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Small-Fiber Neuropathy (SFN) is a disorder of the peripheral nervous system, characterised by neuropathic pain; approximately 11% of cases are linked to variants in Voltage-Gated Sodium Channels (VGSCs). This study aims to broaden the genetic knowledge on painful SFN by applying Whole-Exome Sequencing (WES) in Early-Onset (EO) cases. A total of 88 patients from Italy (n = 52) and the Netherlands (n = 36), with a disease onset at age ≤ 45 years old and a Pain Numerical Rating Score ≥ 4, were recruited. After variant filtering and classification, WES analysis identified 142 potentially causative variants in 93 genes; 8 are Pathogenic, 15 are Likely Pathogenic, and 119 are Variants of Uncertain Significance. Notably, an enrichment of variants in transient receptor potential genes was observed, suggesting their role in pain modulation alongside VGSCs. A pathway analysis performed by comparing EO cases with 40 Italian healthy controls found enriched mutated genes in the "Nicotinic acetylcholine receptor signaling pathway". Targeting this pathway with non-opioid drugs could offer novel therapeutic avenues for painful SFN. Additionally, with this study we demonstrated that employing a gene panel of reported mutated genes could serve as an initial screening tool for SFN in genetic studies, enhancing clinical diagnostics. [ABSTRACT FROM AUTHOR]

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) often requires prolonged ongoing treatment to prevent worsening. The efficacy of rituximab in preventing worsening after the discontinuation of immunoglobulin therapy in CIDP patients was assessed. In this randomized, double-blind, placebo-controlled study, conducted at seven Italian hospitals, CIDP patients under immunoglobulin therapy were assigned to receive either rituximab (1g on days 1, 15, and 180±7) or placebo. Both groups continued their regular immunoglobulin doses for six months post-intervention. The primary endpoint was the proportion of patients who worsened in any of the following three measures at month 12, within six months after immunoglobulin discontinuation: a decrease of at least one point on the adjusted INCAT score, two points on the MRC sum score, or four points on the RODS centile score. Secondary endpoints included the proportion of patients deteriorating at month 18 (within 12 months after immunoglobulin discontinuation), treatment cessation due to adverse events or voluntary reasons, and the time until deterioration after immunoglobulin discontinuation. This study was registered with ClinicalTrials.gov (NCT06325943) and EUDRACT (number 2017-005034-36), and it is complete. From April 2019 to March 2022, 39 patients were recruited; two withdrew consent. The remaining 37 patients were assigned to rituximab (n=19) or placebo (n=18). Median age was 53 (IQR 45-64), with 11 (30%) females. A similar proportion of patients in both the rituximab (12/19, 63.2%) and placebo (12/18, 66.6%) groups worsened at month 12 (OR 0.86; 95% CI 0.22-3.32). No significant differences were noted at month 18 (OR 0.62; 95% CI 0.14-2.70), or in the mean scores of each scale at months 6, 12, and 18. The median time to worsening was 5 months for rituximab and 2 months for placebo (Log-rank p=0.4372). Treatment was suspended due to adverse events in one rituximab patient. In this study, rituximab was not more effective than placebo in preventing clinical deterioration following the discontinuation of immunoglobulin therapy in CIDP. Further studies might evaluate the efficacy of more frequent or earlier administration of rituximab., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Purpose: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated., Methods: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP., Results: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did., Conclusions: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)