Early Age Of Seizure Onset Research Articles

MRI analysis in temporal lobe epilepsy: Cortical thinning and white matter disruptions are related to side of seizure onset

Past studies reported more widespread structural brain abnormalities in patients with left compared to right temporal lobe epilepsy (TLE), but the profile of these differences remains unknown. This study investigated the relationship between cortical thinning, white matter compromise, epilepsy variables, and the side of seizure onset, in patients with TLE. We performed diffusion tensor imaging tractography and cortical thickness analyses of 18 patients with left TLE (LTLE), 18 patients with right TLE (RTLE), and 36 controls. We investigated the relationship among brain structural abnormalities, side of seizure onset, age of seizure onset, and disease duration. Patients with TLE displayed cortical thinning and white matter compromise, predominately on the side ipsilateral to the seizure onset. Relative to RTLE, patients with LTLE showed more widespread abnormalities, particularly in white matter fiber tracts. Greater compromise in white matter integrity was associated with earlier age of seizure onset, whereas cortical thinning was marginally associated with disease duration. These data support previous findings of LTLE showing greater structural compromise than RTLE, and suggest that mechanisms may not be uniform for gray and white matter compromise in patients with LTLE and RTLE. These results may indicate that LTLE is different from RTLE, possibly due to greater vulnerability of the left hemisphere to early injury and the progressive effects of seizures.

Theory of mind in frontal and temporal lobe epilepsy: Cognitive and neural aspects

Theory of mind (ToM) is an important prerequisite to social behavior. This study evaluated ToM in patients with temporal (TLE) or frontal lobe epilepsy (FLE) aiming to determine the cognitive aspects, severity, and pathophysiologic mechanisms of ToM impairment in focal epilepsy. One hundred thirty-eight patients with TLE (n = 109) or FLE (n = 29) and 69 healthy subjects underwent the Faux Pas task (FPT), which evaluates the recognition and comprehension of others' mental states, and neuropsychological tests for other cognitive functions. Factor analysis of all test scores yielded two ToM factors (Recognizing faux pas, FP; Excluding nonexistent FP) distinct from the Control, Language, Matching, and Praxis factors. With respect to healthy subjects, both TLE and FLE patients showed correct exclusion of nonexistent FPs but significantly lower recognition and comprehension of real FPs. FLE patients were also impaired with respect to TLE patients. In the whole patient group, schooling and group membership predicted ToM impairment. In FLE patients, the comprehension of mental states was predicted by disease duration, whereas TLE patients' comprehension of affects and intentions was associated with early age of seizure onset and medial temporal lobe sclerosis (MTLS). Focal epilepsy impairs advanced ToM abilities. FLE may affect online performances owing to long-lasting dysfunctions of the prefrontal areas. MTLS may provoke selective ToM deficits due to medial temporal damage, prefrontal dysfunctions, or early interference with cognitive development. Future studies are needed to determine the implications of ToM impairment on behavior and quality of life.

Medically refractory epilepsy in autism

Epilepsy and electroencephalographic abnormalities are frequent in idiopathic autism, but there is little information regarding treatment-resistant epilepsy (TRE) in this group. We sought to define the clinical and electrophysiologic characteristics and treatment outcomes in these patients. We retrospectively reviewed clinical and laboratory data of patients with idiopathic autism evaluated at NYU Epilepsy Center during a 20-year period. One hundred twenty-seven patients had idiopathic autism and at least one epileptic seizure; 33.9% had TRE and 27.5% were seizure free. The remaining 38.6% of patients had infrequent seizures or insufficient data to categorize. Patients with TRE had a significantly earlier onset of seizures than seizure-free patients, and a trend for more developmental regression and motor and language delays. Three patients had surgical resection (two had limited improvement and one had no improvement) and one had an anterior callosotomy (no improvement). Vagus nerve stimulator (VNS) implantation provided limited improvement (2 patients) and no improvement (7). This study found that TRE is common in idiopathic autism and more common with early age of seizure onset. Relatively few patients underwent surgical resection due to multifocal partial epilepsy, comorbid generalized epilepsy, or limited impact of ongoing partial seizures given other problems related to autism. Our small sample suggests that surgical and VNS outcomes in this group are less favorable than in other TRE populations.

Epilepsy with occipital features in children: Factors predicting seizure outcome and neuroimaging abnormalities

Purpose The objective of this retrospective study was to identify clinical and EEG features in children with occipital epilepsy that predict MR imaging abnormalities and seizure outcome. Methods Patients with clinical and/or EEG features indicating occipital lobe involvement were identified from the epilepsy database at a tertiary children’s hospital. The clinical and EEG features were analyzed to identify the most important predictors of abnormal MR imaging and seizure outcome. Results Sixty-six patients were identified: 21 had symptomatic epilepsy with abnormal MR imaging; 12 patients had probable symptomatic epilepsy based on an abnormal neurological exam; 33 patients had normal neurological development, normal neurological examination and normal neuroimaging. Twenty-two of these 33 patients satisfied criteria for idiopathic occipital syndromes: Panayiotopoulos syndrome (9 patients), Gastaut type idiopathic childhood occipital epilepsy (12 patients) and idiopathic photosensitive occipital epilepsy (1 patient). Eleven patients could not be classified. Early age of seizure onset and an abnormal neurological examination were significant predictors of abnormal MR imaging. None of the variables examined were strong predictors of seizure outcome. Conclusion Early age of seizure onset and an abnormal neurological examination are the best predictors of abnormal MR imaging in children with epilepsy with occipital features.

Altered white matter integrity in temporal lobe epilepsy: association with cognitive and clinical profiles.

Diffusion tensor imaging (DTI) studies have reported substantial white matter abnormalities in patients with temporal lobe epilepsy (TLE). However, limited data exist regarding the extent of white matter tract abnormalities, cognitive effects of these abnormalities, and relationship to clinical factors. The current study examined these issues in subjects with chronic TLE. DTI data were obtained in 12 TLE subjects and 10 age-matched healthy controls. Voxel-wise statistical analysis of fractional anisotropy (FA) was carried out using tract-based spatial statistics (TBSS). White matter integrity was correlated with cognitive performance and epilepsy-related clinical parameters. Subjects with TLE, as compared to healthy controls, demonstrated four clusters of reduced FA, in anterior temporal lobe, mesial temporal lobe, and cerebellum ipsilateral, as well as frontoparietal lobe contralateral to the side of seizure onset. Mean FA was positively correlated with delayed memory, in anterior temporal lobe; and immediate memory, in mesial temporal lobe. Lower FA values in the posterior region of corpus callosum were related to earlier age of seizure onset. TLE is associated with widespread disturbances in white matter tracts and these changes have important cognitive and clinical consequences.

Prognosis of patients with mesial temporal lobe epilepsy due to hippocampal sclerosis

Hippocampal sclerosis (HS) is the most common pathology in mesial temporal lobe epilepsy (MTLE). There are a few reports concerning prognosis in patients with MTLE-HS treated medically. The study was carried out to determine the clinical risk factors affecting prognosis. We enrolled 287 patients with MTLE-HS treated medically. Gender, age at onset of epilepsy, history of trauma, infection, febrile convulsion, status epilepticus, mental retardation, handedness, consanguinity, side of hippocampal sclerosis, additional extrahippocampal temporal lesion, aura, seizures types, antiepileptic drugs, psychiatric disturbances and seizure frequency were noted. All patients were divided into three groups. Group I: patients seizure-free during follow up, Group II: patients with improved seizure control whose seizure frequency had decreased >50% after the treatment, and Group III: patients with poor seizure control whose seizure frequency had no change or increased. Each clinical feature was also compared among three subgroups statistically. Early age of seizure onset [Group II-III (p=0.000) and Group I-III (p=0.0004)], age of head trauma [Group II-III (p=0.04)], the presence of mental retardation (p=0.04) and female sex (p=0.03) were risk factors for poor prognosis. However, the other parameters did not affect prognosis. Recognizing bad prognostic features such as the presence of mental retardation, early age of seizure onset, age of head trauma and female gender may help physicians to identify risk groups with MTLE-HS and drug resistance seizures for epilepsy surgery.

Preserved Proper Naming Following Left Anterior Temporal Lobectomy Is Associated with Early Age of Seizure Onset

Anterior temporal lobectomy (ATL) is an effective surgical option for managing pharmacoresistant temporal lobe epilepsy. Many patients with left ATL develop postsurgical difficulties with proper name retrieval, although curiously, some patients have entirely intact proper naming following left ATL. Here, we tested the hypothesis that early age of seizure onset would be a reliable factor "protecting" patients from developing proper naming defects following left ATL. Proper naming of unique persons (Famous Faces Test, 155 items) and places (Landmark Test, 65 items) was measured in 23 patients who had undergone left ATL for pharmacoresistant epilepsy. Data were collected for a number of variables, including age of seizure onset, age at surgery, handedness, IQ, and seizure outcome. The patients were sorted into two groups based on proper naming performance: (1) Unimpaired: 7 patients performed normally on both the Faces and Landmark tests; (2) Impaired: 16 patients performed abnormally on one or both of the tests. In support of our hypothesis, the Unimpaired group had a significantly earlier age of seizure onset (M = 2.1 years) than the Impaired group (M = 15.1 years). Moreover, a correlation analysis indicated a strong association between age of seizure onset and naming outcome (R =-0.569). The groups were comparable (and statistically indistinguishable) on nearly all other variables. These findings document the importance of age of seizure onset in predicting proper naming outcome following left ATL (with earlier being better), and extend understanding of brain reorganization and plasticity.

Age of seizure onset, functional reorganization, and neuropsychological outcome in temporal lobectomy

Patients with early onset seizure disorder tend to have less cognitive decline following surgical resection than patients with late onset seizure disorder. Differential opportunity for presurgical cerebral functional reorganization has been proposed to account for this “age of onset” effect. However, the relationships between age of seizure onset, functional organization, and neuropsychological outcome remain incompletely understood. To shed additional light on these issues, we investigated 66 patients with anterior temporal lobectomies (37 left; 29 right), all of whom completed comprehensive neuropsychological assessment prior to and following surgical resection. The sample was divided into two groups: 34 patients with early onset (EO) epilepsy and 32 patients with late onset (LO) epilepsy. We found the typical age of onset effect: post-surgically, EO patients demonstrated relatively better outcome in multiple neuropsychological domains, especially verbal memory, compared to LO patients. Based on presurgical Wada testing, 23 patients were classified as having traditional cerebral functional organization (TFO) and 35 were classified as having nontraditional cerebral functional organization (NTFO). The NTFO group had an earlier age of seizure onset than the TFO group, and NTFO was more frequent in EO patients (70%) than LO patients (50%). NTFO patients demonstrated relatively better post-surgical outcome in several neuropsychological domains, compared to TFO patients. Our findings are consistent with the notion that functional reorganization may be an explanatory factor for the better neuropsychological outcome of EO epilepsy patients following anterior temporal lobectomy.

Mental retardation and relation to seizure and tuber burden in tuberous sclerosis complex

In patients with tuberous sclerosis complex (TSC), the high rates of mental retardation are associated with cortical tubers, seizure activity, and genetic factors. The goal of the study was to investigate the relationship between bilateral cortical tubers and seizure variables and mental retardation in individuals with TSC. The records of 27 patients with TSC (age 6 months to 33 years) undergoing neuropsychological assessment and the following clinical variables were examined: bilateral versus non-bilateral cortical tubers, the age of seizure onset, and presence of infantile spasms. Results were statistically analyzed. Bilateral cortical tubers (p=0.02) and early age of seizure onset (p=0.04) were significantly related to impaired cognitive functioning. Only one of the seven patients with normal cognitive functioning had bilateral tubers, whereas 13/21 patients with intellectual impairment had bilateral tubers. Patients with normal cognitive functioning experienced a mean age of seizure onset after 6 years. A trend was observed between infantile spasms and cognitive functioning (p=0.06); the lack of statistical significance likely reflects the small sample size. Neither age nor gender was related to cognitive status. Further investigation incorporating additional neuroimaging factors, antiepileptic treatment effects, and genetic variables, is needed.

The pathological basis of temporal lobe epilepsy in childhood.

To characterize the pathologic findings of temporal lobe epilepsy (TLE) in children undergoing temporal lobectomy for refractory seizures and to correlate these findings with clinical presentation. The authors reviewed the charts of all children who underwent anterior temporal lobectomy for refractory TLE from 1979 through 1999. A new neuropathologic analysis was performed blinded to clinical features and outcome. Twenty-two children met inclusion criteria. Mean age at onset of epilepsy was 3 years, 7 months (range 1 month to 10 years). Mean age at surgery was 10 years, 11 months (range 1 to 18 years). All patients had complex partial seizures, 48% with secondary generalization. Most had daily seizures. Auras were reported in 45% of patients. Post-resection follow-up averaged 5 years, 2 months (range 2 to 19 years). Seizure-free status was achieved in 41% of patients, and 14% had residual auras only. The most frequent neuropathologic abnormalities were cortical dysplasia (CD) of the temporal neocortex (14 of 22) and mesial temporal sclerosis (MTS) (12 of the 15 children with available hippocampal tissue). These two findings coexisted in seven children. MTS was associated with extra-hippocampal pathology in 8 of 12 (67%) of the cases. MTS occurs frequently in association with CD in this population of children. The high incidence of dual pathology could explain the early age of seizure onset and high seizure frequency rate observed. TLE in childhood may constitute a different entity than in adults, from both the clinical and neuropathologic perspectives.

Treatment outcome in patients with mesial temporal sclerosis

The long-term prognosis of pharmacological therapy in patients with mesial temporal sclerosis (MTS) is generally considered poor. On the contrary, successful surgical therapy is frequently reported. We performed a retrospective case record survey of patients with MTS in a comprehensive epilepsy center between 1993 and 1999 in order to develop treatment strategies. The time period allowed access to high-resolution qualitative magnetic resonance imaging (MRI) and a minimum of 1-year outcome assessment. Eighty-three patients with intractable partial epilepsy with MRI and electroencephalograph (EEG) abnormalities and seizure semiology consistent with temporal lobe epilepsy were identified. Thirty-six patients were treated pharmacologically and surgically and 47 patients received only pharmacotherapy. The number of patients who became seizure free was in total 37 (45%); in the surgical group 26 and in the non-surgical group 11. The proportions of seizure-free patients in each group were 72% (surgical) and 23% (non-surgical). Clinical factors such as age, gender, lesion side, previous medical history, duration of illness, seizure frequency and IQ did not correlate to prognosis. A good seizure outcome was associated with early age of seizure onset, low number of previously used antiepileptic drugs (AEDs) and surgical treatment. There is a better long-term outcome in patients with MTS receiving surgical therapy in comparison with medical therapy.

Wisconsin Card Sorting performance in patients with temporal lobe epilepsy: clinical and neuroanatomical correlates.

A sizable proportion of patients with temporal lobe epilepsy (TLE) display impairments on tests of executive function. Previous studies have suggested several factors that may explain such performance, including the presence of hippocampal sclerosis, electrophysiological disruption to extratemporal regions, and early age of seizure onset. However, no clear determinants have been found that consistently explain such executive dysfunction. The present study investigated the contribution of several clinical variables and temporal lobe neuroanatomic features to performance on the Wisconsin Card Sorting Test (WCST) in a series of patients with TLE. Eighty-nine patients with lateralized TLE (47 left, 42 right) were examined. Seventy-two patients from this series underwent anterior temporal lobectomy (ATL). Regression analysis was used to examine the effects of age, education, age at seizure onset, seizure duration, seizure laterality, history of secondary generalized seizures, and MRI-based volumes of the right and left hippocampi on preoperative WCST performance (number of categories completed, perseverative errors). Further univariate analyses examined whether the presence of bilateral hippocampal sclerosis, mesial temporal lobe abnormalities beyond the hippocampus, or temporal neocortical abnormalities affected preoperative WCST performance. In addition, we examined whether becoming seizure free after ATL affected change in WCST performance. Overall regression analysis was not significant. However, an examination of individual partial correlations revealed that patients with a history of secondary generalized seizures performed more poorly on the preoperative WCST than did patients without such history. In addition, patients who were seizure free after ATL did not exhibit better WCST outcome than patients who did not become seizure free. The presence of bilateral hippocampal sclerosis, extrahippocampal mesial temporal atrophy, or temporal neocortical lesions did not affect WCST performance. These results indicate that the presence of temporal lobe structural abnormalities do not significantly affect executive function as measured by the WCST. The present study does suggests that the critical determinants of WCST performance in patients with TLE lie outside the temporal lobe and likely relate to metabolic disruption to frontostriatal neural network systems.

Intracarotid Amobarbital Procedure and Prediction of Postoperative Memory in Patients with Left Temporal Lobe Epilepsy and Hippocampal Sclerosis

Although temporal lobe epilepsy (TLE) patients with dominant hemisphere hippocampal sclerosis generally have good cognitive outcome after anterior temporal lobectomy (ATL), a minority of patients experience at least mild post-ATL decline on one or more standardized measures of episodic and semantic memory. The goal of this investigation was to determine whether memory outcome in this group could be predicted from preoperative intracarotid amobarbital procedure (IAP) recognition memory scores. Data from 22 left TLE patients were studied retrospectively. All were left hemisphere language dominant and had IAP scores for each hemisphere, a significant degree of pathology-confirmed left hippocampal sclerosis (HS+), and no positive MRI findings other than atrophy. Cognitive outcome status was represented by the number of pre- to post-ATL declines across three tests, as defined by 90th percentile Reliable Change Index (RCI) criteria. Only 14% of the sample exhibited decline on more than one memory test. Low right IAP (left hemisphere injection) scores and relatively high preoperative cognitive ability and age at surgery predicted a greater risk of post-ATL memory decline. A minority of left TLE HS+ patients experience at least a mild degree of RCI-defined decline in episodic or semantic memory after ATL. The right hemisphere IAP memory score, which reflects the functional reserve of the contralateral hemisphere, can help predict the risk of postoperative memory decline for TLE patients in whom HS+ is likely based on the presence of hippocampal atrophy on MRI or early age of seizure onset.

The prognosis for control of seizures with medications in patients with MRI evidence for mesial temporal sclerosis.

Mesial temporal sclerosis (MTS) is the most common and important pathology in temporal lobe epilepsy (TLE), and its presence in magnetic resonance imaging (MRI) scans is strongly correlated with a successful surgical outcome. Despite the general assumption that patients with MTS respond poorly to medication, the long-term prognosis for such patients has not yet been investigated. We studied the overall clinical prognosis of patients with MTS and analyzed the factors related to the degree of medical responsiveness. Case patients were actively followed up at the Yonsei Epilepsy Clinic in Seoul, Korea, for >2 years. A structured interview and a thorough clinical evaluation were conducted. MRI scans, at the field strength of 1.0 or 1.5 Tesla, were performed with T1- and T2-weighted coronal and axial spin-echo images. All coronal slices were < or = 5-mm thick with no gap. Two neurologists and one radiologist determined the presence of MTS in MRIs by visual analysis. The MTS group consisted of 104 patients. Of these, 26 (25%) were completely controlled with adequate therapy, and 40 (38%) were intractable, despite aggressive anticonvulsant polytherapy. The remaining 37% had their seizure frequencies reduced by > or = 50%, but were not seizure free. The age of seizure onset was significantly younger in the intractable group than in the well-controlled group. Patients with a history of febrile convulsions or with epileptiform discharges in their electroencephalogram (EEG) had poorer seizure control (p < 0.05) than those who did not. Among the 16 patients who had no previous treatment, five (31%) became seizure free, and two were intractable. Not all patients with MTS are medically intractable; 25% of the patients in our study achieved complete control while receiving medication. Poor seizure control was related to an early age of seizure onset, a history of febrile convulsions, and epileptiform discharges on the EEG.

Neuroimaging of children with partial seizures

The predictive value of abnormal neurological findings on neuroimaging (NI) of children with partial seizures (PS) was studied. The sample comprised 143 children and adolescents with PS from 1979 to 1996. Fifty patients had the following abnormal NI findings: diffuse atrophy and porencephalic cyst (5.6% each), hemiatrophy, tumors, neurocutaneous syndrome brain lesions, and dysgenesis (4.2% each), and arachnoid cyst and hydrocephalus (2.1% each). There were significantly more NI abnormalities among those with simple PS than among the other groups of complex PS or PS with secondary generalization. All cases of porencephalic cyst (n = 8), and hemiatrophy (n = 6) were in the hemiparetic group, all cases of tumor (n = 6) were in the normal group, while most cases of diffuse atrophy were in the mentally retarded group. Patients with abnormal NIs had a significantly earlier age of seizure onset than the others. The chance of finding a treatable abnormality in neuroimaging was 5% for tumors and 2% for arachnoid cysts in the group of patients with PS and normal neurological findings. Neither an abnormality detected in a neurological examination nor the type of seizure are predictive parameters for suggesting the presence of a resectable brain tumor. All patients with newly diagnosed PS should undergo an MRI.

Reorganization of Verbal Memory Function in Early Onset Left Temporal Lobe Epilepsy

The purpose of this investigation was to examine the issue of reorganization of verbal memory function following early insult to the left mesial temporal region. It was hypothesized that reorganization of memory function was most likely to occur in those patients with an early age of seizure onset who have a more limited degree of extra-hippocampal neuropathology. Fifty-four patients with epilepsy of unequivocal left temporal lobe origin were classified into four groups on the basis of the presence/absence of hippocampal sclerosis and degree of postoperative seizure relief. Measures of verbal learning and memory as well as nonmemory measures were administered both before and 6 to 8 months after anterior temporal lobectomy. Findings were consistent with the reorganization proposal. The clinical and theoretical significance of the findings are discussed.