Original Article
Transient Restricted Diffusion of Corpus Callosum and Subcortical White Matter Following Febrile Status Epilepticus
Journal of Child Neurology 2015, Vol. 30(6) 757-759 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814535497 jcn.sagepub.com
Puneet Jain, MD, DM1, Suvasini Sharma, MD, DM1, Dhulika Dhingra, MD1, and Satinder Aneja, MD1
Abstract We describe the case of a 4½-year-old girl with prolonged febrile status followed by abnormal behavior and loss of speech. Interesting findings on diffusion-restricted imaging were noted. The clinicoradiologic possibilities are discussed. Keywords febrile status epilepticus, peri-ictal MRI, diffusion weighted imaging, AESD, MERS Received March 03, 2014. Received revised April 05, 2014. Accepted for publication April 14, 2014.
Case Summary A 4½-year-old girl presented high-grade fever for few hours followed by generalized tonic-clonic status-epilepticus (lasting approximately 90 minutes). The seizures were aborted by intravenous midazolam followed by loading with valproate. She had persisting altered sensorium for 48 hours. Investigations revealed normal hemogram, electrolytes, and cerebrospinal fluid analysis. Electroencephalography (EEG) showed generalized delta slowing. Magnetic resonance imaging (MRI) of the brain showed restricted diffusion in bilateral subcortical white matter (Figure 1). The metabolic profile including serum ammonia, arterial lactate, blood tandem mass spectroscopy, and urine gas chromatography–mass spectroscopy was normal. She was a developmentally normal child with a history of 2 simple febrile seizures. Following recovery, she was very hyperactive with abnormal screaming, biting, and picking at clothes. She had lost speech and made only incomprehensible sounds. A repeat MRI brain, done 14 days after the onset of symptoms, was normal (Figure 2). She showed gradual improvement on oral valproate and risperidone.
partial seizure. Widespread reversible white matter changes have also been reported on serial diffusion tensor imaging in children with prolonged febrile seizures.3 Other studies have reported numerous other reversible peri-ictal MRI abnormalities predominantly in adults.4 The precise pathogenesis of these changes is unknown. Prolonged seizures lead to increased metabolic demand and blood flow, and disruption of blood-brain barrier, leading to vasogenic edema. If seizures continue, energy failure, increased membrane ion permeability, abnormal glutamate release, cytotoxic edema, and irreversible neuronal damage ensues. This cytotoxic edema appears hyperintense on diffusion-weighted images and hypointense on apparent diffusion coefficient maps. Another possibility is the 2 closely related encephalopathy syndromes—acute encephalopathy with biphasic seizures and late reduced diffusion and mild encephalopathy with a reversible splenial lesion.5 Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has been reported from East Asian infants and is characterized by prolonged febrile status epilepticus followed by secondary seizures after 4 to 6 days with subsequent variable neurologic sequelae. There is associated reversible restricted
Discussion The Consequences of Prolonged Febrile Seizures in Childhood, or FEBSTAT, study reported various hippocampal and extrahippocampal abnormalities in children following febrile status epilepticus but did not report any symmetrical white matter changes as seen in our case.1 Kano et al2 reported similar reversible bilateral symmetrical, restricted diffusion in the frontoparietal white matter and corpus callosum in an adult following a complex-
1
Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi, India
Corresponding Author: Suvasini Sharma, MD, DM, Division of Pediatric Neurology, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi 110001, India. Email: [email protected]
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Journal of Child Neurology 30(6)
Figure 1. Magnetic resonance imaging brain of the child at presentation. The diffusion-weighted images (A) show areas of restricted diffusion in bilateral symmetrical, predominantly subcortical white matter in the frontal and parieto-occipital areas with diffuse involvement of corpus callosum with corresponding low signal on ADC maps (B). Note that T2-weighted (C), T1-weighted, and fluid-attenuated inversion recovery (not shown) axial images were normal. There was no contrast enhancement (not shown).
Figure 2. Magnetic resonance imaging brain of the child after 14 days. It shows resolution of the previous changes on diffusion-weighted (A), ADC maps (B), and T2-weighted images (C).
diffusion in subcortical white matter. Our case lacked the classical biphasic seizures. Clinically mild encephalitis/ encephalopathy with a reversible splenial lesion (MERS) presents with delirious behavior, altered sensorium, and seizures with gradual recovery. There is reversible restricted diffusion in splenium with or without subcortical white matter involvement. Influenza and Human Herpes viruses 6 and 7 have been implicated in few cases.
Author Contributions SS, PJ, and DD worked up the case under the supervision of SA. PJ drafted the manuscript, which was then critically reviewed and approved by all the authors.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Jain et al Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval Informed consent was taken from the parents for publication of the case report.
References 1. Shinnar S, Bello JA, Chan S, et al. MRI abnormalities following febrile status epilepticus in children: the FEBSTAT study. Neurology. 2012;79:871-877.
759 2. Kano O, Iwamoto K, Nakamura Y, et al. Transient restricted diffusion of whole corpus callosum and symmetrical white matter in epilepsy. Intern Med. 2009;48:583-584. 3. Yoong M, Seunarine K, Martinos M, et al. Prolonged febrile seizures cause reversible reductions in white matter integrity. NeuroImage Clin. 2013;3:515-521. 4. Chatzikonstantinou A, Gass A, Fo¨rster A, et al. Features of acute DWI abnormalities related to status epilepticus. Epilepsy Res. 2011;97:45-51. 5. Takanashi J. Two newly proposed infectious encephalitis/encephalopathy syndromes. Brain Dev. 2009;31:521-528.
Transient Restricted Diffusion of Corpus Callosum and Subcortical White Matter Following Febrile Status Epilepticus
Journal of Child Neurology 2015, Vol. 30(6) 757-759 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814535497 jcn.sagepub.com
Puneet Jain, MD, DM1, Suvasini Sharma, MD, DM1, Dhulika Dhingra, MD1, and Satinder Aneja, MD1
Abstract We describe the case of a 4½-year-old girl with prolonged febrile status followed by abnormal behavior and loss of speech. Interesting findings on diffusion-restricted imaging were noted. The clinicoradiologic possibilities are discussed. Keywords febrile status epilepticus, peri-ictal MRI, diffusion weighted imaging, AESD, MERS Received March 03, 2014. Received revised April 05, 2014. Accepted for publication April 14, 2014.
Case Summary A 4½-year-old girl presented high-grade fever for few hours followed by generalized tonic-clonic status-epilepticus (lasting approximately 90 minutes). The seizures were aborted by intravenous midazolam followed by loading with valproate. She had persisting altered sensorium for 48 hours. Investigations revealed normal hemogram, electrolytes, and cerebrospinal fluid analysis. Electroencephalography (EEG) showed generalized delta slowing. Magnetic resonance imaging (MRI) of the brain showed restricted diffusion in bilateral subcortical white matter (Figure 1). The metabolic profile including serum ammonia, arterial lactate, blood tandem mass spectroscopy, and urine gas chromatography–mass spectroscopy was normal. She was a developmentally normal child with a history of 2 simple febrile seizures. Following recovery, she was very hyperactive with abnormal screaming, biting, and picking at clothes. She had lost speech and made only incomprehensible sounds. A repeat MRI brain, done 14 days after the onset of symptoms, was normal (Figure 2). She showed gradual improvement on oral valproate and risperidone.
partial seizure. Widespread reversible white matter changes have also been reported on serial diffusion tensor imaging in children with prolonged febrile seizures.3 Other studies have reported numerous other reversible peri-ictal MRI abnormalities predominantly in adults.4 The precise pathogenesis of these changes is unknown. Prolonged seizures lead to increased metabolic demand and blood flow, and disruption of blood-brain barrier, leading to vasogenic edema. If seizures continue, energy failure, increased membrane ion permeability, abnormal glutamate release, cytotoxic edema, and irreversible neuronal damage ensues. This cytotoxic edema appears hyperintense on diffusion-weighted images and hypointense on apparent diffusion coefficient maps. Another possibility is the 2 closely related encephalopathy syndromes—acute encephalopathy with biphasic seizures and late reduced diffusion and mild encephalopathy with a reversible splenial lesion.5 Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has been reported from East Asian infants and is characterized by prolonged febrile status epilepticus followed by secondary seizures after 4 to 6 days with subsequent variable neurologic sequelae. There is associated reversible restricted
Discussion The Consequences of Prolonged Febrile Seizures in Childhood, or FEBSTAT, study reported various hippocampal and extrahippocampal abnormalities in children following febrile status epilepticus but did not report any symmetrical white matter changes as seen in our case.1 Kano et al2 reported similar reversible bilateral symmetrical, restricted diffusion in the frontoparietal white matter and corpus callosum in an adult following a complex-
1
Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi, India
Corresponding Author: Suvasini Sharma, MD, DM, Division of Pediatric Neurology, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi 110001, India. Email: [email protected]
758
Journal of Child Neurology 30(6)
Figure 1. Magnetic resonance imaging brain of the child at presentation. The diffusion-weighted images (A) show areas of restricted diffusion in bilateral symmetrical, predominantly subcortical white matter in the frontal and parieto-occipital areas with diffuse involvement of corpus callosum with corresponding low signal on ADC maps (B). Note that T2-weighted (C), T1-weighted, and fluid-attenuated inversion recovery (not shown) axial images were normal. There was no contrast enhancement (not shown).
Figure 2. Magnetic resonance imaging brain of the child after 14 days. It shows resolution of the previous changes on diffusion-weighted (A), ADC maps (B), and T2-weighted images (C).
diffusion in subcortical white matter. Our case lacked the classical biphasic seizures. Clinically mild encephalitis/ encephalopathy with a reversible splenial lesion (MERS) presents with delirious behavior, altered sensorium, and seizures with gradual recovery. There is reversible restricted diffusion in splenium with or without subcortical white matter involvement. Influenza and Human Herpes viruses 6 and 7 have been implicated in few cases.
Author Contributions SS, PJ, and DD worked up the case under the supervision of SA. PJ drafted the manuscript, which was then critically reviewed and approved by all the authors.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Jain et al Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval Informed consent was taken from the parents for publication of the case report.
References 1. Shinnar S, Bello JA, Chan S, et al. MRI abnormalities following febrile status epilepticus in children: the FEBSTAT study. Neurology. 2012;79:871-877.
759 2. Kano O, Iwamoto K, Nakamura Y, et al. Transient restricted diffusion of whole corpus callosum and symmetrical white matter in epilepsy. Intern Med. 2009;48:583-584. 3. Yoong M, Seunarine K, Martinos M, et al. Prolonged febrile seizures cause reversible reductions in white matter integrity. NeuroImage Clin. 2013;3:515-521. 4. Chatzikonstantinou A, Gass A, Fo¨rster A, et al. Features of acute DWI abnormalities related to status epilepticus. Epilepsy Res. 2011;97:45-51. 5. Takanashi J. Two newly proposed infectious encephalitis/encephalopathy syndromes. Brain Dev. 2009;31:521-528.
