Occipital nerve stimulation in primary headache syndromes

Introduction Chronic cluster headache is rare and some of these patients become drug-resistant. Occipital nerve stimulation has been successfully employed in open studies to treat chronic drug-resistant cluster headache. Data from large group of occipital nerve stimulation-treated chronic cluster headache patients with long duration follow-up are advantageous. Patients and methods Efficacy of occipital nerve stimulation has been evaluated in an experimental monocentric open-label study including 35 chronic drug-resistant cluster headache patients (mean age 42 years; 30 men; mean illness duration: 6.7 years). The primary end-point was a reduction in number of daily attacks. Results After a median follow-up of 6.1 years (range 1.6-10.7), 20 (66.7%) patients were responders (≥50% reduction in headache number per day): 12 (40%) responders showed a stable condition characterized by sporadic attacks, five responders had a 60-80% reduction in headache number per day and in the remaining three responders chronic cluster headache was transformed in episodic cluster headache. Ten (33.3%) patients were non-responders; half of these have been responders for a long period (mean 14.6 months; range 2-48 months). Battery depletion (21 patients 70%) and electrode migration (six patients - 20%) were the most frequent adverse events. Conclusions Occipital nerve stimulation efficacy is confirmed in chronic drug-resistant cluster headaches even after an exceptional long-term follow-up. Tolerance can occur years after improvement.

Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study

Introduction: Chronic cluster headache (CCH) is a severely disabling form of trigeminal autonomic cephalalgia, often refractory to pharmacological treatment. In recent years, peripheral neuromodulation through occipital (ONS) and supraorbital (SON) nerve stimulation has emerged as a promising alternative for selected drug-resistant patients.Method: To describe the clinical outcomes of patients with refractory cluster headache treated with occipital nerve stimulation (ONS), and to evaluate the potential benefits of combining supraorbital nerve stimulation (SONS) in selected cases.Discussion: These findings are consistent with previous reports supporting the efficacy of peripheral neuromodulation for refractory CCH. The high responder rate and absence of adverse events reinforce the role of ONS and SON as safe and effective options in carefully selected cases. Despite the limited sample size, the sustained improvement observed justifies further investigation into optimization parameters and predictors of response.Conclusions: Occipital and supraorbital nerve stimulation proved to be a safe and effective treatment for refractory chronic cluster headache, resulting in a significant reduction in attack frequency and high patient adherence.

Chronic headache represents a very significant public health and economic issue. One treatment modality for chronic refractory headache involves the use of subcutaneous implanted neurostimulator leads in the occipital region. Varied types of headache etiologies including migraine, transformed migraine, chronic daily headache, cluster headache, hemicrania continua, occipital neuralgia, and cervicogenic headache have been studied with peripheral nerve field stimulation and found responsive to stimulation of the suboccipital region, known commonly as occipital nerve stimulation (ONS). To evaluate the strength of evidence that occipital nerve stimulation is an effective treatment of benign headache. A systematic review of occipital nerve stimulation for the treatment of chronic headache. A systematic review of the literature through EMBASE and PubMed/Medline for clinical studies was performed. The Agency for Healthcare Research and Quality (AHRQ) criteria was utilized to assess the evidence regarding occipital nerve stimulators and arrives at conclusions as to their efficacy in the treatment of headache. Studies were also graded using AHRQ criteria. The overall body of evidence was then graded on a 5 level scale from Level I (conclusive), Level II (strong), Level III (moderate), Level IV (limited) to Level V (indeterminate). Ten observational studies, of which 4 were prospective, and a number of case series, case reports, and reviews were identified. No randomized controlled trials (RCT) were identified. All of the articles reported positive outcomes including improved pain relief, reduced frequency, intensity, and duration of headaches with reduced medication consumption. ONS was reportedly successful for 70 - 100% of patients. Reduction of pain in patients with occipital headaches and transformed migraine is significant and rapid; for cluster patients the improvement may be less dramatic and it may take several months of occipital stimulation to achieve relief. No long-term adverse events occurred. Several short-term incidents occurred including infection, lead displacement, and battery depletion. The body of evidence as a whole is a level of strength of IV, limited. ONS is a useful tool in the treatment of chronic severe headaches with at least Level IV (limited) evidence based on multiple positive studies.

Background: Chronic cluster headache is a severely disabling neurological disorder. Evidence from open-label case series suggest that occipital nerve stimulation may be effective for the treatment of chronic cluster headache. Objective: To evaluate the effectiveness of a microstimulator for chronic cluster headache. Study Design: Prospective, observational feasibility study plus medical record review. Settings: Academic medical center. Methods: Four patients with medically refractory chronic cluster headache underwent implantation of a unilateral bion microstimulator. In-person follow-up was conducted for 12 months after implantation, and a prospective follow-up chart review was carried out to assess long term outcome. Results: Three of the participants returned their headache diaries for evaluation. The mean duration of chronic cluster headache was 14.3 years (range 3 to 29 years). Pain was predominantly or exclusively retroocular/periocular. One participant demonstrated a positive response (> 50% reduction in cluster headache frequency) at 3 months postimplant, while there were 2 responders at 6 months. At least one of the participants continued to show > 60% reduction in headache frequency at 12 months. A chart review showed that at 58-67 months post-implant, all 3 participants reported continued use and benefit from stimulation. No side-shift in attacks was noted in any participant. Adverse events were limited to 2 participants with neck pain and/or cramping with stimulation at high amplitudes; one required revision for a faulty battery. Limitations: Small patient population without control group. Not blinded or randomized. Conclusion: Unilateral occipital nerve stimulation, using a minimally invasive microstimulator, may be effective for the treatment of medically refractory chronic cluster headache. This benefit may occur immediately after implantation, remain sustained up to 5 years after implantation, and occur despite the anterior location of the pain. Prospective, randomized controlled trials of occipital nerve stimulation in chronic cluster headache should proceed. Key words: chronic headache, bion, peripheral nerve stimulation, cluster headache, migraine, occipital

Cluster headache is a primary headache involving repeated attacks of excruciatingly severe headache usually occurring several times a day. Most patients with chronic cluster headache (CCH) have an unremitting illness requiring daily preventive therapy for years. To describe the clinical outcome of occipital nerve stimulation (ONS) for 14 patients with intractable CCH. Fourteen patients with medically intractable CCH were implanted with bilateral electrodes in the suboccipital region for ONS and a retrospective assessment of their clinical outcome obtained. At a median follow-up of 17.5 months (range 4-35 months), 10 of 14 patients reported improvement and 9 of these recommend ONS. Three patients noticed a marked improvement of 90% or better (90%, 90%, and 95%), 3 a moderate improvement of 40% or better (40%, 50%, and 60%), and 4 a mild improvement of 20-30% (20%, 20%, 25%, and 30%). Improvement occurred within days to weeks for those who responded most and patients consistently reported their attacks returned within hours to days when the device was off. One patient found that ONS helped abort acute attacks. Adverse events of concern were lead migrations and battery depletion. Intractable chronic cluster headache (CCH) is a devastating, disabling condition that has traditionally been treated with cranially invasive or neurally destructive procedures. ONS offers a safe, effective option for some patients with CCH. More work is required to evaluate and understand this novel therapy.

Chronic cluster headache is a rare, highly disabling primary headache condition. When medically intractable, occipital nerve stimulation can offer effective treatment. Open-label series have provided data on small cohorts only. We analyzed 51 subjects to evaluate the long-term outcomes of highly intractable chronic cluster headache with occipital nerve stimulation. Patients with intractable chronic cluster headache were implanted with occipital nerve stimulators during the period 2007-2014. The primary endpoint was improvement in daily attack frequency. Secondary endpoints included attack severity, attack duration, quality-of-life measures, headache disability scores and adverse events. We studied 51 patients [35 males; mean age at implant 47.78 (range 31-70) years; mean follow-up 39.17 (range 2-81) months]. Nineteen patients had other chronic headache types in addition in chronic cluster headache. At final follow-up, there was a 46.1% improvement in attack frequency (P < 0001) across all patients, 49.5% (P < 0.001) in those with cluster headache alone and 40.3% (P = 0.036) in those with multiple phenotypes. There were no significant differences in response in those with or without multiple headache types. The overall response rate (defined as at least a 50% improvement in attack frequency) was 52.9%. Significant reductions were also seen in attack duration and severity. Improvements were noted in headache disability scores and quality-of-life measures. Triptan use of responders dropped by 62.56%, resulting in significant cost savings. Adverse event rates were highly favorable. Occipital nerve stimulation appears to be a safe and efficacious treatment for highly intractable chronic cluster headache even after a mean follow-up of over 3 years.

Our aim was to assess the effectiveness and complication rate of occipital nerve stimulation (ONS) using a recently developed anchoring lead dedicated to ONS in patients treated for refractory chronic cluster headache (rCCH). Patients with rCCH were included in a prospective multicenter ONS registry from 2019 to 2024 and treated by ONS using anchored ONS-dedicated leads. The effectiveness of ONS was evaluated by the frequency of chronic cluster headache (CCH) attacks, abortive and preventive medication use, quality of life (EuroQol-5 Dimensions scale), and the functional (Headache Impact Test-6) and emotional (Hospital Anxiety and Depression Scale) impacts. Complications were monitored, focusing on electrode migration, device malfunction, infections, and local pain. Overall, 40 (16 women, mean age 46 years) and 24 patients were followed for one and two years after ONS, respectively. The mean weekly attack frequency significantly decreased, from 24.3 before ONS to 12.7 (p = 0.006) at one year and to 11.7 (p = 0.002) at two years. Functional and emotional impacts and quality of life significantly improved. During the follow-up period, 16 patients experienced device-related complications, including infection (7.5%), lead migration (5%), hardware dysfunction (15%), and pain at the lead insertion site (12.5%). ONS using ONS-dedicated leads showed similar effectiveness, while also presenting a low risk of migration, to ONS using other leads reported in previous studies. The Clinicaltrials.gov registration number for the study is NCT01842763.

Occipital nerve stimulation has shown promising results in attack prevention in patients with chronic cluster headache, but evidence from controlled trials is scarce. Conventional (tonic) occipital nerve stimulation elicits paresthesia, hampering blinded comparison to placebo. Using paresthesia-free burst occipital nerve stimulation, we conducted a randomized, placebo-controlled trial. The study is an investigator-initiated, double-blind, randomized, placebo-controlled clinical trial involving participants with chronic cluster headache. It comprised a four-week baseline, a 12-week trial with transcutaneous electrical nerve stimulation, occipital nerve stimulator implantation, a 12-week randomized, double-blind burst occipital nerve stimulation treatment period, and a 12-week open-label tonic occipital nerve stimulation treatment period. The primary outcomes were safety and the proportion of participants reporting a ≥30% reduction in attack frequency in the randomized and open-label trial phases. Participants were enrolled between August 2021 and October 2023. 116 chronic cluster headache patients were assessed for eligibility. Sixty-five were excluded, and 51 entered baseline observation. Before occipital nerve stimulator implantation and randomization, an additional 13 were excluded. Thirty-eight participants underwent occipital nerve stimulator implantation and were randomly assigned to burst occipital nerve stimulation (n = 19) or placebo (n = 19). After the randomized trial phase, the proportion of ≥30% responders was 18.81% (95%CI 0.28%–37.87%) in the burst occipital nerve stimulation group and 50.02% (95%CI 26.87%–73.09%) in the placebo group. The likelihood of reaching the primary endpoint was 31.20% (95%CI 1.29%–61.23%, p = 0.042) higher in the placebo group. After the open-label phase, 42.09% (95%CI 19.91%–64.34%) in the burst occipital nerve stimulation group and 51.11% (95%CI 27.32%–74.88%) in the placebo group had ≥30% frequency reduction. In total, 20 adverse events were registered; eight were treatment-related serious adverse events. The most common adverse event was temporary occipital dysesthesia in eight participants. Occipital nerve stimulation reduced attack frequency but was not superior to placebo. The treatment had an acceptable safety profile and was well-tolerated. The results call for attention to sufficient placebo control when planning further studies. The trial is registered at clinicaltrials.gov (identifier NCT05023460).Study registration date: July 27th 2021.

Chronic cluster headache (CCH) is a rare but severely debilitating primary headache condition. A growing amount of evidence suggests that occipital nerve stimulation (ONS) can offer effective treatment in patients with severe CCH for whom conventional medical therapy does not have a sufficient effect. The paresthesia evoked by conventional (tonic) stimulation can be bothersome and may thus limit therapy. Burst ONS produces paresthesia-free stimulation, but the amount of evidence on the efficacy of burst ONS as a treatment for intractable CCH is scarce. In this case series, we report 15 patients with CCH treated with ONS at Aarhus University Hospital, Denmark, from 2013 to 2020. Nine of these received burst stimulation either as primary treatment or as a supplement to tonic stimulation. The results were assessed in terms of the frequency of headache attacks per week and their intensity on the Numeric Rating Scale, as well as the Patient Global Impression of Change (PGIC) with ONS treatment. At a median (range) follow-up of 38 (16-96) months, 12 of the 15 patients (80%) reported a reduction in attack frequency of ≥50% (a reduction from a median of 35 to 1 attack/week, p < 0.001). Seven of these patients were treated with burst ONS. A significant reduction was also seen in maximum pain intensity. Overall, 10 patients stated a clinically important improvement in their headache condition following ONS treatment, rated on the PGIC scale. A total of 16 adverse events (nine of which were in the same patient) were registered. Occipital nerve stimulation significantly reduced the number of weekly headache attacks and their intensity. Burst ONS seems to function well alone or as a supplement to conventional tonic ONS as a preventive treatment for CCH; however, larger prospective studies are needed to determine whether the effect can be confirmed and whether the efficacy of the two stimulation paradigms is even.

BackgroundChronic cluster headache (CCH) is a debilitating primary headache disorder. Occipital nerve stimulation (ONS) has shown the potential to reduce attack frequency, but the occipital paresthesia evoked by conventional (tonic) stimulation challenges a blinded comparison of active stimulation and placebo. Burst ONS offers paresthesia-free stimulation, enabling a blinded, placebo-controlled study.Identification of a feasible preoperative test would help select the best candidates for implantation.This study aims to explore ONS as a preventive treatment for CCH, comparing burst stimulation to tonic stimulation and placebo, and possibly identifying a potential preoperative predictor.MethodsAn investigator-initiated, double-blinded, randomized, placebo-controlled trial is conducted, including 40 patients with CCH. Eligible patients complete a trial with the following elements: I) four weeks of baseline observation, II) 12 weeks of transcutaneous electrical nerve stimulation (TENS) of the occipital nerves, III) implantation of a full ONS system followed by 2 week grace period, IV) 12 weeks of blinded trial with 1:1 randomization to either placebo (deactivated ONS system) or burst (paresthesia-free) stimulation, and V) 12 weeks of tonic stimulation.The primary outcomes are the reduction in headache attack frequency with TENS and ONS and treatment safety. Secondary outcomes are treatment efficacy of burst versus tonic ONS, the feasibility of TENS as a predictor for ONS outcome, reduction in headache pain intensity (numeric rating scale), reduction in background headache, the patient’s impression of change (PGIC), health-related quality of life (EuroQoL-5D), self-reported sleep quality, and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale, HADS).Data on headache attack characteristics are registered weekly. Data on patient-reported outcomes are assessed after each trial phase.DiscussionThe study design allows a comparison between burst ONS and placebo in refractory CCH and enables a comparison of the efficacy of burst and tonic ONS. It will provide information about the effect of burst ONS and explore whether the addition of this stimulation paradigm may improve stimulation protocols.TENS is evaluated as a feasible preoperative screening tool for ONS outcomes by comparing the effect of attack prevention of TENS and tonic ONS.Trial registrationThe study is registered at Clinicaltrials.gov (trial registration number NCT05023460, registration date 07–27-2023).

Neuromodulation has been recognized as a valuable surgical treatment option for patients with refractory chronic cluster headache (CCH). Due to the small number of afflicted individuals, the knowledge about this specific therapy is limited. In this study, we present our experiences with bilateral occipital nerve stimulation (ONS) in patients with CCH focusing on patient selection, pre- and postoperative evaluation, surgical procedures, and outcome. Since December 2008, 10 patients with CCH have been treated with ONS at our department. Patients were recruited and clinically followed by a neurologist and a neurosurgeon. Baseline data records on frequency, intensity, and duration of attacks as well as the use of medication were assessed with a 30-day diary. Standardized questionnaires were used pre- and postoperatively and during the follow-up on a regular basis. Surgical procedure and stimulation parameters were standardized for all patients. Lead implantation was followed by a test period of 30 days prior to implantation of the permanent generator. Mean follow-up time was 12 months (range 3-18). All patients responded to the stimulation treatment. Frequency, duration, and severity of the cluster attacks were reduced in 90% of the patients. One patient had a significant reduction of his concomitant tension headache. 70 % of the patients needed less medication during the attacks. All patients reported an improvement in their quality of life. The SF-36 showed a tendency toward objective improvement in the field of psychological comfort. As a major adverse event, one generator had to be exchanged due to a local infection. Another patient had to be reoperated due to a scar tissue formation around the thoracic connector. ONS is a valuable tool in the treatment of patients with refractory CCH. According to our data, the potential side effects and complication rates of the operation are small. With a meticulous selection of patients by an interdisciplinary team, CCH can bed improve in the majority of the patients. Yet, the optimal parameters for the stimulation regarding pulse width and frequency remain unclear. For this reason, we started a prospective single-center observational trial at our center in October 2009, including patients with ONS, to identify the best stimulation parameters.

Chronic refractory migraine is estimated to affect 1.3 – 5.1% of the global population (1) Once medical therapies and other conservative have been exhausted, patients with migraine often have little choice but to self-manage their symptoms. (2) Neuromodulation is a possible treatment that can improve their lives and reduce their medications. Occipital Nerve Stimulation has been used in various primary headache syndromes with positive results. (3,4, 5)

Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH.

About 10% of cluster headache patients have the chronic form. At least 10% of this chronic group is intractable to or cannot tolerate medical treatment. Open pilot studies suggest that occipital nerve stimulation (ONS) might offer effective prevention in these patients. Controlled neuromodulation studies in treatments inducing paraesthesias have a general problem in blinding. We have introduced a new design in pain neuromodulation by which we think we can overcome this problem. We propose a prospective, randomised, double-blind, parallel-group international clinical study in medically intractable, chronic cluster headache patients of high- versus low-amplitude ONS. Primary outcome measure is the mean number of attacks over the last four weeks. After a study period of six months there is an open extension phase of six months. Alongside the randomised trial an economic evaluation study is performed. The ICON study will show if ONS is an effective preventive therapy for patients suffering medically intractable chronic cluster headache and if there is a difference between high- and low-amplitude stimulation. The innovative design of the study will, for the first time, assess efficacy of ONS in a blinded way.