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Neuropathic pain is a chronic condition representing a significant burden for society. It is estimated 1 out of 10 people over the age of 30 that in the US have been diagnosed with neuropathic pain. Most of the available treatments for neuropathic pain have moderate efficacy over time which limit their use; therefore, other therapeutic approaches are needed for patients. Spinal cord stimulation is an established and cost-effective modality for treating severe chronic pain. In this article we will review the current approved indications for the use of spinal cord stimulation in the US and the novel therapeutic options which are now available using this therapy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN. OBJECTIVE: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN. METHODS: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process. RESULTS: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria. CONCLUSION: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.

Prolonged squatting is a well-documented cause of common peroneal neuropathy, wherein the common peroneal nerve is thought to be compressed between the biceps femoris tendon and the lateral head of the gastrocnemius muscle or the fibular head. However, deep peroneal neuropathy resulting from prolonged squatting has not been previously reported. We present the case of a tile installer who developed unilateral deep peroneal neuropathy following extended squatting, diagnosed through ultrasonography, which identified the bilateral division of the common peroneal nerves between the knee joint and the fibular head. This case underscores the value of ultrasonography, particularly when electrodiagnostic results are inconsistent with clinical expectations. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune nodopathy (AN) is a new entity in the field of peripheral neuropathies and is defined by the presence of auto-antibodies against structures of the node of Ranvier combined with specific clinicopathophysiological features and therapy response in affected patients. The target-specific antibodies do not only serve as diagnostic biomarkers but also for treatment evaluation during follow-up. Case report: We report a 66-year-old female patient with various autoimmune diseases, including a history of membranous glomerulonephritis which presented with acute-onset, sensorimotor tetraparesis, cranial nerve involvement, and mild respiratory insufficiency. Under the suspicion of Guillain--Barreé syndrome, she received intravenous immunoglobulins (IVIg) and achieved remission. At 8 months later, she relapsed with now a poor response to IVIg and developed additional features such as severe sensory ataxia, tremor, and neuropathic pain. Anti-contactin-1 IgG2 antibodies were detected, and the diagnosis was reverted to AN. Plasma exchange and rituximab treatment led to a serological remission and corresponding significant clinical improvement, and the therapy was paused. At 2 years after symptom onset, her condition worsened again with sensorimotor symptoms and severe neuropathic pain despite seronegativity for contactin-1. However, serum binding assays to teased nerve fiber staining showed recurring antibody reactivity against paranodal structures. Caspr-1 was identified as a new target antigen via cell-based assay, and high-titer antibodies of the IgG4 subclass were confirmed via ELISA. Hence, a new cycle of plasma exchange and regular rituximab treatment was initiated, with subsequent clinical improvement and serological remission. The serum neurofilament light chain (sNFL) levels were assessed retrospectively and rose and fell together with the antibody titer. Discussion: This case demonstrates that autoimmunity to (para)nodal structures can reoccur especially in patients prone to autoimmune disorders and can switch its target antigen and subclass in the course of disease. The presence of autoantibodies against different targets at the node of Ranvier has direct implications for therapeutic management. We suggest a close follow-up of patients with AN after successful therapy. In case of deterioration despite seronegativity, nonspecific tests such as teased fiber assays and repeated screening for different target antigens should be considered. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Critical illness polyneuropathy (CIP) has been linked to neurocardiac dysfunction mediated by autonomic nervous system dysregulation, which increases mortality. We aimed to assess if heart rate variability (HRV) biofeedback could improve neurocardiac function in CIP.We randomly allocated (1:1) patients with electrophysiologically confirmed CIP undergoing early inpatient neurological rehabilitation to additional HRV or sham biofeedback over 14 days. We evaluated neurocardiac function via standard deviation of normal‐to‐normal intervals (SDNN) as the primary outcome, as well as HRV frequency domains, sympathetic cutaneous sudomotor and vasomotor functions and disability at baseline, post intervention and 4 weeks later. The study is registered on the German Clinical Trials Register (DRKS00028911).We included 30 patients with CIP (40% females, median [interquartile range] age 64.6 [56, 72] years). We observed an increase in SDNN and the predominantly parasympathetic high frequency domain post intervention (ß = 16.4, 95% confidence interval [CI] 0.2, 32.6 [p = 0.047] and ß = 1179.2, 95% CI 119.9, 2158.5 [p = 0.018]), which was sustained at the 4‐week follow‐up (ß = 25.7, 95% CI 6.0, 45.4 [p = 0.011] and ß = 25.7, 95% CI 6.0, 45.4 [p = 0.011]). Patients who underwent HRV biofeedback displayed a higher adjusted Barthel index, indicating less severe disability 4 weeks after the intervention compared to those in the sham group (ß = 23.3, 95% CI 5.5, 41.1 [p = 0.014]). Low frequency and sympathetic skin functions did not differ between groups (p = nonsignificant).Our study provides pilot data suggesting that, in patients with CIP, HRV biofeedback can improve neurocardiac function with a predominant effect on the parasympathetic nervous system and has a beneficial effect on functional recovery. [ABSTRACT FROM AUTHOR]

Neuropathy is a complex condition characterized by nerve damage and a wide range of symptoms, creating significant challenges in clinical management. Traditional pharmacological treatments often present partial efficacy and adverse side effects, prompting increasing interest in botanical interventions. This review evaluates the effectiveness of various plants in treating neuropathy and neuropathic pain, focusing on their pharmacological properties, mechanisms of action, clinical studies, dosage, and safety profiles. Notable plants include Crocus sativus (saffron), Citrullus colocynthis (bitter apple), Curcuma longa (turmeric), Lavandula angustifolia (lavender), and Cannabis sativa. These botanicals demonstrate anti-inflammatory, antioxidative, and analgesic effects, highlighting their potential to reduce neuropathic pain and improve patients' quality of life. Future research should focus on optimizing dosages, clarifying long-term effects, and integrating botanicals into broader treatment protocols for neuropathic care. [ABSTRACT FROM AUTHOR]

Background: The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction and failure of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. Present study was aimed to study associated comorbidities and microvascular/macrovascular complications in diabetic patients attending a tertiary care center. Material and Methods: Present study was Cross sectional study, conducted in Type 1 and Type 2 Diabetes mellitus or newly diagnosed diabetes mellitus patients. Results: In present study regarding the eGFR maximum patients 47 (46.54%) were in stage III-B (G3a) followed by 37 (36.63%) were in stage IV (G4), 9 (8.91%) were in stage 5 (G5) and 8 (7.92%) in stage III-A (G3b) of chronic kidney disease. Data revealed that majority of patient's eGFR was moderately decreased. Majority of patients 93 (92.08%) lies in very high risk as per KDIGO classification and remaining 8 (7.92%) were at high risk. In present study out of 101 patients 48 (47.52%) had retinopathy. Among the 48 cases of retinopathy maximum patients 43 (89.58%) were having non-proliferative diabetic retinopathy (NDRP) followed by 4 (8.33%) were having mixed NDRP/PDR and single case was having proliferative retinopathy. Majority 81 (80.20%) not having neuropathy and 20 (19.80%) had neuropathy. Regarding macrovascular complication majority of patients 30 (29.70%) had unstable angina followed by myocardial infarction in 25 (24.75%), Heart failure in 18 (17.82%) and 15 (14.85%) had stroke. In present study maximum patients 97 (96.04%) were discharged and 4 (3.96%) were died during the study period. Further data reveals significant correlation between stages of CKD with outcome as p<0.05. Maximum mortality was seen in progressive stage of CKD. Conclusion: Among diabetic population, advancing age, gender, concomitant hypertension, increasing duration of diabetes and the presence of macrovascular complication were found to be important risk factors. [ABSTRACT FROM AUTHOR]

We report a case of SYNE1-associated autosomal recessive spinocerebellar ataxia (SCAR8) presenting with a complex multisystemic phenotype, including highly elevated creatine kinase levels and lower-leg muscle atrophy. In addition to identifying two novel pathogenic variants in the SYNE1 gene, whole-exome sequencing revealed three variants of uncertain significance in the DYSF gene. Electromyography and muscle magnetic resonance imaging indicated a neurogenic pattern of muscle involvement. These findings, along with the segregation analysis of the variants, allowed us to exclude DYSF-associated muscular dystrophy; however, we cannot entirely rule out the possibility that the DYSF gene variants may act as modifiers of the patient's phenotype. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy (DN) is a common complication of long-lasting type 1 and type 2 diabetes, with no curative treatment available. Here, we tested the effect of the incretin mimetic liraglutide in DN in mice with early-stage type 1 diabetes bred in a standard laboratory or enriched environment. With a single i.p. injection of streptozotocin 150 mg/kg, we induced murine diabetes. Liraglutide (0.4 mg/kg once daily, i.p. for ten days since the eighth post-streptozotocin day) failed to decrease the glycemia in the diabetic mice; however, it alleviated their antinociceptive behavior, as tested with formalin. The second phase of the formalin test had significantly lower results in liraglutide-treated mice reared in the enriched environment vs. liraglutide-treated mice under standard conditions [2.00 (0.00–11.00) vs. 29.00 (2.25–41.50) s, p = 0.016]. Liraglutide treatment, however, decreased the threshold of reactivity in the von Fray test. A significantly higher neopterin level was demonstrated in the diabetic control group compared to treatment-naïve controls and the liraglutide-treated diabetic mice (p < 0.001). The glutamine/glutamate ratio in both liraglutide-treated groups, either reared under standard conditions (p = 0.003) or an enriched environment (p = 0.002), was significantly higher than in the diabetic controls. This study demonstrates an early liraglutide effect on pain sensation in two streptozotocin-induced diabetes mouse models by reducing some inflammatory and oxidative stress parameters. [ABSTRACT FROM AUTHOR]

The chemotherapeutic agent vincristine is commonly used for a variety of hematologic cancers, as well as solid tumors of the head and neck, bronchial carcinoma, as part of the procarbazine, lomustine and vincristine (PCV) regimen, for glioma. Damage to nerve tissue (neuropathy) is often dose-limiting and restricts treatment. Nimodipine is a calcium antagonist that has also shown neuroprotective properties in preliminary studies. In this approach here, we investigated the effects of the combination of vincristine and nimodipine on three cancer cell lines (A549, SAS and LN229) and neuronal cells (RN33B, SW10). Fluorescence microscopy, lactate dehydrogenase (LDH) assays and Western blot analyses were used. Nimodipine was able to enhance the cell death effects of vincristine in all tumor cells, while neuronal cells were protected and showed less cell death. There was an opposite change in the protein levels of Ak strain transforming/protein kinase B (AKT) in tumor cells (down) and neuronal cells (up), with simultaneous increased protein levels of cyclic adenosine monophosphate response element-binding protein (CREB) in all cell lines. In the future, this approach may improve tumor response to chemotherapy and reduce unwanted side effects such as neuropathy. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting an increasing number of cancer survivors worldwide. However, insights into its pathophysiology and availability of effective therapies remain lacking. Dorsal root ganglia (DRG) have been studied as a key component of chemotherapeutic drug toxicity and a potential therapeutic target for CIPN treatment. This comprehensive review aims to synthesize, summarize, and correlate the results of both preclinical and clinical studies relevant to the pathophysiology and management of CIPN in relation to the DRG. Design: Review. A thorough literature search was conducted using the terms 'dorsal root ganglion' and 'chemotherapy-induced peripheral neuropathy', along with appropriate variations. Searched databases included PubMed, EMBASE, Medline, Cochrane Library, Wiley Library, and Web of Science. Inclusion criteria targeted all English language, peer-reviewed original research from the inception of these databases to the present year. Review articles, book chapters, and other nonoriginal publications were excluded. Of 134 relevant studies identified, the majority were preclinical studies elucidating how various chemotherapeutic agents, especially taxanes, disrupt neurotransmission, inflammatory processes, and apoptotic pathways within sensory neurons of DRG. Not only do these effects correlate with the presentation of CIPN, but their disruption has also been shown to reduce CIPN symptoms in preclinical models. However, clinical studies addressing DRG interventions are very limited in number and scope at this time. These results reveal various pathways within DRG that may be effective targets for CIPN treatment. While limited, clinical studies do offer promise in the utility of DRG neuromodulation in managing painful CIPN. In the future, clinical trials are needed to assess interventions aimed at these neuronal and nonneuronal pathological targets to better treat this complex condition. [ABSTRACT FROM AUTHOR]

Familial dysautonomia (FD) is a rare sensory and autonomic neuropathy that results from a mutation in the ELP1 gene. Virtually all patients report gastrointestinal (GI) dysfunction and we have recently shown that FD patients have a dysbiotic gut microbiome and altered metabolome. These findings were recapitulated in an FD mouse model and moreover, the FD mice had reduced intestinal motility, as did patients. To understand the cellular basis for impaired GI function in FD, the enteric nervous system (ENS; both female and male mice) from FD mouse models was analyzed during embryonic development and adulthood. We show here that not only is Elp1 required for the normal formation of the ENS, but it is also required in adulthood for the regulation of both neuronal and non-neuronal cells and for target innervation in both the mucosa and in intestinal smooth muscle. In particular, CGRP innervation was significantly reduced as was the number of dopaminergic neurons. Examination of an FD patient's gastric biopsy also revealed reduced and disoriented axons in the mucosa. Finally, using an FD mouse model in which Elp1 was deleted exclusively from neurons, we found significant changes to the colon epithelium including reduced E-cadherin expression, perturbed mucus layer organization, and infiltration of bacteria into the mucosa. The fact that deletion of Elp1 exclusively in neurons is sufficient to alter the intestinal epithelium and perturb the intestinal epithelial barrier highlights a critical role for neurons in regulating GI epithelium homeostasis. [ABSTRACT FROM AUTHOR]

This study investigated the beneficial effects and mechanisms of Lactobacillus plantarum (LP) on neuropathy in type-2 diabetic mice. Twenty db/db mice were randomly assigned to either a control group (group C) or a treated group (group LP). Weekly blood glucose levels were measured using a glucose meter. Neuropathy was assessed through thermal sensation, Von Frey responses and sensory nerve conduction velocity. Tight junction protein expression in colorectal tissues was analysed via immunofluorescence. ELISA measured serum inflammatory factors, while faecal samples at the intervention's end assessed gut microbiota changes. Western blot analysed the JAK-STAT signalling pathway in mouse brain tissue. Group LP showed significantly lower blood glucose levels and improved thermal nociceptive sensitivity in db/db mice compared to group C. Additionally, LP intervention increased the expression of the intestinal tight junction protein occludin and enhanced intestinal flora diversity, including higher levels of probiotics like Akkermansia muciniphila. In group LP, serum levels of the anti-inflammatory factor IL-10 increased significantly, while pro-inflammatory factors TNF-α, IL-6, IL-17A and LPS decreased. Additionally, the JAKSTAT signalling pathway was notably inhibited in the brain tissue of these mice. LP may potentially alleviate neuropathy in type-2 diabetic mice by modulating the immune system, repairing the intestinal mucosal barrier, and balancing the gut microbiome. [ABSTRACT FROM AUTHOR]

Background: Research on Qi Gong (QG) supports promising health benefits. Both interest and use of QG in U.S. adults has increased over the past decade. Shared Medical Appointments (SMAs) are a novel, cost-effective, and time efficient health care delivery approach associated with patient and clinician satisfaction. Objectives: A telehealth delivered QG SMA was pilot tested among a diverse demographic population within an integrative medicine practice at an academic medical center to assess feasibility and acceptability. Methods: This was a feasibility/acceptability pilot study conducted at a large New York City academic medical center's Integrative Health and Wellness center from January to July 2023. A QG instructor-acupuncturist and an integrative medicine physician-acupuncturist co-led 3 separate series (5 Element QG, Eight-Section Brocade, and Joint-Mobilizing/Sinew Strengthening exercises) of weekly 30-45-minute sessions of QG SMA on a weekday afternoon via telemedicine. The first session included an overview of QG and Traditional Chinese Medicine (TCM) research while follow-up sessions included a check-in, didactic demonstration followed by QG practice, and a debrief to answer questions. Video links were provided for home practice. Surveys assessing satisfaction were sent pre/post series. Results: 18 sessions of QG SMA were offered over a 6-month period. A total of 40 unique participants from diverse demographics (gender, race/ethnicity, primary residence) attended, for a total of 197 virtual visits. A total of 20 participants enrolled in Series 1 (8 weeks), 23 enrolled in Series 2 (7 weeks), and 16 enrolled in Series 3 (3cweeks). For each session, group attendance ranged from 8-16 with an average of 11 participants. Attendance was high with participants attending an average of 72% of the sessions. Participants attended 88% of the first 8-week series, 54% of the second 7-week series, and 60% of the third series. Participant interest persisted over time with 35% of the 40 participants attending more than 1 series, and 12.5% attending all 3 series. Participants' diagnoses and health symptoms included pain (62.5%), cancer (45%) anxiety/depression (40%), cardiovascular disease (CVD) or metabolic conditions (32.5%), gastrointestinal (GI) symptoms/diagnoses (27.5%), stress (22.5%), osteopenia/osteoporosis (17.5%), and insomnia (17.5%). Pre-series [n = 27] participants endorsed symptoms including sleep disturbances, fatigue, pain, stress, weakness, GI symptoms, psychological symptoms, hot flashes, and brain fog. Post-program survey results [n = 11] suggested QG program addressed common symptoms including fatigue, insomnia, anxiety, stress, pain, weakness, and gastrointestinal symptoms. Participants reported incorporating QG, breathing techniques, and meditation into their daily routine. All participants reported their goals were met and that they would recommend the program to others. Regarding delivery preferences, 73% preferred telehealth, 27% hybrid, and none preferred in-person. Participants appreciated the format, new skills, community, and instructors. Conclusion: While the Virtual QG SMA series provided to diverse demographic population with mixed diagnoses is feasible, acceptable, and shows promising positive impact in this pilot, caution in interpreting the data is advised due to the low response rate of the post-program survey. Robust studies with longer follow-ups are recommended. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Small‐fiber neuropathy (SFN) affects only unmyelinated and thin myelinated fibers. It may be caused by amyloidogenic mutations of the transthyretin (TTR) gene, but not all TTR gene variants are pathogenic. The nonamyloidogenic c.76G>A (rs1800458) and c.337‐18G>C (rs36204272) variants of TTR were recently reported to be associated with SFN. We investigated this putative association by analyzing TTR gene sequencing data retrospectively for two cohorts of patients, one with SFN and a control group.In this retrospective single‐center study, we analyzed the frequency of the c.76G>A and c.337‐18G>C TTR gene variants in a cohort of patients meeting a strict definition of SFN, with or without dysautonomia, a control cohort of patients investigated for nonneurological conditions, and the gnomAD international database.We included 55 SFN patients in this study, 17 of whom had dysautonomia. The allelic frequencies of the two variants in our cohort of 55 SFN patients were 7.27% for c.76G>A TTR and 5.25% for c.337‐18G>C. The frequencies of both variants were statistically similar in the 337 control patients and the gnomAD database.The c.76G>A and c.337‐18G>C TTR gene variants are not associated with SFN. [ABSTRACT FROM AUTHOR]

Introduction: Pathogenic variants in the XK gene are associated with dysfunction or loss of XK protein leading to McLeod syndrome (MLS), a rare X-linked neuroacanthocytosis syndrome with multisystemic manifestation. Here we present clinical, genetic and immunological data on a patient originally admitted to our clinic for presumed post-COVID-19 syndrome, where thorough clinical work-up revealed a novel frameshift deletion in XK causal for the underlying phenotype. We additionally review the clinicogenetic spectrum of reported McLeod cases in the literature. Methods: We performed in-depth clinical characterization and flow cytometry of cerebrospinal fluid (CSF) in a patient where multi-gene panel sequencing identified a novel hemizygous frameshift deletion in XK. Additionally, Kell (K) and Cellano (k) antigen expression was analysed by Fluorescence-activated Cell Sorting (FACS). KEL gene expression was examined by RNA sequencing. Results: A novel hemizygous frameshift deletion in the XK gene resulting in premature termination of the amino acid chain was identified in a 46-year old male presenting with decrease in physical performance and persisting fatigue after COVID-19 infection. Examinations showed raised creatine kinase (CK) levels, neuropathy and clinical features of myopathy. FACS revealed the K-k+ blood type and reduced Cellano density. CSF flow cytometry showed elevation of activated T Cells. Conclusion: In-depth clinical, genetic, immunological and ribonucleic acid (RNA) expression data revealed axonal neuropathy, myopathy and raised levels of activated CSF-T-lymphocytes in a patient with a previously unpublished frameshift deletion in the XK gene. [ABSTRACT FROM AUTHOR]

The long-term tolerability of linezolid is low because of mitochondrial toxicity, whereas tedizolid may represent a better option for suppressive therapy. We report a first presumed case of tedizolid-associated optic neuropathy after a very prolonged (18-month) intake and believe that screening for optic neuropathy should be considered for patients undergoing tedizolid suppression. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Contraceptive implant migration is a rare complication associated with contraceptive implants: migration to the ulnar nerve, emphasizing the importance of accurate diagnosis, imaging, and a multidisciplinary approach to mitigate neurovascular risks during insertion and removal procedures. The case report demonstrates the necessity for careful removal techniques and thorough patient follow‐up to ensure positive outcomes and prevent long‐term nerve damage. There are some potential risks and complications associated with contraceptive implants, including neurovascular injury. The aim of this case report is to report a rare complication associated with contraceptive implants. A 32‐year‐old female, right‐hand dominant, presented to the orthopedic clinic for the extraction of a contraceptive implant (Implanon) from her left arm. She reported intermittent numbness in the ring and little fingers. Upon examination, the Implanon was not palpable. Both Phalen's test and Tinel signs were negative. An x‐ray of the arm revealed the implant's position. Under local anesthesia through a longitudinal incision, the Implanon was found within the perineurium of the ulnar nerve. Two weeks after the operation, the patient returned to the clinic. Upon examination, there were no indications of ulnar nerve neuropathy. If a patient undergoes subdermal implant‐associated pain or is at risk of neurovascular damage during removal, it is advisable to refer the patient to a family planning specialist experienced in handling challenging implant removals, and subsequently to a peripheral nerve surgeon, to optimize outcomes. The migration of a contraceptive implant to the ulnar nerve is an exceedingly rare but possible complication. [ABSTRACT FROM AUTHOR]

Charcot–Marie–Tooth type 1B (CMT1B) is a peripheral neuropathy caused by mutations in the gene encoding myelin protein zero (MPZ), a key component of the myelin sheath in Schwann cells. Mutations in the MPZ gene can lead to protein misfolding, unfolded protein response (UPR), endoplasmic reticulum (ER) stress, or protein mistrafficking. Despite significant progress in understanding the disease mechanisms, there is currently no effective treatment for CMT1B, with therapeutic strategies primarily focused on supportive care. Gene therapy represents a promising therapeutic approach for treating CMT1B. To develop a treatment and better design preclinical studies, an in-depth understanding of the pathophysiological mechanisms and animal models is essential. In this review, we present a comprehensive overview of the disease mechanisms, preclinical models, and recent advancements in therapeutic research for CMT1B, while also addressing the existing challenges in the field. This review aims to deepen the understanding of CMT1B and to encourage further research towards the development of effective treatments for CMT1B patients. [ABSTRACT FROM AUTHOR]

The absence of an early diagnosis of cardiac autonomic neuropathy might increase the risk of the disease, progressing to an irreversible stage. Therefore, this study aims to investigate the APOE gene isoforms in patients with cardiac autonomic neuropathy to identify early markers for predicting this disease in the Kazakh population. A total of 147 patients with cardiac neuropathy and 153 controls were examined in this case–control study. Patients were genotyped for two polymorphisms of the APOE gene using real-time PCR. Statistical calculations were performed using binary logistic regression. As a result of our study, we found that there was no statistically significant difference in the frequency of any APOE gene isoforms (APOE (ε2/ε2), APOE (ε2/ε3), APOE (ε2/ε4), APOE (ε3/ε3), or APOE (ε4/ε4)) between the patient group and the control group (p = 0.69, p = 0.64, p = 0.19, p = 0.22, p = 0.97, respectively). Thus, cardiac autonomic neuropathy is not associated with APOE gene isoforms in the Kazakh population. [ABSTRACT FROM AUTHOR]

Objective of this randomized, controlled, multi-site clinical trial was to compare long-term safety and efficacy of mPNS in patients with chronic, intractable, post-traumatic or post-surgical neuropathic pain to comprehensive Conventional Medical Management (CMM). Methods: A total of 65 patients with post-traumatic, post-surgical neuropathy were treated within a multicenter, randomized, clinical trial comparing the safety and effectiveness of mPNS + CMM to CMM alone. Patients were randomized 1:1 and followed through 90 days. The primary endpoint is a proportion of responders, 50% or greater reduction in pain at Day 90. The secondary endpoints included the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) and Patient Global Impression of Change (PGIC). Results: At 3 months, 71% of subjects were considered responders (> 50% pain relief) in the mPNS + CMM group vs 13% of subjects in the CMM group. The mPNS + CMM group had a mean reduction in VAS scores at Day 90 of 3.8 points (> 50% reduction), while CMM showed less than a 1-point (0.7 point) mean reduction or ~10% reduction (p < 0.0001). The EQ-5D-3L score increased in the mPNS + CMM study group, whereas the CMM group showed no improvement in EQ-5D-3L at Day 90. PGIC responder rates were 80.6% and 4.3% at Day 90 for mPNS + CMM and CMM groups, respectively. Conclusion: mPNS + CMM was superior to CMM in a randomized prospective study when used for treatment of post-traumatic, post-surgical neuropathy. Due to the lack of other effective non-invasive treatments for neuropathic pain, mPNS should be considered much earlier in the treatment algorithm. [ABSTRACT FROM AUTHOR]

Background: Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM). Methods/Design: This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study. Discussion: The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone. Plain Language Summary: Peripheral nerve stimulation (PNS) has been used for decades to treat neuropathic pain of peripheral origin. This therapy typically involves the placement small (~1 mm diameter) cylindrical electrodes (leads) near the nerve(s) in question, which is then followed by the delivery mild electrical pulses to the target, thereby blocking the pain signal from reaching the central nervous system. Despite the clinical success of this approach, there are few randomized controlled trials (RCTs) demonstrating PNS efficacy in the treatment of peripheral neuralgia/neuropathy. This may be, in large part, due to a paucity of PNS devices that are small enough to deliver this therapy at multiple locations in the extremities and the torso. For example, most implantable pulse generators (IPGs) range in size from 14 to 40 cm3 in volume. The purpose of this RCT is to demonstrate the safety and efficacy of an externally powered micro-IPG (< 1.5 cm3 in volume), in the delivery of PNS to treat peripheral neuropathic pain. Active Arm subjects will receive therapy with the micro-IPG and continue to use conventional medical management (CMM); Control Arm subjects will be treated with CMM only. The primary endpoint is the responder rate at 3-months, in both arms, defined as the percentage of subjects with ≥ 50% pain reduction from baseline following implantation of the micro-IPG. Control Arm subjects will be given the option to crossover to the Active Arm at 3-months. Study subjects in both arms are followed out to 36 months. [ABSTRACT FROM AUTHOR]

Nuclear erythroid 2-related factor 2 (Nrf2) and its downstream effector heme oxygenase 1 (HO-1) are commonly activated in response to cellular stresses. The elevated expression of HO-1 has been associated with markedly accelerated peripheral nerve regeneration. This study aimed to evaluate the impact of a naturally occurring dietary Nrf2/HO-1 activator—sulforaphane (SFN)—on regeneration in a murine sciatic nerve crush model. The beneficial safety profile of SFN has been thoroughly investigated and confirmed several times. Here, SFN was administered daily, starting immediately after C57BL/6 mice were subjected to sciatic nerve crush injury. Injured sciatic nerves were excised at various time points post injury for molecular, immunohistochemical and morphometric analyses. Moreover, functional assessment was performed by grip strength analysis and electrophysiology. Following SFN treatment, the early response to injury includes a modulation of autophagic pathways and marked upregulation of Nrf2/HO-1 expression. This enhancement of HO-1 expression was maintained throughout the regeneration phase and accompanied by a significant increase in repair Schwann cells. In these cells, elevated proliferation rates were observed. Significant improvements in grip strength test performance, nerve conduction velocity and remyelination were also noted following SFN treatment. Collectively, SFN modulates cytoprotective and autophagic pathways in the injured nerve, increasing the number of repair Schwann cells and contributing to effective nerve regeneration. Given the availability of SFN as a nutritional supplement, this compound might constitute a novel regenerative approach with broad patient accessibility and further studies on this topic are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic cancer-related pain, caused by surgery, radiotherapy, or systemic treatments, affects almost half of all breast cancer patients, and current therapeutic options are insufficient. Pain neuroscience education (PNE) has provided relief in many chronic pain syndromes but has been rarely applied in the cancer field. PNE is also without side effects and could therefore be implemented at different moments of the patient's journey. We analyzed trials investigating PNE efficacy for managing breast cancer-related pain, identifying methodological issues that should be addressed in future studies to obtain high-quality data. Chronic pain is a common consequence of breast cancer (BC) and its treatments. Pain neuroscience education (PNE) is a non-pharmacological intervention that adopts a biopsychosocial approach and has already been proven to be effective for different chronic pain syndromes. The present review aims to critically assess clinical trials comparing the efficacy of PNE to traditional biomedical education (BME) in reducing BC-related pain and improving quality of life. We conducted a literature search in scientific databases, including all studies regarding PNE use specifically for BC-related pain. Ongoing randomized controlled and observational studies were identified from ClinicalTrials.gov and congress proceedings. A total of eight clinical trials met the review criteria. The participants were all administered physical therapy and assigned to receive either BME or PNE interventions. Among the completed clinical studies, one reported no statistically relevant differences between the two groups, whereas the other showed lower levels of pain-related indexes in the PNE population compared to the BME one. While the current literature is inconclusive regarding the effectiveness of PNE for managing BC pain, we strongly support the need for further trials, as PNE could empower BC patients in both prevention of and coping with pain, offering the advantage of having no side effects. [ABSTRACT FROM AUTHOR]

The development of combination antiretroviral therapy (cART) has transformed human immunodeficiency virus (HIV) infection from a lethal diagnosis into a chronic disease, and people living with HIV on cART can experience an almost normal life expectancy. However, these individuals often develop various complications that lead to a decreased quality of life, some of the most significant of which are neuropathic pain and the development of painful peripheral sensory neuropathy (PSN). Critically, although cART is thought to induce pain pathogenesis, the relative contribution of different classes of antiretrovirals has not been systematically investigated. In this study, we measured the development of pathological pain and peripheral neuropathy in mice orally treated with distinct antiretrovirals at their translational dosages. Our results show that only nucleoside reverse transcriptase inhibitors (NRTIs), not other types of antiretrovirals such as proteinase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, and CCR5 antagonists, induce pathological pain and PSN. Thus, these findings suggest that NRTIs are the major class of antiretrovirals in cART that promote the development of neuropathic pain. As NRTIs form the essential backbone of multiple different current cART regimens, it is of paramount clinical importance to better understand the underlying mechanism to facilitate the design of less toxic forms of these drugs and/or potential mitigation strategies. [ABSTRACT FROM AUTHOR]

Background The initiation of type-2 diabetes mellitus (T2DM) is frequently asymptomatic and gradual. One reason newly diagnosed type-2 diabetes mellitus patients have a higher risk of microvascular problems is untreated long-standing hyperglycemia. The objective of our study was to evaluate the frequency of microvascular problems in recently diagnosed patients with type 2 diabetes mellitus at a tertiary care hospital in India. Material and Methods: A cross-sectional study was undertaken in the medicine department of a tertiary care hospital. The study included a cohort of 100 patients who were recently diagnosed with type 2 diabetes mellitus. Microvascular complications were diagnosed after a thorough study of the patient's medical history, clinical assessment, and pertinent diagnostic tests. Results: Subjects who had an IDRS score of 60 or higher showed a higher occurrence of peripheral neuropathy (86.5% vs 13.5%, p=0.371), retinopathy (91.7% vs 8.3%, p=0.157), and nephropathy (77.8% vs 22.2%, p=0.410) compared to subjects with an IDRS score below 60. However, there was no statistically significant difference in the occurrence of microvascular problems between the two IDRS subgroups. Those diagnosed with nephropathy exhibit a statistically significant higher average IDRS score compared to those without nephropathy (65.00±17.32 vs 62.66±12.50, p-value = 0.037). However, no statistically significant difference was detected in the mean values of the IDRS scores of the other two microvascular complications. Conclusion: IDRS is a valuable tool for predicting newly diagnosed type 2 diabetes mellitus. However, further large, multi-centric studies will be required to detect its usefulness in microvascular complications. [ABSTRACT FROM AUTHOR]

Introduction: Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18 months. Methods: The primary endpoints were the response rate, defined as those patients with an increase of < 2 points on the Neurological Impairment Score (NIS) from baseline, and the change in the NIS score from baseline. Secondary endpoints included the Quantitative Sensory Test, 10-m walk test, quality of life (Norfolk), and disability (Rasch-built Overall Disability Scale). As safety parameters, the evidence of graft rejection, changes in immunosuppressive trough levels and changes in antiviral and allogeneic cellular immunity before and 12 months after tafamidis treatment were also assessed. Results: Six patients (85.7%) had responded at 18-months. Compared to baseline, we observed non-statistically significant improvement in mean NIS score at 6 months (− 2.54 points, CI − 5.92 to 0.84), 12 months (− 3.25 points; CI − 6.63 to 0.13), and 18 months (− 2.35 points; CI − 5.74 to 1.02). Changes in the Quantitative Sensory Test, 10-m walk tests and the quality of life and disability questionnaires were not statistically significant. The use of tafamidis did not induce relevant side effects or drug interactions. Also, no acute rejections events nor changes in functional adaptive immunity were observed. Conclusion: Our study supports the safety and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Tafamidis shows promise as a useful treatment in the clinical management of these patients. Future randomized placebo-controlled clinical trials with longer follow-up durations are needed. [ABSTRACT FROM AUTHOR]

Introduction: Compressive neuropathy of the brachial plexus is a common issue following laparoscopic and robotic surgeries. Case Report: A 71-year-old male, post-lumbar spinal surgery, presented with excruciating right upper extremity pain and paresthesias. A supraclavicular brachial plexus (SBP) block with bupivacaine provided significant pain relief, lasting 36 hours. Subsequent physical therapy led to gradual pain and weakness improvement in compressive neuropathy. Discussion: The SBP block, facilitated by ultrasound guidance, is a safe procedure with few serious complications. It proves beneficial for managing postoperative compressive neuropathy, allowing patients to break pain cycles and participate in rehabilitation. Conclusion: The SBP block is an effective addition to the management of postoperative compressive neuropathy, given its ease, safety, and potency. Although regional anesthesia provides only temporary relief, patients can experience a break in debilitating pain cycles associated with compressive neuropathy. [ABSTRACT FROM AUTHOR]

Background We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ). Methods This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue. Results Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P  = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P  < .001) and grade 2/3 neuropathy (17% vs 7%; P  = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations. Conclusion FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation. CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944). [ABSTRACT FROM AUTHOR]

The purpose of the work was to analyze a clinical case of the course of war trauma and presents the experience of providing comprehensive medical and psychological clinical rehabilitation to a patient who suffered as a result of a terrorist attack. Patient D., 65 years old, sustained a mine-blast injury (MBI) to the right upper limb extremity during shelling. The optimal restoration of the functions of the upper injured limb and the patient's health (physical, somatic, mental) was carried out according to the algorithm of comprehensive medical and psychological clinical rehabilitation. As a result of the course of comprehensive medical and psychological clinical rehabilitation, significant positive dynamics was observed, including a decrease in edematous, painful, and inflammatory syndromes. The range of motion in the right upper limb and cervical-thoracic spine increased. Supination and pronation of the right hand became clearer and less painful (from 8 to 2 points), movement in the fingers of the right hand increased and became more steady, a clear pulsation appeared in the area of the skin defect on the right forearm, regression of pain in the elbow and shoulder joints on the right was noted, and the patient began to walk without a mobilization bandage. The course helped to reduce anxiety (from -1.82 to 0.85), asthenic symptoms (from 0.48 to 3.71), obsessive-phobic symptoms (from -1.96 to 1.74), and autonomic disorders (from -0.83 to 2.03). Low cortisol levels (61 nmol/l) in against acute stress indicated the development of post-traumatic stress disorder. Upon completion of the rehabilitation course, cortisol levels rose to a healthy level (246 nmol/l), indicating the effectiveness of the process of restoring the psychophysiological state and adapting to a stressful situation. War trauma is a complex and severe condition that requires an integrated approach to treatment and rehabilitation, covering not only physical but also psychological and social aspects of patients' health.

Abstract Neuropathy is a complex condition characterized by nerve damage and a wide range of symptoms, creating significant challenges in clinical management. Traditional pharmacological treatments often present partial efficacy and adverse side effects, prompting increasing interest in botanical interventions. This review evaluates the effectiveness of various plants in treating neuropathy and neuropathic pain, focusing on their pharmacological properties, mechanisms of action, clinical studies, dosage, and safety profiles. Notable plants include Crocus sativus (saffron), Citrullus colocynthis (bitter apple), Curcuma longa (turmeric), Lavandula angustifolia (lavender), and Cannabis sativa. These botanicals demonstrate anti-inflammatory, antioxidative, and analgesic effects, highlighting their potential to reduce neuropathic pain and improve patients’ quality of life. Future research should focus on optimizing dosages, clarifying long-term effects, and integrating botanicals into broader treatment protocols for neuropathic care.

Uncommon spontaneous haematomas of the iliacus muscle are observed in patients on anticoagulant medication or in those with blood dyscrasias like haemophilia. Femoral neuropathy, which may involve pain and paralysis, can arise as a result of these haematomas. Delays in the evacuation of haematomas can lead to protracted or irreversible impairment, as therapeutic options for femoral nerve involvement are not well established. The case discussed in this report is an unusual instance of a spontaneous haematoma of the iliacus muscle in a 67-year-old female patient, who presented with left lower limb pain, swelling, and weakness. She had a history of long-term Warfarin use for cardiac prosthetic valve replacement. An ultrasonography and doppler study of the affected region quickly revealed the concerning presence of an iliacus haematoma causing femoral nerve compression. Further Computed Tomography (CT) imaging illustrated the extent of the haematoma, which ultimately required drainage. Following the drainage of the haematoma and relief of compression on the femoral nerve, the patient showed dramatic improvement in her presenting complaints. This report highlights the need for a high level of clinical acumen and suspicion for spontaneous bleeding episodes with atypical or unusual presentations in patients on Warfarin therapy. Furthermore, the case underscores the importance of rapid ultrasonographical evaluation of the involved region and subsequent non surgical intervention for drainage.

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes; so, a nerve conduction study (NCS) is conducted to detect the type of neuropathy that is present. To discuss the NCS findings in diabetic patients. An observational study was conducted in the Physiology Department of AIIMS, Bhopal, in collaboration with the Medicine Department of the Institute. Seventy-two diagnosed type 2 diabetes mellitus (T2DM) patients were examined using NCS (Nihon Kohden Neuropack XI Machine). Microsoft Excel was utilized for data compilation and result analysis. Based on NCS, 94% of patients were abnormal, and 6% were normal. Of abnormal patients, 89% had asymmetrical involvement, and 5% had symmetrical involvement. About 74% had mixed neuropathy, 11% had motor neuropathy, and 10% had sensory neuropathy. Mixed involvement was seen in 60% of patients and axonal involvement in 35% of patients, and 5% were normal. Lower limb involvement was seen predominately. The most common bilaterally involved motor nerve was the peroneal nerve, seen in 49% of cases, whereas the most common bilaterally involved sensory nerve was the sural nerve involved in 59% of cases. The left tibial nerve was the most common unilaterally involved motor nerve seen in 32% of cases, and the left sural nerve was the most common sensory nerve involved in 54% of cases. Asymmetric sensorimotor involvement with mixed involvement (axonal + demyelinating) was seen in diabetic patients. Peroneal and sural nerves were the most common bilaterally involved motor and sensory nerves, respectively. Similarly, the left tibial and left sural nerves were the most common unilaterally affected motor and sensory nerves, respectively.

Abstract Background Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), a relatively common cause of late-onset progressive ataxia, is a genetic disease characterised by biallelic pentanucleotide AAGGG repeat expansion in intron 2 of the replication factor complex subunit 1 gene. Herein, we describe the first molecularly confirmed CANVAS family with five affected siblings from Turkey. Case presentation The family comprised seven siblings born from healthy non-consanguineous parents. CANVAS phenotype was present in five of them; two were healthy and asymptomatic. Chronic cough was the first symptom reported in all five siblings, followed by the development of sensory symptoms, oscillopsia and imbalance. Clinical head impulse test (HIT) was positive in all cases and video HIT performed on three patients revealed very low vestibulo-ocular reflex gains bilaterally. Magnetic resonance imaging and nerve conduction studies revealed cerebellar atrophy and sensory neuronopathy, respectively. RP-PCR confirmed the homozygous presence of the AAGGG repeat expansion in all five cases. Conclusion Genetic screening for CANVAS should be considered in all patients with late-onset ataxia, sensory disturbances and vestibular involvement, especially in the presence of chronic cough.

Medial elbow pain is a common musculoskeletal problem among individuals engaging in repetitive activities. Medial epicondylitis is the predominant cause of this pain. However, other potential causes must be considered as part of the differential diagnosis. This article discusses several etiologies of medial elbow pain, including medial epicondylitis, ulnar neuropathy, snapping triceps syndrome, ulnar collateral ligament injury, medial antebrachial cutaneous neuropathy, and diseases of the elbow joint, with an emphasis on ultrasound (US) findings. Awareness of possible diagnoses and their US features can assist radiologists in establishing a comprehensive diagnosis for medial elbow pain.

The diversity of clinical forms of amyloidosis is related to differences in amyloidogenic precursor proteins. Cardiac involvement is characteristic of AL- and ATTR-amyloidosis, with cardiac involvement developing in the vast majority of patients with AL-amyloidosis and in 50-60 % of patients with ATTR-amyloidosis. ATTR- (transthyretin) amyloidosis is one of the types of systemic amyloidosis, the precursor protein of which is transthyretin in the presence of mutations in its molecule (familial forms) or age-related disorders of its tetrameric secretion. Until recently, it was believed that transthyretin amyloidosis did not occur in Russia. However, the introduction of molecular genetic diagnostic methods for transthyretin mutations has demonstrated the occurrence of ATTR amyloidosis in Russia with a frequency close to the European average for non-endemic areas. The article presents the case report of systemic amyloidosis in a middle-aged woman. The disease presented at the age of 54 years with carpal tunnel syndrome. Subsequently, chronic heart failure refractory to treatment became the dominant manifestation of the disease. Heterogeneity of structure and significant myocardial thickening with preserved ejection fraction detected in dynamics in combination with new symptoms (diarrhea, orthostatic arterial hypotension, periorbital purpura, proteinuria) were considered as an infiltrative heart lesion within the framework of systemic amyloidosis. The result was a fatal asystole. Autopsy findings confirmed the diagnosis of systemic amyloidosis. The article discusses the issues of differential diagnosis of AL- and ATTR- amyloidosis based on the analysis of anamnestic and clinical data. The onset of the disease with carpal tunnel syndrome, the progressive distal neuropathy combined with autonomic dysfunction, the dominant cardiac involvement, the absence of renal amyloidosis according to autopsy data, and the duration of the disease from the time of clinical manifestation to death of 43 months are more indicative of ATTR amyloidosis. The article also discusses modern approaches to diagnostics of amyloid heart lesion in clinical practice, points out the difficulties arising in this case, emphasizes the importance of early diagnosis of cardiac amyloidosis, which allows to realize the possibilities of modern methods of amyloidosis treatment.

Abstract Background In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity. Methods Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups. Results Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p

Background: Chemotherapy Induced Peripheral Neuropathy (CIPN) is dose dependent nerve damaging adverse reaction with prevalence rate of 68.1% at the 1st month; 60.0 % at the 3rd month; and 30% at the 6th month of chemotherapy. Objective: to determine the effectiveness of an Intervention (Effleurage and Petrissage) on severity of CIPN among patients receiving chemotherapy Methods: 60 patients either having third or fourth cycle of platinum based chemotherapy were subjected to quantitative approch. Random assignment were used among two groups with a pre- and post-test design. Interventional group received effleurage and petrissage prior to chemotherapy for a period of one month and comparison of CIPN level among both groups were done at 7th, 14th, 21st day & 1st month by using FACT/GOG-Ntx subscale. Results: Pretest Mean+SD of CIPN in Intervention (17.17+4.907) and in Conventional care (17.10+ 4.421) group at t valve .055 and p value .956NS as measured by FACT/GOG-Ntx subscale. Posttest Mean+SD of CIPN in intervention (10.70±2.855) and conventional care (16.27±3.039) group after receiving effleurage and petrissage for one month at p value 0.000*. Conclusions: Study concludes that Intervention (Effleurage and Petrissage) is effective, lucrative for decline in CIPN level among patients.

Chaperone-assisted selective autophagy (CASA) is a highly selective pathway for the disposal of misfolding and aggregating proteins. In muscle, CASA assures muscle integrity by favoring the turnover of structural components damaged by mechanical strain. In neurons, CASA promotes the removal of aggregating substrates. A crucial player of CASA is HSPB8 (heat shock protein family B (small) member 8), which acts in a complex with HSPA, their cochaperone BAG3, and the E3 ubiquitin ligase STUB1. Recently, four novel HSPB8 frameshift (fs) gene mutations have been linked to neuromyopathies, and encode carboxy-terminally mutated HSPB8, sharing a common C-terminal extension. Here, we analyzed the biochemical and functional alterations associated with the HSPB8_fs mutant proteins. We demonstrated that HSPB8_fs mutants are highly insoluble and tend to form proteinaceous aggregates in the cytoplasm. Notably, all HSPB8 frameshift mutants retain their ability to interact with CASA members but sequester them into the HSPB8-positive aggregates together with two autophagy receptors SQSTM1/p62 and TAX1BP1. This copartitioning process negatively affects the CASA capability to remove its clients and causes a general failure in proteostasis response. Further analyses revealed that the aggregation of the HSPB8_fs mutants occurs independently of the other CASA members or from the autophagy receptors interaction, but it is an intrinsic feature of the mutated amino acid sequence. HSPB8_fs mutants aggregation alters the differentiation capacity of muscle cells and impairs sarcomere organization. Collectively, these results shed light on a potential pathogenic mechanism shared by the HSPB8_fs mutants described in neuromuscular diseases.Abbreviations : ACD: α-crystallin domain; ACTN: actinin alpha; BAG3: BAG cochaperone 3; C: carboxy; CASA: chaperone-assisted selective autophagy; CE: carboxy-terminal extension; CLEM: correlative light and electron microscopy; CMT2L: Charcot-Marie-Tooth type 2L; CTR: carboxy-terminal region; dHMNII: distal hereditary motor neuropathy type II; EV: empty vector; FRA: filter retardation assay; fs: frameshift; HSPA/HSP70: heat shock protein family A (Hsp70); HSPB1/Hsp27: heat shock protein family B (small) member 1; HSPB8/Hsp22: heat shock protein family B (small) member 8; HTT: huntingtin; KO: knockout; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MD: molecular dynamics; MTOC: microtubule organizing center; MYH: myosin heavy chain; MYOG: myogenin; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; NSC34: Neuroblastoma X Spinal Cord 34; OPTN: optineurin; polyQ: polyglutamine; SQSTM1/p62: sequestosome 1; STUB1/CHIP: STIP1 homology and U-box containing protein 1; TARDBP/TDP-43: TAR DNA binding protein; TAX1BP1: Tax1 binding protein 1; TUBA: tubulin alpha; WT: wild-type.

In this study, we aimed to explore whether circulating microRNA-27b (miR-27b) is affected in diabetic patient with microvascular complicationsMethods This study was conducted on 90 participants, 30 had type 2 diabetes with chronic limb ischemia, 30 diabetics without chronic limb ischemia and 30 healthy controls. The relative expression of microRNA 27b was assessed in the patient groups and its relation between diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN).Results Concerning relation between miR-27b and other microvascular complications, DR & DN, miR-27b plasma expression showed no significant difference between T2DM patients with increased VPT compared to those with normal VPT. Comparably, there was no significant difference in the plasma miR-27b expression between patients with DR and those with normal fundus examination. Additionally, neither DR nor VPT correlated with plasma miR-27bexpression.Conclusion Plasma miR-27b expression showed no change between the patient groups and there was no correlation with microvascular complications and miR-27b expression.

Background: The understanding of neuropathic pain remains incomplete, highlighting the need for research on biomarkers for improved diagnosis and treatment. This review focuses on identifying potential biomarkers in blood and cerebrospinal fluid for neuropathic pain in different neuropathies. Methods: Searches were performed in six databases: PubMed, Web of Science, Scopus, Cochrane Library, EMBASE, and CINAHL. Included were observational studies, namely cross-sectional, cohort, and case-control, that evaluated quantitative biomarkers in blood or cerebrospinal fluid. Data were qualitatively synthesized, and meta-analyses were conducted using R. The study is registered with PROSPERO under the ID CRD42022323769. Results: The literature search resulted in 16 studies for qualitative and 12 for quantitative analysis, covering patients over 18 years of age with painful neuropathies. A total of 1403 subjects were analyzed, identifying no significant differences in levels of C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-alpha) between patients with and without pain. Despite the high inter-rater reliability and adequate bias assessment, the results suggest negligible differences in inflammatory biomarkers, with noted publication bias and heterogeneity among studies, indicating the need for further research. Conclusions: Our review underscores the complex nature of neuropathic pain and the challenges in identifying biomarkers, with no significant differences found in CRP, IL-6, and TNF-alpha levels between patients with and without pain. Despite methodological robustness, the results are limited by publication bias and heterogeneity. This emphasizes the need for further research to discover definitive biomarkers for improved diagnosis and personalized treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

Abstract Purpose Oxaliplatin-containing adjuvant chemotherapy yields a significant survival benefit in stage III colon cancer and is the standard of care. Simultaneously, it causes dose-dependent peripheral neuropathy that may increase the risk of fall-related injury (FRI) such as fracture and laceration. Because these events carry significant morbidity and the global burden of colon cancer is on the rise, we examined the association between treatment with a full versus shortened course of adjuvant chemotherapy and post-treatment FRI and fracture. Methods In this overlap propensity score weighted, retrospective cohort study, we included patients aged ≥ 18 years with resected stage III colon cancer diagnosed 2007–2019 and treated with oxaliplatin-containing adjuvant chemotherapy (oxaliplatin plus a fluoropyrimidine; capecitabine [CAPOX] or 5-fluorouracil and leucovorin [FOLFOX]). Propensity score methods facilitate the separation of design from analysis and comparison of baseline characteristics across the weighted groups. Treatment groups were defined as 50% (4 cycles CAPOX/6 cycles FOLFOX) and > 85% (7–8 cycles CAPOX/11–12 cycles FOLFOX) of a maximal course of adjuvant chemotherapy to approximate the treatment durations received in the IDEA collaboration. The main outcomes were time to any FRI and time to fracture. We determined the subdistribution hazard ratios (sHR) estimating the association between FRI/fracture and treatment group, accounting for the competing risk of death. Results We included 3,461 patients; 473 (13.7%) received 50% and 2,988 (86.3%) received > 85% of a maximal course of adjuvant therapy. For post-treatment FRI, median follow-up was 4.6 years and total follow-up was 17,968 person-years. There were 508 FRI, 301 fractures, and 692 deaths. Treatment with > 85% of a maximal course of therapy conferred a sHR of 0.84 (95% CI 0.62–1.13) for post-treatment FRI and a sHR of 0.72 (95% CI 0.49–1.06) for post-treatment fracture. Conclusion For patients with stage III colon cancer undergoing treatment with oxaliplatin-containing adjuvant chemotherapy, any potential neuropathy associated with longer durations of treatment was not found to result in greater rates of FRI and fracture. Within the limits of this retrospective study, our findings suggest concern about FRI, while mechanistically plausible, ought not to determine treatment duration.

Abstract Background Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats. Methods Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs’ antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis. Results According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration. Conclusion The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy. Graphical Abstract

Background: Peripheral nerve injury is a recognized complication after reverse shoulder arthroplasty (RSA) that has mainly been studied at the level of the brachial plexus and its proximal branches. However, the impact of RSA on distal peripheral nerves and the influence of elbow and wrist position is not known. This cadaveric study aimed to analyze the effect of RSA implantation and upper limb position on tension in the distal median and radial nerves. The hypothesis was that RSA increased distal nerve tension, which could be further affected by elbow and wrist position. Methods: 12 upper limbs in 9 full fresh-frozen cadavers were dissected. Nerve tension was measured in the median nerve at the level of the proximal arm, elbow, and distal forearm, and in the radial nerve at the level of the elbow, using a customized three-point tensiometer. Measurements were carried out before and after RSA implantation, using a semi-inlay implant (Medacta, Castel San Pietro, Switzerland). Two different configurations were tested, using the smallest and largest available implant sizes. Three upper-limb key positions were considered (plexus at risk, plexus relief, and neutral), from which the effect of elbow and wrist position was further tested. Results: RSA implantation significantly increased median and radial nerve tension throughout the upper limb. The distal nerve segments were particularly dependent on elbow and wrist position. The plexus at risk position induced the most tension in all nerve segments, especially with the large implant configuration. On the other hand, the plexus relief position induced the least amount of tension. Flexing the elbow was the most efficient way to decrease nerve tension in all tested nerve segments and key positions. Wrist flexion significantly decreased nerve tension in the median nerve, whereas wrist extension decreased tension in the radial nerve. Conclusion: RSA significantly increases tension in the median and radial nerves and makes them more susceptible to wrist and elbow positioning. The mechanism behind distal peripheral neuropathy after RSA may thus result from increased compression of tensioned nerves against anatomical fulcrums rather than nerve elongation alone. Elbow flexion was the most effective way to decrease nerve tension, while elbow extension should be avoided when implanting the humeral component. Further studies are needed to assess the ulnar nerve.

Abstract Background Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review. Methods The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases. Results In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases. Conclusion Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept.

Background Patients with anti-MAG neuropathy present with distal demyelinating polyneuropathy, IgM monoclonal gammopathy, and elevated titers of anti-MAG antibodies.

Abstract Introduction Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18 months. Methods The primary endpoints were the response rate, defined as those patients with an increase of

Alia Arianti,1,&ast; Emma Rusmayani,2,&ast; Viona Viona3,&ast; 1Department of Neuro-Ophthalmology, Jakarta Eye Center (JEC) Eye Hospitals and Clinics, Jakarta, Indonesia; 2Department of Glaucoma, Jakarta Eye Center (JEC) Eye Hospitals and Clinics, Jakarta, Indonesia; 3Department of Research, Jakarta Eye Center (JEC) Eye Hospitals and Clinics, Jakarta, Indonesia&ast;These authors contributed equally to this workCorrespondence: Alia Arianti, Department of Neuro-Ophthalmology, Jakarta Eye Center (JEC) Eye Hospitals and Clinics, Terusan Arjuna Utara/ 1 Kedoya, West Jakarta, Jakarta, 11520, Indonesia, Email alia.arianti@jec.co.idAbstract: This case series aims to report the manifestation of acute secondary optic neuropathy attributed to optic nerve injury associated with a singular episode of markedly elevated intraocular pressure (IOP) during an acute glaucoma attack. The correlation between acute primary angle-closure (APAC) and non-arteritic anterior ischemic optic neuropathy (NAION) remains uncertain within the context of current knowledge. Definitive conclusions regarding the causal relationship between APAC and NAION or their mutual influence cannot be established based on the current evidence. The association between these conditions is recognized as a potential link, and comprehensive research is imperative to elucidate their interrelationship thoroughly. This case series emphasizes the importance of promptly addressing acute optic nerve injury and neuropathy associated with elevated intraocular pressure (IOP) in patients with crowded disc anatomical risk factors. It underscores the need for proactive interventions to prevent irreversible damage, highlighting the infrequent yet vision-compromising occurrence of non-arteritic anterior ischemic optic neuropathy (NAION) in acute primary angle-closure (APAC).Keywords: AACG, NAION, Acute Glaucoma Attack, Neuropathy

Abstract Background To determine whether sensory nerve conduction stimulus threshold measurements of the infraorbital nerve are able to differentiate horses with idiopathic trigeminal-mediated headshaking (i-TMHS) from healthy horses and from horses with secondary trigeminal-mediated headshaking (s-TMHS). In a prospective trial, headshaking horses were examined using a standardized diagnostic protocol, including advanced diagnostics such as computed tomography and 3-Tesla-magnetic resonance imaging (MRI), to differentiate s-TMHS from i-TMHS. Clinically healthy horses served as controls. Within this process, patients underwent general anesthesia, and the minimal sensory nerve conduction stimulus threshold (SNCT) of the infraorbital nerve was measured using a bipolar concentric needle electrode. Sensory nerve action potentials (SNAP) were assessed in 2.5–5 mA intervals. Minimal SNCT as well as additional measurements were calculated. Results In 60 horses, SNAP could be recorded, of which 43 horses had i-TMHS, six had suspected s-TMHS, three horses had non-facial headshaking, and eight healthy horses served as controls. Controls had a minimal SNCT ≥ 15 mA, whereas 14/43 horses with i-TMHS and 2/6 horses with s-TMHS showed a minimal SNCT ≤ 10 mA. Minimal SNCT ≤ 10 mA showed 100% specificity to distinguish TMHS from controls, but the sensitivity was only 41%. Conclusion A minimal SNCT of the infraorbital nerve ≤ 10 mA was able to differentiate healthy horses from horses with TMHS. Nevertheless, a higher minimal SNCT did not exclude i-TMHS or s-TMHS and minimal SNCT does not distinguish s-TMHS from i-TMHS.

Abstract Background Paclitaxel administration is considered a keystone in the management of many types of cancers. However, paclitaxel chemotherapy often leads to peripheral neuropathy which is the most prominent adverse effect that reduces the patient’s quality of life and demands dose reduction leading to decreased disease curing. Paclitaxel induces peripheral neuropathy through disruption of microtubules, distorted function of ion channels, axonal degeneration, and inflammatory events. So far, there is no standard medication to prevent the incidence of paclitaxel-induced peripheral neuropathy (PIPN). Main body Numerous preclinical studies in rats and rodents showed that several therapeutic agents have neuroprotective mechanisms and reduce the incidence of PIPN, proving their effectiveness in the prevention of PIPN in animal models. Different mechanisms, such as reduction of the expression of inflammatory mediators, quenching of reactive oxygen species, prevention of neuronal damage, and other mechanisms, have been explored. Moreover, many clinical trials have further established the neuroprotective effect of several investigational drugs on PIPN. Twenty preclinical studies of pharmacological interventions were reviewed for their preventive effect on neuropathy. These medications targeted cannabinoid receptors, oxidative stress, inflammatory response, and ion channels. Additionally, 25 clinical studies with pharmacological preventive interventions of PIPN have been reviewed, of which only 10 showed preventive action in PIPN. Conclusion Prevention of PIPN is currently considered an emergent field of research. This review highlights the potential interventions and presents recent findings from both preclinical and clinical studies on the significant prevention of PIPN to help in effective decision-making. However, further well-designed research is required to ascertain recommendations for clinical practice.