• Harith Akram, Sarah Miller, Susie Lagrata, Marwan Hariz, John Ashburner, Tim Behrens, Manjit Matharu, and Ludvic Zrinzo.
• From the Unit of Functional Neurosurgery (H.A., M.H., L.Z.), Sobell Department of Motor Neuroscience and Movement Disorders, and Wellcome Trust Centre for Neuroimaging (J.A., T.B.), UCL Institute of Neurol... more ogy, University College London; Victor Horsley Department of Neurosurgery (H.A., L.Z.), National Hospital for Neurology and Neurosurgery; Headache Group (S.M., S.L., M.M.), UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK; Department of Clinical Neuroscience (M.H.), Umeå University, Sweden; and Centre for Functional MRI of the Brain (T.B.), John Radcliffe Hospital, Oxford, UK. Harith.akram.12@ucl.ac.uk. less
• Neurology. 2017 Nov 14; 89 (20): 2083-2091.

ObjectiveTo investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area.MethodsSeven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of ≥30% in headache load.ResultsThere was no surgical morbidity. Average follow-up was 34 ± 14 months. Patients showed reductions of 76 ± 33% in headache load, 46 ± 41% in attack severity, 58 ± 41% in headache frequency, and 51 ± 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas.ConclusionsWe identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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