Is streamlined evaluation of children for epilepsy surgery possible?

Background: The presurgical evaluation of children with intractable epilepsy includes evaluation by an experienced clinician, MRI, video EEG, and functional imaging techniques to localize seizure onset. However, the contributions of each investigation to surgical decision making has not been systematically assessed.
Method: Data used for decision on eligibility for surgery on 353 children was discussed at a presurgical multidisciplinary meeting and systematically recorded. The relationships between MRI, EEG, SPECT findings, and the probability of being offered epilepsy surgery were investigated retrospectively using a quick unbiased statistical tree (QUEST).
Results: Sixteen children were offered nonresective surgery. Of the remaining, 236 (70%) were offered resective surgery. The proportion of children with a localized lesion on MRI offered resective surgery was 92%[95% CI: 88 to 95%], and EEG telemetry did not modify decision making in this group (p < 0.001). In children with bilateral MRI changes or normal scan the probability of being offered resective surgery was 78% in those with localized ictal onset on EEG compared to 9% with nonlocalized EEG (p < 0.001). SPECT did not appear to systematically influence decision making in any group.
Conclusion: Children with medically intractable epilepsy and localized lesions on MRI may not necessarily need ictal EEG recordings or SPECT prior to offering resective surgery. More targeted use of EEG telemetry could allow more children with less obvious surgical targets to be investigated without increasing resources.     

Is it necessary to define the ictal onset zone with EEG prior to performing resective epilepsy surgery?

When evaluating candidates for neurosurgical treatment for medically intractable epilepsy, is it always necessary to define the region of seizure onset with EEG? A simple answer to this question is not possible. There are specific situations where surgery is commonly performed without clear EEG ictal localization, and other situations where electrical localization is mandatory. However, opinions differ in many other situations.What are the core issues for determining when EEG localization is necessary? Neuroimaging is imperfect. It does not always accurately identify the site of seizure origination, because seizures do not always arise from visible structural lesions. EEG localization is also imperfect, as well as expensive and time consuming. Sometimes the site of origin is not identified, or a region of spread is misidentified as site of origin. False localization and lateralization can occur. Finally, epilepsy surgery is imperfect. It can produce life-changing results, but it carries risk, and surgical failure is not rare.The limitations of these methods, and the high stakes of epilepsy surgery imply that we should be very cautious to omit EEG studies. The desire to improve access to epilepsy surgery, and to minimize the expense and risk from inpatient EEG studies, must be weighed against the possibility of an ineffective resection. To improve outcomes, improvements in both neuroimaging and EEG techniques are needed.     

Why does surgery fail to cure limbic epilepsy? Seizure functional anatomy may hold the answer

Surgery for the mesial temporal lobe epilepsy syndrome is highly effective in controlling seizures in as many as 80% of the patients who undergo this procedure. However, the majority of the patients with successful operations still require medications to control their seizures. Only a small minority are able to stop medications and remain seizure free, patients who would be considered cured. Why are so few patients cured by this procedure? The answer may lie in the relation of the critical seizure circuits to the tissue that is actually resected. In this paper we will discuss two hypotheses for the functional anatomy of limbic epilepsy in light of what is known about the pathology and physiology of limbic epilepsy. Combining the clinical and scientific observations with these constructs for seizure initiation may lead us to a better understanding of this particular epilepsy syndrome as well as to more effective surgical approaches.     

Therapeutic ultrasound: The future of epilepsy surgery?

Epilepsy is one of the leading neurological diseases in both adults and children and in spite of advancement in medical treatment, 20 to 30% of patients remain refractory to current medical treatment. Medically intractable epilepsy has a real impact on a patient's quality of life, neurologic morbidity and even mortality. Actual therapy options are an increase in drug dosage, radiosurgery, resective surgery and non-resective neuromodulatory treatments (deep brain stimulation, vagus nerve stimulation). Resective, thermoablative or neuromodulatory surgery in the treatment of epilepsy are invasive procedures, sometimes requiring long stay-in for the patients, risks of permanent neurological deficit, general anesthesia and other potential surgery-related complications such as a hemorrhage or an infection. Radiosurgical approaches can trigger radiation necrosis, brain oedema and transient worsening of epilepsy. With technology-driven developments and pursuit of minimally invasive neurosurgery, transcranial MR-guided focused ultrasound has become a valuable treatment for neurological diseases. In this critical review, we aim to give the reader a better understanding of current advancement for ultrasound in the treatment of epilepsy. By outlining the current understanding gained from both preclinical and clinical studies, this article explores the different mechanisms and potential applications (thermoablation, blood brain barrier disruption for drug delivery, neuromodulation and cortical stimulation) of high and low intensity ultrasound and compares the various possibilities available to patients with intractable epilepsy. Technical limitations of therapeutic ultrasound for epilepsy surgery are also detailed and discussed.     

Failed epilepsy surgery: is this the end?

Resective epilepsy surgery can lead to sustained seizure control in 70–80% of patients evaluated for epilepsy surgery, indicating that up to 30% of patients still have recurrent seizures after surgery. Definitions of failed epilepsy surgery vary amongst studies. This review focuses on seizure outcome predictors after reoperation, possible mechanisms of failure and best management for this difficult patient population.     

Does epilepsy surgery lower the mortality of drug-resistant epilepsy?

Drug-resistant epilepsy has proved to be associated with an increased standardized mortality ratio (SMR), primarily due to seizure-related fatalities including sudden unexpected death (SUDEP). Recent studies have suggested that the surgical cure of temporal lobe epilepsy (TLE) was likely to normalize the SMR of patients suffering from refractory TLE. However, these studies raise a number of methodological issues, which have not always been fully addressed. Some conclusions have relied on previously reported data, indicating a SMR of approximately 5, and a SUDEP incidence of 9/1000 patient-years in drug-resistant epilepsy. In fact, as shown in this review, SMR varied considerably, from 2 to 16, in the various series of patients with refractory epilepsy, whereas the average SUDEP incidence in the same populations was calculated at 3.7/1000 patient-years. Other conclusions were based on the comparison of either surgically and medically treated patients, or cured and non-cured operated patients. In both situations, the two groups included a different proportion of excellent and poor surgical candidates. The biological differences that distinguish these two populations might explain part of the differences observed in their mortality rate, regardless of the effect of surgery. In particular, temporal-plus epilepsies involving the insula, the frontal orbital, or the frontal operculum region, might favour ictal arrhythmias, central apnoea and secondary generalization, which in turn would increase the risk of SUDEP. Future studies are thus warranted to specifically address these issues.     

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.     

Is it worth pursuing surgery for epilepsy in patients with normal neuroimaging?

OBJECTIVE: To determine whether it is worth pursuing surgery for the treatment of epilepsy in patients with normal neuroimaging. METHODS: Two patient populations were studied: (1) 136 consecutive patients who were surgically treated; (2) 105 consecutive patients assessed with chronically implanted intracranial electrodes within the same period. Sixty patients belonged to both groups, and included all 21 patients who had normal neuroimaging. RESULTS: There were no differences in the proportion of patients with favourable outcome between those with normal and those with abnormal neuroimaging, irrespective of whether intracranial recordings were required. Among the 19 operated patients with normal neuroimaging, 74% had a favourable outcome (Engel's seizure outcome grades I and II), and among the 93 patients with abnormal neuroimaging, 73% had favourable outcome (p = 0.96). In patients with temporal resections, 92% of the 13 patients with normal neuroimaging had a favourable outcome, whereas among the 70 patients with abnormal neuroimaging, 80% had a favourable outcome (p = 0.44). In patients with extratemporal resections, two of the six patients with normal neuroimaging had a favourable outcome, while 12 of the 23 patients with abnormal neuroimaging had a favourable outcome (p = 0.65). Among the 105 patients studied with intracranial electrodes, five suffered transitory deficits as a result of implantation, and two suffered permanent deficits (one hemiplegia caused by haematoma and one mild dysphasia resulting from haemorrhage). CONCLUSIONS: It is worth pursuing surgery in patients with normal neuroimaging because it results in good seizure control and the incidence of permanent deficits associated with intracranial studies is low.     

EEG source localization in focal epilepsy: Where are we now?

Electroencephalographic source localization (ESL) by noninvasive means is an area of renewed interest in clinical epileptology. This has been driven by innovations in the computer-assisted modeling of dipolar and distributed sources for the investigation of focal epilepsy; a process fueled by the ever-increasing computational power available to researchers for the analysis of scalp EEG recordings. However, demonstration of the validity and clinical utility of these mathematically derived source modeling techniques has struggled to keep pace. This review evaluates the current clinical "fitness' of ESL as applied to the focal epilepsies by examining some of the key studies performed in the field, with emphasis given to clinical work published in the last five years. In doing so, we discuss why ESL techniques have not made an impact on routine epilepsy practice, underlining some of the current problems and controversies in the field. We conclude by examining where ESL currently sits alongside magnetoencephalography and combined EEG-functional magnetic resonance imaging in the investigation of focal epilepsy.     

Seizure Anticipation: Do Mathematical Measures Correlate with Video‐EEG Evaluation?

PURPOSE: Analysis of the EEG signal has recently shown evidence of dynamic changes preceding ictal onset in seizures selected from patients with clear epileptogenic foci. Most of the studies were conducted in highly selected EEG epochs and patients. In addition, these studies relied mostly on mathematical approaches and neglected clinical and visual EEG parameters. We therefore performed a systematic comparison of a nonlinear method (the similarity measure) with classic visual inspection of the EEG and the patient's clinical state. METHODS: We analyzed the dynamics of long epochs of intracranial EEG containing 129 electroclinical and 45 electrographic seizures in 13 successive unselected patients undergoing presurgical evaluation. RESULTS: (a) The similarity measure detected preictal dynamical changes of the EEG signal in two thirds of the seizures whether or not a clear focus was identified, and whether seizures were electroclinical or purely electrographic. The mean duration of preictal changes was 12 min. (b) The preictal changes were correlated with various visually detectable EEG changes in 78.9% of electroclinical seizures. (c) 81.5% of the preictal dynamic changes were correlated with changes of vigilance or behavior. (d) Fluctuations of the dynamics were not necessarily followed by seizures. CONCLUSIONS: Our results indicate that EEG dynamics frequently change before seizures. These preictal changes are most often associated with the EEG changes accompanying transitions between states of vigilance. The preictal dynamic changes may represent physiologic changes acting as facilitating factors or pathologic changes reflecting a network dysfunction.     

Epilepsy: Efficacy of epilepsy surgery: what are the questions today?

Consistent with previous findings, two recent studies of temporal lobectomy from Kerala, India demonstrate that early seizure recurrence bodes poorly for long-term seizure control, and that relapse following drug discontinuation affects one-third of patients. Key questions in the field now concern advanced preoperative and intraoperative techniques for improving surgical outcomes.     

Which electroencephalography (EEG) for epilepsy? The relative usefulness of different EEG protocols in patients with possible epilepsy

Background and aim

Electroencephalography (EEG) is an essential investigative tool for use in young people with epilepsy. This study assesses the effects of different EEG protocols on the yield of EEG abnormalities in young people with possible new epilepsy.

Methods

85 patients presenting to the unit underwent three EEGs with differing protocols: routine EEG (r‐EEG), sleep‐deprived EEG (SD‐EEG), EEG carried out during drug‐induced sleep (DI‐EEG). The yield of EEG abnormalities was compared using each EEG protocol.

Results

98 patients were recruited to the study. Of the 85 patients who completed the study, 33 (39%) showed no discernible abnormality on any of their EEG recordings. 36 patients (43%) showed generalised spike and wave during at least one EEG recording, whereas 15 (18%) had a focal discharge evident at some stage. SD‐EEG had a sensitivity of 92% among these patients, whereas the sensitivity of DI‐EEG and r‐EEG was 58% and 44%, respectively. The difference between the yield from SD‐EEG was significantly higher than that from other protocols (p<0.001). Among the 15 patients showing focal discharges, SD‐EEG provoked abnormalities in 11 (73%). r‐EEG and DI‐EEG each produced abnormalities in 40% and 27%, respectively. 7 patients (47%) had changes seen only after sleep deprivation. In 2 (13%), the only abnormalities were seen on r‐EEG. In only 1 patient with focal discharges (7%) was the focal change noted solely after drug‐induced sleep. These differences did not reach significance.

Conclusion

EEG has an important role in the classification of epilepsies. SD‐EEG is an easy and inexpensive way of increasing the yield of EEG abnormalities. Using this as the preferred protocol may help reduce the numbers of EEGs carried out in young patients presenting with epilepsy.Electroencephalography (EEG) is an essential investigative tool for use in young people with epilepsy.^1,2,3,4,5 The clinical onset of the idiopathic generalised epilepsies (IGEs) is most common in adolescence and early adulthood, and this is when EEG is most valuable.⁵ Differentiation of IGE from partial epilepsy should be done as early as possible, because of the important implications it will have on treatment choice,⁶ planned duration of treatment⁶ and prognosis.⁷ Despite its utility, EEG is not always easily available in many parts of the UK. Clinical targeting is desirable to allow efficient use of this resource.⁸The effect of sleep deprivation on EEG has long been recognised.^2,3,9 For reasons that are unclear, the incidence of epileptiform abnormalities on EEG is increased by sleep deprivation. Some authors feel that this effect leads to an enhanced yield of epileptiform abnormalities even when compared with routine EEG (r‐EEG) that includes a period of sleep,³ although one study did not support the special effect of sleep deprivation.⁴Although the role of the EEG in early epilepsy is widely recognised in this age group, there are few data on the relative sensitivity of EEG protocols in detecting epileptiform changes. One study⁹ looked at the incidence and frequency of epileptiform abnormalities after EEG with drug‐induced sleep (DI‐EEG) and EEG after sleep deprivation (SD‐EEG). This cohort consisted largely of patients already on treatment for localisation‐related epilepsies.Carpay et al¹⁰ repeated SD‐EEG in a cohort of younger people with normal r‐EEG and found that 34% of them showed various epileptiform abnormalities. The age range and selection criteria limit the applicability of these data. An earlier study¹¹ had carried out SD‐EEG in 114 patients who had a previously normal r‐EEG, some of whom were receiving drugs for epilepsy. Despite this, 47 patients exhibited some clearly ictal activity, but this selection precluded direct comparison of elicited epileptiform changes in different protocols.In young adults with newly diagnosed epilepsies, the role of provocative testing (either SD‐EEG or DI‐EEG) remains unclear, as the relative yield of generalised discharges in each protocol has yet to be properly compared. In young adults with newly diagnosed epilepsy, which EEG protocol is best? Should SD‐EEG be the preferred protocol? Is DI‐EEG as sensitive or specific as SD‐EEG in detecting abnormalities?     

How safe is it to withdraw antiepileptic drugs following successful surgery for mesial temporal lobe epilepsy?

Purpose: To investigate the feasibility of antiepileptic drug (AED) withdrawal following anterior temporal lobectomy (ATL) and to identify the predictors of post withdrawal seizure recurrence. Methods: We prospectively studied the seizure outcome of 310 consecutive patients, who were followed for a minimum of 5 years following ATL for medically refractory mesial temporal lobe epilepsy. In seizure‐free patients, we started AED tapering at 3 months in patients on duotherapy/polytherapy and at 1 year after ATL for those on monotherapy. We used Kaplan‐Meier survival curves to estimate the probability of seizure recurrence and complete AED discontinuation, and compared the attributes of recurred and nonrecurred groups of patients by univariate and multivariate logistic regression analyses. Key Findings: Immediately after ATL, 197 patients were on duotherapy and 101 were on monotherapy. We attempted AED withdrawal in 258 patients (83.2%). Sixty‐four patients (24.8%) had seizure recurrence while reducing AEDs. Of 26 patients who had seizure recurrence after complete AED withdrawal, 24 (92.3%) again became seizure‐free after restarting the AEDs. Absence of hippocampal sclerosis on pathologic examination and abnormal postoperative electroencephalogram (EEG) predicted seizure recurrence on multivariate analysis. At the end of follow‐up duration of 8.0 ± 2.0 years, 163 patients (52.6%) were AED free. The cumulative probability of achieving AED‐free status among patients in whom AED withdrawal was attempted, was 44% at fourth year, 65% at sixth year, 71% at eighth year, and 77% at 10th year after ATL. Significance: AED withdrawal can be safely attempted following successful ATL. Seizure recurrences are few and can be managed easily.