Crespi, Joan

Background: Cluster headache (CH) is one of the most painful conditions in humans and there is limited epidemiological data on this debilitating condition. Objectives: To describe the epidemiology of CH in Norway Methods: We conducted a nationwide study to investigate the prevalence, incidence, and comorbidity of CH in Norway between January 1 2008 and December 31 2016. Treatment and outcome data from the Norwegian patient registry and the Norwegian prescription database were linked on an individual basis. Results: Among 3,892,260 individuals ≥18 years old of age, we identified a total of 1891 patients with CH. The prevalence of CH was 48.6 per 100,000, and the male-to-female ratio was 1.47. The estimated incidence of CH was 3.0 per 100,000/year. Among patients with CH, increased age and sex adjusted odds ratios ([OR], all with p-values <0.0001, were observed for medication-induced headache (OR 50.7, 95% CI 36.7–69.9), migraine (OR 25.2, 95% CI 22.5–28.3), chronic posttraumatic headache (OR 22.2, 95% CI 12.8–38.45), history of cranial trauma (OR 1.9, 95% CI 1.5–2.4), somatoform disorders (OR 4.2, 95% CI 3.0–5.8), suicide attempt (OR 3.9, 95% CI 2.6–5.8), personality disorder (OR 3.6, 95% CI 2.6–4.9), bipolar disorder (OR 3.6, 95% CI 2.8–4.8), peptic ulcer (OR 2.8, 95% CI 2.3–3.3), depression (OR 2.8, 95% CI 2.4–3.1), substance abuse (OR 2.6, 95% CI 2.0–3.3), and cerebrovascular disease (OR 2.4, 95% CI 1.8–3.1). Use of opioid analgesics during the study period was more common among patients with CH compared to others (81% vs. 22%, sex and age adjusted OR 23.4, 95% CI 20.8–26.2, p < 0.0001).

Background The otic ganglion (OG) provides parasympathetic innervation to the cerebral circulation and cranial structures and may be involved in the pathophysiology of trigeminal autonomic headaches. This structure has never been targeted in any headache disorder. Objective To investigate the safety of injecting onabotulinumtoxin A (BTA) toward the OG in 10 patients with intractable chronic cluster headache and to collect efficacy data. Methods A total of 10 patients with chronic cluster headache were enrolled in this open‐label, multi‐dose pilot safety study. All patients were recruited and treated on an out‐patient basis at St Olav's University Hospital (Norway). In 5 patients each, the OG was the injection target with 12.5 IU of BTA or 25 IU, respectively. The primary outcome measure was adverse events (AEs) and the main secondary outcome was the number of attacks per week measured at baseline and in the second month following injection. Results For the primary endpoint, we analyzed data for all 10 patients. There were a total of 17 AEs in 6 of the 10 patients. All AEs were considered mild and disappeared by the end of follow‐up. The median number of attacks per week at baseline was 17.0 [7.8 to 25.8] vs 14.0 [7.3 to 20.0] in the second month following injection; difference: 3 (95%CI: −0.3 to 7.9), P = .063. Conclusions Injection with BTA toward the OG appears to be safe. We did not find a statistically significant reduction in the number of attacks per week at month 2 after injection compared to the baseline. This study suggests that the OG is not an important target for the treatment of chronic cluster headache. A future study employing more precise targeting of the OG may be indicated.

Background The sphenopalatine ganglion (SPG) has previously been targeted in trigeminal neuralgia (TN), but its role in this condition has not been established. Objective To investigate the safety of injecting onabotulinumtoxinA (BTA) toward the SPG using the MultiGuide ® in 10 patients with refractory classical TN, and collect preliminary efficacy data. Methods Twenty‐five international units (IU) of BTA were injected toward the SPG in a prospective, open‐label study in 10 patients with refractory classical TN. All patients were recruited and treated on an out‐patient basis at St. Olav's University Hospital in Trondheim (Norway). Primary outcome: adverse events (AEs). Primary efficacy outcome: number of TN attacks at weeks 5‐8 after injection compared to baseline. A treatment responder was predefined as at least 50% reduction in the median number of attacks per day between baseline and weeks 5‐8. Other efficacy outcomes were intensity of attacks (numeric rating scale, 0 to 10) and functional level (1 to 4; 1 best and 4 worst) at weeks 5‐8 after injection compared to baseline. Percentage of the day with concomitant persistent pain was registered at baseline and at weeks 1‐4, 6, 8, and 12 after injection. Patient global impression of change (PGIC) was ascertained at month 3. Results For the primary endpoint, we analyzed data for all 10 patients. For efficacy outcomes we analyzed data for 9 patients (1 patient violated protocol). We registered 13 AEs, none of which were serious. The median number of TN attacks during the 4‐week baseline and weeks 5‐8 after injection was 5.5 (range: 1.0‐51.5) and 5 (range: 0‐225.0), respectively ( P = .401). Four patients were treatment responders. The median intensity of attacks at baseline and weeks 5‐8 after injection was 6 (range: 3.0‐8.5) and 3 (range: 0.0‐9.0) respectively ( P = .024). The median functional level at baseline was 2 (range: 1.0‐3.3) and at month 2, 1 (range 1.0‐4.0; P = .750). Median percentage of the day with concomitant persistent pain was 75% (minimum 37.5%, maximum 100%) at baseline and 18.75% (minimum 0%, maximum 100%) at week 8 ( P = .023). Conclusions Injection of BTA toward the SPG using the MultiGuide ® in patients with TN appears to be safe and well tolerated. This study was negative for the main efficacy endpoint (reduction in the number of attacks from baseline to weeks 5‐8). Further studies examining the role of the SPG in TN are necessary.

Background: The otic ganglion (OG) is a cranial parasympathetic ganglion located in the infratemporal fossa under the foramen ovale (FO) and adjacent to the medial part of the mandibular nerve. Parasympathetic innervation of intracranial vessels from the OG has been shown both in animal and human models and evidence suggests that the OG plays an important role in the cranial vasomotor response. We review the evidence that positions the OG as a viable target for headache disorders. The OG is a small structure and not detectable on medical imaging. The FO is easily identifiable on CT scans and the mandibular nerve on MRI, hence, the position of the OG may be predicted if the mean distance from the FO is known. Objective: The objective is to describe the average distance between the FO and the OG in a sample of 18 infratemporal fossae from 21 cadavers. Methods: A total of 21 high definition photographs of 21 infratemporal fossae from 18 cadavers were analyzed. The distance between the inferior edge of the medial part of the FO to the OG was measured. Results: Four photographs of infratemporal fossae of four cadavers were excluded due to the inability to localize the inferior edge of the FO. A total of 15 infratemporal fossae from 17 cadavers were measured. The mean distance from the FO to the OG was 4.5 mm (SD 1.7), range 2.1–7.7 mm. Conclusions: We have described the average distance from the OG to an easily identifiable anatomical landmark that is visible in CT scans, the FO. This anatomical study may aid in the development of strategies to localize the OG in order to explore its role as a therapeutic target for headache disorders.

Background: The sphenopalatine ganglion (SPG) is a target for several headache syndromes. Most of the groups targeting the SPG do not localize it directly, and this might account for some therapeutic failures. As the SPG cannot be seen on computerized tomography (CT) scans, magnetic resonance image (MRI) must be used to visualize the ganglion. It would be advantageous to be able to predict the location of the SPG on CT scans for those using fluoroscopy or CT-guided injections and for those in whom MRI is not accessible or contraindicated. Methods: We localized the SPG in 21 Caucasian patients (21 right and 17 left ganglia; total 38) in 3 tesla MR images subsequently fused with CT scans. We measured the distance from the SPG to two bony landmarks identified on CT scans. We then applied the average distances to find an estimated position of the SPG. The first landmark was the center of the anterior opening of the vidian canal (VC). The second landmark was a point on the sphenoidal bone, defined in an axial plane at the level of the center of the VC (S-point). The predicted position of the SPG measured from the VC and the sphenoidal bone were referred to as, respectively, vcSPG and sSPG. Finally, the distances between the SPG, as seen on MRI, and predicted vcSPG/sSPG were calculated. Results: The average distance between SPG as seen on the MRI images and the estimated position based on CT images were 1.82 mm (SD 0.83, range 0.22–3.57 mm) for vcSPG and 2.09 mm (SD 0.99, range 0.71–4.79 mm) for sSPG. Conclusions: The localization of the SPG can be predicted on CT images using bony landmarks. Localization of the SPG may be important in achieving successful therapeutic outcomes for treatments that are directed toward the SPG.