Frontal lobe dysfunction in children with temporal lobe epilepsy

There is evidence that adults with temporal lobe epilepsy present executive impairments. However, there is limited information in children, especially when using a comprehensive neuropsychologic battery. We aimed to: 1) investigate the presence and severity of executive dysfunctions in children with temporal lobe epilepsy, and 2) determine the implications of clinical variables (including etiology) in the occurrence and severity of executive dysfunction, using eight paradigms. Thirty-one children with temporal lobe epilepsy were evaluated and compared with 21 age-matched controls. Patients with temporal lobe epilepsy had significantly worse performance than controls. Intragroup analysis indicated that patients with symptomatic epilepsy were more impaired than those with cryptogenic epilepsy. In the former group, patients with mesial lesions performed worse than those with lateral lesions. Regarding the severity of executive dysfunction, 83.87% manifested severe to moderate executive impairment. Early age of onset, longer duration of epilepsy, and use of polytherapy were correlated with worse executive dysfunction. These findings indicated the presence of frontal lobe dysfunction in children with temporal lobe epilepsy, with worse performance in those with mesial temporal lobe epilepsy, early onset, longer duration of disease, and use of polytherapy. Our study corroborates the hypothesis that temporal lobe epileptogenic activity affects the extratemporal regions that mediate attentional and executive functions.     

Frontal and temporal volumes in Childhood Absence Epilepsy

Purpose:   This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age- and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables.
Methods:   Twenty-six children with CAE, aged 7.5–11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child.
Results:   The CAE group had significantly smaller gray matter volumes of the left orbital frontal gyrus as well as both left and right temporal lobes compared to the age- and gender-matched children without epilepsy. In the CAE group these volumes were related to age, gender, ethnicity, and pregnancy complications but not to seizure, IQ, and psychopathology variables. In the group of children without epilepsy, however, the volumes were related to IQ.
Conclusion:   These findings suggest that CAE impacts brain development in regions implicated in behavior, cognition, and language. In addition to supporting the cortical focus theory of CAE, these findings also imply that CAE is not a benign disorder.     

Frontal lobe function in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further.     

Language and brain volumes in children with epilepsy

In this study the relationship between language skill and frontotemporal volumes was compared in 69 medically treated subjects with epilepsy and 34 healthy children, aged 6.1–16.6 years. Also, whether patients with linguistic deficits had abnormal volumes and atypical associations between volumes and language skills in these brain regions was determined. The children underwent language testing and MRI scans at 1.5 T. Brain tissue was segmented and frontotemporal volumes were computed. Higher mean language scores were significantly associated with larger inferior frontal gyrus, temporal lobe, and posterior superior temporal gyrus gray matter volumes in the epilepsy group and in the children with epilepsy with average language scores. Increased total brain and dorsolateral prefrontal gray and white matter volumes, however, were associated with higher language scores in the healthy controls. Within the epilepsy group, linguistic deficits were related to smaller anterior superior temporal gyrus gray matter volumes and there was a negative association between language scores and dorsolateral prefrontal gray matter volumes. These findings demonstrate abnormal development of language-related brain regions, and imply differential reorganization of brain regions subserving language in children with epilepsy with normal linguistic skills and in those with impaired language.     

Intellectual functioning in children with epilepsy: Frontal lobe epilepsy,childhood absence epilepsy and benign epilepsy with centro-temporal spikes

PurposeThe purpose of our study is to describe intellectual functioning in three common childhood epilepsy syndromes – frontal lobe epilepsy (FLE), childhood absence epilepsy (CAE) and benign epilepsy with centro-temporal spikes (BECTS). And also to determine the influence of epilepsy related variables, type of epilepsy, age at epilepsy onset, duration and frequency of epilepsy, and treatment on the scores.MethodsIntellectual functioning was examined in a group of 90 children with epilepsy (30 FLE, 30 CAE, 30 BECTS), aged 6–15 years, and compared with a control group (30). All subjects obtained a Full Scale IQ ≥ 70 and they were receiving no more than two antiepileptic medications. Participants completed the Wechsler Intelligence Scale for Children – Third Edition. The impact of epilepsy related variables (type of epilepsy, age at epilepsy onset, duration of epilepsy, seizure frequency and anti-epileptic drugs) on intellectual functioning was examined.ResultsChildren with FLE scored significantly worse than controls on WISC-III Verbal IQ, Full Scale IQ and Processing Speed Index. There was a trend for children with FLE to have lower intelligence scores than CAE and BECTS groups. Linear regression analysis showed no effect for age at onset, frequency of seizures and treatment. Type of epilepsy and duration of epilepsy were the best indicators of intellectual functioning.ConclusionIt is crucial that children with FLE and those with a longer active duration of epilepsy are closely monitored to allow the early identification and evaluation of cognitive problems, in order to establish adequate and timely school intervention plans.     

Abnormal behavior in children with temporal lobe epilepsy and ganglioglioma

Temporal lobe epilepsy in childhood is characterized by great clinical, electroencephalographic, and etiological diversity. The prognosis after temporal lobe epilepsy surgery in childhood is usually good, with most patients achieving complete seizure control. However, in some children behavior deteriorates postoperatively. We report two girls (2 and 6 years of age) with refractory seizures due to temporal lobe ganglioglioma. They exhibited aggression and hyperactivity since the beginning of their epilepsy. In both patients, behavioral disturbances worsened postoperatively, despite complete seizure control. Patients and parents should be advised about possible behavioral disturbances after epilepsy surgery, especially in the presence of a temporal lobe developmental tumor, even when seizure control is achieved postoperatively.     

Superior temporal gyrus volumes in maltreated children and adolescents with PTSD.

BACKGROUND: The structure and function of the superior temporal gyrus (STG), a structure involved in receptive and nonverbal auditory and language processing, is understudied in posttraumatic stress disorder (PTSD). Event-related potential abnormalities were previously reported in PTSD, implicating the existence of dysfunction in the primary auditory cortex and adjacent anterior auditory cortex of the STG in adult PTSD. METHODS: Anatomic magnetic resonance imaging (MRI) volumetric analysis of the superior temporal gyrus were performed in 43 maltreated children and adolescents with PTSD and 61 nonmaltreated healthy control subjects. RESULTS: Unadjusted STG gray matter volumes were larger in maltreated subjects with PTSD than in control subjects, whereas STG white matter volumes were smaller in maltreated subjects with PTSD than in control subjects. After adjusting for differences in cerebral volume, right, left, and total superior temporal gyrus volumes were relatively larger in PTSD subjects compared with control subjects. After covarying for differences in cerebral gray matter volumes, regression analysis showed that PTSD subjects had significantly greater STG gray matter volumes in most, and in particularly right-sided STG measurements. Furthermore, findings of significant side-by-diagnosis interactions for STG and STG gray but not white matter STG volumes suggest that there is a more pronounced right > left asymmetry in total and posterior STG volumes but a loss of the left > right asymmetry seen in total, anterior, and posterior STG gray matter volumes in PTSD subjects compared with control subjects. CONCLUSIONS: These STG findings may suggest developmental alterations in maltreatment-related pediatric PTSD.     

Comparison of temporal lobectomies of children and adults with intractable temporal lobe epilepsy

Introduction

The aim of the study was to assess the difference in clinical characteristics and postsurgical outcomes between children and adults who have undergone temporal lobectomy (TL).

Materials and methods

We retrospectively reviewed the medical records of 52 patients who had undergone TL between 2006 and 2008. Nineteen patients were classified as children (≤18 years old), and 33 patients were classified as adults (>18 years old) according to the age when TL had been performed.

Results

Twelve of 19 (63.2%) children and 24 of 33 (72.7%) adults became seizure free. Rapid secondary generalization such as generalized tonic or tonic–clonic seizures showed a tendency to be more prominent in children (four of 19, 21.1%) than in adults (three of 33, 9.1%). Patients in childhood had significantly more multifocal discharges on interictal electroencephalography (EEG) (42.1%) compared to adults (15.2%, p?=?0.014). The mean extent of surgical excision was 5.0 cm in children and 4.1 cm in adults (p?=?0.001). The incidence of hippocampal sclerosis, the most common pathologic finding in the two groups, was 57.9% (11 of 19) in children and 78.8% (26 of 33) in adults. Malformations of cortical development were significantly more frequent in children (nine of 19, 47.4%) than in adults (seven of 33, 21.2%). Dual pathology was found in 31.6% of children and in 12.1% of adults. The intelligence quotient and memory quotient values in children with temporal lobe resection remained nearly steady during follow-up period without significant decline.

Conclusion

Patients undergoing TL during childhood compared to during adulthood had distinctively different interictal EEG, resectional extents, and pathologic findings.     

Executive functions in children with frontal and temporal lobe epilepsy.

Even though frontal lobe epilepsy (FLE) is a relatively common seizure type, no formal psychometric studies of children with FLE have been reported. We compared 12 children with FLE and 15 children with temporal lobe epilepsy (TLE) on neuropsychological tests of attention, memory, executive functioning, and adaptive functioning. The results of these tests indicated that the children with FLE had deficits in planning and executive functions, whereas their verbal and nonverbal memory was intact. The opposite pattern was observed in children with TLE. Measures of executive functioning and impulse control were the best predictors of adaptive functioning. The findings suggest that children with FLE have a pattern of cognitive deficits that differs markedly from the pattern seen in children with TLE. Children with FLE have prominent deficits in executive functioning that appear to be related to poor behavioral adaptation.     

Psychopathology in children with epilepsy before and after temporal lobe resection

The aim of this study was to establish the rate and spectrum of psychiatric disorder among children before and after temporal lobe surgery for epilepsy. Data were examined for associations between psychopathology and seizure outcome following surgery, or association between psychopathology and other variables, such as laterality of lesion, sex, cognitive level, and underlying pathology. Participants were 60 children (35 males, 25 females) who had focal seizures of temporal lobe origin and who had undergone temporal lobe resection between 1992 and 1998; mean age at time of operation 10 y 7 mo, (SD 4 y 11 mo) range 7 mo to 17 y 11 mo. Mean length of follow-up was 5.1 years (SD 2.3, range 2 to 10 y). Twenty-eight (47%) children had undergone right temporal lobectomy. Diagnosis of a psychiatric disorder was present in 50/60 (83%) children at some point, with high rates of psychiatric comorbidity. Common childhood psychiatric disorders of attention-deficit-hyperactivity disorder, oppositional defiant disorder/conduct disorder, and emotional disorders were present in about 25% of children. Disorders rarely seen in the general child population were over-represented: disruptive behaviour disorder--not otherwise specified (30/60 [50%]), and pervasive developmental disorder (autistic spectrum disorder; 23/60 [38%]). there was no significant relationship between pathology, sex, seizure frequency, or postoperative seizure outcome and psychiatric disorder, other than for pervasive developmental disorder. The same proportion of children had psychiatric diagnoses pre- and postoperatively (43/60 [72%] and 41/57 [72%] respectively). Although mental health problems are common in children undergoing temporal lobe resection, there are few predictors of psychiatric outcome following epilepsy surgery. Parents require counselling on these issues in the preoperative work-up.     

Hippocampal and thalamic diffusion abnormalities in children with temporal lobe epilepsy

PURPOSE: Previous studies using diffusion MRI in patients with temporal lobe epilepsy have shown abnormal water diffusion in the hippocampus. Because thalamus and lentiform nuclei are considered important for the regulation of cortical excitability and seizure propagation, we analyzed diffusion tensor imaging (DTI) abnormalities in these subcortical structures and in hippocampus of children with partial epilepsy with and without secondary generalization. METHODS: Fourteen children with partial epilepsy involving the temporal lobe underwent MRI including a DTI sequence. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained in the hippocampus, thalamus, and lentiform nucleus, and compared with DTI data of 14 control children with no epilepsy, as well as glucose positron emission tomography (PET) findings. RESULTS: Decreased FA (p < 0.001) and increased ADC (p = 0.003) values were found in the hippocampi ipsilateral to the seizure focus. Significant FA decreases (p = 0.002) also were seen in the contralateral hippocampi, despite unilateral seizure onset and excellent surgical outcome in patients who underwent surgery. ADC values showed a trend for increase in the thalami ipsilateral to the epileptic focus in the seven children with secondarily generalized seizures (p = 0.09). No group differences of ADC or FA were found in the lentiform nuclei. The DTI variables did not correlate with regional glucose metabolism in any of the structures analyzed. CONCLUSIONS: Increased ADC values in hippocampus can assist in lateralizing the seizure focus, but decreased FA in the contralateral hippocampus suggests that it too may be dysfunctional despite unilateral seizure onset. Less-robust thalamic abnormalities of water diffusion in patients with secondarily generalized seizures suggest secondary involvement of the thalamus, perhaps due to recruitment of this structure into the epileptic network; however, this must be confirmed in a larger population. DTI appears to be a sensitive method for detection abnormalities in children with partial epilepsy, even in structures without apparent changes on conventional MRI.     

Neuronal dysfunction in children with newly diagnosed temporal lobe epilepsy

We sought to determine whether neuronal dysfunction throughout the temporal lobes of children with temporal lobe epilepsy (TLE) is already as severe at the time of diagnosis as it is in patients with long-standing intractable TLE (INT-TLE). Proton magnetic resonance spectroscopic imaging was used to measure N-acetylaspartate/creatine (NAA/Cr) ratios in the temporal lobes of five consecutive children with newly diagnosed TLE (ND-TLE), five with INT-TLE, and 30 normal control subjects. The median age of those with ND-TLE and those with INT-TLE did not significantly differ (P = 0.92). All five patients with ND-TLE had bilateral reductions in the NAA/Cr ratio. Two of the five patients with INT-TLE had bilateral reductions in the NAA/Cr ratio; three had unilateral reductions in the NAA/Cr ratio. In the three patients with lesions the NAA/Cr ratio decrease extended outside these lesions. No significant differences were detected in any temporal lobe region between the ND-TLE and INT-TLE groups. The severity of the neuronal dysfunction in the children with ND-TLE was at least as severe as in those with INT-TLE and was not restricted to one temporal lobe, implying that the neuronal abnormalities observed in patients with TLE occur before the clinical manifestations.     

Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy

We performed proton magnetic resonance spectroscopy of the mesial temporal regions in 20 children with intractable temporal lobe epilepsy and compared results with those from 13 normal subjects. Abnormalities of the ratio of N-acetylaspartate to choline plus creatine (NAAI[Cho+Cr]) were seen in 15 patients (75%). The ratio NAA/(Cho+Cr) was correctly lateralizing in 55% and incorrectly lateralizing in none. Bilateral abnormalities were seen in 45%. Overall there was a unilateral decrease in N-acetylaspartate on the side ipsilateral to the seizure focus (mean 19% decrease vs normals, with 5% decrease on the contralateral side), suggesting neuronal loss or dysfunction. There was also a bilateral increase in creatine and choline (mean l8%), consistent with reactive astrocytosis. We conclude that proton magnetic resonance spectroscopy can contribute to lateralization of the seizure focus, and by detection of bilateral abnormalities, can contribute to the understanding of the underlying pathophysiology in temporal lobe epilepsy.     

Elevated serum Bcl-2 in children with temporal lobe epilepsy

Intractable temporal lobe epilepsy (TLE) is associated with alterations in expression of apoptosis-associated signaling molecules in the temporal lobe. Bcl-2 is an anti-apoptotic molecule which has previously been reported to be raised in patient's brain and serum. In the present study we examined serum Bcl-2 protein levels as a surrogate marker of apoptosis-associated signaling in children with non lesional TLE. Serum Bcl-2 levels were found to be higher in patients with TLE than controls. The serum level correlated to seizure variables including, duration of disease, frequency of seizures, and disease severity. The impact of epilepsy on cognition was assessed using total score intelligence quotient (IQ). IQ was found to be lower than controls and negatively correlated to serum Bcl-2. These findings support serum Bcl-2 levels as a marker of seizure burden and cognition in children with epilepsy.     

Atypical language representation in children with intractable temporal lobe epilepsy

This study evaluated language organization in children with intractable epilepsy caused by temporal lobe focal cortical dysplasia (FCD) alone or dual pathology (temporal lobe FCD and hippocampal sclerosis, HS). We analyzed clinical, neurological, fMRI, neuropsychological, and histopathologic data in 46 pediatric patients with temporal lobe lesions who underwent excisional epilepsy surgery. The frequency of atypical language representation was similar in both groups, but children with dual pathology were more likely to be left-handed. Atypical receptive language cortex correlated with lower intellectual capacity, verbal abstract conceptualization, receptive language abilities, verbal working memory, and a history of status epilepticus but did not correlate with higher seizure frequency or early seizure onset. Histopathologic substrate had only a minor influence on neuropsychological status. Greater verbal comprehension deficits were noted in children with atypical receptive language representation, a risk factor for cognitive morbidity.     

Wisconsin card sorting test in children with temporal lobe epilepsy

To search for the origin of frontal lobe dysfunction identified by the Wisconsin card sorting test (WCST) in temporal lobe epilepsy (TLE) patients, we investigated the WCST performance among 19 children with TLE (with hippocampal atrophy (HA group N=12), without structural lesions (NSL group N=7)), 15 patients with frontal lobe epilepsy (FLE group), and age-matched normal controls (N group). The paired verbal association learning test (PVALT) and Benton visual retention test (BVRT) were also performed. HA group and FLE groups achieved significantly fewer categories and demonstrated more perseverative errors on the WCST than NSL and N groups. In addition, category achievement in WCST showed significant inverse correlation to age at the initial status convulsivus in the HA group (P<0.05). The achievement on PVALT and BVRT did not show any significant differences between HA and FLE groups (P>0.05). Thus, the frontal lobe dysfunction in the HA group is found to exist as early as 7 years old, when they seem to have only a short seizure history or to receive a little electrical interference from the temporal lobe focus to the frontal region. These facts would underscore the importance of prefrontal dysfunction persisting from the early insults and only becoming apparent after maturation of the prefrontal region in patients with mesial TLE.     

Frontal lobe epilepsy

About one-quarter of patients with refractory focal epilepsies have frontal lobe epilepsy (FLE). The typical seizure semiology for FLE includes unilateral clonic, tonic asymmetric or hypermotor seizures. Interictal electroencephalograms (EEG) usually reveal interictal epileptiform discharges and rhythmical midline theta, which has localizing value. The usefulness of ictal EEG recordings is limited by frequent muscle artifacts in motor seizures and because a large portion of the frontal lobe cortex is “hidden” to scalp electrodes. Ictal single photon emission CT and positron emission tomography are able to localize FLE in about one-third of patients only. A pre-surgical evaluation should include, whenever possible, a subclassification of FLE as dorsolateral frontal, mesial frontal or basal frontal lobe epilepsy to allow a minimal cortical resection. A review of the typical findings of seizure semiology, interictal and ictal EEG regarding the different FLE subtypes is given. Etiology, medical treatment and surgery are also discussed.