AAN 2026: Sex and Gender’s Impact on TBI Survival and Recovery

A recent study presented at the American Academy of Neurology’s 2026 Annual Meeting reveals that biological sex and gender independently influence survival and recovery outcomes following traumatic brain injury (TBI), with distinct patterns emerging across both dimensions. The findings, drawn from a multicenter analysis of over 12,000 TBI patients treated between 2020 and 2025, indicate that while biological sex affects acute physiological responses to injury, gender-related social and behavioral factors play a significant role in longer-term rehabilitation trajectories.

Researchers from the University of California, San Francisco, and the Mayo Clinic collaborated on the prospective cohort study, which stratified patients by biological sex (male/female) and self-reported gender identity (cisgender man, cisgender woman, transgender/nonbinary) using standardized clinical intake forms. The primary outcomes measured were 30-day mortality, functional independence at six months as assessed by the Glasgow Outcome Scale-Extended (GOS-E), and return to pre-injury activity levels at one year.

At the acute stage, male patients exhibited a 12% higher risk of death within 30 days compared to female patients, even after adjusting for injury severity, age, and comorbidities. This disparity was most pronounced in cases of severe TBI, where males showed greater susceptibility to secondary brain swelling and hypoxic injury. Researchers suggest these differences may stem from known sex-based variations in cerebral blood flow regulation, inflammatory response, and blood-brain barrier integrity following trauma.

In contrast, gender identity emerged as a stronger predictor of recovery quality in the subacute and chronic phases. Transgender and nonbinary patients were 30% less likely to achieve good functional recovery (GOS-E ≥ 6) at six months compared to cisgender counterparts, independent of biological sex. Cisgender women, despite lower acute mortality, reported higher rates of persistent post-concussive symptoms such as fatigue, sleep disturbance, and emotional lability, which correlated with reduced participation in rehabilitation programs.

Social determinants appeared to mediate many of these gender-related disparities. Transgender and nonbinary individuals were significantly more likely to experience delays in accessing rehabilitation services due to insurance barriers, provider unfamiliarity with gender-affirming care in neurologic contexts, and prior experiences of discrimination in healthcare settings. Cisgender women, meanwhile, often reported assuming caregiving roles for family members shortly after injury, which limited their ability to adhere to intensive therapy schedules.

The study’s lead author, Dr. Elena Rodriguez of UCSF’s Department of Neurology, emphasized that biological sex and gender are not interchangeable variables in neurologic outcomes. “We’ve long observed sex differences in TBI epidemiology, but this analysis shows that gender — shaped by identity, social experience, and structural inequities — operates through separate pathways,” she stated. “Ignoring either dimension leads to incomplete models of recovery and risks misdirecting interventions.”

These findings align with growing evidence in neurotrauma research that biological and sociocultural factors intersect in complex ways. A 2024 meta-analysis in JAMA Neurology found that while males account for approximately two-thirds of TBI hospitalizations, females report higher symptom burden during recovery. Similarly, a 2023 study from the Veterans Health Administration highlighted that transgender veterans with TBI face unique challenges in navigating both neurologic and gender-affirming care systems.

The researchers caution that the study’s gender categories, while informed by current clinical best practices, may not fully capture the diversity of gender experiences, particularly among non-Western populations or younger age groups. They also note that unconscious bias in neurological assessment tools — many of which were normed on predominantly male, cisgender cohorts — could influence outcome measurements.

Moving forward, the team advocates for routine collection of gender identity data in TBI registries and clinical trials, alongside sex, to enable more precise prognostic modeling. They also recommend that rehabilitation programs incorporate gender-sensitive approaches, such as flexible scheduling, culturally competent provider training, and tailored mental health support, to address disparities in access and engagement.

The study was funded by the National Institute of Neurological Disorders and Stroke and the Patient-Centered Outcomes Research Institute. No industry conflicts of interest were disclosed. The findings were presented as a platform abstract at AAN 2026 on April 18, 2026, in San Diego, California, and are under peer review for publication in Neurology.