Reciprocal inhibition and corticospinal transmission in the arm and leg in patients with autosomal dominant pure spastic paraparesis (ADPSP).

The pathophysiological mechanisms underlying the development of spasticity are not clear, but the excitability of the disynaptic reciprocal inhibitory pathway is affected in many patients with spasticity of different origin. Patients with genetically identified autosomal dominant pure spastic paraparesis (ADPSP) develop spasticity and paresis in the legs, but usually have no symptoms in the arms. Comparison of the spinal and supraspinal control of the legs and arms in these patients may therefore provide valuable information about the pathophysiology of spasticity. In the present study, we tested the hypothesis that one of the pathophysiological mechanisms of spasticity in these patients is abnormal corticospinal transmission and that this may lead to decreased reciprocal inhibition. Ten patients and 15 healthy age-matched control subjects were investigated. The patients were all spastic in the legs (with hyperactive tendon reflexes, increased muscle tone and Babinski sign), but had no neurological symptoms in the arms (except for one patient). Disynaptic reciprocal Ia inhibition of flexor carpi radialis (FCR) and soleus (SOL) motoneurons was measured (as the depression of the background FCR and SOL EMG activity and as the short latency inhibition of the FCR and SOL H-reflex evoked by radial and peroneal nerve stimulation). In addition, the latency of motor evoked potentials (MEPs) in the FCR muscle and the tibialis anterior (TA) muscle was measured. In the patients, the mean reciprocal inhibition was normal in the arms, while it was significantly decreased in the leg compared with the healthy subjects. In the patients, the average latency of MEPs in the FCR muscle was normal, while the latency to the MEP in TA muscle was significantly longer than that found in healthy subjects. Four patients, however, differed from the other patients by having significant reciprocal inhibition in the leg and a significantly shorter latency of TA MEPs than found in the other patients. The six patients without reciprocal inhibition in the leg instead had significant short latency facilitation of the SOL H-reflex and a longer TA MEP latency than seen in the healthy subjects and in the four patients with retained reciprocal inhibition. These findings support the hypothesis that disynaptic reciprocal inhibition and short latency facilitation are involved in the development of spasticity and, furthermore, they suggest a positive correlation between impairment of corticospinal transmission and decrease of reciprocal inhibition/appearance of reciprocal facilitation.