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Background and Purpose— In recovered subcortical stroke, the pattern of motor network activation during motor execution can appear normal or not, depending on the task. Whether this applies to other aspects of motor function is unknown. We used functional MRI to assess motor imagery (MI), a promising new approach to improve motor function after stroke, and contrasted it to motor execution. Methods— Twenty well-recovered patients with hemiparetic subcortical stroke (14 males; mean age, 66.5 years) and 17 aged-matched control subjects were studied. Extensive behavioral screening excluded 8 patients and 4 control subjects due to impaired MI abilities. Subjects performed MI and motor execution of a paced finger–thumb opposition sequence using a functional MRI paradigm that monitored compliance. Activation within the primary motor cortex (BA4a and 4p), dorsal premotor, and supplementary motor areas was examined. Results— The pattern of activation during affected-hand motor execution was not different from control subjects. Affected-hand MI activation was also largely similar to control subjects, including involvement of BA4, but with important differences: (1) unlike control subjects and the nonaffected hand, activation in BA4a and dorsal premotor was not lower during MI as compared with motor execution; (2) the hemispheric balance of BA4p activation was significantly less lateralized than control subjects; and (3) ipsilesional BA4p activation positively correlated with motor performance. Conclusions— In well-recovered subcortical stroke, the motor system, including ipsilesional BA4, is activated during MI despite the lesion. It, however, remains disorganized in proportion to residual motor impairment. Thus, components of movement upstream from execution appear differentially affected after stroke and could be targeted by rehabilitation in more severely affected patients.

Background: There is no proven treatment for stroke progression in patients with subcortical infarcts. Eptifibatide, a glycoprotein IIb/IIIa inhibitor, might halt stroke progression by improving flow in the microcirculation. Methods: We conducted a retrospective analysis of patients with subcortical stroke who experienced deterioration and were treated with eptifibatide (loading dose 180 μg/kg; infusion 2 μg/kg/min) for 24–48 h. Oral antiplatelet agents were started 6 h before discontinuation of eptifibatide. Results: Twenty-four patients with subcortical strokes were treated. The median admission NIHSS score was 5.0, which worsened to 8.5 (motor 5.0) before starting eptifibatide. The median NIHSS score 24 h after starting eptifibatide was 5.5. At 24 h, 42% had motor NIHSS scores less than or equal to pre-deterioration scores (50% for total NIHSS), and 50% had improved at least 1 motor point compared to pre-eptifibatide scores, which was sustained until hospital discharge. At discharge, the median total NIHSS score was 4.5. Ninety-two percent of patients were discharged home or to inpatient rehabilitation. Treatment was stopped early in 1 case due to a platelet drop Conclusions: Eptifibatide infusion may be safe in patients with subcortical ischemic strokes. Future studies are needed to test the safety and potential efficacy of this agent in subcortical stroke progression.

The intensity dependence of the auditory-evoked potentials (IDAP) is inversely related to serotonergic tone. Depression is frequently observed after stroke, associated with cognitive impairment and increased mortality. Aim of this study was to investigate the serotonergic tone in acute stroke patients by IDAP. Consecutive patients with an acute stroke admitted in our stroke unit were evaluated using clinical and instrumental examinations and compared with healthy controls. The IDAP was calculated as the linear amplitude/stimulus intensity function (ASF) slope, by measuring the peak-to-peak amplitude of Nl-P2 on four blocks of different stimulus intensities. Twenty patients were enrolled; 11 had a right brain infarction; nine had depressive symptoms (DS). The ASF slope of the auditory-evoked potentials was markedly increased in stroke patients compared with controls (P = 0.021). Stroke patients with DS had a significant steeper ASF slope than controls (P = 0.017). There was no statistical difference in ASF slope between stroke patients without DS and controls. Post-stroke depression pathophysiology is still debated. Our study suggests that in acute stroke patients with DS, there is a direct involvement of the serotonergic system, regardless the degree of disability and the site of the lesion.

Background. The effects of physiotherapy are difficult to assess in very impaired early stroke patients. Objective. The aim of the study was to characterize the impact of 4 weeks of passive proprioceptive training of the wrist on brain sensorimotor activation after stroke. Methods. Patients with a subcortical ischemic lesion of the pyramidal tract were randomly assigned to a control or a wrist-training group. All patients had a single pure motor hemiplegia with severe motor deficit. The control group (6 patients) underwent standard Bobath rehabilitation. The second, “trained,” group (7 patients) received Bobath rehabilitation plus 4 weeks of proprioceptive training with daily passive calibrated wrist extension. Before and after the training period, patients were examined with validated clinical scales and functional MRI (fMRI) while executing a passive movement versus rest. The effect of standard rehabilitation on sensorimotor activation was assessed in the control group on the wrist, and the effect of standard rehabilitation plus proprioceptive training was assessed in the trained group. The effect of 4-week proprioceptive training alone was statistically evaluated by difference between groups. Results. Standard rehabilitation along with natural recovery mainly led to increases in ipsilesional activation and decreases in contralesional activation. On the contrary, standard rehabilitation and paretic wrist proprioceptive training increased contralesional activation. Proprioceptive training produced change in the supplementary motor area (SMA), prefrontal cortex, and a contralesional network including inferior parietal cortex (lower part of BA 40), secondary sensory cortex, and ventral premotor cortex (PMv). Conclusion. We have demonstrated that purely passive proprioceptive training applied for 4 weeks is able to modify brain sensorimotor activity after a stroke. This training revealed fMRI change in the ventral premotor and parietal cortices of the contralesional hemisphere, which are secondary sensorimotor areas. Recent studies have demonstrated the crucial role of these areas in severely impaired patients. We propose that increased contralesional activity in secondary sensorimotor areas likely facilitates control of recovered motor function by simple proprioceptive integration in those patients with poor recovery.

While it is widely accepted that multiple nonprimary motor areas such as the dorsal premotor cortex contribute to recovery from stroke, the contribution of the ipsilesional and contralesional primary motor cortex (M1) is controversial. It has been suggested that re-instating 'near normal' activation patterns is a good strategy for recovery of function [Baron et al., (2004) Cerebrovasc. Dis., 18, 260-267; Ward & Cohen, (2004) Arch. Neurol., 61, 1844-1848]. The present study addressed this aspect of stroke recovery by combining transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) in a cross-sectional design on nine patients with well-recovered motor function 17.6 +/- 5.5 months (mean +/- SD) after subcortical stroke. While TMS was applied to probe the integrity of the cortico-spinal tract (CST) at rest, MEG was used to test for recruitment of CST pathways during a motor challenge [cortico-muscular coherence (CMC) in a precision grip task]. With both techniques, crossed cortico-spinal connectivity could be demonstrated. A significant correlation (r = 0.85) of CMC magnitude and recovered muscle strength underlined the functional relevance of crossed CST integrity for successful recovery. In conclusion, at the descriptive level, crossed CST connectivity is a common finding in well-recovered patients with capsular stroke. This renders it likely that maintaining or regaining use of crossed CST fibers is one way to achieve effective recovery.

Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a promising tool to deliver proteins to select body areas. This study aimed to analyze whether UTMD was able to deliver brain-derived neurotrophic factor (BDNF) to the brain, enhancing functional recovery and white matter repair, in an animal model of subcortical stroke induced by endothelin (ET)-1. UTMD was used to deliver BDNF to the brain 24 h after stroke. This technique was shown to be safe, given there were no cases of hemorrhagic transformation or blood brain barrier (BBB) leakage. UTMD treatment was associated with increased brain BDNF levels at 4 h after administration. Targeted ultrasound delivery of BDNF improved functional recovery associated with fiber tract connectivity restoration, increasing oligodendrocyte markers and remyelination compared to BDNF alone administration in an experimental animal model of white matter injury.

Background The role of the CYP 2C19 genotype on clopidogrel efficacy has been studied widely, with data suggesting reduced clopidogrel efficacy in loss‐of‐function variant carriers taking clopidogrel after percutaneous coronary intervention; however, data are limited regarding the association between CYP 2C19 genetic variants and outcomes in stroke patients. We investigated whether CYP 2C19 metabolizer status affects the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy with aspirin and clopidogrel. Methods and Results CYP 2C19*2 and CYP 2C19*17 were genotyped in 522 patients treated with dual antiplatelet therapy from the Secondary Prevention of Small Subcortical Strokes ( SPS 3) study. CYP 2C19 metabolizer status was inferred from genotype, and associations with the risk of recurrent stroke and major bleeding were assessed in the overall cohort and by race/ethnic group with logistic regression modeling. In the overall cohort, there were no differences in outcomes by CYP 2C19 metabolizer status (recurrent stroke, odds ratio 1.81 [95% CI 0.76 to 4.30]; major bleeding, odds ratio 0.67 [95% CI 0.22 to 2.03]). In white participants, those with CYP 2C19 intermediate or poor metabolizer status had higher odds of recurrent stroke (odds ratio 5.19 [95% CI 1.08 to 24.90]) than those with extensive or ultrarapid metabolizer status, but there was no evidence of difference in major bleeding. Conclusions There were significant differences in recurrent stroke by CYP2C19 genotype‐inferred metabolizer status in white subcortical stroke patients receiving dual antiplatelet therapy with aspirin and clopidogrel, consistent with cardiovascular studies on CYP 2C19 and clopidogrel; however, the bleeding risk that led to early termination of the antiplatelet arm of the SPS 3 trial does not appear to be explained by CYP 2C19 genotype. This study was relatively underpowered; therefore, these findings should be interpreted with caution and warrant replication. Clinical Trial Registration URL : www.clinicaltrials.gov . Unique identifier: NCT 00059306.

The objective of this study was to assess the prevalence of restless legs syndrome (RLS) among patients with stroke and to examine the anatomical correlation between location of stroke and RLS symptoms.We administered a pre-structured sleep questionnaire to consecutive stroke patients seen in our neurology services department over a 3-year period. Unconscious (Glasgow Coma Scale score15) or aphasic, renally impaired, or neuropathic patients were excluded. Diagnosis of RLS was established according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG), and polysomnography was conducted.Of 346 stroke patients, 35 (10.11%) fulfilled IRLSSG diagnostic criteria for RLS, which had existed for an average (±standard deviation) of 60 ± 40 months before stroke. The mean age of onset was 52.94 (±10.32) years. Twenty-four patients (68%) had RLS symptoms contralateral to the hemisphere involved in the stroke (eight with unilateral and 16 with grossly asymmetrical RLS). Twenty-nine of 35 patients (82.86%) had imaging evidence of subcortical (16 with hemorrhagic and 13 with ischemic) stroke. Patients with pre-stroke RLS differed from those without it only by subcortical location of the stroke (82.9% vs 31.5% respectively, p 0.001). The most significant differentiating factor between patients with subcortical stroke and those with cortical stroke was pre-stroke RLS (22.83% vs 2.74%, p 0.001), the others being history of hypertension and hemorrhagic stroke type.RLS, especially unilateral or asymmetrical, might frequently pre-exist in patients presenting with subcortical stroke. The common laterality may suggest an important predictive value for RLS, and may form an important point for future research.

et al., [Background and Purpose]: Translational research is beginning to reveal the importance of trophic factors as a therapy for cellular brain repair. The purpose of this study was to analyze whether brain-derived neurotrophic factor (BDNF) administration could mediate oligodendrogenesis and remyelination after white matter injury in subcortical stroke. [Methods]: Ischemia was induced in rats by injection of endothelin-1. At 24 hours, 0.4 μg/kg of BDNF or saline was intravenously administered to the treatment and control groups, respectively. Functional evaluation, MRI, and fiber tract integrity on tractography images were analyzed. Proliferation (KI-67) and white matter repair markers (A2B5, 2,3-cyclic-nucleotide 3-phosphodiesterase [CNPase], adenomatous polyposis coli [APC], platelet-derived growth factor receptor alpha [PDGFR-α], oligodendrocyte marker O4 [O4], oligodendrocyte transcription factor [Olig-2], and myelin basic protein [MBP]) were analyzed at 7 and 28 days. [Results]: The BDNF-treated animals showed less functional deficit at 28 days after treatment than the controls (P, This study was supported by research grants PS12/01754 (P.I.: Dr Díez-Tejedor), INVICTUS Spanish Neurovascular Network RD12/0014/0006 (Dr Fuentes and J. Ramos-Cejudo) and Sara Borrell postdoctoral fellowship CD12/00706 (Dr Otero-Ortega) from the Research Institute Carlos III, Ministry of Science and Innovation of Spain.

Movements of the paretic hand in patients with chronic subcortical stroke are associated with high interhemispheric inhibition (IHI) targeting the motor cortex in the lesioned hemisphere relative to healthy controls. The purpose of this investigation was to determine whether this abnormality also involves IHI operating during movements of the non-paretic hand. Here, we studied IHI in the process of generation of voluntary index finger movements by the paretic and non-paretic hands in a simple reaction time paradigm in a group of patients with chronic subcortical stroke. With movements of the non-paretic index finger, IHI targeting the contralateral primary motor cortex ((c)M1) decreased progressively to turn into facilitation at around movement onset, similar to healthy controls. In contrast, movements of the paretic index finger resulted in significantly deeper inhibition at all premovement timings relative to the non-paretic hand. In conclusion, these results document a deeper premovement IHI with paretic than non-paretic hand movements of patients with chronic subcortical stroke, a possible mechanism underlying deficits in motor control.

Five patients with left striatocapsular infarction were studied twice with PET during auditory-cued right thumb-index tapping, around 2 months after stroke and again around 8 months after stroke. At PET1 and PET2, the ipsilesional primary sensorimotor (SM1) activation peak Talairach coordinates were compared to those from seven aged-matched healthy controls. At PET1, there was a significant posterior displacement of SM1 activation peak, which confirms a previous report and may represent unmasking/disinhibition of motor representations. Over time, there was no significant change in the coordinates, and no significant correlation between coordinate changes from PET1 to PET2 and concomitant motor recovery. The implications of posterior displacement of SM1 activation peak for recovery therefore remain elusive.

Introduction Since early days after stroke, the brain undergoes a complex reorganization to allow compensatory mechanisms that promote functional recovery. Characterizing specific neurophysiological markers of motor recovery after stroke could improve clinical decision making. Objectives: To track the time-course of motor cortical reorganization in a stroke patients group, and to individuate the neurophysiological markers associated to clinical outcome. Patients & methods Ten patients in the sub-acute phase of ischemic subcortical stroke were evaluated within 20 days and after 40, 60 and 180 days after stroke. For each time-point, cortical reactivity and cortical oscillations changes, evoked by 80 single TMS pulses, were assessed over the motor cortex of the affected and unaffected hemisphere, combining TMS-EEG. These measurements were paralleled with motor and clinical evaluations. Repeated measures ANOVA and Friedman test were used to evaluate changes over time of all measures. Results Our data showed specific cortical oscillatory activity changes in the alpha band, in a specific time point of the longitudinal evaluation only in the affected hemisphere. Stroke patients showed a significant increase in TMS-evoked alpha oscillations, as highlighted by spectral perturbation analysis. Notably, these changes occurred at 60 days after stroke, indicating that crucial mechanisms of cortical reorganization occur in this short-time window. Moreover, a cortical reactivity increase was observed at 40 days after stroke onset in affected hemisphere respect to other times and respect to unaffected hemisphere. These changes coincided with the clinical and behavioural amelioration. Conclusion For the first time, this study demonstrates the possibility to track longitudinally the motor cortical changes following stroke, by means a multimodal approach. These findings could allow, not only to identify neurophysiological markers of stroke pathophysiology, but also to provide new insight into how and when neuromodulatory interventions could drive neuroplasticity in a functional direction.

Methods: Eighteen patients with stroke and 8 healthy volunteers were tested twice within a 1-week period by 2 examiners using TMS to determine MEPs and TMCT for the abductor pollicis brevis muscle of their affected and unaffected hands.Results: The authors found moderate to perfect reliability of TMS-induced MEPs in healthy volunteers, noninfarcted hemispheres (perfect agreement), and infarcted hemispheres (Kappa's = 0.45-0.87). Reliability of TMCT was good to excellent in the volunteers (intraclass correlation coefficients = 0.77-0.97), excellent in the noninfarcted hemispheres (intraclass correlation coefficients = 0.97-1.00), and poor to excellent in the infarcted hemispheres (intraclass correlation coefficients = 0.44-0.90).Conclusions: The reliability of TMS-induced MEPs and TMCT measurements in healthy volunteers and the noninfarcted hemisphere of patients with stroke with an upper paretic limb was good to excellent. In contrast, TMS measurements in the infarcted hemisphere were less consistent. Based on the lower reproducibility of TMCT measurements in the infarcted hemisphere, we recommend to repeat the TMCT measurements to improve the reliability of tests.Purpose: Motor evoked potentials (MEPs) and total motor conduction time (TMCT) induced by transcranial magnetic stimulation (TMS) are used to make assumptions about the prognosis of motor outcome after stroke. Understanding the different sources of variability is fundamental to the concept of reliability. Reliability testing of TMS-MEPs and TMCTs within and between two independent examiners in healthy and stroke subjects is still an unexplored field in the clinical neurophysiology. Assessing the reproducibility of TMS measurements requires studies to investigate the test-retest reliability of TMS-induced MEPs and TMCT. The authors set out to test the reliability of these TMS measurements.

In this issue of Clinical Neurophysiology, Takechi and colleagues publish a paper entitled “Longitudinal changes of motor cortical excitability and transcallosal inhibition after subcortical stroke” that represents a long-overdue examination of changes in inter-hemispheric interactions during an important period for the recovery of motor function after stroke. It has been suspected that this type of recovery to neuronal damage represents a type of neuroplasticity, potentially with both adaptive and maladaptive processes. But in order to demonstrate plasticity, one has to demonstrate change over time.

A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow (CBF) has been described after subcortical stroke with positron emission tomography. However, this imaging modality cannot be applied routinely to stroke patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might be interesting in the assessment of these effects. Dynamic T2-weighted echo planar imaging was used to produce DSC-MR images during an intravenous bolus injection of gadopentetate dimeglumine in 9 patients who experienced a subcortical stroke involving thalamus or basal ganglia and in 8 control subjects. A series of 50 consecutive images at 1-second intervals was acquired at the anatomic level of the centrum semiovale quite distant from the subcortical lesion, rCBF and rCBV were determined over frontal and parietal regions of interest and through the entire cortical mantle. DSC-MRI enabled the detection of hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF values showed that the hemodynamic parameters were significantly decreased on the affected side. In controls mean rCBF and rCBV values recorded over the whole cortical mantle of each hemisphere showed no significant interhemispheric asymmetry.

The utility of the Clock Drawing Test (CDT) in localizing lesions has not been thoroughly examined to date. In the present study, six scoring systems (Freedman et al., 1994; Ishiai, Sugishita, Ichikawa, Gono, & Watabiki, 1993; Mendez, Ala, & Underwood, 1992; Rouleau, Salmon, Butters, Kennedy, & McGuife, 1992; Sunderland et al., 1989; Tuokko, Hadjistavropoulos, Miller, & Beattie, 1992; Watson, Arfken, & Birge, 1993; Wolf-Klein, Silverstone, Levy, & Brod, 1989) were used to assess clock drawings by 76 stroke patients and 71 normal controls. Significant differences were found between normals and stroke patients on all scoring systems for both quantitative and qualitative features of the CDT. Quantitative indices were not helpful in differentiating between various stroke groups (left versus right versus bilateral stroke; cortical versus subcortical stroke; anterior versus posterior stroke). Qualitative features were helpful in lateralizing lesion site and differentiating subcortical from cortical groups. Correlational analyses revealed that CDT performance was related to visuospatial processing and measures commonly used in cognitive screening.

White matter stroke is a common clinical problem, which leads to distinct histological changes that are different than immune-mediated demyelination. The temporal changes occurring in white matter stroke such as acute loss of axons and astrocytic and microglia responses are likely to change the milieu of the stroke white matter into an inhibitory environment to the remyelination process. Based on the limited number of studies investigating acute and chronic injury states of demyelination, it is yet unclear if a window of opportunity exists after white matter stroke to enhance white matter repair. Although stroke-specific inhibitory mechanisms are not well known, a comprehensive list of pro- and anti-remyelination factors derived from non-stroke white matter diseases is in place to guide further investigation.

Objective A general lack of longitudinal studies on interhemispheric interactions following stroke led us to use transcranial magnetic stimulation (TMS) to examine changes in corticospinal/intracortical excitability and transcallosal inhibition over a 1-year period following subcortical stroke. Methods We measured TMS parameters such as motor threshold (MT), short-interval intracortical inhibition (SICI), and ipsilateral silent period (iSP) and evaluated clinical scores at three time-points (T1, T2, and T3) in 24 patients and 25 age-matched healthy subjects. Results At T1, we observed reduced MTs and SICIs with prolonged iSPs in the unaffected hemisphere (UH). In contrast, increased MTs and reduced SICIs were observed in the affected hemisphere (AH). These abnormalities gradually reduced and no MEP response to TMS at T1 predicted a worse prognosis. The prolonged iSP at T1 was associated with more severe impairments, but it did not necessarily predict a worse prognosis after 1 year. Conclusions UH excitability was increased at the post-acute time-period, which may have resulted in enhanced transcallosal inhibition to the AH. However, it is unclear whether there was a causal relationship between the enhanced transcallosal inhibition and the extent of clinical recovery. Significance This is the first study to demonstrate changes in transcallosal inhibition over a longitudinal period following stroke.

A large number of functional imaging studies have focused on the understanding of motor-related neural activities after ischemic stroke. However, the knowledge is still limited in the structural and functional changes of the interhemispheric connections of the bilateral primary motor cortices (M1s) and their potential influence on motor function recovery following stroke. Twenty-four stroke patients with right hemispheric subcortical infarcts and 25 control subjects were recruited to undergo multimodal magnetic resonance imaging examinations. Structural impairments between the bilateral M1s were measured by fractional anisotropy. Functional changes of the bilateral M1s were assessed via M1-M1 resting-state functional connectivity. Task-evoked activation analysis was applied to identify the roles of the bilateral hemispheres in motor function recovery. Compared with control subjects, unilateral subcortical stroke patients revealed significantly decreased fractional anisotropy and functional connectivity between the bilateral M1s. Stroke patients also revealed higher activations in multiple brain regions in both hemispheres and that more regions were located in the contralesional hemisphere. This study increased our understanding of the structural and functional alterations between the bilateral M1s that occur in unilateral subcortical stroke and provided further evidence for the compensatory role played by the contralesional hemisphere for these alterations during motor function recovery.

Objective: To study serial changes in motor cortical excitability and transcallosal inhibition during post-acute and chronic phases up to one year after subcortical stroke.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are well-established tools for investigating the human motor system in-vivo. We here studied the relationship between movement-related fMRI signal changes in the primary motor cortex (M1) and electrophysiological properties of the hand motor area assessed with neuronavigated TMS in 17 healthy subjects. The voxel showing the highest task-related BOLD response in the left hand motor area during right hand movements was identified for each individual subject. This fMRI peak voxel in M1 served as spatial target for coil positioning during neuronavigated TMS. We performed correlation analyses between TMS parameters, BOLD signal estimates and effective connectivity parameters of M1 assessed with dynamic causal modeling (DCM). The results showed a negative correlation between the movement-related BOLD signal in left M1 and resting as well as active motor threshold (MT) obtained for left M1. The DCM analysis revealed that higher excitability of left M1 was associated with a stronger coupling between left supplementary motor area (SMA) and M1. Furthermore, BOLD activity in left M1 correlated with ipsilateral silent period (ISP), i.e. the stronger the task-related BOLD response in left M1, the higher interhemispheric inhibition effects targeting right M1. DCM analyses revealed a positive correlation between the coupling of left SMA with left M1 and the duration of ISP. The data show that TMS parameters assessed for the hand area of M1 do not only reflect the intrinsic properties at the stimulation site but also interactions with remote areas in the human motor system. Hum Brain Mapp, 2011. (c) 2011 Wiley-Liss, Inc.

Vascular cognitive impairment (VCI) is characterized by cognitive compromise predominantly of executive dysfunction. OBJECTIVES: To assess cognitive functions in VCI, focusing on executive functions, to observe functional losses in relation to activities of daily living (ADLs) and to detect early symptoms prior to the onset of dementia. METHODS: We evaluated healthy subjects matched for gender, education and age to patients with diagnosis of subcortical vascular disease who had a stroke classified into three groups: 1) vascular lesions and no impairment; 2) vascular cognitive impairment with no dementia (VCIND); 3) vascular dementia (VaD). RESULTS AND DISCUSSION: The performance on neuropsychological tests differed among groups, worsening with increased impairment level. The probable VaD group demonstrated impaired performance in memory, processing speed and verbal production, while the VCIND group showed attention deficits. CONCLUSION: Impairment in executive functions and difficulties in ADLs allow us to differentiate levels of impairment in groups of subcortical vascular disease. O comprometimento cognitivo vascular (CCV) é caracterizado por comprometimento cognitivo predominantemente sob a forma de disfunção executiva. OBJETIVOS: Avaliar as funções cognitivas no CCV, enfocando as funções executivas, observar as perdas funcionais em relação às atividades cotidianas (AVDs) e detectar os primeiros sintomas antes do início da demência. MÉTODOS: Foram avaliados indivíduos controles saudáveis pareados por sexo, escolaridade e idade com pacientes com diagnóstico de doença vascular subcortical que sofreram derrame classificados em três grupos: 1) lesões vasculares sem déficit; 2) comprometimento cognitivo vascular sem demência (CCVSD); 3) demência vascular (DV). RESULTADOS E DISCUSSÃO: O desempenho em testes neuropsicológicos diferiu entre os grupos, sendo o desempenho tanto pior quanto maior o comprometimento. O grupo DV provável demonstrou desempenho prejudicado na memória, velocidade de processamento e produção verbal, enquanto o grupo CCVSD apresentou déficit de atenção. CONCLUSÃO: Prejuízos nas funções executivas e dificuldades em AVDs permitem diferenciar os níveis de comprometimento nos grupos de doença vascular subcortical.

After acute stroke several changes in cortical excitability occur involving affected (AH) and unaffected hemisphere (UH) but whether they contribute to motor recovery is still controversial. We performed transcranial magnetic stimulation mapping of several upper limb muscles over the two hemispheres in thirteen patients at 4-12 days from subcortical stroke and after 1 month. The occurrence of mirror movements (MMs) on the healthy side during contraction of paretic muscles was measured. At baseline, cortical excitability parameters over the AH decreased in comparison with controls, while excitability over the UH increased correlating with severity of motor deficits of the affected arm at baseline as well as with poor recovery. At follow-up, map parameters of the UH became closer to those of controls independently from recovery, while for the AH the number of responsive sites increased significantly. Ipsilateral motor evoked responses (iMEPs) in the affected arm were never elicited. We observed an early impairment in dexterity of the ipsilesional hand that recovered over-time but persistently differed in comparison with controls. MMs occurrence increased at baseline correlating with reduced cortical excitability of the AH as well as with increased map density over the UH. The acute increased excitability of the UH after stroke has a negative prognostic value on recovery and negatively affects motor performance of the ipsilesional hand. Moreover, the absence of iMEPs and the normalization of motor cortical excitability at follow-up indicate that the UH primary motor area does not contribute to recovery.

Background and Purpose Previous studies have noted changes in resting-state functional connectivity during motor recovery following stroke. However, these studies always uncover various patterns of motor recovery. Moreover, subgroups of stroke patients with different outcomes in hand function have rarely been studied. Materials and Methods We selected 24 patients who had a subcortical stroke in the left motor pathway and displayed only motor deficits. The patients were divided into two subgroups: completely paralyzed hands (CPH) (12 patients) and partially paralyzed hands (PPH) (12 patients). Twenty-four healthy controls (HC) were also recruited. We performed functional connectivity analysis in both the ipsilesional and contralesional primary motor cortex (M1) to explore the differences in the patterns between each pair of the three diagnostic groups. Results Compared with the HC, the PPH group displays reduced connectivity of both the ipsilesional and contralesional M1 with bilateral prefrontal gyrus and contralesional cerebellum posterior lobe. The connectivity of both the ipsilesional and contralesional M1 with contralateral primary sensorimotor cortex was reduced in the CPH group. Additionally, the connectivity of the ipsilesional M1 with contralesional postcentral gyrus, superior parietal lobule and ipsilesional inferior parietal lobule was reduced in the CPH group compared with the PPH group. Moreover, the connectivity of these regions was positively correlated with the Fugl-Meyer Assessment scores (hand+wrist) across all stroke patients. Conclusions Patterns in cortical connectivity may serve as a potential biomarker for the neural substratum associated with outcomes in hand function after subcortical stroke.

In a single case longitudinal study, a 70 year old female subject who has had a subcortical stroke 8 years prior, was tested three times in fMRI using an interactive MRI-compatible VR environment. The subject performed sequential finger movements with her right (unaffected) hand. Her hand motion (recorded with the data glove) animated either the ipsilateral (corresponding) or contralateral (mirrored) virtual hand model. In a visual feedback control condition, the virtual hand models were replaced with ellipsoids. In between the second and third session, the patient participated in an intensive, two-week long VR-based training of her affected upper extremity. When comparing activation in the mirrored versus the non-mirrored virtual visual feedback condition, no significant activation was noted in motor or premotor areas in the baseline 1 or baseline 2 sessions. However, increased activation in the ipsilesional motor cortex occurred as a result of training, despite the absence of active involvement of the ipsilesional motor cortex in this condition. The left motor cortex was also recruited in this condition (though weaker) despite the subtracted out ellipsoid condition (in which subjects also moved their hand). Thus, the contralateral (mirrored) visual feedback may have had a facilitory effect bilaterally. These findings might have some important implications for the development of novel therapies in the acute phase, when paresis and the potential for neural remapping are greatest.

Background. Motor imagery may enhance motor recovery after stroke. Objectives. To estimate the proportion of patients able to perform motor imagery, the feasibility of delivery of motor imagery training (MIT), and the effects of MIT on motor recovery in an exploratory study. Methods. An immediate pretreatment and posttreatment single-group design was used to study 10 patients after subcortical stroke with neuromuscular weakness in the upper limb. MIT that included upper limb activities reflecting everyday tasks was provided for 10 consecutive working days. Measures included assessment of chaotic motor imagery, patient report of tolerability of MIT, Motricity Index (MI), Nine Hole Peg Test (9HPT), and quality of movement (MAL-QOM). MIT dose was changed in response to patient feedback. Graphed motor function scores were inspected visually for clinically important changes. Results. Four of the 10 patients were unable to perform motor imagery. Patient opinion was positive about the content and shaped daily dose of MIT given in two 20-minute periods separated by a 10-minute rest. Clinically important changes in motor scores were found. Four patients increased MI score (range 8-16), 3 patients increased 9HPT score (range 0.02-0.04 pegs/second), and 4 patients increased MAL-QOM score (range 0.63-1.29). Conclusions. MIT was received positively by patients, but 40% were unable to perform imagery and interindividual variations were found on motor function.

The nature of impairment in hand motor control after stroke and its relationship to hand function are still not well understood. In this study, we investigated digit independence in patients with subcortical stroke (n = 8) and moderate hand impairment, defined by wrist and hand Fugl-Meyer scale scoresor =25/33, and age-matched controls (n = 8). Subjects made cyclical flexion-extension movements of an instructed digit while keeping the other digits as still as possible. Movements of the metacarpo-phalangeal (MCP) joints of the five digits were measured using an instrumented glove. The ability to move an instructed digit individually (individuation index), and the ability to keep a noninstructed digit as still as possible (stationarity index) were determined for each digit. Contrary to the finding of normal thumb individuation in a recent study of patients with variable hand motor impairment after stroke, we found that independent movement for all digits was significantly impaired, although individuation and stationarity were differentially affected for each digit. All the digits, including the thumb, showed a similar impairment in individuation. In contrast, stationarity was affected in a digit-dependent pattern: the thumb was affected least, and the middle finger was most impaired. Stroke subjects did not extend their digits fully to the baseline position, and the angular displacement at maximum digit extension correlated significantly with digit individuation. Contrary to expectation, digit independence correlated weakly with clinical tests of hand function, which emphasize grasp. This suggests that corticospinal projections might be separated with respect to function rather than finger topography.

Stroke patients may present an altered hemodynamic response compared to healthy subjects. The magnitude of the BOLD fMRI response may considerably differ from the hemodynamic response function (hrf) commonly used in the analysis of the fMRI data, and, as a consequence, a BOLD signal may fail to be detected in stroke patients. The aim of the work is to develop a new method for the fMRl data analysis, suitable for the detection of cerebral activated areas in stroke patients. An analysis of the signal variance is used in order to calculate, for the anatomic areas of interest, the average BOLD signal time-course, to be used in turn as the reference function (hrf) in a correlation analysis. This way of analyzing fMRI data allows the detection of activation in the cortical sensorimotor areas not detected by a statistical analysis that uses a standard hrf as reference function.

Objective: Motor evoked potential (MEP) amplitude and threshold are predictors of functional outcome in the early stages after stroke, and improvement in these parameters usually accompanies motor recovery. The aim of this study in patients with subcortical stroke was to determine whether there is a correlation between MEP amplitude and threshold and the degree of recovery of strength and dexterity in the affected hand. Methods: MEP amplitude and threshold were measured on the affected and unaffected sides in 23 patients who had suffered a subcortical ischaemic stroke up to 23 years previously. Grip strength was measured using a hand-held dynamometer and dexterity was assessed using a modification of the McCarron test battery. Results: Grip strength correlated with both MEP amplitude and threshold (r=0.49 and r=−0.54, respectively, P

It remains uncertain if the contralesional primary sensorimotor cortex (CL_PSMC) contributes to motor recovery after stroke. Here we investigated longitudinal changes in the resting-state functional connectivity (rsFC) of the CL_PSMC and their association with motor recovery. Thirteen patients who had experienced subcortical stroke underwent a series of resting-state fMRI and clinical assessments over a period of 1 year at 5 time points, i.e., within the first week, at 2 weeks, 1 month, 3 months, and 1 year after stroke onset. Thirteen age- and gender-matched healthy subjects were recruited as controls. The CL_PSMC was defined as a region centered at the voxel that had greatest activation during hand motion task. The dynamic changes in the rsFCs of the CL_PSMC within the whole brain were evaluated and correlated with the Motricity Index (MI) scores. Compared with healthy controls, the rsFCs of the CL_PSMC with the bilateral PSMC were initially decreased, then gradually increased, and finally restored to the normal level 1 year later. Moreover, the dynamic change in the inter-hemispheric rsFC between the bilateral PSMC in these patients was positively correlated with the MI scores. However, the intra-hemispheric rsFC of the CL_PSMC was not correlated with the MI scores. This study shows dynamic changes in the rsFCs of the CL_PSMC after stroke and suggests that the increased inter-hemispheric rsFC between the bilateral PSMC may facilitate motor recovery in stroke patients. However, generalization of our findings is limited by the small sample size of our study and needs to be confirmed.

We prospectively studied 5 patients while they were recovering from left-sided subcortical stroke affecting the cortico-spinal tract, and examined them twice with H(2)(15)O-PET over several months while performing an identical task with the affected hand. Concomitant motor recovery was assessed by measuring the number of thumb-to-index tappings performed in 15 s at each PET session. Across patients, the hemispheric activation balance tended to shift over time toward the unaffected hemisphere, but the magnitude of this shift was highly variable from patient to patient and significantly correlated with recovery. Thus, in subcortical stroke, a shift of activation balance towards the unaffected hemisphere appears associated with lesser initial recovery and, conversely, the more this physiological balance is maintained over time the better the recovery.

The present study has investigated the long-term changes in the organisation of the corticomotor projection to the hand in a group of subjects who had sustained a subcortical hemispheric stroke up to 15 years previously and had subsequently recovered normal or near-normal motor function. Transcranial magnetic cortical stimulation (TMCS) was employed to map the topography of the primary corticomotor projection to the hand and to obtain measures of cortical motor threshold, long-latency intracortical inhibition and corticospinal conduction. Changes in motor threshold and in motor-evoked potential (MEP) amplitude and latency in keeping with persisting impairment of conduction in the corticospinal pathway were still present in the majority of subjects, whereas the duration of the post-MEP silent period, reflecting the strength of long-latency intracortical inhibition, was usually normal. Topographic shifts in the corticomotor representation relative to the unaffected side were found in the majority of subjects. In some the shifts were in the mediolateral axis suggesting reorganisation within the primary motor cortex, while in the others anteroposterior shifts were present in keeping with recruitment of premotor or postcentral cortex. The present findings indicate that changes in the physiological properties of the corticomotor projection to the hand are frequently present in subjects who have recovered motor function after a subcortical stroke and may persist indefinitely. We postulate that these changes are the result of reorganisation at cortical level and that cortical reorganisation is one of the processes which contribute to motor recovery after a subcortical lesion and which may compensate for persisting impairment of conduction in the corticospinal pathway.

WCN 2013 No: 1745 Topic: 2 — Movement Disorders Posterior SMA syndrome after subcortical stroke: Contralateral akinesia reversed by visual control N. Radman, S. Cacioppo, L. Spierer, E. Schmidlin, E. Mayer, J.-M. Annoni. Laboratory for Cognitive and Neurological Sciences, Department for Medicine, Neurology, University of Fribourg, Fribourg, Switzerland; High Performance Electrical Neuroimaging Laboratory, CCSN, Department of Psychology, University of Chicago, Chicago, IL, USA; Department of Medicine, Physiology, University of Fribourg, Fribourg, Switzerland; Departement of Neurology, Geneva University Hospital

Objective To correlate motor deficit with involvement of corticofugal fibres in patients with subcortical stroke. The descending motor corticofugal fibres originate from the primary motor cortex (M1), dorsal and ventral premotor area (PMdv) and supplementary motor area (SMA). Design Retrospective study. Setting Single tertiary teaching hospital. Participants 57 patients (57% men) with subcortical infarcts on MRI (2009–2011) were included. The mean age was 64.3±14.4 years. Interventions None. Primary and secondary outcome measures National Institute of Health Stroke Scale subscores for arm and leg motor deficit at 90 days. Results An area under the receiver operating characteristics curve (AUC) for the volume of overlap with infarct (and M1/PMdv/SMA fibres) and motor outcome was calculated. The AUC for the association with arm motor deficit from M1 fibres involvement was 0.80 (95% CI 0.66 to 0.94), PMdv was 0.76 (95% CI 0.61 to 0.91) and SMA was 0.73 (95% CI 0.58 to 0.88). The AUC for leg motor deficit from M1 fibres involvement was 0.69 (95% CI 0.52 to 0.85), PMdv was 0.67 (95% CI 0.50 to 0.85), SMA was 0.66 (95% CI 0.48 to 0.84). Conclusions Following subcortical stroke, the correlations between involvement of the corticofugal fibres for upper and lower limbs motor deficit were variable. A poor motor outcome was not universal following subcortical stroke.