Minor Motor Impairment Research Articles

P.151Motor performances in exon-2 duplication of the dystrophin gene

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive weakening and wasting of skeletal muscles, which usually leads to loss of ambulation between 12-14 years. DMD is caused by mutations in the dystrophin gene: 70% deletions, 15-30% point mutations and 10% duplications that induce a frameshift in the protein-coding sequence. Here we report on a 18-year-old DMD patient harboring exon-2 duplication and presenting with a milder-than-expected phenotype. When he was 6-year-old, a muscle biopsy was performed because of incidental detection of elevated CK. Complete absence of dystrophin was observed and the diagnosis of DMD was genetically confirmed by exon-2 duplication. At present, the patient is able to walk > 400 meters at the 6MWT and still run. Muscle biopsy was repeated when he was 15 and faint dystrophin was detected at immunostaining and western blotting. The finding of minor motor impairment after age 16 is exceptional in DMD. To investigate the influence of exon-2 duplication on the disease phenotype, we performed an explorative survey to assess the outcome of these patients. We collected data from 27 patient, whose 16 above age 14. At age 14 and 16, the percentage of ambulant patients was 50%, and still the 30% of patients could walk at age 20. Preliminary results in few patients suggest that late ambulant patients display faint dystrophin band at the western blotting assay. In conclusion, it is important to consider such variability as a confounding factor when analyzing outcomes of newly available treatments. Moreover, a better understanding of the mechanisms that protect these patients may provide new avenues for treatment.

Recovery of kinematic arm function in well-performing people with subacute stroke: a longitudinal cohort study

BackgroundMost motor function improvements in people who have experienced strokes occur within the first 3 months. However, individuals showing complete or nearly complete arm function recovery, as assessed using clinical scales, still show certain movement kinematic deficits at 3 months, post-stroke. This study evaluated the changes in upper extremity kinematics, in individuals demonstrating minor clinical motor impairments, 3–12 months post-stroke, and also examined the association between kinematics and the subjects’s self-perceived hand abilities during the chronic stage, 12 months post-stroke.MethodsForty-two subjects recovering from strokes and having Fugl-Meyer upper extremity motor assessment scores ≥60 were included from the Stroke Arm Longitudinal Study at the University of Gothenburg (SALGOT). Kinematic analyses of a drinking task, performed 3, 6, and 12 months post-stroke, were compared with kinematic analyses performed in 35 healthy controls. The Stroke Impact Scale-Hand domain was evaluated at the 12-month follow-up.ResultsThere were no significant changes in kinematic performance between 3 and 12 months, post-stroke. The patients recovering from stroke showed lower peak elbow extension velocities, and increased shoulder abduction and trunk displacement during drinking than did healthy controls, at all time points. At 12 months, post-stroke, better self-perceived arm functions correlated with improved trunk displacements, movement times, movement units, and time to peak velocity percentages.ConclusionKinematic movement deficits, observed at 3 months post-stroke, remained unchanged at 12 months. Movement kinematics were associated with the patient’s self-perceived ability to use their more affected hand.Trial registrationClinicalTrials: NCT01115348.

Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies

Aim of the study: Neuropathy associated with IgM monoclonal gammopathy (MGUS) represents distinctive clinical syndrome, characterized by male predominance, late age of onset, slow progression, predominantly sensory symptoms, deep sensory loss, ataxia, minor motor impairment. More than 50% of patients with neuropathy-associated MGUS possess antibodies against myelin-associated glycoprotein (MAG). Purpose of our study was to assess effects on disease progression of demographic, clinical and neurophysiological variables in our large cohort of patients. Materials and Methods: Forty-three Caucasians patients were followed every eight months for median duration time of 93 months. Extremity strength was assessed with Medical Research Council (MRC) Scale, disability with overall disability status scale (ODSS), modified Rankin Scale and sensory function with Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale (ISS). Statistical analyses were conducted with parametric or non-parametric measures as appropriate. Survival analysis was used to test predictive value of clinical, demographical and neurophysiological variables. Variance analysis was conducted to explain difference on MRC between patients and groups at different time from onset. Results: Results showed that demyelinating pattern, older age and absence of treatment were significant risk factors for disability worsening. No other factors emerged as predictors including gender, ataxia and tremor at baseline, level of anti-MAG and IgM protein concentration in serum. Despite worsening of all outcome measures between first and last visit, quality of life (HRQol) judged by patients did not vary significantly. Conclusions: Our study provides evidence that electrophysiologic pattern, age of onset and absence of treatment are strong predictor of prognosis in anti-MAG polyneuropathy.

Successful outcome after endovascular thrombolysis for acute ischemic stroke with basis on perfusion-diffusion mismatch after 24 h of symptoms onset.

Background:Although intravenous thrombolysis is the Food and Drug Administration-approved treatment for acute ischemic stroke (AIS) within 3 h, combined intravenous and intra-arterial thrombolysis with endovascular techniques may be able to extend this traditional time window.Case Description:We present the clinical evolution of a 45-year-old male presenting with acute left hemiparesis. Magnetic resonance imaging revealed a small diffusion restriction at the right basal ganglia with perfusion compromise in the entire right middle cerebral artery (MCA) territory. Angiography revealed a complete occlusion of MCA at its M1 segment. The patient underwent endovascular mechanical thrombectomy with additional intra-arterial thrombolysis more than 24 hours after the onset of the initial symptoms and experienced complete vessel recanalization. At 1 year, the patient had global independence with minor residual motor impairment in the left arm.Conclusions:We report the case of a successful thrombolytic therapy following AIS performed more than 24 h after the initial symptoms based on the presence of a perfusion-diffusion mismatch. This report is expected to stimulate the development of future prospective studies with special focus on the role of perfusion-diffusion mismatch in patient selection for treatment of AIS, especially in those presenting outside the traditional time window.

Quality of Life and low back pain in primary caregivers of children with cerebral palsy

The aim of this study was to evaluate the quality of life of primary caregivers of children with CP, correlating with the presence of low back pain and motor impairment level of the child. For this research to have been carried out there was the participation of 55 primary caregivers that completed the questionnaires of Roland & Morris (QRM) and WHOQOL-Bref. The evaluation of children's motor impairment was measured by Gross Motor function Classification System (GMFCS). The results show that primary caregivers of children with CP had a loss in their quality of life, especially in the environmental domain and facet pain and discomfort (30.45), negative feelings (34.09), and recreation and leisure (37.27). There were no significant correlations between motor impairment in children with CP, the quality of life of their primary caregivers, and the symptoms of low back pain. However, it was observed that the average symptoms of low back pain are lower in caregivers of children with minor motor impairment (p=0.488), and that there is a significant negative correlation (r=-0.508, p<0.001) between the symptoms of back pain and quality of life of caregivers.

20. Movement sequencing abnormalities in schizophrenia: Changes in cortical activity during finger-tapping task

Minor motor and sensory impairments, including movement sequencing, are frequent symptoms in schizophrenia. In a previous study ( Kasparek et al., 2012 ) we showed abnormal cortico-cerebellar functional connectivity during execution of motor task only in schizophrenia patients (SZP) with sequencing deficit. This suggests that the abnormal connectivity reflects rather symptoms that are domain-specific, than the diagnoses of schizophrenia per se. In order to parse out the differences in brain activity during motor learning that are disease-specific (i.e. common to all SZP relative to healthy controls) versus domain-specific (i.e. specific only to SZP with sequencing deficit), we conducted a new and more detailed analysis of the data from the previous study. We used functional magnetic resonance imaging to examine brain activity during finger-tapping task in 24 SZP and 24 healthy control participants. The task had two experimental conditions, in which participants had to execute blocks of sequenced finger movements (SQ condition) and non-sequenced movements (ALL condition). Prior to the imaging session, outside the scanner the movement sequencing skills were assessed through Neurological Evaluation Scale (NES). Based on the NES scores the patients were subdivided into two groups, those with sequencing abnormalities (SQ+), and those without movement sequencing deficit (SQ-). We performed whole brain analysis to identify regions with higher activation during SQ as compared to ALL blocks and we analyze these results as a function of movement sequencing skill. In the left motor and parietal cortices all patients had higher activation than healthy subjects in both ALL and SQ conditions. However, our analysis revealed that this effect was driven mainly by the SQ- subgroup in motor cortex, and by SQ + group in parietal cortex. No such differences were seen in the contra-lateral cortices. We conclude that executing a non-sequenced motor task is more demanding for SZP than controls (disease-specific), since they show constantly higher activation in left motor and parietal cortex. Notably, although the overactivation of motor cortex seems to be a good compensating strategy to achieve adequate motor performance, the hyperactivation of parietal cortex seems to be linked to motor deficit symptoms (domain-specific). Acknowledgement The study was supported by the Ministry of Health of the Czech Republic (research Grant No. NT13437) and by the University Hospital Brno from the Institutional Support Fund.

Validation of a Haptic-Based Simulation to Test Complex Figure Reproduction Capability

The objective of this research was to develop a new computer-based system for psychomotor skill assessment. The focus was on the simulation of the Rey-Osterrieth Complex Figure (ROCF) reproduction test incorporating a haptic interface. Various system functions were created to support customized testing protocols that are based on specific user requirements, facilitate semiautomated scoring of tests, and produce quantitative test output. Advanced technologies of pattern recognition were reviewed and adapted for the system development. This approach yielded an application for recording freehand drawings and recognizing and normalizing drawing strokes for semiautomated scoring according to a standard. The new simulator system was validated by comparison with traditional paper-based tests in which participants were asked to use their nondominant hand to simulate a minor motor impairment. Results demonstrated the simulator to be sensitive to functional differences between dominant and nondominant hand use. The computerized scoring software also appeared to be valid for generating ROCF scores, which were consistent with manual scores determined by a trained rater for the same drawing stimuli.

Mouse models of SMA: tools for disease characterization and therapeutic development

Mouse models of human disease are an important tool for studying disease mechanism and manifestation in a way that is physiologically relevant. Spinal muscular atrophy (SMA) is a neurodegenerative disease that is caused by deletion or mutation of the survival motor neuron gene (SMN1). The SMA disease is present in a spectrum of disease severities ranging from infant mortality, in the most severe cases, to minor motor impairment, in the mildest cases. The variability of disease severity inversely correlates with the copy number, and thus expression of a second, partially functional survival motor neuron gene, SMN2. Correspondingly, a plethora of mouse models has been developed to mimic these different types of SMA. These models express a range of SMN protein levels and extensively cover the severe and mild types of SMA, with neurological and physiological manifestation of disease supporting the relevance of these models. The SMA models provide a strong background for studying SMA and have already shown to be useful in pre-clinical therapeutic studies. The purpose of this review is to succinctly summarize the genetic and disease characteristic of the SMA mouse models and to highlight their use for therapeutic testing.

Genetic testing and HIV dementia: teasing out the molecular mechanisms of disease

Genetic testing and HIV dementia: teasing out the molecular mechanisms of disease

Bilateral pallidal stimulation in children and adolescents with primary generalized dystonia – Report of six patients and literature-based analysis of predictive outcomes variables

Introduction: Primary generalized dystonia is a rare movement disorder. Medical treatment rarely relieves symptoms. The aim of this study was to investigate the efficacy and safety of bilateral pallidal stimulation in 6 children and adolescents with primary generalized dystonia. In addition, we strived to find predictors for treatment outcome by review and analysis of previously published studies. Methods: Six patients with primary generalized dystonia underwent chronic bilateral stimulation of the globus pallidus internus. A PubMed and MEDLINE search was performed in order to identify children and adolescents who underwent deep brain stimulation for primary generalized dystonia. The primary efficacy endpoint was the relative change of the Burke-Fahn-Marsden-Dystonia-Rating-Scale (movement score) after surgery. Results: Forty-four patients were found to meet the inclusion criteria. The mean age at onset of the disease was 7.8 ± 2.8 years and the mean age at surgery was 14.2 ± 3.5 years. The mean Burke-Fahn-Marsden-Dystonia-Rating-Scale (movement score) was 56.9 ± 22.7 before surgery and 23.7 ± 23.2 at a mean follow up of 13.0 ± 4.8 months ( p < 0.001). The improvement in the DYT1-positive group was significantly higher compared to the DYT1-negative group (77% ± 24% and 44% ± 30%, respectively, p < 0.001). A positive correlation between the movement score before and after surgery was found in both the DYT1-positive and DYT1-negative cohort (rs = 0.624, p < 0.001 and rs = 0.734, p < 0.001, respectively). Conclusion: DBS is an effective treatment in children and adolescents with primary generalized dystonia. Predictive factors for a better treatment outcome are DYT1-positive status and minor motor impairment before surgery.

A combined neuropsychological and brain imaging study of obstructive sleep apnea

Patients with obstructive sleep apnea (OSA) show neuropsychological impairments ranging from vigilance decrements, attentional lapses and memory gaps to decreased motor coordination, but their cognitive profile, and the origin of the impairments, remain unclear. We sought to establish the neuropsychological profile of 16 newly diagnosed apneics and to highlight both their morphological and functional brain abnormalities. We used an extensive neuropsychological test battery to investigate attention and vigilance, executive functions, episodic memory and motor domains. For brain imaging, we used the optimized voxel-based morphometry procedure for the MRI data, resting-state (18)F-fluoro-2-deoxy-D-Glucose positron emission tomography ((18)FDG-PET) with correction for partial volume effects (PVEs) and voxel-based analyses. In terms of neurobehavioral performance, our patients displayed objective daytime somnolence but little impairment in memory and motor domains. Cerebral data revealed gray matter loss in the frontal and temporo-parieto-occipital cortices, the thalamus, hippocampal region, some basal ganglia and cerebellar regions, mainly in the right hemisphere. The decrease in brain metabolism was also right-lateralized, but more restricted than the gray matter density changes, and involved the precuneus, the middle and posterior cingulate gyrus, and the parieto-occipital cortex, as well as the prefrontal cortex. To conclude, despite the presence of only minor memory and motor impairments, our patients displayed significant cerebral changes in terms of both gray matter density and metabolic levels, and may have benefited from cognitive reserve and compensatory mechanisms. Thus, cerebral changes in OSA patients may precede the onset of notable neuropsychological consequences.

Abnormal cerebral MRI findings and neuroimpairments in very low birth weight (VLBW) adolescents

Background High prevalence of abnormal cerebral MRI findings as well as major and minor motor, perceptual and cognitive impairments has been reported in very low birth weight (VLBW) children. Aim To investigate whether cerebral MRI pathology relates to different types of neuroimpairments in adolescents with VLBW. Methods At age 15, 55 adolescents with birth weight ⩽1500 g (VLBW) were examined. Motor function was evaluated by Movement Assessment Battery for Children (ABC) and the Grooved Pegboard (GP) test, cognitive function by Wechsler Intelligence Scales, and visuo-motor and visual perceptual function by The Developmental Test of Visual-Motor Integration (VMI) with the supplementary tests of Visual Perception (VP), and Motor Coordination (MC). Executive functions were assessed by Wisconsin Card Sorting Test (WCST) and the Stroop test. Cerebral MRI was assessed semi-quantitatively for ventricular, white and grey matter pathology. Results There was a rather weak relationship between MRI pathology and neuroimpairments. Poor performance on the WCST was related with ventricular dilatation (VD), white matter reduction and corpus callosum thinning. There was a correlation between results on the VMI test and the Movement ABC test and MRI pathology, but the correlation became much weaker when children with cerebral palsy were excluded. There was no relationship between MRI findings and estimated intelligence quotient (IQ) scores. Normal MRI predicted normal or near normal neuropsychological functioning. Conclusion Cerebral MRI pathology suggestive of perinatal white matter injury was related to disadvantages in performances on executive functions, to a lesser degree to motor and visual perceptual problems, but not to cognitive impairments in VLBW adolescents.

Are there critical periods for brain growth in children born preterm?

Background: Children born very preterm who attend mainstream schools have a high prevalence of minor motor, behavioural, and learning disorders. These appear to be associated with reduced postnatal growth, particularly...

Quality of motor performance in preterm and full-term 3-year-old children.

A combined assessment of motor performance and behaviour (CAMPB) was introduced previously for use in a longitudinal study of children who needed neonatal intensive care (NIC) and were born very preterm (n = 68), moderately preterm (n = 81) and full-term (n = 77) and in a reference group of neonatally healthy full-term children (n = 72). Aim To follow up the quality of motor performance at 3 years of age in the above groups of children. A detailed assessment of motor performance and an assessment of co-ordination were performed according to the CAMPB protocol. The results were compared between the different groups of children, and the relation between the two ways of assessing quality of motor performance was examined. The detailed assessment showed that the very preterm children had a significantly higher total score of deviations than any of the other gestational age groups of children. Also, some types of deviations were much more frequently observed in the very preterm children than in the other three groups. Some types of deviations were more often seen in children with pronounced incoordination than in children with no incoordination. The results from the two ways of assessing motor performance were strongly correlated. At 3 years of age, NIC children born very preterm have a lower quality of motor performance than NIC children born at a higher gestational age and healthy children born at term. The two ways of assessing quality of motor performance proved useful in identifying children with deviations indicating minor motor impairments.

Caudate and hippocampal volumes, intelligence, and motor impairment in 7-year-old children who were born preterm.

Children who survive very preterm birth without major disability have a high prevalence of learning difficulty, attention deficit, and minor motor impairment (MMI). To determine whether these difficulties are associated with structural brain abnormalities, we studied 105 preterm children (<32 wk) at 7 y with tests of IQ and MMI (Movement ABC) and detailed magnetic resonance brain scans. Scans were assessed qualitatively for visible cerebral lesions. Volume measurements of the caudate nuclei and hippocampal formations were made. Total brain volume (TBV) was estimated from the head circumference. Qualitative assessment of the scans showed evidence of cerebral lesions in 20 (19%), which were associated with lower IQ and more frequent MMI. IQ correlated with right and left caudate volume (Spearman's rho 0.304 and 0.349; p < 0.01). This association persisted (except for verbal IQ) when caudate volume was expressed as a percentage of estimated TBV to allow for overall brain size. No significant correlations with hippocampal volumes were observed. These differences persisted when only scans from children without visible lesions on scan were considered. MMI was significantly associated only with TBV and was more common in children with evidence of thinning of the posterior corpus callosum, although most children with MMI have a normal corpus callosum. Lower IQs in children who were born preterm are related to poorer development of the caudate relative to the rest of the brain, independent of other lesions. These findings suggest abnormal brain development after perinatal injury or postnatal nutritional deficits is responsible for cognitive deficits in preterm children.

Magnetic Resonance Imaging and T2 Relaxometry of Cerebral White Matter and Hippocampus in Children Born Preterm

The objective of this study was to determine whether intelligence and minor motor impairments in children who are born preterm without major disability are associated with cerebral white matter (CWM) and hippocampal abnormalities on magnetic resonance imaging (MRI). A total of 103 preterm children were studied at age 7 y with detailed magnetic resonance brain scans, including a T2-mapping sequence from which T2 relaxation times of the CWM and hippocampal formations were calculated. All of the children had no major motor disability, attended normal school, and had undergone assessment of IQ and a test for minor motor impairment (MMI). Twenty children had visible lesions on MRI, which were associated with lower IQ and more frequent MMI. Mean (SD) IQ was 90 (14.1). Twenty-five children were shown to have MMI (Movement ABC at below the fifth centile). This group was shown to have significantly longer T2 relaxation times for CWM (mean difference 2.1 ms right, 3.1 ms left) but not the hippocampus than the children without MMI. These differences persisted when only children without visible lesions on scans were considered (mean difference 1.5 ms bilaterally). There was no significant correlation between IQ and T2 relaxation times. Children who are born preterm without subsequent major neurodisability may, in addition to visible lesions on MRI scans, have a diffuse abnormality of CWM, manifest as an increase in T2 relaxation time. This abnormality shows a close correlation with minor motor impairment but not with full-scale IQ.

Upper motor neuron lesions: Their effect on muscle performance and appearance in stroke patients with minor motor impairment

Objective: To evaluate muscular performance and appearance in patients with prior stroke who were ambulatory. Design: Nonrandomized study. Setting: University hospital laboratory. Subjects: Sixteen persons (11 men, 5 women) with minor motor impairments, 6 to 24 months after stroke, were included. As reference, data were used from a population-based sample of 144 men and women. Main Outcome Measurements: Muscle performance was evaluated using a Kin-Com dynamometer in both the affected and the nonaffected leg. Peak isometric strength was measured at a 60° angle in both extension and flexion. Maximal isokinetic strength was measured at 60°/sec and at 180°/sec. Endurance was evaluated during isometric and dynamic knee extensions. Muscle biopsies were taken on nine patients and muscle tissue areas were determined with computed tomography. Results: The affected leg was weaker but not different in relative endurance compared with the nonaffected side. The performance of the nonaffected side was somewhat lower than that of a matched reference population. No major difference in fiber composition between the affected and nonaffected legs was noted, except for a lower degree of capillarization in the affected leg. Conclusion: In well-functioning stroke patients with good motor performance, further muscle training that includes resistance exercise might be indicated.

Segmental effects on motor function following different intrathecal receptor agonists and antagonists in rabbits.

The occurrence of motor impairment after intrathecal drug administration is infrequently reported in the literature and the methods of determining motor function vary. Motor function was examined in rabbits after a wide dose range of a variety of intrathecally administered opioid agonists, alpha-adrenergic agonists, non-competitive NMDA antagonists, a benzodiazepine agonist, a sigma agonist, paracetamol, isotonic and acidified saline. The opioids, sigma agonist and NMDA antagonists were additionally examined following pretreatment with naloxone. The opioid antagonists naltrindole and MR2266 (delta- and kappa-opioid receptor antagonists, respectively) were administered before the delta agonist and the kappa agonist. The alpha 2-adrenergic antagonist yohimbine was given before administration of dexmedetomidine and xylazine. Motor function was evaluated by a five-point scale of motor impairment ranging from normal function to total paralysis of the hindlegs. DPDPE (delta agonist), paracetamol, naloxone, naltrindole, yohimbine, isotonic and acidified saline did not affect motor function. MR2266 produced minor motor impairment. The alpha-adrenergic agonist dexmedetomidine reduced motor function slightly and dose independently. The remaining compounds affected motor function in a dose-dependent fashion. High doses of morphine produced hypersensitivity and myoclonus. An irreversible paralysis of the hindlegs was observed following intrathecal administration of the sigma agonist SKF10047 in high doses. Naloxone and MR2266 attenuated the effects of U50488H (kappa agonist). The present results reveal a dose-dependent reduction in motor function after intrathecal administration of some of the investigated compounds. The mechanisms behind these effects appear to be multifactorial.

Effects of physostigmine on novelty-related location preferences

Novelty-related location preferences and activity in an exploration box were recorded for male and female Wistar albino rats following intraperitoneal injections of 0.04 or 0.08 mg/kg of either physostigmine or neostigmine. Although rearing was reduced by the highest dose of both drugs and ambulation was reduced by the same dose of neostigmine, neither agent affected the significant preferences for novelty that typified all subjects. In a second experiment designed to assess the effects of 0.08 mg/kg of the two drugs administered during rather than after confinement to the familiar half of the apparatus, neostigmine reduced rearing, walking, and ambulation while increasing defecation, but physostigmine did not affect any response. While some minor motor impairment may have arisen from its peripheral effects, the lack of changes in novelty-related location preferences failed to support facilitation of either novelty avoidance or habituation by physostigmine suggested in previous studies.