Open-Label, Multi-Dose, Pilot Safety Study of Injection of OnabotulinumtoxinA Toward the Otic Ganglion for the Treatment of Intractable Chronic Cluster Headache.
Adult
Aged
Botulinum Toxins, Type A
/ administration & dosage
Chronic Disease
Cluster Headache
/ drug therapy
Drug-Related Side Effects and Adverse Reactions
Female
Ganglia, Parasympathetic
/ drug effects
Humans
Injections
Male
Middle Aged
Neuromuscular Agents
/ administration & dosage
Outcome Assessment, Health Care
Pilot Projects
botulinum toxin
chronic cluster headache
otic ganglion
pterygopalatine ganglion
sphenopalatine ganglion
trigeminal autonomic cephalalgia
Journal
Headache
ISSN: 1526-4610
Titre abrégé: Headache
Pays: United States
ID NLM: 2985091R
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
06
01
2020
revised:
18
05
2020
accepted:
18
05
2020
pubmed:
26
6
2020
medline:
9
11
2021
entrez:
26
6
2020
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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
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.
Substances chimiques
Neuromuscular Agents
0
Botulinum Toxins, Type A
EC 3.4.24.69
onabotulinum toxin A
EC 3.4.24.69
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1632-1643Subventions
Organisme : NTNU (Norwegian University of Science and Technology) and "The Liaison Committee for Education, Research and Innovation in Central Norway" (Samarbeidsorganet)
ID : 46056923
Informations de copyright
© 2020 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.
Références
Crespi J, Bratbak D, Dodick DW, et al. Anatomical landmarks for localizing the otic ganglion: A possible new treatment target for headache disorders. Cephalalgia Rep. 2019;2:1-7.
Fischera M, Marziniak M, Gralow I, Evers S. The incidence and prevalence of cluster headache: A meta-analysis of population-based studies. Cephalalgia. 2008;28:614-618.
Leone M, Cecchini AP, Mea E, Tullo V, Bussone G. Epidemiology of fixed unilateral headaches. Cephalalgia. 2008;28(Suppl. 1):8-11.
Jensen RM, Lyngberg A, Jensen RH. Burden of cluster headache. Cephalalgia. 2007;27:535-541.
Akerman S, Holland PR, Lasalandra MP, Goadsby PJ. Oxygen inhibits neuronal activation in the trigeminocervical complex after stimulation of trigeminal autonomic reflex, but not during direct dural activation of trigeminal afferents. Headache. 2009;49:1131-1143.
Crespi J, Bratbak D, Dodick DW, et al. Measurement and implications of the distance between the sphenopalatine ganglion and nasal mucosa: A neuroimaging study. J Headache Pain. 2018;19:14.
Gray H, Warwick R, William PI. Gray's Anatomy, 39th edn. London: Churchill Livingstone; 2005.
Senger M, Stoffels H-J, Angelov DN. Topography, syntopy and morphology of the human otic ganglion: A cadaver study. Ann Anat. 2014;196:327-335.
Uddman R, Hara H, Edvinsson L. Neuronal pathways to the rat middle meningeal artery revealed by retrograde tracing and immunocytochemistry. J Auton Nerv Syst. 1989;26:69-75.
Walters BB, Gillespie SA, Moskowitz MA. Cerebrovascular projections from the sphenopalatine and otic ganglia to the middle cerebral artery of the cat. Stroke. 1986;17:488-494.
Suzuki N, Hardebo JE, Owman C. Origins and pathways of cerebrovascular vasoactive intestinal polypeptide-positive nerves in rat. J Cereb Blood Flow Metab. 1988;8:697-712.
Andres KH, Kautzky R. Kleine vegetative Ganglien im Bereich der Schädelbasis des Menschen. Deut Zeitschr Nervenheilk. 1956;174:272-282.
Suzuki N, Hardebo JE. Anatomical basis for a parasympathetic and sensory innervation of the intracranial segment of the internal carotid artery in man: Possible implication for vascular headache. J Neurol Sci. 1991;104:19-31.
Mathew NT. Is cluster headache due to indolent inflammation in the cavernous sinus? Cephalalgia. 1998;18:172.
Afra J, Cecchini AP, Schoenen J. Craniometric measures in cluster headache patients. Cephalalgia. 1998;18:143-145.
Tfelt-Hansen P, Paulson OB, Krabbe AA. Invasive adenoma of the pituitary gland and chronic migrainous neuralgia. A rare coincidence or a causal relationship? Cephalalgia. 1982;2:25-28.
Koenigsberg AD, Solomon GD, Kosmorsky G. Psuedoaneurysm within the cavernous sinus presenting as cluster headache. Headache. 1994;34:111-113.
Goadsby PJ, Lambert GA, Lance JW. The peripheral pathway for extracranial vasodilatation in the cat. J Auton Nerv Syst. 1984;10:145-155.
Silberstein SD, Dodick DW, Pearlman S. Defining the pharmacologically intractable headache for clinical trials and clinical practice. Headache. 2010;50:1499-1506.
Bratbak DF, Nordgard S, Stovner LJ, et al. Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic cluster headache. Cephalalgia. 2016;36:503-509.
Bratbak DF, Nordgard S, Stovner LJ, et al. Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic migraine. Cephalalgia. 2017;37:356-364.
Crespi J, Bratbak D, Dodick DW, Matharu M, Jamtoy KA, Tronvik E. Pilot study of injection of onabotulinumtoxinA toward the sphenopalatine ganglion for the treatment of classical trigeminal neuralgia. Headache. 2019;59:1229-1239.
Riesco N, Perez-Alvarez AI, Verano L, et al. Prevalence of cranial autonomic parasympathetic symptoms in chronic migraine: Usefulness of a new scale. Cephalalgia. 2016;36:346-350.
Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA. 1983;249:1743-1745.
Diener HC, Schorn CF, Bingel U, Dodick DW. The importance of placebo in headache research. Cephalalgia. 2008;28:1003-1011.