Early predictors of medical intractability in childhood epilepsy

The goal of this study is identify early predictors of intractability in childhood epilepsy. A cohort of epileptic children living in the northwest sector of Hong Kong was prospectively identified and monitored. Treatment effect was analyzed at the last follow-up before July 1, 2000. Cases were patients who had an average of at least one unprovoked seizure per month during an observational period of at least 2 years. Controls were children having achieved at least 2 seizure-free years. Strong univariate association was observed between intractability and the following factors: high initial seizure frequency, remote symptomatic etiology, infantile spasms and mixed seizure types, abnormal neurologic status, history of status epilepticus, neonatal seizures, and early breakthrough attacks after treatment initiation. Independent predictors of intractability with multiple regression were abnormal neurodevelopmental status, symptomatic etiology, and more than three seizures in the second 6 months after treatment. Our study suggested that risk of developing intractable epilepsy might be predicted, to some extent, at the early course of illness in children with abnormal neurologic status and lack of early response to treatment.     

The Prevalence and Incidence of Convulsive Disorders in Children

Summary: Each year, about 150,000 children and adolescents in the United States will come to medical attention for evaluation of a newly occurring seizure disorder of some type. Between 2% and 4% of all children in Europe and the United States experience at least one convulsion associated with a febrile illness before the age of 5 years. The cumulative incidence of febrile convulsions among children ranges from about 1% in China to more than 8% in Japan and 14% in Guam. The peak incidence of a first febrile convulsion occurs in the second year of life. Between 0.5% and 1% of children and adolescents experience a seizure associated with other acute metabolic or neurologic insults; most of these occur in the neonatal period. The incidence of epilepsy (recurrent unprovoked seizures) in children and adolescents seems relatively consistent across all populations studied, ranging from 50 to 100/100,000. The highest incidence of epilepsy is in the first year of life. West syndrome accounts for about 2% of all childhood epilepsy, Lennox-Gastaut syndrome for 1–2%, childhood absence epilepsy (pyknolepsy) for 10–15%, juvenile myoclonic epilepsy for 5%, and idiopathic localization-related epilepsy for 10%. Between 0.5 and 1% of children experience a nonrecurrent, single, unprovoked convulsive episode. Following are the estimated numbers of children and adolescents with newly diagnosed convulsive disorders in the United States for the year 1990: febrile seizures, 100,000; neonatal seizures, 4,000; other provoked seizures, 6,000; single unprovoked seizures, 10,000; and epilepsy, 30,000.     

The Prevalence and Incidence of Convulsive Disorders in Children

Summary: Each year, about 150,000 children and adolescents in the United States will come to medical attention for evaluation of a newly occurring seizure disorder of some type. Between 2% and 4% of all children in Europe and the United States experience at least one convulsion associated with a febrile illness before the age of 5 years. The cumulative incidence of febrile convulsions among children ranges from about 1% in China to more than 8% in Japan and 14% in Guam. The peak incidence of a first febrile convulsion occurs in the second year of life. Between 0.5% and 1% of children and adolescents experience a seizure associated with other acute metabolic or neurologic insults; most of these occur in the neonatal period. The incidence of epilepsy (recurrent unprovoked seizures) in children and adolescents seems relatively consistent across all populations studied, ranging from 50 to 100/100,000. The highest incidence of epilepsy is in the first year of life. West syndrome accounts for about 2% of all childhood epilepsy, Lennox-Gastaut syndrome for 1–2%, childhood absence epilepsy (pyknolepsy) for 10–15%, juvenile myoclonic epilepsy for 5%, and idiopathic localization-related epilepsy for 10%. Between 0.5 and 1% of children experience a nonrecurrent, single, unprovoked convulsive episode. Following are the estimated numbers of children and adolescents with newly diagnosed convulsive disorders in the United States for the year 1990: febrile seizures, 100,000; neonatal seizures, 4,000; other provoked seizures, 6,000; single unprovoked seizures, 10,000; and epilepsy, 30,000.     

Underlying neurologic disorders and recurrence rates of status epilepticus in childhood

Background: The underlying neurologic disorders of status epilepticus (SE) in childhood remain poorly characterized. Methods: We reviewed 249 consecutive patients with SE, aged 1 month to 18 years, who were referred to Tottori University Hospital from 1984 to 2002. After exclusion of SE patients with acute symptomatic etiology and progressive encephalopathy, such as acute encephalitis/encephalopathy, meningitis, head trauma, or metabolic disorders, we analyzed 112 patients, aged 3 months to 14 years, and focused on the epilepsy classification and perinatal brain damage in these patients. Results: Major underlying neurologic disorders were non-symptomatic epilepsy (41 patients, 36.6%), perinatal brain damage (15 patients, 13.4%), non-syndromic mental retardation (17 patients, 15.2%), and congenital disorders including chromosomal abnormalities (13 patients, 11.6%). In non-symptomatic epilepsy, childhood epilepsy with occipital paroxysms (Panayiotopoulos syndrome, 11 patients) and severe myoclonic epilepsy in infancy (SMEI, 6 patients) were common and had high recurrence rates (81.8% and 66.7%, respectively). In patients with a history of perinatal brain damage, preterm birth, neonatal seizure, asphyxia, and neonatal hypoglycemia were frequent. Neonatal hypoglycemia and neonatal seizure were related to the recurrence of SE (100% and 87.5%, respectively). They were mostly diagnosed as symptomatic occipital lobe epilepsy. Parieto-occipital paroxysms were associated with a high recurrence rate of SE (80.6%). Conclusions: Although the underlying neurologic disorders of SE are heterogeneous, three specific epileptic syndromes (Panayiotopoulos syndrome, SMEI, and symptomatic occipital lobe epilepsy secondary to neonatal hypoglycemia and neonatal seizure) were the most common causes of SE and were associated with higher recurrence rates.     

Convulsive Status Epilepticus in Children

Summary: Status epilepticus (SE) occurs most commonly in infancy and childhood. Children with prior neurological abnormalities are most susceptible. More than 90% of cases are convulsive and the majority are generalized. SE may occur in the setting of an acute illness, in patients with established epilepsy or as a first unprovoked seizure. The etiology can be classified as idiopathic, remote symptomatic, febrile, acute symptomatic, or associated with a progressive encephalopathy. The morbidity and mortality of status have dramatically declined in recent years. Overall mortality in recent pediatric series was 3–10%, with almost all fatalities associated with acute central nervous system insults or progressive neurologic disorders. Neurological sequelae in children with idiopathic or febrile status are rare. Neurologically normal children with SE as their first unprovoked seizure have the same risk of experiencing subsequent seizures of any type as children who present with a brief first seizure. The risk of recurrent episodes of convulsive SE approaches 50% in neurologically abnormal children but is very low in neurologically normal children. The favorable outcome of SE in children may be related to advances in therapy and to the resistance of the immature brain to damage from seizures.     

Recommendations for the management of "febrile seizures" Ad hoc Task Force of LICE Guidelines Commission

Febrile seizures are the most common seizure disorder in childhood, affecting 2–5% of children. Simple febrile seizure is defined as a short (<15 min) generalized seizure, not recurring within 24 h, that occurs during a febrile illness not resulting from an acute disease of the nervous system in a child aged between 6 months and 5 years, with no neurologic deficits and no previous afebrile seizures. These recommendations address the instructions for management of the first febrile seizures, giving criteria for hospital admission, diagnosis, differential diagnosis, and treatment of a prolonged seizure. The authors stressed the benign prognosis of the majority of cases and the risk factors for recurrence of febrile seizures and appearance of epilepsy later on. Both continuous and intermittent anticonvulsant therapy are efficacious in preventing single febrile seizures, but side effects may be so important to overcome the benefits. These treatments are indicated in very selected patients.     

The behavioral and emotional correlates of epilepsy in adolescence: a 7-year follow-up study

This 7-year follow-up study examined the behavioral and emotional adjustment of 29 adolescents who experienced regular moderate seizures during middle childhood. Compared with national nonreferred norms on Achenbach checklists, both mothers and adolescents reported clinically significant difficulties in multiple areas regardless of current seizure status. Adolescents who currently experience regular seizures (N=10) reported no differences on psychological outcomes compared with nonseizing counterparts; in contrast, current seizure status was a strong predictor of mother-reported externalizing problems. Hierarchical regression analyses indicated that feelings about having or having had a seizure disorder and mother-adolescent relationship factors were significant predictors of current adjustment over and above current seizure status. Early mother-child relationship process variables and early medical risk were not associated with current adolescent outcomes. The findings are discussed in terms of the multidetermined nature of psychological adjustment to chronic medical illness and factors that may produce versus maintain behavioral and emotional problems in children and adolescents with seizure disorders.     

Discontinuing Medication in Epileptic Children: A Study of Risk Factors Related to Recurrence

We studied 70 children who had experienced at least two seizures before age 12 years, excluding febrile seizures, neonatal seizures, or seizures occurring during a metabolic, or infectious insult to the central nervous system (CNS) and who had been seizure free for at least 2 years. Twenty children (28.5%) experienced a recurrence, 75% during antiepileptic (AED) drug discontinuation or less than 6 months after discontinuation. Risk factors statistically related to seizure recurrence were greater than 10 seizures before seizure control, an abnormal EEG in the year before AED discontinuation, presence of focal neurologic signs and/or mental retardation, and presence of a mixed seizure pattern. Fourteen children (70%) with recurrence had two or more risk factors, whereas 36 (72%) without recurrence had no risk factor or only one. We conclude that a selected group of epileptic children who remain seizure-free for a period of at least 2 years can have AEDs discontinued based on presence or absence of risk factors.     

Epilepsy in hemiplegic cerebral palsy due to perinatal arterial ischaemic stroke

Aim The aim of this study was to describe the frequency, risk factors, manifestations, and outcome of epilepsy in children with hemiplegic cerebral palsy (CP) due to perinatal arterial ischaemic stroke (AIS). Method The study group comprised 63 participants (41 males, 22 females) from a population‐based CP register whose brain imaging showed perinatal AIS. Information collected included occurrence of neonatal seizures, family history of epilepsy, motor function and epilepsy onset, treatment, and outcome. Electroclinical findings were classified according to seizure semiology, seizure type, and epilepsy syndrome. Results Mean age of participants at the time of study was 10 years 6 months (SD 4y 7mo, range 4–20y). Gross Motor Function Classification System levels I and II were reported in 96% of participants, and Manual Ability Classification System levels I and II were reported in 79% of children. Thirty‐four children (54%) developed epilepsy. Term delivery and more severe motor impairment were associated with epilepsy, but neonatal seizures and family history of epilepsy were not. Initial seizures were epileptic spasms, focal seizures, or myoclonic seizures. Focal seizure semiology suggested Rolandic or occipital seizure origin in the majority of children. Focal epileptic discharges in children with focal seizures had features of idiopathic partial epilepsy. Only 15% of children had active epilepsy 10 years after onset. Interpretation Despite a high incidence of epilepsy in children with hemiplegic CP due to AIS, the prognosis for seizure remission is good. Many children have clinical features, electroencephalography findings, and remission typical of idiopathic partial epilepsy.     

Low-grade focal cortical dysplasia is associated with prenatal and perinatal brain injury

Purpose: Prenatal and perinatal adverse events are reported to have a pathogenetic role in focal cortical dysplasia (FCD). However, no data are available regarding the prevalence and significance of this association. A cohort of children with significant prenatal and perinatal brain injury and histologically proven mild malformations of cortical development (mMCD) or FCD was analyzed. Methods: We retrospectively evaluated a surgical series of 200 patients with histologically confirmed mMCD/FCD. Combined historical and radiologic inclusion criteria were used to identify patients with prenatal and perinatal risk factors. Electroclinical, imaging, neuropsychological, surgical, histopathologic, and seizure outcome data were reviewed. Results: Prenatal and perinatal insults including severe prematurity, asphyxia, bleeding, hydrocephalus, and stroke occurred in 12.5% of children with mMCD/FCD (n = 25). Their epilepsy was characterized by early seizure onset, high seizure frequency, and absence of seizure control. Patients with significant prenatal and perinatal risk factors had more abnormal neurologic findings, lower intelligence quotient (IQ) scores, and slower background EEG activity than mMCD/FCD subjects without prenatal or perinatal brain injury. MRI evidence of cortical malformations was identified in 74% of patients. Most patients underwent large multilobar resections or hemispherectomies; 54% were seizure‐free 2 years after surgery. Histologically “milder” forms of cortical malformations (mMCD and FCD type I) were observed most commonly in our series. Conclusions: Surgically remediable low‐grade cortical malformations may occur in children with significant prenatally and perinatally acquired encephalopathies and play an important role in the pathogenesis of their epilepsy. Presurgical detection of dysplastic cortex has important practical consequences for surgical planning.     

Febrile Seizures: Clinical Characteristics and Initial EEG

We examined the relationship between clinical characteristics and EEG classification in all children with febrile seizures examined at the University Pediatric Clinic, Skopje, Yugoslavia between 1982 and 1984. This is the only facility in Macedonia providing EEG or neurologic consultation for children. EEGs were classified as paroxysmally abnormal if they contained spikes, sharp waves, or spike-wave complexes considered abnormal for age. In all, 22% of the 676 children had an abnormal initial EEG. The most common basis for classification as abnormal was spike-wave complexes greater than 3 Hz; the next most common basis was the presence of spikes. Birth weight, gender, accompanying illness, and family history of seizures, and whether the index seizure was single or multiple were not associated with differences in rate of abnormal EEG. Clinically focal index seizures and longer duration were associated with EEG abnormality. Number of previous febrile seizures was associated with an increasing rate of EEG abnormality, from 18% in children with no previous seizures to 63% in those with four or more previous seizures. Age at EEG was linearly related to likelihood of paroxysmal EEG abnormality, both for the total cohort and for the 376 children with no previous seizures. In the total cohort, logistic regression identified leading predictors of abnormal initial EEG to be older age, number of previous febrile seizures, preexisting motor abnormality, and focal seizures. For children with a first febrile seizure, leading predictors were focal seizure, older age, and preexisting motor abnormality.     

Prenatal and perinatal determinants of neonatal seizures occurring in the first week of life

To evaluate prenatal and perinatal risk factors for early neonatal seizures, we conducted a case-control study including 100 newborns with neonatal seizures in the first week of life and 204 controls randomly selected from a list of healthy newborns born in the same hospital during the study period. Generalized tonic seizures were the most common seizures observed (29%), although the majority of newborns (71%) experienced more than one type of seizure. The most frequent presumed etiology of neonatal seizures was hypoxic-ischemic encephalopathy (30%). A history of epilepsy in first-degree relatives was found only for cases. Neonatal seizures were found to be associated with maternal disease in the 2 years before pregnancy, mother's weight gain > 14 kg during pregnancy, placental pathology, preeclampsia, low birthweight, low gestational age, and jaundice in the first 3 days of life. The need for cardiopulmonary resuscitation was found only for cases (37%). The causal pathways for neonatal seizures often begin before birth, and some of the factors identified may be preventable.     

Predictors of Intractable Childhood Epilepsy

Our study sought to identify early predictive factors of medically intractable childhood epilepsy. A cohort of epileptic children from the city of Mersin was retrospectively investigated. All patients received care from the same Department of Pediatric Neurology. The epileptic cohort was divided into a drug-responsive epilepsy group and an intractable epilepsy group. Intractable epilepsy is defined as continued seizures in children despite adequate therapy with two or more antiepileptic drugs for more than 18 months. Strong univariate association was observed between intractability and several factors: age of onset, high initial seizure frequency, symptomatic etiology, mixed seizure types, previous history of status epilepticus, febrile and neonatal seizures, mental and motor developmental delay, multiple seizures in 1 day, electroencephalogram abnormalities, magnetic resonance imaging findings, and specific epileptic syndromes. Logistic regression analysis revealed that a previous history of epilepticus status, abnormal electroencephalogram results, and multiple seizures in 1 day comprise independent predictors of medically intractable childhood epilepsy. We suggest that medical intractability in childhood epilepsy can be predicted by monitoring these factors. Along with early prediction, alternative therapies may be designed to provide patients better seizure control and quality of life.     

Profile of childhood epilepsy in Bangladesh

Very little is known about childhood epilepsies in Bangladesh. This study was conducted within a national children's hospital in Dhaka city to provide baseline information on diagnosis and clinical outcomes of 151 children (98 males, 53 females, age range between 2 months to 15 years, median age of 3 years). Participants who presented with recurrent unprovoked seizures were followed up in an epilepsy clinic for at least 1 year. Of presenting families, 68.3% were from middle-income and lower-income groups. A history of perinatal asphyxia and neonatal seizures was present in 46.4% and 41.1% of participants respectively. Generalized, partial, and unclassifiable epilepsy were found in 63.6%, 25.2%, and 11.2% respectively. Severe outcome (malignant) epilepsy syndromes were diagnosed in 14.6%. Symptomatic epilepsy was found in 61%. Poor cognitive development was present in 72.8% and poor adaptive behaviour in 57%. Poor seizure remission occurred in 50.3%. Factors most predictive of poor seizure remission were: multiple types of seizures, poor cognition at presentation, high rates of seizures, associated motor disability, and EEG abnormalities. The study suggests that most children presenting at tertiary hospitals for seizure disorders come late and with associated neurodevelopmental morbidities. Specialized services are needed closer to their homes. The process for establishing early referral and comprehensive management of childhood epilepsies in Bangladesh requires further study.     

Pediatric epilepsy evaluations from the prenatal perspective

Prenatal contributions to childhood epilepsy include malformations and acquired injuries, which can occur from conception and throughout gestation. Five case histories from the Pediatric Epilepsy Service are discussed that exemplify maternal, fetal, and placental conditions that contribute to childhood epilepsy. Two full-term neonates presented with neonatal seizures, with or without accompanying encephalopathy. Placental pathology suggested antepartum maternal-placental diseases that caused or contributed to their brain disorders. Two children presented as preterm infants with systemic organ system diseases that also implicated brain injury. One child had a complicated maternal history with both genetic and acquired illnesses. Two children required epilepsy surgery, with improved seizure control despite persistent neurocognitive and neurobehavioral deficits related to diffuse encephalopathies. Dual pathology should include prenatal contributions to childhood epilepsy on both a genetic and acquired basis. Epileptologists should consider an ontogenetic approach to study the epileptic condition from a fetal neurology perspective.     

Predictive clinical factors for the differential diagnosis of childhood extratemporal seizures

PURPOSE: To describe predictive clinical factors for the differentiation between childhood frontal lobe epilepsy (FLE) and posterior cortex epilepsy (PCE). METHODS: Two independent, blinded investigators analyzed 177 seizures from 35 children (aged 11 months to 12 years) with extratemporal epilepsy selected by postoperative seizure-free outcome. Semiologic seizure components and different periictal signs were observed. Age at onset, auras, seizure frequency, and nocturnal dominance, as well as surgical and histopathologic data, were collected from medical charts. RESULTS: Twenty patients had FLE, and 15 had PCE. Patients from both groups had daily seizures without significant differences in frequency but with higher nocturnal dominance in children with FLE (p < 0.05). Visual aura, nystagmus, and versive seizure were observed exclusively in the PCE group, whereas somatosensory aura and hypermotor seizures appeared only in FLE. Tonic seizures were significantly more frequent in FLE (p < 0.01), whereas the presence of clonic seizure (FLE; p = 0.07) and postictal nose-wiping (PCE; p = 0.05) showed only a trend to localize the seizure-onset zone. Myoclonic seizures, epileptic spasms, psychomotor seizures, atonic seizures, oral and manual automatisms, as well as vocalization and eye deviation appeared in both groups without significant differences in their frequency. CONCLUSIONS: Characteristic features described in adults' extratemporal epilepsies were frequently missing during childhood seizures, especially in infants and preschool children. Ictal features help only a little in differentiating childhood FLE from PCE. Nocturnal appearance and the type of aura have high localizing value; therefore an accurate history taking is still an essential element of pediatric presurgical evaluation.     

Risk factors for developing epilepsy after neonatal seizures

The objective of this study was to determine clinical and polysomnographic risk factors that might be early predictors for the development of postnatal epilepsy in a cohort of infants with seizures. The study sample included 158 infants who presented two or more clinically proven seizures. Gestational, perinatal, and polysomnographic data were obtained retrospectively. A questionnaire designed to detect patients with epilepsy in the community was prospectively given to all families, and the positive cases were reassessed for confirmation of epilepsy. Epilepsy rate after neonatal seizures was 22% within 12 months of follow-up and 33.8% within 48 months. Transient electrolytic imbalance and perinatal asphyxia were the most frequent etiologic factors associated with neonatal seizures. More than one seizure type was detected in 17.3% (n = 22) of cases and strongly associated with central nervous system infection (relative risk [RR] = 3.02, 95% confidence interval [CI] = 1.24-7.40, P = 0.02). Focal symptomatic epilepsy (P = 0.01) and syndromes not determined as focal or generalized (P = 0.04) were also associated with central nervous system infection. Abnormal polysomnographic recordings (P = 0.09) and abnormal neurologic examination on discharge (P < 0.01) were correlated with postnatal epilepsy. No differences were observed between premature and term infants concerning outcome. Neonatal seizures were associated with a high incidence of postnatal epilepsy in the cohort, including epileptic syndromes with catastrophic evolution. Abnormal neurologic examination on discharge was a good predictor of an unfavorable outcome and abnormal polysomnographic recording a moderate predictor.     

Prenatal and perinatal antecedents of febrile seizures

We examined prenatal and perinatal characteristics as possible risk factors for febrile seizures in a large pediatric population. Family history was among the few identified factors that made an important contribution to vulnerability to febrile seizures; however, no more than 6% of febrile seizures could be attributed to a characteristic of family history. Maternal illness, smoking history, and a few rare neonatal characteristics were associated with increases in risk. No complication of labor or delivery was an important risk factor for febrile seizures.     

The relationship of prenatal and perinatal complications to cognitive functioning at age 7 in the New England Cohorts of the National Collaborative Perinatal Project

Previous literature shows that children who later develop schizophrenia have elevated rates of prenatal and perinatal complications (PPCs) and neuropsychological deficits in childhood. However, little is known about the relationship of these risk factors to each other. We evaluated the relationship between PPCs and neuropsychological functioning at age 7 in a large epidemiological study of pregnancy, birth, and development: the National Collaborative Perinatal Project (NCPP). Thirteen standardized measures of cognitive abilities were acquired on 11,889 children at approximately age 7. Principal components analysis was used to create three neuropsychological measures: academic achievement skills, verbal-conceptual abilities, and perceptual-motor abilities. We measured the relationship between these factors and three measures of PPCs: low birth weight (LBW), probable hypoxicischemic complications, and chronic hypoxia. All three measures of PPCs were significantly associated with lower neuropsychological performance, after controlling for various confounders. LBW had the strongest association with neuropsychological performance, followed by an index of presumed hypoxic insults. The effect sizes between PPCs and cognitive factors at age 7 were consistently largest with perceptual-motor abilities, followed by academic achievement skills and verbal-conceptual abilities. Future studies will evaluate the effects of specific PPCs and genetic risk factors for psychosis on cognitive functioning in childhood.     

Clinical and electroencephalographic follow-up after a first unprovoked seizure

We studied the role of clinical and electroencephalographic factors in the follow-up of children and adolescents after a first unprovoked seizure, and their correlation with recurrence and risk for epilepsy. We conducted a 24-month follow-up of 109 patients aged 1 month to 16 years who had a first unprovoked seizure. We analyzed the characteristics of the first seizure, perinatal history, family history of seizures, electroencephalographic patterns and their influence on seizure recurrence, and calculated risk for subsequent epilepsy. Fifty-six patients (51.4%) had recurrent seizures. The bivariate statistical analysis revealed that maternal prenatal disease (relative risk = 2.02, P = 0.03) and an abnormal electroencephalogram (relative risk = 2.89, P = 0.0003) were significantly associated with seizure recurrence. Other factors (male sex, partial first seizure, vaginal delivery, family history of seizures, and sleep state) approached statistical significance. Logistic regression revealed that the only variable significantly associated with recurrence was an abnormal electroencephalographic pattern on the first examination (relative risk = 2.48, P = 0.003). Cumulative risk ranged from 50-68% at 24 months when the first electroencephalogram was abnormal, and from 26-36% when it was normal. We concluded that the electroencephalogram may have an important diagnostic value in the prognosis of epileptic seizure recurrence in children and adolescents.