Interlimb reflexes and synaptic plasticity become evident months after human spinal cord injury

Abstract

Persons with long-standing injury to the cervical spinal cord resulting in complete or partial paralysis typically develop a wide spectrum of involuntary movements in muscles receiving innervation caudal to the level of injury. We have previously shown that these movements include brief and discrete contraction of muscles in the hand and forearm in response to innocuous sensory stimulation to the feet and legs, but we have been unable to replicate these interlimb reflexes in able- bodied subjects. Properties of these muscle responses indicate that the synaptic contacts between ascending sensory fibres and motor neurones of the cervical enlargement are more efficacious than normal. If these connections are present at all times, and require the more rostrally-placed spinal cord injury to allow their emergence, one might expect their appearance relatively soon following injury, as has been shown for studies of 'latent' synapses. Conversely, delayed appearance of these interlimb reflexes would suggest either the development of new synaptic connections or a profound strengthening of existing circuits in the cervical spinal cord due to a combination of afferent target loss and motor neurone denervation from motor tracts originating rostral to the injury site. In this study, we used repeated examinations of persons with acute injury to the cervical spinal cord to examine the time post-injury at which interlimb reflexes are first seen. Using tibial nerve stimulation at the knee as a screening test, a total of 24 subjects were found to develop interlimb reflexes following spinal cord injury. Latencies between stimulation and EMG were as brief as 32 ms for muscles of the forearm and 44 ms for muscles in the hand. These minimal delays all but rule out a supraspinal route for these interlimb reflexes. Interlimb reflexes first became evident no sooner than approximately 6 months following injury, and in some individuals were not seen until well over 1 year post-injury. Enhanced lower limb segmental excitability had emerged in nearly all of these subjects weeks or months prior to the first appearance of interlimb reflexes, arguing against a manifestation of traditional post-traumatic spasticity as a basis for this activity. This prolonged delay between time of injury and emergence of interlimb reflex activity lends support to the hypothesis that this activity represents an example of plasticity-and perhaps 'regenerative sprouting'-in the human spinal cord following traumatic injury.

Spinal shock revisited: a four-phase model

“…Other observations suggest that the timing of late reflex changes relates to axon length. Hyperactive flexor reflexes yield flexor spasms by 1-3 months after SCI, whereas hyperactive stretch reflexes yield extensor spasms by 3-6 months 37,105,106 and interlimb hyperreflexia by 6-12 months; 107 spinal interneurons have shorter axon lengths than the long central processes of IA afferent axons and the long interlimb axons. In cats with spinal cord transection, the latest changes in cutaneomuscular hyper-reflexia also precede the latest changes in tibial H-reflex hyper-reflexia; 55 again, this suggests earlier synapse growth in short-axoned spinal interneurons relaying cutaneomuscular reflexes than in long-axoned Ia afferents relaying the tibial H-reflex.…”

“…In spastic muscles, these motor neurons may segregate into either reflex-controlled or voluntarily controlled. 107 SCI neuropathic pain may be another undesirable effect of new synapse growth by spinal afferents on pain relay neurons in the dorsal horn. 87,117 Electrical activation promotes synaptic maturation and refinement of neural circuits.…”

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

“…For example, electromyographic (EMG) activity in human leg muscles reappeared during assisted locomotion a few months after complete cervical or thoracic SCI [6]. Importantly for inter-limb coordination, EMG activity in human upper extremity muscles began to be evoked by tibial nerve stimulation months after complete cervical SCI [7]. Comparably, Basso, Beattie, and Bresnahan open field locomotor rating scale scores [8] indicate that slight movement of a rat hind-limb joint occurred by 1 week after thoracic spinal cord transection and that slight-toextensive joint movements were seen thereafter [9].…”

Motor unit number estimation of the tibialis anterior muscle in spinal cord injury

“…Neurological plasticity could extend from the cervical to the sacral cord. 18 Therefore, the plastic changes in MUs might underlie, at least partially, changes in the MUNE parameters after SCI, which were often presented as S-MUAP. However, neither increase in S-MUAP size nor changes of its value was found during the follow-up period in the subacute and chronic SCI group.…”