The 10,000-Fold-Effect-Retrograde Neurotransmission-a Newer Concept for Paraplegia's Physiological Revival-use of Intrathecal Sodium Nitroprusside in 100 Cases-A Priliminary Report
Authors: Tewari Vinod , Husain Mazhar , Gupta Hari Kushan Das 
Published: April 2016

Background

Methylprednisolone has shown level-1-benefit (20%) in traumatic paraplegia cases (but within-8hrs) yet disproved by many studies. Patients wait long for physiological recovery. Intrathecal-Sodium-Nitroprusside (ITSNP) has been used in literature to relieve vasospasm-due-to-subarachnoid-hemorrhage. ITSNP has been studied here for physiological recovery in paraplegia cases of various etiologies in a wide-window-period-range. Two mechanisms for acute-cases and one-mechanism for chronic-cases, which are interrelated, are being proposed for physiological recovery. (a) Retrograde-Neurotransmission (acute-cases). 1. During Normal excitatory impulse: at synaptic-level, glutamate activates NMDA-receptors, having Nitric-Oxide-Synthetase(NOS) on postsynaptic-membrane, for further propagation by calcium-calmodulin-complex. Nitric-Oxide (NO produced by NOS) travels backward across chemical synapse, binding to axon terminal (NO-receptor/sGC) of presynaptic-neuron, regulating-Anterograde-Neurotransmission (ANT) called Retrograde-Neurotransmission (RNT). The-haem is the ligand binding site of NO receptor/sGC. The affinity of haem exhibits 10,000-fold excess for NO than Oxygen (THE=10,000-FOLD effect) completes in 20msec. 2. In Pathological conditions: normal-ANT, synaptic-activity including-RNT is-absent. NO-donor(SNP) release NO from NOS at postsynaptic-region. NO travels backward across a chemical-synapse to bind to the haem of NO-receptor at axon-terminal of a presynaptic-neuron, generates-impulse, as in normal-condition. (b) Vasospasm (acute-cases). Perforators show vasospastic activity. NO vasodilates the perforators by NO cAMP pathway. (c) Long Term Potentiation (LTP) (chronic-cases). NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS, and at neuromuscular junction. The LTP has been reviewed both generally and with respect to specific brain regions for memory/learning. LTP plays an important factor for relief from paraplegia in chronic cases. Aims/Study Design: Principle of “generation-of-impulses from presynaptic-region to postsynaptic-region by-RNT, vasodilatation of arteriolar-perforators and LTP is the basis-of-authors” hypothesis to treat-acute-and-chronic-paraplegia-cases. Case-control-prospective-study. Material/Methods: 200 paraplegia patients {100 patients taken as control (50 with no superfusion and 50 with dextrose 5% superfusion) and 100 patients taken as in ITSNP-group} were studied here. The mean time for superfusion was 14.11 days. ITSNP administered at a dosage of 0.2 mg/kg bo wt at L3/4 level by 24 G LP needle. Pre and post ITSNP was monitored by SSEP/MEP.

Results

AFTER-2-HOURS in ITSNP-group MEAN-CHANGE-FROM-BASELINE-ASIA MOTOR/SENSORY-SCORE 13.84%/13.10%, after-24 hours MOTOR-1.27-points decrease(3.77%) and SENSORY 10.5 points-increase(6.22%)as compared with Control-group no-change noted upto 24 hours, At-7days ITSNP motor/sensory;11.56%/6.22% as compared with Control-group 7.60/4.48%, At-2months in ITSNP 27.69%/6.22% as compared with Control-group 16.02/4.5%. SSEP/MEP-documented-improvements-noted.

Conclusions

ITSNP, a-swift-acting-drug in treatment-of-paraplegia, is effective within-two-hours (mean-change-MOTOR-13.84%andSENSORY-13.10%) on-mean14.11th postparaplegia-day with a small-detrimental-response after-24 hours which-recovers-fast