Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by PMP22 overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol’s effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.

TSH Combined with TSHR Aggravates Diabetic Peripheral Neuropathy by Promoting Oxidative Stress and Apoptosis in Schwann Cells

Subclinical hypothyroidism (SCH) is associated with diabetic peripheral neuropathy (DPN); however, the mechanism underlying this association remains unknown. This study is aimed at examining neurofunctional and histopathological alterations in a type 2 diabetes (T2DM) mouse model of SCH and investigating the impact of thyroid-stimulating hormone (TSH) in an in vitro DPN cell model established using RSC96 cells under high glucose (HG) and palmitic acid (PA) stimulation. Our results indicated that T2DM, in combination with SCH, aggravated abnormal glucose and lipid metabolism in T2DM and dramatically destroyed the peripheral nervous system by increasing paw withdrawal latency, decreasing motor nerve conduction velocity, and exacerbating ultrastructural deterioration of the damaged sciatic nerve caused by diabetes. Furthermore, the results of our in vitro experiments showed that TSH intensified HG/PA-induced RSC96 cell damage by inducing oxidative stress, mitochondrial dysfunction, and apoptosis. More importantly, TSHR knockout or inhibition of PA-induced TSHR palmitoylation could alleviate the apoptosis induced by TSH. Overall, in this study, the novel mechanisms by which TSH, as an independent risk factor for DPN progression, aggravating Schwann cell apoptosis and demyelination, are elucidated. These findings indicate that TSHR could be a potential target for both the prevention and treatment of DPN and, possibly, other microvascular diseases, and have implication in the clinical management of patients with DPN.

The Effect of Local Cooling at the Elbow on Nerve Conduction Velocity and Motor Unit Behaviour: An Exploration of a Novel Neurological Assessment

Background: This study aimed to determine the effects of a standard therapeutic cooling protocol using crushed ice on the elbow to explore if changes in the motor unit (MU) firing rates in the first dorsal interosseous (FDI) muscle are comparable to known changes in sensory and motor nerve conduction velocity (NCV) due to a regional temperature drop around a peripheral nerve. Methods: Twelve healthy individuals were assessed before cooling, immediately after cooling, and 15 min of rewarming. Assessments included two standard non-invasive nerve conduction velocity tests and a non-invasive investigation of the MU firing rates using surface electromyography decomposition (dEMG). Results: Repeated ANOVAs showed significant differences in the MU firing rates and NCV between time points (p = 0.01 and p < 0.001). All measures showed significant differences between pre and post cooling and between pre-cooling and 15 min of passive re-warming, however, no changes were seen between post cooling and rewarming except in the sensory NCV, which increased but did not return to the pre-cooled state. Conclusions: This current study showed a significant, temporary, and reversible reduction in ulnar NCV across the elbow in healthy subjects, which was associated with a significant decrease in mean MU firing rates in the FDI muscle.

The application of Sheng-Mai Injection in diabetes mellitus and related complications: a systematic review and meta-analysis

Background: Diabetes mellitus (DM) is a metabolic disorder characterized by progressive β cell dysfunction. Sheng-Mai Injection (SMI), a Traditional Chinese medicine preparation, is widely used for DM and related complications. Objective: The study aims to summarize the applications of SMI in DM and related complications by meta-analysis. Methods: Eight databases were searched, and meta-analyses were performed. Results : Fifteen studies, including 1273 participants, were included. All studies and participants are from China. Pooled effects showed that SMI might reduce glycated hemoglobin (MD -0.46%; 95% CI -0.89 to -0.03; P < 0.01), fasting blood glucose (MD -0.83 mmol/L; 95% CI -1.30 to -0.36; P < 0.01), two-hour Postprandial glucose (MD -1.27 mmol/L; 95% CI -1.96 to -0.58; P < 0.01), 24-hour urinary protein (MD -0.28 mg; 95% CI -0.51 to -0.06; P = 0.01), blood urea nitrogen (MD -1.31 mg; 95% CI -2.08 to -0.54; P < 0.05), Scr (MD -2.60; 95% CI -3.43 to -1.77; P < 0.05), ulnar nerve motor nerve conduction velocity (MNCV) (MD 1.45; 95% CI 0.03 to 2.87; P < 0.05) and tibial nerve Sensory nerve conduction velocity (SNCV) (MD 1.84; 95% CI 0.1 to 3.58; P < 0.05). There was no evidence of effect on common peroneal nervous MNCV and SNCV, tibial nerve MNCV, median nerve MNCV and SNCV. Adverse effects included less frequent gastrointestinal reactions, elevated transaminase, leucopenia, fever, and rash. Conclusion: SMI may be effective in DM and diabetic nephropathy. For diabetic peripheral neuropathy, the effectiveness cannot yet be proven considering the inconsistency of the evidence.

Effect of Neurodynamic Mobilisation Plus Core Stability on Pain and Motor Nerve Conduction Velocity in Athletes with Lumbar Radiculopathy

Introduction. Lumbar radiculopathy (LR) is a common debilitating disorder of neuromuscular origin that affects athletes. Material and Methods. This study was a parallel group design and a total of 24 clinically diagnosed athletes with LR were recruited for the study and randomly assigned to one of the two groups, i.e. neurodynamic mobilisation plus core stability group (NDS plus CS) and core stability group only (CS). NDS plus CS underwent neural mobilisation of the tibial nerve and core stability exercises, while CS group performed core stability for a total of 14 sessions on alternate days. The outcome measures of motor nerve conduction velocity (m NCV) of the tibial nerve and pain intensity were recorded before the start of the intervention, at midpoint (7th session) and at the end of the intervention (14th session). Results. Baseline scores of pain and m NCV (NDS plus CS: 6.75 ± 0.62, 38.10 ± 7.21 and CS: 6.58 ± 0.79, 38.92 ± 6.37) were non-significant. The outcome measures improved significantly during treatment in NDS plus CS group (baseline to 7th session, 7th to 14th session and overall mean change for pain and m NCV was found to be 4.74 ± 0.37 and -6.43 ± 3.08, respectively. Non-significant improvement was reported for CS group. Two-way repeated measures (2 x 3) ANOVA was used to analyse the change in the outcome measures and revealed that NDS plus CS group showed statistically significant main effects for group on pain level (F (2, 5.34) = 0.89, p < 0.001 and m NCV (F (2, 5.21) = 0.40, p < 0.03. Significant time and group x time interaction effects were also found. Conclusions. The findings of the study revealed that neurodynamic mobilisation plus core stability were found effective in improving pain level and motor nerve conduction velocity of the tibial nerve in athletes with lumbar radiculopathy.

Triphala Churna—A Traditional Formulation in Ayurveda Mitigates Diabetic Neuropathy in Rats

Neuropathy is a common complication of diabetes affecting a large number of people worldwide. Triphala churna is a formulation mentioned in Ayurveda-a traditional system of medicine. It is a simple powder formulation consisting of powders of three fruits, Emblica officinalis L., Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. Individual components of Triphala churna have anti-diabetic and antioxidant activities. Hence, this study was designed to evaluate the effect of Triphala churna on diabetic neuropathy. Diabetes was induced with streptozotocin (STZ, 55 mg/kg, i. p.) in rats. Animals were grouped and treated orally with Triphala churna at a dose of 250, 500, and 1,000 mg/kg after 6 weeks of diabetes induction for the next 4 weeks. At the end of study, parameters such as body weight, plasma glucose level, motor nerve conduction velocity were determined. The effect of Triphala churna on thermal hyperalgesia, mechanical hyperalgesia, and mechanical allodynia was also determined at the end of study. The plasma cytokine levels like TGF-β1, TNF-α, and IL-1β were determined by ELISA assay. Histopathology study of the sciatic nerve was studied. Western blotting was performed to study the expression of neuronal growth factor.Treatment with Triphala churna showed a significant reduction in plasma glucose and a significant rise in body weight. Triphala treatment significantly increased the motor nerve conduction velocity and decreased the thermal and mechanical hyperalgesia, as well as mechanical allodynia. The treatment significantly inhibited levels of circulatory cytokines like TGF-β1, TNF-α, and IL-1β. Histopathology study confirmed the neuroprotective effect of Triphala churna. The expression of NGF was significantly increased in sciatic nerves after treatment with Triphala churna. From the results, it can be concluded that Triphala churna delays the progression of neuropathy in diabetic rats.

Clinical and Neuroimaging Features in Charcot–Marie–Tooth Patients with GNB4 Mutations

Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the GNB4 gene cause dominant intermediate CMT type F (CMTDIF). The aim of this study is to investigate phenotypic heterogeneities and characteristics of CMT patients with GNB4 mutations. We enrolled 1143 Korean CMT families and excluded 344 families with a PMP22 duplication. We further analyzed the 799 remaining families to find their GNB4 mutations using whole-exome sequencing (WES). We identified two mutations (p.Gly77Arg and p.Lys89Glu) in three families, among which a heterozygous p.Gly77Arg mutation was novel. In addition, a significant uncertain variant (p.Thr177Asn) was observed in one family. The frequency of the GNB4 mutation in the Korean population is 0.38% in PMP22 duplication-negative families. All three families showed de novo mutation. Electrophysiological findings regarding the p.Lys89Glu mutation showed that the motor nerve conduction velocity (MNCV) of the median nerve was markedly reduced, indicating demyelinating neuropathy, and sural nerve biopsy revealed severe loss of myelinated axons with onion bulb formation. Lower extremity Magnetic Resonance Imaging (MRI) demonstrated relatively more severe intramuscular fat infiltrations in demyelinating type (p.Lys89Glu mutation) patients compared to intermediate type (p.Gly77Arg mutation) patients. The anterolateral and superficial posterior compartment muscles of the distal calf were preferentially affected in demyelinating type patients. Therefore, it seems that the investigated GNB4 mutations do cause not only the known intermediate type but also demyelinating-type neuropathy. We first presented three Korean families with GNB4 mutations and found phenotypic heterogeneities of both intermediate and demyelinating neuropathy. We suggest that those findings are useful for the differential diagnosis of CMT patients with unknown GNB4 variants.

A Cross-Sectional Study to Assess Motor Performance of the Hands and Its Association with Workplace Factors in the Laboratory Workers of Jawaharlal Nehru Medical College, Belagavi

BACKGROUND Human motor performance (MP) and motor skills are essential aspects of the various daily activities. Skilled laboratory workers involved in prolonged duration of skillful, repetitive work by hands are susceptible to carpal tunnel syndrome (CTS). This study was conducted to assess MP of the hands and determine the relation between MP and workplace factors. METHODS Present cross-sectional study was conducted among 94 laboratory workers (technicians and attenders). Participants were categorised into two groups namely, attenders and technicians, each of which was further divided into two sub-groups of normal participants and those diagnosed with CTS. MP was assessed by median motor nerve conduction velocity (MNCV), work done and fatiguability, hand grip strength and bimanual coordination. Unpaired ‘t’ test / analysis of variance (ANOVA) was used to compare the mean values of selected parameters at a P < 0.05 threshold of significance. RESULTS Mean values of median MNCV, work done and time for onset of fatigue were similar across both groups. In the CTS group, hand grip strength (19.00 ± 5.94 Kg) and efficiency index (89.54 ± 8.47) were slightly diminished, while the duration of error in task execution (29.20 ± 21.67 sec) was slightly more than the normal group; however, these differences were statistically insignificant (P > 0.05). Work done, hand grip strength, error and efficiency index significantly differed between technicians and attenders (P < 0.05). CONCLUSIONS Most of MP measures being normal in those with CTS suggest that they are at early stages of development of CTS, hence requiring suitable preventive measures. Moreover, workplace factors may adversely affect their work performance. KEYWORDS Motor Performance (MP), Median Motor Nerve Conduction Velocity (MNCV), Mosso’s Ergography, Hand Grip Strength, Bimanual Coordination