David Roh

Background: Early neurological deterioration (END) after intracerebral hemorrhage (ICH) is associated with poor prognosis, but its independent contribution to mortality and disability beyond baseline severity remains undetermined. Using causal inference methods, we estimated the effect of END on 3-month outcomes and the population-level impact of preventing END. Methods: Consecutive patients with acute ICH presenting within 12 h of symptom onset at a comprehensive stroke center (2014–2023) were retrospectively analyzed. END was defined as a ≥4-point increase in National Institutes of Health Stroke Scale (NIHSS) score or a ≥2-point decrease in Glasgow Coma Scale (GCS) score within 24 h. Multivariable logistic regression identified baseline predictors of END. The average treatment effect (ATE) of END on the 3-month mortality rate and poor functional outcome rate (mRS of 4–6) was estimated using G-computation, inverse probability weighting, and targeted maximum likelihood estimation (TMLE; primary), adjusting for baseline severity and clinical confounders. TMLE-based counterfactual analyses estimated the population-level impact of preventing END. Results: Among 690 patients (median age of 71 [interquartile: 60–81] years; 308 (44.6%) female), 273 (39.6%) developed END. Across the estimators, END increased the absolute risk of 3-month mortality by 23.1–23.9% and poor functional outcomes by 20.2–22.8%, with no significant effect on disability among the survivors. Counterfactual analyses projected that preventing END would reduce the mortality rate from 31.6% to 21.3% (population attributable fraction of 32.5%) and poor functional outcomes from 56.8% to 48.8% (population attributable fraction of 14.2%). Conclusions: In this single-center cohort, END was associated with a substantially higher 3-month mortality rate and poor functional outcomes, independent of measured baseline severity and other clinical confounders. If this is causal, then END is a potential target for early intervention and a candidate early efficacy endpoint for ICH trials; whether preventing END improves outcomes requires prospective evaluation.

Brain activation to verbal commands can be detected by EEG in clinically unresponsive patients. These patients with cognitive motor dissociation (CMD) are unable to communicate with the environment despite preserved consciousness. Advanced brain-computer interfaces (BCI) are promising to support motor function in patients with motor neuron disease or spinal cord injury. Our primary objective was to determine if clinically unresponsive patients can control a self-paced, one-way BCI early after acute brain injury. Secondarily, we assessed the association of BCI control with short- and long-term outcomes. We conducted a prospective single-centre cohort study in 41 clinically unresponsive, critically ill and acutely brain injured patients, as well as in a convenience sample of 8 healthy volunteers and 22 conscious critically ill patients. The self-paced BCI analysed EEG in real time and modulated frequency and pitch of a tone that patients controlled by attempting a motor task: patients were provided with instructions ‘to make the beep sound faster, keep opening and closing your right hand’ alternating with ‘to make the beep sound slower, stop opening and closing your right hand’. CMD was detected by applying machine learning to EEG recorded while patients listened to motor commands. Clinical outcomes were recovery of consciousness by hospital discharge, assessed with the Coma Recovery Scale–Revised, and recovery of functional independence at 12 months, defined as a Glasgow Outcome Scale–Extended score of 4 or higher (denoting the ability to function independently for 8 h or more). Additionally, we invited conscious patients as well as family members of conscious and clinically unresponsive patients to complete a survey on perceived utility and challenges associated with the BCI. In this study, 13 clinically unresponsive patients (32%) achieved BCI control and 8 of 41 (20%) were CMD-positive. All healthy volunteers and nine conscious patients (41%) were able to control the BCI. Median signal delay for BCI control was 49.8 [interquartile range (IQR) 39.9–75.6] seconds for clinically unresponsive patients, 17.1 (IQR 7.8–19.9) for conscious patients and 15.5 (IQR 12.9–21.2) for healthy volunteers. In the group of 41 clinically unresponsive patients, 4 of 13 patients with (31%) and 1 of 28 without BCI control (4%) recovered clinical consciousness at hospital discharge [odds ratio (OR) 21.2; 95% confidence interval (CI) 2.3–930.7]. At 12 months, 6 of 13 patients with (46%) and 2 of 28 without BCI control (7%) recovered functional independence (OR 9.9; 95% CI 1.8–81.6). None of the patients that were unable to control the BCI and were CMD-negative recovered. Patients with BCI control had shorter times to recovery of functional independence by 12 months than those who did not (hazards ratio 6.0; 95% CI 1.2–30.6). All respondents of the BCI survey (n = 37) expressed strong support for the potential future use of BCI devices. These results suggest that BCI control is a strong predictor of outcomes following acute brain injury and provide initial evidence that a bedside, EEG-based BCI system might permit bidirectional communication in critically ill unresponsive patients.

Background: The Functional Outcome in Patients with Primary Intracerebral Hemorrhage (FUNC) score was initially validated for prediction of functional independence on the Glasgow Outcome Scale (GOS) 90 days after intracerebral hemorrhage (ICH), but recovery often extends beyond three months. Aims: Our objective was to extend the FUNC score for prediction of 12-month functional independence to strengthen its utility for family counseling and research methodology. Methods: We conducted a single-center prospective cohort study enrolling adult patients with primary ICH between February 2009 and January 2018. We calculated FUNC scores at admission and assessed GOS 12 months after ICH. The primary outcome was 12-month functional independence, defined as a GOS score ≥4. We calculated the area under the receiver operating characteristic curve (AUC) of the FUNC score using logistic regression, handling missing GOS with multiple imputation by chained equations. We evaluated score calibration using a calibration curve and the Brier score, and we assessed clinical utility using decision curve analysis. We explored the statistical efficiency gains of using FUNC-based sliding dichotomy thresholds for favorable outcome definitions by running simulations of a clinical trial with 1:1 randomization. We ran 5000 simulations for each sample size (100 to 1000, in increments of 10) and treatment effect (odds ratio of 1.5, 2.0 and 2.5) combination and calculated efficiency gains for each respective treatment effect as the percentage reduction in sample size required to have 80% power using sliding versus fixed dichotomy thresholds. Results: A total of 535 patients were included (median [IQR] age 68 [54-79], 237 [44%] female, median [IQR] NIHSS 16 [6-25], median [IQR] FUNC 8 [6-9]). Overall, 99 of 445 (22%) patients with known 12-month GOS achieved functional independence. The FUNC score had an AUC of 0.79 (95%-CI: 0.75-0.84) for 12-month functional independence. The calibration plot was reasonable, with modest evidence of overestimation at low predicted probabilities, and the Brier score was 0.15. A net benefit was observed across 5-50% threshold probabilities. Sliding dichotomy had an efficiency gain of 27% for a treatment effect of OR=2.0, and a gain of 22% for a treatment effect of OR=2.5. The efficiency gain for a treatment effect of OR=1.5 could not be calculated because the fixed dichotomy did not reach 80% power despite a sample size of 1000 patients. Conclusions: The FUNC score’s predictive performance for 12-month functional independence was comparable to its originally validated 3-month discrimination. Following external validation across centers, the FUNC score may be leveraged to counsel families on global measures of long-term functional independence and to implement sliding dichotomy methodology in ICH research.

Background: Evidence suggests that thrombo-inflammation underlies post-acute sequelae of SARS CoV-2 (PASC). Rotational Thromboelastometry (ROTEM) identifies hypercoagulability related to thrombo-inflammation in hospitalized patients. We sought to determine whether COVID-19 acute lung injury/acute respiratory distress syndrome (ALI/ARDS) survivors with PASC have evidence of hypercoagulability identifiable on ROTEM at 15 months after discharge. Methods: We conducted a single-center prospective cohort study of 93 adults hospitalized for COVID-19 ALI/ARDS in 2020. At 15-month follow-up, participants not receiving dual antiplatelet therapy or anticoagulation and without genetic coagulation disorders underwent ROTEM testing and completed symptom questionnaires. Cross-sectional associations between ROTEM parameters and PASC using the 12 symptoms and scoring from the RECOVER definition were tested using generalized additive models with propensity score adjustment for demographics, comorbidities, and aspirin use. Sensitivity analyses evaluated associations with specific PASC symptom phenotypes: patient-reported moderate or greater post-exertional malaise (PEM), fatigue, or brain fog. Results: Participants had a mean age of 55 years (SD, 11); 40% were women; 54% required mechanical ventilation, 18% received non-rebreather mask or non-invasive ventilation only, and 28% received nasal cannula oxygen only. At 15-month follow-up, 24% had PASC, 43% had PEM, 27% had fatigue, and 20% had brain fog. In adjusted analyses, increased fibrinogen contribution to clot strength (FIBTEM maximum clot firmness [MCF]), showed direct, linear associations with PASC risk. FIBTEM MCF values above reference ranges were more common in those with PASC (13 [59%] vs 20 [28%], p < 0.01). Similar associations were observed for PEM and fatigue, but not brain fog. Conclusions: Among survivors of COVID-19 ALI/ARDS, at 15 months after hospitalization, PASC, PEM, and fatigue, but not brain fog, are associated with subclinical hypercoagulable clotting characteristics identified on ROTEM that are driven by fibrinogen dysregulation. Further work is needed to evaluate the role of long-term coagulation abnormalities in persistent post-COVID physical symptoms and to explore potential therapeutic approaches.

Objective: Impairment of consciousness is frequent in patients with supratentorial brain injury, but underlying mechanisms are poorly understood. Large‐scale network dysfunction has been suggested as a unifying concept for the diverse focal infra‐ and supratentorial brain lesions associated with unconsciousness. Functional imaging studies have revealed that lesions in different locations that cause the same symptom can be linked to common networks using lesion network mapping (LNM). Methods: To identify a commonly injured network for impaired consciousness, LNM was used in a prospective, bi‐center observational cohort of 115 humans suffering from focal brain injury due to supratentorial intracerebral hemorrhage (ICH). Results: Contrasting patients with preserved (n = 45) and impaired consciousness (n = 70), we identified a common network of brain regions more likely to be connected to focal brain lesions associated with impaired consciousness. Lesions in unconscious patients were more likely connected to a network including fronto–insulo–limbic association cortex, subcortical arousal and neuromodulatory nodes, and the ventral striato‐pallidal circuitry. Data suggested preferential connectivity to a combination of arousal circuitry and association cortices. Interpretation: Patients with impaired consciousness shared a common pattern of distributed network involvement that we infer to be mechanistically relevant to the regulation of consciousness that may serve as promising targets of neuromodulatory therapies. ANN NEUROL 2026;100:206–221

BACKGROUND AND OBJECTIVES: Best platelet transfusion practices are unclear across intracranial hemorrhage (ICH) types, given the mortality risk. Reasons for this risk are unknown, but ABO-incompatible platelet transfusions may confer risk in certain populations. We assessed contemporary ICH platelet transfusion practices and whether ABO-incompatible platelet transfusions increase ICH mortality risk. METHODS: Adult patients with spontaneous intracerebral hemorrhage (sICH), traumatic ICH, and aneurysmal subarachnoid hemorrhage hospitalizations between 2019 and 2024 were assessed from a multicenter transfusion network. Relationships of platelet transfusions with 30-day mortality were assessed using logistic regression models adjusting for demographics, ICH type/severity, comorbidities, and other hemorrhage control therapies/transfusions. Among those receiving platelet transfusions, relationships of major ABO-incompatible platelet units with mortality risk were investigated using Cox models adjusting for similar covariates. Analyses were performed across the cohort and stratified by ICH subtype. RESULTS: Among 13 068 patients with ICH, 60% were male individuals, mean age was 66 (±19) years, 23% were from sICH, 69% from traumatic ICH, and 8% from aneurysmal subarachnoid hemorrhage cohorts. Acute platelet transfusions were given to 12% of the patients. Thrombocytopenia (<100 000 platelets/μL) and neurosurgical procedures, seen in 6% and 18% of the patients, respectively, were largest factors for platelet transfusions. In regression analyses, platelet transfusions themselves did not associate with mortality (adjusted hazard ratio [HR]: 1.14 [0.96-1.35]). However, among patients with ICH receiving platelet transfusions, ABO-incompatible units were common (37%) and had dose-dependent relationships with mortality (adjusted HR ≥2 exposures: 1.78 [1.18-2.70]). Stratified analyses revealed that patients with sICH were particularly vulnerable to mortality from even single exposures of ABO-incompatible units (adjusted HR 1 exposure: 1.97 [1.13-3.45]; ≥2 exposures: 2.78 [0.98-7.87]) compared with other ICH subtypes. CONCLUSION: Acute platelet transfusion practice remains prevalent in ICH, and platelet transfusion–related 30-day mortality risk may be influenced by ABO-incompatible platelet units. Clinical trials are needed to assess whether transfusion practice changes in providing ABO-matched platelets can improve outcomes in certain patients with ICH.

Atrial fibrillation detected after stroke (AFDAS) refers to newly identified atrial fibrillation occurring after an index cerebrovascular event, most commonly ischemic stroke, but little is known about its occurrence and clinical implications in patients with spontaneous intracerebral hemorrhage (ICH). We aimed to characterize AFDAS risk factors in ICH and AFDAS' relationship with long-term ICH outcomes. We retrospectively analyzed consecutively admitted and enrolled patients with spontaneous ICH to a single tertiary comprehensive stroke center between 2009 and 2018 who underwent continuous cardiac monitoring. Patients were categorized as having sinus rhythm [SR (reference)], atrial fibrillation detected after stroke (AFDAS, defined here as atrial fibrillation (AF) detected during the index ICH hospitalization), and known AF. Demographic, clinical, imaging, and hospitalization complication data were compared across rhythm groups. Poor modified Rankin scale (mRS 4-6) at 3-month follow-up was assessed as the primary clinical outcome. Multivariable logistic regression assessed independent relationships of AFDAS with poor outcomes adjusting for demographics, ICH severity, and AFDAS risk factors. Amongst 532 patients with ICH, AFDAS occurred in 5% on median ICH hospital day 3. Outside of increased hypertension prevalence, patients with AFDAS had fewer baseline cardiovascular comorbidities compared with patients with known AF yet had similar cardiac risk profiles and structural/function measurements on echocardiogram compared with patients with SR. Baseline ICH characteristics and severity were similar between groups, but patients with AFDAS were more likely to have hospitalization infection complications (67% vs. 32% in known AF, 42% in SR, p = 0.01). Poor 3-month outcome was more common in patients with AFDAS (94%) compared with those with known AF (78%) and sinus rhythm (65%) (p = 0.01), and AFDAS was independently associated with poor outcomes [adjusted odds ratio (OR) 11.07, 95% confidence interval (CI) 1.30-94.27]. We identified that patients with ICH and AFDAS have less severe cardiovascular comorbidities yet are more likely to have worse long-term outcomes. Further prospective studies are required to confirm these results and characterize drivers for AFDAS development and links between AFDAS and poor ICH outcomes to assess whether AFDAS detection and prevention can improve ICH.

Objective: Cognitive motor dissociation (CMD) is associated with long-term recovery in acute brain injury, but CMD testing is only available in few centers. Our objective was to identify surface EEG patterns with high sensitivity or positive predictive value (PPV) for CMD in patients with acute disorders of consciousness to refine allocation of this resource-intensive test. Methods: In this observational cohort study, we enrolled clinically unresponsive, acutely brain injured patients who underwent continuous surface EEG and CMD assessments. CMD was detected by applying a machine learning algorithm to EEG acquired during a motor command paradigm presentation. Electroencephalographers blinded to CMD test results applied standardized ACNS criteria to the EEGs acquired during CMD assessments. We calculated accuracy measures of surface EEG findings for CMD test results using generalized estimating equations, with an exchangeable matrix and accounting for repeated measures per patient. Results: We included 185 patients (mean age: 62 ± 17; 85 [46%] female) and 282 CMD assessments. CMD testing was positive in 39 (14%) assessments. Sensitivity and PPV of normal background voltage, symmetry and continuity were respectively 77% (95%-CI: 60-88%) and 19% (95%-CI: 13-26%), 74% (95%-CI: 58-86%) and 14% (95%-CI: 10-20%), and 74% (95%-CI: 58-86%) and 14% (95%-CI: 9-19%). All EEGs with burst suppression, suppression, sporadic epileptiform discharges, lateralized periodic discharges, bilateral independent periodic discharges, electrographic seizures and brief potentially ictal rhythmic discharges had negative CMD tests. Interpretation: Surface EEG findings are not reliable to screen for CMD or to identify patterns conferring higher CMD pretest probability.

Background Cerebral ischemia is frequently detected after intracerebral hemorrhage (ICH) on diffusion-weighted imaging (DWI) and is associated with worse outcomes. Although the mechanism is uncertain, cerebral autoregulation impairment due to severe hypertension has been suggested from prior studies. We tested the hypothesis that more severe left ventricular hypertrophy (LVH), a marker of chronic hypertension-mediated organ damage, is associated with DWI lesions after ICH. Methods Using a single-center observational cohort study, we included all patients with spontaneous ICH between 2009 and 2019 with available magnetic resonance imaging (MRI) who underwent transthoracic echocardiography (TTE) during the index hospitalization. LVH was primarily categorized as none/mild or moderate/severe based on the TTE report and was secondarily defined using calculated left ventricular mass index (LVMI) measurement. The primary outcome measure was acute DWI lesion presence on brain MRI. The number of DWI lesions was assessed as a secondary outcome. Results A total of 187 patients (mean [SD] age 66.4 [14.5] years, 50.8% female) with a median baseline ICH volume of 12.6 (interquartile range 4.0–32.0) mL had TTE and DWI performed. Moderate/severe LVH was present in 23.5% of patients, and DWI lesions were detected in 30.5% of the cohort. Using multivariable logistic regression, the primary analysis found that moderate/severe LVH was associated with DWI lesion presence with adjustment for ICH severity (adjusted odds ratio [aOR] 2.74, confidence interval [CI] 1.32–5.71; p = 0.01). A similar association was demonstrated between the highest LVMI quartile and DWI lesion presence (aOR 3.60, CI 1.48–8.77; p = 0.01). Linear regression models found moderate/severe LVH was associated with greater DWI lesion count (adjusted B 1.32, CI 0.89–1.76; p < 0.01). Conclusions Greater LVH severity was associated with the presence and burden of DWI lesions after acute ICH. Echocardiography may be a tool to inform secondary ischemia risk stratification and prevention strategies.

Background: Ambulatory ability after intracerebral hemorrhage (ICH) is important to patients. We tested whether asymmetry between ipsi‐ and contra‐lesional corticospinal tracts (CSTs) assessed by diffusion tensor imaging (DTI) is associated with post‐ICH ambulation. Methods: Patients with spontaneous supratentorial ICH were recruited from 8 US sites between 2017 and 2024. For each patient, fractional anisotropy (FA) asymmetry index (AI) was computed for the whole CST and on a subset of fibers restricted to the cerebral peduncle (CP). Clinical and radiographic features were collected. The primary outcome was Barthel Index Mobility Score (BIMS) at 3 months (dichotomized outcome [DO]: BIMS 15 = good [independent ambulation]; BIMS < 15 = poor [non‐independent ambulation]; ordinal outcome [OO]: BIMS 0, 5, 10, 15). Two imputation‐based multiple logistic regression analyses accounted for whether ICH prevented tracking of CSTs. Odds ratios (ORs) were reported for a change of 0.1 and 95% confidence intervals (CIs). Results: At 3 months, 124 patients were eligible for inclusion. In addition to known clinical variables, CST and CP FA AI were associated with poor BIMS (OR 2.97, CI 1.12–7.90, p = 0.029; OR 3.80, CI 1.63–8.84, p = 0.002). In Model 1, unresolved FA (FA zero) was not correlated with lower BIMS (DO: OR 3.25, CI 0.62–17.07, p = 0.163; ordinal outcomes: OR 2.02, CI 0.48–8.55, p = 0.341). In Model 2, the combination of CST FA AI and FA zero correlated with lower BIMS (DO: joint p ‐value =0.041; OO: p = 0.030). CP FA asymmetry was associated with lower BIMS (DO: OR 3.96, CI 1.25–12.55, p = 0.019; OO: OR 3.39, CI 1.24–9.27, p = 0.017). Conclusion: DTI‐assessed CST integrity may be an additional tool physicians can utilize to guide post‐ICH ambulatory expectations.