title: Vitamin B12-responsive severe leukoencephalopathy and autonomic dysfunction in a patient with "normal" serum B12 levels.
abstract: Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B(12) levels (<200 pg/ml), in addition to psychiatric changes, neuropathy, dementia and subacute combined degeneration. Elevated homocysteine and methylmalonic acid levels are considered more sensitive and specific for evaluating truly functional B(12) deficiency. A previously healthy 62-year-old woman developed depression and cognitive deficits with autonomic dysfunction that progressed over the course of 5 years. The patient had progressive, severe leukoencephalopathy on multiple MRI scans over 5 years. Serum B(12) levels ranged from 267 to 447 pg/ml. Homocysteine and methylmalonic acid levels were normal. Testing for antibody to intrinsic factor was positive, consistent with pernicious anaemia. After treatment with intramuscular B(12) injections (1000 μg daily for 1 week, weekly for 6 weeks, then monthly), she made a remarkable clinical recovery but remained amnesic for major events of the last 5 years. Repeat MRI showed partial resolution of white matter changes. Serum B(12), homocysteine and methylmalonic acid levels are unreliable predictors of B(12)-responsive neurologic disorders, and should be thoroughly investigated and presumptively treated in patients with unexplained leukoencephalopathy because even long-standing deficits may be reversible.
authors.affiliation: Department of Neuro-oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Graber
authors.forename: F T
authors.initials: FT
authors.lastname: Sherman
authors.forename: H
authors.initials: H
authors.lastname: Kaufmann
authors.forename: E H
authors.initials: EH
authors.lastname: Kolodny
authors.forename: S
authors.initials: S
authors.lastname: Sathe
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001342:Autonomic Nervous System Diseases / Q000097:blood / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003072:Cognition Disorders / Q000097:blood / Q000188:drug therapy*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007437:Intrinsic Factor / Q000276:immunology; D056784:Leukoencephalopathies / Q000097:blood / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008609:Mental Status Schedule / Q000706:statistics & numerical data; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D011594:Psychometrics; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000188:drug therapy*; D014807:Vitamin D / Q000008:administration & dosage
chemical_list: D001323:Autoantibodies; D006710:Homocysteine; D014807:Vitamin D; D008764:Methylmalonic Acid; D007437:Intrinsic Factor; D014805:Vitamin B 12