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There are several issues that remain unresolved in the understanding of the pathophysiology of the TACs, although activation of the trigeminal\u2013autonomic reflex and ipsilateral hypothalamic activation both play a central role. The discovery of the central role of the hypothalamus led to its use as a therapeutic target. After the good results obtained with hypothalamic stimulation, other peripheral neuromodulation targets were tried in the management of refractory cluster headache (CH) and other TACs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review is a summary both of CH pathophysiology and of efficacy of the different neuromodulation techniques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In chronic cluster headache (CCH) patients, hypothalamic deep brain stimulation (DBS) produced a decrease in attack frequency of more than 50% in 60% of patients. Occipital nerve stimulation (ONS) also elicited favorable outcomes with a reduction of more than 50% of attacks in around 70% of patients with medically intractable CCH. Stimulation of the sphenopalatine ganglion (SPG) with a miniaturized implanted stimulator produced a clinically significant improvement in 68% of patients (acute, preventive, or both). Vagus nerve stimulation (VNS) with a portable device used in conjunction with standard of care in CH patients resulted in a reduction in the number of attacks. DBS and ONS have been used successfully in some cases of other TACs, including hemicrania continua (HC) and short\u2010lasting unilateral headache attacks (SUNHA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DBS has good results, but it is a more invasive technique and can generate serious adverse events. ONS has good results, but frequent and not serious adverse events. SPG stimulation (SPGS) is also efficacious in the acute and prophylactic treatment of refractory cluster headache. At this moment, ONS and SPG stimulation techniques are recommended as first line therapy in refractory cluster patients. New recent non\u2010invasive approaches such as the non\u2010invasive vagal nerve stimulator (nVNS) have shown efficacy in a few trials and could be an interesting alternative in the management of CH, but require more testing and positive randomized controlled trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.12874","type":"journal-article","created":{"date-parts":[[2016,8,4]],"date-time":"2016-08-04T01:56:29Z","timestamp":1470275789000},"page":"327-335","source":"Crossref","is-referenced-by-count":41,"title":["Cluster headache and other TACs: Pathophysiology and neurostimulation options"],"prefix":"10.1111","volume":"57","author":[{"given":"Miguel JA","family":"L\u00e1inez","sequence":"first","affiliation":[{"name":"Department of Neurology Hospital Cl\u00ednico Universitario de Valencia Valencia Spain"},{"name":"Department of Neurology Universidad Cat\u00f3lica de Valencia  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edelmira","family":"Guillam\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Cl\u00ednico Universitario de Valencia Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12213"},{"key":"e_1_2_13_3_1","unstructured":"Headache Classification Committee of the International Headache Society 2013 Cephalalgia 629 808"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-013-1365-1"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.1983.0301021.x"},{"key":"e_1_2_13_6_1","first-page":"783","volume-title":"The Headaches","author":"Waldenlind E","year":"1999"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000362517"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(02)00104-7"},{"key":"e_1_2_13_9_1","first-page":"27","article-title":"Chronic paroxysmal hemicrania (CPH). 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