar ataxia SIN: scanning
speech, intention tremor, nystagmus Flexion of neck produces an
electrical sensation down the spine
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- A 45-year-old man with worsening weakness in his right leg and
double vision Horizontal diplopia during lateral gaze in both
eyes
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- Diagnosis & Treatment CSF : Mildly elevated protein level
with increased -globulin, Oligoclonal bands, moderate pleiocytosis
in 1/3rd cases MRI: for distribution of lesions during active
disease Treatment Acute relapse - High dose methylprednisolone
Chronic (a) Disease modifying drugs-e.g., interferon-beta (b)
Monoclonal antibody-natalizumab (c) Cytotoxic-cyclophosphamide;
methotrexate; azathioprine Prognosis 70% of patients alive 25 years
after diagnosis
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- Non-immune process Loss of myelin in center of pons Follows
rapid correction of hyponatremia In alcoholism and severe
electrolyte imbalance - rapidly evolving quadriplegia Central
pontine myelinolysis
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- Leukodystrophies Abnormal myelin, mostly autosomal recessive
Morphology: White matter diffusely abnormal in color (gray and
translucent) and volume (decreased) Brain atrophy, ventricles
enlarge, secondary changes in gray matter Loss of myelin
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- Metabolic DisorderInheritanceAbnormality Metachromatic
leukodystrophy AR Arylsulfatase A deficiency Krabbe diseaseAR
Galactocerebroside -galactosidase deficiency
AdrenoleukodystrophyX-Recessive Peroxisomal defects; elevated very
long chain fatty acids Canavan diseaseAR Aspartoacylase deficieny
Pelizaeus-Merzbacher disease X Mutations in proteolipid protein
Vanishing white matter disease AR Translation initiation factor
Alexander diseaseAR Mutations in GFAP
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- Summary Diseases of myelin - widespread, severe neurologic
deficits Demyelinating (normal myelin is broken down)
Dysmyelinating (abnormal myelin) Multiple sclerosis: most common
demyelinating disease, autoimmune, affects young adults,
relapsing-remitting course with progressive neurologic
deficits
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- Nutritional Diseases - Thiamine Deficiency Beri Wernicke
encephalopathy : confusion, abnormal eye movement and ataxia
Korsakoff syndrome: profound memory disturbances Causes: chronic
alcoholism, gastric carcinoma, chronic gastritis Treatment:
Thiamine
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- Nutritional Diseases - Thiamine Deficiency Morphology
Hemorrhage and necrosis in mammillary bodies Lesions in medial
dorsal nucleus of thalamus correlate with memory disturbance in
Korsakoff syndrome
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- Vitamin B 12 deficiency Pernicious anemia Sub-acute combined
degeneration of spinal cord Initially ataxia/numbness/tingling can
progress to paraplegia Clinical improvement with vitamin
replacement therapy
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- Degenerative Diseases and Dementias Primary Neurodegenerative
Disorders Alzheimer disease Pick disease, frontotemporal
degenerations Parkinson disease, diffuse Lewy body disease
Progressive supranuclear palsy Huntington disease Motor neuron
disease Infections Prion-associated disorders (Creutzfeldt-Jakob
disease, fatal familial insomnia, others) HIV encephalopathy (AIDS
dementia complex) Progressive multifocal leukoencephalopathy
Miscellaneous forms of viral encephalitis Neurosyphilis Chronic
meningitis Vascular and Traumatic Diseases Multi-infarct dementia,
chronic vascular disorders Global hypoxic-ischemic brain injury
Chronic subdural hematomas Metabolic and Nutritional Diseases
Thiamine deficiency (Wernicke-Korsakoff syndrome) Vitamin B 12
deficiency Niacin deficiency (pellagra) Endocrine diseases
Miscellaneous Brain tumors Neuronal storage diseases Toxic injury
(mercury, lead, manganese, bromides)
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- Alzheimer Disease Most common cause of dementia in elderly
1.Impaired higher intellectual functions with mood/behavior
alterations 2.Progressive disorientation, memory loss, and aphasia
3.Disabled, mute, immobile Prominent early sign is decline in
short-term memory Accumulation of amyloid (A) in brain Death from
pneumonia/other infections
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- Alzheimer Disease Sporadic early onset - related to
apolipoprotein gene E Familial early onset type of AD (