Vitamin B12-responsive severe leukoencephalopathy and autonomic dysfunction in a patient with “normal” serum B12 levels
- 1Department of Neuro-oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- 2Department of Geriatrics and Adult Development and Medicine, Mount Sinai School of Medicine, New York, New York, USA
- 3New York University School of Medicine, New York, New York, USA
- 4Division of Neurogenetics, Department of Neurology, New York University School of Medicine, New York, New York, USA
- Correspondence to Dr Swati Sathe, Division of Neurogenetics, Department of Neurology, 403 E 34th St 2nd floor, New York NY 10016, USA;
Contributors Study concept and design: Drs Graber, Sherman, Kolodny and Sathe. Acquisition of data: Drs Sherman, Kaufmann and Sathe. Analysis and interpretation: Drs Graber, Kaufmann, Sherman, Kolodny and Sathe. Drafting of the manuscript: Drs Graber, Sherman and Sathe. Critical revision of the manuscript for important intellectual content: Drs Kaufmann, Sherman, Kolodny and Sathe. Study supervision: Drs Sherman, Kolodny and Sathe.
- Received 20 March 2009
- Revised 14 July 2009
- Accepted 15 July 2009
- Published Online First 28 June 2010
Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B12 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 B12 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 B12 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 B12 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 B12, homocysteine and methylmalonic acid levels are unreliable predictors of B12-responsive neurologic disorders, and should be thoroughly investigated and presumptively treated in patients with unexplained leukoencephalopathy because even long-standing deficits may be reversible.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.