Ventral tegmental area deep brain stimulation for trigeminal autonomic cephalalgias: a comprehensive literature review

Trigeminal autonomic cephalalgias (TACs) - including chronic cluster headache (CCH), short-lasting unilateral neuralgiform headache attacks (SUNHA, encompassing SUNCT and SUNA), and paroxysmal hemicrania - are rare but severely disabling primary headache disorders. A systematic search of PubMed, Embase, and Cochrane (inception to December 2024) identified studies on deep brain stimulation (DBS) for TACs. A meaningful proportion of patients remain refractory to optimized pharmacotherapy, and neuromodulation has emerged as a promising avenue. The ventral tegmental area (VTA), a dopaminergic midbrain nucleus implicated in pain modulation and affective processing, has gained recognition as a DBS target. This review synthesizes the pathophysiological rationale for VTA-DBS, clinical efficacy outcomes, comparative insights against hypothalamic DBS, patient selection, laterality, long-term neuroplastic adaptations, implications for synucleinopathies, and future directions. Emerging evidence demonstrates that VTA-DBS significantly reduces headache frequency, severity, and duration in CCH and SUNHA, with approximately 60-67% of patients achieving a clinically meaningful response. Improvements in mood, anxiety, and quality of life are observed without cognitive impairment. Compared with hypothalamic DBS, VTA stimulation offers a broader therapeutic footprint and a more favorable safety profile. Most data derive from small observational studies; randomized controlled trials and multicentre registries are essential to consolidate VTA-DBS as a standardized treatment.