Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) progressively impairs motor function, compromising speech and limiting communication. Augmentative and alternative communication (AAC) is essential to maintain autonomy, social participation, and quality of life for people with ALS (PALS). This review maps technological developments in AAC, from low-tech tools to advanced brain–computer interface (BCI) systems. Methods: We conducted a scoping review following the PRISMA extension for scoping reviews. PubMed, Web of Science, SciELO, MEDLINE, and CINAHL were screened for studies published up to 31 August 2025. Peer-reviewed RCT, cohort, cross-sectional, and conference papers were included. Single-case studies of invasive BCI technology for ALS were also considered. Methodological quality was evaluated using JBI Critical Appraisal Tools. Results: Thirty-seven studies met inclusion criteria. High-tech AAC—particularly eye-tracking systems and non-invasive BCIs—were most frequently studied. Eye tracking showed high usability but was limited by fatigue, calibration demands, and ocular impairments. EMG- and EOG-based systems demonstrated promising accuracy and resilience to environmental factors, though evidence remains limited. Invasive BCIs showed the highest performance in late-stage ALS and locked-in syndrome, but with small samples and uncertain long-term feasibility. No studies focused exclusively on low-tech AAC interventions. Conclusions: AAC technologies, especially BCIs, EMG and eye-tracking systems, show promise in supporting autonomy in PALS. Implementation gaps persist, including limited attention to caregiver burden, healthcare provider training, and the real-world use of low-tech and hybrid AAC. Further research is needed to ensure that communication solutions are timely, accessible, and effective, and that they are tailored to functional status, daily needs, social participation, and interaction with the environment.

Multiple sclerosis (MS) is a heterogeneous autoimmune disease driven by peripheral immune dysregulation and compartmentalized central nervous system (CNS) inflammation. Despite more than 20 approved disease-modifying therapies, disability accrual remains common, particularly in patients with highly active relapsing disease and progressive phenotypes characterized by silent progression and smoldering neuroinflammation. Two emerging therapeutic strategies address these unmet needs: Bruton’s tyrosine kinase (BTK) inhibitors and autologous haematopoietic stem cell transplantation (HSCT). Although mechanistically distinct, both aim to overcome limitations of conventional immunosuppression by intervening more deeply in the autoimmune cascade. This narrative review synthesized mechanistic, clinical, and translational evidence identified through a comprehensive search of PubMed, Scopus, Web of Science, and ClinicalTrials.gov from January 2010 to August 2025. BTK inhibitors are oral, CNS-penetrant therapies that selectively modulate B-cell signaling and CNS-resident myeloid cells without broad lymphocyte depletion, enabling continuous immunomodulation. Phase II–III trials of evobrutinib, tolebrutinib, and fenebrutinib show consistent MRI activity suppression but variable effects on relapses and disability, suggesting relevance in microglial-driven, relapse-independent disease. HSCT is a one-time immune reconstitution therapy that eradicates autoreactive immune clones and restores immune tolerance. Randomized and real-world studies demonstrate profound suppression of inflammatory activity, stabilization or improvement of disability, and durable treatment-free remission in selected patients with highly active relapsing–remitting MS, although procedure-related risks require strict eligibility criteria and experienced centers. Together with BTK inhibitors, HSCT represents a complementary strategy within an increasingly personalized MS treatment paradigm, emphasizing biomarker-guided patient selection and optimized therapeutic sequencing.

Background: Although multiple sclerosis (MS)-associated tremor and ataxia are well described in the neurological literature, other extrapyramidal movement disorders (MDs), including Holmes tremor, dystonia, chorea, myoclonus, parkinsonism, and restless legs syndrome, have received far less attention and are generally regarded as rare manifestations of MS. Rationale: Although MS is traditionally considered a white matter disease, increasing evidence has demonstrated clinically relevant grey matter involvement, particularly within the basal ganglia, thalamus, and cerebellar–brainstem pathways. Understanding extrapyramidal MDs in MS may therefore provide important insights into the functional networks disrupted by demyelination and inflammation. Aim: This review aims to highlight the available literature on extrapyramidal MDs in MS, outlining their clinical presentations, lesion correlates, and proposed mechanisms. We examined reported cases, reviews, and findings in the literature explaining these disorders and their occurrence in association with acute relapses, as well as their development during the progressive phase of MS. Conclusions: By integrating clinical and pathophysiological evidence, this review highlights how rare extrapyramidal MDs may reflect underlying grey matter pathology and network-level disruption, with potential implications for diagnosis, monitoring, and treatment.