Lack of intracortical facilitation to paired-pulse TMS in patients with “idiopathic RBD”: a preclinical marker of synucleinopathy?

Background and aims: Transcranial magnetic stimulation (TMS) provides several measures of motor cortex excitability in vivo, even subclinically. TMS changes, namely a reduced intracortical inhibition and facilitation, have been reported in Parkinson’s disease, even in its early stage. REM sleep behavior disorder (RBD) often precedes the onset of synucleinopathies, although very few TMS studies have been carried out so far. Methods: 60 patients with idiopathic RBD (median age 62.0 years, range 57.0-72.0; median disease duration: 3 years, range 1-4) and six age-matched healthy subjects (median age 62.0 years, range 56.0-65.0) underwent single- and pairedpulse TMS. Resting motor threshold, cortical silent period, latency and amplitude of motor evoked potentials, central motor conduction time, short-latency intracortical inhibition, and intracortical facilitation (ICF) were recorded through a figure-of-eight coil from the right first dorsal interosseus muscle. All participants were right-handed and drug-free. A screening for cognitive status, depressive symptoms, and diurnal sleepiness was also performed. Results: Neurological examination was normal and no cognitive deficit, depression, or excessive sleepiness were detected in all participants. Compared to controls, patients exhibited a significant loss of ICF (median 0.6, range 0.1-1.1 vs. 1.4, range 1.4-1.8; p<0.05). The other TMS measures did not differ between the groups. Conclusion: This finding suggests a subclinical electrocortical dysfunction in patients with RBD, raising the possibility that impaired ICF might precede the onset of an overt extrapyramidal syndrome. Such an impairment may result from an excitatory/inhibitory imbalance within intracortical motor circuits. RBD confirms to be a potential determinant of future neurodegeneration also at the TMS level.