Dataset Information

Repeated Intrastriatal Botulinum Neurotoxin-A Injection in Hemiparkinsonian Rats Increased the Beneficial Effect on Rotational Behavior.

ABSTRACT: Injection of botulinum neurotoxin-A (BoNT-A) into the striatum of hemiparkinsonian (hemi-PD) rats reduced apomorphine-induced rotation behavior significantly, for at least 3 months. Thereafter, rotation behavior increased again. We injected hemi-PD rats with 1 ng BoNT-A twice, the second injection following 6 months after the first one and tested the rats for apomorphine-induced rotations and spontaneous motor behaviors, i.e., corridor task and stepping test. To test the hypothesis that BoNT-A reduced striatal hypercholinism in hemi-PD rats, the acetylcholinesterase inhibitor donepezil was injected prior to separate apomorphine-induced rotation tests. In hemi-PD rats, the first BoNT-A injection led to a clear reduction of the apomorphine-induced rotations, and the second BoNT-A injection to a more massive and prolonged reaction. In hemi-PD rats whose apomorphine-induced rotation behavior was strongly reduced by an intrastriatal BoNT-A, subsequent donepezil injections led to significant increases of the rotation rate. Concerning corridor task and stepping test, neither first nor second BoNT-A injections changed hemi-PD rats' behavior significantly. The data give evidence for the possibility of repeated intrastriatal administrations of BoNT-A, for treatment of motor symptoms in experimental hemi-PD over a longer time.

SUBMITTER: Hawlitschka A

PROVIDER: S-EPMC6162461 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Repeated Intrastriatal Botulinum Neurotoxin-A Injection in Hemiparkinsonian Rats Increased the Beneficial Effect on Rotational Behavior.

Hawlitschka Alexander A Holzmann Carsten C Wree Andreas A Antipova Veronica V

Toxins 20180911 9

Injection of botulinum neurotoxin-A (BoNT-A) into the striatum of hemiparkinsonian (hemi-PD) rats reduced apomorphine-induced rotation behavior significantly, for at least 3 months. Thereafter, rotation behavior increased again. We injected hemi-PD rats with 1 ng BoNT-A twice, the second injection following 6 months after the first one and tested the rats for apomorphine-induced rotations and spontaneous motor behaviors, i.e., corridor task and stepping test. To test the hypothesis that BoNT-A r ...[more]

PMID: 30208596

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Project description:ImportanceThere is an unmet need for safe and efficacious treatments for upper-extremity dystonic tremor (DT). To date, only uncontrolled retrospective case series have reported the effect of botulinum neurotoxin (BoNT) injections on upper-extremity DT.ObjectiveTo assess the effect of BoNT injections on tremor in patients with upper-extremity DT.Design, setting, and participantsIn this placebo-controlled, parallel-group randomized clinical trial, 30 adult patients with upper-extremity DT treated at a movement disorder clinic in a tertiary care university hospital were randomized in a 1:1 ratio to BoNT or saline injection, 0.9%, using a computer-generated randomization sequence. Randomization was masked using opaque envelopes. The participant, injector, outcome assessor, and statistician were blinded to the randomization. Participants were recruited between November 20, 2018, and December 12, 2019, and the last follow-up was completed in March 2020.InterventionsParticipants received electromyographically guided intramuscular injections of BoNT or placebo into the tremulous muscles of the upper extremity. Injection patterns and doses were individualized according to tremor phenomenologic findings.Main outcomes and measuresThe primary outcome was the total score on the Fahn-Tolosa-Marin Tremor Rating Scale 6 weeks after the intervention. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. All patients were offered open-label BoNT injections after 12 weeks and reassessed 6 weeks later.ResultsA total of 48 adult patients with a diagnosis of brachial dystonia with DT were screened. Fifteen were ineligible and 3 refused consent; therefore, 30 patients (mean [SD] age, 46.0 [18.6] years; 26 [86.7%] male) were recruited, with 15 randomized to receive BoNT and 15 to receive placebo. In the intention-to-treat group, the Fahn-Tolosa-Marin Tremor Rating Scale total score was significantly lower in the BoNT group at 6 weeks (adjusted mean difference, -10.9; 95% CI, -15.4 to -6.5; P < .001) and 12 weeks (adjusted mean difference, -5.7; 95% CI, -11.0 to -0.5; P = .03). More participants in the BoNT group reported global improvement on the Global Impression of Change (PGIC) assessment (PGIC 1, 2, and 3: BoNT: 4 [26.7%], 6 [40.0%], and 5 [33.3%]; placebo: 5 [33.3%], 10 [66.7%], and 0, respectively; P = .047). Subjective hand weakness (BoNT: 6 [40.0%]; placebo: 4 [28.6%], P = .52) and dynamometer-assessed grip strength (mean difference, -0.2 log10[kgf/m2]2/Hz-Hz; 95% CI, -0.9 to 0.4 log10[kgf/m2]2/Hz-Hz; P = .45) were similar in both groups.Conclusions and relevanceIn this randomized clinical trial, botulinum neurotoxin injections were superior to placebo in reducing tremor severity in upper-extremity DT. An individualized approach to muscle selection and dosing was beneficial without unacceptable adverse effects.Trial registrationClinical Trials Registry of India (http://ctri.nic.in) Identifier: CTRI/2018/02/011721.

Project description:Botulinum toxin-A (BoNT-A) is an effective treatment for cervical dystonia (CD) and spastic paresis (SP), but it requires in-depth knowledge of anatomy and injection techniques. The Ixcellence Network® is an educational programme to provide neurology, neuropaediatrics, and physical medicine and rehabilitation (PMR) specialists with access to best clinical practices and innovations regarding SP and CD management with BoNT-A. To assess the benefits of such educational programmes and identify unmet needs, a multidisciplinary scientific committee designed INPUT (INjection Practice, Usage & Training), an international multicentric survey describing training and practices among this trained and experienced population. A self-completed questionnaire was sent online to 553 trainees and 14 trainers from the Ixcellence Network®. Among the 131 respondents, 92% specialized in PMR (48%) or neurology (44%), with a mean experience of 15.5 years in their clinical fields and 10.9 years of BoNT-A injection. Most of them (98%) reported having received training before performing their first BoNT-A injection and attending specific courses on how to perform it without any instrumental guidance (76%), and with ultrasound (73%), electrical stimulation (44%) or electromyography (41%). In terms of practices, 92% of respondents reported using at least one guidance technique while injecting, with ultrasound being the most used technique (48%). Attending specific courses was significantly associated with greater self-confidence and use, e.g. for injection with ultrasound, mean self-confidence, on a scale from 1 (not confident) to 10 (fully confident), was 7.9 for trained respondents (vs 4.0 for untrained respondents, p < 0.001) of whom 70% stated that they used this technique regularly or systematically (vs. 11% of untrained healthcare professionals (HCPs), p < 0.0001). Moreover, 84% of respondents reported having trained colleagues, residents or fellows through theoretical (70%) or practical teaching in individuals (80%) or in small groups (65%). Overall, 86% of respondents reported a notable increase over the past 5 years of the number of patients treated with BoNT-A. INPUT is the first international survey describing training and practices in SP and CD management of physicians who attended a dedicated educational programme. The results highlighted the importance of training for self-confidence, and the use of specific techniques and new approaches.

Dataset Information

Repeated Intrastriatal Botulinum Neurotoxin-A Injection in Hemiparkinsonian Rats Increased the Beneficial Effect on Rotational Behavior.

Publications

Repeated Intrastriatal Botulinum Neurotoxin-A Injection in Hemiparkinsonian Rats Increased the Beneficial Effect on Rotational Behavior.

Similar Datasets

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