Autonomic dysfunction after moderate-severe traumatic brain injury: symptom spectrum and clinical testing outcomes

Background and Objective: Survivors of moderate-severe traumatic brain injury (msTBI) frequently experience chronic, debilitating somatic symptoms, which are largely unexplained. The phenomenon of paroxysmal sympathetic hyperactivity, reflecting hyperacute autonomic dysfunction, is well-documented after msTBI. Limited animal and human studies, using experimental measures, have found evidence for autonomic dysfunction after msTBI. However, no studies have investigated the range and type of autonomic symptoms and autonomic dysfunction existing in msTBI. We set out to investigate the presence and type of subjective and objective autonomic dysfunction in msTBI. Methods: We conducted two cohort studies. Cohort 1 comprises msTBI patients prospectively recruited from a regional TBI outpatient clinic, in whom we assessed burden of autonomic symptoms using the Composite Autonomic Symptom Score (COMPASS31) autonomic symptom questionnaire. Cohort 2 comprises msTBI patients who had standard clinical autonomic function testing (supine/tilted catecholamine levels, head-up tilt, Valsalva manoeuvre, respiratory sinus arrhythmia assessment), retrospectively identified from the database of a regional clinical autonomic unit. Results: Cohort 1 comprises 29 msTBI patients (6 females, median age 40 years, range 19-76), with a median time since injury of 19 months (range 4-105). There was multi-domain symptom burden, with all but 3 patients reporting symptoms on the COMPASS31 questionnaire, and 17/29 reporting symptoms in 3+ domains. The most commonly reported symptoms were gastrointestinal (22/29), followed by orthostatic (17/19), pupillomotor (14/29), secretomotor (14/29), bladder (12/29) and, least commonly, vasomotor (6/29). Cohort 2 comprises 19 msTBI patients (7 females, median age 44 years, range 21-64), with a median time between injury and testing of 65 months (range: 2-416). The majority of patients (16/19) had orthostatic symptoms as part of the reason for referral. Clinical autonomic function testing revealed a broad spectrum of autonomic dysfunction: 4/19 had evidence of sympathetic dysfunction, 10/19 had evidence of parasympathetic dysfunction, of which 6 had evidence of mixed dysfunction. Discussion: Our results provide evidence for clinically relevant autonomic dysfunction after moderate-severe TBI, even at the chronic stage. Our study advocates for routine enquiry about potential autonomic symptoms in this population, and the utility of formal clinical autonomic testing in providing diagnoses.