Motor disinhibition in affected and unaffected hemisphere in the early period of recovery after stroke.

OBJECTIVES: To investigate motor disinhibition in affected and unaffected motor areas in the acute stage after stroke and during the early period of recovery. METHODS: Fifteen patients with moderate to severe hemiparesis after acute unilateral stroke were compared with 10 healthy age-matched controls. We used paired transcranial magnetic stimulation to study intracortical inhibition and facilitation from the thenar eminence muscles on both sides. F-wave from the median nerve on both sides were recorded. The recordings were performed 5-7 days (T1) and 30 days after stroke. RESULTS: In 10 patients who showed the presence of reliable motor evoked potentials on the affected side, intracortical inhibition was significantly reduced. On the unaffected side intracortical inhibition (ICI) was significantly reduced in all patients. Patients who presented significant motor recovery after 30 days showed persistence of abnormal disinhibition in the affected hemisphere but a return to normal ICI in the unaffected hemisphere. Patients with poor motor recovery showed persistence of abnormal disinhibition on both sides. No significant changes were observed in F-wave amplitude. CONCLUSIONS: Motor disinhibition occurs on both sides after stroke in all acute stage patients. Changes in motor disinhibition on unaffected side also are related to motor recovery.     

Enhanced motor cortical excitability in the unaffected hemisphere after hemispherectomy

We evaluated motor cortical excitability of the unaffected hemisphere in three patients with intractable epilepsy who underwent hemispherectomy, using transcranial magnetic stimulation (TMS) and PET. TMS of the unaffected hemisphere evoked motor responses not only in the contralateral muscles but also in the ipsilateral ones in all the patients. A PET study in one patient showed activation of the unaffected motor cortex by movement of either arm. All of these responses were enhanced after the hemispherectomy, probably due to motor cortical disinhibition by transection of the corpus callosum. The PET study also showed postoperative activation of the premotor area of the unaffected hemisphere. These phenomena indicate posthemispherectomy neuroplastic reorganization leading to preservation of the motor function after the operation.     

Motor cortex disinhibition of the unaffected hemisphere after acute stroke

We studied motor cortex excitability in the nonlesioned hemisphere of patients with a large cortical infarction. Patients with a severe hemiparesis due to a stroke were compared with age-matched, healthy controls. Paired transcranial magnetic stimuli were applied over the unaffected hemisphere to investigate intracortical inhibition and facilitation. In the patient group, intracortical inhibition was reduced. We suggest that this disinhibition is due to an impairment of transcallosal fibers and may affect recovery.     

The role of the intact hemisphere in recovery of midline muscles after recent monohemispheric stroke

Transcranial magnetic stimulation (TMS) of the motor cortex was used to study basic mechanisms of motor reorganization after major hemispheric stroke in humans. We sought to clarify the possible role of the intact hemisphere in motor recovery of the lingual muscles, and to evaluate the compensatory use of preexisting uncrossed motor pathways projecting to these midline muscles. TMS and bilateral surface recordings from the lingual muscles were carried out in six selected stroke patients who presented with a unilateral lingual paralysis after a limited monohemispheric ischemia. The first examination was performed during the symptomatic stage (t ₁) and was repeated after complete recovery of lingual function had been established (t ₂). The cortical motor output patterns were analyzed and compared with the data from 40 healthy controls. In the controls TMS of either hemisphere invariably produced contralateral and ipsilateral compound muscle action potentials (CMAPs), elicited through crossed and uncrossed central motor pathways, respectively. In most individuals an asymmetric cortical motor output pattern was found, as significantly greater mean CMAPs of shorter onset latencies were recorded from the contralateral lingual muscles than from the ipsilateral responses. In the six patients with a unilateral lingual paralysis a similar pattern was found on initial examination by stimulating the intact hemisphere, whereas TMS of the affected hemisphere failed to elicit any CMAP bilaterally. At t ₂ all patients had regained normal lingual function. Only one patient showed evidence of a complete recovery of the primarily affected hemisphere, as TMS now elicited normal CMAPs bilaterally. In the remaining five patients the unilateral interruption of the corticonuclear pathways persisted in spite of complete functional recovery. In these subjects the recovery of symmetric lingual movements must be attributed to the intact hemisphere. From this it is concluded that recovery of a unilateral lingual paralysis after restricted monohemispheric lesions is possible without recovery of the cortical motor projections from the affected hemisphere. In these cases the intact hemisphere is responsible for restoration of normal lingual movements, most likely by potentiating the effect of preexisting uncrossed motor pathways. Received: 26 March 1998 Accepted: 24 June 1998     

Periinfarct rewiring supports recovery after primary motor cortex stroke

After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with recovery involves the periinfarct or more remote regions. We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were assessed at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of recovery were investigated at three spatial scales, (i) ipsilesional non-infarcted M1, (ii) core motor network (M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and (iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Hand dexterity was impaired only in the acute phase (P = 0.036). At a small spatial scale, clinical recovery was more frequently associated with connections involving ipsilesional non-infarcted M1 (Odds Ratio = 6.29; P = 0.036). At a larger scale, recovery correlated with increased FC strength in the core network compared to the extended motor network (rho = 0.71;P = 0.006). These results suggest that FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. Core motor regions, and more specifically ipsilesional non-infarcted M1, could hence become primary targets for restorative therapies.     

Early motor network connectivity after stroke: An interplay of general reorganization and state‐specific compensation

Motor recovery after stroke relies on functional reorganization of the motor network, which is commonly assessed via functional magnetic resonance imaging (fMRI)‐based resting‐state functional connectivity (rsFC) or task‐related effective connectivity (trEC). Measures of either connectivity mode have been shown to successfully explain motor impairment post‐stroke, posing the question whether motor impairment is more closely reflected by rsFC or trEC. Moreover, highly similar changes in ipsilesional and interhemispheric motor network connectivity have been reported for both rsFC and trEC after stroke, suggesting that altered rsFC and trEC may capture similar aspects of information integration in the motor network reflecting principle, state‐independent mechanisms of network reorganization rather than state‐specific compensation strategies. To address this question, we conducted the first direct comparison of rsFC and trEC in a sample of early subacute stroke patients (n = 26, included on average 7.3 days post‐stroke). We found that both rsFC and trEC explained motor impairment across patients, stressing the clinical potential of fMRI‐based connectivity. Importantly, intrahemispheric connectivity between ipsilesional M1 and premotor areas depended on the activation state, whereas interhemispheric connectivity between homologs was state‐independent. From a mechanistic perspective, our results may thus arise from two distinct aspects of motor network plasticity: task‐specific compensation within the ipsilesional hemisphere and a more fundamental form of reorganization between hemispheres.     

健侧大脑低频阈上rTMS对急性期脑梗死患者运动功能恢复的价值

目的 观察低频阈上重复经颅磁刺激(rTMS)作用于急性期脑梗死患者健侧大脑对患者运动功能恢复的价值. 方法 选取自2007年9月至2009年2月在苏州大学附属第二医院神经内科治疗的大脑中动脉供血区脑梗死患者26例,按随机数字表法分为健侧刺激组及对照组,每组各13例.在发病后3～5 d,健侧刺激组患者行rTMS治疗[频率1 HZ,70％输出强度(约2.1T实际输出强度),1200脉冲/d,连续10 d],对照组不接受rTMS治疗.在治疗前(试验第1天)和治疗后第10、40天记录2组患者患侧脑区运动诱发电位(MEP)潜伏期、中枢运动传导时间(CMCT)值及美国国立卫生研究院卒中量表(NIHSS)评分、改良Barthel指数(MBI). 结果 治疗前2组患者临床功能评分和神经电生理指标比较差异无统计学意义(P＞0.05).治疗后第10、40天2组患者临床功能评分均较治疗前改善,差异均有统计学意义(P＜0.05),且健侧刺激组NIHSS评分及MBI均明显优于对照组,差异亦有统计学意义(P＜0.05).治疗后2组患者神经电生理指标均较治疗前改善,其中健侧刺激组MEP潜伏期在第40天、CMCT值在第10、40天较治疗前差异有统计学意义(P＜0.05),且健侧刺激组CMCT值较对照组在第10、40天均有明显缩短,差异有统计学意义(P＜0.05). 结论 频率1 HZ、70％输出强度(约2.1T实际输出强度)rTMS作用于急性期脑梗死患者健侧大脑能缩短CMCT值,对患者的运动功能恢复有促进作用.     

Imaging neurovascular function and functional recovery after stroke in the rat striatum using forepaw stimulation

Negative functional magnetic resonance imaging (fMRI) response in the striatum has been observed in several studies during peripheral sensory stimulation, but its relationship between local field potential (LFP) remains to be elucidated. We performed cerebral blood volume (CBV) fMRI and LFP recordings in normal rats during graded noxious forepaw stimulation at nine stimulus pulse widths. Albeit high LFP–CBV correlation was found in the ipsilateral and contralateral sensory cortices (r=0.89 and 0.95, respectively), the striatal CBV responses were neither positively, nor negatively correlated with LFP (r=0.04), demonstrating that the negative striatal CBV response is not originated from net regional inhibition. To further identify whether this negative CBV response can serve as a marker for striatal functional recovery, two groups of rats (n=5 each) underwent 20- and 45-minute middle cerebral artery occlusion (MCAO) were studied. No CBV response was found in the ipsilateral striatum in both groups immediately after stroke. Improved striatal CBV response was observed on day 28 in the 20-minute MCAO group compared with the 45-minute MCAO group (P<0.05). This study shows that fMRI signals could differ significantly from LFP and that the observed negative CBV response has potential to serve as a marker for striatal functional integrity in rats.     

Low‐frequency rTMS of the unaffected hemisphere in stroke patients: A systematic review

The aim of this review was to summarize the evidence for the effectiveness of low‐frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere in promoting functional recovery after stroke. We performed a systematic search of the studies using LF‐rTMS over the contralesional hemisphere in stroke patients and reviewed the 67 identified articles. The studies have been gathered together according to the time interval that had elapsed between the stroke onset and the beginning of the rTMS treatment. Inhibitory rTMS of the contralesional hemisphere can induce beneficial effects on stroke patients with motor impairment, spasticity, aphasia, hemispatial neglect and dysphagia, but the therapeutic clinical significance is unclear. We observed considerable heterogeneity across studies in the stimulation protocols. The use of different patient populations, regardless of lesion site and stroke aetiology, different stimulation parameters and outcome measures means that the studies are not readily comparable, and estimating real effectiveness or reproducibility is very difficult. It seems that careful experimental design is needed and it should consider patient selection aspects, rTMS parameters and clinical assessment tools. Consecutive sessions of rTMS, as well as the combination with conventional rehabilitation therapy, may increase the magnitude and duration of the beneficial effects. In an increasing number of studies, the patients have been enrolled early after stroke. The prolonged follow‐up in these patients suggests that the effects of contralesional LF‐rTMS can be long‐lasting. However, physiological evidence indicating increased synaptic plasticity, and thus, a more favourable outcome, in the early enrolled patients, is still lacking. Carefully designed clinical trials designed are required to address this question. LF rTMS over unaffected hemisphere may have therapeutic utility, but the evidence is still preliminary and the findings need to be confirmed in further randomized controlled trials.     

The unsolved role of heightened connectivity from the unaffected hemisphere to paretic arm muscles in chronic stroke

ObjectiveIpsilateral connectivity from the non-stroke hemisphere to paretic arm muscles appears to play little role in functional recovery, which instead depends on contralateral connectivity from the stroke hemisphere. Yet the incidence of ipsilateral projections in stroke survivors is often reported to be higher than normal. We tested this directly using a sensitive measure of connectivity to proximal arm muscles.MethodTMS of the stroke and non-stroke motor cortex evoked responses in pre-activated triceps and deltoid muscles of 17 stroke survivors attending reaching training. Connectivity was defined as a clear MEP or a short-latency silent period in ongoing EMG in ≥ 50% of stimulations. We measured reaching accuracy at baseline, improvement after training and upper limb Fugl-Meyer (F-M) score.ResultsIncidence of ipsilateral connections to triceps (47%) and deltoid (58%) was high, but unrelated to baseline reaching accuracy and F-M scores. Instead, these were related to contralateral connectivity from the stroke hemisphere. Absolute but not proportional improvement after training was greater in patients with ipsilateral responses.ConclusionsDespite enhanced ipsilateral connectivity, arm function and learning was related most strongly to contralateral pathway integrity from the stroke hemisphere.SignificanceFurther work is needed to decipher the role of ipsilateral connections.     

Imaging motor recovery after stroke

Most patients show improvement in the weeks or months after a stroke. Recovery is incomplete, however, leaving most with significant impairment and disability. Because the brain does not grow back to an appreciable extent, this recovery occurs on the basis of change in function of surviving tissues. Brain mapping studies have characterized a number of processes and principles relevant to recovery from stroke in humans. The findings have potential application to improving therapeutics that aim to restore function after stroke.     

Dynamic brain structural changes after left hemisphere subcortical stroke

This study aimed to quantify dynamic structural changes in the brain after subcortical stroke and identify brain areas that contribute to motor recovery of affected limbs. High‐resolution structural MRI and neurological examinations were conducted at five consecutive time points during the year following stroke in 10 patients with left hemisphere subcortical infarctions involving motor pathways. Gray matter volume (GMV) was calculated using an optimized voxel‐based morphometry technique, and dynamic changes in GMV were evaluated using a mixed‐effects model. After stroke, GMV was decreased bilaterally in brain areas that directly or indirectly connected with lesions, which suggests the presence of regional damage in these “healthy” brain tissues in stroke patients. Moreover, the GMVs of these brain areas were not correlated with the Motricity Index (MI) scores when controlling for time intervals after stroke, which indicates that these structural changes may reflect an independent process (such as axonal degeneration) but cannot affect the improvement of motor function. In contrast, the GMV was increased in several brain areas associated with motor and cognitive functions after stroke. When controlling for time intervals after stroke, only the GMVs in the cognitive‐related brain areas (hippocampus and precuneus) were positively correlated with MI scores, which suggests that the structural reorganization in cognitive‐related brain areas may facilitate the recovery of motor function. However, considering the small sample size of this study, further studies are needed to clarify the exact relationships between structural changes and recovery of motor function in stroke patients. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Coherent neural oscillations inform early stroke motor recovery

Neural oscillations may contain important information pertaining to stroke rehabilitation. This study examined the predictive performance of electroencephalography‐derived neural oscillations following stroke using a data‐driven approach. Individuals with stroke admitted to an inpatient rehabilitation facility completed a resting‐state electroencephalography recording and structural neuroimaging around the time of admission and motor testing at admission and discharge. Using a lasso regression model with cross‐validation, we determined the extent of motor recovery (admission to discharge change in Functional Independence Measurement motor subscale score) prediction from electroencephalography, baseline motor status, and corticospinal tract injury. In 27 participants, coherence in a 1–30 Hz band between leads overlying ipsilesional primary motor cortex and 16 leads over bilateral hemispheres predicted 61.8% of the variance in motor recovery. High beta (20–30 Hz) and alpha (8–12 Hz) frequencies contributed most to the model demonstrating both positive and negative associations with motor recovery, including high beta leads in supplementary motor areas and ipsilesional ventral premotor and parietal regions and alpha leads overlying contralesional temporal–parietal and ipsilesional parietal regions. Electroencephalography power, baseline motor status, and corticospinal tract injury did not significantly predict motor recovery during hospitalization (R ² = 0–6.2%). Findings underscore the relevance of oscillatory synchronization in early stroke rehabilitation while highlighting contributions from beta and alpha frequency bands and frontal, parietal, and temporal–parietal regions overlooked by traditional hypothesis‐driven prediction models.     

卒中后吞咽困难预后的预测指标

吞咽困难是脑卒中后常见的症状和严重的并发症,会降低经口摄食的安全性,导致营养不良、吸入性肺炎、高死亡率和不良的卒中预后.准确预测卒中后吞咽困难的恢复情况是临床医生决定喂养模式、采取适当的康复措施和加强并发症防控的关键,但目前这种预测主要依赖于医生的主观经验和风险评估.鉴于缺乏系统的预测方法和指标,本文系统回顾了脑卒中后...     

Transcranial direct current stimulation of the unaffected hemisphere in stroke patients

Recovery of function after a stroke is determined by a balance of activity in the neural network involving both the affected and the unaffected brain hemispheres. Increased activity in the affected hemisphere can promote recovery, while excessive activity in the unaffected hemisphere may represent a maladaptive strategy. We therefore investigated whether reduction of the excitability in the unaffected hemisphere by cathodal transcranial direct current stimulation could result in motor performance improvement in stroke patients. We compared these results with excitability-enhancing anodal transcranial direct current stimulation of the affected hemisphere and sham transcranial direct current stimulation. Both cathodal stimulation of the unaffected hemisphere and anodal stimulation of the affected hemisphere (but not sham transcranial direct current stimulation) improved motor performance significantly. These results suggest that the appropriate modulation of bihemispheric brain structures can promote motor function recovery.     

Functional neuroimaging in motor recovery after stroke

Neuroimaging techniques provide information on the neural substrates underlying functional recovery after stroke, the number one cause of long-term disability. Despite the methodological difficulties, they promise to offer insight into the mechanisms by which therapeutic interventions can modulate human cortical plasticity. This information should lead to the development of new, targeted interventions to maximize recovery.     

Unawareness of deficits after right hemisphere stroke: double-dissociations of anosognosias

OBJECTIVES: The aim was to study whether anosognosia for hemiparesis, anosognosia for neglect and general unawareness of illness double-dissociate, indicating that anosognosias are specific and independent impairments of awareness. On the other hand, anosognosias may be associated with one another and with general cognitive dysfunction, which decreases awareness of deficits. The persistence and predictive value of anosognosias was examined during a 1-year follow-up. PATIENTS AND METHODS: Fifty-seven consecutive patients with acute right hemisphere infarction underwent neurological and neuroradiological examinations, neuropsychological testing and an interview 10 days, 3 months and 1 year after onset. RESULTS: Anosognosia for neglect and anosognosia for hemiparesis double-dissociated, as did unawareness of illness and anosognosia for neglect. Patients showing unawareness of illness or anosognosia for neglect and anosognosia for hemiparesis had poorer orientation and verbal memory than patients who were aware of these defects. Unawareness of illness and anosognosia for hemiparesis disappeared during 3-month follow-up. CONCLUSION: Double-dissociations demonstrate that anosognosias for different defects are independent and specific impairments of awareness, although general cognitive disorder may also reduce awareness of defects. Unawareness of illness and anosognosia for hemiparesis disappear rapidly and can hardly be direct causes of poor long-term recovery. However, transient anosognosia may be associated with persistent disorders which result in poor outcome.     

Combination of early constraint-induced movement therapy and fasudil enhances motor recovery after ischemic stroke in rats

Purpose: Constraint-induced movement therapy (CIMT) is a promising technique for the recovery of upper extremity movement in chronic stroke patients. However, the effectiveness of its use in acute ischemia has not been confirmed. Myelin-associated inhibitors, which have upregulated functions in tissues affected by acute focal infarction, limit axonal regeneration via activation of the Rho–Rho-associated protein kinase (ROCK) pathway. The present study examined whether early CIMT combined with the ROCK inhibitor fasudil promotes motor recovery after acute ischemic stroke. Materials and Methods: Rats were trained to perform the skilled-reach test and then subjected to middle cerebral artery occlusion (MCAO), producing a stroke affecting the preferred forelimb. Rats were assigned to one of four groups (N = 6/group): (nontreated) Control, CIMT, Fasudil, or CIMT+fasudil. CIMT and/or intraperitoneal infusion of fasudil were initiated 1 day postMCAO. Skilled reach and foot fault test data were collected once before and repeatedly over 4 weeks after the operation. Infarct volumes were calculated. Results: All four groups showed similar forelimb impairment before treatment. The performance of CIMT alone group was similar to that of controls on both tests. Fasudil alone facilitated recovery in the foot-fault test, but not in the skilled-reach test. Rats in the CIMT+fasudil group demonstrated enhanced recovery in both tests, including better performance over time than the Fasudil group on the foot-fault test. Infarct size did not differ significantly between the groups. Conclusions: Early CIMT promotes motor recovery after acute ischemic stroke when it is administered with fasudil pharmacotherapy, but not without it.