Jos N. van der Geest

Motor Recovery and Cortical Reorganization After Mirror Therapy in Chronic Stroke Patients A Phase II Randomized Controlled Trial

Objective. To evaluate for any clinical effects of home-based mirror therapy and subsequent cortical reorganization in patients with chronic stroke with moderate upper extremity paresis. Methods. A total of 40 chronic stroke patients (mean time post .onset, 3.9 years) were randomly assigned to the mirror group (n = 20) or the control group (n = 20) and then joined a 6-week training program. Both groups trained once a week under supervision of a physiotherapist at the rehabilitation center and practiced at home 1 hour daily, 5 times a week. The primary outcome measure was the Fugl-Meyer motor assessment (FMA). The grip force, spasticity, pain, dexterity, hand-use in daily life, and quality of life at baseline—posttreatment and at 6 months—were all measured by a blinded assessor. Changes in neural activation patterns were assessed with functional magnetic resonance imaging (fMRI) at baseline and posttreatment in an available subgroup (mirror, 12; control, 9). Results. Posttreatment, the FMA improved more in the mirror than in the control group (3.6 ± 1.5, P < .05), but this improvement did not persist at follow-up. No changes were found on the other outcome measures (all Ps >.05). fMRI results showed a shift in activation balance within the primary motor cortex toward the affected hemisphere in the mirror group only (weighted laterality index difference 0.40 ± 0.39, P < .05). Conclusion. This phase II trial showed some effectiveness for mirror therapy in chronic stroke patients and is the first to associate mirror therapy with cortical reorganization. Future research has to determine the optimum practice intensity and duration for improvements to persist and generalize to other functional domains.

Effect of Simvastatin on Cognitive Functioning in Children With Neurofibromatosis Type 1: A Randomized Controlled Trial

CONTEXT Neurofibromatosis type 1 (NF1) is among the most common genetic disorders that cause learning disabilities. Recently, it was shown that statin-mediated inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase restores the cognitive deficits in an NF1 mouse model. OBJECTIVE To determine the effect of simvastatin on neuropsychological, neurophysiological, and neuroradiological outcome measures in children with NF1. DESIGN, SETTING, AND PARTICIPANTS Sixty-two of 114 eligible children (54%) with NF1 participated in a randomized, double-blind, placebo-controlled trial conducted between January 20, 2006, and February 8, 2007, at an NF1 referral center at a Dutch university hospital. INTERVENTION Simvastatin or placebo treatment once daily for 12 weeks. MAIN OUTCOME MEASURES Primary outcomes were scores on a Rey complex figure test (delayed recall), cancellation test (speed), prism adaptation, and the mean brain apparent diffusion coefficient based on magnetic resonance imaging. Secondary outcome measures were scores on the cancellation test (standard deviation), Stroop color word test, block design, object assembly, Rey complex figure test (copy), Beery developmental test of visual-motor integration, and judgment of line orientation. Scores were corrected for baseline performance, age, and sex. RESULTS No significant differences were observed between the simvastatin and placebo groups on any primary outcome measure: Rey complex figure test (beta = 0.10; 95% confidence interval [CI], -0.36 to 0.56); cancellation test (beta = -0.19; 95% CI, -0.67 to 0.29); prism adaptation (odds ratio = 2.0; 95% CI, 0.55 to 7.37); and mean brain apparent diffusion coefficient (beta = 0.06; 95% CI, -0.07 to 0.20). In the secondary outcome measures, we found a significant improvement in the simvastatin group in object assembly scores (beta = 0.54; 95% CI, 0.08 to 1.01), which was specifically observed in children with poor baseline performance (beta = 0.80; 95% CI, 0.29 to 1.30). Other secondary outcome measures revealed no significant effect of simvastatin treatment. CONCLUSION In this 12-week trial, simvastatin did not improve cognitive function in children with NF1. Trial Registration isrctn.org Identifier: ISRCTN14965707.

Visuomotor Cerebellum in Human and Nonhuman Primates

In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula–nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed.

Mirror-Induced Visual Illusion of Hand Movements: A Functional Magnetic Resonance Imaging Study

OBJECTIVE To identify neural networks associated with the use of a mirror to superimpose movement of 1 hand on top of a nonmoving contralateral hand (often referred to as mirror therapy or mirror-induced visual illusion). DESIGN A functional magnetic resonance imaging (fMRI) study of mirror-induced visual illusion of hand movements using a blocked design in a 1.5T magnetic resonance imaging scanner. Neural activation was compared in a no-mirror experiment and a mirror experiment. Both experiments consisted of blocks of finger tapping of the right hand versus rest. In the mirror experiment, movement of the left hand was simulated by mirror reflection of right hand movement. SETTING University medical center. PARTICIPANTS Eighteen healthy subjects. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Differences in fMRI activation between the 2 experiments. RESULTS In the mirror experiment, we found supplementary activation compared with the no-mirror experiment in 2 visual areas: the right superior temporal gyrus (STG) and the right superior occipital gyrus. CONCLUSIONS In this study, we found 2 areas uniquely associated with the mirror-induced visual illusion of hand movements: the right STG and the right superior occipital gyrus. The STG is a higher-order visual region involved in the analysis of biological stimuli and is activated by observation of biological motion. The right superior occipital gyrus is located in the secondary visual cortex within the dorsal visual stream. In the literature, the STG has been linked with the mirror neuron system. However, we did not find activation within the frontoparietal mirror neuron system to support further a link with the mirror neuron system. Future studies are needed to explore the mechanism of mirror induced visual illusions in patient populations in more detail.

The neuronal correlates of mirror therapy: an fMRI study on mirror induced visual illusions in patients with stroke

Aim To investigate the neuronal basis for the effects of mirror therapy in patients with stroke. Methods 22 patients with stroke participated in this study. The authors used functional MRI to investigate neuronal activation patterns in two experiments. In the unimanual experiment, patients moved their unaffected hand, either while observing it directly (no-mirror condition) or while observing its mirror reflection (mirror condition). In the bimanual experiment, patients moved both hands, either while observing the affected hand directly (no-mirror condition) or while observing the mirror reflection of the unaffected hand in place of the affected hand (mirror condition). A two-factorial analysis with movement (activity vs rest) and mirror (mirror vs no mirror) as main factors was performed to assess neuronal activity resultant of the mirror illusion. Results Data on 18 participants were suitable for analysis. Results showed a significant interaction effect of movement×mirror during the bimanual experiment. Activated regions were the precuneus and the posterior cingulate cortex (p<0.05 false discovery rate). Conclusion In this first study on the neuronal correlates of the mirror illusion in patients with stroke, the authors showed that during bimanual movement, the mirror illusion increases activity in the precuneus and the posterior cingulate cortex, areas associated with awareness of the self and spatial attention. By increasing awareness of the affected limb, the mirror illusion might reduce learnt non-use. The fact that the authors did not observe mirror-related activity in areas of the motor or mirror neuron system questions popular theories that attribute the clinical effects of mirror therapy to these systems.

Cognition and gait show a distinct pattern of association in the general population

With brain aging, cognition and gait deteriorate in several domains. However, the interrelationship between cognitive and gait domains remains unclear. We investigated the independent associations between cognitive and gait domains in a community‐dwelling population.

Determinants of cerebellar and cerebral volume in the general elderly population

In a population-based study of 3962 community-dwelling nondemented elderly we investigated the relation of age, sex, cardiovascular risk factors, and the presence of infarcts with cerebellar volume, and its interrelationship with cerebral volumes. Cerebellar and cerebral gray and white matter were segmented using Freesurfer version 4.5 (http://surfer.nmr.mgh.harvard.edu/). We used linear regression analyses to model the relationship between age, sex, cardiovascular risk factors, brain infarcts, white matter lesions (WMLs) and cerebellar and cerebral volume. Smaller cerebellar volumes with increasing age were mainly driven by loss of white matter. Diabetes, higher serum glucose and lower cholesterol levels were related to smaller cerebellar volume. No association was found between hypertension, smoking, apolipoprotein E (ApoE) genotype, and cerebellar volume. Supratentorial lacunar infarcts and WMLs were related to smaller cerebellar volume. Infratentorial infarcts were related to smaller cerebellar white matter volume and total cerebral volume. This study suggests that determinants of cerebellar volume do not entirely overlap with those established for cerebral volume. Furthermore, presence of infarcts or WMLs in the cerebrum can affect cerebellar volume.

Trajectories of decline in cognition and daily functioning in preclinical dementia

Although preclinical dementia is characterized by decline in cognition and daily functioning, little is known on their temporal sequence. We investigated trajectories of cognition and daily functioning in preclinical dementia, during 18 years of follow‐up.

Gait patterns in COPD: the Rotterdam Study

Gait disturbances in patients with chronic obstructive pulmonary disease (COPD) may lead to disability and falls. As studies assessing gait kinematics in COPD are sparse, we investigated associations of COPD with various gait domains and explored a potential link with falling. Gait was measured within the prospective, population-based Rotterdam Study (age ≥55 years) using an electronic walkway and summarised into seven gait domains: Rhythm, Variability, Phases, Pace, Tandem, Turning and Base of Support. Rhythm is a temporal gait aspect that includes cadence and reflects how quickly steps are taken. Persons with COPD (n=196) exhibited worse Rhythm (−0.21 sd, 95% CI −0.36– −0.06 sd) compared with persons with normal lung function (n=898), independent of age, sex, height, education, smoking or analgesic use, especially when dyspnoea and severe airflow limitation or frequent exacerbations (Global Initiative for Chronic Obstructive Lung Disease group D: −0.83 sd, 95% CI −1.25– −0.41 sd) were present. A lower forced expiratory volume in 1 s was associated with worse Rhythm and Pace, including lower cadence and gait velocity, respectively. Importantly, fallers with COPD had significantly worse Rhythm than nonfallers with COPD. This study demonstrates that persons with COPD exhibit worse Rhythm, especially fallers with COPD. The degree of Rhythm deterioration was associated with the degree of airflow limitation, symptoms and frequency of exacerbations. This study comprehensively investigates, in a large, population-based cohort, the gait pattern in COPD http://ow.ly/HQbc3

Structural and Microstructural Brain Changes Predict Impairment in Daily Functioning

BACKGROUND Brain changes on magnetic resonance imaging (MRI) reflect accumulating pathology and have clinically disabling consequences, such as dementia. However, little is known on the relation of these MRI markers with daily functioning in nondemented individuals. We investigated whether structural and microstructural brain changes are associated with impairment in activities of daily living in a community-dwelling population. METHODS Between 2005 and 2009, 2025 stroke-free nondemented participants (aged 59.9 years) from the population-based Rotterdam Study underwent brain MRI, yielding global MRI markers, focal MRI markers, and microstructural MRI markers. We used the Stanford Health Assessment Questionnaire to assess basic activities of daily living, and the Instrumental Activities of Daily Living Scale to assess instrumental activities of daily living. Follow-up on activities of daily living was obtained between 2008 and 2013 (mean follow-up 5.7 years). We used linear regression to analyze continuous scores of daily living and logistic regression for incident impairment. RESULTS Eighty-two participants became impaired in basic and 33 in instrumental activities of daily living. Smaller brain and hippocampal volume and higher diffusivity were associated with larger change in activities of daily living. Smaller brain volume (odds ratio [OR] 4.05 per SD; 95% confidence interval [CI], 1.81-9.02), larger white matter lesion volume (OR 1.33/SD; 95% CI 1.02-1.72) and higher mean (OR 1.55/SD; 95% CI, 1.11-2.15), axial (OR 1.49/SD; 95% CI, 1.08-2.07), and radial diffusivity (OR 1.51/SD; 95% CI, 1.09-2.10) were associated with higher risk of impairment in basic activities of daily living. CONCLUSIONS In community-dwelling individuals, brain changes are associated with deterioration and incident impairment in daily functioning.