Lesional Focal Epilepsy Research Articles

Outcomes of resective surgery in children and adolescents with focal lesional epilepsy: The experience of a tertiary epilepsy center.

This study aimed to investigate the efficacy of resective surgery in children with focal lesional epilepsy by evaluating the predictive value of pre- and postsurgical factors in terms of seizure freedom. This study included 61 children aged between 2 and 18years who were admitted to the pediatric video-EEG unit for presurgical workup. Each patient was evaluated with a detailed history, video-EEG, neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. All the possible factors including history, etiology, presurgical evaluation, surgical procedures, and postsurgical results were analyzed for their predictive value for postoperative seizure freedom. Of the 61 patients, 75% were diagnosed as having temporal lobe epilepsy (TLE), and 25% were diagnosed with extra-TLE. Two years after the surgery, 78.6% were seizure-free, of which 89% had TLE, and 50% had extra-TLE (p<0.05). Patients were more likely to have a favorable outcome for seizure freedom if they had rare seizure frequency, focal EEG findings, and focal seizures; had a temporal epileptogenic zone; or had TLE and hippocampal sclerosis. On the other hand, patients were more likely to have unfavorable results for seizure freedom if they had younger age of seizure onset, frequent seizures before the surgery, a frontal or multilobar epileptogenic zone, secondarily generalized seizures, extra-TLE with frontal lobe surgery, or focal cortical dysplasia. Resective surgery is one of the most effective treatment methods in children with intractable epilepsy. A history of young age of seizure onset, frequent seizures before surgery, secondarily generalized seizures, a multilobar epileptogenic zone, frontal lobe surgery, and focal cortical dysplasia (FCD) are the most important predictive factors indicating that a patient would continue having seizures after surgery. On the other hand, focal seizure semiologies, temporal lobe localization, and hippocampal sclerosis indicate that a patient would have better results in terms of seizure freedom.

Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy.

The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy. The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants. The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills. Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology.

Transition in lesional focal epilepsy, and following epilepsy surgery.

Children with intractable epilepsy benefit from early surgical treatment when possible to reduce long-term morbidity. Issues for transition are variable according to type and timing of surgery, and the outcome. When surgery is successful, cognitive and behavioral improvements may not be apparent for several years. The value of continuing antiepileptic drug (AED) treatment after successful surgery remains unclear, and the adjustment to a life without seizures may be challenging.

Focal cortical dysplasia and epilepsy surgery.

Focal cortical dysplasia (FCD) is the most commonly encountered developmental malformation that causes refractory epilepsy. With advances in neuroimaging techniques, in particular MRI, recent studies have revealed a higher prevalence of FCD than previously estimated and have improved the preoperative identification and classification of these abnormalities. However, MRI frequently does not show any abnormalities in patients with pathologically proven FCD. In this situation, functional neuroimaing such as FDG-PET and ictal SPECT can be helpful. FCD is thought to be intrinsically epileptogenic, because the dysplastic tissues contain aberrant neural networks that are highly susceptible to abnormal excitation. The response to the medical treatment of epilepsy has been documented as consistently poor. Therefore, surgical resection has been an important alternative treatment for patients with intractable epilepsy related to FCD. Incomplete resection of FCD has been consistently known to be a poor prognostic factor. However, the complete removal of FCD is often difficult because the demarcation of the lesion is frequently poor, and dysplastic tissues tend to be more extensive than is apparent on MRI. Evidence indicates that even patients with MRI abnormalities who have resective epilepsy surgery for FCD have worse surgical outcomes than those of patients who have surgery for other focal lesional epilepsy syndromes. Careful planning of evelauation using intracranial electrodes is necessary for successful epilepsy surgery.

Widespread EEG Changes Precede Focal Seizures

The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal), and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline). Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma) and high-frequency bands (ripples and fast ripples). At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development), but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures.

To speak, or not to speak? The feasibility of imaging overt speech in children with epilepsy

We systematically compared fMRI results for covert (silent) and overt (spoken) versions of a language task in a representative sample of children with lesional focal epilepsy being considered for neurosurgical treatment (N=38, aged 6-17 years). The overt task was advantageous for presurgical fMRI assessments of language; it produced higher quality scans, was more sensitive for identifying activation in core language regions on an individual basis, and provided an online measure of performance crucial for improving the yield of presurgical fMRI.

Sleep-Wake Patterns of Seizures in Children With Lesional Epilepsy

This study examined diurnal patterns of seizures and their occurrence during wakefulness and sleep in children with lesional focal epilepsy. We reviewed 332 consecutive children with lesional focal epilepsy and video-electroencephalogram monitoring during a 3-year period. Data were analyzed in relationship to clock time, wakefulness/sleep, and seizure localization. The distribution of lesions in 66 children (259 seizures) included mesial temporal, 29%; neocortical temporal, 18%; frontal, 29%; parietal, 13.5%; and occipital, 12%. Seizures in patients with frontal lesions occurred mostly during sleep (72%). Seizures in mesial temporal (64%), neocortical temporal (71%), and occipital (66%) lesional epilepsy occurred mostly during wakefulness. Temporal lobe seizures occurred more frequently during wakefulness (66%), compared with extratemporal seizures (32%) (odds ratio, 2.67; 95% confidence interval, 1.61-4.42). Temporal lobe seizures peaked between 9:00 am and noon and 3:00-6:00 pm, whereas extratemporal seizures peaked between 6:00-9:00 am. Sleep, not clock time, provides a more robust stimulus for seizure onset, especially for frontal lobe seizures. Temporal lobe seizures are more frequent during wakefulness than are extratemporal seizures. Circadian patterns of seizures may provide additional diagnostic and treatment options, such as differential medication dosing and sleep-schedule adjustments.

Epilepsy Surgery Outcome in Coexisting Symptomatic Refractory Focal Epilepsy and Benign Focal Epilepsy of Childhood

Epilepsy surgery may successfully treat refractory symptomatic focal epilepsy in patients with coexisting benign focal epileptiform discharges. Reported here is the outcome after resective epilepsy surgery in three children with pharmacoresistant lesional focal epilepsy in whom seizures of benign focal epilepsy of childhood had been recorded. Two patients had left temporal epilepsy due to a malformation of cortical development; one of these had dual pathology, with additional ipsilateral hippocampal sclerosis. One child had catastrophic left hemispheric epilepsy due to left hemimegalencephaly. Frequent, habitual seizures of symptomatic epilepsy resolved after surgery (follow-up duration, 32-55 months); however, rare benign focal seizures of childhood have continued. These cases demonstrate that lesional pharmacoresistant focal epilepsy can be successfully treated with resective epilepsy surgery even when coexisting with benign focal epilepsy of childhood. During postoperative follow-up, careful documentation of breakthrough seizures due to benign focal epilepsy of childhood is important, so that these patients are not labeled as surgical failures.

INFLUENCE OF MOTOR FUNCTIONAL MAGNETIC RESONANCE IMAGING ON THE SURGICAL MANAGEMENT OF CHILDREN AND ADOLESCENTS WITH SYMPTOMATIC FOCAL EPILEPSY

To determine the clinical value of motor functional magnetic resonance imaging (fMRI) in the presurgical evaluation of a large group of children and adolescents with epilepsy caused by lesions close to the central sulcus. Forty-three patients (19 males; mean age, 13 years) with lesional focal epilepsy underwent motor fMRI as part of a multidisciplinary standardized presurgical evaluation between 2000 and 2006. fMRI data were analyzed using statistical parametric mapping (SPM2) and screened for the presence of movement-related artifacts. The ways in which the results of motor fMRI influenced the decision-making process were reviewed. The success rate of motor fMRI was 93% and data were of high quality in 67.5% of the patients. Together with other clinical considerations, motor fMRI results contributed to the surgical management of 32 patients (74%). They helped 1) to determine the type of surgery in 23 patients (72%; 12 cases with and 11 cases without invasive functional mapping), 2) to indicate a reduced benefit-risk ratio with the consequence that surgery was not further considered in 5 patients (16%), and 3) to indicate that surgery was not an appropriate option because of the high risk of motor function deficit in 4 patients (12%). Motor fMRI can be performed with a high degree of success and good data quality in this population of patients. It has an important additive role in the discussion of the feasibility of resective surgery contributing to the decision-making process for children with epilepsy caused by brain lesions close to the central sulcus.

Tiagabine-induced generalised non convulsive status epilepticus in patients with lesional focal epilepsy

To report 3 cases with focal lesional epilepsy that had non-convulsive status epilepticus (NCSE) induced by treatment with tiagabine (TGB) and review the previously published cases. Drugs that enhance GABAnergic transmission are recognised to promote absence seizures in patients with generalised epilepsy syndromes and may on occasions even induce NCSE. However, that TGB can also induce NCSE in focal lesional epilepsy is not widely recognised in clinical practice. The clinical history, EEG and MRI findings were reviewed in 3 patients with lesional focal epilepsy who presented to our epilepsy programs over a 12 month period with TGB-induced NCSE. All previously reported cases in the English medical literature were reviewed. The three patients had longstanding complex partial and secondarily generalised seizures refractory to multiple different anti-epileptic drugs. In two cases, MRI demonstrated a focal malformation of cortical development in the left parieto-occipital region and in the third left mesial temporal sclerosis. Following commencement of TGB in one patient and dose escalation in two, prolonged episodes of confusion and poor responsiveness were noted. Prolonged EEG monitoring demonstrated continuous high amplitude, generalised, 2-4 Hz delta activity with intermingled spikes during the episodes of unresponsiveness, consistent with NCSE. The clinical and EEG activity normalised following the administration of IV clonazepam followed by dose reduction or withdrawal of the TGB. Eleven previously reported cases of patients with partial epilepsy and a focal underlying lesion on MRI were identified, all of whom had similar features to that seen in our cases. These cases illustrate that TGB may induce generalised NCSE in patients with focal lesional epilepsy, in addition to those with generalised syndromes. We hypothesise that patients may have developed an acquired alteration in the sensitivity of their thalamocortical circuitry that renders them more sensitive to the effects of drugs that enhance GABAnergic activity.

Discriminatory Effect of Cyclic Alternating Pattern in Focal Lesional and Benign Rolandic Interictal Spikes During Sleep

Twenty epileptic patients (10 male and 10 female) were polygraphically recorded during nocturnal sleep. Ten subjects, with a wide age range, were affected by focal lesional epilepsy, and 10 were children affected by benign epilepsy with rolandic spikes (BERS). In five cases a bihemispheric expression of the focal lesional bursts emerged occasionally during the night recordings. The behavior of interictal electroencephalographic (EEG) paroxysms were analyzed with respect to the two arousal states of non-rapid-eye-movement (REM) sleep: (a) the cyclic alternating pattern (CAP), expressed by biphasic EEG periodic activities and related to long-lasting fluctuations between greater (phase A) and lesser (phase B) arousal levels; and (b) the non-CAP (NCAP), manifested by EEG stationarities that reflect a sustained relative stability of arousal. The CAP/NCAP modality affected the spiking activity and distribution of the focal lesional EEG paroxysms, which appeared enhanced during CAP and which were mostly collected in phase A. The even more powerful influence of CAP and especially phase A on the secondary bisynchronous bursts suggests a crucial integration among thalamocortical circuits, arousal modulation, and epileptic generalization mechanisms. Conversely, in the BERS recordings no significant differences emerged throughout CAP and NCAP. The intense activity of the rolandic foci induced by sleep as such could be explained on the basis of the greater dependence of these functional cortical EEG abnormalities on the degree of synchronization during sleep.