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Background High-dose of methylcobalamin promotes nerve regeneration in rats with acrylamide neuropathy. A double-blind controlled trial suggested that high-dose methylcobalamin could increase compound muscle action potentials in patients with amyotrophic lateral sclerosis (ALS). A large-scale extended period human trial is now on-going in ALS ( Clinicaltrial.gov NCT00444613 ). We attempted to study whether high-dose methylcobalamin can improve symptoms or retard progression of motor dysfunction in the wobbler mouse model of ALS. Methods After initial diagnosis of the disease at the postnatal age of 3–4 weeks, wobbler mice received methylcobalamin (3 or 30 mg/kg, n = 10/group) or vehicle (n = 10), daily for 4 weeks by intraperitoneal administration in a blinded fashion. We compared clinical symptoms and pathological changes among all groups. Vitamin B12 concentrations were measured in the serum, the skeletal muscle and the spinal cord of three groups (n = 5/group). Results In comparison with vehicle, mice treated with ultra-high dose (30 mg/kg) of methylcobalamin significantly inhibited muscle weakness and contracture in the forelimb, and increased the weight of the bicep muscles and the number of musculocutaneous nerves. Methylcobalamin-treated mice significantly elevated vitamin B12 concentrations of the serum, the bicep muscle and the spinal cord compared to vehicle. Conclusion Our results suggest that treatment with methylcobalamin could delay progression of motor symptoms and neuropathological changes in wobbler mouse motor neuron disease if very high doses are used.

Despite intensive searches for therapeutic agents, few substances have been convincingly shown to enhance nerve regeneration in patients with peripheral neuropathies. Recent biochemical evidence suggests that an ultra-high dose of methylcobalamin (methyl-B12) may up-regulate gene transcription and thereby protein synthesis. We examined the effects of ultra-high dose of methyl-B12 on the rate of nerve regeneration in rats with acrylamide neuropathy, using the amplitudes of compound muscle action potentials (CMAPs) after tibial nerve stimulation as an index of the number of regenerating motor fibers. After intoxication with acrylamide, all the rats showed equally decreased CMAP amplitudes. The animals were then divided into 3 groups; rats treated with ultra-high (500 micrograms/kg body weight, intraperitoneally) and low (50 micrograms/kg) doses of methyl-B12, and saline-treated control rats. Those treated with ultra-high dose showed significantly faster CMAP recovery than saline-treated control rats, whereas the low-dose group showed no difference from the control. Morphometric analysis revealed a similar difference in fiber density between these groups. Ultra-high doses of methyl-B12 may be of clinical use for patients with peripheral neuropathies.

We report a patient who presented progressive cerebellar ataxia associated with vitamin B(12) deficiency. Brain magnetic resonance imaging (MRI) demonstrated a diffuse leukoencephalopathy. Six months after the initiation of methylcobalamin therapy, there were clinical improvement and reduction in the MRI abnormalities.

Vitamin B1- and B-deficient encephalopathy was produced in adult Wistar rats and the effect of methylcobalamin was studied. These experiments were performed in vitamin B1- or B-deficient rats with or without the administration of guanidine, a magnesium antagonist. These encephalopathic rats showed symmetrical lesions in the pontine tegmentum. No pathological changes in the brainstem were seen in guanidine-administered rats. This suggests that guanidine itself doesn't produce these brainstem lesions. Moderate to severe pathological changes occurred in vitamin B-deficient rats with guanidine administration, whereas these pathological changes were milder in vitamin B1-deficient rats with guanidine administration and in vitamin B1- and B-deficient rats with the combination of the guanidine and methylcobalamin administrations. These facts suggest that vitamin B12, methylcobalamin, plays an important preventive role in the development of the pontine lesions in this experiment.