The impact of epilepsy surgery on quality of life in children.

OBJECTIVE: To determine if epilepsy surgery is effective in improving the quality of life (QOL) of children with intractable seizures using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). METHODS: The authors conducted a prospective study of the families of 35 children with intractable epilepsy who underwent epilepsy surgery. Parents completed the QOLCE preoperatively and again 6 to 18 months after surgery. At both assessment dates parents indicated the severity of their child's seizures during the past 6 months and the frequency of their child's seizures during the past 4 weeks on Likert-type scales. Children were split into two groups according to surgery outcome: seizure free vs persistent seizures. Statistical analyses were conducted to determine if children rendered seizure free showed a greater improvement in QOL compared to those with persistent seizures postoperatively. RESULTS: Greater improvement in QOL was documented for children rendered seizure free vs children with persistent seizures. This was significant for the overall QOLCE QOL score and subscales assessing cognitive, social, emotional, behavioral, and physical domains of life. CONCLUSIONS: Epilepsy surgery improves the quality of life of children rendered seizure free. Families can be counseled preoperatively of the potential benefits of surgery beyond seizure reduction.

Memory function in childhood epilepsy syndromes.

OBJECTIVE: Children with epilepsy are at risk of specific cognitive deficits. We aimed to compare and characterize the memory function of children with childhood absence epilepsy (CAE), frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). METHODS: Epilepsy syndrome was identified by clinical data, seizure semiology, interictal and ictal electroencephalogram (EEG). Seventy children aged 6-18 years with CAE, FLE or TLE had neuropsychological assessment including memory function. After adjusting for epilepsy variables, neuropsychological results of the syndrome groups and normative data were compared. RESULTS: Children from all three syndrome groups were at risk of memory difficulties. The duration of epilepsy correlated negatively with memory function. Children with TLE had the worst memory function, significantly lower in verbal memory tasks than children with CAE (P = 0.02) and children with FLE (P = 0.01). The performance of children with TLE was significantly below the normed mean across all verbal and most visual tasks. Compared to the normed means, children with FLE had results that were statistically lower in some verbal and visual tasks, and children with CAE were lower in two visual tasks only. CONCLUSIONS: This study demonstrates memory dysfunction in three common childhood epilepsy syndromes. Children with TLE had the greatest impairment, children with FLE had memory difficulties not previously reported, and children with CAE had subtle memory deficits. Qualitative differences were also evident. Longer duration of intractable epilepsy was associated with reduced memory ability. Memory function and its potential impact on academic achievement are vital considerations when managing children with epilepsy.

The health-related quality of life of childhood epilepsy syndromes.

OBJECTIVE: There is increasing awareness of the importance of assessing physical, psychological, social and behavioural well-being in chronic disease. The aim of this study was to examine the health-related quality of life (HRQoL) of children with common epilepsy syndromes and to explore if there are HRQoL differences between those syndromes. METHODS: Each child had their epilepsy syndrome defined according to the International League Against Epilepsy classification. Epilepsy syndromes included symptomatic frontal, temporal, parietal/occipital lobe and partial unlocalized epilepsy, and two idiopathic epilepsies, childhood absence epilepsy (CAE) and benign rolandic epilepsy (BRE). Seizure semiology and ictal/interictal electroencephalogram (EEG) were determined for symptomatic partial epilepsy syndromes by video-EEG monitoring. HRQoL was evaluated with an epilepsy-specific instrument, the Quality of Life in Childhood Epilepsy Questionnaire, and two generic instruments, the Child Health Questionnaire and Child Behavior Checklist. RESULTS: Children with symptomatic partial epilepsy syndromes were affected by epilepsy in a similar way and did not have unique HRQoL profiles. However, these children had significantly lower HRQoL scores compared to those with CAE or BRE. All children with epilepsy regardless of syndrome had a higher frequency of behavioural problems compared to normative data. CONCLUSION: These results indicate that children with epilepsy regardless of syndrome require evaluation of the psychosocial implications. There is a greater impact on HRQoL in symptomatic epilepsy compared to idiopathic epilepsy. Specific symptomatic partial syndromes did not differ in the degree they affect HRQoL. These findings have important implications for clinicians caring for children with epilepsy.

Survival after pulmonary edema due to enterovirus 71 encephalitis.

BACKGROUND: A distinctive pattern of enterovirus 71 (EV71) infection, characterized by fever, exanthem, acute pulmonary edema (PE), brainstem encephalitis, and flaccid paresis, affects infants and young children. Most die rapidly owing to respiratory failure and fulminant PE. METHOD: The authors report short- and long-term outcome of six survivors of the acute illness. RESULTS: In the context of acute PE and widespread weakness, recognition of the underlying neurologic disorder was facilitated by the distinctive pattern of MRI signal abnormalities in posterior pons and medulla. EV71-specific PCR of clinical samples helped confirm the diagnosis. Acute PE was managed with mechanical ventilation, afterload reduction, and inotrope support, and resolved completely over days. One patient with minimal neurologic recovery died 9 weeks after disease onset. The other patients have residual neurologic dysfunction, varying from subtle monoparesis to severe bulbar dysfunction, central and peripheral respiratory failure, and flaccid quadriparesis. Faster neurologic recovery was associated with less long-term deficit. Long-term outcome was similar in patients treated with and without pleconaril or IV immunoglobulin. Three long-term survivors treated with IV corticosteroids had less severe long-term neurologic disability than two not treated with steroids. CONCLUSION: Acute pulmonary edema and encephalomyelitis occurs with EV71 infection in infants. Long-term neurologic outcome varied from minor, focal weakness to profound, global motor dysfunction with respiratory failure.

Clinical, EEG, and quantitative MRI differences in pediatric frontal and temporal lobe epilepsy.

OBJECTIVE: To examine the clinical, electrographic, and quantitative MRI differences between frontal lobe (FLE) and mesial temporal lobe epilepsy (MTLE) in children. METHODS: The population included children who underwent video-EEG monitoring between 1995 and 2000 who were classified as either FLE (n = 39) or MTLE (n = 17) according to the criteria of the International League Against Epilepsy. Clinical, EEG, and quantitative MRI data (including frontal cortical volumes) were compared between the two syndromes and a control group (n = 42). RESULTS: In FLE, seizures were significantly briefer, more frequent, and predominantly from sleep, and had differing motor characteristics. The rates of bilateral epileptiform interictal and ictal EEG abnormalities were significantly higher in FLE. A nonlesional MRI was significantly more common in FLE. Mean frontal cortical volume in FLE was significantly lower than MTLE and controls. Seizure freedom after surgery was lower in FLE. CONCLUSIONS: The clinical syndrome of FLE is clearly distinct from MTLE. The etiology of this disorder is unknown in the majority of cases despite extensive investigation. Because of a lack of a clearly defined etiology and frequent nonlateralizing EEG changes, few of these children are considered optimal surgical candidates. The demonstration of bilateral frontal cortical volume loss and bilateral EEG abnormalities suggests that FLE is a bilateral disease in a high proportion of patients. The outcome in those patients who were deemed surgical candidates was significantly worse than the MTLE cases.

The health-related quality of life of children with refractory epilepsy: a comparison of those with and without intellectual disability.

PURPOSE: To determine whether refractory epilepsy affects the health-related quality of life (HRQOL) of children with or without intellectual disability (ID), and if the presence of ID independently compromises HRQOL in children with refractory epilepsy. METHODS: Subjects were parents of children with refractory epilepsy, whose syndrome had been defined using ILAE (International League Against Epilepsy) criteria and video-EEG monitoring. Children had the presence or absence of ID determined by formal neuropsychological or educational assessment. The relative effect of epilepsy on the two intellectual ability groups was determined using relevant clinical variables. Parents completed a valid epilepsy-specific HRQOL questionnaire for children, the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), and, depending on intellectual ability level, the Child Behaviour Checklist or Developmental Behaviour Checklist. RESULTS: Both intellectually normal children with epilepsy and children with epilepsy and ID were more likely to have psychosocial problems compared with their respective intellectual ability reference populations. The results also revealed that children with ID had reduced HRQOL compared with intellectually normal children; a result independent of epilepsy. Analysis of the relationship between epilepsy variables and HRQOL revealed that the QOLCE was the most sensitive in detecting variation in age at onset, seizure frequency, and medications taken. CONCLUSIONS: The HRQOL of children with refractory epilepsy is greatly affected, regardless of intellectual ability level. The presence of ID in children with epilepsy independently depresses HRQOL outcomes. Compared with two generic HRQOL measures, the QOLCE was the most sensitive measure to variation in epilepsy variables.

Predictors of hippocampal, cerebral, and cerebellar volume reduction in childhood epilepsy.

PURPOSE: We examined the factors related to brain volume reduction in a pediatric sample of patients that included those with nonintractable epilepsy. METHODS: Entry criteria were children less than 18 years old with epilepsy referred for MRI, including a whole brain volumetric sequence. The sample size was 231. Risk factors were ascertained from interviews and reviews of medical records. Factors included age of onset, seizure years, family history, status epilepticus, intellectual disability, and febrile convulsions. MRI data were obtained for 44 normal childhood control subjects. RESULTS: Cerebral and cerebellar volumes were significantly associated with age, gender, moderate-to-severe intellectual disability (p < 0.001), seizure years, and status epilepticus (p < 0.03). Compared with controls, the brain volume of all patients was reduced by 10% (p < 0.001). Hippocampal volume was significantly associated with total brain volume, age (p < 0.001), focal cerebral ischemic injury, and complex febrile convulsions (p < 0.05). CONCLUSIONS: Significant brain volume reduction is present in children with epilepsy. A component of this reduction is due to acquired insults. The reduction is seen even in children with infrequent seizures over a brief time, suggesting an innate structural abnormality. When evaluating possible etiologic factors in the development of hippocampal volume reduction, one must control for total brain volume. We have confirmed the association of complex febrile convulsions with unilateral hippocampal volume reduction.

Cerebral and cerebellar volume reduction in children with intractable epilepsy.

PURPOSE: Adult epilepsy studies have demonstrated cerebral and cerebellar volume reduction beyond the epileptogenic zone, correlating this with an inferior surgical outcome. We determined whether brain volumes were reduced in childhood epilepsy and the significance of this. METHODS: Cerebral, cerebellar, and hippocampal volumes were measured by quantitative magnetic resonance imaging on 112 children (ages 4-18) with epilepsy syndrome determined by video-EEG telemetry. Eighty-seven had partial epilepsy and 25 had generalized epilepsy or indeterminate syndrome. Normative volumes were obtained from 44 child controls from the community. RESULTS: A significant reduction in cerebral (12.6%) and cerebellar (7.9%) volume was present in the epilepsy group compared with controls. Analysis of subgroups revealed that cerebral volume was significantly decreased in frontal lobe and nonlocalized partial epilepsies. The mean hippocampal ratio of 0.73 for mesial temporal lobe epilepsy was significantly less than for all other syndromes and controls. There was no difference in the rate of hippocampal volume reduction between syndromes. There was a significant correlation between IQ and cerebral and cerebellar volume, but not duration or age of onset of epilepsy. CONCLUSIONS: Cerebral and cerebellar volume reduction is common in intractable epilepsy syndromes of childhood. These cross-sectional data suggest that brain volume reduction is present at epilepsy onset and is not a result of intractable seizures. Hippocampal asymmetry is more sensitive than volume reduction as a marker for mesial temporal lobe epilepsy, but neither measure is specific.

Evaluation of SPECT in the assessment and treatment of intractable childhood epilepsy.

The authors retrospectively examined the role of SPECT in 65 children undergoing video-EEG telemetry. SPECT was concordant in most children whose lesions were already localized by MRI and epilepsy syndrome and provided localizing data in more than half not localized by these modalities. Ictal SPECT provided no additional prognostic benefit in patients undergoing epilepsy surgery (n = 23) who have a localized MRI lesion. In patients without lesions, however, ictal SPECT provides useful additional localization that may be used as a guide to intracranial implantation.

Validation of a new quality of life measure for children with epilepsy.

PURPOSE: There is no adequate measure of health-related quality of life (HRQOL) specifically for children with epilepsy. The aim of this study was to develop an epilepsy-specific HRQOL questionnaire for children, covering five domains: physical function, emotional well-being, cognitive function, social function, and behavior. Second, we aimed to demonstrate the instrument's reliability and validity, and its sensitivity to differences in epilepsy severity. METHODS: The subjects were guardians of children with refractory epilepsy, whose syndrome had been defined by using video-EEG monitoring. Each family completed the developed epilepsy-specific HRQOL scale for children and two standard, generic measures of HRQOL. RESULTS: The results indicated that each of the scales of the questionnaire had good internal consistency reliability. Furthermore, each scale correlated more highly with theoretically similar scales on established, generic health measures than with theoretically dissimilar scales (construct validity). The sensitivity of the questionnaire to differences in epilepsy severity also was demonstrated. As seizure severity increased, HRQOL subscale scores decreased, independent of age, gender, age of seizure onset, and IQ. Further, there was a negative relation between the number of antiepileptic medications taken and measures of memory and language performance, which was independent of age, gender, age of seizure onset, IQ, and seizure severity. CONCLUSIONS: This study demonstrated that the developed HRQOL instrument is a reliable and valid measure and is sensitive to differences in epilepsy. These results indicate that this new instrument may be a viable medical or surgical outcome measure for children with epilepsy.

Paroxysmal non-epileptic events in children: a retrospective study over a period of 10 years.

OBJECTIVE: To determine the frequency, nature and clinical characteristics of paroxysmal non-epileptic events in children diagnosed by video electroencephalogram (EEG) monitoring at a tertiary referral centre. METHODOLOGY: A retrospective study of children with paroxysmal non-epileptic events, aged 2 weeks to 17 years inclusive was undertaken. The study group consisted of children who had video EEG monitoring during a 10-year period (1988-99). Telemetry files, medical charts, events recorded on video and record sheets were reviewed. RESULTS: A total of 666 children were analysed, 269 had epileptic events recorded, 285 had non-epileptic events and 112 had no events recorded. In children with non-epileptic events, 43% were developmentally delayed, 25% had an abnormal neurological examination and 40% had epilepsy. In the study sample an epileptiform interictal EEG was common (24%). The major subgroups of non-epileptic events were: staring (34%), sleep phenomena - benign sleep myoclonus (15%), arousals (13%), motor tics (11%) and shuddering (7%). Developmental delay (57%) was common in children who presented with staring spells. A diagnosis of a specific non-epileptic event was reached in 96% of cases. CONCLUSION: Paroxysmal non-epileptic events can cause diagnostic confusion, particularly in children with developmental delay, epilepsy or an epileptiform EEG. Accurate diagnosis can be reached in the majority of cases using video EEG monitoring.

ILAE-defined epilepsy syndromes in children: correlation with quantitative MRI.

PURPOSE: The role of quantitative magnetic resonance imaging (MRI) in evaluation of childhood epilepsy remains poorly defined, with minimal published data. Previous work from our center questioned the specificity of hippocampal asymmetry (HA) in an outpatient group whose epilepsy was defined by using clinical and interictal data only. By using childhood volunteer controls and defining epilepsy syndromes using video-EEG monitoring, we readdressed the utility of HA in differentiating mesial temporal lobe epilepsy (MTLE) from other partial and generalized epileptic syndromes in children. METHODS: Seventy children were enrolled; entry criteria were age younger than 18 years with predominant seizure type recorded on video-EEG telemetry with volumetric MRI in all cases. Thirty healthy child volunteers had volumetric MRI. Epilepsy syndrome classification was according to ILAE. RESULTS: Control data revealed symmetric hippocampi, mean smaller/larger ratio of 0.96 (0.95-0.97, 95% CI) with no gender or right/left predominance. Overall 23% of patients had significant HA. Mean hippocampal ratio for MTLE was 0.78 (95% CI, 0.70-0.86), significantly lower than controls and from all other epilepsy syndromes. HA was highly specific (85%) to the syndrome of MTLE. Other potential epileptogenic lesions were found in 27 (39%) patients, lowest yield in frontal and mesial temporal syndromes. Dual pathology was present in 10% of patients. There was no significant association between HA and risk factors. CONCLUSIONS: In this study, we found that HA in children with a well-defined epilepsy syndrome is highly sensitive and specific for MTLE. Whether this will correlate with surgical outcome, as in adults, is the subject of ongoing study.

Outcome of neonates with electrographically identified seizures, or at risk of seizures.

A prospective study was conducted to investigate survival at 1 month and survival and developmental outcome at 1 year in a cohort of 53 neonates either suspected of or at risk of having seizures. For all patients, presence of seizures, diagnoses, and structural abnormalities were identified. If seizures were present, seizure variables were quantified. Correlations between neonatal parameters and subsequent outcome were investigated. Forty-three patients survived the first month of life. Background EEG was the only significant predictor of survival at 1 month. Three patients died after 1 month, and 2 of the three had extremely depressed interictal EEGs. Development outcome at 1 year was determined for all available surviving patients. Abnormal findings from brain imaging studies and number of independent electrographic seizure foci were correlated with some aspects of outcome at 1 year. No other correlations were identified between neonatal parameters and outcome.

The effects of morphine and midazolam on EEGs in neonates.

We investigated the effect of morphine, midazolam and their active metabolites on background electroencephalogram (EEG) in 6 neonates undergoing extracorporeal membrane oxygenation (ECMO) by conducting simultaneous EEGs and serum drug levels. Despite serum levels that were sufficient to produce adequate sedation, no patients had burstsuppressed or flat EEG backgrounds. We did, however, note that scalp oedema caused by prolonged immobility led to artefactual attenuation of EEG background. We conclude that an EEG prior to sedation will provide important baseline information that allows subsequent comparison and an awareness that scalp oedema after prolonged sedation and immobility will reduce misinterpretation of artefactual EEG attenuation.

Quantitative MRI in outpatient childhood epilepsy.

PURPOSE: In adult studies, MRI volumetrics is a proven technique in presurgical assessment of epilepsy. Hippocampal volume loss is maximal in the syndrome of mesial temporal lobe epilepsy. We aimed (a) to validate this methodology in a pediatric outpatient epilepsy population (b) to determine the relationship of hippocampal asymmetry (HA) to epileptic syndromes and risk factors. METHODS: Two neurologists classified the epileptic syndrome in 79 pediatric outpatients, according to the International Classification of Epilepsies and Epileptic Syndromes (ILAE). Hippocampal volumetrics were performed in all patients. HA was defined according to adult control values. RESULTS: Inter-rater variability on measurement of HA was very small (Correlation of test retest of 0.97 on 17 children <3 years old). The rate of HA was 44/79 (57%). In 21 patients, (27%) potentially epileptogenic lesions (other than HA) were identified (cerebral dysgenesis n = 11). HA was present in 9/15 (60%) of temporal lobe epilepsy and in 15/28 (54%) extratemporal onset epilepsy and 5/11 (46%) of generalized symptomatic epilepsy. Analysis confined to <13 years also showed HA was not specific for epileptic syndrome. There was no significant association of febrile convulsions (13%) with HA or temporal lobe epilepsy. CONCLUSIONS: There is a high incidence of HA in childhood epilepsy. HA was not confined to clinically defined temporal lobe epilepsy. The poor correlation of epileptic syndrome to quantitative MRI findings may be due to the inadequacies of epilepsy classification in the younger child, with the clinical semiology providing misleading localizing information. Normative childhood data for hippocampal volumes and symmetry is needed.

Spatial and temporal characteristics of neonatal seizures.

Thirty-two neonates (26 term and 6 premature) having seizures were prospectively recruited and studied. Using prolonged video/EEG monitoring, we quantified seizure variables (electrographic and clinical seizure durations, interictal periods and electrographic seizure spread) for all 1,420 seizures recorded. The effects of time and antiepileptic drug (AED) therapy were analyzed statistically. Seizures were generally frequent, with limited electrographic spread. However, some neonates had consistently longer interictal periods and 13% had mean interictal periods > 60 min. Seizure variables were relatively stable over time, but they changed with AED therapy. There was a trend to decreased seizure duration, increased length of interictal periods, and decreased electrographic spread. Furthermore, there was evidence of reduced clinical features after sequential AED infusions. Seizures ceased during the monitoring period in 22 neonates. Eighty-five percent of all seizures had no clinical manifestations. Among neonates with clear clinical correlates, clinical observations underestimated electrographic seizures in individual neonates by a mean of 54% (range 0-95%). Seizures generally had limited electrographic spread. Use of only four recording electrodes, characteristic of some portable EEG systems, underestimated seizures in 19 neonates, and missed all seizures in 2.

Clinical features of neonatal seizures.

OBJECTIVE: Identification of seizures in neonates is difficult. This study analyses the clinical features of seizures in a cohort of neonates. METHODOLOGY: The clinical events of 41 neonates referred for investigation of suspected seizures were studied with prolonged video/electroencephalographic (EEG) telemetry. RESULTS: Sixteen neonates had no seizures recorded; 25 had confirmed seizures, 13 with clinical correlates. Each neonate with electroclinical seizures had paroxysms of abnormal movements in stereotyped patterns. These patterns were consistently found to have electrical correlates. Focal clonic movements were seen most frequently. Multiple clinical features characterized the seizure repertoire in six neonates. In five neonates the clinical features became less evident during monitoring and these seizures were difficult to recognize. This change was associated with anticonvulsant administration in three cases. CONCLUSIONS: Electroclinical seizures are characterized by abnormal paroxysmal stereotyped behaviour, often with multiple clinical features. Recommendations for the management of abnormal neonatal events are proposed.

Non-ketotic hyperglycinaemia presenting as pachygyria.

A 2-day-old infant with lethargy and hypoventilation had pachygyria and agenesis of the corpus callosum on CT scan. Increased concentrations of glycine in plasma and CSF, together with an increased CSF/plasma ratio, confirmed a clinical diagnosis of non-ketotic hyperglycinaemia. This is the first report of pachygyria in this disorder, although agenesis of the corpus callosum is well recognized, and non-specific gyral malformations have been described previously. The specific diagnosis of an inborn error of metabolism in infants with structural brain malformations is of critical importance for accurate genetic counseling.

Non-accidental head injury in children.

AIMS: To analyse the clinical features, social circumstances, investigations and outcome of 49 children with significant non-accidental head injury admitted to The Prince of Wales Children's Hospital between 1979 and 1993. CLINICAL FEATURES: Age ranged from one month to eight years, with 30 children less than one year old. There were 28 boys and 21 girls. Thirty-three were in the care of a parent. Eleven of these were known to the Department of Community Services and 22 were from families with stressed socioeconomic circumstances characterised by deprivation. In 44 cases the history was incompatible with the clinical findings. On admission, 21 had marked depression of awareness, with a Glasgow Coma Scale score (GCS) of 9 or less. Eleven of this group were fitting. Seizures were present in a further 13 children who were semi-purposeful (GCS > 9). Twenty-eight had retinal haemorrhages and 35 had soft tissue scalp contusions, 23 in association with skull fracture. Twenty-six had associated injuries. Seven children died. Of the 42 survivors at the time of discharge, 19 had severe motor disability associated with other deficits. Twenty-four were returned to the care of their families. CONCLUSIONS: Retinal haemorrhage and unconsciousness on admission (GCS < or = 9) were positively associated with a poor outcome (P < 0.001 and 0.002, respectively). Cerebral oedema found on computerised tomography was positively associated with severe motor disability on discharge (P < 0.001). Lowest socioeconomic circumstances appeared to be a risk factor for occurrence of injury: 22 of 49 children came from circumstances of deprivation.