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Objective: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune neuropathy characterized by progressive or relapsing–remitting weakness and sensory deficits. This study aims to evaluate the utility of corneal confocal microscopy (CCM) in diagnosing and monitoring CIDP. Methods: We analysed 100 CIDP patients and 31 healthy controls using CCM to measure corneal nerve fiber density (CNFD), length (CNFL), and branch density (CNBD). Standardized clinical and electroneurographic evaluation were conducted, and statistical analyses were performed to compare CCM parameters between groups and across disease stages. Results: CIDP patients and subgroups exhibited significant reduction in CNFD, CNFL, and CNBD compared to controls. This reduction was observed in late disease stages and severe overall disability sum score (ODSS), and Inflammatory Neuropathy Cause and Treatment Sensory Sum Score (ISS). CCM parameters correlated with axonal pathology in electroneurography of sensory, but not motor nerves. Despite the significant differences, the diagnostic sensitivity (41%) and specificity (77%) of CCM parameters were limited. Conclusion: While CCM effectively differentiates CIDP patients from healthy controls and was associated with disease severity, its diagnostic accuracy for routine clinical use is a posteriori. However, CCM shows promise as a non-invasive tool for monitoring sensory axonal pathology in CIDP. [ABSTRACT FROM AUTHOR]

Obesity management through laparoscopic sleeve gastrectomy can occasionally lead to rare but severe complications, including Guillain-Barré Syndrome (GBS). This report analyzes two cases of GBS following LSG, highlighting differences in symptoms, diagnosis, and management. The first patient experienced rapid onset neurological symptoms post-surgery, confirmed as GBS through clinical and electrophysiological assessments, and responded well to intravenous immunoglobulin. The second patient showed similar symptoms but received only multivitamins and physiotherapy due to financial constraints, with a slow but progressive recovery. These cases underscore the necessity for vigilant postoperative monitoring for GBS, reflecting on potential immune dysregulation and microbiota changes as contributory factors. This awareness is crucial for improving patient outcomes and understanding the neurological impacts of bariatric surgery. [ABSTRACT FROM AUTHOR]

Guillain-Barré syndrome (GBS) is a complex autoimmune disorder characterized by acute onset of motor weakness, often following an infectious illness. The pathophysiology of GBS involves a multifaceted interplay between immune mechanisms and environmental factors, leading to demyelination or axonal degeneration. This systematic review aims to elucidate the autoimmune mechanisms underlying the various subtypes of GBS, including acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS). A thorough literature search identified 71 studies published between 2010 and 2024 that provided insights into the immunopathological features, clinical implications, and future directions for research. Key findings indicate that specific autoantibodies, such as anti-GM1 and anti-GQ1b, are associated with distinct subtypes of GBS, contributing to the disease's heterogeneity. Understanding these autoimmune mechanisms is crucial for improving diagnostic accuracy, therapeutic strategies, and prognostic indicators in GBS. This review highlights significant gaps in current research, emphasizing the need for further studies to explore the genetic and environmental factors that influence GBS susceptibility and the role of vaccinations in triggering autoimmune responses. Trial registration: PROSPERO CRD42024606718. [ABSTRACT FROM AUTHOR]

This article deals with peripheral neuroimmunological diseases and briefly outlines the currently most important aspects and treatment developments. Idiopathic inflammatory myopathies have different mechanisms of development, manifestations and prognoses. New classification systems and more specific treatment concepts have been developed. The IIMs include different subgroups. These entities can have specific autoantibodies. Diagnostically, a muscle biopsy is generally desirable for a precise diagnosis and is essential in unclear cases. Primary systemic vasculitides can be divided into different groups based on the predominant pattern of involvement, while secondary vasculitides and single organ vasculitides are also differentiated. Vasculitic myopathy cannot be equated with myositis and a reliable distinction is currently only possible by a muscle biopsy. Treatment concepts should be developed on an interdisciplinary basis. Chronic inflammatory demyelinating polyneuropathy is the most frequent immune-mediated neuropathy and is characterized by a predominant demyelination of the motor and sensory nerves. The disease course runs in phases or is progressive and leads to significant disability and reduction in quality of life, despite current standard treatment. Novel treatment approaches are currently undergoing clinical trials. Myasthenia gravis, with the leading symptom of exercise-induced muscle weakness, is caused by autoantibodies against structures of the neuromuscular endplate. Autoantibody testing is the most important pillar in the diagnosis and is now also increasingly guiding treatment decisions. Overall, peripheral neuroimmunological diseases represent a heterogeneous group. Increasing knowledge of the pathophysiology is the key to numerous developments in diagnostics and treatment, which could lead to far-reaching practical changes in the future. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates a higher prevalence of polyneuropathy (PNP) in Parkinson's disease (PD). However, the involvement of large fiber neuropathy in PD still remains poorly understood. Given the lack of longitudinal data, we investigated the course of PNP associated with PD. Methods: In total, 41 PD patients underwent comprehensive clinical evaluation including motor and non-motor assessments as well as nerve conduction studies at baseline and at 2 years of follow-up. The definition of PNP was based on electrophysiological standard criteria. Common causes of PNP were excluded. Results: At baseline, PNP was diagnosed in 65.85% of PD patients via electroneurography. Patients with PNP presented with higher age (p = 0.019) and PD motor symptom severity (UPDRS III; p < 0.001). Over the course of 2 years, PNP deteriorated in 21.95% of cases, and 26.83% remained without PNP. Deterioration of nerve amplitude was most prevalent in the median sensory nerve affecting 57.58% of all PD cases with an overall reduction of median sensory nerve amplitude of 45.0%. With regard to PD phenotype, PNP progression was observed in 33.33% of the tremor dominant and 23.81% of the postural instability/gait difficulties subtype. Decrease of sural nerve amplitude correlated with lower quality of life (PDQ-39, p = 0.037) and worse cognitive status at baseline (MoCA, p = 0.042). Conclusion: The study confirms the high PNP rate in PD, and demonstrates a significant electrophysiological progression also involving nerves of the upper extremities. Longitudinal studies with larger cohorts are urgently needed and should elucidate the link between PD and PNP with the underlying pathomechanisms. [ABSTRACT FROM AUTHOR]

Background: To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation. Methods: Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier's antibodies-negative CIDP (Ab− CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model. Results: In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential. Conclusion: The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by extracellular amyloid plaques containing amyloid-β (Aβ) peptides, intraneuronal neurofibrillary tangles, extracellular neuropil threads, and dystrophic neurites surrounding plaques composed of hyperphosphorylated tau protein (pTau). Aβ can also deposit in blood vessel walls leading to cerebral amyloid angiopathy (CAA). While amyloid plaques in AD brains are constant, CAA varies among cases. The study focuses on differences observed between rare and poorly studied patient groups with APP duplications (APPdup) and Down syndrome (DS) reported to have higher frequencies of elevated CAA levels in comparison to sporadic AD (sAD), most of APP mutations, and controls. We compared Aβ and tau pathologies in postmortem brain tissues across cases and Aβ peptides using mass spectrometry (MS). We further characterized the spatial distribution of Aβ peptides with MS-brain imaging. While intraparenchymal Aβ deposits were numerous in sAD, DS with AD (DS-AD) and AD with APP mutations, these were less abundant in APPdup. On the contrary, Aβ deposits in the blood vessels were abundant in APPdup and DS-AD while only APPdup cases displayed high Aβ deposits in capillaries. Investigation of Aβ peptide profiles showed a specific increase in Aβx-37, Aβx-38 and Aβx-40 but not Aβx-42 in APPdup cases and to a lower extent in DS-AD cases. Interestingly, N-truncated Aβ2-x peptides were particularly increased in APPdup compared to all other groups. This result was confirmed by MS-imaging of leptomeningeal and parenchymal vessels from an APPdup case, suggesting that CAA is associated with accumulation of shorter Aβ peptides truncated both at N- and C-termini in blood vessels. Altogether, this study identified striking differences in the localization and composition of Aβ deposits between AD cases, particularly APPdup and DS-AD, both carrying three genomic copies of the APP gene. Detection of specific Aβ peptides in CSF or plasma of these patients could improve the diagnosis of CAA and their inclusion in anti-amyloid immunotherapy treatments. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an autosomal recessive disease associated with alterations in mitochondrial DNA (mtDNA). The typical age of onset of MNGIE is between the first and second decade of life. Diagnosis requires the presence of several key clinical features: sensorimotor neuropathy, external ophthalmoplegia, ocular ptosis, leukoencephalopathy, and gastrointestinal (GI) dysmotility. Unfortunately, MNGIE diagnosis is very challenging, and patients often undergo multiple diagnostic and surgical operations that are unnecessary. Case presentation: This case is of a 51-year-old male presenting with a 2-year history of limb weakness, GI problems and cachexia. There was also a 1-year history of progressive ptosis and ophthalmoplegia. The patient's uncle and brother had both died from GI-related issues prior to the age of 40. On physical examination, ocular motility was impaired in all directions and there was atrophy and reduction in power in both lower and upper extremities. FLAIR and T2-weighted sequences of brain MRI demonstrated diffuse cerebral white matter hyperintensity (leukoencephalopathy). On discharge, the patient was referred for genetic consultation for bone marrow transplantation and had regular follow-up with a gastroenterology specialist. Conclusion: In patients presenting with chronic progressive ophthalmoplegia, severe gastrointestinal complications, sensorimotor neuropathy and white matter lesions on MRI, it is important to consider investigating for MNGIE. [ABSTRACT FROM AUTHOR]

Introduction: There is an increasing need for a reproducible and sensitive outcome measure in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy (PN) due to the emergence of disease modifying therapies. In the current study, we aimed to investigate the role of quantitative muscle ultrasound (QMUS) as a disease biomarker in ATTRv-PN. Methods: Twenty genetically confirmed ATTRv amyloidosis patients (nine symptomatic, 11 pre-symptomatic) were enrolled prospectively between January to March 2023. Muscle ultrasound was performed on six muscles at standardized locations. QMUS parameters included muscle thickness (MT) and muscle echo intensity (EI). Twenty-five age- and sex-matched healthy controls were recruited for comparison. Significant QMUS parameters were correlated with clinical outcome measures. Results: Muscle volume of first dorsal interosseus (FDI) muscle [measured as cross-sectional area (CSA)] was significantly lower in symptomatic patients compared to healthy controls and pre-symptomatic carriers (98.3 ± 58.0 vs. 184.4 ± 42.5 vs. 198.3 ± 56.8, p < 0.001). EI of biceps and FDI for symptomatic ATTRv-PN patients were significantly higher compared to the other two groups (biceps: 76.4 ± 10.8 vs. 63.2 ± 11.5 vs. 59.2 ± 9.0, p = 0.002; FDI: 48.2 ± 7.5 vs. 38.8 ± 7.5 vs. 33.0 ± 5.3, p < 0.001). CSA of FDI and EI of biceps and FDI correlated with previous validated outcome measures [polyneuropathy disability score, neuropathy impairment score, Karnofsky performance scale, Rasch-built overall disability scale, European quality of life (QoL)-5 dimensions and Norfolk QoL questionnaire—diabetic neuropathy]. Conclusion: QMUS revealed significant difference between ATTRv amyloidosis patients and healthy controls and showed strong correlation with clinical outcome measures. QMUS serves as a sensitive and reliable biomarker of disease severity in ATTRv-PN. [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]

Metachromatic leukodystrophy (MLD) is a neuro-metabolic disorder due to arylsulfatase A deficiency, causing demyelination of the central and peripheral nervous system. Hematopoietic cell transplantation (HCT) can provide a symptomatic and survival benefit for pre-symptomatic and early symptomatic patients by stabilizing CNS disease. This case series, however, illustrates the occurrence of severely progressive polyneuropathy shortly after HCT in two patients with late-infantile, one with late-juvenile, and one with adult MLD, leading to the inability to walk or sit without support. The patients had demyelinating polyneuropathy before HCT, performed at the ages of 2 years in the first two patients and at 14 and 23 years in the other two patients. The myeloablative conditioning regimen consisted of busulfan, fludarabine and, in one case, rituximab, with anti-thymocyte globulin, cyclosporine, steroids, and/or mycophenolate mofetil for GvHD prophylaxis. Polyneuropathy after HCT progressed parallel with tapering immunosuppression and paralleled bouts of infection and graft-versus-host disease (GvHD). Differential diagnoses included MLD progression, neurological GvHD or another (auto)inflammatory cause. Laboratory, electroneurography and pathology investigations were inconclusive. In two patients, treatment with immunomodulatory drugs led to temporary improvement, but not sustained stabilization of polyneuropathy. One patient showed recovery to pre-HCT functioning, except for a Holmes-like tremor, for which a peripheral origin cannot be excluded. One patient showed marginal response to immunosuppressive treatment and died ten months after HCT due to respiratory failure. The extensive diagnostic and therapeutic attempts highlight the challenge of characterizing and treating progressive polyneuropathy in patients with MLD shortly after HCT. We advise to consider repeat electro-neurography and possibly peripheral nerve biopsy in such patients. Nerve conduction blocks, evidence of the presence of T lymphocytes and macrophages in the neuronal and surrounding nerve tissue, and beneficial effects of immunomodulatory drugs may indicate a partially (auto)immune-mediated pathology. Polyneuropathy may cause major residual disease burden after HCT. MLD patients with progressive polyneuropathy could potentially benefit from a more intensified immunomodulatory drug regime following HCT, especially at times of immune activation. [ABSTRACT FROM AUTHOR]

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Creatine kinase (CK) has been associated with neuropathy, but the mechanisms are uncertain. We hypothesized that peripheral nerve function is impaired in subjects with persistent CK elevation (hyperCKemia) compared to age- and sex matched controls in a general population. The participants were recruited from the population based Tromsø study in Norway. Neuropathy impairment score (NIS), nerve conduction studies (NCS) and electromyography (EMG) in subjects with persistent hyperCKemia (n = 113; 51 men, 62 women) and controls (n = 128; 61 men, 67 women) were performed. The hyperCKemia group had higher NIS score than the controls (p = 0.050). NCS of the tibial nerve showed decreased compound motor action potential amplitude (p < 0.001), decreased motor conduction velocity (p < 0.001) and increased F-wave latency (p = 0.044). Also, reduced sensory amplitudes of the median, ulnar, and sural nerves were found. EMG showed significantly increased average motor unit potential amplitude in all examined muscles. CK correlated positively with glycated hemoglobin and non-fasting glucose in the hyperCKemia group, although not when controlled for covariates. The length dependent polyneuropathy demonstrated in the hyperCKemia group is unexplained, but CK leakage and involvement of glucose metabolism are speculated on. [ABSTRACT FROM AUTHOR]

In the last decade, the landscape of treating autoimmune diseases has evolved with the emergence and approval of novel targeted therapies. Several new biological agents offer selective and target-specific immunotherapy and therefore fewer side effects, such as neonatal Fc receptor (FcRn)-targeting therapy. Neonatal Fc receptor-targeted therapies are engineered to selectively target FcRn through various methods, such as Fc fragments or monoclonal anti-FcRn antibodies. These approaches enhance the breakdown of autoantibodies by blocking the immunoglobulin G recycling pathway. This mechanism reduces overall plasma immunoglobulin levels, including the levels of pathogenic autoantibodies, without affecting the other immunoglobulin class immunoglobulin A, immunoglobulin E, immunoglobulin M, and immunoglobulin D levels. Drugs that inhibit FcRn include efgartigimod, rozanolixizumab, batoclimab, and nipocalimab. These medications can be administered either intravenously or subcutaneously. Numerous clinical trials are currently underway to investigate their effectiveness, safety, and tolerability in various neurological conditions, including myasthenia gravis and other neurological disorders such as chronic inflammatory demyelinating polyneuropathy, myositis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. Positive results from clinical trials of efgartigimod and rozanolixizumab led to their approval for the treatment of generalized myasthenia gravis. Additional clinical trials are still ongoing. Neonatal Fc receptor inhibitor agents seem to be well tolerated. Reported adverse events include headache (most commonly observed with efgartigimod and rozanolixizumab), upper respiratory tract infection, urinary tract infection, diarrhea, pyrexia, and nausea. Additionally, some of these agents may cause transient hypoalbuminemia and hypercholesterolemia notably reported with batoclimab and nipocalimab. In this review, we discuss the available clinical data for FcRN inhibitor agents in treating different neurological autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed. Methods: Autonomic and clinical features, quantitative cardiovascular autonomic function, and potential autonomic prognostic markers of disease progression were recorded in a cohort of individuals with hereditary transthyretin amyloidosis and in asymptomatic carriers of TTR variants at disease onset (T0) and at the time of the first quantitative autonomic assessment (T1). The severity of peripheral neuropathy and its progression was stratified with the polyneuropathy disability score. Results: A total of 124 individuals were included (111 with a confirmed diagnosis of hereditary transthyretin amyloidosis, and 13 asymptomatic carriers of TTR variants). Symptoms of autonomic dysfunction were reported by 27% individuals at T0. Disease duration was 4.5 ± 4.0 years [mean ± standard deviation (SD)] at autonomic testing (T1). Symptoms of autonomic dysfunction were reported by 78% individuals at T1. Cardiovascular autonomic failure was detected by functional testing in 75% individuals and in 64% of TTR carriers. Progression rate from polyneuropathy disability stages I/II to III/IV seemed to be shorter for individuals with autonomic symptoms at onset [2.33 ± 0.56 versus 4.00 ± 0.69 years (mean ± SD)]. Conclusions: Cardiovascular autonomic dysfunction occurs early and frequently in individuals with hereditary transthyretin amyloidosis within 4.5 years from disease onset. Cardiovascular autonomic failure can be subclinical in individuals and asymptomatic carriers, and only detected with autonomic function testing, which should be considered a potential biomarker for early diagnosis and disease progression. [ABSTRACT FROM AUTHOR]

Critical illness survivors commonly face impairments, such as intensive care unit-acquired weakness (ICUAW) which is characterized by muscle weakness and sensory deficits. Despite these symptoms indicating potential balance deficits, systematic investigations and validated assessments are lacking. Therefore, we aimed to assess balance function using the Mini-BESTest, evaluate its psychometric properties, and identify associated variables. Balance was assessed post-ICU discharge (V1) and at discharge from inpatient neurorehabilitation (V2) in patients with ≥ 5 days of invasive ventilation. Mini-BESTest measurement characteristics were evaluated in an ambulatory subgroup. A multiple linear regression was conducted. The prospective cohort study comprised 250 patients (34% female, 62 ± 14 years, median ICU stay 55 days). Median Mini-BESTest scores improved significantly from V1 (5 (IQR 0–15)) to V2 (18.5 (10–23)) with a large effect size. Excellent inter-rater and test–retest reliabilities of the Mini-BESTest were observed (ICC = 0.981/0.950). Validity was demonstrated by a very high correlation with the Berg Balance Scale (ρ = 0.90). No floor or ceiling effects were detected. Muscle strength, cognitive function, cerebral disease, critical illness polyneuropathy/myopathy, and depression were significantly associated with balance. Despite significant improvements during the rehabilitation period, balance disorders were prevalent in critical illness survivors. Ongoing therapy is recommended. Due to its excellent psychometric properties, the Mini-BESTest is suitable for use in critical illness survivors. Registration: The study was registered at the German Clinical Trials Register (DRKS00021753, date of registration: 2020-09-03). [ABSTRACT FROM AUTHOR]

This article is a case report published in the Journal of Neurology. It describes the medical history and clinical findings of a 66-year-old male patient who was suspected of having Guillain-Barré syndrome (GBS). The patient had rapidly progressive tetraparesis, leg pareses, and urinary and fecal incontinence. The patient had a previous diagnosis of angioimmunoblastic T cell lymphoma (AITL) and had received chemotherapy. The article discusses the diagnostic procedures, therapy, and further course of the patient's condition. The authors highlight the complexity of diagnosing polyneuropathy in lymphoma patients and the importance of considering AITL in autoimmune phenomena. [Extracted from the article]

Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide directed to TTR, which is being developed by Ionis Pharmaceuticals and AstraZeneca for the treatment of TTR-mediated amyloidosis (ATTR). Eplontersen, which is targeted to the liver by a ligand containing three N-acetyl galactosamine residues, binds to wild-type and variant TTR mRNA, thus reducing the levels of circulating TTR protein and amyloid deposition. Subcutaneous eplontersen reduced serum TTR levels, inhibited neuropathy progression and improved health-related quality of life in patients with polyneuropathy of hereditary ATTR (ATTRv-PN; v for variant) in a phase III trial. Based on these results, eplontersen was approved in the USA for the treatment of ATTRv-PN on 21 December 2023 and is currently undergoing regulatory review for a similar indication in the EU, the UK, Switzerland and Canada. Eplontersen is also undergoing phase III development for ATTR cardiomyopathy. This article summarizes the milestones in the development of eplontersen leading to this first approval for ATTRv-PN. [ABSTRACT FROM AUTHOR]

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration. [ABSTRACT FROM AUTHOR]

Background: Neurological complications, including peripheral polyneuropathy, have been reported in β-thalassemia patients that negatively impact their quality of life. Chronic hypoxia, iron overload, average age, and iron chelators-induced neurotoxicity might contribute to the development of neuropathy. However, the leading offender of this complication remains not clear. We aimed to study the frequency and potential risk factors of polyneuropathy in β-thalassemia patients. We performed a cross-section study on 150 transfusion-dependent β-thalassemia major patients with a mean age of 16.44 ± 3.32 years. We performed electrophysiological studies for motor and sensory nerves. Results: We found that 31.3% of cases had neurological manifestations with significant relation to age, duration of the disease, and frequent transfusion. Out of 47 patients with neurological manifestations, 12 (25.5%) had abnormal nerve conduction velocity (NCV). Abnormal median, peroneal, and tibial nerve motor amplitudes were detected in 10.6%, 10.6%, and 14.9% of patients respectively. Abnormal median, peroneal, and sural nerve sensory amplitudes were detected in 4.3%, 2.2%, and 10.6% of patients respectively. Apart from a significant relation between abnormal NCV and older ages, no significant relation was detected with other studied clinical and laboratory parameters. Conclusion: We detected a high frequency of motor and sensory polyneuropathy in B-thalassemia patients. Polyneuropathy was predominately detected in older ages highlighting that neuropathy in thalassemia patients is probably age-dependent. Other factors including disease duration, transfusion frequency, and iron overload might have a contributing effect, however, that could not be confirmed in this study. Further studies are needed to verify the frequency and predictors of polyneuropathy in B-thalassemia patients. [ABSTRACT FROM AUTHOR]

Background: The recreational use of nitrous oxide (N2O) has gained popularity over recent years. We present a case series of excessive N2O users with neurological complications. Methods: In this retrospective three-centre study, we used a text mining algorithm to search for patients who used N2O recreationally and visited a neurologist. Results: We identified 251 patients. The median duration of N2O use was 11 months (interquartile range [IQR], 3–24) and the median amount of N2O used per occasion 1.6 kg (IQR 0.5–4.0). Clinically, polyneuropathy (78%), myelopathy (41%), and encephalopathy (14%) were the most common diagnoses. An absolute vitamin B12 deficiency of < 150 pmol/L was found in 40% of cases. In 90%, at least one indicator of functional vitamin B12 status (vitamin B12, homocysteine, or methylmalonic acid) was abnormal. MRI showed signs of myelopathy in 30/55 (55%) of cases. In 28/44 (64%) of those who underwent electromyography, evidence of axonal polyneuropathy was found. Most (83%) patients were treated with vitamin B12 supplementation, and 23% were admitted to the hospital. Only 41% had follow-up for ≥ 30 days, and 79% of those showed partial or complete recovery. Conclusions: In this case series of excessive N2O users, we describe a high prevalence of polyneuropathy, myelopathy, and encephalopathy. Stepwise testing for serum levels of vitamin B12, homocysteine, and methylmalonic acid may support the clinical diagnosis. Due to low sensitivity, MRI of the spinal cord and electromyography have limited value. Effective treatment should incorporate supplementation of vitamin B12 and strategies to prevent relapses in N2O use. [ABSTRACT FROM AUTHOR]

This document provides a summary of various studies on the neurological side effects associated with targeted therapy (TT) for melanoma. The studies found that neurological adverse events (NAE) were reported in patients receiving TT, particularly those who had previously received immune checkpoint inhibitors (ICI). The NAE observed included conditions such as polyradiculoneuritis, encephalitis/meningoencephalitis, peripheral facial palsy, and sensory-motor axonal polyneuropathy. Treatment for NAE varied, with some patients receiving symptomatic treatment alone, while others received intravenous immunoglobulins or steroids. Most cases of NAE completely recovered or improved after treatment discontinuation. The studies emphasize the importance of accurate diagnosis and management of NAE to minimize long-term effects. [Extracted from the article]

Copyright of Die Urologie is the property of Springer Nature 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.)

This document is a letter to the editor published in the journal Neurological Sciences. The letter discusses a case of a rare syndrome known as "person in the barrel" syndrome, which is characterized by brachial diplegia. The case being reported is unique because it is caused by a traumatic cervical injury, which has not been previously documented. The letter provides a detailed description of the case and highlights the importance of considering traumatic cervical injuries as potential causes of the syndrome. The authors also propose using the gender-neutral term "person in the barrel" instead of "man in the barrel" to be more inclusive. [Extracted from the article]

Background: Previous studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC). Methods: 3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data. Results: The sciatic nerve's MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r = − 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve's MTR peroneal NCV (r = − 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016). Conclusions: Lower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D. Trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT03022721. 16 January 2017. Relevance statement: Magnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes. Key points: • Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients. • Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes. • Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes. [ABSTRACT FROM AUTHOR]

Background Hepatitis "C" virus (HCV) infection has become a growing global health concern. Chronic HCV infection is usually accompanied by extra-hepatic manifestations. Peripheral neuropathies are the most common neurological complications. Electrophysiological tests play an important role in diagnosing polyneuropathy and identifying its pathophysiology. This study aimed at highlighting the sensitivity of non-conventional, quantitative, electrophysiological techniques in the detection of neuropathy in patients having HCV infection. Forty-five HCV patients were recruited for this study. Conventional motor and sensory conduction studies (NCS) were initially performed followed by interference pattern analysis (IPA). Two quantitative nerve conduction scores were also studied: motor amplitude score (MAS) and sensory amplitude score (SAS). Results In the two patients' subgroups (having numbness versus having no numbness), MAS showed a significant difference, while the SAS showed a non-significant difference. In the two subgroups (with normal NCS versus those with abnormal/suspected NCS), the MAS and the SAS mean values were significantly different. Also, there was a positive significant correlation found between the IPA mean amplitude and the SAS parameter. Finally, we presented the results of the diagnostic performance of the MAS and the SAS in detecting abnormal NCS. Conclusions MAS and/or SAS scores could be used as good screening tools for the detection of neuropathy. We here recommend expanding the non-conventional NCSs to other etiologies of polyneuropathy. [ABSTRACT FROM AUTHOR]

Background: Anti-Hu antibody neuropathy is considered a rare acquired peripheral neuropathy, but common among paraneoplastic syndromes. Typically, is described as subacute sensory neuronopathy and electrophysiological findings are usually suggestive of a sensory axonal neuropathy. Case presentation: We report the case of a 67-year-old man referred to our clinic with a 4-month history of progressive pain and paresthesias of distal lower limbs. He had a 30-year history of alcohol abuse and smoking. Alcoholic neuropathy was considered the most likely diagnosis, considering his history and evaluation. The patient's neurological examination revealed symmetric bilateral superficial and deep sensory loss in the lower extremities, reduced Achilles tendon reflexes and wide based gait. Electrophysiological testing was suggestive of axonal sensory-motor polyneuropathy and small fiber involvement. Even though alcohol consumption was discontinued, symptoms gradually worsened. Further testing was performed and the patient was found seropositive for anti-Hu antibody. Small-cell lung cancer was detected later, but patient passed away before treatment for cancer was administrated. Conclusions: The aim of our paper is to report a case of a rare paraneoplastic syndrome that can cause progressive sensory-motor neuropathy with large and small fiber involvement, which should be rapidly differentially diagnosed from other neuropathies, so that the underlying cause can be identified and, potentially, treated. [ABSTRACT FROM AUTHOR]

Background: Vestibular impairment is a common pathology in patients with type 2 diabetes mellitus (DM) due to ischemia of the vestibular end organs and lysis of the myelin of the vestibular nerve. We aimed to evaluate function of the vestibular end organs and vestibular nerve in patients with type 2 DM with polyneuropathy and compare results to those of the patients without polyneuropathy. Method: The participants consisted of three groups: thirty patients with type 2 diabetes mellitus without polyneuropathy (DM), thirty patients with type 2 diabetes mellitus with polyneuropathy (DPN), and thirty healthy non-diabetic individuals as the control group. Clinical examination, videonystagmography, cervical vestibular evoked myogenic potential(cVEMP), ocular vestibular evoked myogenic potential (oVEMP), Gans Sensory Organization Performance (SOP) test, and nerve conduction study were all performed on all groups. Results: P1 and N1 cVEMP latencies and n1 and p1 oVEMP latencies were statistically significantly delayed in both the DM and DPN groups than the control. Also, amplitudes of P1-N1 and n1-p1 were statistically significantly lower in the DM and DPN groups than the control group. DPN patients had longer latencies and lower amplitude of the cVEMP and oVEMP response compared to diabetes patients without neuropathy. There was a statistically significant prevalence of BPPV in the DPN group compared to the control and DM groups. DPN included the following: 4 (13.3%) had vestibular pattern, 12 had polyneuropathic pattern, and 5 (16.7%) had vestibular and polyneuropathic pattern as regards the Gans Sensory Organization Performance (SOP) test. Conclusion: VEMP is considered a promising objective tool in the assessment of the vestibular end organ disorders in patients with type 2 DM with and without polyneuropathy. Diabetics with prominent diabetic polyneuropathy showed higher vestibular impairment than diabetics without DPN, which may increase the risk of falling. [ABSTRACT FROM AUTHOR]

Background: Glial fibrillary acidic protein (GFAP) is expressed by astrocytes in the central nervous system (CNS), but also by immature and regenerative Schwann cells in the peripheral nervous system (PNS). GFAP antibodies (GFAP-Abs) in cerebrospinal fluid (CSF) have been mainly described in patients with meningoencephalomyelitis. We aimed to study PNS symptoms in patients with CSF GFAP-Abs. Methods: We retrospectively included all patients tested positive for GFAP-Abs in the CSF by immunohistochemistry and confirmed by cell-based assay expressing human GFAPα since 2017, from two French reference centers. Results: In a cohort of 103 CSF GFAP-Abs patients, 25 (24%) presented with PNS involvement. Among them, the median age at onset was 48 years and 14/25 (56%) were female. Abnormal electroneuromyography was observed in 11/25 patients (44%), including eight isolated radiculopathies, one radiculopathy associated with polyneuropathy, one radiculopathy associated with sensory neuronopathy, and one demyelinating polyradiculoneuropathy. Cranial nerve involvement was observed in 18/25 patients (72%). All patients except one had an associated CNS involvement. The first manifestation of the disease concerned the PNS in three patients. First-line immunotherapy was administered to 18/24 patients (75%). The last follow-up modified Rankin Scale was ≤ 2 in 19/23 patients (83%). Patients with PNS involvement had significantly more bladder dysfunction than patients with isolated CNS involvement (68 vs 40.3%, p = 0.031). Conclusions: PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease. [ABSTRACT FROM AUTHOR]

Silencing the transthyretin (TTR) gene is an effective strategy in the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. Vutrisiran (Amvuttra®), an RNA interference (RNAi) therapeutic targeting TTR mRNA, is approved in the USA and EU for the treatment of adults with polyneuropathy of hATTR amyloidosis. N-acetylgalactosamine conjugation and enhanced stabilisation chemistry are utilised to target vutrisiran to the liver and increase stability, respectively, allowing for subcutaneous administration once every 3 months. In a pivotal phase 3 study in patients with hATTR amyloidosis with polyneuropathy, subcutaneous vutrisiran 25 mg every 3 months significantly reduced neuropathy impairment versus external placebo. Vutrisiran was also associated with significant improvements in neuropathy-specific quality of life, gait speed, nutritional status and disability scores. Vutrisiran was generally well tolerated; the only common adverse events to occur at a greater incidence than with external placebo were pain in extremity and arthralgia. Vutrisiran reduces serum vitamin A levels and vitamin A supplementation is recommended. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, which has the potential advantage of infrequent subcutaneous dosage. Plain Language Summary: Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive and disabling disease caused by variants in the transthyretin (TTR) gene, which cause destabilisation and misfolding of the TTR protein. Deposition of misfolded TTR protein (amyloid) around nerves causes a range of neuropathic symptoms. Vutrisiran (Amvuttra®) silences the TTR gene via RNA interference (RNAi). Vutrisiran, administered subcutaneously once every 3 months, is approved in the USA and EU for the treatment of polyneuropathy of hATTR amyloidosis in adults. In a phase 3 study in patients with hATTR amyloidosis with polyneuropathy, vutrisiran significantly reduced neuropathy impairment and improved other disease-related outcomes versus external placebo. Vutrisiran was generally well tolerated, with most adverse events being mild or moderate in severity. As vutrisiran decreases vitamin A levels, patients undergoing vutrisiran treatment should supplement with vitamin A. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, with a convenient dosage regimen. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of hereditary ATTR polyneuropathy (ATTRv-PN) is important since treatment options have become available, which are most effective early in the disease course. ATTRv-PN is likely underdiagnosed as patients might be misdiagnosed with idiopathic polyneuropathy. It is uncertain if it is useful to test for TTR gene mutations in patients with a typical presentation for chronic idiopathic axonal polyneuropathy (CIAP) and which are the distinguishing clinical features. Methods: We carried out a retrospective cohort study to assess the yield of TTR gene sequencing in patients with polyneuropathy and assessed if the identified patients with ATTRv-PN had a clinical presentation typical of CIAP. Additionally, we assessed which clinical features, including previously defined red flag symptoms, can differentiate between patients with CIAP and ATTRv-PN and assessed the performance of the TTR suspicion index. Results: Out of 338 patients with polyneuropathy, 10 patients had a pathogenic TTR gene mutation (all p.Val50Met) and none had a clinical presentation typical of CIAP. Patients with ATTRv-PN more often had bilateral CTS, motor involvement of arms, cardiac involvement, family history suggestive of hATTRv, and autonomic symptoms than patients with CIAP. All patients with ATTRv-PN as well as 70% of patients with CIAP fulfilled the suspicion index. Conclusion: Routine TTR gene sequencing in patients with a typical presentation for CIAP is not useful. However, red flag symptoms can differentiate patients with ATTRv-PN from patients with CIAP. We propose an adjusted version of the TTR suspicion index to increase diagnostic yield. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary transthyretin (ATTRv; v for variant) amyloidosis, also known as hATTR amyloidosis, is a progressive and fatal disease associated with rapid deterioration of physical function and patients' quality of life (QOL). Vutrisiran, a subcutaneously administered RNA interference (RNAi) therapeutic that reduces hepatic production of transthyretin, was assessed in patients with ATTRv amyloidosis with polyneuropathy in the pivotal HELIOS-A study. Methods: The phase 3 open-label HELIOS-A study investigated the efficacy and safety of vutrisiran in patients with ATTRv amyloidosis with polyneuropathy, compared with an external placebo group from the APOLLO study of the RNAi therapeutic patisiran. Measures of QOL and physical function were assessed. Results: At month 18, vutrisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score (least squares mean difference [LSMD] in change from baseline [CFB]: –21.0; p = 1.84 × 10–10) and Norfolk QOL-DN domain scores, compared with external placebo. This benefit relative to external placebo was evident across all baseline polyneuropathy disability (PND) scores and most pronounced in patients with baseline PND scores I–II. Compared with external placebo, vutrisiran also demonstrated benefit in EuroQoL-Visual Analog Scale (EQ-VAS) score (LSMD in CFB: 13.7; nominal p = 2.21 × 10–7), 10-m walk test (LSMD in CFB: 0.239 m/s; p = 1.21 × 10–7), Rasch-built Overall Disability Score (LSMD in CFB: 8.4; p = 3.54 × 10–15), and modified body mass index (mBMI) (LSMD in CFB: 140.7; p = 4.16 × 10–15) at month 18. Overall, Norfolk QOL-DN, EQ-VAS, and mBMI improved from pretreatment baseline with vutrisiran, whereas all measures worsened from baseline in the external placebo group. At month 18, Karnofsky Performance Status was stable/improved from baseline in 58.2/13.1% with vutrisiran versus 34.7/8.1% with external placebo. Conclusion: Vutrisiran treatment provided significant clinical benefits in multiple measures of QOL and physical function in patients with ATTRv amyloidosis with polyneuropathy. Benefits were most pronounced in patients with earlier-stage disease, highlighting the importance of early diagnosis and treatment. Trial Registration Number: ClinicalTrials.gov: NCT03759379. [ABSTRACT FROM AUTHOR]

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy that typically presents with progressive or relapsing, symmetric, proximal, and distal weakness of upper and lower limbs, sensory involvement of at least two limbs, and decreased or absent deep tendon reflexes. The symptoms of CIDP can be similar to those of other neuropathies, making diagnosis difficult, which can often lead to delays in correct diagnosis and treatment. The updated European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021 guideline outlines a set of diagnostic criteria that help to identify CIDP with high accuracy and provides recommendations for the treatment of CIDP. The aim of this podcast, featuring Dr. Urvi Desai (Professor of Neurology, Wake Forest School of Medicine and Atrium Health Neurosciences Institute Wake Forest Baptist, Charlotte), is to discuss how the new guideline impacts diagnosis and treatment decisions in her everyday clinical practice. Using a patient case study example, the updated guideline recommends assessing a patient for clinical, electrophysiological, and supportive criteria for CIDP, enabling a more straightforward diagnosis of either typical CIDP, a CIDP variant, or an autoimmune nodopathy. A second patient case study highlights how the new guideline no longer considers autoimmune nodopathies as CIDP, as patients with these disorders do not meet hallmark CIDP criteria. This leaves an unmet need in terms of guidance on how to treat this subset of patients. Although the new guideline has not necessarily changed treatment preference in clinical practice, the addition of subcutaneous immunoglobulin (SCIG) into the guideline now better reflects clinical practice. The guideline helps to define and categorize CIDP more simply and consistently, allowing quicker and more accurate diagnosis, leading to a positive impact on treatment response and prognosis. These real-world insights into the diagnosis and management of patients with CIDP could help guide best clinical practice and help facilitate optimization of patient outcomes. [ABSTRACT FROM AUTHOR]

Background: We have aimed to assess whether muscle thickness ultrasound (US) shows differences between patients with chronic inflammatory demyelinating polyneuropathy (CIDP), chronic axonal polyneuropathy (CAP), and other neuromuscular (NM) diseases compared to controls and to each other. Methods: We performed a cross-sectional study from September 2021 to June 2022. All subjects underwent quantitative sonographic evaluation of muscle thickness in eight relaxed muscles and four contracted muscles. Differences were assessed using multivariable linear regression, correcting for age and body mass index (BMI). Results: The study cohort consisted of 65 healthy controls, and 95 patients: 31 with CIDP, 34 with CAP, and 30 with other NM diseases. Both relaxed and contracted muscle thickness in all patient groups were lower than in the healthy controls, after controlling for age and body mass index (BMI). Regression confirmed that the differences persisted between patient groups and healthy controls. Differences between patient groups were not apparent. Conclusion: The current study shows that muscle ultrasound thickness is not specific in NM disorders, but shows a global reduction in thickness compared with healthy controls after corrections for age and BMI. [ABSTRACT FROM AUTHOR]

Background and Objective: Variants of the transthyretin (TTR) gene cause hereditary transthyretin-mediated (hATTR) amyloidosis, or ATTRv amyloidosis (v for variant), which results from deposition of misfolded TTR protein as amyloid in organs and tissues. Patisiran is an RNA interference (RNAi) therapeutic that suppresses the hepatic production of TTR protein. Patisiran improves multiple clinical manifestations of hATTR amyloidosis in patients without liver transplantation (LT). Because the liver is the predominant source of circulating TTR, LT has been prescribed to eliminate the production of the variant TTR. However, the continued production of wild-type TTR can contribute to disease progression after LT. Patisiran could potentially address an unmet need in these affected patients. This clinical trial was conducted to evaluate the safety, efficacy, and pharmacokinetics (PK) and pharmacodynamics (PD) of patisiran in patients with hATTR amyloidosis with polyneuropathy progression after LT. In this paper, we describe the PK/PD of patisiran in post-LT patients and compare it with prior patisiran studies in healthy subjects and patients without LT. Methods: In an open-label study, patients (N = 23) with hATTR amyloidosis with polyneuropathy progression after LT received 0.3 mg/kg patisiran intravenously every 3 weeks (q3w) for 12 months. As a post hoc analysis, the PK and PD results from the current study were compared with prior patisiran studies in healthy volunteers from a Phase 1 study and in patients with hATTR amyloidosis without LT from Phase 2 and 3 studies. Results: The PK profile of patisiran siRNA (ALN-18328) and its 2 lipid excipients, DLin-MC3-DMA and PEG2000-C-DMG, in hATTR amyloidosis patients after LT was consistent with prior patisiran studies in non-LT subjects. Plasma PK profiles of ALN-18328 and DLin-MC3-DMA exhibited 2 phases, the first characterized by a short distribution half-life and the second by a minor peak and relatively long elimination half-life. The plasma concentrations of PEG2000-C-DMG reached Cmax at the end of infusion and declined in a multiphasic manner. There was no appreciable accumulation at steady state. Consistent with prior studies in non-LT subjects, the post-LT patients showed a robust, and sustained TTR reduction; with median TTR reduction from baseline of 91% (average of Month 6 and Month 12). No anti-drug antibodies were observed in any patient. Conclusions: The consistency of patisiran PK and PD between patients with and without LT suggests that neither LT nor concomitantly administered immunosuppressants influence hepatic uptake or RNAi activity of patisiran. The patisiran dosing regimen of 0.3 mg/kg q3w is appropriate for hATTR amyloidosis patients with or without LT. Clinical Trial Registration No: NCT03862807. [ABSTRACT FROM AUTHOR]

Objectives. To study the efficacy of the drug Cytoflavin in patients with diabetic polyneuropathy (DPN) by assessing the blood tumor necrosis factor-α (TNF-α) concentration. Materials and methods. An open, comparative, prospective observation of patients with a history of DPN for more than five years and high blood TNF-α levels was carried out. All patients received basic oral combined hypoglycemic therapy; patients in group 1 received Cytoflavin (10 ml per 200 ml 0.9% sodium chloride i.v.) for 10 days, followed by switching to oral Cytoflavin, 2 tablets twice a day for one month. The main indication for the use of Cytoflavin was the presence of cerebrovascular disease in all the patients studied. The severity of the clinical manifestations of DPN and patients' quality of life (QoL) were assessed, and TNF-α levels were determined as an indicator of inflammation. Results. Cytoflavin use was associated with increases in quality of life indicators, decreases in the severity of sensory disturbances, and decreases in TNF-α levels, which may indicate a possible anti-inflammatory mechanism of action for this drug. Conclusions. Use of Cytoflavin can inhibit inflammation and reduce the severity of sensory disorders in patients with DPN. [ABSTRACT FROM AUTHOR]

Organophosphates (OP) are one of the most common neurotoxic xenobiotics. In acute OP poisoning, as a result of suppression of synaptic acetylcholinesterase (AChE) activity, a cholinergic syndrome develops, which can transform into status epilepticus. Within a few days after acute poisoning, the so-called an intermediate syndrome can develop, which is associated with prolonged inhibition of AChE, desensitization of nicotinic receptors, and functional degradation of synapses and muscle fibers. In 10–20 days after a single acute or repeated subacute poisoning, OP-induced delayed polyneuropathy (OPIDN) can develop—a neurodegenerative disease, the signs of which are ataxia, loss of function of the distal sensory and motor axons of peripheral nerves. The occurrence of a neuropsychiatric disorder (NPD) caused by chronic exposure to relatively low-toxicity organophosphorus compounds is usually not associated with acute poisoning; symptoms include cognitive impairment, chronic fatigue, and extrapyramidal symptoms. The list of possible diseases or pathological conditions (syndromes) that develop as a result of acute, subacute or chronic effects of OP on the human body has expanded in recent years due a number of known neurodegenerative diseases (Alzheimer's, Parkinson's, multiple sclerosis, etc.). The aging of the body in general and the aging of the brain in particular are considered in the review from the point of view of the consequences of OP poisoning, which can serve as a nonspecific trigger of aging and related neurodegenerative diseases. Gulf syndrome is not a consequence of OP intoxication, but is also of interest and is considered in the context of OP-induced pathology, since its etiology and pathogenesis are associated with the exposure to cholinesterase inhibitors. The review presents data indicating the important role of the vascular endothelium in the development of OP-induced pathology; The first suggestions were made by clinicians in the late 1980s, and the first experimental data were obtained in the early 2000s. The principles of therapy for acute poisoning are outlined, taking into account experimental data from recent years. Some methods for studying OP in experiments in vitro, ex vivo and in vivo with laboratory animals, including the use of carboxylesterase inhibitors, are presented. The most important part of in vivo investigations has been and remains the search for new biomarkers to assess the effectiveness of adjuvant and regenerative therapies. [ABSTRACT FROM AUTHOR]

Background and aims: Although dysautonomia is a well-recognized complication of acute demyelinating polyradiculoneuropathy, it is rarely reported and evaluated in chronic demyelinating neuropathies. The purpose of this review is to search and synthesize the current literature on the prevalence and type of autonomic dysfunction (AD) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods: PubMed and Web of Science were searched for studies reporting AD in CIDP. Results: Twelve studies, including 346 patients with CIDP, were found eligible for the review. Seven studies used autonomic tests only as an additional component of the comprehensive clinical evaluation, and found that dysautonomia in CIDP may indicate the presence of a comorbid disease (e.g., diabetes) and facilitate the differentiation of CIDP from other neuropathies (e.g., amyloid neuropathy). Five studies performed quantitative assessment of autonomic function in CIDP as a primary goal. Two studies have used the Composite Autonomic Severity Score (CASS) to assess severity and distribution of dysautonomia. The reported prevalence of dysautonomia in CIDP during quantitative assessment of autonomic function ranged from 25 to 89%, depending on the battery of tests used, with CASS not exceeding 4 points. The abnormalities in autonomic tests indicated both sympathetic and parasympathetic dysfunction and did not correlate with the duration, severity and variant of CIDP. Conclusions: Clinical or subclinical involvement of the ANS has been shown to be common and relatively mild in CIDP. The impact of autonomic impairment on disability and of its possible response to therapy in CIDP needs to be further investigated. [ABSTRACT FROM AUTHOR]

Pain-related evoked potentials with concentric surface electrodes (PREP with CE) have been increasingly used in the diagnostics of polyneuropathies as well as in pain research. However, the study results are partly inconsistent regarding their utility to distinguish between normal and abnormal findings. The present systematic review aimed to summarise and compare study results, where PREP with CE were used in healthy subjects or patients and to identify possible influencing factors. We found 36 research articles, of which 21 investigated disorders in patients compared to healthy controls, while the other 15 focussed on basic research in healthy subjects. Patients with polyneuropathies showed the most consistent PREP results with similar prolonged latencies and reduced amplitude values. Findings in other patient groups or in healthy subjects were more heterogeneous. There was evidence for an influence by age and height as well as by central effects like emotions, which should be considered in further studies. Further systematic research analysing PREP results depending on individual and disease-specific factors is needed to develop optimal normative values. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy may cause serious complications such as foot ulcers and Charcot joint which can prevent by early diagnosis. We aimed to analyze the diagnostic value of ultrasonographic measurements of nerves and muscles in distal symmetric axonal polyneuropathy (DSAP). Study included 51 DSAP patients and 51 controls. Nerve conduction studies were performed. Median, ulnar, tibial, superficial peroneal, and sural nerves and the abductor pollicis brevis (APB), abductor digiti minimi (ADM), first dorsal interosseous (FDI), extensor digitorum brevis (EDB), abductor hallucis (AH) and tibialis anterior (TA) muscles were evaluated with ultrasound. The Toronto clinical scoring system (TCSS) was used to assess the severity of neuropathy. The median, ulnar, and tibial nerve cross-sectional areas (CSA) were higher in the DSAP group (p = 0.025, p = 0.011, p < 0.001 respectively) while superficial peroneal and sural nerve CSAs were not differed. Only AH and EDB ultrasonographic findings from the muscles differed between the two groups. Effect of diabetes and DSAP on sonographic findings were assessed with two-way ANOVA. Results indicated that only DSAP had a significant effect on sonographic nerve and muscle examination. The area under the ROC curve was 0.831 ± 0.042 for tibial nerve CSA (p < 0.001) with a cut-off value of 15.5 mm2 (sensitivity 74% and specificity 83%). Median, ulnar and tibial nerve CSAs were found to be larger in polyneuropathy patients and they were associated with the clinical and electrophysiological severity of polyneuropathy. ROC analysis showed that tibial nerve CSA may have a predictive value in the diagnosis of DSAP. [ABSTRACT FROM AUTHOR]

This study compared the clinical outcomes of the two main neurophysiological types of Guillain-Barré Syndrome (GBS). Sixty-two GBS patients were examined clinically at onset using Medical Research Council (MRC), Hughes disability scales (HDS), and nerve conduction studies were evaluated in four limbs. The Modified Erasmus GBS outcome score (MEGOS) was assessed 2 weeks after onset. Outcomes were measured after 3 months using MRC and HDS scores. According to electrophysiological data two main groups identified acute inflammatory demyelinating polyneuropathy (AIDP = 31 cases) or acute axonal GBS including inexcitable forms (26 cases). The number of days between onset of weakness and admission was significantly shorter, and gastrointestinal symptoms were significantly higher among the axonal type than AIDP. MRC sum scores at onset and at nadir were significantly worse in the axonal type than in AIDP. Neck muscle weakness, impaired cough reflex, the need for mechanical ventilation, hypoalbuminemia, and hypernatremia were more common in the axonal type. At outcome, 74% of the AIDP were healthy/minor symptoms versus 38.46% of the axonal type. There was a high prevalence of the axonal variant (41.9%) compared with European and North American populations. The axonal type had a significantly worse outcome than AIDP type. [ABSTRACT FROM AUTHOR]

Intensive care unit-acquired weakness (ICUAW) is one of the most common neuromuscular complications in intensive care medicine. The clinical diagnosis and assessment of the severity using established diagnostic methods (e.g., clinical examination using the Medical Research Council Sum Score or electrophysiological examination) can be difficult or even impossible, especially in sedated, ventilated and delirious patients. Neuromuscular ultrasound (NMUS) has increasingly been investigated in ICUAW as an easy to use noninvasive and mostly patient compliance-independent diagnostic alternative. It has been shown that NMUS appears to be a promising tool to detect ICUAW, to assess the severity of muscular weakness and to monitor the clinical progression. Further studies are needed to standardize the methodology, to evaluate the training effort and to optimize outcome predication. The formulation of an interdisciplinary neurological and anesthesiological training curriculum is warranted to establish NMUS as a complementary diagnostic method of ICUAW in daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: Intravenous immune globulin (IVIg) is frequently used in some neurological diseases and is also the first-line therapy in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. We aimed to evaluate the frequency and characteristics of headaches, which is one of the most common side effects of IVIg treatment. Methods: Patients who received IVIg treatment for neurological diseases were prospectively enrolled in 23 centers. Firstly, the characteristics of patients with and without IVIg-induced headaches were analyzed statistically. Then, patients with IVIg-induced headaches were classified into three subgroups determined by their history: no primary headache, tension-type headache (TTH), and migraine. Results: A total of 464 patients (214 women) and 1548 IVIg infusions were enrolled between January and August 2022. The frequency of IVIg-related headaches was 27.37% (127/464). A binary logistic regression analysis performed with significant clinical features disclosed that female sex and fatigue as a side effect were statistically more common in the IVIg-induced headache group. IVIg-related headache duration was long and affected daily living activities more in patients with migraine compared to no primary headache and TTH groups (p = 0.01, respectively). Conclusion: Headache is more likely to occur in female patients receiving IVIg and those who develop fatigue as a side effect during the infusion. Clinicians' awareness of IVIg-related headache characteristics, especially in patients with migraine, may increase treatment compliance. [ABSTRACT FROM AUTHOR]

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare progressive or relapsing inflammatory disease. Intravenous immunoglobulin (IVIG) is recommended as a first-line therapy. The aim of this study was to describe real-world treatment patterns and outcomes of patients with CIDP in the Define initiating IVIG treatment. Methods: This cohort study used health insurance claims data from the Merative MarketScan Research Databases (2008–2018). Adult patients (≥ 18 years old) with CIDP without prior immunoglobulin treatment were identified using International Statistical Classification of Diseases and Related Health Problems (ICD) codes, and patients subsequently initiating IVIG were included in the analysis. Real-world IVIG treatment patterns and treatment and safety outcomes (assessed via ICD codes) were described. Results: In total, 3975 patients (median age 58 years) with CIDP who initiated IVIG were identified. After the initial IVIG loading period, patients received IVIG at a median dosing interval of 21 days (quartile [Q]1, Q3: 7, 28), and continued treatment for a median of 129 days (Q1, Q3: 85, 271). After the 2-year follow-up period, 55% of patients had discontinued all IVIG treatment; more than one-half of these discontinuations occurred within 4 months. Diagnoses of impaired functional status were evident in more than 30% of patients at baseline, but at lower rates during follow-up. Rates of new-onset safety outcomes after IVIG treatment were low. Conclusion: This real-world analysis of IVIG treatment patterns and treatment and safety outcomes of patients with CIDP who initiated IVIG highlights the unmet need for improved long-term management. Further research is needed to evaluate the use of functional status measures as endpoints for immunoglobulin treatment effectiveness. Plain Language Summary: Chronic inflammatory demyelinating polyradiculoneuropathy, also called CIDP, is a rare disease that causes the body's immune system to attack its nerves. Treatments for CIDP include antibodies, which are also called immunoglobulins. Immunoglobulins may be given intravenously, meaning they are administered into a vein. Intravenous immunoglobulin, also called IVIG, is recommended as one of the first treatments that patients with CIDP receive in their therapy and involves giving antibodies through a drip into a vein. This study aimed to gather information on the day-to-day use of IVIG by patients with CIDP. Information from 2008 to 2018 was collected from a large health insurance database in the USA. Information was taken from the records of patients aged 18 years or older who had received IVIG during the information collection period. In total, records from 3975 patients with an average age of 58 years were included in the study. On average, patients received IVIG every 21 days for 129 days. By 2 years, 55% of patients had stopped receiving IVIG; most of those patients had stopped within 4 months of first receiving the treatment. In the 6 months before receiving IVIG, over 30% of patients experienced limitations owing to their CIDP that affected their daily lives, although this percentage became smaller once patients started to receive IVIG. In addition, a low number of patients experienced side effects because of their IVIG treatment. This study highlights that improved long-term care for patients with CIDP is needed. Further research into ways of measuring the impact of CIDP on patients' daily lives is required, which may help doctors to work out how effective IVIG is at treating CIDP. [ABSTRACT FROM AUTHOR]

Introduction: Intravenous immunoglobulin (IVIG) is recommended as first-line therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), an immune-mediated neuropathy. The clinical profile of patients with CIDP newly initiating IVIG is poorly characterized. This claims-based cohort study describes characteristics of US patients with CIDP initiating IVIG treatment. Methods: Adult immunoglobulin (IG)-naïve patients with CIDP diagnosed between 2008 and 2018 and a subgroup of patients subsequently initiating IVIG were identified in the Merative MarketScan Research Databases. Demographics, clinical characteristics, and diagnostic procedures were described for patients initiating IVIG. Results: Of 32,090 patients with CIDP identified, 3975 (mean age 57 years) subsequently initiated IVIG. In the 6 months prior to IVIG initiation, diagnoses of comorbidities including neuropathy (75%), hypertension (62%), and diabetes (33%) were frequent, as were CIDP features/symptoms/markers of functional status including chronic pain (80%), difficulty walking (30%), and weakness (30%). CIDP-related laboratory/diagnostic procedures were performed in approximately 20– > 40% of patients in the 3 months prior to IVIG initiation (63.7% underwent electrodiagnostic/nerve conduction testing in the 6 months prior to IVIG initiation). Patient characteristics by initial IVIG product differed only in IVIG initiation year, US geographic region, and insurance type. Comorbidities, CIDP severity or functional status markers, and other clinical variables were generally well balanced across initial IVIG product groups. Conclusion: A heavy burden of symptoms, comorbidities, and diagnostic testing exists in patients with CIDP initiating IVIG. Characteristics of patients with CIDP initiating different IVIG products are well balanced, suggesting an absence of clinical or demographic determinants underlying IVIG selection. Plain Language Summary: Intravenous immunoglobulin, also called IVIG, involves giving antibodies through a drip into a vein. IVIG is recommended as one of the first treatments that patients receive if they have chronic inflammatory demyelinating polyradiculoneuropathy, also called CIDP, which is a rare disease that causes the body's immune system to attack its nerves. Our study described the characteristics of patients with CIDP who received IVIG in the USA. Information was collected from a large health insurance database and included records of patients aged ≥ 18 years who were diagnosed with CIDP between 2008 and 2018. Overall, 3975 patients with CIDP who received IVIG were included in the study. In the 6 months before starting IVIG, patients frequently had diagnoses of other diseases in addition to their CIDP; these included neuropathy (75% of patients), hypertension (62%), and diabetes (33%). CIDP features and symptoms that affected patients' daily lives were also frequently reported in these 6 months, including long-lasting pain (80%), difficulty walking (30%), and weakness (30%). In the 3 months before starting IVIG treatment, 20% to > 40% of patients underwent diagnostic procedures related to their CIDP. Different IVIG products were used similarly, but the year of IVIG initiation, geographic region, and insurance type all differed by IVIG product. In conclusion, patients with CIDP who receive IVIG experience a heavy burden caused by their symptoms, other diseases, and CIDP-related procedures. Patient characteristics were generally similar between patients receiving different IVIG products, suggesting that no specific characteristics are factored in when doctors select an IVIG product. [ABSTRACT FROM AUTHOR]

Cardiac autonomic neuropathy (CAN), widely assessed by heart rate variability (HRV), is a common complication of long-term diabetes. We hypothesized that HRV dynamics during tonic cold pain in individuals with type 1 diabetes mellitus (T1DM) could potentially demask CAN. Forty-eight individuals with long-term T1DM and distal symmetrical polyneuropathy and 21 healthy controls were included. HRV measures were retrieved from 24-h electrocardiograms. Moreover, ultra-short-term HRV recordings were used to assess the dynamic response to the immersion of the hand into 2 °C cold water for 120 s. Compared to healthy, the T1DM group had expectedly lower 24-h HRV measures for most components (p < 0.01), indicating dysautonomia. In the T1DM group, exposure to cold pain caused diminished sympathetic (p < 0.001) and adynamic parasympathetic (p < 0.01) HRV responses. Furthermore, compared to healthy, cold pain exposure caused lower parasympathetic (RMSSD: 4% vs. 20%; p = 0.002) and sympathetic responses (LF: 11% vs. 73%; p = 0.044) in the T1MD group. QRISK3-scores are negatively correlated with HRV measures in 24-h and ultra-short-term recordings. In T1DM, an attenuated sympathovagal response was shown as convincingly adynamic parasympathetic responses and diminished sympathetic adaptability, causing chronometric heart rhythm and rigid neurocardiac regulation threatening homeostasis. The findings associate with an increased risk of cardiovascular disease, emphasizing clinical relevance. [ABSTRACT FROM AUTHOR]

Background: Despite the primary myelin-related pathophysiology, small fiber neuropathy (SFN) and axonal degeneration are also considered to be involved and associated with disabling symptoms and impaired quality of life in chronic inflammatory demyelinating polyneuropathy (CIDP). Demonstration of SFN usually requires complex or invasive investigations. Objects: In vivo corneal confocal microscopy (IVCCM) has evolved as a non-invasive, easily applied method for quantification of small fiber involvement in peripheral nerve disorders. We aimed to investigate the potential role of IVCCM in CIDP. Methods: In this cross-sectional study, 15 patients with CIDP underwent assessment with clinical disability scales, neuropathic pain (NP) and autonomic symptom questionnaires, nerve conduction studies, and IVCCM. IVCCM parameters were analyzed and compared to those from 32 healthy controls. Results: Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) were significantly decreased in the CIDP group, compared to those in controls (p = 0.03 and p = 0.024, respectively). Langerhans cells and fiber tortuosity were increased in CIDP patients (p = 0.005 and p = 0.001, respectively). IVCCM parameters were significantly lower in patients with NP compared to those in patients without NP. Conclusion: IVCCM shows promise as a non-invasive complementary biomarker in the assessment of demyelinating polyneuropathies, providing insights into the potential pathophysiology of these non-length-dependent neuropathies. [ABSTRACT FROM AUTHOR]

Postmenopausal status is a risk factor for distal sensory polyneuropathy—the most common type of peripheral neuropathy. We aimed to investigate associations between reproductive factors and history of exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States using data from the National Health and Nutrition Examination Survey 1999–2004, and to explore the modifying effects of ethnicity on these associations. We conducted a cross-sectional study among postmenopausal women aged ≥ 40 years. Women with a history of diabetes, stroke, cancer, cardiovascular disease, thyroid disease, liver disease, weak or failing kidneys, or amputation were excluded. Distal sensory polyneuropathy was measured using a 10-g monofilament test, and a questionnaire was used to collect data on reproductive history. Multivariable survey logistic regression was used to test the association between reproductive history variables and distal sensory polyneuropathy. In total, 1144 postmenopausal women aged ≥ 40 years were included. The adjusted odds ratios were 8.13 [95% confidence interval (CI) 1.24–53.28] and 3.18 (95% CI 1.32–7.68) for age at menarche < 11 years and time since menopause > 20 years, respectively, which were positively associated with distal sensory polyneuropathy; adjusted odds ratios were 0.45 for the history of breastfeeding (95% CI 0.21–0.99) and 0.41 for exogenous hormone use (95% CI 0.19–0.87) were negatively associated. Subgroup analysis revealed ethnicity-based heterogeneity in these associations. Age at menarche, time since menopause, breastfeeding, and exogenous hormone use were associated with distal sensory polyneuropathy. Ethnicity significantly modified these associations. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to formulate an effective therapeutic candidate against V30M mutant transthyretin (TTR) protein to hinder its pathogenic misfolding. Nicotiana alata Defensin 1 (NaD1) Antimicrobial Peptide (AMP) was availed due to its tendency to aggregate, which may compete for aggregation-prone regions of pathogenic TTR protein. Based on NaD1's potential to bind to V30M TTR, we proposed NaD1-derived tetra peptides: CKTE and SKIL to be initial therapeutic candidates. Based on their association with mutant TTR protein, CKTE tetra peptide showed considerable interaction and curative potential as compared to SKIL tetra peptide. Further analyses from discrete molecular dynamics simulation corroborate CKTE tetra peptide's effectiveness as a 'beta-sheet breaker' against V30M TTR. Various post-simulation trajectory analyses suggested that CKTE tetra peptide alters the structural dynamics of pathogenic V30M TTR protein, thereby potentially attenuating its beta-sheets and impeding its aggregation. Normal mode analysis simulation corroborated that V30M TTR conformation is altered upon its interaction with CKTE peptide. Moreover, simulated thermal denaturation findings suggested that CKTE-V30M TTR complex is more susceptible to simulated denaturation, relative to pathogenic V30M TTR; further substantiating CKTE peptide's potential to alter V30M TTR's pathogenic conformation. Moreover, the residual frustration analysis augmented CKTE tetra peptide's proclivity in reorienting the conformation of V30M TTR. Therefore, we predicted that the tetra peptide, CKTE could be a promising therapeutic candidate in mitigating the amyloidogenic detrimental effects of V30M TTR-mediated familial amyloid polyneuropathy (FAP). [ABSTRACT FROM AUTHOR]