Botulinum Toxin Treatment in Hereditary Spastic Paraplegia-A Comprehensive Review and Update.

Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 September 2025) on botulinum neurotoxin therapy for hereditary spastic paraplegia (HSP). Nine studies were conducted in adults and one in children. Only one of the ten studies was double-blind and placebo-controlled. The search strategy included only articles published in English and articles providing basic information such as the type of the study, type and dose of the toxin and results of the treatment. Articles not in English, case reports and review articles were excluded. A total of 258 patients were included across all studies. The injected toxin in the open-label studies was botulinumtoxin-A (Botox or Dysport or Xeomin), whereas in the blinded study, the investigators used Prosigne. All open-label studies, which used FDA approved botulinumtoxin-A neurotoxins, demonstrated a degree of motor and non-motor improvement, whereas treatment with Prosigne did not improve patients' function. The possible reasons for this discrepancy between the blinded study and the open-label studies are discussed. We found no studies on the effect of BoNTs on bladder dysfunction in HSP. There is a need for double-blind, placebo-controlled studies assessing the efficacy of FDA-approved botulinum neurotoxins in children and adults affected by hereditary spastic paraparesis. Such studies should also investigate the effect(s) of early botulinum neurotoxin therapy in this disorder. The novelty of this review is that it represents a comprehensive and critical literature review on this subject, with no other studies of this kind published previously. It also includes data not present in previous reviews of this subject.