[Downloaded free from http://www.neurologyindia.com on Tuesday, June 09, 2015, IP: 61.16.135.116]
The Editorial Debate
Electrophysiologic evaluation of snake bite Fear of snakes is a powerful, primordial, and, possibly innate human emotion that has fascinated experimental psychologists and evolutionists.[1] Envenoming by poisonous animals (snakes, scorpions, wasps, ants, and spiders) is an occupational hazard to farmers and farm laborers.[2] Snakebite is one of the most common causes of acute flaccid paralysis[3] and a leading cause of death in young earning members of families.[2] Considering the large magnitude of its burden and the limited resources available in tropical and subtropical regions, snakebite has been classified by the World Health Organisation as a neglected tropical disease.[4] Of more than 3000 known species of snakes, only about 300 are venomous and in India, there are about 216 identifiable species of snakes, of which 52 are known to be poisonous.[2] Snake venoms causing human toxicity include those affecting the nervous system (neurotoxic), the cardiovascular system (cardiotoxic) and the hematological system (hemotoxic/ vasculotoxic). Recent data have challenged the traditional concepts of toxicity in snake envenoming, and highlight the rich diversity of snake toxins. Snake venoms are now recognized to be the most complex of all natural poisons. Snake venoms do not contain a homogenous single toxin but are a complex cocktail of enzymes, polypeptides, nonenzymatic proteins, nucleotides, and other substances, many of which may have different neurotoxic properties. Some examples of diversity of toxins present in various snake types are ‑ Cobra Naja spp. (alpha‑cobratoxin, cobrotoxin, cardiotoxin, toxin alpha, weak toxin); Krait, Bungarus spp. (alpha‑bungarotoxin, beta‑bungarotoxin, kappa bungarotoxin, candoxin); Russell’s viper, Daboia spp. (phospholipase A2 activity, daboia neurotoxin‑1, viperotoxin‑F); Mamba, Dendroa spp. (dendrotoxins, Access this article online Website: www.neurologyindia.com DOI: 10.4103/0028-3886.158159 PMID: xxxxx
304
Quick Response Code
fasciculins, muscarinic toxins, calciseptine); Rattlesnake, Crotalus spp. (Crotoxin, Mojave toxin).[5] The peripheral neuromuscular weakness after a snakebite results from a defective neuromuscular junction (NMJ) transmission. Traditionally, it has been considered that snake venom toxins cause two types of neuromuscular blockade, presynaptic and postsynaptic; but this view may be oversimplistic and needs to be reviewed in view of the recent insights into neuromuscular transmission and descriptions of different patterns of neurotoxicity. Even the traditionally considered “vasculotoxic snakes,” the vipers, have a significant potential of causing neurological toxicity. The mechanism of causation of neurological toxicity by these vasculotoxic snakes was initially thought as only an indirect affliction of the vasculature of central/peripheral nervous system.[6] Now, however, the direct neuromuscular toxicity by these snakes is recognized. The site of action of the venom determines the clinical manifestations of the patients. The management of snake bite envenomation is usually guided by the patient’s clinical response. An objective assessment of the severity of neuroparalytic syndrome and effectiveness of treatment protocol used may be provided by a detailed neurophysiological study. Three patterns of neuromuscular transmission failures have been observed in the neurophysiological studies in these patients:[5,7,8] • Postsynaptic reversible neuromuscular blockade (Cobra spp. ‑ Naja‑naja, Naja‑nigricollis, Naja‑haje) • Postsynaptic irreversible blockade ‑ alpha‑bungarotoxin • Presynaptic blockade with inhibition of release of acetylcholine – Beta‑ and gamma‑bungarotoxin, phospholipase A2 activity, viperotoxin F. While a decremental response at low‑frequency repetitive nerve stimulation (RNS) is suggestive of a postsynaptic neuromuscular blockade, low amplitude compound muscle action potentials (CMAPs) are representative of a presynaptic disorder of neuromuscular transmission.
Neurology India / May 2015 / Volume 63 / Issue 3
[Downloaded free from http://www.neurologyindia.com on Tuesday, June 09, 2015, IP: 61.16.135.116]
Takkar and Kharbanda: Electrophysiological eveluation of snake bite
Observation of fibrillation potentials in the electromyographic evaluation may also support a presynaptic site of action.
highlights the electrophysiological changes in vasculotoxic/ viper bites.
Limited human data are available on the neurophysiological changes after a snake bite. Furthermore, interpretation of the findings from these studies is difficult, as different methods have been used by various researchers (e.g., different sample sizes, different rates of repetitive stimulation, time of study after snake bite, and specifications of treatment modalities used while undergoing neurophysiological examination).
A detailed neurophysiological study in the patients of snake bite envenomation may help in establishing appropriate management protocols, specifically when the clinical scenario is not classical. It should also be borne in mind that even the traditionally considered “vasculotoxic snakes” ‑ the vipers have a significant potential of causing neurological toxicity.
Singh et al. in their study of twelve patients envenomed with B. caeruleus noted two pertinent neurophysiological abnormalities:[9] (a) Reduction in the amplitudes of CMAPs; and, (b) decremental response to 3 Hz RNS.
Despite the large magnitude of burden of snake bites in the Indian subcontinent, studies on its neurophysiological evaluation are lacking. Studies directed toward evaluating the neurophysiological effects of snake envenomation would be helpful in providing a comprehensive and objective model of the type and magnitude of neurological dysfunction. Further research focusing on these aspects of snake envenomation would greatly aid in the clinical decision‑making in these patients.
They also noted a good correlation between the neurophysiological abnormalities and the clinical findings/ severity of neuromuscular paralysis. They interpreted that neuromuscular manifestations of snake bite are a result of both pre‑ and post‑synaptic blockade at the NMJ.[9] A study of three cases envenomed by Papuan taipan snake (Oxyuranus scutellatus canni) demonstrated reduced CMAP, postactivation potentiation and decremental response on 5 Hz RNS. An increased jitter with blocking on single‑fiber electromyography was also noted in this study. A probable presynaptic site of neuromuscular blockade was postulated.[10] Watt et al. reported a decremental response at 5 Hz RNS in two patients poisoned by a Philippine cobra. They postulated a postsynaptic neuromuscular blockade as a cause in their patients.[11] Seneviratne and Dissanayake carried out edrophonium test in eight of their patients having a snake bite. Seven patients showed a positive response. The offending snakes were kraits in three, Rusell viper in two, and unidentified snakes in two patients. A positive edrophonium response in these patients was considered to be due to the blockade at the postsynaptic NMJ.[12] In this issue, Patwari et al. studied the electrophysiological profile of 40 patients envenomed by a snake bite.[13] They have analyzed the electrophysiology in neurotoxic and vasculotoxic snake bites separately and did not find any major abnormalities or statistically significant difference in amplitude, distal latency and conduction velocities in either groups. On RNS study, they noted a decremental response at 3 Hz (with significant postexercise decrement) in either groups in both median as well as the facial nerve. Even the patient group envenomed by vasculotoxic snake bite had significant electrophysiological changes despite not having any neurological manifestations. The study despite having limitations, being a single center study with small sample size,
Aastha Takkar, Parampreet S. Kharbanda Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. E‑mail: [email protected]
References 1. 2.
Warrell DA. Snake bite. Lancet 2010;375:77‑88. Bawaskar HS, Bawaskar PH. Snake bite poisoning. J Mahatma Gandhi Inst Med Sci 2015;20:5‑14. 3. Kaushik R, Kharbanda PS, Bhalla A, Rajan R, Prabhakar S. Acute Flaccid paralysis in adults: Our experience. J Emerg Trauma Shock 2014;7:149‑54. 4. Harrison RA, Hargreaves A, Wagstaff SC, Faragher B, Lalloo DG. Snake envenoming: A disease of poverty. PLoS Negl Trop Dis 2009;3:e569. 5. Ranawaka UK, Lalloo DG, de Silva HJ. Neurotoxicity in snakebite – The limits of our knowledge. PLoS Negl Trop Dis 2013;7:e2302. 6. Narang SK, Paleti S, Azeez Asad MA, Samina T. Acute ischemic infarct in the middle cerebral artery territory following a Russell’s viper bite. Neurol India 2009;57:479‑80. 7. Chang CC. Studies on the mechanism of curare‑like action of Bungarus multicinctus venom. Effect on the phrenic nerve‑diaphragm preparation of the rat. J Formos Med Assoc 1960;59:315‑23. 8. Dowdall MJ, Fohlman JP, Eaker D. Inhibition of high‑affinity choline transport in peripheral cholinergic endings by presynaptic snake venom neurotoxins. Nature 1977;269:700‑2. 9. Singh G, Pannu HS, Chawla PS, Malhotra S. Neuromuscular transmission failure due to common krait (Bungarus caeruleus) envenomation. Muscle Nerve 1999;22:1637‑43. 10. Connolly S, Trevett AJ, Nwokolo NC, Lalloo DG, Naraqi S, Mantle D, et al. Neuromuscular effects of Papuan Taipan snake venom. Ann Neurol 1995;38:916‑20. 11. Watt G, Theakston RD, Hayes CG, Yambao ML, Sangalang R, Ranoa CP, et al. Positive response to edrophonium in patients with neurotoxic envenoming by cobras (Naja naja philippinensis). A placebo‑controlled study. N Engl J Med 1986;315:1444‑8.
Neurology India / May 2015 / Volume 63 / Issue 3
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[Downloaded free from http://www.neurologyindia.com on Tuesday, June 09, 2015, IP: 61.16.135.116]
Takkar and Kharbanda: Electrophysiological eveluation of snake bite
12. Seneviratne U, Dissanayake S. Neurological manifestations of snake bite in Sri Lanka. J Postgrad Med 2002;48:275‑8. 13. Patwari P, Sangle S, Mane AA, Doshi S, Kadam D. Comparative study of electrophysiological changes in snake bites. Neurol India 2015;63:378-81.
306
How to cite this article: Takkar A, Kharbanda PS. Electrophysiologic evaluation of snake bite. Neurol India 2015;63:304-6. Source of Support: Nil, Conflict of Interest: None declared.
Neurology India / May 2015 / Volume 63 / Issue 3
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
The Editorial Debate
Electrophysiologic evaluation of snake bite Fear of snakes is a powerful, primordial, and, possibly innate human emotion that has fascinated experimental psychologists and evolutionists.[1] Envenoming by poisonous animals (snakes, scorpions, wasps, ants, and spiders) is an occupational hazard to farmers and farm laborers.[2] Snakebite is one of the most common causes of acute flaccid paralysis[3] and a leading cause of death in young earning members of families.[2] Considering the large magnitude of its burden and the limited resources available in tropical and subtropical regions, snakebite has been classified by the World Health Organisation as a neglected tropical disease.[4] Of more than 3000 known species of snakes, only about 300 are venomous and in India, there are about 216 identifiable species of snakes, of which 52 are known to be poisonous.[2] Snake venoms causing human toxicity include those affecting the nervous system (neurotoxic), the cardiovascular system (cardiotoxic) and the hematological system (hemotoxic/ vasculotoxic). Recent data have challenged the traditional concepts of toxicity in snake envenoming, and highlight the rich diversity of snake toxins. Snake venoms are now recognized to be the most complex of all natural poisons. Snake venoms do not contain a homogenous single toxin but are a complex cocktail of enzymes, polypeptides, nonenzymatic proteins, nucleotides, and other substances, many of which may have different neurotoxic properties. Some examples of diversity of toxins present in various snake types are ‑ Cobra Naja spp. (alpha‑cobratoxin, cobrotoxin, cardiotoxin, toxin alpha, weak toxin); Krait, Bungarus spp. (alpha‑bungarotoxin, beta‑bungarotoxin, kappa bungarotoxin, candoxin); Russell’s viper, Daboia spp. (phospholipase A2 activity, daboia neurotoxin‑1, viperotoxin‑F); Mamba, Dendroa spp. (dendrotoxins, Access this article online Website: www.neurologyindia.com DOI: 10.4103/0028-3886.158159 PMID: xxxxx
304
Quick Response Code
fasciculins, muscarinic toxins, calciseptine); Rattlesnake, Crotalus spp. (Crotoxin, Mojave toxin).[5] The peripheral neuromuscular weakness after a snakebite results from a defective neuromuscular junction (NMJ) transmission. Traditionally, it has been considered that snake venom toxins cause two types of neuromuscular blockade, presynaptic and postsynaptic; but this view may be oversimplistic and needs to be reviewed in view of the recent insights into neuromuscular transmission and descriptions of different patterns of neurotoxicity. Even the traditionally considered “vasculotoxic snakes,” the vipers, have a significant potential of causing neurological toxicity. The mechanism of causation of neurological toxicity by these vasculotoxic snakes was initially thought as only an indirect affliction of the vasculature of central/peripheral nervous system.[6] Now, however, the direct neuromuscular toxicity by these snakes is recognized. The site of action of the venom determines the clinical manifestations of the patients. The management of snake bite envenomation is usually guided by the patient’s clinical response. An objective assessment of the severity of neuroparalytic syndrome and effectiveness of treatment protocol used may be provided by a detailed neurophysiological study. Three patterns of neuromuscular transmission failures have been observed in the neurophysiological studies in these patients:[5,7,8] • Postsynaptic reversible neuromuscular blockade (Cobra spp. ‑ Naja‑naja, Naja‑nigricollis, Naja‑haje) • Postsynaptic irreversible blockade ‑ alpha‑bungarotoxin • Presynaptic blockade with inhibition of release of acetylcholine – Beta‑ and gamma‑bungarotoxin, phospholipase A2 activity, viperotoxin F. While a decremental response at low‑frequency repetitive nerve stimulation (RNS) is suggestive of a postsynaptic neuromuscular blockade, low amplitude compound muscle action potentials (CMAPs) are representative of a presynaptic disorder of neuromuscular transmission.
Neurology India / May 2015 / Volume 63 / Issue 3
[Downloaded free from http://www.neurologyindia.com on Tuesday, June 09, 2015, IP: 61.16.135.116]
Takkar and Kharbanda: Electrophysiological eveluation of snake bite
Observation of fibrillation potentials in the electromyographic evaluation may also support a presynaptic site of action.
highlights the electrophysiological changes in vasculotoxic/ viper bites.
Limited human data are available on the neurophysiological changes after a snake bite. Furthermore, interpretation of the findings from these studies is difficult, as different methods have been used by various researchers (e.g., different sample sizes, different rates of repetitive stimulation, time of study after snake bite, and specifications of treatment modalities used while undergoing neurophysiological examination).
A detailed neurophysiological study in the patients of snake bite envenomation may help in establishing appropriate management protocols, specifically when the clinical scenario is not classical. It should also be borne in mind that even the traditionally considered “vasculotoxic snakes” ‑ the vipers have a significant potential of causing neurological toxicity.
Singh et al. in their study of twelve patients envenomed with B. caeruleus noted two pertinent neurophysiological abnormalities:[9] (a) Reduction in the amplitudes of CMAPs; and, (b) decremental response to 3 Hz RNS.
Despite the large magnitude of burden of snake bites in the Indian subcontinent, studies on its neurophysiological evaluation are lacking. Studies directed toward evaluating the neurophysiological effects of snake envenomation would be helpful in providing a comprehensive and objective model of the type and magnitude of neurological dysfunction. Further research focusing on these aspects of snake envenomation would greatly aid in the clinical decision‑making in these patients.
They also noted a good correlation between the neurophysiological abnormalities and the clinical findings/ severity of neuromuscular paralysis. They interpreted that neuromuscular manifestations of snake bite are a result of both pre‑ and post‑synaptic blockade at the NMJ.[9] A study of three cases envenomed by Papuan taipan snake (Oxyuranus scutellatus canni) demonstrated reduced CMAP, postactivation potentiation and decremental response on 5 Hz RNS. An increased jitter with blocking on single‑fiber electromyography was also noted in this study. A probable presynaptic site of neuromuscular blockade was postulated.[10] Watt et al. reported a decremental response at 5 Hz RNS in two patients poisoned by a Philippine cobra. They postulated a postsynaptic neuromuscular blockade as a cause in their patients.[11] Seneviratne and Dissanayake carried out edrophonium test in eight of their patients having a snake bite. Seven patients showed a positive response. The offending snakes were kraits in three, Rusell viper in two, and unidentified snakes in two patients. A positive edrophonium response in these patients was considered to be due to the blockade at the postsynaptic NMJ.[12] In this issue, Patwari et al. studied the electrophysiological profile of 40 patients envenomed by a snake bite.[13] They have analyzed the electrophysiology in neurotoxic and vasculotoxic snake bites separately and did not find any major abnormalities or statistically significant difference in amplitude, distal latency and conduction velocities in either groups. On RNS study, they noted a decremental response at 3 Hz (with significant postexercise decrement) in either groups in both median as well as the facial nerve. Even the patient group envenomed by vasculotoxic snake bite had significant electrophysiological changes despite not having any neurological manifestations. The study despite having limitations, being a single center study with small sample size,
Aastha Takkar, Parampreet S. Kharbanda Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. E‑mail: [email protected]
References 1. 2.
Warrell DA. Snake bite. Lancet 2010;375:77‑88. Bawaskar HS, Bawaskar PH. Snake bite poisoning. J Mahatma Gandhi Inst Med Sci 2015;20:5‑14. 3. Kaushik R, Kharbanda PS, Bhalla A, Rajan R, Prabhakar S. Acute Flaccid paralysis in adults: Our experience. J Emerg Trauma Shock 2014;7:149‑54. 4. Harrison RA, Hargreaves A, Wagstaff SC, Faragher B, Lalloo DG. Snake envenoming: A disease of poverty. PLoS Negl Trop Dis 2009;3:e569. 5. Ranawaka UK, Lalloo DG, de Silva HJ. Neurotoxicity in snakebite – The limits of our knowledge. PLoS Negl Trop Dis 2013;7:e2302. 6. Narang SK, Paleti S, Azeez Asad MA, Samina T. Acute ischemic infarct in the middle cerebral artery territory following a Russell’s viper bite. Neurol India 2009;57:479‑80. 7. Chang CC. Studies on the mechanism of curare‑like action of Bungarus multicinctus venom. Effect on the phrenic nerve‑diaphragm preparation of the rat. J Formos Med Assoc 1960;59:315‑23. 8. Dowdall MJ, Fohlman JP, Eaker D. Inhibition of high‑affinity choline transport in peripheral cholinergic endings by presynaptic snake venom neurotoxins. Nature 1977;269:700‑2. 9. Singh G, Pannu HS, Chawla PS, Malhotra S. Neuromuscular transmission failure due to common krait (Bungarus caeruleus) envenomation. Muscle Nerve 1999;22:1637‑43. 10. Connolly S, Trevett AJ, Nwokolo NC, Lalloo DG, Naraqi S, Mantle D, et al. Neuromuscular effects of Papuan Taipan snake venom. Ann Neurol 1995;38:916‑20. 11. Watt G, Theakston RD, Hayes CG, Yambao ML, Sangalang R, Ranoa CP, et al. Positive response to edrophonium in patients with neurotoxic envenoming by cobras (Naja naja philippinensis). A placebo‑controlled study. N Engl J Med 1986;315:1444‑8.
Neurology India / May 2015 / Volume 63 / Issue 3
305
[Downloaded free from http://www.neurologyindia.com on Tuesday, June 09, 2015, IP: 61.16.135.116]
Takkar and Kharbanda: Electrophysiological eveluation of snake bite
12. Seneviratne U, Dissanayake S. Neurological manifestations of snake bite in Sri Lanka. J Postgrad Med 2002;48:275‑8. 13. Patwari P, Sangle S, Mane AA, Doshi S, Kadam D. Comparative study of electrophysiological changes in snake bites. Neurol India 2015;63:378-81.
306
How to cite this article: Takkar A, Kharbanda PS. Electrophysiologic evaluation of snake bite. Neurol India 2015;63:304-6. Source of Support: Nil, Conflict of Interest: None declared.
Neurology India / May 2015 / Volume 63 / Issue 3
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
