A ten-week clinical case investigation conducted at the Cerebral Palsy Reference Center of the University Hospitals Leuven demonstrated that combining daily L-leucine supplementation with a structured plantar flexor resistance training program yielded improvements in functional strength and overall fat-free mass in a seven-year-old girl with spastic cerebral palsy, yet failed to reverse pre-existing deficits in medial gastrocnemius muscle volume and cross-sectional area. The pediatric patient, who was diagnosed with bilateral diplegic spastic cerebral palsy classified at Gross Motor Function Classification System level II, showed high adherence to the nutritional protocol alongside moderate completion of the exercise regimen, with no biochemical side effects or adverse events documented throughout the trial. Despite these functional and systemic gains, macroscopic ultrasound imaging confirmed that targeted muscle hypertrophy remained absent over the study window, underscoring the complex morphological barriers that characterize neuromuscular pathology in this population.

Cerebral palsy represents the leading etiology of physical disability during childhood, presenting an estimated prevalence of 1.48 cases per 1,000 live births in Belgium. The underlying condition arises from a non-progressive insult to the developing fetal or infant brain, which subsequently triggers musculoskeletal alterations that advance progressively as children age. Among these progressive structural changes, alterations in muscle morphology emerge from an early age, typically characterized by reduced muscle belly length, diminished cross-sectional area, and restricted overall muscle volume relative to typically developing peers. While traditional resistance training programs have been widely promoted to stimulate muscle protein synthesis in children with cerebral palsy, published evidence regarding their direct capacity to enhance muscle size remains inconclusive. Combining resistance exercise with amino acid supplementation has therefore been proposed to counteract progressive muscle wasting by delivering targeted anabolic stimuli.

Within skeletal muscle physiology, dietary protein increases alone do not automatically induce muscular growth, directing scientific interest toward the unique properties of leucine. This specific branched-chain essential amino acid functions as a fundamental regulator capable of both driving muscle protein synthesis and suppressing muscle protein breakdown, largely through its selective capacity to modulate anabolic signaling via the mechanistic target of rapamycin pathway. Prior clinical investigation exploring this pathway evaluated a ten-week regimen of L-leucine supplementation in adolescents and adults with cerebral palsy, measuring combined biceps brachii and brachialis volume alongside elbow flexor strength. That earlier randomized controlled trial identified a 25.4 percent gain in muscle strength and a 3.6 percent expansion in muscle volume, accompanied by a 59.1 percent reduction in systemic C-reactive protein levels. However, that prior trial neither incorporated an active exercise component nor included pediatric subjects, leaving unaddressed whether nutritional supplementation combined with mechanical muscle activation is feasible or effective in younger children facing early-onset muscle growth impairments.

The participant recruited for this preliminary feasibility protocol was a seven-year-old girl with bilateral spastic cerebral palsy primarily affecting her right lower extremity. Her medical background linked the cerebral palsy to periventricular leukomalacia situated predominantly within the parieto-occipital regions following premature delivery at 32 weeks of gestation, accompanied by cerebral visual impairment and delayed motor milestones with independent ambulation achieved at roughly 21 months. Although capable of independent indoor and outdoor ambulation and enrolled in mainstream education, she experienced notable difficulties negotiating irregular terrain or cycling. Her standard therapeutic management included physical therapy sessions three times weekly, bilateral daytime Leaf Spring ankle-foot orthoses worn during school hours, and a rigid ankle-foot orthosis fitted to her right leg during nighttime rest. Additionally, she had received an intramuscular injection of botulinum neurotoxin in the right medial gastrocnemius at five years of age, without any history of surgical intervention.

Conducted under an institutional ethics committee-approved protocol registered under identifier NCT06044168 on ClinicalTrials.gov, the intervention integrated daily oral amino acid supplementation with a personalized plantar flexor strengthening routine over a ten-week period. Based on pediatric ESPGHAN nutritional guidelines and prior clinical literature, the child received oral L-leucine powder administered at a dosage of 150 milligrams per kilogram of body weight per day. The total daily allocation was divided into two equal morning and evening servings, which her parents routinely dissolved in milk using a shaker bottle to accommodate her beverage preferences. The complementary exercise program was customized according to her baseline performance on a 30-second repetition maximum heel-raise test using the Holten diagram to calibrate intensity. On three non-consecutive days each week, the training targeted 80 percent of maximal capacity through three sets of 8 to 12 repetitions involving bilateral heel raises followed by unilateral heel lowering. On the remaining four days, the regimen involved a single set of 20 to 30 bilateral heel raises and bilateral descents at 50 percent capacity, consistently scheduled within one hour following supplement ingestion.

The feasibility of the dual protocol was systematically evaluated through parent-completed daily logbooks, weekly telephone check-ins, and scheduled clinical evaluations. Exercise performance was supervised at home by the child’s parents following detailed instruction, alongside technical verification by her regular physical therapist during weekly clinical sessions and during a formal hospital evaluation at two weeks. Across the full ten weeks, overall compliance reached 84 percent for L-leucine supplement intake and 66 percent for completion of the prescribed calf exercise sessions. The child’s parents recorded that although the taste of the unflavored amino acid powder was described as unpleasant, the supplement was ingested smoothly when blended into milk. In contrast, parental logs documented variable ease in securing daily adherence to the physical exercise regimen. No clinical adverse events were reported by the family on the structured post-intervention safety questionnaire.

Laboratory evaluations of blood and urine samples obtained at enrolment and during week two revealed no contraindications to amino acid administration, with subsequent testing demonstrating an absence of biochemical side effects. Notably, circulating prealbumin concentrations increased from a baseline level of 0.18 grams per liter to 0.21 grams per liter at the conclusion of the ten weeks. Prealbumin, synthesized by the liver, serves as a sensitive indicator of fluctuations in systemic protein status and is recognized as a surrogate marker for lean tissue mass. Nutritional assessments using a three-day estimated food record at baseline documented an intake of 89.34 kilocalories per kilogram per day and 3.98 grams of protein per kilogram per day, positioning her baseline intake at the upper threshold of age-specific dietary recommendations. Animal sources accounted for 58.30 percent of dietary protein, plant sources supplied 38.57 percent, and mixed sources provided 3.40 percent, distributed across the day as 13.38 percent in the morning, 41.44 percent at midday, and 45.19 percent in the evening. A post-intervention three-day food record confirmed comparable dietary energy and protein consumption independent of the experimental supplement.

Macroscopic alterations within the right medial gastrocnemius were evaluated at four formal hospital milestones utilizing three-dimensional freehand ultrasonography, which synchronized B-mode probe scanning with optical motion tracking markers to reconstruct anatomical structures. Absolute linear measurements showed modest elongations in muscle belly length, tendon length, and total muscle-tendon unit length from pre- to post-intervention, alongside concurrent reductions in cross-sectional area and overall muscle volume. Nevertheless, none of these observed changes exceeded the established intra-rater inter-session standard error of measurement, indicating that the dimensional fluctuations fell within normal technical scanning variance. Deficit z-scores derived from normative percentile curves demonstrated persistent muscle deficits relative to typically developing peers, with slight reductions in belly and tendon length deficits counterbalanced by expanding deficits in muscle volume and cross-sectional area.

Crucial context for interpreting the ultrasound findings emerged from the child’s pre-intervention longitudinal history, which included four sequential ultrasound assessments recorded between 3.95 and 6.85 years of age during an earlier observational tracking study. Across this extended developmental timeline, absolute muscle volume and cross-sectional area exhibited two distinct downward trajectories. The initial contraction occurred following the botulinum neurotoxin injection administered to the right medial gastrocnemius between the first and second follow-up measurements. A secondary downward trend commenced at the third follow-up milestone, aligning with progressive natural history trajectories documented across broader clinical databases of children with spastic cerebral palsy. Consequently, the anatomical shrinkage noted during the ten-week supplementation and exercise period did not represent an acute adverse response to training, but rather the unbroken continuation of a degenerative trend that had already been established prior to enrollment.

To contextualize the participant’s developmental path, the investigative team mapped her imaging metrics against longitudinal databases comprising 62 typically developing children across 236 assessments and 116 children with spastic cerebral palsy across 383 assessments receiving usual physical therapy and orthotic care without amino acid therapy. Against this broader cohort, the girl’s individual z-scores reflected substantial fluctuations influenced by natural anthropometric changes in height and body mass. Whole-body physiological responses assessed through bio-electrical impedance analysis demonstrated an overall gain of 1.1 kilograms in total body mass, composed of a 1.3-kilogram expansion in fat-free mass alongside a 0.2-kilogram reduction in fat mass. Furthermore, functional strength measurements evaluating the 30-second repetition maximum heel-raise test recorded consistent performance gains across all bilateral and unilateral testing trials, confirming meaningful improvements in operational motor capacity.

In evaluating why systemic fat-free mass and functional strength improved without corresponding local muscle hypertrophy, the researchers highlighted intrinsic histopathological alterations characteristic of spastic cerebral palsy. Skeletal muscle in this condition frequently displays altered cellular composition, characterized by extensive interstitial collagen deposition, intramuscular adipose infiltration, and a reduced proportion of functional contractile elements, which together may diminish responsiveness to mechanical loading and nutritional cues. Furthermore, potential anabolic resistance linked to chronic low-grade inflammation has been postulated in the literature, although empirical proof remains unverified. Concluding that the ten-week trial duration may have been insufficient to stimulate detectable macroscopic remodeling in compromised muscle architecture, the authors recommended future randomized controlled trials incorporating extended intervention periods. Such future studies should implement pre-intervention longitudinal monitoring or double baseline assessments to account for existing negative growth trajectories, rigorously assess baseline nutritional status, and incorporate targeted strategies to sustain rigorous compliance during demanding pediatric exercise routines.

Subject of Research: Feasibility and physiological effects of combined L-leucine supplementation and strength training in pediatric spastic cerebral palsy

Article Title: Leucine supplementation and exercise to enhance muscle development in a child with spastic cerebral palsy: a case report

Article References: Verreydt, I., Van Campenhout, A., Ortibus, E., Rymen, D., & Desloovere, K. (2026). Leucine supplementation and exercise to enhance muscle development in a child with spastic cerebral palsy: a case report. Discover Medicine, 3(1), Article 136. https://doi.org/10.1007/s44337-026-00699-1

Image Credits: AI Generated

DOI: 10.1007/s44337-026-00699-1

Keywords: Cerebral palsy, L-leucine, Pediatric rehabilitation, Muscle growth, Resistance training, Medial gastrocnemius, Three-dimensional ultrasonography, Bio-electrical impedance analysis, Leucine, supplementation, exercise, enhance