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Background and purpose: Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3–6. Multivariate analysis was performed to identify risk factors for late HE, poor 3‐month outcome (modified Rankin Scale score ≥ 4) and mortality. Results: Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10–15], ICH volume of 11 (IQR, 5–24) mL and were 71 (IQR, 61–76) years old. A total of 56% (n = 76) received early DVT prophylaxis, 37% (n = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4–18.5) vs. 17.5 (IQR, 8–29) mL, P = 0.038] and were more often comatose (26% vs. 10%, P = 0.025). Significant late HE [n = 5/134 (3.7%)] was associated with larger initial ICH volume (P = 0.02) and lower thrombocyte count (P = 0.03) but not with early DVT prophylaxis (P = 0.36). Early DVT prophylaxis was not associated with worse outcome. Conclusion: Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH. [ABSTRACT FROM AUTHOR]

Background and Purpose: Prognostication in patients with spontaneous subarachnoid hemorrhage (SAH) can be challenging. The aim of this study was to assess whether cerebrospinal fluid (CSF) red blood cell (RBC) count and total protein (TP) concentration are associated with SAH prognosis., Methods: Patients with SAH treated at the neurological intensive care unit (ICU) in Innsbruck were included in this real-world, observational study. Longitudinal CSF samples were collected as part of routine diagnostics. RBC count and CSF TP at the time of admission (RBC first , TP first ), in Week 1 (RBC Days1-7 , TP Days1-7 ), Week 2 (RBC Days8-14 , TP Days8-14 ), and Week 3 or thereafter (RBC Day>14 , TP Day>14 ), the highest detected value (RBC highest , TP highest ), as well as the RBC count adjusted for disease duration (RBC adjusted ) were assessed. Primary outcomes were good functional outcome after 3 months, defined as modified Rankin scale score ≤2 and ICU survival., Results: A total of 183 SAH patients with a female predominance (69%), a median (interquartile range [IQR]) age of 60 (50-70) years and median (IQR) Hunt and Hess score of 4 (3-5) were included. Multivariable analyses revealed that lower values of RBC first , RBC adjusted , RBC highest , TP first and TP highest were associated with good functional outcome and hospital survival. Lower TP concentrations in Weeks 1, 2 and 3 were associated with good functional outcome, and in Weeks 1 and 2 with ICU survival. Early RBC measurements (Week 1) were associated with good functional outcome and ICU survival., Conclusions: Low CSF RBC counts and TP concentrations were associated with good functional outcome and ICU survival in a real-world cohort of SAH patients requiring external ventricular drainage., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

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., (© 2024. The Author(s).)

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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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-R 2  = 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., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Patients with spontaneous subarachnoid hemorrhage (SAH) frequently encounter cognitive dysfunction and mental health issues with negative effects on health-related quality of life (HR-QoL). Here, we aimed to describe the prevalence of cognitive deficits, mental health problems, and HR-QoL impairments 1 year after SAH., Methods: In this prospective observational study, 177 patients with SAH admitted to our neurointensive care unit over a time span of ten years followed the invitation for an in-person 1-year follow-up, including a standardized neuropsychological test battery. Mental health issues (anxiety and depression) and HR-QoL were evaluated using questionnaires (Hospital Anxiety and Depression Scale; 36-item Short Form questionnaire). Functional outcome was assessed with the modified Rankin Scale (mRS) score., Results: Patients were 54 years of age (interquartile range 47-62 years) and presented with a median Hunt and Hess score of 2 (interquartile range 1-3) at admission. Most patients (93%) achieved good functional 1-year outcomes (mRS score 0-2). Seventy-one percent of patients had deficits in at least one cognitive domain, with memory deficits being the most prevalent (51%), followed by deficits in executive functions (36%), visuoconstruction (34%), and attention (21%). Even patients with perimesencephalic SAH (18%) or with full functional recovery (mRS score = 0, 46%) had a comparable prevalence of cognitive deficits (61% and 60%, respectively). Symptoms of depression and anxiety were reported by 16% and 33% of patients, respectively. HR-QoL was impaired in 37% (55 of 147). Patients with cognitive deficits (p = 0.001) or mental health issues (p < 0.001) more frequently reported impaired HR-QoL., Conclusions: Most patients with SAH have cognitive deficits and mental health issues 1 year after SAH. These deficits impair patients' quality of life., (© 2023. The Author(s).)

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.

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., (© 2024. The Author(s).)

Background: The limited representation from developing countries in the original COME TOGETHER survey gave us an impetus to conduct this survey in the Indian subcontinent., Methods: This cross-sectional online survey was conducted from August through September 2022. Participants were health care physicians caring for patients with coma and disorders of consciousness. Fischer's exact test or the Mann-Whitney U-test was used to compare respondents who agreed or disagreed with the preestablished coma definition. Fleiss κ values were calculated to assess agreement among respondents. A p value less than 0.05 was considered statistically significant., Results: The survey was completed by 130 physicians. We found substantial interrater agreement on absence of wakefulness (71.54%; κ = 0.71), Glasgow Coma Score ≤ 8 (78.46%; κ = 0.78), and failure to respond purposefully to visual, verbal, or tactile stimuli (66.15%; κ = 0.66). Reported common etiologies of coma included traumatic brain injury (50.76%), ischemic stroke (30%), and intracerebral hemorrhage (29.23%). The most common clinical assessment tools used for coma included the Glasgow Coma Score (92.3%) and neurological examination (60.8%). Neurological examination was the most common diagnostic tool used (100%), followed by magnetic resonance imaging (89.2%), basic laboratory studies (88.5%), and head computed tomography/angiography (86.9%). Pharmacological interventions used to stimulate arousal in patients with coma were sedation vacation (91.5%), electrolyte/endocrine correction (65.4%), osmotic therapy with mannitol (60%), hypertonic saline (54.6%), modafinil (46.9%), and antidote for drugs (45.4%). Among the nonpharmacological interventions, sensory stimulation (57.7%) was the most commonly used modality. The most common discharge disposition for comatose patients who survived hospitalization were home with or without services (70.0%)., Conclusions: Differences from the global survey were noted regarding the following: traumatic brain injury being the most common etiology of coma in India, more frequent practice of sedation interruption, less frequent use of electroencephalography in India, rare use of pharmacological neurostimulants, and home being the most common discharge disposition in India., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: Long-term consequences after COVID-19 include physical complaints, which may impair physical recovery and quality of life., Design: We assessed body composition and physical ability in patients 12 months after COVID-19. Consecutively recruited patients recovering from mild to severe COVID-19 were assessed using bioelectrical impedance analysis, 6-min-walk test, additional scales for physical performance and health-related quality of life., Results: Overall physical recovery was good (i.e., Glasgow Outcome Scale-Extended ≥7 in 96%, Modified Rankin Scale ≤1 in 87%, Eastern Cooperative Oncology Group ≤1 in 99%). Forty-four percent of the 69 patients experienced a significant body mass index increase in the year after COVID-19 (≥1 kg/m 2 ), whereas skeletal muscle mass index was reduced in only 12%. Patients requiring intensive care treatment ( n = 15, 22%) during acute COVID-19 more often had a body mass index increase ( P = 0.002), worse 6-min-walk test-performance ( P = 0.044), and higher body fat mass ( P = 0.030) at the 1-yr follow-up when compared with patients with mild ( n = 22, 32%) and moderate ( n = 32, 46%) acute COVID-19. Body mass index increase was also more frequent in patients who had no professional rehabilitation ( P = 0.014)., Conclusions: Although patients with severe COVID-19 had increased body mass index and body fat and performed worse in physical outcome measures 1 yr after COVID-19, overall physical recovery was satisfying. Translating these findings to variants beyond the Alpha strain of severe acute respiratory syndrome coronavirus 2 virus needs further studies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Lumbar puncture (LP) is recommended in patients with thunderclap headache and negative computed tomography to rule out spontaneous subarachnoid haemorrhage (SAH). Blood contamination of cerebrospinal fluid (CSF) due to traumatic LP poses a diagnostic dilemma. Therefore, routine CSF parameters were investigated to distinguish between SAH and a traumatic LP. CSF red blood cell (RBC), white blood cell (WBC) count, total protein, CSF colour and supernatant were used for group comparisons of patients with SAH and 'symptomatic controls'. Due to variable time intervals between bleeding onset and LP in SAH patients in contrast to patients with traumatic LP, where blood contamination of CSF occurs at the time of LP, CSF variables were adjusted for decay in time to allow comparability. Logistic regression analysis identified bloody CSF [odds ratio (OR) 32.6], xanthochromic supernatant [OR 15.5] and WBC adjusted [OR 4.5 (per increase of 100/µl)] as predictors of SAH, while age, sex and CSF total protein adjusted were no predictors. Optimal cut-point of RBC adjusted (determined at day 1 after bleeding) was > 3667/µl to identify SAH patients with a 97% sensitivity and 94% specificity. Combination of low RBC and clear CSF supernatant was found in none of SAH patients. Combined CSF RBC count and CSF supernatant reliably distinguished traumatic LP from SAH., (© 2023. The Author(s).)

Background: Cerebral microdialysis (CMD) has become an established bedside monitoring modality but its implementation remains complex and costly and is therefore performed only in a few well-trained academic centers. This study investigated the relationship between cerebrospinal fluid (CSF) and CMD glucose and lactate concentrations., Methods: Two centers retrospective study of prospectively collected data. Consecutive adult (>18 years) acutely brain injured patients admitted to the Intensive Care Unit between 2010 and 2021 were eligible if CSF and CMD glucose and lactate concentrations were concomitantly measured at least once., Results: Of 113 patients being monitored with an external ventricular drainage and CMD, 49 patients (25 from Innsbruck and 24 from Brussels) were eligible for the final analysis, including a total of 96 measurements. Median CMD glucose and lactate concentrations were 1.15 (0.51-1.57) mmol/L and 3.44 (2.24-5.37) mmol/L, respectively; median CSF glucose and lactate concentrations were 4.67 (4.03-5.34) mmol/L and 3.40 (2.85-4.10) mmol/L, respectively. For the first measurements, no correlation between CSF and CMD glucose concentrations (R 2 <0.01; p = 0.95) and CSF and CMD lactate concentrations (R 2 =0.16; p = 0.09) was found. Considering all measurements, the repeated measure correlation analysis also showed no correlation for glucose (r rm = -0.01; 95% Confidence Intervals -0.306 to 0.281; p = 0.93) and lactate (r rm = -0.11; 95% Confidence Intervals -0.424 to 0.236; p = 0.55)., Conclusions: In this study including acute brain injured patients, no correlation between CSF and brain tissue measurements of glucose and lactate was observed. As such, CSF measurements of such metabolites cannot replace CMD findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests regarding this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Olfactory dysfunction (OD) commonly accompanies coronavirus disease 2019 (COVID-19). We investigated the kinetics of OD resolution following SARS-CoV-2 infection (wild-type and alpha variant) and its impact on quality of life, physical and mental health., Methods: OD prevalence was assessed in an ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and an observational cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up). Co-occurrence of OD with other symptoms and effects on quality of life, physical and mental health were analyzed by multi-dimensional scaling, association rule mining and semi-supervised clustering., Results: Both in the ambulatory COVID-19 survey study (72%) and the observational ambulatory and hospitalized cohort (41%) self-reported OD was frequent during acute COVID-19. Recovery from self-reported OD was slow (survey: median 28 days, observational cohort: 90 days). By clustering of the survey data, we identified a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorders (median recovery: 90 days) but low frequency of post-acute fatigue, respiratory or neurocognitive symptoms. This smell and taste disorder cluster was characterized by a high rating of physical performance, mental health, and quality of life as compared with convalescents affected by prolonged fatigue or neurocognitive complaints., Conclusion: Our results underline the heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype is characterized by good clinical, physical, and mental recovery and may pose a minor challenge for public health., Study Registration: ClinicalTrials.gov: NCT04661462 (survey study), NCT04416100 (observational cohort)., (© 2023. The Author(s).)

Background and Purpose: Red blood cell (RBC) degradation after subarachnoid haemorrhage (SAH) negatively affects functional outcome. Although the detection of RBCs in the cerebrospinal fluid (CSF) is a widely available part of neurological routine diagnostics, the prognostic value as a biomarker remains unclear. This study was undertaken to investigate whether CSF RBC count correlates with established radiological markers of SAH volume and whether the CSF RBC count can predict functional outcome in SAH patients., Methods: A total of 121 consecutive spontaneous SAH patients were retrospectively analyzed. CSF was collected from external ventricular drain as part of routine diagnostic procedures. We used multivariable binary logistic regression to investigate associations between CSF RBC counts and functional outcome 3 months after SAH or hospital survival. Good functional outcome was defined as modified Rankin Scale ≤ 2., Results: Patients' age was 60 ± 14 years, and the median admission Hunt & Hess grade (H&H) was 4. CSF samples were collected 2 days after intensive care unit admission. High CSF RBC counts positively correlated with radiological measurements for SAH volume, for example, modified Fisher score (p = 0.002) and Hijdra ventricle score (p = 0.016). Multivariable regression analysis adjusted for age, H&H grade, modified Fisher and Hijdra scores showed that low CSF RBC counts predicted hospital survival (per 100,000 CSF RBCs: adjusted odds ratio [adjOR] = 0.74, 95% confidence interval [CI] = 0.61-0.89, p = 0.001) and good functional outcome after 3 months (per 100,000 CSF RBC: adjOR = 0.76, 95% CI = 0.60-0.96, p = 0.020)., Conclusions: CSF RBC counts correlate with radiographic scores quantifying SAH volume and may serve as an early independent biomarker for hospital survival and good functional 3-month outcome in patients requiring ventriculostomy after SAH., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Nimodipine is recommended to prevent delayed cerebral ischemia in patients with spontaneous subarachnoid hemorrhage (SAH). Here, we studied hemodynamic side effects of different nimodipine formulations (per os [PO] and intravenous [IV]) in patients with SAH undergoing continuous blood pressure monitoring., Methods: This observational cohort study includes consecutive patients with SAH (271 included in the IV group, 49 in the PO group) admitted to a tertiary care center between 2010 and 2021. All patients received prophylactic IV or PO nimodipine. Hemodynamic responses were evaluated based on median values within the first hour after continuous IV nimodipine initiation or PO nimodipine application (601 intakes within 15 days). Significant changes were defined as > 10% drop in systolic blood pressure (SBP) or diastolic blood pressure from baseline (median values 30 min before nimodipine application). With the use of multivariable logistic regression, risk factors associated with SBP drops were identified., Results: Patients were admitted with a median Hunt & Hess score of 3 (2-5; IV 3 [2-5], PO 1 [1-2], p < 0.001) and were 58 (49-69) years of age. Initiation of IV nimodipine was associated with a > 10% SBP drop in 30% (81/271) of patients, with a maximum effect after 15 min. A start or increase in noradrenaline was necessary in 136/271 (50%) patients, and colloids were administered in 25/271 (9%) patients within 1 h after IV nimodipine initiation. SBP drops > 10% occurred after 53/601 (9%) PO nimodipine intakes, with a maximum effect after 30-45 min in 28/49 (57%) patients. Noradrenaline application was uncommon (3% before and 4% after nimodipine PO intake). Hypotensive episodes to an SBP < 90 mm Hg were not observed after IV or PO nimodipine application. In multivariable analysis, only a higher SBP at baseline was associated with a > 10% drop in SBP after IV (p < 0.001) or PO (p = 0.001) nimodipine application, after adjusting for the Hunt & Hess score on admission, age, sex, mechanical ventilation, days after intensive care unit admission, and delayed cerebral ischemia., Conclusions: Significant drops in SBP occur in one third of patients after the start of IV nimodipine and after every tenth PO intake. Early recognition and counteracting with vasopressors or fluids seems necessary to prevent hypotensive episodes., (© 2023. The Author(s).)

Background: Intensive care unit (ICU) acquired weakness is a major contributor to poor functional outcome of ICU patients. Quantification of temporal muscle volume assessed on routine computed tomography (CT) scans may serve as a biomarker for muscle wasting in patients suffering from acute brain injury., Methods: This is a retrospective analysis of prospectively collected data. Temporal muscle volume was assessed on head CT scans of consecutive patients with spontaneous subarachnoid hemorrhage within prespecified time frames (on admission, then weekly ± 2 days). Whenever possible, temporal muscle volume was assessed bilaterally and averaged for the analysis. Poor functional outcome was defined as a 3-month modified Rankin Scale Score ≥ 3. Statistical analysis was performed using generalized estimating equations to handle repeated measurements within individuals., Results: The analysis comprised 110 patients with a median Hunt & Hess score of 4 (interquartile range 3-5). Median age was 61 (50-70) years, 73 patients (66%) were women. Baseline temporal muscle volume was 18.5 ± 0.78 cm 3 and significantly decreased over time (p < 0.001) by a mean of 7.9% per week. Higher disease severity (p = 0.002), hydrocephalus (p = 0.020), pneumonia (p = 0.032), and bloodstream infection (p = 0.015) were associated with more pronounced muscle volume loss. Patients with poor functional outcome had smaller muscle volumes 2 and 3 weeks after subarachnoid hemorrhage compared with those with good outcome (p = 0.025). The maximum muscle volume loss during ICU stay was greater in patients with poor functional outcome (- 32.2% ± 2.5% vs. - 22.7% ± 2.5%, p = 0.008). The hazard ratio for poor functional outcome was 1.027 (95% confidence interval 1.003-1.051) per percent of maximum muscle volume loss., Conclusions: Temporal muscle volume, which is easily assessable on routine head CT scans, progressively decreases during the ICU stay after spontaneous subarachnoid hemorrhage. Because of its association with disease severity and functional outcome, it may serve as a biomarker for muscle wasting and outcome prognostication., (© 2023. The Author(s).)

Inflammation of the spinal cord and the adjacent structures can be caused by viruses, bacteria, fungi and parasites. Viruses predominantly infect the spinal cord and the nerve roots directly or trigger a secondary immune response, whereas bacteria, fungi and parasites tend to form abscesses, granulomas and cysts and can lead to a secondary compression of the spinal cord, similar to a destructive osteomyelitis. The etiological clarification of an acute or subacute spinal process is carried out based on the clinical presentation, the time course of the development of symptoms, the immune status, neuroimaging and microbial and/or molecular biological examinations of cerebrospinal fluid and serum. The tropism of individual pathogens to certain fiber structures and cellular clusters in the spinal cord in synopsis with the clinical presentation, neuroimaging and a history of exposure, can often quickly lead to a focused clarification and diagnosis. This article deals with important pathogens of spinal and paraspinal infections, the geographical distribution, the clinical and neuroimaging presentation with special consideration of the anatomical and topographical localization and recent epidemiological developments. Particular attention is paid to the outbreak of poliomyelitis due to circulating vaccine-derived poliovirus (cVDPV)., (© 2023. The Author(s).)

Background: Recovery trajectories from coronavirus disease 2019 (COVID-19) call for longitudinal investigation. We aimed to characterise the kinetics and status of clinical, cardiopulmonary and mental health recovery up to 1 year following COVID-19., Methods: Clinical evaluation, lung function testing (LFT), chest computed tomography (CT) and transthoracic echocardiography were conducted at 2, 3, 6 and 12 months after disease onset. Submaximal exercise capacity, mental health status and quality of life were assessed at 12 months. Recovery kinetics and patterns were investigated by mixed-effect logistic modelling, correlation and clustering analyses. Risk of persistent symptoms and cardiopulmonary abnormalities at the 1-year follow-up were modelled by logistic regression., Findings: Out of 145 CovILD study participants, 108 (74.5%) completed the 1-year follow-up (median age 56.5 years; 59.3% male; 24% intensive care unit patients). Comorbidities were present in 75% (n=81). Key outcome measures plateaued after 180 days. At 12 months, persistent symptoms were found in 65% of participants; 33% suffered from LFT impairment; 51% showed CT abnormalities; and 63% had low-grade diastolic dysfunction. Main risk factors for cardiopulmonary impairment included pro-inflammatory and immunological biomarkers at early visits. In addition, we deciphered three recovery clusters separating almost complete recovery from patients with post-acute inflammatory profile and an enrichment in cardiopulmonary residuals from a female-dominated post-COVID-19 syndrome with reduced mental health status., Conclusion: 1 year after COVID-19, the burden of persistent symptoms, impaired lung function, radiological abnormalities remains high in our study population. Yet, three recovery trajectories are emerging, ranging from almost complete recovery to post-COVID-19 syndrome with impaired mental health., Competing Interests: Conflict of interest: P. Tymoszuk owns the Data Analytics as a Service data science enterprise and is (from May 2021 on) a freelance data scientist working in his own enterprise; he received honoraria for the statistical analysis of the CovILD study. All other authors have no conflict of interest related to this study to declare., (Copyright ©The authors 2023.)

Background and Purpose: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations., Methods: The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors., Results: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N = 449, 29.5%), stroke (N = 392, 25.7%), sleep-wake disturbances (N = 250, 16.4%), dysautonomia (N = 224, 14.7%), peripheral neuropathy (N = 145, 9.5%), movement disorders (N = 142, 9.3%), ataxia (N = 134, 8.8%), and seizures (N = 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome., Conclusions: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19., (© 2022 European Academy of Neurology.)

Background and Purpose: Non-traumatic subarachnoid hemorrhage (SAH) is a devastating disease associated with high morbidity and mortality. A higher blood burden and the presence of intraparenchymal extension of the bleeding (intracerebral hemorrhage [ICH]) are well known predictors of poor outcome. Only few studies have addressed the role of hematoma location on patient's functional outcome. The main aims were to compare clinical and radiographic characteristics between SAH patients with and without ICH and to compare different ICH localizations in relation to long-term functional outcome., Methods: We prospectively collected data on 280 consecutive SAH patients (aneurysmal and non-aneurysmal) admitted to a tertiary care hospital between 2010 and 2017 and assessed the initial computed tomography scans of the brain acquired after intensive care unit admission. Poor functional outcome was defined as a modified Rankin Scale score >2, 3 months after SAH. We used multivariable logistic linear regression to investigate associations between ICH location and clinical variables as well as functional outcome., Results: Intraparenchymal extension of the hemorrhage was observed in 59/280 patients (21%). The median (interquartile range) ICH volume was 11.3 (4.9-16.2) ml and the location was supratentorial in 55/59 patients (93%). Most parenchymal hemorrhages were located in the frontal (n = 24.41%) and temporal lobes (n = 12.21%), followed by insular ICH (n = 7.12%), corpus callosum (n = 6.10%), parietal (n = 2.3%) and occipital locations (n = 2.3%). Among SAH patients with ICH, those with lesions located in the corpus callosum (n = 6/59) had a significantly higher risk of 3-month poor functional outcome in comparison to all other ICH locations, even after adjusting for Hunt and Hess grade and age (adjusted odds ratio [adjOR] 50.5, 95% confidence interval [CI] 1.3-2004.2, p = 0.034). These results remained robust when comparing the whole SAH cohort (adjOR 21.7, 95% CI 1.4-347.8, p = 0.030).  CONCLUSIONS: Intraparenchymal bleeding in patients with non-traumatic SAH, in particular that involving the corpus callosum, strongly predicts functional outcome., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Despite improvements in the critical care management of subarachnoid hemorrhage (SAH), a substantial number of patients still suffer from disabilities. In most areas of the world, longitudinal follow-up is not routinely performed, and the patient's trajectory remains unknown., Methods: We prospectively collected data of 298 consecutive patients with spontaneous SAH and evaluated clinical trajectories at discharge, 3 months, and 1 year after SAH. In a subgroup of patients transferred to a local neurorehabilitation center (Rehab-Hochzirl), we studied the effects of rehabilitation intensity on clinical trajectories. Any decrease in the modified Rankin Scale (mRS) was defined as an improvement, with mRS ≤ 2 indicating good outcome. We used multivariate generalized linear models to investigate associations with clinical trajectories., Results: Out of the 250 surviving patients, 35% were transferred directly to Rehab-Hochzirl (n = 87 of 250; mRS at discharge = 4), 11% were transferred to another rehabilitation center (n = 27 of 250; mRS = 1), 1% were transferred to a nursing home (n = 3 of 250; mRS = 5), 21% were transferred to their country of origin (n = 52 of 250; mRS = 4), and 32% (n = 79 of 250; mRS = 1) were discharged home. Functional outcome improved in 57% (n = 122 of 215) of patients during the first 3 months, with an additional 16% (35 of 215) improving between 3 and 12 months, resulting in an overall improvement in 73% (n = 157 of 215) of survivors. After 1 year, 60% (n = 179 of 250) of patients were functionally independent. A lower Hunt and Hess scale score at intensive care unit admission, younger age, a lower mRS at intensive care unit discharge, fewer days on mechanical ventilation, and male sex were independently associated with better functional recovery. Although the subgroup of patients transferred to Rehab-Hochzirl were more severely affected, 60% (52 of 87) improved during inpatient neurorehabilitation., Conclusions: Our results indicate ongoing functional improvement in a substantial number of patients with SAH throughout a follow-up period of 12 months. This effect was also observed in patients with severe disability receiving inpatient neurorehabilitation., (© 2022. The Author(s).)

Subarachnoid haemorrhage is a devastating disease that results in neurocognitive deficits and a poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long-term functional and neuropsychological outcomes in poor-grade subarachnoid haemorrhage patients. We recruited 55 consecutive non-traumatic subarachnoid haemorrhage patients who underwent multimodal neuromonitoring, including cerebral microdialysis. Mitochondrial dysfunction was defined as lactate-to-pyruvate ratio >30 together with pyruvate >70 mmol/L and metabolic distress as lactate-to-pyruvate ratio >40. The multidimensional 12-month outcome was assessed by means of the modified Rankin scale (poor outcome: modified Rankin scale ≥4) and a standardized neuropsychological test battery. We used multivariable generalized estimating equation models to assess associations between total microdialysate-tau levels of the first 10 days after admission and hospital complications and outcomes. Patients were 56 ± 12 years old and presented with a median Hunt & Hess score of 5 (interquartile range: 3-5). Overall mean total microdialysate-tau concentrations were highest within the first 24 h (5585 ± 6291 pg/mL), decreased to a minimum of 2347 ± 4175 pg/mL on Day 4 ( P < 0.001) and remained stable thereafter ( P = 0.613). Higher total microdialysate-tau levels were associated with the occurrence of delayed cerebral ischaemia ( P = 0.001), episodes of metabolic distress ( P = 0.002) and mitochondrial dysfunction ( P = 0.034). Patients with higher tau levels had higher odds for a poor 12-month functional outcome (adjusted odds ratio: 2.61; 95% confidence interval: 1.32-5.17; P = 0.006) and impaired results in the trail making test-B (adjusted odds ratio: 3.35; 95% confidence interval: 1.16-9.68; P = 0.026) indicative of cognitive flexibility. Total microdialysate-tau levels significantly decreased over the first 10 days ( P < 0.05) in patients without delayed cerebral ischaemia or good functional outcomes and remained high in those with delayed cerebral ischaemia and poor 12-month outcomes, respectively. Dynamic changes of total tau in the cerebral microdialysate may be a useful biomarker for axonal damage associated with functional and neurocognitive recovery in poor-grade subarachnoid haemorrhage patients. In contrast, ongoing axonal damage beyond Day 3 after bleeding indicates a higher risk for delayed cerebral ischaemia as well as a poor functional outcome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Increasing evidence suggests persistent cognitive dysfunction after COVID-19. In this cross-sectional study, frontal lobe function was assessed 12 months after the acute phase of the disease, using tailored eye tracking assessments. Individuals who recovered from COVID-19 made significantly more errors in all eye tracking tasks compared to age/sex-matched healthy controls. Furthermore, patients who were treated as inpatients performed worse compared to outpatients and controls. Our results show impaired inhibitory cortical control in individuals who recovered from COVID-19. The association between disease severity and its sequelae may contribute to a better understanding of post-COVID-19 cognitive function., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID)., Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration., Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022., Exposures: Symptomatic SARS-CoV-2 infection., Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age., Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months., Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

The epidemiology of coma is unknown because case ascertainment with traditional methods is difficult. Here, we used crowdsourcing methodology to estimate the incidence and prevalence of coma in the UK and the USA. We recruited UK and US laypeople (aged ≥18 years) who were nationally representative (i.e. matched for age, gender and ethnicity according to census data) of the UK and the USA, respectively, utilizing a crowdsourcing platform. We provided a description of coma and asked survey participants if they-'right now' or 'within the last year'-had a family member in coma. These participants (UK n  = 994, USA n  = 977) provided data on 30 387 family members (UK n  = 14 124, USA n  = 16 263). We found more coma cases in the USA ( n  = 47) than in the UK ( n  = 20; P  = 0.009). We identified one coma case in the UK (0.007%, 95% confidence interval 0.00-0.04%) on the day of the survey and 19 new coma cases (0.13%, 95% confidence interval 0.08-0.21%) within the preceding year, resulting in an annual incidence of 135/100 000 (95% confidence interval 81-210) and a point prevalence of 7 cases per 100 000 population (95% confidence interval 0.18-39.44) in the UK. We identified five cases in the USA (0.031%, 95% confidence interval 0.01-0.07%) on the day of the survey and 42 new cases (0.26%, 95% confidence interval 0.19-0.35%) within the preceding year, resulting in an annual incidence of 258/100 000 (95% confidence interval 186-349) and a point prevalence of 31 cases per 100 000 population (95% confidence interval 9.98-71.73) in the USA. The five most common causes were stroke, medically induced coma, COVID-19, traumatic brain injury and cardiac arrest. To summarize, for the first time, we report incidence and prevalence estimates for coma across diagnosis types and settings in the UK and the USA using crowdsourcing methods. Coma may be more prevalent in the USA than in the UK, which requires further investigation. These data are urgently needed to expand the public health perspective on coma and disorders of consciousness., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Long COVID, defined as the presence of coronavirus disease 2019 (COVID-19) symptoms ≥28 days after clinical onset, is an emerging challenge to healthcare systems. The objective of the current study was to explore recovery phenotypes in nonhospitalized individuals with COVID-19., Methods: A dual cohort, online survey study was conducted between September 2020 and July 2021 in the neighboring European regions Tyrol (TY; Austria, n = 1157) and South Tyrol (STY; Italy, n = 893). Data were collected on demographics, comorbid conditions, COVID-19 symptoms, and recovery in adult outpatients. Phenotypes of acute COVID-19, postacute sequelae, and risk of protracted recovery were explored using semi-supervised clustering and multiparameter least absolute shrinkage and selection operator (LASSO) modeling., Results: Participants in the study cohorts were predominantly working age (median age [interquartile range], 43 [31-53] years] for TY and 45 [35-55] years] for STY) and female (65.1% in TY and 68.3% in STY). Nearly half (47.6% in TY and 49.3% in STY) reported symptom persistence beyond 28 days. Two acute COVID-19 phenotypes were discerned: the nonspecific infection phenotype and the multiorgan phenotype (MOP). Acute MOP symptoms encompassing multiple neurological, cardiopulmonary, gastrointestinal, and dermatological symptoms were linked to elevated risk of protracted recovery. The major subset of individuals with long COVID (49.3% in TY; 55.6% in STY) displayed no persistent hyposmia or hypogeusia but high counts of postacute MOP symptoms and poor self-reported physical recovery., Conclusions: The results of our 2-cohort analysis delineated phenotypic diversity of acute and postacute COVID-19 manifestations in home-isolated patients, which must be considered in predicting protracted convalescence and allocating medical resources., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)