Fear of falling is a common and distressing concern among people with multiple sclerosis due to the gait and balance impairments associated with the disease. Clinicians and researchers often assume that the degree of fear of falling, typically measured with the Falls Efficacy Scale International (FES-I), is proportional to activity restrictions or rehabilitation engagement. However, a low or high level of fear of falling alone does not indicate whether fear of falling influences individual's performance of daily living activities. Fear of falling can either be adaptive (when aligned with functional capacity and actual fall risk) or maladaptive (when disproportionate to functional capacity and actual fall risk). In this personal viewpoint, I discuss the importance of contextualizing fear of falling assessment within the performance of daily living activities and propose that a function-focused assessment of fear of falling may enhance our understanding of whether it is adaptive or maladaptive. This approach may also provide targeted information to guide the development of interventions to address fear of falling in people with multiple sclerosis, help identify who requires intervention, and the type of intervention needed.

Cerebral small vessel disease (cSVD) is a common, potentially modifiable cause of poor balance control and falls in older people, but its early effects on balance control are difficult to detect. In this exploratory study, 20 older people with a broad range of cSVD on head MRI scans (median age 74.5 years, interquartile range 68-79 years) had their balance perturbed by motorised pulls at the shoulder. Body movements, ground reaction forces and prefrontal functional near-infrared spectroscopy (fNIRS) haemodynamic responses were recorded. Head MRI scans were reviewed to produce a score of cSVD burden ranging from 0 to 7 points based on lacunes (0-3), white matter hyperintensities (0-3), and cerebral microbleeds (0-1). Participants were divided into "low" (0-2 points) and "moderate" (3-7 points) cSVD burden subgroups, each of 10 participants. Moderate vs. low cSVD burden associated with worse cognitive function. Balance and gait measures (Short Physical Performance Battery test score, tandem walking, stepping responses to manual retropulsion) were similar in the two cSVD burden groups, as were pull-related body sway and resisting ground reaction forces. More cSVD associated with less pull force to induce steps, and with greater balance-related fNIRS prefrontal cortical haemodynamic responses. Prefrontal cortical activation was the most significant measure, explaining 33% of the variation in cSVD burden, while the stepping force threshold explained 17%. Our results suggest that, in addition to cognition, prefrontal cortical responses and stepping force thresholds are likely sensitive to effects of cSVD.

Brain cholinergic systems changes are implicated in the pathophysiology of postural instability and gait difficulties in Parkinson's disease. The presence of postural instability and gait difficulties is associated with cholinergic terminal deficits or downregulation of cholinergic neurotransmission. Preservation or upregulation of cholinergic neurotransmission may mitigate other Parkinson's disease-associated deficits to prevent postural instability and gait difficulties that are dependent on effective sensorimotor, cognitive, and emotional integration functions. Emerging evidence also suggests that dopaminergic neurotransmission is up- and downregulated in extra-striatal regions. This expanded view of complex whole brain up and downregulatory cholinergic and dopaminergic interactive processes requires a re-appraisal of pathophysiologic changes underlying mobility disturbances in Parkinson's disease. The goal of this review is to propose a novel expanded heuristic model of dynamic cholinergic and dopaminergic systems changes underlying habitual and goal-directed motor behaviors in Parkinson's disease. We hypothesize a hierarchical topographic whole-brain model where variable combinations of up- and down-regulation of cholinergic and dopaminergic neurotransmission differentially explain habitual and goal-directed motor behavior abnormalities underlying axial motor impairments. We propose that levodopa-unresponsive freezing of gait is the culmination of combined cholinergic and dopaminergic losses in selective thalamic, (para-) limbic, thalamic complex, upper tectum, upper tegmental (especially periaqueductal gray), and cerebellar brain regions. This model is based on a comparison of literature findings of cholinergic topographic deficits underlying postural instability and gait difficulties motor findings, complemented by emerging and preliminary evidence of extra-striatal dopaminergic system changes across the spectrum of Parkinson's disease. In contrast, different topographic cholinergic system deficits, associated with freezing of gait, such as the mesencephalic and cerebellar locomotor regions, diffuse striatal, and peri-central cortices - that are key pathways of dopaminergic-dependent habitual motor behaviors - are seen with levodopa-responsive but not with unresponsive freezing of gait. Cholinergic upper tegmental, including periaqueductal gray, and limbic deficits associated with levodopa-unresponsive freezing of gait also plays a role in emotional regulation. Failure of this circuitry may lead to a context-dependent downward spiral of fear of falling, which in turn compromises the motivation to move and worsens or triggers levodopa-unresponsive freezing of gait. Cholinergic losses in the periaqueductal gray upper tegmental region may acutely block goal-directed motor behavior, contributing to the panic disorder subtype of freezing of gait. Such a freezing of gait subtype may be a naturally protective defense mechanism that, in the context of the high inherent risk of freezing of gait-associated falling, becomes counterproductive. Future research should test this heuristic model.

Background and Objectives: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which gait and balance disturbances substantially increase the risk of falls and loss of independence. Pharmacological treatment alleviates several motor symptoms but has limited effects on postural instability. Backward walking (BW), a demanding locomotor task, has recently been investigated as both an assessment tool and a rehabilitation strategy in PD. The purpose of this focused systematic review is to analyse the benefits and limitations of retro walking in relation to the gait parameters and balance control of PD patients. Materials and Methods: A structured literature search (2015-2025) was conducted across multiple databases in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Eligibility criteria, screening procedures, and qualitative synthesis methods were predefined. Nine studies (including two randomized controlled trials) met the inclusion criteria. Methodological quality was assessed using PEDro and ROBINS-I tools, and the certainty of evidence was evaluated using GRADE. Results: The research results indicate within-group improvements in balance and gait parameters following BW training. Some of the included studies also suggest that BW may be a sensitive marker of balance deficits and fall risk. However, the evidence is limited by small sample sizes, heterogeneity of interventions, and a predominance of non-randomized designs. Conclusions: Current evidence regarding BW in PD remains preliminary. While BW may be considered as a supplementary component of rehabilitation, its specific efficacy cannot be clearly distinguished from general exercise effects. Further high-quality randomized controlled trials with standardized protocols and long-term follow-up are required.

(1) Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by gait and postural impairments. Recently, physical activity has emerged as a key strategy in PD management. This study aimed to evaluate the effectiveness of an innovative technology-assisted rehabilitation program in improving gait and reducing fall risk in older adults with PD. (2) Methods: Fifty-eight patients were randomly assigned to three groups: conventional rehabilitation (CG), or conventional therapy combined with technology-assisted rehabilitation using Tymo (TG) or Walker View (WG). The intervention consisted of 10 sessions over 5 weeks. Assessments were conducted at baseline (T0), post-intervention (T1), and at 6-month follow-up (FW). Outcomes included gait and balance performance, fear of falling, quality of life, activities of daily living, and physical function. (3) Results: The CG showed no significant improvements, with a decline in Barthel Index from T1 to FW. The WG demonstrated significant improvement in POMA Gait scores, while the TG improved both POMA Total and Balance scores at T1. Post-treatment, TG and WG outperformed CG in POMA outcomes; however, these differences were lost at follow-up. (4) Conclusions: Technology-assisted rehabilitation can improve gait and balance in older adults with PD, although sustained or repeated interventions may be necessary to maintain long-term benefits.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disorder characterized by misfolded ataxin-3 aggregation and neuronal intranuclear inclusions. Its primary symptom is progressive ataxia, progressively restricting daily living activities. While repetitive transcranial magnetic stimulation (rTMS) may alleviate symptoms, the effects and mechanisms of specific rTMS paradigms, particularly intermittent and continuous theta burst stimulation (iTBS/cTBS), remain unclear in SCA3. This study therefore aimed to investigate the impacts of iTBS and cTBS on motor coordination, cerebellar neuroinflammation, and autophagy in SCA3 transgenic mice. Thirty 14-week-old SCA3 transgenic mice were randomly divided into sham, cTBS, and iTBS groups. Cerebellar stimulation was delivered at 30% maximum output (600 pulses/session, once daily, 5 days/week for 2 weeks). Motor coordination was assessed via rotarod and CatWalk gait analysis. Pathological changes were evaluated by measuring ataxin-3 protein and ubiquitin-positive inclusions. Cerebellar neuroinflammation was analyzed using Iba-1, CD206, and a cytokine array, while autophagy was assessed via Beclin-1 and LC3B expression. iTBS significantly improved motor coordination in SCA3 mice, reducing rotarod falls (vs. sham P < 0.001, vs. cTBS P < 0.05) and improving gait symmetry (vs. sham P < 0.05) and regularity index (vs. sham P < 0.01, vs. cTBS P < 0.01). It also alleviated cerebellar pathology, lowering ataxin-3 expression (vs. sham P < 0.01, vs. cTBS P < 0.01) and ubiquitin-positive inclusions (vs. sham P < 0.01, vs. cTBS P < 0.05). While both iTBS and cTBS increased Iba-1-positive cells (P < 0.05 and P < 0.05, respectively, vs. sham), only iTBS raised CD206-positive cells (vs. sham P < 0.05) and downregulated pro-inflammatory cytokines. Furthermore, iTBS activated autophagy, enhancing Beclin-1 (vs. sham P < 0.05) and LC3B expression (vs. sham P < 0.0001, vs. cTBS P < 0.001). iTBS improved motor coordination and alleviated core cerebellar pathology in SCA3 mice. This effect may be mediated through the downregulation of cerebellar neuroinflammation and the activation of autophagy. Furthermore, the therapeutic efficacy of iTBS was superior to that of cTBS across multiple dimensions, demonstrating distinct paradigm specificity.

Variants in COA7 (cytochrome c oxidase assembly factor 7) are a rare cause of mitochondrial disease, with limited clinical descriptions and phenotypic variability. We describe 2 siblings carrying compound heterozygous COA7 variants, one of which (c.457C>T; p.Leu153Phe) is novel. Both presented with early-onset, slowly progressive axonal sensorimotor neuropathy, with differences in severity and associated features.

Parkinson disease (PD) can significantly impair the quality of life of affected individuals. Especially, motor symptoms are challenging, as they worsen over time and increase the risk of falls and further injuries. This paper presents a wearable-based pro-adaptive assistive system (AS) for detecting PD-related symptoms and predicting disease progression. To this end, we present the initial structure and components of a pro-adaptive AS, which uses AI models to enable pro-adaptive decision-making based on the patient's condition. The developed wrist-worn wearable device uses an accelerometer to detect resting tremors and falls and can store sensor data locally on a microSD card. In the event of fall, this device can automatically emit a signal to alert caregivers. The proposed pro-adaptive AS enables adaptive assistance based on the patient's current condition.

Ataxia with vitamin E deficiency (AVED) is a chronic progressive syndrome with low vitamin E levels, caused by biallelic pathogenic variants in the alpha-tocopherol transfer protein (TTPA) gene on chromosome 8q13.1. According to family segregation studies, we describe a novel putative variant in compound heterozygosity with a known pathogenic variant.

Rosai-Dorfman disease (RDD) is a rare, benign, non-neoplastic histiocytic proliferative disorder. Involvement of the distal femur with intra-articular extension is uncommon and can pose diagnostic challenges. Physiotherapy plays a critical role in postoperative recovery; however, structured rehabilitation guidelines for such cases remain limited in the literature. This case report describes a rare presentation of intraosseous RDD and highlights the clinical outcomes of a phased, impairment-based physiotherapy protocol following surgical excision and bone grafting. The patient presented with gradually progressive left-sided knee pain that worsened over several months. Radiographic evaluation demonstrated a mixed lytic-sclerotic lesion in the distal femur with intra-articular extension. The patient underwent intra-articular curettage with allograft bone grafting; biopsy confirmed intraosseous RDD. She was referred for physiotherapy five weeks after immobilization. Postoperatively, she presented with restricted knee flexion range of motion (ROM) to 70°, extensor lag, fear of falling, swelling in the patellar region, a healed surgical scar, quadriceps and calf muscle atrophy, altered gait, pelvic drop during stance, reduced quadriceps, hamstring, and hip abductor strength (manual muscle testing (MMT) 3-), and impaired proprioception of the knee joint. A structured, phase-wise physiotherapy program was initiated with the goals of protecting the graft, gradually restoring knee mobility, improving muscle strength, facilitating gait re-education, and enhancing proprioception. The patient demonstrated progressive improvement in knee range of motion, muscle strength, gait symmetry, and functional independence without complications. This case underscores the importance of early, goal-oriented, phase-based physiotherapy following surgical management of intraosseous RDD of the distal femur. A structured rehabilitation protocol complemented surgical treatment, facilitating the recovery of mobility and function and helping to prevent long-term disability. This report contributes clinically relevant guidance to the limited literature on postoperative physiotherapy management in rare cases of RDD.

Turning is a complex motor behavior that frequently triggers freezing of gait and falls in Parkinson's disease (PD), yet its neural dynamics in naturalistic settings remain unknown. Using chronic at-home intracranial recordings in four subjects with PD, we show that turning is marked by premotor cortical beta desynchronization driven by reduced burst rate. These findings identify a robust signature of ecological turning and implicate beta dynamics in adaptive motor transitions.