• White matter is mostly myelin Þ Demyelinating diseases affects white matter
• Gray matter also contains myelin Þ may also be affected by demyelinating disease
• Axons are NOT primarily affected by demyelinating diseases; therefore neurologic function may be relatively preserved
• When axons degenerate, so does their myelin

• First three are much more common than the last three
• Metachromatic Leukodystrophy
• Defect: Arylsulfatase A – normally cleaves the sulfate from sulfate lipids (sulfatides)
• Genetics: AR; >3 genes
• Pathology: Metachromatic – cells take on color different from orig. dye due to accumulation of sulfatides
• Demyelination with gliosis (astrocyte hypertrophy and hyperplasia in response to CNS injury)
• Megencephaly: no
• PNS: yes
• Extraneural Symptoms: yes
• Treatment: BMT
• Krabbe Disease
• Defect: Galactocerebroside b -galactosidase (GC) – defect does not cause accumulation of GC
• Genetics: AR on Ch 14
• Pathology: Globoid cells – aggregation of macrophages around blood vessels
• Loss of myelin and oligodendrocytes
• Megencephaly: no
• PNS: yes
• Extraneural Symptoms: no
• Treatment: BMT
• Adrenoleukodystrophy
• Defect: Peroxisomal membrane protein – inability to properly catabolize very long chain fatty acids (VLCFA)
• Genetics: X-linked
• Pathology: Perivascular lymphocytes and gliosis. Atrophy of adrenal cortex. Demylination of CNS and peripheral
• Megencephaly: no
• PNS: yes
• Extraneural Symptoms: yes, adrenal
• Treatment: BMT, Lorenzo’s Oil
• Pelizaeus-Merzbacher
• Defect: Myelin proteolipid protein – major protein of CNS myelin
• Genetics: X-linked
• Pathology: "Trigoid" appearance to cerebral hemishperes from remaining patches of white matter
• Megencephaly: no
• PNS: no
• Extraneural Symptoms: no
• Treatment: None
• Canavan’s Disease
• Defect: Aspartoacylase
• Genetics: AR
• Pathology: Spongy degeneration of white matter with Alzheimer type II cells
• Megencephaly: yes
• PNS: no
• Extraneural Symptoms: no
• Treatment: None
• Alexander’s Disease
• Defect: Unknown astrocyte
• Genetics: Presumably AR
• Pathology: Rosenthal fibers – eosinophilic structures within astrocytic processes that are found within regions of longstanding gliosis
• Megencephaly: yes
• PNS: no
• Extraneural Symptoms: no
• Treatment: None

Metabolic Leukoencephalopathy – Central Pontine Myelinolysis

• Pathogenesis: During rapid correction of hyponatremia (ß Na⁺), there is a greater increase in the osmolality (outside the cell) than organic osmolytes (inside the cell). The cell produces amino acids to try and maintain cell function during the threat of increasing extracellular osmolality; this pulls water out of the cell.
• Pathology: Symmetrical demyelinating lesions in the central part of the middle and upper pons
• Extra-pontine myelinolysis may coexist (10% of cases in thalamus, corpus callosum, spinal cord)
• Clinical presentation: rapidly evolving quadriplegia