Neuromuscular Junctions in Cerebral Palsy: Presence of Extrajunctional Acetylcholine Receptors

BACKGROUND: Cerebral palsy (CP) is the most prevalent neurologic disease in children. A primary deficit in CP is neuromuscular dysfunction; however, neuromuscular junctions in children with CP have not been studied. Evidence exists that up-regulation of acetylcholine receptors (AChRs) may be present in children with CP, and the current study was undertaken to examine this possibility. METHODS: Thirty-nine children with spastic CP and 25 neurologically normal children were enrolled in the study. Paraspinal muscles underwent biopsy during scheduled spinal fusion surgery. Two sets of assessments were performed on the biopsy specimens: (1) reverse-transcription polymerase chain reaction and Western blotting to evaluate the expression of the gamma subunit of the AChR; and (2) histologic evaluation using a double-stain technique for AChR and acetylcholinesterase, wherein acetylcholinesterase staining defined the limits of the neuromuscular junction, and AChR staining that appeared outside of these limits indicated an abnormal distribution of AChRs. RESULTS: Reverse-transcription polymerase chain reaction and Western blot analyses showed that neither the CP nor non-CP samples had detectable gamma-AChR subunit. Histologic analysis indicated that 11 of 39 children with CP and none of 20 children with idiopathic scoliosis scored positive for the presence of AChR outside of the neuromuscular junction (P = 0.0085). CONCLUSION: A subset of children with CP have an abnormal distribution of AChR relative to the acetylcholinesterase found at the neuromuscular junction. The altered distribution of AChR in CP was not associated with a detectable presence of the gamma-AChR subunit, suggesting that the nonjunctional AChRs in CP does not contain the gamma subunit.