Physiological studies of spinal inhibitory pathways in patients with hereditary hyperekplexia

Abstract

Because hereditary hyperekplexia results from a defect in the glycine receptor, we studied in five patients several spinal inhibitory pathways that are thought to use either glycine or gamma-aminobutyric acid as a neurotransmitter. Three patients had a mutation in the alpha1 subunit of the glycine receptor, whereas two sisters with the same clinical syndrome did not have this mutation. Compared with normal subjects, reciprocal inhibition between flexor and extensor muscles of the forearm was diminished during the first period of inhibition and preserved during the second period of inhibition in all three patients tested. Facilitation after the early period of inhibition was prominent. Recurrent inhibition of the soleus H reflex was normal in four patients, as was inhibition of the H reflex produced by Achilles' tendon vibration. There was no significant difference in nonreciprocal (Ib) inhibition between patients and normal individuals, The findings suggest that disynaptic reciprocal inhibition in humans is mediated through glycinergic interneurons, but that recurrent inhibition may have a contribution from nonglycinergic mechanisms.