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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 51, Num. 1, 2003, pp. 102-103

Neurology India, Vol. 51, No. 1, Jan-Mar, 2003, pp. 102-103

Case Report

Three cases of recurrent epileptic seizures caused by Endosulfan

S. Kutluhan,1 G. Akhan,1 F. Gultekin,2 E. Kurdoglu3

Suleyman Demirel University, School of Medicine, 1Department of Neurology, and 2Biochemistry and Clinical Biochemistry, Isparta, Turkey. 3Emergency Service of Kütahya State Hospital, Kütahya, Turkey.
Dr. Suleyman Kutluhan, Suleyman Demirel University, School of Medicine, Department of Neurology, Isparta-32040, Turkey. E-mail : skutluhan@hotmail.com

Accepted on 19.02.2002.

Code Number: ni03030

To commit suicide, three young adults swallowed a relatively small amount of a widely used insecticide containing endosulfan. They developed recurrent epileptic seizures. After hospitalization they were treated and recovered without any sequel. These seizures were classified as acute symptomatic or provoked seizures. We suggest that if one faces acute repetitive seizures, especially in the rural areas, an intoxication such as endosulfan intoxication should be considered when the etiology is uncertain even in the absence of any signs of intoxication.

Key Words: Insecticide, Endosulfan, Provoked seizure, Acute symptomatic seizure.

A provoked or acute symptomatic seizure is defined as a temporary seizure together with an acute systemic, metabolic, or toxic insult in association with an acute central nervous system insult (infection, stroke, cranial trauma, intracerebral hemorrhage, or acute alcohol intoxication or withdrawal). They are often isolated epileptic events, but may also be recurrent or produce status epilepticus when the acute condition repeats, e.g., alcohol withdrawal seizures.1,2

Poisoning by chlorinated hydrocarbon insecticides is well known. One such insecticide is endosulfan (6,7,8,9,10,10- hexachloro 1,5,5a,6,9,9a-hexahydro-6-methano-2,4,3-hexadithioxanthiepin 3-oxide), and has been widely used in agriculture since 1960.3 Accidental and suicidal poisoning with endosulfan are reported in literature.4-9

We present three cases of endosulfan poisoning (suicidal) with a favorable outcome admitted to the Kütahya State Hospital within three years.

Case Reports

Patient 1: A 15-year-old male was brought unconscious with two seizures in 2-3 hours. There was no past or family history of epilepsy. In the intensive care, he had six secondary generalized tonic-clonic seizures starting in the right hand for six hours. The convulsions were controlled with diazepam. The following day, he recovered and became conscious. He reported that he had swallowed two teaspoonful of "Hektionex 35 WP" (active ingredient: endosulfan; each teaspoonful contained approximately 300 mg endosulfan) three hours before the first seizure. The routine laboratory tests such as hemogram, glucose, urea, aspartate amino transferase, alanine amino transferase, prothrombine time, partial protrambine time, total lipid, total cholesterol, urine analyses, cerebrospinal fluid analyses, and cranial CT were non-specific. However, his first EEG showed bilateral synchronized intermittent delta activity during hyperventilation which persisted in the EEGs taken ten days and two years later. Although we did not start any antiepileptic treatment, the patient had no more seizures for five years after discharge.

Patient 2: An 18-year-old woman was admitted with the history of two seizures within two hours before being brought to the hospital. She had two generalized tonic-clonic seizures in the emergency room within three hours. Eight hours after the first seizure in the hospital, she became conscious and reported that she tried to commit suicide by drinking one teaspoonful of "Bayer Endosulfan 35% WP" (active ingredient: endosulfan). Her laboratory tests, as in the previous case, were normal. Her EEG fifteen days later showed a few bilateral bursts, synchronized intermittent delta activity during the routine records, and these were provoked by hyperventilation. Two years later, her EEG showed the same findings as in the first EEG but fewer, and occurred during and after hyperventilation. Since the patient had no history of epilepsy, we assumed that seizures were only due to endosulfan intoxication; therefore we did not initiate any therapy. She did not report any seizures the following five years.

Patient 3: A 20-year-old married female, without any personal or family history of epilepsy, had eight seizures at fifteen-minute intervals before she was brought to the emergency room. She had three more generalized tonic-clonic seizures at the hospital. Intravenous diazepam was given to control seizures. As soon as she gained consciousness, she told that she had taken Hektionex 35 WP (active ingredient: endosulfan), about one teaspoon to commit suicide. The laboratory findings were normal. She was discharged and recommended an EEG a week later. On the 12th day, her EEG showed bilateral synchronized intermittent delta activity which was occasionally dominant on the left frontotemporal region and which increased during hyperventilation. A follow-up EEG, nearly 18 months later, recorded during awake period and short spontaneous sleep, was normal. After acute therapy, she was free of seizures and we did not start any further antiepileptic treatment. During the five year follow-up period, no seizures recurred.

Discussion

Acute symptomatic seizures require urgent therapy. The etiology should be found out immediately and treated accordingly. In the above cases, the laboratory findings were nonspecific. The patients had no personal or family history of epilepsy, and there was no etiology except history of taking endosulfan as a motive of self-harm.

In endosulfan intoxication, seizures are observed in a period of half an hour to six hours and in case the dose exceeds 25 mg/kg orally, hematuria and proteinuria followed by anuria can occur.3 Gill et al showed that endosulfan caused a decrease in the total lipid, cholesterol and protein contents whereas an increase in the free fatty acid, glucose, total phosphate and lactic acid levels in the blood of fish.10 Blanco-Coronada et al reported six cases of intoxication with endosulfan, five of them had metabolic acidosis, thrombocytopenia (76,000-184,000/mm3) and hyperglycemia (226-670 mg%).4 Venkateswarlu et al reported 44 cases with endosulfan poisoning and concluded that endosulfan poisoning can be suspected from the primary CNS manifestations with or without clinical or laboratory evidence of dysfunction of organs like liver, kidney and muscle.6

Tiberin et al found convulsions and unconsciousness in the cases who had dermal absorption of endosulfan powder. They reported seizure discharges consisting of short bursts of bilateral synchronous high voltage 3-4 Hz spike and wave complexes, irregular spikes and multiple spikes and slow waves with frontal predominance in one of their patients. Intermittent runs of 6 Hz waves, notched by 12 Hz activity and positive spikes forming flat-topped waves over temporal areas occurred in the second patient. EEG record of the last patient showed generalized dysrhythmic activity with occasional bursts of high voltage theta waves. The seizures were controlled by medical treatment and by discarding endosulfan usage.5 EEG of our first case at one year follow-up revealed a mild background abnormality characterized by occasional bursts of 3 Hz spikes and wave activity. EEGs of the other two cases showed normal background activity.

It is reported that endosulfan inhibits calmodulin-dependent Ca++ ATPase activity in the brain and causes fluctuations in the serotoninergic system and decreases activity of GABA on neuronal membrane.11-13 The decrease in the activity of GABA releases the synaptic inhibition on the neurons and makes the excitation of neurons easy.11,14 These effects are augmented if a person has an epileptogenic tendency. When endosulfan is eliminated from the body, the epileptic seizures stop.

In our cases, we did not start any long-term antiepileptic treatment and seizures did not recur. Similarly, Blanco-Coronado et al gave only diazepam treatment in the acute phase.4

We suggest that if one faces acute repetitive seizures, especially in the rural areas, even in the absence of any other sign of intoxication, endosulfan intoxication should be considered as one possibility when the etiology is uncertain.

References

  1. Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-99.
  2. Commission on Epidemiology and Prognosis, International League Against Epilepsy: Guidelines for epilepsy for Epidemiologic Studies on Epilepsy. Epilepsia 1993;34:592-6.
  3. Smith AG. Chlorinated hydrocarbon insecticides. In: Hayes WJ, Laws ER, eds. Handbook of pesticide toxicology. san Diego: Academic Press; 1991. pp. 731-45.
  4. Blanco-Coronado JL, Repetto M, Ginestal RJ, Vicente JR, Yelamos F, Lardelli A. Acute intoxication by endosulfan. J Toxicol Clin Toxicol 1992;30:575-83.
  5. Tiberin P, Kristal N, Israeli R. EEG findings in poisoning by endosulfan (C9H6O3Cl6S). Electroencephalogr Clin Neurophysiol 1970;28:642.
  6. Venkateswarlu K, Suryarao K, Srinivas V, Sivaprakash N, Jagannadharao NR, Mythilai A. Endosulfan poisoning-a clinical profile. J Assoc Physicians India 2000;48:323-5.
  7. Sood AK, Yadav SP, Sood S. Endosulphan poisoning presenting as status epilepticus. Indian J Med Sci 1994;48:68-79.
  8. Chugh SN, Dhawan R, Agrawal N, Mahajan SK. Endosulfan poisoning in Northern India: a report of 18 cases. Int J Clin Pharmacol Ther 1998;36:474-7.
  9. Singh N, Singh CP, Kumar H, Brar GK. Endosulfan poisoning: a study of 22 cases. J Assoc Physicians India 1992;40:87-8.
  10. Gill TS, Pande J, Tewari H. Effects of endosulfan on the blood and organ chemistry of freshwater fish, Barbus conchonius Hamilton. Ecotoxicol Environ Saf 1991;21:80-91.
  11. Gilbert ME. Proconvulsant activity of endosulfan in Amygdala kingling. Neurotoxicol Teratol 1992;14:143-9.
  12. Gilbert ME. A characterization of chemical kindling with the pesticide endosulfan. Neurotoxicol Teratol 1992;14:151-8.
  13. Casida EJ. Insecticide action at the GABA-Gated chloride channel: Recognition, Progress and prospects. Arch Insect Biochem Physiol 1993;22: 13-23.
  14. Agrawal AK, Anand M, Zaidi NF, Seth PK. Involvement of serotonergic receptors in endosulfan neurotoxicity. Biochem Pharmacol 1983;32:3591-3.

Copyright 2003 - Neurology India. Also available online at http://www.neurologyindia.com

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