Friedman's Gradient-Boosting Algorithm Predicts Lactate-Pyruvate Ratio Trends in Cases of Intracerebral Hemorrhages.

OBJECTIVE: The local effects of an intracerebral hemorrhage (ICH) on surrounding brain tissue can be detected bedside using multimodal brain monitoring techniques. The aim of this study is to design a gradient boosting regression model using the R package boostmtree with the ability to predict lactate-pyruvate ratio measurements in ICH. METHODS: We performed a retrospective analysis of 6 spontaneous ICH and 6 traumatic ICH patients who underwent surgical removal of the clot with microdialysis catheters placed in the perihematomal zone. Predictors of glucose, lactate, pyruvate, age, sex, diagnosis, and operation status were used to design our model. RESULTS: In a holdout analysis, the model forecasted lactate-pyruvate ratio trends in a representative in-sample testing set. We anticipate that boostmtree could be applied to designs of similar regression models to analyze trends in other multimodal monitoring features across other types of acute brain injury. CONCLUSIONS: The model successfully predicted hourly lactate-pyruvate ratios in spontaneous ICH and traumatic ICH cases after the hemorrhage evacuation and displayed significantly better performance than linear models. Our results suggest that boostmtree may be a powerful tool in developing more advanced mathematical models to assess other multimodal monitoring parameters for cases in which the perihematomal environment is monitored.

iPad-Based Neurocognitive Testing (ImPACT-QT) in Acute Adult Mild Traumatic Brain Injury/Concussion: Study on Practicality and Bedside Cognitive Scores in a Level-1 Trauma Center.

BACKGROUND: There lacks rapid standardized bedside testing to screen cognitive deficits following mild traumatic brain injury (mTBI). Immediate Post-Concussion Assessment & Cognitive Testing-Quick Test (ImPACT-QT) is an abbreviated-iPad form of computerized cognitive testing. The aim of this study is to test ImPACT-QT utility in inpatient settings. We hypothesize ImPACT-QT is feasible in the acute trauma setting. METHOD: Trauma patients ages 12-70 were administered ImPACT-QT (09/2022-09/2023). Encephalopathic/medically unstable patients were excluded. Mild traumatic brain injury was defined as documented-head trauma with loss-of-consciousness <30 minutes and arrival Glasgow Coma Scale 13-15. Patients answered Likert-scale surveys. Bivariate analyses compared demographics, attention, motor speed, and memory scores between mTBI and non-TBI controls. Multivariable logistic regression assessed memory score as a predictor of mTBI diagnosis. RESULTS: Of 233 patients evaluated (36 years [IQR 23-50], 71% [166/233] female), 179 (76%) were mTBI patients. For all patients, mean test-time was 9.3 ± 2 minutes with 93% (73/76) finding the test "easy to understand." Mild traumatic brain injury patients than non-TBI control had lower memory scores (25 [IQR 7-100] vs 43 [26-100], P = .001) while attention (5 [1-23] vs 11 [1-32]) and motor score (14 [3-28] vs 13 [4-32]) showed no significant differences. Multivariable-regression (adjustment: age, sex, race, education level, ISS, and time to test) demonstrated memory score predicted mTBI positive status (OR .96, CI .94-.98, P = .004). DISCUSSION: Immediate Post-Concussion Assessment & Cognitive Testing-Quick Test is feasible in trauma patients. Preliminary findings suggest acute mTBIs have lower memory but not attention/motor scores vs non-TBI trauma controls.

Cerebral microdialysis demonstrates improvements in brain metabolism with cerebrospinal fluid diversion in spontaneous intracerebral hemorrhage.

Background: Cerebral microdialysis (CMD) is an FDA-approved multimodal invasive monitoring technique that provides local brain metabolism measurements through continuous interstitial brain fluid sampling at the bedside. The past applications in traumatic brain injury and subarachnoid hemorrhage show that acute brain injury (ABI) can lead to a metabolic crisis reflected by changes in cerebral glucose, pyruvate, and lactate. However, limited literature exists on CMD in spontaneous intracerebral hemorrhage (ICH). Case Description: A 45-year-old woman presented with a Glasgow Coma Scale of 8T and left frontal ICH with a 6 mm midline shift. She underwent craniotomy and ICH evacuation. Intraoperatively, CMD, brain tissue oxygenation (PbtO2), intracranial pressure (ICP), and cerebral blood flow (CBF) catheters were placed, targeted toward the peri-hematoma region. Postoperatively, ICP was normal; however, PbtO2, CBF, glucose, and lactate/ pyruvate ratio were abnormal. Due to concern for the metabolic crisis, poor examination, and hydrocephalus on computed tomography of the head (CTH), she underwent external ventricular drainage (EVD). Post-EVD, all parameters normalized (P < 0.05 on Student's t-test). Monitors were removed, and she was discharged to a nursing facility with a modified Rankin scale of 4. Conclusion: Here, we demonstrate the safe implementation of CMD in ICH and the use of CMD in tandem with PbtO2/ICP/CBF to guide treatment in ICH. Despite a normal ICP, numerous cerebral metabolic derangements existed and improved after cerebrospinal fluid diversion. A normal ICP may not reflect underlying metabolic-substrate demands of the brain during ABI. CMD and PbtO2/CBF monitoring augment traditional ICP monitoring in brain injury. Further prospective studies will be needed to understand further the interplay between ICP, PbtO2, CBF, and CMD values in ABI.

Association of Epileptiform Activity With Outcomes in Toxic-Metabolic Encephalopathy.

The clinical significance of epileptiform abnormalities (EAs) specific to toxic-metabolic encephalopathy (TME) is unknown. OBJECTIVES: To quantify EA burden in patients with TME and its association with neurologic outcomes. DESIGN SETTING AND PARTICIPANT: This is a retrospective study. A cohort of patients with TME and EA (positive) were age, Sequential Organ Failure Assessment Score, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score matched to a cohort of TME patients without EA (control). Univariate analysis compared EA-positive patients against controls. Multivariable logistical regression adjusting for underlying disease etiology was performed to examine the relationship between EA burden and probability of poor neurologic outcome (modified Rankin Score [mRS] 4-6) at discharge. Consecutive admissions to inpatient floors or ICUs that underwent continuous electroencephalography (cEEG) monitoring at a single center between 2012 and 2019. Inclusion criteria were 1) patients with TME diagnosis, 2) age greater than 18 years, and 3) greater than or equal to 16 hours of cEEG. Patients with acute brain injury and cardiac arrest were excluded. MAIN OUTCOMES AND MEASURES: Poor neurologic outcome defined by mRS (mRS 4-6). RESULTS: One hundred sixteen patients were included, 58 with EA and 58 controls without EA, where matching was performed on age and APACHE-II score. The median age was 66 (Q1-Q3, 57-75) and median APACHE II score was 18 (Q1-Q3, 13-22). Overall cohort discharge mortality was 22% and 70% had a poor neurologic outcome. Peak EA burden was defined as the 12-hour window of recording with the highest prevalence of EAs. In multivariable analysis adjusted for Charlson Comorbidity Index and primary diagnosis, presence of EAs was associated with poor outcome (odds ratio 3.89; CI [1.05-14.2], p = 0.041). Increase in peak EA burden from 0% to 100% increased probability of poor discharge neurologic outcome by 30%. CONCLUSIONS AND RELEVANCE: Increasing burden of EA is associated with worse discharge outcomes in patients with TME. Future studies are needed to determine whether short-term treatment with anti-seizure medications while medically treating the underlying metabolic derangement improves outcomes.

Association of Traumatic Brain Injury With the Risk of Developing Chronic Cardiovascular, Endocrine, Neurological, and Psychiatric Disorders.

Importance: Increased risk of neurological and psychiatric conditions after traumatic brain injury (TBI) is well-defined. However, cardiovascular and endocrine comorbidity risk after TBI in individuals without these comorbidities and associations with post-TBI mortality have received little attention. Objective: To assess the incidence of cardiovascular, endocrine, neurological, and psychiatric comorbidities in patients with mild TBI (mTBI) or moderate to severe TBI (msTBI) and analyze associations between post-TBI comorbidities and mortality. Design, Setting, and Participants: This prospective longitudinal cohort study used hospital-based patient registry data from a tertiary academic medical center to select patients without any prior clinical comorbidities who experienced TBI from 2000 to 2015. Using the same data registry, individuals without head injuries, the unexposed group, and without target comorbidities were selected and age-, sex-, and race-frequency-matched to TBI subgroups. Patients were followed-up for up to 10 years. Data were analyzed in 2021. Exposures: Mild or moderate to severe head trauma. Main Outcomes and Measures: Cardiovascular, endocrine, neurologic, and psychiatric conditions were defined based on International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Associations between TBI and comorbidities, as well as associations between the comorbidities and mortality, were analyzed. Results: A total of 4351 patients with mTBI (median [IQR] age, 45 [29-57] years), 4351 patients with msTBI (median [IQR] age, 47 [30-58] years), and 4351 unexposed individuals (median [IQR] age, 46 [30-58] years) were included in analyses. In each group, 45% of participants were women. mTBI and msTBI were significantly associated with higher risks of cardiovascular, endocrine, neurologic, and psychiatric disorders compared with unexposed individuals. In particular, hypertension risk was increased in both mTBI (HR, 2.5; 95% CI, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9) groups. Diabetes risk was increased in both mTBI (HR, 1.9; 95% CI, 1.4-2.7) and msTBI (HR, 1.9; 95% CI, 1.4-2.6) groups, and risk of ischemic stroke or transient ischemic attack was also increased in mTBI (HR, 2.2; 95% CI, 1.4-3.3) and msTBI (HR, 3.6; 95% CI, 2.4-5.3) groups. All comorbidities in the TBI subgroups emerged within a median (IQR) of 3.49 (1.76-5.96) years after injury. Risks for post-TBI comorbidities were also higher in patients aged 18 to 40 years compared with age-matched unexposed individuals: hypertension risk was increased in the mTBI (HR, 5.9; 95% CI, 3.9-9.1) and msTBI (HR, 3.9; 95% CI, 2.5-6.1) groups, while hyperlipidemia (HR, 2.3; 95% CI, 1.5-3.4) and diabetes (HR, 4.6; 95% CI, 2.1-9.9) were increased in the mTBI group. Individuals with msTBI, compared with unexposed patients, had higher risk of mortality (432 deaths [9.9%] vs 250 deaths [5.7%]; P < .001); postinjury hypertension (HR, 1.3; 95% CI, 1.1-1.7), coronary artery disease (HR, 2.2; 95% CI, 1.6-3.0), and adrenal insufficiency (HR, 6.2; 95% CI, 2.8-13.0) were also associated with higher mortality. Conclusions and Relevance: These findings suggest that TBI of any severity was associated with a higher risk of chronic cardiovascular, endocrine, and neurological comorbidities in patients without baseline diagnoses. Medical comorbidities were observed in relatively young patients with TBI. Comorbidities occurring after TBI were associated with higher mortality. These findings suggest the need for a targeted screening program for multisystem diseases after TBI, particularly chronic cardiometabolic diseases.

Simulation-Based Training Improves Fellows' Competence in Brain Death Discussion and Declaration.

BACKGROUND: Despite well-defined American Academy of Neurology guidelines for death by whole brain criteria (brain death), there is marked variability in national practice, which some have attributed to lack of formal education. Further, communication with surrogates and families about brain death is integral to brain death declaration. As such, we developed a targeted brain death curriculum combining didactics and simulation-based education to improve examination and subsequent communication skills with families. METHODS: Multidisciplinary critical care fellows participated in (1) didactic and case-based curriculum, (2) brain death simulated examination (SimMan3G mannequin), and (3) a standardized family scenario with delivery of a brain death diagnosis to a surrogate "family member". Fellows completed a precurriculum and postcurriculum multiple choice knowledge test and survey (Likert 1 to 10 scale) evaluating measures regarding diagnosis and communication of brain death. t Test and 2-tailed Wilcoxon signed rank test were used for statistical analysis (P<0.05). RESULTS: Thirteen critical care fellows participated in the curriculum. Most fellows [80% (N=12)] had only participated in 0 to 5 brain death declarations before this intervention. There was significant improvement across all measures: self-rated knowledge (P=0.004), perceived knowledge relative to peers (P=0.002), confidence (P=0.001), and comfort (P=0.001) with performing a brain death exam, and comfort with family discussion (P=0.01). Objective test scores improved from 56 to 73% after simulation (P=0.004). All fellows found the curriculum beneficial. CONCLUSION: Trainees may lack sufficient exposure to brain death education. Didactics with simulation-based education can improve objective knowledge and subjective measures of comfort with brain death declaration and surrogate communication.

A Qualitative Identification of Gaps in Understanding About Brain Death Among Trainees, Health Care Personnel and Families at an Academic Medical Center.

BACKGROUND AND PURPOSE: Death by whole brain criteria (brain death) is a clinical diagnosis. We sought to identify aspects of brain death that were unclear to both health care personnel and patient families. METHODS: Institutional review board approved cross-sectional survey study of attendings, medical trainees (residents and fellows), senior medical students, advanced practice providers (APPs), and critical care nursing (registered nurses [RNs]) at a tertiary referral center over 6 months (March 2018 to September 2018). Surveys were completed on paper or electronically. Participants supplied the top 3 of (1) their own personal questions regarding brain death and (2) questions received from patient families about brain death from a prepared list of questions. RESULTS: Two hundred twenty-nine individuals participated in the survey, with a response rate of 46%. Participation rates in brain death declaration among attendings (92%), RNs (84%), APPs (100%), and trainees of which included fellows (92%) and residents (85%) were high. Most frequently asked questions by trainees and health care personnel were "What are brain death mimics?" and "What is the gold standard testing?". Questions received from patient families most commonly include "What is brain death?" and "Is brain death reversible?". All medical students had questions about brain death. Greater than 75% of attendings endorsed having questions regarding brain death. CONCLUSION: Many health care personnel are involved with brain death declaration, but there are gaps in their understanding about fundamentals regarding brain death. We identify a need for early and targeted brain death education regarding brain death and family communication for various members of the health care profession.

Encephalopathy only stroke codes (EoSC) do not result in rt-PA treatments.

BACKGROUND: Isolated mental status changes as a presenting sign (EoSC+), are not uncommon stroke code triggers. As stroke alerts, they still require the same intensive resources be applied. We previously showed that EoSC+ strokes (EoSC+ Stroke+) account for 0.1-0.2% of all codes. Whether these result in thrombolytic treatment (rt-PA), and the characteristics/ risk factor profiles of EoSC+ Stroke+ patients, have not been reported. METHODS: Retrospective analysis of stroke codes from an IRB approved registry, from 2004 to 2018, was performed. EoSC+ was defined as a NIHSS>0 for Q1a, 1b, or 1c with remaining elements scored 0. Characteristics and risk factors were compared for EoSC+, EoSC-, EoSC+ Stroke+, and rt-PA (EoSC+ Stroke+TPA+) patients. RESULTS: EoSC+ occurred in 55/2982 (1.84%) of all stroke codes. EoSC+ Stroke+ occurred in 8/55 (14.5%) of EoSC+ codes and 8/2982 (0.27%) of all stroke codes. 6/8 (75%) of EoSC+ Stroke+ scored NIHSS=1. When comparing EoSC++versus EoSC-, Hispanic ethnicity (p=0.009), hypertension (p=0.02), and history of stroke/TIA (p=0.002) were less common in EoSC+. No demographic/risk factor differences were noted for EoSC+ Stroke+ vs. EoSC+ Stroke-. No cases of rt-PA eligibility/treatment were noted. In EoSC+ Stroke+ analysis, imaging positive stroke/intracranial hemorrhage was noted on only 3 cases (3/2982=0.10% of all stroke codes) and none were posterior stroke. CONCLUSIONS: EoSC+ rarely results in stroke/TIA (0.27%) or stroke (0.10%), and in our analysis never (0%) resulted in rt-PA. Sub-analysis did not show missed rt-PA or posterior strokes. Understanding characteristics, and knowing that EoSC+ Stroke+ patients are unlikely to receive rt-PA, may help triage stroke resources.

Moyamoya Presenting after Whole Body Cryotherapy.

BACKGROUND PURPOSE: Moyamoya syndrome is the progressive stenosis of intracranial carotids with secondary collateralization. Whole body cryotherapy (WBC) involves external cooling and is used in holistic and sports medicine, its neurologic effects are unknown. CASE REPORT: We report a first case of symptoms of moyamoya syndrome presenting following WBC and diagnosed with classic MRI ( "Brush Sign", "Ivy sign") and digital subtracted angiography. CONCLUSION: WBC may provoke symptoms of moyamoya syndrome possibly through hyperventilation or vasoconstriction. Practitioners should be aware of possible consequences of WBC in patients with poor cerebrovascular reserve.

PREMISE: Posterior Circulation Results Comparing Embolectomy to Medical Intervention in Stroke Emergencies.

Background Intravenous (IV) tissue plasminogen activator (rt-PA) is a proven therapy for stroke in the acute treatment window. Recent published data has shown efficacy for embolectomy for acute ischemic strokes within up to six, 16 and 24 hours in the anterior circulation but there is no guideline for optimal therapy for patients with posterior circulation stroke, specifically basilar artery occlusion (BAO) outside the standard IV rt-PA treatment window. Aim To evaluate differences in outcomes between maximal medical treatment versus thrombectomy in BAO. Method We retrospectively evaluated prospectively collected acute stroke code patients from our stroke registry from 7/2004 to 7/2016. Patients who received IV rt-PA were excluded. Patients with evidence of posterior circulation ischemia and a hyper dense artery sign on initial non-contrast CT were included as a surrogate for direct vessel data before 2014. Patients after 9/2014 were selected by evidence of BAO on vessel imaging. All patients were categorized either as endovascular therapy or standard medical treatment alone. Demographics, hospital discharge location and Modified Rankin Scale (mRS) at 90 days were compared. Two-sample t-test and Fisher's exact test compared continuous and categorical variables across groups respectively. Results A total of 18 patients were included (three embolectomy and 15 medical therapy only). There were no significant differences in demographic data (age, gender, race, ethnicity, blood pressure, diabetes mellitus, hypertension, atrial fibrillation, tobacco use, alcohol use and initial NIHSS). Results for outcome and efficacies showed no statistical difference between medical management and endovascular intervention for functional outcome mRS (0-3) at 90 days (p = 0.2) and discharge location of home/inpatient rehabilitation vs other locations (p = 0.52). Conclusions Our single-center review showed the expected transition from predominantly medically treated posterior circulation BAOs, to a mixed pattern including embolectomy. Although the sample size was small, this study also illustrates the lack of clear efficacy data for optimal treatment strategies, and the ongoing treatment challenges in posterior circulation stroke population in a population of patients outside the rt-PA window.

Timing of symptomatic intracerebral hemorrhage after rt-PA treatment in ischemic stroke.

BACKGROUND: We investigated patterns in the time from recombinant tissue-type plasminogen activator (rt-PA) treatment to symptomatic intracranial hemorrhage (sICH) onset in acute ischemic stroke. METHODS: We retrospectively reviewed all admitted "stroke code" patients from 2003 to 2017 at the University of California San Diego Medical Center from a prospective stroke registry. We selected patients that received IV rt-PA within 4.5 hours after onset/last known well and had sICH prehospital discharge. sICH diagnosis was made by prospective review. Endovascular-treated patients were excluded, given the variability of practice. sICH was prospectively defined as any new radiographic (CT/MRI) hemorrhage after rt-PA treatment and any worsened neurologic examination. Time to sICH was the time from rt-PA administration start to documented STAT head CT order time with the first evidence of new hemorrhage. Charts were reviewed for examination time metrics, demographics, clinical history, and neuroimaging. RESULTS: sICH was identified in 28 rt-PA-only treated patients. The mean time to sICH was 18.28 hours (range 2.4-34 hours). Median time to sICH was 18.25 hours. sICH was correlated with increased age (p = 0.02) and increased NIH Stroke Scale (p = 0.01). CONCLUSIONS: Our findings suggest that rt-PA patients have the highest risk of post rt-PA sICH within the first 24 hours after treatment. This supports monitoring of rt-PA-treated patients in specialized settings such as neuro-intensive care units or stroke units. Our findings suggest that the probability of sICH is low 36 hours post rt-PA. Future larger studies are warranted to identify the patterns of bleeding after rt-PA administration.

Emerging Subspecialties in Neurology: Medical education.

Medical education is the understanding of how medical knowledge is taught and practiced and encompasses not just medical students, but resident trainees, colleagues, and the community. While there is a growing emphasis in medicine on "clinician-educators," neurology training has only slowly developed formal opportunities in medical education. Here we highlight the current opportunities in residency and beyond, and explore options for further medical education infrastructure within neurology.

Mapping a Reliable Stroke Onset Time Course Using Signal Intensity on DWI Scans.

BACKGROUND AND PURPOSE: Identifying a last known well (LKW) time surrogate for acute stroke is vital to increase stroke treatment. Diffusion-weighted imaging (DWI) signal intensity initially increases from onset of stroke but mapping a reliable time course to the signal intensity has not been demonstrated. METHODS: We retrospectively reviewed stroke code patients between 1/2016 and 6/2017 from the prospective; Institutional review board (IRB) approved University of California San Diego Stroke Registry. Patients who had magnetic resonance imaging of brain from onset, with or without intervention, are included. All ischemic strokes were confirmed and timing from onset to imaging was calculated. Raw DWI intensity is measured using IMPAX software and compared to contralateral side for control for a relative DWI intensity (rDWI). LKW and magnetic resonance imaging (MRI) time were collected by chart review. Correlation is assessed using Pearson correlation coefficient between DWI intensity, rDWI, and time to MRI imaging. 1.5T, 3T, and combined modalities were examined. RESULTS: Seventy-eight patients were included in this analysis. Overall, there was statistically significant positive correlation (.53, P < .001) between DWI intensity and LKW time irrespective of scanner strength. Using 1.5T analyses, there was good correlation (.46, P < .001). 3T MRI analysis further showed comparatively stronger positive correlation (.66, P < .001). CONCLUSIONS: There is good correlation between DWI intensity and minutes from onset to MRI. This suggests a time-dependent DWI intensity response and supports the potential use of DWI intensity measurements to extrapolate an LKW time. Further studies are being pursued to increase both experience and generalizability.

"Encephalopathy Only Stroke Codes" (EoSC) Rarely Result in Stroke as Final Diagnosis.

Stroke codes prompted by isolated encephalopathy often result in nonstroke final diagnoses but require intensive stroke center resources. We assessed the likelihood of "Encephalopathy only Stroke Codes (EoSC)" resulting in a true stroke (EoSC CVA+) final diagnosis. 3860 patients were analyzed in a prospective stroke code registry from 2004 to 2016. EoSC was defined using a standard and an exploratory definition. Definition 1 included EoSC patients as stroke codes where NIHSS was nonzero for LOC questions (questions la, 1b, and lc) but remainder of the NIHSS was zero. Definition 2 included the same definition but allowed symmetric pairings on motor questions (5a/5b, 6a/6b, or Question 4 scoring a 3). Groups were assessed for final diagnosis of stoke (EoSC CVA+) or not stroke (EoSC CVA-). EoSC accounted for 60/3860 (1.55%) of total stroke codes. EoSC CVA+ was found in 5/3860 (0.13%) of all stroke codes, 5/60 (8.33%) of EoSC stroke codes, and 5/1514 (0.33%) of all strokes. For Definition 2, EoSC accounted for 96/3860 (2.5%) of total stroke codes. EoSC CVA+ was found in 9/3860 (0.23%) of all stroke codes, 9/96 (9.38%) of EoSC stroke codes, and 9/1514 (0.59%) of all strokes. On multivariable logistic regression analysis, diabetes was the highest predictor of stroke (p=0.05). Encephalopathy only Stroke Codes only rarely result in cases with a true final diagnosis of stroke (EoSC CVA+), accounting for 0.1-0.2% of all stroke codes and 8-9% of EoSC stroke codes. This may have important significance for mobilization of limited acute stroke code resources in the future.