Author's Accepted Manuscript
Increasing Blurriness of the Borders between Focal and Generalized as well as Cryptogenic and Idiopathic Epilepsies in defining the role for Focal Epilepsy Surgery Yu-Tze Ng MD, FRACP
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S1071-9091(14)00038-2 http://dx.doi.org/10.1016/j.spen.2014.04.019 YSPEN485
To appear in: Semin Pediatr Neurol
Cite this article as: Yu-Tze Ng MD, FRACP, Increasing Blurriness of the Borders between Focal and Generalized as well as Cryptogenic and Idiopathic Epilepsies in defining the role for Focal Epilepsy Surgery, Semin Pediatr Neurol , http://dx.doi.org/10.1016/j.spen.2014.04.019 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.
Increasing Blurriness of the Borders between Focal and Generalized as well as Cryptogenic and Idiopathic Epilepsies in defining the role for Focal Epilepsy Surgery
Yu-Tze Ng, MD, FRACP
Department of Neurology University of Oklahoma Medical Center 711 Stanton L Young Blvd #215 Oklahoma City, OK 73104, USA
Corresponding author: Associate Professor Yu-Tze Ng Email: [email protected] Tel: 1 (405) 271 4113 Fax: 1 (405) 271 5723 Manuscript word count: 630
Dr Ng is on the Medical Advisory Board for Lundbeck Pharmaceuticals, Eisai Pharmaceuticals, Upsher-Smith Pharmaceuticals and the speakers’ bureau for UCB Pharma, Lundbeck Pharmaceuticals, Supernus Pharmaceuticals. This Case Studies Issue includes two excellent, intriguing case reports.1,2 The title of the case report by Wirrell is a little confusing as following the surgical work-up, no surgery ensued once the diagnosis of the syntaxin binding protein 1 (STXBP1) gene c901delC
mutation had been made.1 Thorough work-up to that point had localized fairly well the seizures to be arising from the left temporo-parietal region. In view of the genetic diagnosis and good response to vigabatrin, he was considered to not be a surgical candidate. However with recent, rapid advances in diagnosing genetic diseases in not just epilepsy but numerous disorders, many previously cryptogenic(/unknown cause) cases now have a genetic etiology.3 Indeed, successful temporal lobectomies have been performed in two patients (one with hippocampal sclerosis and one without) with SCN1B mutations and temporal lobe epilepsy phenotypes with them both becoming seizure free.4 Certainly a genetic diagnosis of an idiopathic(/genetic) epilepsy currently would make one think twice about performing focal epilepsy surgery however should not be a complete contraindication and I believe many more focal epilepsy surgeries will be performed successfully in these patients as increasingly more genetic mutations are discovered. We all certainly hope this reported case of the young boy’s seizures remain controlled however should they become refractory; he may still be cured of epilepsy by a tailored left temporo-parietal focal resection.1 The case report by Fine and Nickels is equally fascinating and educational.2 Landau-Kleffner syndrome is a mysterious condition that is not 100% well-defined. The Japanese have bravely tried to determine the incidence and prevalence in Japan of this rare disorder with resultant incidence of about one in a million of children aged 5-14 years and prevalence of one in about 300,000-410,000 of children aged 5-19 years.5 I believe this disorder that has even been described as being on the severe spectrum of the idiopathic localization-related epilepsy, Benign Epilepsy with Centro-Temporal Spikes (BECTS) to be simply a descriptive cluster of various symptoms, not unlike Lennox-
2
Gastaut syndrome.6,7 Hence some cases are probably purely immune-mediated which may respond well to steroids whilst others are simply a cryptogenic, localization-related epilepsy with rapid or even instantaneous generalization. A reminder that “cryptogenic epilepsy” or “epilepsy of unknown cause” other than realistically meaning we the medical providers are too stupid to know why this particular patient has epilepsy, in today’s day and age implies a normal or non-lesional magnetic resonance imaging (MRI) scan.8 However this case clearly illustrates the limitations of our epilepsy classification system as the post-resection pathological diagnosis with gliosis would mean to me that the patient’s localization-related epilepsy subsequently was upgraded or rather downgraded from “cryptogenic” to “symptomatic”!9 In actual fact subtraction ictal SPECT coregistered to MRI (SISCOM) on this patient localized the area of abnormality very well.2 Positron emission tomography (PET) scanning was not performed but may have helped further localize the lesion. Perhaps at some point “positive” SPECT or PET scans may mean the localization-related epilepsy is symptomatic, no longer cryptogenic even if the MRI scan is normal. How about a very localizing magnetoencephalography (MEG) study or even electroencephalogram (EEG)?
Despite the somewhat generalized nature of the EEG findings, this child clearly had a localization-related epilepsy as proven by the curative epilepsy surgery and excellent outcome.2 The hypothalamic hamartoma model is often an example of a generalized epileptic encephalopathy without localizing features which similarly is proven to be a focal onset, localization-related epilepsy that can be cured by resection of the usually small lesion.10,11 Ergo, every (refractory) epilepsy case should be reviewed on
3
an individual basis and particularly if there is a lesion or at least some very localizing features on various investigations should be considered for potential epilepsy surgery; at times regardless of the scalp EEG findings or whether the epilepsy is cryptogenic or even idiopathic (genetic) in origin.
4
References
1. Wirrell E: Early onset focal seizures and spasms – is it surgical? Semin Pediatr Neurol 2014
2. Fine A, Nickels K. Temporoparietal resection in a patient with Landau Kleffner syndrome. Semin Pediatr Neurol 2014
3. De novo mutations in epileptic encephalopathies. Epi4K Consortium, Epilepsy Phenome/Genome Project, Allen AS, et al. Nature 501:217-21, 2013
4. Scheffer IE1, Harkin LA, Grinton BE et al. Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. Brain 130:100-109, 2007
5. Kaga M, Inagaki M, Ohta R. Epidemiological study of Landau-Kleffner syndrome (LKS) in Japan. Brain Dev 36:284-286, 2014
6. Datta AN, Oser N, Ramelli GP, et al. BECTS evolving to Landau-Kleffner Syndrome and back by subsequent recovery: a longitudinal language reorganization case study using fMRI, source EEG, and neuropsychological testing. Epilepsy Behav 27:107-114, 2013 7. Van Straten AF, Ng YT. Update on the management of Lennox-Gastaut syndrome. Pediatr Neurol 47:153-161, 2012
8. Ng YT, Kerrigan JF, Rekate HL. Neurosurgical treatment of status epilepticus. J Neurosurgery 105:378-381, 2006
9. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 51:676-685, 2010
10. Ng YT, Hastriter EV, Wethe J, et al. Surgical Resection of Hypothalamic Hamartomas for Severe Behavioral Symptoms. Epilepsy Behav 20:75-78, 2011
5
11. Pati S, Deep A, Troester MM, Kossoff E, Ng YT. Lennox-Gastaut Syndrome symptomatic to Hypothalamic hamartoma: Evolution and long-term outcome following surgery. Pediatr Neurol 49:25-30, 2013
6
Increasing Blurriness of the Borders between Focal and Generalized as well as Cryptogenic and Idiopathic Epilepsies in defining the role for Focal Epilepsy Surgery Yu-Tze Ng MD, FRACP
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S1071-9091(14)00038-2 http://dx.doi.org/10.1016/j.spen.2014.04.019 YSPEN485
To appear in: Semin Pediatr Neurol
Cite this article as: Yu-Tze Ng MD, FRACP, Increasing Blurriness of the Borders between Focal and Generalized as well as Cryptogenic and Idiopathic Epilepsies in defining the role for Focal Epilepsy Surgery, Semin Pediatr Neurol , http://dx.doi.org/10.1016/j.spen.2014.04.019 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.
Increasing Blurriness of the Borders between Focal and Generalized as well as Cryptogenic and Idiopathic Epilepsies in defining the role for Focal Epilepsy Surgery
Yu-Tze Ng, MD, FRACP
Department of Neurology University of Oklahoma Medical Center 711 Stanton L Young Blvd #215 Oklahoma City, OK 73104, USA
Corresponding author: Associate Professor Yu-Tze Ng Email: [email protected] Tel: 1 (405) 271 4113 Fax: 1 (405) 271 5723 Manuscript word count: 630
Dr Ng is on the Medical Advisory Board for Lundbeck Pharmaceuticals, Eisai Pharmaceuticals, Upsher-Smith Pharmaceuticals and the speakers’ bureau for UCB Pharma, Lundbeck Pharmaceuticals, Supernus Pharmaceuticals. This Case Studies Issue includes two excellent, intriguing case reports.1,2 The title of the case report by Wirrell is a little confusing as following the surgical work-up, no surgery ensued once the diagnosis of the syntaxin binding protein 1 (STXBP1) gene c901delC
mutation had been made.1 Thorough work-up to that point had localized fairly well the seizures to be arising from the left temporo-parietal region. In view of the genetic diagnosis and good response to vigabatrin, he was considered to not be a surgical candidate. However with recent, rapid advances in diagnosing genetic diseases in not just epilepsy but numerous disorders, many previously cryptogenic(/unknown cause) cases now have a genetic etiology.3 Indeed, successful temporal lobectomies have been performed in two patients (one with hippocampal sclerosis and one without) with SCN1B mutations and temporal lobe epilepsy phenotypes with them both becoming seizure free.4 Certainly a genetic diagnosis of an idiopathic(/genetic) epilepsy currently would make one think twice about performing focal epilepsy surgery however should not be a complete contraindication and I believe many more focal epilepsy surgeries will be performed successfully in these patients as increasingly more genetic mutations are discovered. We all certainly hope this reported case of the young boy’s seizures remain controlled however should they become refractory; he may still be cured of epilepsy by a tailored left temporo-parietal focal resection.1 The case report by Fine and Nickels is equally fascinating and educational.2 Landau-Kleffner syndrome is a mysterious condition that is not 100% well-defined. The Japanese have bravely tried to determine the incidence and prevalence in Japan of this rare disorder with resultant incidence of about one in a million of children aged 5-14 years and prevalence of one in about 300,000-410,000 of children aged 5-19 years.5 I believe this disorder that has even been described as being on the severe spectrum of the idiopathic localization-related epilepsy, Benign Epilepsy with Centro-Temporal Spikes (BECTS) to be simply a descriptive cluster of various symptoms, not unlike Lennox-
2
Gastaut syndrome.6,7 Hence some cases are probably purely immune-mediated which may respond well to steroids whilst others are simply a cryptogenic, localization-related epilepsy with rapid or even instantaneous generalization. A reminder that “cryptogenic epilepsy” or “epilepsy of unknown cause” other than realistically meaning we the medical providers are too stupid to know why this particular patient has epilepsy, in today’s day and age implies a normal or non-lesional magnetic resonance imaging (MRI) scan.8 However this case clearly illustrates the limitations of our epilepsy classification system as the post-resection pathological diagnosis with gliosis would mean to me that the patient’s localization-related epilepsy subsequently was upgraded or rather downgraded from “cryptogenic” to “symptomatic”!9 In actual fact subtraction ictal SPECT coregistered to MRI (SISCOM) on this patient localized the area of abnormality very well.2 Positron emission tomography (PET) scanning was not performed but may have helped further localize the lesion. Perhaps at some point “positive” SPECT or PET scans may mean the localization-related epilepsy is symptomatic, no longer cryptogenic even if the MRI scan is normal. How about a very localizing magnetoencephalography (MEG) study or even electroencephalogram (EEG)?
Despite the somewhat generalized nature of the EEG findings, this child clearly had a localization-related epilepsy as proven by the curative epilepsy surgery and excellent outcome.2 The hypothalamic hamartoma model is often an example of a generalized epileptic encephalopathy without localizing features which similarly is proven to be a focal onset, localization-related epilepsy that can be cured by resection of the usually small lesion.10,11 Ergo, every (refractory) epilepsy case should be reviewed on
3
an individual basis and particularly if there is a lesion or at least some very localizing features on various investigations should be considered for potential epilepsy surgery; at times regardless of the scalp EEG findings or whether the epilepsy is cryptogenic or even idiopathic (genetic) in origin.
4
References
1. Wirrell E: Early onset focal seizures and spasms – is it surgical? Semin Pediatr Neurol 2014
2. Fine A, Nickels K. Temporoparietal resection in a patient with Landau Kleffner syndrome. Semin Pediatr Neurol 2014
3. De novo mutations in epileptic encephalopathies. Epi4K Consortium, Epilepsy Phenome/Genome Project, Allen AS, et al. Nature 501:217-21, 2013
4. Scheffer IE1, Harkin LA, Grinton BE et al. Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. Brain 130:100-109, 2007
5. Kaga M, Inagaki M, Ohta R. Epidemiological study of Landau-Kleffner syndrome (LKS) in Japan. Brain Dev 36:284-286, 2014
6. Datta AN, Oser N, Ramelli GP, et al. BECTS evolving to Landau-Kleffner Syndrome and back by subsequent recovery: a longitudinal language reorganization case study using fMRI, source EEG, and neuropsychological testing. Epilepsy Behav 27:107-114, 2013 7. Van Straten AF, Ng YT. Update on the management of Lennox-Gastaut syndrome. Pediatr Neurol 47:153-161, 2012
8. Ng YT, Kerrigan JF, Rekate HL. Neurosurgical treatment of status epilepticus. J Neurosurgery 105:378-381, 2006
9. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 51:676-685, 2010
10. Ng YT, Hastriter EV, Wethe J, et al. Surgical Resection of Hypothalamic Hamartomas for Severe Behavioral Symptoms. Epilepsy Behav 20:75-78, 2011
5
11. Pati S, Deep A, Troester MM, Kossoff E, Ng YT. Lennox-Gastaut Syndrome symptomatic to Hypothalamic hamartoma: Evolution and long-term outcome following surgery. Pediatr Neurol 49:25-30, 2013
6
