A recent study published in "Lancet Neurology," involving the Kiel Pain Clinic, shows that occipital nerve stimulation (ONS) is a promising treatment alternative for patients with drug-resistant chronic cluster headaches. In half of the patients, the frequency of attacks was reduced by at least 50% with this electrical stimulation, which is similar to a pacemaker. Almost all participants in the study would recommend ONS to other sufferers, with approximately three-quarters of them recommending it strongly.
Cluster headache is the most common type of trigeminal autonomic cephalalgia. The severe pain attacks usually affect the same side of the face in the area of the trigeminal nerve in the temporal region or around the eye. Approximately 75% of those affected are men. Due to its high intensity, the pain significantly impairs the quality of life of those affected. Inhalation of pure oxygen and subcutaneous administration of sumatriptan have become established as acute therapies. For the prophylaxis of cluster headache attacks, guidelines recommend the use of verapamil. Lithium can also be used, although there are no randomized controlled trials on this. Corticosteroids are frequently used for short-term prophylaxis to bridge the time until prophylaxis such as verapamil takes effect. Their efficacy was recently scientifically demonstrated in a German study [2]. Another treatment option for therapy-resistant cluster headache, or "MICCH" ("medically intractable chronic cluster headache"), is occipital nerve stimulation (ONS). Similar to a pacemaker, a small electrical pulse generator is implanted under the skin, from which thin electrodes extend to the neck, towards the two occipital nerves. The stimulation triggers tingling or numbness in the stimulated area. The mechanism of action is thought to involve a modification of pain signals in the brainstem by the electrical signals. Previous studies on ONS were uncontrolled or open-label and small (ten patient populations with a total of 274 patients), the baseline data were very heterogeneous, and not all primary endpoints were available for all patients.
An international, multicenter phase III trial involving the Kiel Pain Clinic (centers in the Netherlands, Belgium, Germany, and Hungary) has now been published. This trial was the first to evaluate the clinical efficacy of ONS (Onset Consciousness) in a large, uniformly defined population using a randomized, double-blind, controlled trial (2010 to 2017). The patients were on average 44 ± 13 years old and had been suffering from headache attacks for an average of seven years. They experienced attacks at least four times per week and had not responded to (or were intolerant to/had contraindications for) at least three prophylactic medications (including verapamil, lithium, methysergide, topiramate, and gabapentin).
Initially, there was a 12-week observation phase, followed by 24 weeks of ONS (Onset Nerve Stimulation), randomized into two groups with either 100% or 30% stimulation intensity on a previously individually determined scale between the paresthesia threshold and the maximum tolerated current (double-blind phase; n=65 in the 100% ONS group and n=66 in the 30% ONS group). A double-blind comparison versus placebo (i.e., implantation but without stimulation) would not have been practical, as the stimulation is often recognized by the patients. Subsequently, from weeks 25 to 48, stimulation continued with individually optimized ONS doses (open-label phase). The primary endpoint was the weekly attack frequency (in weeks 21–24) compared to baseline frequencies. The current follow-up period is two years.
Overall, both stimulation protocols led to a rapid and sustained reduction in attack frequency by an average of 50%, and pain intensity decreased by one-third. The median weekly attack frequency at baseline was 15.75 (IQR 9.44–24.75) and decreased to 7.38 (IQR 2.5–18.5) by week 24: in the 100% group from a median of 17.58 (9.83–29.33) to 9.5 (3.0–21.25) and in the 30% group from 15.0 (9.25–22.33) to 6.75 (1.5–16.5). The median group difference in mean weekly attack frequency at the end of the masked phase (weeks 21–24) was -2.42 (-5.17–3.33). In the blinded study phase, 129 adverse events occurred in the 100% group and 95 in the 30% group. None of these events were unusual; 17/129 and 8/95 events, respectively, required brief hospitalization. Most commonly, these involved local pain, impaired wound healing, neck stiffness, and hardware problems. Overall, ONS was safe and well-tolerated. When asked, over 90% of participants in both groups would recommend the therapy to other MICCH patients.
Professor Hartmut Göbel, head physician of the Kiel Pain Clinic and one of the scientists participating in the study, said: “The data offer severely affected individuals another treatment option for cluster headaches that are otherwise untreatable. Careful diagnosis and indication in specialized centers are essential. The results finally offer hope for patients who have not been able to receive adequate treatment until now.”
Sources
Press release from the German Society for Neurology
Leave a comment