| Summary: | Background: Deep brain stimulation (DBS) has been successfully used for the treatment of circuitopathies including movement, anxiety, and behavioral disorders. The hypothalamus is a crucial integration center for many peripheral and central pathways relating to cardiovascular, metabolic, and behavioral functions and constitutes a potential target for neuromodulation in treatment-refractory conditions. To conduct a systematic review, investigating hypothalamic targets in DBS, their indications, and the primary clinical findings. Methods: PubMed, Scopus, and Web of Science databases were searched in accordance with the PRISMA guideline to identify papers published in English studying DBS of the hypothalamus in humans. Results: After screening 3,148 papers, 34 studies consisting of 412 patients published over two decades were included in the final review. Hypothalamic DBS was indicated in refractory headaches (n = 238, 57.8%), aggressive behavior (n = 100, 24.3%), mild Alzheimer’s disease (n = 58, 14.1%), trigeminal neuralgia in multiple sclerosis (n = 5, 1.2%), Prader-Willi syndrome (n = 4, 0.97%), and atypical facial pain (n = 3, 0.73%). The posterior hypothalamus was the most common DBS target site across 30 studies (88.2%). 262 (63.6%) participants were males, and 110 (26.7%) were females. 303 (73.5%) patients were adults whereas 33 (8.0%) were pediatrics. The lowest mean age of participants was 15.25 ± 4.6 years for chronic refractory aggressiveness, and the highest was 68.5 ± 7.9 years in Alzheimer’s disease patients. The mean duration of the disease ranged from 2.2 ± 1.7 (mild Alzheimer’s disease) to 19.8 ± 10.1 years (refractory headaches). 213 (51.7%) patients across 29 studies (85.3%) reported symptom improvements which ranged from 23.1% to 100%. 25 (73.5%) studies reported complications, most of which were associated with higher voltage stimulations. Conclusions: DBS of the hypothalamus is feasible in selected patients with various refractory conditions ranging from headaches to aggression in both pediatric and adult populations. Future large-scale studies with long-term follow-up are required to validate the safety and efficacy data and extend these findings.
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