Mark D. Holmes

Are “Generalized” Seizures Truly Generalized? Evidence of Localized Mesial Frontal and Frontopolar Discharges in Absence

Summary:  Purpose: To determine whether specific regions of cerebral cortex are activated at the onset and during the propagation of absence seizures.

Spatial spectral analysis of human electrocorticograms including the alpha and gamma bands.

Spatial spectral analysis is essential for deriving spatial patterns from simultaneous recordings of electrocorticograms (ECoG), in order to determine the optimal interval between electrodes in arrays, and to design spatial filters, particularly for extraction of information about the dynamics of human gamma activity. ECoG were recorded from up to 64 electrodes 0.5 mm apart in a linear array 3.2 cm long, which was placed on the exposed superior temporal gyrus or motor cortex of volunteers undergoing diagnostic surgery. Visual displays of multiple traces revealed broad spectrum oscillations in episodic bursts having a common aperiodic wave form with recurring patterns of spatial amplitude modulation (AM patterns) on selected portions of the array. The one-dimensional spatial spectrum of the human ECoG was calculated at successive time samples and averaged over periods of up to 20 s. Log power decreased monotonically with increasing log spatial frequency in cycles/mm (c/mm) to the noise level approximately 2 log units below maximal power at minimal frequency (0.039+/-0.002 c/mm). The inflection point at 0.40+/-0.05 c/mm specified an optimal value for a low pass spatial filter to remove noise, and an optimal interelectrode spacing of 1.25 mm to avoid undersampling and aliasing. An 8 x 8 array with that spacing would be 10 x 10 mm.

Aperiodic phase re-setting in scalp EEG of beta–gamma oscillations by state transitions at alpha–theta rates

We evaluated the rapid changes in regional scalp EEG synchronization in normal subjects with spatial and temporal resolution exceeding prior art 10‐fold with a high spatial density array and the Hilbert transform. A curvilinear array of 64 electrodes 3 mm apart extending 18.9 cm across the scalp was used to record EEG at 200/sec. Analytic amplitude (AA) and phase (AP) were calculated at each time step for the 64 traces in the analog pass band of 0.5–120 Hz. AP differences approximated the AP derivative (instantaneous frequency). The AP from unfiltered EEG revealed no reproducible patterns. Filtering was necessary in the β and gamma ranges according to a technique that optimized the correlation of the AP differences with the activity band pass filtered in the alpha range. The sizes of temporal AP differences were usually within ±0.5 radian from the average step corresponding to the center frequency of the pass band. Large AP differences were often synchronized over distances of 6 to 19 cm. An optimal pass band to detect and measure these recurring jumps in AP in the β and γ ranges was found by maximizing the α peak in the cospectrum of the correlation between unfiltered EEG and the band pass AP differences. Synchronized AP jumps recurred in clusters (CAP) at α and theta rates in resting subjects and with EMG. Cortex functions by serial changes in state. The Hilbert transform of EEG from high‐density arrays can visualize these state transitions with high temporal and spatial resolution and should be useful in relating EEG to cognition. Hum. Brain Mapping 19:248–272, 2003.

Outcome after surgery in patients with refractory temporal lobe epilepsy and normal MRI.

Our purpose is to determine predictors of outcome in patients with refractory temporal lobe epilepsy and normal high resolution magnetic resonance imaging (MRI) who undergo surgical therapy. We identified 23 patients who underwent temporal lobectomy and had normal pre-operative MRI, including surface coil phased array temporal lobe imaging. All were followed at least 2 years after surgery. We graded outcome as seizure-free, > 75% reduction in seizures, or < 75% reduction in seizures. We examined pre-operative interictal and ictal electroencephalographic (EEG) findings, age of onset, gender, duration of epilepsy, risk factors, family history, physical findings, age at operation, side of operation, and pathology of resected tissue in order to determine if any of these factors were associated with outcome. Overall, 48% (11/23) of patients were seizure-free, 39% (9/23) had > 75% reduction in seizures, while 13% (3/23) had < 75% reduction in seizures. Only the EEG findings were useful in predicting outcome. When ictal onsets arose from basal-temporal regions, 61% (11/18) of patients were seizure-free, while none (0/5) were seizure-free when seizures arose from mid-posterior temporal regions (P = 0.04). Interictally, if all epileptiform patterns were localized exclusively to one basal-temporal region, a finding that invariably correlated with ictal onsets, 78% (7/9) of patients were seizure-free, while only 29% (4/14) were seizure-free if discharges were bilateral or multifocal (P = 0.04). We conclude that surgery may be a reasonable treatment for some patients with intractable temporal lobe seizures and normal MRI. The best outcomes occur when seizure onsets and interictal epileptiform patterns are exclusive to one basal-temporal region. Unfavorable outcomes are most likely to occur when ictal origins are from mid-posterior temporal regions and when interictal discharges are bitemporal or multifocal in distribution.

Dexmedetomidine sedation during awake craniotomy for seizure resection: effects on electrocorticography.

Patients with refractory seizures may undergo awake craniotomy and cortical resection of the seizure area, using intraoperative functional mapping and electrocorticography (ECoG). We used dexmedetomidine in 6 patients, transitioning successively from the asleep-awake-asleep method, through a combined propofol/dexmedetomidine sedative infusion, to dexmedetomidine as the only sedation. Initial experience with the asleep-awake-asleep method in 2 patients was successful with the replacement of propofol/laryngeal mask anesthesia, 20 to 30 minutes before ECoG testing, by dexmedetomidine infusion, maintained at 0.2 mcg kg−1 h−1 throughout neurocognitive testing. Propofol anesthesia was reintroduced for resection. One patient received combined dexmedetomidine (0.2 mcg kg−1 h−1) and propofol (200 mcg kg−1 min−1) infusions for sedation. Both infusions were stopped 15 minutes before ECoG. Subsequently, they were restarted and the epileptic foci resected. Three patients received dexmedetomidine as the sole sedative agent, together with scalp block local anesthesia, and incremental boluses totaling 150 to 175 mcg of fentanyl per case. Dexmedetomidine was started with 0.3 mcg kg−1 boluses and maintained with 0.2 to 0.7 mcg kg−1 h−1 for craniotomy, testing, and resection. The infusion was paused for 20 minutes in 1 patient to allow improvement in neurocognitive testing. This occurred within 10 minutes. All patients enjoyed good hemodynamic control, with blood pressure maintained within 20% of initial values, and made uneventful recoveries. The surgical conditions were all reported as favorable. Dexmedetomidine can be used singly for sedation in awake craniotomy requiring ECoG. Individual dose ranges vary, but a bolus of 0.3 mcg kg−1 with an infusion of 0.2 mcg kg−1 min−1 is a good starting point, allowing accurate mapping of epileptic foci and subsequent resection.

Cognitive impairment is not equal in patients with epileptic and psychogenic nonepileptic seizures.

Summary:  Purpose: Patients with psychogenic nonepileptic seizures (PNES) and those with epileptic seizures (ES) purportedly have roughly equal neurocognitive deficits. However, recent findings suggest that patients with somatoform disorders exhibit more variable effort on neurocognitive testing than do controls. We reexamined neurocognitive function in patients with ESs and PNES by using symptom validity testing to control for variability in effort.

Factors Predicting Outcome of Surgery for Intractable Epilepsy with Pathologically Verified Mesial Temporal Sclerosis

Summary:  Purpose: To examine the subgroup of patients with medically intractable epilepsy receiving temporal lobectomies who have pathologically verified mesial temporal sclerosis (MTS) and to determine the relation of demographic and clinical factors, results of diagnostic testing, and details of the surgical procedure with prognosis for achieving control of seizures.

Interictal, unifocal spikes in refractory extratemporal epilepsy predict ictal origin and postsurgical outcome

OBJECTIVES To evaluate the significance of exclusively unifocal, unilateral, interictal epileptiform patterns on scalp electroencephalography (EEG) in surgical candidates with medically intractable extratemporal epilepsy. METHODS We reviewed 126 patients with refractory extratemporal partial seizures who underwent epilepsy surgery at our center. All were followed for at least 2 years after resections. Surgery was based on ictal EEG recordings. We examined ictal onsets and surgical outcome in subjects whose preoperative, interictal scalp EEGs during long-term monitoring (LTM) demonstrated only unilateral, well-defined focal discharges, and outcome in patients whose interictal EEGs during LTM showed bilateral, non-localized, or multifocal epileptiform patterns. RESULTS We found that 26 subjects exhibited only unilateral, unifocal, interictal epileptiform patterns. In all 26 cases (100%) clinical seizures arose from the regions expected by the interictal findings (P<0.0001, Sign test). At last follow-up 77% (20/26) of these patients were seizure-free, while 23% (6/26) had >75% reduction in seizures. This compares to the remaining patients, of whom 34% (34/100) were seizure-free, 41% (41/100) had >75% reduction in seizures, and 25% (25/100) had <75% reduction in seizures (P=0.0001, Fishers Exact test). CONCLUSIONS Strictly unifocal, interictal epileptiform patterns on scalp EEG, though seen in a minority of subjects, may be an important, independent factor in evaluating subjects with intractable extratemporal, localization-related epilepsy for surgical therapy. This finding is highly predictive of both ictal onsets and successful postsurgical outcome.

Is Partial Epilepsy Progressive? Ten‐Year Follow‐Up of EEG and Neuropsychological Changes in Adults with Partial Seizures

Summary: Purpose: This study was undertaken to determine what changes, if any, occur in the electroencephalogram (EEG) and in neuropsychological test findings of adults with medically intractable complex partial epilepsy over a 10‐year period.

Effect of vagus nerve stimulation on adults with pharmacoresistant generalized epilepsy syndromes.

INTRODUCTION Although vagus nerve stimulation (VNS) therapy is approved for the treatment of partial onset seizures, its efficacy for generalized seizures has not been fully evaluated. This Investigational Device Exemption assessed the outcome of VNS therapy among patients with generalized epilepsy syndromes. METHODS Sixteen patients with pharmacoresistant generalized epilepsy syndromes and stable antiepileptic drug (AED) regimens were implanted with the VNS therapy device and were evaluated for changes in seizure frequency and type between baseline and follow-up of 12-21 months. RESULTS The patients experienced a statistically significant overall median seizure frequency reduction of 43.3% (P = 0.002, Wilcoxon signed rank test) after 12-21 months of VNS therapy. Types of seizures that may involve a fall or collapse decreased with reductions in the frequency of myoclonic (60% reduction, n = 9; P = 0.016, Wilcoxon signed rank test), tonic (75% reduction, n = 8, NS), atonic (98.6%, n = 3, NS), and clonic seizures (86.7%, n = 1, NS). CONCLUSION The benefits of reduced seizure frequency and reduced risk of injury merit consideration of VNS therapy for patients with pharmacoresistant generalized seizure syndromes.