Nurten UZUN, Karaali Feray SAVRUN, Meral E. KIZILTAN

Kronik toulen ve n-heksan intoksikasyonunda periferik sinir sistemi hasarı: Elektrofizyolojik inceleme

Bu çalışmada nörotoksik olduğu bilinen iki tür organik hidrokarbonun (toluen/ metil benzen ve n-heksan) kronik kullanımda periferik nöropati oluşturma potansiyeli elektrofizyolojik olarak incelenmiştir. Ortalama olarak 3 yıldır inhalasyon yolu ile toluen'i kötüye kullanan asemptomatik 25 olgu ile endüstriyel amaçlı olarak n-heksan ile işyerlerinde deri veya inhalasyon yoluyla temas halinde bulunan ortalama çalışma süresi 28 ay olan asemptomatik 10 olgu ve çalışma süresi ortalaması 32,3 ay olan 19 semptomatik olgunun sinir iletim hızı çalışmaları ve elektromiyografi incelemeleri yapılmıştır. Toluen grubunda, %12 oranında hafif düzeyde sensorimotor tipte, asemptomatik n-heksan grubunda %60, semptomatik n-heksan grubundaki olguların tümünde orta-ağır düzeyde motor ağırlıklı sensorimotor polinöropati saptandı. n-Heksan' a maruz kalan asemptomatik grupta elektrofizyolojik olarak %60 oranında polinöropati saptanmasının yanı sıra, semptomatik grupta çalışma süreleri uzun olan erişkinlerde polinöropatik hasarın miyelin komponentinde daha belirgin olması dikkat çekici idi. Çalışmamızda gerek muayene ile saptanan patolojik bulgulara, gerekse periferik sinir sistemi ile ilgili elektrofizyolojik verilere dayanarak n-heksan grubunda yüksek oranda ve ağır düzeyde polinöropati bulguları saptanırken, toluen kullanımında periferik tutulumdan ziyade merkezi sinir sistemi hasarı gözlenmiştir.

Peripheral nerve system damage in chronic toluene and n-hexane intoxication: Electrophysiologic investigation

Background and Design.- We present electrophysiological features of neuropathy due to chronic exposure to different organic hydrocarbon derivatives (toluene/methyl benzene and n-hexane) that are known to be neurotoxic. Twenty-five subjects who abuse toluene by sniffing and 29 subjects who have been exposed to n-hexane by way of inhalation and skin contact have been included in the study. None of the sub-jects who abused toluene for an average of 3 years had any complaint. Ten subjects with exposure to n-hexane were asympto-matic, however 19 patients had symptoms of varying severity. The mean exposure time to n-hexane was 32.3 months, and 28 months in the groups of subjects with and without symptoms respectively. Electroneuromyographic examination was performed in these patients. Results.- Mild sensorymotor polyneuropathy was detected in 12% of subjects in the toluene group, and 60% of subjects in the asymptomatic n-hexane group. Neurological examination disclosed predominant central nervous system involvement in subjects with exposure to toluene. Motor and less severe sensory polyneuropathy of moderate to se-vere degree was noted in all of the patients in the symptomatic n-hexane group. Involve-ment of myelin component was more prominent in the adult patients with longer period of exposure to n-hexane. Conclusion.- We propose that n-hexane leads to predominantly peripheral nervous system damage, whereas toluene leads to central nervous system involvement.

PDF

___

1. Hormes JT, Filley CM, Rosenberg NL. Neurologic sequelae of chronic solvent vapor abuse. Neurology 1986; 36: 698-702. 2. Linder RL, Lerner SE, Wesson DR. Solvent sniffing: a continuing problem among youth. J Drug Educ 1974; 4: 469-473. 3. Press E, Done AK. Solvent sniffing: physiologic effects and community control measures. Pediatrics 1967; 39: 451-461, 611-622. 4. Meadows R, Verghese A. Medical complications of glue sniffing. South Med J 1996; 89: 455-462. 5. Arif A. Abuse of Volatile Solvents and Inhalants: Papers presented at a WHO Advisory Meeting 1988; 1-7. 6. Ron MA. Volatile substance abuse; a review of possible long-term neurological, intellectual and psychiatric sequelae. Br J Psych 1986; 148: 253-246. 7. Juntunen T, Matikainen E. Nervous system effects of long-term occupational exposure to toluene. Acta Neurol Scand 1985; 72: 512-517. 8. Dittmer DK, Jhamandas JH, Johnson ES. Glue-sniffing neuropathies. Can Fam Physician 1993; 39: 1965-1971. 9. Watson JM. Solvent abuse by children and young adults; A review. Brit J Addict 1980; 75: 27-36. 10. Meredith TJ, Ruprach M, Lidle A. Diagnosis and treatment of acute poisoning with volatile substance abuse. Human Toxicol 1989; 8: 277-286. 11. Bruckner JV, Peterson RG. Evaluation of toluene toxicity, utilizing the mouse as an animal model of human solvent abuse. Pharmacology 1976; 18: 244. 12. Devathasan G, Low D, Teoh PC, Wan SH, Wong PK. Complications of chronic glue (toluene) abuse In adolescents. Aust N Z J Med 1984; 14: 39-43. 13. Hayden JW, Peterson RE, Bruckner JV. Toxicology of toluene (methylbenzene). Review of current literature. Clin Toxicol 1977; 11: 549-559. 14. Altenkirch H, Mager J, Stoltenburg G, Helmbrecht J. Toxic Polyneuropathies after Sniffing a Glue Thinner. J Neurol 1977; 214: 137-152. 15. Altenkirch H, Stoltenburg G, Wagner H.M. Experimental Studies on Hydrocarbon Neuropathies by Methyl-Ethyl-Ketone (MEK). J Neurol 1978; 219: 159-170. 16. Chang CM, Yu CW, Fong KY, et al. n-Hexane Neuropathy in Offset Printers. J Neurol Neurosurg Psych 1993; 56: 538-542. 17. Cianchetti C, Abbritti G, Perticoni G, et al. Toxic Polyneuropathy of Shoe industry Workers. J Neurol Neurosurg Psych 1976; 39: 1151-1161. 18. Duncan ID, Griffithhs IR. Peripheral Nervous System in a Case of Canine Giant Axonal Neuropathy. Neuropathol Appl Neurobiol 1979; 5: 25-39. 19. Graham D. Hexane Neuropathy: A Proposal for Pathogenesis of a Hazard of Occupational Exposure and Inhalant Abuse. Chem Biol Interact 1980; 32: 339-345. 20. Schaumburg H, Spencer PS. Degeneration in Central and Peripheral Nervous System Produced by Pure n-Hexane: An Experimental Study. Brain 1976; 99: 183-192. 21. Korobkin R, Asbury AK, Sumner AJ, Nielsenn SL. Glue-Sniffing Neuropathy. Arch Neurol 1975; 32: 158-162. 22. Smith GA, Albers WJ. n-Hexane neuropathy due to rubber cement sniffing. Muscle and Nerve 1997; 20: 1445-1450. 23. Ruff RL, Petito CK, Acheson LS. Neuropathy Associated with Chronic Low Level Exposure to n-Hexane. Clin Toxicol 1981; 18: 515-519. 24. Athony DC, Boekelheide K, Graham DG. The Effect of 3,4-Dimethyl Substitution on the Neurotoxicity of 2,5-Hexanedionne. Toxicol Appl Pharmacol 1983; 71: 362- 371. 25. Couri D, Milks M. Toxicity and Metabolism of the Neurotoxic Hexacarbones n-Hexane, 2-Hexanone, and, 2,5-Hexanedione. Ann Rev Pharmacol Toxicol 1982; 22: 145-166. 26. DeCaprio AP, Strominger N, Weber P. Neurotoxicity and Protein binding of 2,5-Hexanedione in the Hen. Toxicol Appl Pharmacol 1983; 68: 297-307. 27. Cardona A, Marhuenda D, Marti J, et al. Biological Monitoring of Occupational Exposure to n-Hexane by Measurement of Urinary 2,5-Hexanedione. Int Arch Occup Environ Health 1993; 65: 71-74. 28. Graham DG, Anthony DC, Szakal-Quin G, Gottfried MR, Boekelheide K. Covalent Cross-linking of Neurofilaments in the Pathogenesis of n-Hexane Neuropathy. Neurotoxicol 1985; 6: 55-64. 29. Selkoe D, Luckenbill-Edds L, Shelanski ML. Effects of Neurotoxic Industrial Solvents on Cultured Neuroblastoma cells: Methyl n-Butyl Ketone, n-Hexane and Derivatives. Brain 1978; 105: 768-789. 30. Davenport JG, Farrell DF, Sumi S.M. 'Giant Axonal Neuropathy' Caused by Industrial Chemicals: Neurofilamentous Axonal Masses in Man. Neurology 1976; 26: 919-923. 31. De Lisa JA, Mackenzie K. Manual of Nerve Conduction Velocity Techniques. Raven Press, New York 1982; 32. Rosen I. Neurophysiological aspects of organic solvent toxicity. Acta Nuerol Scand 1984; 70: 101-106. 33. Altenkirch H, Wagner HM, Stoltenburg G, Spencer PS. Nervous System Responses of Rats to Subchronic Inhalation of n-Hexane and n-Hexane+ Methyl- Ethyl- Ketone Mixtures. J Neurol Sci 1982; 57: 209-219. 34. Ikeda T, Katakura Y, Kishi R, Miyake H. Acute Neurobehavioral Effects of Co-inhalation of Toluene and n-Hexane on Schedule-Controlled Behavior in Rats. Environ Res 1993; 63: 70-81. 35. Pryor G, Rebert C. Interactive Effects of Toluene and Hexane on Behavior and Neurophysiologic Responses in Fischer-344 Rats. Neuro Toxicol 1992; 13: 225-234. 36. Takeuchi Y, Ono Y, Hisanaga N. An experimental study on the combined effects of n-hexane and toluene on the peripheral nerve of the rat. Brit J Indus Med 1981; 38: 14-19. 37. Goto I, Matsumura M, Inoe N, et al. Toxic polyneuropathy due to glue sniffing. J Neurol Neurosurg Psychiatry 1974; 37: 848-53. 38. Pryor GT, Howell RA, Rebert CS. Developmental long-term effect of inhalants in animals. Final Report, NIDA Contract No. 271-80-3712 March, 1984b. 39. Lazar RB, Ho SV, Melen O, Daghestani AN. Multifocal central nervous system damage caused by toluene abuse. Neurol 1983; 33: 1337-1340. 40. Streicher HZ, Gabow PA, Moss AH. Syndromes of toluene sniffing in adults. Ann Int Med 1981; 94: 758-762. 41. Heuser M. Toluolsucht. Medizinische Klinik 1968; 63: 1888-1890. 42. Shirabe T, Tsuda T, Terao A, Araki S. Toxic polyneuropathy due to glue sniffing; report of two cases with a light and electron microscopic study of the peripheral nerves and muscles. J Neurol Sci 1974; 21: 101-113. 43. Towfighi J, Gonatas NK, Pleasure D. Glue sniffers neuropathy. Neurology 1976; 26: 243-248. 44. Passero S, Battistini N, Cioni K. Toxic polyneuropathy of shoe workers in Italy; A clinical, neurophysiological and follow-up study. Ital J Neurol Sci 1983; 4: 463-472. 45. Pastore C, Marhuenda D, Marti J, Cardonna A. Early Diagnosis of n-Hexane-Caused Neuropathy. Muscle and Nerve 1994; 17: 981-986. 46. Seppalainen AM. Neurophysiological Approach's to the Detection of Early Neurotoxicity in Humans. CRC Crit Rev Toxicol 1988; 18: 245-298. 47. Baslo MB. Çıraklık yapan çocuklarda subklinik n-heksan nöropatisinin klinik ve elektrofizyolojik incelemesi. Uzmanlık tezi. İstanbul Üniversitesi İstanbul Tıp Fakültesi Nöroloji Anabilim Dalı 1988; 48. Öge AE, Yazıcı J, Boyacıyan A, Eryıldız D, Örnek I, et al. Peripheral and Central Conduction in n-Hexane Polyneuropathy. Muscle and Nerve 1994; 17: 1416-1430. 49. Kendirli Y. Uçucu madde bağımlılığında nöro-fizyolojik ve nöropsikolojik değerlendirme. Uzmanlık tezi. Bakırköy Ruh ve Sinir Hastalıkları Hastanesi 2. Nöroloji Kliniği 1994.