Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension

Abstract

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity,sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions.During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation(weekly frequency of attacks decrease [50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).

Fig. 1

Design of the study. The randomized phase of the study included two 1-month treatment periods (week 8 to week 12 and week 13 to week 17) separated by a 1-week washout period. Patients were evaluated at inclusion, 1 week before surgery; 4 weeks after surgery (before active or sham stimulation) and at the end of the first randomization period (weeks 12 and 17). This randomized phase was followed by a 10-month open phase. Patients were evaluated at the end of this phase (week 52)

Fig. 2

Postoperative tridimensional MRI (patient C1P4), T1 weighted images after gadolinium injection, axial (a) and saggital (b) slices, showing the location of the stimulating contact (white circle) within the black artifact generated by the electrode. Dotted line indicates the projection of the electrode trajectory on the slice

Fig. 3

Individual changes in weekly attack frequency in the 11 patients between baseline (before surgery) and the end of the open phase