Women experience persistent symptoms, longer recovery after TBI compared with men

Findings from a prospective cohort study of patients with mild traumatic brain injury demonstrated that women were more likely than men to experience persistent cognitive and somatic symptoms related to the injury.

Researchers published results from the study, which also showed that postconcussion symptoms were worse in women aged 35 to 49 years compared with younger and older women, in JAMA Network Open. They noted that the findings regarding age require additional research to corroborate the link and to determine the mechanisms involved in the result.

“Despite progress in characterizing sex differences in the trajectory of recovery from [mild] TBI, there remain gaps in knowledge of the epidemiology, mechanisms and effect of persisting [post-concussion syndrome] in women,” the researchers wrote. “The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) pilot study, a forerunner to the present project, reported a sex [and] age interaction on [mild] TBI symptom measures at 6 months after injury in 100 young adult patients with [mild] TBI aged 18 to 39 years, with more persistent TBI-related symptoms in women aged 30 to 39 years than younger women and men in both the 19- to 29-year and 30- to 39-year subgroups. However, it was unclear whether sex differences on symptom measures were specific to [mild] TBI, because the TRACK-TBI study lacked a non-TBI traumatic injury control group.”

In the current study, Harvey Levin, PhD, professor of physical medicine and rehabilitation at Baylor College of Medicine in Houston and research scientist at Michael E. DeBakey Veterans Affairs Medical Center in Houston, and colleagues aimed to determine sex-related differences in mild TBI recovery and, secondarily, to examine age differences among women who have poorer outcomes following TBI.

The researchers recruited 2,000 patients with mild TBI from February 26, 2014, to July 3, 2018, as well as 299 patients with orthopedic trauma — who served as controls — from Jan. 26, 2016, to July 27, 2018, all from 18 level one trauma centers, for the TRACK-TBI study. They followed patients for 12 months and analyzed data from August 19, 2020, to March 3, 2021.

Outcome measures included the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a self-report scale that evaluates postconcussion symptom severity in the preceding 7 days relative to preinjury; the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, which measures severity of posttraumatic stress disorder symptoms; the Patient Health Questionnaire-9 (PHQ-9), a scale that measures depression based on symptom frequency in the past 2 weeks; and the Brief Symptom Inventory-18 (BSI-18), a scale of psychological distress that is split into depression and anxiety subscales.

The patient population included 1,331 men (67%; mean age, 41 years; 78% white) and 669 women (33%; mean age, 43 years; 76% white).

Following adjustments for multiple comparisons, Levin and colleagues observed significant associations between TBI and sex for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.8; 5% false discovery rate-corrected P = .02), with worse symptoms among women with mild TBI compared with men. However, the researchers observed no sex difference for symptoms in control patients with orthopedic trauma. Among the women included in the study, the researchers found a significant interaction between TBI and age for somatic RPQ symptoms, which were worse in women aged 35 to 49 years with mild TBI compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02).

“The finding of sex differences in RPQ symptoms in the [mild] TBI but not the [orthopedic trauma] group suggests that the higher propensity of women to experience prolonged [mild] TBI recovery may not be a consequence of sex differences in preinjury symptoms or reporting biases,” the researchers wrote. “Furthermore, these differences may not be the result of the nonspecific effects of trauma; rather, the sex differences may be a direct result of differences in susceptibility to brain injury symptoms.”

Levin and colleagues called the finding that women aged 35 to 49 years experienced more severe somatic post-concussion syndrome after mild TBI “preliminary” and noted that it should therefore be “interpreted accordingly.” They also called for further research into this finding, specifically research that examines psychosocial stress and sex hormone levels to examine the mechanisms that underlie this interaction between mild TBI and age.

“Implications of this cohort study for individualized clinical management of [mild] TBI include educating female patients about the greater risk of persistent symptoms and lengthier recovery after [mild] TBI,” the researchers wrote. “Our findings suggest that female sex is a risk factor of which clinicians should be aware when triaging patients for follow-up.”