Author's Accepted Manuscript
Editorial Comment Agustin Legido MD, PhD, MBA
PII: DOI: Reference:
www.elsevier.com/locate/enganabound S1071-9091(14)00039-4 http://dx.doi.org/10.1016/j.spen.2014.04.020 YSPEN486
To appear in: Semin Pediatr Neurol
Cite this article as: Agustin Legido MD, PhD, MBA, Editorial Comment, Semin Pediatr Neurol , http://dx.doi.org/10.1016/j.spen.2014.04.020 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Case 3 EDITORIAL COMMENT This case addresses relevant practical issues in the evaluation of children with refractory epilepsy. Importantly, it generates the discussion about how to define the type of epilepsy. Until recently, it has been thought that focal brain lesions are usually associated with focal electroencephalographic (EEG) abnormalities, and that generalized EEG abnormalities defined generalized epilepsy. This is not always the case, and it has important practical therapeutic implications. In our experience we found that in a group of children with epilepsy studied with both routine and prolonged EEG monitoring, the latter changed the diagnosis of the type of epilepsy in more than 50% of the patients. Specifically in those patients with focal and rapid seizure generalization, the routine EEG usually suggested a generalized type of epilepsy, missing the focal origin of the epileptic activity.1 Therefore, the type of EEG technique used is important for an accurate definition of the type of epilepsy. Recent studies with dense array EEG have suggested that generalized epilepsies, like absence and juvenile myoclonic epilepsy (JME) are not truly generalized, but rather have a focal origin and use selective cortical networks during propagation involving regions of frontal and temporal cortex.2,3 Some patients with infantile spasms and generalized pattern of hypsarrhythmia and multifocal bilateral interictal epileptiform discharges have shown to have this EEG pattern due to focal structural or functional abnormalities, which respond very well to focal surgical resection.4 The patient presented here had a large hemispheric cortical malformation and, as in the cases of infantile spasms, showed not only focal EEG epileptiform discharges, but also abundant generalized or bilateral epileptiform discharges, including electric status epilepticus during sleep (ESES). The mechanisms are unknown, but these discharges could be a manifestation of potentially reversible secondary epileptogenesis, resulting from an interaction between the early lesions and the developing brain.5 In the evaluation of smaller brain dysgenesis, like cortical dysplasias, and in younger children, the use of ictal SPECT and PET may be helpful to better define the diagnosis and the epileptic area.4,6-8 This case also emphasizes the need to consult members of an experienced epilepsy program, as soon as possible: 1) when the initial approach to management with the usual antiepileptic drugs (AEDs) does not work and the diagnosis of refractory epilepsy is entertained, 2) when there is the presence of an obvious cerebral malformation or when a cortical dysplasia is suspected, and 3) when there is a discrepancy between cerebral abnormalities and EEG abnormalities. The input from an expert epileptologist is crucial to plan an aggressive therapeutic approach, as it was the case in the patient under discussion. An early surgical treatment of a child 1
with refractory epilepsy associated to brain malformation, who is a candidate for such type of therapy, will be associated with better seizure control and neurocognitive outcome, as it happened in this case. Agustin Legido, MD, PhD, MBA St. Christopher’s Hospital for Children Drexel University College of Medicine Philadelphia, PA [email protected]
References 1. Foley CM, Legido A, Miles DK, et al: Long-term computer-assisted outpatient electroencephalogram monitoring in children and adolescents. J Child Neurol 15:49-55, 2000 2. Holmes MD, Brown M, Tucker DM: Are”generalized” seizures truly generalized? Evidence of localized mesial frontal and frontopolar discharges in absence. Epilepsia 45:1568-1579, 2004 3. Holmes MD, Quiring J, Tucker DM: Evidence that juvenile myoclonic epilepsy is a disorder of frontotemporal corticothalamic networks. Epilepsia 49:80-93, 2010 4. Chugani HT, Shields WD, Shewmon DA, et al: Infantile spasms. I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment. Ann Neurol 27:406-413, 1990 5. Wyllie E, Lachhwani DK, Gupta A, et al: Successful surgery for epilepsy due to early brain lesions despite EEG generalized findings. Neurology 69:389-397, 2007 6. Kudr M, Krsek P, Maton B, et al: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia. Epileptic Disord 15:383-391, 2013 7. Salamon N, Kung J, Shaw SJ, et al: FDG-PET/MRI coregistration improves detection of cortical dysplasia in patients with epilepsy. Neurology 71:1594-1601, 2008 8. Wakamoto H, Cgugani DC, Juhász C, et al: Alpha-methyl-l-tryptophan positron emission tomography in epilepsy with cortical developmental malformations. Pediatr Neurol 39:181-188, 2008
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Editorial Comment Agustin Legido MD, PhD, MBA
PII: DOI: Reference:
www.elsevier.com/locate/enganabound S1071-9091(14)00039-4 http://dx.doi.org/10.1016/j.spen.2014.04.020 YSPEN486
To appear in: Semin Pediatr Neurol
Cite this article as: Agustin Legido MD, PhD, MBA, Editorial Comment, Semin Pediatr Neurol , http://dx.doi.org/10.1016/j.spen.2014.04.020 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Case 3 EDITORIAL COMMENT This case addresses relevant practical issues in the evaluation of children with refractory epilepsy. Importantly, it generates the discussion about how to define the type of epilepsy. Until recently, it has been thought that focal brain lesions are usually associated with focal electroencephalographic (EEG) abnormalities, and that generalized EEG abnormalities defined generalized epilepsy. This is not always the case, and it has important practical therapeutic implications. In our experience we found that in a group of children with epilepsy studied with both routine and prolonged EEG monitoring, the latter changed the diagnosis of the type of epilepsy in more than 50% of the patients. Specifically in those patients with focal and rapid seizure generalization, the routine EEG usually suggested a generalized type of epilepsy, missing the focal origin of the epileptic activity.1 Therefore, the type of EEG technique used is important for an accurate definition of the type of epilepsy. Recent studies with dense array EEG have suggested that generalized epilepsies, like absence and juvenile myoclonic epilepsy (JME) are not truly generalized, but rather have a focal origin and use selective cortical networks during propagation involving regions of frontal and temporal cortex.2,3 Some patients with infantile spasms and generalized pattern of hypsarrhythmia and multifocal bilateral interictal epileptiform discharges have shown to have this EEG pattern due to focal structural or functional abnormalities, which respond very well to focal surgical resection.4 The patient presented here had a large hemispheric cortical malformation and, as in the cases of infantile spasms, showed not only focal EEG epileptiform discharges, but also abundant generalized or bilateral epileptiform discharges, including electric status epilepticus during sleep (ESES). The mechanisms are unknown, but these discharges could be a manifestation of potentially reversible secondary epileptogenesis, resulting from an interaction between the early lesions and the developing brain.5 In the evaluation of smaller brain dysgenesis, like cortical dysplasias, and in younger children, the use of ictal SPECT and PET may be helpful to better define the diagnosis and the epileptic area.4,6-8 This case also emphasizes the need to consult members of an experienced epilepsy program, as soon as possible: 1) when the initial approach to management with the usual antiepileptic drugs (AEDs) does not work and the diagnosis of refractory epilepsy is entertained, 2) when there is the presence of an obvious cerebral malformation or when a cortical dysplasia is suspected, and 3) when there is a discrepancy between cerebral abnormalities and EEG abnormalities. The input from an expert epileptologist is crucial to plan an aggressive therapeutic approach, as it was the case in the patient under discussion. An early surgical treatment of a child 1
with refractory epilepsy associated to brain malformation, who is a candidate for such type of therapy, will be associated with better seizure control and neurocognitive outcome, as it happened in this case. Agustin Legido, MD, PhD, MBA St. Christopher’s Hospital for Children Drexel University College of Medicine Philadelphia, PA [email protected]
References 1. Foley CM, Legido A, Miles DK, et al: Long-term computer-assisted outpatient electroencephalogram monitoring in children and adolescents. J Child Neurol 15:49-55, 2000 2. Holmes MD, Brown M, Tucker DM: Are”generalized” seizures truly generalized? Evidence of localized mesial frontal and frontopolar discharges in absence. Epilepsia 45:1568-1579, 2004 3. Holmes MD, Quiring J, Tucker DM: Evidence that juvenile myoclonic epilepsy is a disorder of frontotemporal corticothalamic networks. Epilepsia 49:80-93, 2010 4. Chugani HT, Shields WD, Shewmon DA, et al: Infantile spasms. I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment. Ann Neurol 27:406-413, 1990 5. Wyllie E, Lachhwani DK, Gupta A, et al: Successful surgery for epilepsy due to early brain lesions despite EEG generalized findings. Neurology 69:389-397, 2007 6. Kudr M, Krsek P, Maton B, et al: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia. Epileptic Disord 15:383-391, 2013 7. Salamon N, Kung J, Shaw SJ, et al: FDG-PET/MRI coregistration improves detection of cortical dysplasia in patients with epilepsy. Neurology 71:1594-1601, 2008 8. Wakamoto H, Cgugani DC, Juhász C, et al: Alpha-methyl-l-tryptophan positron emission tomography in epilepsy with cortical developmental malformations. Pediatr Neurol 39:181-188, 2008
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