Baseline Motor Research Articles

Multi-focal Stimulation of the Cortico-cerebellar Loop During the Acquisition of a Novel Hand Motor Skill in Chronic Stroke Survivors

Impairment of hand motor function is a frequent consequence after a stroke and strongly determines the ability to regain a self-determined life. An influential research strategy for improving motor deficits is the combined application of behavioral training and non-invasive brain stimulation of the motor cortex (M1). However, a convincing clinical translation of the present stimulation strategies has not been achieved yet. One alternative and innovative approach is to target the functionally relevant brain network-based architecture, e.g., the dynamic interactions within the cortico-cerebellar system during learning. Here, we tested a sequential multifocal stimulation strategy targeting the cortico-cerebellar loop. Anodal transcranial direct current stimulation (tDCS) was applied simultaneously to a hand-based motor training in N = 11 chronic stroke survivors during four training sessions on two consecutive days. The tested conditions were: sequential multifocal (M1-cerebellum (CB)-M1-CB) vs. monofocal control stimulation (M1-sham-M1-sham). Additionally, skill retention was assessed 1 and 10 days after the training phase. Paired-pulse transcranial magnetic stimulation data were recorded to characterize stimulation response determining features. The application of CB-tDCS boosted motor behavior in the early training phase in comparison to the control condition. No faciliatory effects on the late training phase or skill retention were detected. Stimulation response variability was related to the magnitude of baseline motor ability and short intracortical inhibition (SICI). The present findings suggest a learning phase-specific role of the cerebellar cortex during the acquisition of a motor skill in stroke and that personalized stimulation strategies encompassing several nodes of the underlying brain network should be considered.

The effect of levodopa treatment on vascular endothelial function in Parkinson's disease.

There has been increasing awareness that micro-vascular alteration or vascular inflammation has been associated with levodopa-induced dyskinesia in PD. Vascular endothelial function assessed by flow mediated dilation (FMD) is known to reflect early microvascular change. We compare the impact of levodopa or dopamine agonist treatment on the change of FMD in de novo PD patients. This retrospective study used a selected sample from registry. We identified de-novo PD patients who underwent FMD at baseline, and follow-up FMD after 1year (± 2month) of levodopa (n = 18) or dopamine agonist (n = 18) treatment. FMD decreased after levodopa (8.60 ± 0.46 to 7.21 ± 0.4, p = 0.002) but there were no significant changes after DA treatment (8.33 ± 0.38 to 8.22 ± 0.33, p = 0.26). Homocysteine rose (11.52 ± 0.45 to 14.33 ± 0.68, p < 0.05) during levodopa treatment, but dopamine agonist had no effect (10.59 ± 0.38 to 11.38 ± 0.67, p = 0.184). Correlation analysis revealed that the changes in homocysteine level had non-significant correlation with FMD change (r = - 0.30, p = 0.06). FMD change was not associated with age (p = 0.47), disease duration (p = 0.81), baseline motor UPDRS (p = 0.43), motor UPDRS change (p = 0.64), levodopa equivalent dose change (p = 0.65). We found that 1-year levodopa treatment may adversely affect vascular endothelial function in de novo PD. Further studies are needed to clarify the exact pathogenesis and clinical implication of levodopa-induced endothelial dysfunction in PD.

Baseline Gait and Motor Function Predict Long-Term Severity of Neurological Outcomes of Viral Infection.

Neurological dysfunction following viral infection varies among individuals, largely due to differences in their genetic backgrounds. Gait patterns, which can be evaluated using measures of coordination, balance, posture, muscle function, step-to-step variability, and other factors, are also influenced by genetic background. Accordingly, to some extent gait can be characteristic of an individual, even prior to changes in neurological function. Because neuromuscular aspects of gait are under a certain degree of genetic control, the hypothesis tested was that gait parameters could be predictive of neuromuscular dysfunction following viral infection. The Collaborative Cross (CC) mouse resource was utilized to model genetically diverse populations and the DigiGait treadmill system used to provide quantitative and objective measurements of 131 gait parameters in 142 mice from 23 CC and SJL/J strains. DigiGait measurements were taken prior to infection with the neurotropic virus Theiler's Murine Encephalomyelitis Virus (TMEV). Neurological phenotypes were recorded over 90 days post-infection (d.p.i.), and the cumulative frequency of the observation of these phenotypes was statistically associated with discrete baseline DigiGait measurements. These associations represented spatial and postural aspects of gait influenced by the 90 d.p.i. phenotype score. Furthermore, associations were found between these gait parameters with sex and outcomes considered to show resistance, resilience, or susceptibility to severe neurological symptoms after long-term infection. For example, higher pre-infection measurement values for the Paw Drag parameter corresponded with greater disease severity at 90 d.p.i. Quantitative trait loci significantly associated with these DigiGait parameters revealed potential relationships between 28 differentially expressed genes (DEGs) and different aspects of gait influenced by viral infection. Thus, these potential candidate genes and genetic variations may be predictive of long-term neurological dysfunction. Overall, these findings demonstrate the predictive/prognostic value of quantitative and objective pre-infection DigiGait measurements for viral-induced neuromuscular dysfunction.

Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory.

In human Alzheimer's disease (AD) patients and AD mouse models, both differential pre-disease brain features and differential disease-associated memory decline are observed, suggesting that certain neurological features may protect against AD-related cognitive decline. The combination of these features is known as brain reserve, and understanding the genetic underpinnings of brain reserve may advance AD treatment in genetically diverse human populations. One potential source of brain reserve is brain microstructure, which is genetically influenced and can be measured with diffusion MRI (dMRI). To investigate variation of dMRI metrics in pre-disease-onset, genetically diverse AD mouse models, we utilized a population of genetically distinct AD mice produced by crossing the 5XFAD transgenic mouse model of AD to 3 inbred strains (C57BL/6J, DBA/2J, FVB/NJ) and two wild-derived strains (CAST/EiJ, WSB/EiJ). At 3 months of age, these mice underwent diffusion magnetic resonance imaging (dMRI) to probe neural microanatomy in 83 regions of interest (ROIs). At 5 months of age, these mice underwent contextual fear conditioning (CFC). Strain had a significant effect on dMRI measures in most ROIs tested, while far fewer effects of sex, sex*strain interactions, or strain*sex*5XFAD genotype interactions were observed. A main effect of 5XFAD genotype was observed in only 1 ROI, suggesting that the 5XFAD transgene does not strongly disrupt neural development or microstructure of mice in early adulthood. Strain also explained the most variance in mouse baseline motor activity and long-term fear memory. Additionally, significant effects of sex and strain*sex interaction were observed on baseline motor activity, and significant strain*sex and sex*5XFAD genotype interactions were observed on long-term memory. We are the first to study the genetic influences of brain microanatomy in genetically diverse AD mice. Thus, we demonstrated that strain is the primary factor influencing brain microstructure in young adult AD mice and that neural development and early adult microstructure are not strongly altered by the 5XFAD transgene. We also demonstrated that strain, sex, and 5XFAD genotype interact to influence memory in genetically diverse adult mice. Our results support the usefulness of the 5XFAD mouse model and convey strong relationships between natural genetic variation, brain microstructure, and memory.

Dynamic motor practice improves movement accuracy, force control and leads to increased corticospinal excitability compared to isometric motor practice.

The central nervous system has a remarkable ability to plan motor actions, to predict and monitor the sensory consequences during and following motor actions and integrate these into future actions. Numerous studies investigating human motor learning have employed tasks involving either force control during isometric contractions or position control during dynamic tasks. To our knowledge, it remains to be elucidated how motor practice with an emphasis on position control influences force control and vice versa. Furthermore, it remains unexplored whether these distinct types of motor practice are accompanied by differential effects on corticospinal excitability. In this study, we tested motor accuracy and effects of motor practice in a force or position control task allowing wrist flexions of the non-dominant hand in the absence of online visual feedback. For each trial, motor performance was quantified as errors (pixels) between the displayed target and the movement endpoint. In the main experiment, 46 young adults were randomized into three groups: position control motor practice (PC), force control motor practice (FC), and a resting control group (CON). Following assessment of baseline motor performance in the position and force control tasks, intervention groups performed motor practice with, augmented visual feedback on performance. Motor performance in both tasks was assessed following motor practice. In a supplementary experiment, measures of corticospinal excitability were obtained in twenty additional participants by application of transcranial magnetic stimulation to the primary motor cortex hot spot of the flexor carpi radialis muscle before and following either position or force control motor practice. Following motor practice, accuracy in the position task improved significantly more for PC compared to FC and CON. For the force control task, both the PC and FC group improved more compared to CON. The two types of motor practice thus led to distinct effects including positive between-task transfer accompanying dynamic motor practice The results of the supplementary study demonstrated an increase in corticospinal excitability following dynamic motor practice compared to isometric motor practice. In conclusion, dynamic motor practice improves movement accuracy, and force control and leads to increased corticospinal excitability compared to isometric motor practice.

Differences between myelomeningocele and myeloschisis lesions in patients undergoing open in-utero spina bifida repair

Spina bifida lesions are broadly classified as myelomeningocele (MMC: with sac) and myeloschisis (MSC: without sac) lesions, with MSC being the most severe type. Although prenatal repair methods are similar, baseline differences, surgical management, and postnatal outcomes remains largely unknown. The objective was to compare prenatal findings, closure methods, and 12-month outcomes. A prospective cohort of 111 open in-utero repair consecutive patients at a single institution were assessed (2011-2022). Lesion type was defined by ultrasound for the presence of a sac elevated from the lesion. Surgical eligibility was similar to the MOMS study, but expanded BMI inclusion criteria to ≤40 from 2018. Intraoperative management was pediatric neurosurgeon dependent. We compared preoperative differences in ventricular sizes, tonsillar herniation levels, extremity function, skin patch requirement, and neonatal outcomes including cerebrospinal fluid (CSF) leakage, wound dehiscence, and CSF diversion procedures until 12 months of age. Significance was considered at a p=0.05. Ultrasound and MRI identified 60 cases that were MMC and 51 as MSC. Maternal demographics, the gestational age (GA) at prenatal evaluation and the upper level of lesion were similar between groups (Table 1). Preoperative ventricular measurements were greater in the MMC cases. There were no differences in the upper level of lesions. MSC has severe baseline tonsillar herniation compared to MMC. There was higher talipes and loss of baseline motor function in the MMC group. The need for a skin closure patch was 21.7% in MMC vs 43.1% in MSC (p=0.002; Table 2). The length of NICU stay was 17 days longer in the MSC vs. the MMC group. There were no differences in ventricular diversion rates within a year from birth. Prenatally diagnosed MMC is associated with greater ventriculomegaly and talipes, and with less tonsillar herniation and fetal movement than those with MSC defects. Longer NICU stays in the MSC group is secondary to the higher need for skin closure with a patch and delayed healing.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

EXplainable AI Allows Predicting Upper Limb Rehabilitation Outcomes in Sub-Acute Stroke Patients.

While stroke is one of the leading causes of disability, the prediction of upper limb (UL) functional recovery following rehabilitation is still unsatisfactory, hampered by the clinical complexity of post-stroke impairment. Predictive models leading to accurate estimates while revealing which features contribute most to the predictions are the key to unveil the mechanisms subserving the post-intervention recovery, prompting a new focus on individualized treatments and precision medicine in stroke. Machine learning (ML) and explainable artificial intelligence (XAI) are emerging as the enabling technology in different fields, being promising tools also in clinics. In this study, we had the twofold goal of evaluating whether ML can allow deriving accurate predictions of UL recovery in sub-acute patients, and disentangling the contribution of the variables shaping the outcomes. To do so, Random Forest equipped with four XAI methods was applied to interpret the results and assess the feature relevance and their consensus. Our results revealed increased performance when using ML compared to conventional statistical approaches. Moreover, the features deemed as the most relevant were concordant across the XAI methods, suggesting good stability of the results. In particular, the baseline motor impairment as measured by simple clinical scales had the largest impact, as expected. Our findings highlight the core role of ML not only for accurately predicting the individual outcome scores after rehabilitation, but also for making ML results interpretable when associated to XAI methods. This provides clinicians with robust predictions and reliable explanations that are key factors in therapeutic planning/monitoring of stroke patients.

Associations of Sensory and Motor Functions in Midlife with Longitudinal Blood‐Based Biomarker Levels of Alzheimer’s Disease and Neurodegeneration

AbstractBackgroundDementia has a long preclinical phase and pathological fluid biomarker levels change decades before clinical symptoms. Thus, early detection of people at risk for neurodegenerative and pathological changes, especially in midlife, might improve future treatments and preventions. Sensory and motor changes are common in aging adults and may be early markers of neurodegeneration since they are associated with cognition and risk factors of neurodegeneration. However, their associations with blood‐based neurodegenerative and AD biomarkers are not yet known. We aimed to determine if midlife sensory and motor functions are associated with long‐term changes in blood‐based biomarkers of neurodegeneration and AD (neurofilament light chain(NfL), total tau(TT), and amyloid beta(Aβ)).MethodThis longitudinal study is based on n=1529 (54% women, mean age 49years) Beaver Dam Offspring Study (BOSS) participants. The BOSS started in 2005 and had 5‐year and 10‐year follow‐up exams. We assessed sensory (pure‐tone audiometry, contrast sensitivity, olfactory identification) and motor (Grooved Pegboard) function, plus multiple potential confounding risk factors at baseline. NfL, TT, Aβ42, and Aβ40 levels were analyzed in serum samples from all three waves (SIMOA, Quanterix). We used linear mixed‐effects models with baseline hearing, vision, olfaction, and motor function as determinant and repeated biomarker levels as outcome and adjusted for age, sex, education, random intercept, random slope (if model fit was improved), and other confounders. NfL and TT were log‐transformed. Due to sex interactions, Aβ42/Aβ40 models were sex‐stratified.ResultsOverall, NfL increased 3% and TT 1% per year. Aβ42/Aβ40 decreased 0.5/year in women and 0.24/year in men. Individuals with hearing and vision impairment showed faster NfL level increase over time (0.8%/year; CI 0.3,1.4;p=.004; 0.5%/year; CI ‐0.1,1;p=.09; respectively). Worse motor function was associated with faster NfL increase (0.4%/year per 20s test time; CI 0.2,0.7;p&lt;.001). These effects compared to effects of 2‐3 months of aging. There were no significant associations with Aβ42/Aβ40 or TT.ConclusionWe found associations between midlife sensory and motor functions and long‐term changes in NfL levels, a non‐specific marker of neurodegeneration, while there were no associations with AD‐specific biomarkers. Future studies with longer follow‐up should determine if sensory and motor changes are more reflective of general neurodegenerative than AD‐specific pathology.

Association of Physical Activity With Neurofilament Light Chain Trajectories in Autosomal Dominant Frontotemporal Lobar Degeneration Variant Carriers

Physical activity is associated with cognitive health, even in autosomal dominant forms of dementia. Higher physical activity is associated with slowed cognitive and functional declines over time in adults carrying autosomal dominant variants for frontotemporal lobar degeneration (FTLD), but whether axonal degeneration is a potential neuroprotective target of physical activity in individuals with FTLD is unknown. To examine the association between physical activity and longitudinal neurofilament light chain (NfL) trajectories in individuals with autosomal dominant forms of FTLD. This cohort study included individuals from the ALLFTD Consortium, which recruited patients from sites in the US and Canada. Symptomatic and asymptomatic adults with pathogenic variants in one of 3 common genes associated with FTLD (GRN, C9orf72, or MAPT) who reported baseline physical activity levels and completed annual blood draws were assessed annually for up to 4 years. Genotype, clinical measures, and blood draws were collected between December 2014 and June 2019; data were analyzed from August 2021 to January 2022. Associations between reported baseline physical activity and longitudinal plasma NfL changes were assessed using generalized linear mixed-effects models adjusting for baseline age, sex, education, functional severity, and motor symptoms. Baseline physical activity levels reported via the Physical Activity Scale for the Elderly. To estimate effect sizes, marginal means were calculated at 3 levels of physical activity: 1 SD above the mean represented high physical activity, 0 SD represented average physical activity, and 1 SD below the mean represented low physical activity. Annual plasma NfL concentrations were measured with single-molecule array technology. Of 160 included FTLD variant carriers, 84 (52.5%) were female, and the mean (SD) age was 50.7 (14.7) years. A total of 51 (31.8%) were symptomatic, and 77 carried the C9orf72 variant; 39, GRN variant; and 44, MAPT variant. Higher baseline physical activity was associated with slower NfL trajectories over time. On average, NfL increased 45.8% (95% CI, 22.5 to 73.7) over 4 years in variant carriers. Variant carriers with high physical activity demonstrated 14.0% (95% CI, -22.7 to -4.3) slower NfL increases compared with those with average physical activity and 30% (95% CI, -52.2 to -8.8) slower NfL increases compared with those with low physical activity. Within genotype, C9orf72 and MAPT carriers with high physical activity evidenced 18% to 21% (95% CI, -43.4 to -7.2) attenuation in NfL, while the association between physical activity and NfL trajectory was not statistically significant in GRN carriers. Activities associated with higher cardiorespiratory and cognitive demands (sports, housework, and yardwork) were most strongly correlated with slower NfL trajectories (vs walking and strength training). In this study, higher reported physical activity was associated with slower progression of an axonal degeneration marker in individuals with autosomal dominant FTLD. Physical activity may serve as a primary prevention target in FTLD.

Long-term efficacy of nusinersen and its evaluation in adolescent and adult patients with spinal muscular atrophy types 1 and 2

BackgroundsThe efficacy of nusinersen and its evaluation in patients with spinal muscular atrophy (SMA) has been established in clinical trials only for pediatric patients, not for adolescent and adult patients who developed SMA in infancy or early childhood. We report a long-term follow-up in adolescent and adult patients with SMA types 1 and 2. MethodsNusinersen-treated patients with SMA types 1 and 2 between 2017 and 2022 were retrospectively reviewed. We compared baseline motor function tests with those after the final treatment. Physical and occupational therapists performed Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Functional Motor Scale-Expanded (HFMSE), and Revised Upper Limb Module (RULM). The Landau and Galant reflexes were not performed in CHOP-INTEND. Meaningful improvement was defined as CHOP-INTEND, 4; HFSME, 3; and RULM, 2. ResultsSeven patients with SMA (type 1, 1; type 2, 6) with a median age of 23 (range, 12–40)years were treated with nusinersen for 3.55 (1.78–4.53)years. Improvement was detected in CHOP-INTEND (pre, 5 [0–31]; post, 21 [0–39]; difference, 5 [0–26]; p = 0.100) without significance, although not in HFMSE (pre, 0 [0–3]; post, 0 [0–5]; difference, 0 [0–2]; p = 0.346) and RULM (pre, 1 [0–20]; post, 3 [0–21]; difference, 1 [0–2]; p = 0.089). Owing to prolonged treatment intervals with the COVID-19 pandemic, RULM worsened in two patients. ConclusionNusinersen was effective in long-term follow-up. Only CHOP-INTEND showed meaningful improvement. The interval between doses of nusinersen should not be prolonged even with the COVID-19 pandemic.

Failure to Obtain Baseline Signals of Transcranial Motor-Evoked Potentials in Spine Surgery: Analysis of the Reasons

Among the various intraoperative neurophysiologic monitoring (IONM) techniques, transcranial motor-evoked potential (Tc-MEP) has recently become the most widely used method to monitor motor function. However, we often find that Tc-MEP is not sufficiently detected at the start of surgery. Therefore, we aimed to analyze the reasons and risk factors for not detecting sufficient baseline signal of Tc-MEP from the beginning of spinal surgery. We categorized IONM data from 1058 patients who underwent spine surgeries at a single institution from 2014 to 2020 and categorized them into 2 groups: 1) "poor MEP" if Tc-MEP could not be sufficiently obtained and 2) "normal MEP" if Tc-MEP could be sufficiently obtained from the surgery. We analyzed the patient's age, gender, underlying disease, operation type, level numbers, baseline motor function, existence of pathologic reflex, myelopathy, and duration from the onset and clinical diagnosis. The rate of failure to obtain sufficient baseline Tc-MEP signals in spine surgery was 21.8% (231/1058). Multivariate analysis showed significant associations of existence of diabetes mellitus, myelopathy, thoracic spine surgery, baseline motor deficit and tumor, and trauma disease with loss of meaningful and interpretable signals in baseline Tc-MEP (P < 0.05). Only 15 of 231 patients (6.4%) showed a trend of signal recovery after decompression procedures. Various factors (myelopathy, diabetes mellitus, thoracic surgery, baseline motor deficit, tumor, and trauma) were closely related to not obtaining sufficient baseline signals for Tc-MEP. When operating on patients with these considerations, we need to consider the efficacy and usefulness of Tc- MEP.

Myostatin is a negative regulator of adult neurogenesis after spinal cord injury in zebrafish.

Intrinsic and extrinsic inhibition of neuronal regeneration obstruct spinal cord (SC) repair in mammals. In contrast, adult zebrafish achieve functional recovery after complete SC transection. While studies of innate SC regeneration have focused on axon regrowth as a primary repair mechanism, how local adult neurogenesis affects functional recovery is unknown. Here, we uncover dynamic expression of zebrafish myostatin b (mstnb) in a niche of dorsal SC progenitors after injury. mstnb mutants show impaired functional recovery, normal glial and axonal bridging across the lesion, and an increase in the profiles of newborn neurons. Molecularly, neuron differentiation genes are upregulated, while the neural stem cell maintenance gene fgf1b is downregulated in mstnb mutants. Finally, we show that human fibroblast growth factor 1 (FGF1) treatment rescues the molecular and cellular phenotypes of mstnb mutants. These studies uncover unanticipated neurogenic functions for mstnb and establish the importance of local adult neurogenesis for innate SC repair.

Association of cholesterol level with dopamine loss and motor deficits in Parkinson disease: A cross-sectional study.

Cholesterol is vital in neuronal function; however, the influence of cholesterol levels on parkinsonism is unclear. This study investigated the relationship between baseline total cholesterol (TC) levels, dopamine loss, and motor symptoms in drug-naïve Parkinson disease (PD). This cross-sectional study enrolled 447 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging. Multivariate linear regression was used to investigate the effect of cholesterol levels on Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) total score and each subscore after adjusting for the covariates. An interaction analysis was performed to examine the interaction between TC levels and statin use on the UPDRS-III scores. No significant correlation was found between TC levels and DAT availability after adjusting for potential confounders. Multivariate linear regression showed that TC levels were significantly and negatively associated with the UPDRS-III total score (β=-0.116, p=0.013) and bradykinesia subscore (β=-0.145, p=0.011). Dichotomized analysis according to TC levels showed that TC levels were significantly associated with UPDRS-III total score, and rigidity, bradykinesia, and axial subscores only in the low TC group. There was an interaction effect between TC levels and statin use for the axial subscores (β=-0.523, p=0.025). Subgroup analysis showed that TC levels were significantly and negatively associated with the axial subscore in statin users; however, no association was found in statin nonusers. This study suggests that TC levels affect parkinsonian motor symptoms, especially in subjects with low cholesterol status, whereas the severity of axial motor symptoms is negatively associated with TC levels only in statin users.

Montreal Cognitive Assessment Predicts the Short-Term Risk of Lewy Body Disease in Isolated REM Sleep Behavior Disorder with Reduced MIBG Scintigraphy.

Long-term follow-up of isolated rapid eye movement (REM) sleep behavior disorder (IRBD) patients reveals a high risk of α-synucleinopathies. We explored the early clinical predictive factors of phenoconversion from IRBD to Parkinson's disease (PD) or dementia with Lewy bodies (DLB). We assessed baseline office-based cognitive test scores (Montreal Cognitive Assessment [MoCA-J], Mini-Mental State Examination [MMSE], and Frontal Assessment Battery [FAB]), motor function, and olfactory function in 36 consecutive polysomnography (PSG)-confirmed IRBD patients with reduced metaiodobenzylguanidine (MIBG) accumulation. PD or DLB was confirmed by medical chart review retrospectively. Of 36 IRBD patients, 19 (n=19, 52.8%) with abnormal MoCA-J score (< 26) had significantly lower scores in trail making B, phonetic verbal fluency sub-items in the executive domain, and in delayed recall in the memory domain. In total, 12 (33.3%) patients developed PD or DLB; seven of 12 patients (58.3%) developed DLB at a mean follow-up period of 6.8 years. In the normal MoCA-J group (n=17, 47.2%), two patients developed PD, but none developed dementia. Furthermore, in the abnormal MoCA-J group, seven patients developed DLB and three developed PD without dementia. The phenoconverter group had significantly lower scores in delayed recall in the memory domain compared to the disease-free group. Cox hazard analysis showed that MoCA-J was superior to MMSE. Among IRBD patients with reduced cardiac MIBG accumulation, MoCA-J score of <26 (Mild Cognitive Impairment-Lewy body) and a low sub-item score for delayed recall predicted short-term progression to probable DLB.

Mild behavioral impairment as a potential marker of predementia risk states in motor neuron diseases.

Mild behavioral impairment (MBI) has been increasingly regarded as the neurobehavioral axis of predementia risk states, but a specific investigation of its detection as a potential marker of prodromal dementia in motor neuron diseases (MNDs) is still lacking. The aims of our study were therefore to explore MBI in MNDs both at onset and over the disease course, and to evaluate its relationship with baseline and longitudinal cognitive features. Sixty MND patients with cognitive/behavioral, mood, and motor examinations were recruited and followed longitudinally for up to 15 months. Associations between baseline MBI symptoms and clinical features were tested using the Spearman correlation coefficient. Based on longitudinal data, relative deltas of variation for each cognitive measure were generated, and linear regression models were then used to evaluate the role of baseline MBI symptoms in predicting longitudinal rates of cognitive decline. At disease onset, the most impaired MBI domain was affective/emotional dysregulation, followed by impulse dyscontrol, apathy, and social inappropriateness. Greater MBI symptoms correlated with more severe baseline motor, cognitive/behavioral, and mood disturbances (p values from <0.001 to 0.05). Longitudinally, the greatest decline was observed in the affective/emotional dysregulation domain, followed by impulse dyscontrol, apathy, and social inappropriateness. Greater MBI symptoms at onset were significant predictors of more severe longitudinal cognitive decline in both amyotrophic lateral sclerosis (ALS)-specific and ALS-nonspecific functions (p values from <0.001 to 0.03). MBI represents a valuable clinical marker of incident cognitive decline in MNDs, and its evaluation has good potential for detecting dementia in its preclinical/prodromal phase.

Improved Design of a Six-Phase Squirrel Cage Induction Motor With Pseudo-Concentrated Windings

Pseudoconcentrated winding seems to be a promising solution for the six-phase induction motors (6PIMs) because it exposes advantages of concentrated windings (CWs) over the distributed windings (DWs). In addition, this winding has an air gap flux density with higher amplitude of the fundamental frequency and lower total harmonic distortion value compared to the conventional CWs, which results in considerably higher performance. In this article, a design algorithm and an analytical model are developed for a 6PIM to cope with pseudoconcentrated winding. Then, a sensitivity analysis is performed to enhance motor performance. The designed motor with pseudoconcentrated winding shows superior performance compared to the baseline motor with the DWs. The designed motor is manufactured to verify the accuracy of the design procedure, performance calculation, and finite element simulation results.

P.207 Muscle magnetic resonance imaging in Myotonic dystrophy type 1: Longitudinal study for 5 years

Myotonic dystrophy type 1 is the most common genetic muscle disease in adults, caused by increased expansion of CTG repeats in the DMPK gene. It is characterized by progressive distal dominant muscle weakness and myotonia. The aim of this study was to evaluate objective longitudinal changes in the muscle magnetic resonance imaging in DM1 patients over five years. Eighteen genetically diagnosed DM1 patients were enrolled at baseline. The mean age was 44.86±9.83, mean CTG repeat length was 465±328.86 and a disease duration of 18.29±9.43 years. The baseline motor function such as medical research council sum score, Muscular impairment rating scale and 6-minute walk test were evaluated at the baseline and after 5 years of follow up. The pulmonary function and serum creatine kinase levels were also evaluated. The muscle magnetic resonance imaging was performed at baseline and after 5 years. The individual muscles were semi-quantitatively graded using five-point Mercuri scores. The thirteen upper muscle groups and twenty one lower limb muscles were evaluated. The lower muscle groups including gluteus muscles. The fatty infiltrative changes progressed after 5 years of follow up, with significant score changes were most prominently observed in lower limb muscles including gastrocnemius, soleus, tibialis anterior, gastrocnemius and tensor fascia latae muscles. Among upper limb muscles, latissimus dorsi showed most significant fatty infiltrative changes, followed by serratus and rhomboid muscles. Bases on the longitudinal follow up of the muscle MRI, DM1 showed significant deterioration in the lower limb muscles, with prominent changes in the crural muscles. This is the first longitudinal muscle MRI study and more studies are warranted to understand muscle degeneration in DM1.

Rehabilitation in children and adolescents undergoing stem cell transplantation: A pilot study focused on motor performance.

The aim of this pilot trial is evaluating the preliminary effectiveness of two in-hospital interventions in the maintenance of motor performance in children/adolescents undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives investigated the interventions' feasibility, impact on fatigue and to what degree the subjects' maintained their ankle dorsiflexion range of movement (ROM), functional mobility, muscle strength and flexibility. This trial included 5- to 18-year-old participants, affected by oncological and non-oncological diseases during hospitalisation for autologous/allogenic HSCT. The subjects were assigned to an exercise group (EG), or a counselling group based on a cluster model based on inpatient timeframe. The EG subjects performed strengthening, stretching and aerobic exercises for 30 min/5 days a week. Both groups followed rehabilitation counselling indications (RCI), 7 days a week. Forty-nine participants were enrolled (median age = 12.9 years) (EG n = 36). In both groups the participants maintained their baseline motor performance and ankle ROM, and the children/adolescents and parents reduced their levels of fatigue. However, the interventions were not effective in maintaining strength. In maintaining the subjects' motor performance, the RCI results are significant because they pave the way for the application in clinical practice contexts where there are poor rehabilitation resources. Clinical Trials registration NCT03842735.

Remote versus In-Person Health Education: Feasibility, Satisfaction, and Health Literacy for Diverse Older Adults.

Health education may improve health in geriatric patients. To evaluate differences between remote and in-person education, the DREAMS (Developing a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors) health seminar series compared in-person and remote learning groups to assess feasibility, satisfaction, adherence, health literacy, and cognitive outcomes. Nonrandomized two-arm interventions occurred remotely or in-person. About 130 diverse, older adults (M age: 70.8 ± 9.2 years; in-person n = 95; remote, n = 35) enrolled. Data from 115 completers (In-person n = 80; Remote n = 35) were analyzed for performance outcomes. Feasibility, adherence, and satisfaction benchmarks were evaluated at baseline, immediately post intervention, and 8 weeks post intervention. Adjusting for baseline performances, outcomes on health literacy and cognitive measures were compared between groups after intervention (at posttest and at 8-week follow-up) using adjusted mean differences (β coefficients). Eighty in-person and all remote participants completed at least six modules. Both programs had high satisfaction, feasibility, and strong adherence. After adjusting for demographic covariates and baseline values, cognitive and motor cognitive measures between groups were domain specific (e.g., global cognition, executive function, spatial memory, mental tracking capacity, and cognitive integration). This work explores feasible measures of knowledge acquisition and its link to health literacy and cognitive outcomes. Identifying effective delivery methods may increase involvement in clinical research. Future studies may encourage remote learning for increased accessibility.

A 6-month longitudinal study on worsening of Parkinson’s disease during the COVID-19 pandemic

Further studies are required to investigate the impact of the COVID-19 pandemic on Parkinson’s disease (PD) progression. This study investigated the motor and non-motor progression of people with PD (PWP) at 6 months during the COVID-19 pandemic compared with that during the pre-pandemic period. Patients were recruited from Ain Shams University Hospitals, Cairo, in the period between April 2019 and December 2020. Fifty patients were included, of whom 17 and 33 patients were followed for 6 months before and during the pandemic, respectively. All patients were assessed at baseline and at 6 months using the MDS-UPDRS, Schwab and England scale (S&E), Hoehn and Yahr scale (H&Y), Berg Balance Scale, Timed Up and Go test (TUG), International Physical Activity Questionnaire, New Freezing of Gait Questionnaire, Non-Motor Symptoms Scale, and Beck Depression Inventory (BDI). Both groups were matched in age, gender, and disease characteristics. Patients followed during the pandemic showed more significant worsening of the total, part I and motor part of MDS-UPDRS, and balance scores (p < 0.001) than those followed during the pre-COVID-19 period. Gait (TUG), balance, and physical activity worsening were significantly correlated with baseline BDI, gait and balance scores, total and part I MDS-UPDRS scores, H&Y, and S&E OFF scores. Gait deterioration (TUG) was correlated with baseline physical activity (r = −0.510, p = 0.002). PWP showed worsening of motor and non-motor symptoms during the COVID-19 pandemic at the 6-month follow-up. Worsening of gait, balance, and physical activity was correlated with baseline motor and physical activity OFF scores.