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The prevalence of chronic polyneuropathy will increase due to the aging population, and therefore, it becomes ever so important to optimize the diagnostic process. However, it is uncertain which blood tests are required and when nerve conduction studies (NCS) should be done in the workup of chronic polyneuropathy. We aimed to investigate the methodology used to develop national polyneuropathy guidelines and to provide an overview and strength of evidence of the recommendations. We searched PubMed and websites of national neurological associations as listed on the website of the World Federation of Neurology to identify national guidelines pertaining to the workup of chronic polyneuropathy by neurologists in an outpatient clinic setting. We identified three national guidelines in the United States and seven national guidelines in Denmark, France, Germany, the Netherlands, Norway, Spain, and Turkey. The methodology used to develop the guidelines differed greatly. All guidelines recommend a series of blood tests. Some guidelines advise to conduct NCS in all patients, while other guidelines advise to conduct NCS when certain symptoms are present. There is variation in recommendations about the extensiveness of NCS, but all mention measuring the sural nerve and the motor peroneal nerve. The evidence for the recommendations is graded as low. Despite some overlap, there are disparities between guidelines regarding the workup that is advised to do in patients with chronic polyneuropathy. It remains unclear which combination of blood tests are to be strongly recommended. Furthermore, it is undetermined whether NCS are always necessary. [ABSTRACT FROM AUTHOR]

Background and Aims: Ultrasound nerve cross‐sectional area (CSA) of patients affected with axonal neuropathy usually shows normal value. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) seems to represent an exception, showing smaller CSA, but previous reports did not test for biallelic RFC1 gene repeat expansions. Methods: We compared nerve CSA from CANVAS patients (tested positive for biallelic RFC1 gene repeat expansions) with the CSA from a group of patients with chronic idiopathic axonal polyneuropathy (CIAP) who tested negative for RFC1 gene repeat expansions, hereditary axonal neuropathy (Charcot‐Marie‐Tooth type 2, CMT2), and Friedreich ataxia (FRDA). Results: We enrolled 15 CANVAS patients (eight men, mean age 66.3 ± 11.5 years, mean disease duration 9.3 ± 4.1 years), affected with sensory axonal neuronopathy. Controls consisted of 13 CIAP (mean age 68.5 ± 12.8 years, seven men), seven CMT2 (mean age 47.9 ± 18.1 years, four men), 12 FRDA (mean age 33.7 ± 8.8, five men). Nerve ultrasound was performed at median, ulnar, sciatic, sural, and tibial nerves and brachial plexus, bilaterally. The nerve CSA from CANVAS patients was significantly smaller than the one from the other cohorts at several sites with significant and high accuracy at Receiver‐operating characteristic (ROC) curve analyses. RFC1 AAGGG pentanucleotide expansion, disease duration, and disability did not correlate with CSA at any site, after Bonferroni correction. Interpretation: Decreased sonographic nerve sizes, in arms and legs, in patients with sensory neuropathy and normal motor conduction studies could point to CANVAS‐spectrum disease and help guide appropriate genetic testing. [ABSTRACT FROM AUTHOR]

Background: Hereditary transthyretin amyloidosis (ATTRv) is a hereditary disease that affects multiple bodily systems. Although sonography generally reveals enlargement of nerves in the limbs, the brachial plexus, and vagus nerve, the clinical significance of these findings remains unclear. Methods: We performed sonographic measurements of the median nerve, cervical spinal nerves at the C5–C7 level, and the vagus nerve in patients with ATTRv and healthy controls. Clinical profiles and cardiac and gastrointestinal examination results were also collected for linear regression analysis. Results: We recruited 47 patients with ATTRv (males/females: 34/13, age: 65.6 ± 5.3 years). The sampled segments were all significantly larger than those of the controls. In the clinical profiles, the sum of the Z scores of the neck triangle nerves (cervical spinal nerves and vagus nerve) and of all nerves (cervical spinal nerves, vagus nerve, and median nerve at the wrist) significantly correlated with the familial amyloid polyneuropathy stage, onset of autonomic nervous system (ANS) symptoms, and autonomic symptom scores. On cardiac examinations, several ultrasonography and magnetic resonance imaging parameters (primarily those that reflect heart volume) were found to be significantly correlated with the sum of the Z scores of the cervical spinal nerves but not with the Z score of the vagus nerve. In gastrointestinal evaluation, the cross‐sectional area of the vagus nerve was correlated with gastric emptying time parameters on scintigraphy. Conclusions: Neck triangle nerve enlargement on sonography correlated with parameters related to ANS dysfunction, indicating that nerve enlargement observed on ultrasonography may serve as a potential surrogate biomarker of ATTRv. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction/Aims Methods Results Discussion Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a paraneoplastic syndrome due to an underlying plasma cell dyscrasia. Polyneuropathy in POEMS syndrome may present as a subacute or chronic symmetric sensorimotor polyneuropathy, with electrophysiological features suggesting demyelination. Motor conduction block (CB), which is mostly seen in chronic inflammatory demyelinating polyneuropathy (CIDP), is considered an atypical electrophysiological feature in POEMS syndrome. We examined the frequency of motor CB in POEMS syndrome.Patients with POEMS syndrome from the database of our department who had been examined between August 2017 and December 2022 were included in this study. All of the patients' clinical and electrophysiological data were retrospectively collected and analyzed.We present the data of seven POEMS syndrome patients. Twenty‐eight upper extremity motor nerve conduction studies were performed on these patients, and partial CB was detected in seven upper extremity motor nerves (25%) of six of the patients. One patient had motor CB in both the median and ulnar nerves.The distinction between POEMS syndrome and CIDP is important since these conditions require different treatments. Motor CB in POEMS may be more common than has been generally believed. Clinicians should consider this when evaluating patients with demyelinating polyneuropathies and be meticulous in identifying CB. Data from much larger numbers of patients are needed. [ABSTRACT FROM AUTHOR]

Background: Gabapentin, a widely prescribed medication for various neuropathic pain conditions, has demonstrated efficacy in managing diverse neurological disorders. While conventional side effects are well‐documented, a growing body of evidence suggests the existence of atypical side effects, necessitating comprehensive exploration. This paper aims to systematically review and summarize the literature on the atypical side effects of gabapentin, shedding light on manifestations beyond the conventional spectrum. Methods: A systematic review was conducted, encompassing peer‐reviewed articles published up to the knowledge cutoff date in November 2023. Databases, specifically PubMed, were searched for relevant studies, focusing on atypical side effects such as myoclonus, ataxia, pediatric aggression, respiratory depression, pneumonia, pregnancy complications, sleep interference, encephalopathy, peripheral edema, suicidal ideation, dyskinesia, anorgasmia, and myopathy. Inclusion criteria comprised studies with a focus on gabapentin‐related atypical side effects, published in recognized journals and involving human subjects. Results: The review identified a spectrum of atypical side effects associated with gabapentin use, ranging from neurological manifestations like myoclonus and ataxia to behavioral changes such as pediatric aggression and suicidal ideation. Additionally, respiratory complications, pregnancy‐related issues, sleep disturbances, and rare complications like encephalopathy and myopathy were observed. Literature synthesis provided insights into the incidence, clinical presentation, and potential mechanisms underlying these atypical side effects. Conclusion: This comprehensive review highlights the diverse range of atypical side effects associated with gabapentin use, expanding beyond conventional knowledge. Healthcare practitioners must be cognizant of these manifestations, recognizing their potential impact on patient well‐being. As clinical decision‐making relies on a thorough understanding of a medication's side effect profile, this review contributes to enhancing awareness and fostering informed practices in the prescription and management of gabapentin. Further research is warranted to elucidate the mechanisms and risk factors associated with these atypical side effects, refining our understanding of gabapentin's safety profile. [ABSTRACT FROM AUTHOR]

The article discusses a case of α‐Methylacyl‐CoA racemase (AMACR) deficiency in a 56-year-old female with unique neurological features, including ataxia, spasticity, and segmental dystonia. AMACR deficiency is a rare disorder characterized by elevated levels of certain acids and can manifest in adulthood or the neonatal period. The patient's diagnosis was confirmed through genetic testing and laboratory findings, highlighting the importance of considering AMACR deficiency in patients with undiagnosed cerebellar ataxia and seizure. The article emphasizes the need for timely diagnosis and appropriate management in such cases. [Extracted from the article]

Objectives Methods Results Conclusions IgPro20, a subcutaneous immunoglobulin replacement therapy, is approved in Japan for chronic inflammatory demyelinating polyneuropathy (CIDP). This post‐marketing surveillance study characterized real‐world treatment patterns and safety profile of injection site reactions associated with IgPro20 treatment in Japanese patients with CIDP.Patients with CIDP initiating IgPro20 between October 2019 and September 2022 at medical institutions in Japan were followed for 6 months. The primary outcome was the incidence of injection site reactions. Other outcomes included patient clinicodemographic characteristics, IgPro20 treatment status, CIDP‐related concomitant medications and any concurrent therapies.The analysis included 108 patients from 38 sites. CIDP subtypes were typical (61.1%), multifocal acquired demyelinating sensory and motor neuropathy (multifocal; 19.4%), others (14.8%) or unknown (4.6%). Approximately one‐fifth (21.3%) of patients commenced IgPro20 at a dosage of <200 mg/kg, 27.8% at ≥200 to ≤300 mg/kg, 37.0% at >300 to ≤400 mg/kg and 11.1% at >400 mg/kg. Most doses (82.7%) were given at home: 62.0% self‐administered, 11.7% with caregiver and 8.9% with healthcare professional assistance. A total of 55 patients used CIDP‐related concomitant medications, including corticosteroids (35.2%), immunosuppressants (19.4%) or intravenous immunoglobulin G (7.4%). The data also showed that various treatment patterns were used for these combinations. A total of 40 patients (37.0%) experienced injection site reactions, most frequently injection site erythema (21.3%) and injection site swelling (17.6%); one case of ulcer occurred (0.9%). No significant relationship between injection dosage/speed and the incidence of injection site reactions was observed.This study of the use of subcutaneous IgPro20 for CIDP in Japan showed a real‐world safety profile consistent with phase III trial data. [ABSTRACT FROM AUTHOR]

Introduction: The revised international standards for neurological classification of spinal cord injury (ISNCSCI) have facilitated the documentation of non‐spinal cord injury‐related impairments, such as chronic peripheral nerve injuries and muscle weakness due to immobility. This advancement addresses potential biases in muscle strength examinations. Utilizing electrically evoked contractions from paralyzed muscles, enhanced by electrodiagnosis, holds promise in identifying false‐negative diagnoses of non‐responsiveness to neuromuscular electrical stimulation. This concept prompts the exploration of polyneuromyopathy arising from nonuse in paralyzed muscles. Case Series Presentation: To substantiate our hypothesis, we recruited nine participants for a case series aimed at elucidating the potential benefits of incorporating the stimulus electrodiagnostic test (SET) to mitigate non‐responsiveness during preparation for functional electrical stimulation (FES)‐assisted cycling. In our convenience sample (n = 5), we conducted neurological mapping based on ISNCSCI and applied SET on the quadriceps. The SET guided optimal dosimetry for evoking contractions and revealed responses similar to those observed in peripheral neuropathies, with α coefficients equal to or lower than 2.00. This observation is likely attributable to nonuse of paralyzed muscles, indicative of an ongoing polyneuropathy in individuals with chronic spinal cord injury (SCI). Discussion: Among the nine initially recruited subjects, seven exhibited responsiveness to neuromuscular electrical stimulation (78% responsiveness), with two participants excluded based on exclusion criteria. In the final five reported cases, all displayed α coefficient values indicating impaired neuromuscular accommodation, and one presented no α coefficient within the normal range. The inclusion of electrodiagnosis appears effective in averting non‐responsiveness, suggesting the presence of ongoing polyneuropathies in paralyzed muscles. [ABSTRACT FROM AUTHOR]

The article in "Movement Disorders Clinical Practice" discusses a case of a 49-year-old man with unilateral upper-limb tremor linked to C6 radiculopathy and demyelinating neuropathy. The patient experienced left-arm tremors triggered by elbow flexion, along with sensory symptoms in the feet. Treatment with onabotulinumtoxinA improved the tremor significantly. The study suggests that the tremor's origin was peripheral due to C6 nerve root pathology and coexistent multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). [Extracted from the article]

Background and purpose: The amplitude, timing, and determinants of improvement with available treatments are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Our primary objective was to quantify categorized outcomes with routine care. Methods: We retrospectively studied treatment response within 36 months from initiation in 112 consecutive subjects with CIDP. Response was classified into a proposed new "CIDP treatment‐response category" (CT‐RC), based on achieved endpoints. Determinants of the CT‐RC, of timing of maximum improvement, and of treatment discontinuation were ascertained. Results: The CT‐RC demonstrated high concurrent validity with current outcome measures. Thirty‐six subjects (32.1%) achieved a "complete response," 37 (33%) a "good partial response," 10 (8.9%) a "moderate partial response," and 15 (13.4%) a "poor partial response." Fourteen subjects (12.5%) were "nonresponsive." The CT‐RC was independently predicted only by age. Mean time to maximum improvement was 12.1 months (range = 1–36) and was not associated with any pretreatment covariate. Treatment discontinuation occurred in 24 of 62 (38.2%) partial responders and was only associated with shorter pretreatment disease duration. Nonresponders were older and received a similar number of treatments compared to responders. Conclusions: CT‐RC classification indicates persistent disability in >60% of treatment responders in CIDP. Timing of maximum improvement is variable, frequently delayed, and unpredictable. Treatment withdrawal without deterioration is achievable in approximately 40% of subjects and may be more likely with prompt treatment. Treatment withdrawal in partial responders and limited escalation in nonresponders suggest implication of physician‐ and patient‐related factors in suboptimal response. More effective treatments/treatment methods and better understanding of other factors influencing response are needed in CIDP. [ABSTRACT FROM AUTHOR]

Objectives: Hereditary transthyretin (TTR) amyloidosis (ATTRv) is frequently complicated by polyneuropathy (ATTRv‐PN) and cardiomyopathy (ATTRv‐CM). The long‐term efficacy of diflunisal on both polyneuropathy and cardiomyopathy in ATTRv patients, especially those with non‐V30M genotypes, has not been fully investigated and compared with that of tafamidis. Methods: We compared the structural and biochemical characteristics of A97S‐TTR complexed with tafamidis with those of diflunisal, and prospectively followed up and compared the progression of polyneuropathy and cardiomyopathy between ATTRv‐PN patients taking diflunisal and those taking tafamidis. Results: Both diflunisal and tafamidis effectively bind to the two thyroxine‐binding sites at the A97S‐TTR dimer–dimer interface and equally and almost sufficiently reduce amyloid fibril formation. Thirty‐five ATTRv‐PN patients receiving diflunisal and 22 patients receiving tafamidis were enrolled. Compared with no treatment, diflunisal treatment significantly delayed the transition of FAP Stage 1 to 2 and Stage 2 to 3 and decreased the deterioration in parameters of the ulnar nerve conduction study (NCS). The progression of FAP stage or NCS parameters did not differ between patients treated with diflunisal and those treated with tafamidis. Both diflunisal and tafamidis treatments significantly decreased radiotracer uptake on 99mTc‐PYP SPECT and stabilized cardiac wall thickness and blood pro‐B‐type natriuretic peptide levels. No significant adverse events occurred during diflunisal or tafamidis treatment. Interpretations: The binding patterns of both tafamidis and diflunisal to A97S‐TTR closely resembled those observed in the wild type. Diflunisal can effectively delay the progression of polyneuropathy and cardiomyopathy with similar efficacy to tafamidis and may become a cost‐effective alternative treatment for late‐onset ATTRv‐PN. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 30-year-old man with slowly progressive gait disturbances and imbalance since childhood. The patient also developed slurred speech and had high levels of blood cholesterol. Clinical examination revealed a wide-based gait, areflexia, and decreased vibration sense in the lower limbs, but no oculomotor apraxia. Brain MRI showed cerebellar atrophy and dentate nuclei abnormalities. Genetic testing identified a compound heterozygous mutation in the APTX gene, which is associated with ataxia with oculomotor apraxia type 1 (AOA1). The patient's phenotype was milder than typical AOA1 cases, possibly due to the specific genotype. The study highlights the importance of considering AOA1 as a diagnosis even without oculomotor apraxia, especially when suggestive brain MRI findings are present. [Extracted from the article]

Objective: To evaluate the efficacy and safety of a low‐dose, long‐term rituximab regimen in the treatment of idiopathic CIDP. Methods: This study included 15 CIDP patients treated with rituximab. Patients were administered 600 mg of rituximab intravenously every 6 months. Baseline evaluation was conducted before the initiation of rituximab treatment and subsequent evaluations were conducted 6 months after each rituximab infusion at on‐site visits. Clinical improvement was objectively determined by improvement of scale score at least decrease ≥1 INCAT or mRS or increase ≥4 MRC or ≥8 cI‐RODS after each infusion compared to baseline evaluation. Results: Fifteen CIDP patients were included and 10 of them were typical CIDP and five were distal CIDP. Nine in 15 (60%) patients after first infusion and three in six (50%) patients after second infusion exhibited significant clinical improvement compared to baseline evaluation. Additionally, rituximab facilitated a reduction or cessation of other medications in 73% of patients at last visit. The safety profile was favorable, with no reported adverse events. Conclusion: Rituximab presents a promising therapeutic option for idiopathic CIDP, offering both efficacy and safety with a low‐dose, long‐term regimen. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Patients affected by chronic inflammatory demyelinating polyradiculoneuropathy require close follow up due to the neuronal demyelination along with axonal degeneration associated with the disease process, giving the opportunity to the medical team of adequating therapeutics and other medical interventions, according to the evolution of the symptoms, to prevent irreversible axonal degeneration. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) have shown a change in the prognosis of multiple malignancies, but a wide range of immune‐related adverse events (irAE) can occur. We present a case of a 72‐year‐old Caucasian male treated with Durvalumab for epidermic lung cancer, who developed a sclerosis‐like syndrome and myositis. The patient was admitted to our hospital with respiratory failure due to muscular weakness and pulmonary hypertension. Differential diagnoses pointed to scleroderma secondary to ICI. We report a rare case of ICI‐induced axonal polyneuropathy, myopathy and RNA polymerase III positive scleroderma. As this therapy is widely recommended, adverse effects may become more frequent. Early identification and treatment are warranted. We report a rare case of ICI‐induced axonal polyneuropathy, myopathy and RNA polymerase III positive scleroderma. As this therapy is widely recommended, adverse effects may become more frequent. Early identification and treatment are warranted. [ABSTRACT FROM AUTHOR]

Guillain–Barré Syndrome (GBS) is an acute polyneuropathy commonly preceded by infection, with growing recognition of the human immunodeficiency virus (HIV) as a trigger. We present a case of a 44‐year‐old male with HIV‐associated GBS refractory to intravenous immunoglobulin (IVIG) therapy, who achieved remission upon starting highly active antireroviral therapy (HAART). There remains a lack of consensus on the management of this condition across the spectrum of disease, and the interplay between the therapeutic options is poorly understood. This report aims to add to the current body of knowledge on this rare condition and highlight the need for retrospective analysis of the currently available literature. [ABSTRACT FROM AUTHOR]

The article discusses the concept of post-intensive care syndrome (PICS), which refers to the new or worsening health impairments that occur after a critical illness and persist beyond hospitalization. PICS can affect physical, cognitive, and mental health, and it can have a significant impact on daily functioning, quality of life, and ability to return to work. The article emphasizes the need for healthcare professionals to focus on optimal survivorship for critical care patients, considering both morbidity and mortality. It also highlights the challenges in quantifying and addressing PICS due to the lack of standardized outcome measures and the heterogeneity of critical care patient populations. The article calls for further research, education, and support to minimize the burden of PICS and improve recovery for critical care survivors. [Extracted from the article]

Background and purpose: Peripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV‐induced neuropathy (BV‐CN) is a mild distal sensory axonal polyneuropathy. Severe BV‐induced inflammatory neuropathies (BV‐IN) have been described. BV‐IN contribute to lymphoma‐associated morbidity but might be immunotherapy‐responsive. Our primary objective was to evaluate the rate of BV‐IN. Our secondary objectives were to determine risk factors and warning signs. Methods: We conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV‐induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV‐IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV‐CN. Results: Among 83 patients, 41 (49%) developed neuropathy: 35 BV‐CN and 6 BV‐IN. Thus, the rate of BV‐IN was 7.2%. Compared to patients with BV‐CN, no predisposing factor was identified. However, patients with BV‐IN more frequently presented muscle weakness (67% vs. 5.7%, p < 0.05), gait disorders (83% vs. 20%, p < 0.05), or acute or subacute onset (67% vs. 14%, p < 0.05). BV‐IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%, p < 0.05). Four patients were treated with immunotherapy. Conclusions: Brentuximab vedotin‐induced neuropathy is an overlooked complication. Based on four easily identifiable "red flags", we provide an algorithm to help non‐neurologist physicians that care for BV‐treated patients to detect BV‐IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy. [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]

Aims: We recently reported that genetic variability in the TKT gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent‐onset diabetes. Here, we aimed to substantiate these findings in a population‐based KORA F4 study. Materials and Methods: In this cross‐sectional study, we assessed seven single nucleotide polymorphisms (SNPs) in the transketolase gene in 952 participants from the KORA F4 study with normal glucose tolerance (NGT; n = 394), prediabetes (n = 411), and type 2 diabetes (n = 147). DSPN was defined by the examination part of the Michigan Neuropathy Screening Instrument (MNSI) using the original MNSI > 2 cut‐off and two alternative versions extended by touch/pressure perception (TPP) (MNSI > 3) and by TPP plus cold perception (MNSI > 4). Results: After adjustment for sex, age, BMI, and HbA1c, in type 2 diabetes participants, four out of seven transketolase SNPs were associated with DSPN for all three MNSI versions (all p ≤ 0.004). The odds ratios of these associations increased with extending the MNSI score, for example, OR (95% CI) for SNP rs62255988 with MNSI > 2: 1.99 (1.16–3.41), MNSI > 3: 2.27 (1.26–4.09), and MNSI > 4: 4.78 (2.22–10.26); SNP rs9284890 with MNSI > 2: 2.43 (1.42–4.16), MNSI > 3: 3.46 (1.82–6.59), and MNSI > 4: 4.75 (2.15–10.51). In contrast, no associations were found between transketolase SNPs and the three MNSI versions in the NGT and prediabetes groups. Conclusions: The link of genetic variation in transketolase enzyme to diabetic polyneuropathy corroborated at the population level strengthens the concept suggesting an important role of pathways metabolising glycolytic intermediates in the evolution of diabetic polyneuropathy. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN). Materials and Methods: Cross‐sectional analyses were based on 1032 participants aged 61–82 years from the population‐based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1‐SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini–Hochberg procedure. Results: Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), pB‐H = 0.044) and PDGFRα (platelet‐derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), pB‐H = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM‐B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all pB‐H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all pB‐H>0.05). Conclusions: This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination. [ABSTRACT FROM AUTHOR]

Neuromuscular ultrasound is a painless, radiation‐free, high‐resolution imaging technique for assessing the peripheral nervous system. It can accurately depict changes in the nerves and muscles of individuals with neuromuscular conditions, and it is therefore a robust diagnostic tool for the assessment of individuals with polyneuropathies. This review will outline the typical ultrasonographic changes found in a wide variety of polyneuropathies. In general, demyelinating conditions result in greater nerve enlargement than axonal conditions, and acquired conditions result in more patchy nerve enlargement compared to diffuse nerve enlargement in hereditary conditions. This review is data‐driven, but more nuanced anecdotal findings are also described. The overall goal of this paper is to provide clinicians with an accessible review of the ultrasonographic approaches and findings in a wide variety of polyneuropathies. [ABSTRACT FROM AUTHOR]

Background: ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded transthyretin protein (TTR). Small nerve fiber neuropathy is an early clinical manifestation of this disease resulting from the dysfunction of the Aδ and C small nerve fibers. Tafamidis, a selective TTR stabilizer, has proven its efficacy in the earlier stages of hATTR. Objectives: To evaluate the clinical course and utility of cutaneous pathological biomarkers in patients with ATTR amyloidosis treated with tafamidis compared to control patients. Methods: Forty patients diagnosed with early stages of ATTRv amyloidosis (polyneuropathy disability [PND] scores 0‐II) underwent small and large nerve fiber neurological evaluations, and annual skin biopsies for intraepidermal nerve fiber density (IENFD) and amyloid deposition index (ADI) estimation. Thirty patients were allocated to receive tafamidis, and 10 patients served as controls. Tafamidis pharmacokinetics analysis was performed in patients who received the treatment. Results: At baseline, 12% of patients in stage PND 0 and 28% in PND I displayed small nerve fiber denervation in the distal thigh, whereas 23% and 38%, respectively, in the distal leg. Similarly, 72% and 84% had amyloid deposition in the distal thigh and 56% and 69% in the distal leg. Following 1 year of treatment, the tafamidis group showed significant clinical improvement compared to the control group, revealed by the following mean differences (1) −9.3 versus −4 points (p = <.00) in the patient's neuropathy total symptom score 6 (NTSS‐6) questionnaire, (2) −2.5 versus +2.8 points (p = <.00) in the Utah Early Neuropathy Score (UENS), and (3) +1.2°C versus −0.6 (p =.01) in cold detection thresholds. Among the patients who received tafamidis, 65% had stable or increased IENFD in their distal thigh and 27% in the distal leg. In contrast, all patients in the control group underwent denervation. The ADI either decreased or remained constant in 31% of the biopsies in the distal thigh and in 24% of the biopsies in the distal leg of the tafamidis‐treated patients, whereas it rose across all the biopsies in the control group. At the 4‐year follow‐up, the tafamidis group continued to display less denervation in the distal thigh (mean difference [MD] of −3.0 vs. −9.3 fibers/mm) and the distal leg (mean difference [MD] −4.9 vs. −8.6 fibers/mm). ADI in tafamidis‐treated patients was also lower in the distal thigh (10 vs. 30 amyloid/mm2) and the distal leg (23 vs. 40 amyloid/mm2) compared to control patients. Plasma tafamidis concentrations were higher in patients with IENFD improvement and in patients with reduced amyloid deposition. Patients without amyloid deposition in the distal leg at baseline displayed delayed disease progression at 4 years. Conclusions: Cutaneous IENFD and amyloid deposition assessments in the skin of the distal thigh and distal leg are valuable biomarkers for early diagnosis of ATTR amyloidosis and for measuring the progression of small nerve fiber neuropathy. Early treatment with tafamidis slows the clinical progression of the disease, skin denervation, and amyloid deposition in the skin. Higher plasma concentrations of tafamidis are associated with better disease outcomes, suggesting that increasing the drug dose could achieve better plasma concentrations and response rates. This study describes the longest small nerve fiber neuropathy therapeutic trial with tafamidis and is the first to report small fiber symptoms, function, and structural assessments as outcomes. [ABSTRACT FROM AUTHOR]

Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty‐five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3–71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)‐6, IL‐17, CXCL10, and tumor necrosis factor alpha (TNF‐α), were elevated in CIDP compared to controls in most of the studies. IL‐6 and TNF‐α levels are also correlated with disability. In MMN patients, IL‐1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL‐6, IL‐17, CXCL10, and TNF‐α might play a role in CIDP pathogenesis. Larger studies are needed in MMN. [ABSTRACT FROM AUTHOR]

Background and Aims: To further substantiate the role of antibody‐mediated complement activation in multifocal motor neuropathy (MMN) immunopathology, we investigated the distribution of promotor polymorphisms of genes encoding the membrane‐bound complement regulators CD46, CD55, and CD59 in patients with MMN and controls, and evaluated their association with disease course. Methods: We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of CD46, CD55, and CD59 in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters. Results: The genotype frequencies of rs28371582, a 21‐bp deletion in the CD55 promotor region, were altered in patients with MMN as compared to controls (p.009; Del/Del genotype 16.8% vs. 7.7%, p.005, odds ratio: 2.43 [1.27–4.58]), and patients carrying this deletion had a more favorable disease course (mean difference 0.26 Medical Research Council [MRC] points/year; 95% confidence interval [CI]: 0.040–0.490, p.019). The presence of CD59 rs141385724 was associated with less severe pre‐diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083–1.80, p.032). Interpretation: MMN susceptibility is associated with a 21‐bp deletion in the CD55 promotor region (rs2871582), which is associated with lower CD55 expression. Patients carrying this deletion may have a more favorable long‐term disease outcome. Taken together, these results point out the relevance of the pre‐C5 level of the complement cascade in the inflammatory processes underlying MMN. [ABSTRACT FROM AUTHOR]

Aims/Introduction: This study aimed to investigate the diagnostic potential of two simplified tests, a point‐of‐care nerve conduction device (DPNCheck™) and a coefficient of variation of R‐R intervals (CVR‐R), as an alternative to traditional nerve conduction studies for the diagnosis of diabetic polyneuropathy (DPN) in patients with diabetes. Materials and Methods: Inpatients with type 1 or type 2 diabetes (n = 167) were enrolled. The study population consisted of 101 men, with a mean age of 60.8 ± 14.8 years. DPN severity was assessed using traditional nerve conduction studies, and differentiated based on Baba's classification (BC). To examine the explanatory potential of variables in DPNCheck™ and CVR‐R regarding the severity of DPN according to BC, a multiple regression analysis was carried out, followed by a receiver operating characteristic analysis. Results: Based on BC, 61 participants (36.5% of the total) were categorized as having DPN severity of stage 2 or more. The multiple regression analysis yielded a predictive formula with high predictive power for DPN diagnosis (estimated severity of DPN in BC = 2.258 – 0.026 × nerve conduction velocity [m/s] – 0.594 × ln[sensory nerve action potential amplitude (μV)] + 0.528In[age(years)] – 0.178 × ln[CVR‐R], r = 0.657). The area under the curve in receiver operating characteristic analysis was 0.880. Using the optimal cutoff value for DPN with severer than stage 2, the predictive formula showed good diagnostic efficacy: sensitivity of 83.6%, specificity of 79.2%, positive predictive value of 51.7% and negative predictive value of 76.1%. Conclusions: These findings suggest that DPN diagnosis using DPNCheck™ and CVR‐R could improve diagnostic efficiency and accessibility for DPN assessment in patients with diabetes. [ABSTRACT FROM AUTHOR]

This article presents a case study of a patient with ankylosing spondylitis who developed a severe neurological condition called mononeuritis multiplex after receiving infliximab treatment. The patient also experienced a skin rash and had positive antibodies. The article discusses the adverse effects of anti-TNF-α drugs and emphasizes the importance of early recognition and management of these complications. Additionally, the article presents three cases of mononeuritis multiplex in patients receiving TNFi treatment, highlighting the need to consider potential neurological side effects. [Extracted from the article]

Key Clinical Message: Bing–Neel syndrome (BNS) is a rare manifestation in individuals suffering from Waldenström macroglobulinemia (WM). Neurological signs and symptoms in this syndrome are almost difficult to be differentiated from other common neurological manifestations of hyper‐viscosity or Waldenström‐associated polyneuropathy. In this paper, we report a new case of WM with concurrent BNS, then review the clinical picture and treatment of this syndrome. [ABSTRACT FROM AUTHOR]

Objective: Guillain–Barré Syndrome (GBS) is an autoimmune degenerative disease commonly presenting with acute progressive sensorimotor paralysis, sometimes associated with dysautonomia, facial diplegia and severe respiratory distress. Gastroenteritis due to Campylobacter jejuni and respiratory infection secondary to Epstein–Barr virus usually precede GBS; however, vaccination or recent dengue infection as temporal causes are rarely reported. Case Presentation: Here, we present a 20‐year‐old man, who complained of a 5‐day history of a progressively worsening tingling sensation isolated in the hands and feet, and unilateral Bell's palsy on the left side of his face, which occurred 2 weeks after his severe acute respiratory syndrome coronavirus 2 vaccination and 6 weeks from his recent hospitalization from Dengue fever. Except for the left complete unilateral facial paralysis, weakness in the intrinsic hands and feet muscles, and sensory ataxia, the rest of his physical examination was unremarkable. On work‐up, the findings of albuminocytological dissociation and distal sensorimotor demyelinating polyneuropathy in the nerve conduction study supported the diagnosis of GBS. Conclusion: The enhanced immune response from a recent dengue infection and severe acute respiratory syndrome coronavirus 2 vaccination might increase the risk of GBS. The predominantly distal GBS phenotype has rarely been reported in the literature, adding to the peculiarity of this case. [ABSTRACT FROM AUTHOR]

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

Background and purpose: Clinical symptoms and laboratory indices for acute inflammatory demyelinating polyneuropathy (AIDP), a variant of Guillain−Barré syndrome, and acute‐onset chronic inflammatory demyelinating polyneuropathy (A‐CIDP) were analyzed to identify factors that could contribute to early differential diagnosis. Methods: A retrospective chart review was performed on 44 AIDP and 44 A‐CIDP patients looking for any demographic characteristics, clinical manifestations or laboratory parameters that might differentiate AIDP from acutely presenting CIDP. Results: In Guillain−Barré syndrome patients (N = 63), 69.84% (N = 44) were classified as having AIDP, 19.05% (N = 12) were found to have acute motor axonal neuropathy, 6.35% (N = 4) were found to have acute motor and sensory axonal neuropathy, and 4.76% (N = 3) were found to have Miller Fisher syndrome. Serum uric acid (UA) was higher in A‐CIDP patients (329.55 ± 72.23 μmol/L) than in AIDP patients (221.08 ± 71.32 μmol/L) (p = 0.000). Receiver operating characteristic analyses indicated that the optimal UA cutoff was 283.50 μmol/L. Above this level, patients were more likely to present A‐CIDP than AIDP (specificity 81.80%, sensitivity 81.80%). During the follow‐up process, serum samples were effectively collected from 19 AIDP patients during the rehabilitation phase and 28 A‐CIDP patients during the remission stage, and it was found that UA levels were significantly increased in A‐CIDP (remission) (298.9 ± 90.39 μmol/L) compared with AIDP (rehabilitation) (220.1 ± 108.2 μmol/L, p = 0.009). Conclusion: These results suggest that serum UA level can help to differentiate AIDP from A‐CIDP with high specificity and sensitivity, which is helpful for early diagnosis and guidance of treatment. [ABSTRACT FROM AUTHOR]

The article discusses a cross-sectional observational study on the relationship between oral levodopa therapy, vitamin B6 levels, and peripheral neuropathy in Parkinson's disease patients. The study found that higher levodopa doses were associated with lower B6 levels and increased severity of peripheral neuropathy. Vitamin B12, folic acid, and homocysteine did not show a significant association with peripheral neuropathy. The study suggests further research on B6 supplementation as a potential preventive or therapeutic measure for peripheral neuropathy in levodopa-treated patients. [Extracted from the article]

Background and Aims. Gait impairment is a common manifestation of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, clinicians lack an effective monitoring tool, as no gait test has been validated for CIDP. The aim of this study was to determine the usefulness of three tests in monitoring the clinical course of patients with CIDP: Timed Up and Go (TUG), 10-Meter Walk Test (10MWT), and 30-Second Chair Stand (30SCS). Methods. This is a prospective, single-center observational study. We included newly diagnosed CIDP patients starting treatment or relapsed CIDP patients requiring new treatment. We monitored the clinical course using CIDP-validated clinical scales and correlated changes in clinical status with the results of the gait tests. A ROC curve was developed, and we chose the cut-off point on each scale with the best specificity and sensitivity to detect change in clinical status. Results. A total of 20 patients have been recruited. The 3 tests show a statistical correlation with objective clinical improvement. In patients who have showed clinical improvement during the follow-up examination, a mean reduction of 4.8 seconds in TUG and 2.6 in 10MWT and a gain of 3 repetitions in 30SCS have been observed. The optimal cut-off points for each test were TUG ≤ 1 seconds, 10 MWT ≤ 1 seconds, and 30 SCS ≥ 1 repetition. The TUG test has the highest sensitivity (82.6%), and the 30SCS test has the highest specificity (100%) for detecting clinical improvement. Conclusions. The study found that the TUG and 30SCS tests could become effective tools for monitoring treatment response in CIDP patients. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are a group of drugs that have improved outcomes for patients with various cancers. Generally considered safe and well tolerated, these drugs are occasionally linked to immune-mediated or immune-related adverse events. Among these, autoimmune neurological events are rare, displaying varying incidence rates across different studies. Peripheral neuropathy, although one of the more common neurological immune-related events, is at times underestimated. This case report highlights an adult patient diagnosed with metastatic intrahepatic cholangiocarcinoma. Initially, the patient underwent chemoimmunotherapy with gemcitabine, cisplatin, and durvalumab for eight cycles, achieving partial response without significant toxicity. Following this, the patient continued with maintenance monotherapy with durvalumab every 28 days. After completing six cycles of maintenance therapy, the patient suddenly experienced paresthesia and hypoesthesia in four limbs, accompanied by apraxia in the hands that was more pronounced on the right side. Additionally, the patient reported neuropathic pain in the right arm and encountered limitations in certain instrumental activities of daily living. Diagnostic studies, including laboratory and electrophysiological studies, combined with the clinical presentation, identified immune-related peripheral polyneuropathy. Durvalumab was suspended and prednisolone therapy was initiated, resulting in a rapid resolution of all neuropathic symptoms. In addition to the clinical case, this article reviews the literature on immunotherapy-associated peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background and purpose: Identifying patients with inflammatory motor neuropathies (IMNs) is warranted since effective treatments are available and the prognosis of these patients differs from that of amyotrophic lateral sclerosis patients. Methods: Between January 2019 and May 2022, 102 consecutive treatment‐naïve lower motor neuron syndrome (LMNS) patients were recruited; these patients were suspected of having multifocal motor neuropathy, pure motor chronic inflammatory demyelinating polyneuropathy or amyotrophic lateral sclerosis with initial lower motor neuron presentation. Neuromuscular ultrasound (US) and nerve conduction studies (NCSs) were conducted at baseline. Relevant diagnostic investigations were performed if clinically warranted. The proposed US evidence of IMN was as follows: (i) nerve enlargement at ≥1 of the predetermined sites or (ii) absence of high intensity fasciculations in predefined muscle groups. Final diagnoses were made by experienced physicians after a prolonged follow‐up period (≥12 months). IMN patients were defined as LMNS patients who experienced convincing improvements in response to immunotherapies. IMN patients without electrodiagnostic demyelinating features were diagnosed with treatment‐responsive LMNS (TR‐LMNS). Results: In total, 16 patients were classified as IMN, including nine chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy patients and seven TR‐LMNS patients. Six TR‐LMNS patients were identified by neuromuscular US. The sensitivity and specificity of NCSs, nerve US and muscle US were 56.3% and 100%, 43.8% and 90.7% and 68.8% and 97.7%, respectively. When these three modalities were combined, the sensitivity and specificity were 93.8% and 88.4%, respectively. Conclusion: Neuromuscular US studies are supplementary modalities to NCSs, and the combined use of these techniques might improve the identification of IMNs in LMNS patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease with humoral and cellular autoimmunity causing demyelination of peripheral nerves, commonly treated with intravenous immunoglobulins (IVIg). The neonatal Fc receptor (FcRn), encoded by the FCGRT gene, prevents the degradation of immunoglobulin G (IgG) by recycling circulating IgG. A variable number of tandem repeat (VNTR) polymorphism in the promoter region of the FCGRT gene is associated with different expression levels of mRNA and protein. Thus, patients with genotypes associated with relatively low FcRn expression may show a poorer treatment response to IVIg due to increased IVIg degradation. Methods: VNTR genotypes were analyzed in 144 patients with CIDP. Patients' clinical data, including neurological scores and treatment data, were collected as part of the Immune‐Mediated Neuropathies Biobank registry. Results: Most patients (n = 124, 86%) were VNTR 3/3 homozygotes, and 20 patients (14%) were VNTR 2/3 heterozygotes. Both VNTR 3/3 and VNTR 2/3 genotype groups showed no difference in clinical disability and immunoglobulin dosage. However, patients with a VNTR 2 allele were more likely to receive subcutaneous immunoglobulins (SCIg) than patients homozygous for the VNTR 3 allele (25% vs. 9.7%, p = 0.02) and were more likely to receive second‐line therapy (75% vs. 54%, p = 0.05). Conclusions: The VNTR 2/3 genotype is associated with the administration of SCIg, possibly reflecting a greater benefit from SCIg due to more constant immunoglobulin levels without lower IVIg levels between the treatment circles. Also, the greater need for second‐line treatment in VNTR 2/3 patients could be an indirect sign of a lower response to immunoglobulins. [ABSTRACT FROM AUTHOR]

Background and purpose: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. Methods: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. Results: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory‐predominant CIDP (7%), 10 motor CIDP (3%), and eight motor‐predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F‐wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor‐predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory‐predominant CIDP did. Conclusions: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients. [ABSTRACT FROM AUTHOR]

Background: Accelerated neuropathy is a rare syndrome of rapidly worsening peripheral neuropathy, typically described in end‐stage kidney disease (ESKD) patients undergoing dialysis. In our center, we encountered a surge in the occurrence of accelerated neuropathy among ESKD patients undergoing hemodialysis, which prompted systematic research. Methods: In this case–control study, we present the clinical features, electrophysiologic findings, and outcome of a series of patients who developed accelerated neuropathy after commencing hemodialysis for ESKD. Those who initiated hemodialysis and did not develop accelerated neuropathy were included as controls. We used logistic regression to identify predictors of accelerated neuropathy. Results: Among 436 ESKD patients who initiated hemodialysis over 4 years, 17 were diagnosed with accelerated neuropathy. The median‐time (interquartile range) from hemodialysis initiation to presentation with accelerated neuropathy was 3 weeks (2–6). It typically presented as acute onset of unsteadiness of gait necessitating assistance for ambulation. Electrophysiology revealed length‐dependent symmetric sensorimotor axonal neuropathy. Diabetes mellitus (odds ratio [OR] 4.1, 95% CI 1.2–13.9, p = 0.02), pre‐existing peripheral neuropathy (OR 9.25, 95% CI 2.79–30.6, p < 0.001), and serum alkaline phosphatase (OR 1.2 for every 10 U increase, 95% CI 1.00–1.52, p = 0.04) significantly predicted accelerated neuropathy. With continued dialysis and supportive care, neurologic status improved, total‐neuropathy score (summary score of peripheral nerve dysfunction incorporating clinical and electrophysiological parameters) declined from 26.5 to 18.4 (p < 0.001) and most regained unassisted ambulation. Conclusion: This study presents the largest series of patients with accelerated neuropathy and has identified predictors. However, in view of the unusually high incidence of accelerated neuropathy we speculate that other unidentified factor(s) could be underlying its pathogenesis. [ABSTRACT FROM AUTHOR]

Background: There are limited data relating to the effects of metformin‐associated vitamin B12 deficiency on the risk of distal symmetrical polyneuropathy (DSPN) and megaloblastic anaemia in well‐characterised community‐based cohorts. Aims: To assess inter‐relationships between metformin therapy, vitamin B12 deficiency assessed using serum active B12 concentrations, and DSPN and anaemia in 1492 Fremantle Diabetes Study Phase 2 (FDS2) participants with type 2 diabetes. Methods: Prevalence rates of vitamin B12 deficiency (total <80 pmol/L, active <23 pmol/L) and borderline deficiency (total ≥80 and ≤200 pmol/L, active ≥23 and ≤35 pmol/L) were determined using baseline sera. The relationship between vitamin B12 status and both DSPN and anaemia was assessed using multivariable analyses. Results: Most FDS2 participants (94.4%) were vitamin B12 replete (total serum concentration >200 pmol/L, active >35 pmol/L), 2.0% were deficient (total <80 pmol/L, active <23 pmol/L) and the remainder (3.6%) borderline. Although metformin treatment increased the odds of deficiency (4.2%, 3.1% borderline) in a dose‐dependent fashion (odds ratio (95% confidence interval) 39.4 (4.90–316) for >2000 mg daily compared with no treatment; P < 0.001), there was no significant association between vitamin B12 status and DSPN, anaemia (haemoglobin ≤130 g/L males, ≤120 g/L females), haemoglobin concentration or mean corpuscular volume (P ≥ 0.147). Metformin increased the likelihood of anaemia, especially at high doses, independent of vitamin B12 deficiency. Conclusions: Since nutritional sources likely attenuate metformin‐associated vitamin B12 malabsorption and its clinical sequelae in developed countries such as Australia, there is no need for routine/opportunistic serum vitamin B12 screening in metformin‐treated patients. [ABSTRACT FROM AUTHOR]

Neurofilament light protein (NfL) is a part of the neuronal skeleton, primarily expressed in axons, and is released when nerves are damaged. NfL has been found to be a potential diagnostic biomarker in different types of polyneuropathies. However, whether NfL levels can be used as a predictor for the risk of disease progression is currently less understood. We searched MEDLINE (PubMed), Embase, Cochrane Library, and Web of Science Searches and included longitudinal studies with a baseline and follow‐up examination of adult patients with polyneuropathy and NfL measured in blood. Twenty studies investigating NfL as a predictor of disease progression were identified, examining eight polyneuropathy subtypes. The results from studies in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) patients were divergent, with two out of five studies finding a significant association between NfL levels and clinical outcomes. Meta‐analysis of the three Guillian‐Barré Syndrome (GBS) studies found higher odds for the inability to run after 1 year in patients with high levels of NfL (odds ratio 2.18, 95% confidence interval 1.04–4.56). Results from studies examining other subacute or chronic polyneuropathies like Charcot–Marie–Tooth (CMT) varied in study design and results. Our findings suggest NfL can be used as a predictor of disease progression, particularly in polyneuropathies such as CIDP and GBS. However, NfL may not serve as a reliable and cost‐effective biomarker for slowly progressive polyneuropathies like CMT. Future standardized studies considering NfL as a prognostic blood biomarker in patients with different types of polyneuropathies are warranted. [ABSTRACT FROM AUTHOR]

Aims/Introduction: This prospective cohort study aims to identify the optimal measure of glycated hemoglobin (HbA1c) variability and to explore its relationship with the development of new diabetic sensorimotor polyneuropathy (DSPN) in individuals with type 2 diabetes mellitus, building upon previous cross-sectional studies that highlighted a significant association between HbA1c visit-to-visit variability and DSPN. Materials and Methods: In a prospective study, 321 participants diagnosed with type 2 diabetes mellitus underwent comprehensive clinical assessments, neurophysiologic studies, and laboratory evaluations at enrollment and follow-up. Various indices, including HbA1c standard deviation (HbA1c SD), coefficient of variation (HbA1c CV), HbA1c change score (HbA1c HVS), and average real variability (HbA1c ARV), were employed to calculate the visit-to-visit variability HbA1c based on 3 month intervals. The investigation focused on examining the associations between these indices and the development of new DSPN. Results: The average follow-up duration was 16.9 ± 6.9 months. The Cox proportional hazards model identified age (P = 0.001), diabetes duration (P = 0.024), and HbA1C ARV (P = 0.031) as the sole factors associated with the development of new DSPN. Furthermore, the cumulative risk of developing DSPN over 1 year demonstrated a significant association with HbA1C ARV (P = 0.03, log-rank test). Conclusions: Apart from age and diabetes duration, HbA1c variability emerged as a robust predictor for the occurrence of new DSPN. Among the various measures of HbA1c variability evaluated, HbA1c ARV demonstrated the highest potential as a reliable indicator for anticipating the onset of new DSPN. [ABSTRACT FROM AUTHOR]

Objective: To evaluate magnetic resonance neurography (MRN) for the longitudinal assessment of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods: Prospective examination of twelve CIDP patients by neurological assessment, MRN, and nerve conduction studies in 2016 and 6 years later in 2022. Imaging parameters were compared with matched healthy controls and correlated with clinical and electrophysiological markers. The MRN protocol included T2‐weighted imaging, diffusion tensor imaging (DTI), T2 relaxometry, and magnetization transfer imaging (MTI). Results: Nerve cross‐sectional area (CSA) was increased in CIDP patients compared to controls (plexus: p = 0.003; sciatic nerve: p < 0.001). Over 6 years, nerve CSA decreased in CIDP patients, most pronounced at the lumbosacral plexus (p = 0.015). Longitudinally, changes in CSA correlated with changes in the inflammatory neuropathy cause and treatment validated overall disability sum score (INCAT/ODSS) (p = 0.006). High initial nerve CSA was inversely correlated with changes in the INCAT/ODSS over 6 years (p < 0.05). The DTI parameter fractional anisotropy (FA) showed robust correlations with electrodiagnostic testing both cross‐sectionally and longitudinally (p < 0.05). MTI as a newly added imaging technique revealed a significantly reduced magnetization transfer ratio (MTR) in CIDP patients (p < 0.01), suggesting underlying changes in macromolecular tissue composition, and correlated significantly with electrophysiological parameters of demyelination (p < 0.05). Interpretation: This study provides evidence that changes in nerve CSA and FA reflect the clinical and electrophysiological course of CIDP patients. Initial nerve hypertrophy might predict a rather benign course or better therapy response. [ABSTRACT FROM AUTHOR]

Autoimmune neuropathies are a heterogeneous group of rare and disabling diseases in which the immune system is thought to target antigens in the peripheral nervous system: they usually respond to immune therapies. Guillain–Barré syndrome is divided into several subtypes including "acute inflammatory demyelinating polyradiculoneuropathy," "acute motor axonal neuropathy," "acute motor sensory neuropathy," and other variants. Chronic forms such as chronic inflammatory demyelinating polyneuropathy (CIDP) and other subtypes and polyneuropathy associated with IgM monoclonal gammopathy; autoimmune nodopathies also belong to this group of auto‐immune neuropathies. It has been shown that immunoglobulin G from the serum of about 30% of CIDP patients immunolabels nodes of Ranvier or paranodes of myelinated axons. Whatever the cause of myelin damage of the peripheral nervous system, the initial attack on myelin by a dysimmune process may begin either at the internodal area or in the paranodal and nodal regions. The term "nodoparanodopathy" was first applied to some "axonal Guillain–Barré syndrome" subtypes, then extended to cases classified as CIDP bearing IgG4 antibodies against paranodal axoglial proteins. In these cases, paranodal dissection develops in the absence of macrophage‐induced demyelination. In contrast, the mechanisms of demyelination of other dysimmune neuropathies induced by macrophages are unexplained, as no antibodies have been identified in such cases. The main objective of this presentation is to show that the pathology illustrates, confirms, and may explain such mechanisms. [ABSTRACT FROM AUTHOR]

Aims: HELIOS‐A was a Phase 3, open‐label study of vutrisiran, an RNA interference therapeutic, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. This analysis evaluated vutrisiran's impact on exploratory cardiac endpoints in HELIOS‐A patients. Methods and results: Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months or intravenous patisiran 0.3 mg/kg every 3 weeks (reference group) for 18 months. Exploratory cardiac endpoints included change from baseline in N‐terminal prohormone of brain‐type natriuretic peptide (NT‐proBNP) and echocardiographic parameters versus external placebo (APOLLO study). The modified intent‐to‐treat (mITT) population comprised randomized patients receiving any study drug (n = 122). A cardiac subpopulation with evidence of cardiac amyloid involvement (n = 40) was prespecified. 99mTc scintigraphy exploratory assessments in a planned vutrisiran‐treated cohort at select sites were compared with baseline. At Month 18, vutrisiran demonstrated beneficial effects on NT‐proBNP versus external placebo in the mITT and cardiac subpopulations (adjusted geometric mean fold change ratio [95% confidence interval] 0.480 [0.383–0.600], p = 9.606 × 10−10 and 0.491 [0.337–0.716], p = 0.0004, respectively). Benefits or trends towards benefit in echocardiographic parameters versus external placebo were observed for both populations. In 99mTc scintigraphy assessments, 32/47 (68.1%) and 31/48 (64.6%) patients exhibited reduced normalized left ventricular total uptake and heart‐to‐contralateral lung ratio, respectively. Perugini grade was reduced or unchanged versus baseline in 55/57 (96.5%) evaluable patients. No increase in cardiac adverse events was observed with vutrisiran versus external placebo. Conclusions: Vutrisiran demonstrated evidence of potential benefit on cardiac manifestations in patients with ATTRv amyloidosis with polyneuropathy, with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Introduction: Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades. Methods: The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized. Results: The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra‐spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain‐phenotyping and genotyping based on patient‐specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism‐based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise. Conclusions: The diagnosis of PDPN evolves toward pheno‐and genotyping and treatment should be mechanism‐based. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective study. In the study, 6,338 patients with diabetes who had been treated by diabetes specialists were registered in 2007–2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using the t‐test, χ2‐test and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Of the total participants, 5,451 patients (mean age 61.4 years, duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased the risk for DSPN: age (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42–1.73), duration of diabetes (OR 1.32, 95% CI 1.21–1.43), body mass index (OR 1.19, 95% CI 1.09–1.30), systolic blood pressure (OR 1.06, 95% CI 1.01–1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09–1.22), biguanides (OR 1.22, 95% CI 1.06–1.39) and insulin therapy (OR 1.59, 95% CI 1.36–1.84). The following factors decreased the risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96–1.00) and exercise therapy (OR 0.85, 95% CI 0.73–0.98). The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also showed the risk factors of DSPN. [ABSTRACT FROM AUTHOR]

Background and purpose: The role of high‐resolution nerve ultrasound (HRUS) and corneal confocal microscopy (CCM) in the early detection of taxane‐induced polyneuropathy (TIPN) is unclear. The present prospective longitudinal controlled observational pilot study estimates the role of HRUS and CCM in the early diagnosis of TIPN in breast cancer patients. Methods: Fifteen breast cancer patients receiving paclitaxel and 15 healthy age matched controls were included. Visits before and 3 weeks, 8 weeks and 6 months after treatment included clinical examination, the total neuropathy score, nerve conduction studies (NCS), monocular CCM including corneal nerve fibre length, density and branching and HRUS of bilateral median, ulnar, radial, tibial, peroneal and sural nerves. Patients were compared between different visits and to healthy controls. Results: Total neuropathy score increased from 2.2 at baseline to 5.8 (p < 0.001) at week 8. NCS showed a decreased sensory amplitude in the sural, radial, ulnar and median nerve after 6 months (p < 0.001). HRUS revealed a significant increase of cross‐sectional area in the sural nerve (p = 0.004), the median nerve (p = 0.003) at the carpal tunnel and the ulnar nerve in the forearm (p = 0.006) after 6 months. CCM showed no changes at different visits. Conclusions: Corneal confocal microscopy and HRUS do not detect early signs of TIPN during the paclitaxel treatment period. HRUS and NCS might detect congruent signs of an axonal, predominantly sensory polyneuropathy after 6 months. The clinical examination remains the most sensitive tool in the early detection of TIPN in breast cancer patients. [ABSTRACT FROM AUTHOR]

Hereditary transthyretin (ATTRv) amyloidosis is a rare, fatal systemic disease, associated with polyneuropathy and cardiomyopathy, that is caused by mutant transthyretin (TTR). In addition to liver transplantation, several groundbreaking disease‐modifying drugs (DMDs) such as tetrameric TTR stabilizers and TTR gene‐silencing therapies have been developed for ATTRv amyloid polyneuropathy. They were based on a working hypothesis of the mechanisms of ATTRv amyloid formation. In this retrospective cohort study, we investigated survival of all 201 consecutive patients with ATTRv amyloidosis in our center. The effects of DMDs on survival improvements were significant not only in early‐onset patients but also in late‐onset patients. ANN NEUROL 2024;95:230–236 [ABSTRACT FROM AUTHOR]

With the deepening of aging in China, the prevalence of diabetes in older people has increased noticeably, and standardized diabetes management is critical for improving clinical outcomes of diabetes in older people. In 2021, the National Center of Gerontology, Chinese Society of Geriatrics, and Diabetes Professional Committee of Chinese Aging Well Association organized experts to write the first guideline for diabetes diagnosis and treatment in older people in China, the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition). The guideline emphasizes that older patients with diabetes are a highly heterogeneous group requiring comprehensive assessment and stratified and individualized management strategies. The guideline proposes simple treatments and de‐intensified treatment strategies for older patients with diabetes. This edition of the guideline provides clinicians with practical and operable clinical guidance, thus greatly contributing to the comprehensive and full‐cycle standardized management of older patients with diabetes in China and promoting the extensive development of clinical and basic research on diabetes in older people and related fields. In the past 3 years, evidence‐based medicine for older patients with diabetes and related fields has further advanced, and new treatment concepts, drugs, and technologies have been developed. The guideline editorial committee promptly updated the first edition of the guideline and compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). More precise management paths for older patients with diabetes are proposed, for achieving continued standardization of the management of older Chinese patients with diabetes and improving their clinical outcomes. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 7-year-old boy with a foot ulcer, resorption of digits, and anhidrosis. The boy had protruding ears, leg length discrepancy, calluses on the hands, and self-inflicted biting injuries in the mouth. The diagnosis was determined to be hereditary sensory autonomic neuropathy type IV, which is a rare condition characterized by impaired sweating, touch, and thermal perception. The article highlights the difficulty in differentiating this condition from childhood leprosy and emphasizes the importance of accurate diagnosis and appropriate management. [Extracted from the article]