Vitamin B₁₂-responsive neuropathies: A case series

Abstract

Objectives: Neuropathies often accompany vitamin B₁₂ deficiency. Since many neuropathies are linked to oxidative stress and since B₁₂ has both antioxidant and neurotrophic properties, B₁₂ may also be effective treatment in non-deficient subjects. Thus, the characteristics and predictors of B₁₂-responsive neuropathies and their relationship to disorders associated with increased oxidative stress (oxidant risks) were examined.

Methods: Retrospective review of 78 subjects with neurological abnormalities treated with B₁₂ and evaluated by the measurement of B₁₂ and the B₁₂-dependent metabolites, methylmalonic acid (MMA), and homocysteine.

Results: Sixty-five subjects had neurological improvement (83%), including 35 with other known causes of neuropathy. Only two responders had B₁₂-responsive macrocytosis. Pretherapy B₁₂, MMA, and homocysteine values were normal in 72, 33 and 54% of responders, with all three normal in 23%. Moreover, B₁₂ therapy did not significantly decrease elevated MMA and homocysteine levels in 20 and 37%, respectively, of responders tested but did decrease both metabolites in 75% of evaluable non-responders. At least one oxidant risk was present in 41 of the 46 responders with normal B₁₂ levels (89%). Oral therapy was effective, but parenteral B₁₂ improved responses in four subjects.

Discussion: B₁₂-responsive neuropathies are thus (1) common even when confounding disorders are present; (2) dissociated from the presence of hematological abnormalities; (3) dissociated from the presence of B₁₂-responsive metabolical abnormalities; and (4) associated with the presence of oxidant risks when B₁₂ levels are normal. Since no predictors of responses to B₁₂ therapy were identified, empiric trials with parenteral B₁₂ should be considered in appropriate subjects.

Keywords:

• Neuropathy
• Vitamin B₁₂
• Oxidative stress
• Cobalamin
• Methylmalonic acid
• Homocysteine

Acknowledgements

The author thanks D. Bonke (Merck, Darmstadt, Germany) for his suggestion regarding the possible effect of oxidative stress on B₁₂ metabolism and Dr R. Green (UC Davis, Sacremento, CA, USA) for his suggestion on the possible therapeutic use of reduced forms of vitamin B₁₂.

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