Association of Lesion Location and Depressive Symptoms Poststroke.

BACKGROUND: Depressive symptoms are a common stroke sequela, yet their neurobiological substrates are still unclear. We sought to determine if they are associated with specific lesion locations. METHODS: In a prospective observational study, 270 patients with stroke were tested twice with the Hospital Anxiety and Depression Scale around day 6 and again 6 months poststroke and voxel-based lesion behavior mapping was performed. RESULTS: Frequency of depressive symptoms (depression subscale of the Hospital Anxiety and Depression Scale >7) after 6 months was 19.6 %. Higher Hospital Anxiety and Depression Scale scores for depression around day 6 were the only variable associated with depressive symptoms after 6 months in a multiple logistic regression. Lesions in the right putamen were significantly associated with depressive symptoms after 6 months in the voxel-based lesion behavior mapping. CONCLUSIONS: Lesions in the right basal ganglia might increase the risk of depressive symptoms 6 months poststroke.

Resolution of diaschisis contributes to early recovery from post-stroke aphasia.

Diaschisis is a phenomenon observed in stroke that is defined as neuronal dysfunction in regions spared by the infarction but connected to the lesion site. We combined lesion network mapping and task-based functional MRI in 71 patients with post-stroke aphasia to investigate, whether diaschisis and its resolution contribute to early loss and recovery of language functions. Language activation acquired in the acute, subacute and chronic phase was analyzed in compartments with high and low normative resting-state functional connectivity to the lesion site on an individual basis. Regions with high compared to regions with low lesion connectivity showed a steeper increase in language reactivation from the acute to the subacute phase. This finding is compatible with the assumption of resolution of diaschisis. Additionally, language performance in the subacute phase and improvement from the subacute to the chronic phase significantly correlated with the diaschisis effect and its resolution, respectively, suggesting a behavioral relevance of this effect. We therefore assume that undamaged but functionally connected regions become dysfunctional due to missing input from the lesion contributing to the aphasic deficit. Since these regions are structurally intact, dysfunction resolves over time contributing to the rapid early behavioral improvement observed in aphasic stroke patients. Our results demonstrate that diaschisis and its resolution might be a relevant mechanism of early loss and recovery of language function in acute stroke patients.

Association of Lesion Location and Depressive Symptoms Poststroke.

BACKGROUND AND PURPOSE: Poststroke depression is a common stroke sequel, yet its neurobiological substrates are still unclear. We sought to determine whether specific lesion locations are associated with depressive symptoms after stroke. METHODS: In a prospective study, 270 patients with first ever stroke were repeatedly tested with the depression subscale of the Hospital Anxiety and Depression Scale within the first 4 weeks and 6 months after stroke. Voxel-based lesion behavior mapping based on clinical imaging was performed to test for associations between symptoms of depression and lesion locations. RESULTS: Frequency of poststroke depression (Hospital Anxiety and Depression Scale-D score >7) after 6 months was 19.6%. Higher Hospital Anxiety and Depression Scale-D scores for depression within the first 4 weeks were the only independent predictor for poststroke depression after 6 months in a multiple logistic regression also including age, sex, lesion volume, stroke severity, Barthel-Index, and the anxiety subscale of the Hospital Anxiety and Depression Scale. Nonparametric permutation-test based voxel-based lesion behavior mapping identified a cluster of voxels mostly within the left ventrolateral prefrontal cortex where lesions were significantly associated with more depressive symptoms after 6 months. No such association was observed within the right hemisphere despite better lesion coverage. CONCLUSIONS: Lesions in the left ventrolateral prefrontal cortex increase the risk of depressive symptoms 6 months poststroke. Lesions within the right hemisphere are unrelated to depressive symptoms. Recognition of left frontal lesions as a risk factor should help in the early diagnosis of poststroke depression through better risk stratification. The results are in line with evidence from functional imaging and noninvasive brain stimulation in patients without focal brain damage indicating that dysfunction in the left lateral prefrontal cortex contributes to depressive disorders.

Tissue Outcome Prediction in Patients with Proximal Vessel Occlusion and Mechanical Thrombectomy Using Logistic Models.

Perfusion CT is established to aid selection of patients with proximal intracranial vessel occlusion for thrombectomy in the extended time window. Selection is mostly based on simple thresholding of perfusion parameter maps, which, however, does not exploit the full information hidden in the high-dimensional perfusion data. We implemented a multiparametric mass-univariate logistic model to predict tissue outcome based on data from 405 stroke patients with acute proximal vessel occlusion in the anterior circulation who underwent mechanical thrombectomy. Input parameters were acute multimodal CT imaging (perfusion, angiography, and non-contrast) as well as basic demographic and clinical parameters. The model was trained with the knowledge of recanalization status and final infarct localization. We found that perfusion parameter maps (CBF, CBV, and Tmax) were sufficient for tissue outcome prediction. Compared with single-parameter thresholding-based models, our logistic model had comparable volumetric accuracy, but was superior with respect to topographical accuracy (AUC of receiver operating characteristic). We also found higher spatial accuracy (Dice index) in an independent internal but not external cross-validation. Our results highlight the value of perfusion data compared with non-contrast CT, CT angiography and clinical information for tissue outcome-prediction. Multiparametric logistic prediction has high potential to outperform the single-parameter thresholding-based approach. In the future, the combination of tissue and functional outcome prediction might provide an individual biomarker for the benefit from mechanical thrombectomy in acute stroke care.

fMRI informed voxel-based lesion analysis to identify lesions associated with right-hemispheric activation in aphasia recovery.

Several mechanisms have been attributed to post-stroke loss and recovery of language functions. However, the significance and timing of domain-general and homotopic right-hemispheric activation is controversial. We aimed to examine the effect of left-hemispheric lesion location and time post-stroke on right-hemispheric activation. Voxel-based lesion analyses were informed by auditory language-related fMRI activation of 71 patients with left middle cerebral artery stroke examined longitudinally in the acute, subacute and early chronic phase. Language activation was determined in several right-hemispheric regions of interest and served as regressor of interest for voxel-based lesion analyses. We found that an acute to chronic increase of language activation in the right supplementary motor area was associated with lesions to the left extreme capsule as part of the ventral language pathway. Importantly, this activation increase correlated significantly with improvement of out-of-scanner comprehension abilities. We interpret our findings in terms of successful domain-general compensation in patients with critical left frontotemporal disconnection due to damage to the ventral language pathway but relatively spared cortical language areas.