Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.

OBJECTIVE: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. METHODS: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. RESULTS: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). CONCLUSIONS: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.

Reduced CMRO2 and cerebrovascular reserve in patients with severe intracranial arterial stenosis: a combined multiparametric qBOLD oxygenation and BOLD fMRI study.

Multiparametric quantitative blood oxygenation level dependent (mqBOLD) magnetic resonance Imaging (MRI) approach allows mapping tissular oxygen saturation (StO2 ) and cerebral metabolic rate of oxygen (CMRO2 ). To identify hemodynamic alteration related to severe intracranial arterial stenosis (SIAS), functional MRI of cerebrovascular reserve (CVR BOLD fMRI) to hypercapnia has been proposed. Diffusion imaging suggests chronic low grade ischemia in patients with impaired CVR. The aim of the present study was to evaluate how oxygen parameters (StO2 and CMRO2 ), assessed with mqBOLD approach, correlate with CVR in patients (n = 12) with SIAS and without arterial occlusion. The perfusion (dynamic susceptibility contrast), oxygenation, and CVR were compared. The MRI protocol conducted at 3T lasted approximately 1 h. Regions of interest measures on maps were delineated on segmented gray matter (GM) of middle cerebral artery territories. We have shown that decreased CVR is spatially associated with decreased CMRO2 in GM of patients with SIAS. Further, the degree of ipsilateral CVR reduction was well-correlated with the amplitude of the CMRO2 deficit. The altered CMRO2 suggests the presence of a moderate ischemia explained by both a decrease in perfusion and in CVR. CVR and mqBOLD method may be helpful in the selection of patients with SIAS to advocate for medical therapy or percutaneous transluminal angioplasty-stenting.

Vicarious function within the human primary motor cortex? A longitudinal fMRI stroke study.

While experimental studies in the monkey have shown that motor recovery after partial destruction of the hand motor cortex was based on adjacent motor reorganization, functional MRI (fMRI) studies with isolated primary motor cortical stroke have not yet been reported in humans. Based on experimental data, we designed a study to test if recovery after stroke within primary motor cortex (M1) was associated with reorganization within the surrounding motor cortex, i.e. the motor cortex was able to vicariate. Since motor recovery is time-dependent and might be inflected according to the tested task, the delay after stroke and two motor tasks were included in our design. We examined four patients with one ischaemic stroke limited to M1, and four sex- and age-matched healthy controls in a temporally balanced prospective longitudinal fMRI study over three sessions: <20 days, 4 months and 2 years after stroke. The paradigm included two motor tasks, finger tapping (FT) and finger extension (FE). Distinct patterns of motor activation were observed with time for FT and FE. At the first session, FT-related activation was lateralized in the ipsilateral hemisphere while FE-related activation was contralateral, involving bilateral cerebellar regions for both tasks. From 4 months, skilled motor recovery was associated with contralateral dorsal premotor and sensorimotor cortex and ipsilateral cerebellum motor-related activations, leading to lateralized motor patterns for both tasks. For the left recovered hand, FT and FE-related activations within M1 were more dorsal in patients than in controls. This dorsal shift progressively increased over 2 years, reflecting functional reorganization in the motor cortex adjacent to the lesion. In addition, patients showed a reverse representation of FT and FE within M1, corresponding to a greater dorsal shift for FT than for FE. This functional dissociation might reflect the structural subdivision of M1 with two distinct finger motor representations within M1. Recovery of FT, located within the lesioned depth of the rolandic sulcus in controls, might be related to the re-emergence of a new representation in the intact dorsal M1, while FE, located more dorsally, underwent minor reorganization. This is the first fMRI study of humans presenting with isolated M1 stroke comparable with experimental lesions in animals. Despite the small number of patients, our findings showing the re-emergence of a fingers motor task in the intact dorsal M1 instead of in ventral M1 are consistent with 'vicariation' models of stroke recovery.

The French stroke program.

The French healthcare system is organised according to a political, geographical and demographic framework. In France today, less than 20 hospitals have dedicated intensive care units for acute stroke patients. In the 1999 national survey, 94% of stroke patients were admitted to public hospitals, 35% were treated in neurological wards and 4% had access to an intensive care stroke unit. To improve the quality of care and resource utilisation, a national plan for stroke will be implemented at regional level during the next five-year plan. After a long period of status quo, many positive actions for stroke care have been initiated within a couple of years, based on the evidence of more effective stroke treatments, such as thrombolysis and the specialist care provided by stroke units.