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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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>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 (<jats:italic>n<\/jats:italic>\u2009=\u2009238, 57.8%), aggressive behavior (<jats:italic>n<\/jats:italic>\u2009=\u2009100, 24.3%), mild Alzheimer\u2019s disease (<jats:italic>n<\/jats:italic>\u2009=\u200958, 14.1%), trigeminal neuralgia in multiple sclerosis (<jats:italic>n<\/jats:italic>\u2009=\u20095, 1.2%), Prader-Willi syndrome (<jats:italic>n<\/jats:italic>\u2009=\u20094, 0.97%), and atypical facial pain (<jats:italic>n<\/jats:italic>\u2009=\u20093, 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\u2009\u00b1\u20094.6 years for chronic refractory aggressiveness, and the highest was 68.5\u2009\u00b1\u20097.9\u00a0years in Alzheimer\u2019s disease patients. The mean duration of the disease ranged from 2.2\u2009\u00b1\u20091.7 (mild Alzheimer\u2019s disease) to 19.8\u2009\u00b1\u200910.1\u00a0years (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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00701-025-06430-w","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T21:38:26Z","timestamp":1738705106000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Deep brain stimulation of the hypothalamic region: a systematic review"],"prefix":"10.1007","volume":"167","author":[{"given":"Mohammad","family":"Mofatteh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulkadir","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Sadegh","family":"Mashayekhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios P.","family":"Skandalakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Neudorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Arfaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ArunSundar","family":"MohanaSundaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadmahdi","family":"Sabahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayush","family":"Anand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabii","family":"Aboulhosn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuxing","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyoumars","family":"Ashkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"6430_CR1","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1227\/neu.0000000000002752","volume":"94","author":"AK Ahmed","year":"2024","unstructured":"Ahmed AK, Zhuo J, Gullapalli RP, Jiang L, Keaser ML, Greenspan JD, Chen C, Miller TR, Melhem ER, Sansur CA, Eisenberg HM, Gandhi D (2024) Focused Ultrasound Central Lateral Thalamotomy for the Treatment of Refractory Neuropathic Pain: Phase I Trial. 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