Reports of neurological involvement during Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection course are increasingly described. The aim of this review is to provide a clinical approach of SARS-CoV-2 neurological complications based on the direct or indirect (systemic/immune-mediated) role of the SARS-CoV-2 in their genesis. A review of the current literature has been carried out up to May 20th 2020 according to the PRISMA guidelines. All case series and reports of adult neurological manifestations associated to SARS-CoV-2 published in English were considered. Review and fundamental research studies on Coronaviruses neuroinvasive potential were analyzed to support pathogenic hypothesis and possible underlying mechanisms. Clinical patterns were subdivided into three groups according to putative underlying mechanisms: direct invasion of central or peripheral nervous system, systemic disorders leading to acute CNS injuries and post-infectious neurological syndromes (PINS). Sixteen case series and 26 case reports for a total of 903 patients were identified presenting with neurological involvement during SARS-CoV-2 infection. Hypo/anosmia and dys/ageusia were found in 826 patients and mainly attributed to direct viral invasion. Cerebrovascular complications occurred in 51 patients and related to viral infection associated systemic inflammation. PINS were described in only 26 patients. A wide heterogeneity of these reports emerged concerning the extension of the clinical examination and ancillary exams performed. Neurological complications of SARS-CoV-2 are mainly related to olfactory and gustatory sensory perception disorders through possible direct nervous system invasion while cerebrovascular disease and PINS are rare and due to distinct and indirect pathophysiological mechanisms.

BACKGROUND: Intravenous thrombolysis (IVT) in patients with recent ingestion of direct oral anticoagulants (DOACs) is a frequent challenge and remains controversial. The benefit of DOAC reversal before IVT is uncertain. METHODS: Using target trial methodology, we analyzed data from 28 comprehensive stroke centers. Patients on DOACs were included if they met IVT criteria, had a National Institutes of Health Stroke Scale score of ≥2, and last DOAC intake within 48 hours or was undeterminable. Safety and efficacy outcomes (symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, major bleeding, 90-day mortality, and good functional outcome [modified Rankin Scale score of 0–2 or return to baseline]) were compared between those receiving IVT versus no IVT and IVT with versus without reversal. In addition, a comparison was made with patients from the New Zealand stroke registry, all of whom underwent reversal with idarucizumab. We adjusted for covariates known to be associated with safety and efficacy outcomes, including age, stroke severity, intended thrombectomy, blood glucose, blood pressure, DOAC reversal, and time from last intake. RESULTS: Overall, 1342 patients fulfilled the target trial criteria. The median age was 80 (interquartile range, 73–86) years, median National Institutes of Health Stroke Scale score was 11, 50% were female, and 52% of patients received endovascular therapy. IVT was given in 342 of 1342 (25%) patients. Of these, 141 (41.2%) had verified DOAC intake <12 hours before admission, and 92 (26.9%) within 12 to 24 hours. Symptomatic intracerebral hemorrhage occurred in 10 of 328 (3.0%) of patients receiving IVT and 54 of 921 (5.9%) patients not receiving IVT (adjusted difference, −2.1% [95% CI, −5.3% to +1.2]). Patients receiving IVT were more likely to have good functional outcomes (adjusted difference, +14.4% [95% CI, +7.1% to +21.8%]). Comparing 289 patients with reversal (from the additional New Zealand registry) and 283 patients without reversal before IVT (from the target trial population), there was no significant difference in symptomatic intracerebral hemorrhage, major bleeding, or efficacy outcomes. CONCLUSIONS: This target trial confirms previous observational data regarding the safety of off-label IVT in patients with recent DOAC intake. More data and dedicated trials are needed for patients with confirmed high DOAC plasma levels and regarding the efficacy and safety of DOAC reversal before IVT.

Cytotoxic lesions of the corpus callosum are lesions secondary to different medical conditions. Radiologically, lesions are identified on magnetic resonance imaging as a hyperintense signal on diffusion-weighted imaging and decreased apparent diffusion coefficient values of the splenium of corpus callosum. Signal changes are reversible in almost totality of the cases. Previous cases of cytotoxic lesions of the corpus callosums have been associated with several metabolic disturbances, but ketotic hyperglycemia has never been reported. We here discussed the case of 28-year-old patient with complex visual hallucinations presenting with cytotoxic lesions of the corpus callosums and type I diabetes. Treatment of hyperglycemia was followed by full clinical recovery and complete regression of the radiological abnormalities at 3-month follow-up. Elevated levels of circulating pro-inflammatory mediators associated with ketotic hyperglycemia in type I diabetes support an implication of cytokines in the pathophysiology of the cytotoxic lesions of the corpus callosums.

Introduction: Primary angiitis of the CNS (PACNS) is a rare inflammatory disorder affecting blood vessels of the brain and spinal cord causing acute stroke. This study aimed to describe clinical, biochemical, imaging and histopathological findings of a retrospective single-center PACNS cohort in comparison to a cohort of secondary angiitis of CNS (SACNS).Methods: All consecutive patients diagnosed with PACNS or SACNS between 2000 and 2023 were identified using our institutional database. Univariate comparison between both groups and multivariate analysis for independent predictors was performed, as well as Receiving Operating Characteristic analysis for white blood cell count predictive of PACNS. Kaplan–Meier curves were used for evaluating survival outcomes.Results: We identified 20 patients in each group. PACNS patients presented more frequently with seizures (40% vs. 5%, p = 0.02) and pseudotumoral lesions (45% vs. 10%, p = 0.014). In PACNS patients, median serum WBC count at diagnosis was lower (8.4×10³/mm³ [6.4–9.9] vs. 11.2×10³/mm³ [9–13.6] p = 0.027) and [18F]FDG-PET/CT (p = 0.001) was negative in all cases. No significant differences were observed for lumbar puncture profiles and diffusion weighted imaging patterns. Small-vessel vasculitis with a lymphocytic pattern was the most represented histologic phenotype in both groups. Serum WBC count ≤9.93 ×10³/mm³ was the only independent predictor of PACNS using multivariate analysis [OR 95%CI 5.107, (1.177–22.159)]. Both groups did not differ in terms of mortality, relapse and clinical outcome.Conclusion: In our study, PACNS patients presented more often with pseudotumoral lesions, seizures and small-vessel involvement and lymphocytic histologic pattern. WBC count ≤9.93×10³/mm³ was an independent predictor of PACNS diagnosis.