Lower Motor Function Research Articles

Clinicogenetic characterization and response to disease-modifying therapies in spinal muscular atrophy: real-world experience from a reference center in Southern Brazil

ObjectiveSpinal Muscular Atrophy linked to chromosome 5q (SMA) is an autosomal recessive neurodegenerative disease characterized by progressive proximal muscle atrophy and weakness. This study addresses the scarcity of research on novel disease-modifying therapies for SMA in Latin America by reporting a real-world experience in Southern Brazil. MethodologyThis is a single-center historical cohort that included all patients diagnosed with spinal muscular atrophy at a Regional Reference Service for rare diseases. ResultsEighty-one patients were included, of whom 7 died during follow-up. Of the remaining 74 patients, 5.4 % were classified as pre-symptomatic, 24.3 % with SMA type 1, 28.4 % with type 2, 36.5 % with type 3, and 5.4 % with type 4. The mean follow-up time ranged from 1.8 years for pre-symptomatic cases to 8.7 years for SMA types 2 and 3. Approximately 42 % of these patients received specific disease-modifying therapy, of these, 96.8 % received Nusinersen, with 19.4 % transitioning to gene therapy using Onasemnogene Abeparvovec, and 6.4 % starting Risdiplam. Most patients with SMA type 1 were on disease-modifying treatment, whereas only slightly over a third of patients with type 2 and about 10 % of type 3 were receiving such treatments. Among treated patients, 80 % demonstrated improvement in motor performance during the follow-up, with a lesser therapeutic response being associated with late initiation of treatment and low motor function scores at baseline. ConclusionThis real-world study reinforces the effectiveness of disease-modifying therapies for SMA in Brazil within the context of low- and middle-income countries, which is greater the earlier and the better the patient's functional status.

The Injected Plasma of Myasthenia Gravis Patient with A Low T-reg Level Caused Clinical Myasthenic Syndromes in Swiss-Webster Mice

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease affecting neuromuscular junction involvement. The finding that T-reg level in MG patients was lower than that in normal persons leads to the idea that the primary pathology of the disease is T-reg dependent. The T-reg level of MG patients seems to be decreasing compared to that of normal persons. The study was conducted to observe the contribution of T-reg level in plasma injected into Swiss-Webster mice to develop clinically and pathologically myasthenic syndromes.METHODS: Swiss-Webster mice were grouped into three groups: the groups received plasma with normal, low, and high T-reg levels, respectively. The T-reg levels of the mice were measured with flow cytometry analysis and a human regulatory T-cell cocktail for T-cell surface cell marker. The motor function, interleukin (IL)-2, interferon (IFN)-γ, and thymus weight of mice were measured after the injection. Histopathological examination was performed to analyze mice’s muscles and thymus.RESULTS: The result identified that the motor function (2-week treatment group: p=0.021 and 3-week treatment group: p=0.032) and muscle width (p=0.014, p=0.032 and p≤0.001) were significantly lower in the low T-reg level plasma group compared to control and high T-reg level plasma groups. The thymus showed an increase in weight without an increase in the cortex-medulla ratio of the thymus, indicating hyperplasia. Both IL-2 and IFN-γ levels were lower in the low and high T-reg level groups compared with the control group, indicating the autoimmune process.CONCLUSION: Low T-reg level was associated with lower motor function, muscle width, increased thymus weight, as well as lower IL-2 and IFN-γ levels. T-reg level contributed to clinical myasthenic syndromes but not pathological findings. This research method is expected to be a basis for the development of animal models with Swiss-Webster mice.KEYWORDS: animal model, Myasthenia gravis, Swiss-Webster mice

Comparative analysis of neurofilaments and biomarkers of muscular damage in amyotrophic lateral sclerosis.

Diagnosis of the fatal neurodegenerative disease amyotrophic lateral sclerosis is challenging. Neurofilaments, indicative of neuronal damage, along with creatine kinase, creatinine, myoglobin, and troponin T, representing muscular damage, have been identified as promising fluid biomarkers. This study aims to comprehensively assess and compare their diagnostic and prognostic potential in a 'real-world' cohort of patients with amyotrophic lateral sclerosis. About 77 patients with amyotrophic lateral sclerosis and its clinical variants, and 26 age- and sex-matched controls with various neuromuscular and neurodegenerative diseases, were retrospectively included in this monocentric, cross-sectional study. Neurofilaments in cerebrospinal fluid and biomarkers of muscular damage in serum were measured and correlated with demographic features, motor function, survival time, clinical phenotypes, and the extent of upper and lower motor neuron involvement. Neurofilament, myoglobin, and troponin T concentrations were higher in patients with amyotrophic lateral sclerosis compared to disease controls. Higher neurofilament levels correlated with lower motor function and faster disease progression rate, while higher creatine kinase and creatinine concentrations were linked to preserved motor function. In contrast, troponin T elevation indicated poorer fine and gross motor functions. Increased neurofilament levels were associated with shorter survival, whereas biomarkers of muscular damage lacked survival correlation. Neurofilament concentrations were higher in classical amyotrophic lateral sclerosis than in progressive muscular atrophy, while myoglobin and troponin T levels were elevated in progressive muscular atrophy compared to primary lateral sclerosis. Neurofilaments were predominantly linked to upper motor neuron involvement. Our findings confirmed the robust diagnostic and prognostic value of neurofilaments in amyotrophic lateral sclerosis. Elevated neurofilament concentrations were associated with higher disease severity, faster disease progression, shorter survival, and predominant upper motor neuron degeneration. Biomarkers of muscular damage were inferior in distinguishing amyotrophic lateral sclerosis from other neuromuscular and neurodegenerative diseases. However, they may serve as complementary biomarkers and support in discriminating clinical variants of amyotrophic lateral sclerosis.

Effects of motor cortical and peripheral axonal hyperexcitability on survival in amyotrophic lateral sclerosis

BackgroundIncreased ‘cortical’ and ‘peripheral’ excitability are reportedly associated with shorter survival in amyotrophic lateral sclerosis (ALS) patients, suggesting that hyperexcitability contributes to motor neuron death. However, whether upper or lower...

Malnutrition in Institutionalized and Non-Institutionalized Neurologically Impaired Children in Bulgaria

Introduction: The nutritional status of children with neurological impairment affects their health and quality of life. Bulgaria has many abandoned disabled children in residential homes. Lack of parental care puts them at risk for poor growth, suboptimal nutrition, and physical and mental development. Our study aims to identify factors associated with poor nutrition in Bulgarian children with neurological impairment living in different environments. Methods: From January to December 2017, a cross-sectional study was conducted in northeastern Bulgaria. We recruited 109 residential and nonresidential children. The study included demographics, medical history, anthropometric measurements, biochemical tests, nutritional assessment, and gastrointestinal signs and symptoms. Data were analyzed with Jamovi 2.2.5 at a 0.05 significance level. Logistic regression was used to predict wasting in both environmental settings. Results: About 70% of the neurologically impaired children living in residential settings have malnutrition based on weight-for-age Z-score, compared to 25% of the non-residential children. Prematurity, low gross motor function (as measured by the gross motor function classification system), pureed food consumption, birth before 37 weeks, and living in residential care homes are linked to poor nutrition. Conclusion: Neurologically impaired children have a poor nutritional state, especially those living in residential homes. The study underscores the pressing need for the allocation of additional nutrition resources to effectively address the nutritional and developmental needs of children with neurological disabilities in Bulgaria.

Association of Motor Function With Cognitive Trajectories and Structural Brain Differences: A Community-Based Cohort Study.

The association of motor function with cognitive health remains controversial, and the mechanisms underlying this relationship are unclear. We aimed to examine the association between motor function and long-term cognitive trajectories and further explore the underlying mechanisms using brain MRI. In the Rush Memory and Aging Project, a prospective cohort study, a total of 2,192 volunteers were recruited from the communities in northeastern Illinois and followed up for up to 22 years (from 1997 to 2020). Individuals with dementia, disability, missing data on motor function at baseline, and missing follow-up data on cognitive function were excluded. At baseline, global motor function was evaluated using the averaged z scores of 10 motor tests covering dexterity, gait, and hand strength; the composite score was tertiled as low, moderate, or high. Global and domain-specific cognitive functions-including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed-were measured annually through 19 cognitive tests. A subsample (n = 401) underwent brain MRI scans and regional brain volumes were measured. Data were analyzed using linear mixed-effects models and linear regression. Among the 1,618 participants (mean age 79.45 ± 7.32 years) included in this study, baseline global motor function score ranged from 0.36 to 1.82 (mean 1.03 ± 0.22). Over the follow-up (median 6.03 years, interquartile range 3.00-10.01 years), low global motor function and its subcomponents were related to significantly faster declines in global cognitive function (β = -0.005, 95% CI -0.006 to -0.005) and each of the 5 cognitive domains. Of the 344 participants with available MRI data, low motor function was also associated with smaller total brain (β = -25.848, 95% CI -44.902 to -6.795), total white matter (β = -18.252, 95% CI -33.277 to -3.226), and cortical white matter (β = -17.503, 95% CI -32.215 to -2.792) volumes, but a larger volume of white matter hyperintensities (β = 0.257, 95% CI 0.118-0.397). Low motor function is associated with an accelerated decline in global and domain-specific cognitive functions. Both neurodegenerative and cerebrovascular pathologies might contribute to this association.

Exploration of Gross Motor Function in Aicardi-Goutières Syndrome.

Background: Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by a spectrum of motor abilities. While the Aicardi-Goutières syndrome severity score favors severely impacted individuals, there is an unmet need to define tools measuring function across the Aicardi-Goutières syndrome spectrum as potential outcome assessments for future clinical trials. Methods: Gross Motor Function Measure-88 (GMFM-88) and AGS Severity Scale were administered in individuals affected by Aicardi-Goutières syndrome (n = 71). We characterized the performance variability by genotype. Derived versions of the GMFM-88, including the GMFM-66, GMFM-66 item set (GMFM-66IS), and GMFM-66 Basal&Ceiling (GMFM-66BC) were calculated. The Aicardi-Goutières syndrome cohort was divided into severe (AGS Severity Scale score <4) or attenuated (≥4). Performance on the AGS Severity Scale highly correlated with total GMFM-88 scores (Spearman Correlation: R = 0.91). To assess variability of the GMFM-88 within genotypic subcohorts, interquartile ranges (IQRs) were compared. Results: GMFM-88 performance in the TREX1 cohort had least variability while the SAMHD1 cohort had the largest IQR (4.23 vs 81.8). Floor effect was prominent, with most evaluations scoring below 20% (n = 46, 64.79%), particularly in TREX1- and RNASEH2-cohorts. Performance by the GMFM-66, GMFM-66IS, and GMFM-66BC highly correlated with the full GMFM-88. The Aicardi-Goutières syndrome population represents a broad range of gross motor skills. Conclusions: This work identified the GMFM-88 as a potential clinical outcome assessment in subsets of the Aicardi-Goutières syndrome population but underscores the need for additional validation of outcome measures reflective of the diverse gross motor function observed in this population, including low motor function. When time is limited by resources or patient endurance, shorter versions of the GMFM-88 may be a reasonable alternative.

Association of motor function with cognitive trajectories, risk of mild cognitive impairment, and structural brain differences

AbstractBackgroundThe impact of motor function (MF) on cognitive trajectories and mild cognitive impairment (MCI) remains unclear. This study aimed to examine the association of MF with cognitive trajectories, risk of MCI, and structural brain differences on magnetic resonance imaging (MRI).MethodWithin the Rush Memory and Aging Project, 1,216 cognitively intact participants (mean age: 78.60±7.25 years) were followed for up to 22 years. Baseline global MF was assessed by averaging the z‐scores of 10 motor tests and categorizing these scores tertiles (low middle, and high). Global and domain‐specific cognitive functions – including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed – were assessed annually through 19 cognitive tests. Incident MCI was detected and diagnosed based on standard criteria. A subsample (n = 284) underwent brain MRI and regional structural brain volumes were measured. Data were analyzed using linear mixed‐effects models, Cox regression, and linear regression.ResultAt baseline, global MF scores ranged from 0.46 to 1.82 (mean score: 1.06 ± 0.22). During the follow‐up (median, 6.98 years; interquartile range, 3.08‐10.75 years), 553 participants (45.48%) developed MCI. Compared to participants with high MF, those with low MF had faster decline in global cognition (β = ‐0.05, 95% confidence interval [CI]: ‐0.06 to ‐0.03), episodic memory (β = ‐0.05, 95% CI: ‐0.07 to ‐0.03), semantic memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.02), working memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.03), visuospatial ability (β = ‐0.03, 95% CI: ‐0.04 to ‐0.02), and perceptual speed (β = ‐0.04, 95% CI: ‐0.06 to ‐0.03) over the follow‐up. The multi‐adjusted hazard ratio (95% CI) of MCI was 1.84 (1.41 to 2.42) for the lowest MF tertile compared to the highest. Furthermore, the low MF was related to a significantly greater volume of white matter hyperintensities (β = 0.16, 95% CI: 0.01 to 0.32), but not total brain, white matter, or gray matter volumes (all P &gt;0.05).ConclusionLow MF is associated with faster cognitive decline (including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed) and a moderately increased risk of MCI. Vascular pathologies might play an important role in the MF‐MCI association.

Maternal exposure to air pollution during pregnancy and child's cognitive, language, and motor function: ECLIPSES study

Prenatal exposure to air pollution, even at low levels, has been associated with negative effects on a child's neuropsychological functioning. The present work aimed to investigate the associations between prenatal exposure to air pollution on a child's cognitive, language, and motor function at 40 days of age in a highly exposed area of Spain. From the ECLIPSES study population, the present work counted 473 mother-child pairs. Traffic-related air pollution levels at home addresses during the whole pregnancy were estimated including particulate matter (PM) with an aerodynamic diameter <2.5 μm (PM2.5), <10 μm (PM10) and 2.5–10 μm (PMcoarse), PM2.5absorbance, nitrogen dioxide (NO2), other nitrogen oxides (NOx), and ozone (O3) using land-use regression models developed within ESCAPE and ELAPSE projects. Children's cognitive, language, and motor functions were assessed using the Bayley Scales of Infant Development 3rd edition (BSID-III) at around 40 days of age. Linear regression models were adjusted for maternal biological, sociodemographic and lifestyle characteristics, area deprivation index, and amount of greenness around the home's address. All air pollutants assessed, except PM2.5 absorbance, were associated with lower motor function in children, while no association was observed between prenatal exposure to air pollution and cognitive and language functions. This finding highlights the need to continue raising awareness of the population-level impact that maternal exposure to air pollution even at low levels can have on the neuropsychological functions of children.

Scanning Imaging Study of Patients with Parkinson's Disease Lower Urinary Tract Dysfunction Based on Linear Equation.

A predictive method based on a linear equation was proposed to study the factors influencing lower urinary tract dysfunction in Parkinson's disease. A 10-month follow-up of 200 selected Parkinson's patients from January to December 2020 used a linear regression equation to analyze whether depletion function was associated with a specific nonmotor function loss, and a linear regression equation was used for analysis. A loss of emptiness function was used to determine whether there are complications associated with lower motor function and cognitive function. The experimental results showed that dysuria in Parkinson's disease was related to the following nonmotility disorders: gastrointestinal dysfunction (OR 2.52, 95% CI 1.57-3.92, P < 0.001), cardiovascular dysfunction (OR 2.31, 95% CI 1.23~4.11, P = 0.014), respiratory dysfunction (OR 1.72, 95% CI 1.32~3.24, P = 0.029), cutaneous autonomic dysfunction (OR 1.91, 95% CI 1.15~3.08, P = 0.023), and sleep disorders (OR 2.01, 95% CI 1.32~3.14, P = 0.001). In addition, dysuria was associated with higher UPDRS-III (regression coefficient 1.74, 95% CI 0.56-2.67, P = 0.001). Thus, nonmotor disorders have been shown to be associated with early impairment.

Participation restriction of children with cerebral palsy living in Thailand and influential factors: A cross-sectional study

ABSTRACT Objective To explore participation in daily activities of children with cerebral palsy(CP) in Thailand and influential factors. Methods A convenience sample of family-caregivers of 80 children with CP, 6–18 year-old, completed self-administered questionnaires (i.e., frequency of participation, Gross Motor Function Classification System-Family Report) during clinic visits at a university hospital. Results Family-caregivers reported that more than one-third of the children never participated in outdoor activities. The gap in the frequency of participation between groups with high versus low motor function was very high. Better gross motor and communication were strong predictors of participation. Caregiver’s education and family income were associated with participation in art/cultural, leisure and tourist activities. Conclusions Family-caregiver-report suggests that Thai-children with CP, especially those with severe impairments, have limited participation in daily activities. Increasing mobility and communication may promote the participation. Comprehensive intervention is needed to narrow the participation gap found between high and low functioning children.

Maternal intake of folate during pregnancy and risk of cerebral palsy in the MOBAND-CP cohort

Folate prevents neural tube defects and may play a role in some neurodevelopmental disorders. We investigated whether higher intakes of periconceptional or midpregnancy folate, as recommended, were associated with a reduced risk of offspring cerebral palsy (CP). We included participants from the Nordic collaboration cohort consisting of mother-child dyads in the Danish National Birth Cohort and the Norwegian Mother, Father, and Child Cohort Study [combined as MOthers and BAbies in Norway and Denmark (MOBAND-CP)]. A total of 190,989 live-born children surviving the first year of life were included. Missing covariate data were multiply imputed. Our exposures were defined as any or no folic acid supplementation in gestational weeks (GWs) -4 to 8 (periconceptional), 9 to 12, and -4 to 12, and supplemental, dietary, and total folate during midpregnancy (GWs 22-25). CP overall and the unilateral and bilateral spastic subtypes, as well as CP with low or moderate/high gross motor function impairments, were our outcomes of interest. Periconceptional folic acid supplementation was not associated with CP [adjusted odds ratio (aOR), 1.02; 95% CI: 0.82-1.28]. However, supplementation in GWs 9 to 12 was associated with a reduced risk of CP (aOR, 0.74; 95% CI: 0.57-0.96), and inverse associations were indicated for both the unilateral (aOR, 0.68; 95% CI: 0.46-1.02) and bilateral (aOR, 0.70; 95% CI: 0.49-1.02) spastic subtypes, although the associations were not statistically significant. Supplemental or dietary folate in midpregnancy alone were not associated with CP. Strong inverse associations were observed with low gross motor function impairment (aOR, 0.49; 95% CI: 0.29-0.83), while for unilateral CP the aOR was 0.63 (95% CI: 0.34-1.22) for intakes of≥500 compared to≤199 dietary folate equivalents/day during midpregnancy. Our findings suggest that folate intakes in GWs 9 to 12 and midpregnancy were associated with lower risks of CP, while no association was observed for periconceptional supplementation.

The Effects of Facial Exercise on Mental Health, Facial Expression and EEG in Community-Dwelling Older People

Although it is well documented that exercising is good for the mental health and cognitive function as well as the physical condition in elderly people, exercising is difficult in elderly individuals with a low motor function. To develop an exercise program targeting elderly individuals unsuited for whole-body exercises, we assessed the effects of facial exercises on the mental health and mood in healthy elderly people. Community-dwelling older adults (N = 75, age range = 65-87 yrs) were randomly divided into a facial exercises group and a wait-listed control group. A facial exercises program of 30 min was given twice a week for 12 weeks. This program consisted of rhythmic facial movement, muscle stretching, facial yoga, and Tanden breathing. The GHQ-12 for mental health were administered to both groups before and after the 12-week study period. In addition, facial expression and EEG were measured. Fifty-three participants completed the protocol. In the intervention group, the GHQ-12, facial expression, and α wave in frontal lobe improved post-intervention. These results suggest that facial exercises are effective in improving the mental health, facial expression, α wave in frontal lobe of elderly people, and that exercises may be useful as a therapeutic modality in this population.

The Effects of Facial Exercise on Mental Health, Facial Expression and EEG in Community-Dwelling Older Adults

Although it is well documented that exercising is good for the mental health and cognitive function as well as the physical condition in elderly people, exercising is difficult in elderly individuals with a low motor function. To develop an exercise program targeting elderly individuals unsuited for whole-body exercises, we assessed the effects of facial exercises on the mental health and mood in healthy elderly people. Community-dwelling older adults (N = 75, age range = 65-87 yrs) were randomly divided into a facial exercises group and a wait-listed control group. A facial exercises program of 30 min was given twice a week for 12 weeks. This program consisted of rhythmic facial movement, muscle stretching, facial yoga, and Tanden breathing. The GHQ-12 for mental health were administered to both groups before and after the 12-week study period. In addition, facial expression and EEG were measured. Fifty-three participants completed the protocol. In the intervention group, the GHQ-12, facial expression, and α wave in frontal lobe improved post-intervention. These results suggest that facial exercises are effective in improving the mental health, facial expression, α wave in frontal lobe of elderly people, and that exercises may be useful as a therapeutic modality in this population.

Gait Speed and Grip Strength Are Predictors of Cognitive Decline and Dementia in Older Individuals.

Lower gait speed and grip strength are common in older adults. However, the results of lower motor function on cognitive outcomes have been mixed. We examined the longitudinal association between baseline slow gait speed and weak grip strength, alone and in combination, with risk of incident dementia or cognitive decline in a cohort of older adults. Participants (n=19,114) aged 70 and over (65 if U.S. minority) without documented evidence of dementia, significant cognitive impairment, physical disability or previous cardiovascular disease at baseline, were recruited from community settings. Incident dementia was adjudicated by an expert panel using DSM-IV criteria. Incident cognitive decline was defined as a persistent intra-individual decline in score of >1.5 SD from baseline on any of the cognitive tests. Using cox proportional hazard models, slow gait speed at baseline was associated with an increased risk of dementia (63%) and cognitive decline (43%), over a median 4.7 years. Weak grip strength was not as strong a predictor, but was also associated with risk (43% and 11%, respectively). Both outcomes showed higher risk for dementia than cognitive decline. There was no gender-specific interaction. When considered together (adjusted for one another), gait speed and grip strength were both independently associated with cognitive decline and dementia. The synergistic association of these physical measures, each of which is readily administered in the clinic or home, serve as effective early markers of increasing risk of cognitive decline and incident dementia and thus, should be considered for routine health assessments for older adults.

Impact of oral health guidance on the tongue-lip motor function of outpatients at a dental hospital.

ObjectiveTo clarify the effect of oral health guidance on tongue‐lip motor function in the outpatients visiting the Showa University Dental Hospital (Tokyo, Japan).BackgroundThe management of the oral function of older people visiting a dental hospital is important. Previous studies have revealed that tongue‐lip motor function is easy to improve. However, the impact of oral health guidance on tongue‐lip motor function in the outpatients of dental hospital requires further elucidation.Materials and MethodsThe participants (n = 35) included patients who were diagnosed with low tongue‐lip motor function on evaluation by oral diadochokinesis (ODK) at the outpatient clinic. They underwent a second examination approximately 6‐12 months later. Their demographic characteristics were recorded. Oral health guidance was provided through an educational leaflet on oral hypofunction when the participants visited the clinic. It included content on tongue twisters, voice training and a range of movement and muscle training of the tongue and lip.ResultsFollowing oral health guidance on tongue‐lip motor function, the ODK values changed from 5.6 at the first examination to 6.0 at the second for /pa/, from 5.6 to 5.8 for /ta/ and from 5.2 to 5.4 for /ka/. This improvement was not significantly associated with age, sex, measurement period or number of visits.ConclusionThe findings of this longitudinal study suggested that oral health guidance using an oral hypofunction educational leaflet may be effective in improving the tongue‐lip motor function of outpatients who had low tongue‐lip motor function, regardless of the measurement period or the number of visits to the dental hospital.

Longitudinal motor function in proximal versus distal DMD pathogenic variants.

There is considerable heterogenicity in clinical outcomes in Duchenne muscular dystrophy (DMD). The aim of this study was to assess whether dystrophin gene (DMD) pathogenic variant location influences upper or lower extremity motor function outcomes in a large prospective cohort. We used longitudinal timed and quantitative motor function measurements obtained from 154 boys with DMD over a 10-y period by the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS) to understand how the trajectories of motor function differ based on proximal versus distal DMD pathogenic variants. Proximal variants were defined as located proximal to 5' DMD intron 44, and distal variants as those including nucleotides 3' DMD including intron 44. Distal DMD variants are predicted to alter the expression of short dystrophin isoforms (Dp140, Dp116, and Dp71). We compared various upper extremity and lower extremity motor function measures in these two groups, after adjusting for total lifetime corticosteroid use. The time to loss-of-ambulation and timed motor function measurements of both upper and lower limbs over a 10-y period were comparable between boys with proximal (n=53) and distal (n=101) DMD pathogenic variants. Age had a significant effect on several motor function outcomes. Boys younger than 7y of age (n=49) showed gain in function whereas boys 7y and older (n=71) declined, regardless of dystrophin pathogenic variant location. The longitudinal decline in upper and lower motor function is independent of proximal versus distal location of DMD pathogenic variants.

How do multimorbidity and lifestyle factors impact the perceived health of adults with intellectual disabilities?

Adults with intellectual disability (ID) have poorer physical and perceived health than the general population. Knowledge of perceived health predictors is both limited and important for guiding the development of preventive actions. The aims of this study were to investigate (1) the associations between perceived health and demographics, degree of ID, physical health conditions, and weight and physical activity level and (2) lifestyle factors and multimorbidity as predictors for perceived health adjusted for age, gender, and level of ID. The North Health in Intellectual Disability study is a community based cross-sectional survey. The POMONA-15 health indicators were used. Univariate and multivariate logistic regression analyses with poor versus good health as the dependent variable were applied. The sample included 214 adults with a mean age 36.1 (SD 13.8) years; 56% were men, and 27% reported perceiving their health as poor. In univariate analyses, there were significant associations between poor health ratings and female gender, lower motor function, number of physical health conditions and several indicators of levels of physical activity. In the final adjusted model, female gender [odds ratio (OR) 2.4, P<0.05], level of ID (OR 0.65, P<0.05), numbers of physical health conditions (OR 1.6, P<0.001) and lower motor function (OR 1.5 P<0.05) were significant explanatory variables for poor perceived health, with a tendency to independently impact failure to achieve 30min of physical activity daily (OR 2.0, P=0.07). Adults with ID with female gender, reduced motor function and more physical health conditions are at increased risk of lower perceived health and should be given attention in health promoting interventions. A lack of physical activity tends to negatively influence perceived health.

Revisiting Poststroke Upper Limb Stratification: Resilience in a Larger Cohort

Background Upper limb (UL) impairment in stroke survivors is both multifactorial and heterogeneous. Stratification of motor function helps identify the most sensitive and appropriate assessments, which in turn aids the design of effective and individualized rehabilitation strategies. We previously developed a stratification method combining the Grooved Pegboard Test (GPT) and Box and Block Test (BBT) to stratify poststroke UL motor function. Objective To investigate the resilience of the stratification method in a larger cohort and establish its appropriateness for clinical practice by investigating limitations of the GPT completion time. Methods Post hoc analysis of motor function for 96 community-dwelling participants with stroke (n = 68 male, 28 female, age 60.8 ± 14 years, 24.4 ± 36.6 months poststroke) was performed using the Wolf Motor Function Test (WMFT), Fugl-Meyer Assessment (F-M), BBT, and GPT. Hypothesis-free and hypothesis-based hierarchical cluster analyses were conducted to determine the resilience of the stratification method. Results The hypothesis-based analysis identified the same functional groupings as the hypothesis-free analysis: low (n = 32), moderate (n = 26), and high motor function (n = 38), with 3 exceptions. Thirty-three of the 38 participants with fine manual dexterity completed the GPT in ≤5 minutes. The remaining 5 participants took 6 to 25 minutes to place all 25 pegs but used alternative movement strategies to complete the test. The GPT time restriction changed the functional profile of the moderate and high motor function groups leading to more misclassifications. Conclusion The stratification method unambiguously classifies participants by UL motor function. While the inclusion of a 5-minute cutoff time for the GPT is preferred for clinical practice, it is not recommended for stratification purposes.

Clinical Aspects of Neonatal Hypoglycemia: A Mini Review.

Introduction: Neonatal hypoglycemia is common and a preventable cause of brain damage. The goal of management is to prevent or minimize brain injury. The purpose of this mini review is to summarize recent advances and current thinking around clinical aspects of transient neonatal hypoglycemia.Results: The groups of babies at highest risk of hypoglycemia are well defined. However, the optimal frequency and duration of screening for hypoglycemia, as well as the threshold at which treatment would prevent brain injury, remains uncertain. Continuous interstitial glucose monitoring in a research setting provides useful information about glycemic control, including the duration, frequency, and severity of hypoglycemia. However, it remains unknown whether continuous monitoring is associated with clinical benefits or harms. Oral dextrose gel is increasingly being recommended as a first-line treatment for neonatal hypoglycemia. There is some evidence that even transient and clinically undetected episodes of neonatal hypoglycemia are associated with adverse sequelae, suggesting that prophylaxis should also be considered. Mild transient hypoglycemia is not associated with neurodevelopmental impairment at preschool ages, but is associated with low visual motor and executive function, and with neurodevelopmental impairment and poor literacy and mathematics achievement in later childhood.Conclusion: Our current management of neonatal hypoglycemia lacks a reliable evidence base. Randomized trials are required to assess the effects of different prophylactic and treatment strategies, but need to be adequately powered to assess outcomes at least to school age.