Andreas V. Alexopoulos

Video-electrographic and clinical features in patients with ictal asystole.

Objective: Ictal asystole (IA) is a rare event mostly seen in patients with temporal lobe epilepsy (TLE) and a potential contributor to sudden unexplained death in epilepsy (SUDEP). Clinical and video-electroencephalographic findings associated with IA have not been described, and may be helpful in screening for high risk patients. Methods: A database search was performed of 6,825 patients undergoing long-term video-EEG monitoring for episodes of IA. Results: IA was recorded in 0.27% of all patients with epilepsy, eight with temporal (TLE), two with extratemporal (XTLE), and none with generalized epilepsy. In 8 out of 16 recorded events, all occurring in patients with TLE, seizures were associated with a sudden atonia on average 42 seconds into the typical semiology of a complex partial seizure. The loss of tone followed after a period of asystole usually lasting longer than 8 seconds and was associated with typical EEG changes seen otherwise with cerebral hypoperfusion. Clinical predisposing factors for IA including cardiovascular risk factors or baseline ECG abnormalities were not identified. Conclusion: Ictal asystole is a rare feature of patients with focal epilepsy. Delayed loss of tone is distinctly uncommon in patients with temporal lobe seizures, but may inevitably occur in patients with ictal asystole after a critical duration of cardiac arrest and cerebral hypoperfusion. Further cardiac monitoring in patients with temporal lobe epilepsy and a history of unexpected collapse and falls late in the course of a typical seizure may be warranted and can potentially help to prevent sudden unexplained death in epilepsy.

Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy

PURPOSE To retrospectively review our experience with VNS in pediatric patients with pharmacoresistant epilepsy and examine the seizure-frequency outcome and rates of discontinuation in two age groups: adolescent and pre-adolescent children. RESULTS Complete pre- and post-VNS data were available for 46/49 patients. Median age at implantation was 12.1 (range 2.3-17.9) and median duration of epilepsy 8.0 (1.9-16.9) years. Twenty-one patients (45.6%) were under 12 years at the time of surgery. Median follow-up was 2 years; follow-up exceeded 4 years in 9/46 patients. As compared to baseline, median seizure-frequency reduction in the setting of declining numbers was 56% at 3 months, 50% at 6, 63% at 12, 83% at 24 and 74% at 36 months. When a last observation carried forward analysis was employed median seizure-frequency reduction in the range of 60% was observed at 1, 2 and 3 years post-VNS. Twenty patients (43.5%) had >75% seizure-frequency reduction. No response (increase or <50% reduction) was observed in 19/46 (41.3%). Five patients (10.1%) were seizure-free for more than 6 months by their last follow-up. There was no difference in the number of AEDs used before and after VNS. The long-term discontinuation rate was 21.7% and reflected a lack of clinical response or infection. CONCLUSIONS In this series VNS was well-tolerated and effective as add-on therapy for refractory seizures in children of all ages. Response was even more favorable in the younger group (<12 years at implantation). Infection and lack of efficacy were the most common reasons for discontinuation of long-term VNS therapy in this group.

Stereoelectroencephalography in the "difficult to localize" refractory focal epilepsy: early experience from a North American epilepsy center.

Purpose:  Stereo‐electroencephalography (SEEG) enables precise recordings from deep cortical structures, multiple noncontiguous lobes, as well as bilateral explorations while avoiding large craniotomies. Despite a long reported successful record, its application in the United States has not been widely adopted. We report on our initial experience with the SEEG methodology in the extraoperative mapping of refractory focal epilepsy in patients who were not considered optimal surgical candidates for other methods of invasive monitoring. We focused on the applied surgical technique and its utility and efficacy in this subgroup of patients.

Ripple classification helps to localize the seizure-onset zone in neocortical epilepsy

Purpose:  Fast ripples are reported to be highly localizing to the epileptogenic or seizure‐onset zone (SOZ) but may not be readily found in neocortical epilepsy, whereas ripples are insufficiently localizing. Herein we classified interictal neocortical ripples by associated characteristics to identify a subtype that may help to localize the SOZ in neocortical epilepsy. We hypothesize that ripples associated with an interictal epileptiform discharge (IED) are more pathologic, since the IED is not a normal physiologic event.

Resective surgery to treat refractory status epilepticus in children with focal epileptogenesis

Prolonged high-dose suppressive therapy (HDST) is a mainstay in the management of refractory status epilepticus (RSE), albeit with high morbidity and mortality. The authors studied 10 patients who were carefully selected for epilepsy surgery after failing prolonged (>2 weeks) HDST. Status epilepticus was stopped acutely in all of them with no mortality and no substantial morbidity. At follow-up (median 7 months), 7 (70%) of 10 patients were seizure free, and 3 (30%) of 10 had significant improvement in their epilepsy.

Robot-Assisted Stereotactic Laser Ablation in Medically Intractable Epilepsy: Operative Technique

BACKGROUND: Stereotactic laser ablation offers an advantage over open surgical procedures for treatment of epileptic foci, tumors, and other brain pathology. Robot-assisted stereotactic laser ablation could offer an accurate, efficient, minimally invasive, and safe method for placement of an ablation catheter into the target. OBJECTIVE: To determine the feasibility of placement of a stereotactic laser ablation catheter into a brain lesion with the use of robotic assistance, via a safe, accurate, efficient, and minimally invasive manner. METHODS: A laser ablation catheter (Visualase, Inc) was placed by using robotic guidance (ROSA, Medtech Surgical, Inc) under general anesthesia into a localized epileptogenic periventricular heterotopic lesion in a 19-year-old woman with 10-year refractory focal seizure history. The laser applicator (1.65 mm diameter) position was confirmed by using magnetic resonance imaging (MRI). Ablation using the Visualase system was performed under multiplanar imaging with real-time thermal imaging and treatment estimates in each plane. A postablation MRI sequence (T1 postgadolinium contrast injection) was used to immediately confirm the ablation. RESULTS: MRI showed accurate skin entry point and trajectory, with the applicator advanced to the lesions distal boundary. Ablation was accomplished in less than 3 minutes of heating. The overall procedure, from time of skin incision to end of last ablation, was approximately 90 minutes. After confirmation of proper lesioning by using a T1 contrast-enhanced MRI, the applicator was removed, and the incision was closed using a single stitch. No hemorrhage or other untoward complication was visualized. The patient awoke without any complication, was observed overnight after admitting to a regular floor bed, and was discharged to home the following day. CONCLUSION: This technique, using a combination of Visualase laser ablation, ROSA robot, and intraoperative MRI, facilitated a safe, efficacious, efficient, and minimally invasive approach that could be used for placement of 1 or multiple electrodes in the future. ABBREVIATIONS: EEG, electroencephalography SEEG, stereoelectroencephalography

Circadian patterns of pediatric seizures

Objective: To evaluate the relationship of sleep/wake and day/night pattern to various seizure subtypes and epilepsy localizations. Methods: Charts of 380 consecutive pediatric patients with epilepsy undergoing video-EEG (V-EEG) over 2 years were reviewed for seizure semiology, EEG localization, occurrence during the day (6 am–6 pm) or night, during wakefulness and sleep, 3-hour time blocks throughout 24 hours, and various epilepsy localizations, and etiology. Results: A total of 1,008 seizures were analyzed in 225 children (mean age 8.5 ± 5.7 years). Sleep and wakefulness predicted seizure semiology and localization more reliably than daytime and nighttime. Auras, gelastic, dyscognitive, atonic, hypomotor, and myoclonic seizures, and epileptic spasms occurred more often in wakefulness, while tonic, tonic-clonic, automotor, and hypermotor seizures occurred more frequently in sleep (p < 0.05). Clonic, atonic, myoclonic, and hypomotor seizures occurred more frequently during daytime. Hypermotor and automotor seizures occurred more frequently at night (p < 0.05). Generalized seizures (6 am–12 pm), temporal lobe seizures (9 pm–9 am), frontal lobe seizures (12 am–6 am), parietal lobe seizures (6 am–9 am), and occipital lobe seizures (9 am–noon and 3–6 pm) revealed specific circadian patterns (p < 0.05). In addition, generalized and temporal lobe seizures occurred more frequently in wakefulness, while frontal and parietal seizures occurred more frequently in sleep, independent of day or night pattern (p < 0.05). Conclusion: Sleep and wakefulness, as well as time of day and night, are important considerations in proper characterization of seizure types and epilepsy localization. These findings may contribute to a better understanding of the mechanisms of nonrandom distribution of seizures, and may provide information for individualized treatment options.

A longitudinal study of surgical outcome and its determinants following posterior cortex epilepsy surgery.

Purpose:  To investigate the longitudinal seizure outcome and identify potential prognostic indicators following posterior cortex epilepsy (PCE) surgery.

Effects of eyelid closure, blinks, and eye movements on the electroencephalogram

OBJECTIVE To characterize the effects of the eyeball and eyelid positions during eyeblinks on electroencephalographic (EEG) potentials. METHODS Movements of the upper eyelids and eyes were measured in two healthy subjects using the magnetic search coil technique during horizontal and vertical eye rotations, eyeblinks, and lid closure. Corresponding signal changes were recorded simultaneously on the electroencephalogram (EEG). RESULTS Spontaneous blinks produced small eye movements directed down and inward, whereas slow or forced blinks were associated with delayed upward eye rotations (i.e. Bells phenomenon); both types of blinks caused positive EEG potentials with bifrontal distribution maximum at Fp1 and Fp2. CONCLUSIONS In prior reports, these positive EEG artifacts have been attributed to upward eyeball rotation during blinks-Bells phenomenon. By contrast, our findings indicate that movements of the eyelid contribute to a greater extent to these EEG potentials than do upward eyeball rotations. SIGNIFICANCE Care is required in attributing EEG artifacts to movements of either eyeball or eyelid, since our findings suggest that they both contribute to these potentials.

The pathology of magnetic-resonance-imaging-negative epilepsy

Patients with magnetic-resonance-imaging (MRI)-negative (or ‘nonlesional’) pharmacoresistant focal epilepsy are the most challenging group undergoing presurgical evaluation. Few large-scale studies have systematically reviewed the pathological substrates underlying MRI-negative epilepsies. In the current study, histopathological specimens were retrospectively reviewed from MRI-negative epilepsy patients (n=95, mean age=30 years, 50% female subjects). Focal cortical dysplasia cases were classified according to the International League Against Epilepsy (ILAE) and Palmini et al classifications. The most common pathologies found in this MRI-negative cohort included: focal cortical dysplasia (n=43, 45%), gliosis (n=21, 22%), hamartia+gliosis (n=12, 13%), and hippocampal sclerosis (n=9, 9%). The majority of focal cortical dysplasia were ILAE type I (n=37) or Palmini type I (n=39). Seven patients had no identifiable pathological abnormalities. The existence of positive pathology was not significantly associated with age or temporal/extratemporal resection. Follow-up data post surgery was available in 90 patients; 63 (70%) and 57 (63%) attained seizure freedom at 6 and 12 months, respectively. The finding of positive pathology was significantly associated with seizure-free outcome at 6 months (P=0.035), but not at 12 months. In subgroup analysis, the focal cortical dysplasia group was not significantly correlated with seizure-free outcome, as compared with the negative-pathology groups at either 6 or 12 months. Of note, the finding of hippocampal sclerosis had a significant positive correlation with seizure-free outcome when compared with the negative-pathology group (P=0.009 and 0.004 for 6- and 12-month outcome, respectively). Absence of a significant histopathology in the resected surgical specimen did not preclude seizure freedom. In conclusion, our study highlights the heterogeneity of epileptic pathologies in MRI-negative epilepsies, with focal cortical dysplasia being the most common finding. The existence of positive pathology in surgical specimen may be a good indication for short-term good seizure outcome. There is a small subset of cases in which no pathological abnormalities are identified.