Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache.

BACKGROUND: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. OBJECTIVE: To evaluate ONS long-term efficacy in rCCH. METHODS: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. RESULTS: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%). CONCLUSION: Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.

Neuromodulation techniques for acute and preventive migraine treatment: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Several neuromodulation methods exists for migraine treatment. The aim of the present study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) focusing on migraine treatment using neurostimulation methods. METHODS: We searched Medline and Embase up to July 1, 2020 for RCTs reporting acute or preventive treatment of migraine with either non-invasive or invasive neurostimulation methods. Two researchers independently assessed the eligibility of the retrieved studies and extracted data. Outcomes for the quantitative synthesis were 2 h pain free for acute treatment and headache days per month for preventive treatment. We performed subgroup analyses by treatment (stimulation method and site of application). Estimates were pooled using random-effects meta-analysis. RESULTS: Thirty-eight articles were included in the qualitative analysis (7 acute, 31 preventive) and 34 in the quantitative evaluation (6 acute, 28 preventive). Remote electrical neuromodulation (REN) was effective for acute treatment. Data were insufficient to draw conclusions for any other techniques (single studies). Invasive occipital nerve stimulation (ONS) was effective for migraine prevention, with a large effect size but considerable heterogeneity, whereas supra-orbital transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation (PENS), and high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) were effective, with small to medium effect sizes. Vagus-nerve stimulation, left prefrontal cortex rTMS, and cathodal transcranial direct current stimulation (tDCS) over the M1 had no significant effect and heterogeneity was high. CONCLUSION: Several neuromodulation methods are of potential interest for migraine management, but the quality of the evidence is very poor. Future large and well-conducted studies are needed and could improve on the present results.

QAPSA: post-marketing surveillance of capsaicin 8% patch for long-term use in patients with peripheral neuropathic pain in France.

OBJECTIVE: To describe the characteristics of patients treated with the capsaicin 8% patch, prescribing conditions, long-term effects of repeat treatment on pain intensity and perception, quality of life, and impact on concomitant medication. METHODS: A national, longitudinal, prospective, non-interventional, post-marketing open study was conducted in 50 French pain centers. Adult volunteer non-diabetic patients with peripheral neuropathic pain receiving capsaicin 8% patch treatment were consecutively enrolled. Treatment could be repeated over a 12-month period, with 6 months' follow-up after last application. RESULTS: A total of 684 patients (age: 53.0 ± 14.9 years, mean ± standard deviation; post-traumatic/surgical peripheral neuropathic pain: 76.3%; pain intensity: 6.2 ± 1.7; pain duration: 3.0 years, median) were treated with 1 to 5 patches at 3/4 month intervals; 70.3% were naive to capsaicin 8% patch treatment at inclusion. Six months after last application, treatment was considered as successful for 21.8% (95% confidence interval: 17.5%-26.7%) of patients by a stringent criterion combining improvement according to the patient's global impression of change (PGIC) and at least 30% improvement on a numerical pain rating scale (NPRS). Clinically relevant improvement in health-related quality of life was observed at end-of-study. No unexpected safety concerns were observed with capsaicin 8% patch repeat treatment. CONCLUSIONS: The data of this post-marketing study meets the request by the French authorities for additional data on conditions of use in everyday practice. They confirmed the tolerance and long-term effect of capsaicin 8% patch in patients with peripheral neuropathic pain in real-world conditions.

Peripheral Nerve Stimulation of Brachial Plexus Nerve Roots and Supra-Scapular Nerve for Chronic Refractory Neuropathic Pain of the Upper Limb.

OBJECTIVES: We report the outcome of a consecutive series of 26 patients suffering from chronic medically-refractory neuropathic pain of the upper limb (including 16 patients with complex regional pain syndrome), topographically limited, treated by brachial plexus (BP) nerve roots or supra-scapular nerve (SSN) peripheral nerve stimulation (PNS). MATERIALS AND METHODS: The technique consisted in ultrasound-guided percutaneous implantation of a cylindrical lead (Pisces-Quad, Medtronic) close to the SSN or the cervical nerve roots within the BP, depending on the pain topography. All the patients underwent a positive trial stimulation before lead connection to a subcutaneous stimulator. Chronic bipolar stimulation mean parameters were: frequency 55.5 Hertz, voltage 1.17 Volts. The voltage was set below the threshold inducing muscle contractions or paresthesias. RESULTS: Two patients were lost immediately after surgery. At last follow-up (mean 27.5 months), the 20 patients still using the stimulation experienced a mean pain relief of 67.1%. Seventeen patients were improved ≥50%, including 12 improved ≥70%. In 11 patients with a follow-up >2 years, the mean pain relief was 68%. At last follow-up, respectively, six out of the nine (67%) patients treated by SSN stimulation and 10 out of 17 patients (59%) treated by BP stimulation were improved ≥50%. At last follow-up, 12 out of 20 patients still using the stimulation were very satisfied, six were satisfied, and two were poorly satisfied. Complications were: stimulation intolerance due to shock-like sensations (three cases), superficial infection (1), lead fractures (2), and migration (1). CONCLUSION: In this pilot study, SSN or BP roots PNS provided a relatively safe, durable and effective option to control upper limb neuropathic pain.

Occipital nerve stimulation improves the quality of life in medically-intractable chronic cluster headache: Results of an observational prospective study.

Background Occipital nerve stimulation (ONS) has been proposed to treat chronic medically-intractable cluster headache (iCCH) in small series of cases without evaluation of its functional and emotional impacts. Methods We report the multidimensional outcome of a large observational study of iCCH patients, treated by ONS within a nationwide multidisciplinary network ( https://clinicaltrials.gov NCT01842763), with a one-year follow-up. Prospective evaluation was performed before surgery, then three and 12 months after. Results One year after ONS, the attack frequency per week was decreased >30% in 64% and >50% in 59% of the 44 patients. Mean (Standard Deviation) weekly attack frequency decreased from 21.5 (16.3) to 10.7 (13.8) ( p = 0.0002). About 70% of the patients responded to ONS, 47.8% being excellent responders. Prophylactic treatments could be decreased in 40% of patients. Functional (HIT-6 and MIDAS scales) and emotional (HAD scale) impacts were significantly improved, as well as the health-related quality of life (EQ-5D). The mean (SD) EQ-5D visual analogic scale score increased from 35.2 (23.6) to 51.9 (25.7) ( p = 0.0037). Surgical minor complications were observed in 33% of the patients. Conclusion ONS significantly reduced the attack frequency per week, as well as the functional and emotional headache impacts in iCCH patients, and dramatically improved the health-related quality of life of responders.

Neuromodulation in cluster headache.

Medically refractory chronic cluster headache (CH) is a severely disabling headache condition for which several surgical procedures have been proposed as a prophylactic treatment. None of them have been evaluated in controlled conditions, only open studies and case series being available. Destructive procedures (radiofrequency lesioning, radiosurgery, section) and microvascular decompression of the trigeminal nerve or the sphenopalatine ganglion (SPG) have induced short-term improvement which did not maintain on long term in most of the patients. They carried a high risk of complications, including severe sensory loss and neuropathic pain, and consequently should not be proposed in first intention.Deep brain stimulation (DBS), targeting the presumed CH generator in the retro-hypothalamic region or fibers connecting it, decreased the attack frequency >50 in 60 % of the 52 patients reported. Complications were infrequent: gaze disturbances, autonomic disturbances, and intracranial hemorrhage (2).Occipital nerve stimulation (ONS) was efficient (decrease of attack frequency >50 %) in about 70 % of the 60 patients reported, with a low risk of complications (essentially hardware related). Considering their respective risks, ONS should be proposed first and DBS only in case of ONS failure.New on-demand chronically implanted SPG stimulation seemed to be efficient to abort CH attacks in a pilot controlled trial, but its long-term safety needs to be further studied.

Salvage treatment of trigeminal neuralgia by occipital nerve stimulation.

BACKGROUND: Although most patients suffering from trigeminal neuralgia (TN) respond to medical or surgical treatment, nonresponders remain in very severe painful condition. CASE RESULT: We describe for the first time a case of severe refractory classical TN treated successfully (follow-up one year) by chronic bilateral occipital nerve stimulation (ONS), because other classic medical and surgical options failed or could not be performed. CONCLUSIONS: This single case suggests that ONS might be offered to TN patients refractory both to standard drugs and interventions, with a favorable risk/benefit ratio, although its long-term efficacy remains unknown.

Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study.

BACKGROUND: The pain and autonomic symptoms of cluster headache (CH) result from activation of the trigeminal parasympathetic reflex, mediated through the sphenopalatine ganglion (SPG). We investigated the safety and efficacy of on-demand SPG stimulation for chronic CH (CCH). METHODS: A multicenter, multiple CH attack study of an implantable on-demand SPG neurostimulator was conducted in patients suffering from refractory CCH. Each CH attack was randomly treated with full, sub-perception, or sham stimulation. Pain relief at 15 minutes following SPG stimulation and device- or procedure-related serious adverse events (SAEs) were evaluated. FINDINGS: Thirty-two patients were enrolled and 28 completed the randomized experimental period. Pain relief was achieved in 67.1% of full stimulation-treated attacks compared to 7.4% of sham-treated and 7.3% of sub-perception-treated attacks ( P < 0.0001). Nineteen of 28 (68%) patients experienced a clinically significant improvement: seven (25%) achieved pain relief in ≥50% of treated attacks, 10 (36%), a ≥50% reduction in attack frequency, and two (7%), both. Five SAEs occurred and most patients (81%) experienced transient, mild/moderate loss of sensation within distinct maxillary nerve regions; 65% of events resolved within three months. INTERPRETATION: On-demand SPG stimulation using the ATI Neurostimulation System is an effective novel therapy for CCH sufferers, with dual beneficial effects, acute pain relief and observed attack prevention, and has an acceptable safety profile compared to similar surgical procedures.

Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation.

BACKGROUND: Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. METHODS: Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. RESULTS: After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. CONCLUSIONS: Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.

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.

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).

Short-term restoration of facial sensory loss by motor cortex stimulation in peripheral post-traumatic neuropathic pain.

We report a case in which motor cortex stimulation (MCS) improved neuropathic facial pain due to peripheral nerve injury and restored tactile and thermal sensory loss. A 66-year-old man developed intractable trigeminal neuropathic pain after trauma of the supraorbital branch of the Vth nerve, associated with tactile and thermal sensory loss in the painful area. MCS was performed using neuronavigation and transdural electric stimulation to localize the upper facial area on the motor cortex. One month after surgery, pain was decreased from 80/100 to 20/100 on visual analogic scale, and sensory discrimination improved in the painful area. Two months after surgery, quantitative sensory testing confirmed the normalization of thermal detection thresholds. This case showed that MCS could restore tactile and thermal sensory loss, resulting from peripheral nerve injury. Although the mechanisms leading to this effect remain unclear, this observation enhanced the hypothesis that MCS acts through modulation of the sensory processing.

Economic impact of migraine and other episodic headaches in France: data from the GRIM2000 study.

BACKGROUND: Migraine is a prevalent and incapacitating condition that affects individuals in the prime of their productive life, thus generating an economic burden for both society and healthcare systems. The direct annual healthcare costs of migraine in France were assessed over 10 years ago, and the current study updates these figures. OBJECTIVE: The objective of this study was to determine the economic cost (primarily direct costs) of migraine and other episodic headache in France based on a general population survey of headache, the GRIM2000 (Groupe de Researche Interdisciplinaire sur la Migraine). DESIGN: From a representative general population sample of 10,585 individuals aged > or = 15 years in France in 1999, 1486 individuals experiencing headaches were identified and interviewed regarding healthcare resource consumption in the previous 6 months. By applying unit costs to the resource data, costings (in 1999 values) were determined for physician consultations, hospitalisation, medication use and diagnostic/laboratory tests, and evaluated from a healthcare system perspective. Information on absenteeism and lost productivity was derived from the Migraine Disability Assessment Score (MIDAS) questionnaire. RESULTS: The prevalence of migraine (including migrainous disorder) was determined to be 17%. Total annual direct healthcare costs were estimated to be Euros 128 per individual with migraine in 1999, corresponding to Euros 1044 million when extrapolated to all individuals experiencing migraine and aged > or = 15 years. Around two-thirds of this cost accrued to the social security system (Euros 698 million; Euros 85 per individual). The total annual direct cost of other forms of episodic headache was much lower at Euros 28 per individual (social security cost Euros 18); with a prevalence of 9.2%, the annual national direct cost for other forms of episodic headache totalled Euros 124 million. The principal cost element was physician consultations. However, it was found that many individuals had never consulted a physician for their headaches, and self-medication contributed substantially to the medication costs (the second greatest cost factor for migraine). The cost per individual rose steeply with increasing severity of headache. CONCLUSIONS: The direct healthcare costs of migraine do not seem to have risen significantly over the past decade. A small minority of individuals with more severe headaches consume most of the healthcare resources devoted to migraine, while most individuals generate relatively low direct costs. The total annual direct costs in France for migraine are almost 10-fold higher than those of other episodic headache.