Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy.
Delayed demyelination is a rare and poorly understood complication of hypoxic brain injury. A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma. MRI showed diffuse white matter signal changes, and brain biopsy demonstrated a noninflammatory demyelinating process. Proton magnetic resonance spectroscopy revealed elevated choline and lactate and reduced N-acetyl aspartate signal in the affected white matter, consistent with demyelination and a shift to anaerobic metabolism. Arylsulfatase A activity from peripheral leukocytes was approximately 50% of normal, consistent with a "pseudodeficiency" phenotype. These findings confirm the hypothesis that relative arylsulfatase A deficiency predisposes susceptible individuals to delayed posthypoxic leukoencephalopathy and implicates lactic acidosis in the pathogenesis of this disorder.
Gottfried
J A
JA
Department of Physiology, New York University Medical Center, NY, USA.
Mayer
S A
SA
Shungu
D C
DC
Chang
Y
Y
Duyn
J H
JH
D000140:Acidosis, Lactic / Q000150:complications / Q000175:diagnosis / Q000201:enzymology*; D000328:Adult; D002553:Cerebroside-Sulfatase / Q000172:deficiency*; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000201:enzymology* / Q000209:etiology; D062787:Drug Overdose / Q000150:complications; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000175:diagnosis / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011522:Protons; D013997:Time Factors
D011522:Protons; D002553:Cerebroside-Sulfatase