Can loss of muscle spindle afferents explain the ataxic gait in Riley-Day syndrome?

Abstract

The Riley-Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10-30 µA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high-intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains their loss of deep tendon reflexes. Moreover, we suggest that their ataxic gait is sensory in origin, due to the loss of functional muscle spindles and hence a compromised sensorimotor control of locomotion.

Figures

Figure 1

Intraneural recordings from muscle fascicles of the common peroneal nerve during muscle stretch in a control subject (A), a patient with HSAN III (B) and a patient with HSAN IV (C). (A) A single-unit recording from a muscle spindle secondary ending located in the extensor hallucis longus muscle; the afferent responded during passive plantar-flexions of the big toe. (B) A complete absence of muscle spindle afferent activity in the peronei fascicle during muscle stretch induced by passive inversion of the foot. (C) A single-unit recording from a muscle spindle primary ending located in the extensor digitorum longus muscle; the afferent responded dynamically during passive plantar-flexions of the toes. The black horizontal bars indicate periods of passive muscle stretch.

Figure 2

Mean firing rates of 15 spontaneously active muscle spindles recorded from healthy controls and of five spontaneously active muscle spindles recorded from the two patients with HSAN IV. There were no significant differences in mean firing rates. No spontaneous (or stretch-evoked) activity could be recorded in the 10 patients with HSAN III.

Figure 3

Intraneural recording from a cutaneous fascicle of the common peroneal nerve in a patient with HSAN III. The sensory innervation of the skin appeared normal, as illustrated by this multi-unit recording from the cutaneous fascicle supplying the dorsum of the foot. Cutaneous mechanoreceptors were excited during stroking of the skin within the fascicular innervation territory.