Intracranially recorded interictal spikes: Relation to seizure onset area and effect of medication and time of day

Objective

The relationship between seizures and interictal spikes remains undetermined. We analyzed intracranial EEG (icEEG) recordings to examine the relationship between the seizure onset area and interictal spikes.

Methods

80 unselected patients were placed into 5 temporal, 4 extratemporal, and one unlocalized groups based on the location of the seizure onset area. We studied 4-h icEEG epochs, removed from seizures, from day-time and night-time during both on- and off-medication periods. Spikes were detected automatically from electrode contacts sampling the hemisphere ipsilateral to the seizure onset area.

Results

There was a widespread occurrence of spikes over the hemisphere ipsilateral to the seizure onset area. The spatial distributions of spike rates for the different patient groups were different (p < 0.0001, chi-square test). The area with the highest spike rate coincided with the seizure onset area only in half of the patients.

Conclusion

The spatial distribution of spike rates is strongly associated with the location of the seizure onset area, suggesting the presence of a distributed spike generation network, which is related to the seizure onset area.

Significance

The spatial distribution of spike rates, but not the area with the highest spike rate, may hold value for the localization of the seizure onset area.     

Reduced percentage of neurocysticercosis cases among patients with late-onset epilepsy in the new millennium

Objective

To determine if the number of neurocysticercosis cases among patients with late-onset epilepsy has decreased over the past two decades.

Design

Retrospective cohort study of 431 consecutive patients with recurrent seizures starting after the age of 20 years evaluated at our Institution from 1990 to 2009.

Methods

Patients were classified according to the year in which they were first seen. Group I included 129 patients evaluated between 1990 and 1994, Group II included 108 patients evaluated between 1995 and 1999, Group III included 106 patients evaluated between 2000 and 2004, and Group IV included 88 patients evaluated between 2005 and 2009. We correlated the percentage of persons with cryptogenic and symptomatic epilepsy between the groups to determine if there was any change in the causes of late-onset epilepsy.

Results

One hundred seventy-one patients had cryptogenic and 260 had symptomatic epilepsy. Common causes of symptomatic epilepsy were neurocysticercosis in 120 cases, cerebrovascular disease in 68, and brain tumors in 40. We found a reduction in the number of patients with symptomatic epilepsy (p = 0.0007) as well as a reduction in the number of neurocysticercosis cases (p = 0.0004) over the study years. There was a reduction in the weight of neurocysticercosis as an etiological factor for symptomatic late-onset epilepsy related to a drop in the number of patients with this condition evaluated between 2005 and 2009 (p = 0.0045).

Conclusion

The number of neurocysticercosis cases among patients with late-onset epilepsy has changed over the years. This parasitic disease is no longer the most common cause of symptomatic late-onset epilepsy in our population.     

Does photoparoxysmal response in children represent provoked seizure? Evidence from simultaneous motor task during EEG

Objectives

Acute cognitive changes during epileptiform discharges have been studied using computer assisted cognitive tasks. We aimed to demonstrate acute behavioral change (using a simple motor response task MRT) during photoparoxysmal response (PPR) in children below 18 years.

Methods

Children performed a simple repetitive motor task during intermittent photic stimulation (IPS). All episodes of PPR not associated with obvious clinical change (as observed by the technologist or reported by the patient) were analyzed for this study. The average time interval between two successive motor responses across a PPR (test time) was compared to the average time interval between two successive motor responses during IPS not associated with PPR (control time) using Wilcoxon signed ranks test.

Results

21 children who had PPR successfully completed the MRT. The difference between the mean durations was 0.894 s (p = 0.002). More than 50% increase compared to the control time was considered a delay in MRT during PPR. 10 children showed slowing of MRT during PPR.

Conclusion

By definition, acute behavioral change during generalized epileptiform discharges represent provoked seizures. Detecting subclinical seizures can have important safety implications in children (skiing, skating and driving) with PPR on EEG, but no clinical seizures. We recommend MRT during IPS.     

Seizure outcomes of lesionectomy in pediatric lesional epilepsy with brain tumor – Single institute experience

Purpose

To determine the clinical characteristics, surgical strategy, and outcome in pediatric lesional epilepsy patients younger than 5 years of age undergoing surgery in a single institute.

Method

Retrospective data were collected and analyzed on patients younger than 5 years of age who underwent lesionectomy for lesional epilepsy at single institute from January 2001 to August 2010. Fourteen pediatric lesional epilepsy patients were enrolled in this study. Engel classification was used to classify seizure outcome.

Results

Median preoperative seizure period was 1 month (range, 1–21). Median post-operative follow up period was 35 months (range 13–84). Ten patients who underwent gross total resection of tumor showed Engel class Ia seizure outcome without any antiepileptic drug (AED). Subtotal resection was performed in four patients to avoid eloquent area injury. Two of these four patients with subtotal removal became seizure-free (Engel class Ia) without AED, while two were in Engel class Ib with AED medication. There was no significant surgical morbidity or mortality.

Conclusion

Lesionectomy in children younger than 5 years of age is relatively safe and effective in controlling seizures. Short preoperative seizure periods and total removal of tumor might be associated with good outcome. Therefore, early and complete lesionectomy alone may help allow for seizure freedom and optimal brain development in pediatric patients.     

Changing ictal-onset EEG patterns in children with cortical dysplasia

Purpose

Cortical dysplasia (CD) is intrinsically epileptogenic. We hypothesize that CDs clinically emerging in the early developing brain tend to extend into multifocal or larger epileptic networks to pronounce intractability in contrast to CDs which clinically emerge at a later age.

Methods

We evaluated the spatial and temporal profiles of ictal-onset EEG patterns in children with histopathologically confirmed CD. We designated Group A as children with changing ictal-onset EEG patterns over time, and Group B without change. We compared seizure profiles, consecutive scalp video-EEGs (VEEGs), MRI, MEG, and surgical outcomes.

Results

We found 14 children consisting of 10 Group A patients (7 girls) and 4 Group B patients (all boys). Eight (80%) Group A patients had their seizure onset < 5 years while all Group B patients had seizure onset ? 5 years (p < .05). Changes of ictal onset EEG pattern in Group A consisted of bilateral (4 patients), extending (2); extending and bilateral (2); and generalized (2). We saw MRI lesions (6) and single clustered MEG spike sources (MEGSSs) in (5). Six patients underwent surgery before 15 years of age, and 4 of them attained seizure freedom. All 4 Group B patients had MRI lesions and single clustered MEGSSs. Three patients underwent surgery after 15 years of age. All 4 patients attained seizure freedom.

Conclusion

Ictal-onset EEG patterns change over time in children with early seizure onset and intractable epilepsy caused by CD. Younger epileptic children with CD more frequently have multifocal epileptogenic foci or larger epileptogenic foci. Early resection of CD, guided by MRI, MEG, and intracranial video EEG, resulted in seizure freedom despite changes in ictal-onset EEG patterns.     

Network characteristics in benign epilepsy with centro-temporal spikes patients indicating defective connectivity during spindle sleep: A partial directed coherence study of EEG signals

Objective

To investigate the changes in EEG connectivity in children with the typical presentation of benign epilepsy with centro-temporal spikes (BECTS).

Pregabalin in patients with primary brain tumors and seizures: a preliminary observation

Objectives

Patients with brain tumors and seizures should be treated with non-enzyme-inducing antiepileptic drugs (AED). Some of the newer drugs seem particularly suited in these patients.

Methods

Here we describe our experience with pregabalin (PGB); its effectiveness was retrospectively studied in nine consecutive patients with primary brain tumors and seizures.

Results

Six subjects had secondarily generalized and three simple partial seizures. Patients mostly suffered from WHO grade IV gliomas. PGB replaced enzyme inducing, inefficacious or bad tolerated AED, as add-on or monotherapy. Median follow-up was 5 (2–19) months; three patients died of their tumor. Daily median dosage was 300 mg. All subjects experienced at least a 50% seizure reduction, six were seizure-free. Side effects were reported in four patients, leading to PGB discontinuation in two.

Conclusion

PGB appears to have a promising effectiveness in this setting, even as a monotherapy. Based on these results we embarked on a prospective controlled trial.     

Repeated seizures induce prefrontal growth disturbance in frontal lobe epilepsy

Background

The possible consequences of seizures in the immature brain have been the subject of much conjecture. We prospectively measured frontal and prefrontal lobe volumes using three-dimensional (3D) magnetic resonance imaging (MRI)-based volumetry in patients with frontal lobe epilepsy (FLE) presenting with the same seizure semiology. The pathogenesis of repeated seizure-induced brain damage is discussed herein.

Methods

Serial changes in regional cerebral volumes were measured in two patients with FLE presenting with intractable clinical courses and cognitive impairments/behavioral problems (FLE(+)) and four FLE patients without cognitive impairments/behavioral problems (FLE(−)). Eleven normal subjects (4–13 years old) served as controls. Volumes of the frontal and prefrontal lobes were determined using a workstation, and the prefrontal-to-frontal lobe volume ratio was calculated.

Results

Frontal and prefrontal lobe volumes revealed growth disturbance in FLE(+) compared with those of FLE(−) and control subjects. In addition, prefrontal-to-frontal lobe volume ratio increased serially in FLE(−) similarly to controls, but was stagnant or decreased in FLE(+). Prefrontal growth also revealed more rapid recovery in a FLE(+) patient with shorter active seizure period.

Conclusion

These findings suggest that repeated seizures may lead to prefrontal growth disturbance. The occurrence of frequent seizures in patients with FLE may be associated with prefrontal lobe growth retardation, which relates to neuropsychological problems and ultimate neuropsychological outcome.     

Rolandic epilepsy clinical variants and their influence on the prognosis

Introduction

Benign epilepsy with central-temporal spikes (BECTS) is the most common epileptic syndrome in childhood. It is an age-dependent, genetically determined and benign condition. The aim of this study is to describe the clinical course and prognosis in 60 patients with BECTS diagnosed in our hospital.

Patients and methods

We made a retrospective review of patients diagnosed with BECTS in a University Hospital (1995-2009). They were divided into 2 groups: 1) Patients who met all BECTS classical criteria. 2) Patients who met all the criteria but one (less than 4 years; diurnal seizures; atypical EEG abnormalities).

Results

A total of 60 patients, 34 males and 26 females were included, with 31 patients in group 1 and 29 in group 2. The mean age at onset in group 1: 7.45 years, group 2: 6.55 years. Medical treatment was indicated in 32.2% of patients in group 1 and 41.3% in group 2. The outcome was favourable in the majority: 58% in group 1 and 62.1% in group 2 were free of seizures after 1 year. Average age in which it disappeared: 8.54 years in group 1 and 7.84 years in group 2. There were no statistically significant differences in any of these parameters.

Conclusions

Unlike that published by some authors, we have not identified any poor outcome factors in patients with BECTS in this study, meaning that an accurate diagnosis correlates with a good prognosis and excellent neurological outcome.     

Childhood epilepsy: Management in resource-limited setting

Objective:

To optimize the use of phenobarbital and/or phenytoin as frontline drugs for treatment of childhood epilepsy.

Design:

Before-and -after study.

Setting:

Epilepsy clinic at paediatric OPD, Sassoon General Hospital, Pune.

Materials and Methods:

Epilepsy is a condition in which seizures are triggered recurrently from within the brain. For epidemiological classification purpose epilepsy is considered to be present when two or more unprovoked seizures occur at an interval greater than twenty four hours apart. Seizures were classified as generalized and partial seizures, with underlying etiology investigated with EEG, CT scan in majority of the patients. Follow - up rate, seizure - control and antiepileptic drugs used among 151 children enrolled as on 31 March 2005 were compared with 106 children with new onset epilepsy enrolled as on February 2006. Eight children with breakthrough convulsion after a seizure free period of five to eighteen months were followed up after injection vitamin D. Nineteen children with poor control of seizures receiving polytherapy with newer antiepileptic drugs were assessed with frontline antiepileptic medication of phenobarbital and/or phenytoin. Serum calcium, phosphorus, alkaline phosphatase were done in seventy two consecutive children with seizure disorder.

Results:

During post protocol period good seizure control was achieved in 84.8% as against 80.7% and use of phenobarbital and/or phenytoin increased to 65.11% from 22.87%. Of the 8 cases with breakthrough seizures seven remained seizure free after vitamin D administration and with no dose enhancement of AED medications of the nineteen. Children receiving polytherapy thirteen children could be successfully switched to phenobarbital and/or phenytoin. Forty four (61%) children had hypocalcemia (less than 9 mg%), fifty seven (79%) children had raised alkaline phosphatase levels (more than 270 IU).

Comments:

Phenobarbital and/or phenytoin have been found to be effective frontline AED. Periodic administration of vitamin D plays a supportive role.     

Temporal lobe gangliogliomas associated with chronic epilepsy: Long-term surgical outcomes

Objective

To review the clinical features and surgical outcome in patients with temporal lobe gangliogliomas associated with intractable chronic epilepsy.

Methods

The Rush University Surgical Epilepsy Database was queried to identify patients with chronic intractable epilepsy who underwent resection of temporal lobe gangliogliomas at Rush University Medical Center. Medical records were reviewed for age of seizure onset, delay to referral for surgery, seizure frequency and characteristics, pre-operative MRI results, extent of resection, pathological diagnosis, complications, length of follow-up, and seizure improvement.

Results

Fifteen patients were identified. Average duration between seizure onset and surgery was 14.3 years. Complex partial seizures were the most common presenting symptom. Detailed operative data was available for 11 patients – of these, 90.9% underwent complete resection of the amygdala and either partial or complete resection of the hippocampus, in addition to lesionectomy. Average follow-up was 10.4 years (range 1.6–27.5 years), with 14 patients improving to Engel's class I and one patient to Engel's class III. There were no recurrences, and permanent complications were noted in one patient.

Conclusions

Long-term follow-up of patients with temporal lobe gangliogliomas associated with chronic intractable epilepsy demonstrates excellent results in seizure improvement with surgery and increasingly low incidence of complications with improvements in microsurgical techniques.     

Is seizure detection based on EKG clinically relevant?

Objective

Real-time EKG-based automated seizure detection is emerging as a complement or supplement to that based on cortical signals, but its value is unproven. This study assesses the clinically relevance of EKG-based seizure detection by comparing the information content in EKG and ECoG.

Methods

ECoGs (6935 h; 241 clinical and 4311 sub-clinical seizures) with simultaneous EKG from 81 subjects undergoing surgical evaluation were used in these analyses. Differences, if any, between clinical and sub-clinical seizures in variables such as intensity, duration and their product severity, were investigated with a multi-variate regression model.

Results

Highly statistically significant differences in severity between clinical and sub-clinical seizures were discerned with EKG and ECoG. Furthermore, EKG-based seizure severity was linearly correlated with that estimated using ECoG.

Conclusions

These findings support the notion that EKG-based seizure detection is clinically relevant in certain localization-related epilepsies, providing similar information to that yielded by neuronal electrical signals.

Significance

The information content equivalence between EKG and ECoG would enable automated seizure detection, quantification and therapy delivery, without resorting to cortical monitoring. The considerably higher S/N and ease of acquisition and processing of EKG compared to ECoG/EEG may foster widespread clinical applications of this novel detection approach.     

Vagus nerve stimulation has a positive effect on mood in patients with refractory epilepsy

Background

Preliminary research on the efficacy of vagus nerve stimulation (VNS) indicated additional effects on neuropsychological variables like mood and quality of life (QOL).

Objectives

The objectives of this prospective longitudinal observational cohort study were to assess the effects of VNS on mood, QOL and cognition in patients with refractory epilepsy and to determine whether these effects occur dependent of seizure control.

Methods

We included 41 patients with refractory epilepsy; treated with VNS as part of usual patient care. A neuropsychological battery was performed during baseline and repeated after 6 months of VNS in order to compare neuropsychological variables before and after VNS. All patients completed seizure diaries.

Results

Significant improvements were observed for both mood and QOL after 6 months of VNS; based on the results in the POMS and QOLIE-89 questionnaires (p < 0.05). There was no significant change in cognition. Mean percentage change in seizure frequency was −9.0%, while 20% of the patients achieved a seizure frequency reduction of 50% or more. No significant correlation was found between changes in seizure frequency and improvements in mood or QOL.

Conclusions

VNS is associated with improvements in both mood and QOL in patients with refractory epilepsy. Since these improvements appeared to be independent of seizure control, the results of this study indicate an additional antidepressant effect of VNS, which can be of extra value in view of the high co-morbidity of mood disturbances in patients with epilepsy.     

Multimodality language mapping in patients with left-hemispheric language dominance on Wada test

Objective

We determined the utility of electrocorticography (ECoG) and stimulation for detecting language-related sites in patients with left-hemispheric language-dominance on Wada test.

Methods

We studied 13 epileptic patients who underwent language mapping using event-related gamma-oscillations on ECoG and stimulation via subdural electrodes. Sites showing significant gamma-augmentation during an auditory-naming task were defined as language-related ECoG sites. Sites at which stimulation resulted in auditory perceptual changes, failure to verbalize a correct answer, or sensorimotor symptoms involving the mouth were defined as language-related stimulation sites. We determined how frequently these methods revealed language-related sites in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions.

Results

Language-related sites in the superior-temporal and inferior-frontal gyri were detected by ECoG more frequently than stimulation (p < 0.05), while those in the dorsolateral-premotor and inferior-Rolandic regions were detected by both methods equally. Stimulation of language-related ECoG sites, compared to the others, more frequently elicited language symptoms (p < 0.00001). One patient developed dysphasia requiring in-patient speech therapy following resection of the dorsolateral-premotor and inferior-Rolandic regions containing language-related ECoG sites not otherwise detected by stimulation.

Conclusions

Language-related gamma-oscillations may serve as an alternative biomarker of underlying language function in patients with left-hemispheric language-dominance.

Significance

Measurement of language-related gamma-oscillations is warranted in presurgical evaluation of epileptic patients.     

Effectiveness and tolerability of rufinamide in children and young adults with Lennox–Gastaut syndrome: A single center study in Korea

Purpose

Rufinamide is a novel antiepileptic drug (AED), which is known to be effective in the treatment of partial seizures and drop attacks in patients with Lennox–Gastaut syndrome (LGS). The aim of this study is to evaluate the efficacy and tolerability of rufinamide in those with LGS.

Methods

Patients with LGS who had received rufinamide adjunctive therapy were enrolled in this study. We retrospectively reviewed these patient's baseline clinical characteristics, and the reduction of seizure frequency and adverse events after the use of rufinamide.

Results

Twenty-three patients (15 males and 8 females, ages 4–22 years) were enrolled in the study. All the patients suffered from daily head drops and tonic seizures despite multiple antiepileptic drugs. After one month of rufinamide, one patient (4.3%) achieved freedom from seizures, ten (43.5%) achieved a ≥50% decrease in seizure frequency. After six months of rufinamide, eight patients (34.8%) maintained a satisfactory response (seizure free in one, and greater than 50% seizure reduction in seven). Adverse events were reported in six (26.0%) patients, which were somnolence in three, aggressive behavior in two, and aggravation of seizure in one patient.

Conclusions

Our results suggest that rufinamide is effective and safe in children and young adults with LGS.     

Is ictal cognitive dysfunction predictable?

Objective

Accurate prediction of electrographic seizure onset may reduce injuries and improve quality of life in pharmaco-resistant epileptics. However, because sub-clinical, far out-number clinical seizures, indiscriminate issuance of warnings may have a paralyzing effect on these patients. This study investigates the predictability of ictal cognitive dysfunction.

Methods

Latency and percentage of correct responses to a reaction time test triggered by automated seizure detections were compared to those obtained inter-ictally in 14 subjects undergoing surgery evaluation. Since accurate prediction of seizures is elusive, early detection was used, as it indirectly but reliably investigates for the existence of a cognitive pre-ictal state.

Results

Significant differences between ictal and inter-ictal cognitive performance were not uncovered until late into the temporal evolution of “focal” seizures.

Conclusions

These observations suggest that cognitive dysfunction is unpredictable in seizures originating from discrete cortical regions, as the transition into unawareness seems abrupt.

Significance

Prediction of electrographic seizure onsets with worthwhile accuracy would likely result in large numbers of daily warnings, the great majority for sub-clinical seizures. This outcome would considerably increase, without safety justification, patients’ psychological burden inherent to each forecast, thus further diminishing quality of life.     

Factors associated with electroencephalographic and clinical remission of benign childhood epilepsy with centrotemporal spikes

Purpose

Benign childhood epilepsy with centrotemporal spikes (BECTS) is strongly related to age, both to age at the time of seizure onset and to age at remission. However, the age of remission varies. The present study analyzed factors associated with remission of BECTS.

Clinical and ictal characteristics of infantile seizures: EEG correlation via long-term video EEG monitoring

Purpose

The semiology of infantile seizures often shows different characteristics from that of adults. We performed this study to describe clinical and ictal characteristics of infantile seizures at less than two years of age.

Methods

A retrospective study was done for infants with epilepsy (ages: 1–24 months) who underwent long-term video electroencephalography (EEG) monitoring at Samsung medical center between November 1994 and February 2012. We analyzed the clinical and ictal characteristics of the 56 cases from 51 patients.

Results

In 69% of the patients, the seizure onset was before six months of age and the etiology was symptomatic in one third of the patients. Twelve seizure types were identified; spasms (24%), unilateral motor seizures (18%), and generalized tonic seizures (15%) were the three frequent types of seizure.All partial seizures were well correlated with the partial-onset ictal EEG, however 19.4% (7/36) of clinically generalized seizures revealed partial-onset ictal EEG. About one-thirds (4/11) of generalized tonic seizures had its ictal onset on unilateral or bilateral frontal areas and two out of seven generalized myoclonic seizures showed unilateral frontal rhythmic activities. Hypomotor seizures mainly arose from the temporal areas and hypermotor seizures from the frontal regions.

Conclusions

Even though most of the seizure semiology of infants is well correlated with ictal EEG, some of the generalized tonic seizures or myoclonic seizures revealed partial-onset ictal EEG suggesting localized epileptic focus. Accurate definition of seizures via video EEG monitoring is necessary for proper management of seizures in infancy, especially in some clinically generalized seizures.     

Bandpass filter settings differentially affect measurement of P50 sensory gating in children and adults

Objective

This study investigated the effect of four different bandpass filter settings on measures of the P50 component and the signal-to-noise ratios (SNR) of averaged ERPs obtained from a sensory gating paradigm employing paired-click stimuli.

Methods

Participants were adults (n = 18) 20–55 years old and children (n = 25) 5–10 years old who were free of neurological disorders.

Results

Results show that the filter settings (0.23–75 Hz, 10–50 Hz, 10–75 Hz, and 10–200 Hz) differentially affected the P50 amplitude, noise power and SNR measures of the conditioning and test clicks, and P50 T/C ratios.

Conclusions

The 10–50 Hz filter setting may be optimal in studies that include only adults as these settings resulted in the smallest mean P50 T/C ratio, a reasonable standard deviation (SD) for the ratio, and the highest SNRs. The 10–200 Hz filter may be the best for studying young children as this setting had the smallest mean and SD of P50 T/C ratios for these participants.

Significance

In studies that include both adults and children investigators are advised to use the 10–200 Hz filter setting because the smaller variability of sensory gating in the child group helps ensure better homogeneity of variance measures between the groups.     

Identification and comparison of adverse events for preparations of IVIG in patients with neuromuscular diseases

Objective

Risk factors for adverse events in intravenous immunoglobulin (IVIG) therapy are uncertain. We sought to determine the associations of IVIG-related adverse events in patients with neuromuscular disorders.

Patients and methods

We determined the prevalence of adverse events with the use of different forms of IVIG in a tertiary care patient population with neuromuscular diseases. A retrospective assessment for over two decades of patient care was performed.

Results

Adverse events occurred in 43% of patients over time and during 10% of infusions. Prevalence of adverse events, especially headache, was higher for lyophilized forms of IVIG, and increased with cumulative IVIG delivery. Fortunately, serious adverse events were rare for all IVIG preparations. Discontinuation of IVIG therapy occurred most commonly due to perceived inefficacy or adverse events with lyophilized forms of IVIG.

Conclusion

IVIG is generally well tolerated and only rarely associated with serious adverse events, but lyophilized forms of IVIG may be associated with greater prevalence of adverse events in patients with neuromuscular diseases.