Innovative approaches in treating paroxysmal sympathetic hyperactivity following traumatic brain injury: a comprehensive review

INTRODUCTION: Paroxysmal Sympathetic Hyperactivity (PSH) is a historically underrecognized yet increasingly acknowledged syndrome following traumatic brain injury (TBI), characterized by episodic surges in sympathetic nervous system activity. Despite increasing awareness, effective therapy remains unavailable due to diagnostic uncertainty and therapeutic heterogeneity. AREAS COVERED: In this review, the authors synthesize the recent advances and emerging fronts in the treatment of PSH, encompassing mechanistic understanding, drug discovery, non-pharmacological treatment, and trials in progress. They also outline areas of knowledge deficit and offer suggestions for future research. EXPERT OPINION: There are several ongoing challenges, including variability in diagnostic approaches and inconsistent outcome measures. There is also an absence of unified treatment protocols that limit clinical consistency and hamper research comparability. Improving alignment between acute ICU management and long-term rehabilitation is similarly important. Moving forward, precision medicine, predictive biomarker development, and individualized treatment modeling offer significant promise. There is optimism that identifying at-risk populations or individuals earlier could enable timely treatment and support the development of more targeted, mechanism-based management strategies that combine both pharmacologic and non-pharmacologic interventions.