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Seizures after myelography with lopamidol
Seizures After Myelography With lopamidol JON OLSEN, MD A 32-year-old man presented to the emergency department (ED) with
seizures 6 hours after a lumbar myelogram with iopamidol (Isovue-M 200, Squibb, Princeton, NJ). Seizures are a rare complication atter my elography with the current nonionic contrast agents and have not been previously reported in the emergency medicine literature. Emergency physicians should be aware of this potential complication because outpatient myelogramr are frequently performed, and these patients may present to the ED afler seizures. (Am J Emerg Med 1994;12:329-330. Copyright 0 1994 by W.B. Saunders Company)
lopamidol (Isovue-M nonionic, water-soluble myelography. One of the this agent is seizures, as
200, Squibb, Princeton, NJ) is a contrast media frequently used in more severe complications of using is presented in this case report.
CASE REPORT A 32-year-old man presented to the emergency department (ED) by ambulance after his girlfriend witnessed a generalized tonicclonic seizure with urinary incontinence lasting 2 minutes followed by a postictal state. On arrival at the ED, the patient was noted to be confused and combative. Initial vital signs were a blood pressure, 114/70 mm Hg; pulse. 124 beats/min; respirations, 24 breaths/min; and temperature, 38°C tympanic. Within minutes the patient suffered another generalized tonic-clonic seizure lasting 10 minutes. He received 20 mg of intravenous diazepam followed by 3 mg of midazolam and 1 g of phenytoin during a 30-minute period, resulting in control of seizure activity. Medical history showed that the patient had undergone an outpatient lumbar myelogram 6 hours before presentation for evaluation of low back pain. The procedure was performed without complications using 15mL of iopamidol. The contrast was not removed after instillation. He had no history of seizures, but did have only one functioning kidney for unknown reasons. He denied drug or alcohol abuse. His only medication was acetaminophenihydrocodone. He was allergic to aspirin, Physical examination after seizure control showed an alert male oriented to person, place, and time. Head and neck examination was normal with a supple neck and flat optic disks. Heart, lung, abdominal, and extremity examinations were normal. Neurological examination showed intact cranial nerves with no focal findings. Laboratory studies showed a white blood cell count of 12,000/ mm3 without left shift; hemoglobin, 15.7 g/dL; hematocrit, 44.9%; CO,, 140 mmol/L; potassium, 4.1 mmoUL; chloride, 108 mmol/L; CO’, 15 mmoYL; blood urea nitrogen, 10 mmoUL; creatinine, 1.2 mmol/L; glucose, 217 mmol/L; magnesium, 2.9 mmoVL; and calcium, 9.9 mmol/L. Arterial blood gas on a 100% nonrebreather was pH, 6.98; PcoZ, 36; and PO,. 293. A repeat blood gas 8 hours later was normal. A drug screen was positive for propoxyphene and no
From the Department of Emergency Medicine, Lutheran General Hospital, Park Ridge, IL. Manuscript received July 9, 1993; revision accepted October 11, 1993. Address reprint requests to Dr Olsen, Lutheran General Hospital, Department of Emergency Medicine, 1775 W Dempster, Park Ridge, 1L60068. Key Words: lopamidol, myelography, seizures. Copyright 0 1994 by W.3. Saunders Company 0735-6757/94/l 20%0017$5.00/0
alcohol was detected. An electrocardiogram showed sinus tachycardia. A cranial computed tomography scan showed contrast material throughout the subarachnoid space (Figure 1). The patient was admitted to the hospital, hydrated, and continued on phenytoin. He was discharged 2 days later and has remained seizure-free off medication after 7-months follow-up.
DISCUSSION Radiological examination of the spinal cord was first performed in the early 1900s with air myelography. In the early 1940s iophendylate gained popularity as the first contrast agent to be used. Iophendylate is oil based and high in viscosity, which results in inadequate filling of nerve root sleeves. It is insoluble in cerebrospinal fluid and should be removed by aspiration after administration to minimize side effects. These include acute and chronic meningeal reactions resulting in headaches, fever, altered mental status, seizures, dizziness, cranial nerve palsies, myoclonus, and adhesive arachnoiditis. l-3 In the following decades, ionic, water-soluble agents, such as methylglucamine iothalamate (Conray, Mallinckrod and Medical, St Louis, MO) and iocarmate meglumine were developed. Because of their hyperosmolarity, they were found to be excessively neurotoxic.2 In 1972, metrizamide was introduced as a first generation nonionic, water-soluble contrast agent for myelography.4 Metrizamide has been a satisfactory agent, but side effects have persisted. Seizures occur in 0.2% to 0.6% of cases.‘.’ Headaches occur in 30% to 50% of patients, and nauseal vomiting occur in 10% to 20% of patients.‘,’ A transient encephalopathy resulting in neuropsychiatric behaviors such as disorientation, haiIucinations, paranoia, and amnesia may be seen in 5% to 35% of patients.‘.2*‘,” Because of these persistent side effects, two new nonionic contrast agents have been developed, iopamidol (Isovue) and iohexol. These agents have been found to cause fewer neuropsychiatric complications than metrizamide, but a similar incidence of headache, nausea, and vomiting.3.7.8 It has been postulated that the symptoms of headache, nausea, and vomiting may be the result of the spinal tap itself rather than the contrast agent.9.‘0”9 Seizures have rarely been reported after iopamidol myelography’,“-14 and iohexol myelography’5*‘6; one of which also resulted in intracerebral hemorrhage.16 The mechanism of seizure induction is poorly understood, but is probably related to a direct neurotoxic effect’.3,s,‘6 or possibly idiosyncratic reactions.‘**” After intrathecal injection, contrast slowly diffuses rostrally against gravity and can be demonstrated in the posterior fossa within 6 hours.‘,‘2 The seizures typically develop within 12 hours of the procedure and are usually self-limited8.‘2.‘3 although they may persist for several days-l4 Additional severe complications reported with the newer agents include aseptic meningitis with iopamidol” and paraplegia after iohexol. r’ Data on the treatment of seizures after myelography are 329
330
AMERICAN
JOURNAL
OF EMERGENCY
MEDICINE
n Volume 12, Number 3 n May 1994
should be considered. Treatment is supportive and by using standard anticonvulsants. The seizures are typically selflimited. REFERENCES
FIGURE 1.
Contrast material through the subarachnoid
space.
limited, but includes standard therapy with a benzodiazepine, phenytoin, and supportive care.13*14 Factors that may decrease the incidence of side effects after myelography include elevation of the head for 6 hours after the study,‘,6.‘6 and avoidance of drugs that may lower the seizure threshold such as phenothiazines, monoamine oxidase inhibitors, tricyclic antidepressants,2,‘.6 or alcohol.‘* Adequate hydration4,6.‘6 and prophylaxis with anticonvulsants have also been recommended.5 Increased risk of seizures has been associated with increased spill of contrast into the brain such as during cervical myelography.6,‘3 Aspiration of water-soluble agents is not usually necessary,3 although it has been advocated by some to reduce side effects after lumbar myelography.’ Despite the low but still present risk of seizures after myelography, the patients should not drive or be alone for 24 hours after the procedure.i5*r9 Computed tomography findings include increased density of the brain parenchyma, which returns to normal within a few days. This is because of the passage of contrast media from the cerebral spinal fluid to the brain parenchyma.5
SUMMARY In patients presenting to the emergency department with seizures, a history of recent myelography as an etiology
1. Junck M, Marshall WH: Neurotoxicity of radiological agents. Ann Neurol 1983;13:489-484 2. Ansell G, Wilkins RA: Complications in Diagnostic Imaging. ed 2. New York, NY, Blackwell/Year Book Publishers, 1987, pp 31 O-323 3. Drayer BP, Vassallo C, Sudilovsky A, et al: A double-blind clinical trial of iopamidol versus metrizamide for lumbosacral myelography. J Neurosurg 1983;58:531-537 4. Meador K, Hamilton WJ, Gammel T, et al: Irreversible neurologic complications of metrizamide myelography. Neurology 1984;34:817-821 5. Centeno RS, Sovak M, Hackney D, et al: Brain changes on computed tomography following metrizamide myelographySignificance and therapeutic implications. Spine 1986;6:509512 6. Killebrew K, Whaley RA, et al: Complications of metrizamide myelography. Arch Neurol 1983;40:78-80 7. Bassi P, Cecchini A, Dettori P, et al: Myelography with iopamidol, a nonionic water-soluble contrast medium: Incidence of complications. Neuroradiology 1982;24:85-908 8. Sobel DF, Rowe R, Zyroff J, et al: Adverse reactions to iopamidol and iohexol myelography with special attention to headache: Role of myelographic technique. Headache 1989;519-522 9. Sand T, Stovner LJ, Dale L, et al: Side effects after diagnostic lumbar puncture and lumbar iohexol myelography. Neuroradiology 1987;29:385-388 10. Sand T, Myhr G, Stovner L, et al: Side effects after lumbar iohexol myelography-Relation to radiologic diagnosis, sex, and age. Neuroradiology 1990;31:523-528 11. Carella A, Federico F, Cuonzo F, et al: Adverse side effects of metrizamide and iopamidol in myelography. Neuroradiology 1982;22:247-249 12. Carchietti E, Baldassarre M, Pence T, et al: lopamidol300induced epilepsy: Intensive treatment and pathogenic hypothesis. Neuroradiology 1988;30:256-257 13. Levey Al, Weiss H, Yu R, et al: Seizures following myelography with iopamidol. Ann Neurol 1988;23:397-399 14. Lipman JC, Wang AM, Brooks M, et al: Seizure after intrathecal administration of iopamidol. AJNR 1988;9:787-788 15. Dalen K, Kerr HH, Wang A, et al: Seizure activity after iohexol myelography. Spine 1991;16:384 16. Van de Kelft E, Bosmans J, Parizel P, et al: lntracerebral hemorrhage after lumbar myelography with iohexol: A case report and review of the literature. 1991;28:570-574 17. Noda K, Miyamoto K, Bepper H, et al: Prolonged paraplegia after iohexol myelography. Lancet 1991;337:681 18. Robinson C, Fon G: Adverse reaction to iopamidol. Med J Austr 1986;144:553 19. Skalpe IO, Nakstad P: Myelography with iohexol (Omnipaque); A clinical report with special reference to the adverse effects. Neuroradiology 1988;30:169-174
seizures 6 hours after a lumbar myelogram with iopamidol (Isovue-M 200, Squibb, Princeton, NJ). Seizures are a rare complication atter my elography with the current nonionic contrast agents and have not been previously reported in the emergency medicine literature. Emergency physicians should be aware of this potential complication because outpatient myelogramr are frequently performed, and these patients may present to the ED afler seizures. (Am J Emerg Med 1994;12:329-330. Copyright 0 1994 by W.B. Saunders Company)
lopamidol (Isovue-M nonionic, water-soluble myelography. One of the this agent is seizures, as
200, Squibb, Princeton, NJ) is a contrast media frequently used in more severe complications of using is presented in this case report.
CASE REPORT A 32-year-old man presented to the emergency department (ED) by ambulance after his girlfriend witnessed a generalized tonicclonic seizure with urinary incontinence lasting 2 minutes followed by a postictal state. On arrival at the ED, the patient was noted to be confused and combative. Initial vital signs were a blood pressure, 114/70 mm Hg; pulse. 124 beats/min; respirations, 24 breaths/min; and temperature, 38°C tympanic. Within minutes the patient suffered another generalized tonic-clonic seizure lasting 10 minutes. He received 20 mg of intravenous diazepam followed by 3 mg of midazolam and 1 g of phenytoin during a 30-minute period, resulting in control of seizure activity. Medical history showed that the patient had undergone an outpatient lumbar myelogram 6 hours before presentation for evaluation of low back pain. The procedure was performed without complications using 15mL of iopamidol. The contrast was not removed after instillation. He had no history of seizures, but did have only one functioning kidney for unknown reasons. He denied drug or alcohol abuse. His only medication was acetaminophenihydrocodone. He was allergic to aspirin, Physical examination after seizure control showed an alert male oriented to person, place, and time. Head and neck examination was normal with a supple neck and flat optic disks. Heart, lung, abdominal, and extremity examinations were normal. Neurological examination showed intact cranial nerves with no focal findings. Laboratory studies showed a white blood cell count of 12,000/ mm3 without left shift; hemoglobin, 15.7 g/dL; hematocrit, 44.9%; CO,, 140 mmol/L; potassium, 4.1 mmoUL; chloride, 108 mmol/L; CO’, 15 mmoYL; blood urea nitrogen, 10 mmoUL; creatinine, 1.2 mmol/L; glucose, 217 mmol/L; magnesium, 2.9 mmoVL; and calcium, 9.9 mmol/L. Arterial blood gas on a 100% nonrebreather was pH, 6.98; PcoZ, 36; and PO,. 293. A repeat blood gas 8 hours later was normal. A drug screen was positive for propoxyphene and no
From the Department of Emergency Medicine, Lutheran General Hospital, Park Ridge, IL. Manuscript received July 9, 1993; revision accepted October 11, 1993. Address reprint requests to Dr Olsen, Lutheran General Hospital, Department of Emergency Medicine, 1775 W Dempster, Park Ridge, 1L60068. Key Words: lopamidol, myelography, seizures. Copyright 0 1994 by W.3. Saunders Company 0735-6757/94/l 20%0017$5.00/0
alcohol was detected. An electrocardiogram showed sinus tachycardia. A cranial computed tomography scan showed contrast material throughout the subarachnoid space (Figure 1). The patient was admitted to the hospital, hydrated, and continued on phenytoin. He was discharged 2 days later and has remained seizure-free off medication after 7-months follow-up.
DISCUSSION Radiological examination of the spinal cord was first performed in the early 1900s with air myelography. In the early 1940s iophendylate gained popularity as the first contrast agent to be used. Iophendylate is oil based and high in viscosity, which results in inadequate filling of nerve root sleeves. It is insoluble in cerebrospinal fluid and should be removed by aspiration after administration to minimize side effects. These include acute and chronic meningeal reactions resulting in headaches, fever, altered mental status, seizures, dizziness, cranial nerve palsies, myoclonus, and adhesive arachnoiditis. l-3 In the following decades, ionic, water-soluble agents, such as methylglucamine iothalamate (Conray, Mallinckrod and Medical, St Louis, MO) and iocarmate meglumine were developed. Because of their hyperosmolarity, they were found to be excessively neurotoxic.2 In 1972, metrizamide was introduced as a first generation nonionic, water-soluble contrast agent for myelography.4 Metrizamide has been a satisfactory agent, but side effects have persisted. Seizures occur in 0.2% to 0.6% of cases.‘.’ Headaches occur in 30% to 50% of patients, and nauseal vomiting occur in 10% to 20% of patients.‘,’ A transient encephalopathy resulting in neuropsychiatric behaviors such as disorientation, haiIucinations, paranoia, and amnesia may be seen in 5% to 35% of patients.‘.2*‘,” Because of these persistent side effects, two new nonionic contrast agents have been developed, iopamidol (Isovue) and iohexol. These agents have been found to cause fewer neuropsychiatric complications than metrizamide, but a similar incidence of headache, nausea, and vomiting.3.7.8 It has been postulated that the symptoms of headache, nausea, and vomiting may be the result of the spinal tap itself rather than the contrast agent.9.‘0”9 Seizures have rarely been reported after iopamidol myelography’,“-14 and iohexol myelography’5*‘6; one of which also resulted in intracerebral hemorrhage.16 The mechanism of seizure induction is poorly understood, but is probably related to a direct neurotoxic effect’.3,s,‘6 or possibly idiosyncratic reactions.‘**” After intrathecal injection, contrast slowly diffuses rostrally against gravity and can be demonstrated in the posterior fossa within 6 hours.‘,‘2 The seizures typically develop within 12 hours of the procedure and are usually self-limited8.‘2.‘3 although they may persist for several days-l4 Additional severe complications reported with the newer agents include aseptic meningitis with iopamidol” and paraplegia after iohexol. r’ Data on the treatment of seizures after myelography are 329
330
AMERICAN
JOURNAL
OF EMERGENCY
MEDICINE
n Volume 12, Number 3 n May 1994
should be considered. Treatment is supportive and by using standard anticonvulsants. The seizures are typically selflimited. REFERENCES
FIGURE 1.
Contrast material through the subarachnoid
space.
limited, but includes standard therapy with a benzodiazepine, phenytoin, and supportive care.13*14 Factors that may decrease the incidence of side effects after myelography include elevation of the head for 6 hours after the study,‘,6.‘6 and avoidance of drugs that may lower the seizure threshold such as phenothiazines, monoamine oxidase inhibitors, tricyclic antidepressants,2,‘.6 or alcohol.‘* Adequate hydration4,6.‘6 and prophylaxis with anticonvulsants have also been recommended.5 Increased risk of seizures has been associated with increased spill of contrast into the brain such as during cervical myelography.6,‘3 Aspiration of water-soluble agents is not usually necessary,3 although it has been advocated by some to reduce side effects after lumbar myelography.’ Despite the low but still present risk of seizures after myelography, the patients should not drive or be alone for 24 hours after the procedure.i5*r9 Computed tomography findings include increased density of the brain parenchyma, which returns to normal within a few days. This is because of the passage of contrast media from the cerebral spinal fluid to the brain parenchyma.5
SUMMARY In patients presenting to the emergency department with seizures, a history of recent myelography as an etiology
1. Junck M, Marshall WH: Neurotoxicity of radiological agents. Ann Neurol 1983;13:489-484 2. Ansell G, Wilkins RA: Complications in Diagnostic Imaging. ed 2. New York, NY, Blackwell/Year Book Publishers, 1987, pp 31 O-323 3. Drayer BP, Vassallo C, Sudilovsky A, et al: A double-blind clinical trial of iopamidol versus metrizamide for lumbosacral myelography. J Neurosurg 1983;58:531-537 4. Meador K, Hamilton WJ, Gammel T, et al: Irreversible neurologic complications of metrizamide myelography. Neurology 1984;34:817-821 5. Centeno RS, Sovak M, Hackney D, et al: Brain changes on computed tomography following metrizamide myelographySignificance and therapeutic implications. Spine 1986;6:509512 6. Killebrew K, Whaley RA, et al: Complications of metrizamide myelography. Arch Neurol 1983;40:78-80 7. Bassi P, Cecchini A, Dettori P, et al: Myelography with iopamidol, a nonionic water-soluble contrast medium: Incidence of complications. Neuroradiology 1982;24:85-908 8. Sobel DF, Rowe R, Zyroff J, et al: Adverse reactions to iopamidol and iohexol myelography with special attention to headache: Role of myelographic technique. Headache 1989;519-522 9. Sand T, Stovner LJ, Dale L, et al: Side effects after diagnostic lumbar puncture and lumbar iohexol myelography. Neuroradiology 1987;29:385-388 10. Sand T, Myhr G, Stovner L, et al: Side effects after lumbar iohexol myelography-Relation to radiologic diagnosis, sex, and age. Neuroradiology 1990;31:523-528 11. Carella A, Federico F, Cuonzo F, et al: Adverse side effects of metrizamide and iopamidol in myelography. Neuroradiology 1982;22:247-249 12. Carchietti E, Baldassarre M, Pence T, et al: lopamidol300induced epilepsy: Intensive treatment and pathogenic hypothesis. Neuroradiology 1988;30:256-257 13. Levey Al, Weiss H, Yu R, et al: Seizures following myelography with iopamidol. Ann Neurol 1988;23:397-399 14. Lipman JC, Wang AM, Brooks M, et al: Seizure after intrathecal administration of iopamidol. AJNR 1988;9:787-788 15. Dalen K, Kerr HH, Wang A, et al: Seizure activity after iohexol myelography. Spine 1991;16:384 16. Van de Kelft E, Bosmans J, Parizel P, et al: lntracerebral hemorrhage after lumbar myelography with iohexol: A case report and review of the literature. 1991;28:570-574 17. Noda K, Miyamoto K, Bepper H, et al: Prolonged paraplegia after iohexol myelography. Lancet 1991;337:681 18. Robinson C, Fon G: Adverse reaction to iopamidol. Med J Austr 1986;144:553 19. Skalpe IO, Nakstad P: Myelography with iohexol (Omnipaque); A clinical report with special reference to the adverse effects. Neuroradiology 1988;30:169-174