Hatton CL, Terrey M, Presa M
… +5 more, Ryan J, Perkins S, Kennedy V, Lutz CM, Burgess RW
J Peripher Nerv Syst
· 2025 Sep · PMID 40798926
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BACKGROUND: Degeneration of peripheral motor and sensory axons is a key aspect of the pathophysiology of Charcot-Marie-Tooth disease and related inherited neurodegenerative conditions. AIMS: Given that mutations in many...BACKGROUND: Degeneration of peripheral motor and sensory axons is a key aspect of the pathophysiology of Charcot-Marie-Tooth disease and related inherited neurodegenerative conditions. AIMS: Given that mutations in many (> 100) genes can cause these disorders, it is unclear if a generalized therapeutic strategy can be identified that will apply across these disease subtypes; however, strategies to prevent or slow axon degeneration are attractive candidates. Wallerian axon degeneration is an active process following insults such as nerve injury, and SARM1 is a central mediator of this process. When SARM1 is inhibited, axons distal to the site of injury persist for weeks rather than degenerating. In addition, SARM1 inhibition or genetic deletion has been shown to provide benefit in acquired neuropathies such as diabetic/metabolic neuropathy and chemotherapy-induced neuropathy in animal models. Here we examined the effects of genetically deleting Sarm1 in mouse models of CMT. METHODS: We bred knockout mice lacking Sarm1 to three different mouse models of CMT or related disorders. These include mice lacking Gjb1, modeling CMT1X, mice with mutations in Kif1a, modeling hereditary sensory neuropathy IIC and spastic paraplegia type 30, and mice lacking Fig4, modeling CMT4J and Yunis-Varon syndrome. Clinically relevant outcomes measures including survival (Kif1a and Fig4), grip strength and motor behavior, peripheral neurophysiology, molecular biomarkers, and nerve histopathology were assessed for each model with and without Sarm1 expression. RESULTS: No improvement in the mutant phenotype was found for any model, although elevated levels of circulating neurofilament light chain levels were delayed in the Fig4 mice. Kif1a mice showed deficits slightly earlier in the absence of Sarm1. INTERPRETATION: While we found no benefit from deleting Sarm1 in these mouse models, they were chosen for their human disease relevance and not for biochemical indicators that SARM1 may be a good target. Thus, SARM1 inhibition may still be effective in other forms of inherited neuropathy, but additional research will be required to identify those candidate subtypes.
Ghadban FA, Bay-Smidt CN, Bjørnkær A
… +6 more, Gaist LM, Holbech JV, Gaist D, Wirenfeldt M, Sindrup SH, Krøigård T
J Peripher Nerv Syst
· 2025 Sep · PMID 40791097
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BACKGROUND AND AIMS: Skin biopsies are the primary diagnostic test for small fiber neuropathy, but recently corneal confocal microscopy (CCM) has been developed as an alternative. We compared the correlations of each of...BACKGROUND AND AIMS: Skin biopsies are the primary diagnostic test for small fiber neuropathy, but recently corneal confocal microscopy (CCM) has been developed as an alternative. We compared the correlations of each of these morphometric assessments with peripheral nerve function evaluated through comprehensive quantitative sensory testing (QST) in a mixed etiology polyneuropathy cohort. METHODS: CCM and skin biopsies were performed in a prospective cohort of unselected patients undergoing polyneuropathy diagnostic work-up. We used predefined criteria to identify patients with small or mixed fiber neuropathy. The correlations between corneal nerve fiber density (CNFD), fiber length (CNFL), branch density (CNBD), and tortuosity (CNFT) and the intraepidermal nerve fiber density (IENFD) at the distal leg and the results of QST at the foot were determined. RESULTS: Two-hundred and forty-four patients were included in the analysis. CNFD was negligibly correlated with warm detection threshold (WDT) (r = -0.15; p = 0.023), while there was no statistically significant correlation with other QST measures. There were no statistically significant correlations between neither CNFL nor CNBD and any of the QST measures. CNFT correlated negligibly with WDT (r = 0.17; p = 0.008) and vibration detection threshold (VDT) (r = -0.13; p = 0.044). IENFD correlated moderately with WDT (r = -0.33; p < 0.0001) and mechanical pain threshold (r = -0.37; p < 0.0001) and weakly with cold detection threshold (r = 0.21; p = 0.0008), mechanical detection threshold (r = -0.21; p = 0.0008) and VDT (r = 0.23; p = 0.0004). INTERPRETATION: IENFD correlated better with small and large fiber function at the foot than CCM measures in patients with mixed etiology polyneuropathy. Longitudinal studies are needed to assess the clinical utility for neuropathy progression.
Qaiser F, McHugh J, Mullins G
… +4 more, Farrell M, Shakerdi L, Byrne JO, Murphy SM
J Peripher Nerv Syst
· 2025 Sep · PMID 40790338
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BACKGROUND AND AIMS: Mitochondrial trifunctional protein deficiency (MTPD) is an inherited disorder of fatty acid β-oxidation caused by mutations in HADHA or HADHB genes. It typically presents with cardiomyopathy or hepa...BACKGROUND AND AIMS: Mitochondrial trifunctional protein deficiency (MTPD) is an inherited disorder of fatty acid β-oxidation caused by mutations in HADHA or HADHB genes. It typically presents with cardiomyopathy or hepatic failure in early childhood; however, it may rarely present in adulthood with the neuromyopathic form. METHODS: We describe a patient with MTPD with isolated neuropathy mimicking Charcot-Marie-Tooth disease (CMT) as the first and only presenting symptom. Clinical and electrophysiological examinations were conducted, including nerve conduction studies, needle electromyography, muscle and nerve biopsies. The diagnosis was confirmed with genetic testing and enzymatic analysis of cultured skin fibroblasts. RESULTS: We report a 40-year-old man diagnosed with axonal CMT2 in childhood. He had pes cavus and hammer toes, mild distal lower limb weakness, and loss of vibration sense with areflexia. He later developed fatigability, improved exercise tolerance with alcohol and an episode of chest infection causing neurological decompensation without evidence of rhabdomyolysis. Neurophysiology showed non-length-dependent axonal sensorimotor neuropathy without myopathic features. Genetic testing confirmed that he was compound heterozygous for two HADHA variants, one of them novel, and enzymatic analysis of cultured skin fibroblasts confirmed MTPD. INTERPRETATION: We report a very rare isolated neuropathic phenotype of MTPD and confirm the pathogenicity of the novel variant c.1003G>A, p.(Glu335Lys). This case also highlights the need for HADHA and HADHB to be included in neuropathy gene panels as MTPD may present as CMT. Given that dietary management may prevent some complications of MTPD, achieving a diagnosis early is important.
BACKGROUND AND AIMS: The GDAP1 gene encodes a mitochondrial outer membrane protein crucial for mitochondrial function. Mutations in this gene are associated with different subtypes of Charcot-Marie-Tooth (CMT) disease, i...BACKGROUND AND AIMS: The GDAP1 gene encodes a mitochondrial outer membrane protein crucial for mitochondrial function. Mutations in this gene are associated with different subtypes of Charcot-Marie-Tooth (CMT) disease, inherited in either an autosomal recessive or dominant manner. In this study, we discuss the clinical and genetic aspects of 11 unrelated Iranian GDAP1-related CMT families. METHODS: The probands were selected from a large CMT cohort after whole exome sequencing (WES) analysis. 11 GDAP1-related CMT families-16 patients-were included in this study. Co-segregation analysis was performed to confirm the candidate variants. RESULTS: In total, eight exonic variants in GDAP1 were identified; two were novel. Among all known variants, a deep intronic variant, c.311-23A>G, was found in two families. 11/16 patients were AR-CMT2K, three were CMT4A, and only two had AD-CMT2K. INTERPRETATION: Among our variants, two were more significant: c.311-23A>G, which has only been documented in another Iranian family and may represent a founder mutation within our population, and c.347T>G, which has exclusively been reported within the Italian population and is recognized as a founder mutation in that country. We found this variant in three unrelated families, suggesting that this variant is not confined to Italy and that codon 347 may be a hotspot codon. Our findings extend the clinical and genetic aspects of GDAP1-related CMT and emphasize the need to consider intronic variants in genetic analysis. Additionally, we highlight that AD-CMT2K has a milder phenotype than other GDAP1-related disease types, which could result in an underestimation of the number of AD-CMT2K cases.
Shumeri E, Mandorah E, Martini N
… +8 more, Boyer A, Halbert C, Puma A, Chaussenot A, Delmont E, N'guyen K, Attarian S, Bonello-Palot N
J Peripher Nerv Syst
· 2025 Sep · PMID 40588830
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BACKGROUND AND AIMS: Charcot-Marie-Tooth disease (CMT) is a rare hereditary neuropathy that affects peripheral nerves in the upper and lower limbs. To distinguish between the different forms of the disease, electrophysio...BACKGROUND AND AIMS: Charcot-Marie-Tooth disease (CMT) is a rare hereditary neuropathy that affects peripheral nerves in the upper and lower limbs. To distinguish between the different forms of the disease, electrophysiological criteria are essential. Furthermore, identifying the genetic cause is crucial for providing accurate genetic counseling. The genetic complexity of CMT is partly explained by digenism, where mutations in two distinct genes might contribute to the disease. Two genes involved in mitochondrial dynamics, MFN2 and GDAP1, have been identified in digenic cases of CMT. This retrospective study reports MFN2/GDAP1 digenism cases identified in patients affected by CMT in our laboratory. METHODS: We conducted a retrospective analysis of 1665 patients who underwent NGS using the CMT gene panel between 2016 and 2024. These patients affected by CMT were addressed from neurology reference centers in France. The results were analyzed with bioinformatics tools, initially using the hg19 reference genome and then the hg38 version. RESULTS: Out of 1665 patients, 367 positive cases were identified, corresponding to a 22% molecular diagnostic rate, excluding PMP22 duplications. Among these, 15 cases involved variants in two distinct genes, resulting in a 4% digenism rate. Five cases involved MFN2/GDAP1 variants, accounting for 1.4% of the total positive results and 33% of all digenic cases. INTERPRETATION: The cases of digenism have a significant prevalence in CMT disease and may explain the severity of the phenotype in our patients. Multilocus variants complicate genetic counseling due to non-Mendelian inheritance. In addition, it is important to distinguish between digenism and modifier genes.
BACKGROUND: Hereditary amyloid transthyretin (ATTRv) is caused by TTR gene mutations, which lead to multisystem amyloid deposits. A misdiagnosis is common, which delays treatment. We assessed the prevalence of TTR mutati...BACKGROUND: Hereditary amyloid transthyretin (ATTRv) is caused by TTR gene mutations, which lead to multisystem amyloid deposits. A misdiagnosis is common, which delays treatment. We assessed the prevalence of TTR mutations in patients with neuropathy of unknown cause at the first stage of assessment. METHODS: This prospective study, conducted in western France, assessed patients with neuropathy aged 18-90 years. We excluded individuals with known causes or prior screening of TTR mutations. Genetic analyses of TTR mutations were done using Sanger sequencing. Clinical, biochemical, and electrophysiological data were collected. Statistical analyses estimated the prevalence of TTR amyloidosis in this cohort. RESULTS: Among 400 patients, four (1%) were identified as having a heterozygous TTR mutation. The mean age of these patients with a TTR mutation was 75 years, with a mean duration of neuropathy of 2.5 years. The initial symptoms varied, with one patient experiencing mixed sensory impairment, another with motor and sensory issues, one with purely motor symptoms, and one with small-fiber sensory impairment. Notably, none had cardiological or renal impairments, and all exhibited sensorimotor neuropathy upon electromyography. Three patients had an axonal profile, and one showed demyelinating neuropathy, which highlighted the diagnostic challenges. INTERPRETATION: We identified a 1% prevalence of TTR mutations, which is lower than that reported previously, and highlights the influence of selective inclusion criteria on such estimates. Our data emphasize the need for early detection because patients frequently lack red-flag symptoms. Ultimately, early screening allows for prompt management and minimizes long-term complications in individuals with unexplained neuropathy. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT03190577.
O'Donnell LF, Zhang V, Carganillo R
… +8 more, Rossor AM, Laura M, Skorupinska M, Gilbertson JA, Rowczenio D, Razvi Y, Gillmore JD, Reilly MM
J Peripher Nerv Syst
· 2025 Sep · PMID 40580033
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OBJECTIVE: Gene silencing therapy for ATTRv has revolutionised treatment. In minimally symptomatic, early neuropathic disease, skin biopsy can aid in the diagnosis of ATTRv-PN, assessing both amyloid deposition and IENFD...OBJECTIVE: Gene silencing therapy for ATTRv has revolutionised treatment. In minimally symptomatic, early neuropathic disease, skin biopsy can aid in the diagnosis of ATTRv-PN, assessing both amyloid deposition and IENFD. Our aim was to study the value of performing skin biopsies in the diagnosis of ATTRv-PN in UK patients and to assess the influence of this on accessing gene silencing treatment. METHODS: Seventy-three patients had skin biopsies performed between July 2021 and October 2023. These were stained for amyloid, typed by immunohistochemistry, and analysed for IENFD. RESULTS: The Thr60Ala (30%), Val122Ile (23%) and Val30Met (22%) variants represented the largest number of cases. Normal/equivocal neurophysiology was demonstrated in 78% of cases. 40% of patients had abnormal IENFD, 33% had positive amyloid and 16% had both. This allowed 33% of patients to start gene silencing therapy, 75% of whom had a preceding amyloid cardiomyopathy diagnosed. CONCLUSIONS: Skin biopsy is a useful, minimally invasive method for diagnosing ATTRv-PN. It allowed a substantial number of patients to commence gene silencing treatment. As Thr60Ala and Val122Ile are the commonest TTR variants in the UK and patients often present with cardiomyopathy, early diagnosis of ATTRv-PN is critical for treatment decisions.
J Peripher Nerv Syst
· 2025 Sep · PMID 40560091
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BACKGROUND: Chronic itch, or pruritus, is a common discomfort of the skin. Chronic itch has been described as a symptom of small fiber neuropathy (SFN), a disorder affecting the small myelinated Aδ- and unmyelinated C-fi...BACKGROUND: Chronic itch, or pruritus, is a common discomfort of the skin. Chronic itch has been described as a symptom of small fiber neuropathy (SFN), a disorder affecting the small myelinated Aδ- and unmyelinated C-fibers. While prior studies report itch rates in SFN ranging from 63%-68%, a distinct pattern has not been identified. AIM: This study aimed to describe the clinical characteristics of itch in a large cohort of SFN patients. METHODS: Between May 2016 and August 2022, 1415 patients filled out an exploratory questionnaire about characteristics of their itch symptoms. 83% were diagnosed with SFN based on the Besta criteria. RESULTS: Itch was reported in 66% of SFN patients, mainly experienced as tickling, prickling, and tingling sensations. Itch was most common in the evening, with 98% reporting continuous or episodic symptoms during this time. The itch was predominantly localized to the distal extremities, especially the lower legs and feet (over 50% of patients), with additional reports on the back (25%) and face (27%). Unlike the typical stocking-glove distribution seen with neuropathic pain, itch showed a slightly more proximal locus. SFN patients were more likely to report itching in the hands and feet than non-SFN patients. INTERPRETATION: This study reveals that itch in SFN is a frequent, heterogeneous symptom that may differ from neuropathic pain in its distribution. Itch, particularly in the hands and feet, may provide diagnostic guidance and suggest SFN as a potential diagnosis. This finding warrants further research on itch mechanisms and its diagnostic value in SFN.
INTRODUCTION: Krabbe disease, or globoid cell leukodystrophy, is a rare autosomal recessive neurodegenerative disorder characterized by deficient activity of the lysosomal enzyme galactosylceramidase (GALC). This deficie...INTRODUCTION: Krabbe disease, or globoid cell leukodystrophy, is a rare autosomal recessive neurodegenerative disorder characterized by deficient activity of the lysosomal enzyme galactosylceramidase (GALC). This deficiency leads to the toxic accumulation of psychosine, resulting in progressive demyelination and neuronal death. The clinical manifestations of Krabbe disease progress through different stages, starting with irritability, stiffness, and feeding difficulties, followed by myoclonic-like jerks in the upper and lower extremities, hypertonicity, and eventually severe hypotonia and lack of movement. METHODS: This case report features two newborn screening patients with (NBS)-positive Krabbe disease who underwent electrodiagnostic (EDX) testing and hematopoietic stem cell transplantation (HSCT) soon after birth. RESULTS: The EDX results indicated severe sensory-motor polyneuropathy of mixed demyelinating and axonal types. Biochemical analyses confirmed significantly reduced GALC enzyme activity and elevated psychosine levels in both cases. Genetic testing identified pathogenic variants, including compound heterozygous deletions and mutations within the GALC gene. At 6-month follow-up post-HSCT, one patient showed age-appropriate milestones and improvement in motor amplitudes on repeat nerve conduction studies. DISCUSSION: EDX testing is helpful in assessing NBS-positive Krabbe disease before confirmatory testing results become available. In conjunction with genetic confirmation and GALC enzyme levels, EDX test results were useful to counsel families that their seemingly normal newborn has severe disease and facilitated discussion toward timely treatment with HSCT. We suggest that EDX be included in the initial and follow-up evaluation of patients with Krabbe disease undergoing HSCT.
Jahan I, Ahmed R, Ahmed J
… +8 more, Afsar NA, Biswas PP, Khurshid S, Mohammad QD, Endtz HP, Huizinga R, Jacobs BC, Islam Z
J Peripher Nerv Syst
· 2025 Sep · PMID 40558063
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BACKGROUND AND AIMS: Intravenous immunoglobulin (IVIg) is the primary treatment for Guillain-Barré syndrome (GBS), yet its immunological mechanisms underlying variable clinical outcomes remain unclear. This study investi...BACKGROUND AND AIMS: Intravenous immunoglobulin (IVIg) is the primary treatment for Guillain-Barré syndrome (GBS), yet its immunological mechanisms underlying variable clinical outcomes remain unclear. This study investigated the immunomodulatory effect of IVIg on regulatory T cells (Tregs), cytokines, and their association with treatment response and clinical outcomes. METHODS: In this prospective case-controlled study, 57 GBS patients and 57 age- and sex-matched healthy controls (HCs) were investigated. CD4CD25FoxP3 Treg percentages, cytokine production (IL-10, TNF-α, IFN-γ, and IL-12), and serum C3 levels were measured using flow cytometry, Luminex assay, and turbidimetric methods, respectively. Treatment response was defined as ≥ 1-point GBS-disability score improvement during evaluation. RESULTS: GBS patients exhibited lower CD4CD25FoxP3 Tregs frequencies compared to HCs (p = 0.006), which were inversely associated with serum C3 levels (p = 0.003) during the acute phase. At 4 weeks post-onset, patients with normal C3 levels (90-180 mg/dL) exhibited higher Treg frequencies (p = 0.005) compared to acute GBS, whereas patients with persistently elevated C3 levels showed reduced Treg percentage (p = 0.009). Among I VIg-treated patients, Tregs significantly increased at 2 and 4 weeks post-treatment, alongside significantly higher IL-10 and lower TNF-α, IFN-γ, and IL-12 levels at 4 weeks. However, patients with supportive care showed no such changes in Tregs and cytokine levels. Furthermore, Tregs elevated significantly in patients responsive to IVIg at 2 and 4 weeks (p < 0.05), but not in non-responsive or supportive care patients. INTERPRETATION: IVIg treatment modulates immune dysregulation in GBS by expanding CD4CD25FoxP3 Tregs and altering cytokines and serum C3 levels, which are associated with clinical improvement. These findings indicate Tregs as potential biomarkers for monitoring initial clinical response to IVIg in GBS.
Mondschein AS, DiPersio MR, Zajaceskowski J
… +12 more, Nimmagadda H, Acheta J, Salinero AE, Haslam S, Poitelon E, Elston S, McFarland E, Beck B, Zuloaga KL, Rumora AE, Poitelon Y, Belin S
J Peripher Nerv Syst
· 2025 Jun · PMID 40522084
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BACKGROUND AND AIMS: Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes, with Schwann cell dysfunction increasingly implicated in disease progression. This study aimed to investigate how high...BACKGROUND AND AIMS: Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes, with Schwann cell dysfunction increasingly implicated in disease progression. This study aimed to investigate how high-fat diet (HFD)-induced metabolic syndrome (MetS) affects Schwann cells and peripheral nerve function in male and female mice. METHODS: Male and female C57BL/6J mice were fed a standard diet (SD) or HFD for 33 weeks. Metabolic phenotyping included body weight, fasting blood glucose, and glucose tolerance tests. Peripheral nerve function was assessed via motor and sensory nerve conduction velocities (NCVs), behavioral tests (grip strength, thermal preference, Von Frey), intraepidermal nerve fiber density (IENFD) counts, and sciatic nerve morphological analysis. Myelin protein expression was analyzed by Western blotting and immunohistochemistry. RESULTS: Both sexes developed MetS features, though males exhibited more pronounced hyperglycemia. HFD mice showed thermal hyperalgesia, reduced IENFD, and slowed NCVs, consistent with DPN. Morphological studies revealed sex-specific myelin thinning and structural abnormalities without significant axonal degeneration. In males, HFD was associated with reduced muscular strength, a decrease in myelin thickness of small-caliber axons, and an increase in the Peripheral Myelin Protein 2 (PMP2), a fatty acid chaperone. In females, although HFD led to myelin decompaction, it was not associated with muscle strength deficits or changes in myelin composition. INTERPRETATION: HFD-induced MetS impairs Schwann cell function and peripheral nerve health in a sex-dependent manner. Myelin defects and PMP2 upregulation suggest that altered lipid metabolism contributes to neuropathy progression. These findings highlight Schwann cells as key mediators of MetS-associated peripheral neuropathy and underscore the need for sex-specific therapeutic strategies.
Kramarz C, Masingue M, Bouhour F
… +9 more, Vial C, Latour P, Vandendries C, Maisonobe T, Coebergh J, Blake J, Reilly MM, Stojkovic T, Rossor AM
J Peripher Nerv Syst
· 2025 Jun · PMID 40420622
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BACKGROUND AND AIMS: Peripheral neuropathy may present with a variety of phenotypes depending on the pattern of weakness and sensory loss, the neurophysiological characteristics (axonal or demyelinating) and additional f...BACKGROUND AND AIMS: Peripheral neuropathy may present with a variety of phenotypes depending on the pattern of weakness and sensory loss, the neurophysiological characteristics (axonal or demyelinating) and additional features such as involvement of the autonomic nervous system or the cranial nerves. The most common phenotype is a symmetrical length-dependent sensory and motor neuropathy. Other phenotypes include non-length-dependent forms such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or a sensory neuronopathy or ganglionopathy. Asymmetric forms of neuropathy are mostly represented by mononeuritis multiplex and Lewis-Sumner syndrome or focal CIDP. Unilateral weakness or sensory loss respecting the midline is mainly due to pathology in the central nervous system and is unusual in peripheral neuropathy. METHODS: We evaluated the clinical and genetic features of three unrelated individuals with a peripheral neuropathy affecting one side of the body. RESULTS: We describe three unrelated patients (two female and one male) with a slowly progressive peripheral neuropathy restricted to one side of the body. Each case is marked by onset in early childhood with the absence of a family history or a structural lesion of the central nervous system. Neurophysiology demonstrated an axonal type of neuropathy in two cases and conduction slowing supportive of a demyelinating neuropathy type in one. Genetic testing was performed in the three cases, specifically looking for variants in genes associated with Charcot-Marie-Tooth disease (CMT) but none were identified in DNA extracted from blood. INTERPRETATION: A unilateral, slowly progressive peripheral neuropathy is a rare phenomenon, and we propose the cause of this unusual phenotype to be due to a mosaic or chimeric form of Charcot-Marie-Tooth disease (CMT).
Michael MR, van Veen R, Wieske L
… +3 more, Merkies ISJ, van Schaik IN, Eftimov F
J Peripher Nerv Syst
· 2025 Jun · PMID 40420525
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BACKGROUND AND AIMS: Validated objective measures for balance in immune mediated neuropathies are lacking. In this study, we investigated the clinimetric properties of posturography using a force platform, a quantitative...BACKGROUND AND AIMS: Validated objective measures for balance in immune mediated neuropathies are lacking. In this study, we investigated the clinimetric properties of posturography using a force platform, a quantitative assessment of postural control. METHODS: We assessed patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and IgM-related polyneuropathy (IgM-PNP) using sway parameters (path, area and amplitude) measured at multiple time points. Validity was investigated by assessing differences in sway path between patients with and without reported balance symptoms and by assessing correlations of sway path with (established) impairment measures related to balance, disability and quality of life (QoL). Responsiveness was assessed by means of an anchor-based approach, using a patient anchor and two disability scales. RESULTS: We included 52 CIDP and 13 IgM-PNP patients. In CIDP, sway path was 25% longer in patients reporting balance symptoms relative to patients without balance symptoms (p = 0.03). There was excellent reliability between consecutive measurements in both CIDP and IgM-PNP. Moderate to good correlations were observed between sway path and an ataxia scale (CIDP: Spearman's ρ = 0.46, 95% CI: 0.2-0.69; IgM-PNP: Spearman's ρ = 0.72, 95% CI: 0.28-0.96) while correlations with related disability measures and QoL were poor. Changes in sway parameters over time were not consistently associated with changes in other outcome measures. INTERPRETATION: Posturography measurements showed poor validity and responsiveness. Therefore, despite excellent reliability, using a force platform in clinical practice or trials for immune-mediated neuropathies cannot be recommended.
Pi BK, Lee AJ, Nam SH
… +2 more, Chung KW, Choi BO
J Peripher Nerv Syst
· 2025 Jun · PMID 40396389
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BACKGROUND AND AIMS: The SLC5A6 gene encodes a transmembrane protein responsible for transporting biotin, pantothenic acid, and lipoic acid. Mutations in SLC5A6 have shown a wide spectrum of clinical phenotypes, such as...BACKGROUND AND AIMS: The SLC5A6 gene encodes a transmembrane protein responsible for transporting biotin, pantothenic acid, and lipoic acid. Mutations in SLC5A6 have shown a wide spectrum of clinical phenotypes, such as sodium-dependent multivitamin transporter deficiency (SMVTD), childhood-onset biotin-responsive peripheral motor neuropathy (COMNB), and mixed axonal and demyelinating sensory motor neuropathy. The purpose of this study was to identify pathogenic SLC5A6 mutations in the Korean CMT cohort. METHODS: This study performed whole exome sequencing to identify the genetic cause for two independent patients with early onset axonal sensorimotor polyneuropathy and SMVTD. We also examined the therapeutic effects of multivitamin replenishment on a patient with SLC5A6 mutations. RESULTS: We identified compound heterozygous variants of SLC5A6 in two patients (p.Arg94X and p.Phe522Ser in patient 1; p.Cys443Tyr and p.Phe513_Lys515delinsLeu in patient 2). In patient 2, an oral regimen comprising biotin, lipoic acid, and pantothenic acid demonstrated significant therapeutic effects, including cessation of cyclic vomiting, resolution of skin lesions on the fingers, and improvements in muscle weakness affecting both the upper and lower extremities. INTERPRETATION: This study represents the first report of novel heterozygous SLC5A6 mutations in patients with axonal CMT and SMVTD, expanding the phenotypic spectrum associated with SLC5A6 mutations. Notably, we observed significant therapeutic effects from multivitamin treatment in a patient.
Hilbig-Vlatten L, Grauberger JN, Engmann TF
… +6 more, Stadelmeier LF, Dunn RM, Mandeville R, Ko JH, D'Hemecourt P, Dowlatshahi S
J Peripher Nerv Syst
· 2025 Jun · PMID 40391847
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Soleal sling syndrome is a rare cause of lower extremity neuropathy due to compression of the proximal tibial nerve under the fibromuscular arch of the soleus muscle. It presents with plantar numbness/paresthesias, calf...Soleal sling syndrome is a rare cause of lower extremity neuropathy due to compression of the proximal tibial nerve under the fibromuscular arch of the soleus muscle. It presents with plantar numbness/paresthesias, calf pain, and tenderness over the proximal calf. Chronic compression can lead to toe flexor weakness. This study reviews the clinical presentation, diagnostic workup, and treatment options for soleal sling syndrome. A query of the PubMed database up until August 30, 2022, was conducted to gather relevant clinical, anatomic, and radiographic findings. The literature review identified key features of soleal sling syndrome, highlighting the importance of considering it in patients with calf pain/tenderness and plantar foot neurosensory changes. Diagnosis typically relies on history and physical examination, often with a positive Tinel's sign, though imaging modalities show inconsistent utility. Soleal sling syndrome is underrecognized and overlaps with other syndromes. Radiological imaging modalities can rule out secondary causes of proximal tibial nerve compression but lack consistency for diagnosing idiopathic cases. Surgical decompression of the nerve, via a medial or posterior approach, is the definitive treatment for all causes of tibial nerve compression.