The issue of potential adverse reactions or toxicities of pharmacotherapies used for chronic diseases in people with HIV is still to be clarified. This study targeted potential effects on neurocognition and mood from prescription opioids, alone or in combination with other classes of drugs, using cross-sectional data from 400 participants in the multicenter CNS HIV Anti-Retroviral Therapy Effects Research study. We found that prescription opioid use alone was not associated with neurocognitive performance (β = -1.05, Standard error [SE] = 0.80, P = 0.18) or depressive mood (β = -0.08, SE = 0.19, P = 0.65). However, if used in combination with antidepressants, prescription opioid use significantly correlated with reduced neurocognitive performance (β = -2.58, SE = 1.17, P = 0.03). Also, combinations of prescription opioids and antidepressants with statins (β = -2.87, SE = 1.49, P = 0.05) or lipid-lowering agents other than statins (β = -2.88, SE = 1.39, P = 0.04) were associated with lower neurocognitive performance. The interaction of prescription opioid use with the presence of distal sensory polyneuropathy (DSP) was significant ( P = 0.03). In those without DSP, prescription opioid use was associated with better neurocognitive performance (β = 4.25, SE = 2.13, P = 0.04); by contrast, in those with DSP, the direction of the effect was reversed. No modifying effect on neurocognition was obtained considering distal neuropathic pain, lifetime substance disorder, lifetime major depression diagnosis, or detectable viral load. These findings underscore the importance of neurocognition impact from drug combinations and careful consideration of opioid prescriptions in combination with other medications in the management of people with HIV.

Invasive Lobular Carcinoma forms 10-15% of all breast cancers. ILC is usually ER positive and HER-negative and characterized by Loss of E-cadherin expression. These features contribute to the infiltrative growth pattern to GI tract, peritoneum, and orbit. GI metastasis represents 1% of cases. Hence, an additional orbital involvement is very uncommon. We present a 54-year-old postmenopausal female with a positive family history of breast cancer who presented with bilateral upper outer quadrant breast masses. Biopsy showed bilateral grade II ILC, positive for ER and progesterone receptor (PR), and negative for HER-2. Staging CT revealed bilateral breast lesions with axillary lymphadenopathy, gastric and colonic wall thickening, ascites, and pelvi-ureteric junction constriction. There were no metastases to the lung or liver. Brain MRI showed a right intraconal orbital lesion that was initially suspected of being metastasis. The patient received 12 cycles of paclitaxel (80mg/m²) followed by tamoxifen and goserelin maintenance. Due to recurrent vomiting and right-sided ptosis, imaging and ophthalmologic evaluation were repeated, identifying the orbital lesion as an inflammatory pseudotumor that responded to corticosteroids. Bone scans showed no osseous deposits. Neurologic evaluation revealed axonal motor polyneuropathy attributed to chemotherapy, which was managed with plasma exchange. The patient maintained stable disease until loss to follow-up in early 2023. This case demonstrates a rare gastric metastasis in bilateral ILC in addition to a diagnostic challenge of differentiating orbital metastasis from pseudotumor.

Rate of incident polyneuropathy in patients with transthyretin amyloid cardiomyopathy.

Liver-kidney transplantation in methylmalonic acidemia (MMA) improves metabolic control but does not eliminate neurological risk. Peripheral neuropathy is increasingly recognized in transplanted patients, yet its pathophysiology and surveillance strategies remain poorly defined. We describe a severe axonal sensorimotor polyneuropathy that occurred 12 years after combined liver and kidney transplantation in a 20-year-old patient with mut0 methylmalonic acidemia (MMA), compound heterozygous for MMUT gene mutations and lacking fibroblast MCM enzymatic activity. Clinical, electrophysiological, and biochemical investigations were performed, including cerebrospinal fluid analysis, anti-ganglioside antibody testing, and measurement of circulating biomarkers of neuroaxonal injury (NfL) and mitochondrial dysfunction (FGF21, GDF15). Electrophysiological studies demonstrated a purely axonal process with active denervation. Cerebrospinal fluid protein and cell count were normal, anti-ganglioside antibodies were negative, and neuroimaging was unremarkable, excluding Guillain-Barré syndrome variants. Plasma NfL was markedly elevated (4083 pg/mL, 204× ULN), exceeding levels reported in hereditary and acquired neuropathies. FGF21 (1682 pg/mL) and GDF15 (1438 pg/mL) indicated mitochondrial stress. This case demonstrates that neurological stability is not guaranteed in mut0 MMA even 12 years post-transplantation. Management included switching from tacrolimus to everolimus and optimizing vitamin B12 supplementation. We propose NfL, FGF21, and GDF15 as monitoring tools for MMA transplant recipients.

Diabetic peripheral neuropathy (DPN) is a length-dependent, symmetric sensorimotor polyneuropathy with a substantial global and regional burden. Current pharmacologic options are largely symptomatic and do not modify the disease. Lymphovenous bypass (LVB), a supermicrosurgical procedure established for lymphedema, may modulate lymphatic-immune-microvascular dysfunction relevant to DPN. The primary objective is to determine whether LVB combined with standard of care (SOC) improves small-fiber and autonomic function compared with SOC alone at 6 months. Secondary objectives are to evaluate the effects of LVB on large-fiber function, neuropathic pain, ulcer healing, quality of life, and relevant biomarkers, as well as to characterize the safety profile of LVB. This is a SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials)-aligned, single-center, randomized, controlled, parallel-group superiority trial with a 2:1 allocation (LVB+SOC vs SOC alone). Randomization is stratified based on the presence or absence of active diabetic foot ulcers, as defined by the International Working Group on the Diabetic Foot and Infectious Diseases Society of America criteria. In total, 60 adults aged 20 to 80 years with confirmed DPN will be enrolled. LVB involves lymphatic-venous anastomosis to venules ≤0.8 mm. SOC consists of guideline-based glycemic and risk-factor management, pain control, and standardized wound care. Outcome assessors and statisticians are blinded. The primary outcomes are changes in clinical neuropathy burden and pain severity at 6 and 12 months. Secondary outcomes comprise objective measures of somatic and autonomic physiology, histopathological nerve fiber density, biological serum markers, and longitudinal ulcer epithelialization parameters. Data analysis will use mixed-effects models for repeated measures, with a sample size of 60 adults providing 80% power to detect a conservative between-group effect size of Cohen d=0.70. Recruitment commenced in February 2026 and is planned to continue through July 31, 2027, with follow-up through July 31, 2028. As of May 2026, we have enrolled 3 participants. The first participant has been treated, and a second participant is scheduled to undergo treatment. Data analysis and reporting are anticipated between late 2027 and early 2028. No outcome data are included. This trial tests a mechanism-based, nonpharmacologic adjunct targeting lymphatic-immune-microvascular dysfunction in DPN. If effective, LVB could inform phenotype-directed treatment algorithms and motivate multicenter evaluation and health economic analyses.

ObjectivesTo determine the prevalence and clinical characteristics associated with polyneuropathy in kidney transplant recipients (KTRs).DesignCross-sectional study.SettingSENS study at the University Medical Center Groningen, the Netherlands, December 2021–May 2023.ParticipantsKTR, participating in the ongoing TransplantLines Biobank and Cohort Study, ≥12 months post-transplantation.Main outcome measuresParticipants underwent a structured neurological assessment including history taking, neurological examination, quantitative sensory testing and nerve conduction studies. An expert panel classified participants into no/possible, probable/definite large fibre polyneuropathy or small fibre neuropathy. Large-fibre subtypes included axonal or demyelinating, pure sensory, pure motor and sensorimotor. To assess potential associations with clinical characteristics, logistic regression analysis was conducted.ResultsWe included 160 KTRs with a mean age of 59.8±11.6 years at a median of 6.1 (95% CI 3.9 to 13.1) years post-transplantation, with 16 KTRs (10%) diagnosed with polyneuropathy before study inclusion. In total, 84 KTRs (53%) were identified with large fibre polyneuropathy and 7 KTRs (4%) with small fibre neuropathy. KTRs with large fibre polyneuropathy presented with either sensor-predominant polyneuropathy (40 KTR (48%)) or sensorimotor polyneuropathy (44 KTR (52%)). We found no neurophysiological characteristics of demyelination. Overall, 18% (95% CI 11% to 27%) of KTRs with large fibre polyneuropathy were asymptomatic. Higher age (OR=1.04 (1.01 to 1.08), p=0.01), male sex (OR=2.55 (1.19 to 5.60), p=0.02), diabetes (OR=5.58 (1.36 to 38.14), p=0.03) and elevated urea levels (OR=1.12 (1.04 to 1.23), p=0.01) were significantly associated with polyneuropathy in KTR.ConclusionsIn contrast with previous studies, axonal sensory or sensorimotor polyneuropathy is highly prevalent and often underdiagnosed in KTR. Next to higher age and male sex, it was independently associated with diabetes and higher urea levels. Further research is needed to reveal the aetiology and course of polyneuropathy in KTRs.Trial registration numberNCT04664426.

Human immunodeficiency virus is a harrowing illness that causes significant sequelae besides immune suppression. One of the long-term effects of both virus and antiviral medication is distal sensory polyneuropathy. Treating this HIV-induced neuropathy is a difficult challenge for clinicians, with standard of care medications having significant side effects. Recently, 8% topical capsaicin patches have been shown to help with various other forms of neuropathy, but no systematic review has investigated the potential benefit of HIV-induced neuropathy. A thorough systematic review of five databases (PubMed, Embase, Scopus, Web of Science, Cochrane) was conducted in October 2025. Retrieved articles were screened for the primary outcome of pain scores both before and after application of the topical capsaicin patch. Statistical analysis was stepwise, with an initial heterogeneity test (Higgins I2), followed by a random-effects meta-analytics based on the moderately high degree of heterogeneity. Our investigation found a total of seven articles that fit our inclusion and exclusion criteria. The overall effect size for the most common patch-application duration was d = 0.991 (95%CI: 0.619-1.36) for improvement in pain score. To control for our high heterogeneity, a leave-out analysis was conducted on the studies with highest risk of bias, with repeat meta-analytics denoting a d = 0.96. Our systematic review and meta-analysis notes that topical 8% capsaicin patches are effective in reducing neuropathic pain in patients with HIV-neuropathy. Future larger studies should be conducted to investigate the place of 8% capsaicin patches in the treatment algorithm for HIV-neuropathy. www.crd.york.ac.uk/prospero identifier CRD420251114796.

This study aimed to identify the frequency and types of peripheral nervous system involvement, associated clinical features, treatment options, and prognosis in patients receiving immune checkpoint inhibitors (ICIs) for the treatment of malignancy. This is a retrospective cross-sectional study. We included the data of patients who presented to our electromyography laboratory with neurologic complaints and were using ICIs between January 2019 and August 2024. We retrieved all medical and electrophysiologic records. In patients with multiple examinations, the first appropriate examination was included. Demographic data, oncologic diagnoses, neurologic diagnoses, and medications used were extracted from patient files and are presented here. During the study period, we reviewed the records of 31 patients. Seven patients were excluded. The rough prevalence of newly developed neurologic findings attributed to peripheral nervous system involvement after using ICIs was 8%. The most common peripheral complications were sensory or sensory-motor axonal polyneuropathy and myopathy. The most commonly associated medications for these neurologic manifestations were pembrolizumab, nivolumab, and atezolizumab. Nonambulatory patients received immunomodulatory therapy and demonstrated functional improvement. ICIs have been increasingly used in cancer treatment and can cause immune-related effects. As demonstrated in our study, the most common peripheral nervous system involvement associated with ICIs is axonal polyneuropathy, followed by myopathy. The type of ICI, cancer type, and prior chemotherapeutic treatments the patients previously received may play a role in the occurrence of these neurologic complications.

To evaluate the concordance between clinical preliminary diagnoses and electrophysiological diagnoses obtained through electromyography (EMG) in patients referred with suspected entrapment neuropathies or polyneuropathy. In this retrospective descriptive study, 3,683 EMG reports from patients referred to the EMG unit of Samsun Physical Medicine and Rehabilitation Hospital between June 1, 2023, and February 10, 2025, were reviewed. All EMG procedures were performed and interpreted by the same physiatrist. Patient age, sex, clinical preliminary diagnoses, and final electrophysiological findings were recorded. Statistical significance was set at p < 0.05. Of the patients, 75.4% were female, with a mean age of 54.6 ± 14.1 years. The most common referral diagnoses were carpal tunnel syndrome (CTS) (62.4%), polyneuropathy (PNP) (34.1%), cubital tunnel syndrome (CuTS) (2.6%), meralgia paresthetica (MP) (0.7%), and tarsal tunnel syndrome (TTS) (0.2%). EMG. The concordance between clinical and EMG diagnoses was generally moderate. In CTS and PNP, specificity was notably low. Improving clinical assessment and referral accuracy may enhance diagnostic precision and reduce unnecessary testing and patient waiting times.

ObjectivesVariants in COA7 (cytochrome c oxidase assembly factor 7) are a rare cause of mitochondrial disease, with limited clinical descriptions and phenotypic variability. We describe 2 siblings carrying compound heterozygous COA7 variants, one of which (c.457C>T; p.Leu153Phe) is novel. Both presented with early-onset, slowly progressive axonal sensorimotor neuropathy, with differences in severity and associated features.MethodsPatients were identified based on clinical presentation and evaluated through longitudinal neurologic, neurophysiologic, genetic, biochemical, and neuroimaging assessments.ResultsThe elder brother developed symptoms at age 12, including muscle cramps, tremors, and falls, whereas the sister showed motor impairment with difficulty walking and running from age 5, along with more prominent cerebellar involvement. Shared features included distal weakness, impaired gait, areflexia, tremor, pes cavus, sensory disturbances, and cognitive difficulties, which were milder in the older brother. Nerve conduction studies demonstrated axonal sensorimotor polyneuropathy. Genetic analysis identified 2 compound heterozygous COA7 variants. Skin biopsy revealed reduced mitochondrial complex IV activity. Brain MRI findings were unremarkable in both siblings.DiscussionThese cases expand the clinical spectrum of COA7-related disorders and illustrate the potential for intrafamilial phenotypic variability. The identification of a novel variant and extended clinical follow-up provide further insight into the features associated with COA7 variants.

The central nervous system (CNS) processes information, coordinates movements, and enables communication-both within the body and with the environment: Perception and response to sensory impressions are controlled by the brain, with afferent and efferent pathways passing through the spinal cord. The peripheral nervous system (PNS) mediates between the environment and the CNS. As we age, the PNS undergoes changes, resulting in aweakening of muscle reflexes and proprioception. This must be distinguished from polyneuropathies (PNP), which are pathological changes in the PNS. The causes are manifold: in addition to metabolic, immune-mediated, hereditary, toxic, and infectious etiologies, polyneuropathies can be amanifestation of systemic diseases. Neuropathies associated with diabetes, monoclonal gammopathies, and malignancies are more common in older people, and the proportion of cryptogenic neuropathies also increases with age. PNPs contribute to impaired mobility and an increased risk of falls, which necessitates the assessment of functional abilities. Pain and sensory disturbances have anegative impact on activities of daily living. As aresult, communication with the living environment is impaired. Ageriatric approach enables not only an accurate diagnosis but also comprehensive therapy tailored to individual needs.

The classification of chronic inflammatory demyelinating polyneuropathy (CIDP) is evolving with the discovery of autoantibodies against nodal and paranodal proteins, leading to the recognition of "autoimmune nodopathies." While anti-neurofascin-155 (NF155) and anti-contactin-1 (CNTN1) antibodies are well-characterized, the phenotype of anti-gliomedin (GLDN) antibodies remains poorly defined. We present a comprehensive case to delineate its clinical and serological profile. We report a detailed longitudinal case of a patient with anti-GLDN antibody-positive CIDP, including clinical presentation, electrophysiological and imaging studies, serological testing, treatment response, and follow-up. A 48-year-old woman presented with an 11-month history of relapsing-remitting, symmetric sensorimotor polyneuropathy, triggered by immune-activating events. Electrodiagnostic studies confirmed a demyelinating polyneuropathy meeting definitive European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) criteria. Cerebrospinal fluid (CSF) analysis showed marked albuminocytological dissociation (protein 1631mg/L). Serology was positive for anti-GLDN IgG (cell-based assay titer 1:32). The patient exhibited an excellent but transient response to intravenous immunoglobulin (IVIg), leading to multiple relapses. Subsequent B-cell targeted therapy with rituximab resulted in sustained clinical stabilization, effective B-cell depletion, and negative conversion of anti-GLDN IgG antibody. This case suggests that anti-GLDN antibody-associated CIDP may be associated with a recognizable phenotype within the autoimmune nodopathy spectrum. Potential key features include a relapsing course following immune stimulation, markedly elevated cerebrospinal fluid protein, a unique pattern of robust but unsustained response to intravenous immunoglobulin (IVIg), and a favorable response to B-cell depletion therapy as evidenced by clinical remission and seroconversion.

Spinocerebellar ataxia type 27B (SCA27B) is an autosomal dominant late-onset cerebellar ataxia caused by a pathogenic GAA repeat expansion in theFGF14gene. Although oculomotor abnormalities, particularly downbeat nystagmus, are well recognized, afferent visual pathway involvement has not been systematically investigated. We report a 67-year-old man with genetically confirmed SCA27B who presented with a two-year history of progressive cerebellar and somatosensory ataxia, with a Scale for the Assessment and Rating of Ataxia (SARA)score of 13. Neurological examination revealed typical oculomotor abnormalities, including downbeat nystagmus elicited during head-shaking testing. Brain MRI showed mild cerebellar atrophy. Electrophysiological studies demonstrated axonal sensory polyneuropathy and prolonged central conduction times on somatosensory evoked potentials. Comprehensive ophthalmological examination, including optical coherence tomography, showed no structural abnormalities. Pattern-reversal visual evoked potentials, recorded according to ISCEV standards, demonstrated mild bilateral prolongation of P100 latency, measuring 116ms in the left eye and 115ms in the right eye, with preserved amplitudes. Compared with laboratory normative data from individuals aged 60-70years, these values exceeded the upper age-related reference limit. This case suggests possible subclinical functional involvement of the post-retinal afferent visual pathways in SCA27B. However, the findings should be interpreted cautiously and confirmed in larger, age-matched cohorts.

Allgrove syndrome, also known as Triple-A syndrome, is a rare autosomal recessive disorder characterized by the triad of alacrima, achalasia, and adrenal insufficiency, alongside a broad spectrum of neurological and autonomic dysfunctions. We present a compound heterozygosity for the pathogenic NM_015665.6:c.787T > C, p.(Ser263Pro) and the not previously described in the literature NM_015665.6:c.1442A > G, p.(His481Arg), as a possible cause for Allgrove syndrome. Exome sequencing was performed in a female patient with achalasia, alacrima, optic atrophy, asymmetrical axonal sensorimotor polyneuropathy, segmental demyelination, and chronic denervation, revealing the above-mentioned compound heterozygosity. Segregation analysis was performed in three siblings of the proband and in the mother. The affected brother of the proband (presenting with achalasia, alacrimia, motor neuropathy, autonomic dysfunction, optic atrophy and osteoporosis), was found to be compound heterozygotes for the same variants. Although the paternal genotype was not available, the absence of the p.(His481Arg) variant in the mother indicates paternal inheritance of this variant, providing indirect evidence that the two AAAS variants are located on different alleles (in trans). The proband and her affected sibling were found to carry compound heterozygosity for the known pathogenic AAAS variant p.(Ser263Pro) and the novel p.(His481Arg) variant. Segregation analysis in available family members supports a contributory role of p.(His481Arg) in the context of autosomal recessive inheritance, however, phase could not be directly confirmed due to the unavailability of the paternal sample. Functional validation and/or identification of the variant in unrelated affected individuals would be required to further clarify its pathogenic significance. We also provide a comprehensive review of reported Allgrove syndrome cases in the literature carrying compound heterozygosity for the NM_015665.6:c.787T > C, p.(Ser263Pro) variant and the respective wide spectrum of this syndrome.

Neuromuscular disorders-predominantly critical illness myopathy (CIM), critical illness polyneuropathy (CIP), and critical illness neuromyopathy-commonly occur in intensive care unit (ICU) patients. Given the limitations of the neurologic examination in the setting of ICU-acquired weakness, electrophysiology is very helpful in localizing the cause of weakness and defining its etiology. In CIM, motor unit potentials have typical myopathic features, but motor unit potential activation may be limited. In addition, there are features of sarcolemmal inexcitability reflected in low motor responses that may have prolonged durations. In CIP, the findings are usually those of a recent onset generalized axonal sensorimotor polyneuropathy; however, it is essential to note that sensory conductions may be prone to artifacts and other confounders in the ICU. Critical illness neuromyopathy has features of both CIM and CIP. For research studies and in some clinical situations, direct muscle stimulation may be used to help differentiate CIP and CIM. Histopathologic studies may be useful in confirming CIM and identifying other neuromuscular causes of weakness. In addition, identifying evolving reductions in fibular/peroneal motor amplitudes in ICU patients can help predict developing neuromuscular weakness. Knowledge of the various neuromuscular disorders that can occur in critically ill patients, their risk factors, and associated electrodiagnostic findings enables a rational approach to diagnosing the causes of neuromuscular weakness in ICU patients.

This study aimed to summarize evidence on peripheral nerve enlargement in patients with diabetes, with and without diabetic sensorimotor polyneuropathy (DSP), compared with healthy controls. PubMed and Embase were systematically searched for ultrasound studies measuring the cross-sectional area (CSA) of peripheral nerves in patients with diabetes with and without DSP. The primary outcome was the weighted inter-group mean difference in CSA at all reported upper- and lower extremity sites. Forty-seven studies were identified, of which 41 were included in the meta-analyses. Patients with diabetes without DSP showed significantly larger CSA values than healthy controls at 3 of 11 anatomical locations, all located in the lower extremity. Patients with diabetes and DSP demonstrated increased CSA compared with controls at 9 of 14 sites, particularly at distal compression sites of the median and tibial nerves. Compared with patients with diabetes without DSP, those with DSP had significantly larger CSA values at 14 of 21 sites, with the greatest difference observed 4-5cm proximal to the medial malleolus (pooled mean difference+5.26mm2, 95% CI 0.94-9.57). In conclusion, peripheral nerve CSA is increased in diabetes and further enlarged in the presence of DSP, with the largest effects at distal compression sites.

AB-064. Anti-SRP immune-mediated necrotizing myopathy with concomitant sensorimotor polyneuropathy: a case report

To evaluate the relationship between Pacinian corpuscle (PC) count on forefoot MRI in diabetic sensorimotor polyneuropathy (DSP) and large-fiber sensory dysfunction as quantified by nerve conduction studies (NCS). Thirty-nine patients with type 2 diabetes and neurologically confirmed DSP (mean age 67.9 ± 13.5 years; 29 males) underwent forefoot MRI and NCS, including compound muscle and sensory nerve action potentials (cMAP, sNAP) and conduction velocities of tibial, peroneal, and sural nerves. PC counts were assessed in the subcutaneous and deep regions of each digit. Spearman's rank correlation analysis examined the relationship between total PC counts and sural sNAP amplitudes. Based on motor and sensory amplitudes and age-adjusted conduction velocities of NCS, 10 patients were classified as having mild-to-moderate DSP, and 29 as having severe DSP. Severe DSP was associated with sensory large-fiber impairment, with 86.1% of patients showing abolished sural sNAP amplitudes. Total PC counts were significantly lower in severe cases compared to mild-to-moderate polyneuropathy (54.1 ± 40.6 vs 146.1 ± 43.2; p < 0.001). Spearman's rank correlation analysis revealed a strong positive association between PC counts and sural sNAP amplitudes (ρ = 0.638, p < 0.001). Likewise, patients with severe DSP had substantially reduced or absent sural sNAP amplitudes (median [range]: 0.1 [0.1-1.7] µV) and lower PC counts, while those with mild-to-moderate DSP showed both higher sural sNAP amplitudes (median [range]: 2.3 [0.9-11.4] µV) and PC counts (p < 0.001). Forefoot MRI-detected PC counts closely correlate with large-fiber sensory function in DSP, supporting their potential as noninvasive imaging biomarkers of polyneuropathy severity. Question DSP is linked to loss of PC on forefoot MRI; however, it remains unclear whether the number of PC correlates with DSP severity. Findings Forefoot MRI showed lower PC counts in patients with severe DSP than in those with mild-to-moderate disease and indicated a strong association between PC loss and electrophysiological measures of large-fiber sensory dysfunction. Clinical relevance MRI-based PC quantification is a promising imaging biomarker for large-fiber sensory dysfunction in DSP, complementing established clinical and electrophysiological methods for diagnosing and assessing DSP severity.

Peripheral neuropathies may present with vascular skin lesions, such as livedo racemosa, ulcers, palpable purpura, or necrosis. These rare neurocutaneous associations can be severe and life-threatening. To determine (1) whether phenotypic correlations exist between neuropathy profiles and vascular skin lesion subtypes, and (2) whether these syndromes share a specific mechanism. We conducted a monocentric retrospective study at Montpellier University Hospital (1993-2022) including patients with peripheral neuropathy and vascular skin lesion(s) occurring as a syndrome. Clinical, electrophysiological, and histopathological data were analyzed. Forty-one patients (median age 54years) were included: 27 had mononeuritis multiplex (MM) and 14 polyneuropathy (PNP). Purpura (p = 0.001) and livedo (p < 0.05) were associated with MM, while ulcers were linked to PNP (p < 0.001). Ulcers were plantar in PNP and supraplantar in MM. Median delay between neuropathy and skin lesion was 1month in MM versus 58months in PNP (p < 0.001). In PNP subgroup, the neuropathy systematically preceded skin lesion. MM etiologies involved ischemic mechanisms related to vasculitis and/or vaso-occlusion [systemic angiitis (n = 19), type I cryoglobulinemia (n = 6), and primary antiphospholipid syndrome (n = 2)], whereas PNP was due to diabetes (n = 9), chronic renal failure (n = 1), alcohol (n = 1), leprosy (n = 1), or transthyretin-amyloidosis (n = 2). MM correlates with livedo, purpura, and supraplantar ulcers, reflecting ischemia from vasculitis or vaso-occlusion. Conversely, plantar ulcers result from chronic PNP affecting large and small fibers. Skin lesion type may guide neuropathy phenotype and underlying etiology.

Hereditary transthyretin amyloidosis (ATTRv) is a genetic disorder caused by more than 100 autosomal dominant mutations in the TTR gene. Owing to its marked clinical heterogeneity—particularly in its cardiac manifestations—ATTRv is frequently underdiagnosed and requires comprehensive clinical evaluation. The disease commonly presents as a progressive axonal sensorimotor polyneuropathy with autonomic involvement. Despite advances in disease-modifying therapies, including the availability of Tafamidis, delayed diagnosis remains a major challenge, contributing to increased morbidity and mortality. Therefore, the identification of reliable biomarkers for early detection, disease staging, and therapeutic monitoring is essential. One promising candidate is neurofilament light chain (NfL), a structural axonal protein released into the circulation following neuronal injury, which has been proposed as a biomarker of neuroaxonal damage in ATTRv in other populations. The present study aimed to evaluate plasma NfL (pNfL) levels in Brazilian patients with ATTRv and to investigate their association with neuropathy severity. Symptomatic and asymptomatic patients with genetically confirmed ATTRv followed at a specialized university reference center were included, along with healthy volunteer controls. A subgroup of symptomatic patients was receiving Tafamidis therapy. Clinical and demographic data were collected during routine visits, and neuropathy severity was assessed using validated instruments, including the Neuropathy Impairment Score (NIS) and the Polyneuropathy Disability (PND) score. Plasma NfL concentrations were measured using the ultrasensitive SIMOA SR-X platform. Statistical analyses were performed to compare pNfL levels across groups and to assess correlations with clinical parameters. Symptomatic patients not receiving Tafamidis exhibited significantly higher pNfL levels compared with treated symptomatic patients, asymptomatic mutation carriers, and healthy controls. Moreover, pNfL concentrations showed a positive correlation with NIS scores, indicating increasing axonal damage with disease progression. Z-score analyses further supported the ability of pNfL to discriminate between disease stages. In conclusion, plasma NfL emerges as a promising biomarker for assessing disease severity, progression, and treatment response in ATTRv, supporting its potential utility in Brazilian clinical practice.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-48524-0.