Comment on: White matter, red flag (letter to the editor, Parkhurst Exchange, sent 2010-4-12)

The Q&A response to the question “What could multiple hyperdensities on brain MRI in the absence of migraine indicate?” (Parkhurst Exchange, April 2010, p28) did not include B12 deficiency as a possible cause. There are a number of case reports (1-4) reporting the finding of white matter hyperintensities on T2-weighted MRIs of the brain in association with B12 deficiency, with the brain lesions improving or resolving with B12 treatment. Even B12 status in the normal range was found to be associated with severity of white-matter lesions, in a population-based study (5). With prevalences of low B12 in the elderly ranging up to 31.8% (in the U.K., (6)), clinicians should have a high index of suspicion.
As B12 levels may not provide an accurate indication of functional B12 deficiency states (7), it may be advisable to obtain homocysteine and methylmalonic acid levels, or holotranscobalamin II levels if available. Finally, if the clinical picture is consistent with B12 deficiency, a trial of supplementation with B12 is worthwhile, given its low risk. Time is of the essence, as cognitive and other neurological impairments caused by B12 deficiency will become irreversible if left untreated too long.
1. Chatterjee A, Yapundich R, Palmer CA, Marson DC, Mitchell GW. Leukoencephalopathy associated with cobalamin deficiency. Neurology. 1996;46:832-834.
2. Stojsavljevic N, Levic Z, Drulovic J, Dragutinovic G. A 44-month clinical-brain MRI follow-up in a patient with B12 deficiency. Neurology. 1997;49:878-881.
3. Su S, Libman RB, Diamond A, Sharfstein S. Infratentorial and supratentorial leukoencephalopathy associated with vitamin B12 deficiency. J Stroke Cerebrovasc Dis. 2000;9:136-138.
4. Vry MS, Haerter K, Kastrup O, Gizewski E, Frings M, Maschke M. Vitamine-B12-deficiency causing isolated and partially reversible leukoencephalopathy. J Neurol. 2005;252:980-982.
5. de Lau LM, Smith AD, Refsum H, Johnston C, Breteler MM. Plasma vitamin B12 status and cerebral white-matter lesions. J Neurol Neurosurg Psychiatry. 2009;80:149-157.
6. McLean E, de Benoist B, Allen LH. Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr Bull. 2008;29:S38-51.
7. Carmel R, Brar S, Agrawal A, Penha PD. Failure of assay to identify low cobalamin concentrations. Clin Chem. 2000;46:2017-2018.
The original Q & A article:

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