Real-life prognosis of neurological complications of botulinum toxin: A nationwide pharmacovigilance study of adverse drug reactions reported in France between 1994 and 2020

Abstract

Background: Botulinum toxin is commonly used in the treatment of neurological disorders. Although neurological complications predominate and can lead to respiratory failure or death, no observational studies have specifically described their clinical features or prognoses.

Objectives: To characterise real-life clinical features and prognoses of botulinum toxin-related neurological complications.

Methods: Observational, retrospective, nationwide pharmacovigilance study of all neurological adverse drug reactions (ADRs) related to the use of botulinum toxin in France for neurological indications between 1994 and 2020. The characteristics of neurological complications were collected.

Results: In total, 141 people with systemic neurologic complications (ie, distant from the injection site) and 50 with local complications were included. Median (IQR) age was 53 (36; 66) years, and 107 (56 %) were women. The estimated incidence range (min-max) was 25 - 413 neurologic ADRs per 100 000 injection sessions for neurological indications. Except for 3 miscellaneous cases, all presented symptoms within the clinical spectrum of botulism, either as an isolated symptom (41 %) or as multiple symptoms (59 %), with a time to onset of 12 (7; 15) days after injection and a duration of 54 (28; 90) days. A total of 87 % of cases recovered spontaneously or were recovering on the date of the notification. Drug types were not different between cases with systemic or local ADRs, although the doses were higher in cases with systemic ADRs (P < 0.001). Serious cases were more frequent for systemic ADRs (67 % versus 34 %; P < 0.001). Three complications resulted in death, all after treatment for cervical dystonia or sialorrhea.

Conclusion: In this pharmacovigilance study, the outcomes of botulism spectrum symptoms occurring after a botulinum toxin injection for a neurological indication were mostly favourable, although symptoms were often initially serious.

Keywords: Botulinum toxins; Drug monitoring; Neurological manifestations; Pharmacovigilance.