Introduction: Vitamin B6 is a water-soluble vitamin that is naturally present in many foods and is accessible in many dietary supplements. The three natural forms are pyridoxine, pyridoxal, and pyridoxamine. Both vitamin B6 deficiency and high B6 intake have been described as risk factors for developing peripheral neuropathy (PN). The aim of this systematic review is to characterize and comprehensively describe B6-related PN. Method: A systematic, computer-based search was conducted using the PubMed database. Twenty articles were included in this review. Results: Higher vitamin B6 levels, which usually occur following the taking of nutritional supplements, may lead to the development of a predominantly, if not exclusively, sensory neuropathy of the axonal type. After pyridoxine discontinuation, such patients subjectively report improved symptoms. However, although low vitamin B6 levels can be seen in patients suffering from peripheral neuropathy of various etiologies, there is no firm evidence that low B6 levels have a direct causal relationship with PN. Many studies suggest subjective improvement of neuropathy symptoms in patients suffering from PN of various etiologies after receiving B6 supplementation; however, no data about B6 administration as a monotherapy exist, only as part of a combination treatment, usually with other vitamins. Therefore, the potential therapeutic role of B6 cannot be confirmed to date. Supplementation with vitamin B6, even as part of a nutritional multivitamin supplement, has not been proven harmful at permitted daily doses in patients who already suffer from PN. Conclusion: Current scientific evidence supports a neurotoxic role of B6 at high levels. Although some studies suggest that low B6 is also a potential risk factor, further studies in this area are needed.

Introduction: Multiple Sclerosis (MS) is associated with a wide range of debilitating symptoms, and conventional therapies often fail to adequately address the disease’s multifaceted challenges. Cannabidiol (CBD) 13.0% + Delta9-tetrahydrocannabinol (THC) 9.0% (CBD13/THC9), a vaporized cannabis-based medicinal product, presents a novel therapeutic option for managing MS symptoms. Methods: This single-center longitudinal study followed 69 MS patients over a six-month period. Participants were assessed at treatment initiation and at three- and six-month intervals. Key measures included muscle spasticity, urine bladder dysfunction, and the evaluation of disability progression rate. The evaluation included the Modified Ashworth Scale (MAS), the Post Void Residual (PVR) volume, and the Expanded Disability Status Scale (EDSS). Results: Significant improvement was observed across all outcome assessments. The EDSS score was decreased over time (p = 0.009), indicating a slight reduction in disability progression rate, while MAS scores showed substantial improvement in muscle spasticity (p < 0.001). Urine bladder function improved significantly, with PVR volume showing notable improvement between baseline and the six-month assessment (p < 0.001). Correlation analyses revealed that a gradual increase in vaporized CBD13/THC9 dose was correlated with slightly lower EDSS scores, while the adverse effects were negatively associated with the frequency of cannabinoid use. Finally, patients who were smokers used CBD13/THC9 more frequently. Conclusions: The vaporized CBD13/THC9 formulation demonstrated notable efficacy in slightly improving disability progression rate via reduction in muscle spasticity and urine bladder dysfunction in MS patients. This highlights its addon therapeutic value during rehabilitation in MS patients with debilitating disability symptoms.

Background/Objectives: Neuropsychological impairment (NI) is common in newly diagnosed patients with multiple sclerosis (pwMS). This study has two main objectives; the systematic review aims to describe the relationship between NI and molecular biomarkers in newly diagnosed pwMS, and the meta-analysis aims to explore the relationship between NI, age, disability status, and disease duration in this patient group. Methods: We conducted a systematic review, with 20 studies meeting the inclusion criteria. Out of these, 12 studies were included in the meta-analysis. We analyzed three key cognitive measures—the Symbol Digit Modalities Test (SDMT), the Paced Auditory Serial Addition Test (PASAT), and the Selective Reminding Test–long-term storage (SRT-LTS)—in relation to demographic and MS-related characteristics. Results: Neurofilament light chain (NfL) levels were consistently associated with NI, especially a slower information processing speed (IPS). Other biomarkers, including chitinase 3-like 1 (CHI3L1), brain-derived neurotrophic factor (BDNF), apolipoprotein E4 allele (APOE4), and vitamin D, also showed promising correlations with NI. A meta-regression analysis of 2380 pwMS indicated a negative association between SDMT score and disability status (p = 0.01). No significant associations were found for the PASAT with age, disability status, or disease duration (p > 0.05). Conclusions: These findings highlight the role of NfL as a biomarker related to NI in newly diagnosed pwMS and the association between IPS and disability status. Further research is needed with more homogeneous samples in terms of the disease duration, along with standardized cognitive assessments and a broader range of biomarkers, to improve our understanding and management of cognitive difficulties in the early stages of MS.

Stavrogianni K, et al. J Clin Neurol. 2024 Nov;20(6):591-598. https://doi.org/10.3988/jcn.2024.0149

Introduction: Neuropathic pain (NP) in neuromyelitis optica spectrum disorder (NMOSD) represents a significant and often under-recognized complication arising from central nervous system (CNS) lesions. Unlike other demyelinating disorders, NMOSD involves a distinct immunopathogenesis primarily driven by aquaporin-4 antibodies (AQP4-IgG), leading to severe inflammatory damage. NP is typically the consequence of inflammatory damage to the spinothalamic tract or dorsal columns, resulting in both acute and chronic pain syndromes. Methods: A systematic review and meta-analysis were conducted following a comprehensive search of Medline and Scopus, identifying nine eligible studies reporting on NP in NMOSD. Results: Pooled prevalence was estimated using a random-effects metaprop meta-analysis with Freeman–Tukey transformation and REML-based heterogeneity estimation. The pooled prevalence of NP among patients with NMOSD was 56.2% (95% CI: 41.7–70.1%; I² = 95.3%, p < 0.001). Sensitivity analysis including only AQP4-IgG⁺ cohorts revealed a prevalence of 63.2% (95% CI: 23.4–94.7%; I² = 98.1%, p < 0.001). No significant difference was found between mixed and AQP4-IgG⁺-only populations (53.05% vs. 63.27%, p = 0.63). Meta-regression showed no significant associations between NP prevalence and age (β = 0.01, p = 0.33) or disability (β = 0.08, p = 0.18). Qualitative synthesis demonstrated an association between thoracic spinal cord lesions and NP, and also indicated that NP was often resistant and refractory to standard pharmacologic therapies. Conclusions: NP affects one in two NMOSD patients, and is associated with thoracic spinal cord lesions. In comparison with multiple sclerosis, NP in NMOSD is primarily structural and immunopathological in origin. Treatment strategies remain inadequate, emphasizing the need for early recognition and a disease-specific therapeutic approach.