Computed tomography angiography in the diagnosis of brain death: Implementation and results in Germany.

BACKGROUND: Computed tomography angiography (CTA) has been investigated as a confirmatory study (CS) for the diagnosis of brain death (BD). International consensus regarding its use, study parameters, and evaluation criteria is lacking. In the German BD guideline, a CTA protocol was first introduced in 2015. METHODS: The authors obtained a comprehensive dataset of all BD examinations in adults from the German organ procurement organization to investigate implementation, results, and impact of CTA on BD determination during the first 4 years. RESULTS: In 5152 patients with clinically absent brain function, 1272 CTA were reported by 676 hospitals. Use of CTA increased from 17.2% of patients in the first year to 29.7% in the final year. CTA replaced other CS such as electroencephalography without increasing overall CS frequency. Technical failure was rare (0.9%); 89.3% of studies were positive. Negative results (9.8%) were more frequent with secondary brain injury, longer duration of the clinical BD syndrome, or unreliable clinical assessment. Median time to diagnosis was longer with CTA (2.6 h) versus other CS (1.6 h). CTA had no differential impact on the rate of confirmed BD and did not improve access of small hospitals to CS for BD determination. CONCLUSIONS: CTA expands the range of available CS for the diagnosis of BD in adults. Real-world evidence from a large cohort confirms usability of the German CTA protocol within the guideline-specified context.

Outcomes After Decompressive Surgery for Severe Cerebral Venous Sinus Thrombosis Associated or Not Associated with Vaccine-Induced Immune Thrombosis with Thrombocytopenia: A Multicenter Cohort Study.

BACKGROUND: Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome. METHODS: This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS. RESULTS: Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission (p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months (p = 0.043). CONCLUSIONS: Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.

[Diagnosis of brain death in Germany-Implementation of the guidelines of the German Medical Association]. / Feststellung des irreversiblen Hirnfunktionsausfalls in Deutschland ­ Umsetzung der Richtlinie der Bundesärztekammer.

BACKGROUND: The 4th update of the guidelines of the German Medical Association on the diagnosis of irreversible loss of brain function (brain death, BD) has introduced important new regulations regarding the required qualification of the examiners, approved procedures for ancillary testing, and a clarification regarding the sequencing of diagnostic steps. OBJECTIVE: Investigation of the implementation and practical effects on the diagnosis of brain death. METHOD: Descriptive evaluation of the routine documentation of the German Organ Procurement Organization, comparing the periods July 2011-June 2015 (3rd update) and July 2015-June 2019 (4th update). RESULTS: Patient numbers decreased from 6100 to 5403. The largest decrease affected hospitals without neurosurgery. Children were not affected. With the 4th update, clinical diagnostics were increasingly performed during on-call hours by external neurologists. Of the patients 83.8% now received ancillary tests compared to 80.1% previously. Computed tomography angiography (CTA), first introduced in the 4th update, was applied in 23.2% and established complete loss of cerebral circulation in 89.4%. The time between first documentation of the clinical signs of BD and certification of BD increased from 7.0 ± 12.7 h to 8.2 ± 14.2 h. The diagnosis was slightly less frequent with 95.3% compared to 96.6%. CONCLUSION: The updated standards were implemented in accordance with the guidelines. The demand for external consulting neurologists and neurosurgeons as well as the time required for BD assessment have increased. Negative effects on pediatric BD diagnostics were not apparent. CTA is widely and successfully used in adults as a new ancillary diagnostic procedure.

Influence of Patient-Specific Covariates on Test Validity of Two Delirium Screening Instruments in Neurocritical Care Patients (DEMON-ICU).

BACKGROUND: Delirium screening instruments (DSIs) should be used to detect delirium, but they only show moderate sensitivity in patients with neurocritical illness. We explored whether, for these patients, DSI validity is impacted by patient-specific covariates. METHODS: Data were prospectively collected in a single-center quality improvement project. Patients were screened for delirium once daily using the Intensive Care Delirium Screening Checklist (ICDSC) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference was the daily assessment using criteria from the Diagnostic and Statistical Manual, 4th Edition, Text Revision (DSM-IV-TR). In a two-step receiver operating characteristics regression analysis adjusting for repeated measurements, the impact of acute diagnosis of stroke or transient ischemic attack (TIA), neurosurgical intervention, Richmond Agitation Sedation Scale, and ventilation status on test validity was determined. RESULTS: Of 181 patients screened, 101 went into final analysis. Delirium incidence according to DSM-IV-TR was 29.7%. For the first complete assessment series (CAM-ICU, ICDSC, and DSM-IV-TR), sensitivity for the CAM-ICU and the ICDSC was 73.3% and 66.7%, and specificity was 91.8% and 94.1%, respectively. Consideration of daily repeated measurements increased sensitivity for the CAM-ICU and ICDSC to 75.7% and 73.4%, and specificity to 97.3% and 98.9%, respectively. Receiver operating characteristics regression revealed that lower Richmond Agitation Sedation Scale levels significantly impaired validity of the ICDSC (p = 0.029) and the CAM-ICU in its severity scale version (p = 0.004). Neither acute diagnosis of stroke or TIA nor neurosurgical intervention or mechanical ventilation significantly influenced DSI validity. CONCLUSIONS: The CAM-ICU and ICDSC perform well in patients requiring neurocritical care, regardless of the presence of acute stroke, TIA, or neurosurgical interventions. Yet, even very light or moderate sedation can significantly impair DSI performance.

Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial.

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation. Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation. Design, Setting, and Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020. Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194). Main Outcomes and Measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death). Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy. Conclusions and Relevance: Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded. Trial Registration: ClinicalTrials.gov Identifier: NCT02377167.

[Update on Intensive Care Unit Management of Stroke]. / Aktuelle Aspekte in der Intensivtherapie des Schlaganfalls.

In this review, we provide an update on the intensive care unit (ICU) management of ischemic stroke. Over the last decade, new evidence has led to rapid changes in the early management of patients admitted with acute ischemic stroke. Nevertheless, stroke remains a leading cause of disability. Consequently, a significant number of patients with acute ischemic stroke require ICU level care. The most frequent reasons for ICU admissions are large infarction with potential swelling, reduced level of consciousness, secondary hemorrhagic transformation, acute symptomatic seizures or respiratory failure and stroke-related disorders of the brain-heart interaction. Moreover, there is an increasing number of patients receiving intravenous thrombolysis or mechanical thrombectomy with a subsequent need of ICU monitoring. Several studies have shown that the implementation of specialized neuro-intensive care teams help to improve functional outcome after acute ischemic stroke. The main goal in the ICU management of stroke patients is to prevent secondary brain injury. To this end, a comprehensive approach to optimize systemic physiological homeostasis, control intracranial pressure, cerebral perfusion, hemodynamic and respiratory parameters is needed. Here, we summarize recent advances in invasive and non-invasive neuro-monitoring, decision making in decompressive neurosurgery for large supratentorial or cerebellar infarction, specific cardiorespiratory management, nutrition, temperature management and mobilization strategies in ischemic stroke.

Regional Brain Net Water Uptake in Computed Tomography after Cardiac Arrest - A Novel Biomarker for Neuroprognostication.

BACKGROUND: Selective water uptake by neurons and glial cells and subsequent brain tissue oedema are key pathophysiological processes of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Although brain computed tomography (CT) is widely used to assess the severity of HIE, changes of brain radiodensity over time have not been investigated. These could be used to quantify regional brain net water uptake (NWU), a potential prognostic biomarker. METHODS: We conducted an observational prognostic accuracy study including a derivation (single center cardiac arrest registry) and a validation (international multicenter TTM2 trial) cohort. Early (<6 h) and follow-up (>24 h) head CTs of CA patients were used to determine regional NWU for grey and white matter regions after co-registration with a brain atlas. Neurological outcome was dichotomized as good versus poor using the Cerebral Performance Category Scale (CPC) in the derivation cohort and Modified Rankin Scale (mRS) in the validation cohort. RESULTS: We included 115 patients (81 derivation, 34 validation) with out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). Regional brain water content remained unchanged in patients with good outcome. In patients with poor neurological outcome, we found considerable regional water uptake with the strongest effect in the basal ganglia. NWU >8% in the putamen and caudate nucleus predicted poor outcome with 100% specificity (95%-CI: 86-100%) and 43% (moderate) sensitivity (95%-CI: 31-56%). CONCLUSION: This pilot study indicates that NWU derived from serial head CTs is a promising novel biomarker for outcome prediction after CA. NWU >8% in basal ganglia grey matter regions predicted poor outcome while absence of NWU indicated good outcome. NWU and follow-up CTs should be investigated in larger, prospective trials with standardized CT acquisition protocols.

Brain death determination in patients with veno-arterial extracorporeal membrane oxygenation: A systematic study to address the Harlequin syndrome.

PURPOSE: The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO system supply different parts of the body with different paCO2-levels. The purpose of this study was to compare two variants of paCO2-analysis to account for the Harlequin syndrome during apnea testing (AT) in brain death (BD) determination. MATERIALS AND METHODS: Twenty-seven patients (median age 48 years, 26-76 years; male n = 19) with VA-ECMO treatment were included who underwent BD determination. In variant 1, simultaneous arterial blood gas (ABG) samples were drawn from the right and the left radial artery. In variant 2, simultaneous ABG samples were drawn from the right radial artery and the postoxygenator ECMO circuit. Differences in paCO2-levels were analysed for both variants. RESULTS: At the start of AT, median paCO2-difference between right and left radial artery (variant 1) was 0.90 mmHg (95%-confidence intervall [CI]: 0.7-1.3 mmHg). Median paCO2-difference between right radial artery and postoxygenator ECMO circuit (variant 2) was 3.3 mmHg (95%-CI: 1.5-6.0 mmHg) and thereby significantly higher compared to variant 1 (p = 0.001). At the end of AT, paCO2-difference according to variant 1 remained unchanged with 1.1 mmHg (95%-CI: 0.9-1.8 mmHg). In contrast, paCO2-difference according to variant 2 increased to 9.9 mmHg (95%-CI: 3.5-19.2 mmHg; p = 0.002). CONCLUSIONS: Simultaneous paCO2-analysis from right and left distal arterial lines is the method of choice to reduce the risk of adverse effects (e.g. severe respiratory acidosis) while performing AT in VA-ECMO patients during BD determination.

Prognosis and management of acute symptomatic seizures: a prospective, multicenter, observational study.

BACKGROUND: Acute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%. METHODS: Inclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey. RESULTS: Eleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%-16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8-69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0-9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate. CONCLUSIONS: Even in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment.

Effectiveness of Lumbar Cerebrospinal Fluid Drain Among Patients With Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

Importance: After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome. Objective: To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage. Design, Setting, and Participants: The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours. Intervention: A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage. Main Outcomes and Measures: Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage. Results: Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, -0.12; 95% CI, -0.23 to -0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, -0.11; 95% CI, -0.22 to 0; P = .04). Conclusion and Relevance: In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage. Trial Registration: ClinicalTrials.gov Identifier: NCT01258257.

[Intracranial hypertension - Therapeutic options]. / Der erhöhte intrakranielle Druck - Therapiemaßnahmen.

Increased intracranial pressure can be the result of different intracranial pathologies. Sustained intracranial pressure above 20-25 mmHg may cause secondary brain injury by impaired cerebral perfusion or direct pressure with neuronal injury, with in consequence deterioration of neurological outcome. A main cause of critically increased intracranial pressure is traumatic brain injury. Most treatment strategies for increased intracranial pressure were developed and studied on these patients. Most of them were transferred to other pathologies with increased intracranial pressure.Treatment is based on general measures, which can be escalated for medical and surgical options in case of failure to sufficiently decrease intracranial pressure below the established threshold. Despite its enormous medical and socio-economical relevance, the evidence for most treatment strategies of intracranial hypertension, though published in guidelines, is weak.

[Multimodal neuromonitoring - indications and methodes]. / Der erhöhte intrakranielle Druck - Multimodales Neuromonitoring - Indikationen und Methoden.

Managing patients after severe traumatic brain injury and aneurysmal subarachnoid hemorrhage is a challenging task of modern intensive care. Most patients do require sedation for mechanical ventilation due to respiratory distress or treatment of increased intracranial pressure. Besides standard ICP monitoring, a variety of continuous monitoring technologies for bedside use exists. The paper discusses the 5 methods most frequently used and their significance for multimodal neuromonitoring.

[Intracranial hypertension in various brain diseases - Specific therapy and outcome]. / Der erhöhte intrakranielle Druck - Therapiestrategien und Outcomerelevanz bei unterschiedlichen neurologischen und neurochirurgischen Krankheitsbildern.

Elevated intracranial pressure (ICP) in various brain diseases has for long time been treated according to guidelines for traumatic brain injury. First data of randomized study reveal, that specific treatment options like decompressive craniectomy, hyperosmotic agents, hyperventilation, hypothermia and steroids should have specific indications to control elevated ICP in future. In general, optimal ICP-treatment should also target sufficient cerebral perfusion and oxygenation.

Loss of cerebral blood flow and cerebral perfusion pressure in brain death: A transcranial Duplex ultrasonography study.

PURPOSE: We investigated cerebral perfusion pressure (CPP) at the time loss of cerebral blood flow (CBF) occurred during brain death (BD). We hypothesized that a critical closing pressure (CrCP) may be reached before CPP drops to 0 mmHg. MATERIALS AND METHODS: 14 patients with increasing intracranial pressure (ICP) leading to BD were included. Transcranial Duplex (TCD) ultrasonography was used to investigate CBF. Starting at a CPP of 30 mmHg, TCD was repeated until waveforms indicated loss of CBF. We then analyzed CPP by the time TCD indicated absent CBF and clinical BD was established. RESULTS: In 12 patients, CPP was positive when clinical BD was manifest and TCD illustrated absent CBF. Across all patients, mean CPP at clinical BD manifestation was 10.0 mmHg (range 0-20 mmHg); mean CPP by the time CBF stopped was 7.5 mmHg (0-20 mmHg). In four patients, clinical BD preceded loss of CBF. Here, the mean CPP difference from clinical BD to loss of CBF was 8.8 mmHg (5-15 mmHg). CONCLUSIONS: CrCP may be reached although CPP is still positive, resulting in complete loss of CBF and BD. By including bedside TCD, neuromonitoring may contribute to early identification of patients at risk to experience loss of CBF and subsequent BD.

Early recognition and treatment of pre-VITT syndrome after adenoviral vector-based SARS-CoV-2 vaccination may prevent from thrombotic complications: review of published cases and clinical pathway.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but highly morbid complication after adenoviral vector-based SARS-CoV-2 vaccination. The pre-VITT syndrome is defined as vaccine-induced immune thrombocytopenia without thrombosis typically presenting with new-onset headache. This review aims to identify at-risk patients before complications such as cerebral venous sinus thrombosis occur. We review previously published reports of 19 patients (median age 35 years, range 23-74; 16 females) who met the diagnostic criteria for a pre-VITT syndrome. Seven patients progressed to VITT, 12 patients did not. Patients who experienced VITT received delayed treatment. The median interval between the onset of headache and VITT-treatment (i.e. anticoagulation, immune globulins, or corticosteroids) was 5 days (range 1-8 days) compared with 2 days (0-5 days) in those without subsequent VITT (P = 0.033). The interval from onset of headache to anticoagulation was longer in patients with VITT (median 7 vs. 2 days; range 3-9 vs. 0-7 days; P = 0.01). Anticoagulation was safe in all patients with a pre-VITT syndrome as no haemorrhagic complications occurred after anticoagulation was started despite low platelets. The transient decline of platelet count after admission was significantly more pronounced in patients who progressed to VITT (median 67 vs. 0 × 103/µL; range 0-77 × 103/µL vs. 0-10 × 103/µL; P = 0.005). d-dimers did not differ between groups. Pre-VITT syndrome is a 'red flag' and allows to identify and preemptively treat patients at-risk of further progression to VITT. However, it must be distinguished from post-vaccination immune thrombocytopenia.

IGNITE Status Epilepticus Survey: A Nationwide Interrogation about the Current Management of Status Epilepticus in Germany.

We aimed to evaluate the current management of status epilepticus (SE) in intensive care units (ICUs) in Germany, depending on the different hospital levels of care and the ICU specialty. We performed a nationwide web-based anonymized survey, including all German ICUs registered with the German Society for Neurointensive and Emergency Care (Deutsche Gesellschaft für Neurointensiv- und Notfallmedizin; DGNI). The response rate was 83/232 (36%). Continuous EEG monitoring (cEEG) was available in 86% of ICUs. Regular written cEEG reports were obtained in only 50%. Drug management was homogeneous with a general consensus regarding substance order: benzodiazepines-anticonvulsants-sedatives. Thereunder first choice substances were lorazepam (90%), levetiracetam (91%), and propofol (73%). Data suggest that network structures for super-refractory SE are not permeable, as 75% did not transfer SE patients. Our survey provides "real world data" concerning the current management of SE in Germany. Uniform standards in the implementation of cEEG could help further improve the overall quality. Initial therapy management is standardized. For super-refractory SE, a concentration of highly specialized centers establishing network structures analogous to neurovascular diseases seems desirable to apply rescue therapies with low evidence carefully, ideally collecting data on this rare condition in registries and clinical trials.

COVID-19 and Intracranial Hemorrhage: A Multicenter Case Series, Systematic Review and Pooled Analysis.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). RESULTS: Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3% of patients experienced the critical stage of COVID-19, 62.7% of patients were on anticoagulation and 27.5% of the patients received ECMO. The prevalence of ICH was at 0.85% and the mortality at 52.18%, respectively. CONCLUSION: ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future.

Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis.

Excitability and recruitment patterns of spinal motoneurons in human sleep as assessed by F-wave recordings.

This study examines the excitability and recruitment of spinal motoneurons in human sleep. The main objective was to assess whether supraspinal inhibition affects the different subpopulations of the compound spinal motoneuron pool in the same way or rather in a selective fashion in the various sleep stages. To this end, we studied F-conduction velocities (FCV) and F-tacheodispersion alongside F-amplitudes and F-persistence in 22 healthy subjects in sleep stages N2, N3 (slow-wave sleep), REM and in wakefulness. Stimuli were delivered on the ulnar nerve, and F-waves were recorded from the first dorsal interosseus muscle. Repeated sets of stimuli were stored to obtain at least 15 F-waves for each state of vigilance. F-tacheodispersion was calculated based on FCVs using the modified Kimura formula. Confirming the only previous study, excitability of spinal motoneurons was generally decreased in all sleep stages compared with wakefulness as indicated by significantly reduced F-persistence and F-amplitudes. More importantly, F-tacheodispersion showed a narrowed range of FCV in all sleep stages, most prominently in REM. In non-REM, this narrowed range was associated with a shift towards significantly decreased maximal FCV and mean FCV as well as with a trend towards lower minimal FCV. In REM, the lowering of mean FCV was even more pronounced, but contrary to non-REM sleep without a shift of minimal and maximal FCV. Variations in F-tacheodispersion between sleep stages suggest that different supraspinal inhibitory neuronal circuits acting on the spinal motoneuron pool may contribute to muscle hypotonia in human non-REM sleep and to atonia in REM sleep.