SLR - April 2012 - Gina Hild
Reference: Jacobs, A. M., & Cheng, D. (2011). Management of diabetic small-fiber neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate. Rev Neurol Dis, 8(1-2), 39-47.
Scientific Literature Review
Reviewed by: Gina Hild, DPM
Residency Program: Cleveland Clinic Foundation/Kaiser Permanente
Podiatric Relevance:
In the context of current trends focusing on preventative medicine, this study is extremely important for anyone caring for diabetic patients. Epidermal nerve fiber density (ENFD) testing allows the practitioner to evaluate subjective data regarding small-fiber sensory loss in the diabetic patient who may not be experiencing clinic symptoms. Early detection of this sensory loss can lead to early intervention and treatment. Appropriate treatment, with a disease-modifying agent, can result in the replenishment of nerve fibers, which may prevent or at least delay neuropathy, ulceration, infection, and limb loss that could occur.
Methods:
Eleven consecutive patients with a history of paresthesias, spontaneous pain or dysesthesias of the lower extremity, as well as Type II diabetic mellitus were recruited for this study. Patients were excluded if they had any neuropathy not related to diabetes or if they were currently on any medication for diabetic neuropathy. ENFD was performed at the calf (10 cm proximal to the lateral malleolus) and patients were then placed on twice daily oral combination of L-methylfolate, methylcobalamin, pyridoxal 5’-phosphate (LMF-MC-PP) for six months. Repeat calf ENFD was again performed at 6-month mark.
Results:
No adverse reactions were seen in response to oral combination LMF-MC-PP over the 6-month trial period. No adverse reactions were seen to the biopsy. ENFD average increased from 1.56 fibers/mm at baseline to 3.07 fibers/mm after six months of oral therapy. This represented a 97 percent average increase in nerve fibers. Of the eleven study participants, eight (73 percent) showed an increase in ENFD at the six month histologic re-evaluation. Clinical symptoms also decreased in 82 percent of study participants.
Conclusions:
ENFD provides objective early assessment for detecting small-fiber neuropathy in the diabetic patient. Its application can also be extended to provide definitive and objective follow up of response that an individual has to a disease-modifying agents such as an oral-combination of LMF-MC-PP. This study demonstrated an 82 percent improvement in clinical neurologic symptoms after six months of therapy. An increase in calf ENFD was also noted in 73 percent of participants after six months of oral therapy. Limitations of this study are significant and include a small sample size, non-standardized method of patient selection, lack of control group, lack of control for insulin and glucose control, subjective VAS scoring system and possible volunteer bias. With this in mind, however, continued study in this area is important when one considers the clinical implications for the diabetic patient. Long term safety and efficacy of these oral agents is still unknown.