Occipital nerve stimulation reduces the intensity of the persistent chronic cluster headache

According to research published in TheLancet Neurology, stimulating the occipital nerve at 100% and 30% intensity can significantly reduce the frequency of attack in patients with medically intractable chronic cluster headache.

Occipital nerve stimulation, a preventive treatment for medically untreatable chronic cluster headache, has shown promising results in previous small, uncontrolled studies. In the current study, the researchers tried to expand “the preventive treatment options” for this patient population. The researchers also hoped to determine how occipital nerve stimulation works and how it could be explored in future clinical research.

The current study (ClinicalTrials.gov identifier NCT01151631) was an international, multicenter, randomized, double-blind, electrically dose-controlled phase 3 clinical study initiated by investigators that comprised 4 study periods: a 12-week period for the initial observation, a run-in phase with Implant implantation and 10-day 10% occipital nerve stimulation and a 24-week randomized, double-blind treatment phase with a gradual increase in treatment intensity.

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Adult participants with at least 4 medically untreatable chronic cluster headaches per week were admitted to 7 hospitals in the Netherlands, Belgium, Germany and Hungary. After the baseline period, participants were randomly assigned in a 1: 1 ratio to either 100% or 30% of the individually accepted stimulation dose of the occipital nerve.

The primary study result was the mean frequency of attacks per week in the last 4 weeks of the masked study period, in weeks 21 to 24 after the run-in phase. Secondary endpoints included the mean attack frequency for each 4-week period, the weekly mean attack intensity, the proportion of participants with a greater than 50% reduction in the mean attack frequency in weeks 24 and 48 from baseline, and patient satisfaction in weeks 24 and 48, among other results.

The cohort consisted of 150 patients who were included between 2010 and 2017; After the 12-week baseline period, 131 patients were randomly assigned to a treatment group (100% group, n = 65; 30% group, n = 66). The majority of the patients (n = 122) came from Dutch centers. In each treatment group, 1 participant was lost to follow-up.

At baseline, the weekly mean attack frequencies were skewed, with some participants reporting a high frequency of attacks. For most, however, the individual mean attack frequencies remained stable over the entire observation period of the baseline.

After the start of treatment, the median mean weekly attack frequency was 7.38 (interquartile range) [IQR], 2.50-18.50), which corresponds to a median decrease of -5.21 (IQR, 11.18 to -0.19). In the 100% group, the median decrease was -4.08 (IQR, -11.92 to -0.25), while the median decrease was -6.50 (IQR, -10.83 to -0.08) in of the 30% group. No difference in decrease was found between weeks 21 and 24 from baseline (-2.42; 95% CI, -5.17 to 3.33).

During the first 4 weeks of treatment, the median weekly mean attack frequency was “already reduced” in the entire study population, according to the researchers. The median relative change in the total study population between weeks 21 and 24 was -42.56% (IQR, -80.05 to -1.80); median changes of -41.06 and -46.00 were recorded in the 100% and 30% groups, respectively.

During the open label phase, the median weekly mean attack frequency “did not increase much” and no significant differences between study centers were reported. About half of the study population experienced a reduction in the mean frequency of attacks by at least 50% between weeks 21 to 24 and 45 to 48.

A total of 7 participants were seizure-free in weeks 1 to 4, 9 were seizure-free in weeks 21 to 24, and 16 were seizure-free in weeks 45 to 48.

At the beginning of the study, the investigators found that the average attack intensities were “very stable” for most of the participants over 12 weeks. In the general population, the weekly mean attack intensity decreased over the study period with similar results in both groups.

At week 24, approximately 91% of participants said they would recommend occipital nerve stimulation to other patients, and 74% of them were willing to “strongly recommend” the treatment. Only 5% of the participants would not recommend it and 5% had a neutral opinion.

At week 48, 97% of participants were ready to recommend occipital nerve stimulation, with 73% strongly recommending treatment.

Overall, the mean summary physical health score increased from 52 to 58 between baseline and week 24, with a further increase to 62 after 48 weeks. The average summary mental health scores also increased from 50 to 58 to 61 at the same time. The results were similar between the groups.

The researchers registered 59 serious adverse events in 46 participants. Of these events, 35 Serious Adverse Events, occurring in 31 participants, were hardware related, including replacement of empty implantable pulse generators (IPGs) or lead or lead dislodgement, failure, or breakage. The most serious adverse event occurred in a patient with multiple vascular risk factors; this patient suffered a transient ischemic attack of the right middle cerebral artery 1 month and 15 days after implantation. However, it was determined that this event was unrelated to the procedure or the device.

Limitations of the study include a long patient admission period due to reimbursement issues, the use of evidence to determine efficacy, and lowering pre-determined treatment intensities in 20 patients in the 100% treatment group due to patient complaints.

“Although the results of our study showed no difference in response to treatment between the different groups, there is evidence that [occipital nerve stimulation] is an effective, well tolerated and safe therapy of last choice for [medically intractable chronic cluster headaches], even at electrical doses lower than what is currently recommended in the field of neurostimulation, ”the researchers write.

Disclosure: This clinical study was sponsored by Medtronic. For a full list of the author’s disclosures, see the original reference.

reference

Wilbrink LA, de Coo IF, Doesborg PGG, et al .; for the ICON study group. Safety and efficacy of occipital nerve stimulation for attack prevention in medically untreatable chronic cluster headache (ICON): a randomized, double-blind, multicenter phase 3 study with electrical dose control. Lancet Neurol. 2021; 20 (7): 515-525. doi: 10.1016 / S1474-4422 (21) 00101-0

This article originally appeared on Clinical Pain Advisor