Skolka MP, Swart G, Shelly S
… +10 more, Wannarong T, Stålberg S, Stålberg B, Gardner A, Price J, Laughlin RS, Dubey D, Mills JR, Mandrekar J, Klein CJ
J Peripher Nerv Syst
· 2025 Dec · PMID 41414759
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BACKGROUND AND AIMS: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a common, treatable, autoimmune, neuropathy frequently misdiagnosed. The complex electrodiagnostic (EDX) criteria required for diag...BACKGROUND AND AIMS: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a common, treatable, autoimmune, neuropathy frequently misdiagnosed. The complex electrodiagnostic (EDX) criteria required for diagnosis are challenging to apply in routine practice. This study evaluates the effectiveness of a machine-assisted EDX tool in real-time identification of demyelinating nerve conduction studies (NCS) stipulated by 2021-EAN/PNS CIDP criteria in conjunction with an online CIDP clinical probability calculator. METHODS: We prospectively evaluated 100 consecutive patients with referral or EDX diagnosis of polyradiculoneuropathy beginning January 1, 2024. Fifty patients were included, each from Jacksonville and Rochester Mayo Clinics. Routine electromyography (EMG) reports were compared to a machine-assisted support tool applying 2021-EAN/PNS CIDP EDX criteria to NCS assessing demyelination. The EDX-assistant performance was compared to the final clinical diagnosis and our previously reported online CIDP clinical prediction tool (https://news.mayocliniclabs.com/cidp-calculator/). RESULTS: Among 100 patients (60% male; median age 64), 30 had a final clinical CIDP diagnosis with 29 having intravenous immunoglobulin follow-up; 27 (93%) improved and 2 (7%) stabilized. Routine EMGs reported demyelination in 14 of 30 (47%), with 46% sensitivity and 79% specificity. The EDX-assistant identified CIDP demyelination in 28 of 30 (93%), with 93% sensitivity and 57% specificity. The clinical calculator detected CIDP in 30 of 30 (100%) with 86% specificity, increasing to 94% after excluding false positives lacking demyelinating features on the EDX tool. INTERPRETATION: A real-time machine-assisted EDX support tool, used with a clinical web-based calculator, streamlines CIDP assessment by improving standardized identification of 2021-EAN/PNS CIDP demyelinating NCS criteria and aiding clinical decisions.
Bozovic I, Gwathmey K, Peric S
… +4 more, Kacar A, Lazovic J, Sadjadi R, Basta I
J Peripher Nerv Syst
· 2025 Dec · PMID 41410018
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BACKGROUND AND AIMS: In most studies to date, generic health-related quality of life (QoL) questionnaires have been used in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Unfortunately, t...BACKGROUND AND AIMS: In most studies to date, generic health-related quality of life (QoL) questionnaires have been used in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Unfortunately, these tools are often considered insufficient for capturing the unique characteristics of this specific, rare disease. The Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI) is a measure which specifically targets patients with chronic immune-mediated polyneuropathies. This is the first study which longitudinally assessed QoL and functionality by CAP-PRI in patients with active CIDP. METHODS: CAP-PRI testing was conducted at three time points (baseline, year one and year four) in 57 CIDP patients with active disease at baseline. In addition, the Medical Research Council Sum Score (MRC-SS), Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Inflammatory Rasch-built Overall Disability Scale (I-RODS), and the generic QOL instrument, the Short Form 36 (SF-36) were used in all tested patients at all three time points. RESULTS: At the baseline and two other time points, CAP-PRI showed strong correlations with impairment (MRC-SS), functionality (INCAT, I-RODS), and the SF-36. At year one and year four, CAP-PRI was able to make a differentiation between patients whose impairment/disability improved compared to patients who deteriorated, and it performed better than SF-36. One- and four-year changes in CAP-PRI correlated with a change in MRC-SS, INCAT, and I-RODS. INTERPRETATION: CAP-PRI is a highly reliable and sensitive measure for assessing QoL in patients with active CIDP. Its consistent performance over time supports its utility in monitoring CIDP patients with active disease in clinical and research settings.
Zhang VJW, Ritter LM, Hoskote C
… +4 more, Siddiqui A, Lunn M, Gillmore J, Reilly MM
J Peripher Nerv Syst
· 2025 Dec · PMID 41383038
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BACKGROUND: Treatment options for central nervous system (CNS) manifestations of ATTRv amyloidosis remain limited, with no disease-modifying therapy. However, previous case series have indicated that tafamidis (a transth...BACKGROUND: Treatment options for central nervous system (CNS) manifestations of ATTRv amyloidosis remain limited, with no disease-modifying therapy. However, previous case series have indicated that tafamidis (a transthyretin stabiliser) crosses the blood-brain barrier in small quantities. We present long-term follow-up data on two patients with CNS manifestations of ATTRv who received high-dose (61 mg) oral tafamidis. METHODS: Patient one is a 48-year-old man with p.Gly73Ala ATTRv peripheral neuropathy and commenced on gene-silencing therapy. He was subsequently diagnosed with early ATTRv CNS involvement, prompting the addition of tafamidis since age 45. Patient two is a 27-year-old woman with p.Gly67Arg ATTRv with significant CNS involvement resulting in epilepsy and encephalopathy. Since age 21, she has been on gene-silencing therapy and tafamidis. RESULTS: Following 3 years of therapy, patient one has remained clinically asymptomatic. However, brain magnetic resonance imaging (MRI) and cerebrospinal fluid assessment have demonstrated progression of his CNS ATTRv. Followed 6 years of therapy, patient two has continued to have seizures requiring escalation of anti-seizure medications and MRI brain has shown progression of CNS disease. CONCLUSIONS: In our two patients, progression of CNS disease occurred whilst on high-dose tafamidis, highlighting the importance of further studies into the monitoring and treatment of CNS manifestations of ATTRv.
Kreß L, Meyer Zu Altenschildesche C, Egenolf N
… +3 more, Sommer C, Hornemann T, Üçeyler N
J Peripher Nerv Syst
· 2025 Dec · PMID 41376410
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BACKGROUND AND AIMS: Dysfunctional sphingolipid metabolism leads to nerve fiber degeneration, particularly of small caliber Aδ and C fibers, in hereditary sensory and autonomic neuropathies. We aimed to investigate the a...BACKGROUND AND AIMS: Dysfunctional sphingolipid metabolism leads to nerve fiber degeneration, particularly of small caliber Aδ and C fibers, in hereditary sensory and autonomic neuropathies. We aimed to investigate the association of blood 1-deoxysphingolipid (1-deoxySL) profiles and skin denervation in idiopathic small fiber neuropathy (SFN). METHODS: Seventy-five patients with idiopathic SFN were recruited prospectively. Patients underwent a skin punch biopsy at the lower leg and upper thigh for intraepidermal nerve fiber density (IENFD) quantification. IENFD was correlated with individual blood 1-deoxySL levels, amino acid profiles, and determinants of glucose and lipoprotein metabolism. RESULTS: Median distal IENFD in SFN patients was 5.3 fibers/mm. In 38/75 (51%) patients, IENFD was ≤ 5.3 fibers/mm (i.e., "low fiber density," LFD), while in 37/75 (49%) patients, IENFD was > 5.3 fibers/mm (i.e., "high fiber density," HFD). 1-deoxySL was higher in patients with LFD compared to HFD (p < 0.05). Fasting plasma glucose was also higher in patients with LFD than in patients with HFD (p < 0.01), while HDL was lower in patients with LFD compared to HFD (p < 0.001). INTERPRETATION: 1-deoxySL, lipoprotein metabolism, and glucose levels are associated with the extent of epidermal denervation in SFN, supporting the role of this metabolic axis in small nerve fiber pathology.
Maino A, Hazane-Puch F, Petiot P
… +4 more, Roux-Buisson N, Rendu J, Fauré J, Hardy G
J Peripher Nerv Syst
· 2025 Dec · PMID 41363019
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BACKGROUND AND AIMS: Variants in the myelin protein zero coding MPZ gene are responsible for a broad spectrum of peripheral demyelinating and axonal neuropathies, including different types of Charcot-Marie-Tooth diseases...BACKGROUND AND AIMS: Variants in the myelin protein zero coding MPZ gene are responsible for a broad spectrum of peripheral demyelinating and axonal neuropathies, including different types of Charcot-Marie-Tooth diseases, challenging for genotype-phenotype correlation. METHODS: Minigene splicing reporter assay was used to unveil the pathogenic mechanism of a novel MPZ(NM_000530.8) c.234 + 1G>C p.(?) heterozygous splice variant. RESULTS: The variant was identified in a 47-year-old female patient presenting with atypical clinical features, including balance disturbance with positive Romberg, absent Achilles tendon reflexes, distal hypoesthesia and bulbar involvement, including dysarthria and dysphagia. Electromyography revealed a sensory-motor neuropathy with moderately reduced nerve conduction velocities. In silico analysis predicted this variant to disrupt the consensual donor splice site located in intron 2 of MPZ. Minigene construction confirmed the functional impact of this variant, revealing exon 2 skipping and the apparition of a premature termination codon. INTERPRETATION: This case expends the genotype-phenotype correlations of MPZ-related Charcot-Marie-Tooth diseases, associating atypical mild phenotype with a rare splice dominant variant, and provides new insights into MPZ haploinsufficiency and pathogenic mechanisms.
J Peripher Nerv Syst
· 2025 Dec · PMID 41362955
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BACKGROUND AND AIMS: Vasculitides are a heterogeneous group of immune-mediated inflammatory disorders that compromise the vascuar wall, leading to luminal narrowing and tissue ischemia. When inflammation selectively affe...BACKGROUND AND AIMS: Vasculitides are a heterogeneous group of immune-mediated inflammatory disorders that compromise the vascuar wall, leading to luminal narrowing and tissue ischemia. When inflammation selectively affects the vasa nervorum without systemic involvement, it results in nonsystemic vasculitic neuropathy (NSVN), an underrecognized condition. NSVN presents diagnostic challenges due to its variable clinical manifestations and reliance on nerve biopsy for definitive diagnosis. This study aimed to characterize the clinical, neurophysiological, and histopathological features of NSVN in a Brazilian cohort. METHODS: We conducted a cross-sectional, ambispective cohort study combining retrospective chart review and prospective patient assessments. Inclusion required histopathological confirmation of isolated peripheral nerve vasculitis; cases with systemic or secondary vasculitis were excluded. Data collection included clinical evaluation, neurophysiology, and nerve biopsy. RESULTS: A total of 14 patients were included (9 female, 64%; mean age: 61). Most (n = 8, 57%) had subacute onset of painful sensory or sensorimotor deficits. Multiple mononeuropathies predominated (n = 11, 78%), but a subset exhibited chronic progression (n = 5, 35%) and axonal polyneuropathy (n = 3, 21%). Electrophysiological studies revealed a consistent axonal pattern. Biopsies confirmed possible vasculitis in six (43%), and probable vasculitis in six (42%), with only two (14%) fulfilling criteria for definite vasculitis. Serologies were nonspecific. Treatment involved corticosteroid pulse therapy, with immunosuppression in refractory cases. INTERPRETATION: These findings highlight that NSVN often presents with painful sensorimotor symptoms and may clinically mimic progressive axonal polyneuropathies. Given its potential for significant morbidity if left untreated, early recognition and consideration of nerve biopsy remain critical. The diagnostic complexity and variability in presentation suggest that NSVN may be underrecognized. We hope this cohort contributes to a broader understanding of its clinical spectrum and informs future diagnostic strategies.
Behanan N, Mohamed S, Chen R
… +2 more, Mak G, Lu JQ
J Peripher Nerv Syst
· 2025 Dec · PMID 41362154
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Human cytomegalovirus (HCMV) is a neurotropic, double-stranded DNA virus from the Herpesviridae family. It has a large genome, infects the majority of populations, and typically causes asymptomatic infections in healthy...Human cytomegalovirus (HCMV) is a neurotropic, double-stranded DNA virus from the Herpesviridae family. It has a large genome, infects the majority of populations, and typically causes asymptomatic infections in healthy individuals. After the initial infection with established lifelong latency, HCMV can reactivate and cause disorders including neuropathies. Besides the infections typically in immunocompromised patients, HCMV may also trigger autoimmunity leading to tissue injury and associated pathologies. HCMV-associated neuropathies are a pathogenically heterogeneous group of peripheral nervous system (PNS) disorders that include direct HCMV infection of the nerve(s), as well as non-infectious associated neuropathies such as axonal or degenerative, vasculitic/ischemic or necrotizing, inflammatory demyelinating, and immune-mediated forms. Congenital HCMV-associated neuropathies primarily involve the cochlear/auditory and optic nerves with somewhat distinct pathogenic mechanisms compared with their postnatal counterparts, largely due to the immaturity of the fetal immune system. This article reviews the pathophysiology of PNS involvement in HCMV infection, followed by congenital HCMV-associated neuropathies with a case demonstration, and various postnatal HCMV-associated neuropathies, including a detailed review of HCMV-associated optic neuropathies, from pathogenic mechanisms to clinical and therapeutic implications. As the PNS has a few immune protective mechanisms against pathogens, direct HCMV infection of nerves is rare and occurs only in immunocompromised patients; most HCMV-associated neuropathies are secondary with multiple pathogenic mechanisms including varying degrees of autoimmunity. While the clinical manifestations of HCMV-associated neuropathies are variable, their treatment is typically empirical and case-based, focusing on antiviral therapy often combined with immunomodulatory approaches. Prompt and appropriate management can improve outcomes of HCMV-associated neuropathies.
Nakano Y, Fukui Y, Deguchi K
… +11 more, Matsuoka C, Kawano T, Taira Y, Matsuo A, Osakada Y, Yunoki T, Nomura E, Takemoto M, Morihara R, Yamashita T, Ishiura H
J Peripher Nerv Syst
· 2025 Dec · PMID 41328533
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BACKGROUND AND AIMS: Retinopathy-sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic...BACKGROUND AND AIMS: Retinopathy-sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1. Here, we report a case of a Japanese patient with RETSNS. METHODS: Clinical, neuroradiological, and electrophysiological findings were documented. Whole-genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants. RESULTS: The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole-genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild-type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization. INTERPRETATION: We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants.
J Peripher Nerv Syst
· 2025 Dec · PMID 41325768
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BACKGROUND: Sensory ataxic neuropathies (SAN) are rare large fibre sensory neuropathies characterised by progressive sensory loss and ataxia. They may be inherited or acquired. When inherited they are more commonly seen...BACKGROUND: Sensory ataxic neuropathies (SAN) are rare large fibre sensory neuropathies characterised by progressive sensory loss and ataxia. They may be inherited or acquired. When inherited they are more commonly seen as part of a broader syndrome involving cerebellar ataxia or mitochondrial dysfunction. Isolated inherited SAN are rare, and the causes are limited, including RFC1 expansions (CANVAS), POLG variants and variants in COX20 and RNF170. Spinocerebellar ataxia type 15 (SCA15), caused by deletions in the ITPR1 gene, is another potential genetic cause of SAN, as peripheral neuropathy is commonly associated with various spinocerebellar ataxias. METHODS: A 35-year-old female who presented with an asymmetrical upper limb predominant sensory ataxic neuropathy which had initially been treated as a vasculitic neuropathy at her local hospital, underwent further evaluation. RESULTS: Genetic analysis identified an approximately 6.5 Mb terminal deletion of chromosome 3p, including the ITPR1 gene. CONCLUSIONS: This case report adds to the growing body of literature on ITPR1-related diseases, highlighting the phenotypic variability of ITPR1 and identifying it as a potential cause of isolated SAN. While a connection to Sjögren's syndrome cannot be excluded, the role of ITPR1 as the primary cause remains the focus. We propose that the neuropathy community consider screening SAN patients for ITPR1 deletions, as additional cases may help clarify its clinical significance.
Cai H, Zhou F, Li T
… +7 more, Li Z, Luo J, Hu J, Deng M, Sun C, Zhao C, Lin J
J Peripher Nerv Syst
· 2025 Dec · PMID 41287201
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BACKGROUND AND AIMS: Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy characterized by progressive flaccid paralysis. The standard treatments include intravenous immunoglobulin (IVIg) and plasm...BACKGROUND AND AIMS: Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy characterized by progressive flaccid paralysis. The standard treatments include intravenous immunoglobulin (IVIg) and plasma exchange (PE), with limited accessibility to these treatments. Efgartigimod is an FcRn antagonist that reduces IgG levels, similar to PE, serving as a potential alternative. This study aims to compare the efficacy of Efgartigimod with standard IVIg in GBS. METHODS: This was a multicenter observational study in China. Eligible participants were aged ≥ 16 years, meeting the diagnostic criteria for GBS, and presented with a GBS Disability Scale score ≤ 5 at baseline assessment. Participants received efgartigimod (10 mg/kg per week up to 4 doses) or IVIg (2 g/kg once). Outcomes were assessed at baseline, week 1, and week 2 post-treatment, and at the last follow-up. The primary efficacy endpoint was the proportion of participants improving at least 1 point on the GBS-DS. RESULTS: Between January and October 2024, 22 GBS patients were enrolled, including 11 in each group. At week 1, 14 patients improved in GBS-DS, with 7 (63.6%) in the efgartigimod group and 7 (63.6%) in the IVIg group. Median time to improvement was 4 days in the efgartigimod group and 8 days in the IVIg group. At week 2, GBS-DS response rates were 90.9% (10/11) for efgartigimod and 81.8% (9/11) for IVIg. INTERPRETATION: Based on our preliminary findings, intravenous efgartigimod may be potentially tolerated in GBS over the short term. However, this study cannot establish comparative efficacy given the methodological limitations, and large-scale well-controlled head-to-head trials remain imperative.
Voth J, von Gall C, Gmahl N
… +5 more, Werner NM, Meyer Zu Hörste G, Meuth SG, Pawlitzki M, Masanneck L
J Peripher Nerv Syst
· 2025 Dec · PMID 41257389
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BACKGROUND AND AIMS: Previous studies suggest that patients with chronic inflammatory demyelinating polyneuropathy (CIDP) experience impaired sleep, contributing to fatigue. Traditional methods like polysomnography or qu...BACKGROUND AND AIMS: Previous studies suggest that patients with chronic inflammatory demyelinating polyneuropathy (CIDP) experience impaired sleep, contributing to fatigue. Traditional methods like polysomnography or questionnaires are resource-intensive and may not capture sleep in natural settings. We explored whether widely available consumer-grade smartwatches offer a feasible way to assess sleep quality in this population. METHODS: The Electronic Monitoring of Disease Activity in patients with CIDP (EMDA-CIDP) study was a prospective observational study conducted from January 2023 to July 2024 at the University Hospitals of Düsseldorf and Münster. 46 patients had nighttime sleep recorded for 6 months via smartwatch. Additionally, clinical scores (e.g., Inflammatory Rasch-built Overall Disability Scale), sleep (PSQI, Pittsburgh Sleep Quality Index), and quality of life (QoL) questionnaires were collected every 3 months. RESULTS: Of 46 participants, 40 met adherence criteria (≥ 75% wear time on ≥ 75% of nights, median age: 66 years [IQR: 59.5-70.3], 9 [22.5%] female). Median PSQI score was 6 (4-7.6), sleep efficiency 93% (92-95), and WASO (wake after sleep onset) 32 min (24-42). Smartwatch-derived objective sleep measures - sleep efficiency and WASO - correlated significantly with PSQI (Spearman's R = -0.49, R = 0.40), clinical scores, and QoL. INTERPRETATION: Sleep is impaired in patients with CIDP and contributes to the overall disease burden. Our findings suggest that sleep disturbances can be tracked longitudinally using smartwatch-derived markers. Integrating digital health data presents promising opportunities for long-term sleep monitoring in this population. Larger studies, ideally incorporating polysomnography, are warranted to validate these findings.
Lee AJ, Nam SH, Lee S
… +4 more, Lee SM, Lee KS, Choi BO, Chung KW
J Peripher Nerv Syst
· 2025 Dec · PMID 41253107
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BACKGROUND AND AIMS: De novo mutations provide a fundamental source of gene pool changes, driving genomic microevolution. Charcot-Marie-Tooth disease (CMT), which is a group of genetically and clinically heterogeneous pe...BACKGROUND AND AIMS: De novo mutations provide a fundamental source of gene pool changes, driving genomic microevolution. Charcot-Marie-Tooth disease (CMT), which is a group of genetically and clinically heterogeneous peripheral neuropathic disorders, is characterized by progressive muscle weakness, hand and foot deformities, and occasional involvement of other organs. This study conducted the first cohort study of de novo mutations in CMT patients. METHODS: De novo mutations were examined in 151 genetically diagnosed father-mother-child trio autosomal dominant CMT families except for CMT1A. RESULTS: We identified 49 de novo point or small indel mutations in 61 patients. The frequency of de novo mutations was 40.4%, with gene-specific rates in their distribution. Haplotype analysis revealed predominant paternal origin, consistent with previous reports for CMT1A. Frequent substitutions at highly methylated CpG sites suggested that CpG methylation strongly contributes to the induction of de novo mutations. In particular, this study observed an anticipation of earlier onset in the affected children compared to their parents (founders) with de novo mutations. INTERPRETATION: This study reports de novo mutations that occur frequently in CMT families. Characterization of de novo pathogenic mutations is expected to provide valuable insights not only into the genetic diagnosis and treatment of rare genetic diseases, but also into the evolutionary genomic study of deleterious alleles.
Noushad MA, Al-Areed A, Iqbal R
… +3 more, Freiha J, Osman C, Rajabally YA
J Peripher Nerv Syst
· 2025 Dec · PMID 41248672
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BACKGROUND: Long-term functional outcomes are uncertain in immunoglobulin-treated multifocal motor neuropathy (MMN). METHODS: We retrospectively studied consecutive subjects with MMN from two neuromuscular centres in Sou...BACKGROUND: Long-term functional outcomes are uncertain in immunoglobulin-treated multifocal motor neuropathy (MMN). METHODS: We retrospectively studied consecutive subjects with MMN from two neuromuscular centres in Southampton and Birmingham, UK. Initial and latest MMN-Rasch-built Overall Disability Scale (MMN-RODS) scores and latest immunoglobulin doses were collected. Latest dose alterations and resulting MMN-RODS changes were ascertained. RESULTS: We included 32 subjects with MMN (14 females and 18 males). Mean age was 60.0 years (SD: 11.7). Over a mean of 6.2 years, MMN-RODS scores improved in 29 out of 32 (90.6%) subjects and worsened in 3 out of 32 (9.4%) subjects. Mean latest centile MMN-RODS was improved compared to mean initial centile MMN-RODS (81.53 [SD: 14.14] vs. 63.47 [SD: 13.82]; p < 0.001). Mean latest immunoglobulin dose was 26.3 g/week (range: 4-70). There were no associations of the latest immunoglobulin dose with age/disease duration/weight/gender/comorbidities/initial disability/latest disability. There were no inter-centre differences in age/disease duration/weight/gender/comorbidities/initial disability/latest disability. The latest mean immunoglobulin dose was higher in Birmingham than in Southampton (33.9 g/week [SD: 17.1] vs. 18.8 g/week [SD: 8.0]; p = 0.004). Immunoglobulin dose dependency was observed in 16 out of 17 subjects whose last dose alteration was incremental, and in only 3 out of 15 subjects whose last dose alteration was decremental. Dose dependency was demonstrated in a greater proportion of subjects from Birmingham compared to Southampton (13/16 vs. 6/16; p = 0.03). CONCLUSIONS: Function as ascertained by the MMN-RODS shows sustained improvement over > 6 years with individualised immunoglobulin dosing in most subjects with MMN. The large inter-centre/inter-individual dosing and dose dependency variations observed may suggest implications of patient- and physician-related factors, which require further study.
Kulsirichawaroj P, Phochaisarn A, Limpaninlachat S
… +5 more, Vorasan N, Likasitwattanakul S, Ramchandren S, Shy ME, Sanmaneechai O
J Peripher Nerv Syst
· 2025 Dec · PMID 41243398
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BACKGROUND AND AIMS: Charcot-Marie-Tooth disease (CMT) is a hereditary neuropathy that causes progressive muscle weakness, sensory deficits, and impaired mobility, significantly affecting quality of life (QoL). The Pedia...BACKGROUND AND AIMS: Charcot-Marie-Tooth disease (CMT) is a hereditary neuropathy that causes progressive muscle weakness, sensory deficits, and impaired mobility, significantly affecting quality of life (QoL). The Pediatric Charcot-Marie-Tooth Quality of Life (pCMT-QoL) instrument was developed specifically for children with CMT. However, a validated Thai version is not yet available. METHODS: We conducted a cross-sectional study at the Pediatric Neuromuscular Clinic from July 2023 to December 2024. Using a forward-backward translation method, we adapted the pCMT-QoL into Thai. Twenty-three children with CMT and their caregivers completed the Thai questionnaire. We evaluated internal consistency using Cronbach's alpha and test-retest reliability using intraclass correlation coefficients (ICCs). Convergent validity was examined via Pearson correlation between child self-reports and parent-proxy reports across functional, mental, and physical domains. RESULTS: The Thai pCMT-QoL demonstrated high test-retest reliability (ICC > 0.85) and satisfactory internal consistency (Cronbach's alpha > 0.7) across most domains. Convergent validity was strong for the total and mental domains but weaker for the physical domain, reflecting differences in perception between children and parents. Parents generally reported higher QoL scores than children did, a finding consistent with studies in other neuromuscular diseases. Most participants completed the questionnaire within 15 min, suggesting good feasibility. INTERPRETATION: The Thai pCMT-QoL is a reliable, culturally adapted tool for assessing QoL in children with CMT. It is suitable for both remote and in-clinic administration. Future studies with larger cohorts are needed to confirm its responsiveness to clinical changes and to broaden its application in diverse settings.
Pozzi E, Serra MP, Boi M
… +10 more, Canta A, Chiorazzi A, Capelli C, Invernizzi C, Ballarini E, Rodriguez-Menendez V, Kraus MF, Quartu M, Cavaletti G, Alberti P
J Peripher Nerv Syst
· 2025 Dec · PMID 41239998
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BACKGROUND AND AIMS: Oxaliplatin (OHP) induced peripheral neurotoxicity (OIPN) is a complex spectrum comprising an acute and a chronic form. Acute OIPN leads to unpleasant transient sensations in the 24-72 h after chemot...BACKGROUND AND AIMS: Oxaliplatin (OHP) induced peripheral neurotoxicity (OIPN) is a complex spectrum comprising an acute and a chronic form. Acute OIPN leads to unpleasant transient sensations in the 24-72 h after chemotherapy, due to a temporary dysfunction in ion channels (i.e., axonal hyperexcitability in the absence of anatomical damage). Whereas chronic OIPN is characterized by painful manifestations. Literature data showed that a more pronounced acute OIPN could be an early predictor of chronic OIPN; thus, acute OIPN is becoming a possible target to prevent chronic OIPN. We went back to the bench side to characterize the complexity of painful phenomena experienced by OHP-treated patients. METHODS: Female OHP-treated (3 mg/Kg, 2qwx4ws, iv) and control rats (n = 10/group) were studied. Acute OIPN was detected via nerve excitability testing (NET), whereas chronic OIPN was assessed via behavioral tests, nerve conduction studies (NCS), and neuropathology (including immunohistochemistry on lumbar spinal cord specimens) both at the end of the full chemotherapy treatment (4 weeks) and at 6 weeks of follow-up. NET was also performed 1 week after treatment completion. RESULTS: NET alterations related to acute OIPN were resolved within a week after chemotherapy. Whereas, chronic OIPN encountered only partial recovery over time, with prominent small fiber damage. Immunolabeling of the spinal cord at the end of treatment and after the follow-up period was consistent with persistent neuropathic pain. INTERPRETATION: Our data supports the statement that unpleasant manifestations due to acute and chronic OIPN mirror different underlying phenomena and assessment as two separate entities should be considered in both clinical and preclinical studies.
Imamura M, Mizutani H, Nakahara K
… +7 more, Ogata H, Taguchi T, Imura M, Nomura T, Misumi Y, Isobe N, Ueda M
J Peripher Nerv Syst
· 2025 Dec · PMID 41236406
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BACKGROUND AND AIMS: Autoimmune nodopathy with anti-neurofascin-155 (NF155) antibodies is increasingly recognized as a distinct disease entity. Although these patients have been described, not all aspects have been fully...BACKGROUND AND AIMS: Autoimmune nodopathy with anti-neurofascin-155 (NF155) antibodies is increasingly recognized as a distinct disease entity. Although these patients have been described, not all aspects have been fully elucidated. We investigated clinical phenotypes, biomarker profiles, and treatment outcomes in patients with anti-NF155 antibody-positive autoimmune nodopathy. METHODS: We retrospectively analyzed seven Japanese patients (aged 13-27 years) with anti-NF155 antibody-positive autoimmune nodopathy treated at Kumamoto University Hospital between 2017 and 2020. Clinical, electrophysiological, radiological, and biomarker data were evaluated. One refractory case was followed up for over 80 months, tracking serum neurofilament light chain (sNfL) and anti-NF155 antibody levels in the serum and cerebrospinal fluid (CSF). RESULTS: All patients exhibited severe sensory ataxia and motor dysfunction. Trigeminal nerve hypertrophy was observed in five individuals, without corresponding symptoms, and pes cavus in one patient. All patients demonstrated a pronounced demyelinating neuropathy phenotype. The mean CSF protein level was 343 mg/dL. Intravenous immunoglobulin (IVIg) had minimal efficacy, while corticosteroids produced good responses in four patients and partial responses in three patients. Rituximab markedly improved a refractory case. Anti-NF155 antibody and sNfL levels correlated with clinical status. Magnetic resonance imaging frequently revealed persistent nerve root hypertrophy despite functional improvement. INTERPRETATION: Anti-NF155 nodopathy is a distinct, biomarker-trackable entity; corticosteroids and rituximab outperform IVIg, challenging conventional practice and highlighting the need for antibody testing, especially in young patients with severe demyelinating neuropathy.