Center for Neuro-Oncology

Status epilepticus (SE) is a medical emergency requiring rapid intervention. Despite treatment guidelines, delays in real-world SE management persist, potentially worsening outcomes. The Established Status Epilepticus Treatment Trial (ESETT), while comparing second-line antiseizure medications, also enabled analysis of treatment timelines in emergency settings. This study evaluates the timing of SE treatment steps in ESETT to assess adherence to guideline-recommended timeframes and identify factors contributing to delays. This secondary analysis of ESETT included patients aged ≥ 2 years with generalized convulsive SE unresponsive to benzodiazepines, randomized to receive fosphenytoin, levetiracetam, or valproic acid. Key intervals analyzed included time from emergency department (ED) arrival to first benzodiazepine, initiation of second-line therapy, and other interventions (e.g., intubation, rescue meds). We used descriptive statistics and the Van Elteren test to compare timelines between those who achieved treatment success, defined as seizure cessation and improved mental status at 60 min, and those who did not. Among 487 patients (53% adults, 47% children; 57% male), 46% achieved treatment success. Nearly half did not receive any prehospital benzodiazepines. Median time from ED arrival to first benzodiazepine was 11 min (IQR 5-41), and to second-line antiseizure medications was 26 min (IQR 18-43), both generally aligning with guidelines. Earlier administration of second-line therapy was significantly associated with treatment success (p = 0.03). Although many treatment steps occurred within recommended windows, considerable variability exists. Prehospital benzodiazepine use was often absent, and in-hospital treatment timing was inconsistent. Earlier delivery of second-line therapy correlated with improved outcomes. These real-world data provide a lens through which to better understand the causes and impact of practice variability in time to treatment and assess the extent to which current guidelines on timing may be important, but also how they may be ambiguous or unrealistic.

Patients with disorders of consciousness (DoC) characteristically lack decision-making capacity, a central challenge for shared decision-making, as surrogate decision-makers must navigate the uncertainties of making proxy care decisions. The element of uncertainty is especially prominent considering growing recognition of cognitive motor dissociation or covert consciousness, attributable to advances in neurotechnologies that enable the detection of signatures of responsiveness and recovery capacity that evade routine bedside detection. Professional society guidelines now recommend use of advanced neurotechnologies for some patients, marking their transition from investigational into guideline-directed clinical tests. Yet, advanced neurotechnologies themselves introduce uncertainties to the calculus of shared decision-making, particularly given a paucity of guidance on clinical translation. Through semistructured interviews, we examined attitudes of clinicians and family members of patients with potential covert consciousness during three stages of conversation regarding translation of advanced neurotechnologies into DoC practice.Although clinicians described weighing clinical, prognostic, and logistical factors when deciding to introduce advanced testing, most family members regarded clinicians as ethically obligated to offer advanced neurotechnologies in DoC assessment. There was near consensus that results of advanced neurotechnologies must be shared, even in research contexts. The majority of clinicians and family members posited that results of advanced neurotechnologies should be communicated in ways that are sensitive to families' understanding, background, receptiveness to information, and anticipated decision-making role, and they valued transparency regarding the limitations and uncertainties inherent to these modalities. Clinicians placed higher weight on positive rather than negative results. Half of family members reported that results of advanced neurotechnologies impacted care decisions for their loved ones with DoC. Our findings reveal key points of convergence and divergence between clinicians and family members throughout stages of decision-making, grounding an ethically informed discussion guide that clinicians may use as a roadmap to support shared decision-making in this emerging context.

Intracortical brain-computer interfaces (BCIs) that decode complex movements, such as handwriting and speech, can require substantial training data to achieve high performance. We investigated whether leveraging the neural activity recordings of previous users could reduce this initial data collection burden for new BCI users (an approach we call "cross-brain transfer"). Using intracortical recordings from five BrainGate2 clinical trial participants, we tested cross-brain transfer for both speech and handwriting neural decoders trained and evaluated on general, unconstrained corpora of spoken and written English. We found that cross-brain transfer improved decoding performance when training data from the target user was limited (< 200 sentences), and that dataset-specific input layers to the decoder were critical for combining data across users. Without trainable input layers, transfer failed and performed worse than training from scratch on target user data only. Finally, we measured the effectiveness of cross-brain transfer relative to training with (1) more data from the same user and (2) more electrode-permuted data from the same user, which simulates sampling from another brain with identical neural latent structure. In some cases (T16 speech, T12 handwriting), cross-brain transfer appeared as effective as additional permuted data from the same user, while in others (T12 speech, T15 speech) electrode-permuted data was more beneficial. Our results successfully demonstrate and characterize cross-brain transfer learning between multiple intracortical BCI users, for both speech and handwriting, using a general open-ended dataset not restricted to small sets of words or phrases. This work highlights a promising path towards addressing a key barrier to the clinical translation of BCIs, while clarifying when cross-brain transfer may be most beneficial and the decoder design choices needed to realize those gains.

Patients with cerebellar ataxia experience fatigue, impaired executive function, and psychosocial deficits. Personal social networks affect physical and mental well-being but there are no data on their effect on quality of life (QOL) and function in ataxia. We examined social network metrics in patients with cerebellar ataxia to test the hypothesis that supportive relationships enhance quality of life and physical function. We used a cross-sectional, survey-interview design with the Personal Network Survey for Clinical Research, World Health Organization QOL-BREF (WHOQOL), Functional Staging Scale for Ataxia, Friedreich's Ataxia Rating Scale-Activities of Daily Living (FARS-ADL), and Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia). We used univariate and bivariate descriptive statistics and bivariate correlations to explore relationships between social network characteristics and QOL, and multivariable linear regression for associations between them. In 106 ataxia patients (56 ± 15.3years), social network size averaged 7.6 ± 2.8 people, mostly friends (52%) and family (33%). Social networks were dense (0.7 ± 0.3) and constrained (0.5 ± 0.1). Omnibus test showed that positive relationships, camaraderie, weekly communication, and high levels of emotional support correlated with PROM-Ataxia Total (p = 0.03), PROM-Ataxia Mental health (p = 0.05), WHOQOL (p = 0.03), FARS-ADL and Functional Staging. Those with constrained social networks and fewer positive relationships reported low QOL, as did those with frequent therapy/counseling and organizational involvement. Positive relationships within social networks of cerebellar ataxia patients positively influence QOL and functional measures. Counterintuitive negative associations with external sources of support need further study to explore causality. Network interventions to enhance emotional support and camaraderie may improve quality of life.

The prognostic and predictive value of O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation is not well established in isocitrate dehydrogenase (IDH)-mutant gliomas. This study evaluates the survival impact of MGMTp and other clinical, molecular, and radiologic variables in low-grade and high-grade IDH-mutant gliomas. We retrospectively evaluated 520 consecutive adult patients treated for an initial diagnosis of IDH-mutant glioma, of any histological grade, at two large academic institutions. MGMTp methylation was evaluated by methylation-specific polymerase chain reaction (PCR) analysis. Log-rank test and Cox proportional hazards model were applied to evaluate the association of clinical, molecular, and radiological characteristics with overall survival (OS) and progression-free survival (PFS). Median age was 36.6 years; MGMTp was methylated in 70% and unmethylated in 30%. MGMTp methylation was not significantly associated with OS (P = 0.11) or PFS (P = 0.74) on multivariate analyses. Cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion [HR = 3.26 (1.47, 7.23), P = .006] and an integrated grade 4 classification [HR = 2.08 (1.06, 4.67), P = .048] were strong predictors of OS in astrocytoma, whereas maximal resection [HR = 0.06 (0.01, 0.57), p = 0.016] and radiation [HR = 0.41 (0.18, 0.91), P = .03] were strong prognosticators for PFS in the entire cohort. Maximal resection of the enhancing disease [HR = 0.17 (0.05, 0.96), P = .014] and radiation [HR = 0.47 (0.19, 0.65), P = .046] were strongly associated with PFS in grade 2 and 3 gliomas. MGMTp methylation was not associated with a prognostic or predictive value in our IDH-mutant glioma cohort. CDKN2A/B status and extent of resection were strong predictors of outcomes.

This study evaluates contusion volume and location as predictors of PTE while considering mortality as a competing risk using automated segmentation of acute CT images. Adult TBI patients who visited our center (2014-2025) were identified and categorized into three outcome groups: PTE, post-TBI mortality, and event-free. Clinical covariates were extracted from health records, and CT scans were processed using the BLAST-CT algorithm to segment intraparenchymal hemorrhage (IPH), edema, intraventricular (IVH), and extra-axial hemorrhage (EAH). Five-fold nested cross-validation was performed, with L1-regularized regression used for feature selection within each training fold and model performance evaluated in the corresponding test fold. Within each fold, the selected features were then used to fit separate cause-specific multivariable Cox models for PTE and mortality. Contusion location associations were assessed using both multivariable Cox and sparse canonical correlation analysis. Of 1017 identified patients, 6.1% developed PTE, 10.5% died, and 83.4% had no event. In multivariable analysis, total contusion volumes (p<0.001) were independently predicted both PTE and mortality, meanwhile and EAH volume (p<0.01) predicted mortality only. When regionalized, frontal (p<0.01) and temporal (p<0.01) contusions independently predicted PTE, whereas frontal (p=0.04) contusions also independently predicted mortality. Sparse canonical correlation analysis identified an association of frontotemporal and insular contusions with PTE but not mortality. Automatically measured contusion segmentation from acute CT imaging could help predict post-traumatic epilepsy. A competing risk framework highlighted that contusion volume is associated with both PTE and mortality risk, whereas unique contusion location patterns may aid in post-traumatic epilepsy assessment in a broad TBI population.

Abstract BACKGROUND The prognosis of molecular glioblastoma (mGBM) – isocitrate dehydrogenase (IDH) wildtype, lacking necrosis or microvascular proliferation but with molecular features of glioblastoma (EGFR amplification, TERT promoter mutation, concurrent gain of chromosome 7 and loss of chromosome 10 (+7/-10)) - is incompletely characterized limiting patient inclusion into clinical trials. METHODS We retrospectively evaluated the outcome of patients with mGBM and compared them to those of patients with tumors demonstrating histological features characteristic of glioblastoma (hGBM) treated at Dana-Farber Cancer Institute between 2006 and 2023. Patients were identified from an institutional database. We collected demographic and molecular information, treatment characteristics, and survival outcomes. Median overall survival (OS) and progression-free survival (PFS) were evaluated with Kaplan-Meier and differences between groups with log-rank test. RESULTS 64 patients with mGBM (46.9% female) and 519 patients with hGBM (39.7% female) were identified. mGBM diagnosis was established by a single molecular feature in 39 patients, 2 features in 17 patients, and 3 features in 8 patients. Among mGBM patients, TERT promoter mutation, EGFR amplification and +7/-10 were identified in 39 (61%), 24 (38%) and 32 (50%), respectively. Median age at diagnosis was 57.3 years in mGBM and 60.5 years in hGBM (p=0.13). MGMT promoter was methylated in 39.0% and 34.0% respectively (p=0.49). Median OS was 22.0 months for mGBM and 17.5 months for hGBM (p=&amp;lt;0.001) and median PFS was 10.6 months and 10.0 months respectively (p=0.3). In univariate analysis, TERT promoter mutation, EGFR amplification, and +7/-10 were not associated with OS or PFS in mGBM. Additionally, in 12 patients with mGBM who only had TERT promoter mutation, OS and PFS were not statistically different to those with other mutations or combinations (p=0.6, p=0.7). CONCLUSION mGBM patients had longer OS, but similar PFS, compared to hGBM patients in our cohort. Additional validation in larger multi-institutional cohorts is warranted.

Gait impairments are a well-documented consequence of stroke, yet the impact of transient ischemic attack (TIA) on gait remains underexplored. This study aimed to characterize acute changes in gait patterns within three days of stroke or TIA onset using an accelerometer, and to examine the relationship between gait patterns and questionnaire-based measures of balance confidence. We found that patients with TIA showed significantly lower variability in swing time, stance time, and step time than patients with stroke. Comparisons between patients with TIA and controls indicated that controls had higher mean step velocity and lower step time asymmetry. Additionally, compared with controls, patients with stroke demonstrated a slower and less temporally consistent pace, indicated by shorter step length, lower step velocity, and higher standard deviation (SD) for swing time, stance time, and step time. They also showed greater variability, reflected by higher step length SD, and more pronounced gait asymmetry, with greater asymmetry in swing time, step time, and stance time. The balance confidence was associated with gait parameters in patients with stroke and in controls, but not in patients with TIA. In both groups, higher confidence related to longer step length and faster step velocity; in stroke it was also linked to lower swing time variability and longer step and stance times, and in controls to lower step time variability. These findings demonstrate that TIA involves detectable neurological changes affecting motor control, highlighting the value of detailed accelerometer-based gait analysis for early detection of functional deficits.