Determinants of double discharges in amyotrophic lateral sclerosis and Kennedy disease

OBJECTIVE: Double discharges (DDs) of the motor unit are frequent in amyotrophic lateral sclerosis (ALS) and Kennedy's disease (KD). This likely reflects changes in the intrinsic properties of motor neurons but in ALS changes in corticomotoneuronal inputs may also contribute. We determined the corticomotoneuronal contribution to DDs. METHODS: DD prevalence, intra-doublet interval (IDI) of DDs and their timing with respect to transcranial magnetic stimulation (TMS)-induced primary peaks (PPs) in the peristimulus time histogram (PSTH) were measured in 23 ALS patients (96 motor units), 11 patients with KD (45 motor units) and 13 control subjects (60 motor units). RESULTS: In patients with KD more motor units (82%) fired DDs than in ALS patients (51%) and control subjects (63%); (p=0.013). DDs occurred before (pre-peak), during (peak), and after (post-suppression) the peristimulus time histogram (PSTH) primary peak. The prevalence of pre-peak DD in KD was 4.06-fold higher (95% CI 0.53-2.81; p=0.0014) than in controls. In contrast the prevalence of ALS peak DDs was 4.79-fold higher (95% CI 1.09-21.10; p=0.041) than in controls. Both pre-peak and peak IDIs were significantly prolonged in ALS compared with controls (p>0.003). Motor unit action potential (MUAP) amplitude, size of the excitatory postsynaptic potential (EPSP) and interspike interval (ISI) all correlated significantly with pre-peak, but not peak DD prevalence. CONCLUSIONS: A high peak DD prevalence with prolonged IDIs in ALS are consistent with complex, multiple descending corticomotoneuronal volleys, indicating that the upper motor neuron contributes to the generation of DDs in ALS. SIGNIFICANCE: Although double discharges are a manifestation of reinnervating motor neurons in ALS the corticomotoneuronal descending input is also influential and probably accounts for some of the distinguishing features of DDs in ALS.