Dr. Rodriguez has been a doctor of podiatric medicine in private practice in Uvalde, Texas, for the past 4 years. He specializes in diabetic limb salvage and reconstructive foot surgery. Dr. Rodriguez joined The Podiatry Group of South Texas, PA, on August 1, 2005.

A 75-year-old Hispanic man with non-insulin-dependent diabetes mellitus presented with a 3-year history of progressively painful neuropathy and no previous treatments. The patient also had a past medical history of glaucoma. Socially, the patient denied any history of drug use or other exposure that could contribute to neuropathic pain. Physical findings were positive for decreased protective sensation of bilateral feet (3/10) to 10 g of pressure utilizing a 5.07 Semmes-Weinstein monofilament. The patient also had decreased vibratory sensation to bilateral first metatarsophalangeal joints. Vascular evaluation demonstrated 1/4 dorsalis and posterior tibial pulses bilaterally with biphasic Doppler exam. Hallucal capillary fill time was 3 seconds in the right foot and 4 seconds in the left foot. The patient’s chief complaint was burning sensation to all digits and forefoot of bilateral feet.
The patient was placed on Metanx 1 to 2 tablets by mouth daily and was scheduled for a 2-month follow-up.
At the 2-month follow-up, the patient’s physical signs had not changed, but he reported 30% improvement in the burning sensation to bilateral feet. The patient also mentioned that he had been taking 2 tablets of Metanx per day. Once again, the patient was scheduled for follow-up in 2 months.
At the next follow-up visit, the patient was re-evaluated clinically and was found to have improved vibratory sensation to bilateral first metatarsophalangeal joints as well as improved protective sensation in the right foot (6/10) and left foot (7/10). His circulatory status remained unchanged since previous visits. The patient stated that for the first time in a long time he could “feel” his toes, and the burning sensation no longer kept him from sleeping at night. When asked what percentage of improvement he had since starting on Metanx 4 months previously, he stated 70%.
After an additional 2 months, the patient’s circulatory status demonstrated 1/4 dorsalis pedis pulses bilaterally but a 2/4 posterior tibial pulse to the right and 1/4 to the left. The patient continued to have biphasic Doppler exams, but his hallucal capillary fill time decreased to 2 seconds bilaterally. The patient’s vibratory sensation was now normal bilaterally, and his protective sensation improved in the right foot (8/10) and left foot (9/10). The patient also stated he no longer felt burning sensation to either foot and he felt 90 to 100% improved.
He continues to take Metanx daily.

Commentary
David E. Allie, MD

Clinically, it appears this patient has had a good response to his diabetic neuropathy symptoms with once daily Metanx. I have found even better results with twice-daily dosage. This patient and all patients in this series are at high risk for cardiovascular disease including coronary, carotid, and lower-extremity peripheral arterial disease (PAD). The patient with diabetic neuropathy must be thoroughly worked up for these vascular diseases, as this patient population’s number 1 and number 3 causes of death are myocardial infarction and stroke. Metanx theoretically also has outcome improvement capabilities over the entire cardiovascular tree.

Allen M. Jacobs, DPM

Dr. Jacobs has a private practice, Dr. Allen M. Jacobs & Associates, Ltd., P.C., in St. Louis, Missouri.

The observation of Dr. Rodriguez regarding the improvement in objective or quantifiable neurologic parameters in the context of subjective patient improvement is certainly interesting. The methylcobalamin in Metanx has been demonstrated to facilitate neural regeneration, while pyridoxal 5’-phosphate has long been established as necessary for neural function. Therefore, the findings of Dr. Rodriguez are not surprising. Yaqub et al.1 previously demonstrated the effectiveness of methylcobalamin on diabetic neuropathy. Personally, I have had wonderful success with this agent in many patients troubled with diabetic neuropathy, although I do not frequently observe quantifiable changes.
Dr. Rodriguez noted the loss of vibratory sensation in his patient. The loss of vibratory sensation has been demonstrated to be an important and reliable predictor of long-term complications from diabetes, including ulceration.2 I am pleased to see a neurologic examination of the diabetic foot extend beyond a 5.07 Semmes-Weinstein monofilament.
Dr. Rodriguez also noted the presence of impaired peripheral vascular perfusion in his patient. His patient’s concern of burning could have been due to evolving ischemic neuropathy, and his evaluation of the patient’s peripheral vascular status was most important. The L-methylfolate in Metanx has been shown to increase nitric oxide levels, thereby improving endothelial function. We increasingly see therapeutic interventions, particularly in the arena of wound healing, directed at improvement of nitric oxide tissue levels. Therefore, it would be logical to infer some improvement in ischemic neuropathy by increasing neuronal blood flow by the administration of L-methylfolate. The effects of L-methylfolate might also explain the observed improvement in great toe capillary filling, which was observed in this patient.
Ambrosch et al.3 demonstrated that homocysteine levels are elevated in many patients with diabetic neuropathy. Homocysteine is known to be a risk factor for damage to vascular endothelium. Because Metanx lowers serum homocysteine levels, we might understand the remittive effects of this agent in treating neuropathy in the patient with diabetes, particularly like the patient described by Dr. Rodriguez.