A New Surgical/ Therapeutic Treatment Model for Spinal cord Injured Paraplegics-
Author- R.V. Krishnan

Existing treatment-rehabilitation procedures aimed towards motor restoration-recovery for spinal cord injured (SCI) paraplegics include body-weight support treadmill training, functional electrical stimulation, stem cells therapy, neurotrophic growth factors application, and implantable electrodes. Of these available options some are still in experimental/clinical trials stages.
This author’s published research since 1980 takes a different approach to SCI treatment-rehabilitation. It targets the motor units, spinal motoneuron-interneurons and the cerebral motor cortex. Our research is an onward pursuit of the fundamental discoveries in the spinal cord motor system made by Sperry, Granit, Changeux, Edelman, Kohonen, Grossberg, and Henneman, of whom three are Nobel laureates. This author’s research is summarized below-
  • In SCI, depending on the severity of injury, there is large scale deafferentation of target neuron centers at spinal motoneuron-interneuron pools, thalamus, cerebellar cortex, and somato-sensory-motor cortex.
  • Soon after the injury in the next several weeks, spontaneous, compensatory synaptic sprouts of surviving if any, and local afferent inputs to these centers sprout out and reinnervate the vacated synaptic sites.
  • These compensatory synaptic connections indeed are aberrant, maladaptive connections. Thus motor paralysis in SCI is not only due to the massive loss of the original, function specific connections but as much due to gaining of the maladaptive, aberrant connections.
  • Computational brain modeling and cognitive systems studies describe that the synaptic connections in the target neuron centers indeed represent the learned sensory-motor experiences stored as synaptic memory weights in memory traces.
  • These memory weights evolve gradually from fetal, infant, and throughout adult life as motor-learned experiences in motor learning activity-dependent, competition-based, selection-suppression of synaptic weights- in what is now familiarly known as synaptic competitive learning (SCL). In the intact adult sensory-motor centers SCL mechanisms control and regulate all learn-register-recall- (motor) execute functions.
  • In SCI, these crucial SCL functions partially/completely cease to be operative due to the deletion of original memory weights and the addition of aberrant weights in all those deafferented, compensated target neuron centers.
  • Our research till to-date had shown that SCL can be reinstalled in those centers by any one of the following surgical/ therapeutic procedures- i)controlled neurapraxia of the paretic/ paralyzed limb muscles motor nerves, ii) partial denervation of selected muscles, iii) by injecting small doses of Botulinum toxin in serial/repeat sessions to selected paretic/paralyzed muscles.
The five video clips attachments show the results of controlled neurapraxia treatment of the sciatic nerve trunk in spinal cord complete injury (SCIc) adult paraplegic frogs. One week after the SCIc surgery, controlled neurapraxia surgery of the right hind limb sciatic nerve trunk in the upper posterior thigh was carried out while the left limb was not operated and served as control side. The controlled neurapraxia causes temporary blockade/interruption of nerve impulse transmission in an approximately small percentage of (20-30%) sciatic axons. Meanwhile the intact motor axons intramuscularly sprout out and reinnervate the impulses blocked muscle fibers. When the injured axons recover they innervate their native muscle fibers which are now already reinnervated. Thus redundant control of motor units ensues and competition takes place between the native and reinnervating intramuscular motor axons terminals. In the meantime, within the distal isolated cord the pool motoneurons’ soma sizes increase, concurrent neosynaptogenesis, and synapse competition occurs. The dual SCL at the neuromuscular synapses and at motoneuronal synapses last for four to eight weeks. Spontaneous sprouting of those aberrant, compensatory synaptic weights that otherwise would occur in the distal cord synaptic fields this thus averted. The treatment resizes the motoneurons’ soma, repositions the synaptic weights on the soma-dendrites and rebalances (excitation-inhibition balance) the synaptic weights on the basis of competition and selection. In other words the treatment reinstalls SCL mechanisms in the affected synaptic fields. Motor recovery, stepping, swimming involving full flexion-extension of hip, and knee joints appeared in the treated right limb and remained so for several months. Weak, transient recovery also appeared in the contralateral left hind limb due to tans-neuronal plasticity; however the recovery waned off in the next few weeks.
Until now in human paraplegics botulinum toxin (BoTx) is being used solely for the purpose of spasticity relief in isolated, single muscles. In order to reinstall SCL in several motoneuron pools BoTx should be given in small doses to several selected paretic/paralyzed muscles in serial/repeat sessions. In particular, BoTx-induced SCL procedure offers an effective, non-invasive, relatively less-complex to perform bottom-up treatment strategy as against the still experimental top-down treatment procedures such as stem cells therapy. BoTx due to its ability to induce motoneuron soma size plasticity, motor axonal sprouting, multiply innervate muscle fibers, neosynaptogenesis, and restoring SCL in the aberrantly weighted synaptic fields will emerge as a promising SCL therapeutic tool in the treatment–rehabilitation of SCI paraplegia. The animal model presented here is not meant to replace other existing treatment procedures. It offers an essential complementary and combination treatment for SCI paraplegics.

Pertinent references-
1. Krishnan RV. A theory on the lability-stability of spinal motoneuron soma size and induction of synaptogenesis in the adult spinal cord.Int. J. Neurosci 1983; 21: 279 -92

2. Krishnan RV. Induction of plasticity in the isolated spinal cord in paraplegia. Int J Neurosci. 1991; 56: 81-92.

3.Krishnan RV, Sankar V, Muthusamy R. Recovery of locomotor function in adult paraplegic frogs by inductive lability in the distal isolated spinal cord neural networks. Int. J. Neurosci2001; 108: 43- 54.

4. Krishnan RV. Spinal cord injury repair research: a new combination treatment strategy. Int J Neurosci 2001;108:
5. Krishnan RV. Botulinum toxin: From spasticity reliever to a neuromotor re-learning tool. Int. J. Neurosci. 2005; 115: 145.

6. Krishnan RV. Relearning toward motor recovery in stroke, spinal cord injury and cerebral palsy: A cognitive neural systems perspective. Int. J.Neurosci2006; 116: 127 -40.

7. Krishnan RV. Botulinum toxin as a neuro-relearning drug tool in motor paralytic disorders. Current Drug Thererapy 2009; 4: 101-5.

8. Krishnan RV. Half a century journey from Henneman’s size principle of the motoneuron to cure paraplegia. 2012; (submitted).

Legend to Video clips-
File-1 Animal No-5. Mid-thoracic complete cord injury (SCIc). One week post-injury.
Note the complete paraplegia.

File-2 Animal No-10. SCIc. 95 days post-injury. Note the complete paraplegia; extended hind-limbs and scissoring of the limbs due to adductors spasticity.

File-3.Animal No-31.SCIc 35 days post-injury. Right sciatic nerve neurapraxia. Left sciatic unoperated and is control. Note the flexed resting position of the hind limbs and absence of scissoring of limbs.

File-4. Animal No-31 as in file-3. 120 days post-neurapraxia. Note the swimming performance. Compare the right hind limb (operated) with the left (control) side.

File-5 Animal No-31 same as in file-4. 120 days post-neurapraxia. Note the stepping performance. Compare the right and left limbs.