Marcellina Isabelle Haeberlin

University of Zurich

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Large and Small Cerebral Vessel Involvement in Severe COVID-19

Stroke (2020)

E. Keller Giovanna Brandi Sebastian Winklhofer Lukas L. Imbach Daniel S. Kirschenbaum

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.

Stroke

10.1161/strokeaha.120.031224

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Citations (101)

Central Nervous System Disorders in Severe SARS-CoV-2 Infection: detailed clinical work-up of eight cases

Research Square (Research Square) (2020)

E. Keller Giovanna Brandi Sebastian Winklhofer Lukas L. Imbach Daniel S. Kirschenbaum

Abstract Objective Case series with different clinical presentations indicating central nervous system (CNS) involvement in coronavirus disease 2019 (COVID-19) have been published. Comprehensive work-ups including clinical characteristics, laboratory, electroencephalography (EEG), neuroimaging and cerebrospinal fluid (CSF) findings are needed to understand the mechanisms. Design We evaluated 32 consecutive patients with severe SARS-CoV-2 infection treated at a tertiary care centre from March 09 to April 03, 2020 for concomitant severe central nervous system (CNS) symptoms occurring during their critical disease state. Those with CNS disorders were examined in detail regarding clinical characteristics and undergoing additional examinations, e.g. computed tomography (CT), magnetic resonance imaging (MRI), (EEG), (CSF) analysis and autopsy if they had died. Results Of 32 critically ill patients with COVID-19 eight (18%) had severe CNS involvement (mean [SD] age, 67.6 [6.8] years; seven men; two patients died). All eight patients had cardiovascular risk factors, most frequently arterial hypertension. Two patients presented with lacunar ischemic stroke and one with status epilepticus in the early phase. As most common presentation, six patients presented with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in three of them with additional subarachnoid haemorrhage and in another two with additional small ischemic lesions. In three patients intracranial vessel wall sequence MRI was performed, for the first time to our knowledge. All cases showed contrast-enhancement of vessel walls in large and middle-sized cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. CSF analysis showed normal cells counts and chemistry. RT-PCRs for SARS-CoV-2 in CSF were all negative, and no intrathecal SARS-CoV-2 specific IgG synthesis was detectable. Conclusions CNS disorders are common in patients with severe COVID-19. Different mechanisms might be involved. Besides unspecific encephalopathy and encephalitic syndromes, large vessel strokes might occur early after disease onset. In a later phase, microbleeds and microinfarctions indicate potential CNS small vessel disease. MRI vessel wall contrast enhancement suggests cerebral vascular wall pathologies with an inflammatory component. CNS disorders associated with COVID-19 may lead to long-term disabilities aggravating socio-economic damage. The mechanisms have to be investigated urgently in order to develop preventive and therapeutic neuroprotective strategies.

Concomitant

Stroke

10.21203/rs.3.rs-32488/v1

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Citations (0)

Detection of EEG burst-suppression in neurocritical care patients using an unsupervised machine learning algorithm

Clinical Neurophysiology (2021)

Gagan Narula Marcellina Isabelle Haeberlin J. Balsiger Christian Strässle Lukas L. Imbach

The burst suppression pattern in clinical electroencephalographic (EEG) recordings is an important diagnostic tool because of its association with comas of various etiologies, as with hypoxia, drug related intoxication or deep anesthesia. The detection of bursts and the calculation of burst/suppression ratio are often used to monitor the level of anesthesia during treatment of status epilepticus. However, manual counting of bursts is a laborious process open to inter-rater variation and motivates a need for automatic detection. METHODS: We describe a novel unsupervised learning algorithm that detects bursts in EEG and generates burst-per-minute estimates for the purpose of monitoring sedation level in an intensive care unit (ICU). We validated the algorithm on 29 hours of burst annotated EEG data from 29 patients suffering from status epilepticus and hemorrhage. RESULTS: We report competitive results in comparison to neural networks learned via supervised learning. The mean absolute error (SD) in bursts per minute was 0.93 (1.38). CONCLUSION: We present a novel burst suppression detection algorithm that adapts to each patient individually, reports bursts-per-minute quickly, and does not require manual fine-tuning unlike previous approaches to burst-suppression pattern detection. SIGNIFICANCE: Our algorithm for automatic burst suppression quantification can greatly reduce manual oversight in depth of sedation monitoring.

Burst suppression

Neurointensive care

10.1016/j.clinph.2021.07.018

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Citations (11)

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

Epilepsia (2023)

Amanda Eisele Matthias Schwager Stefan Yu Bögli Ina Reichen Justina Dargvainiene

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.

Refractory (planetary science)

10.1111/epi.17755

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Citations (4)

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

International Journal of Stroke (2019)

Marcellina Isabelle Haeberlin Ulrike Held Ralf W. Baumgartner Dimitrios Georgiadis Philipp O. Valko

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.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.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).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).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.

Stroke

10.1177/1747493019874719

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Citations (11)