Medium-term functional benefits in children with cerebral palsy treated with botulinum toxin type A: 1-year follow-up using gross motor function measure.

Department of Neuropaediatrics and Muscle Disorders, Children's University Hospital, Freiburg, Germany.
European Journal of Neurology (Impact Factor: 4.16). 11/2001; 8 Suppl 5:120-6. DOI: 10.1046/j.1468-1331.2001.00044.x
Source: PubMed

ABSTRACT One of the main goals when treating spasticity is to relieve pain and improve function. Intramuscular injection of botulinum toxin type A (BTX-A) has gained widespread acceptance in the treatment of spastic cerebral palsy. Several studies have clearly shown the short-term functional benefit of BTX-A treatment. Information is limited, however, on the efficacy of medium and long-term regimens, using repeated injection of BTX-A. The aim of the present open-label, prospective study was to evaluate functional outcome in children with spastic cerebral palsy after 1 year of treatment with BTX-A, using the Gross Motor Function Measure (GMFM) as a validated outcome measure. Patients (n=25, age 1.5--15.5 years) were treated with BTX-A for adductor spasm (n=12) or pes equinus (n=13). The local effect was evaluated using passive range of motion and modified Ashworth Scale. Apart from a significant improvement in joint mobility and reduction of spasticity compared to pretreatment values (P < 0.01), we demonstrated a significant improvement of gross motor function after 12 months of treatment, with a median gain of 6% in total and goal scores (P < 0.001). An increase in GMFM scores was particularly evident in younger and moderately impaired children (Gross Motor Function Classification System level III). Whether the observed improvement in gross motor function in children with cerebral palsy is specifically related to therapy with BTX-A or represents at least in part the natural course of motor development still needs clarification.

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    ABSTRACT: With evidence for an atrophic effect of botulinum toxin type A (BoNT-A) documented in typically developing muscles, this study investigated the immediate morphological alterations of muscles in children with cerebral palsy (CP) after BoNT-A treatment. Fifteen children (10 males, five females; age range 5-11y, mean age 8y 5mo, SD 1y 10mo) with spastic diplegic CP [Gross Motor Function Classification System Levels I (n=9) and II (n=6)] receiving BoNT-A injections for spasticity management were included. None of the children was a first-time receiver of BoNT-A. Magnetic resonance imaging and Mimics software assessed muscle volume, timed 2 weeks before and 5 weeks after injection. All participants received BoNT-A bilaterally to the gastrocnemius muscle, and five participants also received BoNT-A bilaterally to the medial hamstring muscles. Functional assessment measures used were the 6-Minute Walk Test (6-MWT), the Timed Up and Go (TUG) test, and hand-held dynamometry. Whilst total muscle group volume of the injected muscle group remained unchanged, a 4.47% decrease in the injected gastrocnemius muscle volume (p=0.01) and a 3.96% increase in soleus muscle volume (p=0.02) was evident following BoNT-A. There were no statistically significant changes in function after BoNT-A as assessed by the TUG. There was also no statistically significant change in distance covered in the 6-MWT. Muscle strength, as assessed using hand-held dynamometry was also not statistically different after BoNT-A treatment. Muscle volume decreases were observed in the injected muscle (gastrocnemius), with synergistic muscle hypertrophy that appeared to compensate for this decrement. The 4% to 5% decrease in the volume of BoNT-A injected muscles are not dramatic in comparison to reports in recent animal studies, and are a positive indication for BoNT-A, particularly as it also did not negatively alter function.
    Developmental Medicine & Child Neurology 06/2013; · 2.68 Impact Factor
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    ABSTRACT: Antigen recognition by T-lymphocytes through the T-cell antigen receptor, TCR-CD3, is a central event in the initiation of an immune response. CD3 proteins may have redundant as well as specific contributions to the intracellular propagation of TCR-mediated signals. However, to date, the relative role that each CD3 chain plays in signaling is controversial. In order to examine the roles of CD3γ chain in TCR signaling, we analyzed proximal and distal signaling events in human CD3γ(-/-) primary and Herpesvirus saimiri (HVS)-transformed T cells. Following TCR-CD3 engagement, certain early TCR signaling pathways (ZAP-70, ERK, p38 and mTORC2 phosphorylation, and actin polymerization) were comparable with control HVS-transformed T cells. However, other signaling pathways were affected, such TCRζ phosphorylation, indicating that the CD3γ chain contributes to improve TCR signaling efficiency and survival. On the other hand, CD3γ(-/-) primary invariant NKT cells (iNKT cells) showed a normal expansion in response to alpha-galactosylceramide (α-GalCer) and TCRVβ11(bright) iNKT cells were preferentially selected in this in vitro culture system, perhaps as a consequence of selective events in the thymus. Our results collectively indicate that a TCR lacking CD3γ can propagate a number of signals through the remaining invariant chains, likely the homologous CD3δ chain, which replaces it at the mutant TCR.
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    ABSTRACT: Aim  Previous studies have shown the efficacy of botulinum toxin type A (BoNT-A) in the management of ambulant individuals with cerebral palsy (CP). There is little evidence on its use in non-ambulant children with CP. This review aimed to investigate indications and efficacy for BoNT-A use in managing pain, care, and comfort, and improving function in children with CP in Gross Motor Function Classification System (GMFCS) levels IV and V. Method  Electronic databases were searched from the earliest available date to June 2012 using a combination of subject headings and free text. Inclusion criteria consisted of studies with (1) participants aged 18 or under, (2) participants with CP in GMFCS levels IV and V, (3) participants receiving BoNT-A treatment, and (4) studies published in English-language peer-reviewed journals. Results  The search resulted in a total of 814 studies, of which 19 met the inclusion criteria. Eighteen studies provided level IV or V evidence and one level I evidence according to the American Academy for Cerebral Palsy and Developmental Medicine guidelines for the development of systematic reviews. Most of the studies were of weak to moderate methodological quality. Interpretation  The evidence that BoNT-A is effective in reducing postoperative pain in children with CP in GMCFS levels IV and V is limited, with only one level I study identified. Remaining indications were general pain reduction, maintaining hip integrity, achieving functional changes, and goal attainment. A high percentage of participants in the studies showed positive changes in these areas. With the poor level of evidence of the included studies, no definite conclusion could be drawn on the indications for BoNT-A use in children with CP in GMCFS levels IV and V. Further investigation by rigorous studies is required.
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