Long-term treatment with lasmiditan in patients with migraine: Results from the open-label extension of the CENTURION randomized trial.

BACKGROUND: Following the CENTURION phase 3 randomized controlled trial's four-month double-blind phase, this 12-month open-label extension collected data for up to one year about dose optimization, patterns of use, migraine-related disability, and quality of life during lasmiditan treatment. METHODS: Migraine patients ≥18 years completing the double-blind phase and treating ≥3 migraine attacks could continue into the 12-month open-label extension. The initial oral lasmiditan dose was 100 mg; the dose could subsequently be adjusted to 50 mg or 200 mg at the investigator's discretion. RESULTS: 477 patients entered and 321 (72.1%) completed the extension; 445 (93.3%) treated ≥1 attack with lasmiditan. Of 11,327 attacks, 8654 (76.4%) were lasmiditan-treated (84.9% of these involved moderate or severe pain). By study end, 17.8%, 58.7%, and 23.4% of patients were taking lasmiditan 50, 100, and 200 mg, respectively. Mean improvements were observed in disability and quality of life. The most common treatment-emergent adverse event was dizziness (35.7% of patients, 9.5% of attacks). CONCLUSIONS: During this 12-month extension, lasmiditan was associated with a high rate of study completion, most attacks were treated with lasmiditan, and patients reported improvements in migraine-related disability and quality of life. No new safety findings were observed with longer exposure.Trial registration: ClinicalTrials.gov (NCT03670810); European Union Drug Regulating Authorities Clinical Trials Database (EUDRA CT: 2018-001661-17).

Type of headache at onset and risk for complications in reversible cerebral vasoconstriction syndrome.

BACKGROUND: In a recent Italian study, 30% of patients with reversible cerebral vasoconstriction syndrome (RCVS) presented without thunderclap headache (TCH), and tended to present more severe forms of RCVS than patients with TCH. We aimed to analyze the risk for complications of RCVS in patients with and without TCH at onset. METHODS: In a pooled cohort of 345 French patients with RCVS, we compared patients with and without TCH at onset regarding rates of neurological complications, and the functional outcome at 3 months. RESULTS: As compared to the 281 patients with TCH at onset, the 64 patients without TCH had a higher risk for any neurological complication (61% vs. 24%, OR 4.9, 95% CI 2.8-8.7, p < 0.001). The association was strongest for cervical artery dissections (28% vs. 5%, OR 8.1, 95% CI 3.7-17.6, p < 0.001), followed by posterior reversible encephalopathy syndrome (17% vs. 3%, OR 7.1, 95% CI 2.7-18.4, p < 0.001), seizures (9% vs. 2.5%, OR 4.1, 95% CI 1.3-12.5, p = 0.019), and subarachnoid hemorrhage (41% vs. 16%, OR 3.5, 95% CI 1.9-6.3, p < 0.001). In multivariable analysis, the risk for any neurological complication remained significantly elevated in the absence of TCH (OR 3.5, 95% CI 1.8-6.8, p < 0.001). The functional outcome was equal in both groups, with a modified Rankin scale score of 0-1 in ≥90% of patients. CONCLUSIONS: Absence of TCH at onset might predict a higher risk of complications in RCVS. Our results warrant further multicentric studies to prove this finding.

Preventing Post-Lumbar Puncture Headache.

Post-lumbar puncture headache is the main adverse event from lumbar puncture and occurs in 3.5% to 33% of patients, causing functional and socio-professional disability. We searched the post-lumbar puncture headache literature and, based on this review and personal expertise, identified and addressed 19 frequently asked questions regarding post-lumbar puncture headache risk factors and prevention. Among the nonmodifiable factors, older age is associated with a lower incidence of post-lumbar puncture headache, while female sex, lower body mass index, and history of headache might be associated with increased risk. The use of atraumatic, noncutting needles is the most effective intervention for post-lumbar puncture headache prevention. These needles are not more difficult to use than cutting needles. Other commonly recommended measures (eg, fluid supplementation, caffeine) appear unhelpful, and some (eg, bed rest) may worsen post-lumbar puncture headache.

Positive effects of lumbar puncture simulation training for medical students in clinical practice.

BACKGROUND: Lumbar puncture (LP) is an invasive medical procedure that can be done by any doctor. Several simulation-based trainings have been built however the evaluations of the theoretical knowledge and the impact of the simulation-based training have never been performed in real life. The objective was to evaluate the impact of a LP training on the theoretical knowledge improvement and the performance of a LP in clinical practice. METHODS: Before and after medical students' training, theoretical knowledge and confidence level were assessed. Over a 6 months period, the impact of simulation training was evaluated by the success rate of students' first LP carried out in hospitalized patients and compared to the results of a no-training control. RESULTS: Students' theoretical knowledge and confidence level showed significant improvement after simulation training on 115 students (p < 0.0001). The evaluation in real life based on 41 students showed that the success rate of the first LP in patients was higher in the LP simulation group compared to the control group (67% vs 14%, p = 0.0025). The technical assistance was also less frequently needed in the LP simulation group (19% vs 57%, respectively, p = 0.017). The rate of students who participated in this educational study was low. DISCUSSION: Simulation-based teaching was an effective way to improve students' theoretical and practical knowledge. Whether this approach translates to other procedural skills in real clinical settings merits further study. The low participation rate in the study is due to the fact that students are not used to be included in educational studies and to the complexity of evaluation in routine clinical practice.

Occipital Nerve Stimulation for Refractory Chronic Cluster Headache: A Cost-Effectiveness Study.

INTRODUCTION: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement. MATERIALS AND METHODS: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and postintervention period) to conventional treatment alone (preintervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at three months, then one year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, was assessed second. RESULTS: The average total cost for three months was €7602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio (ICER) was then €109,676/QALY gained. The average extrapolated total cost for one year was €1344 lower for the ONS strategy (p = 0.5444) with a gain of 0.28 QALY (p < 0.0001), the ICER was then €-4846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant. The average indirect cost for three months was €377 lower for the ONS strategy (p = 0.1261). DISCUSSION: This ONS cost-effectiveness study highlighted the limitations of a short-time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. One-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions. CONCLUSION: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation, and reimbursement by health authorities in this severely disabled population.

Long-Term Outcomes After Reversible Cerebral Vasoconstriction Syndrome.

Background and Purpose- We aimed to further investigate the long-term outcomes after reversible cerebral vasoconstriction syndrome (RCVS). Methods- A longitudinal follow-up study was conducted in 173 RCVS patients. Results- Of the 172 patients who completed a mean follow-up of 9.2±3.3 years, 10 had a recurrent RCVS that was benign in all. Independent predictors of relapse were having a history of migraine and having exercise as a trigger for thunderclap headache during initial RCVS. After new delivery, the rate of postpartum RCVS was 9%. Conclusions- Overall, long-term outcome after RCVS is excellent.

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.

Complications of reversible cerebral vasoconstriction syndrome in relation to age.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) has a heterogenous clinical and radiological presentation. We investigated whether RCVS complications vary according to age. PATIENTS AND METHODS: In a pooled French cohort of 345 patients with RCVS, we assessed (1) rates of clinical and radiological complications, and (2) the functional outcome at 3 months according to age as a continuous variable, and in young patients aged ≤ 49 years versus those aged ≥ 50 years. The Commission Nationale Informatique et Liberté and the local ethics committee approved this study (registration number: 202100733). RESULTS: The risk for any focal deficit and for any brain lesion were independently associated with increasing age (OR 1.4, 95% CI 1.1-1.8; p = 0.014, and OR 1.6, 95% CI 1.2-2.1; p < 0.001, respectively). Subtypes of brain lesions independently associated with increasing age were subarachnoid haemorrhage (OR 1.7, 95% CI 1.3-2.3; p < 0.001) and intracerebral haemorrhage (OR 1.5, 95% CI 1.1-2.2; p = 0.023). Frequency of cervical artery dissections peaked at age 30-39, and young age was independently associated with cervical artery dissections (OR 13.6, 95% CI 2.4-76.6; p = 0.003). Age had no impact on the functional outcome, with a modified Rankin scale score of 0-1 in > 96% of patients. CONCLUSION: Age seems to influence rates and types of complications of RCVS, with young age being associated with cervical artery dissections, and increasing age with haemorrhagic complications. If confirmed in larger prospective studies, recognition of age-specific patterns might help to guide clinical management and to identify complications in cases of RCVS and vice versa.

Impairment of central retinal artery hemodynamics in affected and fellow eyes in giant cell arteritis patients with unilateral vision loss.

OBJECTIVES: Permanent visual impairment is a major complication of giant cell arteritis (GCA). We investigated the added value of color Doppler imaging (CDI) of the central retinal artery (CRA) in patients with suspected GCA for early risk evaluation before temporal artery biopsy (TAB) results become available. METHODS: We conducted a non-interventional observational study of 30 consecutive patients hospitalized for suspected GCA, including a comprehensive analysis of clinical, laboratory, imaging, CDI and pathology data. GCA was diagnosed or excluded (GCA+, GCA-, respectively) according to American College of Rheumatology (ACR) criteria and TAB findings. Three patients not meeting ACR criteria were excluded secondarily. The GCA- group contained ten patients, and the GCA+ group contained 17 patients, including eight with unilateral, transient or permanent clinical visual impairment (CVI). RESULTS: Mean blood flow velocity (mBFV) in the CRA was impaired in the affected eyes of GCA + CVI+ patients (1.9 ± 0.9 cm.s-1, p < 0.001) relative to controls (4.1 ± 1.0 cm.s-1), GCA- patients (3.6 ± 0.7 cm.s-1) and GCA + CVI- patients (3.8 ± 0.8 cm.s-1). The mBFVs of the CRA was similar for affected and fellow eyes (right or left). CRA mBFV measurements effectively differentiated between patients with and without CVI (ROC-curve analysis, AUC = 0.925 [95%CI: 0.700 to 0.996], p < 0.0001, 88% sensitivity, 89% specificity, and cutoff of ≤2.7 cm.s-1 for affected eyes; 75% sensitivity, 100% specificity and cutoff of ≤2.2 cm.s-1 for fellow eyes). CONCLUSION: CDI facilities the early detection of visual ischemia risk in GCA+ patients, justifying urgent high-dose corticosteroid administration to save at least the fellow eye before pathology results become available.

A unique service: how an embedded psychology team can help patients and genetics clinicians within a clinical genetics service.

The Genetics service at Guy's hospital has dedicated in-house psychology provision aimed at supporting patients embarking on genetic testing through to coping with the aftermath of genetic diagnoses. This provision offers assessment and intervention within a brief 6-session therapy model and provides a range of therapeutic approaches. Patient satisfaction with the service is high and referral rates have greatly increased over the recent years. The Psychology Team also provides indirect support for patients as well as support for the Genetics Team such as contributing to MDT and informal case discussions, as well as teaching and training clinicians about psychological concepts. There are many advantages to having an embedded psychology service both for patients and genetics clinicians, such as good opportunities for liaising around referrals and conducting joint clinical sessions, as well as being easily able to identify psychological training needs. The service plans to further develop by offering group interventions and training opportunities to doctoral psychology trainees. We conclude that clinical psychologists can play a highly integral and essential role in the provision of psychosocial support for clinical genetics teams and provide an overview of the first such integrated clinical psychology service within clinical genetics in the United Kingdom.

Hemiplegic Migraine Associated With PRRT2 Variations: A Clinical and Genetic Study.

BACKGROUND AND OBJECTIVE: PRRT2 variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of PRRT2 in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands. METHODS: PRRT2 was analyzed in 860 probands with hemiplegic migraine, and PRRT2 variations were identified in 30 probands. Genotyping of relatives identified a total of 49 persons with variations whose clinical manifestations were detailed. RESULTS: PRRT2 variations were found in 12 of 163 probands who previously tested negative for CACNA1A, ATP1A2, and SCN1A variations and in 18 of 697 consecutive probands screened simultaneously on the 4 genes. In this second group, pathogenic variants were found in 105 individuals, mostly in ATP1A2 (42%), followed by CACNA1A (26%), PRRT2 (17%), and SCN1A (15%). The PRRT2 variations included 7 distinct variants, 5 of which have already been described in persons with paroxysmal kinesigenic dyskinesia and 2 new variants. Eight probands had a deletion of the whole PRRT2 gene. Among the 49 patients with variations in PRRT2, 26 had pure hemiplegic migraine and 16 had hemiplegic migraine associated with another manifestation: epilepsy (8), learning disabilities (5), hypersomnia (4), or abnormal movement (3). Three patients had epilepsy without migraine: 2 had paroxysmal kinesigenic dyskinesia without migraine, and 1 was asymptomatic. DISCUSSION: PRRT2 should be regarded as the fourth autosomal dominant gene for hemiplegic migraine and screened in any affected patient, together with the 3 other main genes. Further studies are needed to understand how the same loss-of-function PRRT2 variations can lead to a wide range of neurologic phenotypes, including paroxysmal movement disorder, epilepsy, learning disabilities, sleep disorder, and hemiplegic migraine.

Spectral analysis of EEG in etiological assessment of patients with transient neurological deficits.

OBJECTIVE: Differentiating transient ischemic attack from stroke mimics may be difficult. Besides clinical evaluation and brain imaging, electroencephalography (EEG) may be a useful diagnostic tool. METHODS: We conducted spectral analysis on 67 EEG of patients who had presented a transient neurological deficit (TND) within the previous seven days. Expert clinicians provided the final diagnosis: transient ischemic attack, migraine with aura, focal seizure or "other". We first calculated the relative power of the four EEG frequency bands (delta, theta, alpha and beta), in the whole hemisphere, then, according to the clinical symptoms, in the relevant electrodes of the symptomatic hemisphere. Finally, we calculated the relative power ratio between symptomatic and asymptomatic hemispheres. RESULTS: Median age was 60.6 years (57% females). The etiological diagnosis was transient ischemic attack (27%), migraine with aura (11%), focal seizures (22%) and "other" (40%). We did not find significant differences in the theta and delta relative power analysis between groups. Over the symptomatic hemisphere only, we found a significant increase of the alpha relative power (p = 0.0026, p < 0.0001, p = 0.0014) in the migraine group compared to transient ischemic attack, migraine and focal seizures groups, and a significant decrease of the beta relative power (p = 0.0034, p = 0.0016, p = 0.0005) compared to the same groups. CONCLUSIONS: Migraine with aura presents a discriminative EEG relative power in comparison to transient neurological deficits of other origins. To further investigate the additive diagnosis value of EEG in other TND, future studies should be performed with an EEG obtained within the first 24 h after the onset of symptoms. SIGNIFICANCE: Spectral EEG analysis discriminates migraine with aura groups from other groups, but not at the individual level.

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.

Concomitant reversible cerebral vasoconstriction syndrome and transient global amnesia.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is a common cause of thunderclap headache (TCH), mainly recurrent, sometimes associated with seizures and/or neurological deficit. Association with amnesia is exceptional. We report a case series of RCVS concomitant with transient global amnesia (TGA) and propose pathophysiologic hypotheses. METHODS: We retrospectively reviewed clinical and radiological features of patients diagnosed with confirmed concomitant RCVS and TGA between 2012 and 2018 in two specialized institutions. RESULTS: Two women aged 67 and 53, and a 64-year-old man had a first thunderclap headache triggered by an acute emotional stress, rapidly followed by TGA. Amnesia resolved within a few hours and RCVS was proven for all, with complete resolution of vasospasms within 3 months. All three patients had excellent outcome. CONCLUSIONS: RCVS and TGA can occur simultaneously, which suggests common mechanisms such as aberrant responses to physical or emotional stress and cerebral vasoconstriction.

[Migraine epidemiological, clinical and therapeutic data]. / Migraine : données épidémiologiques, cliniques et thérapeutiques.

Burden of disease study ranks headache disorders as the second leading cause of years lived with disability worldwide. Migraine has an estimated prevalence of 10 to 14% and is therefore the most common neurological pathology. It concerns young populations, with a female/male ratio of 3/1, and its impact in economic terms is mainly related to indirect costs. Migraine can be episodic or chronic depending on the frequency of headache days (≥ 15 days per month). The diagnosis of migraine is made according to international criteria, which are easy to use, with essential questions to be asked to patients in a logical order and structure. The migraine is explained by an activation of the so-called trigeminocervical system, with release of neuromediators participating in neurogenic inflammation and activation of second-order neurons. Migraine with aura is manifested by neurological symptoms, lasting less than 60 minutes, explained by the phenomenon of cortical spreading depression. Visual symptoms are the most commonly described aura event of migraine, other auras include sensory and speech disturbance. Cortical spreading depression is a slowly propagating wave of near-complete depolarization of neurons and glial cells spreading over the cortex at a speed of ∼3-5 mm/min. First-line acute treatment for migraine consists of nonsteroidal anti-inflammatory drugs (NSAID), triptans and antiemetics. Patients with frequent or chronic headaches warrant prophylactic therapy. Various classes of preventives can be used (ß-blockers, tricyclics, antiepileptics), with the choice of therapy tailored to the patient's risk factors and symptoms. In practice, treatment has two axes: NSAID or triptans for crisis treatment and for background treatment prescribed case by case, the first-intention molecules according to the French recommendations are beta-blockers, then, in case of failure, topiramate, oxetorone or amitriptyline.

Contribution of EEG in transient neurological deficits.

Identification of stroke mimics and 'chameleons' among transient neurological deficits (TND) is critical. Diagnostic workup consists of a brain imaging study, for a vascular disease or a brain tumour and EEG, for epileptiform discharges. The precise role of EEG in this diagnostic workup has, however, never been clearly delineated. However, this could be crucial in cases of atypical or incomplete presentation with consequences on disease management and treatment. We analysed the EEG patterns on 95 consecutive patients referred for an EEG within 7 days of a TND with diagnostic uncertainty. Patients were classified at the discharge or the 3-month follow-up visit as: 'ischemic origin', 'migraine aura', 'focal seizure', and 'other'. All patients had a brain imaging study. EEG characteristics were correlated to the TND symptoms, imaging study, and final diagnosis. Sixty four (67%) were of acute onset. Median symptom duration was 45 min. Thirty two % were 'ischemic', 14% 'migraine aura', 19% 'focal seizure', and 36% 'other' cause. EEGs were recorded with a median delay of 1.6 day after symptoms onset. Forty EEGs (42%) were abnormal. Focal slow waves were the most common finding (43%), also in the ischemic group (43%), whether patients had a typical presentation or not. Epileptiform discharges were found in three patients, one with focal seizure and two with migraine aura. Non-specific EEG focal slowing is commonly found in TND, and may last several days. We found no difference in EEG presentation between stroke mimics and stroke chameleons, and between other diagnoses.

Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Suboccipital steroid injections can be used for preventive treatment of cluster headache but few data are available for the efficacy of this approach in clinical trials. We aimed to assess efficacy and safety of repeated suboccipital injections with cortivazol compared with placebo as add-on therapy in patients having frequent daily attacks. METHODS: In our randomised, double-blind, placebo-controlled trial at the Emergency Headache Centre in Paris, France, we enrolled adults aged 18-65 years with more than two cluster headache attacks per day. We randomly allocated patients to receive three suboccipital injections (48-72 h apart) of cortivazol 3·75 mg or placebo, as add-on treatment to oral verapamil in patients with episodic cluster headache and as add-on prophylaxis for those with chronic cluster headache, on the basis of a computer-generated list (blocks of four for each stratum). Injections were done by physicians who were aware of treatment allocation, but patients and the evaluating physician were masked to allocation. The primary outcome was reduction of the number of daily attacks to a mean of two or fewer in the 72 h period 2-4 days after the third injection. We assessed all patients who received at least one dose of study drug in the intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00804895. FINDINGS: Between November, 2008, and July, 2009, we randomly allocated 43 patients (15 with chronic and 28 with episodic cluster headache) to receive cortivazol or placebo. 20 of 21 patients who received cortivazol had a mean of two or fewer daily attacks after injections compared with 12 of 22 controls (odds ratio 14·5, 95% CI 1·8-116·9; p=0·012). Patients who received cortivazol also had fewer attacks (mean 10·6, 95% CI 1·4-19·9) in the first 15 days of study than did controls (30·3, 21·4-39·3; mean difference 19·7, 6·8-32·6; p=0·004). We noted no serious adverse events, and 32 (74%) of 43 patients had other adverse events (18 of 21 patients who received cortivazol and 14 of 22 controls; p=0·162); the most common adverse events were injection-site neck pain and non-cluster headache. INTERPRETATION: Suboccipital cortivazol injections can relieve cluster headaches rapidly in patients having frequent daily attacks, irrespective of type (chronic or episodic). Safety and tolerability need to be confirmed in larger studies. FUNDING: None.