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Objective: The aim of this study was to provide long-term clinical results-including "sweet spot" identification and connectomic imaging analysis-in a series of patients treated with deep brain stimulation for refractory chronic cluster headache., Background: Deep brain stimulation is a relatively recent indication for the treatment of refractory chronic cluster headache. This indication has generated substantial debate in recent years due to uncertainty surrounding the mechanism of action and the lack of long-term efficacy data., Methods: Case retrospective series of adult patients diagnosed with refractory chronic cluster headache and treated with deep brain stimulation. Demographic and clinical data were registered preoperatively and at 3, 6, 12, and 24 months. The primary endpoint was reduction in headache load, a composite score of frequency, severity, and duration of each attack. Imaging analyses (sweet spot and connectomic analyses) were performed to identify the brain regions most closely correlated with the reduction in headache load and to identify the structural networks involved. Treatment response was categorized according to the reduction in headache load, as follows: poor (<30% reduction), partial (30-50%), or high (>50%)., Results: A total of 14 patients were included, with a mean (standard deviation [SD]) age of 42.4 (10.7) years and mean (SD) headache duration of 8.0 (5.8) years. Headache load scores decreased significantly from baseline to Month 24: mean (SD) 424.2 (325.9) versus 135.9 (155.7) (p = 0.001). In most patients (eight patients [58.0%]), headache load scores decreased by 50% after treatment. The other six patients showed either a partial (three [21.0%]) or poor (three [21.0%]) response. The optimized sweet spot was the lateral ventral tegmental area ((Montreal Neurological Institute) MNI coordinates of the center of mass: x = ± 9.0 mm, y = -10.6 mm, z = -3.5 mm). The connectomic analysis pointed to the probable implication of corticorubral tracts., Conclusion: These findings suggest that a substantial proportion of patients with refractory chronic cluster headache obtain significant long-term clinical benefits from deep brain stimulation. Good responders were characterized by a robust improvement in headache load within 3-6 months after surgery. The lateral ventral tegmental area was identified as the best target for this indication, with the likely participation of corticorubral tracts., (© 2024 American Headache Society.)