EPILEPSY IN CHILDREN – CLINICAL AND SOCIAL ASPECTS Edited by Željka Petelin Gadže Contents Preface IX Part 1 Ethiology and Pathogenesis of Epilepsy: Data from Research 1 Chapter 1 Polymicrogyria: A Clinical and Experimental Approach to Epilepsy 3 Tomoyuki Takano Chapter 2 Sequential Prefrontal Lobe Volume Changes in Epileptic Patients with Continuous Spikes and Waves During Slow Sleep 13 Hideaki Kanemura and Masao Aihara Part 2 Clinical Presentation of Epilepsy and Epileptic Syndromes of Childhood 25 Chapter 3 Neonatal Seizures 27 Isam AL-Zwaini Chapter 4 Epileptic Encephalopathy Syndromes in Infancy 47 Raidah Albaradie Chapter 5 The Lessons from Angelman Syndrome for Research and Management 59 Karine Pelc, Guy Cheron and Bernard Dan Part 3 Therapy of Epilepsy: Medicamentous and Surgical Approach 77 Chapter 6 Novel Neuroprotective Strategies and Targets of Intervention in Epilepsy 79 Ryan D. Readnower, Laurie M. Davis and Patrick G. Sullivan Chapter 7 Zonisamide – An Overview 93 Sowmini Raman, Lakshmi Narasimhan Ranganathan and Sridharan Ramaratnam Chapter 8 Practical Use of the Ketogenic Diet in Childhood Epilepsy 105 Da Eun Jung and Heung Dong Kim Chapter 9 Epilepsy Surgery in Children 115 Vera Cristina Terra, Américo C Sakamoto and Hélio Rubens Machado Chapter 10 Corpus Callosotomy in Pediatric Intractable Epilepsy: Microsurgical Technique Implication and Variation 133 Eun Kyung Park and Dong-Seok Kim Part 4 Social Aspects of Epilepsy 145 Chapter 11 Childhood Age Epilepsy and Family 147 Cicek Hocaoglu and Ayse Koroglu Chapter 12 Health-Related Quality of Life in Children and Adolescents with Epilepsy: A Systematic Review 161 Dejan Stevanovic, Ivana Tadic and Tanja Novakovic Chapter 13 Frontal Lobe Epilepsies: Neuropsychological and Behavioral Consequences in Children 187 Chiara Vago, Sara Bulgheroni, Silvana Franceschetti and Daria Riva Chapter 14 Physiotherapy for Children with Cerebral Palsy 213 Mintaze Kerem Günel Preface Epilepsy is a neurological condition that accompanies mankind probably since its inception. About 400 years before Christ, the disease was already known by Hippocrates, who wrote the book “On The Sacred Disease”, in which he refuted the idea that the upheaval was the work of spirits and wisely related it to the brain. This concept was not fully accepted until modern era (John Hughlings Jackson, 1873). Classically, epilepsy is defined as a chronic condition characterized by an enduring propensity to generate seizures, which are paroxysmal occurring episodes of abnormal excessive or synchronous neuronal activity in the brain. According to WHO epilepsy accounts for about 1% of the total burden of disease worldwide, about the same as breast cancer in women and lung cancer in men. Out of all brain disorders, epilepsy is the one that offers a unique opportunity to understand normal brain functions as derived from excessive dysfunction of neuronal circuits, because the symptoms of epileptic seizures are not the result of usual loss of function that accompanies many disease that affect the brain. I am therefore extremely honoured to present this book. The 15 very interesting chapters of the book cover various fields in epileptology – they encompass the etiology and pathogenesis of the disease, clinical presentation with special attention to the epileptic syndromes of childhood, principles of medical management, surgical approaches, as well as social aspects of the disease. Author Takao dedicated the chapter to the clinical and experimental investigations in polymicrogyria, that were reviewed with special reference to the epileptogenicity of this malformation. The cortical hyperexcitability in polymicrogyria may be reduced by the inhibitory neuronal network constructed by a population of aberrantly migrating inhibitory interneurons, which are mobilized from the ganglionic eminence during the development of polymicrogyria. Authors Kanemura and Aihara wrote about epileptic patients with continuous spikes and waves during slow sleep, in which mentioned electroencephalographic findings were associated with frontal lobe growth disturbance. They state that seizures and paroxysmal anomaly durations may be influenced by prefrontal lobe growth, which relates to neuropsychological problems. Authors Isam et al wrote the chapter about neonatal seizures. Neonatal seizures are common and the incidence is variable according to age and maturity of the neonate, weight and the severity of the underlying condition. It has been estimated that the incidence rate of clinical seizures varies from 1.1 to 8.6 per 1000 live births. No period carries the danger of seizures to the individual person like the first four weeks of life, because of immaturity of the brain cells that are more vulnerable to injury and because of wide range of factors that might cause seizures in this period. Neonatal seizures tend to be brief, because immature neurons are unable to sustain repetitive activity for a long period of time, and to be focal or multifocal. It requires immediate evaluation because of the variable conditions that might insult developing and vulnerable neurons of neonate, some of which might endanger the life of neonate. Some time seizures might be the first and probably the only manifestations of underlying significant dysfunction of the central nervous system of the newborn infant. Furthermore, these seizures are sometimes difficult to be diagnosed clinically, resulting in delaying treatment and worsening of short and long term prognosis. There is still a great debate about pathophysiology, clinical classification, electroencephalographic (EEG) significance and treatment of neonatal seizures. Chapter by authors Dan, Pelc et al is dedicated to patients with Angelman syndrome, that, compared to many other neurodevelopmental disorders, has the remarkably high risk for epilepsy. In particular, early-childhood onset of refractory epilepsy with atypical absences and myoclonic seizures with predisposition to developing nonconvulsive status epilepticus is a common presentation. This may be due to propensity to hypersynchronous neuronal activity, which might be related to abnormal GABAmediated transmission due to lack of UBE3A expression, or other factors. On the one hand, non-epileptic stereotyped or paroxysmal events (including motor or behavioural manifestations) may lead to overdiagnosis. On the other hand, the epileptic nature of relatively subtle manifestations such as absences, myoclonias or non-convulsive status epilepticus may be under-recognised in the context of behavioural and motor features. The neurocognitive effects of seizures are difficult to evaluate. There is a major need for evidence on which to base rational treatment. A diagnostic scheme for patients with epileptic seizures and with epilepsy proposed by ILAE Commission (2001) newly adopted the concept of “epileptic encephalopathy” as one of the new key terms. It is defined as a condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function, but this definition may be ambiguous. Authors Raidah et al state that the proposal include 8 syndromes: early myoclonic encephalopathy, Ohtahara syndrome, West syndrome, Dravet syndrome, myoclonic status in non-progressive encephalopathies, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy with continuous spike-waves during slow-wave sleep. To these syndromes, the migrating partial seizures in infancy and severe epilepsy with multiple independent spike foci may be reasonably added. In the chapter authors concentrate on the epileptic encephalopathies that occur only in infancy. The frontal lobes of the brain constitute more than a third of the human cerebral cortex and are characterized by a complex functional organization supporting higher level integration circuits. The complexity of the frontal lobe, in terms of its neuroanatomy and connections, determines a marked variability in the epileptic manifestations with fast and inter- and intra-hemispheric propagation. Vago et al discuss about the epilepsies involving the frontal lobe – they describe the characteristic EEG discharges, neuropsychological and behavioral consequences, in the light of the complexity of frontal regions, and they also focus on the interactions between EEG features, demographic variables and neuropsychological outcome. Authors Readnower et al discuss about the novel neuroprotective strategies and targets of intervention in epilepsy. Development of new anticonvulsive therapies designed as both an anticonvulsive as well as a neuroprotectant would be the best way to treat acute seizure conditions and to possibly prevent the development of chronic epilepsy. One of the newer broad spectrum antiepileptic drug, widely used in the management of epilepsy, is zonisamide (ZNS). Narasimhan et al state that zonisamide is effective as adjunctive therapy for refractory partial seizures, and as monotherapy for newly diagnosed or refractory partial seizures. It can also be administrated in patients with post-operative seizures, may be useful in the treatment of patients with progressive myoclonic epilepsy (studies have found it to be useful in Unverricht- Lundborg disease), West syndrome, and brain tumour related epilepsy. Chapter by Jung et al will provide practical recommendations to guide the management of the ketogenic diet in childhood epilepsy and give a review on the current state of ketogenic diet. Special chapter written by Günel et al is dedicated to the physiotherapy for children with cerebral palsy. Epilepsy affects 1-2% of children. In childhood, epilepsy is more common in the first year of life, and its incidence decreases progressively with increasing age, affecting approximately 100 children per 100,000 births in the first year of life, 40 children for every 100,000 births in subsequent years, and approximately 20 individuals per 100,000 adolescents. In 75% of these cases, seizures are well controlled with antiepileptic drugs and in the remaining 25% epilepsy is refractory to pharmacological treatment and surgical approach should be considered. Terra et al state that surgery for epilepsy in childhood has become an effective method in treating this condition, and should be indicated as early as possible. Peculiarities of epilepsy in children should be considered to achieve optimal results. Although a reduction of seizures is the primary goal of surgery, the maintenance of cognitive and motor development milestones is essential to allow the child have a quite normal life in adulthood. Extratemporal epilepsy in children closes more cases compared to those observed in adults, but still dominates the temporal lobe as the site of ictal onset, and surgical results are very encouraging. Surgical option should take in account several factors such as child´s age, underlying pathology and lesion extension. Neuronal plasticity can be an ally for the development of minor post-operative neurological deficits. Authors Park and Kim state that callosotomy in pediatric epilepsy is a valuable tool to control seizures early on, in order to protect the developing brain from further damage and to give chance to recover neuropsychological function from damage done by XII Preface seizure itself as well as seizure medication. They advocate that one stage total callosotomy in young patients with medically intractable epilepsy without localizing lesions is especially effective in drop attacks and secondary generalized epilepsy. With improvement in microsurgical techniques, excellent seizure outcome as well as functional outcome may be reached without previously known high rate of morbidity and mortality. Authors Hocaoglu and Koroglu state that childhood epilepsy has a significant effect on the child himself and the family because of its psychological and social results. In the studies the increasing economical responsibility of the families whose children undergo chronic diseases is distinctively described. Still, epilepsy in childhood is different from the other chronic diseases due to the fact that its sudden symptoms and early unpredictable effects are all specific for itself. In many studies about epilepsy, despite the fact that the patient’s quality of life and relationship with the family are examined, in few ones problems belonging to family members that result from epilepsy are pointed. Clinicians should consider both neurological and psychosocial factors, including the family system, when treating psychopathology in children with epilepsy. The chapter by Stevanovic et al systematically reviewed synthesizing different studies that evaluated health-related quality of life (HRQOL) in children and adolescents with epilepsy over 12 past years. The affected domains, predictors, and impacts on HRQOL of specific and non-specific treatments were reviewed. Previous reviews evaluated methodological issues in HRQOL assessment, components of theoretical model, and determinants of HRQOL in pediatric epilepsy. Based on the findings and evidence found, it could be concluded that children and adolescents have more affected HRQOL in physical, psychological, and social domain than healthy children and adolescents. It is important for all of us to raise the awareness and reduce social barriers for individuals with epilepsy. Together we can hope that we will identify ways to improve the treatment of patients with epilepsy and the livelihood of all individuals with epilepsy. Željka Petelin Gadže, M.D., Ph.D. Department of Neurology of the Medical School and University Hospital Centre Zagreb, Referral Centre for Epilepsy of the Ministry of Health and Social Welfare of the Republic of Croatia Croatia