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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]

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]

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]

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]

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]

Introduction: The impact of joint damage on functional capacity in patients with mild haemophilia (PwMH) has yet to be well studied. The primary aim of this study was to investigate the effect of joint impairment on the functional capacity of the lower limb in PwMH. The secondary aim was to identify physical predictors of lower limb functional capacity. Method: Forty‐nine PwMH were evaluated. Dynamic balance was assessed using Time Up and Go (TUG). Thirty‐second sit‐to‐stand (30‐STS) and 60‐second‐STS (60‐STS) were used to assess muscle power and endurance, respectively. Haemophilia Early Arthropathy Detection with Ultrasound (HEAD‐US) was used to assess joint damage. PwMH were divided based on HEAD‐US: with joint damage (≥3 points) and without or with very low joint damage (0–2 points). Univariate ANOVA and multiple regression analyses were performed to identify differences in functional capacity and potential physical predictors. Results: Only 30‐STS showed significant differences between groups (p =.002). TUG and 60‐STS were primarily explained by age (r2 =.21 and r2 =.44, respectively), while for 30‐STS, age combined with joint damage and pain level explains 54% of the variance. Conclusion: Our findings indicate that the 30‐STS is useful for assessing functional deterioration in people with early‐stage haemophilia‐related arthropathy. Our results also indicate that joint damage, combined with ageing and pain, may impact 30‐STS outcomes in PwMH. Furthermore, our findings show that the loss in TUG and 60‐STS performance in PwMH is related to ageing. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

The clinical connectome fingerprint (CCF) was recently introduced as a way to assess brain dynamics. It is an approach able to recognize individuals, based on the brain network. It showed its applicability providing network features used to predict the cognitive decline in preclinical Alzheimer's disease. In this article, we explore the performance of CCF in 47 Parkinson's disease (PD) patients and 47 healthy controls, under the hypothesis that patients would show reduced identifiability as compared to controls, and that such reduction could be used to predict motor impairment. We used source‐reconstructed magnetoencephalography signals to build two functional connectomes for 47 patients with PD and 47 healthy controls. Then, exploiting the two connectomes per individual, we investigated the identifiability characteristics of each subject in each group. We observed reduced identifiability in patients compared to healthy individuals in the beta band. Furthermore, we found that the reduction in identifiability was proportional to the motor impairment, assessed through the Unified Parkinson's Disease Rating Scale, and, interestingly, able to predict it (at the subject level), through a cross‐validated regression model. Along with previous evidence, this article shows that CCF captures disrupted dynamics in neurodegenerative diseases and is particularly effective in predicting motor clinical impairment in PD. [ABSTRACT FROM AUTHOR]

Identifying a whole‐brain connectome‐based predictive model in drug‐naïve patients with Parkinson's disease and verifying its predictions on drug‐managed patients would be useful in determining the intrinsic functional underpinnings of motor impairment and establishing general brain–behavior associations. In this study, we constructed a predictive model from the resting‐state functional data of 47 drug‐naïve patients by using a connectome‐based approach. This model was subsequently validated in 115 drug‐managed patients. The severity of motor impairment was assessed by calculating Unified Parkinson's Disease Rating Scale Part III scores. The predictive performance of model was evaluated using the correlation coefficient (rtrue) between predicted and observed scores. As a result, a connectome‐based model for predicting individual motor impairment in drug‐naïve patients was identified with significant performance (rtrue =.845, p <.001, ppermu =.002). Two patterns of connection were identified according to correlations between connection strength and the severity of motor impairment. The negative motor‐impairment‐related network contained more within‐network connections in the motor, visual‐related, and default mode networks, whereas the positive motor‐impairment‐related network was constructed mostly with between‐network connections coupling the motor‐visual, motor‐limbic, and motor‐basal ganglia networks. Finally, this predictive model constructed around drug‐naïve patients was confirmed with significant predictive efficacy on drug‐managed patients (r =.209, p =.025), suggesting a generalizability in Parkinson's disease patients under long‐term drug influence. In conclusion, this study identified a whole‐brain connectome‐based model that could predict the severity of motor impairment in Parkinson's patients and furthers our understanding of the functional underpinnings of the disease. [ABSTRACT FROM AUTHOR]

Background: Corticospinal tract (CST) injury has been shown to exert a major influence on functional recovery after ischemic stroke. Purpose To evaluate the prognostic value of CST injury estimated using a recent developed tractometry‐based method. Study Type: Prospective. Population: Forty‐eight patients with CST damage induced by stroke lesion who underwent brain magnetic resonance imaging within 7 days from onset. Sequence Diffusion‐weighted imaging (b = 1000 seconds/mm2) and diffusion kurtosis imaging (DKI) spin‐echo echo‐planar sequence with three b‐values (0, 1250, and 2500 seconds/mm2) at 3.0 T. Assessment A recently developed approach that combines tract segmentation and orientation mapping was used for CST‐specific tractography and tractometry. CST injury was estimated using the proposed method with diffusion metrics extracted from DKI sequence and with the first principal component (PC1) of the metrics. We also calculated the weighted lesion load (wLL) for comparison. Clinical evaluation included the National Institutes of Health Stroke Score in the acute phase and the modified Rankin scale at 3 months post‐stroke. The correlations between CST injury and initial motor impairment, as well as the prognostic values of CST injury for functional outcomes were evaluated. Statistical Tests: Pearson correlation and logistic regression. Area under the receiver operating characteristic curve. P < 0.05 was considered statistically significant. Results: CST injury calculated with diffusion metrics except fractional anisotropy all showed significant correlations with initial motor impairment. PC1 achieved the largest correlation coefficient (R = 0.65) compared with wLL and other diffusion metrics. In addition to wLL, DKI_AK, AFD_total, and PC1 maximum all showed predictive values for functional outcomes. Data Conclusion: Structural injury to CST is important for the assessment of the extent of injury and the prediction of functional outcome. The method proposed in our study could provide an imaging indicator to quantify the CST injury after ischemic stroke. Level of Evidence: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Background: Mevidalen is a selective positive allosteric modulator (PAM) of the dopamine D1 receptor subtype. Objective: To assess the safety and efficacy of mevidalen for treatment of cognition in patients with Lewy body dementia (LBD). Methods: PRESENCE was a phase 2, 12‐week study in participants with LBD (N = 344) randomly assigned (1:1:1:1) to daily doses of mevidalen (10, 30, or 75 mg) or placebo. The primary outcome measure was change from baseline on Cognitive Drug Research Continuity of Attention (CoA) composite score. Secondary outcomes included Alzheimer's Disease Assessment Scale‐Cognitive Subscale 13 (ADAS‐cog13), Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), and Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC). Numerous safety measures were collected. Results: Mevidalen failed to meet primary or secondary cognition endpoints. Mevidalen resulted in significant, dose‐dependent improvements of MDS‐UPDRS total score (sum of Parts I−III, 10 mg P < 0.05, 30 mg P < 0.05, 75 mg P < 0.01, compared to placebo). The 30 mg and 75 mg mevidalen doses significantly improved ADCS‐CGIC scores compared to placebo (minimal or better improvement: 30 mg P < 0.01, 75 mg P < 0.01; moderate or better improvement: 30 mg P < 0.05, 75 mg P < 0.001). Increases in blood pressure, adverse events, and cardiovascular serious adverse events were most pronounced at the 75 mg dose. Conclusions: Mevidalen harnesses a novel mechanism of action that improves motor symptoms associated with LBD on top of standard of care while improving or not worsening non‐motor symptoms associated with traditional dopaminergic therapy. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) studies have revealed distinct white matter (WM) characteristics of the brain following diseases. Beyond the lesion‐symptom maps, stroke is characterized by extensive structural and functional alterations of brain areas remote to local lesions. Here, we further investigated the structural changes over a global level by using DTI data of 10 ischemic stroke patients showing motor impairment due to basal ganglia lesions and 11 healthy controls. DTI data were processed to obtain fractional anisotropy (FA) maps, and multivariate pattern analysis was used to explore brain regions that play an important role in classification based on FA maps. The WM structural network was constructed by the deterministic fiber‐tracking approach. In comparison with the controls, the stroke patients showed FA reductions in the perilesional basal ganglia, brainstem, and bilateral frontal lobes. Using network‐based statistics, we found a significant reduction in the WM subnetwork in stroke patients. We identified the patterns of WM degeneration affecting brain areas remote to the lesions, revealing the abnormal organization of the structural network in stroke patients, which may be helpful in understanding of the neural mechanisms underlying hemiplegia. [ABSTRACT FROM AUTHOR]

Coiled‐coil domain containing 134 (CCDC134) has been shown to serve as an immune cytokine to exert antitumor effects and to act as a novel regulator of hADA2a to affect PCAF acetyltransferase activity. While Ccdc134 loss causes abnormal brain development in mice, the significance of CCDC134 in neuronal development in vivo is controversial. Here, we report that CCDC134 is highly expressed in Purkinje cells (PCs) at all developmental stages and regulates mammalian cerebellar development in a cell type‐specific manner. Selective deletion of Ccdc134 in mouse neural stem cells (NSCs) caused defects in cerebellar morphogenesis, including a decrease in the number of PCs and impairment of PC dendritic growth, as well as abnormal granule cell development. Moreover, loss of Ccdc134 caused progressive motor dysfunction with deficits in motor coordination and motor learning. Finally, Ccdc134 deficiency inhibited Wnt signaling but increased Ataxin1 levels. Our findings provide evidence that CCDC134 plays an important role in cerebellar development, possibly through regulating Wnt signaling and Ataxin1 expression levels, and in controlling cerebellar function for motor coordination and motor learning, ultimately making it a potential contributor to cerebellar pathogenesis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop and evaluate a new, open‐source MR‐compatible device capable of assessing unipedal and bipedal lower extremity movement with minimal head motion and high test–retest reliability. To evaluate the prototype, 20 healthy adults participated in two magnetic resonance imaging (MRI) visits, separated by 2–6 months, in which they performed a visually guided dorsiflexion/plantar flexion task with their left foot, right foot, and alternating feet. Dependent measures included: evoked blood oxygen level‐dependent (BOLD) signal in the motor network, head movement associated with dorsiflexion/plantar flexion, the test–retest reliability of these measurements. Left and right unipedal movement led to a significant increase in BOLD signal compared to rest in the medial portion of the right and left primary motor cortex (respectively), and the ipsilateral cerebellum (FWE corrected, p <.001). Average head motion was 0.10 ± 0.02 mm. The test–retest reliability was high for the functional MRI data (intraclass correlation coefficients [ICCs]: >0.75) and the angular displacement of the ankle joint (ICC: 0.842). This bipedal device can robustly isolate activity in the motor network during alternating plantarflexion and dorsiflexion with minimal head movement, while providing high test–retest reliability. Ultimately, these data and open‐source building instructions will provide a new, economical tool for investigators interested in evaluating brain function resulting from lower extremity movement. [ABSTRACT FROM AUTHOR]

Objective: Dravet syndrome (Dravet) is a severe childhood epileptic encephalopathy. The disease begins with a febrile stage, characterized by febrile seizures with otherwise normal development. Progression to the worsening stage features recurrent intractable seizures and the presentation of additional nonepileptic comorbidities, including global developmental delay, hyperactivity, and motor deficits. Later in life, at the stabilization stage, seizure burden decreases, whereas Dravet‐associated comorbidities persist. To date, it remains debated whether the nonepileptic comorbidities result from severe epilepsy or represent an independent phenotypic feature. Methods: Dravet mice (DS) faithfully recapitulate many clinical aspects of Dravet. Using wild‐type (WT) and DS at different ages, we monitored multiple behavioral features as well as background electroencephalogram (EEG) activity during the different stages of Dravet epilepsy. Results: Behavioral tests of WT and DS demonstrated that some deficits manifest already at the pre‐epileptic stage, prior to the onset of convulsive seizures. These include motor impairment and hyperactivity in the open field. Deficits in cognitive functions were detected at the onset of severe spontaneous seizures. Power spectral analysis of background EEG activity, measured through development, showed that DS exhibit normal background oscillations at the pre‐epileptic stage, a marked reduction in total power during the onset of severe epilepsy, and a subsequent smaller reduction later in life. Importantly, low EEG power at the stage of severe frequent convulsive seizures correlated with increased risk for premature death. Significance: Our data provide a comprehensive developmental trajectory of Dravet epilepsy and Dravet‐associated comorbidities in mice, under controlled settings, demonstrating that the convulsive seizures and some nonepileptic comorbidities may be uncoupled. Moreover, we report the existence of an inverse correlation, on average, between the power of background EEG and the severity of epileptic phenotypes, suggesting that such measurements may potentially serve as a biomarker for Dravet severity. [ABSTRACT FROM AUTHOR]

Self‐feeding is a critical self‐care skill that unites motor abilities (e.g., grasping and transporting utensils/food to the mouth) and cognitive abilities (e.g., using a spoon as a tool). This cross‐sectional study assessed self‐feeding behavior in a sample of 38 children with typical development (TD) and compared it between 18 of those children and 18 age‐ and sex‐matched peers with arm movement impairments (MI). Children were assessed with a bowl of cereal and two spoons presented in four different orientations. Results suggested that children with MI were less successful than their TD peers in both motor aspects (e.g., grasp and transport of food and utensils) and cognitive aspects (correct grasp across spoon orientations) of self‐feeding. Novel findings highlight: (a) interesting differences in visual attention between children with TD or MI; (b) the role of hand‐preference in the correct grasping of the spoon(s) and effective self‐feeding; (c) the positive relation between motor and cognitive aspects of self‐feeding; and (d) that greater variability of self‐feeding behavior relates to improved performance of cognitive aspects of the task. These results identify challenging components of self‐feeding for children with MI that should be targeted by early interventions and assistive technologies aimed at increasing self‐feeding independence. [ABSTRACT FROM AUTHOR]

Background: Research suggests that children identified with impaired motor skills can respond well to intensive therapeutic interventions delivered via occupational and physical therapy services. There is, however, a need to explore alternative approaches to delivering interventions outside traditional referral‐based clinic settings because limited resources mean such health services often struggle to meet demand. This review sets out to systematically assess the evidence for and against school‐based interventions targeted at improving the motor skills of children aged between 3 and 12 years old. Method: Five electronic databases were searched systematically (AMED, CINAHL, Cochrane, Medline, and PsycINFO) for peer‐reviewed articles published between January 2012 and July 2018. Studies were eligible if they implemented a school‐based motor skill intervention with a randomized or case‐controlled trial design that objectively measured motor skills as an outcome, which were not specific to an athletic or sporting skill. Participants had to be aged between 3 and 12 years old and free from neurological disorders known to affect muscle function. Risk of bias was assessed using the Cochrane risk of bias tool. Results: Twenty‐three studies met the inclusion criteria. These studies encompassed interventions targeted at training: fundamental movement skills, handwriting, fine, and global motor skills. The majority of these studies reported beneficial impact on motor function specifically, but some interventions also assessed subsequent impacts on activity and participation (but not well‐being). A number of the studies had methodological shortcomings that means these results need to be interpreted with caution. Conclusions: Schools appear to be an effective setting for motor skill interventions, but the extent of benefit likely depends on the type of intervention. Moreover, confirmation is needed as to whether benefits extend beyond motor function into everyday activities, participation, and well‐being. Future research should include follow‐up measures to assess the longer term efficacy of school‐based interventions. [ABSTRACT FROM AUTHOR]

Background: Angelman syndrome (AS) leads to clinical manifestations that include intellectual impairments, developmental delay and poor motor function. Initiatives to develop therapeutics implie an urgent need to identify methods that accurately measure the motor abilities. Methods: Six children with AS (6 to 9 years old) walked on an instrumented walkway to get spatiotemporal parameters (STPs) and center of pressure (CoP). These outcomes were compared to typically developing children (TD): 44 TD 6 to 9 years old and 20 TD 4 to 5 years old. Results: Analysis revealed differences in all STPs and gait variability index when compared to TD individuals. When AS participants were compared to younger TD individuals, except step length, STPs were different. Analysis of the CoP pathway revealed a less consistent and efficient pathway in AS. Conclusions: We could delineate the functional difference between children with AS and TD children. The variability of STP and the CoP were the most valuable components in gait to be considered in AS. [ABSTRACT FROM AUTHOR]

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA‐induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a “reconceptualization” of the pathophysiology. The aim of this work was to investigate DA‐driven aberrant learning as a concurrent cause of bradykinesia, using a comprehensive, biologically inspired neurocomputational model of action selection in the BG. The model includes the three main pathways operating in the BG circuitry, that is the direct, indirect and hyperdirect pathways, and use a two‐term Hebb rule to train synapses in the striatum, based on previous history of rewards and punishments. Levodopa pharmacodynamics is also incorporated. Through model simulations of the Alternate Finger Tapping motor task, we assessed the role of aberrant learning on bradykinesia. The results show that training under drug medication (levodopa) provides not only immediate but also delayed benefit lasting in time. Conversely, if performed in conditions of vanishing levodopa efficacy, training may result in dysfunctional corticostriatal synaptic plasticity, further worsening motor performances in PD subjects. This suggests that bradykinesia may result from the concurrent effects of low DA levels and dysfunctional plasticity and that training can be exploited in medicated subjects to improve levodopa treatment. [ABSTRACT FROM AUTHOR]

Objectives To determine the potential utility of the frontal assessment battery ( FAB) in assessing cognitive impairments in amyotrophic lateral sclerosis ( ALS), we investigated the association between the FAB score and regional gray matter volume, and ascertained whether the regional brain alterations related to cognitive impairments occur in relatively mild stage of ALS. Materials and Methods Twenty-four ALS patients with a Mini-Mental State Examination score of >23, a normal score on the Self-Rating Depression Scale, little or no disturbance in speech and handling utensils on the ALS Functional Rating Scale ( ALSFRS), and normal measures on respiratory tests (respiratory function test and arterial blood gas analysis), and two age-matched normal control groups (one for FAB assessment and the other for brain morphometry) underwent FAB testing and structural magnetic resonance imaging. We applied voxel-based morphometry to investigate the relationship between the FAB score and regional brain alteration, and assessed the relationship between the altered regional brain volume and ALSFRS or respiratory tests. Results Frontal assessment battery scores were significantly lower in ALS patients than in normal controls. Volume reduction in the right orbitofrontal gyrus in ALS was correlated with a lower FAB score. There was no correlation between the right orbitofrontal gyrus volume and ALSFRS or respiratory tests. Conclusions The results suggest that the FAB is an adequate tool for detecting cognitive impairments related to frontal lobe pathology in the relatively mild stage of ALS, independent of physical dysfunctions. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to determine whether antecedents and neuroimaging patterns vary according to the severity of motor impairment in children with cerebral palsy.Material and Methods: A population-based study in which all 309 term-born children with spastic and dyskinetic cerebral palsy born between 1983 and 1994 and 618 matched controls were studied. Antecedents were retrieved from obstetric records. Information on neuroimaging was retrieved from the cerebral palsy Register of Western Sweden. Cases were grouped by severity of motor impairment: mild (walks without aids), moderate (walks with aids) or severe (dependent on wheelchair). Binary logistic regression, the Cochran-Armitage test for trends, interaction analyses and interrelationship analyses were performed.Results: Antecedents associated with mild motor impairment were antepartum (placental weight, maternal weight and antibiotic therapy) or intrapartum and postpartum adverse events (meconium-stained amniotic fluid, low Apgar score, admission to neonatal intensive care unit and neonatal encephalopathy). Antecedents associated with severe motor impairment were antepartum (congenital infection, small head circumference and brain maldevelopment) or intrapartum and postpartum (emergency cesarean section and maternal antibiotic therapy). Comparisons between mild and severe motor impairment revealed congenital infection, maldevelopment, neonatal encephalopathy and meconium aspiration syndrome significantly more often in the group with severe motor impairment (p < 0.05). White matter injury was the most common neuroimaging pattern in mild motor impairment, whereas maldevelopment and cortical/subcortical lesions were most common in the severe motor impairment group.Conclusions: Our results suggest a variation in antecedents associated with cerebral palsy, related to severity of motor impairment. Timing of antecedents corresponded to neuroimaging patterns. [ABSTRACT FROM AUTHOR]

Background Recent studies have linked cognitive impairment in amyotrophic lateral sclerosis to frontotemporal pathology. Aim We examined possible associations between behavior changes and regional gray matter volume in early amyotrophic lateral sclerosis, and assessed whether the volume changes were independent of physical impairments. Methods A total of 17 amyotrophic lateral sclerosis patients with Mini-Mental State Examination score ≥ 24, no need for assistance in daily life and normal respiratory tests (respiratory function test and arterial blood gas analytes), and 11 age-matched controls underwent structural magnetic resonance imaging. Behavioral changes were assessed with family-rating Frontal Systems Behavior Scale. We applied voxel-based morphometry to investigate the correlation between the Frontal Systems Behavior Scale and gray matter volume, and assessed the correlation of volume with amyotrophic lateral sclerosis Functional Rating Scale and respiratory tests. Results Current Frontal Systems Behavior Scale scores were significantly higher than retrospective scores assessing the status before onset, most notably in apathy. The volumes of right middle and left medial frontal gyri in amyotrophic lateral sclerosis were negatively correlated with the Frontal Systems Behavior Scale, whereas they were not correlated with amyotrophic lateral sclerosis Functional Rating Scale and respiratory tests. The volume of the right frontal cluster, but not the left medial frontal cluster, was significantly smaller than that of controls. Conclusions Regional atrophy within the frontal lobe was associated with behavioral dysfunction in early amyotrophic lateral sclerosis, this association was independent of physical factors. [ABSTRACT FROM AUTHOR]

Several neurobiological factors have been found to correlate with functional recovery after brain lesions. However, predicting the individual potential of recovery remains difficult. Here we used multivariate support vector machine (SVM) classification to explore the prognostic value of functional magnetic resonance imaging (fMRI) to predict individual motor outcome at 4-6 months post-stroke. To this end, 21 first-ever stroke patients with hand motor deficits participated in an fMRI hand motor task in the first few days post-stroke. Motor impairment was quantified assessing grip force and the Action Research Arm Test. Linear SVM classifiers were trained to predict good versus poor motor outcome of unseen new patients. We found that fMRI activity acquired in the first week post-stroke correctly predicted the outcome for 86% of all patients. In contrast, the concurrent assessment of motor function provided 76% accuracy with low sensitivity (<60%). Furthermore, the outcome of patients with initially moderate impairment and high outcome variability could not be predicted based on motor tests. In contrast, fMRI provided 87.5% prediction accuracy in these patients. Classifications were driven by activity in ipsilesional motor areas and contralesional cerebellum. The accuracy of subacute fMRI data (two weeks post-stroke), age, time post-stroke, lesion volume, and location were at 50%-chance-level. In conclusion, multivariate decoding of fMRI data with SVM early after stroke enables a robust prediction of motor recovery. The potential for recovery is influenced by the initial dysfunction of the active motor system, particularly in those patients whose outcome cannot be predicted by behavioral tests. Hum Brain Mapp 36:4553-4565, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT The clinical syndrome of Huntington's disease (HD) is notable for a triad of motor, cognitive, and emotional features. All HD patients eventually become occupationally disabled; however, the factors that render HD patients unable to maintain employment have not been extensively studied. This review begins by discussing the clinical triad of HD, highlighting the distinction in the motor disorder between involuntary movements, such as chorea, and voluntary movement impairment, with the latter contributing more to functional disability. Cognitive disorder clearly contributes to disability, though the relative contribution compared to motor is difficult to unravel, especially because many of the tests used to asses 'cognition' have a strong motor component. The role of emotional changes in disability needs more study. The literature on contributions to functional disability, driving impairment, and nursing home placement is reviewed. Relevant experience is presented from the long-standing JHU HD observational study on motor versus cognitive onset, as well as on cognitive and motor features at the time when individuals discontinued working. Finally, we briefly review government policies in several countries on disability determination. We interpret the data from our own studies and from the literature to indicate that there is usually a close relationship between cognitive and motor dysfunction, and that it is critical to take both into consideration in determining disability. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Purpose Lacosamide ( LCM, Vimpat) is an anticonvulsant with a unique mode of action. This provides lacosamide with the potential to act additively or even synergistically with other antiepileptic drugs ( AEDs). The objective of this study was to determine the presence of such interactions by isobolographic analysis. Methods The anticonvulsant effect of LCM in combination with other AEDs including carbamazepine ( CBZ), phenytoin ( PHT), valproate ( VPA), lamotrigine ( LTG), topiramate ( TPM), gabapentin ( GBP), and levetiracetam ( LEV) at fixed dose ratios of 1:3, 1:1, and 3:1, was evaluated in the 6-Hz-induced seizure model in mice. In addition, the impact of the combinations of LCM with the other AEDs on motor coordination was assessed in the rotarod test. Finally, AED concentrations were measured in blood and brain to evaluate potential pharmacokinetic drug interactions. Key Findings All studied AEDs produced dose-dependent anticonvulsant effects against 6-Hz-induced seizures. Combinations of LCM with CBZ, LTG, TPM, GBP, or LEV were synergistic. All other LCM/ AED combinations displayed additive effects with a tendency toward synergism. Furthermore, no enhanced adverse effects were observed in the rotarod test by combining LCM with other AEDs. No pharmacokinetic interactions were seen on brain AED concentrations. Coadministration of LCM and TPM led to an increase in plasma levels of LCM, whereas the plasma concentration of PHT was increased by coadministration of LCM. Significance The synergistic anticonvulsant interaction of LCM with various AEDs, without exacerbation of adverse motor effects, highlights promising properties of LCM as add-on therapy for drug refractory epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To explore the potential diagnostic utility of musculoskeletal ultrasonography (USG) changes in complex regional pain syndrome type 1 (CRPS-1) of the upper extremity. Methods: With informed consent, 18 consecutive patients referred to our institution with CRPS-1 of the upper limb were examined with ultrasound scanning of both upper limbs. Qualitative comparison of the scan of the forearm muscles of the affected side with the unaffected side was made. Results: The muscles affected by CRPS-1 demonstrated increased echogenecity. The outlines of the muscles were either indistinct or completely obliterated. A group of several muscles appeared like one homogenous, hyperechoic mass, with loss of normal architecture. Compared with the unaffected side, the muscle thickness on the CRPS-1 side measured by calipers on ultrasound was reduced irrespective of the duration of disability or disuse of the hand. The flexors and extensor muscles of the forearm were maximally affected. Conclusion: Ultrasonography provides useful anatomical information, regarding structure, kinesiology, and gross pathological changes of muscle, that may prove useful in understanding the motor impairment associated with CRPS-1. USG shows promise as a cost-effective bedside tool for the diagnosis of CRPS-1 and in guiding physical therapy. [ABSTRACT FROM AUTHOR]

Electrophysiological and neuroimaging studies suggest that the integrity of ipsilesional and inter-hemispheric motor circuits is important for motor recovery after stroke. However, the extent to which each of these tracts contributes to the variance in outcome remains unclear. We examined whether diffusion tensor imaging (DTI)-derived measures of corticospinal and transcallosal tracts predict motor improvement in an experimental neurorehabilitation trial. 15 chronic stroke patients received bihemispheric transcranial direct current stimulation and simultaneous physical/occupational therapy for five consecutive days. Motor impairment was assessed prior to and after the intervention. At baseline, the patients underwent DTI; probabilistic fiber tracking was used to reconstruct the pyramidal tract (PT), alternate descending motor fibers (aMF), and transcallosal fibers connecting primary motor cortices (M1-M1). Ipsilesional corticospinal tracts (PT, aMF) and M1-M1 showed significantly decreased fractional anisotropy (FA) and increased directional diffusivities when compared to age-matched healthy controls. Partial correlations revealed that greater gains in motor function were related to higher FA values and lower directional diffusivities of transcallosal and ipsilesional corticospinal tracts. M1-M1 diffusivity had the greatest predictive value. An additional slice-by-slice analysis of FA values along the corticospinal tracts demonstrated that the more the ipsilesional FA profiles of patients resembled those of healthy controls, the greater their functional improvement. In conclusion, our study shows that DTI-derived measures can be used to predict functional potential for subsequent motor recovery in chronic stroke patients. Diffusivity parameters of individual tracts and tract combinations may help in assessing a patient's individual recovery potential and in determining optimal neurorehabilitative interventions. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Luyster RJ, Kuban KCK, O'Shea TM, Paneth N, Allred EN, Leviton A for ELGAN Study investigators. The Modified Checklist for Autism in Toddlers in extremely low gestational age newborns: Individual items associated with motor, cognitive, vision and hearing limitations. Paediatric and Perinatal Epidemiology 2011; 366-376. The Modified Checklist for Autism in Toddlers (M-CHAT) has yielded elevated rates of screening failure for children born preterm or with low birthweight. We extended these findings with a detailed examination of M-CHAT items in a large sample of children born at extremely low gestational age. The sample was grouped according to children's current limitations and degree of impairment. The aim was to better understand how disabilities might influence M-CHAT scores. Fourteen participating institutions of the Extremely Low Gestational Age Newborns (ELGAN) Study prospectively collected information about 1086 infants who were born before the 28th week of gestation and had an assessment at age 24-months. The 24-month visit included a neurological assessment, the Bayley Scales of Infant Development, Second edition (BSID-II), M-CHAT and a medical history form. Outcome measures included the distribution of failed M-CHAT items among groups classified according to cerebral palsy diagnosis, gross motor function, BSID-II scores and vision or hearing impairments. M-CHAT items were failed more frequently by children with concurrently identified impairments (motor, cognitive, vision and hearing). In addition, the frequency of item failure increased with the severity of impairment. The failed M-CHAT items were often, but not consistently, related to children's specific impairments. Importantly, four of the six M-CHAT 'critical items' were commonly affected by presence and severity of concurrent impairments. The strong association between impaired sensory or motor function and M-CHAT results among extremely low gestational age children suggests that such impairments might give rise to false positive M-CHAT screening. [ABSTRACT FROM AUTHOR]

The article presents oral abstracts on intellectual disability research to be presented at the 2010 Society for the Study of Behavioural Phenotypes (SSBP) Annual Scientific Meeting including a study on language impairments and fragile X syndrome (FXS), influence of the parent-of-origin of the supernumerary X chromosome on autistic and schizotypal symptom profiles in Klinefelter syndrome (KS), and the causal effect of seizures on learning and memory and social behaviour phenotypes.

Background and purpose: At high altitudes barometric pressure is reduced and, thus, less oxygen is inhaled. Reduced oxygen concentration in brain tissue can lead to cerebral damage and neurological and cognitive deficits. The present study was designed to explore the effects of high-altitude exposure using a quantitative MRI technique, voxel-based morphometry. Methods: We studied nine world-class mountain climbers before (baseline) and after (follow-up) an extremely high-altitude ascent of Everest and K2. We investigated the effects of repeated extremely high-altitude exposures by comparing mountain climbers’ scans at baseline with scans of 19 controls. In addition, we measured the effects of a single extremely high-altitude expedition by comparing mountain climbers’ scans at baseline and follow-up. Results: A region of reduced white matter density/volume was found in the left pyramidal tract near the primary (BA 4) and supplementary (BA 6) motor cortex when mountain climbers at baseline were compared with controls. Further, when mountain climbers’ scans before and after the expedition were compared, a region of reduced grey matter density/volume was found in the left angular gyrus (BA 39). Conclusion: These findings suggest that extremely high-altitude exposures may cause subtle white and grey matter changes that mainly affect brain regions involved in motor activity. [ABSTRACT FROM AUTHOR]

In this commentary, we accent the accumulating evidence for motor impairment as a common feature of early Alzheimer’s disease (AD) pathology. In addition, we summarize the state of knowledge on this phenotype in experimental mouse models, expressing AD-associated genes like tau or amyloid precursor protein. [ABSTRACT FROM AUTHOR]

Background: Both HIV infection and alcoholism can impair motor abilities involving manual dexterity and postural stability. Given the high prevalence of HIV and alcoholism comorbidity, we examined whether each disease selectively disrupts different components of upper and lower limb motor control and whether these impairments are compounded by disease comorbidity. Methods: Simple and complex upper (speed and finger dexterity) and lower (static posture) limb functions were tested in 31 men with HIV infection, 27 with alcoholism, 43 comorbid for HIV infection and alcoholism, and 22 normal healthy controls to assess whether comorbid patients would demonstrate greater motor impairment relative to those with a single diagnosis. Results: Individuals with HIV infection and those with alcoholism had impaired upper and lower limb motor function. Disease comorbidity compounded deficits in speeded finger movement. Neither Beck Depression Inventory scores, self-reported peripheral neuropathy, nor HIV medication accounted for group differences. Lower limb motor composite scores with eyes open were correlated with upper limb motor scores in the alcoholism group. Conclusions: Overall, the observed impairment patterns indicate the presence of upper and lower limb motor impairment in both HIV infection and alcoholism and the relevance of alcoholism in exacerbating impairment in speeded fine finger movement, when it occurs in HIV infection. [ABSTRACT FROM AUTHOR]

In this paper, different means of assessing cognitive development in children with severe impairments inboththeir expressive language and their motor skills are reviewed. A range of techniques are considered, including traditional cognitive tests and behavioral and physiological measures, but these techniques are generally impractical and minimally informative when it comes to assessing children with both motor and speech impairments. Electrophysiological measures show some promise for the future, but are currently inadequate for wide-ranging cognitive assessment. Development of the Carter Neurocognitive Assessment (CNA) is described. The CNA is appropriate for use in clinical and research settings and was designed to minimalize the impact of severely impaired motor skills and expressive language on performance. The CNA is intended to itemize and quantify a range of skills reflecting a cognitive level up to approximately 18 to 24 months in four areas: Social Awareness, Visual Attention, Auditory Comprehension and Vocal Communication. The use of the CNA to assess the performance and developmental growth of eight children with Holoprosencephaly (HPE), a midline developmental brain malformation, is described. The CNA is a useful tool for the assessment of children with severely compromised motor and verbal skills and has provided a more positive view of the cognitive potential of children with severe handicaps, such as the sample of children with HPE, than that presented in the past. [ABSTRACT FROM AUTHOR]

Background: Sensitivity to the motor-impairing and hypnotic effects of ethanol (EtOH) increases notably during development. Less is known, however, about the ontogeny of EtOH tolerance and the ontogenetic relationship among different types of tolerance. Consequently, we compared the ontogenetic development of acute, rapid, and chronic tolerance to EtOH-induced motor impairment and hypothermia in a swim task. Methods: Preweanling, adolescent, and adult female and male Sprague-Dawley rats were given chronic saline (control group), five daily EtOH exposures before EtOH on test day (chronic group), one EtOH exposure before test day (rapid group), or EtOH exposure only on test day (acute groups). Separate groups of animals in the acute groups were tested at 15, 60, or 105 min after injection to estimate acute tolerance development via calculating slopes of the linear regression of impairment relative to brain alcohol levels at each postinjection interval. Initial EtOH perturbation of swim performance was equated across age by varying EtOH dose. Results: Acute tolerance was evident to the motor-impairing effects of EtOH at all ages. When impairment was indexed relative to brain alcohol levels, rapid and chronic tolerance to the motor-impairing effects of EtOH on latency to reach the start was seen across age, although this tolerance tended to be more pronounced in adults. Somewhat different ontogenetic patterns of tolerance development were observed with EtOH-induced hypothermia, a dependent measure for which EtOH perturbation was not equated across age. Conclusions: The degree of initial perturbation by EtOH seems to be an important predictor of tolerance expression during ontogeny. That is, ontogenetic profiles of tolerance development differ significantly when EtOH-induced motor impairment is equated across age rather than dose of EtOH administered . The role of target response measures and context stress should also be considered when exploring ontogenetic expression of EtOH tolerance. [ABSTRACT FROM AUTHOR]

Epidemiological and neuropathological series have identified three predominant dementing processes; Alzheimer's disease (AD), vascular dementia (VaD) and dementia associated with Lewy bodies (termed Parkinson's disease dementia (PDD) in this paper). While each has its own distinguishing features and by definition all impact upon day to day functioning, no random community derived sample has examined clinical features as defined by gait and balance abnormalities and compared disability ratings of the three dementias simultaneously. Six hundred and forty-seven community dwelling subjects participated in the Sydney Older Persons Study and of these 537 participated in a medical assessment. Of these 537,482 informants rated disability. Gait and balance abnormalities of the three major dementias were identified and the association of the dementias with disability examined. The three major dementias showed evidence of both slowing and ataxia in gait and balance tests. This was maximal in those with PDD. Similarly, all showed evidence of disability that was maximal in those with PDD. In conclusion, this study has identified that gait abnormalities are present in all three dementias to a varying degree. It is hypothesised that the varying levels of disability observed are a consequence of the varying levels of motor impairment, resulting in greater levels of disability in those with PDD. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This research examined individual differences in the ability to self-monitor the effects of alcohol. Thirty-nine male subjects consumed 0.75 ml/kg alcohol and estimated their blood alcohol concentrations (BACs) at peak BAC and on the ascending and descending limbs of the blood alcohol curve. Family history of alcohol dependence did not affect the accuracy of estimation of BACs. Subjects who reported lower levels of subjective intoxication underestimated their BACs more than did subjects who reported higher levels of subjective intoxication. Subjects with less behavioral impairment underestimated their BACs more than subjects with greater behavioral impairment on the ascending limb of the blood alcohol curve. Accuracy was better on the ascending limb compared with peak BAC and the descending limb, and accuracy became worse over time on the descending limb. It appears that cues to the effects of alcohol rapidly become unavailable on the descending limb, which may contribute to decisions concerning further alcohol consumption and driving after drinking. [ABSTRACT FROM AUTHOR]

SUMMARY Comparisons between a group of deaf children and normal-hearing controls on an extensive test-battery revealed that the former group was clearly inferior both in general dynamic coordination and visual-motor coordination. An experimental study, focusing on speed of motor performance, confirmed the general impression that deaf children are relatively slow performers. In particular, the execution of movements is slower in deaf children: the processes involved in this difference require further experimental research. [ABSTRACT FROM AUTHOR]

Aim: Cerebral palsy (CP) is the most common cause of motor impairment in childhood. This study aimed to examine the prevalence, severity and concurrent impairments of CP-related motor impairment among Chinese children.Methods: Children with CP-related motor impairment aged 0-17 years were identified through a national population-based survey based on World Health Organization International Classification of Functioning, Disability and Health. Logistic regression models allowing for weights were used to examine individual and family factors in relation to CP-related motor impairment.Results: The weighted prevalence of CP-related motor impairment was 1.25 per 1000 children (95% confidence interval (CI): 1.16, 1.35) in China. Male children, children in multiples and in families where adults suffered from CP, were more likely to be affected by CP-related motor impairment. For mild, moderate, severe and extremely severe groups of motor impairment, weighted proportions of CP were 14.12% (95%CI: 11.70, 16.95), 20.35% (95%CI: 17.48, 23.56), 27.44% (95%CI: 24.25, 30.87) and 38.09% (95%CI: 34.55, 41.76), respectively; and weighted proportions of concurrent visual, hearing and cognitive impairment were 5.00% (95%CI: 3.59, 6.91), 6.98% (95%CI: 5.34, 9.08) and 71.06% (95%CI: 67.57, 74.31), respectively.Conclusions: Gender, multiple births and family adults with CP were significantly associated with CP-related motor impairment in Chinese children. Proportions of CP and concurrent impairments that increased with severity of motor impairment were observed. [ABSTRACT FROM AUTHOR]