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Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the degeneration of dopamine neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. While motor symptoms such as rigidity, tremor, bradykinesia/akinesia, and postural instability are well-recognized, non-motor symptoms including cognitive decline, depression, and anxiety also significantly impact patients' quality of life. Preclinical research utilizing animal models has been instrumental in understanding PD pathophysiology and exploring therapeutic interventions. Various approaches, including genetic manipulations and toxin-induced insults, aim to recapitulate both motor and non-motor aspects of PD in animal models. However, no single model fully replicates the complex spectrum of PD symptoms. Behavioral assessments play a crucial role in evaluating motor impairments in PD animal models, focusing on the manifestation of Parkinsonian motor phenotype. These assessments encompass locomotor activities, motor behavior abnormalities, and induced rotational behavior. Similarly, non-motor features are assessed through tests evaluating behavioral alterations such as depression, anxiety, and cognitive impairment. Although numerous animal models of PD have been developed, including non-human primates and both mammalian and non-mammalian species, this review focuses on motor and non-motor testing methodologies in rodent models, which are the most commonly used. Emphasizing genetic and toxin-induced PD models in mice and rats, we highlight key testing strategies and the significance of each method in addressing specific research questions and interpreting experimental data. By providing a comprehensive overview of these testing approaches, this review aims to advance understanding and foster progress in PD research. [ABSTRACT FROM AUTHOR]

• PDGFRβ-CreERT2 mice enable Cre-mediated recombination specifically in pericytes. • Pericyte ablation can be titrated based on tamoxifen dose. • Pericyte ablation causes hypoactivity and impairs motor function. • Pericyte ablation increases brain vessel lumen area and induces mild blood–brain barrier leakage. • Pericyte ablation leads to elevated astrocyte and microglia reactivity throughout the brain. Capillary pericytes are important regulators of cerebral blood flow, blood–brain barrier integrity and neuroinflammation, but can become lost or dysfunctional in disease. The consequences of pericyte loss or dysfunction is extremely difficult to discern when it forms one component of a complex disease process. To evaluate this directly, we examined the effect of adult pericyte loss on mouse voluntary movement and motor function, and physiological responses such as hypoxia, blood–brain barrier (BBB) integrity and glial reactivity. Tamoxifen delivery to Pdgfrβ-CreERT2:: Rosa26-DTA transgenic mice was titrated to produce a dose-dependent ablation of pericytes in vivo. 100mg/kg of tamoxifen ablated approximately half of all brain pericytes, while two consecutive daily doses of 300mg/kg tamoxifen ablated >80% of brain pericytes. In the open field test, mice with ∼50% pericyte loss spent more time immobile and travelled half the distance of control mice. Mice with >80% pericyte ablation also slipped more frequently while performing the beam walk task. Our histopathological analyses of the brain revealed that blood vessel density was unchanged, but vessel lumen width was increased. Pericyte-ablated mice also exhibited: mild BBB disruption; increased neuronal hypoxia; astrogliosis and increased IBA1+ immunoreactivity, suggestive of microgliosis and/or macrophage infiltration. Our results highlight the importance of pericytes in the brain, as pericyte loss can directly compromise brain health and induce behavioural alterations in mice. [ABSTRACT FROM AUTHOR]

Objective: Advancements in neuroimaging technologies have significantly deepened our understanding of the neural physiopathology associated with stroke. Nevertheless, the majority of studies ignored the characteristics of dynamic changes in brain networks. The relationship between dynamic changes in brain networks and the severity of motor dysfunction after stroke needs further investigation. From the perspective of multilayer network module reconstruction, we aimed to explore the dynamic reorganization of the brain and its relationship with motor function in subcortical stroke patients. Methods: We recruited 35 healthy individuals and 50 stroke patients with unilateral limb motor dysfunction (further divided into mild-moderate group and severe group). Using dynamic multilayer network modularity analysis, we investigated changes in the dynamic modular reconfiguration of brain networks. Additionally, we assessed longitudinal clinical scale changes in stroke patients. Correlation and regression analyses were employed to explore the relationship between characteristic dynamic indicators and impairment and recovery of motor function, respectively. Results: We observed increased temporal flexibility in the Default Mode Network (DMN) and decreased recruitment of module reconfiguration in the Attention Network (AN), Sensorimotor Network (SMN), and DMN after stroke. We also observed reduced module loyalty following stroke. Additionally, correlation analysis showed that hyper-flexibility of the DMN was associated with better lower limb motor function performance in stroke patients with mild-to-moderate impairment. Regression analysis indicated that increased flexibility within the DMN and decreased recruitment coefficient within the AN may predict good lower limb function prognosis in patients with mild to moderate motor impairment. Conclusions: Our study revealed more frequent modular reconfiguration and hyperactive interaction of brain networks after stroke. Notably, dynamic modular remodeling was closely related to the impairment and recovery of motor function. Understanding the temporal module reconfiguration patterns in multilayer networks after stroke can provide valuable information for more targeted treatments. [ABSTRACT FROM AUTHOR]

Stroke is one of the leading causes of death and disability worldwide and poses a tremendous socioeconomic burden upon individuals, countries and healthcare systems. It causes debilitating symptoms and thus interferes with many aspects of the patient's life, including physical functioning, cognition, emotional status, activities of daily living, social reintegration and quality of life. Post-stroke patients frequently experience functional motor disabilities of the upper limb, which restrict autonomy and self-efficacy and cause limitations in engagement with activities and social participation, as well as difficulties in performing important occupations. It is therefore not surprising that motor impairment or loss of motor function of the upper limb is one of the most devastating sequelae of stroke. On these grounds, achieving optimal functioning of the upper limb after stroke remains a fundamental goal of stroke rehabilitation. Mirror therapy (MT) represents one of the several rehabilitation techniques used for restoring the upper limb's motor function after a stroke. However, conflicting results about the role of MT in the rehabilitation of the upper limb's motor deficits have been reported in the literature. Accordingly, the aim of this narrative review is to summarize existing evidence regarding the effects of MT on the upper limb's motor function in post-stroke patients and to further explore its role when applied in different phases of stroke. [ABSTRACT FROM AUTHOR]

Purpose: Participation in everyday life activities is important for the development of children and is an important topic in rehabilitation practices. This qualitative study aimed to unveil the perspectives and experiences of teenagers with vision impairments (VIs) or motor impairments (MIs) regarding their participation in leisure activities. Materials and methods: 13 teenagers with VIs and 12 teenagers with MIs (age range: 11–15 years) participated in this study. Data were collected using semi-structured interviews. Verbatim transcripts were analyzed following the steps of the phenomenological approach. Results: A total of 623 significant statements were identified and assigned to 221 meaning units. Finally, 13 themes emerged. Teenagers with VIs and MIs shared many experiences and perspectives regarding participation in leisure activities. Conclusions: Teenagers reported that they can sufficiently indicate what they experience as pleasant and sufficient considering their participation, as well as the challenges they encountered, such as their impairment, limited transport possibilities, or concerns from parents. Overall, teenagers with VIs or MIs were generally satisfied with the degree and frequency of their participation in leisure activities and felt sufficiently involved. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the combination of acupuncture and mirror therapy can improve motor impairment in stroke patients. Design: A systematic review and meta-analysis of randomised controlled trials. Data sources: CNKI, Wanfang, PubMed, Embase, Vip, web of since, Cochrane database and CBM database. Eligibility criteria for selecting studies: The included randomized controlled trials compared the efficacy of acupuncture therapy (AT) combined with mirror therapy (MT) against AT, MT, and conventional rehabilitation therapy on limb motor impairment in stroke patients, with independent data extraction and study quality assessment conducted. A META analysis using fixed-effect and random-effect models was performed to calculate the mean difference (MD) in motor scores and the Total effective rate RR (Risk ratio) between the AT combined with MT group and the control group. Main outcome measures: The Fugl-Meyer Assessment (FMA) for motor function includes the FMA-T (total FMA), FMA-UE (upper extremity FMA), and FMA-L (lower extremity FMA). Results: A total of 42 randomized controlled trials were included, involving 3,340 patients with post-stroke motor impairment. AT combined with MT was more favorable for FMA-UE (mean difference [MD] = 6.67, 95% CI [5.60–7.93], Z = 11.42, P < 0.0001), FMA-L [MD = 3.37, 95% CI (2.99–3.76), Z = 17.31, P < 0.001], and FMA-T [MD = 6.84, 95% CI (5.92–7.77), Z = 14.48, P < 0.001]. The combined AT and MT treatment was more favorable for the Modified Barthel Index (MBI) score in post-stroke motor impairment [MD = 10.82, 95% CI (8.52–13.12), Z = 9.22, P < 0.001]. AT combined with MT was more favorable for the Modified Ashworth Scale (MAS) [MD = −0.34, 95% CI (−0.66 to −0.03), Z = 14.48, P < 0.001]. AT combined with MT was more favorable for the Total effective rate in treating post-stroke motor impairment (relative risk = 1.27, 95% confidence interval [CI] [1.19–1.37], Z = 6.54, P < 0.001). Conclusions: AT combined with MT can effectively improve patients' motor function and daily living abilities. Systematic Review Registration: PROSPERO, identifier, CRD42024559992. [ABSTRACT FROM AUTHOR]

Background and aim: Traumatic brain injury (TBI) affects brain functions, often leading to a range of cognitive and motor impairments, necessitating effective rehabilitation. It is expedient for physiotherapists to have adequate knowledge, an appropriate attitude, and practice towards managing cognitive and motor impairments in adults with TBI. This study assessed physiotherapists' knowledge, attitudes, and practices of cognitive and motor impairments in adult patients with TBI. Methods: This cross-sectional study involved 75 physiotherapists recruited from 8 hospitals in South-West Nigeria via purposive sampling. A self-developed questionnaire administered via Google Forms® was used to assess the knowledge, attitude, and practice (KAP) of physiotherapists towards cognitive and motor impairments in adult patients with TBI. Descriptive statistics of mean, median, range, percentages, and frequency distribution tables were used in summarizing the KAP, while the association/correlation between KAP scores and selected demographic/profession-related characteristics was also investigated using inferential statistics of the Man-Whitney U, Kruskal Wallis, and Spearman ranked correlation. The level of significance was set at p < 0.05. Results: The mean age of the participants was 28.73 ± 7.093 years, predominantly female (53.3%), with a bachelor's degree in physiotherapy (78.7%), and specializing in neuro-physiotherapy. Most respondents demonstrated knowledge of cognitive 45 (60%) and motor 42 (56%) impairments in adult TBI patients. There was a (rho = 0.259) positive significant correlation (p = 0.025) between the age of the physiotherapist and their knowledge of the management of cognitive and motor impairment in adult patients with TBI. Conclusion: Many physiotherapists in South-West Nigeria demonstrate good knowledge of TBI, with this knowledge increasing with age. This study underscores the importance of continuous educational training for physiotherapists, a consequence of which should be better rehabilitation and functional outcomes for people with TBI. [ABSTRACT FROM AUTHOR]

Background: Neurobrucellosis presents diverse clinical challenges and risks of long-term complications. Objective: We aimed to assess the relationship between the duration of antibiotic therapy, clinical factors, and the outcome of neurobrucellosis with a case report combined with a systematic review of the literature. Methods: We present a case of a 31 years-old man successfully treated at our Institution. We then searched Ovid MEDLINE, Embase and Scopus for articles that encompassed neurobrucellosis cases, duration of treatment, and outcome. The primary outcome was to assess an association between the duration of treatment and the risk of sequelae or relapses. Univariate, multivariate and sensitivity analysis were carried out to define which variables affect​ed​ the clinical outcome. Quality assessment was performed using a dedicated tool. Results: A total of 123 studies were included, totaling 221 patients. Median duration of treatment was 4 months (IQR 3 – 6), 69% patients recovered without sequelae, 27% had sequelae. Additionally, five patients had a relapse, and 4 patients died. Multivariate analysis found that the duration of treatment, age, and the use of ceftriaxone were not associated with a higher risk of sequelae or relapses. A significant association was found for corticosteroids use (OR 0.39, 95% IC 0.16 – 0.96, p = 0.038), motor impairment (OR 0.29, 95% IC 0.14 – 0.62, p = 0.002), and hearing loss (OR 0.037, 95% IC 0.01 – 0.11, p < 0.001). Conclusions: This study highlights the variability in clinical presentations and treatment approaches for neurobrucellosis. Patients with factors indicating higher sequelae risk require meticulous follow-up. [ABSTRACT FROM AUTHOR]

Abstract Background and aim Traumatic brain injury (TBI) affects brain functions, often leading to a range of cognitive and motor impairments, necessitating effective rehabilitation. It is expedient for physiotherapists to have adequate knowledge, an appropriate attitude, and practice towards managing cognitive and motor impairments in adults with TBI. This study assessed physiotherapists’ knowledge, attitudes, and practices of cognitive and motor impairments in adult patients with TBI. Methods This cross-sectional study involved 75 physiotherapists recruited from 8 hospitals in South-West Nigeria via purposive sampling. A self-developed questionnaire administered via Google Forms® was used to assess the knowledge, attitude, and practice (KAP) of physiotherapists towards cognitive and motor impairments in adult patients with TBI. Descriptive statistics of mean, median, range, percentages, and frequency distribution tables were used in summarizing the KAP, while the association/correlation between KAP scores and selected demographic/profession-related characteristics was also investigated using inferential statistics of the Man-Whitney U, Kruskal Wallis, and Spearman ranked correlation. The level of significance was set at p

The associations among increased pain sensitivity, obesity, and systemic inflammation have not been described as related to BBB dysfunctions. To analyze the metabolic, behavioral, and inflammatory effects of a high-fat diet (HFD) and ultrastructural modifications in brain regions, we used an in vivo experimental model. Adult male Wistar rats were randomly assigned to one of two conditions, an ad libitum control group or an HFD (60%)-fed group, for eight weeks. At the end of the protocol, glucose and insulin tolerance tests were performed. Additionally, we analyzed the response to a normally innocuous mechanical stimulus and changes in motor coordination. At the end of the protocol, HFD-fed rats presented increased HOMA–IR and metabolic syndrome (MetS) prevalence. HFD-fed rats also developed an increased nociceptive response to mechanical stimuli and neurological injury, resulting in impaired motor function. Hypothalamus and cerebellum neurons from HFD-fed rats presented with nuclear swelling, an absence of nucleoli, and karyolysis. These results reveal that HFD consumption affects vital brain structures such as the cerebellum, hippocampus, and hypothalamus. This, in turn, could be producing neuronal damage, impairing cellular communication, and consequently altering motricity and pain sensitivity. Although direct evidence of a causal link between BBB dysfunction and sensory-motor changes was not observed, understanding the association uncovered in this study could lead to targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Patient‐rated motor symptoms (PRMS) and clinician‐rated motor symptoms (CRMS) often differ in Parkinson's disease (PD). Objective: Our goal was to investigate the determinants and clinical implications of PRMS compared with CRMS in PD. Methods: This retrospective, observational cohort study analyzed the cross‐sectional associations and longitudinal impacts of PRMS as assessed by the Movement Disorders Society‐sponsored Unified PD Rating Scale (MDS‐UPDRS) part 2, while controlling for CRMS measured by MDS‐UPDRS part 3. Longitudinal analyses used Cox proportional hazards models and multiple linear mixed‐effects random intercepts/slope models, adjusting for many clinical predictors. We conducted propensity score matching (PSM) to reinforce our analyses' robustness and surface‐based morphometry to investigate neural correlates. Results: We enrolled 442 patients with early‐stage PD. At baseline, regardless of CRMS, PRMS were associated with the severity of postural instability and gait disturbance (PIGD). Notably, PRMS independently and more accurately predicted faster long‐term deterioration in motor function than CRMS (Hoehn and Yahr 4, adjusted hazard ratio per +1 point = 1.19 [95% confidence intervals, 1.08–1.32]), particularly in PIGD (PIGD subscore, β‐interaction = 0.052 [95% confidence intervals, 0.018–0.086]). PSM confirmed these findings' robustness. Surface‐based morphometry suggested that enhanced sensory processing was distinctively associated with PRMS. Conclusions: In early‐stage PD, PRMS weighed different aspects of symptoms and more effectively predicted motor deterioration compared to CRMS, with distinctive brain structural characteristics. The superior sensitivity of PRMS to subtle declines in drug‐refractory symptoms like PIGD likely underlie our results, highlighting the importance of understanding the differential clinical implications of PRMS to prevent long‐term motor deterioration. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Frailty is a geriatric, multi‐dimensional syndrome that reflects multisystem physiological change and is a transversal measure of reduced resilience to negative events. It is characterized by weakness, frequent falls, cognitive decline, increased hospitalization and dead and represents a risk factor for the development of Alzheimer's disease (AD). The fact that frailty is recognized as a reversible condition encourages the identification of earlier biomarkers to timely predict and prevent its occurrence. SAMP8 (Senescence‐Accelerated Mouse Prone‐8) mice represent the most appropriate preclinical model to this aim and were used in this study to carry transcriptional and metabolic analyses in the brain and plasma, respectively, upon a characterization at cognitive, motor, structural, and neuropathological level at 2.5, 6, and 9 months of age. At 2.5 months, SAMP8 mice started displaying memory deficits, muscle weakness, and motor impairment. Functional alterations were associated with a neurodevelopmental deficiency associated with reduced neuronal density and glial cell loss. Through transcriptomics, we identified specific genetic signatures well distinguishing SAMP8 mice at 6 months, whereas plasma metabolomics allowed to segregate SAMP8 mice from SAMR1 already at 2.5 months of age by detecting constitutively lower levels of acylcarnitines and lipids in SAMP8 at all ages investigated correlating with functional deficits and neuropathological signs. Our findings suggest that specific genetic alterations at central level, as well as metabolomic changes in plasma, might allow to early assess a frail condition leading to dementia development, which paves the foundation for future investigation in a clinical setting. [ABSTRACT FROM AUTHOR]

This study investigated alterations in functional connectivity (FC) within cortico–basal ganglia–thalamo–cortical (CBTC) circuits and identified critical connections influencing poststroke motor recovery, offering insights into optimizing brain modulation strategies to address the limitations of traditional single‐target stimulation. We delineated individual‐specific parallel loops of CBTC through probabilistic tracking and voxel connectivity profiles‐based segmentation and calculated FC values in poststroke patients and healthy controls, comparing with conventional atlas‐based FC calculation. Support vector machine (SVM) analysis distinguished poststroke patients from controls. Connectome‐based predictive modeling (CPM) used FC values within CBTC circuits to predict upper limb motor function. Poststroke patients exhibited decreased ipsilesional connectivity within the individual‐specific CBTC circuits. SVM analysis achieved 82.8% accuracy, 76.6% sensitivity, and 89.1% specificity using individual‐specific parallel loops. Additionally, CPM featuring positive connections/all connections significantly predicted Fugl‐Meyer assessment of upper extremity scores. There were no significant differences in the group comparisons of conventional atlas‐based FC values, and the FC values resulted in SVM accuracy of 75.0%, sensitivity of 67.2%, and specificity of 82.8%, with no significant CPM capability. Individual‐specific parallel loops show superior predictive power for assessing upper limb motor function in poststroke patients. Precise mapping of the disease‐related circuits is essential for understanding poststroke brain reorganization. [ABSTRACT FROM AUTHOR]

Motor delays in children with autism spectrum disorder (ASD) are being increasingly recognized using a brief screening tool, called the Developmental Coordination Disorder‐Questionnaire (DCD‐Q). Further validation of these motor delays using a more robust normed, developmental measure is clearly warranted. In this analysis, a nationally representative sample from the SPARK study was used wherein parents completed the DCD‐Q and a more widely used developmental/adaptive functioning measure, called the Vineland Adaptive Behavior Scales (VABS); which comprises of various developmental domains including the motor domain (N = 2,644 completed the DCD‐Q and VABS). Eighty two percent children with ASD had a motor delay based on their DCD‐Q scores whereas 77% children with ASD had a motor delay based on their VABS motor domain scores. Approximately 70% children with ASD had concurrent motor delay on the DCD‐Q and the VABS (i.e., positive predictive value of DCD‐Q). Furthermore, there was 81.2% accuracy in reporting a risk/no risk of motor delay across both measures. Overall, these statistics align with the recent reports on proportions of children with ASD having motor delays. Parents of ~70% children with ASD are reporting motor delays that are corroborated across two different motor measures. This not only validates the motor delays reported based on the DCD‐Q but also indicates the need for concurrent motor screening using both DCD‐Q and VABS for better detection of motor delays in children with ASD. Only 10%–32% of the current SPARK sample received any physical or recreational therapies. This mismatch between presence of motor delays and the lack of access to motor services highlights the need for more motor intervention referrals for children with ASD. Lay Summary: Motor delays were studied in children with autism spectrum disorder (ASD) using two parent questionnaires: the Developmental Coordination Disorder‐Questionnaire (DCD‐Q) screener and the Vineland Adaptive Behavior Scales. Parents of 70% children with ASD reported motor delays using both measures. This indicates the need for concurrent motor screening using both DCD‐Q and VABS for better detection of motor delays in children with ASD. However, only 10%–32% of the current SPARK sample received any physical or recreational therapies. The mismatch between reported motor delays and the lack of access to motor services highlights the need for more motor intervention referrals for children with ASD. [ABSTRACT FROM AUTHOR]

Individuals with multiple disabilities are among the most challenging to serve and AAC teams often lack direction in determining effective interventions. The purpose of this scoping review was to summarize the research evidence on AAC interventions for individuals with complex communication needs and simultaneous motor, and visual impairments as part of their multiple disabilities; to consider implications for practice; and to determine gaps and directions for future research. A total of 27 studies were identified and reviewed, involving 55 unique participants with multiple disabilities. Most studies focused on direct intervention to increase requesting or choice-making, with little focus on social communication. Only two studies focused on training communication partners. Results indicated that AAC interventions can be highly effective to increase communication for individuals with multiple disabilities. However, there is an urgent need for increased rigor and more detailed participant information in future AAC intervention research with this population. Future research should investigate AAC intervention to improve social communication and increase language development, not just expression of needs and wants. Future research should focus on the needs of individuals with multiple disabilities from culturally and linguistically diverse backgrounds and on implementation of AAC within natural environments. [ABSTRACT FROM AUTHOR]

Objectives: This review quantitatively evaluates the effectiveness of gross-motor-based interventions in children with developmental coordination disorder (DCD), examining treatment aspects such as group interventions, therapy duration, and frequency. Methods: A systematic literature review, spanning January 2010 to December 2022, identified 11 relevant articles involving 492 children. Results: Positive outcomes were observed, with a moderate to large overall effect size (Cohen's d) indicating significant improvements in motor function through strategies emphasizing activity, bodily function, games, and small group events. Notably, interventions targeting complex motor skills were crucial for enhancing preparedness and activity engagement, improving fitness, and preventing obesity in children with DCD. Conclusions: The review underscores the effectiveness of activity-oriented and body-function-focused therapies in enhancing motor skills and functioning, emphasizing the need for interventions aligned with real-world activities. Future research should explore the long-term effects and retention of motor improvements, offering valuable insights for designing targeted interventions to promote overall well-being in children with DCD. [ABSTRACT FROM AUTHOR]

PurposeParticipation in everyday life activities is important for the development of children and is an important topic in rehabilitation practices. This qualitative study aimed to unveil the perspectives and experiences of teenagers with vision impairments (VIs) or motor impairments (MIs) regarding their participation in leisure activities.Materials and methods13 teenagers with VIs and 12 teenagers with MIs (age range: 11–15 years) participated in this study. Data were collected using semi-structured interviews. Verbatim transcripts were analyzed following the steps of the phenomenological approach.ResultsA total of 623 significant statements were identified and assigned to 221 meaning units. Finally, 13 themes emerged. Teenagers with VIs and MIs shared many experiences and perspectives regarding participation in leisure activities.ConclusionsTeenagers reported that they can sufficiently indicate what they experience as pleasant and sufficient considering their participation, as well as the challenges they encountered, such as their impairment, limited transport possibilities, or concerns from parents. Overall, teenagers with VIs or MIs were generally satisfied with the degree and frequency of their participation in leisure activities and felt sufficiently involved.

Objective: To investigate the combined effect of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation on improving lower limb function in stroke patients. Design: Randomized controlled trial. Subjects/Patients: Subacute stroke patients. Methods: 169 post-stroke hemiplegia patients were randomly divided into 4 groups (control, transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, and transcutaneous auricular vagus nerve stimulation combined with transcranial direct current stimulation) and evaluated using the Fugl-Meyer Assessment-Lower Extremity (FMA-LL), Timed Up-and-Go (TUG) test, Modified Barthel Index (MBI), Berg Balance Scale (BBS), gait parameters, and surface electromyography (sEMG). Results: Significant improvements in FMA-LL, MBI, BBS, TUG, gait parameters, and sEMG were noted in the intervention groups compared with the control, with the transcutaneous auricular vagus nerve stimulation combined with transcranial direct current stimulation group showing the most pronounced improvements. Differences in some outcomes were also notable between the transcutaneous auricular vagus nerve stimulation and transcranial direct current stimulation groups. Conclusion: The combination of transcutaneous auricular vagus nerve stimulation and transcranial direct current stimulation effectively enhances gait, balance, and daily living activities in subacute stroke patients. These benefits are likely due to transcutaneous auricular vagus nerve stimulation activating the solitary and trigeminal nuclei and transcranial direct current stimulation stimulating the motor cortex. Wearable gait analysis systems and electromyography are valuable in clinical gait assessment for these patients.

ObjectiveTo investigate whether the combination of acupuncture and mirror therapy can improve motor impairment in stroke patients.DesignA systematic review and meta-analysis of randomised controlled trials.Data sourcesCNKI, Wanfang, PubMed, Embase, Vip, web of since, Cochrane database and CBM database.Eligibility criteria for selecting studiesThe included randomized controlled trials compared the efficacy of acupuncture therapy (AT) combined with mirror therapy (MT) against AT, MT, and conventional rehabilitation therapy on limb motor impairment in stroke patients, with independent data extraction and study quality assessment conducted. A META analysis using fixed-effect and random-effect models was performed to calculate the mean difference (MD) in motor scores and the Total effective rate RR (Risk ratio) between the AT combined with MT group and the control group.Main outcome measuresThe Fugl-Meyer Assessment (FMA) for motor function includes the FMA-T (total FMA), FMA-UE (upper extremity FMA), and FMA-L (lower extremity FMA).ResultsA total of 42 randomized controlled trials were included, involving 3,340 patients with post-stroke motor impairment. AT combined with MT was more favorable for FMA-UE (mean difference [MD] = 6.67, 95% CI [5.60–7.93], Z = 11.42, P

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition leading to progressive muscle weakness, atrophy, and ultimately death. Traditional ALS clinical evaluations often depend on subjective metrics, making accurate disease detection and monitoring disease trajectory challenging. To address these limitations, we developed the nQiALS toolkit, a machine learning-powered system that leverages smartphone typing dynamics to detect and track motor impairment in people with ALS. The study included 63 ALS patients and 30 age- and sex-matched healthy controls. We introduce the three core components of this toolkit: the nQiALS-Detection, which differentiated ALS from healthy typing patterns with an AUC of 0.89; the nQiALS-Progression, which separated slow and fast progression at specific thresholds with AUCs ranging between 0.65 and 0.8; and the nQiALS-Fine Motor, which identified subtle progression in fine motor dysfunction, suggesting earlier prediction than the state-of-the-art assessment. Together, these tools represent an innovative approach to ALS assessment, offering a complementary, objective metric to traditional clinical methods and which may reshape our understanding and monitoring of ALS progression. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. Methods: Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0–53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0–70.0] years, 55.7% female) completed in‐person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form‐36 physical/mental summary scores, social attainment). Results: Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%–29.4%) than controls (2.9%, CI 1.4–4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06–18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19–72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01–1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68–11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10–0.84, Sensory: OR 0.35, CI 0.13–0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22–5.72). Conclusions: In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL. [ABSTRACT FROM AUTHOR]

Our team designed an innovative, observation-based motor impairment measure—the Pediatric Stroke Hemiplegic Motor Impairment Scale (Pedi HEMIs). Here we present the results of a survey describing common practices in the pediatric stroke community and the initial psychometric properties of the upper extremity subscale of the Pedi HEMIs (Pedi HEMIs-UE). This is a cross-sectional study whereby participants completed a battery of assessments including the novel Pedi HEMIs-UE. Internal consistency was measured via Cronbach alpha (α). Intraclass correlation (ICC) was used to assess inter-rater reliability (IRR). Concurrent validity was investigated using Pearson or polychoric correlations and simple linear regressions. The study sample consisted of 18 children aged 1.08 to 15 years. Two participants completed two sets of evaluations, totaling 20 data sets. Cronbach α, a measure of internal consistency, was on average 0.91 (range: 0.89 to 0.92). IRR was excellent with the six raters in almost perfect agreement (ICC = 0.91; 95% confidence interval [CI]: 0.83 to 0.96). Pearson correlation coefficient between the Pedi HEMIs-UE and logit Assisting Hand Assessment (AHA)/mini-AHA was −0.938 (95% CI: −0.979 to −0.827, P < 0.001), indicating excellent concurrent validity. We found excellent feasibility, reliability, and validity of the Pedi HEMIs-UE in a convenience sample of youth with hemiparesis after stroke. [ABSTRACT FROM AUTHOR]

Background: Upper limb motor impairment commonly occurs after stroke, impairing quality of life. Brain network reorganization likely differs between subgroups with differing impairment severity. This study explored differences in functional connectivity (FC) and corticospinal tract (CST) integrity between patients with mild/moderate versus severe hemiplegia poststroke to clarify the neural correlates underlying motor deficits. Method: Sixty chronic stroke patients with upper limb motor impairment were categorized into mild/moderate and severe groups based on Fugl‐Meyer scores. Resting‐state FC was assessed using functional near‐infrared spectroscopy (fNIRS) to compare connectivity patterns between groups across motor regions. CST integrity was evaluated by inducing motor evoked potentials (MEP) via transcranial magnetic stimulation. Results: Compared to the mild/moderate group, the severe group exhibited heightened premotor cortex–primary motor cortex (PMC–M1) connectivity (t = 4.56, p < 0.01). Absence of MEP was also more frequent in the severe group (χ2 = 12.31, p = 0.01). Bayesian models effectively distinguished subgroups and identified the PMC–M1 connection as highly contributory (accuracy = 91.30%, area under the receiver operating characteristic curve [AUC] = 0.86). Conclusion: Distinct patterns of connectivity and corticospinal integrity exist between stroke subgroups with differing impairments. Strengthened connectivity potentially indicates recruitment of additional motor resources to compensate for damage. These findings elucidate the neural correlates underlying motor deficits poststroke and could guide personalized, network‐based therapies targeting predictive biomarkers to improve rehabilitation outcomes. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) affects more than 6 million people worldwide. Along withmotor impairments, patients and animalmodels exhibiting PD symptoms also experience cognitive impairment, fatigue, anxiety, and depression. Currently, there are no drugs available for PD that alter the progression of the disease. A body of evidence suggests that increased GABA levels contribute to the reduced expression of tyrosine hydroxylase (TH) and accompanying behavioral deficits. TH expression may be restored by blocking GABAA receptors. We hypothesized that golexanolone (GR3027), a well-tolerated GABAA receptor-modulating steroid antagonist (GAMSA), may improve Parkinson's symptoms in a rat model of PD. Objectives: The aims of this study were to assess whether golexanolone can ameliorate motor and non-motor symptoms in a rat model of PD and to identify some underlying mechanisms. Methods: We used the unilateral 6-OHDA rat model of PD. The golexanolone treatment started 4 weeks after surgery. Motor symptoms were assessed using Motorater and CatWalk tests. We also analyzed fatigue (using a treadmill test), anhedonia (via the sucrose preference test), anxiety (with an open field test), and short-termmemory (using a Ymaze). Glial activation and key proteins involved in PD pathogenesis were analyzed using immunohistochemistry and Western blot. Results: Rats with PD showed motor incoordination and impaired locomotor gait, increased fatigue, anxiety, depression, and impaired short-term memory. Golexanolone treatment led to improvements in motor incoordination, certain aspects of locomotor gait, fatigue, anxiety, depression, and short-term memory. Notably, golexanolone reduced the activation of microglia and astrocytes, mitigated TH loss at 5 weeks after surgery, and prevented the increase of a-synuclein levels at 10 weeks. Conclusions: Golexanolone may be useful in improving both motor and non-motor symptoms that adversely affect the quality of life in PD patients, such as anxiety, depression, fatigue, motor coordination, locomotor gait, and certain cognitive alterations. [ABSTRACT FROM AUTHOR]

Bergamot essential oil shows anxiolytic‐relaxant effects devoid of sedative action and motor impairment typical of benzodiazepines. Considering the potential for clinical of these effects, it is important to understand the underlying mechanisms of the phytocomplex. Modulation of glutamate group I and II metabotropic receptors is involved in stress and anxiety disorders, in cognition and emotions and increases locomotor activity and wakefulness. Interestingly, early data indicate that bergamot essential oil modulates glutamatergic transmission in specific manifestations of the central nervous system. The aim of this work is to investigate if selective antagonists of metabotropic glutamate 2/3 and 5 receptors affect behavioral parameters modulated by the phytocomplex. Male Wistar rats were used to measure behavioral parameters to correlate anxiety and motor activity using elevated plus maze (EPM), open field (OF), and rotarod tasks. Bergamot essential oil increases in EPM the time spent in open/closed arms and reduces total number of entries. The essential oil also increases immobility in EPM and OF and not affect motor coordination in rotarod. Pretreatment with the metabotropic glutamate antagonists does not affect the time spent in open/close arms, however, differently affects motor behavior measured after administration of phytocomplex. Particularly, glutamate 2/3 antagonist reverts immobility and glutamate 5 antagonist potentiates this parameter induced by the phytocomplex. Our data show that modulation of both metabotropic glutamate receptors is likely involved in some of behavioral effects of bergamot essential oil. [ABSTRACT FROM AUTHOR]

Focal damage due to stroke causes widespread abnormal changes in brain function and hemispheric asymmetry. In this study, functional near‐infrared spectroscopy (fNIRS) was used to collect resting‐state hemoglobin data from 85 patients with subacute stroke and 26 healthy controls, to comparatively analyze the characteristics of lateralization after stroke in terms of cortical activity, functional networks, and hemodynamic lags. Higher intensity of motor cortical activity, lower hemispheric autonomy, and more abnormal hemodynamic leads or lags were found in the affected hemisphere. Lateralization metrics of the three aspects were all associated with the Fugl‐Meyer score. The results of this study prove that three lateralization metrics may provide clinical reference for stroke rehabilitation. Meanwhile, the present study piloted the use of resting‐state fNIRS for analyzing hemodynamic lag, demonstrating the potential of fNIRS to assess hemodynamic abnormalities in addition to the study of cortical neurological function after stroke. [ABSTRACT FROM AUTHOR]

Rotenone (RTN) induces neurotoxicity and motor dysfunction in rats, mirroring the pathophysiological traits of Parkinson's disease (PD), including striatal oxidative stress, mitochondrial dysfunction, and changes in neural structure. This makes RTN a valuable model for PD research. Berberine (BBR), an isoquinoline alkaloid recognized for its antioxidative, anti-inflammatory, and neuroprotective properties, was evaluated for its ability to counteract RTN-induced impairments. Rats received subcutaneous RTN at 0.5 mg/kg for 21 days, resulting in weight loss and significant motor deficits assessed through open-field, bar catalepsy, beam-crossing, rotarod, and grip strength tests. BBR, administered orally at 30 or 100 mg/kg doses, one hour prior to RTN exposure for the same duration, effectively mitigated many of the RTN-induced motor impairments. Furthermore, BBR treatment reduced RTN-induced nitric oxide (NO) and lipid peroxidation (LPO) levels, bolstered antioxidative capacity, enhanced mitochondrial enzyme activities (e.g., succinate dehydrogenase (SDH), ATPase, and the electron transport chain (ETC)), and diminished striatal neuroinflammation and apoptosis markers. Notably, the co-administration of trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, significantly attenuated BBR's protective effects, indicating that BBR's neuroprotective actions are mediated via the Nrf2 pathway. These results underscore BBR's potential in ameliorating motor impairments akin to PD, suggesting its promise in potentially delaying or managing PD symptoms. Further research is warranted to translate these preclinical findings into clinical settings, enhancing our comprehension of BBR's therapeutic prospects in PD. [ABSTRACT FROM AUTHOR]

This Joel A. DeLisa Lecture on endovascular brain-computer interfaces was presented by Dr Thomas Oxley on February 23, 2023, at the Association of Academic Physiatrists Annual Scientific Meeting. The lecture described how brain-computer interfaces replace lost physiological function to enable direct communication between the brain and external digital devices, such as computers, smartphones, and robotic limbs. Specifically, the potential of a novel endovascular brain-computer interface technology was discussed. The brain-computer interface uses a stent-electrode array delivered via the jugular vein and is permanently implanted in a vein adjacent to the motor cortex. In a first-in-human clinical trial, participants with upper limb paralysiswho received the endovascular brain-computer interface could use the system independently and at home to operate laptop computers for various instrumental activities of daily living. A Food and Drug Administration-approved trial of the endovascular brain-computer interface in the United States is in progress. Future development of the system will provide recipients with continuous autonomy through digital access with minimal caregiver assistance. Physiatrists and occupational therapists will have a vital role in helping people with paralysis achieve the potential of implantable brain-computer interfaces. [ABSTRACT FROM AUTHOR]

Children with congenital heart disease (CHD) have a higher prevalence of motor impairment secondary to brain injury, resulting in cerebral palsy (CP). The purpose of this study is to determine the prevalence of CP in CHD in a single-center cohort, stratify risk based on surgical mortality using Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) categories and identify risk factors. Retrospective cohort study of pediatric patients registered in the University of Florida (UF) Society of Thoracic Surgeons Congenital Heart Surgery database from 2006 to 2017 with a diagnosis of CHD who continued follow-up for more than two years at UF. A total of 701 children with CHD met inclusion criteria. Children identified to have CP were 54 (7.7%). Most common presentation was spastic hemiplegic CP with a Gross Motor Function Classification System of level 2. Analysis of surgical and intensive care factors between the two groups showed that children with CHD and CP had longer time from admission to surgery (P = 0.003), higher STAT categories 4 and 5 (P = 0.038), and higher frequency of brain injury and seizures (P < 0.001). Developmental disabilities and rehabilitation needs were significantly greater for children with CHD and CP when compared with those with CHD alone (P < 0.001). In our cohort, 7.7% children with CHD develop CP; this is significantly higher than the 2010 US population estimate of 0.3%. Our study suggests higher STAT categories, brain injury, and seizures are associated with developing CP in children with CHD. [ABSTRACT FROM AUTHOR]

• Mismatch negativity paradigm (MMN) showed compromised early auditory and pre-attentive processes in manifest Huntington Disease (HD). • In premanifest HD, MMN amplitude was similar to manifest HD, but theta coherence was increased compared to manifest HD and controls. • Initial decline of Mismatch Negativity, together with changes in theta power coherence, could characterize HD in the pre-manifest phase. The aim of this study was to investigate the characteristics of the electrophysiological brain response elicited in a passive acoustic oddball paradigm, i.e. mismatch negativity (MMN), in patients with Huntington's disease (HD) in the premanifest (pHD) and manifest (mHD) phases. In this regard, we correlated the results of event-related potentials (ERP) with disease characteristics. This was an observational cross-sectional MMN study. In addition to the MMN recording of the passive oddball task, all subjects with first-degree inheritance for HD underwent genetic testing for mutant HTT, the Huntington's Disease Rating Scale, the Total Functional Capacity Scale, the Problem Behaviors Assessment short form, and the Mini-Mental State Examination. We found that global field power (GFP) was reduced in the MMN time window in mHD patients compared to pHD and normal controls (NC). In the pHD group, MMN amplitude was only slightly and not significantly increased compared to mHD, while pHD patients showed increased theta coherence between trials compared to mHD. In the entire sample of HD gene carriers, the main MMN traits were not correlated with motor performance, cognitive impairment and functional disability. These results suggest an initial and subtle deterioration of pre-attentive mechanisms in the presymptomatic phase of HD, with an increasing phase shift in the MMN time frame. This result could indicate initial functional changes with a possible compensatory effect. An initial and slight decrease in MMN associated with increased phase coherence in the corresponding EEG frequencies could indicate an early functional involvement of pre-attentive resources that could precede the clinical expression of HD. [ABSTRACT FROM AUTHOR]

Patients with motor impairments (e.g., stroke, bone fracture, Parkinson's) are sensitive to the wearing experience of rehabilitation devices, and they often have difficulty accurately positioning them at an accurate position. While solutions involving optical systems or IMUs could potentially help alleviate the issue, they often introduce other challenges such as privacy concerns or discomforting experiences. With the emergence of wearable soft sensors during the last few decades, researchers widely apply soft sensors in rehabilitation to improve the wearing experience. However, these approaches have primarily focused on analyzing the sensor readings to improve accuracy rather than addressing the needs of patients and healthcare providers, and there is a lack of comprehensive design investigation and need assessment based on soft sensor-based rehabilitation systems for motor-impaired patients and their doctors. In this study, we developed an application, RehabFAB, utilizing fabric sensors for rehabilitation purposes. Besides, we evaluated our application and device and investigated the needs of patients and doctors for potential home rehabilitation applications. The investigation was conducted through thematic analysis, correlation analysis and System Usability Scale. The experimental results validated the efficacy, reliability and usability of our approach, with a SUS score of 81.75. In addition, the RehabFAB meets the expectations of motor-impaired patients and medical professionals as a home rehabilitation tool. Our core contributions lie in a thorough evaluation of the needs of motor-impaired patients in order to design a stable and reliable motion-tracking device based on soft sensors for their recovery. [ABSTRACT FROM AUTHOR]

A reserve in the motor domain may underlie the capacity exhibited by some patients to maintain motor functionality in the face of a certain level of disease. This form of "motor reserve" (MR) could include cortical, cerebellar, and muscular processes. However, a systematic definition has not been provided yet. Clarifying this concept in healthy individuals and patients would be crucial for implementing prevention strategies and rehabilitation protocols. Due to its wide application in the assessment of motor system functioning, non-invasive brain stimulation (NIBS) may support such definition. Here, studies focusing on reserve in the motor domain and studies using NIBS were revised. Current literature highlights the ability of the motor system to create a reserve and a possible role for NIBS. MR could include several mechanisms occurring in the brain, cerebellum, and muscles, and NIBS may support the understanding of such mechanisms. [ABSTRACT FROM AUTHOR]

Abstract This study investigated alterations in functional connectivity (FC) within cortico–basal ganglia–thalamo–cortical (CBTC) circuits and identified critical connections influencing poststroke motor recovery, offering insights into optimizing brain modulation strategies to address the limitations of traditional single‐target stimulation. We delineated individual‐specific parallel loops of CBTC through probabilistic tracking and voxel connectivity profiles‐based segmentation and calculated FC values in poststroke patients and healthy controls, comparing with conventional atlas‐based FC calculation. Support vector machine (SVM) analysis distinguished poststroke patients from controls. Connectome‐based predictive modeling (CPM) used FC values within CBTC circuits to predict upper limb motor function. Poststroke patients exhibited decreased ipsilesional connectivity within the individual‐specific CBTC circuits. SVM analysis achieved 82.8% accuracy, 76.6% sensitivity, and 89.1% specificity using individual‐specific parallel loops. Additionally, CPM featuring positive connections/all connections significantly predicted Fugl‐Meyer assessment of upper extremity scores. There were no significant differences in the group comparisons of conventional atlas‐based FC values, and the FC values resulted in SVM accuracy of 75.0%, sensitivity of 67.2%, and specificity of 82.8%, with no significant CPM capability. Individual‐specific parallel loops show superior predictive power for assessing upper limb motor function in poststroke patients. Precise mapping of the disease‐related circuits is essential for understanding poststroke brain reorganization.

Stroke is recognized as a network communication disorder. Advances in neuroimaging technologies have enhanced our comprehension of dynamic cerebral alterations. However, different levels of motor function impairment after stroke may have different patterns of brain reorganization. Abnormal and adaptive patterns of brain activity in mild-to-moderate motor function impairments after stroke remain still underexplored. We aim to identify dynamic patterns of network remodeling in stroke patients with mild-to-moderate impairment of motor function. fMRI data were obtained from 30 stroke patients and 31 healthy controls to establish a spatiotemporal multilayer modularity model. Then, graph-theoretic measures, including modularity, flexibility, cohesion, and disjointedness, were calculated to quantify dynamic reconfiguration. Our findings reveal that the post-stroke brain exhibited higher modular organization, as well as heightened disjointedness, compared to HCs. Moreover, analyzing from the network level, we found increased disjointedness and flexibility in the Default mode network (DMN), indicating that brain regions tend to switch more frequently and independently between communities and the dynamic changes were mainly driven by DMN. Notably, modified functional dynamics positively correlated with motor performance in patients with mild-to-moderate motor impairment. Collectively, our research uncovered patterns of dynamic community reconstruction in multilayer networks following stroke. Our findings may offer new insights into the complex reorganization of neural function in post-stroke brain.

Background: The recovery of upper extremity motor impairment after stroke remains a challenging task. The clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS), which is believed to aid in the recovery process, is still uncertain. Methods: A systematic search was conducted in Medline (Ovid), Cochrane and Embase electronic databases from March 28, 2014, to March 28, 2023. The inclusion criteria consisted of randomized controlled trials that assessed the effects of rTMS on the recovery of upper limb motor impairment among stroke patients. Various measurements, including the Fugl Meyer Assessment Upper Extremity Scale (FMA-UE), Brunnstrom recovery stage, Action Research Arm Test (ARAT), and Barthel index, were evaluated both before and after the intervention. Results: Nineteen articles with 865 patients were included. When considering only the rTMS parameters, both inhibitory and excitatory rTMS improved FMAUE (MD = 1.87, 95% CI = [0.88]-[2.86], p < 0.001) and Barthel index (MD = 9.73, 95% CI = [4.57]-[14.89], p < 0.001). When considering only the severity of upper limb hemiplegia, both less severe (MD = 1.56, 95% CI = [0.64]-[2.49], p < 0.001) and severe (MD = 2.05, 95% CI = [1.09]-[3.00], p < 0.001) hemiplegia benefited from rTMS based on FMA-UE. However, when considering the rTMS parameters, severity of hemiplegia and stroke stages simultaneously, inhibitory rTMS was found to be significantly effective for less severe hemiplegia in the acute and subacute phases (MD = 4.55, 95% CI = [2.49]-[6.60], p < 0.001), but not in the chronic phase based on FMA-UE. For severe hemiplegia, inhibitory rTMS was not significantly effective in the acute and subacute phases, but significantly effective in the chronic phase (MD = 2.10, 95% CI = [0.75]-[3.45], p = 0.002) based on FMA-UE. Excitatory rTMS was found to be significantly effective for less severe hemiplegia in the acute and subacute phases (MD = 1.93, 95% CI = [0.58]-[3.28], p = 0.005) based on FMA-UE. The improvements in Brunnstrom recovery stage and ARAT need further research. Conclusion: The effectiveness of rTMS depends on its parameters, severity of hemiplegia, and stroke stages. It is important to consider all these factors together, as any single grouping method is incomplete. [ABSTRACT FROM AUTHOR]

Pediatric stroke can result in long-term impairments across attention, functional communication and motor domains. The current paper utilized parent reports of the Behavioral Assessment System for Children 2nd Edition and the Pediatric Stroke Outcome Measure to examine children’s social skills and withdrawal behavior within a pediatric stroke population. Using the Canadian Pediatric Stroke Registry at The Hospital for Sick Children, data were analyzed for 312 children with ischemic stroke. Children with ischemic stroke demonstrated elevated parent-reported social skills problems (observed = 20.51%, expected = 14.00%) and clinically elevated social withdrawal (observed = 11.21%, expected = 2.00%). Attentional problems significantly contributed to reduced social skills, F (3,164) = 30.68, p < 0.01, while attentional problems and neurological impairments accounted for increased withdrawal behavior, F (2, 164) = 7.47, p < 0.01. The presence of a motor impairment was associated with higher social withdrawal compared to individuals with no motor impairment diagnosis, t(307.73) = 2.25, p < .025, d = 0.25, 95% CI [0.42, 6.21]. The current study demonstrates that children with stroke who experience motor impairments, attentional problems, reduced functional communication skills, and neurological impairments can experience deficits in their social skills and withdrawal behavior. [ABSTRACT FROM AUTHOR]

Objective: Glucosylceramidase (GBA) variants and onset age significantly affect clinical phenotype and progression in Parkinson's disease (PD). The current study compared clinical characteristics at baseline and cognitive and motor progression over time among patients having GBA‐related PD (GBA‐PD), early‐onset idiopathic PD (early‐iPD), and late‐onset idiopathic PD (late‐iPD). Methods: We recruited 88 GBA‐PD, 167 early‐iPD, and 488 late‐iPD patients in this study. A subset of 50 GBA‐PD, 81 early‐iPD, and 223 late‐iPD patients was followed up at least once, with a 3.0‐year mean follow‐up time. Linear mixed‐effects models helped evaluate the rate of change in the Unified Parkinson's Disease Rating Scale motor and Montreal Cognitive Assessment scores. Results: At baseline, the GBA‐PD group showed more severe motor deficits and non‐motor symptoms (NMSs) than the early‐iPD group and more NMSs than the late‐iPD group. Moreover, the GBA‐PD group had more significant cognitive and motor progression, particularly bradykinesia and axial impairment, than the early‐iPD and late‐iPD groups at follow‐up. However, the early‐onset GBA‐PD (early‐GBA‐PD) group was similar to the late‐onset GBA‐PD (late‐GBA‐PD) group in baseline clinical features and cognitive and motor progression. Conclusion: GBA‐PD patients exhibited faster cognitive and motor deterioration than early‐iPD and late‐iPD patients. Thus, subtype classification based on genetic characteristics rather than age at onset could enhance the prediction of PD disease progression. [ABSTRACT FROM AUTHOR]

Abstract Background Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. Methods Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0–53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0–70.0] years, 55.7% female) completed in‐person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form‐36 physical/mental summary scores, social attainment). Results Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%–29.4%) than controls (2.9%, CI 1.4–4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure 2036 mg/m2 versus none (OR 12.61, CI 2.19–72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01–1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68–11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10–0.84, Sensory: OR 0.35, CI 0.13–0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22–5.72). Conclusions In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL.

BackgroundParkinson's disease (PD) affects more than 6 million people worldwide. Along with motor impairments, patients and animal models exhibiting PD symptoms also experience cognitive impairment, fatigue, anxiety, and depression. Currently, there are no drugs available for PD that alter the progression of the disease. A body of evidence suggests that increased GABA levels contribute to the reduced expression of tyrosine hydroxylase (TH) and accompanying behavioral deficits. TH expression may be restored by blocking GABAA receptors. We hypothesized that golexanolone (GR3027), a well-tolerated GABAA receptor-modulating steroid antagonist (GAMSA), may improve Parkinson's symptoms in a rat model of PD.ObjectivesThe aims of this study were to assess whether golexanolone can ameliorate motor and non-motor symptoms in a rat model of PD and to identify some underlying mechanisms.MethodsWe used the unilateral 6-OHDA rat model of PD. The golexanolone treatment started 4 weeks after surgery. Motor symptoms were assessed using Motorater and CatWalk tests. We also analyzed fatigue (using a treadmill test), anhedonia (via the sucrose preference test), anxiety (with an open field test), and short-term memory (using a Y maze). Glial activation and key proteins involved in PD pathogenesis were analyzed using immunohistochemistry and Western blot.ResultsRats with PD showed motor incoordination and impaired locomotor gait, increased fatigue, anxiety, depression, and impaired short-term memory. Golexanolone treatment led to improvements in motor incoordination, certain aspects of locomotor gait, fatigue, anxiety, depression, and short-term memory. Notably, golexanolone reduced the activation of microglia and astrocytes, mitigated TH loss at 5 weeks after surgery, and prevented the increase of α-synuclein levels at 10 weeks.ConclusionsGolexanolone may be useful in improving both motor and non-motor symptoms that adversely affect the quality of life in PD patients, such as anxiety, depression, fatigue, motor coordination, locomotor gait, and certain cognitive alterations.

Abstract Background With the rapid aging trend of China's population, the issue of drug rational use in older adults has become more and more prominent. Parkinson’s disease (PD) is the one of the most common age-related neurodegenerative disorders. Pharmaceutical treatment plays a cardinal role in alleviating motor and non-motor symptoms to improve the quality of life of patients with PD. Patients with PD have complex medical needs yet little is known about the use of potentially inappropriate medications (PIM) among them in China. We quantify the prevalence of PIM use and identify its predictors among older persons with PD in China. Methods We conducted a cross-sectional analysis using a national representative database of all medical insurance beneficiaries across China, extracting records of ambulatory visits of older adults with PD between 2015 and 2017. Beneficiaries aged 65 and above were eligible for inclusion. The prevalence of patients exposed to overall PIMs and PIMs related to motor and cognitive impairment was calculated based on Beers Criteria 2015 version. Potential predictors of PIM concerning patients’ characteristics were estimated using multivariate logistic regression. Results A total of 14,452 older adults with PD were included. In total, 8,356 (57.8%) patients received at least one PIM; 2,464 (17.1%) patients received at least one motor-impairing PIM and 6,201 (42.9%) patients received at least one cognition-impairing PIM. The prevalence of overall PIM use was higher in patients of older age group (54.7% [65–74] vs. 59.5% [75–84; OR, 1.22; 95% CI, 1.14–1.31] vs.65.5% [≥ 85; OR, 1.58; 95% CI, 1.38–1.80) and females (61.4% [female] vs. 55.0% [males; OR, 0.77; 95% CI, 0.72–0.82). Conclusions Prescribing PIMs for older adults with PD was common in China, especially for females and older age groups, yet younger patients were more inclined to be prescribed with motor or cognition-impaired PIMs. Our findings represent a clear target awaiting multidimensional efforts to promote the rational prescribing of medications for this vulnerable population.

This study attempts to answer the question of whether mice with biallelic and monoallelic disruption of the St3gal5 (GM3 synthase) gene might benefit from GM1 replacement therapy. The GM3 produced by this sialyltransferase gives rise to downstream GD3 and the ganglio‐series of gangliosides. The latter includes the a‐series (GM1 + GD1a), which has proved most essential for neuron survival and function (especially GM1, for which GD1a provides a reserve pool). These biallelic mice serve as a model for children with this relatively rare autosomal recessive condition (ST3GAL5−/−) who suffer rapid neurological decline including motor loss, intellectual disability, visual and hearing loss, failure to thrive, and other severe conditions leading to an early death by 2–5 years of age without supportive care. Here, we studied both these mice, which serve as a model for the parents and close relatives of these children who are likely to suffer long‐term disabilities due to partial deficiency of GM1, including Parkinson's disease (PD). We find that the movement and memory disorders manifested by both types of mice can be resolved with GM1 application. This suggests the potential therapeutic value of GM1 for disorders stemming from GM1 deficiency, including GM3 synthase deficiency and PD. It was noteworthy that the GM1 employed in these studies was synthetic rather than animal brain‐derived, reaffirming the therapeutic efficacy of the former.

Abstract Background Ipsilesional motor impairments of the arm are common after stroke. Previous studies have suggested that severity of contralesional arm impairment and/or hemisphere of lesion may predict the severity of ipsilesional arm impairments. Historically, these impairments have been assessed using clinical scales, which are less sensitive than robot-based measures of sensorimotor performance. Therefore, the objective of this study was to characterize progression of ipsilesional arm motor impairments using a robot-based assessment of motor function over the first 6-months post-stroke and quantify their relationship to (1) contralesional arm impairment severity and (2) stroke-lesioned hemisphere. Methods A total of 106 participants with first-time, unilateral stroke completed a unilateral assessment of arm motor impairment (visually guided reaching task) using the Kinarm Exoskeleton. Participants completed the assessment along with a battery of clinical measures with both ipsilesional and contralesional arms at 1-, 6-, 12-, and 26-weeks post-stroke. Results Robotic assessment of arm motor function revealed a higher incidence of ipsilesional arm impairment than clinical measures immediately post-stroke. The incidence of ipsilesional arm impairments decreased from 47 to 14% across the study period. Kolmogorov–Smirnov tests revealed that ipsilesional arm impairment severity, as measured by our task, was not related to which hemisphere was lesioned. The severity of ipsilesional arm impairments was variable but displayed moderate significant relationships to contralesional arm impairment severity with some robot-based parameters. Conclusions Ipsilesional arm impairments were variable. They displayed relationships of varying strength with contralesional impairments and were not well predicted by lesioned hemisphere. With standard clinical care, 86% of ipsilesional impairments recovered by 6-months post-stroke.

A reserve in the motor domain may underlie the capacity exhibited by some patients to maintain motor functionality in the face of a certain level of disease. This form of “motor reserve” (MR) could include cortical, cerebellar, and muscular processes. However, a systematic definition has not been provided yet. Clarifying this concept in healthy individuals and patients would be crucial for implementing prevention strategies and rehabilitation protocols. Due to its wide application in the assessment of motor system functioning, non-invasive brain stimulation (NIBS) may support such definition. Here, studies focusing on reserve in the motor domain and studies using NIBS were revised. Current literature highlights the ability of the motor system to create a reserve and a possible role for NIBS. MR could include several mechanisms occurring in the brain, cerebellum, and muscles, and NIBS may support the understanding of such mechanisms.

15q11.2 deletions and duplications have been linked to autism spectrum disorder, schizophrenia, and intellectual disability. Recent evidence suggests that dysfunctional CYFIP1 (cytoplasmic FMR1 interacting protein 1) contributes to the clinical phenotypes observed in individuals with 15q11.2 deletion/duplication syndrome. CYFIP1 plays crucial roles in neuronal development and brain connectivity, promoting actin polymerization and regulating local protein synthesis. However, information about the impact of single nucleotide variants in CYFIP1 on neurodevelopmental disorders is limited. Here, we report a family with 2 probands exhibiting intellectual disability, autism spectrum disorder, spastic tetraparesis, and brain morphology defects and who carry biallelic missense point mutations in the CYFIP1 gene. We used skin fibroblasts from one of the probands, the parents, and typically developing individuals to investigate the effect of the variants on the functionality of CYFIP1. In addition, we generated Drosophila knockin mutants to address the effect of the variants in vivo and gain insight into the molecular mechanism that underlies the clinical phenotype. Our study revealed that the 2 missense variants are in protein domains responsible for maintaining the interaction within the wave regulatory complex. Molecular and cellular analyses in skin fibroblasts from one proband showed deficits in actin polymerization. The fly model for these mutations exhibited abnormal brain morphology and F-actin loss and recapitulated the core behavioral symptoms, such as deficits in social interaction and motor coordination. Our findings suggest that the 2 CYFIP1 variants contribute to the clinical phenotype in the probands that reflects deficits in actin-mediated brain development processes. [ABSTRACT FROM AUTHOR]

Background: With the rapid aging trend of China's population, the issue of drug rational use in older adults has become more and more prominent. Parkinson's disease (PD) is the one of the most common age-related neurodegenerative disorders. Pharmaceutical treatment plays a cardinal role in alleviating motor and non-motor symptoms to improve the quality of life of patients with PD. Patients with PD have complex medical needs yet little is known about the use of potentially inappropriate medications (PIM) among them in China. We quantify the prevalence of PIM use and identify its predictors among older persons with PD in China. Methods: We conducted a cross-sectional analysis using a national representative database of all medical insurance beneficiaries across China, extracting records of ambulatory visits of older adults with PD between 2015 and 2017. Beneficiaries aged 65 and above were eligible for inclusion. The prevalence of patients exposed to overall PIMs and PIMs related to motor and cognitive impairment was calculated based on Beers Criteria 2015 version. Potential predictors of PIM concerning patients' characteristics were estimated using multivariate logistic regression. Results: A total of 14,452 older adults with PD were included. In total, 8,356 (57.8%) patients received at least one PIM; 2,464 (17.1%) patients received at least one motor-impairing PIM and 6,201 (42.9%) patients received at least one cognition-impairing PIM. The prevalence of overall PIM use was higher in patients of older age group (54.7% [65–74] vs. 59.5% [75–84; OR, 1.22; 95% CI, 1.14–1.31] vs.65.5% [≥ 85; OR, 1.58; 95% CI, 1.38–1.80) and females (61.4% [female] vs. 55.0% [males; OR, 0.77; 95% CI, 0.72–0.82). Conclusions: Prescribing PIMs for older adults with PD was common in China, especially for females and older age groups, yet younger patients were more inclined to be prescribed with motor or cognition-impaired PIMs. Our findings represent a clear target awaiting multidimensional efforts to promote the rational prescribing of medications for this vulnerable population. [ABSTRACT FROM AUTHOR]