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The treatment of early triple-negative breast cancer (eTNBC) has improved patients' prognosis but often leads to adverse events and sequelae affecting quality of life (QoL). Pain Neuroscience Education (PNE) is a promising non-pharmacological intervention in this field. Preliminary data have shown the beneficial effect of PNE in BC survivors. However, there are still gaps in knowledge regarding its optimal use in eTNBC. To address this issue, a prospective pilot study will enroll 30 consecutive patients diagnosed with eTNBC at IRCCS Humanitas Research Hospital. The PNE program will consist of 10 weekly sessions to be started within 4 weeks of the onset or worsening of a pain syndrome (PS). QoL, pain, and disability will be assessed before, during, at the end of, and 6 months after PNE using validated questionnaires. Peripheral venous blood samples will be taken before and at the end of PNE to evaluate inflammatory serum biomarker levels. The primary objective is to evaluate whether PNE leads to clinical improvement in QoL and pain. If successful, it will be validated in a larger multi-centric cohort, potentially leading to its widespread implementation as a standard pain management tool for eTNBC patients. [ABSTRACT FROM AUTHOR]

Background: Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE. Methods: In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO. Key Results: Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006). Conclusions & Inferences: Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO. [ABSTRACT FROM AUTHOR]

Background: The factors underlying the topography of nitrous oxide (N2O)‐induced neurological complications are unknown. Methods: We included all consecutive patients admitted to the university hospital of Marseille for N2O‐induced neurological complications in a prospective observational study. Patients underwent neurological examination, spinal cord magnetic resonance imaging, and nerve conduction studies within the first 4 weeks after admission. Results: In total, 61 patients were included: 45% with myeloneuropathy, 34% with isolated myelopathy, and 21% with isolated neuropathy. On multivariable analysis, the odds of myelopathy were associated with the amount of weekly N2O consumption (~600 g cylinder per week, odds ratio [OR] = 1.11, 95% confidence interval [CI] = 1.001–1.24). The extent of the myelopathy (number of vertebral segments) was correlated with the number of ~600‐g cylinders consumed weekly (ρ = 0.40, p < 0.005). The odds of neuropathy were associated with the duration of consumption (per month; OR = 1.29, 95% CI = 1.05–1.58). Mean lower‐limb motor nerve amplitude was correlated with the duration of consumption (in months; ρ = −0.34, p < 0.05). Conclusions: The odds of myelopathy increased with the amount of N2O consumption, and the odds of neuropathy increased with the duration of N2O exposure, which suggests distinct pathophysiological mechanisms underlying these two neurological complications. [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]

We describe the baseline ophthalmic and cardiovascular risk factors across countries, race, and sex for the Quark207 treatment trial for acute nonarteritic anterior ischemic optic neuropathy (NAION). Prospective, randomized controlled clinical trial. Adults 50 to 80 years of age with acute NAION recruited from 80 sites across 8 countries. Ophthalmic features of NAION and cardiovascular risk factors. We evaluated demographics and clinical and ophthalmologic data, including best-corrected visual acuity (BCVA) and average visual field total deviation (TD), in affected eyes and cup-to-disc ratio in fellow eyes at enrollment. We report the prevalence (mean and standard devition, and median and interquartile range [IQR]) of ophthalmic features and cardiovascular risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn's test with Bonferroni correction for continuous variables and chi-square testing with Holm-Bonferroni correction for categorical variables. The study enrolled 500 men and 229 women with a median age of 60 and 61 years (P = 0.027), respectively. Participants were predominantly White (n = 570) and Asian (n = 149). The study eye BCVA was 71 characters (IQR, 53–84 characters; approximately 0.4 logarithm of the minimum angle of resolution), and the TD was –16.5 dB (IQR, –22.2 to –12.6 dB) for stimulus III and –15.7 dB (IQR, –20.8 to –10.9 dB) for stimulus V. The vertical and horizontal cup-to-disc ratio was 0.1 (IQR, 0.1–0.3) for unaffected fellow eyes. The prevalence of cardiovascular risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmologic features, which differed between Asian and White races. Men and women differed with respect to a few clinically meaningful features. The cardiovascular risk factors in the NAION cohort varied among the 7 countries, race, and sex, but were not typically more prevalent than in the general population. Ophthalmic features, typical of NAION, generally were consistent across countries, race, and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice that of women. Having a small cup-to-disc ratio in the fellow eye was the most prevalent risk factor across all demographics. This study suggests that factors, not yet identified, may contribute to the development of NAION. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Small-Fiber Neuropathy (SFN) is a disorder of the peripheral nervous system, characterised by neuropathic pain; approximately 11% of cases are linked to variants in Voltage-Gated Sodium Channels (VGSCs). This study aims to broaden the genetic knowledge on painful SFN by applying Whole-Exome Sequencing (WES) in Early-Onset (EO) cases. A total of 88 patients from Italy (n = 52) and the Netherlands (n = 36), with a disease onset at age ≤ 45 years old and a Pain Numerical Rating Score ≥ 4, were recruited. After variant filtering and classification, WES analysis identified 142 potentially causative variants in 93 genes; 8 are Pathogenic, 15 are Likely Pathogenic, and 119 are Variants of Uncertain Significance. Notably, an enrichment of variants in transient receptor potential genes was observed, suggesting their role in pain modulation alongside VGSCs. A pathway analysis performed by comparing EO cases with 40 Italian healthy controls found enriched mutated genes in the "Nicotinic acetylcholine receptor signaling pathway". Targeting this pathway with non-opioid drugs could offer novel therapeutic avenues for painful SFN. Additionally, with this study we demonstrated that employing a gene panel of reported mutated genes could serve as an initial screening tool for SFN in genetic studies, enhancing clinical diagnostics. [ABSTRACT FROM AUTHOR]

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]

A 54‐year‐old man with diabetes mellitus presented with fever, pain, muscle weakness, and sensory disturbances in the lower limbs. His serum C‐reactive protein level was markedly increased; However, no autoantibodies, other than anti‐glutamic acid decarboxylase antibody, were detected. Nerve conduction studies revealed axonal polyneuropathy. 18F‐fluorodeoxyglucose positron emission tomography/computed tomography revealed patchy uptake patterns specific to restricted lower‐limb vasculitis. The muscle and nerve biopsy specimens suggested vasculitic neuropathy. Treatment with oral prednisolone and cyclophosphamide pulse therapy markedly improved his lower‐limb weakness and paresthesia. Clinicians should consider the involvement of vasculitic neuropathy, as well as myopathy, in patients with restricted lower‐limb vasculitis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We report on the successful use of chemotherapy for treatment of stage 2B testicular seminoma in a carrier of the Leber's hereditary optic neuropathy 11778 mitochondrial mutation. Neurotoxic chemotherapy may not prompt disease conversion. [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]

To report a rare case of bilateral optic neuropathy in a patient with diffuse cutaneous systemic sclerosis with interstitial lung disease. Retrospective case report. A middle-aged female, who was a known case of systemic sclerosis with interstitial lung disease, was presented with sudden painless bilateral loss of vision for a month. The fundoscopy findings were suggestive of bilateral optic atrophy. Anti-topoisomerase I was found in the serum. Serum B12 and folate levels were reduced. HRCT Chest was suggestive of interstitial lung disease. MRI brain was normal and MRI orbit showed kinking of the left optic nerve. The findings were suggestive of diffuse cutaneous systemic sclerosis with interstitial lung disease and bilateral optic neuropathy. This is a rare case of bilateral optic neuropathy in a patient with diffuse cutaneous systemic sclerosis and interstitial lung disease with profound vision loss, in the absence of renal or cardiac involvement. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Oncology Nursing Journal is the property of Pappin Communications and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Oxaliplatin is a platinum-based chemotherapy agent that often causes chemotherapy-induced peripheral neuropathy (CIPN). This effect limits the potential activity and decreases the cancer patient's quality of life. Melanocortin and transient receptor potential ankyrin 1 (TRPA1) pathways are believed to be essential in recruiting an allodynia response. Based on previous studies, curcumin has shown antioxidant and anti-inflammatory activities that could potentially be useful for decreasing the allodynia effects of oxaliplatin treatment. This study investigated the effect of curcumin on CIPN conditions. In addition, we further elaborated to measure the involvement of spinal melanocortin and the TRPA1 system. Materials and Methods: A total of 30 male Balb/C mice aged 6-7 weeks old and weighing 20-30 g were used in this study. Mice were injected with oxaliplatin 3 mg/kg four times in the first week of the study. In the second week of the study, curcumin 30, 60, and 120 mg/kg was injected intraperitoneally for 7 days. Allodynia response was measured using the von Frey filament test. Melanocortin 4 receptor (Mc4r), Proopiomelanocortin (Pomc) and Trpa1 mRNA expressions were measured using RT-qPCR. Results: Oxaliplatin-induced mechanical allodynia response in mice, characterized by a decrease in the 50% withdrawal threshold parameter, was followed by a significant decrease in the Mc4r, Pomc, and Trpa1 mRNA expressions in the spinal cord. Curcumin administration in all doses improves the 50% withdrawal threshold parameter in mice induced by oxaliplatin. Furthermore, curcumin increases the Mc4r and Pomc, but not the Trpa1 mRNA expressions in the spinal cord. Conclusion: Curcumin significantly reduces the allodynia response induced by oxaliplatin. In addition, curcumin ameliorates the melanocortin, but not TRPA1, downregulation in the spinal cord. [ABSTRACT FROM AUTHOR]

Chemotherapy-provoked peripheral neuropathy and its associated affective disorders are important adverse effects in cancer patients, and its treatment is not completely resolved. A recent study reveals a positive interaction between molecular hydrogen (H2) and a heme oxygenase (HO-1) enzyme inducer, cobalt protoporphyrin IX (CoPP), in the inhibition of neuropathic pain provoked by nerve injury. Nevertheless, the efficacy of CoPP co-administered with hydrogen-rich water (HRW) on the allodynia and emotional disorders related to paclitaxel (PTX) administration has not yet been assessed. Using male C57BL/6 mice injected with PTX, we examined the effects of the co-administration of low doses of CoPP and HRW on mechanical and thermal allodynia and anxiodepressive-like behaviors triggered by PTX. Moreover, the impact of this combined treatment on the oxidative stress and inflammation caused by PTX in the amygdala (AMG) and dorsal root ganglia (DRG) were studied. Our results indicated that the antiallodynic actions of the co-administration of CoPP plus HRW are more rapid and higher than those given by each of them when independently administered. This combination inhibited anxiodepressive-like behaviors, the up-regulation of the inflammasome NLRP3 and 4-hydroxynonenal, as well as the high mRNA levels of some inflammatory mediators. This combination also increased the expression of NRF2, HO-1, superoxide dismutase 1, glutathione S-transferase mu 1, and/or the glutamate-cysteine ligase modifier subunit and decreased the protein levels of BACH1 in the DRG and/or AMG. Thus, it shows a positive interaction among HO-1 and H2 systems in controlling PTX-induced neuropathy by modulating inflammation and activating the antioxidant system. This study recommends the co-administration of CoPP plus HRW as an effective treatment for PTX-provoked neuropathy and its linked emotive deficits. [ABSTRACT FROM AUTHOR]

Introduction: Charcot--Marie--Tooth disease type 4C (CMT4C) OMIM#601596 stands out as one of the most prevalent forms of recessive motor sensory neuropathy worldwide. This disorder results from biallelic pathogenic variants in the SH3TC2 gene. Methods: Within a cohort comprising 700 unrelated Russian patients diagnosed with Charcot--Marie--Tooth disease, we conducted a gene panel analysis encompassing 21 genes associated with hereditary neuropathies. Among the cohort, 394 individuals exhibited demyelinating motor and sensory neuropathy. Results and discussion: Notably, 10 cases of CMT4C were identified within this cohort. The prevalence of CMT4C among Russian demyelinating CMT patients lacking the PMP22 duplication is estimated at 2.5%, significantly differing from observations in European populations. In total, 4 novel and 9 previously reported variants in the SH3TC2 gene were identified. No accumulation of amajor variant was detected. Three previously reported variants, c.2860C>Tp. (Arg954*), p. (Arg658Cys) and c.279G>A p. (Lys93Lys), recurrently detected in unrelated families. Nucleotide alteration p. (Arg954*) is present in most of our patients (30%). [ABSTRACT FROM AUTHOR]

Background: Gowing number of studies have demonstrated the association between gut microbiome and T2DM microvascular complications, however the causal relationship remains unclear. Therefore, we using the Mendelian randomization (MR) approach to investigate this causal relation. Methods: Using gut microbiome data from the International MiBioGen Consortium genome-wide association study (GWAS) and T2DM microvascular complications data from the FinnGen Consortium GWAS to perform MR analyses. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), the inverse variance weighting (IVW) method was used as the primary analysis method, and the results were tested for heterogeneity and horizontal pleiotropy. Results: Our research identified that there are 5 known microbial species and 2 unknown microbial species in the gut microbiome that were causally related to T2DM retinopathy. Besides, three and seven known microbial species causal relationships between the gut microbiome and T2DM neuropathy and T2DM nephropathy, respectively. Conclusions: Using MR methods, we demonstrated the causal relationship between gut microbiome and microvascular complications in T2DM, providing a new strategy for the prevention and treatment of it. [ABSTRACT FROM AUTHOR]

Introduction: As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of aging, age- related diseases, and lifestyle-related diseases, including diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of NE-(carboxymethyl)lysine (CML) and N"-(carboxymethyl) arginine (CMA) during the incubation of collagen- derived gelatin with ribose. Materials and methods: EH was purchased from Uchida Wakan-yaku Co., and a MeOH extract was prepared. Several steps of column chromatography purified the extract. Each fraction was tested for inhibitory activity by ELISA using monoclonal antibodies for CML and CMA. Results: After activity-guided fractionation and purification by column chromatography, three new prenylflavonoids [named Koreanoside L (1), Koreanoside E1 (2), and Koreanoside E2 (3)] and 40 known compounds (4-43) were isolated from EH, and their inhibitory effects against CML and CMA formation were tested. Among these, epimedokoreanin B (8), epimedonin E (21), epicornunin B (22), and epicornunin F (24) inhibited the formation of both CML and CMA, with epimedokoreanin B (8) having the most potent inhibitory effect among the isolated compounds. To obtain the structure-activity relationships of 8, the phenolic hydroxy groups of 8 were methylated by trimethylsilyl-diazomethane to afford the partially and completely methylated compounds of 8. Prenyl derivatives of propolis (artepillin C, baccharin, and drupanin) were used in the assay. Discussion: As only 8 showed significant activity among these compounds, the catechol group of the B ring and the two prenyl groups attached to the flavanone skeleton were essential for activity. These data suggest that 8 could prevent the clinical complications of diabetes and age-related diseases by inhibiting AGEs. [ABSTRACT FROM AUTHOR]

The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), the so-called chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN can be long-lasting or even permanent, and it is detrimental for the quality of life of cancer survivors, being associated with persistent disturbances such as sensory loss and neuropathic pain at limb extremities due to a mostly sensory axonal polyneuropathy/neuronopathy. In the state of the art, there is no efficacious preventive/curative treatment for this condition. Among the reasons for this unmet clinical and scientific need, there is an uncomplete knowledge of the pathogenetic mechanisms. Ion channels and transporters are pivotal elements in both the central and peripheral nervous system, and there is a growing body of literature suggesting that they might play a role in CIPN development. In this review, we first describe the biophysical properties of these targets and then report existing data for the involvement of ion channels and transporters in CIPN, thus paving the way for new approaches/druggable targets to cure and/or prevent CIPN. [ABSTRACT FROM AUTHOR]

The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background—in particular, accelerated progress is being made in understanding molecular biological mechanisms—some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles. [ABSTRACT FROM AUTHOR]

Background: Echinococcosis, commonly known as hydatid disease, is a zoonotic infection resulting from the tapeworm Echinococcus granulosus. The occurrence of hydatid cysts in the orbital region is uncommon, representing less than 1% of all reported hydatid cases. This report details a unique case of an intramuscular hydatid cyst in the orbital region that led to compressive optic neuropathy. Case Presentation: A 22-year-old male from Kabul, Afghanistan presented with a five-month history of progressive proptosis in his left eye, associated with a gradual decrease in vision over the past three weeks. The left eye exhibited upward globe dystopia, ocular motility limitation, mild conjunctival injection, and chemosis. Diagnosis was achieved through imaging and histopathological examination. Treatment involves surgical removal of the cyst and prolonged albendazole therapy. The postoperative course showed significant improvement in the patient's condition and restoration of his vision. Conclusions: Despite its rarity, this case underscores the importance of awareness and knowledge of hydatid disease among physicians, especially those working in endemic areas. It emphasizes the importance of including hydatid disease in the differential diagnosis of orbital masses, particularly in endemic regions. [ABSTRACT FROM AUTHOR]

Neuropathy is a damage, disease, or dysfunction of one or more nerves especially of the peripheral nervous system. One of the most common disease causing neuropathy is diabetes mellitus. Diabetic neuropathy is a serious consequence that arises when nerve tissue is damaged by prolonged hyperglycemia. It affects a considerable portion of those who have the disease. This article covers every component of this complexed disease. We will discuss the definition, etiology, risk factors that patients can control and that are uncontrollable, and forms of neuropathies linked to diabetes such as peripheral, autonomic and focal. For more clinical approach signs and symptoms, diagnostic methods which are a mix of clinical evaluations, neurological exams, electrophysiological testing, and, in certain situations, imaging modalities and complicated nature of treating diabetic neuropathy will be explored. Moreover, challenges in treating this disease and future directions and research will be elaborated. What is more it interdisciplinary care will be explored as a key element in addressing complexed nature of diabetic neuropathy. In addition to highlighting the complexity of neuropathy in diabetes mellitus and emphasizing the vital significance of early recognition and specialized interventions for the best possible patient outcomes, the article aims to present a thorough grasp of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

No previous study has evaluated the effectiveness of routine physical therapy with and without neural mobilization for patients with chronic musculoskeletal neck disorders and cervical radiculopathy. The objective is to evaluate the effectiveness of routine physical therapy with and without neural mobilization on pain and mobility in patients with chronic musculoskeletal neck disorders and cervical radiculopathy. A systematic review with meta-analysis of randomized clinical trials involving the use of neural mobilization techniques for the treatment of chronic musculoskeletal neck disorders and cervical radiculopathy was conducted. Methodological quality was assessed by the Cochrane Risk of Bias Tool and PEDro scale. Data were pooled and a meta-analysis was performed using a random effects model with Review Manager 5 software. Seven articles were included in our review. Significant differences were found in mobility but not in pain in favor of using routine physical therapy with neural mobilization for the treatment of chronic musculoskeletal neck disorders and cervical radiculopathy. Our results show that routine physical therapy accompanied by neural mobilization is superior for improving mobility in comparison with routine physical therapy alone in patients with musculoskeletal neck disorders and cervical radiculopathy. [ABSTRACT FROM AUTHOR]

Background: Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review. Methods: The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases. Results: In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases. Conclusion: Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept. [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: The role of the choroid in Leber hereditary optic neuropathy (LHON) remains unclear. The literature is scarce, with conflicting results and lacks axial length measurements. Therefore, we aimed to analyse the choriocapillaris (CC) vessel density (VD) and choroidal thickness (ChT) in all stages of LHON using swept source (SS) technology and considering the possible influence of axial length on choroidal parameters. Methods: This was a prospective cross‐sectional observational study. A total of 119 eyes of 60 patients with molecularly confirmed LHON across all stages and 120 eyes of 60 control participants were included. We obtained the CC VD using optical coherence tomography angiography maps centred on the fovea. ChT was measured from the Bruch's membrane to the choroid‐sclera interface in the macular and peripapillary regions. Results: The CC VD was not significantly affected in any sector or average, except for a slight change in the superior region of chronic eyes (52.08 ± 1.62% vs. 53.50 ± 2.29%, p = 0.002). ChT demonstrated a trend towards decreased values in asymptomatic eyes and increased values in the symptomatic stages that failed to reach statistical significance in sectors corresponding to the papillomacular bundle except for the macular nasal inner sector of chronic eyes (281.10 ± 67.12 μm vs. 252.08 ± 70.55 μm, p = 0.045). No significant correlations were observed between visual acuity and CC VD or ChT. Conclusion: The CC VD remained stable across the LHON stages. Choroidal vasculature does not appear to play a role in LHON pathophysiology. Further research is needed on ChT as a potential biomarker of LHON. [ABSTRACT FROM AUTHOR]

Background and Aim: Recreational use of nitrous oxide (N2O) has been associated with the development of severe nitrous oxide‐induced neuropathy (N2On). Follow‐up of these patients poses challenges, and their clinical progression remains largely unknown. The identification of prognostic factors is made difficult by the lack of standardized longitudinal assessments in most studies. The objective was to document the course of neuropathy through systematic follow‐up assessments in N2On patients to identify prognostic factors for persistent disability after 6 months. Methods: We gathered demographic, clinical, biological, and electrophysiological data from N2On patients hospitalized in the Referral center in Marseille, both at baseline and during a standardized follow‐up assessment at 6 months. Results: We retrospectively included 26 N2On patients (mean age 22.6 ± 4.4). Significant improvements were observed in all main clinical scores including Rankin, ONLS, and MRC testing (p <.01). Electrophysiological studies (EDX) revealed a predominantly motor neuropathy with marked reduction in CMAP in the lower limbs at baseline, and no significant improvement in motor parameters (p =.543). Rankin score at 6 months correlated with the initial weekly N2O consumption (r =.43, p =.03) and the CMAP sum score in the lower limbs at the first EDX (r = −.47, p =.02). Patients with and without myelitis showed similar Rankin and ONLS score after 6 months. Interpretation: The clinical course generally improved favorably at 6 months with notable amelioration in the primary disability scores, sensory deficits, and ataxia. However, distal motor impairment associated with peripheral neuropathy persisted, with distal axonal loss emerging as the main prognostic factor for long‐term disability in these young patients. [ABSTRACT FROM AUTHOR]

Background: Femoral cannulated extracorporeal membrane oxygenation (ECMO) has been associated with neurologic complications in the lower extremity ipsilateral to the cannulation. There is uncertainty about the prevalence of these complications and their mechanisms of development. Objective: Aim of this systematic review was to investigate the prevalence of neurological complications after ECMO and to describe possible underlying mechanisms. Method: A systematic literature search was performed in Medline-Ovid, Embase, Cochrane Library, CINAHL, and PEDro until April 2021 for clinical trials in English or German language which quantified neurologic complications in the lower extremity ipsilateral to the ECMO cannulation of adults. The complications had to be delimitable to intensive care unit–acquired weakness. Methodological quality was assessed by 2 independent investigators using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung, and Blood Institute. Results: Eight observational studies were included in the synthesis. Study quality was good to fair in 88% of the papers. Overall, 47 of 202 patients (23.3%; ranging from 3% to 48% across studies) with femoral ECMO cannulation showed neurologic complications of the lower extremity ipsilateral to the cannulation. Peripheral ischemia and compression of nerves by the ECMO cannula are discussed as mechanisms of injury. Conclusion: The occurrence of neurological complications after ECMO was common and can lead to long-term impairment. The mechanisms are largely unknown but currently there is no sufficient evidence for the involvement of ECMO. Standardized assessments are needed to systematically screen for neurological complications early after ECMO, to enable countermeasures and prevent further complications. [ABSTRACT FROM AUTHOR]

Tropical ataxic neuropathy (TAN) is characterised by ataxic polyneuropathy, degeneration of the posterior columns and pyramidal tracts, optic atrophy, and sensorineural hearing loss. It has been attributed to nutritional/toxic etiologies, but evidence for the same has been equivocal. TAN shares common clinical features with inherited neuropathies and mitochondrial disorders, it may be hypothesised that genetic abnormalities may underlie the pathophysiology of TAN. This study aimed to establish evidence for mitochondrial dysfunction by adopting an integrated biochemical and multipronged genetic analysis. Patients (n = 65) with chronic progressive ataxic neuropathy with involvement of visual and/or auditory pathways underwent deep phenotyping, genetic studies including mitochondrial DNA (mtDNA) deletion analysis, mtDNA and clinical exome sequencing (CES), and respiratory chain complex (RCC) assay. The phenotypic characteristics included dysfunction of visual (n = 14), auditory (n = 12) and visual + auditory pathways (n = 29). Reduced RCC activity was present in 13 patients. Mitochondrial DNA deletions were noted in five patients. Sequencing of mtDNA (n = 45) identified a homoplasmic variant (MT-ND6) and a heteroplasmic variant (MT-COI) in one patient each. CES (n = 45) revealed 55 variants in nuclear genes that are associated with neuropathy (n = 27), deafness (n = 7), ataxia (n = 4), and mitochondrial phenotypes (n = 5) in 36 patients. This study provides preliminary evidence that TAN is associated with a spectrum of genetic abnormalities, including those associated with mitochondrial dysfunction, which is in contradistinction from the prevailing hypothesis that TAN is related to dietary toxins. Analysing the functional relevance of these genetic variants may improve the understanding of the pathogenesis of TAN. [ABSTRACT FROM AUTHOR]

Background: Hereditary sensory and autonomic neuropathies (HSANs) are rare heterogeneous group of neurological disorders caused by peripheral nerve deterioration. The HSANs sub-clinical classes have clinical and genetic overlap which often lead to misdiagnosis. In the present study a Pakistani family with five affected members suffering from severe neuropathy were genetically analyzed to identify the disease causative element in the family. Methods: Genome wide high-density single nucleotide polymorphism (SNP) microarray analysis was carried out followed by whole exome sequencing of the affected proband and another affected sibling. Shared homozygous regions in all severely affected members were identified through homozygosity mapping approach. Results: The largest homozygous region of 14.1 Mb shared by the five severely affected members of the family was identified on chromosome 2. Subsequent exome sequencing identified a novel single nucleotide deletion c.2658del; p.(Ser887Profs*64) in KIF1A. Segregation analysis revealed that this mutation was homozygous in all five affected individuals of the family with severe clinical manifestation, while members of the family that were heterozygous carriers shared abnormal skin features (scaly skin) only with the homozygous affected members. Conclusions: A novel frameshift mutation p.(Ser887Profs*64) in KIF1A is the potential cause of severe HSANIIC in a Pakistani family along with incomplete penetrance in mutation carriers. We demonstrate that using a combination of different techniques not only strengthens the gene finding approach but also helps in proper sub-clinical characterization along with identification of mutated alleles exhibiting incomplete penetrance leading to intrafamilial clinical variability in HSAN group of inherited diseases. [ABSTRACT FROM AUTHOR]

Few reports describe the risks of late ocular toxicities after radiation therapy (RT) for childhood cancers despite their effect on quality of life. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) ocular task force aims to quantify the radiation dose dependence of select late ocular adverse effects. Here, we report results concerning retinopathy, optic neuropathy, and cataract in childhood cancer survivors who received cranial RT. A systematic literature search was performed using the PubMed, MEDLINE, and Cochrane Library databases for peer-reviewed studies published from 1980 to 2021 related to childhood cancer, RT, and ocular endpoints including dry eye, keratitis/corneal injury, conjunctival injury, cataract, retinopathy, and optic neuropathy. This initial search yielded abstracts for 2947 references, 269 of which were selected as potentially having useful outcomes and RT data. Data permitting, treatment and outcome data were used to generate normal tissue complication probability models. We identified sufficient RT data to generate normal tissue complication probability models for 3 endpoints: retinopathy, optic neuropathy, and cataract formation. Based on limited data, the model for development of retinopathy suggests 5% and 50% risk of toxicity at 42 and 62 Gy, respectively. The model for development of optic neuropathy suggests 5% and 50% risk of toxicity at 57 and 64 Gy, respectively. More extensive data were available to evaluate the risk of cataract, separated into self-reported versus ophthalmologist-diagnosed cataract. The models suggest 5% and 50% risk of self-reported cataract at 12 and >40 Gy, respectively, and 50% risk of ophthalmologist-diagnosed cataract at 9 Gy (>5% long-term risk at 0 Gy in patients treated with chemotherapy only). Radiation dose effects in the eye are inadequately studied in the pediatric population. Based on limited published data, this PENTEC comprehensive review establishes relationships between RT dose and subsequent risks of retinopathy, optic neuropathy, and cataract formation. [ABSTRACT FROM AUTHOR]

• Motor evoked potential amplitudes may be small and difficult to monitor during surgery in some patients. • Tetanic stimulation of peripheral nerves improves motor evoked potential amplitudes. • Tetanic stimulation can also be used in patient with myelopathy and peripheral neuropathy, with some cautions. Tetanic stimulation of a peripheral nerve prior to transcranial electrical stimulation (TES) may enhance motor evoked potential (MEP) amplitudes. The purpose of this study was to investigate the post-tetanic MEP (p-MEP) technique in improving MEP amplitudes. Conventional TES MEPs (c-MEP) and p-MEPs with left upper limb stimulation (p-MEP UL) or left lower limb stimulation (p-MEP LL) were performed in 26 patients. Bilateral hand and foot MEP amplitudes obtained with each protocol were compared. Subgroup comparisons were performed for myelopathy and peripheral neuropathy patients. Within-subject amplitude differences between c-MEP and each p-MEP technique were compared using a Wilcoxon test. The mean age of the patients was 52.7 years (range, 12–79 years). Overall, p-MEP UL resulted in MEP improvement in 25 of 26 (96%) patients, and p-MEP LL improved MEPs in 19 of 26 (73%) patients. The increase in MEP amplitudes were statistically significant in all muscle groups except left foot. Similar improvements were seen in the myelopathy group; in the neuropathy group, p-MEP UL produced similar results, but p-MEP LL did not. The p-MEP technique can improve MEP amplitudes, including in patients with myelopathy. In patients with peripheral neuropathy, the results were mixed. Tetanic stimulation can enhance intraoperative MEP amplitudes. [ABSTRACT FROM AUTHOR]

Leigh syndrome spectrum (LSS) is a primary mitochondrial disorder defined neuropathologically by a subacute necrotizing encephalomyelopathy and characterized by bilateral basal ganglia and/or brainstem lesions. LSS is associated with variants in several mitochondrial DNA genes and more than 100 nuclear genes, most often related to mitochondrial complex I (CI) dysfunction. Rarely, LSS has been reported in association with primary Leber hereditary optic neuropathy (LHON) variants of the mitochondrial DNA, coding for CI subunits (m.3460G>A in MT-ND1, m.11778G>A in MT-ND4 and m.14484T>C in MT-ND6). The underlying mechanism by which these variants manifest as LSS, a severe neurodegenerative disease, as opposed to the LHON phenotype of isolated optic neuropathy, remains an open question. Here, we analyse the exome sequencing of six probands with LSS carrying primary LHON variants, and report digenic co-occurrence of the m.11778G > A variant with damaging heterozygous variants in nuclear disease genes encoding CI subunits as a plausible explanation. Our findings suggest a digenic mechanism of disease for m.11778G>A-associated LSS, consistent with recent reports of digenic disease in individuals manifesting with LSS due to biallelic variants in the recessive LHON-associated disease gene DNAJC30 in combination with heterozygous variants in CI subunits. [ABSTRACT FROM AUTHOR]

Mutations in the Microrchidia CW-type zinc finger 2 (MORC2) GHKL ATPase module cause a broad range of neuropathies, such as Charcot-Marie-Tooth disease type 2Z; however, the aetiology and therapeutic strategy are not fully understood. Previously, we reported that the Morc2a p.S87L mouse model exhibited neuropathy and muscular dysfunction through DNA damage accumulation. In the present study, we analysed the gene expression of Morc2a p.S87L mice and designated the primary causing factor. We investigated the pathological pathway using Morc2a p.S87L mouse embryonic fibroblasts and human fibroblasts harbouring MORC2 p.R252W. We subsequently assessed the therapeutic effect of gene therapy administered to Morc2a p.S87L mice. This study revealed that Morc2a p.S87L causes a protein synthesis defect, resulting in the loss of function of Morc2a and high cellular apoptosis induced by high hydroxyl radical levels. We considered the Morc2a GHKL ATPase domain as a therapeutic target because it simultaneously complements hydroxyl radical scavenging and ATPase activity. We used the adeno-associated virus (AAV)-PHP.eB serotype, which has a high CNS transduction efficiency, to express Morc2a or Morc2a GHKL ATPase domain protein in vivo. Notably, AAV gene therapy ameliorated neuropathy and muscular dysfunction with a single treatment. Loss-of-function characteristics due to protein synthesis defects in Morc2a p.S87L were also noted in human MORC2 p.S87L or p.R252W variants, indicating the correlation between mouse and human pathogenesis. In summary, CMT2Z is known as an incurable genetic disorder, but the present study demonstrated its mechanisms and treatments based on established animal models. This study demonstrates that the Morc2a p.S87L variant causes hydroxyl radical-mediated neuropathy, which can be rescued through AAV-based gene therapy. [ABSTRACT FROM AUTHOR]

Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6 -associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker. [ABSTRACT FROM AUTHOR]

Background: Ulnar neuropathy after a distal radius fracture is rare and has limited reports in literature. As such, there is no consensus regarding the optimal treatment and management of such injuries. We report our experience with managing these uncommon injuries. Methods: A retrospective review was conducted where patients presenting with ulnar neuropathy after sustaining a distal radius fracture were identified from January 2021 to December 2023 from our hospital database. Results: A total of four patients were identified. All of them underwent surgical fixation for their respective fractures. None of them underwent immediate or delayed exploration and decompression of the ulnar nerve. All patients had clinical improvement at 3 months after their initial injuries. Three patients eventually had resolution of the neuropathy between 5 and 9 months post injury, while one had partial recovery and developed a neuroma but declined surgery due to symptoms minimally affecting work and daily activities. Conclusions: Ulnar neuropathy after distal radius fractures may not be as rare as previously thought. Expectant management of the neuropathy would be a reasonable treatment as long as there is no evidence of nerve discontinuity or translocation and that there is clinical and/or electrodiagnostic improvement at 3–4 months after the initial injury. Level of Evidence: Level IV (Therapeutic) [ABSTRACT FROM AUTHOR]

Background: Diabetic sensorimotor polyneuropathy (DSPN) is the most common complication of type 2 diabetes mellitus (T2DM) and the major cause of nontraumatic lower limb amputation. We aimed in the current research to investigate miR-191-5p as a noninvasive predictive biomarker of DSPN among patients recently diagnosed with T2DM in associations with clinical and electrophysiological tests. Methods: We conducted fifty cases recently diagnosed with T2DM and 50 healthy control subjects. contributors were evaluated by clinical and laboratory investigations in addition to nerve conduction studies. circulatory miR-191-5p assessed using the Real-Time PCR method. Results: miR-191-5p levels were lower in patients with DSPN compared to patients without DSPN and controls. Remarkably, miR-191-5p levels were significantly negatively correlated with cardiometabolic risk factors and neuropathy scores; Neuropathy Disability Score (NDS), Neuropathy Symptom Score (NSS), and Toronto Clinical Scoring System (TCSS), p <0.001*. The linear regression test revealed that TCSS, HbA1c, and LDL were the main independent variables against Mir-191-5p levels in patients with DSPN, p <0.001*. To assess the predictive values of miR-191-5p we applied the ROC curve the cutoff values of miR-191-5p as a predictive marker for DSPN was (0.559), with a sensitivity of (95%) and a specificity of (98.7%), with the AUC was 0.958 (0.922-0.993), p <0.001*). Conclusion: circulating miR-191-5p was significantly downregulated in patients recently diagnosed with T2DM, more specifically in patients with DSPN, and it could be used as a biomarker for predicting diabetes and DSPN. [ABSTRACT FROM AUTHOR]

(1) Background: Neurologic and musculoskeletal diseases represent a considerable portion of the underlying etiologies responsible for the widely prevalent symptoms of pain, weakness, numbness, and paresthesia. Because of the subjective and often nonspecific nature of these symptoms, different diagnostic modalities have been explored and utilized. (2) Methods: Literature review. (3) Results: Nerve and muscle biopsy remains the gold standard for diagnosing many of the responsible neurological and musculoskeletal conditions. However, the need for invasive tissue sampling is diminishing as more investigations explore alternative diagnostic modalities. Because of this, it is important to explore the current role of neurosurgical intervention for nerve and muscle biopsies and its current relevance in the diagnostic landscape of neurological and musculoskeletal disorders. With consideration of the role of nerve and muscle biopsy, it is also important to explore innovations and emerging techniques for conducting these procedures. This review explores the indications and emerging techniques for neurological intervention for nerve and muscle biopsies. (4) Conclusions: The role of neurosurgical intervention for nerve and muscle biopsy remains relevant in diagnosing many neurological and musculoskeletal disorders. Biopsy is especially relevant as a supportive point of evidence for diagnosis in atypical cases. Additionally, emerging techniques have been explored to guide diagnostics and biopsy, conduct less invasive biopsies, and reduce risks of worsening neurologic function and other symptoms secondary to biopsy. [ABSTRACT FROM AUTHOR]

Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the SPTLC1 or SPTLC2 variants. These variants modify the preferred substrate of serine palmitoyl transferase, responsible for the first step of de novo sphingolipids synthesis, leading to accumulation of cytotoxic deoxysphingolipids. Diagnosis of HSAN1 is based on clinical symptoms, mainly progressive loss of distal sensory keep, and genetic analysis. Aim: Identifying new SPTLC1 or SPTLC2 "gain-of-function" variants raises the question as to their pathogenicity. This work focused on characterizing six new SPTLC1 variants using in silico prediction tools, new meta-scores, 3D modeling, and functional testing to establish their pathogenicity. Methods: Variants from six patients with HSAN1 were studied. In silico, CADD and REVEL scores and the 3D modeling software MITZLI were used to characterize the pathogenic effect of the variants. Functional tests based on plasma sphingolipids quantification (total deoxysphinganine, ceramides, and dihydroceramides) were performed by tandem mass spectrometry. Results: In silico predictors did not provide very contrasting results when functional tests discriminated the different variants according to their impact on deoxysphinganine level or canonical sphingolipids synthesis. Two SPTLC1 variants were newly described as pathogenic: SPTLC1 NM_006415.4:c.998A>G and NM_006415.4:c.1015G>A. Discussion: The combination of the different tools provides arguments to establish the pathogenicity of these new variants. When available, functional testing remains the best option to establish the in vivo impact of a variant. Moreover, the comprehension of metabolic dysregulation offers opportunities to develop new therapeutic strategies for these genetic disorders. [ABSTRACT FROM AUTHOR]

Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study was to investigate peripheral nerve damage, and to correlate clinical, epidemiological and neurophysiological findings, in patients diagnosed with Alcohol Use Disorder (AUD). Ninety alcohol-dependent subjects on inpatient basis were enrolled in this prospective study over a 3-year period. Every subject was assessed by the Neuropathy Symptoms Score (NSS) questionnaire and the Neuropathy Impairment Score (NIS) clinical examination grading scale, followed by Nerve Conduction Studies, Quantitative Sensory Testing and Sympathetic Skin Response (SSR) testing. Peripheral neuropathy was diagnosed in 54 subjects (60%), by abnormal neurophysiological tests and presence of clinical signs or symptoms. Among them, pure large fiber neuropathy (LFN) was found in 18 subjects, pure small fiber neuropathy (SFN) in 12 subjects, and both large and small fiber neuropathy was diagnosed in 24 subjects. Using linear regression, we found that higher NSS and NIS scores correlated with lower amplitudes of the sural sensory nerve action potential and of the SSR. We also found a significant longer duration of alcohol abuse in subjects with neuropathy, using Student's t-test (p = 0.024). Additionally, applying NIS abnormal cut-off score ≥4, using ROC analysis, we predicted the majority of subjects with LFN, confirming 95.23% sensitivity and 93.75% specificity. Our study confirmed that peripheral neuropathy involving large and small nerve fibers, with a symmetrical length-dependent pattern, is common between patients with AUD and related to the duration of the disorder. We suggest that NSS and NIS scales could be used for the assessment of neuropathy in clinical practice, when the essential neurophysiological testing is not available. • Peripheral neuropathy with feet affected before hands is common in patients with alcohol use disorder. • Alcohol-related peripheral neuropathy correlates with the duration of the abuse. • Neurophysiological testing is essential for the diagnosis of alcohol-related peripheral neuropathy. • Clinical neuropathy scales could be useful for assessing alcohol-related peripheral neuropathy. • Proposed cut-off scores are ≥4 for Neuropathy Impairment Score and ≥1 for Neuropathy Symptoms Score. [ABSTRACT FROM AUTHOR]

Background: Paclitaxel administration causes peripheral neuropathy. Auraptene is a natural bioactive monoterpene with anti-inflammatory and anti-neuropathic effects that is widely used. Objectives: We aimed to study auraptene effects on paclitaxel-induced neuropathy. Materials and Methods: This study was comprised of two steps of evaluation of the preventive and treatment effects of auraptene in mice. In the first step, mice were randomly allocated into three groups of six animals, including the negative control (NEG CTL): animals injected with paclitaxel (PTX) together with normal saline, PTX (paclitaxel 2 mg/kg given on days 1, 3, 5, and 7), and PREVENTION: PTX + auraptene 100 mg/kg on days 1, 3, 5, and 7. In the second step, animals were allocated into six groups of six: NEG CTL (normal saline), PTX (paclitaxel 10 mg/kg given on days 1, 3, 5, and 7), PTX AUR (PTX + auraptene 50, 75, and 100 mg/kg), and a positive control (PTX-treated animals receiving imipramine 10 mg/kg). Intraperitoneal injection of PTX 2 mg/kg on days 1, 3, 5, and 7 was used in order to induce neuropathy. In both steps of the study, a hot plate test was done on day 7 in order to determine the response to heat. After the scarification of animals, the interleukin-6 (IL-6) level in the sciatic nerve was assessed by western blotting. Results: In the preventive group, auraptene could reduce hyperalgesia significantly. In the treatment step, the AUR 100 mg/kg compared to NEG CTL groups had significantly increased heat latency. The expression of IL-6 protein in the sciatic nerve was remarkably decreased in both the preventive and treatment groups compared to NEG CTL. Conclusion: Taken together, our results confirmed that AUR could decrease paclitaxel-induced hyperalgesia in mice and IL-6 protein content in sciatic nerve samples. [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]

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history. Plain language title: A case study of two elderly patients with vitamin B12 deficiency and neurological and cognitive complaints Plain language summary: Vitamin B12 deficiency in elderly patients can be easily overlooked as symptoms can also be caused by other age-related diseases or the aging process. In our article we present two elderly patients, a 71-year-old male and a 74-year-old female, with neurological complaints, such as severe fatigue, cognitive decline, and walking impairment. The male patient had a history of small bowel surgery, and the female patient mentioned that she had several siblings with B12 deficiency. Additionally, the male patient suffered from depressive symptoms and mild disorientation, and the female had severe pain in her legs. The male patient already received B12 injections because of an earlier B12 diagnosis, but with a relatively low frequency. The B12 levels of the female patients were within the normal range. However, her diagnoses could be confirmed with additional laboratory measurements, such as homocysteine and methylmalonic acid. Treatment with frequent B12 injections and other supplements significantly improved their cognitive, emotional, and motor functions. Our study shows that clinicians should carefully consider the possibility of B12 deficiency in elderly patients with cognitive and neurological complaints, also in patients with B12 levels within the normal range, but with risk factors such as family members with B12 deficiency or conditions that may impair the vitamin B12 uptake, such as previous stomach or small bowel surgery. [ABSTRACT FROM AUTHOR]

To estimate the proportion of people with self-reported diabetes receiving eye and foot examinations in Latin America and the Caribbean (LAC). Cross-sectional analysis of national health surveys in nine countries. Adults aged 25–64 years with self-reported diabetes. We quantified the proportion who reported having an eye examination in the last two years or a foot examination in the last year. We fitted multilevel Poisson regressions to assess socio-demographic (age and sex) and clinical (oral hypoglycemic medication and insulin treatment) variables associated with having had examinations. There were 7435 people with self-reported diabetes included in the analysis. In three countries (Chile [64%; 95% CI: 56%-71%], British Virgin Islands [58%; 95% CI: 51%-65%], and Brazil [54%; 95% CI: 50%-58%]), >50% of people with diabetes reported having had an eye examination in the last two years. Fewer participants (<50% across all countries) reported having had a foot examination in the last year, with Ecuador having the lowest proportion (12%; 95% CI: 8%-17%). Older people, and those taking oral medication or insulin, were more likely to have eye/foot examinations. The proportion of eye and foot examinations in people with self-reported diabetes across nine countries in LAC is low. • There were no data on the frequency of eyes/foot examination in diabetics in LAC. • In only three countries >50% of adults with diabetes have had an eye examination. • Chile was close to having 50% of adults with diabetes who received foot examination. • Eye/foot examinations to prevent complications warrants further investment in LAC. [ABSTRACT FROM AUTHOR]