Improvement in cranial nerve palsies following treatment of intracranial aneurysms with flow diverters: Institutional outcomes, systematic review and study-level meta-analysis.

BACKGROUND: Cranial nerve (CN) palsies are rare presenting symptoms of intracranial aneurysms. Our objectives were to report our institutional outcomes and study-level meta-analysis summarizing rates of improvement and identifying factors associated with recovery from CN symptoms after flow diversion. METHODS: We conducted a retrospective review of our institutional database for patients with intracranial aneurysms presenting with CN palsies who underwent treatment with flow diversion between 2015 and 2023. Systematic review of the literature was performed using Medline, EMBASE, Cochrane, as well as manual citation searches. Random effects meta-analysis was used. RESULTS: Thirteen of 136 studies were included in the meta-analysis and were combined with our institutional data. The pooled rate of improvement in any CN palsies following flow diversion was 71 % (95 %CI, 60 %-82 %, n=322). Patients presenting with CN II deficits were less likely to improve following treatment compared to other CN deficits (pooled OR [pOR] 0.32, 95 %CI, 0.16-0.63, n=224). The pooled rate of clinical improvement was 53 % in CNII deficits (95 %CI, 42 %-65 %, n=80) and 80 % in other CN deficits (95 %CI, 71 %-88 %, n=106). An increased rate of improvement was associated with acute intervention (pOR 9.12, 95 % CI, 2.26-36.73, n = 71) and radiographic aneurysm occlusion (pOR 5.29, 95 %CI, 1.66-16.90, n=118). CONCLUSIONS: Flow diversion improves CN palsy outcomes in patients with symptomatic intracranial aneurysms. The lower rate of improvement in visual acuity compared to other CN deficits may point to a different mechanism of injury or potential recoverability in these patients.

Rocky Mountain Spotted Fever Encephalitis and "Starry Sky" Pattern on MRI: A Case Report.

INTRODUCTION: Rocky Mountain Spotted Fever (RMSF) is a tick-borne disease caused by Rickettsia rickettsii (R. rickettsii). RMSF presents after a tick bite with fever, rash, and headache but can also cause more serious neurological manifestations. We report a case of RMSF encephalitis presenting with altered sensorium and rapid progression to coma, fever, and petechial rash, and an magnetic resonance imaging (MRI) brain notable for a "starry sky" pattern. CASE REPORT: A 61-year-old woman presented with confusion and fever and was diagnosed with a urinary tract infection. Two days later, she became comatose. MRI brain revealed lacunar infarcts in the right centrum semiovale and splenium of the corpus callosum. Lumbar puncture was notable for neutrophilic pleocytosis and elevated protein with negative bacterial and viral cultures. Empiric meningitis therapy was initiated, and she was transferred to our institution. On transfer, she was febrile, comatose, and had a diffuse petechial rash. Repeat MRI brain demonstrated diffuse, innumerable punctate foci of diffusion restriction with susceptibility-weighted signal attenuation throughout cerebral hemispheres in a "starry sky" pattern. Skin biopsy revealed perivascular lymphocytic infiltrates. Serologic RSMF antibody titers were obtained, and doxycycline was initiated for presumed RMSF encephalitis. The family opted to pursue palliative measures, given no clinical improvement. RSMF titers and postmortem PCR from brain tissue were positive for R. rickettsii. CONCLUSIONS: This case report highlights the clinical presentation of RMSF encephalitis. RMSF encephalitis should be suspected in a patient presenting with encephalopathy, fever, petechial rash, and MRI brain findings of diffuse punctate foci of diffusion restriction and susceptibility-weighted signal attenuation in a "starry-sky" pattern.

Variability in temperature control practices amongst the Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial.

AIM: Temperature control is a complex bundled intervention; the synergistic impact of each individual component is ill defined and underreported. Resultantly, the influence of parameter optimization on temperature control's overall neuroprotective effect remains poorly understood. To characterize variability in temperature control parameters and barriers to short pre-induction and induction times, we surveyed sites enrolling in an ongoing multicenter clinical trial. METHODS: This was a cross-sectional, survey study evaluating temperature control practices within the Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial (NCT04217551). A 23-question web-based survey (Qualtrics) was distributed to the site principal investigators by email. Respondents were asked about site practices pertaining to the use of temperature control, including the request to upload individual institutional protocols. Open-ended responses were analyzed qualitatively by categorizing responses into identified themes. To complement survey level data, records pertaining to the quality of temperature control were extracted from the ICECAP trial database. RESULTS: The survey response rate was 75% (n = 51) including 23.5% (n = 12) survey respondents who uploaded institutional protocols. Most sites reported having institutional protocols for temperature control (n = 41; 80%), including 62.5% (n = 32) who had separate protocols for initiation of temperature control in the emergency department (ED). Fewer sites had protocols specific to sedation or neuromuscular blockade (NMB) management (n = 35, 68.6%). Use of NMB during temperature control induction was variable; 61.7% (n = 29) of sites induced paralysis less than 20% of the time. While most institutional protocols (n = 11, 83.3%) commented on the importance of early initiation of temperature control, this was incongruent with the largest reported barrier, which was clinical nihilism regarding the importance of early temperature control initiation (n = 30, 62.5%). Within the ICECAP trial database, 1 in 2 patients were treated with NMB however, use of NMB and time to initiation of temperature control device varied widely between sites. CONCLUSION: Amongst ICECAP trial sites, there was significant variability in resources, methods, and barriers for early temperature control initiation. Defining and standardizing high-quality temperature control must be prioritized, as it may impact the interpretation of past and current clinical trial findings.

Antiseizure Medication Withdrawal, Risk of Epilepsy, and Longterm EEG Trends in Acute Symptomatic Seizures or Epileptic EEG Patterns.

Background and Objectives: Patients with acute symptomatic seizures (ASyS) and acute epileptiform findings on EEG are common. They are often prescribed long-term antiseizure medications (ASMs); it is unknown whether or when this is necessary. Primary outcome was late unprovoked seizure occurrence and association with ASM taper. The secondary outcome was EEG pattern evolution over time. Methods: This is a retrospective cohort study of patients from 2015 to 2021 with ASyS (clinical or electrographic) and/or epileptiform findings on index hospitalization EEGs who were discharged on ASMs and had subsequent follow-up including an outpatient EEG at Yale New Haven Hospital. All patients were seen in our postacute symptomatic seizure (PASS) clinic after hospital discharge. We also developed a simple predictive score, Epilepsy-PASS (EPI-PASS), using variables independently associated with seizure recurrence based on stepwise regression; each of the 3 identified variables was assigned a score of 0 (absent) or 1 (present), for a total score of 0-3. Results: Of 190 patients screened, 58 were excluded, leaving a final cohort of 112 patients. Twenty-four percent (27/112) patients developed a late unprovoked seizure (i.e., epilepsy). Independent predictors of epilepsy were persistence of epileptiform abnormalities on follow-up EEGs [56% developed epilepsy vs 19% without, 0.002, OR 7.18 (1.36-37.88)], clinical ASyS [32% vs 13%, p = 0.002, OR 7.45 (2.31-54.36)], and cortical involvement on imaging [40% vs 11%, p = 0.003, OR 7.63 (1.96-29.58)]. None of the 23 patients with none of these predictors (0 points on EPI-PASS) developed epilepsy, vs 13% with 1 predictor (EPI-PASS = 1) and 46% with 2 or 3 predictors (EPI-PASS = 2-3) at 1-year follow-up. ASM taper was not associated with seizure recurrence. Abnormal EEG findings in the index hospitalization usually resolved [54/69 (78%) patients] on subsequent EEGs. Discussion: Most patients with clinical ASyS or acute epileptiform EEG findings do not require long-term ASMs. Index hospitalization EEG findings usually resolve, but if they do not, there is a >50% chance of developing epilepsy. Other predictors of epilepsy are cortical involvement on imaging and clinical ASyS. A simple 4-point scale using these 3 predictors (EPI-PASS) may help predict the risk of developing epilepsy but requires independent validation.

A practical magnetic-resonance imaging score for outcome prediction in comatose cardiac arrest survivors.

AIM: Magnetic Resonance Imaging (MRI) is an important prognostic tool in cardiac arrest (CA) survivors given its sensitivity for detecting hypoxic-ischemic brain injury (HIBI), however, it is limited by poorly defined objective thresholds. To address this limitation, we evaluated a qualitative MRI score for predicting neurological outcome in CA survivors. METHODS: Adult comatose CA survivors who underwent MRI were retrospectively identified at a single academic medical center. Two blinded neurointensivists qualitatively scored HIBI amongst 12 MRI brain regions. Scores were summated to form four distinct score groups: cortex, deep grey nuclei (DGN), cortex-DGN combined, and total (cortex, DGN, brainstem, and cerebellum). Poor neurological outcome was defined as Cerebral Performance Category (CPC) score 3-5 at hospital discharge. Inter-rater reliability was tested using intra-class correlation (ICC) and discrimination of poor neurological outcome assessed using area under the receiver operating curve (AUC). RESULTS: Our cohort included 219 patients with median time to MRI of 96 (IQR 81-110) hours. ICC (95% CI) was good to excellent across all MRI scores: cortex 0.92 (0.89-0.94), DGN 0.88 (0.80-0.92), cortex-DGN 0.94 (0.92-0.95), and total 0.93 (0.91-0.95). AUC (95% CI) for poor outcome was good across all MRI scores: cortex 0.84 (0.78-0.90), DGN 0.83 (0.77-0.89), cortex-DGN 0.83 (0.77-0.89), and total 0.83 (0.77-0.88). CONCLUSION: A simplified, qualitative MRI score had excellent reliability and good discrimination for poor neurologic outcome. Further work is necessary to externally validate our findings in an independent, ideally prospective, cohort.

Temperature Control Parameters Are Important: Earlier Preinduction Is Associated With Improved Outcomes Following Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: Temperature control trials in cardiac arrest patients have not reliably conferred neuroprotective benefit but have been limited by inconsistent treatment parameters. To evaluate the presence of a time dependent treatment effect, we assessed the association between preinduction time and clinical outcomes. METHODS: In this retrospective, single academic center study between 2014 and 2022, consecutive out-of-hospital cardiac arrest (OHCA) patients treated with temperature control were identified. Preinduction was defined as the time from hospital arrival to initiation of a closed-loop temperature feedback device [door to temperature control initiation time], and early door to temperature control device time was defined a priori as <3 hours. We assessed the association between good neurologic outcome (cerebral performance category 1 to 2) and door to temperature control device time using logistic regression. The proportion of patients who survived to hospital discharge was evaluated as a secondary outcome. A sensitivity analysis using inverse probability treatment weighting, created using a propensity score, was performed to minimize measurable confounding. RESULTS: Three hundred and forty-seven OHCA patients were included; the early door to temperature control device cohort included 75 (21.6%) patients with a median (interquartile range) door to temperature control device time of 2.50 (2.03 to 2.75) hours, whereas the late door to temperature control device cohort included 272 (78.4%) patients with a median (interquartile range) door to temperature control device time of 5.18 (4.19 to 6.41) hours. In the multivariable logistic regression model, early door to temperature control device time was associated with improved good neurologic outcome and survival before [adjusted odds ratio (OR) (95% confidence interval) 2.36 (1.16 to 4.81) and 3.02 (1.54 to 6.02)] and after [adjusted OR (95% confidence interval) 1.95 (1.19 to 3.79) and 2.14 (1.33 to 3.36)] inverse probability of treatment weighting, respectively. CONCLUSION: In our study of OHCA patients, a shorter preinduction time for temperature control was associated with improved good neurologic outcome and survival. This finding may indicate that early initiation in the emergency department will confer benefit. Our findings are hypothesis generating and need to be validated in future prospective trials.

Cerebral Edema Monitoring and Management Strategies: Results from an International Practice Survey.

BACKGROUND: Cerebral edema is a common, potentially life-threatening complication in critically ill patients with acute brain injury. However, uncertainty remains regarding best monitoring and treatment strategies, which may result in wide practice variations. METHODS: A 20-question digital survey on monitoring and management practices was disseminated between July 2022 and May 2023 to clinicians who manage cerebral edema. The survey was promoted through email, social media, medical conferences, and the Neurocritical Care Society Web site. We used the χ2 test, Fisher's exact test, analysis of variance, and logistic regression to report factors associated with practice variation, diagnostic monitoring methods, and therapeutic triggers based on practitioner and institutional characteristics. RESULTS: Of 321 participants from 160 institutions in 30 countries, 65% were from university-affiliated centers, 74% were attending physicians, 38% were woman, 38% had neurology training, and 55% were US-based. Eighty-four percent observed practice variations at their institutions, with "provider preference" being cited most (87%). Factors linked to variation included gender, experience, university affiliation, and practicing outside the United States. University affiliates tended to use more tests (median 3.87 vs. 3.43, p = 0.01) to monitor cerebral edema. Regarding management practices, 20% of respondents' preferred timing for decompressive hemicraniectomy was after 48 h, and 37% stated that radiographic findings only would be sufficient to trigger surgery. Fifty percent of respondents reported initiating osmotic therapy based on radiographic indications or prophylactically. There were no significant associations between management strategies and respondent or center characteristics. Twenty-seven percent of respondents indicated that they acquired neuroimaging at intervals of 24 h or less. Within this group, attending physicians were more likely to follow this practice (65.5% vs. 34.5%, p = 0.04). CONCLUSIONS: Cerebral edema monitoring and management strategies vary. Features associated with practice variations include both practitioner and institutional characteristics. We provide a foundation for understanding practice patterns that is crucial for informing educational initiatives, standardizing guidelines, and conducting future trials.

Later Midline Shift Is Associated with Better Outcomes after Large Middle Cerebral Artery Stroke.

Background/Objective: Space occupying cerebral edema is the most feared early complication after large ischemic stroke, occurring in up to 30% of patients with middle cerebral artery (MCA) occlusion, and is reported to peak 2-4 days after injury. Little is known about the factors and outcomes associated with peak edema timing, especially when it occurs after 96 hours. We aimed to characterize differences between patients who experienced maximum midline shift (MLS) or decompressive hemicraniectomy (DHC) in the acute (<48 hours), average (48-96 hours), and subacute (>96 hours) groups and determine whether patients with subacute peak edema timing have improved discharge dispositions. Methods: We performed a two-center, retrospective study of patients with ≥1/2 MCA territory infarct and MLS. We constructed a multivariable model to test the association of subacute peak edema and favorable discharge disposition, adjusting for age, admission Alberta Stroke Program Early CT Score (ASPECTS), National Institute of Health Stroke Scale (NIHSS), acute thrombolytic intervention, cerebral atrophy, maximum MLS, parenchymal hemorrhagic transformation, DHC, and osmotic therapy receipt. Results: Of 321 eligible patients with MLS, 32%, 36%, and 32% experienced acute, average, and subacute peak edema. Subacute peak edema was significantly associated with higher odds of favorable discharge than non-subacute swelling, adjusting for confounders (aOR, 1.85; 95% CI, 1.05-3.31). Conclusions: Subacute peak edema after large MCA stroke is associated with better discharge disposition compared to earlier peak edema courses. Understanding how the timing of cerebral edema affects risk of unfavorable discharge has important implications for treatment decisions and prognostication.

Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate-Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society.

BACKGROUND: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI). METHODS: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. RESULTS: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. CONCLUSIONS: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).

Comparison of induction agents for rapid sequence intubation in refractory status epilepticus: A single-center retrospective analysis.

Endotracheal intubation, frequently required during management of refractory status epilepticus (RSE), can be facilitated by anesthetic medications; however, their effectiveness for RSE control is unknown. We performed a single-center retrospective review of patients admitted to a neurocritical care unit (NCCU) who underwent in-hospital intubation during RSE management. Patients intubated with propofol, ketamine, or benzodiazepines, termed anti-seizure induction (ASI), were compared to patients who received etomidate induction (EI). The primary endpoint was clinical or electrographic seizures within 12 h post-intubation. We estimated the association of ASI on post-intubation seizure using logistic regression. A sub-group of patients undergoing electroencephalography during intubation was identified to evaluate the immediate effect of ASI on RSE. We screened 697 patients admitted to the NCCU for RSE and identified 148 intubated in-hospital (n = 90 ASI, n = 58 EI). There was no difference in post-intubation seizure (26 % (n = 23) ASI, 29 % (n = 17) EI) in the cohort, however, there was increased RSE resolution with ASI in 24 patients with electrographic RSE during intubation (ASI: 61 % (n = 11/18) vs EI: 0 % (n = 0/6), p =.016). While anti-seizure induction did not appear to affect post-intubation seizure occurrence overall, a sub-group of patients undergoing electroencephalography during intubation had a higher incidence of seizure cessation, suggesting potential benefit in an enriched population.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement From the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement from the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

BACKGROUND: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. METHODS: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. RESULTS: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05). CONCLUSIONS: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Characterization of CSF inflammatory markers after hemorrhagic stroke and their relationship to disease severity.

Background: The inflammatory response within the central nervous system is a key driver of secondary brain injury after hemorrhagic stroke, both in patients with intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to characterize inflammatory molecules in the blood and cerebrospinal fluid (CSF) of patients within 72 hours of hemorrhage to understand how such molecules vary across disease types and disease severity. Methods: Biological samples were collected from patients admitted to a single-center Neurosciences Intensive Care Unit with a diagnosis of ICH or aSAH between 2014 and 2022. Control CSF samples were collected from patients undergoing CSF diversion for normal pressure hydrocephalus. A panel of immune molecules in the plasma and CSF samples was analyzed using Cytometric Bead Array assays. Clinical variables, including demographics, disease severity, and intensive care unit length of stay were collected. Results: Plasma and/or CSF samples were collected from 260 patients (188 ICH patients, 54 aSAH patients, 18 controls). C-C motif chemokine ligand-2 (CCL2), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF), were detectable in the CSF within the first 3 days after hemorrhage, and all were elevated compared to plasma. Compared with controls, CCL2, IL-6, IL-8, G-CSF, and VEGF were elevated in the CSF of both ICH and aSAH patients (p<0.01 for all comparisons). VEGF was increased in ICH patients compared to aSAH patients (p<0.01). CCL2, G-CSF, and VEGF in the CSF were associated with more severe disease in aSAH patients only. Conclusions: Within 3 days of hemorrhagic stroke, proinflammatory molecules can be detected in the CSF at higher concentrations than in the plasma. Early concentrations of some pro-inflammatory molecules may be associated with markers of disease severity.

Temperature Control in the Era of Personalized Medicine: Knowledge Gaps, Research Priorities, and Future Directions.

Hypoxic-ischemic brain injury (HIBI) is the leading cause of death and disability after cardiac arrest. To date, temperature control is the only intervention shown to improve neurologic outcomes in patients with HIBI. Despite robust preclinical evidence supporting hypothermia as neuroprotective therapy after cardiac arrest, there remains clinical equipoise regarding optimal core temperature, therapeutic window, and duration of therapy. Current guidelines recommend continuous temperature monitoring and active fever prevention for at least 72 h and additionally note insufficient evidence regarding temperature control targeting 32 °C-36 °C. However, population-based thresholds may be inadequate to support the metabolic demands of ischemic, reperfused, and dysregulated tissue. Promoting a more personalized approach with individualized targets has the potential to further improve outcomes. This review will analyze current knowledge and evidence, address research priorities, explore the components of high-quality temperature control, and define critical future steps that are needed to advance patient-centered care for cardiac arrest survivors.

Detection of Intracerebral Hemorrhage Using Low-Field, Portable Magnetic Resonance Imaging in Patients With Stroke.

BACKGROUND: Neuroimaging is essential for detecting spontaneous, nontraumatic intracerebral hemorrhage (ICH). Recent data suggest ICH can be characterized using low-field magnetic resonance imaging (MRI). Our primary objective was to investigate the sensitivity and specificity of ICH on a 0.064T portable MRI (pMRI) scanner using a methodology that provided clinical information to inform rater interpretations. As a secondary aim, we investigated whether the incorporation of a deep learning (DL) reconstruction algorithm affected ICH detection. METHODS: The pMRI device was deployed at Yale New Haven Hospital to examine patients presenting with stroke symptoms from October 26, 2020 to February 21, 2022. Three raters independently evaluated pMRI examinations. Raters were provided the images alongside the patient's clinical information to simulate real-world context of use. Ground truth was the closest conventional computed tomography or 1.5/3T MRI. Sensitivity and specificity results were grouped by DL and non-DL software to investigate the effects of software advances. RESULTS: A total of 189 exams (38 ICH, 89 acute ischemic stroke, 8 subarachnoid hemorrhage, 3 primary intraventricular hemorrhage, 51 no intracranial abnormality) were evaluated. Exams were correctly classified as positive or negative for ICH in 185 of 189 cases (97.9% overall accuracy). ICH was correctly detected in 35 of 38 cases (92.1% sensitivity). Ischemic stroke and no intracranial abnormality cases were correctly identified as blood-negative in 139 of 140 cases (99.3% specificity). Non-DL scans had a sensitivity and specificity for ICH of 77.8% and 97.1%, respectively. DL scans had a sensitivity and specificity for ICH of 96.6% and 99.3%, respectively. CONCLUSIONS: These results demonstrate improvements in ICH detection accuracy on pMRI that may be attributed to the integration of clinical information in rater review and the incorporation of a DL-based algorithm. The use of pMRI holds promise in providing diagnostic neuroimaging for patients with ICH.

Polygenic Risk of Epilepsy and Post-Stroke Epilepsy.

Background and Aims: Epilepsy is highly heritable, with numerous known genetic risk loci. However, the genetic predisposition's role in post-acute brain injury epilepsy remains understudied. This study assesses whether a higher genetic predisposition to epilepsy raises post-stroke or Transient Ischemic Attack (TIA) survivor's risk of Post-Stroke Epilepsy (PSE). Methods: We conducted a three-stage genetic analysis. First, we identified independent epilepsy-associated ( p <5x10 -8 ) genetic variants from public data. Second, we estimated PSE-specific variant weights in stroke/TIA survivors from the UK Biobank. Third, we tested for an association between a polygenic risk score (PRS) and PSE risk in stroke/TIA survivors from the All of Us Research Program. Primary analysis included all ancestries, while a secondary analysis was restricted to European ancestry only. A sensitivity analysis excluded TIA survivors. Association testing was conducted via multivariable logistic regression, adjusting for age, sex, and genetic ancestry. Results: Among 19,708 UK Biobank participants with stroke/TIA, 805 (4.1%) developed PSE. Likewise, among 12,251 All of Us participants with stroke/TIA, 394 (3.2%) developed PSE. After establishing PSE-specific weights for 39 epilepsy-linked genetic variants in the UK Biobank, the resultant PRS was associated with elevated odds of PSE development in All of Us (OR:1.16[1.02-1.32]). A similar result was obtained when restricting to participants of European ancestry (OR:1.23[1.02-1.49]) and when excluding participants with a TIA history (OR:1.18[1.02-1.38]). Conclusions: Our findings suggest that akin to other forms of epilepsy, genetic predisposition plays an essential role in PSE. Because the PSE data were sparse, our results should be interpreted cautiously.

Clinical implications of Peri-hematomal edema microperfusion fraction in intracerebral hemorrhage intravoxel incoherent motion imaging - A pilot study.

BACKGROUND AND PURPOSE: Perihematomal edema (PHE) represents the secondary brain injury after intracerebral hemorrhage (ICH). However, neurobiological characteristics of post-ICH parenchymal injury other than PHE volume have not been fully characterized. Using intravoxel incoherent motion imaging (IVIM), we explored the clinical correlates of PHE diffusion and (micro)perfusion metrics in subacute ICH. MATERIALS AND METHODS: In 41 consecutive patients scanned 1-to-7 days after supratentorial ICH, we determined the mean diffusion (D), pseudo-diffusion (D*), and perfusion fraction (F) within manually segmented PHE. Using univariable and multivariable statistics, we evaluated the relationship of these IVIM metrics with 3-month outcome based on the modified Rankin Scale (mRS). RESULTS: In our cohort, the average (± standard deviation) age of patients was 68.6±15.6 years, median (interquartile) baseline National Institute of Health Stroke Scale (NIHSS) was 7 (3-13), 11 (27 %) patients had poor outcomes (mRS>3), and 4 (10 %) deceased during the follow-up period. In univariable analyses, admission NIHSS (p < 0.001), ICH volume (p = 0.019), ICH+PHE volume (p = 0.016), and average F of the PHE (p = 0.005) had significant correlation with 3-month mRS. In multivariable model, the admission NIHSS (p = 0.006) and average F perfusion fraction of the PHE (p = 0.003) were predictors of 3-month mRS. CONCLUSION: The IVIM perfusion fraction (F) maps represent the blood flow within microvasculature. Our pilot study shows that higher PHE microperfusion in subacute ICH is associated with worse outcomes. Once validated in larger cohorts, IVIM metrics may provide insight into neurobiology of post-ICH secondary brain injury and identify at-risk patients who may benefit from neuroprotective therapy.