Despite efforts to enhance peripheral nerve regeneration, there has been little progress in improving clinical outcomes. Recently, a method of brief post‐surgical low frequency electrical stimulation of surgically repaired nerves has been developed. It was shown to accelerate axon outgrowth across the repair site and it hastened target reinnervation. In this brief review, we describe the mechanistic insights and functional impacts of the post‐surgical electrical stimulation that have been gained through animal studies. Brain‐derived neurotrophic factor, cyclic AMP and regeneration‐associated genes play a vital role in expediting the outgrowth of axons across the injury site. The method of stimulation has also been shown to be effective in patients with severe compressive neuropathy as well as those with digital nerve laceration. Its clinical feasibility and positive impact open the door of further clinical translation in other peripheral nerve injuries.

BackgroundShoulder dysfunction is common after neck dissection for head and neck cancer (HNC). Brief electrical stimulation (BES) is a novel technique that has been shown to enhance neuronal regeneration after nerve injury by modulating brain-derived neurotrophic growth factor (BDNF) pathways. The objective of this study was to evaluate the effect of BES on postoperative shoulder function following oncologic neck dissection.MethodsAdult participants with a new diagnosis of HNC undergoing Level IIb +/− V neck dissection were recruited. Those in the treatment group received intraoperative BES applied to the spinal accessory nerve (SAN) after completion of neck dissection for 60 min of continuous 20 Hz stimulation at 3-5 V of 0.1 msec balanced biphasic pulses, while those in the control group received no stimulation (NS). The primary outcome measured was the Constant-Murley Shoulder (CMS) Score, comparing changes from baseline to 12 months post-neck dissection. Secondary outcomes included the change in the Neck Dissection Impairment Index (ΔNDII) score and the change in compound muscle action potential amplitude (ΔCMAP) over the same period.ResultsFifty-four patients were randomized to the treatment or control group with a 1:1 allocation scheme. No differences in demographics, tumor characteristics, or neck dissection types were found between groups. Significantly lower ΔCMS scores were observed in the BES group at 12 months, indicating better preservation of shoulder function (p = 0.007). Only four in the BES group compared to 17 patients in the NS groups saw decreases greater than the minimally important clinical difference (MICD) of the CMS (p = 0.023). However, NDII scores (p = 0.089) and CMAP amplitudes (p = 0.067) between the groups did not reach statistical significance at 12 months. BES participants with Level IIb + V neck dissections had significantly better ΔCMS and ΔCMAP scores at 12 months (p = 0.048 and p = 0.025, respectively).ConclusionsApplication of BES to the SAN may help reduce impaired shoulder function in patients undergoing oncologic neck dissection, and may be considered a viable adjunct to functional rehabilitation therapies.Trial registrationClinicaltrials.gov (NCT02268344, October 17, 2014).

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BackgroundCarpal tunnel syndrome (CTS) is the most common form of peripheral nerve injury, affecting approximately 3 % of the population. While surgery is effective in mild and moderate cases, nerve and functional recovery are often not complete in severe cases. Therefore, there is a need for adjuvant methods to improve nerve regeneration in those cases. Acetyl-L-carnitine (ALCAR) is involved in lipid transport, vital for mitochondrial function. Although it has been shown to be effective in various forms of neuropathies, it has not been used in traumatic or compressive peripheral nerve injury.MethodsIn this pilot study we will utilize a double-blind, randomized, placebo-controlled design. Inclusion criteria will include adult patients with severe CTS. This will be confirmed by nerve conduction studies and motor unit number estimation (MUNE). Only those with severe motor unit loss in the thenar muscles (2 standard deviations [SD] below the mean for the age group) will be included. Eligible patients will be randomized to receive 3,000 mg/day of ALCAR orally or placebo following carpal tunnel release surgery for 2 months. The primary outcome will be MUNE with supplementary secondary outcome measures that include: 1) two-point discrimination; 2) Semmes-Weinstein monofilaments for pressure sensitivity; 3) cold and pain threshold for small fiber function; 4) Boston self-assessment Carpal Tunnel Questionnaire and 5) Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire for symptom severity; and 6) Purdue Pegboard Test for hand functional performance. To follow post treatment recovery and monitor safety, patients will be seen at 3 months, 6 months and 1 year. The outcome measures will be analyzed using two-way ANOVA, with treatment assignment and time points being the independent factors. If significant associations are detected, a post hoc analysis will be completed. We aim to recruit ten patients into each of the two groups. Data from this pilot will provide the basis for power calculation for a full-scale trial.DiscussionALCAR is a physiologic peptide crucial for fatty acid transport. ALCAR has been shown to be effective in neuroprotection in the central nervous system and increase peripheral nerve regeneration. This has been applied clinically to various systemic peripheral neuropathies including diabetic neuropathy, antiretroviral toxic neuropathy, and chemotherapy-induced peripheral neuropathy. While animal evidence exists for the benefit of ALCAR in compression neuropathy, there have been no human studies to date. This trial will represent the first use of ALCAR in peripheral nerve injury/compression neuropathy.Trial registrationNCT02141035; 20 April 2015

Background: Carpal tunnel syndrome is very common. Although surgery is effective in mild and moderate cases, recovery is often incomplete in severe cases. Therefore, adjuvant therapy to improve nerve regeneration in those patients is much needed. Acetyl-l-carnitine has been shown to be effective in other neuropathies. The goal of this study is to test the hypothesis that acetyl-l-carnitine can promote nerve regeneration and improve function in patients with severe carpal tunnel syndrome. Methods: In this proof-of-principle, double-blind, randomized, placebo-controlled trial, adults with severe carpal tunnel syndrome were randomized to receive 3000 mg/day of acetyl-l-carnitine orally or placebo following carpal tunnel release surgery for 2 months. Outcomes were assessed at baseline and at 3, 6, and 12 months postoperatively. Symptom severity and functional outcomes were assessed using the Boston Carpal Tunnel Questionnaire and a wide range of physiologic and functional outcome measures. Patient safety was monitored by physical examination, blood work, and serum drug levels. The outcomes were analyzed using repeated measure two-way analysis of variance. Results: Twenty patients with similar baseline characteristics were assigned randomly to the treatment or placebo group in a 1:1 ratio. Sixty percent were women with a mean age ± SD of 59 ± 2. The treatment was safe with no major adverse events reported. Although patients in both groups showed improvements postoperatively, there was no significant difference in any of the outcome measures between the groups. Conclusion: Although acetyl-l-carnitine was well tolerated, it did not improve nerve regeneration or functional recovery in patients with severe carpal tunnel syndrome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.