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Convulsive status epilepticus following intrathecal iopamidol administration
] Epilepsy 1994;7:18-20
© 1994Butterworth-Heinemann
Convulsive Status Epilepticus Following Intrathecal Iopamidol Administration David G. Vossler and 1Sanford J. Wright, Jr.
Rarely, seizures have followed iopamidol, iohexol, and metrizamide myelography. Riskfactorsfor this complicationhave been proposed. A man with no history of epilepsy who previously suffered an intracerebral hemorrhage developed sudden hyperpyrexia and generalized tonic-clordc status epilepticus (SE) after iopamidol cisternography. This is the first report of convulsive SE with this nonionic radiologic contrast medium. Cerebral corticaldamage may be an additional riskfactor for seizures after theintrathecaluse oftheseagents. KeyWords: Status epilepticus--Generalized tonic-clonic seizures--Iopamidol--Myelography.
Water-soluble, nonionic radiologic contrast media such as iohexol, iopamidol, and metrizamide are preferred to ionic agents like iophendylate and iothalamate for myelography and cisternography in part because they produce less frequent central nervous system adverse reactions (1-3). Nevertheless, side effects as serious as generalized tonic-clonic and partial seizures and nonconvulsive status epilepticus (SE) have occasionally occurred after iohexol and metrizamide administration (3-15). Generalized seizures have rarely followed iopamidol myelography (1,3,7,16-19). We did not find any previous reports of generalized tonic-clonic (convulsive) SE following the intrathecal use of these agents.
Case Report A 37-year-old man with a pre-existing arteriovenous malformation (AVM) suffered a spontaneous, large right temporal-occipital intracerebral hemor- .
Received August 2, 1993; accepted August 10, 1993. From the Epilepsy Center, Swedish Medical Center, Seatfie, and the 1Everett Neurological Center, Everett, WA, U.S.A. Address correspondence and reprintrequests to Dr. D. G. Vossler at Epilepsy Center, Swedish Medical Center/Seatfie, 1120 Cherry Street, Suite 400, Seattle, WA 98104-2023, U.S.A. 18 J EP/LEPSY,VOL. 7, NO. 1, 1994
rhage while skiing. He underwent three craniotomies and two vascular embolization procedures for treatment of the hemorrhage and AVM. Portions of the right temporal and occipital lobes and cerebellar hemisphere were resected (Fig. 1). Neurologic deficits included left hemiparesis and hemianesthesia and partial dysfunction of the right cranial nerves III-VIII. Although the patient had no seizures, carbamazepine 600 mg/day was administered prophylactically for 20 months after surgery. Episodes of cerebrospinal fluid (CSF) rhinorrhea resulted in staphylococcal meningitis on two occasions and were treated with antibiotics and a lumbar drain. Four years after the hemorrhage, the patient sneezed and developed nonfebrile CSF rhinorrhea. Computed tomography (CT) of the head revealed pneumocephalus. CSF analysis revealed a 4 WBC/mm 3 (100% lymphocytes) and negative cultures. He was given ceftizoxime 2 g b.i.d., and chronically took dapsone 100 mg/day for dermatitis herpetiformis. Prior to neurosurgical repair of the dural tear, 15 ml of Isovue 300 (300 mg I/ml) was injected intrathecaUy at the L2-L3 level, and the patient was placed supine for temporal region imaging. CT demonstrated CSF leaking into the right middle ear. Eighteen hours later, the patient spiked a fever of 106°F. Two hours later, he developed left-sided clonic limb jerks progressing to leftward eye deviation and then to 45 min
STATUS EPILEPTICUS AFTER IOPAMIDOL
of continuous generalized tonic-clonic convulsive movements. Control of SE required 30 mg diazepam, 4 mg lorazepam, and I g intravenous phenytoin. The patient was mechanically ventilated and externally cooled. He remained comatose for over 24 h. Repeat CSF studies were unchanged. An EEG 4 h after SE demonstrated diffuse 2-5-Hz waves with occasional periods of suppression of the background activity. Repeat CT 6 h after SE revealed a large quantity of contrast medium within the lateral, third, and fourth ventricles (Fig. 2). A fourth CT scan 2 days later showed no intracranial iopamidol. He remained on phenytoin and antibiotics and underwent surgical repair of the CSF leak. Afterwards, substantial cognitive deficits and worsened right hemiparesis improved over several weeks of rehabilitation. No subsequent seizures occurred and phenytoin was discontinued 2 months later.
Discussion
Figure 1. CT scan of the brain without contrast medium prior to myelography. Areas of encephalomalacia and resected tissue are apparent in the right temporal and anterior cerebellar areas.
Figure 2. Brain CT scan without intravenous contrast medium 26 h after cisternography, lopamidol is apparent in the lateral ventricles bilaterally. The cystic area in the right anterior limb of the internal capsule had been seen on several previous CTs and felt to be a microvascular infarction.
Metrizamide has caused partial (3) and generalized tonic-clonic (5,10) seizures, complex partial SE (4), and atypical absence SE (6,9,11-15). Most of these cases of nonconvulsive SE (4,6,11-15) subsided quickly when treated with intravenous benzodiazepines. Newer nonionic media, such as iopamidol and iohexol, have a lower risk than metrizamide of producing a variety of central nervous system adverse effects (1,7, 10,16,20,21). Nevertheless, iohexol has been associated with partial (7) and generalized tonic-clonic (8) seizures, and nonconvulsive SE (9) up to 24 h after administration (8). Moreover, generalized tonicclonic seizures have very rarely followed iopamidol myelography (1,3,7,16-19). The mechanisms by which these media cause seizures are incompletely known. Metrizamide penetrates cerebral gray matter by diffusion (2,5,22). It competitively inhibits hexokinase activity (5), whereas iopamidol probably does not (16). The effects of these agents vary possibly because of small differences in molecular side-chains (23). In experimental animals, metrizamide causes diffuse slowing of EEG activity and generalized seizures (5) and has a higher seizure-inducing potential than iohexol or iopamidol (20). Metrizamide produces increased EEG slow activity in up to 50%, and spikes and sharp waves in up to 17%, of patients (5,10,20,24). Iohexol causes slow waves in 10%, and epileptiform discharges in 0%, of subjects (20,21). Slow activity was statistically significantly greater at 24 than at 6 h, and more marked with metrizamide than iohexol, on both visual and computerized spectral EEG analysis (20,24). Iopamidol produces sharp waves or marked delta activity in j EPILEPSY, VOL. 7, NO. 1, 1994
19
D. G. VOSSLER AND S. J. WRIGHT
the EEGs of 4-6% of patients 6 h after myelography (10,21). These data suggest that the seizure-inducing effects of iohexol (20) and iopamidol (10) may be less than that of metrizamide. Possible risk factors for seizures with nonionic CSF contrast agents include: a history of epilepsy, excessive dose (over 3 g iodine), more rostral levels of myelography (particularly with intracranial contrast entry), concurrent use of drugs that lower the seizure threshold, excessive patient movement, and failure to keep the head elevated (4,5,8,10,16,20). Because our patient's SE began with left-sided motor activity, it is likely that irritation of the damaged areas of cortex played a role in seizure induction. The large dose of iopamidol, hyperpyrexia, intracranial entry of a substantial quantity of contrast medium, and use of ceftizoxime and dapsone may have also contributed. Myelography has become largely an outpatient procedure in the United States. However, patients with injured cerebral cortex or other previously reported risk factors may need to be observed for seizures by medical personnel for up to 24 h after intrathecal administration of these media even w h e n there is no history of epilepsy.
References 1. Lipman JC, Wang A-M, Brooks ML, Schick RM, Rumbaugh CL. Seizure after intrathecal administration of iopamidol. AJNR 1988;9:787-8. 2. Sage MR, Wilcox J, Evill CA, Benness GT. Brain parenchyma penetration by intrathecal ionic and nonionic contrast media. AJNR 1982;3:481-3. 3. Carella A, Federico F, DiCuonzo F, Vinjau E, Lamberti P. Adverse side effects of metrizamide and iopamidole in myelography. Neuroradiology 1982;22:247-9. 4. Russell D, Anke IM, Nyberg-Hansen R, Slettnes O, Sortland O, Veger T. Complex partial status epilepticus following myelography with metrizamide. Ann Neurol 1980;8:325-7. 5. BertoniJM, SchwartzmanRJ, VanHornG, PartinJ. Asterixis and encephalopathy following metrizamide myelography: investigations into possible mechanisms and review of the literature. Ann Neurol 1981;9: 366-70. 6. Pritchard PB, O'NealDB. Nonconvulsive status epileptic'us following metrizamide myelography. Ann Neuro! 1984;16:252--4. 7. Dalen K, Kerr HI-I, Wang A-M, Olson RE, Wesolowski DP, Farah J. Seizure activity after iohexol myelography. Spine 1991;16:384.
20
J E~ILEPSY, VOL. 7, NO. 1, 1994
8. Altschuler EM, Segal R. Generalized seizures following myelography with iohexol (Omnipaque). J Spinal Dis 1990;3:59-61. 9. Ahmed I, Pepple R, Jones RP. Absence status epilepticus resulting from metrizamide and Omnipaque myelography. Clin EEG 1988;19:37-42. 10. Moschini L, Manara O, Bonaldi G, Cassinari V, Quilici N, Belloni G. Iopamidol and metrizamide in cervical myelography: side effects, EEG, and CSF changes. AJNR 1983;4:848-50. 11. Levin R, Lee SI. Nonconvulsive status epilepticus following metrizamide myelogram. Ann Neurol 1985;17: 518-9. 12. Wagner JH. Another report of nonconvulsive status epilepticus after metrizamide myelography. Ann Neurol 1985;18:369-70. 13. Vollmer ME, Weiss H, Beanland C, Krumholz A. Prolonged confusion due to absence status following metrizamide myelography. Arch Neuro11985;42:10058. 14. Elian M, Fenwick P. Metrizamide and the EEG: three case reports and a review. J Neurol 1985;232:341-5. 15. Obeid T, Yaqub B, Panayiotopoulos CP, A1-Jasser S, Shabaan A, Hawass N E-D. Absence status epilepticus with computed tomographic brain changes following metrizamide myelography. Ann Neurol 1988;24:5824. 16. Levey AI, Weiss H, Yu R, Wang H, Krumholz A. Seizures following myelography with iopaminol. Ann Neurol 1988;23:397-9. 17. Grunert P, Pendl G. Cerebral seizure following lumbar myelography with iopamidol. Radiologe 1986;26:5267. 18. Carchietti E, Baldassarre M, Penco T, Leonardi M. Iopamido1300-induced epilepsy: intensive treatment and pathogenic hypothesis. Neuroradiology 1988;30: 256-7. 19. Bassi P, Cecchini A, Dettori P, Signorini E. Myelography with iopamidol, a nonionic water-soluble contrast medium: incidence of complications. Neuroradiology 1982;24:85-90. 20. Maly P, Bach-Gansmo T, Elmqvist D. Risk of seizures after myelography: comparison of iohexol and metrizamide. AJNR 1988;9:879-83. 21. Macpherson P, Teasdale E, Coutinho C, McGeorge A. Iohexol versus iopamidol for cervical myelography: a randomised double blind study. Br J Radiol 1985;58: 849-51. 22. Vincent FM. CT after metrizamide myelography. Neurology 1982;32:685. 23. Nakagawa H, Arita S, Kobayashi S, Ikoma Y, Oshino N. Neurotropic effects of non-ionic contrast media. Nippon Yakurigaku Zasshi 1989;93:187-96. 24. Ropper AH, Chiappa KH, Young RR. The effect of metrizamide on the electroencephalogram: a prospective study in 61 patients. Ann Neurol 1979;6:222-6.
© 1994Butterworth-Heinemann
Convulsive Status Epilepticus Following Intrathecal Iopamidol Administration David G. Vossler and 1Sanford J. Wright, Jr.
Rarely, seizures have followed iopamidol, iohexol, and metrizamide myelography. Riskfactorsfor this complicationhave been proposed. A man with no history of epilepsy who previously suffered an intracerebral hemorrhage developed sudden hyperpyrexia and generalized tonic-clordc status epilepticus (SE) after iopamidol cisternography. This is the first report of convulsive SE with this nonionic radiologic contrast medium. Cerebral corticaldamage may be an additional riskfactor for seizures after theintrathecaluse oftheseagents. KeyWords: Status epilepticus--Generalized tonic-clonic seizures--Iopamidol--Myelography.
Water-soluble, nonionic radiologic contrast media such as iohexol, iopamidol, and metrizamide are preferred to ionic agents like iophendylate and iothalamate for myelography and cisternography in part because they produce less frequent central nervous system adverse reactions (1-3). Nevertheless, side effects as serious as generalized tonic-clonic and partial seizures and nonconvulsive status epilepticus (SE) have occasionally occurred after iohexol and metrizamide administration (3-15). Generalized seizures have rarely followed iopamidol myelography (1,3,7,16-19). We did not find any previous reports of generalized tonic-clonic (convulsive) SE following the intrathecal use of these agents.
Case Report A 37-year-old man with a pre-existing arteriovenous malformation (AVM) suffered a spontaneous, large right temporal-occipital intracerebral hemor- .
Received August 2, 1993; accepted August 10, 1993. From the Epilepsy Center, Swedish Medical Center, Seatfie, and the 1Everett Neurological Center, Everett, WA, U.S.A. Address correspondence and reprintrequests to Dr. D. G. Vossler at Epilepsy Center, Swedish Medical Center/Seatfie, 1120 Cherry Street, Suite 400, Seattle, WA 98104-2023, U.S.A. 18 J EP/LEPSY,VOL. 7, NO. 1, 1994
rhage while skiing. He underwent three craniotomies and two vascular embolization procedures for treatment of the hemorrhage and AVM. Portions of the right temporal and occipital lobes and cerebellar hemisphere were resected (Fig. 1). Neurologic deficits included left hemiparesis and hemianesthesia and partial dysfunction of the right cranial nerves III-VIII. Although the patient had no seizures, carbamazepine 600 mg/day was administered prophylactically for 20 months after surgery. Episodes of cerebrospinal fluid (CSF) rhinorrhea resulted in staphylococcal meningitis on two occasions and were treated with antibiotics and a lumbar drain. Four years after the hemorrhage, the patient sneezed and developed nonfebrile CSF rhinorrhea. Computed tomography (CT) of the head revealed pneumocephalus. CSF analysis revealed a 4 WBC/mm 3 (100% lymphocytes) and negative cultures. He was given ceftizoxime 2 g b.i.d., and chronically took dapsone 100 mg/day for dermatitis herpetiformis. Prior to neurosurgical repair of the dural tear, 15 ml of Isovue 300 (300 mg I/ml) was injected intrathecaUy at the L2-L3 level, and the patient was placed supine for temporal region imaging. CT demonstrated CSF leaking into the right middle ear. Eighteen hours later, the patient spiked a fever of 106°F. Two hours later, he developed left-sided clonic limb jerks progressing to leftward eye deviation and then to 45 min
STATUS EPILEPTICUS AFTER IOPAMIDOL
of continuous generalized tonic-clonic convulsive movements. Control of SE required 30 mg diazepam, 4 mg lorazepam, and I g intravenous phenytoin. The patient was mechanically ventilated and externally cooled. He remained comatose for over 24 h. Repeat CSF studies were unchanged. An EEG 4 h after SE demonstrated diffuse 2-5-Hz waves with occasional periods of suppression of the background activity. Repeat CT 6 h after SE revealed a large quantity of contrast medium within the lateral, third, and fourth ventricles (Fig. 2). A fourth CT scan 2 days later showed no intracranial iopamidol. He remained on phenytoin and antibiotics and underwent surgical repair of the CSF leak. Afterwards, substantial cognitive deficits and worsened right hemiparesis improved over several weeks of rehabilitation. No subsequent seizures occurred and phenytoin was discontinued 2 months later.
Discussion
Figure 1. CT scan of the brain without contrast medium prior to myelography. Areas of encephalomalacia and resected tissue are apparent in the right temporal and anterior cerebellar areas.
Figure 2. Brain CT scan without intravenous contrast medium 26 h after cisternography, lopamidol is apparent in the lateral ventricles bilaterally. The cystic area in the right anterior limb of the internal capsule had been seen on several previous CTs and felt to be a microvascular infarction.
Metrizamide has caused partial (3) and generalized tonic-clonic (5,10) seizures, complex partial SE (4), and atypical absence SE (6,9,11-15). Most of these cases of nonconvulsive SE (4,6,11-15) subsided quickly when treated with intravenous benzodiazepines. Newer nonionic media, such as iopamidol and iohexol, have a lower risk than metrizamide of producing a variety of central nervous system adverse effects (1,7, 10,16,20,21). Nevertheless, iohexol has been associated with partial (7) and generalized tonic-clonic (8) seizures, and nonconvulsive SE (9) up to 24 h after administration (8). Moreover, generalized tonicclonic seizures have very rarely followed iopamidol myelography (1,3,7,16-19). The mechanisms by which these media cause seizures are incompletely known. Metrizamide penetrates cerebral gray matter by diffusion (2,5,22). It competitively inhibits hexokinase activity (5), whereas iopamidol probably does not (16). The effects of these agents vary possibly because of small differences in molecular side-chains (23). In experimental animals, metrizamide causes diffuse slowing of EEG activity and generalized seizures (5) and has a higher seizure-inducing potential than iohexol or iopamidol (20). Metrizamide produces increased EEG slow activity in up to 50%, and spikes and sharp waves in up to 17%, of patients (5,10,20,24). Iohexol causes slow waves in 10%, and epileptiform discharges in 0%, of subjects (20,21). Slow activity was statistically significantly greater at 24 than at 6 h, and more marked with metrizamide than iohexol, on both visual and computerized spectral EEG analysis (20,24). Iopamidol produces sharp waves or marked delta activity in j EPILEPSY, VOL. 7, NO. 1, 1994
19
D. G. VOSSLER AND S. J. WRIGHT
the EEGs of 4-6% of patients 6 h after myelography (10,21). These data suggest that the seizure-inducing effects of iohexol (20) and iopamidol (10) may be less than that of metrizamide. Possible risk factors for seizures with nonionic CSF contrast agents include: a history of epilepsy, excessive dose (over 3 g iodine), more rostral levels of myelography (particularly with intracranial contrast entry), concurrent use of drugs that lower the seizure threshold, excessive patient movement, and failure to keep the head elevated (4,5,8,10,16,20). Because our patient's SE began with left-sided motor activity, it is likely that irritation of the damaged areas of cortex played a role in seizure induction. The large dose of iopamidol, hyperpyrexia, intracranial entry of a substantial quantity of contrast medium, and use of ceftizoxime and dapsone may have also contributed. Myelography has become largely an outpatient procedure in the United States. However, patients with injured cerebral cortex or other previously reported risk factors may need to be observed for seizures by medical personnel for up to 24 h after intrathecal administration of these media even w h e n there is no history of epilepsy.
References 1. Lipman JC, Wang A-M, Brooks ML, Schick RM, Rumbaugh CL. Seizure after intrathecal administration of iopamidol. AJNR 1988;9:787-8. 2. Sage MR, Wilcox J, Evill CA, Benness GT. Brain parenchyma penetration by intrathecal ionic and nonionic contrast media. AJNR 1982;3:481-3. 3. Carella A, Federico F, DiCuonzo F, Vinjau E, Lamberti P. Adverse side effects of metrizamide and iopamidole in myelography. Neuroradiology 1982;22:247-9. 4. Russell D, Anke IM, Nyberg-Hansen R, Slettnes O, Sortland O, Veger T. Complex partial status epilepticus following myelography with metrizamide. Ann Neurol 1980;8:325-7. 5. BertoniJM, SchwartzmanRJ, VanHornG, PartinJ. Asterixis and encephalopathy following metrizamide myelography: investigations into possible mechanisms and review of the literature. Ann Neurol 1981;9: 366-70. 6. Pritchard PB, O'NealDB. Nonconvulsive status epileptic'us following metrizamide myelography. Ann Neuro! 1984;16:252--4. 7. Dalen K, Kerr HI-I, Wang A-M, Olson RE, Wesolowski DP, Farah J. Seizure activity after iohexol myelography. Spine 1991;16:384.
20
J E~ILEPSY, VOL. 7, NO. 1, 1994
8. Altschuler EM, Segal R. Generalized seizures following myelography with iohexol (Omnipaque). J Spinal Dis 1990;3:59-61. 9. Ahmed I, Pepple R, Jones RP. Absence status epilepticus resulting from metrizamide and Omnipaque myelography. Clin EEG 1988;19:37-42. 10. Moschini L, Manara O, Bonaldi G, Cassinari V, Quilici N, Belloni G. Iopamidol and metrizamide in cervical myelography: side effects, EEG, and CSF changes. AJNR 1983;4:848-50. 11. Levin R, Lee SI. Nonconvulsive status epilepticus following metrizamide myelogram. Ann Neurol 1985;17: 518-9. 12. Wagner JH. Another report of nonconvulsive status epilepticus after metrizamide myelography. Ann Neurol 1985;18:369-70. 13. Vollmer ME, Weiss H, Beanland C, Krumholz A. Prolonged confusion due to absence status following metrizamide myelography. Arch Neuro11985;42:10058. 14. Elian M, Fenwick P. Metrizamide and the EEG: three case reports and a review. J Neurol 1985;232:341-5. 15. Obeid T, Yaqub B, Panayiotopoulos CP, A1-Jasser S, Shabaan A, Hawass N E-D. Absence status epilepticus with computed tomographic brain changes following metrizamide myelography. Ann Neurol 1988;24:5824. 16. Levey AI, Weiss H, Yu R, Wang H, Krumholz A. Seizures following myelography with iopaminol. Ann Neurol 1988;23:397-9. 17. Grunert P, Pendl G. Cerebral seizure following lumbar myelography with iopamidol. Radiologe 1986;26:5267. 18. Carchietti E, Baldassarre M, Penco T, Leonardi M. Iopamido1300-induced epilepsy: intensive treatment and pathogenic hypothesis. Neuroradiology 1988;30: 256-7. 19. Bassi P, Cecchini A, Dettori P, Signorini E. Myelography with iopamidol, a nonionic water-soluble contrast medium: incidence of complications. Neuroradiology 1982;24:85-90. 20. Maly P, Bach-Gansmo T, Elmqvist D. Risk of seizures after myelography: comparison of iohexol and metrizamide. AJNR 1988;9:879-83. 21. Macpherson P, Teasdale E, Coutinho C, McGeorge A. Iohexol versus iopamidol for cervical myelography: a randomised double blind study. Br J Radiol 1985;58: 849-51. 22. Vincent FM. CT after metrizamide myelography. Neurology 1982;32:685. 23. Nakagawa H, Arita S, Kobayashi S, Ikoma Y, Oshino N. Neurotropic effects of non-ionic contrast media. Nippon Yakurigaku Zasshi 1989;93:187-96. 24. Ropper AH, Chiappa KH, Young RR. The effect of metrizamide on the electroencephalogram: a prospective study in 61 patients. Ann Neurol 1979;6:222-6.