Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy.

Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68%), we observed a hypothalamic and brainstem-predominant tauopathy of varying severity in which the original research neuropathological criteria were readily applicable. This pathology was observed in younger patients (median age at onset 61 years) with a long disease duration (median 9 years). In contrast, in 7 (32%) patients, the originally described brainstem tauopathy was nearly absent or only minimal in the form of delicate threads, despite mild-to-moderate neurodegenerative features, consistent clinical symptoms and the presence of anti-IgLON5 antibodies in CSF and serum. These patients were older at onset (median 79 years) and had shorter disease duration (median < 1 year). Overall, about one-third of the patients showed concomitant TDP-43 pathology within the regions affected by tau pathology and/or neurodegeneration. Based on these observations and in view of the spectrum of the tau burden in the core regions involved in the disease, we propose a simple staging system: stage 1 mild neurodegeneration without overt or only minimal tau pathology, stage 2 moderate neurodegeneration and mild/ moderate tauopathy and stage 3 prominent neurodegeneration and tau pathology. This staging intends to reflect a potential (age- and time-dependent) progression of tau pathology, supporting the current notion that tau accumulation is a secondary phenomenon related to the presence of anti-IgLON5 antibodies in the CNS. Finally, we adapt the original research criteria of the anti-IgLON5 disease-related tauopathy to include the spectrum of pathologies observed in this larger postmortem series.

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.

Cognitive, Mental Health, Functional, and Quality of Life Outcomes 1 Year After Spontaneous Subarachnoid Hemorrhage: A Prospective Observational Study.

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.

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.

Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2.

BACKGROUND AND PURPOSE: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), rapidly spread across the globe. Tremendous efforts have been mobilized to create effective antiviral treatment options to reduce the burden of the disease. This article summarizes the available knowledge about the antiviral drugs against SARS-CoV-2 from a neurologist's perspective. METHODS: We summarize neurological aspects of antiviral compounds against SARS-CoV-2 with full, conditional, or previous marketing authorization by the European Medicines Agency (EMA). RESULTS: Nirmatrelvir/ritonavir targets the SARS-CoV-2 3c-like protease using combinatorial chemistry. Nirmatrelvir/ritonavir levels are affected by medications metabolized by or inducing CYP3A4, including those used in neurological diseases. Dysgeusia with a bitter or metallic taste is a common side effect of nirmatrelvir/ritonavir. Molnupiravir is a nucleotide analog developed to inhibit the replication of viruses. No clinically significant interactions with other drugs have been identified, and no specific considerations for people with neurological comorbidity are required. In the meantime, inconsistent results from clinical trials regarding efficacy have led to the withdrawal of marketing authorization by the EMA. Remdesivir is a viral RNA polymerase inhibitor and interferes with the production of viral RNA. The most common side effect in patients with COVID-19 is nausea. Remdesivir is a substrate for CYP3A4. CONCLUSIONS: Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.

Lower initial red blood cell count in cerebrospinal fluid predicts good functional outcome in patients with spontaneous subarachnoid haemorrhage.

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.

The location of intraparenchymal bleeding determines functional outcome after spontaneous subarachnoid hemorrhage.

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.

Blood Pressure Changes in Association with Nimodipine Therapy in Patients with Spontaneous Subarachnoid Hemorrhage.

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.

Long-Term Clinical Trajectory of Patients with Subarachnoid Hemorrhage: Linking Acute Care and Neurorehabilitation.

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.

The Loss of Temporal Muscle Volume is Associated with Poor Outcome in Patients with Subarachnoid Hemorrhage: An Observational Cohort Study.

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 cm3 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.

Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae.

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).

[Infections of the spinal cord and adjacent structures]. / Infektionen des Rückenmarks und der angrenzenden Strukturen.

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).

Factors Associated With Prolonged Mechanical Ventilation in Patients With Subarachnoid Hemorrhage-The RAISE Score.

OBJECTIVES: Patients suffering from spontaneous subarachnoid hemorrhage frequently require mechanical ventilation. Here, we aimed to identify factors associated with prolonged mechanical ventilation in subarachnoid hemorrhage patients and to create a new predictive score for prolonged mechanical ventilation. DESIGN: Prospective cohort study with retrospective data analysis. SETTING: Neurocritical care unit at a tertiary academic medical center. PATIENTS: Two hundred ninety-seven consecutive nontraumatic adult subarachnoid hemorrhage patients. METHODS: In patients with mechanical ventilation, we identified factors associated with mechanical ventilation greater than 48 hours, greater than 7 days, and greater than 14 days compared with mechanical ventilation less than or equal to 48 hours, less than or equal to 7 days, or less than or equal to 14 days in multivariable generalized linear models. Ventilated patients who died before 48 hours, 7 days, or 14 days and those never ventilated were excluded from the respective analysis. We incorporated those factors into a new prognostic score (the RAISE score) to predict prolonged mechanical ventilation greater than 7 days. The calculation was based on a random dataset of 60% of subarachnoid hemorrhage patients and was internally validated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were 57 years old (interquartile range, 47-68 yr) and presented with a median Hunt and Hess grade of 3 (1-5). Two hundred forty-two patients (82%) required mechanical ventilation for 9 days (2-20 d). In multivariable analysis, a higher Acute Physiology Score was associated with mechanical ventilation greater than 48 hours, greater than 7 days, and greater than 14 days, a higher Hunt and Hess grade with greater than 7 days and greater than 14 days. Early neuroimaging findings were associated with mechanical ventilation greater than 48 hours (hydrocephalus; high-grade Subarachnoid Hemorrhage Early Brain Edema Score), greater than 7 days (high-grade Subarachnoid Hemorrhage Early Brain Edema Score, co-occurrence of intracerebral bleeding) but not with prolonged mechanical ventilation greater than 14 days. The RAISE score, including age, Acute Physiology Score, Hunt and Hess grade, Subarachnoid Hemorrhage Early Brain Edema Score, and the co-occurrence of intracerebral hemorrhage accurately stratified patients by prolonged mechanical ventilation greater than 7 days (C-statistic 0.932). A RAISE score of 12 predicted 60% likelihood of mechanical ventilation greater than 7 days. CONCLUSIONS: Initial disease severity and neuroimaging findings detected within 24 hours after ICU admission were associated with the need for prolonged mechanical ventilation in patients with subarachnoid hemorrhage. These results may be helpful for patient families and caregivers to better anticipate the course of therapy.

Neurological outcomes 1 year after COVID-19 diagnosis: A prospective longitudinal cohort study.

BACKGROUND AND PURPOSE: Neurological sequelae from coronavirus disease 2019 (COVID-19) may persist after recovery from acute infection. Here, the aim was to describe the natural history of neurological manifestations over 1 year after COVID-19. METHODS: A prospective, multicentre, longitudinal cohort study in COVID-19 survivors was performed. At a 3-month and 1-year follow-up, patients were assessed for neurological impairments by a neurological examination and a standardized test battery including the assessment of hyposmia (16-item Sniffin' Sticks test), cognitive deficits (Montreal Cognitive Assessment < 26) and mental health (Hospital Anxiety and Depression Scale and Post-traumatic Stress Disorder Checklist 5). RESULTS: Eighty-one patients were evaluated 1 year after COVID-19, out of which 76 (94%) patients completed a 3-month and 1-year follow-up. Patients were 54 (47-64) years old and 59% were male. New and persistent neurological disorders were found in 15% (3 months) and 12% (10/81; 1 year). Symptoms at 1-year follow-up were reported by 48/81 (59%) patients, including fatigue (38%), concentration difficulties (25%), forgetfulness (25%), sleep disturbances (22%), myalgia (17%), limb weakness (17%), headache (16%), impaired sensation (16%) and hyposmia (15%). Neurological examination revealed findings in 52/81 (64%) patients without improvement over time (3 months, 61%, p = 0.230) including objective hyposmia (Sniffin' Sticks test <13; 51%). Cognitive deficits were apparent in 18%, whereas signs of depression, anxiety and post-traumatic stress disorders were found in 6%, 29% and 10% respectively 1 year after infection. These mental and cognitive disorders had not improved after the 3-month follow-up (all p > 0.05). CONCLUSION: Our data indicate that a significant patient number still suffer from neurological sequelae including neuropsychiatric symptoms 1 year after COVID-19 calling for interdisciplinary management of these patients.

Caspr2 antibodies in herpes simplex encephalitis: an extension of the spectrum of virus induced autoimmunity? - A case report.

BACKGROUND: Post herpes simplex virus (HSV) autoimmune encephalitis has been reported mainly in association with NMDA receptor antibodies, however, never with Caspr2 antibodies. CASE PRESENTATION: We report an 82-year old female patient with encephalitis who presented with aphasia, left temporo-mesial hyperintense lesion on MRI, epileptiform discharges on spot electroencephalography, cerebrospinal fluid (CSF) lymphocytic pleocytosis and who showed positive HSV polymerase chain reaction in CSF as well as antibodies against contactin-associated protein-like 2 (Caspr2). CONCLUSION: This is the first report of a patient with encephalitis who tested positive for HSV as well as for Caspr2 antibodies.

Characteristics of people with epilepsy in three Eastern African countries - a pooled analysis.

BACKGROUND: Epilepsy is one of the most common neurological disorders worldwide. Yet, its treatment gap is large in some areas and especially in sub-Saharan Africa data on clinical, radiological and semiological characteristics, as well as on treatment of persons with epilepsy (PWE) are still scarce. METHODS: We pooled data from four cross-sectional studies on epilepsy in eastern Africa. Two studies from Malawi and Uganda were community-based; two studies in Tanzania (urban Dar es Salaam and rural Haydom) were hospital-based. Clinical characteristics of PWE were assessed by the same questionnaire. Additionally, data on treatment were collected and computed tomography (CT) scans were performed. RESULTS: Overall, 1179 PWE were included in our analysis (581 (49.3%) female, median age 22 years (IQR 15-32 years)). Up to 25% of the patients had focal onset seizures. Those showed a higher rate of remarkable CT scan findings, with especially post-ischaemic and neurocysticercosis-associated lesions, compared to PWE with generalized onset seizures (35.1% vs. 20%). The majority of the patients experienced tonic-clonic seizures (70-85%). Only 67-78% of PWE received anti-seizure medication (ASM) treatment in the community-based studies, mostly monotherapy with phenobarbital, phenytoin or carbamazepine. Yet, underdosage was frequent and a large proportion of PWE received alternative non-ASM treatment consisting of herbal treatment (up to 83%) and/or scarification (up to 20%). CONCLUSIONS: Epilepsy is common in sub-Saharan Africa, often caused by neurocysticercosis or ischaemic strokes. PWE suffer from high seizure rates and subsequent injuries, as well as from socio-economic consequences due to insufficient ASM treatment. This pooled analysis illustrates the need for structural programmes for adequate identification, education, assessment and treatment of PWE in sub-Saharan Africa.

Factors associated with impaired quality of life three months after being diagnosed with COVID-19.

PURPOSE: To assess patient characteristics associated with health-related quality of life (HR-QoL) and its mental and physical subcategories 3 months after diagnosis with COVID-19. METHODS: In this prospective multicentre cohort study, HR-QoL was assessed in 90 patients using the SF-36 questionnaire (36-item Short Form Health Survey), which consists of 8 health domains that can be divided into a mental and physical health component. Mental health symptoms including anxiety, depression, and post-traumatic stress disorders were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Disorder Checklist-5 (PCL-5) 3 months after COVID-19. Using descriptive statistics and multivariable regression analysis, we identified factors associated with impaired HR-QoL 3 months after COVID-19 diagnosis. RESULTS: Patients were 55 years of age (IQR, 49-63; 39% women) and were classified as severe (23%), moderate (57%), or mild (20%) according to acute disease severity. HR-QoL was impaired in 28/90 patients (31%). Younger age [per year, adjOR (95%CI) 0.94 (0.88-1.00), p = 0.049], longer hospitalization [per day, adjOR (95%CI) 1.07 (1.01-1.13), p = 0.015], impaired sleep [adjOR (95%CI) 5.54 (1.2-25.61), p = 0.028], and anxiety [adjOR (95%CI) 15.67 (3.03-80.99), p = 0.001) were independently associated with impaired HR-QoL. Twenty-nine percent (n = 26) scored below the normal range on the mental health component of the SF-36 and independent associations emerged for anxiety, depression, and self-reported numbness. Impairments in the physical health component of the SF-36 were reported by 12 (13%) patients and linked to hypogeusia and fatigue. CONCLUSION: Every third patient reported a reduction in HR-QoL 3 months after COVID-19 diagnosis and impairments were more prominent in mental than physical well-being.

Intracerebral Iron Accumulation may be Associated with Secondary Brain Injury in Patients with Poor Grade Subarachnoid Hemorrhage.

BACKGROUND: The amount of intracranial blood is a strong predictor of poor outcome after subarachnoid hemorrhage (SAH). Here, we aimed to measure iron concentrations in the cerebral white matter, using the cerebral microdialysis (CMD) technique, and to associate iron levels with the local metabolic profile, complications, and functional outcome. METHODS: For the observational cohort study, 36 patients with consecutive poor grade SAH (Hunt & Hess grade of 4 or 5, Glasgow Coma Scale Score ≤ 8) undergoing multimodal neuromonitoring were analyzed for brain metabolic changes, including CMD iron levels quantified by graphite furnace atomic absorption spectrometry. The study time encompassed 14 days after admission. Statistical analysis was performed using generalized estimating equations. RESULTS: Patients were admitted in a poor clinical grade (n = 26, 72%) or deteriorated within 24 h (n = 10, 28%). The median blood volume in the subarachnoid space was high (SAH sum score = 26, interquartile range 20-28). Initial CMD iron was 44 µg/L (25-65 µg/L), which significantly decreased to a level of 25 µg/L (14-30 µg/L) at day 4 and then constantly increased over the remaining neuromonitoring days (p < 0.01). A higher intraventricular hemorrhage sum score (≥ 5) was associated with higher CMD iron levels (Wald-statistic = 4.1, df = 1, p = 0.04) but not with the hemorrhage load in the subarachnoid space (p = 0.8). In patients developing vasospasm, the CMD iron load was higher, compared with patients without vasospasm (Wald-statistic = 4.1, degree of freedom = 1, p = 0.04), which was not true for delayed cerebral infarction (p = 0.4). Higher iron concentrations in the brain extracellular fluid (34 µg/L, 36-56 µg/L vs. 23 µg/L, 15-37 µg/L) were associated with mitochondrial dysfunction (CMD lactate to pyruvate ratio > 30 and CMD-pyruvate > 70 µM/L, p < 0.001). Brain extracellular iron load was not associated with functional outcome after 3 months (p > 0.5). CONCLUSIONS: This study suggests that iron accumulates in the cerebral white matter in patients with poor grade SAH. These findings may support trials aiming to scavenger brain extracellular iron based on the hypothesis that iron-mediated neurotoxicity may contribute to acute and secondary brain injury following SAH.

Toxin-associated infectious diseases: tetanus, botulism and diphtheria.

PURPOSE OF REVIEW: The incidence rates of the toxin-related infectious diseases, tetanus, diphtheria and botulism declined dramatically over the past decades mainly because of the implementation of immunization programs also in low-and-middle-income countries (LAMICs) and by improving hygiene conditions. But still, single cases occur, and they need fastest possible recognition and management. RECENT FINDINGS: Over the past 20 years, the incidence of neonatal tetanus has declined by more than 90%. This success was achieved by immunizing women in reproductive age in areas of high risk as sub-Saharan Africa and parts of Asia. Larger regional outbreaks of diphtheria have been reported from the former Soviet Union in the 1990s and from India in 2017. Botulism is still rare, mainly seen in infants and, in recent years, in intravenous drug abusers. SUMMARY: Tetanus, diphtheria and botulism are rarities in high-income countries (HICs) with unlimited access to immunization programs and standard hygiene procedures. The diagnosis of all three diseases is still, even in the 21st century, based upon patient's history and clinical signs and symptoms. Neither biochemical bedside tests nor neuroradiological investigations help to confirm the diagnosis in an emergency situation.

Neurological outcome and quality of life 3 months after COVID-19: A prospective observational cohort study.

BACKGROUND AND PURPOSE: To assess neurological manifestations and health-related quality of life (QoL) 3 months after COVID-19. METHODS: In this prospective, multicenter, observational cohort study we systematically evaluated neurological signs and diseases by detailed neurological examination and a predefined test battery assessing smelling disorders (16-item Sniffin Sticks test), cognitive deficits (Montreal Cognitive Assessment), QoL (36-item Short Form), and mental health (Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist-5) 3 months after disease onset. RESULTS: Of 135 consecutive COVID-19 patients, 31 (23%) required intensive care unit (ICU) care (severe), 72 (53%) were admitted to the regular ward (moderate), and 32 (24%) underwent outpatient care (mild) during acute disease. At the 3-month follow-up, 20 patients (15%) presented with one or more neurological syndromes that were not evident before COVID-19. These included polyneuro/myopathy (n = 17, 13%) with one patient presenting with Guillain-Barré syndrome, mild encephalopathy (n = 2, 2%), parkinsonism (n = 1, 1%), orthostatic hypotension (n = 1, 1%), and ischemic stroke (n = 1, 1%). Objective testing revealed hyposmia/anosmia in 57/127 (45%) patients at the 3-month follow-up. Self-reported hyposmia/anosmia was lower (17%) at 3 months, however, improved when compared to the acute disease phase (44%; p < 0.001). At follow-up, cognitive deficits were apparent in 23%, and QoL was impaired in 31%. Assessment of mental health revealed symptoms of depression, anxiety, and posttraumatic stress disorders in 11%, 25%, and 11%, respectively. CONCLUSIONS: Despite recovery from the acute infection, neurological symptoms were prevalent at the 3-month follow-up. Above all, smelling disorders were persistent in a large proportion of patients.