Topographic Mapping of Isolated Thalamic Infarcts Using Vascular and Novel Probabilistic Functional Thalamic Landmarks.

PURPOSE: We aimed to re-evaluate the relationship between thalamic infarct (TI) localization and clinical symptoms using a vascular (VTM) and a novel functional territorial thalamic map (FTM). METHODS: Magnetic resonance imaging (MRI) and clinical data of 65 patients with isolated TI were evaluated (female n = 23, male n = 42, right n = 23, left n = 42). A VTM depicted the known seven thalamic vascular territories (VT: inferolateral, anterolateral, inferomedial, posterior, central, anteromedian, posterolateral). An FTM was generated from a probabilistic thalamic nuclei atlas to determine six functionally defined territories (FT: anterior: memory/emotions; ventral: motor/somatosensory/language; medial: behavior/emotions/nociception, oculomotor; intralaminar: arousal/pain; lateral: visuospatial/somatosensory/conceptual and analytic thinking; posterior: audiovisual/somatosensory). Four neuroradiologists independently assigned diffusion-weighted imaging (DWI) lesions to the territories mapped by the VTM and FTM. Findings were correlated with clinical features. RESULTS: The most frequent symptom was a hemisensory syndrome (58%), which was not specific for any territory. A co-occurrence of hemisensory syndrome and hemiparesis had positive predictive values (PPV) of 76% and 82% for the involvement of the inferolateral VT and ventral FT, respectively. Thalamic aphasia had a PPV of 63% each for involvement of the anterolateral VT and ventral FT. Neglect was associated with involvement of the inferolateral VT/ventral FT. Interrater reliability for the assignment of DWI lesions to the VTM was fair (κ = 0.36), but good (κ = 0.73) for the FTM. CONCLUSION: The FTM revealed a greater reproducibility for the topographical assignment of TI than the VTM. Sensorimotor hemiparesis and neglect are predictive for a TI in the inferolateral VT/ventral FT. The hemisensory syndrome alone does not allow any topographical assignment.

Anticoagulation with warfarin and rivaroxaban ameliorates experimental autoimmune encephalomyelitis.

BACKGROUND: In multiple sclerosis, coagulation factors have been shown to modulate inflammation. In this translational study, we investigated whether long-term anticoagulation with warfarin or rivaroxaban has beneficial effects on the course of autoimmune experimental encephalomyelitis (EAE). METHODS: Female SJL/J mice treated with anticoagulants namely warfarin or rivaroxaban were immunized with PLP139-151. Stable anticoagulation was maintained throughout the entire experiment. Mice without anticoagulation treated with the vehicle only were used as controls. The neurological deficit was recorded during the course of EAE, and histopathological analyses of inflammatory lesions were performed. RESULTS: In preventive settings, both treatment with warfarin and rivaroxaban reduced the maximum EAE score as compared to the control group and led to a reduction of inflammatory lesions in the spinal cord. In contrast, therapeutic treatment with warfarin had no beneficial effects on the clinical course of EAE. Signs of intraparenchymal hemorrhage at the site of the inflammatory lesions were not observed. CONCLUSION: We developed long-term anticoagulation models that allowed exploring the course of EAE under warfarin and rivaroxaban treatment. We found a mild preventive effect of both warfarin and rivaroxaban on neurological deficits and local inflammation, indicating a modulation of the disease induction by anticoagulation.

Thrombolysis with recombinant tissue plasminogen activator under dabigatran anticoagulation in experimental stroke.

OBJECTIVE: Anticoagulation with dabigatran etexilate (DE) has a favorable risk-to-benefit profile for the prevention of ischemic events in patients with atrial fibrillation compared to warfarin. Whereas warfarin constitutes a strong contraindication for thrombolysis, it is unclear whether patients anticoagulated with DE can be thrombolysed. We compared the risk of thrombolysis-associated hemorrhagic transformation (HT) after pretreatment with DE or warfarin in a mouse model of ischemic stroke. METHODS: Thirty-nine C57BL/6 mice were pretreated orally with 75 mg/kg DE, 112.5mg/kg DE, 2mg/kg warfarin, or saline. We performed right middle cerebral artery occlusion for 3 hours, administered recombinant tissue plasminogen activator (rt-PA) directly before reperfusion, and assessed neurological deficit and HT blood volume after 24 hours. RESULTS: Warfarin anticoagulation increased HT secondary to rt-PA treatment as compared to nonanticoagulated controls (6.9 ± 5.5 µl vs 0.8 ± 0.6 µl, p < 0.05). In contrast, the rate of HT after pretreatment with 75 mg/kg DE, which led to plasma levels comparable to the highest plasma levels observed in participants of the RE-LY trial, did not differ significantly from controls (1.6 ± 0.8; p > 0.05 vs control). However, a high-dose group receiving 112.5mg/kg DE showed a considerable extent of HT (9.2 ± 5.6 µl, p < 0.01). INTERPRETATION: Our experimental data suggest that the risk of thrombolysis-associated HT may not be increased under DE pretreatment with standard doses leading to plasma levels of up to 400 ng/ml, a concentration that was not exceeded in the majority of DE trial patients. At higher DE plasma levels, however, the risk of severe HT rises considerably, emphasizing the need for a readily available assay of DE anticoagulant activity.