Charcot-Marie-Tooth disease (CMT) comprises a genetically and clinically heterogeneous group of inherited peripheral neuropathies and remains a major indication for gene-based diagnostic evaluations in neuromuscular practice. Although supportive management has traditionally been applied across most subtypes, there has recently been a notable expansion of disease-modifying approaches due to advances in molecular diagnostics and accumulating preclinical and early clinical evidence. Improved genetic classification, including the recognition of metabolically defined and potentially treatable subtypes, has increased diagnostic precision and the development of subtype-specific therapeutics, with an increasing emphasis on mechanism-based stratification. This review summarizes recent progress in inherited neuropathies from a clinical perspective. We describe ongoing developments in clinical interventions, including combination pharmacotherapy for Charcot-Marie-Tooth disease type 1A (CMT1A), pathway-targeted therapy for CMT associated with sorbitol dehydrogenase deficiency and related metabolic neuropathies, and early biological and gene-based approaches that are being applied in selected subtypes. We also review the evolving preclinical approaches aimed at normalizing the peripheral myelin protein 22 dosage in CMT1A and gene-replacement and other precision therapies for loss-of-function and dominant-negative conditions. Because many subtypes of CMT progress slowly and conventional clinical scales have low sensitivity, we further discuss recent advances in the approaches used in clinical trials, including the refinement of clinical outcome assessments and the identification of candidate biomarkers such as the magnetic resonance imaging-based muscle fat fraction and the circulating level of neurofilament light chain. Collectively these developments are making subtype-specific therapeutic approaches increasingly feasible, although continued progress will depend on aligning disease biology, therapeutic approaches, and outcome measurements.

Idiopathic inflammatory myopathies (IIMs) are heterogeneous immune-mediated muscle disorders with variable extramuscular manifestations and outcomes. Myositis-specific auto-antibodies (MSAs) have transformed the IIM field by enabling a serology-informed taxonomy based on distinct clinical phenotypes, prognostic trajectories, and therapeutic responses. Anti-Jo-1 and other antisynthetase antibodies characterize interstitial lung disease (ILD)-prone forms of disease; anti-MDA5 identifies patients at risk of rapidly progressive ILD and early mortality; anti-TIF1-γ and anti-NXP2 are indicative of cancer-associated myositis; anti-SRP and anti-HMGCR delineate necrotizing myopathies; and anti-cN1A supports the diagnosis of inclusion-body myositis. Beyond diagnosis, MSA profiles provide prognostic information, including about survival, relapse risk, and organ-specific complications, and they are increasingly being used to guide treatment decisions and predict biologic responsiveness. This review summarizes the diagnostic, prognostic, and therapeutic implications of MSAs across the IIM spectrum and highlight their growing importance in clinical practice for risk stratification and patient management.

Background
We aimed to investigate candidates for serological biomarkers of neuropathic pain in individuals with neuromyelitis optica spectrum disorder (NMOSD).
Methods
We analyzed 38 sera samples from 38 participants with NMOSD in National Cancer Center. Neuropathic pain was evaluated using the painDETECT questionnaire. Pain with neuropathic components (painDETECT score ≥ 13) was observed in 22 participants, among whom 17 had definite neuropathic pain (painDETECT score ≥ 19). The remaining 16 participants had non-neuropathic pain (painDETECT score < 13). Serum glial fibrillary acidic protein (GFAP) levels were assessed using a single-molecule array assay. Several cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, and IL-17A, were measured by a multiplex bead-based immunoassay.
Results
In comparison of NMOSD participants with neuropathic pain components (or definite neuropathic pain) and those with non-neuropathic pain, the absolute values of serum GFAP, TNF-α, IL-6, and IL-10 levels were higher in participants with neuropathic pain components (or definite neuropathic pain), but these findings did not reach statistical significance.
Conclusions
Further larger-scale investigations to find reliable serological biomarkers for neuropathic pain in NMOSD are warranted.

Citations

• Neuropathic pain in multiple sclerosis: serum biomarkers and MRI lesion localization
  Mohamed Hamdy Ismail, Amal SE ELmotayam, Sara F. Saadawy, Rabab M. Elfwakhry, Hebatallah M. Fawzy, Noha T. Sarhan
  The Egyptian Journal of Neurology, Psychiatry and .2025;[Epub]     CrossRef
• Shedding light on neuropathic pain: Current and emerging tools for diagnosis, screening, and quantification
  Anas Hamdan, Rafael Galvez, Majed Katati
  SAGE Open Medicine.2024;[Epub]     CrossRef
• Systematic Review and Metanalysis of the Expression of Blood-Based and Cerebrospinal Fluid-Based Biomarkers Related to Inflammatory Mediators in Neuropathic Pain
  Marina Sanz-Gonzalez, Miguel Molina-Alvarez, Carmen Rodriguez-Rivera, David Pascual, Carlos Goicoechea
  Journal of Integrative Neuroscience.2024;[Epub]     CrossRef