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.

Volumetric analysis of a specific language region - the planum temporale.

Planum temporale volumes were determined for 42 control children (ages 4.2-15.7 years) using magnetic resonance imaging. The mean left planum temporale volume was 2729 mm3 (SD = 567) and the mean right planum temporale volume was 2758 mm3 (SD = 546). No significant hemispheric asymmetry was demonstrated. Analysis of co-variance (ANCOVA) showed that the absolute and proportional planum temporale volumes were not significantly associated with age or gender. We also demonstrated a reproducible method for planum temporale volume measurement by acquiring images in the coronal plane and then visualising the sagittal plane to improve accuracy for the posterior border.

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.

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.

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.

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.

The effect of bicarbonate-free artificial cerebrospinal fluid on spontaneous oscillations of the membrane potential in inferior olivary neurons of the rat.

The membrane potential of mature inferior olivary (IO) neurons oscillates spontaneously at frequencies up to about 10 Hz. This behavior has been attributed to the complement of membrane conductances in these cells and electronic coupling of the neurons via dendro-dendritic gap junctions. In this study intracellular recordings of transmembrane potentials were made in 52 neurons in brainstem slices from rats aged 8-23 days postnatal. During the recordings in 31 neurons the extracellular solution was exchanged from a bicarbonate- to a tris-buffered solution with constant pH. In all cells the spontaneous oscillations of the membrane potential ceased within a few minutes and in 14 of these cells the oscillations resumed with re-exposure to bicarbonate-buffered solution. The spontaneous oscillations in another 6 neurons also ceased when they were exposed to bicarbonate-buffered solution containing 10 mmol NH4Cl. These experimental manipulations produce a rise in intracellular pH despite constant extracellular pH. The low- and high-threshold potentials associated with voltage-sensitive calcium conductances in these neurons and the large hyperpolarization that follows these potentials were unaffected by substitution of the extracellular solution. However, the anomalous rectification of the membrane potential in these neurons (which could be abolished by exposure of the neurons to 2 mM CsCl) was significantly increased by 12.6% in the tris-buffered solution. The data are consistent with the hypothesis that the continuity of oscillations of the membrane potential in IO neurons depends on the transfer of current between the dendro-dendritic junctions and the soma of each neuron. This transfer is reduced when rectifying K+ conductances in the neurons are increased and the ensemble properties of the group of neurons, and the membrane potential oscillations, are lost.

IgG monoclonal paraproteinaemia and peripheral neuropathy.

Five patients with peripheral neuropathy and benign IgG monoclonal paraproteinemia are reported, all of whom had a sensorimotor neuropathy with a remitting and relapsing course. The serum paraprotein level did not correlate with the patient's clinical status. Electrophsyiological studies showed marked slowing of conduction velocity and conduction block in four of the patients and mild slowing in the other. Sural nerve biopsies demonstrated a demyelinating neuropathy with inflammatory cell infiltrates in each of the five patients. Three of the patients had evidence of myelin/Schwann cell reactivity on immunofluorescence studies and in all nerves dense expression of major histocompatability complex class I and II molecules was evident within the endoneurium, on invading mononuclear cells, endothelial cells and Schwann cells. All the patients responded to treatment, plasmapheresis being particularly effective. Four patients have achieved prolonged remissions after all treatment had ceased. These five cases of peripheral neuropathy and IgG paraproteinaemia were identical in their clinical, electrophysiological and pathological features to patients with chronic inflammatory demyelinating polyneuropathy.

Development and properties of spontaneous oscillations of the membrane potential in inferior olivary neurons in the rat.

Previous experiments have shown that the conductances that are thought to underlie the spontaneous oscillations of the membrane potential in inferior olivary (IO) neurons of the mature rat are present at 2 days postnatal (PN). In this study intracellular recordings of transmembrane potentials were made in 209 IO neurons in brainstem slices from rats aged 4-25 days PN. Membrane potential oscillations were not found before 9 days PN but were observed in 41% of neurons examined at 10-15 days PN and in 95% of neurons after 16 days PN. These oscillations exhibited a wide range of frequencies (0.5-9.5 Hz) and amplitudes (2-23 mV). The waveforms of the oscillations in different neurons varied from having 2-3 non-harmonic frequencies of unequal amplitude to being almost sinusoidal. There was a positive relationship between the age of the animal and the frequency (P less than 0.0001) and amplitude (P less than 0.002) of the oscillations. The timecourse of development of the membrane potential oscillations is consistent with ultrastructural data which indicate that neuro-neuronal gap junctions in the rat IO nucleus mature between 10 and 15 days PN. Exposure of the neurons to pharmacological agents that induce oscillations in adult IO neurons failed to induce oscillations in neurons less than 9 days PN. Our findings support the hypothesis that oscillations of the membrane potential in IO neurons depend not only on specific membrane conductances but also on electrotonic coupling between the neurons.

Variability of repeated nerve conduction studies.

We have determined the variability of repeated measurements of sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) amplitude and motor and sensory conduction velocity (MCV and SCV) and examined the extent to which limb temperature is responsible for the variability. We made 10 serial measurements of SNAP, CMAP, MCV and SCV in each of 3 nerves in a single normal subject. The coefficients of variation for MCV and SCV ranged from 2.0% to 6.7% and the proportion of the variance due to temperature was 0.3-56%. The coefficients of variation were much greater for serial measurements of compound action potential amplitude. We used the standard deviations for serial measurements in each nerve to calculate the number of subjects required to detect a difference of 1/msec between the means of two sets of measurements with a power of 90%.

Anosmia after doxycycline use.

We report the case of a man who developed anosmia while taking doxycycline tablets for a skin disorder. Two other cases of parosmia occurring in association with doxycycline have been reported to the Adverse Drug Reactions Advisory Committee of the Commonwealth Department of Community Services and Health since 1972. Disturbances of taste but not olfaction have been reported with tetracycline use in the past.