Dr. Ron’s Research Review – May 24, 2017

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This week’s research review focuses on IV methylcobalamin for peripheral neuropathy and ALS.

A phase I/II open label clinical trial examined the safety and efficacy of intravenous ultra-high dose methylcobalamin treatment for peripheral neuropathy. (Shibuya et al., 2014)
Fourteen patients with immune-mediated or hereditary neuropathy in the chronic progressive or stable phase were enrolled. MeCbl, 25 mg/day for 10 days followed by monthly 25 mg for 5 months, was intravenously administered. The patients were evaluated before and 1 year following treatment.
There were no adverse effects in twelve of the patients, whereas treatment was discontinued in two patients who had seborrheic dermatitis at 3 months and respiratory tract infection at 2 months, respectively. Therefore, twelve patients were evaluated for the primary outcomes; the Medical Research Council (MRC) sum score was improved in seven of the patients and unchanged or worsened in the remaining five patients.
Intravenous ultra-high dose MeCbl treatment is a safe and potentially efficacious therapy for patients with peripheral neuropathy and chronic axonal degeneration.

A double-blind controlled study published in Muscle Nerve compared low dose and ultra-high dose methylcobalamin dose (25 and 0.5 mg/day, intramuscularly, for 14 days) on compound muscle action potentials (CMAPs) in amyotrophic lateral sclerosis (ALS).(Kaji et al., 1998)
No significant changes in CMAP amplitude were found in 12 patients who had the low-dose treatment at either 2 or 4 weeks after start of treatment. By contrast, 12 patients assigned to the ultrahigh-dose group demonstrated a significant increase at 4 weeks.

 

Dr. Ron


 

Articles

Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis: a double-blind controlled study.
            (Kaji et al., 1998) Download
To develop a symptomatic treatment for amyotrophic lateral sclerosis, we compared the effects of ultrahigh-dose and low-dose (25 and 0.5 mg/day, intramuscularly, for 14 days) methylcobalamin on averaged compound muscle action potential amplitudes (CMAPs) in a double-blind trial. No significant changes in CMAP amplitude were found in 12 patients who had the low-dose treatment at either 2 or 4 weeks after start of treatment. By contrast, 12 patients assigned to the ultrahigh-dose group demonstrated a significant increase at 4 weeks. This method may provide a clinically useful measure to improve or retard muscle wasting, if a larger extended trial fulfills its promise.

Safety and efficacy of intravenous ultra-high dose methylcobalamin treatment for peripheral neuropathy: a phase I/II open label clinical trial.
            (Shibuya et al., 2014) Download
OBJECTIVE:  No clinically effective treatment for promoting peripheral axonal regeneration has yet been established. Several experimental studies in vitro and in vivo have shown that a high dose of methylcobalamin (MeCbl), an analogue of vitamin B12, promotes axonal growth in peripheral nerve injury. We herein assessed the safety and efficacy of an ultra-high dose MeCbl treatment for patients with peripheral neuropathy and chronic axonal degeneration. METHODS:  Fourteen patients with immune-mediated or hereditary neuropathy in the chronic progressive or stable phase were enrolled. MeCbl, 25 mg/day for 10 days followed by monthly 25 mg for 5 months, was intravenously administered. The patients were evaluated before and 1 year following treatment. The primary endpoints were safety and improvement in the Medical Research Council (MRC) sum score in at least two muscles of the 20 muscles. This trial is registered with the University Hospital Medical Information Network (UMIN) Center in Japan under the ID: UMIN000009359. RESULTS:  There were no adverse effects in twelve of the patients, whereas treatment was discontinued in two patients who had seborrheic dermatitis at 3 months and respiratory tract infection at 2 months, respectively. Therefore, twelve patients were evaluated for the primary outcomes; the MRC sum score was improved in seven of the patients and unchanged or worsened in the remaining five patients. CONCLUSION:  Intravenous ultra-high dose MeCbl treatment is a safe and potentially efficacious therapy for patients with peripheral neuropathy and chronic axonal degeneration.

 

References

Kaji, R, et al. (1998), ‘Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis: a double-blind controlled study.’, Muscle Nerve, 21 (12), 1775-78. PubMed: 9843082
Shibuya, K, et al. (2014), ‘Safety and efficacy of intravenous ultra-high dose methylcobalamin treatment for peripheral neuropathy: a phase I/II open label clinical trial.’, Intern Med, 53 (17), 1927-31. PubMed: 25175124