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Background: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. Materials and methods: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. Results: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09–3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63–1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04–9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19–5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09–0.68), p = 0.007, and OR 0.43, CI (0.22–0.84), p = 0.02, respectively). Conclusion: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN. [ABSTRACT FROM AUTHOR]

Introduction: Uncontrolled blood sugar levels may result in complications, namely diabetic neuropathy. Diabetic neuropathy is a nerve disorder that causes symptoms of numbness, foot deformity, dry skin, and thickening of the feet. The severity of diabetic neuropathy carries the risk of developing diabetic ulcers and amputation. Early detection of diabetic neuropathy can prevent the risk of diabetic ulcers. The purpose: to identify early detection of diabetic neuropathy based on the health belief model. Method: This research searched for articles in 6 databases via Scopus, Ebsco, Pubmed, Sage journal, Science Direct, and SpringerLink with the keywords "screening Neuropathy" AND "Detection Neuropathy" AND "Scoring Neuropathy" AND "Diabetic" published in 2019-2023. In this study, articles were identified based on PICO analysis. Researchers used rayyan.AI in the literature selection process and PRISMA Flow-Chart 2020 to record the article filtering process. To identify the risk of bias, researchers used the JBI checklist for diagnostic test accuracy. Results: This research identified articles through PRISMA Flow-Chart 2020, obtaining 20 articles that discussed early detection of diabetic neuropathy. Conclusion: This review reports on the importance of early detection of neuropathy for diagnosing neuropathy and determining appropriate management. Neuropathy patients who receive appropriate treatment can prevent the occurrence of diabetic ulcers. The most frequently used neuropathy instruments are the vibration perception threshold (VPT) and questionnaire Michigan Neuropathy Screening Instrument (MNSI). Health workers can combine neuropathy instruments to accurately diagnose neuropathy. [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]

Introduction: Diabetic foot ulcers (DFU) are a devastating complication of diabetes. There are numerous challenges with preventing diabetic foot complications and barriers to achieving the care processes suggested in established foot care guidelines. Multi-faceted digital health solutions, which combine multimodal sensing, patient-facing biofeedback, and remote patient monitoring (RPM), show promise in improving our ability to understand, prevent, and manage DFUs. Methods: Patients with a history of diabetic plantar foot ulcers were enrolled in a prospective cohort study and equipped with custom sensory insoles to track plantar pressure, plantar temperature, step count, and adherence data. Sensory insole data enabled patient-facing biofeedback to cue active plantar offloading in response to sustained high plantar pressures, and RPM assessments in response to data trends of concern in plantar pressure, plantar temperature, or sensory insole adherence. Three non-consecutive case participants that ultimately presented with pre-ulcerative lesions (a callus and/or erythematous area on the plantar surface of the foot) during the study were selected for this case series. Results: Across three illustrative patients, continuous plantar pressure monitoring demonstrated promise for empowering both the patient and provider with information for data-driven management of pressure offloading treatments. Conclusion: Multi-faceted digital health solutions can naturally enable and reinforce the integrative foot care guidelines. Multi-modal sensing across multiple physiologic domains supports the monitoring of foot health at various stages along the DFU pathogenesis pathway. Furthermore, digital health solutions equipped with remote patient monitoring unlock new opportunities for personalizing treatments, providing periodic self-care reinforcement, and encouraging patient engagement—key tools for improving patient adherence to their diabetic foot care plan. [ABSTRACT FROM AUTHOR]

Background: Little is known about the impact of the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) on cognition. Objective: Our objective was to determine the frequency and severity of cognitive impairment in RFC1‐positive patients and describe the pattern of deficits. Methods: Participants underwent a comprehensive neuropsychological assessment. Volume of the cerebellum and its lobules was measured in those who underwent a 3 Tesla‐magnetic resonance scan. Results: Twenty‐one patients underwent a complete assessment, including 71% scoring lower than the cutoff at the Montreal Cognitive assessment and 71% having a definite cerebellar cognitive affective/Schmahmann syndrome. Three patients had dementia and seven met the criteria of mild cognitive impairment. Severity of cognitive impairment did not correlate with severity of clinical manifestations. Performance at memory and visuospatial functions tests negatively correlated with the severity of cerebellar manifestations. Conclusion: Cognitive manifestations are frequent in RFC1‐related disorders. They should be included in the phenotype and screened systematically. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: To evaluate and review the current evidence regarding the association between ischemic optic neuropathy (ION) and internal carotid artery dissection (ICAD). Methods: We systematically reviewed studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA), searching three databases (Scopus, Pubmed, and Embase) for relevant articles that clearly described the correlation between ION and ICAD. All studies that examined the association between ICAD and the development of ION were synthesized. Quality assessment using the Newcastle–Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and Case Series were conducted. Results: Our search yielded 198 manuscripts published in the English language. Following study screening, fourteen studies were selected. The number of participants with ION following ICAD ranged from one to four, with sixteen patients experiencing either anterior ION, posterior ION, or a combination of both. The anterior or posterior ischemic optic neuropathy (AION and PION) patients' ages were 48.75 ± 11.75 and 49.62 ± 12.85, respectively. Fourteen out of sixteen patients experienced spontaneous ICAD, whereas the traumatic etiology was ascertained in two patients. Conclusions: Hence, albeit rare, ophthalmologists should consider ICAD a potential cause of ION, especially in young adults with concomitant cephalic pain and vision reduction. [ABSTRACT FROM AUTHOR]

Objective: Do the 3.5 million US veterans, who primarily utilize private healthcare, have similar bum pit exposure and disease compared to the VA Bum Pit registry? Methods: This is an online volunteer survey of Gulf War and Post-9/11 veterans. Results: Bum pit exposure had significantly higher odds of extremity numbness, aching pain and burning, asthma, chronic obstructive pulmonary disease, interstitial lung disease, constrictive bronchiolitis, pleuritis, and pulmonary fibrosis. Chi-square did not reveal a difference in bum pit exposure and cancer diagnoses. Conclusions: These data demonstrate increased risk of neurological symptoms associated with bum pit exposure, which are not covered in the 2022 federal Promise to Address Comprehensive Toxics Act. Additional data will allow for the continued review and consideration for future medical benefits. [ABSTRACT FROM AUTHOR]

Background: Pannexin1 (Panx1) is a membrane channel expressed in different cells of the nervous system and is involved in several pathological conditions, including pain and inflammation. At the central nervous system, the role of Panx1 is already well-established. However, in the periphery, there is a lack of information regarding the participation of Panx1 in neuronal sensitization. The dorsal root ganglion (DRG) is a critical structure for pain processing and modulation. For this reason, understanding the molecular mechanism in the DRG associated with neuronal hypersensitivity has become highly relevant to discovering new possibilities for pain treatment. Here, we aimed to investigate the role of Panx1 in acute nociception and peripheral inflammatory and neuropathic pain by using two different approaches. Methods: Rats were treated with a selective Panx1 blocker peptide (10Panx) into L5-DRG, followed by ipsilateral intraplantar injection of carrageenan, formalin, or capsaicin. DRG neuronal cells were pre-treated with 10Panx and stimulated by capsaicin to evaluate calcium influx. Panx1 knockout mice (Panx1-KO) received carrageenan or capsaicin into the paw and paclitaxel intraperitoneally. The von Frey test was performed to measure the mechanical threshold of rats' and mice's paws before and after each treatment. Results: Pharmacological blockade of Panx1 in the DRG of rats resulted in a dose-dependent decrease of mechanical allodynia triggered by carrageenan, and nociception decreased in the second phase of formalin. Nociceptive behavior response induced by capsaicin was significantly lower in rats treated with Panx1 blockade into DRG. Neuronal cells with Panx1 blockage showed lower intracellular calcium response than untreated cells after capsaicin administration. Accordingly, Panx1-KO mice showed a robust reduction in mechanical allodynia after carrageenan and a lower nociceptive response to capsaicin. A single dose of paclitaxel promoted acute mechanical pain in wildtype (WT) but not in Panx1-KO mice. Four doses of chemotherapy promoted chronic mechanical allodynia in both genotypes, although Panx1-KO mice had significant ablation in the first eight days. Conclusion: Our findings suggest that Panx1 is critical for developing peripheral inflammatory pain and acute nociception involving transient receptor potential vanilloid subtype 1 (TRPV1) but is not essential for neuropathic pain chronicity. [ABSTRACT FROM AUTHOR]

Aim: Neuropathic pain, a debilitating condition often resulting from chemotherapy treatments like oxaliplatin (OXA), poses significant treatment challenges. The molecular mechanisms underlying this condition remain incompletely understood, although microRNAs (miRNAs) have been implicated in its pathophysiology. This study focuses on miRNA-181a, known for its role in neuroinflammation and neuron signaling pathways, and investigates the therapeutic potential of asprosin, a novel hormone implicated in metabolic regulation, for modulating miRNA-181a expression in the context of OXA-induced neuropathy. Materials and Methods: Mouse dorsal root ganglia (DRGs) were exposed to OXA to induce neuropathy, followed by treatment with asprosin. miRNA-181a expression levels were quantified and compared across healthy (control), OXA-treated, and asprosin-treated groups using qRT-PCR. Statistical significance was determined through ANOVA, with pvalues less than 0.05 considered significant. Results: Asprosin treatment did not significantly affect miRNA-181a expression in healthy mouse DRGs. However, OXA treatment resulted in a significant increase in miRNA-181a expression compared to controls (p<0.0001). Notably, asprosin administration significantly reduced miRNA-181a overexpression in OXA-treated DRGs (p<0.0001), suggesting a therapeutic effect of asprosin in modulating miRNA-181a expression under neuropathic conditions. Conclusion: This study highlights the specific modulation of miRNA-181a by asprosin in OXA-induced neuropathic conditions, suggesting a novel therapeutic pathway for managing neuropathic pain. The findings underscore the potential of targeting miRNA pathways, particularly miRNA-181a, in developing treatments for chemotherapy-induced neuropathy. Further research is needed to elucidate the underlying mechanisms of asprosin's effect and its potential application in clinical settings. [ABSTRACT FROM AUTHOR]

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group–neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response. [ABSTRACT FROM AUTHOR]

Paraproteinemia‐associated neuropathy (PAN) develops with paraproteinemia and is mainly caused by the monoclonal proliferation of mature B cells, especially monoclonal gammopathy of undetermined significance (MGUS). PAN tends to increase with age, and in a super‐aging society, its frequency is expected to increase. Among paraproteinemias, the immunoglobulin (Ig)G type is most common, but the frequency of PAN is reported to be higher for the IgM type. IgG/IgA‐type PAN includes MGUS, plasma cell myeloma, and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome. IgM‐type PAN includes anti‐myelin‐associated glycoprotein antibody‐associated neuropathy, chronic ataxic neuropathy with IgM antibody that recognizes disialosyl ganglioside and IgM‐type PAN without anti‐nerve antibodies. Light chain‐type PAN includes immunoglobulin‐related amyloidosis. PAN has the characteristics of a blood disease, as well as an immune‐mediated disease, and is treated by immunotherapy. As an example, anti‐myelin‐associated glycoprotein antibody‐associated neuropathy is treated with rituximab, plasmapheresis and intravenous immunoglobulin therapy, but their effectiveness has not been established. As novel treatments, lenalidomide, Bruton tyrosine kinase inhibitors, B‐cell lymphoma 2 inhibitors and mimetic human natural killer‐1 epitope polymers have been investigated. By analyzing the human natural killer‐1‐related sugar chain structure as an antigen, the selective removal of pathological antibodies might be a new therapeutic target. [ABSTRACT FROM AUTHOR]

Vasculitic neuropathy has a broad range of etiologies, and roughly comprises nonsystemic vasculitic neuropathy and neuropathies accompanied by antineutrophil cytoplasmic antibody‐associated vasculitis (AAV). Recent morphological analyses of sural nerve specimens from patients with vasculitic neuropathy showed some distinct pathogeneses within vasculitic neuropathy. Several randomized, controlled studies and updated practice guidelines cover immunotherapies for AAV, whereas there is a paucity of evidence for vasculitic neuropathy, including neuropathies associated with AAV. Corticosteroids have been the mainstay of immunotherapy for vasculitic neuropathy, and cyclophosphamide is indispensable for refractory cases. Recent AAV guidelines are shifting their recommendations toward minimizing the harm caused by corticosteroids and cyclophosphamide with a reduced‐dose corticosteroid regimen and the recent advent of various optional drugs, especially molecular‐targeted agents. Clinicians expect the efficacy of reduced‐dose corticosteroid regimens and molecular‐targeted agents in treating vasculitic neuropathy to be verified, and clarification of the mechanism of vasculitic neuropathy might lead to the development of the best treatment based on the background pathogenesis of individual cases. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim of this study was to determine the prevalence of anti‐myelin‐associated glycoprotein (MAG) neuropathy and the current status of such patients in Japan. Methods: We conducted a nationwide survey in 2021 using established epidemiological methods. Questionnaires were sent to all neurology and pediatric neurology departments throughout Japan to identify patients with anti‐MAG neuropathy. An initial questionnaire was used to determine the number of patients, with a second one used to collect detailed clinical information. Results: The estimated number of patients with anti‐MAG neuropathy was 353, with a prevalence of 0.28 per 100,000 and an incidence of 0.05 per 100,000. The detailed clinical profiles of 133 patients were available. The median (range) age of onset was 67 (30–87) years, with a prominent peak in the age range 66–70 years, and the male‐to‐female ratio was 3.6. Most patients had distal sensory‐predominant polyneuropathy, and neuropathic pain (50%), or sensory ataxia (42%), while 18% had Waldenström's macroglobulinemia or multiple myeloma. Intravenous immunoglobulin was the most frequently used treatment (65%), but the response rate was <50%, whereas rituximab was given in 32% of patients, and 64% of these showed improvement. At the last visit, 27% of patients could not walk independently. Conclusions: This study on anti‐MAG neuropathy provides updated insights into the epidemiology of this disease, clinical profiles, and treatment approaches in Japan. Rituximab therapy, used for only one‐third of the patients, demonstrated efficacy. During the final visit, a quarter of the patients were unable to walk independently. Further studies are warranted to determine the optimal management of this rare and intractable disorder. [ABSTRACT FROM AUTHOR]

RFC1 disease, caused by biallelic repeat expansion in RFC1 , is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson's coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-Poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multivariate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset [smaller allele hazard ratio (HR) = 2.06, P < 0.001; larger allele HR = 1.53, P < 0.001] and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR = 3.40, P < 0.001; larger allele HR = 1.71, P = 0.002) or loss of independent walking (smaller allele HR = 2.78, P < 0.001; larger allele HR = 1.60; P < 0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions [smaller allele: complex neuropathy rate ratio (RR) = 1.30, P = 0.003; cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) RR = 1.34, P < 0.001; larger allele: complex neuropathy RR = 1.33, P = 0.008; CANVAS RR = 1.31, P = 0.009]. Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I–V β = −1.06, P < 0.001; lobules VI–VII β = −0.34, P = 0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion. [ABSTRACT FROM AUTHOR]

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = −0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker. [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]

Neuropathy affects 7–10% of the general population and is caused by a lesion or disease of the somatosensory system. The limitations of current therapies highlight the necessity of a new innovative approach to treating neuropathic pain (NP) based on the close correlation between oxidative stress, inflammatory process, and antioxidant action. The advantageous outcomes of a novel combination composed of Hop extract, Propolis, Ginkgo Biloba, Vitamin B, and palmitoylethanolamide (PEA) used as a treatment was evaluated in this study. To assess the absorption and biodistribution of the combination, its bioavailability was first examined in a 3D intestinal barrier model that replicated intestinal absorption. Further, a 3D nerve tissue model was developed to study the biological impacts of the combination during the essential pathways involved in NP. Our findings show that the combination could cross the intestinal barrier and reach the peripheral nervous system, where it modulates the oxidative stress, inflammation levels, and myelination mechanism (increased NRG, MPZ, ERB, and p75 levels) under Schwann cells damaging. This study proves the effectiveness of Ginkgo Biloba, Propolis, Hop extract, Vitamin B, and PEA in avoiding nerve damage and suggests a potential alternative nutraceutical treatment for NP and neuropathies. [ABSTRACT FROM AUTHOR]

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]

Inherited optic neuropathies (IONs) are rare genetic diseases characterized by progressive visual loss due the atrophy of optic nerves. The standard diagnostic workup involving next-generation sequencing panels has a diagnostic yield of about forty percent. In the other 60% of the patients with a clinical diagnosis of ION, the underlying genetic variants remain unknown. In this case study, we describe a potentially new disease-associated gene, NSUN3, for IONs. The proband was a young woman with consanguineous parents. She presented with bilateral optic atrophy and nystagmus at the age of seven years. Genetic testing revealed the homozygous variant c.349_352dup p.(Ala118Glufs*45) in NSUN3, with a segregation in the family compatible with autosomal recessive inheritance. Additional functional analysis showed decreased NSUN3 mRNA levels, slightly diminished mitochondrial complex IV levels, and decreased cell respiration rates in patient fibroblasts compared to healthy controls. In conclusion, pathogenic variants in NSUN3 can cause optic neuropathy. Trio whole-exome sequencing should be considered as a diagnostic strategy in ION cases where standard diagnostic analysis does not reveal disease-causing variants. [ABSTRACT FROM AUTHOR]

Background Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. Combination medicines and pure methylcobalamin seems to improve symptoms rather than electrophysiologic outcomes in individuals with diabetic peripheral neuropathy. The aim of present study was to assess the effect of Vitamin B supplementation for diabetic peripheral neuropathy. Methods The present cross-sectional study was conducted at department of general medicine among 100 patients with diabetic peripheral neuropathy who visited during the study period of one year. Patients were divided into two groups (group B and group P). The entire neuropathy and laboratory test were done. With IBM SPSS v25.0, statistical analyses were carried out. Results There were no significant differences between the group B and group P regarding demographics, anthropometric and laboratory measurements. Vitamin B12 levels significantly increased in the group B from 237.8±70.3 pmol/L at baseline to 775.8±234.2 pmol/L at follow-up. In the group B, there was a significant improvement in the vibration perception threshold (VPT), MNSIQ, pain score, quality of life (QoL), sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and electrochemical skin conductance in feet (ESCF) during the follow-up (p =0.001, p = 0.003, p = 0.0001, p = 0.0001, and p = 0.013, respectively). Conclusion Patients with DN who received an oral methylcobalamin treatment for a whole year had improvements in their QoL, pain score, sudomotor function, plasma B12 levels, and all neurorophysiological markers; however, CARTS and MNSIE did not show any improvement. [ABSTRACT FROM AUTHOR]

Aim: Acute lymphoblastic leukaemia (ALL) therapy has been associated with a significant burden of toxicities. The aim of this study was to describe the full spectrum of toxic effects associated with childhood ALL. Methods: Toxicity‐related data were collected from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL‐2008 toxicity registry, in which data on 19 clinically relevant toxicities were registered during ALL treatment, and from patient medical records. All patients treated according to the NOPHO ALL‐2008 protocol in Oulu University Hospital between 2008 and 2020 were included in the study. Results: The cohort consisted of 73 patients, 38 of whom were male. Mean age at diagnosis was 6.6 ± 4.2 (range 1.4–16.0) years. All but one of the patients developed at least one treatment‐related toxicity and more than half had multiple toxicities. Female sex and older age were associated with a higher tendency towards toxicity. The most common toxicity was vincristine‐induced peripheral neuropathy, which was observed in 70 patients. Most toxicities were moderate or severe, but even mild toxicities often affected leukaemia treatment. Conclusion: Moderate and severe treatment‐related toxicities are common, and most toxicities occur in a typical pattern in relation to the treatment phases. [ABSTRACT FROM AUTHOR]

Diagnosis of dysthyroid optic neuropathy (DON) typically relies on a set of diagnostic clinical features, including decreased visual acuity, impaired color vision, presence of relative afferent pupillary defect, optic disc swelling and ancillary tests including visual field (VF), pattern visual evoked potential (pVEP), and apical crowding or optic nerve stretching on neuroimaging. We summarize various diagnostic methods to establish or rule out DON. A total of 95 studies (involving 4619 DON eyes) met the inclusion criteria. All of the studies considered clinical features as evidence of DON, while most of the studies confirmed DON diagnosis by combining clinical features with ancillary tests. Forty studies (42.1%) used at least 2 out of the 3 tests (VF, pVEP and neuroimaging) and 13 studies (13.7%) used all 3 tests to diagnose DON. In 64 % of the published studies regarding DON, the diagnostic methods of DON were not specified. It is important to note the limitations of relying solely on clinical features for diagnosing DON. On the other hand, since some eyes with optic neuropathy can be normal in one ancillary test, but abnormal in another, using more than one ancillary test to aid diagnosis is crucial and should be interpreted in correlation with clinical features. We found that the diagnostic methods of DON in most studies involved using a combination of specific clinical features and at least 2 ancillary tests. [ABSTRACT FROM AUTHOR]

Background: Exertional compartment syndrome (ECS) is an underdiagnosed cause of lower extremity pain among athletes. The condition can be managed operatively by fasciotomy to relieve excess compartment pressure. However, symptom recurrence rates after fasciotomy are considerable, ranging from 3% to 17%. Hypothesis: Leg paresthesia and its distribution during ECS episodes would be a significant predictor of outcomes after fasciotomy. Study Design: Retrospective cohort study. Level of Evidence: Level 4. Methods: We conducted a retrospective chart review of patients who underwent fasciotomy for ECS at our center from 2010 to 2020 (institutional review board no. 21-00107). We measured postoperative outcomes including pain frequency and severity, Tegner activity level, and return to sport. Significant predictors of outcomes were identified using multivariable linear and logistic regression. P values <0.05 were considered significant. Results: A total of 78 legs (from 42 male and 36 female participants) were included in the study with average follow-up of 52 months (range, 3-126 months); 33 participants (42.3%) presented with paresthesia. Paresthesia was an independent predictor of worse outcomes, including more severe pain at rest (P = 0.05) and with daily activity (P = 0.04), reduced postoperative improvement in Tegner scores (P = 0.04), and lower odds of return to sport (P = 0.05). Those with paresthesia symptoms in the tibial nerve distribution had worse outcomes than those without paresthesia in terms of preoperative-to-present improvement in pain frequency (P < 0.01), pain severity at rest (P < 0.01) and with daily activity (P = 0.04), and return to sport (P = 0.04). Conclusion: ECS patients who present with paresthesia have worse pain and activity outcomes after first-time fasciotomy, but prognosis is worst among those with tibial nerve paresthesia. Clinical Relevance: Paresthesia among ECS patients is broadly predictive of more severe recurrent leg pain, reduced activity level, and decreased odds of return to sport after fasciotomy. [ABSTRACT FROM AUTHOR]

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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]

Background/Aim: Oxaliplatin, a platinum-based chemotherapy used in the treatment of colorectal cancer, induces acute neurotoxicity following infusion. The aim of this study was to establish whether alterations in axonal excitability develop progressively with higher cumulative doses and whether there is a recovery in motor axons after each cycle of treatment. Patients and Methods: Twenty consecutive patients with a colorectal cancer diagnosis, referred from the Oncology Department of Aretaieion Hospital of Athens, were enrolled in this study between October 2018 and May 2019. None of the participants had diabetes, alcohol abuse, known neuropathy or were previously treated with another neo-adjuvant therapy. Threshold Tracking techniques and Qtrac software were used for assessing axonal excitability in motor axons. Excitability recordings were undertaken before and immediately after the end of oxaliplatin infusion. Results: Statistically significant changes were found (p<0.01) in axonal excitability (relative refractory period, refractoriness at 2 ms and 2.5 ms, subexcitability and super-excitability) before and after oxaliplatin infusion. No statistically significant changes (p>0.05) were found in threshold electrotonus and strengthduration parameters before and after oxaliplatin infusion. We also did not find statistically significant differences (p>0.05) between means of excitability parameters before infusion at each cycle. Conclusion: Our study confirms oxaliplatin-induced acute neurotoxicity following infusion and suggests that motor axons recover between repeat infusion cycles. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk. [ABSTRACT FROM AUTHOR]

We are engaged in the development and clinical application of a neural magnetic field measurement system that utilizes biomagnetic measurements to observe the activity of the spinal cord and peripheral nerves. Unlike conventional surface potential measurements, biomagnetic measurements are not affected by the conductivity distribution within the body, making them less influenced by the anatomical structure of body tissues. Consequently, functional testing using biomagnetic measurements can achieve higher spatial resolution compared to surface potential measurements. The neural magnetic field measurement, referred to as magnetoneurography, takes advantage of these benefits to enable functional testing of the spinal cord and peripheral nerves, while maintaining high spatial resolution and noninvasiveness. Our magnetoneurograph system is based on superconducting quantum interference devices (SQUIDs) similar to the conventional biomagnetic measurement systems. Various design considerations have been incorporated into the SQUID sensor array structure and signal processing software to make it suitable for detecting neural signal propagation along spinal cord and peripheral nerve. The technical validation of this system began in 1999 with a 3-channel SQUID system. Over the course of more than 20 years, we have continued technological development through medical-engineering collaboration, and in the latest prototype released in 2020, neural function imaging of the spinal cord and peripheral nerves, which could also be applied for the diagnosis of neurological disorders, has become possible. This paper provides an overview of the technical aspects of the magnetoneurograph system, covering the measurement hardware and software perspectives for providing diagnostic information, and its applications. Additionally, we discuss the integration with a helium recondensing system, which is a key factor in reducing running costs and achieving practicality in hospitals. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi. Guillain–Barre syndrome (GBS) is an autoimmune-mediated peripheral neuropathy with a frequent history of prodromal infections, but GBS associated with scrub typhus is very rare. Case presentation: We report a 51-year-old male patient who developed dysarthria and peripheral facial paralysis following the cure of scfrub typhus. CSF examination and electrophysiological findings suggested a diagnosis of GBS. After treatment with intravenous immunoglobulin, the patient's neurological condition improved rapidly. Conclusions: Scrub typhus infection is likely to be a potential predisposing factor in GBS, while scrub typhus-associated GBS has a favorable prognosis. [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]

Background and aims: The evolution of demyelination in individual internodes remains unclear although it has been noticed the paranodal demyelination precedes internodal demyelination in neuropathies with diverse aetiologies. For therapeutic purpose, it is fundamental to know whether the demyelinating procedure in affected internodes can be interrupted. This study aimed to delineate the development of demyelination in individual internodes in avian riboflavin deficient neuropathy. Methods: Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin, a riboflavin deficient diet containing 1.8 mg/kg riboflavin, or initially a riboflavin deficient diet for 11 days and then routine diet plus riboflavin repletion from day 12. Evolution of demyelination in individual internodes was analyzed by teased nerve fibre studies from day 11 to 21. Results: In riboflavin deficient chickens, demyelination was the predominant feature: it was mainly confined to the paranodal region at day 11; extended into internodal region, but less than half of the internodal length in most affected internodes at day 16; involved more than half or whole internode at day 21. In the internode undergoing demyelination, myelin degeneration of varying degrees was noticed in the cytoplasm of the Schwann cell wrapping the internode. Two days after riboflavin repletion, co-existence of remyelination and active demyelination within individual internodes was noticed. Remyelination together with preserved short original internodes was the characteristic feature 4 and 9 days after riboflavin repletion. Conclusion: Riboflavin repletion interrupts the progression from paranodal to internodal demyelination in riboflavin deficient chickens and promotes remyelination before complete internodal demyelination. [ABSTRACT FROM AUTHOR]

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy. [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]

Introduction: Small fiber neuropathy (SFN) is a common cause of neuropathic pain in peripheral neuropathies. Good accessibility of diagnostics and treatment is necessary for an accurate diagnosis and treatment of SFN. Evidence is lacking on the quality performance of the diagnostic SFN service in the Netherlands. Our aim was to determine the patient satisfaction and -accessibility of the diagnostic SFN service, and to identify areas for improvement. Methods: In a single-center, prospective, survey-based cohort study, 100 visiting patients were asked to fill in the SFN patient satisfaction questionnaire (SFN-PSQ), with 10 domains and 51 items. Cut-off point for improvement was defined as ≥ 25% dissatisfaction on an item. A chi-square test and linear regression analyses was used for significant differences and associations of patient satisfaction. Results: From November 2020 to May 2021, 98 patients with SFN-related complaints filled in the online SFN-PSQ within 20 minutes. In 84% of the patients SFN was confirmed, average age was 55.1 (52.5–57.8) years and 67% was female. High satisfaction was seen in the domains 'Waiting List Period', Chest X-ray', 'Consultation with the Doctor or Nurse Practitioner (NP)', 'Separate Consultation with the Doctor or NP about Psychological Symptoms', and 'General' of the SFN service. Overall average patient satisfaction score was 8.7 (IQR 8–10) on a 1-to-10 rating scale. Main area for improvement was shortening the 8-week period for receiving the results of the diagnostic testing (p < 0.05). General health status was statistically significant associated with patient satisfaction (p < 0.05) Conclusion: A good reflection of the high patient satisfaction and -accessibility of the SFN-service is shown, with important points for improvement. These results could help hospitals widely to optimize the logistic and diagnostic pathway of SFN analysis, benchmarking patient satisfaction results among the hospitals, and to improve the quality of care of comparable SFN services. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether prolonged periods of training can be well tolerated. In Charcot-Marie Tooth disease (CMT). We report the effects of an 8-month, adapted motor activity (AMA) program in a 16-years-old CMT1A male patient. The program included strength, mobility, and balance training (two sessions per week, 1 h per session). Measures: Walking ability and walking velocity (Six-Minute Walking Test--6MWT, Ten Meters Walking Test--10mWT), balance (Y-Balance Test--YBT, Berg Balance Scale--BBS), functional mobility (Short Physical Performance Battery--Short physical performance battery), fatigue (Checklist Individual strength questionnaire - CIS20R), health and quality of life (Short Form Health Survey 36 questionnaire--SF-36) were evaluated in three moments: before (T0), after 5 (T1) and 8 (T2) months of adapted motor activity. Dorsal and plantar foot flexion strength (Maximal Voluntary Contraction--maximum voluntary contraction) and neuromuscular functions (Electromyography--sEMG, interpolated twitch technique--ITT) were measured at T1 and T2. Results: Relative to T0, an amelioration of walking ability (6MWT, +9,3%) and balance (with improvements on Y-balance composite normalized mean reach of the right and left limb of 15,3% and 8,5%, respectively) was appreciable. Relative to T1, an increase in foot strength in three out of four movements (right plantar flexion, +39,3%, left plantar flexion, +22,7%, left dorsal flexion, 11,5%) was observed. Concerning voluntary muscle activation, a greater recruitment in the left, unlike right, medial gastrocnemius was observed. Conclusion: Results suggest the safety of an 8-month AMA program in a young patient affected by CMT1A. [ABSTRACT FROM AUTHOR]

[Display omitted] • BDNF from microglia drives neuropathic pain. • Peripheral BDNF drives chronic inflammatory pain. • BDNF does not drive pain in females. In males but not in females, brain derived neurotrophic factor (BDNF) plays an obligatory role in the onset and maintenance of neuropathic pain. Afferent terminals of injured peripheral nerves release colony stimulating factor (CSF-1) and other mediators into the dorsal horn. These transform the phenotype of dorsal horn microglia such that they express P2X4 purinoceptors. Activation of these receptors by neuron-derived ATP promotes BDNF release. This microglial-derived BDNF increases synaptic activation of excitatory dorsal horn neurons and decreases that of inhibitory neurons. It also alters the neuronal chloride gradient such the normal inhibitory effect of GABA is converted to excitation. By as yet undefined processes, this attenuated inhibition increases NMDA receptor function. BDNF also promotes the release of pro-inflammatory cytokines from astrocytes. All of these actions culminate in the increase dorsal horn excitability that underlies many forms of neuropathic pain. Peripheral nerve injury also alters excitability of structures in the thalamus, cortex and mesolimbic system that are responsible for pain perception and for the generation of co-morbidities such as anxiety and depression. The weight of evidence from male rodents suggests that this preferential modulation of excitably of supra-spinal pain processing structures also involves the action of microglial-derived BDNF. Possible mechanisms promoting the preferential release of BDNF in pain signaling structures are discussed. In females, invading T-lymphocytes increase dorsal horn excitability but it remains to be determined whether similar processes operate in supra-spinal structures. Despite its ubiquitous role in pain aetiology neither BDNF nor TrkB receptors represent potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations. Results: We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change. Conclusions: With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance. [ABSTRACT FROM AUTHOR]

Background: Unanticipated symptoms of peripheral nerve damage following surgery are distressing to both the patient and their clinical team, including surgeons, anesthesiologists, and neurologists. The causes that are commonly considered for perioperative neuropathy can include surgical trauma, positioning-related injury, or injury related to a regional anesthetic technique. However, these cases often do not have a clear etiology and can occur without any apparent periprocedural anomalies. Postoperative inflammatory neuropathy is a more recently described, and potentially underrecognized cause of perioperative neuropathy which may improve with corticosteroid therapy. Therefore, it is an important etiology to consider early in the evaluation of perioperative neuropathy. Case presentation: An otherwise healthy patient presented for left anterior cruciate ligament reconstruction. He underwent femoral and sciatic ultrasound-guided single-injection peripheral nerve blocks preoperatively, followed by a general anesthetic for the surgical procedure. He developed postoperative neuropathy in the sciatic distribution with both sensory and motor deficits. The patient received multi-disciplinary consultations, including neurology and pain management, and a broad differential diagnosis was considered. Based on neurological evaluation and imaging studies, a final diagnosis of post-surgical inflammatory neuropathy was made. The patient's course improved with conservative management, but immunosuppressive treatment may have been considered for a more severe or worsening clinical course. Conclusions: There are limited publications describing postoperative inflammatory neuropathy, and this case serves to illustrate a potentially under-recognized and multifactorial cause of postoperative neuropathy. Perioperative neuropathies are a complication that surgeons and anesthesiologists strive to avoid; however, prevention and treatment of this condition have been elusive. Increased reporting and investigation of postoperative inflammatory neuropathy as one cause for this complication will help to further our understanding of this potentially devastating complication. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incidence of neuropathic pain after endodontic treatment with follow-up at 6 months. Materials and Methods: This was a prospective observational clinical study that was carried out on patients who underwent endodontic treatment or retreatment carried out in the Master of Endodontics at the International University of Catalonia (UIC) from January 2022 to December 2022. After the treatment, a six-month follow-up was carried out, determining the presence of persistent pain, and whether the cause was of non-odontogenic origin, through anamnesis and physical examination carried out in the Department of Craniomandibular Dysfunction and Orofacial Pain of the Faculty of Dentistry. Results: A total of 231 treatments were obtained, obtaining a 53% response via telephone call. A descriptive analysis of the results was done, there were 88 patients who did not present pain after 6 months of endodontic treatment (72%); while 35 patients reported pain (28%). 9% of the cases with pain were caused by endodontic failure, in 74% the cause was due to involvement of another tooth and 11% due to periodontal reasons. It was estimated that 1.5% of treated patients had failed endodontic treatments at 6 months of follow-up. The causes of persistent pain were periodontal problems, such as food packaging, dentin hypersensitivity or pulpal origin associated with another tooth. Conclusions: After 6 months of follow-up, no patient presented neuropathic origin pain. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 has caused many deaths on the planet. To date we do not know its long-term impact. Conversion of hospital centers and home reclusion impacted those with a disease. Currently, the presence of pain has been identified as a chronic complication of COVID-19. Objective: to document the impact of COVID-19 on patients with pain and its chronicity. Material and methods: literature search in the PubMed database for documents that contained the words «COVID», «SARS-CoV», «Pain» in the title. No metaanalyses were identified. We found systematized and documentary reviews on which we based our information. Conclusions: COVID-19 presents chronic pain as a long-term manifestation. It is advisable to generate lines of research aimed at documenting this phenomenon. [ABSTRACT FROM AUTHOR]

Background: In vascular medicine, peripheral arterial disease (PAD) and diabetic foot syndrome (DFS) are often considered synonymous with respect to the need for revascularization. In PAD patients, clinical symptoms reflect the degree of atherosclerotic disease, since peripheral innervation, including pain sensation, is not usually compromised. In DFS patients, however, symptoms of relevant foot ischemia are often absent and progression of ischemia goes unnoticed owing to diabetic polyneuropathy, the loss of nociception being the main trigger for foot ulcers. This review analyzes the fundamental differences between PAD and DFS against the background of polyneuropathy. Methods: The literature research for the 2014 revision of the German evidence-based S3-PAD-guidelines was extended to 2023. Results: Vascular examination is imperative for both, PAD and DFS. Stage-dependent revascularization is of utmost importance in PAD patients, especially those suffering from critical limb-threatening ischemia (CLTI). Successful therapy of DFS goes further, including infection and metabolic control, wound management, offloading the foot and lifelong prophylaxis in the course of a multidisciplinary treatment concept. Revascularization is not needed in all cases of DFS. Conclusions: There are fundamental differences between PAD and DFS with respect to pathophysiology, the anatomical distribution of arterial occlusive processes, the clinical symptoms, the value of diagnostic tools such as the ankle-brachial index, and classification. Also, therapeutic concepts differ substantially between the two patient populations. [ABSTRACT FROM AUTHOR]

Light chain amyloidosis is a plasma–cell disorder with a poor prognosis. It is a progressive condition, causing worsening pain, disability, and life-limiting complications involving multiple organ systems. The medical regimen can be complex, including chemotherapy or immunotherapy for the disease itself, as well as treatment for pain, gastrointestinal and cardiorespiratory symptoms, and various secondary symptoms. Patients and their families must have a realistic awareness of the illness and of the goals and limitations of treatments in making informed decisions about medical therapy, supportive management, and end-of-life planning. Palliative care services can thus improve patients' quality of life and may even reduce overall treatment costs. Light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by the excessive secretion of light chains by an indolent plasma cell clone that gradually accumulates in vital organs as amyloid fibrils and leads to end-organ damage. With progressive disease, most patients develop diverse clinical symptoms and complications that negatively impact quality of life and increase mortality. Complications include cardiac problems including heart failure, hypotension, pleural effusions, renal involvement including nephrotic syndrome with peripheral edema, gastrointestinal symptoms leading to anorexia and cachexia, complex pain syndromes, and mood disorders. The prognosis of patients with advanced AL amyloidosis is dismal. With such a complex presentation, and high morbidity and mortality rates, there is a critical need for the establishment of a palliative care program in clinical management. This paper provides an evidence-based overview of the integration of palliative care in the clinical management of AL amyloidosis as a means of reducing ER visits, rehospitalizations, and in-hospital mortality. We also discuss potential future collaborative directions in various aspects of clinical care related to AL amyloidosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE This study was conducted to evaluate the supportive care needs and coping attitudes of breast cancer patients according to their neuropathic pain status. METHODS This case-control study design was conducted with 212 patients who were being treated in the daily chemotherapy unit of a hospital in İstanbul, who agreed to participate in the study and met the inclusion criteria. The S-LANSS pain scale was used to determine the neuropathic pain status of the patients. A Descriptive Information Form, Supportive Care Needs Scale, and Coping Attitudes Scale were used to collect the data. RESULTS The study sample consisted of case group patients with neuropathic pain (n=100) and control group patients without neuropathic pain (n=112). The mean age of the participants was 50 (45-54) in the case group and 49 (45-57) in the control group. In the case group, 24.5% used paclitaxel chemotherapy, and 40.6% had no knowledge about neuropathic pain. In the control group, 21.7% used paclitaxel chemotherapy, and 46.2% had no knowledge about neuropathic pain. There was no statistically significant difference between the groups in terms of total scores and sub-dimensions of the Supportive Care Needs Scale and total scores and sub-dimensions of the Coping Orientations to Problems Experienced scale. CONCLUSION Coping attitudes and supportive care needs of patients do not change according to the presence of neuropathic pain. Nearly half of the patients receiving neurotoxic chemotherapy, which frequently causes neuropathic pain, have no knowledge about neuropathic pain. [ABSTRACT FROM AUTHOR]

Nerves in patients with diabetic neuropathy (DN) show increased susceptibility to local anesthetics, potentially requiring a decreased dose. We investigated whether the minimum effective anesthetic concentration (MEAC) of mepivacaine for successful axillary block is lower in patients with DN than in those without. This prospective observational study included patients with DN (n = 22) and without diabetes (n = 22) at a tertiary care center. Patients received an ultrasound-guided axillary block with 30 mL of mepivacaine for anesthesia. The mepivacaine concentration used in each patient was calculated using Dixon's up-and-down method. A block was considered successful if all four sensory nerves had a score of 1 or 2 within 30 min with no pain during surgery. The primary outcome was the MEAC of mepivacaine, and the secondary outcomes included the minimal nerve stimulation intensity for the musculocutaneous nerve and the occurrence of adverse events. The MEAC50 was 0.55% (95% CI 0.33–0.77%) in patients without diabetes and 0.58% (95% CI 0.39–0.77%) in patients with DN (p = 0.837). The MEAC90 was 0.98% (95% CI 0.54–1.42%) in patients without diabetes and 0.96% (95% CI 0.57–1.35%) in patients with DN (p = 0.949). The stimulation threshold for the musculocutaneous nerve was significantly different between groups (0.49 mA vs. 0.19 mA for patients with vs. without diabetes; p = 0.002). In conclusion, the MEAC of mepivacaine for a successful axillary block is not lower in patients with DN. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties. Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment). Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced. Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception. [ABSTRACT FROM AUTHOR]

To evaluate the utility of peripapillary retinal nerve fiber layer thickness (pRNFLT) for the prediction of visual outcomes, including visual acuity (VA) and visual field (VF), in subjects with acute nonarteritic anterior ischemic optic neuropathy (NAION). Materials and Methods: We performed a retrospective study of data relating to 60 eyes of 60 subjects with acute NAION. Of these, reliable VF values were obtained at both the initial and at 6-month follow-up visits for 30 eyes, which were included in the VF analysis. The pRNFLT was measured globally and separately in all four quadrants (superior, inferior, nasal, and temporal) using optical coherence tomography at the initial visit. Multivariate analysis and the area under the curve (AUC) were used to evaluate the utility of pRNFLT for the prediction of visual outcomes, including favorable VA (VA better than or equal to 20/25) and favorable VF (visual field index (VFI) ≥ 90%), at the 6-month follow-up visit. Results: The median VA and mean VFI at the initial visit were 0.40 (interquartile range (IQR): 0.40, 0.54; logarithm of the minimum angle of resolution (logMAR)) and 73.07% ± 6.73%, respectively. The median VA and mean VFI at the 6-month follow-up visit were 0.30 (IQR: 0.00, 0.70) logMAR and 69.27% ± 28.94%, respectively. Thinner temporal-quadrant pRNFLT was associated with favorable VA (odds ratio 0.98; p = 0.042) with a cut-off value of 128 μm (AUC 0.839, 95% CI: 0.732– 0.947, sensitivity 77.27%, specificity 84.21%). Thinner nasal-quadrant pRNFLT was associated with favorable VF (odds ratio 0.97; p = 0.047) with a cut-off value of 105 μm (AUC 0.780, 95% CI: 0.612– 0.948, sensitivity 90.00%, specificity 70.00%). Conclusions: The pRNFLT is clinically useful for the prediction of visual outcomes in patients with acute NAION. A temporal-quadrant pRNFLT ≤ 128 μm and a nasal-quadrant pRNFLT ≤ 105 μm predict favorable VA and VF at the 6-month follow-up visit, respectively. [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]

OBJECTIVE: The aim of this study was to investigate whether plasma neurofilament light chain (pNfL) concentration was altered in Labrador Retrievers with idiopathic laryngeal paralysis (ILP) compared to a control population. A secondary aim was to investigate relationships between age, height, weight, and body mass index in the populations studied. ANIMALS: 123 dogs: 62 purebred Labrador Retrievers with ILP (ILP Cases) and 61 age-matched healthy medium- to largebreed dogs (Controls). METHODS Dogs, recruited from August 1, 2016, to March 1, 2022, were categorized as case or control based on a combination of physical exam, neurologic exam, and history. Blood plasma was collected, and pNfL concentration was measured. pNfL concentrations were compared between ILP Cases and Controls. Covariables including age, height, and weight were collected. Relationships between pNfL and covariables were analyzed within and between groups. In dogs where 2 plasma samples were available from differing time points, pNfL concentrations were measured to evaluate alterations over time. RESULTS: No significant difference in pNfL concentration was found between ILP Cases and Control (P = .36). pNfL concentrations had moderate negative correlations with weight and height in the Control group; other variables did not correlate with pNfL concentrations in ILP Case or Control groups. pNfL concentrations do not correlate with ILP disease status or duration in Labrador Retrievers. CLINICAL RELEVANCE: There is no evidence that pNfL levels are altered due to ILP disease duration or progression when compared with healthy controls. When evaluating pNfL concentrations in the dog, weight and height should be considered. [ABSTRACT FROM AUTHOR]

The mutations of the feline leukemia virus subgroup C receptor‐related protein 1 (FLVCR1) cause ataxia with retinitis pigmentosa. Recent studies indicated a large variation in the phenotype of FLVCR1‐associated diseases. In this report, we describe an adult male who manifested first with tremors in his third decade, followed by retinitis pigmentosa, sensory ataxia, and sensory neuropathy in his fourth decade. While retinitis pigmentosa and sensory ataxia are well‐recognized features of FLVCR1‐associated disease, tremor is rarely described. Whole‐exome sequencing revealed novel compound heterozygous pathogenic FLVCR1 variants: c.498 G > A; p.(Trp166*) and c.369 T > G; p.(Phe123Leu). In addition, we have highlighted the ultrastructural abnormalities of the sural biopsy in this patient. [ABSTRACT FROM AUTHOR]