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Background and Purpose-Intracranial thrombi can be characterized according to their permeability as measured by contrast agent penetration. Thrombus composition and its associated pathogenesis are important factors affecting treatment and secondary prevention. We aimed to explore the histopathologic factors explaining the heterogeneity of thrombus permeability measures and evaluated potential correlations with stroke pathogenesis. Methods-Thrombus densities were measured in thin-slice noncontrast computed tomography and automatically aligned computed tomographic angiography images of 133 patients with large-vessel occlusions of the middle cerebral artery. Change in thrombus attenuation (Δ t) and corrected void fraction (ε; attenuation increase corrected for contralateral artery densities) were calculated. First, these thrombus perviousness measures were correlated with histological thrombus components (especially fractions of fibrin-platelet accumulation and red blood cells) and stroke pathogenesis (n=32). For validation, an association between perviousness and pathogenesis was assessed in a second, independent cohort (n=101). Results-Thrombus perviousness estimates were correlated with both fibrin/platelets fractions (Δ t : r=0.43, P=0.016/ε: r=0.45, P=0.01) and inversely with red blood cells counts (Δ t : r=−0.46, P=0.01/ε: r=−0.49, P=0.006). In the first cohort, Δ t was substantially higher in samples from patients with cardioembolic stroke pathogenesis as compared with noncardioembolic-derived thrombi (P=0.026). In the validation cohort, thrombus perviousness measures differed significantly between cardioembolic (Δ t : median [ interquartile range]=12.53 [8.70-17.90]; ε: median [interquartile range]=0.054 [0.036-0.082]) and noncardioembolic thrombi (Δ t : median [interquartile range]=3.2 [2.17-6.44], P<0.001; ε: median [interquartile range]=0.020 [0.011-0.027], P<0.001) and were associated with pathogenesis (Δ t : β=0.45, P=0.016/ε: β=83.6, P=0.013) in a binary logistic regression model. Conclusions-Permeable thrombi showed a strong correlation with lower fractions of red blood cells counts and more fibrin/platelets conglomerations, concurrent with an association with cardioembolic origin. This novel information about thrombus perviousness may be valuable as a new and simple to acquire imaging marker for identifying stroke pathogenesis using early and readily available imaging.

IntroductionBlepharospasm is characterized by involuntary eyelid spasms. It can be associated with perioral dystonia (Meige's syndrome or orofacial dystonia). We aimed at studying resting‐state functional brain connectivity in these patients and its potential modulation by therapeutic botulinum toxin injections.MethodsWe performed resting‐state functional MRI and a region of interest‐based analysis of functional connectivity in 13 patients with blepharospasm/Meige's syndrome in comparison to 13 healthy controls. Patients were studied before and 4 weeks after botulinum toxin treatment. Simultaneous facial electromyography was applied to control for involuntary facial movements.ResultsBefore botulinum toxin treatment, patients showed reduced functional connectivity between caudate and primary sensorimotor, somatosensory association and visual cortices as well as between putamen and parietal association cortex. Cerebellar areas displayed decreased functional connectivity to somatosensory and visual association cortices. On the cortical level, connectivity was reduced between the cingulate cortex and the primary sensorimotor/premotor and parietal association cortex, between premotor areas and the primary somatosensory cortices, and between the postcentral gyrus and temporoparietal, secondary somatosensory, cingular, and cerebellar regions. Botulinum toxin treatment modulated functional connectivity, especially between cerebellum and visual cortices.ConclusionsPatients with blepharospasm/Meige's syndrome show altered functional connectivity at rest in widespread brain regions including basal ganglia, cerebellar, primary/secondary sensorimotor, and visual areas. Functionally, this may reflect a predisposition for defective movement inhibition and sensorimotor integration. Botulinum toxin treatment could modulate brain connectivity in blepharospasm by altering visual and sensory input.

The PROTECT technique is a promising new approach to significantly reduce thrombus fragmentation and, hence distal embolization during MT. This safe and efficient technique needs to be validated in larger trials to confirm our results.