Botulinum toxin injections towards Sphenopalatine ganglion for orofacial and headache conditions: Safety and efficacy

Abstract

This dissertation is based on two clinical studies and one retrospective study. The first study was a non-randomized pilot study involving patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and the second study was a randomized, doubleblind, placebo-controlled, exploratory, cross-over study evaluating the effect of blocking the sphenopalatine ganglion (SPG) with onabotulinumtoxinA (BTA) for patients suffering from persisting idiopathic facial pain (PIFP). The third study was a retrospective analysis of our early experience of open-label use of BTA targeting the SPG in patients with chronic cluster headache (CCH) and chronic migraine (CM). This study presents evidence regarding the safety and effectiveness of recurrent treatment with BTA for CCH and CM patients who have not responded to conventional treatments. The main purpose of this paper was to investigate long term safety of the procedure. We examined whether injecting BTA against the SPG with the novel injection tool MultiGuide was a safe treatment option for patients with CRSwNP, CH and CM and a safe and effective treatment for PIFP. MultiGuide is an instrument that is capable of injecting drugs precisely and accurately inside the body, making it ideal for injecting BTA against a small nerve ganglion deep in the skull base. Tentatively, the SPG plays a critical role in several parasympathetic regulatory processes in facial tissues, including the mucous membranes of the nose, mouth, eyes, the salivary glands, and pain modulation in the facial region. There is no established treatment for facial disorders targeting the regulation of parasympathetic activity. The only available treatment targeting these autonomic pathways is expensive, requires anaesthesia and surgery at the risk of complications and long-term side effects. In the first study, we investigated the safety of administering BTA towards the SPG in 10 patients with refractory CRSwNP using the MultiGuide®. We found that injection of BTA toward the SPG in patients with CRSwNP appeared to be safe but with a potential for moderately disabling transient side effects. The study indicated a beneficial effect on nasal obstruction. Five patients were treatment responders with at least a 50% median reduction in nasal obstruction, and four were treatment responders concerning rhinorrhea. The second study showed that there was no significant decrease of PIFP between participants receiving placebo and BTA at weeks 5-8 after injection, but there was a significant reduction in pain in weeks 1-4 after injection. We registered 13 adverse events, none of which were serious; nevertheless, three patients experienced diplopia, which gradually improved and disappeared 12 weeks following injection. The third study revealed that one serious adverse event occurred out of 261 injections. Most (93%) AEs were mild and all were transient. The 50% response to one injection was 81% for CM and 69% for CCH. Response gradually reduced over subsequent months for CM but stayed between 55-67% for CCH. Repeated injections gave marked effects. We concluded that the method was safe for CRSwNP, CM, CCH and PIFP, but with transient bothersome side effects in 8% of the injections with active substance in the PIFP study. The procedure was only partly effective for CRSwNP. In the placebocontrolled trial there was no difference in the reduction of PIFP between the placebo and BTA in weeks 5-8 after injection, even though, there was a significant reduction in pain in the first 4-weeks after injection. Our study shows that modulating the parasympathetic activity of SPG in patients suffering from PIFP may be effective, but in future studies, it would be advisable to conduct a parallel study or apply a significantly longer washout period. Data indicates that repeated BTA injections towards the SPG is an effective treatment for refractory CM and CCH. Larger, randomized, placebo-controlled trials are required.