Epidemiology of diagnosed cluster headache in Norway

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)

Gamma-glutamyl cysteine synthetase and L-buthionine-S,R-sulfoximine (BSO): a new selection strategy for gene-transduced neural and hematopoietic stem/progenitor cells.

In most experimental gene therapy protocols involving stem/progenitor cells, only a small fraction of cells, often therapeutically inadequate, can be transduced and express the therapeutic gene. A promising strategy for overcoming this problem is the use of a dominant selection marker, such as a drug-resistance gene. In this paper, we have explored the potential of the heavy subunit of gamma-glutamyl cysteine synthetase (gamma-GCSh) to act as a selection marker. We found that 3T3 fibroblasts transduced with a bicistronic retroviral vector, coding for gamma-GCSh and the enhanced green fluorescent protein (eGFP), were highly resistant to L-buthionine-S,R-sulfoximine (BSO), a gamma-GCS inhibitor with a very low clinical toxicity profile. The level of resistance was not proportional to the increase in intracellular glutathione. In fact, cells overexpressing both heavy and light gamma-GCS subunits had higher intracellular GSH levels, and a lower level of resistance to the cytotoxic activity of BSO compared to cells overexpressing gamma-GCSh alone. 3T3 fibroblasts overexpressing gamma-GCSh could be selected from cultures containing both naïve and gene-modified cells by application of exogenous BSO selection pressure for 4 days. Also primary neural stem/progenitor cells derived from the lateral ventricles of mouse neonatal brains and primary hematopoietic stem/progenitor cells from mouse bone marrow, transduced with the gamma-GCSh-eGFP vector, could be selected by BSO treatment in vitro. These results provide proof-of-principle that neural and hematopoietic stem/progenitor cells, transduced with a potentially curative gene and co-expressing the simultaneously transduced gamma-GCSh gene, can be selected by treatment with BSO

Measurement and implications of the distance between the sphenopalatine ganglion and nasal mucosa: a neuroimaging study

Background Historical reports describe the sphenopalatine ganglion (SPG) as positioned directly under the nasal mucosa. This is the basis for the topical intranasal administration of local anaesthetic (LA) towards the sphenopalatine foramen (SPF) which is hypothesized to diffuse a distance as short as 1 mm. Nonetheless, the SPG is located in the sphenopalatine fossa, encapsulated in connective tissue, surrounded by fat tissue and separated from the nasal cavity by a bony wall. The sphenopalatine fossa communicates with the nasal cavity through the SPF, which contains neurovascular structures packed with connective tissue and is covered by mucosa in the nasal cavity. Endoscopically the SPF does not appear open. It has hitherto not been demonstrated that LA reaches the SPG using this approach. Methods Our group has previously identified the SPG on 3 T–MRI images merged with CT. This enabled us to measure the distance from the SPG to the nasal mucosa covering the SPF in 20 Caucasian subjects on both sides (n = 40 ganglia). This distance was measured by two physicians. Interobserver variability was evaluated using the intraclass correlation coefficient (ICC). Results The mean distance from the SPG to the closest point of the nasal cavity directly over the mucosa covering the SPF was 6.77 mm (SD 1.75; range, 4.00–11.60). The interobserver variability was excellent (ICC 0.978; 95% CI: 0.939–0.990, p < 0.001). Conclusions The distance between the SPG and nasal mucosa over the SPF is longer than previously assumed. These results challenge the assumption that the intranasal topical application of LA close to the SPF can passively diffuse to the SP

OnabotulinumtoxinA injection towards the SPG for treating symptoms of refractory chronic rhinosinusitis with nasal polyposis: a pilot study

Background and objective The main objective of this prospective, open, uncontrolled pilot study was to investigate the safety of administering onabotulinumtoxinA (BTA) towards the sphenopalatine ganglion (SPG) in 10 patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) using a novel injection tool, the MultiGuide®. Material and methods A one-month baseline period was followed by bilateral injections of 25 U BTA in the SPG and a follow-up of 12 weeks. The primary outcome was adverse events (AE), and the main efficacy outcome was a 50% reduction in visual analogue scale (VAS) symptoms for nasal obstruction and rhinorrhea in months 2 and 3 post-treatment compared to baseline. Results We registered 13 AEs, none of which were serious, however, one patient experienced diplopia which moderately affected his daily activities. The symptoms slowly improved and resolved 4 weeks after injection. Five patients were treatment responders with at least 50% median reduction in the nasal obstruction, and four were treatment responders concerning rhinorrhea. Conclusions Injection of BTA toward the SPG using the MultiGuide® in patients with CRSwNP appears to be safe but with a potential for moderately disabling side effects. The study indicates a beneficial effect on nasal obstruction