The role of neuronal antibodies in cryptogenic new onset refractory status epilepticus.

Most cases with new onset refractory status epilepticus (NORSE) remain cryptogenic despite extensive diagnostic workup. The aim of this study was to analyze the etiology and clinical features of NORSE and investigate known or potentially novel autoantibodies in cryptogenic NORSE (cNORSE). We retrospectively assessed the medical records of adults with status epilepticus at a Swiss tertiary referral center between 2010 and 2021. Demographic, diagnostic, therapeutic, and outcome parameters were characterized. We performed post hoc screening for known or potentially novel autoantibodies including immunohistochemistry (IHC) on rat brain with cerebrospinal fluid (CSF) and serum samples of cNORSE. Twenty patients with NORSE were identified. Etiologies included infections (n = 4), Creutzfeldt-Jakob disease (n = 1), CASPR2 autoimmune encephalitis (n = 1), and carotid artery stenosis with recurrent perfusion deficit (n = 1). Thirteen cases (65%) were cryptogenic despite detailed evaluation. A posteriori IHC for neuronal autoantibodies yielded negative results in all available serum (n = 11) and CSF (n = 9) samples of cNORSE. Our results suggest that neuronal antibodies are unlikely to play a major role in the pathogenesis of cNORSE. Future studies should rather focus on other-especially T-cell- and cytokine-mediated-mechanisms of autoinflammation in this devastating disease, which is far too poorly understood so far.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Impact of intravenous thrombolysis on functional outcome in patients with mild ischemic stroke without large vessel occlusion or rapidly improving symptoms.

BACKGROUND: Optimal treatment strategy in patients with mild ischemic stroke remains uncertain. While functional dependency or death has been reported in up to one-third of non-thrombolyzed mild ischemic stroke patients, intravenous thrombolysis is currently not recommended in this patient group. Emerging evidence suggests two risk factors-rapid early improvement and large vessel occlusion-as main associates of unfavorable outcome in mild ischemic stroke patients not undergoing intravenous thrombolysis. AIMS: To analyze natural course as well as safety and three-month outcome of intravenous thrombolysis in mild ischemic stroke without rapid early improvement or large vessel occlusion. METHODS: Mild ischemic stroke was defined by a National Institute of Health Stroke Scale score ≤6. We used the modified Rankin Scale (mRS) to compare three-month functional outcome in 370 consecutive mild ischemic stroke patients without early rapid improvement and without large vessel occlusion, who either underwent intravenous thrombolysis (n = 108) or received best medical treatment (n = 262). RESULTS: Favorable outcome (mRS ≤ 1) was common in both groups (intravenous thrombolysis: 91%; no intravenous thrombolysis: 90%). Although intravenous thrombolysis use was independently associated with a higher risk of asymptomatic hemorrhagic transformation (OR = 4.62, p = 0.002), intravenous thrombolysis appeared as an independent predictor of mRS = 0 at three months (OR = 3.33, p < 0.0001). CONCLUSIONS: Mild ischemic stroke patients without rapidly improving symptoms and without large vessel occlusion have a high chance of favorable three-month outcome, irrespective of treatment type. Patients receiving intravenous thrombolysis, however, more often achieved complete remission of symptoms, which particularly in mild ischemic stroke may constitute a meaningful endpoint.