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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]

Proprioception plays an important role in both feedforward and feedback processes underlying movement control. This has been shown with individuals who suffered a profound proprioceptive loss and use vision to partially compensate for the sensory loss. The purpose of this study was to specifically examine the role of proprioception in feedback motor responses to visual perturbations by examining voluntary arm movements in an individual with a rare case of selective peripheral deafferentation (GL). We compared her left and right hand movements with those of age-matched female control participants (70.0 years ± 0.2 SEM) during a reaching task. Participants were asked to move their unseen hand, represented by a cursor on the screen, quickly and accurately to reach a visual target. A visual perturbation could be pseudorandomly applied, at movement onset, to either the target position (target jump) or the cursor position (cursor jump). Results showed that despite the continuous visual feedback that was provided, GL produced larger errors in final position accuracy compared to control participants, with her left nondominant hand being more erroneous after a cursor jump. We also found that the proprioceptively-deafferented individual produced less spatially efficient movements than the control group. Overall, these results provide evidence of a heavier reliance on proprioceptive feedback for movements of the nondominant hand relative to the dominant hand, supporting the view of a lateralization of the feedback processes underlying motor control. [ABSTRACT FROM AUTHOR]

Diabetes-induced hyperglycemia leads to excessive production of oxygen free radicals, inflammatory cytokines, and oxidative stress, which initiates diabetic peripheral neuropathy (DPN). Currently, this condition affects 20% of adults with diabetes. Despite significant advances in the treatment of diabetes, the incidence of its complications, including DPN, is still high. Thus, there is a growing research interest in developing more effective and treatment approaches with less side effects for diabetes and its complications. Nigellasativa L. (NS) has received much research attention as an antioxidant, anti-yperglycemic factor, and anti-inflammatory agent. This natural compound demonstrates its antidiabetic neuropathy effect through various pathways, including the reduction of lipid peroxidation, the enhancement of catalase and superoxide dismutase enzyme activity, and the decrease in inflammatory cytokine levels. The present review focuses on the bioactive and nutraceutical components of black cumin (Nigella sativa L.) and their effects on DPN. In addition, we have also summarized the findings obtained from several experimental and clinical studies regarding the antidiabetic neuropathy effect of NS in animal models and human subjects. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. Methods: Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free (“resting”) fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. Results: The study was feasible (74–89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0–100 scale: − 7.9 ± 5.7, effect size [ES] = − 0.9 at mid-intervention; − 4.8 ± 7.3, ES = − 0.5 at post-intervention), CIPN signs (ES = − 1.0 and − 0.1), and physical function (ES = 0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2 = 40–60%) and higher functional connectivity within the salience network (R2 = 20–40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). Conclusion: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. Trial registration: Registered Jan 2017 on ClinicalTrials.gov as NCT03021174. [ABSTRACT FROM AUTHOR]

Background: Oxaliplatin, a major drug in metastatic colorectal cancer (mCRC), is responsible for cumulative, dose-limiting peripheral neuropathy (PN). Whether the hepatic arterial infusion (HAI) route can limit oxaliplatin-induced PN in comparison with the intravenous (IV) route has not been specifically explored so far. Methods: We compared the frequency and severity of PN in oxaliplatin-naive patients with mCRC included in trials that evaluated treatment with oxaliplatin administered either by HAI (ACCORD 04, CHOICE, OSCAR, and PACHA-01 trials) or by IV route (FFCD 2000–05 trial). We retrieved anonymized, prospectively collected data from trial databases for the ACCORD 04, CHOICE, and FFCD 2000–05 trials and through a review of Gustave Roussy patients’ electronic medical records for PACHA-01 and OSCAR trials. The primary endpoint was the incidence of clinically significant PN (grades 2 to 4) according to the cumulative dose of oxaliplatin received. Secondary endpoints were time to onset of neuropathy as a function of the cumulative dose of oxaliplatin, discontinuation of oxaliplatin for neurotoxicity, and safety. Results: A total of 363 patients were included (IV, 300; HAI, 63). In total, 180 patients in the IV group (60%) and 30 patients in the HAI group (48%) developed clinically significant PN, with no significant difference between the two groups (p = 0.23). No difference was shown in the time to onset of PN either (p = 0.23). Conclusion: The administration of oxaliplatin HAI rather than IV in the treatment of mCRC does not reduce the incidence, precocity, and severity of PN. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is associated with increased risk of morbidity and premature mortality due to its various complications. In an Indian study, the prevalence of diabetic peripheral neuropathy (DPN) in type 2 diabetic subjects was shown to be 29.2%. There is increasing evidence that a deficiency of nerve growth factor (NGF) in diabetes, as well as the calcitonin gene–related peptide (CGRP), may also contribute to the development of DPN. The aim of the current study was to evaluate nerve growth factor levels with neuropathy in type 2 DM. Materials and Methods: Forty healthy controls and 40 patients with type 2 DM were recruited; they were asked to report to Dept. of Physiology for initial history taking, general examination and neuropathy examination. A total of 5 mL of blood was collected for neurotrophic factor estimation as well as glycemic profile estimation. Results: The brain-derived neurotrophic factor (BDNF) values were significantly lower in the DM group whereas the insulin levels were also quite high in DM. The hot thresholds for both the upper limb and lower limb were greater in the DM group suggesting the impending neuropathy. Similarly, the Michigan scores were also greater in the DM group. The neuropathy parameters especially the Michigan A and B and the hot thresholds were positively correlated with duration of DM and glucose profile. Conclusion: The neurotrophic factors especially BDNF are drastically reduced in DM patients and are negatively associated with neuropathy, and hence, BDNF can be utilized as a therapeutic target to treat and prevent neuropathy. [ABSTRACT FROM AUTHOR]

Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as well as of one of the most common causes of adult-onset ataxia. In the meantime, the phenotypic spectrum has expanded massively and now includes mimics of multiple system atrophy or parkinsonism. After identifying a patient with a clinical diagnosis of amyotrophic lateral sclerosis (ALS) as a carrier of biallelic pathogenic repeat expansions in RFC1, we studied a cohort of 106 additional patients with a clinical main phenotype of motor neuron disease (MND) to analyze whether such repeat expansions are more common in MND patients. Indeed, two additional MND patients (one also with ALS and one with primary lateral sclerosis/PLS) have been identified as carrier of biallelic pathogenic repeat expansions in RFC1 in the absence of another genetic alteration explaining the phenotype, suggesting motor neuron disease as another extreme phenotype of RFC1 spectrum disorder. Therefore, MND might belong to the expanding phenotypic spectrum of pathogenic RFC1 repeat expansions, particularly in those MND patients with additional features such as sensory and/or autonomic neuropathy, vestibular deficits, or cerebellar signs. By systematically analyzing the RFC1 repeat array using Oxford nanopore technology long-read sequencing, our study highlights the high intra- and interallelic heterogeneity of this locus and allows the identification of the novel repeat motif 'ACAAG'. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN) is a primary complication observed in diabetes that severely affects quality of life. Recent evidence suggests that photobiomodulation (PBM) is a promising therapy against painful conditions and nerve damage. However, the effects of PBM on DPN remains mostly unknown. In the present study, we investigated the efficacy of PBM therapy in modulating proinflammatory cytokine expression in both central and peripheral nervous systems of rats with Streptozotocin (STZ)-induced type 1 diabetes. Male Wistar rats were allocated into control (naïve), diabetic (STZ), and treatment (STZ + PBM) groups. A single intraperitoneal (i.p.) injection of STZ (85 mg/kg) was administered for the induction of diabetes. Animals were subjected to 10 treatment sessions, every other day. The results herein presented indicate that PBM treatment diminishes Receptor for Advanced Glycation End-products (RAGE) and Nuclear Factor Kappa B (NF-ϰB) expression in peripheral nervous system and suppresses TNF-α expression in central nervous system tissues. Furthermore, PBM-therapy in diabetic rats also induces increased levels of the anti-inflammatory protein IL-10 in both peripheral and central nervous system. Collectively, our findings demonstrate compelling evidence that PBM-therapy modulates cytokine dynamics and influences RAGE/NF-ϰB axis in a STZ-induced model of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects and main reasons for affecting quality of life and dose reduction or even discontinuation of treatment in breast cancer patients. One of the most widely prescribed chemotherapies is the "taxanes." Considering that duloxetine has been used in treating neuropathies in recent years, this study aimed to investigate its effectiveness in preventing taxane-related neuropathy. Material and methods: This is a randomized controlled trial on 47 patients: 24 received a placebo and 23 received duloxetine at 30 mg daily in the first week following the injection of paclitaxel and 60 mg during the second week in each chemotherapy cycle. Patients objective (nerve conduction velocity (NCV) values) and subjective symptoms (visual analog scale including; neuropathy, paresthesia, pain, cold sensitivity, and numbness), the grades of the patients' neuropathy (calculated according to Common Terminology Criteria for Adverse Events (CTCAE) v.5), and the presence of complications, before and after each chemotherapy cycle, were recorded. Results: The placebo group experienced significantly higher occurrences of new neuropathy (8/23 in duloxetine vs 16/24 in placebo, P = 0.029) in NCV by tibial nerve latency (− 0.28% vs 19.87%, P = 0.006), tibial amplitude (4.40% vs − 10.88%, P = 0.049), and median nerve latency (8.72% vs 31.16%, P = 0.039); administration of duloxetine significantly reduced the scores of neuropathies (P < 0.001), pain (P = 0.027), during chemotherapy, and 6 weeks later; however, no significant effect was observed on paresthesia, numbness, cold sensitivity, and other NCV measurements. Conclusions: Paclitaxel can cause neuropathy, lasting for a long time. Our study showed duloxetine is potentially an effective medication that can prevent subjective and objective neuropathy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the combined performance of orbital MRI and intracranial visual pathway diffusion kurtosis imaging (DKI) in diagnosing dysthyroid optic neuropathy (DON). Methods: We retrospectively enrolled 61 thyroid-associated ophthalmopathy (TAO) patients, including 25 with DON (40 eyes) and 36 without DON (72 eyes). Orbital MRI–based apical muscle index (MI), diameter index (DI) of the optic nerve (ON), area index (AI) of the ON, apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) of the ON, DKI-based kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) of the optic tract (OT), optic radiation (OR), and Brodmann areas (BAs) 17, 18, and 19 were measured and compared between groups. The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses and compared using the DeLong test. Results: TAO patients with DON had significantly higher apical MI, apical AI, and SIR of the ON, but significantly lower ADC of the ON than those without DON (p < 0.05). Meanwhile, the DON group exhibited significantly lower KFA across the OT, OR, BA17, BA18, and BA19 and lower MK at the OT and OR than the non-DON group (p < 0.05). The model integrating orbital MRI and intracranial visual pathway DKI parameters performed the best in diagnosing DON (AUC = 0.926), with optimal diagnostic sensitivity (80%) and specificity (94.4%), followed by orbital MRI combination (AUC = 0.890), and then intracranial visual pathway DKI combination (AUC = 0.832). Conclusion: Orbital MRI and intracranial visual pathway DKI can both assist in diagnosing DON. Combining orbital and intracranial imaging parameters could further optimize diagnostic efficiency. Clinical relevance statement: The novel finding could bring novel insights into the precise diagnosis and treatment of dysthyroid optic neuropathy, accordingly, contributing to the improvement of the patients' prognosis and quality of life in the future. Key Points: • Orbital MRI and intracranial visual pathway diffusion kurtosis imaging can both assist in diagnosing dysthyroid optic neuropathy. • Combining orbital MRI and intracranial visual pathway diffusion kurtosis imaging optimized the diagnostic efficiency of dysthyroid optic neuropathy. [ABSTRACT FROM AUTHOR]

Objective: To determine the inter-reader reliability and diagnostic performance of classification and severity scales of Neuropathy Score Reporting And Data System (NS-RADS) among readers of differing experience levels after limited teaching of the scoring system. Methods: This is a multi-institutional, cross-sectional, retrospective study of MRI cases of proven peripheral neuropathy (PN) conditions. Thirty-two radiology readers with varying experience levels were recruited from different institutions. Each reader attended and received a structured presentation that described the NS-RADS classification system containing examples and reviewed published articles on this subject. The readers were then asked to perform NS-RADS scoring with recording of category, subcategory, and most likely diagnosis. Inter-reader agreements were evaluated by Conger's kappa and diagnostic accuracy was calculated for each reader as percent correct diagnosis. A linear mixed model was used to estimate and compare accuracy between trainees and attendings. Results: Across all readers, agreement was good for NS-RADS category and moderate for subcategory. Inter-reader agreement of trainees was comparable to attendings (0.65 vs 0.65). Reader accuracy for attendings was 75% (95% CI 73%, 77%), slightly higher than for trainees (71% (69%, 72%), p = 0.0006) for nerves and comparable for muscles (attendings, 87.5% (95% CI 86.1–88.8%) and trainees, 86.6% (95% CI 85.2–87.9%), p = 0.4). NS-RADS accuracy was also higher than average accuracy for the most plausible diagnosis for attending radiologists at 67% (95% CI 63%, 71%) and for trainees at 65% (95% CI 60%, 69%) (p = 0.036). Conclusion: Non-expert radiologists interpreted PN conditions with good accuracy and moderate-to-good inter-reader reliability using the NS-RADS scoring system. Clinical relevance statement: The Neuropathy Score Reporting And Data System (NS-RADS) is an accurate and reliable MRI-based image scoring system for practical use for the diagnosis and grading of severity of peripheral neuromuscular disorders by both experienced and general radiologists. Key Points: • The Neuropathy Score Reporting And Data System (NS-RADS) can be used effectively by non-expert radiologists to categorize peripheral neuropathy. • Across 32 different experience-level readers, the agreement was good for NS-RADS category and moderate for NS-RADS subcategory. • NS-RADS accuracy was higher than the average accuracy for the most plausible diagnosis for both attending radiologists and trainees (at 75%, 71% and 65%, 65%, respectively). [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]

Prolonged hyperglycemic conditions in type 2 diabetes mellitus (T2DM) cause pathological and functional damage to many organs and tissues, including the kidneys, retina, skin, and neuronal tissues, resulting in the development of microvascular diabetic complications. The altered renin angiotensin aldosterone system (RAAS) pathway has been reported to play an important role in the development of insulin resistance in T2DM and associated complications. The current study was carried out to evaluate the association of risk factors and altered expression of RAAS genes in T2DM patients without complications and T2DM patients with complications (retinopathy, nephropathy, and neuropathy). Four hundred and twenty subjects including 140 healthy controls, 140 T2DM patients with diabetic complications, and 140 T2DM patients without diabetic complications were included in the study. Risk factors associated with the development of T2DM and diabetic complications were evaluated. Further, expression analysis of RAAS genes (AGT, ACE, ACE2, and AGT1R) was carried out using qRTPCR in healthy controls, T2DM patients with complications, and T2DM patients without complications. Various risk factors like urban background, higher BMI, alcoholism, smoking, and family history of diabetes among others were found to be associated with the development of T2DM as well as diabetic complications. The expression level of AGT, ACE, and AGT1R was found to be upregulated whereas ACE2 was found to be downregulated in T2DM patients with complications and T2DM patients without complications as compared to controls. Altered expression of the studied genes of RAAS pathway is associated with the development of microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Background: Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications. Methods: Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003–2004 and 2006–2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI]). Result: In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150–4.114] and 1.335 [0.909–1.961]), incident (2.088 [1.185–3.680] and 1.753 [1.275–2.409]), and persistent proteinuria (1.314 [0.418–4.134] and 2.098 [1.274–3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082–2.051] and 1.164 [0.988–1.371]), incident (1.570 [1.161–2.123] and 1.291 [1.112–1.500]), and persistent proteinuria (2.309 [1.407–3.788] and 1.272 [0.945–1.712]). Conclusion: Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria. [ABSTRACT FROM AUTHOR]

To investigate the effectiveness of optic nerve decompression (OND) in the treatment of severe traumatic optic neuropathy (TON) through pterional and supraorbital approaches, and to identify the prognostic factor for postoperative visual acuity (VA) following OND. Patients with severe TON treated with OND through either pterional or supraorbital approach in our institute from September 2019 to June 2022 were retrospectively reviewed in this study. Demographic information, trauma factors, the interval between trauma and complete blindness, the interval between trauma and surgery, and the associated craniofacial traumas were recorded. Hospitalization days and the postoperative VA of patients in two groups were compared. There were 54 severe TON patients with NLP included in this study; 21 patients underwent OND through the pterional approach, and the other 33 underwent the supraorbital approach. Respectively, in groups of pterional and supraorbital approaches, the average hospitalization days were 9.8 ± 3.2 and 10.7 ± 2.9 days (p = 0.58), the mean durations of follow-up were 18.9 ± 4.3 and 20.8 ± 3.7 months (p = 0.09), and the average circumference of OND were 53.14 ± 15.89 ◦ (range 220 ◦ -278◦) and 181.70 ± 6.56◦ (range 173 ◦ -193◦) (p<0.001). The overall improvement rates of pterional and supraorbital approaches are 57.1% and 45.5% (p = 0.40), respectively. Optic canal fracture (OCF) was revealed to be significantly associated with postoperative VA in the supraorbital approach (Binary: p = 0.014, CI: 1.573–57.087; Ordinal: p = 0.003, CI: 1.517–5.503), but not in the pterional approach. In the group of supraorbital approach, patients with OFC had a higher rate of a better outcome (78.6%) than those without (21.4%). Patients with severe traumatic TON may benefit from OND through either the pterional or supraorbital approach. OCF is a potential prognostic factor for postoperative VA following OND through the supraorbital approach. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor published in the journal Neurological Sciences. It discusses a unique case study of a teenager with congenital myasthenic syndrome and demyelinating sensorimotor neuropathy. The patient had a specific genetic mutation and experienced significant improvement in symptoms with salbutamol monotherapy. The letter emphasizes the importance of identifying the genetic basis of each syndrome for genetic counseling and appropriate therapy. The study highlights the variability of clinical manifestations in congenital myasthenic syndromes and the potential efficacy of salbutamol as a treatment option. Further research is needed to understand the effects of salbutamol on demyelinating neuropathy and its overall therapeutic efficacy in AChR deficiency-related congenital myasthenic syndromes. [Extracted from the article]

Objectives: This case series reports clinical features and outcome of four patients with non-systemic vasculitic neuropathy (NSVN) treated with the anti-CD20 agent rituximab. Methods: Clinical, electrophysiological and biopsy data were retrospectively obtained and evaluated. Only patients with pathological definite or probable NSVN were included. Extensive clinical and laboratory work-up excluded systemic vasculitis. Follow-up data for at least 12 months and up to five years is provided. Outcome of the patients was assessed using the MRC-Sum Score, Prineas Score and Neurological Symptom Score. Results: Two of four patients treated with rituximab achieved disease remission and one patient remained stable under anti-CD20 therapy after a required treatment switch due to toxic side effects of cyclophosphamide. One patient deteriorated under rituximab induction. Rituximab was well tolerated in all patients. Discussion: Anti-CD20 therapy might be an alternative in NSVN patients requiring further treatment escalation or treatment switch due to side effects of corticosteroids or cyclophosphamide. [ABSTRACT FROM AUTHOR]

Introduction: Recent diagnostic criteria for optic neuritis include T2-hyperintensity of the optic nerve (ON), even without associated contrast enhancement. However, isolated ON-T2-hyperintensity is a nonspecific finding found in any optic neuropathy or severe retinopathy. We applied the 2022 optic neuritis diagnostic criteria to a cohort of patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one eye, to assess the rate of optic neuritis misdiagnosis using these criteria. Methods: Retrospective study of consecutive patients who underwent brain/orbit MRI with/without contrast between 07/01/2019 and 06/30/2022. Patients with ON-T2-hyperintensity in at least one eye were included. The 2022 optic neuritis diagnostic criteria were applied to patients with noninflammatory optic neuropathies who had an ophthalmologic examination available for review. Results: Of 150 patients included, 85/150 had compressive optic neuropathy; 32/150 had glaucoma; 12/150 had papilledema; 8/150 had hereditary (3), radiation-induced (3), nutritional (1), traumatic (1) optic neuropathies (none fulfilled the criteria); 13/150 had ischemic optic neuropathy and 4 fulfilled the criteria as definite optic neuritis due to contrast enhancement of the ON head. Seven additional patients would have satisfied the diagnostic criteria if red flags for alternative diagnoses had been overlooked. Discussion: The application of the 2022 optic neuritis diagnostic criteria in patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one ON resulted in misdiagnosis of optic neuritis in only 4 patients because of ON head enhancement, all with nonarteritic anterior ischemic optic neuropathy. Neuro-ophthalmologic evaluation and exclusion of the ON head as a location in the MRI criteria would have prevented optic neuritis misdiagnosis in our study. [ABSTRACT FROM AUTHOR]

Purpose: To determine and report the underlying cause of local inflammation causing recurrent neuropathy and multiple operations in a patient with a Barricaid® device. Methods: After removal of this patient's Barricaid® device, we sent local inflammatory tissue to pathology for histochemical analysis. Upon discovery of giant cells formation with polarizable foreign bodies, we performed a literature review regarding the Barricaid® device and its elements. Results: After two previous operations and three trials of conservative management, the presented patient underwent an L5/S1 TLIF with removal of her previously installed Barricaid® device. There were no signs of device instability/failure nor were there obvious signs of infection. Inflamed tissue proximal to the Barricaid® device was discovered, debrided, and sample sent to pathology. Removal of the Barricaid® device led to subsequent and durable relief of her symptoms. During review of this case, we discovered the polyethylene terephthalate (PET) weave used in the Barricaid® device is known to induce foreign body reactions, and this precise finding was seen in the majority of animal data submitted to the FDA for the device's acceptance. Conclusion: Given the constellation of this patient's symptoms, imaging, intraoperative, and pathology findings, previously published reports, and pre-approval data submitted to the FDA, we conclude that the inflammatory response to the PET weave in this patient's Barricaid® device was the ultimate cause of her continued neuropathy despite multiple prior surgical interventions. [ABSTRACT FROM AUTHOR]

Objectives: MR neurography has the ability to detect and depict peripheral nerve injuries. This study evaluated the potential of MR neurography in the diagnosis of post-traumatic trigeminal neuropathy. Methods: Forty-one participants prospectively underwent MR neurography of the lingual and inferior alveolar nerves using a 3D TSE STIR black-blood sequence. Two blinded and independent observers recorded the following information for each nerve of interest: presence of injury, nerve thickness, nerve signal intensity, MR neurography Sunderland class, and signal gap. Afterwards, the apparent nerve-muscle contrast-to-noise ratio and apparent signal-to-noise ratio were calculated. Clinical data (neurosensory testing score and clinical Sunderland class) was extracted retrospectively from the medical records of patients diagnosed with post-traumatic trigeminal neuropathy. Results: Compared to neurosensory testing, MR neurography had a sensitivity of 38.2% and specificity of 93.5% detecting nerve injuries. When differentiated according to clinical Sunderland class, sensitivity was 19.1% in the presence of a low class injury (I to III) and improved to 83.3% in the presence of a high class (IV to V). Specificity remained unchanged. The area under the curve using the apparent nerve-muscle contrast-to-noise ratio, apparent signal-to-noise ratio, and nerve thickness to predict the presence of an injury was 0.78 (p <.05). Signal intensities and nerve diameter increased in injured nerves (p <.05). Clinical and MR neurography Sunderland scores positively correlated (correlation coefficient = 0.53; p =.005). Conclusions: This study shows that MR neurography can accurately differentiate between injured and healthy nerves, especially in the presence of a more severe nerve injury. Clinical relevance statement: MR neurography is not only able to detect trigeminal nerve injuries, but it can also provide information about the anatomical specifications of the injury, which is not possible with clinical neurosensory testing. This makes MR neurography an added value in the management of post-traumatic trigeminal neuropathy. Key Points: • The current diagnosis of post-traumatic trigeminal neuropathy is mainly based on clinical examination. • MR neurography is able to visualize and stratify peripheral trigeminal nerve injuries. • MR neurography contributes to the diagnostic process as well as to further decision-making. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Dysthyroid optic neuropathy (DON) leads to vision loss. This study aimed to investigate a new method that can directly evaluate the change in muscle cone inner volume (MCIV) and distinguish DON orbits from non-DONs. Materials and methods: This study included 54 patients (108 orbits) who were diagnosed with thyroid eye disease and treated at the Beijing Tongren Hospital between December 2019 and September 2021. The extraocular muscle volume (EOMV), orbital fat volume (OFV), and bony orbit volume (BOV) of the patients were measured using three-dimensional reconstruction. MCIV was measured using artificially defined boundaries. The associations between these volumes and clinical indicators were studied, and the diagnostic efficacy of these volumes for DON was described using receiver operating characteristic (ROC) curves. Results: The ROC curve showed that the area under the curve of MCIV/BOV (%) combined with EOMV/BOV (%) reached 0.862 (p < 0.001), with a sensitivity of 85.7% and a specificity of 76.1%. Conclusion: The combination of MCIV/BOV (%) and EOMV/BOV (%) is a good indicator for the diagnosis of DON, which aids in the early detection and intervention of DON. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary transthyretin (ATTRv, v for variant) amyloidosis is a rare, progressive, fatal disease with multisystem manifestations, caused by pathogenic variants in the transthyretin (TTR) gene. Vutrisiran, an RNA interference therapeutic that results in rapid TTR knockdown, improved neuropathy and quality of life (QOL) versus external placebo in patients with ATTRv amyloidosis with polyneuropathy in the phase 3 HELIOS-A study (NCT03759379). This post hoc analysis evaluates the impact of baseline neuropathy severity on response to vutrisiran treatment. Methods: Patients were randomized (3:1) to vutrisiran (n = 122; 25 mg subcutaneous injection once every 3 months) or patisiran (n = 42; 0.3 mg/kg intravenous infusion once every 3 weeks), which served as a reference group. In this post hoc analysis, patients were grouped into quartiles of increasing baseline Neuropathy Impairment Score (NIS): Quartile (Q)1 ≥ 5.0 to ≤ 20.5; Q2 > 20.5 to ≤ 44.1; Q3 > 44.1 to ≤ 73.1; Q4 > 73.1 to ≤ 127.0. Mean change from baseline to Month 18 was summarized by quartile for a range of efficacy endpoints. Results: Across all baseline NIS quartiles, vutrisiran demonstrated benefit versus external placebo in measures of neuropathy severity (modified NIS + 7), QOL (Norfolk Quality of Life-Diabetic Neuropathy), disability (Rasch-built Overall Disability Scale), gait speed (10-m walk test), and nutritional status (modified body mass index). Overall, patients in lower versus higher NIS quartiles (less severe neuropathy) at baseline maintained better scores at Month 18. The external placebo group progressively worsened in all measures at Month 18. Conclusions: Vutrisiran demonstrated benefit in neurologic function and other key efficacy measures versus external placebo across all four baseline neuropathy severity quartiles. Patients initiating vutrisiran earlier in their disease course retained the highest neurologic function level after 18 months, highlighting the importance of early diagnosis and treatment. Trial Registration Number: ClinicalTrials.gov: NCT03759379. [ABSTRACT FROM AUTHOR]

A biomarker for declined methylation capacity is elevation of homocysteine levels. They increase the risk for onset of vascular disease and contribute to progression of chronic neurodegeneration and aging. This narrative review discusses associations between homocysteine, consumption of methyl group-donating vitamins and impact on disease-generating mechanisms in levodopa-treated patients with Parkinson's disease. We conclude to recommend levodopa-treated patients to substitute themselves with methyl group-donating vitamins. This is harmless in terms of application of folic acid, methylcobalamin or hydroxocobalamin. Moreover, we suggest a crucial discussion on the value of the various popular hypotheses on Parkinson's disease-generating mechanisms. Findings from studies with acute levodopa exposure describe oxidative stress generation and impaired methylation capacity, which causes gene dysfunction. Their repeated occurrences contribute to onset of mitochondrial dysfunction, iron enrichment and pathologic protein accumulation in the long term. Current research underestimates these epigenetic, metabolic consequences of chronic levodopa application. Supplementary treatment strategies are recommended to avoid levodopa-related side effects. [ABSTRACT FROM AUTHOR]

Purpose of Review: Diabetic neuropathy is a debilitating complication of diabetes mellitus that affects millions of individuals worldwide. It is characterized by nerve damage resulting from prolonged exposure to high blood glucose levels. Diabetic neuropathy may cause a range of symptoms, including pain, numbness, muscle weakness, autonomic dysfunction, and foot ulcers, potentially causing significant impairment to the quality of life for those affected. This review article aims to provide a comprehensive overview of the pathophysiology of diabetic neuropathy. The etiology of diabetic neuropathy will be discussed, including risk factors, predisposing conditions, and an overview of the complex interplay between hyperglycemia, metabolic dysregulation, and nerve damage. Additionally, we will explore the molecular mechanisms and pathways of diabetic neuropathy, including the impact of hyperglycemia on nerve function, abnormalities in glucose metabolism, the role of advanced glycation end products (AGEs), and inflammatory and immune-mediated processes. We will provide an overview of the various nerve fibers affected by diabetic neuropathy and explore the common symptoms and complications associated with diabetic neuropathy in the pain medicine field. Recent Findings: This review highlights advances in understanding the pathophysiology of diabetic neuropathy as well as reviews potential novel therapeutic strategies and promising areas for future research. Summary: In conclusion, this review article aims to shed light on the pathophysiology of diabetic neuropathy, its far-reaching consequences, and the evolving strategies for prevention and management. In understanding the mechanisms of diabetic neuropathy and the ongoing research in this area, healthcare professionals can better serve patients with diabetes, ultimately improving well-being and reducing complications. [ABSTRACT FROM AUTHOR]

Isolated optic nerve involvement is rare in sarcoidosis. We report three cases describing atypical clinical and radiological features of isolated optic nerve involvement in sarcoidosis to expand the spectrum of neuro-ophthalmic sarcoidosis. Bilateral optic neuritis, sudden vision loss, primary optic atrophy, long segment optic neuritis, and isolated intrao-orbital sarcoidosis are described as atypical features of optic nerve involvement in this case series. [ABSTRACT FROM AUTHOR]

Purpose: In this extensive review work, the important role of AMP-activated protein kinase (AMPK) in causing of diabetes mellitus has been highlighted. Structural feature of AMPK as well its regulations and roles are described nicely, and the association of AMPK with the diabetic complications like nephropathy, neuropathy and retinopathy are also explained along with the connection between AMPK and β-cell function, insulin resistivity, mTOR, protein metabolism, autophagy and mitophagy and effect on protein and lipid metabolism. Methods: Published journals were searched on the database like PubMed, Medline, Scopus and Web of Science by using keywords such as AMPK, diabetes mellitus, regulation of AMPK, complications of diabetes mellitus, autophagy, apoptosis etc. Result: After extensive review, it has been found that, kinase enzyme like AMPK is having vital role in management of type II diabetes mellitus. AMPK involve in enhance the concentration of glucose transporter like GLUT 1 and GLUT 4 which result in lowering of blood glucose level in influx of blood glucose into the cells; AMPK increases the insulin sensitivity and decreases the insulin resistance and further AMPK decreases the apoptosis of β-cells which result into secretion of insulin and AMPK is also involve in declining of oxidative stress, lipotoxicity and inflammation, owing to which organ damage due to diabetes mellitus can be lowered by activation of AMPK. Conclusion: As AMPK activation leads to overall control of diabetes mellitus, designing and developing of small molecules or peptide that can act as AMPK agonist will be highly beneficial for control or manage diabetes mellitus. [ABSTRACT FROM AUTHOR]

Lemierre's disease, a rare condition characterized by bacterial pharyngitis leading to thrombophlebitis of the jugular vein, is discussed in this case report. The patient, a young and healthy man, presented with symptoms including a painful and stiff neck, headache, and slurred speech. He was diagnosed with Lemierre's disease based on clinical and radiological findings, and received multidisciplinary treatment. Unusual manifestations of the disease in this case included ophthalmoplegia and bilateral hypoglossal nerve palsy. The report highlights the challenges in managing Lemierre's disease and the need for prompt recognition and appropriate antimicrobial treatment. [Extracted from the article]

Background: To specify peripheral nerve affection in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) by correlating high-resolution nerve ultrasound and nerve conduction studies. Methods: We assessed a cohort of 11 ARSACS patients with standardized nerve conduction studies and high-resolution ultrasound of peripheral nerves and compared nerve ultrasound findings to a healthy control group matched for age, sex, size and weight. Results: Mean age of patients was 39.0 (± 14.1) years and disease duration at assessment 30.6 (± 12.5) years. All patients presented with a spasticity, ataxia and peripheral neuropathy. Neuropathy appeared to be primarily demyelinating in 9/11 cases and was not classifiable in 2/11 cases due to not evocable potentials. Nerve ultrasound revealed a normal ultrasound pattern sum score (UPSS) in each ARSACS patient and no significant nerve enlargement compared to the control group. Conclusions: Peripheral neuropathy in ARSACS showed primarily demyelinating rather than axonal characteristics and presented without nerve enlargement. As demyelinating neuropathies do commonly present enlarged nerves we recommend further genetic testing of the SACS gene in patients who present with this combination of demyelinating neuropathy without nerve enlargement. ARSACS cases that initially presented only with neuropathy without spasticity or ataxia and therefore were misdiagnosed as Charcot-Marie-Tooth disease are supporting this suggestion. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy is one of the prevalent and debilitating microvascular complications of diabetes mellitus, affecting a significant portion of the global population. Relational preclinical animal models are essential to understand its pathophysiology and develop effective treatments. This abstract provides an overview of current knowledge and advancements in such models. Various animal models have been developed to mimic the multifaceted aspects of human diabetic neuropathy, including both type 1 and type 2 diabetes. These models involve rodents (rats and mice) and larger animals like rabbits and dogs. Induction of diabetic neuropathy in these models is achieved through chemical, genetic, or dietary interventions, such as diabetogenic agents, genetic modifications, or high-fat diets. Preclinical animal models have greatly contributed to studying the intricate molecular and cellular mechanisms underlying diabetic neuropathy. They have shed light on hyperglycemia-induced oxidative stress, neuroinflammation, mitochondrial dysfunction, and altered neurotrophic factor signaling. Additionally, these models have allowed for the investigation of morphological changes, functional alterations, and behavioral manifestations associated with diabetic neuropathy. These models have also been crucial for evaluating the efficacy and safety of potential therapeutic interventions. Novel pharmacological agents, gene therapies, stem cell-based approaches, exercise, dietary modifications, and neurostimulation techniques have been tested using these models. However, limitations and challenges remain, including physiological differences between humans and animals, complex neuropathy phenotypes, and the need for translational validation. In conclusion, preclinical animal models have played a vital role in advancing our understanding and management of diabetic neuropathy. They have enhanced our knowledge of disease mechanisms, facilitated the development of novel treatments, and provided a platform for translational research. Ongoing efforts to refine and validate these models are crucial for future treatment developments for this debilitating condition. [ABSTRACT FROM AUTHOR]

Vagal neuropathy causing vocal fold palsy is an uncommon complication of vagal nerve stimulator (VNS) placement. It may be associated with intraoperative nerve injury or with device stimulation. Here we present the first case of delayed, compressive vagal neuropathy associated with VNS coil placement which presented with progressive hoarseness and vocal cord paralysis. Coil removal and vagal neurolysis was performed to relieve the compression. Larger 3 mm VNS coils were placed for continuation of therapy. Coils with a larger inner diameter should be employed where possible to prevent this complication. The frequency of VNS-associated vagal nerve compression may warrant further investigation. [ABSTRACT FROM AUTHOR]

We aimed to investigate the changes in cupping in chiasmal lesion optic neuropathy (chON) compared to baseline optic disc and glaucoma. We used a novel study design to enroll patients who had fundus photographs incidentally taken during routine health check-ups prior to the onset of optic neuropathy. In 31 eyes (21 patients) with chON and 33 eyes (30 patients) with glaucoma, we investigated the change in cup-to-disc (C/D) area from the baseline to overt cupping using flicker analysis. Compared to the baseline, 23 eyes (74.2%) had increased cup size and 3 (9.7%) had vascular configuration changes in the chONgroup; in contrast, all glaucoma eyes exhibited changes in cup size and vascular configuration. The increase in C/D area ratio was significantly smaller in chON (0.04 ± 0.04) compared to glaucoma (0.10 ± 0.04, P < 0.001); the minimum residual neuroretinal rim width showed a more pronounced difference (29.7 ± 8.2% vs 7.1 ± 3.9%, P < 0.001). The changes distributed predominantly towards the nasal direction in chON, contrasting the changes to the arcuate fibers in glaucoma. In conclusion, our results provide the first longitudinal evidence of true pathological cupping in chONcompared to photographically disease-free baseline. The marked difference in the residual minimum rim width reaffirms the importance of rim obliteration in the differential diagnosis between the two diseases. [ABSTRACT FROM AUTHOR]

Endoscopic optic nerve decompression is a highly effective and reliable approach for patients with select cases of optic neuropathy. It reduces the hydrostatic pressure and helps in relieving the compressive forces within the intracanalicular portion of the optic nerve consequently preserving and arresting the deterioration of vision. The advantages of the endoscopic approach over other procedures include preservation of olfaction, quick recovery, lack of external scars and less morbidity. The objective of the study is to assess the surgical outcome of endoscopic optic nerve decompression in patients with traumatic and atraumatic optic neuropathy. The case records of consequent patients attending ENT department with defective vision due to traumatic and atraumatic causes were reviewed. The outcome was measured in terms of improvement in visual acuity by log MAR scale. Among the 14 patients studied, 57% were females and the median age of presentation was 33 years. As compared to preoperative baseline visual acuity, the overall improvement was achieved in 11 patients, with an effective rate of 78.5% postoperatively. Patients presenting with no light perception and residual vision had significant improvement in visual acuity after surgery. Trans-nasal endoscopic surgery helps in decompressing the optic nerve with proper exposure of the orbital apex and optic canal without any intracranial or intra-orbital complications. Further, being a minimally invasive procedure has great advantage in cases of optic neuropathy. [ABSTRACT FROM AUTHOR]

Autoimmune nodopathies are inflammatory diseases of the peripheral nervous system with clinical and neurophysiological peculiar characteristics. In this nosological category, we find patients with autoantibodies against Neurofascin 140/186 and 155, Contactin1, and Caspr1 directed precisely towards nodal and paranodal structures. These antibodies are extremely rare and cause severe clinical symptoms. We describe the clinical case of a patient with autoimmune nodopathy caused by the coexistence of anti-neurofascin (NF) 186/140 and 155, characterized by progressive weakness in all limbs leading to tetraplegia, involving cranial nerves, and respiratory insufficiency. Response to first-line treatments was good followed by rapid dramatic clinical relapse. There are few reported cases of anti-pan NF neuropathy in the literature, and they present a clinical phenotype similar to our patient. In these cases, early recognition of clinical red flags of nodopathies and serial neurophysiological studies can facilitate the diagnosis. However, the severe clinical relapse suggests a possible early use of immunosuppressive therapies for this rare category of patients. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv, v for variant) is a progressive disease caused by mutations in the TTR gene, leading to sensory-motor, axonal and length-dependent neuropathy. However, some patients may show variable electrophysiological pattern. The aim of this study was to evaluate the electrophysiological features of TTR amyloid neuropathy at the time of the first nerve conduction study (NCS) to assess whether there were distinguishing features useful for early diagnosis. Methods: We retrospectively revised the first electrophysiological findings of ATTRv patients, and we categorized the neuropathy based on nerve conduction slowing, type of involved fibres and distribution pattern of PNS involvement. Cluster analysis was performed to evaluate the prevalence of neuropathy features between the early and late stage of disease, based on disease duration and disability burden assessed by NIS. Results: We recruited 33 patients (27 males) with mean age 63.9 ± 10.8 years, mean disease duration 2.8 ± 2.4 years and mean NIS 47.6 ± 41.8. Overall, the frequency analysis showed that the most common features of ATTRv neuropathy included the categories of axonal, sensory-motor and neuronopathic-like pattern. This electrophysiological pattern of PNS involvement was constant in patients in late stage of disease, whereas ATTRv patients in early stage of disease displayed variable electrophysiological pattern of PNS involvement. Discussion: Our findings demonstrated that ATTRv neuropathy may present at first NCS in a variable way, and it changes over the course of disease. Such heterogeneity makes the suspicion of ATTRv even more challenging at the time of first electrophysiological examination. [ABSTRACT FROM AUTHOR]

Background: Neuropathic tremor occurs in Charcot–Marie–Tooth neuropathy type 1A (CMT1A; hereditary motor and sensory neuropathy, HMSN), although the pathophysiological mechanisms remain to be elucidated. Separately, lower limb tremor has not been explored in CMT1A and could be associated with imbalance as in other neuropathies. The present study aimed to determine tremor characteristics in the upper and lower limbs in CMT1A and relate these findings to clinical disability, particularly imbalance. Methods: Tremor and posturography studies were undertaken in phenotyped and genotyped CMT1A patients. Participants underwent detailed clinical assessment, tremor study recordings, and nerve conduction studies. Tremor stability index was calculated for upper limb tremor and compared to essential tremor. Results: Seventeen patients were enrolled. Postural and kinetic upper limb tremors were evident in 65%, while postural and orthostatic lower limb tremors were seen in 35% of CMT1A patients. Peak upper limb frequencies were lower distally (~ 6 Hz) and higher proximally (~ 9 Hz), were unchanged by weight-loading, and not impacted by fatigue. The tremor stability index was significantly higher in CMT1A than in essential tremor. A 5–6 Hz lower limb tremor was recorded which did not vary along the limb and was unaffected by fatigue. Balance was impaired in patients with postural lower limb tremor. A high frequency peak on posturography was associated with 'good' balance. Conclusions: Tremor is a common clinical feature in CMT1A, distinct from essential tremor, mediated by a complex interaction between peripheral and central mechanisms. Postural lower limb tremor is associated with imbalance; strategies aimed at tremor modulation could be of therapeutic utility. [ABSTRACT FROM AUTHOR]

Purpose of review: Mast cell activation syndrome (MCAS) is a clinical disorder that may explain irritable bowel syndrome (IBS) type symptoms as well as other allergic symptoms experienced by an individual. The diagnosis and treatment of MCAS with specific focus on gastrointestinal (GI) manifestations is reviewed. Recent findings: Although biomarkers for MCAS remain elusive, testing for baseline serum tryptase will distinguish the type of mast cell disorder and urine tests for mast cell mediator metabolites may support the diagnosis. Endoscopy and Colonoscopy with biopsies is not used to diagnose MCAS but is important to rule out other conditions that may cause symptoms. There is increased awareness of the association between MCAS and autonomic dysfunction, small fiber neuropathy, and connective tissue disorders which all impact GI symptoms. Summary: MCAS is a disorder often of unknown etiology (idiopathic) and characterized by intermittent allergy type symptoms that affect multiple organ systems after exposure to a trigger. GI symptoms including abdominal cramping and loose stool are prominent and mimic those of IBS. Diagnostic testing is performed to assess for elevations in mast cell mediators during symptoms and to rule out other conditions. A comprehensive treatment plan includes medications that target mast cells, treatments for associated conditions including autonomic dysfunction, and management of comorbid psychiatric illness and nutritional deficits. [ABSTRACT FROM AUTHOR]

Diabetic painful neuropathy (DPN) is one of the most detrimental complications of diabetes. Alterations in neuroinflammatory mediators play significant roles in the development of DPN. Infiltration of the neutrophils and monocyte/macrophages contributes substantial role in the degenerative process of the distal sciatic nerve by forming neutrophil extracellular traps (NETs) under diabetic condition. Citrullination of histones due to increase in protein arginine deiminase (PAD) enzyme activity under hyperglycemia may promote NET formation, which can further increase the cytokine production by activating macrophages and proliferation of neutrophils. This study reveals that the increase in histone deacetylases (HDAC) is crucial in DPN and inhibition of HDAC using HDAC inhibitor (HDACi) FK228 would suppress NETosis and alleviate diabetic nerve degeneration and pain. FK228, also known as romidepsin, is FDA approved for the treatment of cutaneous T-cell lymphoma yet the molecular mechanisms of this drug are not completely understood in DPN. In this study, type 2 diabetic (T2D) mice with pain were treated with HDACi, FK228 1 mg/kg; I.P. 2 × /week for 3 weeks. The results demonstrate that FK228 treatment can alleviate thermal hyperalgesia and mechanical allodynia significantly along with changes in the expression of HDACs in the dorsal root ganglia (DRG) and spinal cord dorsal horn neurons of diabetic animals. The results also indicate that FK228 treatment can alter the expression of neutrophil elastase (NE), extracellular or cell free DNA (cfDNA), citrullinated histone-3 (CitH3), PADI4, growth-associated protein (GAP)-43, and glucose transporter (GLUT)-4. Overall, this study suggests that FK228 could amend the expression of nerve regeneration markers and inflammatory mediators in diabetic animals and may offer an alternative treatment approach for DPN. [ABSTRACT FROM AUTHOR]

Purpose of Review: To examine the effects and interactions between gut microbia and chronic pain. Recent Findings: The gut microbiome has been an area of interest in both the scientific and general audience due to a growing body of evidence suggesting its influence in a variety of health and disease states. Communication between the central nervous system (CNS) and gut microbiome is said to be bidirectional, in what is referred to as the gut-brain axis. Summary: Chronic pain is a prevalent costly personal and public health burden and so, there is a vested interest in devising safe and efficacious treatments. Numerous studies, many of which are animal studies, have been conducted to examine the gut microbiome's role in the pathophysiology of chronic pain states, such as neuropathy, inflammation, visceral pain, etc. As the understanding of this relationship grows, so does the potential for therapeutic targeting of the gut microbiome in chronic pain. [ABSTRACT FROM AUTHOR]

The objective is to investigate the presentation, complications, management, and outcomes of copper deficiency-induced neurological pathologies due to Wilson disease (WD) overtreatment. We examined the case of a WD patient who developed a low thoracic dorsal myelopathy due to chronic hypocupremia from excessive zinc therapy. A comprehensive literature review was conducted to identify similar cases. Ten additional cases of neurological pathology resulting from copper deficiency in the context of WD over-treatment were identified, all occurring during therapy with zinc salts. Myelopathy and peripheral neuropathy were the most common complications, while two additional groups reported leukoencephalopathy. Early cytopenia was often associated with copper deficiency-related neurological pathology appearing early in the context of copper deficiency. WD patients undergoing treatment, especially with zinc salts, should be closely monitored to prevent over-treatment and the consequent copper deficiency. Regular complete blood counts could provide early detection of copper deficiency, avoiding irreversible neurological damage. Swift recognition of new neurological signs not consistent with WD and timely discontinuation of the decoppering therapy are critical for improving outcomes. The optimal management, including the potential benefit of copper supplementation in patients with WD and subsequent therapy adjustments, remains unclear and necessitates further investigation. Despite the general poor functional neurological outcomes, there were some exceptions that warrant further exploration. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is an hereditary autosomal recessive disease. Recent studies propose including chronic cough (CC) as a symptom of CANVAS. For 10 patients with CANVAS as genetically confirmed by biallelic expansion of the AAGG repeat motif (AAGGGexp) in intron 2 of replication factor C subunit 1 (RFC1), our aim was, as a multidisciplinary team, to describe clinical and functional characteristics and possible causes of CC following European Respiratory Society (ERS) recommendations, and to evaluate CC impact on quality of life (QoL) using self-administered questionnaires (Cough Severity Diary, Leicester Cough Questionnaire, Discrete Emotions Questionnaire, and EQ-5D-5L). In all 10 patients, the CC was a dry cough that developed several years prior to the neurological symptoms (mean 14.2 years); 7 patients had symptoms compatible with gastroesophageal reflux (GER), 5 with pathological GER diagnosed by 24-h esophageal pH testing, and 6 patients had impaired esophageal motility diagnosed by high-resolution esophageal manometry, most frequently ineffective peristalsis. Although further studies are required for confirmation, we conclude that CC may be a characteristic prodrome of CANVAS and may be related to GER and esophageal disorders. Furthermore, CC affects patients' QoL, especially in the psychosocial sphere. [ABSTRACT FROM AUTHOR]

To date, little is known about the usefulness of ultra-high frequency ultrasound (UHF-US, 50–70 MHz) in clinical practice for the diagnosis of dysimmune neuropathies. We present a prospective study aimed at comparing UHF-US alterations of nerves and fascicles in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), distal CIDP (d-CIDP) and anti-MAG neuropathy and their relationships with clinical and electrodiagnostic (EDX) features. 28 patients were included (twelve CIDP, 6 d-CIDP and 10 anti-MAG) and ten healthy controls. Each patient underwent neurological examination, EDX and UHF-US study of median and ulnar nerves bilaterally. UHF-US was reliable in differentiating immune neuropathies from controls when using mean and/or segmental nerve and/or fascicle cross-sectional area (CSA); furthermore, fascicle ratio (fascicle/nerve CSA) was a reliable factor for differentiating d-CIDP from other types of polyneuropathies. The fascicle CSA appears to be more increased in CIDP and its variant than in anti-MAG neuropathy. UHF-US offers information beyond simple nerve CSA and allows for a better characterization of the different forms of dysimmune neuropathies. [ABSTRACT FROM AUTHOR]

Background: To investigate the utility of regular serum VEGF (sVEGF) levels assessment in the monitoring of POEMS syndrome. Methods: We retrospectively reviewed data of 30 patients with POEMS syndrome whose sVEGF was tested regularly every 6 months. sVEGF levels after treatment were measured and correlated with disability (Overall Neuropathy Limitations Scale, ONLS), clinical impairment (measured with the modified Clinical Response Evaluation Scale, mCRES), and relapse-free survival. The ability of sVEGF to predict disease flares during remission and refractory disease was also analysed. Results: Patients with normalised serum VEGF levels (< 1000 pg/ml) at 6 months showed prolonged relapse-free survival (at 3-year 94% for complete VEGF response, 57% partial, 0% none, p < 0.001) and greater later clinical improvement (median ΔmCRES complete VEGF response -5 vs partial -4, p = 0.019, and vs no VEGF response -2, p = 0.006). After remission, the sensitivity of 6-month sVEGF monitoring in predicting clinical relapse was 58% with a specificity of 100%. In patients refractory to treatment, the sensitivity in predicting further clinical worsening was 15%. In addition, in 25% of the patients in remission and 16% of those refractory to therapy, sVEGF levels only increased at the time of relapse. Conclusions: Regular sVEGF assessment is a valid biomarker in the prediction of disease reactivation in POEMS syndrome and was particularly useful during the phase of remission. [ABSTRACT FROM AUTHOR]

Purpose: The middle cluneal nerve (MCN) is a pure sensory nerve around the middle buttock. Its entrapment between the iliac crest and the long posterior sacroiliac ligament elicits low back pain (LBP) that can be treated by MCN neurolysis or neurectomy. Because few studies examined the pathology of MCN entrapment (MCN-E) we subjected 7 neurectomized specimens from 6 LBP patients to pathologic study. Methods: We present 6 consecutive patients (7 sides) with intractable LBP who underwent successful MCN neurectomy. Their symptom duration ranged from 6 to 96 months (average 47.3 months); the follow-up period ranged from 6 to 17 months (average 11.7 months). The surgical outcomes were evaluated using the numerical rating scale (NRS) for LBP and the Roland-Morris Disability Questionnaire (RDQ) score. The resected MCNs underwent neuropathological analysis. Results: Postoperatively, all 6 patients reported immediate LBP amelioration; their NRS and RDQ scores were improved significantly. Pathological study of the 7 resected nerves showed that the myelinated fiber density was decreased in 6 nerves; we observed marked enlargement (n = 5), perineurial thickening and disruption (n = 6), intrafascicular fibrous changes (n = 5), myelinated fibers separated by fibrous cells under the perineurium (n = 4), and Renaut bodies (n = 3). The 7th nerve appeared normal with respect to the density and size of the myelinated fibers, however, the perineurium was slightly thickened. Conclusion: We present pathological evidence at the MCN compression site of 7 nerves from 6 patients whose LBP was alleviated by MCN neurectomy, indicating that MCN entrapment can elicit LBP. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic neuropathy can lead to decreased peripheral sensation and motor neuron dysfunction associated with impaired postural control and risk of falling. However, the relationship between decreased peripheral sensation and impaired vestibular function in diabetes mellitus is poorly investigated. Therefore, the aim of this study was to investigate the relationship between peripheral and autonomic measurements of diabetic neuropathy and measurements of vestibular function. Methods: A total of 114 participants with type 1 diabetes (n = 52), type 2 diabetes (n = 51) and controls (n = 11) were included. Vestibular function was evaluated by video head impulse testing. Peripheral neuropathy was assessed by quantitative sensory testing and nerve conduction. Autonomic neuropathy using the COMPASS 31 questionnaire. Data were analyzed according to data type and distribution. Results: Measurements of vestibular function did not differ between participants with type 1 diabetes, type 2 diabetes or controls (all p-values above 0.05). Subgrouping of participants according to the involvement of large-, small- or autonomic nerves did not change this outcome. Correlation analyses showed a significant difference between COMPASS 31 and right lateral gain value (ρ = 0.23, p = 0.02,), while no other significant correlations were found. Conclusion: Diabetic neuropathy does not appear to impair vestibular function in diabetes, by means of the VOR. Clinical trials: NCT05389566, May 25th, 2022. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is a mitochondrial hereditary disease in which visual loss affects complex 1 activity of the electron transport chain of mitochondria. It first manifests as painless dulling or blurry in one or even both eyes, and as it develops, sharpness and color perception are lost. In addition to primary mitochondrial DNA (mtDNA) mutations, there are also other environmental and epigenetic factors involved in the pathogenesis of LHON. One of the most common locations for deadly pathogenic mutations in humans is the human complex I accessory NDUFS4 subunit gene. The iron-sulfur clusters of the electron input domain were distorted in the absence of NDUFS4, which reduced complex I function and elevated the production of reactive oxygen species. Therefore, here, we studied the epigenetic alterations of NDUFS4 by focusing on histone activation and repressive markers. We isolated peripheral blood mononuclear cells (PBMCs) from LHON patients and healthy individuals and examined epigenetic modifications in ND4 mutant cells and control cells. Chromatin immunoprecipitation-qRT PCR (ChIP-qRT PCR) assays were performed to investigate the modifications of histones. In comparison to their controls, both LHON patients and ND4 mutant cells exhibited a significant enrichment in activation and repressive markers. This finding indicates that these modifications might mitigate the impact of LHON mutations on complex 1 and aid in elucidating the mechanism underlying the progression of LHON disease. Decoding LHON: How Epigenetic Alterations Shield Complex 1 This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author. Leber's hereditary optic neuropathy is a hereditary condition causing swift vision loss due to damage of the retina (light-sensitive layer at the back of the eye) and optic nerve (transmits visual information to the brain). The role of specific changes in mitochondrial DNA (DNA located in the mitochondria, the powerhouses of cells) in this disease and the impact of environmental and genetic factors are still unclear. Scientists studied a gene called NDUFS4, essential for cells' energy production and associated with this condition. They observed alterations in this gene in patients and cell lines with disease-inducing mutations, compared to healthy people and cells. This included examining changes in histone modifications. Significant differences were observed in these modifications between patient samples and controls, offering useful knowledge about the disease's progression. This study could guide future treatments targeting these modifications. [ABSTRACT FROM AUTHOR]

Background: Peripheral neuropathy predisposes to diabetic foot and this predilection is worsened by poorly controlled sugars. Diabetic foot increases the mortality and morbidity associated with diabetes. Thus, it is crucial to screen for diabetic polyneuropathy. Early detection of diabetic polyneuropathy improves foot care and decreases morbidity. This study aimed to assess the sensitivity of Semmes Weinstein monofilament test in the diagnosis of Diabetic Peripheral Neuropathy. Forty-three Type 2 diabetes mellitus patients availing IP/OP services of a Medical College Hospital were included for the study. Patients underwent Semmes Weinstein monofilament test, following which they were subjected to nerve conduction study of both lower limbs. Results: Forty six and half percentage of patients had diabetic peripheral neuropathy, taking NCS as gold standard.Of these 80% of the cases were also detected by the monofilament test.The specificity of the monofilament test was 100%. Positive predictive value was 100% and negative predictive value was 85.19% and the overall accuracy of the test was 90.7%. Conclusions: In this study, we found that sensitivity and specificity of the SWM test are fairly high; thus, it can be used as a valid screening tool for DPN in resource limited settings, such as India. [ABSTRACT FROM AUTHOR]

In today's culture, obesity and overweight are serious issues that have an impact on how quickly diabetes develops and how it causes complications. For the development of more effective therapies, it is crucial to understand the molecular mechanisms underlying the chronic problems of diabetes. The most prominent effects of diabetes are microvascular abnormalities such as retinopathy, nephropathy, and neuropathy, especially diabetes foot ulcers, as well as macrovascular abnormalities such as heart disease and atherosclerosis. MicroRNAs (miRNAs), which are highly conserved endogenous short non-coding RNA molecules, have been implicated in several physiological functions recently, including the earliest stages of the disease. By binding to particular messenger RNAs (mRNAs), which cause mRNA degradation, translation inhibition, or even gene activation, it primarily regulates posttranscriptional gene expression. These molecules exhibit considerable potential as diagnostic biomarkers for disease and are interesting treatment targets. This review will provide an overview of the latest findings on the key functions that miRNAs role in diabetes and its complications, with an emphasis on the various stages of diabetic wound healing. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease with central vision loss as the main symptom. It is one of the diseases that cause vision loss and optic atrophy in young and middle-aged people. The mutations of these three primary mitochondrial mutations, m.11778G>A, m.14484T>C, and m.3460G>A, are the main molecular basis, but their pathogenesis is also affected by nuclear genes, mitochondrial genetic background, and environmental factors. This article summarizes the research progress on molecular pathogenesis, clinical symptoms, and treatment of LHON in recent years, aiming to summarize the genetic pathogenesis and clinical treatment points of LHON. [ABSTRACT FROM AUTHOR]

Neuromuscular diseases encompass a heterogeneous array of disorders characterized by varying onset ages, clinical presentations, severity, and progression. While these conditions can stem from acquired or inherited causes, this review specifically focuses on disorders arising from genetic abnormalities, excluding metabolic conditions. The pathogenic defect may primarily affect the anterior horn cells, the axonal or myelin component of peripheral nerves, the neuromuscular junction, or skeletal and/or cardiac muscles. While inherited neuromuscular disorders have been historically deemed not treatable, the advent of gene-based and molecular therapies is reshaping the treatment landscape for this group of condition. With the caveat that many products still fail to translate the positive results obtained in pre-clinical models to humans, both the technological development (e.g., implementation of tissue-specific vectors) as well as advances on the knowledge of pathogenetic mechanisms form a collective foundation for potentially curative approaches to these debilitating conditions. This review delineates the current panorama of therapies targeting the most prevalent forms of inherited neuromuscular diseases, emphasizing approved treatments and those already undergoing human testing, offering insights into the state-of-the-art interventions. [ABSTRACT FROM AUTHOR]