ZusammenfassungSechs Jahre nach Veröffentlichung soll der Nutzen der ILAE-Konsensus-Klassifikatio... more ZusammenfassungSechs Jahre nach Veröffentlichung soll der Nutzen der ILAE-Konsensus-Klassifikation Fokaler Kortikaler Dysplasien (FCD) bewertet werden. FCDs sind häufige Ursachen frühkindlicher und medikamentös schwierig zu behandelnder fokaler Epilepsien. Die neurochirurgische Therapie bietet oftmals eine große Chance auf dauerhafte Heilung. Dies ist aber wesentlich vom histopathologischen Subtyp abhängig, und das Resektionsfeld muss durch umfassende prächirurgische Diagnostik definiert werden, z. B. durch die vorläufige Abschätzung der Art der FCD anhand des MRT und ihre Nachbarschaftsbeziehung zu eloquenten Arealen, sowie durch iktale und interiktale EEG-Befunde. Die ILAE-Klassifikation grenzt 3 histomorphologisch unterschiedliche FCD-Subtypen ab, welche nach aktuellem Kenntnisstand auch unterschiedlichen Pathomechanismen zugrunde liegen. FCD Typ 1 sind seltene Erkrankungen bei weit überwiegend jungen Kindern mit radiologisch, elektro-klinisch als auch pathologisch schwierig zu diagnostizierenden Epilepsien – mit deutlich geringeren Chancen auf eine postoperative Anfallsfreiheit als dies bei einer FCD Typ 2 der Fall ist. Die FCD Typ 2 stellt eine klinisch-pathologisch gut charakterisierte und chirurgisch oftmals gut behandelbare Gruppe dar. Molekulargenetisch finden sich Mutationen im mTOR-Signalweg, was daran denken lässt, dass zukünftig evtl. eine zielgerichtete medikamentöse Therapie möglich wird. Währenddessen sind assoziierte FCD Typ 3 in der wissenschaftlichen Literatur zwar häufig beschrieben, ihre Entstehung und Eigenständigkeit jedoch umstritten. Klinischer Verlauf und neurochirurgischer Therapieerfolg sind meist von der Hauptläsion abhängig, welche mit Hippocampussklerosen (HS), epilepsieassoziierten Tumoren (LEAT), vaskulären Fehlbildungen, Enzephalitiden und anderen frühkindlichen erworbenen Läsionen ein breites Spektrum abdecken. Eine Revision der bestehenden ILAE-Klassifikation wird bereits diskutiert, v. a. um dem Einzug molekulardiagnostischer Methoden wie in vielen anderen Bereichen der Medizin gerecht zu werden. Wesentliche Änderungen im bestehenden Prinzip in der Einteilung der drei FCD-Typen sind allerding nicht zu erwarten.AbstractWe would like to discuss the benefits as well as ongoing challenges of the International League Against Epilepsy (ILAE) first consensus classification of focal cortical dysplasia (FCD) published in 2011. FCD is a frequent cause of early onset and drug-resistant focal epilepsy. Success of neurosurgical therapy, however, largely depends on the clinico-pathological subtype, which has been classified into three major subtypes: FCD type 1 is a rare disease frequently observed in young children and is a radiologically, electroclinically and histopathologically difficult to diagnose epilepsy. Post-surgical seizure control is less successful compared to FCD type 2A or FCD type 2B. These FCD type 2 variants are radiologically, electroclinically and histopathologically well described and probably share molecular mutations with other mTORopathies, such as hemimegalencephaly and tuberous sclerosis complex. FCD type 3 is associated with other principal lesions, such as hippocampal sclerosis (FCD 3A), epilepsy-associated tumors (FCD 3B), vascular malformations (FCD 3C) and other lesions acquired during early life (FCD 3D). The pathomechanism remains to be elucidated and success of surgical therapy is often similar to that of the principal lesions rather than being a distinct feature. An up-coming revision of the ILAE classification is currently under discussion to cover progress in molecular diagnostics (as shown in other medical disciplines, please refer to the tumor chapter of this issue); however, major changes in the three-tiered classification scheme are not expected.
Publisher Summary This chapter describes the role of hemispherectomy in the treatment of neuronal... more Publisher Summary This chapter describes the role of hemispherectomy in the treatment of neuronal migrational disorders (NMD). The term hemispherectomy is not only for surgeries in which one hemisphere is totally or partially removed, but also used for procedures like hemidecortication or for functional disconnecting techniques like functional hemispherectomy or hemispherotomy. Discussions on risks must differentiate between the risk of perioperative morbidity and perioperative mortality and the risk of late complications. Hemispherectomy is the procedure in epilepsy surgery with the highest rate of perioperative morbidity and mortality. The risk of perioperative deaths is highest in the very young age group, such as in infants below the age of 6 months. Early hydrocephalus seems to occur more often in children with NMDs than with other etiologies. In terms of perioperative morbidity, the hemispherotomy technique may have some advantages over the technique of functional hemispherectomy. It is shown that children with dysplasias have the least favorable prognosis in terms of postoperative seizure-freedom. It is emphasized that the vast majority of patients with NMDs who do not become completely seizure-free after hemispherectomy nevertheless benefit substantially from surgery because of dramatic seizure reduction.
Epileptic disorders : international epilepsy journal with videotape, 2019
This educational review describes the classification of paroxysmal events and a four-dimensional ... more This educational review describes the classification of paroxysmal events and a four-dimensional epilepsy classification system. Paroxysmal events are classified as epileptic and non-epileptic paroxysmal events. Non-epileptic events are, in turn, classified as psychogenic and organic paroxysmal events. The following four dimensions are used to classify epileptic paroxysmal events: ictal semiology, the epileptogenic zone, etiology, and comorbidities. Efforts are made to keep these four dimensions as independent as possible. The review also includes 12 educational vignettes and three more detailed case reports classified using the 2017 classification of the ILAE and the four-dimensional epilepsy classification. In addition, a case is described which is classified using the four-dimensional epilepsy classification with different degrees of precision by an emergency department physician, a neurologist, and an epileptologist. [Published with video sequences on www.epilepticdisorders.com].
Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterize... more Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterized at the clinical, anatomopathological, and molecular level (International League Against Epilepsy [ILAE] FCD classification from 2011). We aimed to describe the clinical phenotype of patients with histopathologically confirmed FCD1A obtained from a single epilepsy center between 2002 and 2016.
Epileptic disorders : international epilepsy journal with videotape, 2017
The risk of unprovoked seizures in population-based cohorts of cerebral infection survivors is 7-... more The risk of unprovoked seizures in population-based cohorts of cerebral infection survivors is 7-8% in developed countries, rising to considerably higher rates in resource-poor countries. The main risk factors for epilepsy after cerebral infection, besides acute seizures, are infection-associated brain lesions and status epilepticus during the acute phase. Despite the high prevalence of pharmacoresistant epilepsies after cerebral infections, especially in patients with MRI-identifiable lesions, only a small minority undergoes epilepsy surgery. However, excellent surgical candidates are particularly those with a history of meningitis or encephalitis in early childhood, hippocampal sclerosis on MRI, as well as a history, seizure semiology, and EEG-findings compatible with the diagnosis of a mesial temporal lobe epilepsy syndrome. More challenging are patients with neocortical/extratemporal lobe epilepsies post cerebral infection. Finally, patients with a severe hemispheric injury with...
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 2017
To identify risk factors for the development of epilepsy after pediatric stroke. Retrospective an... more To identify risk factors for the development of epilepsy after pediatric stroke. Retrospective analysis of hospital charts of 93 children and adolescents with post-neonatal non-traumatic stroke and a minimum follow-up of two years. Seizures during the first 48 h after onset of stroke symptoms were defined as "early seizures"; when two or more seizures occurred after this period, the patient was classified as "epileptic". Early seizures, young age at stroke and MRI evidence of cortical involvement were observed more frequently in the children who developed epilepsy. These factors were, however, significantly interrelated; a stepwise multiple regression analysis in 46/93 patients with complete datasets identified only the occurrence of early seizures as a significant risk factor: 15/19 (79%) children with early seizures developed epilepsy, as opposed to only 7/53 (13%) without early seizures. Children with stroke who show seizures during the first 48 h after onset ...
To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in indiv... more To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes. We performed massive parallel sequencing of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs. We identified 22 patients with heterozygous mutations in GABRB3, including 3 probands from multiplex families. The phenotypic spectrum of the mutation carriers ranged from simple febrile seizures, genetic epilepsies with febrile seizures plus, and epilepsy with myoclonic-atonic seizures to West syndrome and other types of severe, early-onset epileptic encephalopathies. Electrophysiologic analysis of 7 mutations in Xenopus laevis oocytes, using coexpression of wild-type or mutant β3, together with α5 ...
Epileptic disorders : international epilepsy journal with videotape, 2016
Brain tumours are an ever-challenging issue in neurology and related medical disciplines. This ap... more Brain tumours are an ever-challenging issue in neurology and related medical disciplines. This applies in particular to brain tumours associated with childhood-onset epilepsies, in which seizures are the presenting and only neurological symptom, as our current understanding of the biology and clinical behaviour of an individual tumour is far from being evidence-based. Prospective and randomized clinical trials are lacking in the field of epilepsy-associated tumours and a review of the current literature evokes more questions than provides answers. In this review, current areas of controversy in neuropathology, as well as terminology and classification, are discussed from an epileptologist's perspective. An illustrative case report exemplifies this controversy to further promote interdisciplinary discussion and novel research avenues towards comprehensive patient management in the near future.
ZusammenfassungSechs Jahre nach Veröffentlichung soll der Nutzen der ILAE-Konsensus-Klassifikatio... more ZusammenfassungSechs Jahre nach Veröffentlichung soll der Nutzen der ILAE-Konsensus-Klassifikation Fokaler Kortikaler Dysplasien (FCD) bewertet werden. FCDs sind häufige Ursachen frühkindlicher und medikamentös schwierig zu behandelnder fokaler Epilepsien. Die neurochirurgische Therapie bietet oftmals eine große Chance auf dauerhafte Heilung. Dies ist aber wesentlich vom histopathologischen Subtyp abhängig, und das Resektionsfeld muss durch umfassende prächirurgische Diagnostik definiert werden, z. B. durch die vorläufige Abschätzung der Art der FCD anhand des MRT und ihre Nachbarschaftsbeziehung zu eloquenten Arealen, sowie durch iktale und interiktale EEG-Befunde. Die ILAE-Klassifikation grenzt 3 histomorphologisch unterschiedliche FCD-Subtypen ab, welche nach aktuellem Kenntnisstand auch unterschiedlichen Pathomechanismen zugrunde liegen. FCD Typ 1 sind seltene Erkrankungen bei weit überwiegend jungen Kindern mit radiologisch, elektro-klinisch als auch pathologisch schwierig zu diagnostizierenden Epilepsien – mit deutlich geringeren Chancen auf eine postoperative Anfallsfreiheit als dies bei einer FCD Typ 2 der Fall ist. Die FCD Typ 2 stellt eine klinisch-pathologisch gut charakterisierte und chirurgisch oftmals gut behandelbare Gruppe dar. Molekulargenetisch finden sich Mutationen im mTOR-Signalweg, was daran denken lässt, dass zukünftig evtl. eine zielgerichtete medikamentöse Therapie möglich wird. Währenddessen sind assoziierte FCD Typ 3 in der wissenschaftlichen Literatur zwar häufig beschrieben, ihre Entstehung und Eigenständigkeit jedoch umstritten. Klinischer Verlauf und neurochirurgischer Therapieerfolg sind meist von der Hauptläsion abhängig, welche mit Hippocampussklerosen (HS), epilepsieassoziierten Tumoren (LEAT), vaskulären Fehlbildungen, Enzephalitiden und anderen frühkindlichen erworbenen Läsionen ein breites Spektrum abdecken. Eine Revision der bestehenden ILAE-Klassifikation wird bereits diskutiert, v. a. um dem Einzug molekulardiagnostischer Methoden wie in vielen anderen Bereichen der Medizin gerecht zu werden. Wesentliche Änderungen im bestehenden Prinzip in der Einteilung der drei FCD-Typen sind allerding nicht zu erwarten.AbstractWe would like to discuss the benefits as well as ongoing challenges of the International League Against Epilepsy (ILAE) first consensus classification of focal cortical dysplasia (FCD) published in 2011. FCD is a frequent cause of early onset and drug-resistant focal epilepsy. Success of neurosurgical therapy, however, largely depends on the clinico-pathological subtype, which has been classified into three major subtypes: FCD type 1 is a rare disease frequently observed in young children and is a radiologically, electroclinically and histopathologically difficult to diagnose epilepsy. Post-surgical seizure control is less successful compared to FCD type 2A or FCD type 2B. These FCD type 2 variants are radiologically, electroclinically and histopathologically well described and probably share molecular mutations with other mTORopathies, such as hemimegalencephaly and tuberous sclerosis complex. FCD type 3 is associated with other principal lesions, such as hippocampal sclerosis (FCD 3A), epilepsy-associated tumors (FCD 3B), vascular malformations (FCD 3C) and other lesions acquired during early life (FCD 3D). The pathomechanism remains to be elucidated and success of surgical therapy is often similar to that of the principal lesions rather than being a distinct feature. An up-coming revision of the ILAE classification is currently under discussion to cover progress in molecular diagnostics (as shown in other medical disciplines, please refer to the tumor chapter of this issue); however, major changes in the three-tiered classification scheme are not expected.
Publisher Summary This chapter describes the role of hemispherectomy in the treatment of neuronal... more Publisher Summary This chapter describes the role of hemispherectomy in the treatment of neuronal migrational disorders (NMD). The term hemispherectomy is not only for surgeries in which one hemisphere is totally or partially removed, but also used for procedures like hemidecortication or for functional disconnecting techniques like functional hemispherectomy or hemispherotomy. Discussions on risks must differentiate between the risk of perioperative morbidity and perioperative mortality and the risk of late complications. Hemispherectomy is the procedure in epilepsy surgery with the highest rate of perioperative morbidity and mortality. The risk of perioperative deaths is highest in the very young age group, such as in infants below the age of 6 months. Early hydrocephalus seems to occur more often in children with NMDs than with other etiologies. In terms of perioperative morbidity, the hemispherotomy technique may have some advantages over the technique of functional hemispherectomy. It is shown that children with dysplasias have the least favorable prognosis in terms of postoperative seizure-freedom. It is emphasized that the vast majority of patients with NMDs who do not become completely seizure-free after hemispherectomy nevertheless benefit substantially from surgery because of dramatic seizure reduction.
Epileptic disorders : international epilepsy journal with videotape, 2019
This educational review describes the classification of paroxysmal events and a four-dimensional ... more This educational review describes the classification of paroxysmal events and a four-dimensional epilepsy classification system. Paroxysmal events are classified as epileptic and non-epileptic paroxysmal events. Non-epileptic events are, in turn, classified as psychogenic and organic paroxysmal events. The following four dimensions are used to classify epileptic paroxysmal events: ictal semiology, the epileptogenic zone, etiology, and comorbidities. Efforts are made to keep these four dimensions as independent as possible. The review also includes 12 educational vignettes and three more detailed case reports classified using the 2017 classification of the ILAE and the four-dimensional epilepsy classification. In addition, a case is described which is classified using the four-dimensional epilepsy classification with different degrees of precision by an emergency department physician, a neurologist, and an epileptologist. [Published with video sequences on www.epilepticdisorders.com].
Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterize... more Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterized at the clinical, anatomopathological, and molecular level (International League Against Epilepsy [ILAE] FCD classification from 2011). We aimed to describe the clinical phenotype of patients with histopathologically confirmed FCD1A obtained from a single epilepsy center between 2002 and 2016.
Epileptic disorders : international epilepsy journal with videotape, 2017
The risk of unprovoked seizures in population-based cohorts of cerebral infection survivors is 7-... more The risk of unprovoked seizures in population-based cohorts of cerebral infection survivors is 7-8% in developed countries, rising to considerably higher rates in resource-poor countries. The main risk factors for epilepsy after cerebral infection, besides acute seizures, are infection-associated brain lesions and status epilepticus during the acute phase. Despite the high prevalence of pharmacoresistant epilepsies after cerebral infections, especially in patients with MRI-identifiable lesions, only a small minority undergoes epilepsy surgery. However, excellent surgical candidates are particularly those with a history of meningitis or encephalitis in early childhood, hippocampal sclerosis on MRI, as well as a history, seizure semiology, and EEG-findings compatible with the diagnosis of a mesial temporal lobe epilepsy syndrome. More challenging are patients with neocortical/extratemporal lobe epilepsies post cerebral infection. Finally, patients with a severe hemispheric injury with...
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 2017
To identify risk factors for the development of epilepsy after pediatric stroke. Retrospective an... more To identify risk factors for the development of epilepsy after pediatric stroke. Retrospective analysis of hospital charts of 93 children and adolescents with post-neonatal non-traumatic stroke and a minimum follow-up of two years. Seizures during the first 48 h after onset of stroke symptoms were defined as "early seizures"; when two or more seizures occurred after this period, the patient was classified as "epileptic". Early seizures, young age at stroke and MRI evidence of cortical involvement were observed more frequently in the children who developed epilepsy. These factors were, however, significantly interrelated; a stepwise multiple regression analysis in 46/93 patients with complete datasets identified only the occurrence of early seizures as a significant risk factor: 15/19 (79%) children with early seizures developed epilepsy, as opposed to only 7/53 (13%) without early seizures. Children with stroke who show seizures during the first 48 h after onset ...
To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in indiv... more To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes. We performed massive parallel sequencing of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs. We identified 22 patients with heterozygous mutations in GABRB3, including 3 probands from multiplex families. The phenotypic spectrum of the mutation carriers ranged from simple febrile seizures, genetic epilepsies with febrile seizures plus, and epilepsy with myoclonic-atonic seizures to West syndrome and other types of severe, early-onset epileptic encephalopathies. Electrophysiologic analysis of 7 mutations in Xenopus laevis oocytes, using coexpression of wild-type or mutant β3, together with α5 ...
Epileptic disorders : international epilepsy journal with videotape, 2016
Brain tumours are an ever-challenging issue in neurology and related medical disciplines. This ap... more Brain tumours are an ever-challenging issue in neurology and related medical disciplines. This applies in particular to brain tumours associated with childhood-onset epilepsies, in which seizures are the presenting and only neurological symptom, as our current understanding of the biology and clinical behaviour of an individual tumour is far from being evidence-based. Prospective and randomized clinical trials are lacking in the field of epilepsy-associated tumours and a review of the current literature evokes more questions than provides answers. In this review, current areas of controversy in neuropathology, as well as terminology and classification, are discussed from an epileptologist's perspective. An illustrative case report exemplifies this controversy to further promote interdisciplinary discussion and novel research avenues towards comprehensive patient management in the near future.
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