Cortical excitability testing distinguishes Kennedy's disease from amyotrophic lateral sclerosis

Spinobulbomuscular atrophy, or Kennedy's disease (KD), is an X-linked inherited neurodegenerative disorder that clinically may "mimic" amyotrophic lateral sclerosis (ALS). Although KD is regarded as a pure lower motor neuron disorder, recent studies have reported on the presence of corticomotoneuron dysfunction in KD, similar to ALS. To clarify these discordant findings, the present study applied novel threshold tracking transcranial magnetic stimulation (TMS) techniques to gain further insights into corticomotoneuron function and thereby possible pathophysiological processes underlying neurodegeneration in KD.

Cortical excitability studies were undertaken in 7 KD patients, 55 normal controls, 45 ALS patients and 6 patients with the flail arm variant ALS (FAV), a pure lower motor neuron form of ALS. Motor evoked responses were recorded over abductor pollicis brevis.

Short-interval intracortical inhibition (SICI) in KD was similar to controls (KD 6.0+/-1.2%; controls 8.4+/-1.1%, P=0.08), but significantly greater when compared to ALS and FAV patients (ALS 0.7+/-0.7%; FAV -0.8+/-0.7%, P<0.0001). The magnetic stimulus-response curve gradient, motor evoked potential amplitude and cortical silent period duration in KD patients were similar to controls. In ALS and FAV patients, the magnetic stimulus-response curve gradient (ALS and FAV, P<0.01) and motor evoked potential amplitude (ALS and FAV, P<0.05) were significantly increased, while the cortical silent period duration was reduced (ALS, P<0.001) when compared to KD patients.

Threshold tracking TMS techniques have established normal corticomotoneuron function in KD, clearly differentiating KD from ALS.

The present study has established normal cortical excitability in KD, inferring a lack of significant cortical involvement in this disease.