Utility of magnetic source imaging in nonlesional focal epilepsy: a prospective study.

OBJECTIVE: For patients with nonlesional refractory focal epilepsy (NLRFE), localization of the epileptogenic zone may be more arduous than for other types of epilepsy and frequently requires information from multiple noninvasive presurgical modalities and intracranial EEG (icEEG). In this prospective, blinded study, the authors assessed the clinical added value of magnetic source imaging (MSI) in the presurgical evaluation of patients with NLRFE. METHODS: This study prospectively included 57 consecutive patients with NLRFE who were considered for epilepsy surgery. All patients underwent noninvasive presurgical evaluation and then MSI. To determine the surgical plan, discussion of the results of the presurgical evaluation was first undertaken while discussion participants were blinded to the MSI results. MSI results were then presented. MSI influence on the initial management plan was assessed. RESULTS: MSI results influenced patient management in 32 patients. MSI results led to the following changes in surgical strategy in 14 patients (25%): allowing direct surgery in 6 patients through facilitating the detection of subtle cortical dysplasia in 4 patients and providing additional concordant diagnostic information to other presurgical workup in another 2 patients; rejection of surgery in 3 patients originally deemed surgical candidates; change of plan from direct surgery to icEEG in 2 patients; and allowing icEEG in 3 patients deemed not surgical candidates. MSI results led to changed electrode locations and contact numbers in another 18 patients. Epilepsy surgery was performed in 26 patients influenced by MSI results and good surgical outcome was achieved in 21 patients. CONCLUSIONS: This prospective, blinded study showed that information provided by MSI allows more informed icEEG planning and surgical outcome in a significant percentage of patients with NLRFE and should be included in the presurgical workup in those patients.

The clinical impact of integration of magnetoencephalography in the presurgical workup for refractory nonlesional epilepsy.

OBJECTIVE: For patients with nonlesional refractory focal epilepsy (NLRFE), localization of the epileptogenic zone is more arduous, and intracranial electroencephalography (EEG) (icEEG) is frequently required. Planning for icEEG is dependent on combined data from multiple noninvasive modalities. We report the negative impact of lack of integration of magnetoencephalography (MEG) in the presurgical workup in NLRFE. METHODS: Observational MEG case series involving 31 consecutive patients with NLRFE in an academic epilepsy center. For various reasons, MEG data were not analyzed in a timely manner to be included in the decision-making process. The presumed impact of MEG was assessed retrospectively. RESULTS: Magnetoencephalography would have changed the initial management in 21/31 (68%) had MEG results been available by reducing the number of intracranial electrodes, modifying their position, allowing for direct surgery, canceling the intracranial study, or providing enough evidence to justify one. Good surgical outcome was achieved in 11 out of 17 patients who proceeded to epilepsy surgery. Nine out of eleven had MEG clusters corresponding to the resection area, and MEG findings would have allowed for direct surgery (avoiding icEEG) in 2/11. Six patients had poor outcome including three patients where MEG would have significantly changed the outcome by modifying the resection margin. Magnetoencephalography provided superior information in 3 patients where inadequate coverage precluded accurate mapping of the epileptogenic zone. CONCLUSION: In this single center retrospective study, MEG would have changed patient management, icEEG planning, and surgical outcome in a significant percentage of patients with NLRFE and should be considered in the presurgical workup in those patients.

Ictal swearing: a case series and review.

Seizures can manifest with ictal swearing but few studies have investigated the localising value of this epileptic manifestation. In this case series and review of the literature, we attempted to determine whether ictal swearing could help localise the epileptic focus. We review two previously published cases and report eight additional epileptic patients with ictal swearing for whom the epileptic focus was determined based on clinical, structural, electrophysiological, and surgical outcome data. Results indicated that ictal swearing occurs more commonly in male subjects and lateralises to the non-dominant hemisphere, but has poor localisation value, arising either from the frontal, parietal, temporal or occipital lobes in different patients. We discuss the significance of these findings. [Published with video sequences].

Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy.

Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A) receptors that contain the mutant subunit show a lesser amplitude of GABA-activated currents in vitro, indicating that seizures may result from loss of function of this inhibitory ligand-gated channel. Our results confirm that mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy syndrome in humans.

Fronto-polar epilepsy masquerading as juvenile myoclonic epilepsy.

A woman diagnosed with juvenile myoclonic epilepsy for over 30 years presented with stereotyped episodes of abnormal sensations in both arms. Continuous video-EEG monitoring for 14 days and MRI brain revealed that the patient's somatosensory events with associated postictal aphasia, as well as her myoclonic and generalised tonic-clonic seizures, were likely due to a symptomatic left fronto-polar epilepsy. Our case emphasizes the need for clinicians to consider fronto-polar epilepsy as a potential cause of myoclonic seizures, particularly when associated with other semiologic features suggestive of frontal lobe epilepsy. [Published with video sequences].

Audit of EEG reporting temporal abnormalities.

BACKGROUND: To ensure the overall quality of our electroencephalogram (EEG) laboratory, we decided to perform an audit of EEGs interpreted at our institution, focusing initially on EEGs reporting temporal abnormalities. METHODS: Reports of all EEGs performed between January 1st and June 30th, 2006 were reviewed in order to identify tracings mentioning abnormalities in the temporal regions. These records were then independently reviewed by two epileptologists on two distinct occasions, separated by an interval of at least six months. If the recording was considered normal after this process, the cause for misinterpretation was identified and the patient's chart was reviewed to determine if he was epileptic or not based on available evidence until June 2009. RESULTS: In the first half of 2006, 143 out of 773 EEGs mentioned temporal abnormalities (18.5%). In general, intra- and interrater agreement ratios between our two epileptologists were moderate to substantial for normality, presence of epileptic activity and presence of slowing. Forty-five recordings (31.5%) were reported as normal independently by them on two distinct sittings six months apart. The most common causes for misinterpretation were the presence of benign epileptiform variants, normal sharply contoured patterns of somnolence or hyperventilation. Chart review confirmed that most were non-epileptic patients (60% non-epileptic, 27% epileptic, 13% unknown). CONCLUSION: Moderate to substantial intra- and interrater agreement as well as frequent misinterpretation of physiological variants indicate that some corrective measures need to be implemented to improve the consistency of EEG interpretation amongst our group of electroencephalographers.

Revisiting the role of the insula in refractory partial epilepsy.

PURPOSE: Recent evidence suggesting that some epilepsy surgery failures could be related to unrecognized insular epilepsy have led us to lower our threshold to sample the insula with intracerebral electrodes. In this study, we report our experience resulting from this change in strategy. METHODS: During the period extending from October 2004 to June 2007, 18 patients had an intracranial study including 10 with insular coverage. The decision to sample the insula with intracerebral electrodes was made in the context of (1) nonlesional parietal lobe-like epilepsy; (2) nonlesional frontal lobe-like epilepsy; (3) nonlesional temporal lobe-like epilepsy; and (4) atypical temporal lobe-like epilepsy. RESULTS: Intracerebral recordings confirmed the presence of insular lobe seizures in four patients. Cortical stimulation performed in 9 of 10 patients with insular electrodes elicited, in decreasing order of frequency, somatosensory, viscerosensory, motor, auditory, vestibular, and speech symptoms. DISCUSSION: Our results suggest that insular cortex epilepsy may mimic temporal, frontal, and parietal lobe epilepsies and that a nonnegligeable proportion of surgical candidates with drug-resistant epilepsy have an epileptogenic zone that involves the insula.

Microsurgery of epileptic foci in the insular region.

OBJECT: The insular region has long been neglected in the investigation and treatment of refractory epilepsy. Surgery in the insular region is rarely performed because of the risk of injury to the opercula, the arteries transiting on the surface of the insula, and the deep structures such as the basal ganglia and the internal capsule. This study was undertaken to report the results of insular surgery using modern microsurgical techniques in patients with epilepsy. METHODS: The authors performed a retrospective study of cases involving patients who underwent surgery for insular lesions associated with epilepsy over the last 10 years. In the majority of patients, intracranial electrodes were implanted with neuronavigation guidance to confirm the localization of the epileptic foci. RESULTS: Nine patients underwent insular surgery: 7 for refractory epilepsy with no tumor and 2 for tumors associated with seizures. Four of the resections were performed in the left hemisphere. After an average follow-up of 54 months (range 14-122 months), Engel Class IA outcome had been achieved in 6 of 7 cases in the Epilepsy Surgery Group. The remaining patient had an Engel Class III outcome after partial insular resection but later became seizurefree (Engel Class IA) following insular Gamma Knife surgery. Postoperatively, the majority of patients suffered from minor reversible hemipareses that disappeared completely within a few months. There was no surgical mortality. CONCLUSIONS: Insular surgery is both safe and beneficial when it is well planned and performed with modern microsurgical techniques and good anatomical knowledge. Insulectomy is associated with little permanent morbidity and a high rate of seizure control. To the authors' knowledge, this is the first series of insulectomies predominantly performed for refractory epilepsy since those performed by Penfield.

Potentially life-threatening ictal bradycardia in intractable epilepsy.

BACKGROUND: Recently a high prevalence of asystole was found in individuals with refractory epilepsy. OBJECTIVE: To measure the prevalence and characterize the pattern of ictal bradycardia (IB) in our cohort. METHOD: We analyzed ictal heart rate (HR) and seizure localization in 69 consecutive individuals with intractable epilepsy. Ictal bradycardia was defined by HR less than 60 beat per min (bpm) and a fall of more than 30 bpm. RESULTS: Ictal bradycardia was observed in 1.9% of seizures and in five individuals (7.2%), who presented IB in 5.7% of their seizures. Four of them had also relative IB (a decrease of HR of more than l0 bpm) in the majority of their seizures. Four additional individuals showed relative IB. CONCLUSION: Ictal bradycardia occurs more frequently than previously thought in individuals with refractory epilepsy. Recognition of individuals with small to moderate ictal HR decrease may help to identify those at greatest risk for asystole.

Divalproex extended-release versus the original divalproex tablet: results of a randomized, crossover study of well-controlled epileptic patients with primary generalized seizures.

PURPOSE: To compare the safety and efficacy of two formulations of divalproex, extended-release divalproex versus the original divalproex tablet, in adolescent and adult patients with epilepsy. METHODS: Eligible patients were between the ages of 12 and 65 years with primary generalized epilepsy, which was controlled over the month prior to study enrollment with divalproex or valproic acid 1000 mg to 2000 mg/day. The patients were well-controlled; 39 of 43 (91%) had no seizures in the previous year. Patients were randomized to receive 84 days of either divalproex two times a day (b.i.d.)/three times a day (t.i.d.) or extended-release divalproex qd and then (crossed over to) 84 days of the comparator formulation. During the two treatment periods, patients received the same daily dose equivalent of divalproex as was taken during the month prior to study entry. The clinical status of patients was evaluated at a screening visit and at four subsequent visits conducted every 42 days. RESULTS: There was no statistically significant difference between the formulation groups for seizure control rate (95% [41/43] for divalproex and 93% [40/43] for extended-release divalproex). Likewise, the formulation groups were similar based on the incidence of treatment-related adverse events. The most frequently reported (< or =11.4% for either formulation) treatment-related adverse events were asthenia, tremor, nausea, and dizziness. CONCLUSIONS: Extended-release divalproex was similar to divalproex for the treatment of well-controlled, primary generalized epilepsy in terms of overall safety and efficacy parameters.