Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy.

BACKGROUND: Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences. METHODS: A cohort study spanning 10 years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits. RESULTS: Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304 days, IQR 1433-3274) indicated favorable outcomes in both groups. CONCLUSION: This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.

High Somatization Rates, Frequent Spontaneous Recovery, and a Lack of Organic Biomarkers in Post-Covid-19 Condition.

INTRODUCTION: Many patients report neuropsychiatric symptoms after SARS-CoV-2 infection. Data on prevalence of post-COVID-19 condition (PCC) vary due to the lack of specific diagnostic criteria, the report of unspecific symptoms, and reliable biomarkers. METHODS: PCC patients seen in a neurological outpatient department were followed for up to 18 months. Neurological examination, SARS-CoV-2 antibodies, Epstein-Barr virus antibodies, and cortisol levels as possible biomarkers, questionnaires to evaluate neuropsychiatric symptoms and somatization (Patient Health Questionnaires D [PHQ-D]), cognition deficits (Montreal Cognitive Assessment [MoCA]), sleep disorders (ISS, Epworth Sleepiness Scale [ESS]), and fatigue (FSS) were included. RESULTS: A total of 175 consecutive patients (78% females, median age 42 years) were seen between May 2021 and February 2023. Fatigue, subjective stress intolerance, and subjective cognitive deficits were the most common symptoms. Specific scores were positive for fatigue, insomnia, and sleepiness and were present in 95%, 62.1%, and 44.0%, respectively. Cognitive deficits were found in 2.3%. Signs of somatization were identified in 61%, who also had an average of two symptoms more than patients without somatization. Overall, 28% had a psychiatric disorder, including depression and anxiety. At the second visit (n = 92), fatigue (67.3%) and insomnia (45.5%) had decreased. At visit three (n = 43), symptom load had decreased in 76.8%; overall, 51.2% of patients were symptom-free. Biomarker testing did not confirm an anti-EBV response. SARS-CoV-2-specific immune reactions increased over time, and cortisol levels were within the physiological range. CONCLUSION: Despite high initial symptom load, 76.8% improved over time. The prevalence of somatization and psychiatric disorders was high. Our data do not confirm the role of previously suggested biomarkers in PCC patients.

Liberalization of the Systemic Glucose Management is Associated with a Reduced Frequency of Neuroglucopenia in Subarachnoid Hemorrhage Patients: An Observational Cohort Study.

BACKGROUND: Pathologically low brain glucose levels, referred to as neuroglucopenia, are associated with unfavorable outcomes in neurocritical care patients. We sought to investigate whether an increase in serum glucose levels would be associated with a reduction of neuroglucopenia. METHODS: In this retrospective analysis of prospectively collected data, we included 55 consecutive patients with spontaneous subarachnoid hemorrhage who underwent cerebral microdialysis (CMD) monitoring. Neuroglucopenia was defined as CMD-glucose levels < 0.7 mmol/l. We identified systemic glucose liberalization events, defined as a day with median serum glucose levels < 150 mg/dl, followed by a day with median serum glucose levels > 150 mg/dl, and compared concentrations of cerebral metabolites between these days. Unfavorable outcome was defined as modified Rankin Scale score ≥ 3 at 3 months after the bleeding. RESULTS: Episodes of neuroglucopenia were more frequent in patients with unfavorable outcome (19.8% [19.3-20.3%] vs. 10.9% [10.4-11.5%], p = 0.007). Sixty-nine systemic glucose liberalization events were identified in 40 patients. Blood glucose levels increased from 141.2 (138.7-143.6) mg/dl to 159.5 (157.0-162.2) mg/dl (p < 0.001), CMD-glucose levels increased from 1.44 (1.39-1.50) mmol/l to 1.68 (1.62-1.75) mmol/l (p = 0.001), and the frequency of neuroglucopenia decreased from 24.7% (22.9-26.5%) to 20.2% (18.7-21.8%) (p = 0.002) during these events. Liberalization was not associated with changes in CMD-lactate, CMD-pyruvate, CMD-lactate-to-pyruvate ratio, CMD-glutamate, or CMD-glycerol. CONCLUSIONS: In conclusion, the liberalization of serum glucose concentrations to levels between 150 and 180 mg/dl was associated with a significant reduction of neuroglucopenia.

Follow-Up Imaging in Angiography-Negative Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: The aim of this study was to assess the diagnostic yield of follow-up investigations in aneurysm-negative subarachnoid hemorrhage (SAH) patients. METHODS: In 109 (25%) of 435 patients with SAH and initial negative digital subtraction angiography (DSA), the diagnostic yield of repeat DSA and magnetic resonance imaging (MRI) of the brain and craniocervical junction was reviewed. RESULTS: Of the 109 patients with an initial negative DSA, 51 (47%) had perimesencephalic (PM), 54 (50%) had nonperimesencephalic (NPM) blood distribution, and 4 (3.7%) had computed tomography-negative SAH. A delayed bleeding source was determined in 3 of 82 (3.7%) patients who underwent repeat DSA and in 1 of 5 patients who underwent a third DSA. The bleeding patterns of these patients were all NPM (n = 4). Repeat DSA did not identify a bleeding source in patients with PM-SAH. MRI of the brain and craniocervical junction after 2 days revealed a bleeding source in 1 of 105 patients (1%) in a computed tomography-negative SAH. When all diagnostic modalities, including exploratory craniotomy and MRI of the spinal axis, were considered, the rate of delayed diagnosis of the bleeding source was 6.4% (7/109). In addition to the bleeding pattern, patients with delayed diagnosis of the bleeding source were characterized by worse disease severity parameters, worse radiological grading scales, and more in-hospital complications than patients without delayed diagnosis of a bleeding source. CONCLUSIONS: The results of this study support the use of repeat DSA in patients with NPM-SAH; however, routine repeat DSA may not be indicated in PM-SAH patients. The routine use of MRI remains controversial.

Fever Prevention in Patients With Acute Vascular Brain Injury: The INTREPID Randomized Clinical Trial.

Importance: Fever is associated with worse outcomes in patients with stroke, but whether preventing fever improves outcomes is unclear. Objective: To determine whether fever prevention after acute vascular brain injury is achievable and impacts functional outcome. Design, Setting, and Participants: Open-label randomized clinical trial with blinded outcome assessment that enrolled 686 of 1176 planned critically ill patients with stroke at 43 intensive care units in 7 countries from March 2017 to April 2021 (last date of follow-up was May 12, 2022). Intervention: Patients randomized to fever prevention (n = 339) were targeted to 37.0 °C for 14 days or intensive care unit discharge using an automated surface temperature management device. Standard care patients (n = 338) received standardized tiered fever treatment on occurrence of temperature of 38 °C or greater. Main Outcomes and Measures: Primary outcome was daily mean fever burden: the area under the temperature curve above 37.9 °C (total fever burden) divided by the total number of hours in the acute phase, multiplied by 24 hours (°C-hour). The principal secondary outcome was 3-month functional recovery by shift analysis of the 6-category modified Rankin Scale, which is scored from 0 (no symptoms) to 6 (death). Major adverse events included death, pneumonia, sepsis, and malignant cerebral edema. Results: Enrollment was stopped after a planned interim analysis demonstrated futility of the principal secondary end point. In total, 686 patients were enrolled, and 9 were consented but not randomized, leaving a primary analysis population of 677 patients (254 ischemic stroke, 223 intracerebral hemorrhage, 200 subarachnoid hemorrhage; 345 were female [51%]; median age, 62 years) with 433 (64%) completing the study through 12 months. Daily mean (SD) fever burden was significantly lower in the fever prevention group (0.37 [1.0] °C-hour; range, 0.0-8.0 °C-hour) compared with the standard care group (0.73 [1.1] °C-hour; range, 0.0-10.3 °C-hour) (difference, -0.35 [95% CI, -0.51 to -0.20]; P < .001). Between-group differences for the primary outcome by stroke subtype were -0.10 (95% CI, -0.35 to 0.15) for ischemic stroke, -0.50 (95% CI, -0.78 to -0.22) for intracerebral hemorrhage, and -0.52 (95% CI, -0.81 to -0.23) for subarachnoid hemorrhage (all P < .001 by Wilcoxon rank-sum test). There was no significant difference in functional recovery at 3 months (median modified Rankin Scale score, 4.0 vs 4.0, respectively; odds ratio for a favorable shift in functional outcome, 1.09 [95% CI, 0.81 to 1.46]; P = .54). Major adverse events occurred in 82.2% of participants in the fever prevention group vs 75.9% in the standard care group, including 33.8% vs 34.5% for infections, 14.5% vs 14.0% for cardiac disorders, and 24.5% vs 20.5% for respiratory disorders. Conclusions and Relevance: In patients with acute vascular brain injury, preventive normothermia using an automated surface temperature management device effectively reduced fever burden but did not improve functional outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02996266.

Management of patients with neurological diseases considering post-pandemic coronavirus disease 2019 (COVID-19) related risks and dangers - An updated European Academy of Neurology consensus statement.

BACKGROUND AND PURPOSE: In October 2020, the European Academy of Neurology (EAN) consensus statement for management of patients with neurological diseases during the coronavirus disease 2019 (COVID-19) pandemic was published. Due to important changes and developments that have happened since then, the need has arisen to critically reassess the original recommendations and address new challenges. METHODS: In step 1, the original items were critically reviewed by the EAN COVID-19 Task Force. In addition, new recommendations were defined. In step 2, an online survey with the recommendations forged in step 1 was sent to the Managing Groups of all Scientific and Coordinating Panels of EAN. In step 3, the final set of recommendations was made. RESULTS: In step 1, out of the original 36 recommendations, 18 were judged still relevant. They were edited to reflect the advances in knowledge and practice. In addition, 21 new recommendations were formulated to address the new knowledge and challenges. In step 2, out of the 39 recommendations sent for the survey, nine were approved as they were, whilst suggestions for improvement were given for the rest. In step 3, the recommendations were further edited, and some new items were formed to accommodate the participants' suggestions, resulting in a final set of 41 recommendations. CONCLUSION: This revision of the 2020 EAN Statement provides updated comprehensive and structured guidance on good clinical practice in people with neurological disease faced with SARS-CoV-2 infection. It now covers the issues from the more recent domains of COVID-19-related care, vaccine complications and post-COVID-19 conditions.

The effects of bolus compared to continuous administration of adrenaline on cerebral oxygenation during experimental cardiopulmonary resuscitation.

Background: Bolus administration of adrenaline during cardiopulmonary resuscitation (CPR) results in only short-term increases in systemic and cerebral perfusion pressure (CePP) with unclear effects on cerebral oxygenation. The aim of this study was to investigate the effects of bolus compared to continuous adrenaline administration on cerebral oxygenation in a porcine CPR model. Methods: After five minutes of cardiac arrest, mechanical CPR was performed for 15 min. Adrenaline (45 µg/kg) was administered either as a bolus every five minutes or continuously over the same period via an infusion pump. Main outcome parameter was brain tissue oxygen tension (PbtO2), secondary outcome parameters included mean arterial pressure (MAP), intracranial pressure (ICP), CePP and cerebral regional oxygen saturation (rSO2) as well as arterial and cerebral venous blood gases. Results: During CPR, mean MAP (45 ± 8 mmHg vs. 38 ± 8 mmHg; p = 0.0827), mean ICP (27 ± 7 mmHg vs. 20 ± 7 mmHg; p = 0.0653) and mean CePP (18 ± 8 mmHg vs. 18 ± 8 mmHg; p = 0.9008) were similar in the bolus and the continuous adrenaline group. Also, rSO2 (both 24 ± 6 mmHg; p = 0.9903) and cerebral venous oxygen saturation (18 ± 12% versus 27.5 ± 12%; p = 0.1596) did not differ. In contrast, relative PbtO2 reached higher values in the continuous group after five minutes of CPR and remained significantly higher than in the bolus group until the end of resuscitation. Conclusion: Continuous administration of adrenaline improved brain tissue oxygen tension compared with bolus administration during prolonged CPR.

Aneurysmal Wall Enhancement of Non-Ruptured Intracranial Aneurysms after Endovascular Treatment Correlates with Higher Aneurysm Reperfusion Rates, but Only in Large Aneurysms.

INTRODUCTION: Aneurysmal wall enhancement (AWE) of non-ruptured sacular intracranial aneurysms (IA) after endovascular treatment (ET) is a frequently observed imaging finding using AWE-sequences in brain magnetic resonance imaging (MRI). So far, its value remains unclear. We aimed to investigate the effect of AWE on aneurysm reperfusion rates in a longitudinal cohort. METHODS: This is a retrospective MRI study over the timespan of up to 5 years, assessing the correlation of increased AWE of non-ruptured IAs and events of aneurysm reperfusion and retreatment, PHASES Score and grade of AWE. T1 SPACE fat saturation (FS) and T1 SE FS blood suppression sequences after contrast administration were used for visual interpretation of increased AWE. The IAs' sizes were assessed via the biggest diameter. The grade of enhancement was defined in a grading system from grade 1 to grade 3. RESULTS: 127 consecutive non ruptured IA-patients (58.9 ± 9.0 years, 94 female, 33 male) who underwent elective aneurysm occlusion were included. AWE was observed in 40.2% of patients (51/127) after ET, 6 patients already showed AWE before treatment. In large IAs (which were defined as a single maximum diameter of over 7.5 mm), AWE was significantly associated with aneurysm reperfusion in contrast to large aneurysm without AWE). All grades of AWE were significantly associated with reperfusion. CONCLUSIONS: Our data suggests that in patients with initially large IAs, AWE is correlated with aneurysm reperfusion.

Objective and subjective cognitive outcomes one year after COVID-19.

OBJECTIVE: This study aimed to evaluate subjective cognitive, physical, and mental health symptoms as well as objective cognitive deficits in COVID-19 patients 1 year after infection. METHODS: This was a cross-sectional study. Seventy-four patients, who contracted a SARS-CoV-2 infection in 2020, underwent an in-person neuropsychological assessment in 2021. This included standardized tests of memory, attention, and executive functions. In addition, participants also responded to scales on subjective attention deficits, mental health symptoms, and fatigue. Patients' scores were compared to published norms. RESULTS: Patients (N = 74) had a median age of 56 years (42% female). According to the initial disease severity, they were classified as mild (outpatients, 32%), moderate (hospitalized, non-ICU-admitted, 45%), or severe (ICU-admitted, 23%). Hospitalized patients were more often affected than outpatients. In general, deficits were most common in attention (23%), followed by memory (15%) and executive functions (3%). Patients reported increased levels of fatigue (51%), anxiety (30%), distractibility in everyday situations (20%), and depression (15%). An additional analysis suggested an association between lower scores in an attention task and hyperferritinemia. As indicated by a hierarchical regression analysis, subjective distractibility was significantly predicted by current anxiety and fatigue symptoms but not by objective attention performance (final model, adj-R2 = 0.588, P < 0.001). INTERPRETATION: One year after infection, COVID-19 patients can have frequent attention deficits and can complain about symptoms such as fatigue, anxiety, and distractibility. Anxiety and fatigue, more than objective cognitive deficits, have an impact on the patients' experienced impairments in everyday life.

Beyond Control: Temperature Burden in Patients with Spontaneous Subarachnoid Hemorrhage-An Observational Study.

BACKGROUND: Temperature abnormalities are common after spontaneous subarachnoid hemorrhage (SAH). Here, we aimed to describe the evolution of temperature burden despite temperature control and to assess its impact on outcome parameters. METHODS: This retrospective observational study of prospectively collected data included 375 consecutive patients with SAH admitted to the neurological intensive care unit between 2010 and 2022. Daily fever (defined as the area over the curve above 37.9 °C multiplied by hours with fever) and spontaneous hypothermia burden (< 36.0 °C) were calculated over the study period of 16 days. Generalized estimating equations were used to calculate risk factors for increased temperature burdens and the impact of temperature burden on outcome parameters after correction for predefined variables. RESULTS: Patients had a median age of 58 years (interquartile range 49-68) and presented with a median Hunt & Hess score of 3 (interquartile range 2-5) on admission. Fever (temperature > 37.9 °C) was diagnosed in 283 of 375 (76%) patients during 14% of the monitored time. The average daily fever burden peaked between days 5 and 10 after admission. Higher Hunt & Hess score (p = 0.014), older age (p = 0.033), and pneumonia (p = 0.022) were independent factors associated with delayed fever burden between days 5 and 10. Increased fever burden was independently associated with poor 3-month functional outcome (modified Rankin Scale 3-6, p = 0.027), poor 12-month functional outcome (p = 0.020), and in-hospital mortality (p = 0.045), but not with the development of delayed cerebral ischemia (p = 0.660) or intensive care unit length of stay (p = 0.573). Spontaneous hypothermia was evident in the first three days in patients with a higher Hunt & Hess score (p < 0.001) and intraventricular hemorrhage (p = 0.047). Spontaneous hypothermia burden was not associated with poor 3-month outcome (p = 0.271). CONCLUSIONS: Early hypothermia was followed by fever after SAH. Increased fever time burden was associated with poor functional outcome after SAH and could be considered for neuroprognostication.

Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations.

AIMS AND SCOPE: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. METHODS: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. RESULTS: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. CONCLUSIONS: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.

Contemporary management of aneurysmal subarachnoid haemorrhage. An update for the intensivist.

Aneurysmal subarachnoid haemorrhage (aSAH) is a rare yet profoundly debilitating condition associated with high global case fatality and morbidity rates. The key determinants of functional outcome include early brain injury, rebleeding of the ruptured aneurysm and delayed cerebral ischaemia. The only effective way to reduce the risk of rebleeding is to secure the ruptured aneurysm quickly. Prompt diagnosis, transfer to specialized centers, and meticulous management in the intensive care unit (ICU) significantly improved the prognosis of aSAH. Recently, multimodality monitoring with specific interventions to correct pathophysiological imbalances has been proposed. Vigilance extends beyond intracranial concerns to encompass systemic respiratory and haemodynamic monitoring, as derangements in these systems can precipitate secondary brain damage. Challenges persist in treating aSAH patients, exacerbated by a paucity of robust clinical evidence, with many interventions showing no benefit when tested in rigorous clinical trials. Given the growing body of literature in this field and the issuance of contemporary guidelines, our objective is to furnish an updated review of essential principles of ICU management for this patient population. Our review will discuss the epidemiology, initial stabilization, treatment strategies, long-term prognostic factors, the identification and management of post-aSAH complications. We aim to offer practical clinical guidance to intensivists, grounded in current evidence and expert clinical experience, while adhering to a concise format.

Endothelial receptor proteins in acute venous thrombosis and delayed thrombus resolution in cerebral sinus vein thrombosis.

BACKGROUND AND PURPOSE: Cerebral sinus venous thrombosis (CSVT) is a rare but life-threatening disease and its diagnosis remains challenging. Blood biomarkers, including D-Dimer are currently not recommended in guidelines. Soluble endothelial receptor proteins (sICAM-1, sPECAM-1 and sVCAM-1) have been shown to be promising diagnostic biomarkers in deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, we examined endothelial receptor proteins as potential biomarkers for detecting CSVT. METHODS: In this bi-centre, prospective study, we quantified D-Dimer as well as sICAM-1, sPECAM-1 and sVCAM-1 in plasma of patients with clinically suspected CSVT managed in the neurological emergency department (ED) of a tertiary care hospital. All patients underwent cerebral magnetic resonance imaging (MRI) and were followed up after 3, 6 and 12 months to detect thrombus resolution. RESULTS: Twenty-four out of 75 (32%) patients with clinically suspected CSVT presenting with headache to the ED were diagnosed with acute CSVT. These patients had a mean age of 45 ± 16 years and 78% were female. In patients with CSVT, mean baseline D-dimer (p < 0.001) and sPECAM-1 (p < 0.001) were significantly higher compared to patients without CSVT. The combination of D-Dimer and sPECAM-1 yielded the best ROC-AUC (0.994; < 0.001) with a negative predictive value of 95.7% and a positive predictive value of 95.5%. In addition, higher baseline sPECAM-1 levels (> 198 ng/ml) on admission were associated with delayed venous thrombus resolution at 3 months (AUC = 0.83). CONCLUSION: sPECAM-1 in combination with D-Dimer should be used to improve the diagnostic accuracy of acute CSVT and sPECAM-1 may predict long-term outcome of CSVT. Confirmatory results are needed in other settings in order to show their value in the management concept of CSVT patients.

The European Academy of Neurology NeuroCOVID-19 Task Force: A lesson for the future.

BACKGROUND: The COVID-19 pandemic has made its mark on world history forever causing millions of deaths, and straining health systems, economies, and societies worldwide. The European Academy of Neurology (EAN) reacted promptly. A special NeuroCOVID-19 Task Force was set up at the beginning of the pandemic to promote knowledge, research, international collaborations, and raise awareness about the prevention and treatment of COVID-19-related neurological issues. METHODS: Activities carried out during and after the pandemic by the EAN NeuroCOVID-19 Task Force are described. The main aim was to review all these initiatives in detail as an overarching lesson from the past to improve the present and be better prepared in case of future pandemics. RESULTS: During the pandemic, the Task Force was engaged in several initiatives: the creation of the EAN NEuro-covid ReGistrY (ENERGY); the launch of several surveys (neurological manifestations of COVID-19 infection; the pandemic's impact on patients with chronic neurological diseases; the pandemic's impact of restrictions for clinical practice, curricular training, and health economics); the publication of position papers regarding the management of patients with neurological diseases during the pandemic, and vaccination hesitancy among people with chronic neurological disorders; and the creation of a dedicated "COVID-19 Breaking News" section in EANpages. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force was immediately engaged in various activities to participate in the fight against COVID-19. The Task Force's concerted strategy may serve as a foundation for upcoming global neurological emergencies.

Outcome predictors of post-COVID conditions in the European Academy of Neurology COVID-19 registry.

Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5 months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations.

Research considerations for prospective studies of patients with coma and disorders of consciousness.

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to disorders of consciousness. Despite advances in these disease-related forms, there remains uncertainty about whether disorders of consciousness are a disease-agnostic unitary entity with a common mechanism, prognosis or treatment response paradigm. Our knowledge of disorders of consciousness has also been hampered by heterogeneity of study designs, variables, and outcomes, leading to results that are not comparable for evidence synthesis. The different backgrounds of professionals caring for patients with disorders of consciousness and the different goals at different stages of care could partly explain this variability. The Prospective Studies working group of the Neurocritical Care Society Curing Coma Campaign was established to create a platform for observational studies and future clinical trials on disorders of consciousness and coma across the continuum of care. In this narrative review, the author panel presents limitations of prior observational clinical research and outlines practical considerations for future investigations. A narrative review format was selected to ensure that the full breadth of study design considerations could be addressed and to facilitate a future consensus-based statement (e.g. via a modified Delphi) and series of recommendations. The panel convened weekly online meetings from October 2021 to December 2022. Research considerations addressed the nosographic status of disorders of consciousness, case ascertainment and verification, selection of dependent variables, choice of covariates and measurement and analysis of outcomes and covariates, aiming to promote more homogeneous designs and practices in future observational studies. The goal of this review is to inform a broad community of professionals with different backgrounds and clinical interests to address the methodological challenges imposed by the transition of care from acute to chronic stages and to streamline data gathering for patients with disorders of consciousness. A coordinated effort will be a key to allow reliable observational data synthesis and epidemiological estimates and ultimately inform condition-modifying clinical trials.

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

Sustained effort network for treatment of status epilepticus/European academy of neurology registry on adult refractory status epilepticus (SENSE-II/AROUSE).

BACKGROUND: Status Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE. METHODS: Sustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted. DISCUSSION: The data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management. TRIAL REGISTRATION: NCT number: NCT05839418.

Optimal Design of Clinical Trials Involving Persons with Disorders of Consciousness.

BACKGROUND: Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC. METHODS: The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC. RESULTS: There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC. CONCLUSIONS: Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care.