Corticospinal physiology in patients with Prader-Willi syndrome - A transcranial magnetic stimulation study

Background: Prader-Willi syndrome (PWS) is a genetic developmental disorder, mostly caused by a deletion on the paternal chromosome 15 or by a maternal uniparental disomy 15. Some PWS clinical and neurochemical features suggest an involvement of the corticospinal motor structures. Objective: To explore the corticospinal physiology of PWS by transcranial magnetic stimulation. Setting: A community-based hospital. Methods: We studied motor evoked potentials in the first dorsal interosseous muscle of 21 young-adult patients with PWS. Thirteen patients had a deletion at chromosome 15; 8 had a uniparental disomy. We measured the following variables: relaxed motor threshold, central motor conduction time, duration of the central silent period, and short-interval intracortical inhibition and facilitation. We also recorded F waves in the first dorsal interosseous muscle. We had 11 normal controls. Results: In the whole PWS group, motor threshold was higher as compared with controls (P<.05). The central motor conduction time, central silent period, and F waves were normal. Intracortical facilitation was reduced significantly (P<.001). Patients with PWS and a deletion had a weaker intracortical inhibition as compared with patients with PWS and a uniparental disomy (P<.05). Conclusions: Transcranial magnetic stimulation changes in patients with PWS suggested a hypo-excitability of the motor cortical areas. Defective neurogenesis of the cortical tissue and multiple transmitter alterations are the putative causes. Impaired intracortical inhibition might represent an electrical marker for a deletion defect.