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Association of Clinical and Neuroanatomical Factors With Response to Ventral Tegmental Area DBS in Chronic Cluster Headache

Neurology. 2023 Oct 17:10.1212/WNL.0000000000207750. doi: 10.1212/WNL.0000000000207750. Online ahead of print.


BACKGROUND: Deep brain stimulation (DBS) of the ventral tegmental area (VTA) is a surgical treatment option for selected patients with refractory chronic cluster headache (CCH). We aimed to identify clinical and structural neuroimaging factors associated with response to VTA DBS in CCH.

METHODS: This prospective observational cohort study examines consecutive patients with refractory CCH treated with VTA DBS by a multidisciplinary team in a single tertiary neuroscience centre as part of usual care. Headache diaries and validated questionnaires were completed at baseline and regular follow up intervals. All patients underwent T1-weighted structural MRI prior to surgery. We compared clinical features using multivariable logistic regression, and neuroanatomical differences using voxel-based morphometry (VBM) between responders and non-responders.

RESULTS: Over a ten-year period, 43 patients (mean age 53 years, SD 11.9), including 29 males, with a mean duration of CCH 12 years (SD 7.4), were treated and followed up for at least one year (mean follow-up duration 5.6 years). Overall, there was a statistically significant improvement in median attack frequency from 140 to 56 per month (Z = -4.95, p <0.001), attack severity from 10/10 to 8/10 (Z = -4.83, p <0.001) and duration from 110 to 60 minutes (Z = -3.48, p <0.001). Twenty-nine (67.4%) patients experienced ≥50% improvement in attack frequency and were therefore classed as responders. There were no serious adverse events. The most common side effects were discomfort or pain around the battery site (seven patients) and transient diplopia and/or oscillopsia (six patients). There were no differences in demographics, headache characteristics, or comorbidities between responders and non-responders. VBM identified increased neural density in non-responders in several brain regions, including the orbitofrontal cortex, anterior cingulate cortex, anterior insula, and amygdala which were statistically significant (p <0.001).

DISCUSSION: VTA DBS showed no serious adverse events, and, although there was no placebo control, was effective in approximately two-thirds of patients at long-term follow up. This study did not reveal any reliable clinical predictors of response. However, non-responders had increased neural density in brain regions linked to processing of pain and autonomic function, both of which are prominent in the pathophysiology of CCH.

PMID:37848331 | DOI:10.1212/WNL.0000000000207750

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