Safety profile of incobotulinum toxin A [Xeomin(®)] in gastrocnemious muscles injections in children with cerebral palsy: Randomized double-blind clinical trial.

BACKGROUND: The only two preparations of botulinum toxin A for which there are published evidences of efficacy in children with cerebral palsy are onabotulinum toxin A (Botox(®)) and abobotulinum toxin A (Dyport(®)); these toxins should be considered generally safe and appropriate in the treatment for localized upper and lower limb spasticity. AIMS: To establish the safety profile of incobotulinum toxin A (Xeomin(®)) in children with cerebral palsy and muscle spasticity. METHODS: Randomized double-blind controlled trial that involved the recruitment of children of both sexes with spastic hemiplegia or diplegia in cerebral palsy, aged between 3 and 18 years. Children were randomized to either the study group (SG, incobotulinum toxin A) or the control group (CG, onabotulinum toxin A) both to be injected with 5units/kg on gastrocnemius (medialis and lateralis) muscles. The occurrence of adverse events at baseline, after 48 h, 10 days and 3 months was recorded by the caregivers in a checklist that listed both common and uncommon side effects. RESULTS: 35 patients were treated (CG = 18; SG = 17); the 2 groups were well balanced regarding demographics and anthropometry characteristics. At least 1 adverse event occurred in 49% of patients within first 2 days, 46% between 2 and 10 days, and 12% between 10 and 90 days. All the reported events were minor; no serious adverse event was recorded. Fatigue was the most frequent complaint. There was no significant difference in frequency and type of events between the 2 groups. CONCLUSION: Incobotulinum toxin A and onabotulinum toxin A share similar profile of safety in the treatment of lower limb spasticity in CP children.

Multidimensional outcome measure of selective dorsal rhizotomy in spastic cerebral palsy.

BACKGROUND: One of the treatment option to reduce spasticity in cerebral palsy children is selective dorsal rhizotomy. Several studies have demonstrated short and long term improvements in gait and other activities after rhizotomy but this surgery still remains a controversial procedure and patient outcome indicators measures are not uniform. AIMS: To describe our assessment and outcome evaluation protocol and to verify by this protocol short term results of rhizotomy. METHODS: We recruited 9 cerebral palsy children (mean age 7.9 years ± 3.2) affected by mild to moderate spastic diplegia and operated by rhizotomy. Patients were studied preoperatively and at 12 months after surgery by the following clinical and instrumental measures correlated to the International Classification of Functioning: modified Ashworth Scale, passive Range of Motion, Medical Research Council Scale, Selective Motor Control Scale, 3D-motion analysis and energy cost of locomotion measurements (indicators of "body functions"); Gross Motor Functional Measure and Motor Functional Independence Measure (indicators of "activities and participation"). RESULTS: Our data showed, after rhizotomy, reduction of spasticity specially in plantarflexors muscles (p < 0.01), increase of strength of knee flexors/extensors and foot plantar/dorsiflexion muscles (p < 0.01), improvement of selective motor control (p < 0.05), more similar spatio-temporal parameters of gait analysis to healthy subjects, reduced equinus foot and knees hyperflexion as energy cost. CONCLUSION: The complementary use of multiple indicators may improve the evaluation of the results of dorsal rhizotomy. A beneficial outcome measured by these indicators has been found in our spastic diplegic children one year after rhizotomy.

Cytosolic pH buffering during exercise and recovery in skeletal muscle of patients with McArdle's disease.

Cellular pH control is important in muscle physiology, and for interpretation of (31)P magnetic resonance spectroscopy (MRS) data. Cellular acidification in exercise results from coupled glycolytic ATP production mitigated by cytosolic buffering, 'consumption' of H(+) by phosphocreatine (PCr) breakdown, and membrane transport processes. Ex vivo methods for cytosolic buffer capacity are vulnerable to artefact, and MRS methods often require assumptions. (31)P MRS of early exercise, when pH increases unopposed by glycolysis, is conceptually simple, but limited in normal muscle by time resolution and signal-to-noise. A therapeutic trial (Martinuzzi A et al. Musc Nerve 37: 350-357, 2007) in McArdle's disease (glycogen phosphorylase deficiency), where pH does not decrease with exercise, offered the opportunity to test (31)P MRS data obtained throughout incremental plantar flexion exercise and recovery in ten McArdle's patients against the simple model of cellular pH control. Changes in pH, [Pi] and [PCr] throughout exercise and recovery were quantitatively consistent with mean +/- SEM buffer capacity of 10 +/- 1 mM/(pH unit), which was not significantly different from the control subjects under the initial-exercise conditions where the comparison could be made. The simple model of cellular acid-base balance therefore gives an adequate account of cellular pH changes during both exercise and recovery in McArdle's disease.

Randomized, placebo-controlled, double-blind pilot trial of ramipril in McArdle's disease.

McArdle's disease causes limitation in exercise capacity as well as disability, the severity of which has been associated with the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) haplotype-patients with the genotype associated with higher ACE activity show the most severe phenotype. Modulation of ACE activity through the use of inhibitors may thus positively affect disease expression. In a double-blind, randomized, placebo-controlled trial, we assessed the efficacy of an ACE inhibitor (2.5 mg ramipril) in 8 patients with McArdle's disease. End-points were changes in parameters of exercise physiology (cycloergometer and muscle 31P-magnetic resonance spectroscopy), quality of life (QoL) according to the Short Form 36 (SF-36), and disability according to the World Health Organization-Disability Assessment Scale II (WHO-DAS II). Patients had lower QoL and higher disability than controls. Measures of exercise physiology were not changed by ramipril in the whole group, but treatment induced higher peak VO2 (P = 0.017) in ACE D/D patients, yet not in I/D patients. Treatment significantly improved disability (P < 0.05). McArdle's disease is a disabling condition affecting patients' QoL. Treatment with ramipril improves disability and modifies exercise physiology only in D/D patients, raising the possibility of a differential haplotype-linked sensitivity to the treatment.