Impairment of callosal and corticospinal system function in adolescents with early-treated phenylketonuria: a transcranial magnetic stimulation study

The transcranial activation and the conduction properties of corticospinal and callosal neurons were investigated in 12 early-treated adolescents (age d 17.3, SD 3.5 years; range 14-27 years) with phenylketonuria (PKU) by foca l transcranial magnetic stimulation (fTMS) of the motor cortex. The patient s had no functionally relevant motor disturbances in daily life or on clini cal testing. Corticospinally mediated excitatory (response thresholds, ampl itudes, central motor latencies) and inhibitory [duration of postexcitatory inhibition (PI)] effects of FTMS were investigated in contralateral hand m uscles. Transcallosal inhibition (TI) (onset latency, duration, transcallos al latency) of tonic electromyographic (EMG) activity was tested in ipsilat eral muscles. Peripheral motor latencies were determined for responses elic ited by magnetic stimulation over cervical nerve roots. Ten normal subjects served as controls. Since in all PKU patients, central and peripheral moto r latencies were normal, no neurophysiological indication of a demyelinatio n of corticospinal or peripheral motor fibres was found. However, cortical thresholds of corticospinally mediated responses were increased (52.1, SD 1 1.6% versus 35.0, SD 7.4% of maximum stimulator output; P < 0.05; n = 24 ha nds) and their amplitudes reduced (2.9, SD 1.4 mV Versus 6.1, SD 1.5 mV, P < 0.05). The duration of PI was shortened (132, SD 53 ms versus 178, SD 57 ms; P < 0.05). TI was absent in 37.5% of the investigated hands or tended t o be weak. When TI was present, its onset latencies (38.0, SD 3.6 ms versus 34.7, SD 3.3 ms) and transcallosal latencies were prolonged (18.5, SD 3.8 ms versus 14.8, SD 3.2 ms), while its duration was normal. These abnormal e xcitatory and inhibitory effects of fTMS suggest a reduced susceptibility o f cortical excitatory and inhibitory neuronal structures compatible with a loss of neurons or a rarefication of their dendrites.