Effect of Nimodipine and Botulinum Toxin A on Peripheral Nerve Regeneration in Rats: A Pilot Study.

BACKGROUND: Peripheral nerve damage is a frequent problem, with an estimated 2.8%-5.0% of trauma admissions involving peripheral nerve injury. End-to-end, tension-free microsurgical repair (neurorrhaphy) is the current gold standard treatment for complete transection (neurotmesis). While neurorrhaphy reapproximates the nerve, it does not address the complex molecular regenerative process. Evidence suggests that botulinum toxin A (BTX) and nimodipine (NDP) may improve functional recovery, but mechanisms of action remain unknown. METHODS: This research investigates BTX and NDP for their novel capacity to improve neural regeneration in the setting of neurorrhaphy using a Lewis rat tibial nerve neurotmesis model. In a triple-masked, placebo-controlled, randomized study design, we compared functional (rotarod, horizontal ladder walk), electrophysiological (conduction velocity, duration), and stereological (axon count, density) outcomes of rats treated with: NDP+saline injection, BTX+NDP, Saline+placebo, and BTX+placebo. Additional controls included sham surgery +/- BTX. RESULTS: NDP+saline outperformed other treatment groups in the ladder walk. This group had the fewest deep slips (15.07% versus 30.77% in BTX+NDP, P = 0.122), and the most correct steps (70.53% versus 55.58% in BTX+NDP, P = 0.149) in functional testing. NDP+saline also had the fastest nerve conduction velocity (0.811m/s versus 0.598m/s in BTX+NDP, P = 0.126) among treatment groups. BTX+NDP had the highest axon count (10,012.36 versus 7,738.18 in NDP+Saline, P = 0.009). CONCLUSION: This study is the first to test NDP with BTX in a multimodal assessment of nerve recovery following neurotmesis and neurorrhaphy. NDP outperformed BTX+NDP functionally. Future work will focus on nimodipine in an effort to improve nerve recovery in trauma patients.

Cadaveric comparison of the accuracy of ultrasound-guided versus 'blind' perineural injection of the tibial nerve in horses.

During diagnostic evaluation of hindlimb lameness in horses the tibial nerve block is traditionally performed based on anatomical reference points, but it can be difficult to achieve effective local anaesthesia using this blind technique. Ultrasound (US)-guided injection could increase the accuracy of injection. The aim of this study was to compare the accuracy of both techniques. Twenty-one paired sets of cadaver hindlimbs were injected with 1 mL methylene blue using the blind or US-guided technique. There was no significant difference in stain width and length and in coloured nerve length between techniques. However, the successful rate of nerve staining was 85.7% and 47.6% for the US-guided and blind technique, respectively (P = 0.02; odds ratio 6.6; 95% confidence interval, 1.5-29.4). This study suggests that the US-guided technique is more accurate than the blind technique. However, in the treated sample, a single US-guided injection did not consistently result in nerve staining.

Coccydynia relieved by a tarsal tunnel block: a case series.

BACKGROUND: This case series describes, for the first time, to the author's knowledge, a novel treatment for coccydynia. Tarsal tunnel block with lignocaine only brought relief of chronic coccydynia lasting more than 6 months in three patients. The author adopts the theory that the myelin sheath of the posterior tibial nerve will convey the lipid-soluble lignocaine upward toward the dorsal root ganglia and the nerve roots of the lumbar spine through the uninterrupted myelin sheath, which is itself mainly formed of lipids. The author thinks that most coccyx pain is actually a radiating pain from the lumbar spine, which is not always apparent on magnetic resonance imaging of the lumbar spine. Certainly, the author acknowledges that large-scale studies need to be done to prove the efficacy of this new technique and to prove that the myelin sheath can convey the lignocaine chemical upward. CASE PRESENTATION: Three Arab patients presented with chronic coccydynia of more than 6 months' duration in whom conservative management had failed to control their symptoms. They had no past medical history of significance and no history of trauma. The results of physical examination of all of the patients were normal apart from tenderness on palpation of the coccyx. They all received local coccyx injection with steroids on two occasions, which failed to relieve their pain. One patient underwent manipulation under anesthesia, and one underwent coccygectomy with no pain relief. Magnetic resonance imaging results were reported to be normal in two of them, whereas the other one had a prolapsed disc at the L4/L5 level. The three patients described pain relief 30 minutes after tarsal tunnel block with lignocaine only lasting more than 6 months. All patients had heel anesthesia 15 minutes after the tarsal tunnel injection, which lasted only 1 hour. CONCLUSIONS: Tarsal tunnel block with lignocaine can relieve coccyx pain for a long time. Tarsal tunnel block can be done to achieve heel anesthesia before injection of lignocaine into the plantar fascia in patients with plantar fasciitis.

Severe hyperhomocysteinemia and peripheral neuropathy as side effects of nitrous oxide in two patients with sickle cell disease.

Nitrous oxide (N2O) is a widely used anesthetic agent. We report two patients with sickle cell disease (SCD) who presented with complications following the use of N2O. Patient 1, a 15-year-old girl, presented severe hyperhomocysteinemia, pancytopenia, vitamin B12 deficiency, and peripheral polyneuropathy after massive use of N2O for pain management. At the 1-year follow-up, hyperhomocysteinemia and B12 deficiency had resolved, but she had persisting mild symptoms of polyneuropathy. Patient 2, a 17-year-old boy, presented only severe hyperhomocysteinemia, only partially corrected by initial B12 supplementation. Careful monitoring of N2O use, especially in patients with SCD, is mandatory to prevent complications.

Improvement of motor conduction velocity in hereditary neuropathy of LAMA2-CMD dy2J/dy2J mouse model by glatiramer acetate.

OBJECTIVE: Glatiramer acetate (GA), an agent modulating the immune system, has been shown to cause significantly improved mobility and hind limb muscle strength in the dy2J/dy2J mouse model for LAMA2-congenital muscular dystrophy (LAMA2-CMD). In view of these findings and the prominent peripheral nervous system involvement in this laminin-α2 disorder we evaluated GA's effect on dy2J/dy2J motor nerve conduction electrophysiologically. METHODS: Left sciatic-tibial motor nerve conduction studies were performed on wild type (WT) mice (n = 10), control dy2J/dy2J mice (n = 11), and GA treated dy2J/dy2J mice (n = 10) at 18 weeks of age. RESULTS: Control dy2J/dy2J mice average velocities (34.49 ±â€¯2.15 m/s) were significantly slower than WT (62.57 ±â€¯2.23 m/s; p < 0.0005), confirming the clinical observation of hindlimb paresis in dy2J/dy2J mice attributed to peripheral neuropathy. GA treated dy2J/dy2J mice showed significantly improved average sciatic-tibial motor nerve conduction velocity versus control dy2J/dy2J (50.35 ±â€¯2.9 m/s; p < 0.0005). CONCLUSION: In this study we show for the first time improvement in motor nerve conduction velocity of LAMA2-CMD dy2J/dy2J mouse model's hereditary peripheral neuropathy following GA treatment. SIGNIFICANCE: This study suggests a possible therapeutic effect of glatiramer acetate on hereditary peripheral neuropathy in this laminin-α2 disorder.

Injection of Fluoro-Gold into the tibial nerve leads to prolonged but reversible functional deficits in rats.

Tract tracing with neuronal tracers not only represents a straightforward approach to identify axonal projection connection between regions of the nervous system at distance but also provides compelling evidence for axonal regeneration. An ideal neuronal tracer meets certain criteria including high labeling efficacy, minimal neurotoxicity, rapid labeling, suitable stability in vivo, and compatibility to tissue processing for histological/immunohistochemical staining. Although labeling efficacy of commonly used fluorescent tracers has been studied extensively, neurotoxicity and their effect on neural functions remains poorly understood. In the present study, we comprehensively evaluated motor and sensory nerve function 2-24 weeks after injection of retrograde tracer Fluoro-Gold (FG), True Blue (TB) or Fluoro-Ruby (FR) in the tibial nerve in adult Spague-Dawley rats. We found that motor and sensory nerve functions were completely recovered by 24 weeks after tracer exposure, and that FG lead to a more prolonged delay in functional recovery than TB. These findings shed light on the long-term effect of tracers on nerve function and peripheral axonal regeneration, and therefore have implications in selection of appropriate tracers in relevant studies.

Comparative functional analysis of mice after local injection with botulinum neurotoxin A1, A2, A6, and B1 by catwalk analysis.

Botulinum neurotoxins (BoNTs) are potent neurotoxins and are the causative agent of botulism, as well as valuable pharmaceuticals. BoNTs are divided into seven serotypes that comprise over 40 reported subtypes. BoNT/A1 and BoNT/B1 are currently the only subtypes approved for pharmaceutical use in the USA. While several other BoNT subtypes including BoNT/A2 and/A6 have been proposed as promising pharmaceuticals, detailed characterization using in vivo assays are essential to determine their pharmaceutical characteristics compared to the currently used BoNT/A1 and/B1. Several methods for studying BoNTs in mice are being used, but no objective and quantitative assay for assessment of functional outcomes after injection has been described. Here we describe the use of CatWalk XT as a new analytical tool for the objective and quantitative analysis of the paralytic effect after local intramuscular injection of BoNT subtypes A1, A2, A6, and B1. Catwalk is a sophisticated gait and locomotion analysis system that quantitatively analyzes a rodent's paw print dimensions and footfall patterns while traversing a glass plate during unforced walk. Significant changes were observed in several gait parameters in mice after local intramuscular injection of all tested BoNT subtypes, however, no changes were observed in mice injected intraperitoneally with the same BoNTs. While a clear difference in time to peak paralysis was observed between BoNT/A1 and/B1, injection of all four toxins resulted in a deficit in the injected limb with the other limbs functionally compensating and with no qualitative differences between the four BoNT subtypes. The presented data demonstrate the utility of CatWalk as a tool for functional outcomes after local BoNT injection through its ability to collect large amounts of quantitative data and objectively analyze sensitive changes in static and dynamic gait parameters.

Contralateral Botulinum Toxin Improved Functional Recovery after Tibial Nerve Repair in Rats.

BACKGROUND: There is clinical and experimental evidence that botulinum toxin applied to the healthy side of patients with facial paralysis positively affects functional recovery of the paralyzed side. The authors created an experimental model to study the effects of botulinum toxin injection in the gastrocnemius muscle contralateral to the side of tibial nerve lesion/repair in rats. METHODS: Fifty rats were allocated into five groups: group I, control; group II, tibial nerve section; group III, tibial nerve section and immediate neurorrhaphy; group IV, tibial nerve section, immediate neurorrhaphy, and botulinum toxin injected into the contralateral gastrocnemius muscle; and group V, botulinum toxin injected into the gastrocnemius muscle and no surgery. Assessment tools included a walking track, electromyography, gastrocnemius muscle weight measurement, and histologic analysis of the nerve. RESULTS: Paralysis in group V was transient, with function returning to normal at 8 weeks. At 12 weeks, group V had lower latency levels. At week 12, group IV showed higher functional outcomes and amplitude levels than group III, and lower muscle atrophy on the side injected with botulinum toxin compared with group V. CONCLUSION: Transient paralysis of the contralateral gastrocnemius muscle by botulinum toxin type A improved functional recovery in rats that underwent section and repair of the tibial nerve.

Botulinum Toxin Conditioning Enhances Motor Axon Regeneration in Mouse and Human Preclinical Models.

BACKGROUND: Peripheral axon regeneration is improved when the nerve lesion under consideration has recently been preceded by another nerve injury. This is known as the conditioning lesion effect (CLE). While the CLE is one of the most robust and well characterized means to enhance motor axon regeneration in experimental models, it is not considered a clinically feasible strategy. A pharmacological means to re-produce the CLE is highly desirable. OBJECTIVE: To test whether chemodenervation with a clinical grade formulation of botulinum toxin A (BoTX) would be sufficient to reproduce the CLE. METHODS: We examined the effects of a 1-week preconditioning administration of BoTX on motor axon regrowth in both a mouse tibial nerve injury and human embryonic stem cell (hESC)-based model. We assessed neuronal reinnervation in vivo (mice) with retrograde tracers and histological analysis of peripheral nerve tissue after injections into the triceps surae muscle group. We assessed motor neuron neurite outgrowth in vitro (hESC) after incubation in BoTX by immunohistochemistry and morphometric analysis. RESULTS: We found that BoTX conditioning treatment significantly enhanced outgrowth of both murine motor axons in vivo and human MN neurites in vitro. CONCLUSIONS: BoTX preconditioning represents a pharmacological candidate approach to enhance motor axon regeneration in specific clinical scenarios such as nerve transfer surgery. Further studies are needed to elucidate the molecular mechanism.

[A meta-analysis of the effect of occupational exposure to 1-bromopropane on workers' nerve conduction velocity].

Objective: To analysis the occupational exposure to 1-bromopropane on the worker's nerve conduc-tion velocity. Methods: To PubMed, Wanfang, VIP, Chinese Journal Full-text Database (CNKI) and other databases as a data source, searched and screened database to October 2017 on occupational exposure to 1-bromopropane workers on the role of nerve conduction in the paper. According to inclusion and exclusion criteria, we screened literatures, extracted data and evaluated the quality of the included studies, using RevMan5.3 software to test the heterogeneity of the results and us-ing the corresponding mathematical model for data combination analysis. Results: A total of 5 articles were included in the literature. The results showed that the tibial nerve MCV of workers in the 1-bromopropane exposure group was slower than that in the control group (SMD=-0.47,95%CI=-0.70~-0.24) , the difference was statistically significant (Z=4.06, P<0.01). The tibial nerve DL of the exposure group was more prolonged than that of the control group (SMD=0.35,95%CI=0.00~0.69) , with a statistically significant difference (Z=1.99, P=0.05). The sural nerve SCV of the exposure group was slower than that of the control group (SMD=-0.47, 95%CI=-0.78~-0.15), with a statistically significant difference (Z=2.88,P<0.01). Conclusion: Occupational exposure to 1-bromopropane may have an effect on the worker's nerve conduction ve-locity.It's necessary to do broader and deeper neurotoxicity studies about 1-bromopropane.

Analgesic effects of systemic fentanyl on cancer pain are mediated by not only central but also peripheral opioid receptors in mice.

Fentanyl is an opioid commonly prescribed for cancer pain. Using melanoma-bearing mice, we investigated whether peripheral action would contribute to fentanyl analgesia in cancer pain. Intravenous injection of fentanyl inhibited mechanical nociception in healthy mice, which was markedly inhibited by the opioid antagonist naloxone, but not naloxone methiodide, a peripherally acting opioid antagonist. Melanoma-bearing mice showed mechanical allodynia and spontaneous licking, a pain-related behavior, which were suppressed by intravenous and local injections of fentanyl. Both naloxone and naloxone methiodide inhibited the analgesic effect of intravenous fentanyl to the same degree. Electrophysiological analysis showed that melanoma growth increased the spontaneous and mechanical stimuli-evoked activity of the tibial nerve, which were inhibited by intravenous fentanyl. There was a greater expression of µ- opioid receptors in skin with a melanoma mass than in the contralateral normal skin. In addition, we found µ-opioid receptors in cultured melanoma cells. There was no difference between the number of µ-opioid receptors in the dorsal root ganglia and spinal cord of the melanoma-bearing and contralateral skin side. These results suggest that the analgesic effect of systemic fentanyl is produced via central and peripheral µ- opioid receptors in cancer pain, and cancer cells are a key site of peripheral action.

Transplantation of a Peripheral Nerve with Neural Stem Cells Plus Lithium Chloride Injection Promote the Recovery of Rat Spinal Cord Injury.

Transplantation of neural stem cells (NSCs) holds great potential for the treatment of spinal cord injury (SCI). However, transplanted NSCs poorly survive in the SCI environment. We injected NSCs into tibial nerve and transplanted tibial nerve into a hemisected spinal cord and investigated the effects of lithium chloride (LiCl) on the survival of spinal neurons, axonal regeneration, and functional recovery. Our results show that most of the transplanted NSCs expressed glial fibrillary acidic protein, while there was no obvious expression of nestin, neuronal nuclei, or acetyltransferase found in NSCs. LiCl treatment produced less macrosialin (ED1) expression and axonal degeneration in tibial nerve after NSC injection. Our results also show that a regimen of LiCl treatment promoted NSC differentiation into NF200-positive neurons with neurite extension into the host spinal cord. The combination of tibial nerve transplantation with NSCs and LiCl injection resulted in more host motoneurons surviving in the spinal cord, more regenerated axons in tibial nerve, less glial scar area, and decreased ED1 expression. We conclude that lithium may have therapeutic potential in cell replacement strategies for central nervous system injury due to its ability to promote survival and neuronal generation of grafted NSCs and reduced host immune reaction.

Single Local Application of TGF-ß Promotes a Proregenerative State Throughout a Chronically Injured Nerve.

BACKGROUND: The lack of nerve regeneration and functional recovery occurs frequently when injuries involve large nerve trunks because insufficient mature axons reach their targets in the distal stump and because of the loss of neurotrophic support, primarily from Schwann cells (SCs). OBJECTIVE: To investigate whether a single application of transforming growth factor-beta (TGF-ß) plus forskolin or forskolin alone can promote and support axonal regeneration through the distal nerve stump. METHODS: Using a delayed repair rat model of nerve injury, we transected the tibial nerve. After 8 wk, end-to-end repair was done and the repair site was treated with saline, forskolin, or TGF- ß plus forskolin. After 6 wk, nerve sections consisting of the proximal stump, distal to the site of repair, and the most distal part of the nerve stump were removed for nerve histology, axon counts, and immunohistochemistry for activated SCs (S100), macrophages (CD68), cell proliferation (Ki67), p75NGFR, and apoptosis (activated caspase-3). RESULTS: TGF-ß plus forskolin significantly increased the numbers of axons regenerated distal to the repair site and the most distal nerve sections. Both treatments significantly increased the numbers of axons regenerated in the most distal nerve sections compared to saline treated. Both treatments exhibited extended expression of regeneration-associated marker proteins. CONCLUSION: TGF-ß plus forskolin treatment of chronically injured nerve improved axonal regeneration and increased expression of regeneration-associated proteins beyond the repair site. This suggests that a single application at the site of repair has mitogenic effects that extended distally and may potentially overcome the decrease in regenerated axon over long distance.

Antiallodynic Effects of Endomorphin-1 and Endomorphin-2 in the Spared Nerve Injury Model of Neuropathic Pain in Mice.

BACKGROUND: The spared nerve injury (SNI) model is a new animal model that can mimic several characteristics of clinical neuropathic pain. Opioids are recommended as treatment of neuropathic pain. Therefore, the present study was conducted to investigate the antinociceptive effects of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) given centrally and peripherally in the SNI model of neuropathic pain in mice. METHODS: The SNI model was made in mice by sparing the sural nerve intact, when the other 2 of 3 terminal branches of the sciatic nerve (common peroneal and tibial nerves) were tightly ligated and cut. Von Frey monofilaments were used to measure the SNI-induced mechanical allodynia-like behavior. The antiallodynic effects of EM-1 and EM-2 were determined after central and peripheral administration in the SNI model of neuropathic pain. Also, the specific opioid receptor antagonists were used to determine the opioid mechanisms of EMs involved in neuropathic pain. Values were expressed as the mean ± standard deviation. RESULTS: Our results showed that the SNI mice developed prolonged mechanical allodynia-like behavior in ipsilateral paw after surgery, with the withdrawal threshold value being 0.061 ± 0.02 g after 14 days. EM-1 and EM-2 produced significant antiallodynic effects in ipsilateral paw after intracerebroventricular (i.c.v.) administration, more effective than that of morphine. The peak withdrawal thresholds of 10 nmol EM-1 and EM-2 determined at 5 minutes after injection were 0.92 ± 0.36 and 0.87 ± 0.33 g, respectively, higher than that of morphine (0.46 ± 0.20 g). Moreover, both EMs (10 nmol, i.c.v.) exerted significant antiallodynic effects in the contralateral paw, whereas no significant antinociceptive activity was seen after i.c.v. administration of morphine with equimolar dose. It was noteworthy that EM-1 and EM-2 produced antinociception through distinct µ1- and µ2-opioid receptor subtypes, and the EM-2-induced antiallodynia contained an additional component that was mediated by the release of endogenous dynorphin A, acting on κ-opioid receptor. In addition, the antiallodynic activities of peripheral administration of EM-1, EM-2, and morphine were also investigated. Intraplantar, but not subcutaneous administration of EM-1 and EM-2 also exhibited potent antinociception, establishing the peripheral and local effects. Both µ1- and µ2-opioid receptor subtypes, but not the δ- or κ-opioid receptors were involved in the peripheral antiallodynia of EMs. CONCLUSIONS: The present investigation demonstrated that both EM-1 and EM-2 given centrally and peripherally produced potent antiallodynic activities in SNI mice, and differential opioid mechanisms were involved.

Tibial Nerve Block Using an Ultrasound-Guided Inframalleolar Medial Plantar Nerve Perineural Injection: A Technical Note.

Sonographic-guided tibial nerve block allows for rapid anesthetization of the heel and plantar regions of the foot. We describe a variant technique for tibial nerve regional anesthesia utilizing perineural injection of the medial plantar nerve proximal to the sustentaculum tali where the nerve is superficial and readily accessed, with resultant retrograde flow of local anesthetic proximally. Perineural injection of the medial plantar nerve at the inframalleolar level provides a simple, safe, and effective alternative method to achieve tibial nerve block for regional anesthesia in a variety of procedures. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:134-137, 2017.

Medial plantar nerve ligation as a novel model of neuropathic pain in mice: pharmacological and molecular characterization.

Peripheral neuropathic pain is a consequence of an injury/disease of the peripheral nerves. The mechanisms involved in its pathophysiology are not entirely understood. To better understand the mechanisms involved in the development of peripheral nerve injury-induced neuropathic pain, more experimental models are required. Here, we developed a novel peripheral neuropathic pain model in mice by using a minimally invasive surgery and medial plantar nerve ligation (MPNL). After MPNL, mechanical allodynia was established, and mice quickly recovered from the surgery without any significant motor impairment. MPNL causes an increased expression of ATF-3 in the sensory neurons. At 14 days after surgery, gabapentin was capable of reversing the mechanical allodynia, whereas anti-inflammatory drugs and opioids were ineffective. MPNL-induced neuropathic pain was mediated by glial cells activation and the production of TNF-α and IL-6 in the spinal cord. These results indicate MPNL as a reasonable animal model for the study of peripheral neuropathic pain, presenting analgesic pharmacological predictivity to clinically used drugs. The results also showed molecular phenotypic changes similar to other peripheral neuropathic pain models, with the advantage of a lack of motor impairment. These features indicate that MPNL might be more appropriate for the study of neuropathic pain than classical models.

[Postoperative analgesia effect of different background volumes of ropivacaine in continuous tibial nerve block in patients with calcaneal surgery].

OBJECTIVE: To observe the clinical effect of different background volumes of ropivacaine in continuous tibial nerve block of postoperative analgesia after calcaneal surgery. METHODS: This study was a prospective, randomized, controlled study. Sixty cases of calcaneal visual analogue scale (ASA) I or II undergoing elective surgery were selected and randomly assigned to two groups, thirty cases in each group. The patients received popliteal fossa posterior tibial nerve block using ultrasound guided. The continuous stimulation catheter was inserted after successful position and the 0.2% ropivacaine was injected. The background volumes of the A and B groups were 5 mL/h and 3.2 mL/h. The VAS score, the sensory block and motor block of tibial nerve and common peroneal nerve, and the satisfaction of the patients at h 12, h 24 and h 48 were recorded after catheter insertion. RESULTS: The VAS scores at the three time points (h 12, h 24 and h 48) on the two groups of the patients were compared, and the difference was not statistically significant (P > 0.05). The difference of the sensory block and the motor block of the tibial nerve at the three time points (h 12, h 24 and h 48) on the two groups of the patients were also compared, and the difference was not statistically significant (P> 0.05). The difference of the sensory block and the motor block of common peroneal nerve at h 48 hs was statistically significant, group A was higher than the group B (P< 0.05). The difference of the patient satisfaction at the three time points (h 12, h 24 and h 48) on the two groups was not statistically significant (P> 0.05). CONCLUSION: The use of 0.2% ropivacaine with the background volume of 3.2 mL/h in continuous tibial nerve block can provide good analgesia and reduce the incidence of the sensory block and motor block of the common peroneal nerve.

Diabetic neuropathy increases stimulation threshold during popliteal sciatic nerve block.

BACKGROUND: Peripheral nerve stimulation is commonly used for nerve localization in regional anaesthesia, but recommended stimulation currents of 0.3-0.5 mA do not reliably produce motor activity in the absence of intraneural needle placement. As this may be particularly true in patients with diabetic neuropathy, we examined the stimulation threshold in patients with and without diabetes. METHODS: Preoperative evaluation included a neurological exam and electroneurography. During ultrasound-guided popliteal sciatic nerve block, we measured the current required to produce motor activity for the tibial and common peroneal nerve in diabetic and non-diabetic patients. Proximity to the nerve was evaluated post-hoc using ultrasound imaging. RESULTS: Average stimulation currents did not differ between diabetic (n=55) and non-diabetic patients (n=52). Although the planned number of patients was not reached, the power goal for the mean stimulation current was met. Subjects with diminished pressure perception showed increased thresholds for the common peroneal nerve (median 1.30 vs. 0.57 mA in subjects with normal perception, P=0.042), as did subjects with decreased pain sensation (1.60 vs. 0.50 mA in subjects with normal sensation, P=0.038). Slowed ulnar nerve conduction velocity predicted elevated mean stimulation current (r=-0.35, P=0.002). Finally, 15 diabetic patients required more than 0.5 mA to evoke a motor response, despite intraneural needle placement (n=4), or required currents ≥2 mA despite needle-nerve contact, vs three such patients (1 intraneural, 2 with ≥2 mA) among non-diabetic patients (P=0.003). CONCLUSIONS: These findings suggest that stimulation thresholds of 0.3-0.5 mA may not reliably determine close needle-nerve contact during popliteal sciatic nerve block, particularly in patients with diabetic neuropathy. CLINICAL TRIAL REGISTRATION: NCT01488474.

Prolonged central sensory conduction time in patients with chronic arsenic exposure.

BACKGROUND: Many patients from Toroku, Japan, who have chronic arsenic exposure demonstrate whole-body sensory disturbance that is slightly more pronounced in the extremities. Although previous research in this population showed a mild peripheral neuropathy, it is unknown whether these patients have central nervous system impairment. To investigate the lesion sites underlying sensory disturbance related to chronic arsenic poisoning, we analyzed somatosensory evoked potentials (SEP). METHODS: Clinical features, nerve conduction study results, and median and/or tibial SEP were analyzed in patients with chronic arsenic exposure (total, 13 patients; median & tibial, 4; median, 5; tibial, 4) retrospectively. The SEP findings in patients were compared with those in normal controls. RESULTS: The median SEP results indicated a conduction delay between the proximal brachial plexus and the primary sensory cortex, and tibial SEP findings indicated a delay between the dorsal gray matter of the lumbosacral cord and the primary sensory cortex. CONCLUSION: This is the first study to identify an impairment of the central somatosensory pathway in patients with chronic arsenic exposure. Sensory disturbance in these patients is related not only to peripheral neuropathy but also to impairment of the central nervous system.