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Contrast-Induced Seizures After Cardiac Catheterization in a 6-Year-Old Child
Contrast-Induced Seizures After Cardiac Catheterization in a 6-Year-Old Child Valeria Sansone, MD*, Lucienne Piazza, MD†, Gianfranco Butera, MD†, Giovanni Meola, MD*, and Alessandro Fontana, MD‡ Neurologic complications of cardiac catheterization are usually embolic events resulting in stroke or seizures of vascular origin. Contrast-induced seizures have been rarely described in children. This report presents clinical, neuroimaging, and follow-up data of a 6-year-old female subjected to cardiac catheterization for aortic coarctation who developed contrastinduced generalized seizures. Although rare, this condition adds to the neurologic complications of cardiac catheterization in children and should be considered in the differential diagnosis of seizures of vascular origin with obvious therapeutic and prognostic implications. © 2007 by Elsevier Inc. All rights reserved. Sansone V, Piazza L, Butera G, Meola G, Fontana A. Contrast-induced seizures after cardiac catheterization in a 6-year-old child. Pediatr Neurol 2007;36:268-270.
Introduction Left heart catheterization involves a risk of cerebral complications associated with catheterization-related cerebral microemboli responsible for stroke episodes, cognitive impairment, and neuropsychological deficits [1-5]. In these cases, white matter hyperintense lesions and abnormal diffusion-weighted imaging sequences
From the Departments of *Neurology, ‡Neuroradiology, and †Pediatric Cardiac Surgery, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
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may be demonstrated on brain magnetic resonance imaging [1]. Whereas seizures are among the complications of cardiac catheterization, they have not been directly related to angiocardiography but rather to hypoxic-ischemic encephalopathy present as part of global developmental delay and malformations [1]. Although rare, ionic and nonionic contrast-induced seizures after cardiac catheterization or as a complication of enhanced cranial computed tomography have been reported in adults [1,2, 5-8]. So far there has been only one report regarding an 18-month-old male who developed a new-onset focal seizure 12 hours after cardiac catheterization [9]. The present report describes an additional patient, a 6-year-old female who developed contrast-induced generalized seizures half an hour after cardiac catheterization. The clinical, neuroimaging, and follow-up data gathered 1 year later are discussed. Case Report The proband is a 6-year-old female who was referred to the Cardiology and Cardiac Surgery Department for severe aortic isthmic coarctation and systemic hypertension. Family and past medical history were unremarkable. A few months before admission she had a complete cardiologic assessment because she wanted to attend gymnastic courses. On this occasion, the diagnosis of aortic coarctation was made and interventional cardiac catheterization was suggested. On admission her O2 saturation was 97%; she weighed 26.5 kg and her height was 116 cm. Blood pressure in the upper limbs was as follows: right arm 125/75 mm Hg and left arm 130/80; in the lower limbs: right leg 100/60 and left leg 65/60 mm Hg. The echocardiogram demonstrated severe isthmic coarctation (maximal gradient approximately 30 mm Hg with diastolic tail); hypertrophied left ventricle with good systolic function; and mildly dilated ascending aorta associated with dilatation of horizontal aorta. Two days after admission, the patient underwent interventional cardiac catheterization under general anesthesia (atracurium 0.5 mg/kg, midazolam 0.2 mg/kg, fentanyl 1.6 g/kg). A right femoral artery percutaneous sheath was introduced; 100 UI/kg of heparin were administered. An angiographic pigtail catheter was positioned in the ascending aorta for aortography in order to define the anatomy. The lateral and anteroposterior view confirmed severe and tubular isthmic aortic coarctation with a maximal gradient of 40 mm Hg. The coarctation was treated with 3 ⫻ 20 and subsequently with 5 ⫻ 20 SMASH Balloon dilatation (Boston Scientific International, Galway, Ireland). Angiograms disclosed a small aneurysm in the site of the dilatation. Therefore a 34-cover CP stent (Numed. Inc, Hopkinton, NY) mounted on 10 ⫻ 40 Crystal Balloon (BALT, Mont Morency, France) was implanted. The gradient after the implantation successfully fell to 10 mm Hg. Two control angiograms excluded dissection and residual aneurysm. For this procedure, the total amount of iodate contrast (Iobitridolo-Xenetix 350 mg) was 500 mL.
Communications should be addressed to: Dr. Sansone; Department of Neurology; University of Milan; IRCCS Policlinico San Donato; Via Morandi 30; San Donato Milanese; Milan, Italy. E-mail: [email protected]; [email protected] Received July 10, 2006; accepted October 16, 2006.
© 2007 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2006.10.008 ● 0887-8994/07/$—see front matter
Figure 1. (A) A 5-mm brain computed tomographic scan performed in the acute setting. Note all cerebral sulci were of increased density and both cortical circonvolutions and cerebellar folia were clearly visible. (B) A 5-mm repeat brain computed tomographic scan performed the day after the acute onset of seizures; unchanged. Note cerebral edema. (C) Follow-up 5-mm brain computed tomographic scan 7 days after acute onset of seizures. Persistence of white cerebellar sign. 4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™ Throughout the procedure, hemodynamic parameters remained stable. The fluoroscopy time was 35 minutes. The procedure time was 90 minutes. Duration of anesthesia was 2 hours. Five minutes after extubation, while the patient was breathing spontaneously in the recovery room, she developed continuous generalized seizures which required reintubation and ventilatory support. There was a prompt response to 0.5 mg diazepam administered intravenously. Blood pressure and cardiac function were stable. There were no electrolyte abnormalities. Suspecting a thromboembolic event related to the invasive procedure, a computed tomographic scan was performed to exclude acute focal brain lesions (Fig 1A). All cerebral sulci were of increased density, and both cortical gyri and cerebellar folia appeared clearly delineated. The brainstem, cerebral and cerebellar peduncles appeared of relatively low density. The ventricles were scarcely visible because of the “brilliancy” of the choroidal plexuses. These findings were highly suggestive of contrast retention. Both thalami were particularly bright compared with the remaining basal nuclei. The superior sagittal sinus evidenced the delta sign. Two hours later the patient had a new generalized seizure. Diazepam (10 mg) and midazolam (5 mg), both intravenously administered, controlled seizure activity only partially. Phenobarbital 200 mg, administered intravenously, was introduced with resolution of the episode for 1 hour. Clonic movements of the right arm and left leg were observed. In addition, there was spontaneous bilateral internal rotation of the limbs. 15 mg/kg phenytoin in 15 minutes (1 mg/kg/min) was given. Mannitol 0.5 mg/kg four times a day and desamethaxone 4 mg twice daily with gastric protection were also added. On the following day the brain computed tomographic scan was repeated (Fig 1B). There was a general worsening of the previous findings. Diffuse cerebral edema and white cerebellar sign were unchanged. The patient was kept in barbiturate coma for 5 days. No further epileptic episodes occurred. Gradual clinical recovery was observed until she was extubated and transferred to the Pediatric Cardiology ward. Neurologic examination on Day 7 was normal except for a mild motor impairment of the right hand. Computed tomographic scan was repeated and was normal except for the persistence of the white cerebellar sign (Fig 1C). On Day 9 neurologic examination returned to normal. Electroencephalography was normal. On Day 10, 1.5 Tesla brain magnetic resonance imaging was normal: cortical sulci, dimension, and morphology of the ventricular system and flow of the dural sinus were all within normal range. Contrast medium was no longer visible in the cortical sulci or brain parenchyma. Follow-up assessment 1 year later was normal. No further convulsive episodes were reported. Motor milestones were normal since the procedure and no neurologic sequelae were evident. School performance was good. The patient participated in school activities without hesitation and interacted with her schoolmates with no difficulty.
Conclusions Our data emphasize that contrast-induced seizures, although rarely, may occur in children after cardiac catheterization. Thromboembolic seizures, as a manifestation of a stroke, may also occur in children after cardiac catheterization [4,5,10]. Thromboembolic seizures and contrastinduced seizures cannot be distinguished clinically. Indirect signs of a thromboembolic lesion in the acute setting are hyperdense artery sign, swelling of brain tissue, and
Sansone et al: Contrast-Induced Seizures 269
reduced differentiation between gray and white matter. However, these indirect signs were masked by the massive presence of contrast medium in the cerebral sulci and intracranial vessels (Fig 1). The brilliancy of the superior sagittal sinus like that of this patient’s computed tomographic scan is common in patients subjected to a cardiac surgery procedure due to a temporary collapse of the dural sinus. This brilliancy mimics venous thrombosis, which could not be ruled out initially in the patient reported herein. Magnetic resonance imaging at follow-up demonstrated normal flow of the dural sinus, ruling out this hypothesis. Previous authors have well described how contrast media can cause both nonidiosyncratic and idiosyncratic reactions. Nonidiosyncratic reactions are related to the properties of the media such as hyperosmolality and chemotoxicity of the molecule, hypotheses which cannot be ruled out in this patient. Idiosyncratic reactions are allergic-like reactions whose mechanism is not yet well understood and may be multifactorial. Seizures might result from ischemic lesions due to cerebral embolism and hypoxia or intracranial hemorrhage secondary to anticoagulation [3]. Low-dose heparin was used in this patient. Although the characteristics of brain vessel endothelial cells in children affected by aortic coarctation in terms of contrast permeability are not well described, in adults the association between coarctation and brain ischemic-hemorrhagic events has been widely reported [11,12], suggesting that some predisposing factor in this cardiac malformation might have played a role in the patient described in the present report. Seizures, like other neurologic complications after cardiac catheterization, may be related, among other factors, to several conditions such as the prolonged duration of the catheterization procedure and interventional manipulation [1,3]. Contrast medium is normally retained for 24 hours after intravenous administration for cranial tomography and for several hours for cardiac catheterization of young children. The usual doses are 2 mL/kg body weight. Cardiac catheterization in this case lasted 2 hours, mainly because of the complex anatomy of the coarctation, which required more contrast than usual (18 mL/kg); throughout the procedure, the patient was hemodynamically stable, had a good urine output and normal electrolytes.
270
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Patients with hypoxic-ischemic encephalopathy at birth may be particularly susceptible to neurologic complications; children affected by aortic coarctation might be predisposed to brain injuries owing to their hypertensive condition. We believe that the etiology of seizures in the patient described here was multifactorial: parenchymal contrast irritation, the amount of contrast used, the duration of the procedure, and cerebral microvascular abnormalities secondary to the aortic coarctation. To sum up, contrast toxicity should be considered in the differential diagnosis of seizures arising after angiography in children. Identifying the cause of this complication has important prognostic implications and may lead to more effective prevention and treatment. We are grateful to Alasdair McEwen (professional translator) for having read and revised this paper and to Drs. Matteo Bonetti and Biagio Cotticelli for having compiled neuroimaging data.
References [1] Lund C, Nes RB, Ugelstad TP, et al. Cerebral emboli during left heart catheterization may cause acute brain injury. Eur Heart J 2005;26: 1269-75. [2] Furlan AJ, Sila CA, Chimowitz MI, Jones SC. Neurologic complications related to cardiac surgery. Neurol Clin 1992;10:145-66. [3] Liu XY, Wong V, Leung M. Neurologic complications due to catheterization. Pediatr Neurol 2001;24:270-5. [4] Bronster DJ. Neurologic complications of cardiac surgery: Current concepts and recent advances. Curr Cardiol Rep 2006;8:9-16. [5] Agnoletti G, Bonnet C, Boudjemline Y, et al. Complications of paediatric interventional catheterization: An analysis of risk factors. Cardiol Young 2005;15:402-6. [6] Drake TG, Kerr HD. Status epilepticus after cranial CT with contrast media. WMJ 1997;96:46-8. [7] Muruve DA, Steinman TI. Contrast-induced encephalopathy and seizures in a patient with chronic renal insufficiency. Clin Nephrol 1996;45: 406-9. [8] Fischer HW. Occurrence of seizure during cranial computed tomography. Radiology 1980;137:563-4. [9] Frye RE, Newburger JW, Nugent A, Sahin M. Focal seizure and cerebral contrast retention after cardiac catheterization. Pediatr Neurol 2005;32:213-6. [10] Weissman BM, Aram DM, Levinsohn MW, Ben-Shachar G. Neurologic sequelae of cardiac catheterization. Cathet Cardiovasc Diagn 1985;11:577-83. [11] Cheatham JP. Stenting of coarctation of the aorta. Catheter Cardiovasc Intervent 2001;54:112-25. [12] O’Laughilin MP, Perry SB, Lock E, Mullins CE. Use of endovascular stents in congenital heart disease. Circulation 1991;83: 1923-34.
Introduction Left heart catheterization involves a risk of cerebral complications associated with catheterization-related cerebral microemboli responsible for stroke episodes, cognitive impairment, and neuropsychological deficits [1-5]. In these cases, white matter hyperintense lesions and abnormal diffusion-weighted imaging sequences
From the Departments of *Neurology, ‡Neuroradiology, and †Pediatric Cardiac Surgery, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
268
PEDIATRIC NEUROLOGY
Vol. 36 No. 4
may be demonstrated on brain magnetic resonance imaging [1]. Whereas seizures are among the complications of cardiac catheterization, they have not been directly related to angiocardiography but rather to hypoxic-ischemic encephalopathy present as part of global developmental delay and malformations [1]. Although rare, ionic and nonionic contrast-induced seizures after cardiac catheterization or as a complication of enhanced cranial computed tomography have been reported in adults [1,2, 5-8]. So far there has been only one report regarding an 18-month-old male who developed a new-onset focal seizure 12 hours after cardiac catheterization [9]. The present report describes an additional patient, a 6-year-old female who developed contrast-induced generalized seizures half an hour after cardiac catheterization. The clinical, neuroimaging, and follow-up data gathered 1 year later are discussed. Case Report The proband is a 6-year-old female who was referred to the Cardiology and Cardiac Surgery Department for severe aortic isthmic coarctation and systemic hypertension. Family and past medical history were unremarkable. A few months before admission she had a complete cardiologic assessment because she wanted to attend gymnastic courses. On this occasion, the diagnosis of aortic coarctation was made and interventional cardiac catheterization was suggested. On admission her O2 saturation was 97%; she weighed 26.5 kg and her height was 116 cm. Blood pressure in the upper limbs was as follows: right arm 125/75 mm Hg and left arm 130/80; in the lower limbs: right leg 100/60 and left leg 65/60 mm Hg. The echocardiogram demonstrated severe isthmic coarctation (maximal gradient approximately 30 mm Hg with diastolic tail); hypertrophied left ventricle with good systolic function; and mildly dilated ascending aorta associated with dilatation of horizontal aorta. Two days after admission, the patient underwent interventional cardiac catheterization under general anesthesia (atracurium 0.5 mg/kg, midazolam 0.2 mg/kg, fentanyl 1.6 g/kg). A right femoral artery percutaneous sheath was introduced; 100 UI/kg of heparin were administered. An angiographic pigtail catheter was positioned in the ascending aorta for aortography in order to define the anatomy. The lateral and anteroposterior view confirmed severe and tubular isthmic aortic coarctation with a maximal gradient of 40 mm Hg. The coarctation was treated with 3 ⫻ 20 and subsequently with 5 ⫻ 20 SMASH Balloon dilatation (Boston Scientific International, Galway, Ireland). Angiograms disclosed a small aneurysm in the site of the dilatation. Therefore a 34-cover CP stent (Numed. Inc, Hopkinton, NY) mounted on 10 ⫻ 40 Crystal Balloon (BALT, Mont Morency, France) was implanted. The gradient after the implantation successfully fell to 10 mm Hg. Two control angiograms excluded dissection and residual aneurysm. For this procedure, the total amount of iodate contrast (Iobitridolo-Xenetix 350 mg) was 500 mL.
Communications should be addressed to: Dr. Sansone; Department of Neurology; University of Milan; IRCCS Policlinico San Donato; Via Morandi 30; San Donato Milanese; Milan, Italy. E-mail: [email protected]; [email protected] Received July 10, 2006; accepted October 16, 2006.
© 2007 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2006.10.008 ● 0887-8994/07/$—see front matter
Figure 1. (A) A 5-mm brain computed tomographic scan performed in the acute setting. Note all cerebral sulci were of increased density and both cortical circonvolutions and cerebellar folia were clearly visible. (B) A 5-mm repeat brain computed tomographic scan performed the day after the acute onset of seizures; unchanged. Note cerebral edema. (C) Follow-up 5-mm brain computed tomographic scan 7 days after acute onset of seizures. Persistence of white cerebellar sign. 4™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™ Throughout the procedure, hemodynamic parameters remained stable. The fluoroscopy time was 35 minutes. The procedure time was 90 minutes. Duration of anesthesia was 2 hours. Five minutes after extubation, while the patient was breathing spontaneously in the recovery room, she developed continuous generalized seizures which required reintubation and ventilatory support. There was a prompt response to 0.5 mg diazepam administered intravenously. Blood pressure and cardiac function were stable. There were no electrolyte abnormalities. Suspecting a thromboembolic event related to the invasive procedure, a computed tomographic scan was performed to exclude acute focal brain lesions (Fig 1A). All cerebral sulci were of increased density, and both cortical gyri and cerebellar folia appeared clearly delineated. The brainstem, cerebral and cerebellar peduncles appeared of relatively low density. The ventricles were scarcely visible because of the “brilliancy” of the choroidal plexuses. These findings were highly suggestive of contrast retention. Both thalami were particularly bright compared with the remaining basal nuclei. The superior sagittal sinus evidenced the delta sign. Two hours later the patient had a new generalized seizure. Diazepam (10 mg) and midazolam (5 mg), both intravenously administered, controlled seizure activity only partially. Phenobarbital 200 mg, administered intravenously, was introduced with resolution of the episode for 1 hour. Clonic movements of the right arm and left leg were observed. In addition, there was spontaneous bilateral internal rotation of the limbs. 15 mg/kg phenytoin in 15 minutes (1 mg/kg/min) was given. Mannitol 0.5 mg/kg four times a day and desamethaxone 4 mg twice daily with gastric protection were also added. On the following day the brain computed tomographic scan was repeated (Fig 1B). There was a general worsening of the previous findings. Diffuse cerebral edema and white cerebellar sign were unchanged. The patient was kept in barbiturate coma for 5 days. No further epileptic episodes occurred. Gradual clinical recovery was observed until she was extubated and transferred to the Pediatric Cardiology ward. Neurologic examination on Day 7 was normal except for a mild motor impairment of the right hand. Computed tomographic scan was repeated and was normal except for the persistence of the white cerebellar sign (Fig 1C). On Day 9 neurologic examination returned to normal. Electroencephalography was normal. On Day 10, 1.5 Tesla brain magnetic resonance imaging was normal: cortical sulci, dimension, and morphology of the ventricular system and flow of the dural sinus were all within normal range. Contrast medium was no longer visible in the cortical sulci or brain parenchyma. Follow-up assessment 1 year later was normal. No further convulsive episodes were reported. Motor milestones were normal since the procedure and no neurologic sequelae were evident. School performance was good. The patient participated in school activities without hesitation and interacted with her schoolmates with no difficulty.
Conclusions Our data emphasize that contrast-induced seizures, although rarely, may occur in children after cardiac catheterization. Thromboembolic seizures, as a manifestation of a stroke, may also occur in children after cardiac catheterization [4,5,10]. Thromboembolic seizures and contrastinduced seizures cannot be distinguished clinically. Indirect signs of a thromboembolic lesion in the acute setting are hyperdense artery sign, swelling of brain tissue, and
Sansone et al: Contrast-Induced Seizures 269
reduced differentiation between gray and white matter. However, these indirect signs were masked by the massive presence of contrast medium in the cerebral sulci and intracranial vessels (Fig 1). The brilliancy of the superior sagittal sinus like that of this patient’s computed tomographic scan is common in patients subjected to a cardiac surgery procedure due to a temporary collapse of the dural sinus. This brilliancy mimics venous thrombosis, which could not be ruled out initially in the patient reported herein. Magnetic resonance imaging at follow-up demonstrated normal flow of the dural sinus, ruling out this hypothesis. Previous authors have well described how contrast media can cause both nonidiosyncratic and idiosyncratic reactions. Nonidiosyncratic reactions are related to the properties of the media such as hyperosmolality and chemotoxicity of the molecule, hypotheses which cannot be ruled out in this patient. Idiosyncratic reactions are allergic-like reactions whose mechanism is not yet well understood and may be multifactorial. Seizures might result from ischemic lesions due to cerebral embolism and hypoxia or intracranial hemorrhage secondary to anticoagulation [3]. Low-dose heparin was used in this patient. Although the characteristics of brain vessel endothelial cells in children affected by aortic coarctation in terms of contrast permeability are not well described, in adults the association between coarctation and brain ischemic-hemorrhagic events has been widely reported [11,12], suggesting that some predisposing factor in this cardiac malformation might have played a role in the patient described in the present report. Seizures, like other neurologic complications after cardiac catheterization, may be related, among other factors, to several conditions such as the prolonged duration of the catheterization procedure and interventional manipulation [1,3]. Contrast medium is normally retained for 24 hours after intravenous administration for cranial tomography and for several hours for cardiac catheterization of young children. The usual doses are 2 mL/kg body weight. Cardiac catheterization in this case lasted 2 hours, mainly because of the complex anatomy of the coarctation, which required more contrast than usual (18 mL/kg); throughout the procedure, the patient was hemodynamically stable, had a good urine output and normal electrolytes.
270
PEDIATRIC NEUROLOGY
Vol. 36 No. 4
Patients with hypoxic-ischemic encephalopathy at birth may be particularly susceptible to neurologic complications; children affected by aortic coarctation might be predisposed to brain injuries owing to their hypertensive condition. We believe that the etiology of seizures in the patient described here was multifactorial: parenchymal contrast irritation, the amount of contrast used, the duration of the procedure, and cerebral microvascular abnormalities secondary to the aortic coarctation. To sum up, contrast toxicity should be considered in the differential diagnosis of seizures arising after angiography in children. Identifying the cause of this complication has important prognostic implications and may lead to more effective prevention and treatment. We are grateful to Alasdair McEwen (professional translator) for having read and revised this paper and to Drs. Matteo Bonetti and Biagio Cotticelli for having compiled neuroimaging data.
References [1] Lund C, Nes RB, Ugelstad TP, et al. Cerebral emboli during left heart catheterization may cause acute brain injury. Eur Heart J 2005;26: 1269-75. [2] Furlan AJ, Sila CA, Chimowitz MI, Jones SC. Neurologic complications related to cardiac surgery. Neurol Clin 1992;10:145-66. [3] Liu XY, Wong V, Leung M. Neurologic complications due to catheterization. Pediatr Neurol 2001;24:270-5. [4] Bronster DJ. Neurologic complications of cardiac surgery: Current concepts and recent advances. Curr Cardiol Rep 2006;8:9-16. [5] Agnoletti G, Bonnet C, Boudjemline Y, et al. Complications of paediatric interventional catheterization: An analysis of risk factors. Cardiol Young 2005;15:402-6. [6] Drake TG, Kerr HD. Status epilepticus after cranial CT with contrast media. WMJ 1997;96:46-8. [7] Muruve DA, Steinman TI. Contrast-induced encephalopathy and seizures in a patient with chronic renal insufficiency. Clin Nephrol 1996;45: 406-9. [8] Fischer HW. Occurrence of seizure during cranial computed tomography. Radiology 1980;137:563-4. [9] Frye RE, Newburger JW, Nugent A, Sahin M. Focal seizure and cerebral contrast retention after cardiac catheterization. Pediatr Neurol 2005;32:213-6. [10] Weissman BM, Aram DM, Levinsohn MW, Ben-Shachar G. Neurologic sequelae of cardiac catheterization. Cathet Cardiovasc Diagn 1985;11:577-83. [11] Cheatham JP. Stenting of coarctation of the aorta. Catheter Cardiovasc Intervent 2001;54:112-25. [12] O’Laughilin MP, Perry SB, Lock E, Mullins CE. Use of endovascular stents in congenital heart disease. Circulation 1991;83: 1923-34.