Andrea Seiler

Grey matter volumetric changes related to recovery from hand paresis after cortical sensorimotor stroke.

Abstract Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

The role of sleep in recovery following ischemic stroke: A review of human and animal data

Despite advancements in understanding the pathophysiology of stroke and the state of the art in acute management of afflicted patients as well as in subsequent neurorehabilitation training, stroke remains the most common neurological cause of long-term disability in adulthood. To enhance stroke patients’ independence and well-being it is necessary, therefore, to consider and develop new therapeutic strategies and approaches. We postulate that sleep might play a pivotal role in neurorehabilitation following stroke. Over the last two decades compelling evidence for a major function of sleep in neuroplasticity and neural network reorganization underlying learning and memory has evolved. Training and learning of new motor skills and knowledge can modulate the characteristics of subsequent sleep, which additionally can improve memory performance. While healthy sleep appears to support neuroplasticity resulting in improved learning and memory, disturbed sleep following stroke in animals and humans can impair stroke outcome. In addition, sleep disorders such as sleep disordered breathing, insomnia, and restless legs syndrome are frequent in stroke patients and associated with worse recovery outcomes. Studies investigating the evolution of post-stroke sleep changes suggest that these changes might also reflect neural network reorganization underlying functional recovery. Experimental and clinical studies provide evidence that pharmacological sleep promotion in rodents and treatment of sleep disorders in humans improves functional outcome following stroke. Taken together, there is accumulating evidence that sleep represents a “plasticity state” in the process of recovery following ischemic stroke. However, to test the key role of sleep and sleep disorders for stroke recovery and to better understand the underlying molecular mechanisms, experimental research and large-scale prospective studies in humans are necessary. The effects of hospital conditions, such as adjusting light conditions according to the patients’ sleep-wake rhythms, or sleep promoting drugs and non-invasive brain stimulation to promote neuronal plasticity and recovery following stroke requires further investigation.

CPAP as treatment of sleep apnea after stroke: A meta-analysis of randomized trials

Objective To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effectiveness of continuous positive airway pressure (CPAP) in stroke patients with sleep disordered breathing (SDB). Methods In a systematic literature search of electronic databases (MEDLINE, Embase, and the Cochrane Library) from 1980 to November 2016, we identified RCTs that assessed CPAP compared to standard care or sham CPAP in adult patients with stroke or TIA with SDB. Mean CPAP use, odds ratios (ORs), and standardized mean differences (SMDs) were calculated. The prespecified outcomes were adherence to CPAP, neurologic improvement, adverse events, new vascular events, and death. Results Ten RCTs (564 participants) with CPAP as intervention were included. Two studies compared CPAP with sham CPAP; 8 compared CPAP with usual care. Mean CPAP use across the trials was 4.53 hours per night (95% confidence interval [CI] 3.97–5.08). The OR of dropping out with CPAP was 1.83 (95% CI 1.05–3.21, p = 0.033). The combined analysis of the neurofunctional scales (NIH Stroke Scale and Canadian Neurological Scale) showed an overall neurofunctional improvement with CPAP (SMD 0.5406, 95% CI 0.0263–1.0548) but with a considerable heterogeneity (I2 = 78.9%, p = 0.0394) across the studies. Long-term survival was improved with CPAP in 1 trial. Conclusion CPAP use after stroke is acceptable once the treatment is tolerated. The data indicate that CPAP might be beneficial for neurologic recovery, which justifies larger RCTs.

A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke

Aim To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. Methods Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. Results Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. Conclusion Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Rapid eye movements sleep as a predictor of functional outcome after stroke: a translational study

Study Objectives Sleep disturbances are common in acute stroke patients and are linked with a negative stroke outcome. However, it is also unclear which and how such changes may be related to stroke outcome. To explore this link, we performed a sleep electroencephalogram (EEG) study in animals and humans after ischemic stroke. Methods (1) Animal study: 12 male rats were assigned to two groups: ischemia (IS) and sham surgery (Sham). In both groups, sleep architecture was investigated 24 h before surgery and for the following 3 days. (2) Human study: 153 patients with ischemic stroke participating in the SAS-CARE prospective, multicenter cohort study had a polysomnography within 9 days after stroke onset. Functional stroke outcome was assessed by the modified Rankin Scale (mRS) at hospital discharge (short-term outcome) and at a 3-month follow-up (long-term outcome). Results (1) Animal study: rapid eye movement (REM) sleep was significantly reduced in the IS group compared to the Sham group. (2) Human study: patients with poor short-term functional outcome had a reduction of REM sleep and prolonged REM latency during the acute phase of stroke. REM latency was the only sleep EEG variable found to be significantly related to short- and long-term functional impairment in a multiple linear regression analysis. Conclusions Acute ischemic stroke is followed by a significant reduction of REM sleep in animals and humans. In humans, this reduction was linked with a bad stroke outcome; in addition, REM latency was found to be an independent predictor of stroke evolution. Potential explanations for this role of REM sleep in stroke are discussed. Clinical Trial Registration http://clinicaltrials.gov. Unique identifier: NCT01097967.

Periodic limb movements during sleep in stroke/TIA: Prevalence, course, and cardiovascular burden

Objective To define the prevalence, time course, and associated factors of periodic limb movements during sleep (PLMS) in patients with ischemic stroke or TIA. Methods Patients enrolled in the prospective Sleep-Disordered Breathing in Transient Ischemia Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP) Treatment Efficacy (SAS-CARE) study underwent a double polysomnographic investigation in the acute and chronic phases after stroke/TIA, together with a MRI brain scan and a 24-hour blood pressure evaluation. The prevalence of PLMS in patients was compared with that in a matched sample of randomly selected healthy controls from the HypnoLaus cohort. One hundred sixty-nine recordings were performed in the acute phase and 191 after 3 months (210 recordings were obtained from the same 105 patients in both phases) and were compared to those of 162 controls. Results The mean number of PLMS per hour and the percentage of participants with a PLMS index >10 and >15 per hour were similar between patients and controls. PLMS remained stable from the acute to the chronic phase after stroke. Factors positively associated with PLMS were age, body mass index, and history of hypertension. Blood pressure over 24 hours and the burden of cerebrovascular damage were similar between the groups with PLMS and without PLMS. Conclusions PLMS are equally frequent in patients with stroke/TIA and the general population. The absence of higher blood pressure values and of a greater vascular brain damage found in patients with PLMS compared to those without PLMS might be due to a greater use of antihypertensive medication among patients with PLMS, which corresponds to a higher prevalence of previous diagnosis of hypertension in these patients.

Personalized structural image analysis in patients with temporal lobe epilepsy

Volumetric and morphometric studies have demonstrated structural abnormalities related to chronic epilepsies on a cohort- and population-based level. On a single-patient level, specific patterns of atrophy or cortical reorganization may be widespread and heterogeneous but represent potential targets for further personalized image analysis and surgical therapy. The goal of this study was to compare morphometric data analysis in 37 patients with temporal lobe epilepsies with expert-based image analysis, pre-informed by seizure semiology and ictal scalp EEG. Automated image analysis identified abnormalities exceeding expert-determined structural epileptogenic lesions in 86% of datasets. If EEG lateralization and expert MRI readings were congruent, automated analysis detected abnormalities consistent on a lobar and hemispheric level in 82% of datasets. However, in 25% of patients EEG lateralization and expert readings were inconsistent. Automated analysis localized to the site of resection in 60% of datasets in patients who underwent successful epilepsy surgery. Morphometric abnormalities beyond the mesiotemporal structures contributed to subtype characterisation. We conclude that subject-specific morphometric information is in agreement with expert image analysis and scalp EEG in the majority of cases. However, automated image analysis may provide non-invasive additional information in cases with equivocal radiological and neurophysiological findings.

Publisher Correction: Personalized structural image analysis in patients with temporal lobe epilepsy.

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Stroke causes a transient imbalance of interhemispheric information flow in EEG during non-REM sleep

OBJECTIVE Large-scale connectivity, especially interhemispheric connections, plays a crucial role for recovery after stroke. Here we used methods from information theory to characterize interhemispheric information flow in wake- and sleep-EEG after cerebral ischemia. METHODS 34 patients with unilateral ischemic stroke were included. Symbolic Transfer Entropy (STE) was applied between bipolar EEG signals on the left and the right cerebral hemisphere during polysomnographic recordings in the acute phase and 3 months after stroke. RESULTS In the acute phase, we found a sleep stage-dependent preferred interhemispheric asymmetry: during non-REM sleep the information flow was predominantly directed from the contralesional toward the ipsilesional hemisphere. This effect was greatly reduced in a follow-up recording 3 months after stroke onset. CONCLUSION Our findings are consistent with functional imaging studies showing a transient hyperactivity of contralesional areas after stroke. We conclude that STE is a robust method for detecting post-stroke connectivity reorganizations, and that sleep stages have to be taken into account when assessing functional connectivity. SIGNIFICANCE EEG is more widely available than functional MRI. Future studies will have to confirm whether EEG derived STE can be useful in a clinical setting during rehabilitation after stroke.

Die Rolle des Schlafes in der Neurorehabilitation nach einem Hirninfarkt und traumatischen Hirnverletzungen

Zusammenfassung. Der Artikel gibt eine kurze Ubersicht uber die bisherigen Erkenntnisse zum Einfluss des Schlafes im Wiederherstellungsprozess eingeschrankter motorischer und kognitiver Funktionen ...