Shy R, Dragon A, Feely SME
… +6 more, Donlevy G, Cornett K, Mandarakas M, Estilow T, Burns J, Shy ME
J Peripher Nerv Syst
· 2025 Jun · PMID 40391770
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BACKGROUND AND AIMS: The CMT Infant Scale (CMTInfS) enables evaluation of infants/toddlers in clinic. Our aim was to evaluate the feasibility, reliability, and validity of a virtual version of the CMTInfS (vCMTInfS). MET...BACKGROUND AND AIMS: The CMT Infant Scale (CMTInfS) enables evaluation of infants/toddlers in clinic. Our aim was to evaluate the feasibility, reliability, and validity of a virtual version of the CMTInfS (vCMTInfS). METHODS: Children aged 55 months or less were evaluated either in clinic using CMTInfS or remotely via telemedicine using the vCMTInfS. A trained clinical evaluator remotely directed activities with assistance from the parent/caregiver. vCMTInfS scores were calculated using the CMTInfS calculator available at www.ClinicalOutcomeMeasures.org. Clinical evaluators also used the Brazelton Neonatal Behavior assessment scale to give insight into the behavior of the child during the exam. RESULTS: Twenty children (10 males and 10 females) aged 6-55 months with confirmed or at risk for CMT were evaluated. The mean in person (IP) CMT Infant and Toddler Scale (CMTInfS) raw score (4.11, SD = 2.76) was not significantly different from the mean initial virtual (V1) CMTInfS raw score (3.78, SD = 2.59) using a two-tailed test (t = 1.000, p = 0.347). Differences between the first and second (V2) visits as well as between the IP and V2 visits were also nonsignificant. INTERPRETATION: Our data demonstrate that children aged 55 months or less can be effectively evaluated remotely using the vCMTInfS, which will expand the number of very young children who can be evaluated with rare forms of CMT.
J Peripher Nerv Syst
· 2025 Jun · PMID 40366569
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Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated peripheral neuropathies. Despite treatment, patients may report residual deficits, pain, and fatigue with con...Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated peripheral neuropathies. Despite treatment, patients may report residual deficits, pain, and fatigue with considerable impact on quality of life. A systematic review was conducted of the methodological quality of current patient-reported outcome measures (PROMs) for measuring health-related quality of life (HRQoL) in patients with GBS and CIDP. A literature search was conducted in EMBASE, MEDLINE, Web of Science, and Google Scholar. PROMs developed to measure (aspects of) HRQoL in patients with polyneuropathy were classified using the Wilson and Cleary model. Measurement properties were evaluated in accordance with Consensus-based Standards for selection of health Measurement Instruments (COSMIN) guideline. A total of 57 articles identified 31 unique PROMs that are used for measuring HRQoL in patients with polyneuropathies. Of these, 22 measured symptom status, 19 functional status, and 4 general health perception. Eight PROMs were developed or validated in patients with GBS/CIDP. None of the PROMs demonstrated sufficient content validity for recommendation in this population. Only the Rasch-built Fatigue Severity Scale (R-FSS) performed sufficiently across all other measurement properties. The Inflammatory Rasch-built Overall Disability Scale (I-RODS) and IN-QoL are not recommended for use because of insufficient construct validity. GBS Patient Experience Questionnaire, Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI), Fatigue Severity Scale (FSS), R-FSS, Rotterdam Handicap Scale (RHS) and the 36-Item Short Form Health Survey (SF-36) need further validation. PROMs of good quality assessing all relevant aspects of HRQoL are required for better insight in HRQoL in patients with GBS and CIDP.
Gad H, Elgassim E, Mohamud KMA
… +18 more, Al-Naimi NS, Al-Sharshani HA, Mohammed I, Al-Malaheem MA, Quadros DJ, AlJalahma A, Lamine N, Alhaddad AY, Aly HAHZ, Cabibihan JJ, Al-Ali A, Sadasivuni KK, Petropoulos IN, Ponirakis G, Ali HA, AlMohanadi D, Baagar K, Malik RA
J Peripher Nerv Syst
· 2025 Jun · PMID 40366068
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BACKGROUND: Hyperglycemia is a major driver of diabetic peripheral neuropathy (DPN) in type 1 diabetes mellitus (T1DM). Advanced hybrid closed-loop (AHCL) technologies improve glycemic control and reduce glycemic variabi...BACKGROUND: Hyperglycemia is a major driver of diabetic peripheral neuropathy (DPN) in type 1 diabetes mellitus (T1DM). Advanced hybrid closed-loop (AHCL) technologies improve glycemic control and reduce glycemic variability and may improve DPN. METHODS: Patients with T1DM treated for 9.8 ± 0.32 months with the 780G SmartGuard system (n = 14) were compared with patients with T1DM on MDI (n = 20) and healthy controls (n = 15). Time in range (TIR), time above range (TAR), time below range (TBR), glycemic variability, and HbA were evaluated, and corneal confocal microscopy (CCM) was undertaken to quantify corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), and inferior whorl length (IWL). RESULTS: Participants using the 780G system had a significantly higher TIR (p < 0.001), lower glycemic variability (p = 0.02), and less time in level 2 hyperglycemia (p = 0.01), level 1 hyperglycemia (p = 0.04), and level 2 hypoglycemia (p = 0.008) compared with the MDI group. CNFD (p = 0.02), CNBD (p = 0.04), CNFL (p = 0.04), and IWL (p < 0.001) were significantly higher in the 780G group compared with the MDI group and comparable to healthy controls. CONCLUSION: The MiniMed 780G with SmartGuard improves glycemic control and variability with an improvement in small nerve fiber morphology in patients with DPN.
J Peripher Nerv Syst
· 2025 Jun · PMID 40348590
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BACKGROUND: Diabetic neuropathy (DN) is the most frequent complication of diabetes mellitus, contributing to increased morbidity and mortality. Previous clinical studies on DN in sub-Saharan Africa (sSA) have used purely...BACKGROUND: Diabetic neuropathy (DN) is the most frequent complication of diabetes mellitus, contributing to increased morbidity and mortality. Previous clinical studies on DN in sub-Saharan Africa (sSA) have used purely clinical approaches, potentially underestimating the true magnitude of this disease. This study was designed to determine the prevalence of definite diabetic neuropathy and describe the different subtypes using objective small and large fiber function measures. METHODS: This was a hospital-based cross-sectional study that included diabetes and prediabetes patients, followed up at Jordan Medical Services, Yaoundé, Cameroon, between March 2022 and February 2023. The "Toronto Clinical Neuropathy Score" and "Douleur Neuropathique en 4" questionnaires were used for clinical evaluation. Autonomic symptoms were equally recorded. Nerve conduction studies and Sudoscan were used for electrophysiological assessments of large and small fibre functions. RESULTS: Eighty-four participants were included; 91.7% had type 2 DM, 2.4% had type 1 DM, and 6% had glucose intolerance. DN was found in 73/84 (86.9%). Diabetic sensorimotor polyneuropathy (DSP) was the most frequent subtype (63.8%), followed by diabetic autonomic neuropathy (40.5%), mononeuropathy (36.9%), asymmetric axonal sensory neuropathy (4.8%) and treatment-induced neuropathy of diabetes (TIND) in 1.2% of patients. The prevalence of large and small fibre neuropathies was 38.1% and 25.0%, respectively. CONCLUSION: The prevalence of DN and specifically DSP in our study was higher than previously described in African literature. We identified subtypes never before reported in sSA, mainly small fibre neuropathy and TIND. This may have management and policy implications.
Ponirakis G, Peerzada L, Petropoulos IN
… +12 more, Gad H, Abdulshakoor S, Concepcion JM, Khalfalla SH, Elamin ISA, AlZawqari ATH, Elgassim E, Baraka A, Mahfoud ZR, El Deeb MA, Afifi N, Malik RA
J Peripher Nerv Syst
· 2025 Jun · PMID 40345154
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OBJECTIVE: Obesity increases the risk of diabetic neuropathy. This study investigates the impact of visceral (VAT) and subcutaneous adipose tissue (SAT) volume on peripheral neuropathy. METHODS: A total of 302 adults fro...OBJECTIVE: Obesity increases the risk of diabetic neuropathy. This study investigates the impact of visceral (VAT) and subcutaneous adipose tissue (SAT) volume on peripheral neuropathy. METHODS: A total of 302 adults from the Qatar Biobank (QBB) underwent iDXA to measure VAT and SAT volumes, intima media thickness (IMT), and peripheral neuropathy assessments using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire. RESULTS: The QBB cohort was aged 43.9 ± 12.9 years, of whom 43.7% were women, 42.1% had obesity, 17.4% had type 2 diabetes (T2D) and 10.9% had hypertension. VAT was associated with T2D, hypertension, higher HbA1c, diastolic blood pressure, triglycerides, and inflammatory markers, and lower HDL (p < 0.0001). There were no significant associations between SAT and these cardiovascular risk factors. VAT volume was associated with lower corneal nerve inferior whorl length (IWL) (p < 0.05) and higher VPT (p = 0.01), partially mediated by elevated HbA1c (p < 0.05, p = 0.001) and IMT (p < 0.0001), while its association with neuropathic symptoms was fully mediated by systolic blood pressure (p < 0.05), T2D (p < 0.01), and triglycerides (p = 0.05). SAT showed no associations with measures of neuropathy. CONCLUSIONS: VAT but not SAT is associated with peripheral neuropathy. This study underscores the need to target VAT to improve neuropathy.
Borisovs V, Bossi M, Matino L
… +2 more, Marmiroli P, Cavaletti G
J Peripher Nerv Syst
· 2025 Jun · PMID 40251914
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BACKGROUND AND AIMS: Serial block face scanning electron microscopy (SBF-SEM) enables automated 3D imaging of specimens with ultrastructural resolution. However, its application is often restricted due to the complex and...BACKGROUND AND AIMS: Serial block face scanning electron microscopy (SBF-SEM) enables automated 3D imaging of specimens with ultrastructural resolution. However, its application is often restricted due to the complex and labor-intensive nature of the processes involved. This study addresses the challenges associated with sample preparation and the final 3D reconstruction for ultrastructural analysis of peripheral nerves and dorsal root ganglia (DRG) specimens. METHODS: Specimens from the caudal nerve and DRG of mice were prepared for SBF-SEM using three different techniques: (1) manual high molecular weight staining, regarded as the gold standard, (2) automated standard transmission electron microscopy (TEM) preparation, and (3) automated uranyl-free en bloc preparation. The acquired data were processed by combining different software programs for image analysis and 3D rendering. RESULTS: Upon analyzing all samples, the high molecular weight method demonstrated its superiority. Nonetheless, the two alternative methods produced high-quality images of the caudal nerve. Consequently, 3D rendering was successfully achieved for all samples using an automated approach. The investigation of DRG specimens posed greater challenges with the standard TEM preparation due to the low contrast of smaller organelles compared to the cytosol, whereas the uranyl-free protocol provided significantly improved contrast. INTERPRETATION: Our findings indicate that automated uranyl-free staining can effectively compete with the traditional gold standard manual and uranyl-based staining methods, albeit with some limitations. Furthermore, high-quality SBF-SEM imaging is attainable, especially in peripheral nerves, using samples prepared via the standard TEM method, thereby facilitating the analysis of previously embedded samples even if they were not specifically prepared for 3D examination.
Xu K, Li Z, Wang M
… +11 more, Liu L, Zeng S, Li X, Cao W, Huang S, Zhao H, Yang Y, Xie Y, Hu Z, Tang B, Zhang R
J Peripher Nerv Syst
· 2025 Jun · PMID 40211677
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BACKGROUND AND OBJECTIVES: Hereditary sensory neuropathies (HSNs) are a group of genetically and clinically heterogeneous diseases. Our study aims to summarize the genetic and clinical features of HSNs in 10 Chinese fami...BACKGROUND AND OBJECTIVES: Hereditary sensory neuropathies (HSNs) are a group of genetically and clinically heterogeneous diseases. Our study aims to summarize the genetic and clinical features of HSNs in 10 Chinese families. METHODS: Clinical data from 10 families with HSNs were collected retrospectively. Genetic screening was performed by whole exome sequencing (WES). Repeated-primed PCR and capillary electrophoresis were performed for WES-negative patients to analyze repeat expansions in RFC1. RESULTS: Among the 10 probands with HSNs, eight cases were sporadic, and two had a positive family history. Six probands had early-onset (onset age < 20 years). Seven probands presented with pure-HSNs type, and three exhibited HSNs-complex type with ataxia. Variants in the NTRK1, SPTLC1, COX20, PUM1, and RFC1 genes were detected in six probands. A novel variant, c.444C>A (p.N148K), in NTRK1 was identified in an autosomal recessive inheritance family with HSAN-IV, and a novel variant, c.182dup (p.H61Qfs*31), in PUM1 was identified in a proband with adult-onset paresthesia and mild cerebellar ataxia. Additionally, biallelic expansion of the pathogenic variant structure (AAGGG)exp repeat amplification in the RFC1 gene was identified in a proband with sensory neuropathy, ataxia, and right vestibular hypofunction. CONCLUSIONS: The novel variants in NTRK1 and PUM1 expanded the genotypic spectrum of HSNs. This study highlights the associations between sensory neuropathies and other symptoms, particularly cerebellar ataxia. Given the ultra-rarity of HSNs, future multicenter studies with larger cohorts may facilitate the identification of novel variants, improve genetic diagnostic rates, and enhance disease recognition.
Rajabally YA, Englezou C, Cluett G
… +16 more, Bellanti R, Rinaldi S, Chin MW, Hadden R, Roman M, Hewamadduma C, Murray A, Elsaddig A, Lavin T, Cousins O, Nirmalananthan N, Freiha J, Osman C, Evans M, Carr A, Holt JKL
J Peripher Nerv Syst
· 2025 Jun · PMID 40210218
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BACKGROUND: We conducted a survey to determine the current diagnosis and treatment of multifocal motor neuropathy (MMN) in the United Kingdom. METHODS: Demographic, diagnostic and treatment data were collected at nine UK...BACKGROUND: We conducted a survey to determine the current diagnosis and treatment of multifocal motor neuropathy (MMN) in the United Kingdom. METHODS: Demographic, diagnostic and treatment data were collected at nine UK neuroscience centres. RESULTS: Ninety-five subjects were included. Mean age at diagnosis was 49.9 years (SD: 11.4). Males were more commonly affected (ratio: 1.9:1). Diagnostic delay was > 1 year from the time of first neurological assessment, in > 50% of subjects. Applying modified EFNS/PNS 2010 criteria, 69/95 (72.6%) had definite MMN, 10/95 (10.5%) had probable MMN, 15/95 (15.8%) had possible MMN, through treatment responsiveness in 9/15 (60%) and 1/95 (1.1%) did not meet criteria. Cerebrospinal fluid examination, anti-GM1 antibody testing and brachial plexus magnetic resonance imaging were non-contributory. Immunoglobulin response was reported in 90/92 subjects (97.8%), and 84/90 (93.3%) remained on treatment after a mean of 9.4 years, at a mean dose of 26.2 g/week (range: 4-114). Mean long-term immunoglobulin dose was 30%-60% higher than reported in neighbouring countries. Contrasting with previous reports of frequent loss of immunoglobulin response and functional decline, our physician-assessed long-term outcome was favourable (stable or improving) in 74/84 (88.1%) treated subjects. INTERPRETATION: MMN diagnosis and treatment in the United Kingdom are comparable to that of neighbouring countries and follow existing guidelines. Diagnostic delay after the first neurological assessment is considerable. Electrophysiology shows at least one definite/probable conduction block in nearly 90% of cases. The mean long-term immunoglobulin dose is higher in the United Kingdom than reported elsewhere, although highly variable. Whether higher doses of immunoglobulin may improve long-term outcomes requires further study.
Falcão de Campos C, Miranda M, Castro I
… +3 more, Castro J, Oliveira Santos M, Conceição I
J Peripher Nerv Syst
· 2025 Jun · PMID 40194884
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BACKGROUND AND AIMS: Domino liver transplantation (DLT) has been used to address the shortage of donor organs. However, recipients of liver grafts from patients with hereditary transthyretin amyloidosis (ATTRv) develop d...BACKGROUND AND AIMS: Domino liver transplantation (DLT) has been used to address the shortage of donor organs. However, recipients of liver grafts from patients with hereditary transthyretin amyloidosis (ATTRv) develop de novo transthyretin (TTR) amyloidosis. Our aim is to describe the clinical presentation of patients with acquired TTR amyloidosis and compare the rate of neuropathy progression (NP) with untreated ATTRv amyloidosis with neuropathy (ATTRv-NP) patients. METHODS: Patients with acquired TTR amyloidosis after DLT followed at a reference centre were evaluated. Medical records were reviewed for clinical characterization and systematic assessment of neuropathy. NP was defined as an increase in neuropathy impairment score of the lower limbs (NIS-LL) at 12 months and compared to a historical control group of untreated ATTRv amyloidosis patients. RESULTS: Twenty-four patients with acquired ATTR amyloidosis were included. Time from DLT to neuropathy onset was 9 2.0 years and the majority of patients reported feet sensory changes as first symptom. Thirteen patients with ≥ 2 evaluations with 12-months interval were analysed. Almost all patients developed a neuropathic phenotype with small nerve fibre involvement. Neuropathy progression was similar to untreated ATTRv-NP patients. INTERPRETATION: Recipients from liver grafts of ATTRv patients develop de novo amyloidosis with clinical presentation and NP similar to untreated ATTRv amyloidosis patients. Study of these patients might help elucidate the pathways for ATTR fibril formation.
Andrade RJ, Nordez A, Magot A
… +7 more, Couloume L, Plançon JP, Quillard JB, Ware RS, Coppieters MW, Péréon Y, Hug F
J Peripher Nerv Syst
· 2025 Jun · PMID 40189914
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BACKGROUND AND AIMS: Repeated cycles of demyelination and remyelination alter nerve tissue composition, likely affecting its material properties, including stiffness. Using ultrasound shear wave elastography (SWE), we as...BACKGROUND AND AIMS: Repeated cycles of demyelination and remyelination alter nerve tissue composition, likely affecting its material properties, including stiffness. Using ultrasound shear wave elastography (SWE), we assessed nerve shear wave velocity (SWV), a surrogate measure of stiffness, to determine its potential as a biomarker for demyelinating neuropathies, including chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth type 1A, and anti-myelin-associated glycoprotein neuropathy. METHODS: This cross-sectional study compared nerve SWV between 20 patients with demyelinating neuropathies (60.2 ± 13.1 years) and 16 age-matched controls (56.8 ± 10.8 years). Each participant underwent bilateral SWE of the proximal and distal segments of four peripheral nerves in the upper (median, ulnar and radial) and lower (sciatic-tibial) limbs. Measurements were conducted in different limb positions to mimic two nerve tensile states, yielding a total of 32 nerve stiffness measurements per participant. Conventional nerve cross-sectional area was further evaluated for each nerve and location. RESULTS: Individuals with demyelinating polyneuropathy exhibited increased nerve SWV compared to age-matched controls (mean difference = 0.7 m/s, 95%CI [0.5 to 0.9]; p < 0.0001). This difference was observed across all nerves and regions, with the largest difference noted in the tibial. Axial nerve tension amplified these differences. Additionally, moderate to high negative correlations were observed between motor nerve conduction and nerve SWV. INTERPRETATION: This study identifies significant neuropathy-associated alterations in peripheral nerve elasticity. Our findings suggest that nerve stiffness could be a promising biomarker for demyelinating neuropathies, and provide a basis for the development of standardized peripheral nerve SWE protocols.
Wannarong T, Skolka MP, Rattanathamsakul N
… +10 more, Swart G, Dyck JB, Berini SE, Dubey D, Shouman K, Pinto MV, Mauermann ML, Windebank AJ, Staff NP, Klein CJ
J Peripher Nerv Syst
· 2025 Jun · PMID 40189868
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BACKGROUND AND AIMS: Nerve conduction studies (NCS) are integral to diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but their role in predicting treatment outcomes remains underexplored. This...BACKGROUND AND AIMS: Nerve conduction studies (NCS) are integral to diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but their role in predicting treatment outcomes remains underexplored. This study evaluates NCS changes at first follow-up (first NCS changes) as predictors of treatment success in CIDP, focusing on their correlation with clinical outcomes over time. METHODS: Newly diagnosed CIDP patients meeting the 2021 EAN/PNS criteria were retrospectively evaluated. Baseline and first follow-up NCS parameters were compared with clinical outcomes, assessed by the Neuropathy Impairment Score (NIS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. All patients received first-line immunotherapy (intravenous immunoglobulin, corticosteroids, or plasma exchange). RESULTS: Of 39 treated patients, 26 (66.7%) were responders based on improving NIS trends, while 13 (33.3%) were nonresponders. Responders showed significant improvements at the first follow-up in fibular compound muscle action potential (CMAP) amplitude, ulnar CMAP amplitude, summated CMAP amplitudes, and fibular motor conduction velocity. Changes in fibular CMAP amplitude consistently correlated with NIS (R = -0.8 to -0.6, p ≤ 0.004) and INCAT disability score improvements (R = -0.6 to -0.3, p ≤ 0.032) across all follow-up intervals up to 60 months. Ulnar and summated CMAP amplitude changes also correlated with clinical outcomes, though their associations were less sustained than those of fibular CMAP amplitude. INTERPRETATION: The first change in fibular CMAP amplitude is a reliable biomarker for predicting CIDP treatment response, with ulnar and summated CMAP amplitudes as alternatives when the fibular response is absent. Our findings highlight the utility of first NCS changes in monitoring and predicting treatment outcomes in CIDP.
Juros D, Hastings RL, Pendragon A
… +2 more, Kay J, Valdez G
J Peripher Nerv Syst
· 2025 Mar · PMID 40099661
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BACKGROUND AND AIMS: At the neuromuscular junction (NMJ), the synapse between motor neurons and muscle fibers, reside perisynaptic Schwann cells (PSCs) which are specialized glia that regulate the maintenance and repair...BACKGROUND AND AIMS: At the neuromuscular junction (NMJ), the synapse between motor neurons and muscle fibers, reside perisynaptic Schwann cells (PSCs) which are specialized glia that regulate the maintenance and repair of this synapse. While we know how PSC morphology and numbers change in aging and various neuromuscular disorders that adversely affect the NMJ, the molecular mechanisms that alter PSC functions remain unknown. In this study, we investigated whether MEGF10 in PSCs modulates NMJ stability in developing, healthy young adult, middle-aged, and axotomized mice. MEGF10 is a glial phagocytic receptor that is enriched in PSCs compared to other Schwann cells (SCs). METHODS: We isolated PSCs from a transgenic reporter mouse line to assess Megf10 expression at different ages and following nerve injury using qPCR. We then used a conditional mouse lacking Megf10 in all SCs, including PSCs (Megf10 SC-KO mice). We examined NMJs and axonal debris clearance in Megf10 SC-KO mice using confocal microscopy. RESULTS: We found that Megf10 expression in PSCs peaks during development and decreases during aging and following denervation of NMJs. NMJs were morphologically normal in developing and young adult Megf10 SC-KO mice. This was not the case in middle-aged Megf10 SC-KO mice, in which NMJs presented with fewer PSCs, decreased PSC coverage of the endplate, and decreased innervation in comparison to control mice. Following nerve injury-induced damage, axonal debris at the NMJ was cleared faster in Megf10 SC-KO mice; yet, the rate of reinnervation was unchanged compared to control mice. INTERPRETATION: The data in this study suggest that MEGF10 in PSCs functions to maintain PSC number and NMJ innervation during aging. This study also suggests important roles for MEGF10 in mediating the clearance of axonal debris at NMJs following nerve injury.
Lemmen DL, van Eijk RPA, van Unnik JWJ
… +5 more, Allen JA, Rajabally YA, van den Berg LH, van der Pol WL, Goedee HS
J Peripher Nerv Syst
· 2025 Mar · PMID 40099640
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BACKGROUND AND AIMS: Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies characterized by muscle weakness and/or sensory deficits. Identifying t...BACKGROUND AND AIMS: Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies characterized by muscle weakness and/or sensory deficits. Identifying treatment response, relapse, and stability can be challenging in these chronic, sometimes unpredictable, conditions. This study explores the potential of a monitoring app designed to address these challenges. METHODS: Patients were monitored weekly or monthly, based on stability and patient preference, using grip strength, modified timed-up-and go (mTUG), and patient-reported outcome measures (PROMs). User experience was evaluated via a questionnaire addressing content and ease of use (scale 0-10). Adherence was measured as the percentage of completed mandatory assessments. We investigated reliability using intra-class correlation coefficients (ICCs) and standard errors of the mean (SEM) of repeated measurements. Longitudinal changes were analyzed using linear mixed-effects models. RESULTS: We included 38 patients, with a mean follow-up of 11 months (IQR 4.6-19.5). The mean user experience score was 8.35/10 (range 7-10). Adherence was 93% (95% CI: 91.9%-94.1%). Reported remote measurements for grip strength were 1358/1468 (93%), and 1343/1430 (94%) for mTUG. Grip strength and mTUG ICCs were both 0.96 (95% CI: 0.93-0.98 and 0.92-0.99, respectively). The average SEM was 8.46% (95% CI: 6.58-10.28) for grip strength and 8.18% (95% CI: 6.12-10.41) for mTUG. Only grip strength changed significantly, increasing by 3.1 pounds per 6 months (95% CI: 0.61-5.83; p = 0.016). INTERPRETATION: Our study demonstrates that tele-neuromonitoring is feasible and reliable, showing high adherence, positive user experience and high ICCs. We anticipate tele-neuromonitoring could complement routine follow-up, enabling clinicians to make better-informed treatment decisions.
Panrudkevich A, Jabari D, Putko B
… +4 more, Daley C, Lewis RA, Dubey D, Pinto MV
J Peripher Nerv Syst
· 2025 Mar · PMID 40099632
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BACKGROUND AND AIMS: Leucine Zipper 4 (LUZP4)-immunoglobulin G (IgG) is a novel antibody implicated in germ cell tumor-related paraneoplastic neurologic syndrome. We report a case of painful, progressive tetraparesis ass...BACKGROUND AND AIMS: Leucine Zipper 4 (LUZP4)-immunoglobulin G (IgG) is a novel antibody implicated in germ cell tumor-related paraneoplastic neurologic syndrome. We report a case of painful, progressive tetraparesis associated with testicular seminoma and LUZP4-IgG seropositivity. CASE REPORT: A 51-year-old male presented with a 5-week history of lower limb predominant progressive weakness. Nerve conduction studies (NCS) and electromyography (EMG) revealed a subacute axonal polyradiculoneuropathy. MRI lumbar spine showed thickening of the cauda equina and enhancement of the lower thoracic spinal cord/conus. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, three oligoclonal bands, and mildly elevated protein. Initial treatment with intravenous immunoglobulin (IVIG) and prednisone produced temporary improvement. CT targeted retroperitoneal lymph node biopsy revealed a seminoma, which was treated with orchiectomy and chemotherapy. The testicular tissue was consistent with a regressed germ cell tumor. His course was subsequently refractory to IVIG, prednisone, and plasma exchange. LUZP4 antibodies were detected in serum, prompting treatment with cyclophosphamide and prednisone. At the 4-month follow-up, the patient had significant improvement in hand strength and had transitioned from walker to cane. INTERPRETATION: LUZP4-IgG seropositivity and identification of retroperitoneal seminoma confirmed a paraneoplastic neurologic syndrome, which is a CD8+ T-cell-mediated disorder. Aggressive immunotherapy was initiated, resulting in clinical improvement. This case underscores the importance of identifying specific serologic biomarkers that can inform therapeutic decisions and improve outcomes.
Lima MFO, Nogueira VB, Maury W
… +4 more, Wilson ME, Júnior METD, Teixeira DG, Bezerra Jeronimo SM
J Peripher Nerv Syst
· 2025 Mar · PMID 40099626
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BACKGROUND AND AIMS: Guillain-Barré syndrome (GBS) is a rare disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GB...BACKGROUND AND AIMS: Guillain-Barré syndrome (GBS) is a rare disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GBS. The aim of the study was to identify host genes involved in the pathogenesis of GBS when Zika (ZIKV) and Chikungunya viruses (CHIKV) were introduced in Brazil. METHODS: A case-control study of GBS was performed when ZIKV and CHIKV were introduced into a naïve population. GBS was studied during both acute and postacute phases. RNA sequencing was conducted using whole blood. RESULTS: GBS typically manifested a week after rash and fever; acute inflammatory demyelinating polyradiculoneuropathy was more frequent. None of the GBS cases had a poor outcome. Serological assays for ZIKV and CHIKV revealed high titers of immunoglobulin G for both viruses in 9 out of 11 subjects. Metatranscriptomic analyses unveiled an increased abundance of reads attributed to Pseudomonas tolaasii and Toxoplasma gondii in the acute phase. Analysis of differentially expressed host genes during the acute phase revealed altered expression of genes associated with axogenesis, synapse assembly, and presynapse organization. Moreover, genes upregulated during acute GBS were primarily related to inflammation and the inflammasome pathways, including AIM2, NLR family genes and LRR-protein genes, and IL-10. INTERPRETATION: These findings suggest that inflammasome activation via AIM2 could play a role in tissue damage during GBS. Further investigation into the general activation of innate inflammatory responses is warranted to elucidate their potential contribution to the pathology of GBS.
Adhikari U, Gad H, Chatterjee D
… +4 more, Malhotra C, Bhadada SK, Malik RA, Rastogi A
J Peripher Nerv Syst
· 2025 Mar · PMID 40044634
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OBJECTIVES: There are currently no FDA-approved disease-modifying therapies for diabetic peripheral neuropathy (DPN). We evaluated the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in Type...OBJECTIVES: There are currently no FDA-approved disease-modifying therapies for diabetic peripheral neuropathy (DPN). We evaluated the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in Type 2 diabetes mellitus (T2DM) with DPN. RESEARCH DESIGN AND METHODS: In this prospective, open-label, randomised, controlled study, 40 participants with DPN were randomised to receive add-on 10 mg dapagliflozin OD (Group A) to existing oral antidiabetic drugs (OAD) (n = 22) or continue OADs as a standard of care (Group B) (n = 18). Participants underwent assessment of neuropathic symptoms and signs (MNSI), vibration perception threshold (VPT), corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL) and skin biopsy to assess intraepidermal nerve fibre density (IENFD) and plasma markers of oxidative stress at randomisation and after 6 months. RESULTS: HbA1c decreased in Group A (p = 0.002) and Group B (p = 0.003), with no change in weight, body mass index (BMI) or lipids. Total MNSI increased in Group A (p = 0.01) with no change in Group B (p = 0.06). IENFD increased significantly in Group A (p = 0.01) and Group B (p = 0.01), while CNFD (p = 0.002), CNBD (p < 0.001) and CNFL (p = 0.025) increased in Group A with no change in Group B. There was a significant increase in glutathione peroxidase (p = 0.02) in Group A with no change in Group B, and a decrease in malondialdehyde in both groups (p < 0.001). CONCLUSIONS: In participants with T2DM and DPN, dapagliflozin was associated with small nerve fibre regeneration and improvement in markers of oxidative stress. TRIAL REGISTRATION: Clinical Trial Registry India, CRTI Reg. No (CTRI/2022/06/043236); ClinicalTrials.gov Identifier: NCT05162690.
Moritz CP, Tholance Y, Borowczyk C
… +4 more, Jospin F, Paul S, Antoine JC, Camdessanché JP
J Peripher Nerv Syst
· 2025 Mar · PMID 40037793
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BACKGROUND AND AIMS: Immune-mediated sensory neuronopathies (SNN) can occur alongside autoimmune disorders (e.g., Sjögren syndrome), involve autoantibodies (such as anti-FGFR3 or anti-AGO antibodies), or present in isola...BACKGROUND AND AIMS: Immune-mediated sensory neuronopathies (SNN) can occur alongside autoimmune disorders (e.g., Sjögren syndrome), involve autoantibodies (such as anti-FGFR3 or anti-AGO antibodies), or present in isolation. The underlying mechanisms remain unclear. This study aimed to investigate the role of proinflammatory cytokines in these conditions. METHODS: Blood levels of IL-1β, IL-6, IL-17, TNF-α, INF α-2, and INF-γ were measured using a Bioplex T200 platform and the Bio-Plex Pro Reagent Kit III in 113 patients with SNN between 2.4 and 464.4 months after symptom onset, categorized based on disease course (acute, subacute, chronic). Eighteen patients had anti-AGO antibodies, 48 had anti-FGFR3 antibodies, and 14 had an autoimmune disease without detectable anti-AGO or FGFR3 antibodies. Disease extent was measured by the SNN score, while the disease severity was evaluated using the modified Rankin score. Immunoreactivity against IL-6 and INF-γ was measured via ELISA. RESULTS: Multicomponent analysis utilizing cytokines levels identified four distinct patient subgroups characterized by differences in age at onset and SNN score. No significant differences were observed among the subgroups regarding disease course and severity, presence of anti-AGO or anti-FGFR3 antibodies, or association with an autoimmune disease. A small subgroup of three younger patients exhibited the highest levels of TNF-α, IL-6, and IL-1β. Another subgroup of seven patients displayed elevated INF α-2 levels and tended towards highest SNN scores. The largest group (95 subjects) comprised older individuals with relatively lower cytokine levels and decreased anti-IL-6 immunoreactivity. INTERPRETATION: These cytokine profiles suggest diverse underlying mechanisms within immune-mediated SNN. Further investigation is warranted to determine whether certain profiles, particularly those involving young patients with elevated proinflammatory cytokines, might benefit from targeted treatments.
Schilke ED, Cereda D, Fusco ML
… +10 more, Stanzani L, Marzorati L, Ripolone M, Bertolasi L, Frigo M, Molteni F, Farina N, Ferrarese C, Cavaletti G, Balducci C
J Peripher Nerv Syst
· 2025 Mar · PMID 40024618
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BACKGROUND AND AIMS: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disorder; about 20%-30% of patients do not adequately respond to first-line treatments (immunoglobulins, therapeutic...BACKGROUND AND AIMS: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disorder; about 20%-30% of patients do not adequately respond to first-line treatments (immunoglobulins, therapeutic plasmapheresis, and corticosteroids) posing diagnostic and therapeutic challenges. CASE REPORT: We report the case of a 58-year-old man diagnosed with CIDP. During follow-up, he progressively became refractory to all first-line treatments. Therefore, 20 months after the diagnosis, an add-on therapy with Rituximab was tried. Despite previous works supporting the use of Rituximab in refractory CIDP, in our case, the patient experienced relapses and progressive increases in disability. After the exclusion of potential CIDP mimics and considering the histological findings that showed complement activation, we opted for an innovative therapeutic approach with Eculizumab that granted a significant clinical and neurophysiological benefit that persists after 7 months of follow-up. INTERPRETATION: CIDP pathogenesis is characterized by a complex interplay of different immunopathological mechanisms, and the complement system may play a major role. The present case supports the role of complement-dependent toxicity in CIDP and suggests that complement-targeted therapies may represent a well-tolerated and effective alternative for CIDP treatment.