Spread And Effectiveness Of Botulinum Neurotoxin A In Spastic Equinus In Cerebral Palsy

SPREAD AND EFFECTIVENESS OF BOTULINUM NEUROTOXIN A IN SPASTIC EQUINUS IN CEREBRAL PALSY:SHORT-TERM STUDY

Objectives. To study the short-term neurophysiological and clinical outcome of botulinum toxin type A(BoNT-A), injected at standard doses, and assess toxin spread to neighboring uninjected muscles in children with cerebral palsy.

Subjects and methods. The investigators studied 18 ambulatory children with dynamic equinus foot deformity (mean age 6.1 years). The gastrocnemius muscle on the affected side was injected with BoNT-A (Dysport, range from 8.9-19.4 U/kg). As the primary neurophysiological outcome measure, compound muscle action potential (CMAP) areas were assessed in the lateral gastrocnemius (LG) and tibialis anterior(TA) muscles on the treated and untreated side before BoNT-A injections (T0), and on days 10 (T10), and 30 (T30) after injections. Clinical scales were assessed and video gait was analyzed at all three time points.

Results. In all patients, CMAP areas recorded from the LG and TA muscles on the treated side decreased significantly from pre-injection values at T10 (p<0.05) and T30 (p<0.002). Assessment at both time points after injections also showed that ankle spasticity had diminished (p<0.05), equinus foot excursion increased (p<0.05), and functional gait improved (p<0.05).

Conclusion. Although BoNT-A injected at standard doses improves gait in children with spastic equinus foot the toxin spreads to uninjected leg muscles. BoNT-A treatment for cerebral palsy therefore needs individualizing according to the child's clinical features.

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy and Botulinum Toxin
• Intervention / Treatment: Drug: Botulinum Toxin Type A

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 9 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• spasticity refractory to oral medication
• patients able to walk independently or with aid
• no contraindications to BoNT-A treatment such as fixed contracture,aminoglycoside therapy and myasthenia gravis and no other neuromuscular diseases
• no orthopedic surgery before
• normal or mildly declined cognition
• previous treatment at least six months before the study

Exclusion Criteria:

• all contraindications to BoNT-A treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: botulinum toxin A; botulinum toxin A diffusion in cerebral palsy	Drug: Botulinum Toxin Type A; BoNT-A (Dysport, Ipsen) ,into the medial gastrocnemius (MG) and LG muscles unilaterally on the affected spastic hemiplegic side; dose mean± SE, 283.3± 24.7 U.. The mean dose/kg injected was 14.4± 0.8, range from 8.5 to 20 U/kg, diluted in 2.5 ml saline. frequency: once.; Other Names: dysport, ipsen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BoNT-A injected into gastrocnemius within standard dose ranges spreads to surrounding anterior lower-limb muscles in children with CP and induces chemodenervation in injected muscles	As the primary neurophysiological outcome measure of BoNT-A induced paresis and spread, we studied changes in compound muscle action potential (CMAP) areas recorded from the lateral gastrocnemius (LG) muscle after injecting BoNT-A and from the ipsilateral tibialis anterior (TA) muscle in children with spastic hemiplegia. In line with others we considered a decreased CMAP area from LG muscle injected with BoNT-A as the neurophysiological index of BoNT-A-induced paresis	one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the short-term clinical effect of BoNT-A injected within standard dose ranges on changes in gait in children with CP	As the clinical outcome measures clinical scales were assessed and video gait was analyzed before BoNT-A injections (T0), and on days 10 (T10), and 30 (T30) after injections.	30 days

Collaborators and Investigators

• Sponsor: Universita di Verona
• Investigators: Study Director: laura bertolasi, md, Universita di Verona

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: January 10, 2011
• First Submitted That Met QC Criteria: January 12, 2011
• First Posted (Estimate): January 13, 2011

Study Record Updates

• Last Update Posted (Estimate): January 19, 2011
• Last Update Submitted That Met QC Criteria: January 18, 2011
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: BoNT-A-botulinum neurotoxin type A; CMAP-compound muscle action potential; CP-cerebral palsy; LG-lateral gastrocnemius; MG-medial gastrocnemius; TA-tibialis anterior; PROMS-passive range of movement; MAS-modified Ashworth scale; EVGS-Edinburgh visual gait scale; GMF-CS-gross motor function classification system
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Damage, Chronic; Cerebral Palsy; Paralysis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: CE1780