People with multiple sclerosis (pwMS) often experience disability progression even when receiving disease-modifying therapies that effectively suppress relapses. This phenomenon is commonly referred to as progression independent of relapse activity (PIRA). Currently, it is challenging to characterize pwMS who are experiencing disability progression in clinical practice. Existing definitions of PIRA rely primarily on the Expanded Disability Status Scale (EDSS), which is biased towards ambulation and does not effectively capture the gradual accumulation of symptoms and signs across other clinical areas associated with disability progression. Here, we propose a step-by-step approach that neurologists can use in clinical practice to identify pwMS experiencing disability progression irrespective of age, EDSS, or disease duration. By using this approach, neurologists can assess the presence or absence of specific variables to help determine if disability is stable or progressing. This could enable appropriate treatments to be implemented in a timely manner, particularly as new disability-targeting therapies become available.
Amyotrophic Lateral Sclerosis (ALS) shows substantial heterogeneity in clinical presentation and white matter involvement, but conventional diffusion tensor imaging analyses provide limited information on whether tract-level abnormalities follow distinct patient level patterns. This retrospective secondary analysis included 73 patients with ALS and 30 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) from 11 predefined tracts were used as SuStaIn biomarkers, with healthy controls providing the normative reference for Z-score standardization. SuStaIn subtypes and stages were examined against Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), King’s stage, and peak width of skeletonized mean diffusivity (PSMD). The three-subtype model classified patients into cingulate callosal motor mixed subtype (n = 34), hippocampal cingulum posterior projection subtype (n = 32), and posterior callosal projection, MD predominant subtype (n = 7). Exploratory comparisons showed lower PSMD in subtype 0 than subtypes 1 and 2 (both p = 0.026), lower ALSFRS-R in subtype 2 than subtype 1 (p = 0.026), and higher SuStaIn stage in subtype 2 than subtype 0 (p = 0.025). Higher SuStaIn stage correlated with higher King’s stage (rho = 0.318, p = 0.006) and lower ALSFRS-R (rho = − 0.289, p = 0.013). After adjustment, higher SuStaIn stage remained associated with lower ALSFRS-R (β = − 0.333, p = 0.013) and more advanced King’s stage (odds ratio = 1.181, p < 0.001). Tract-level diffusion SuStaIn identified anatomically interpretable patterns of white matter involvement in ALS and provided patient-level stage estimates associated with clinical disease burden.
Parkinson’s disease (PD) is characterized by disabling motor and non-motor symptoms. Although pharmacological and rehabilitation interventions improve many motor and non-motor symptoms, persistent impairments commonly remain in domains, including speech, swallowing, gait, and balance, particularly as the disease progresses. For this reason, over the past few years, alternative rehabilitative approaches, such as singing-based interventions, have been used with the aim of addressing symptoms, such as speech impairment, swallowing difficulties, respiratory dysfunction, and mood. We aim to review the evidences on the efficacy of singing interventions on motor and non-motor symptoms in patients with PD. A comprehensive literature search of PubMed and Google Scholar was conducted for interventional studies published until December 2025. Results were summarized into five symptom domains: motor function, voice quality, breathing, swallowing, and quality of life. Twenty-six studies involving 1057 patients with PD were included. Singing-based interventions were associated with improvements in motor symptoms, gait, posture, voice quality, respiratory control, and maximum phonation time. Several studies also reported enhanced psychological well-being, social connectedness, and quality of life, with reductions in stress, anxiety, and depressive symptoms. Evidence regarding swallowing outcomes was limited and inconsistent. Considerable heterogeneity in study design, intervention protocols, and outcome measures precluded meta-analysis. Singing is a promising adjunct therapy for PD rehabilitation, particularly in domains less responsive to pharmacological treatment. Further high-quality research is needed to establish standardized protocols and assess long-term benefits.
