High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study.

BACKGROUND: We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept. METHODS: Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks. The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables. RESULTS: The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product. CONCLUSIONS: Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05.

Topical capsaicin for the management of painful diabetic neuropathy: a narrative systematic review.

Aim: To investigate the potential benefit of topical capsaicin formulations. Materials & methods: A narrative systematic review was employed. Results: About 8% capsaicin patches were found to significantly reduce symptoms of diabetic peripheral neuropathy. Capsaicin was found to improve sleep quality (p = 0.02). Capsaicin patch exposure for 60 min showed significant reduction in symptoms (-32.8%). Capsaicin cream significantly reduced pain at weeks two and six (p = 0.003 and p = 0.03, respectively), but not at week eight in comparative studies. 0.025% capsaicin gel had an insignificant reduction in pain compared with placebo (p = 0.53), however 0.075% was found to be significant (p = 0.038). Capsaicin cream did not have superior improvement of pain as compared with clonidine gel (p = 0.931). The most common adverse events included application site discomfort, erythema and burning. Conclusion: Topical capsaicin treatments are a potentially beneficial peripherally acting medication. Further research is needed to determine the best means of ameliorating the side effects of treatments.

Painful diabetic neuropathy (DPN) is a serious and common problem affecting those suffering from diabetes. Current treatments of DPN include medications that act on the CNS, rather than the distally affected nerves. Topical capsaicin patches and creams offer potential as alternative treatments to centrally acting neuropathy medications. Topical capsaicin depletes the neurotransmitter for pain signaling at the distally affected nerves. Topical capsaicin in all formulations has been shown to be beneficial in reduction of DPN. However, capsaicin treatments are often irritating to the skin, causing burning and redness at the application site.

The role of the capsaicin 8% patch in the treatment of painful diabetic peripheral neuropathy.

Treatment of painful diabetic peripheral neuropathy (PDPN) is challenging and often limited by drug tolerability and adverse effects. This review article focuses on the high-dose (8%) capsaicin patch that allows for improved efficacy and reduced application frequency in comparison to low-dose capsaicin formulations. Systemic absorption is minimal resulting in fewer systemic side effects than first-line oral medications. There is evidence that capsaicin patch treatment is well-tolerated, safe and provides effective pain relief maintained for several weeks; well-powered studies are needed to confirm these findings. The capsaicin 8% patch may benefit patients at high risk for adverse effects from oral medication, polypharmacy or inadequate pain relief from first-line therapies.

Treatment of nerve pain in the feet and other regions due to nerve damage from diabetes is challenging, often due to the unwanted side effects of medications. This review article focuses on the high-dose (8%) capsaicin patch, which can be applied directly to the feet. It is more potent than the low-dose formulations, allowing patients to apply it less often while also working more effectively compared with low-dose capsaicin creams. Because it acts directly on the skin, there are fewer systemic side effects such as drowsiness or urinary retention. There is evidence that capsaicin patch treatment is safe and provides pain relief for several weeks. More large studies are needed to confirm these findings. The capsaicin 8% patch may benefit patients at high risk for side effects from oral medications or inadequate pain relief from first-line medications.

Effectiveness of Empagliflozin With Vitamin D Supplementation in Peripheral Neuropathy in Type 2 Diabetic Patients.

BACKGROUND: Neuropathy is the most prevalent broad-spectrum microvascular complication of diabetes. The present study aims to evaluate the effect of empagliflozin with vitamin D supplementation on diabetic peripheral neuropathy. METHODS: A prospective, randomized, controlled study was conducted for six months including 150 type 2 diabetic patients, divided into three groups (n=50/group): Group 1, patients on oral hypoglycemic agents; Group 2, patients on empagliflozin and Group 3, patients on empagliflozin with vitamin D. Biochemical parameters were estimated for outcome measurements and patients' neuropathic pain was analysed using Douleur Neuropathique 4 Questions, Neuropathic Pain Symptom Inventory and Ipswich Touch the toes test questionnaire. Data were analysed using a one-way analysis of variance. RESULTS: Diabetic neuropathy in males was more prevalent (more than 50%) as compared to females in all three groups, with an average age of 50±6 years, along with a diabetic history of 15±4.5 years and a glycated hemoglobin A1C (HbA1C) level of >10%. The mean value of serum vitamin D level significantly increased by 64.7% (19±5 to 54±8 ng/mL; p<0.05). A remarkable decrease (by 17.4%) from baseline in the HbA1C level was observed after six months of treatment only in Group 3, whereas in other groups (1 and 2), there was a non-significant decrease in HbA1C levels when compared to baseline. Moreover, a significant improvement in neuropathic condition was seen only in Group 3. CONCLUSION: The results indicated that empagliflozin with vitamin D supplementation significantly controlled or reduced HbA1C and improved diabetic neuropathic symptoms in patients. It is suggested that this combination can be considered as the primary therapeutic approach for neuropathic complications in diabetic patients.

Nutraceutical Approach to Peripheral Neuropathies: Evidence from Clinical Trials.

BACKGROUND: The etiopathogenetic mechanisms of peripheral neuropathies include genetic, traumatic, toxic, metabolic, infectious, nutritional, inflammatory and paraneoplastic causes. Their treatment should primarily address their contributing causes. However, symptomatic therapy is also key in these conditions, particularly in pain relief. METHOD: Relevant studies were identified using the PubMed electronic database in January 2017. After a preliminary search, we focused on the single compounds for which randomized controlled trials versus placebo or comparing high and low doses were performed. Studies in which a combination of different compounds was tested were not considered, with the exception of complex B multivitamins. RESULTS: Several nutraceuticals have been used in the treatment of peripheral neuropathies and seem promising, due to assumed neurotrophic action, low toxicity and favorable metabolic profile. We performed a review of the literature to evaluate safety and effectiveness of nutraceutical compounds in peripheral neuropathies, focusing on the single agents for which randomized controlled trials versus placebo were performed. Vitamin B complex, alpha lipoic acid, L-acetylcarnitine, vitamin E and Coenzyme Q proved effective to different extents in neuropathic pain in polyneuropathies. They all proved less consistently effective on other neuropathic symptoms, neuropathic signs and neurophysiological parameters. All the considered compounds were tolerable even for long periods, however alpha lipoic acid at doses equal or larger than 1200 mg/die was associated with nausea and vomiting in a large number of patients. CONCLUSION: The findings of this review confirm a possible role for some adequately dosed nutraceuticals in the management of peripheral neuropathy.

Clinical Observation of Wrist-ankle Acupuncture plus Bloodletting Cupping for Diabetic Peripheral Neuropathies / 上海针灸杂志

Objective To observe the clinical efficacy of wrist-ankle acupuncture plus bloodletting cupping in treating diabetic peripheral neuropathies (DPN). Method A total of 120 patients were randomized into two groups by using the random number table. Sixty cases in the treatment group were intervened by wrist-ankle acupuncture plus bloodletting cupping; sixty cases in the control group were treated with Mecobalamin tablets. The clinical efficacies were evaluated and electroneurogram was tested after 28-day treatment. Result The total effective rate was 95.0% in the treatment group versus 88.3% in the control group. The clinical efficacy of the treatment group was significantly superior to that of the control group (P<0.05). The treatment group was significantly better than the control group in comparing the major symptoms and signs including numbness, pain, and weakness in limbs (P<0.05); there were no significant between-group differences in comparing symptoms including cold limbs, short of breath and unwilling to speak, lassitude, and thirsty with desire to drink (P>0.05). The treatment group had better effect than the control group in comparing the motor conduction velocity of superficial peroneal nerve and sensory conduction velocity of common peroneal nerve (P<0.05). Conclusion Wrist-ankle acupuncture plus bloodletting cupping is effective in treating DPN, and it benefits the recovery of motor and sensory function of the impaired peripheral nerves.

High dose subcutaneous immunoglobulin for idiopathic inflammatory myopathies and dysimmune peripheral chronic neuropathies treatment: observational study of quality of life and tolerance.

BACKGROUND: In patients with autoimmune diseases who still derive benefit from high dose intravenous immunoglobulin (IVIg) treatment, some physicians resort to subcutaneous (SC) Ig as a replacement therapy. OBJECTIVE: To collect quality of life (QoL) and tolerance data on SCIg in patients for whom the switch from IVIg to SCIg is essential to maintain treatment. METHODS: This observational study included patients with either idiopathic inflammatory myopathies (IIM) or chronic dysimmune peripheral neuropathies (CDPN) treated with IVIg, who had been switched to SCIg administration for at least three months. The main objective was to describe the impact of SCIg on QoL after six months, using the generic Short-Form 36 questionnaire (SF-36). The secondary objectives were to evaluate SCIg tolerance and clinical efficiency. RESULTS: Eight centres recruited 12 IIM patients and two centres recruited 11 CDPN patients. Neither the physical nor the mental health SF-36 component summaries showed any QoL deterioration during the six-month study period and all IIM and CDPN patients remained clinically stable during the same period. The most frequent adverse effects were injection site reactions (50%), cutaneous tissue disorders (18.2%), and nervous system disorders (13.6%). Two serious adverse events (myocarditis and cerebrovascular accident) occurred in two patients. CONCLUSION: In these rare inflammatory diseases, high dose SCIg administration (which can be home based) has no deleterious effect on patient QoL. It appears to be a safe and efficient alternative to hospital-based IVIg.

Processed aconite root and its active ingredient neoline may alleviate oxaliplatin-induced peripheral neuropathic pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Processed aconite root (PA, the root of Aconitum carmichaeli, Ranunculaceae) is a crude drug used in traditional Chinese or Japanese kampo medicine to generate heat in the body and to treat pain associated with coldness. Oxaliplatin (L-OHP) is a platinum-based anticancer drug that frequently causes acute and chronic peripheral neuropathies, including cold and mechanical hyperalgesia. AIM OF THE STUDY: We investigated the effects of PA on L-OHP-induced peripheral neuropathies and identified the active ingredient within PA extract. MATERIALS AND METHODS: L-OHP was intraperitoneally injected into mice, and PA boiled water extract was orally administered. Cold and mechanical hyperalgesia were evaluated using the acetone test and the von Frey filament method, respectively. Dorsal root ganglion (DRG) neurons were isolated from normal mice and cultured with L-OHP with or without PA extract. Cell viability and neurite elongation were evaluated. RESULTS: PA extract significantly attenuated cold and mechanical hyperalgesia induced by L-OHP in mice. In cultured DRG neurons, L-OHP reduced cell viability and neurite elongation in a dose-dependent manner. Treatment with PA extract significantly alleviated the L-OHP-induced reduction of neurite elongation, while the cytotoxicity of L-OHP was not affected. Using activity-guided fractionation, we isolated neoline from PA extract as the active ingredient. Neoline significantly alleviated L-OHP-induced reduction of neurite elongation in cultured DRG neurons in a concentration-dependent manner. Moreover, subcutaneous injection of neoline attenuated cold and mechanical hyperalgesia in L-OHP-treated mice. PA extract and neoline did not show sedation and motor impairment. CONCLUSIONS: The present study indicates that PA and its active ingredient neoline are promising agents to alleviate L-OHP-induced neuropathic pain.

Perceived Benefits of Group Exercise Among Individuals With Peripheral Neuropathy.

Exercise and training programs improve strength, functional balance, and prevent falls in a variety of populations. This article presents the qualitative findings related to the perceived benefits of participants in a randomized controlled trial that compared the effectiveness of group exercise on gait and balance in persons with peripheral neuropathy (PN). Participants with moderately severe PN were randomized into groups that received 10-week classes of Functional Balance Training (FBT) or Tai Chi or education alone. Perceptions of the intervention were overwhelmingly positive regardless of the study group. Perceived benefits reported by participants in the FBT and Tai Chi groups included awareness of how to deal with the effects of neuropathy by implementing balance strategies and a heightened sense of walking to prevent falls. This study offers a guide to design future exercise studies that promote simple balance exercises that can be performed in group settings.

The Effects of Foot Reflexology on Peripheral Neuropathy, Symptom Distress, Anxiety and Depression in Cancer Patients Treated with Oxaliplatin

PURPOSE: This study was done to clarify the effects of foot reflexology on peripheral neuropathy, symptom distress, anxiety and depression in cancer patients treated with oxaliplatin. METHODS: A quasi-experimental design was employed. Changes in the variables were evaluated to test the effects of foot reflexology. Participants were cancer patients treated with oxaliplatin (experimental group 14 and control group 17). Peripheral neuropathy, symptom distress, anxiety and depression were measured before and after reflexology. Data were collected from October, 2010 to April, 2011. chi2-test, Fisher's exact test, t-test, Wilcoxon signed rank test and the Mann-Whitney U test were used to analyze the data. RESULTS: The experimental group who received foot reflexology experienced less peripheral neuropathy and symptom distress than the control group. There was no difference in anxiety and depression between the experimental and control group. CONCLUSION: The foot reflexology program adopted in this study was found to be an effective method to reduce peripheral neuropathy and symptom distress. We recommend foot reflexology for patients with chemotherapy induced peripheral neuropathy.