Reduced Cross-Sectional Muscle Growth Six Months after Botulinum Toxin Type-A Injection in Children with Spastic Cerebral Palsy

Abstract

Botulinum Neurotoxin type-A (BoNT-A) injections are widely used as first-line spasticity treatment in spastic cerebral palsy (SCP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised. Yet, the risk of initiating BoNT-A to reduce muscle growth remains unclear. This study investigated medial gastrocnemius (MG) morphological muscle growth in children with SCP (n = 26, median age of 5.2 years (3.5)), assessed by 3D-freehand ultrasound prior to and six months post-BoNT-A injections. Post-BoNT-A MG muscle growth of BoNT-A naive children (n = 11) was compared to (a) muscle growth of children who remained BoNT-A naive after six months (n = 11) and (b) post-BoNT-A follow-up data of children with a history of BoNT-A treatment (n = 15). Six months after initiating BoNT-A injection, 17% decrease in mid-belly cross-sectional area normalized to skeletal growth and 5% increase in echo-intensity were illustrated. These muscle outcomes were only significantly altered when compared with children who remained BoNT-A naive (+4% and −3%, respectively, p < 0.01). Muscle length growth persevered over time. This study showed reduced cross-sectional growth post-BoNT-A treatment suggesting that re-injections should be postponed at least beyond six months. Future research should extend follow-up periods investigating muscle recovery in the long-term and should include microscopic analysis.

The Short-Term Impact of Botulinum Neurotoxin-A on Muscle Morphology and Gait in Children with Spastic Cerebral Palsy

“…Muscle growth rates, calculated over the period between the two assessments, were not significantly different from the control group. Several studies have reported similar rates of muscle atrophy after BoNT-A injections [ 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 52 ].…”

“…A recent study by De Beukelaer et al was the first to quantify the BoNT-A effect on muscle morphology in an intervention group compared to a control group of children who did not receive BoNT-A treatment. They showed a reduction in anatomical cross-sectional area six months after the first BoNT-A injection, which was not observed in the control group of children, who remained BoNT-A naive during this period [ 26 ]. They did not find any significant between group differences in muscle volume following BoNT-A.…”

“…Yet, knowledge on BoNT-A-impact on muscle morphology in a pediatric SCP population is important, specifically since muscle growth is already impaired in SCP from an early age on [ 24 ]. Moreover, multiple studies showed that muscle volume and muscle quality can be negatively influenced by BoNT-A [ 25 , 26 , 27 , 28 , 29 , 30 ]. It has also been shown that SCP muscles have a reduced number of satellite cells, suggesting that the regenerative capacity of the muscle might not be sufficient to ensure efficient muscle recovery, for example to overcome the potential paralysis-induced atrophy following BoNT-A injections [ 17 , 31 , 32 ].…”

“…Different research centers [ 40 , 41 , 42 ], as well as previous BoNT-A treatment recommendations, reported repeated injections every six months or even less, while other centers reported intervals between repeated BoNT-A sessions of more than one year. Interestingly, the most recent recommendations advise an interval of at least one year [ 18 , 26 , 43 ]. Previous animal [ 22 ] and human [ 21 , 26 ] studies indeed showed that muscles are not recovered after six months.…”

“…Interestingly, the most recent recommendations advise an interval of at least one year [ 18 , 26 , 43 ]. Previous animal [ 22 ] and human [ 21 , 26 ] studies indeed showed that muscles are not recovered after six months. Multiple experts have asserted the need to revise treatment protocols as irreversible muscle atrophy may occur and the detrimental effects might become more severe after multiple injections [ 44 ].…”