Long-term clinical course and treatment outcomes of individuals with Nodding Syndrome.

Nodding Syndrome is a poorly understood epilepsy disorder in sub-Saharan Africa. The cause(s) of the disease, risk factors and long-term outcomes are unknown or controversial. The objectives of this study were to describe the long-term clinical course and treatment outcomes of individuals suffering from Nodding Syndrome. In addition, we aimed to provide a comprehensive characterization of the epileptological and social features of patients with Nodding Syndrome. From 11/2014 to 4/2015, we conducted a hospital-based, cross-sectional and observational study in Mahenge, Tanzania. Seventy-eight individuals (female:male ratio: 40:38, age at examination: 21.1 ± 6.39 (SD) years) have been enrolled, of whom 38 (49%) had also been examined in 2005 and in 2009. The 10-year clinical course analysis of this revisited subgroup revealed a calculated case fatality of 0.8-2.3%. Progressive physical or cognitive deterioration has not been observed in any of the 78 individuals and more than half of the people studied (38/69; 55%) managed to live and work independently. 14/78 individuals (18%) were seizure-free, (no head nodding, no other seizure types), 13 of whom were taking antiseizure medication. Phenytoin was more effective against head nodding seizures (14/19 (74%)) than monotherapy with other available antiseizure medication (phenobarbitone 12/25 (48%) and carbamazepine 7/22 (32%), p = 0.02, chi-square test). Our ten-year clinical outcome data show that Nodding Syndrome is not a fatal disease, however, the response to treatment is worse than in epilepsy patients in general. Phenytoin may be more effective than carbamazepine and phenobarbitone, but further studies are needed to confirm this observation.

Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns.

Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, ß-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.

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.

Neurologic Care of Forcibly Displaced Persons: Emerging Issues in Neurology.

There is a growing number of forcibly displaced persons (FDPs) worldwide. With more than 100 million people forcibly displaced today, there is an urgent mandate to understand the neurologic care needs of this population and how neurologists and other health care workers can most effectively provide that care. In this Emerging Issues in Neurology article, we attempt to (1) define the scope of the problem of providing neurologic care to FDPs, (2) highlight commonly encountered clinical challenges related to neurologic care of FDPs, and (3) provide useful clinical information for neurologists and other clinicians who deliver care to FDPs with neurologic needs. We address the terminology of forcible displacement and how terms may differ across a person's migration journey. Common challenges encountered by FDPs with neurologic needs across settings include loss of support systems, loss of personal health information, language barriers and differing expression of symptoms, differing belief systems, epidemiologic patterns of disease unfamiliar to the clinician, and patients' fear and perceived risks of engaging with health systems. Practical approaches are shared for clinicians who encounter an FDP with a neurologic presentation. Finally, the article discusses many unmet neurologic needs of FDPs, which require significant investment. These include addressing lapses in neurologic care during displacement and understanding the effects of forcible displacement on people with chronic neurologic conditions. Future research and educational resources should focus on improving epidemiologic intelligence for neurologic conditions across geographies, developing curricula for optimizing the neurologic care of FDPs, and evaluating the most appropriate and effective uses of health technologies in humanitarian settings.

Correction: Characteristics of people with epilepsy and Neurocysticercosis in three eastern African countries-A pooled analysis.

[This corrects the article DOI: 10.1371/journal.pntd.0010870.].

Does the presence of a specialist doctor reduce the burden of disease in people with epilepsy in low-resource settings? A comparison of two epilepsy clinics in rural Tanzania.

BACKGROUND: With an estimated lifetime prevalence of epilepsy of 7.6 per 1,000 people, epilepsy represents one of the most common neurological disorders worldwide, with the majority of people with epilepsy (PWE) living in low-income and middle-income countries (LMICs). Adequately treated, up to 70 % of PWE will become seizure-free, however, as many as 85% of PWE worldwide, mostly from LMICs, do not receive adequate treatment. OBJECTIVE: To assess the impact of the presence of a neurologist on the management of PWE in Tanzania. METHODS: Two epilepsy clinics in rural Tanzania, one continuously attended by a neurologist, and one mainly attended by nurses with training in epilepsy and supervised intermittently by specialist doctors (neurologists/psychiatrists) were comparatively analyzed by multivariable linear and logistic regression models with regard to the outcome parameters seizure frequency, the occurrence of side effects of antiepileptic medication and days lost after a seizure. RESULTS: The presence of a neurologist significantly reduced the mean number of seizures patients experienced per month by 4.49 seizures (p < 0.01) while leading to an increase in the occurrence of reported side effects (OR: 2.15, p = 0.02). CONCLUSION: The presence of a neurologist may play a substantial role in reducing the burden of the disease of PWE in LMICs. Hence, specialist training should be encouraged, and relevant context-specific infrastructure established.

Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients.

Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.

Characteristics of people with epilepsy and Neurocysticercosis in three eastern African countries-A pooled analysis.

BACKGROUND: Neurocysticercosis (NCC), a zoonotic disease caused by the pork tapeworm T. solium, represents one of the most common causes of secondary epilepsy but remains often undiagnosed due to lack of awareness and diagnostic facilities. METHODOLOGY: We pooled data from four cross-sectional studies on epilepsy and NCC in eastern Africa. Study sites were in Uganda, Malawi and in Tanzania (Dar es Salaam and Haydom). The study in Uganda and Malawi were community-based, the two studies in Tanzania were hospital-based. The same questionnaire was used for assessment of clinical characteristics of patients with epilepsy. Computed tomography (CT) scans and serological testing were performed in order to diagnose NCC. RESULTS: Overall, 1,179 people with epilepsy were included in our analysis. Of those, 941 PWE underwent CT scanning and were pooled for NCC analysis. Seventy patients were diagnosed with NCC, but NCC prevalence differed considerably between sites ranging from 2.0% (95%CI 0.4% to 3.6%) in Dar es Salaam to 17.5% (95%CI 12.4% to 22.6%) in Haydom. NCC prevalence did not show any association with sex but increased with age and was higher in rural than urban settings. In addition, being a farmer, non-Muslim, eating pork and living with pigs close by was associated with a higher NCC prevalence. PWE with NCC experienced their first epileptic seizure around 3 years later in life compared to PWE without NCC and their epileptic seizures seemed to be better controlled (p<0.001). There was no difference between focal onset seizures and focal signs on neurological examination in both groups (p = 0.49 and p = 0.92, respectively). The rT24H-EITB had a sensitivity for the detection of NCC of 70% (95% confidence interval [CI] 51 to 84%), the LLGP of 76% (95%CI 58 to 89%) and the antigen ELISA of 36% (95% CI 20 to 55%). CONCLUSIONS: NCC is prevalent among PWE in eastern Africa, although it may not be as common as previously stated. Demographic characteristics of PWE with NCC differed from those without NCC, but semiological characteristics and results on neurological examination did not differ compared to PWE without NCC. Interestingly, seizures seemed to be less frequent in PWE with NCC. Being aware of those differences and similarities may help triaging PWE for neuroimaging in order to establish a diagnosis of NCC.

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.

Cerebral Malaria: Current Clinical and Immunological Aspects.

This review focuses on current clinical and immunological aspects of cerebral malaria induced by Plasmodium falciparum infection. Albeit many issues concerning the inflammatory responses remain unresolved and need further investigations, current knowledge of the underlying molecular mechanisms is highlighted. Furthermore, and in the light of significant limitations in preventative diagnosis and treatment of cerebral malaria, this review mainly discusses our understanding of immune mechanisms in the light of the most recent research findings. Remarkably, the newly proposed CD8+ T cell-driven pathophysiological aspects within the central nervous system are summarized, giving first rational insights into encouraging studies with immune-modulating adjunctive therapies that protect from symptomatic cerebral participation of Plasmodium falciparum infection.

Ictal Electroencephalographic Characteristics of Nodding Syndrome: A Comparative Case-Series from South Sudan, Tanzania, and Uganda.

Nodding syndrome (NS) is a poorly understood form of childhood-onset epilepsy that is characterized by the pathognomonic ictal phenomenon of repetitive vertical head drops. To evaluate the underlying ictal neurophysiology, ictal EEG features were evaluated in nine participants with confirmed NS from South Sudan, Tanzania, and Uganda and ictal presence of high frequency gamma oscillations on scalp EEG were assessed. Ictal EEG during the head nodding episode predominantly showed generalized slow waves or sharp-and-slow wave complexes followed by electrodecrement. Augmentation of gamma activity (30-70 Hz) was seen during the head nodding episode in all the participants. We confirm that head nodding episodes in persons with NS from the three geographically distinct regions in sub-Saharan Africa share the common features of slow waves with electrodecrement and superimposed gamma activity. ANN NEUROL 2022;92:75-80.

Early supplemental parenteral nutrition for the achievement of nutritional goals in subarachnoid hemorrhage patients: An observational cohort study.

PURPOSE: Enteral nutrition (EN) often fails to achieve nutritional goals in neurocritical care patients. We sought to investigate the safety and utility of supplemental parenteral nutrition (PN) in subarachnoid hemorrhage (SAH) patients. MATERIALS AND METHODS: Data of 70 consecutive patients with non-traumatic SAH admitted to the neurological intensive care unit of a tertiary referral center were prospectively collected and retrospectively analyzed. We targeted the provision of 20-25 kilocalories per kilogram bodyweight per day (kcal/kg/d) by enteral nutrition. Supplemental PN was given when this target could not be reached. Nutritional data were analyzed for up to 14 days of ICU stay. Hospital complications were tested for associations with impaired enteral feeding. The amounts of EN and PN were tested for associations with the level of protein delivery and functional outcome. Repeated measurements within subjects were handled utilizing generalized estimating equations. RESULTS: Forty (27 women and 13 men) of 70 screened patients were eligible for the analysis. Median age was 61 (IQR 49-71) years, 8 patients (20%) died in the hospital. Thirty-six patients (90%) received PN for a median duration of 8 (IQR 4-12) days. The provision of 20 kcal/kg by EN on at least 1 day of ICU stay was only achieved in 24 patients (60%). Hydrocephalus (p = 0.020), pneumonia (p = 0.037) and sepsis (p = 0.013) were associated with impaired enteral feeding. Neither the amount nor the duration of PN administration was associated with an increased risk of severe complications or poor outcome. Supplemental PN was associated with significantly increased protein delivery (p<0.001). In patients with sepsis or pneumonia, there was an association between higher protein delivery and good functional outcome (p<0.001 and p = 0.031), but not in the overall cohort (p = 0.08). CONCLUSIONS: Enteral feeding was insufficient to achieve nutritional goals in subarachnoid hemorrhage patients. Supplemental PN was safe and associated with increased protein delivery. A higher protein supply was associated with good functional outcome in patients who developed sepsis or pneumonia.

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.

Frequency of Neurologic Manifestations in COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: One year after the onset of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to summarize the frequency of neurologic manifestations reported in patients with COVID-19 and to investigate the association of these manifestations with disease severity and mortality. METHODS: We searched PubMed, Medline, Cochrane library, ClinicalTrials.gov, and EMBASE for studies from December 31, 2019, to December 15, 2020, enrolling consecutive patients with COVID-19 presenting with neurologic manifestations. Risk of bias was examined with the Joanna Briggs Institute scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% confidence intervals (CIs) were calculated for neurologic manifestations. Odds ratio (ORs) and 95% CIs were calculated to determine the association of neurologic manifestations with disease severity and mortality. Presence of heterogeneity was assessed with I 2, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2. RESULTS: Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 patients with COVID-19, 89% of whom were hospitalized. Forty-one neurologic manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurologic symptoms included fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%), and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurologic diagnosis (pooled prevalence 2%). In patients with COVID-19 ≥60 years of age, the pooled prevalence of acute confusion/delirium was 34%, and the presence of any neurologic manifestations in this age group was associated with mortality (OR 1.80, 95% CI 1.11-2.91). DISCUSSION: Up to one-third of patients with COVID-19 analyzed in this review experienced at least 1 neurologic manifestation. One in 50 patients experienced stroke. In those >60 years of age, more than one-third had acute confusion/delirium; the presence of neurologic manifestations in this group was associated with nearly a doubling of mortality. Results must be interpreted with the limitations of observational studies and associated bias in mind. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020181867.

Lifetime prevalence of epilepsy in urban Tanzania - A door-to-door random cluster survey.

OBJECTIVES: Epileptic seizures and epilepsy in urban settings of low-income and middle-income countries (LMIC) are largely under-researched, but their prevalence is necessary for good healthcare planning. This study aimed to determine the lifetime prevalence of epileptic seizures and epilepsy in urban Dar es Salaam. METHODS: Nearly 50,000 people in former Kinondoni district, Dar es Salaam, were screened for epileptic seizures using a set of nine questions. Answers to these nine questions were categorized into generalized, focal, and unspecified seizures. Screening positivity rates were adjusted for questionnaire inaccuracy using two scenarios to analyse true epilepsy prevalences. RESULTS: Overall, 1085 (2.23%) people fulfilled the criteria for ever having had at least one type of epileptic seizure. Two-hundred-ninety-six (0.60%) people screened positive for generalized seizures, 986 (2.02%) for focal seizures, and 32 (0.07%) for unspecified seizures. Women more commonly screened positive than men (2.61% versus 1.72%, p < 0.001), particularly for focal seizures (p < 0.001). Adjusting for different degrees of accuracy of the screening questionnaire yielded true lifetime prevalences for epilepsy of any type between 1.59% and 2.41%. We furthermore observed a considerable variation of screening positivity rates between wards in Kinondoni district (p < 0.001). CONCLUSION: The prevalence of epilepsy, based on a questionnaire survey in urban Tanzania, was higher than previously observed, probably due to the screening questionnaire, which contained questions specifically designed to identify focal seizures. Further studies on epileptic seizures/epilepsy are needed for urban settings in LMIC, preferably with an integrated follow-up of positive cases.

Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: Evaluation, management, and scientific questions.

BACKGROUND: Vaccine induced immune mediated thrombocytopenia or VITT, is a recent and rare phenomenon of thrombosis with thrombocytopenia, frequently including cerebral venous thromboses (CVT), that has been described following vaccination with adenovirus vaccines ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2·S Johnson and Johnson (Janssen/J&J). The evaluation and management of suspected cases of CVT post COVID-19 vaccination are critical skills for a broad range of healthcare providers. METHODS: A collaborative comprehensive review of literature was conducted among a global group of expert neurologists and hematologists. FINDINGS: Strategies for rapid evaluation and treatment of the CVT in the context of possible VITT exist, including inflammatory marker measurements, PF4 assays, and non-heparin anticoagulation.

Individualized blood pressure targets in the postoperative care of patients with intracerebral hemorrhage.

OBJECTIVE: Recent guidelines recommend targeting a systolic blood pressure (SBP) < 140 mm Hg in the early management of patients with spontaneous intracerebral hemorrhage (ICH). The optimal SBP targets for ICH patients after hematoma evacuation (HE) remain unclear. Here, the authors aimed to define the optimal SBP range based on multimodal neuromonitoring data. METHODS: Forty poor-grade ICH patients who had undergone HE and then monitoring of intracerebral pressure, brain tissue oxygen tension (PbtO2), and cerebral metabolism (via cerebral microdialysis [CMD]) were prospectively included. Episodes of brain tissue hypoxia (BTH) (1-hour averaged PbtO2 < 20 mm Hg) and metabolic distress (CMD-lactate/pyruvate ratio [LPR] ≥ 40) were identified and linked to corresponding parameters of hemodynamic monitoring (SBP and cerebral perfusion pressure [CPP]). Multivariable regression analysis was performed using generalized estimating equations to identify associations between SBP levels, PbtO2, and brain metabolism. RESULTS: The mean patient age was 60 (range 51-66) years and the median [IQR] initial ICH volume was 47 [29-60] ml. In multivariable models adjusted for Glasgow Coma Scale score, probe location, ICH volume, and age, lower SBP was independently associated with a higher risk of BTH (≤ 120 mm Hg: adjusted OR 2.9, p = 0.007; 120-130 mm Hg: adj OR 2.4, p = 0.002; 130-140 mm Hg: adj OR 1.6, p = 0.017) compared to a reference range of 140-150 mm Hg at the level of the foramen interventriculare Monroi, which corresponded to a CPP of 70-80 mm Hg and SBP levels between 150 and 160 mm Hg at the heart level. After exclusion of episodes with mitochondrial dysfunction, SBP targets < 140 mm Hg were associated with higher odds of cerebral metabolic distress (≤ 130 mm Hg: OR 2.5, p = 0.041; 130-140 mm Hg: OR 2.3, p = 0.033). Patients with a modified Rankin Scale score ≥ 5 at neurological ICU discharge more often exhibited BTH than patients with better outcomes (51% vs 10%, p = 0.003). CONCLUSIONS: These data suggest that lower SPB and CPP levels are associated with a higher risk for BTH. Further studies are needed to evaluate whether a higher SPB target may prevent BTH and improve outcomes.

Hyperactive delirium in patients after non-traumatic subarachnoid hemorrhage.

PURPOSE: Hyperactive delirium is common after subarachnoid hemorrhage (SAH). We aimed to identify risk factors for delirium and to evaluate its impact on outcome. METHODS: We collected daily Richmond Agitation Sedation Scale (RASS) and Intensive Care Delirium Screening Checklist (ICDSC) scores in 276 SAH patients. Hyperactive delirium was defined as ICDSC ≥4 when RASS was >0. We investigated risk factors for delirium and its association with 3-month functional outcome using generalized linear models. RESULTS: Patients were 56 (IQR 47-67) years old and had a Hunt&Hess (H&H) grade of 3 (IQR 1-5). Sixty-five patients (24%) developed hyperactive delirium 6 (IQR 3-16) days after SAH. In multivariable analysis, mechanical ventilation>48 h (adjOR = 4.46; 95%-CI = 1.89-10.56; p = 0.001), the detection of an aneurysm (adjOR = 4.38; 95%-CI = 1.48-12.97; p = 0.008), a lower H&H grade (adjOR = 0.63; 95%-CI = 0.48-0.83; p = 0.001) and a pre-treated psychiatric disorder (adjOR = 3.17; 95%-CI = 1.14-8.83; p = 0.027) were associated with the development of delirium. Overall, delirium was not associated with worse outcome (p = 0.119). Interestingly, patients with delirium more often had a modified Rankin Scale Score (mRS) of 1-3 (77%) compared to an mRS of 0 (14%) or 4-6 (9%). CONCLUSION: Our data indicate that hyperactive delirium is common after SAH patients and requires a certain degree of brain connectivity based ono the highest prevalence found in SAH patients with intermediate outcomes.