Can electroencephalograms provide guidance for the withdrawal of antiepileptic drugs: A meta-analysis

Objective

The discontinuation of antiepileptic drugs (AEDs) is an important treatment decision for epilepsy patients who have been seizure-free for 2 years or longer. Some patients experience seizures relapse after AED withdrawal. The prognostic value of electroencephalograms (EEGs) for seizure relapse following AED withdrawal is controversial. To our knowledge, this is the first meta-analysis to address whether EEG data can be used to guide the discontinuation of AEDs.

Epilepsy surgery in pediatric epileptic encephalopathy: when interictal EEG counts the most

Purpose

Traditionally, seizure onset localization in ictal electro-encephalography (EEG) is the main factor guiding resective epilepsy surgery. The situation is often different in infantile epileptic encephalopathy. We demonstrate the importance of the underrated interictal (rather than ictal) surface EEG in informing decision-making in epilepsy surgery for children with epileptic encephalopathy caused by subtle focal cortical dysplasia (FCD).

Methods

We present a small case series of three children who had an epileptic encephalopathy with either epileptic spasms or tonic seizures. All three were thought initially to have normal neuroimaging.

Results

Ictal EEG localizing features were seen in none and lateralizing features were seen only clinically in one of the three. However, the interictal EEG showed persistent and consistent focal irregular slowing in all, particularly after medically resolving the diffuse encephalopathy. Subtle FCDs were uncovered in all. Surgery was performed in all with excellent outcome.

Conclusion

In infantile epileptic encephalopathy caused by subtle FCD, the often underrated interictal surface EEG (particularly persistent foal irregular slowing) informs the most; not only to the target area for surgical resection but also to its extent. This may negate the need for unnecessary and sometimes non-informative invasive monitoring in these cases. A matter of “zooming out” to define the extent of a resectable abnormality rather than “zooming in” to define a seemingly localized epileptic focus that may change with time.

     

EEG Monitoring and Antiepileptic Drugs in Children with Severe TBI

Background

Traumatic brain injury (TBI) causes substantial morbidity and mortality in US children. Post-traumatic seizures (PTS) occur in 11–42% of children with severe TBI and are associated with unfavorable outcome. Electroencephalographic (EEG) monitoring may be used to detect PTS and antiepileptic drugs (AEDs) may be used to treat PTS, but national rates of EEG and AED use are not known. The purpose of this study was to describe the frequency and timing of EEG and AED use in children hospitalized after severe TBI.

Methods

Retrospective cohort study of 2165 children at 30 hospitals in a probabilistically linked dataset from the National Trauma Data Bank (NTDB) and the Pediatric Health Information Systems (PHIS) database, 2007–2010. We included children (age <18 years old at admission) with linked NTDB and PHIS records, severe (Emergency Department [ED] Glasgow Coma Scale [GCS] <8) TBI, hospital length of stay >24 h, and non-missing disposition. The primary outcomes were EEG and AED use.

Results

Overall, 31.8% of the cohort had EEG monitoring. Of those, 21.8% were monitored on the first hospital day. The median duration of EEG monitoring was 2.0 (IQR 1.0, 4.0) days. AEDs were prescribed to 52.0% of the cohort, of whom 61.8% received an AED on the first hospital day. The median duration of AED use was 8.0 (IQR 4.0, 17.0) days. EEG monitoring and AED use were more frequent in children with known risk factors for PTS. EEG monitoring and AED use were not related to hospital TBI volume.

Conclusion

EEG use is relatively uncommon in children with severe TBI, but AEDs are frequently prescribed. EEG monitoring and AED use are more common in children with known risk factors for PTS.

     

Usefulness of a simple sleep-deprived EEG protocol for epilepsy diagnosis in de novo subjects

Objective

In case series concerning the role of EEG after sleep deprivation (SD-EEG) in epilepsy, patients’ features and protocols vary dramatically from one report to another. In this study, we assessed the usefulness of a simple SD-EEG method in well characterized patients.

Methods

Among the 963 adult subjects submitted to SD-EEG at our Center, in the period 2003–2010, we retrospectively selected for analysis only those: (1) evaluated for suspected epileptic seizures; (2) with a normal/non-specific baseline EEG; (3) still drug-free at the time of SD-EEG; (4) with an MRI analysis; (5) with at least 1 year follow-up. SD-EEG consisted in SD from 2:00 AM and laboratory EEG from 8:00 AM to 10:30 AM. We analyzed epileptic interictal abnormalities (IIAs) and their correlations with patients’ features.

Results

Epilepsy was confirmed in 131 patients. SD-EEG showed IIAs in 41.2% of all patients with epilepsy, and a 91.1% specificity for epilepsy diagnosis; IIAs types observed during SD-EEG are different in generalized versus focal epilepsies; for focal epilepsies, the IIAs yield in SD-EEG is higher than in second routine EEG.

Conclusions

This simple SD-EEG protocol is very useful in de novo patients with suspected seizures.

Significance

This study sheds new light on the role of SD-EEG in specific epilepsy populations.     

Is interictal EEG activity a biomarker for mood disorders in temporal lobe epilepsy?

Objective

Psychiatric comorbidities are frequent in temporal lobe epilepsy (TLE), and symptoms of these comorbidities may be related to epilepsy activity. Here we evaluated interictal EEG activity in TLE patients with or without psychiatric comorbidities.

Methods

A cohort study of 78 patients with TLE, with evaluation of wake/sleep interictal scalp EEG. All subjects were submitted to a psychiatric structured clinical interview (SCID) for the diagnosis of lifetime psychiatric comorbidities. Three major diagnostic categories were studied: mood disorders, anxiety disorders, and psychosis. We then evaluated differences in interictal EEG activity between patients with and without these psychiatric comorbidities.

Results

Infrequent EEG interictal spikes, defined as less than one event per minute, were significantly associated with mood disorders in TLE (p = 0.02).

Conclusions

Low intensity seizure disorder has been associated with a decrease in interictal EEG discharges and with an increase in psychiatric symptoms in TLE, a phenomenon known as forced normalization. In our study, we observed a low interictal spike frequency on EEG in TLE patients with mood disorders.

Significance

A low spike index might be a neurophysiological marker for depression in temporal lobe epilepsy.     

Épilepsies généralisées idiopathiques chez le sujet âgé : le point de vue du gériatre

Introduction

Long-term follow-up studies indicate a low remission rate in idiopathic generalised epilepsies (IGE) (Martinez-Juarez et al., 2006), suggesting they may persist to an advanced age. However there are few estimates of IGE frequency in the elderly.

Methods

EEGs of 700 patients aged over 70 years, recorded between January 2006 and March 2007, were reviewed for anomalies consistent with IGE. We then examined the clinical history of patients with these anomalies.

Results

A persistent IGE was identified in four female patients (mean age: 79 years); in two cases it was a juvenile myoclonic epilepsy (JME) and in two an epilepsy with grand mal seizures. Seizures in three patients had begun in childhood or adolescence and in one at 40 years. Before hospitalization, few or no seizures were reported and IGE had not been diagnosed. IGE was revealed in each patient by a relatively severe event: an absence status (AS), subcontinuous myoclonic seizures or repeated convulsive generalised seizures (CGS). These events were not situation-related but in one patient the relapse of simple convulsive seizures, may have been related to the withdrawal of anti-epileptic drugs (AED) several months previously. EEG records showed generalised spikes or polyspikes and waves organised in a status epilepticus or in interictal rhythmic discharges. In one case they were evident only from a 24 hours recording. Clonazepam injection was used to suppress the AS episode and the subintrant myoclonia. After the AS, interictal generalised epileptic discharges persisted. Two of the four patients had familial history of epilepsy or febrile seizures but in no case was an epileptogenic lesion evident in brain CT scan or MRI. Clinical exams and biologic parameters were normal. All of the patients had worked and were married with children. Appropriate therapies were followed after the diagnosis of IGE. One patient with JME had been treated by Valproate which was discontinued by the general practitioner because of lethargy and replaced by Carbamazepine; seizures were aggravated under both Carbamazepine and then Lamotrigine and until the patient became seizure-free on Levetiracetam. The antiepiletic treatment was also modified in a second patient, while the two others responded well to Valproate.

Conclusions

IGE can exacerbate in the elderly, as different types of seizures including AS, subintrant myoclonia or repeated CGS. Our data suggest persistent IGE are quite frequent in an aged population and may be underestimated due to difficulties in diagnosis. Correctly diagnosed, adjustment of AED may offer substantial clinical improvements in IGE of the elderly.     

Comparative role of neuropsychological testing in the presurgical evaluation of children with medically intractable epilepsies

Purpose

In the present study, we evaluated the preoperative demographic, clinical, and neuropsychological variables that could predict postoperative seizure outcome in a group of pediatric epileptic patients.

Materials and methods

We studied 40 consecutive pediatric patients, ages ranging from 6 to 16 years, that underwent resective surgery for the treatment of medically intractable epilepsy at the Clinical Hospital of Ribeirão Preto School of Medicine. We performed ictal electroencephalography (EEG), interictal EEG, magnetic resonance imaging (MRI), and a preoperative neuropsychological assessment in the presurgical workup.

Results

The following factors were correlated with seizure outcome: (1) duration of epilepsy, (2) surgery localization, (3) localized Neuropsychological (NPS) Evaluation, (4) ictal EEG, (5) interictal EEG, and (6) MRI. Mental retardation, NPS tests, and the other demographic variables failed to correlate with seizure reduction.

Conclusions

The identification of predictor variables of epilepsy surgery outcome could improve the epileptic prognosis and guarantee the children's full potential development.

     

Transkutane Vagusnervstimulation

Background

Approximately 20-40?% of epilepsy patients show drug resistance and a large number of patients under antiepileptic therapy suffer from side effects including cognitive disorders and depression. Transcutaneous vagus nerve stimulation (t-VNS) can be used for these patients as a supplementary treatment to resection epilepsy surgery.

Aim

The main aims of this investigation were to test the safety, tolerability and practicality of t-VNS in epilepsy patients.

Material and methods

For the proof of concept trial ten patients with pharmacoresistant epilepsy (eight with focal and two with generalized epilepsy) were recruited. For admission to the study a minimum frequency of four seizures per month was necessary. The medication dosage was kept constant in the baseline and in the total treatment phase. The auricular branch of the vagus nerve (ABVN) of the left ear was stimulated. The stimulation pulses were biphasic with a frequency of 10/s and a pulse width of 300 µs. After an initial training period the stimulation was carried out in the morning, midday and evening for 1 h each over a period of 9 months. The subjectively experienced frequency of seizures, continuous video EEG (electroencephalogram) long-term conduction carried out 4 times for 1 week each and cognitive and functional alterations were considered to be end point parameters.

Results

The total treatment period of 9 months was completed by seven patients. Of these seven patients five showed a reduction in the frequency of seizures during the 9-month treatment period and two reported an increase in seizures. In two patients the seizure frequency was reduced by 45 % and 48 % in a comparison between baseline and end of treatment. In two further patients contradictions arose between the subjective report on seizure frequency and the objectively quantified frequency in the video EEG. For one patient the interictal epileptic EEG activity was continually reduced during the course of the 9-month period.

Conclusion

The t-VNS procedure represents a procedure which is well tolerated and practical for long-term treatment.     

Rapid Bedside Evaluation of Seizures in the ICU by Listening to the Sound of Brainwaves: A Prospective Observational Clinical Trial of Ceribell’s Brain Stethoscope Function

Background

Patients suffering from non-convulsive seizures experience delays in diagnosis and treatment due to limitations in acquiring and interpreting electroencephalography (EEG) data. The Ceribell EEG System offers rapid EEG acquisition and conversion of EEG signals to sound (sonification) using a proprietary algorithm. This study was designed to test the performance of this EEG system in an intensive care unit (ICU) setting and measure its impact on clinician treatment decision.

Methods

Encephalopathic ICU patients at Stanford University Hospital were enrolled if clinical suspicion for seizures warranted EEG monitoring. Treating physicians rated suspicion for seizure and decided if the patient needed antiepileptic drug (AED) treatment at the time of bedside evaluation. After listening to 30 s of EEG from each hemisphere in each patient, they reevaluated their suspicion for seizure and decision for additional treatment. The EEG waveforms recorded with Ceribell EEG were subsequently analyzed by three blinded epileptologists to assess the presence or absence of seizures within and outside the sonification window. Study outcomes were EEG set up time, ease of use of the device, change in clinician seizure suspicion, and change in decision to treat with AED before and after sonification.

Results

Thirty-five cases of EEG sonification were performed. Mean EEG setup time was 6?±?3 min, and time to obtain sonified EEG was significantly faster than conventional EEG (p?<?0.001). One patient had non-convulsive seizure during sonification and another had rhythmic activity that was followed by seizure shortly after sonification. Change in treatment decision after sonification occurred in approximately 40% of patients and resulted in a significant net reduction in unnecessary additional treatments (p?=?0.01). Ceribell EEG System was consistently rated easy to use.

Conclusion

The Ceribell EEG System enabled rapid acquisition of EEG in patients at risk for non-convulsive seizures and aided clinicians in their evaluation of encephalopathic ICU patients. The ease of use and speed of EEG acquisition and interpretation by EEG-untrained individuals has the potential to improve emergent clinical decision making by quickly detecting non-convulsive seizures in the ICU.

     

Do seizures in patients with refractory epilepsy vary between wakefulness and sleep?

Aim

To determine the effects of sleep and wakefulness on seizures in patients with refractory epilepsy recorded while undergoing video‐electroencephalography (EEG) telemetry.

Methods

The video‐EEG data of patients who had two or more seizures during video‐EEG telemetry (n = 270) were reviewed. Fifty seven patients who had seizures both in wakefulness and sleep were identified. The video and ictal EEG data were reviewed, paying specific attention to type of seizures, duration, semiology, lateralisation and number of seizures.

Results

Three hundred and sixty two seizures were recorded; 237 seizures while awake and 125 while sleeping. Secondary generalisation occurred more often in sleep than in wakefulness (p<0.01). Overall, there was no significant effect of sleep on the duration of seizures or ictal EEG change. Sleep and awake seizures differed in only eight patients.

Conclusion

Secondary generalisation occurred more often in sleep than in wakefulness, perhaps due to the facilitated spread of seizures during sleep. For the most part, however, seizures recorded during sleep did not differ from those recorded during wakefulness.The interaction between sleep and epilepsy has been recognised as far back as Hippocrates. Recent research has further elucidated this complex relationship. Epilepsy and epileptic drugs can have a profound effect on the sleep–wake cycle and sleep architecture. In addition, sleep can affect seizure occurrence, threshold and spread. Interictal electroencephalography (EEG) abnormalities are often potentiated during sleep, suggesting a change in seizure threshold.^1,2,3,4,5 The sleep–epilepsy relationship varies, however, according to the epilepsy syndrome; in some, such as the frontal lobe epilepsies, sleep may facilitate seizures,⁶ whereas in others, sleep may protect against epilepsy. The finding that frontal lobe seizures have a greater chance of occurring during sleep whereas temporal lobe seizures are more likely to occur during wakefulness implies that sleep has distinct effects on seizure threshold in different brain regions.⁶ Furthermore, sleep can influence the extent of seizure spread, such that seizures in temporal lobe epilepsy are more likely to secondarily generalise during sleep than during wakefulness.^6,7 These observations suggest that sleep may influence the pattern and extent of seizure spread, and therefore the electroclinical characteristics of the seizures. If true, this has critical implications for presurgical assessment, because seizures recorded during the day may yield different information from those recorded during the night. There have, however, been few studies on the influence of time of day on seizure semiology beyond the observation of the increased likelihood of secondary generalisation. The aim of this study was to determine retrospectively the effects of sleep and wakefulness on seizures in individual patients with refractory epilepsy undergoing presurgical assessment in a video‐EEG telemetry unit.     

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.     

SCOPE-mTL: A non-invasive tool for identifying and lateralizing mesial temporal lobe seizures prior to scalp EEG ictal onset

Objective

In mesial temporal lobe (mTL) epilepsy, seizure onset can precede the appearance of a scalp EEG ictal pattern by many seconds. The ability to identify this early, occult mTL seizure activity could improve lateralization and localization of mTL seizures on scalp EEG.

Ear-EEG detects ictal and interictal abnormalities in focal and generalized epilepsy – A comparison with scalp EEG monitoring

Objective

Ear-EEG is recording of electroencephalography from a small device in the ear. This is the first study to compare ictal and interictal abnormalities recorded with ear-EEG and simultaneous scalp-EEG in an epilepsy monitoring unit.

Visual and semi-automatic non-invasive detection of interictal fast ripples: A potential biomarker of epilepsy in children with tuberous sclerosis complex

Objectives

We aim to establish that interictal fast ripples (FR; 250–500?Hz) are detectable on scalp EEG, and to investigate their association to epilepsy.

Does early postoperative drug regimen impact seizure control in patients undergoing temporal lobe resections?

Objective

To evaluate the impact of postoperative antiepileptic drug (AED) load on seizure control in patients who underwent surgical treatment for pharmacoresistant mesiotemporal lobe epilepsy during the first two postoperative years.

Patients and methods

532 consecutive patients (48.7% males and 51.7% females) who underwent surgical treatment for mesiotemporal lobe epilepsy were retrospectively evaluated regarding effects of AED load on seizures control during the first 2 years following epilepsy surgery. We analyzed whether postoperative increases in postoperative AED load are associated with better seizure control in patients initially not seizure free, and if postoperative decreases in postoperative AED load would increase the risk for seizure persistence or recurrence. For statistical analyses, Fisher’s exact and Wilcoxon test were applied.

Results

68.9, 64.0 and 59.1% of patients were completely seizure free (Engel Ia) at 3, 12 and 24 months after surgery, respectively. Patients in whom daily drug doses were increased did not have a higher rate of seizure freedom at any of the three follow-up periods. Of 16 patients achieving secondary seizure control at 12 months after surgery, only one did so with an increase in drug load in contrast to 15 patients who experienced a running down of seizures independent of drug load increases. Decreases in drug load did not significantly increase the risk for seizure recurrence. Of postoperatively seizure free patients at 3 months after surgery in whom AED were consequently reduced, 85% remained completely seizure free at 1 year and 76% at 1 year after surgery, respectively, as opposed to 86% each when AED was not reduced (differences n.s.). Mean daily drug load was significantly lower in seizure free patients at 12 and 24 months compared to patients with ongoing seizures.

Conclusion

In this large patient cohort stratified to the epilepsy syndrome neither did a postoperative reduction in drug load significantly increase the risk for seizure relapse nor did increases in drug dosages lead to improved seizure control. Mean drug load was on average lower in seizure free- than non-seizure free patients at 12 and 24 months of follow-up. Secondary seizure control after initial postoperative seizures in > 90% of cases occurred as a running down, independent of an AED increase. Thus, the effect of the surgical intervention rather than the postoperative drug regimen was the key determinant for seizure control. This finding supports a curative role of temporal lobe surgery rather than an effect rendering the majority of patients’ pharmacoresponsive with a critical role of the antiepileptic drug regime for seizure control.

     

Different seizure-onset patterns in mesiotemporal lobe epilepsy have a distinct interictal signature

Objective

Experimental research demonstrated that distinct underlying mechanisms go along with different seizure-onset patterns on EEG. These different mechanisms may reflect different tissue abnormalities which, we hypothesize, could also be reflected in morphological differences in the interictal epileptic and background EEG activity.

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.     

Brainstem lesions may be important in the development of epilepsy in multiple sclerosis patients: An evoked potential study

Objective

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with epileptic seizures sometimes observed in the same patients. In this study, we used evoked responses to study the pathogenesis of epilepsy in MS.

Methods

Patients with a diagnosis of definite MS and who had EPs performed (visual (VEP), brainstem auditory (BAEP) and short latency somatosensory (upper (USSEP) and lower (LSSEP))) were retrospectively included in this study. They were divided into three groups; Group I: Patients with no epilepsy and who were not taking anti-epileptic drugs (AED); Group II: Patients with epilepsy and taking AEDs; and Group III: Patients with no epilepsy who were taking AEDs for symptoms related to neuropathic pain.

Results

Three hundred and fifty-five patients were included in this study; Group I: 229 patients (64.5%), Group II: 20 patients (5.6%) and Group III: 106 patients (29.9%). The proportion of patients with abnormal BAEP and USSEP was higher in Group II.

Conclusions

A positive association exists between the presence of epilepsy in MS patients and BAEP and USSEP abnormalities. Analysis of Group III ruled out AED use as a factor.

Significance

Brainstem lesions may be the cause of epileptogenicity in MS.     

Interiktale Quellenlokalisation und Vorteile des High-density-EEG

Background

Localization of the source of brain activity using an electroencephalograph (EEG) enables non-invasive visualization of the generators of epilepsy in an anatomical 3?D space. Initially the localization of interictal epileptic discharges with high-density EEG (hdEEG) was established, before techniques are also now being looked for, in order to localize ictal events.

Objective

This article summarizes the current state of the literature on localization of interictal discharges and gives an overview of the current questions.

Material and methods

The most important articles on various parameters, such as documentation of the discharge, marking the time point, role of head models and number of electrodes are discussed and the most important studies with patient cohorts are presented.

Results

In several studies with large patient cohorts, the localization of the source of interictal epileptic discharges was successfully proven with hdEEG. When this is combined with a head model based on the magnetic resonance imaging (MRI) of the patient, a high sensitivity (84%) and specificity (88%) can be achieved, which is superior to the other imaging techniques, such as MRI, PET and SPECT.

Conclusion

The EEG source localization of interictal epileptic discharges is precise and powerful. In view of the clinical relevance EEG source localization should be an established component in the presurgical clarification of patients with drug-refractory epilepsy, in addition to the other widely used imaging techniques.