Clinical presentation and neural correlates of stroke-associated spatial delusions.

BACKGROUND AND PURPOSE: Incongruent beliefs about self-localization in space markedly disturb patients' behavior. Spatial delusions, or reduplicative paramnesias, are characterized by a firm conviction of place reduplication, transformation, or mislocation. Evidence suggests they are frequent after right hemisphere lesions, but comprehensive information about their clinical features is lacking. METHODS: We prospectively screened 504 acute right-hemisphere stroke patients for the presence of spatial delusions. Their behavioral and clinical features were systematically assessed. Then, we analyzed the correlation of their duration with the magnitude of structural disruption of belief-associated functional networks. Finally, we described the syndrome subtypes and evaluated whether the clinical categorization would be predicted by the structural disruption of familiarity-associated functional networks using an unsupervised k-means clustering algorithm. RESULTS: Sixty patients with spatial delusions were identified and fully characterized. Most (93%) localized the misidentified places closer to home than the hospital. The median time duration was 3 days (interquartile range = 1-7 days), and it was moderately correlated with the magnitude of structural-functional decoupling of belief-associated functional networks (r = 0.39, p = 0.02; beta coefficient regressing for lesion volume = 3.18, p = 0.04). Each clinical subtype had characteristic response patterns, which were reported, and representative examples were provided. Clustering based on structural disruption of familiarity- and unfamiliarity-associated functional networks poorly matched the clinical categorization (lesion: Rand index = 0.47; structural disconnection: Rand index = 0.51). CONCLUSIONS: The systematic characterization of the peculiar clinical features of stroke-associated spatial delusions may improve the syndrome diagnosis and clinical approaches. The novel evidence about their neural correlates fosters the clarification of the pathophysiology of delusional misidentifications.

Mapping delusions of space onto a structural disconnectome that decouples familiarity and place networks.

Interpretation of space is an important determinant of human behaviour. Delusions of space, or reduplicative paramnesias, are a particularly disturbing form of spatial disorientation characterized by the patients' strong belief of place reduplication, transformation or mislocation. Their occurrence following focal brain damage provides a unique opportunity to unveil the structural-functional basis of space misinterpretations. First, we identified reports of lesion-associated reduplicative paramnesias with brain images available through a systematic review of the literature (n = 24). Each lesion was matched with 4 stroke controls and the sample was randomly split in an exploratory (n = 60) and in a validation (n = 60) dataset. Second, we used 178 7T tractographies to compute structural disconnectome maps and analysed lesion topography and disconnection patterns. Delusions of space were significantly associated with structural disconnection of right ventrolateral prefrontal and right temporal regions, and this finding was replicated in the validation sample. Third, we performed a functional meta-analysis of syndrome-related terms. We demonstrated that the structural disconnectomes of delusions of space were spatially correlated with the functional meta-analytic maps of familiarity and place, and replicated the previous evidence that the lesion topography maps are spatially correlated with belief-related functional networks. No association was found with control terms. These results reveal that structural disconnection putatively mediates functional changes associated with reduplicative paramnesias and provide a possible neural basis for the content specificity for places that characterizes these delusional beliefs.

Unravelling the Neural Basis of Spatial Delusions After Stroke.

OBJECTIVE: Knowing explicitly where we are is an interpretation of our spatial representations. Reduplicative paramnesia is a disrupting syndrome in which patients present a firm belief of spatial mislocation. Here, we studied the largest sample of patients with delusional misidentifications of space (ie, reduplicative paramnesia) after stroke to shed light on their neurobiology. METHODS: In a prospective, cumulative, case-control study, we screened 400 patients with acute right-hemispheric stroke. We included 64 cases and 233 controls. First, lesions were delimited and normalized. Then, we computed structural and functional disconnection maps using methods of lesion-track and network-mapping. The maps were compared, controlling for confounders. Second, we built a multivariate logistic model, including clinical, behavioral, and neuroimaging data. Finally, we performed a nested cross-validation of the model with a support-vector machine analysis. RESULTS: The most frequent misidentification subtype was confabulatory mislocation (56%), followed by place reduplication (19%), and chimeric assimilation (13%). Our results indicate that structural disconnection is the strongest predictor of the syndrome and included 2 distinct streams, connecting right fronto-thalamic and right occipitotemporal structures. In the multivariate model, the independent predictors of reduplicative paramnesia were the structural disconnection map, lesion sparing of right dorsal fronto-parietal regions, age, and anosognosia. Good discrimination accuracy was demonstrated (area under the curve = 0.80 [0.75-0.85]). INTERPRETATION: Our results localize the anatomic circuits that may have a role in the abnormal spatial-emotional binding and in the defective updating of spatial representations underlying reduplicative paramnesia. This novel data may contribute to better understand the pathophysiology of delusional syndromes after stroke. ANN NEUROL 2021;89:1181-1194.

Undetermined stroke genesis and hidden cardiomyopathies determined by cardiac magnetic resonance.

OBJECTIVE: To determine whether cardiac magnetic resonance imaging (CMR) could be useful in identifying previously undiagnosed cardiomyopathies in a cohort of patients with ischemic stroke who underwent standard etiologic investigation and to describe the type and frequency of these cardiomyopathies. METHODS: We performed a subanalysis of a previously collected prospective cohort of patients with ischemic stroke. Patients with structural changes on echocardiography that are considered causal for stroke in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification were excluded. A 3T CMR was performed. We compared the frequency of the cardiomyopathies that we found with reference values for the general population. RESULTS: One hundred thirty-two patients with a mean age of 68.4 years were included. In 7 patients (5.3%, 95% confidence interval 2.59%-10.54%) CMR identified cardiomyopathy. Four patients had hypertrophic cardiomyopathy, 2 had restrictive cardiomyopathy, and 1 had noncompaction cardiomyopathy. Six of these patients had been classified after standard evaluation as having undetermined stroke and 1 patient as having cardioembolic stroke (atrial fibrillation). We found a higher frequency of hypertrophic cardiomyopathy in the entire cohort and in the undetermined cause group compared to the general population (3.03% and 5.81% vs 0.2%, respectively, p = 0.001 and p < 0.001). The frequency of noncompaction cardiomyopathy was also higher in our cohort (0.76% vs 0.05%, respectively, p < 0.001). CONCLUSIONS: Although rare, cardiomyopathies should be considered as a possible cause of ischemic stroke classified as of undetermined etiology after standard evaluation.

Women Who Have Ischemic Strokes Have a Higher Burden of Left Atrial Fibrosis Than Men.

Background and Purpose- Women with atrial fibrillation (AF) have a higher risk of stroke than men who have AF. Atrial fibrosis is a marker of atrial disease that precedes the appearance of AF increasing the risk of ischemic stroke. We aimed to determine whether female sex is independently associated with left atrial fibrosis in stroke patients. Methods- We prospectively included a consecutive sample of ischemic stroke patients aged over 50 years of age. Late gadolinium enhancement cardiac magnetic resonance imaging was performed to quantify the severity of left atrial fibrosis and the wall pattern of its distribution. A multivariable linear regression analysis was performed to determine whether female sex was independently associated with left atrial fibrosis after adjusting for potential confounders namely AF and age. Results- One hundred twenty-four patients were deemed eligible; 117 patients were included (7 were excluded because of cardiomyopathy identified by cardiac magnetic resonance imaging). All had usable cardiac magnetic resonance imaging data. Fifty-three patients (45.3%) were women. Women were older and were less frequently treated with angiotensin-converting-enzyme inhibitors. Ninety-one patients had any degree of atrial fibrosis. Women had a higher percentage of atrial fibrosis than men-median (interquartile range)-18% (17) versus 10% (20). In a multivariable linear regression model adjusted for demographics, medications, AF, comorbidities, and cardiac parameters, female sex was found to be independently associated with left atrial fibrosis. Women were found to have more 4.70% of left atrial fibrosis than men (95% CI, 0.70-8.71%; P=0.02) after controlling for confounders. Conclusions- Female sex was found to be independently associated with left atrial fibrosis after controlling for confounders such as AF and age. Further studies are needed to understand if this contributes to the increased stroke risk related to AF in women compared with men.