This study provides Class IV evidence that VTA-DBS decreases headache frequency, severity, and headache load in patients with medically intractable chronic cluster headaches.
Objective This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways. Methods We carried out a genome‐wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort. The 2 cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene‐set enrichment, functional variant annotation, prediction and pathway analyses, were performed. Results Initial independent analysis identified 2 replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 × 10−17, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.37–1.66) and rs4519530 (p = 6.98 × 10−17, OR = 1.47, 95% CI = 1.34–1.61) on chromosome 2, rs12121134 on chromosome 1 (p = 1.66 × 10−8, OR = 1.36, 95% CI = 1.22–1.52), and rs11153082 (p = 1.85 × 10−8, OR = 1.30, 95% CI = 1.19–1.42) on chromosome 6. Downstream analyses implicated immunological processes in the pathogenesis of cluster headache. Interpretation We identified and replicated several genome‐wide significant associations supporting a genetic predisposition in cluster headache in a genome‐wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to, for example, treatment response and cluster headache subtypes, could provide unprecedented insights into genotype–phenotype correlations and the pathophysiological pathways underlying cluster headache. ANN NEUROL 2021;90:193–202
Objective:To investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area.Methods:Seven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of ≥30% in headache load.Results:There was no surgical morbidity. Average follow-up was 34 ± 14 months. Patients showed reductions of 76 ± 33% in headache load, 46 ± 41% in attack severity, 58 ± 41% in headache frequency, and 51 ± 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas.Conclusions:We identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.
Greater occipital nerve (GON) infiltration is widely used for the treatment of primary and secondary headache disorders mainly on the basis of open-label evidence, although recent double-blinded placebo-controlled trials have demonstrated its efficacy in cluster headache. The procedure is generally well tolerated although corticosteroid-related side effects, including Cushing's syndrome and local cutaneous changes, can occur. We report the occurrence of cutaneous atrophy and alopecia in 4 patients who underwent GON blockade with triamcinolone and lidocaine. Triamcinolone injection is associated with cutaneous atrophy, especially in superficial injection sites; therefore, alternative steroid preparations like methylprednisolone and betamethasone might be more appropriate for GON blockade.
Background Multiple cranial nerve blocks of the greater and lesser occipital, supraorbital, supratrochlear and auriculotemporal nerves are widely used in the treatment of primary headaches. We present efficacy and safety data for these procedures. Methods In an uncontrolled open-label prospective study, 119 patients with chronic cluster headache, chronic migraine, short lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania were examined. All had failed to respond to greater occipital nerve blocks. Response was defined as a 50% reduction in either daily attack frequency or moderate-to-severe headache days after 2 weeks. Results The response rate of the whole cohort was 55.4%: Chronic cluster headache, 69.2%; chronic migraine, 49.0%; short lasting unilateral neuralgiform attack disorders, 56.3%; new daily persistent headache, 10.0%; hemicrania continua, 83.3%; and chronic paroxysmal hemicrania, 25.0%. Time to benefit was between 0.50 and 33.58 hours. Benefit was maintained for up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania. Only minor adverse events were recorded. Conclusion Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders when greater occipital nerve blocks have been unsuccessful.
IntroductionThe management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) remains challenging in view of the paucity of data and evidence-based treatment recommendations are missing.MethodsIn this single-centre, non-randomised, prospective open-label study, we evaluated and compared the efficacy of oral and parenteral treatments for SUNCT and SUNA in a real-world setting. Additionally, single-arm meta-analyses of the available reports of SUNCT and SUNA treatments were conducted.ResultsThe study cohort comprised 161 patients. Most patients responded to lamotrigine (56%), followed by oxcarbazepine (46%), duloxetine (30%), carbamazepine (26%), topiramate (25%), pregabalin and gabapentin (10%). Mexiletine and lacosamide were effective in a meaningful proportion of patients but poorly tolerated. Intravenous lidocaine given for 7–10 days led to improvement in 90% of patients, whereas only 27% of patients responded to a greater occipital nerve block. No statistically significant differences in responders were observed between SUNCT and SUNA. In the meta-analysis of the pooled data, topiramate was found to be significantly more effective in SUNCT than SUNA patients. However, a higher proportion of SUNA than SUNCT was considered refractory to medications at the time of the topiramate trial, possibly explaining this isolated difference.ConclusionsWe propose a treatment algorithm for SUNCT and SUNA for clinical practice. The response to sodium channel blockers indicates a therapeutic overlap with trigeminal neuralgia, suggesting that sodium channels dysfunction may be a key pathophysiological hallmark in these disorders. Furthermore, the therapeutic similarities between SUNCT and SUNA further support the hypothesis that these conditions are variants of the same disorder.
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