EEG source imaging concordance with intracranial EEG and epileptologist review in focal epilepsy.

EEG source imaging is becoming widely used for the evaluation of medically refractory focal epilepsy. The validity of EEG source imaging has been established in several studies comparing source imaging to the surgical resection cavity and subsequent seizure freedom. We present a cohort of 87 patients and compare EEG source imaging of both ictal and interictal scalp EEG to the seizure onset zone on intracranial EEG. Concordance of EEG source imaging with intracranial EEG was determined on a sublobar level and was quantified by measuring the distance between the source imaging result and the centroid of the active seizure onset zone electrodes. The EEG source imaging results of a subgroup of 26 patients with high density 76-channel EEG were compared with the localization of three experienced epileptologists. Of 87 patients, 95% had at least one analysis concordant with intracranial EEG and 74% had complete concordance. There was a higher rate of complete concordance in temporal lobe epilepsy compared to extratemporal (89.3 and 62.8%, respectively, P = 0.015). Of the total 282 analyses performed on this cohort, higher concordance was also seen in temporal discharges (95%) compared to extratemporal (77%) (P = 0.0012), but no difference was seen comparing high-density EEG with standard (32-channel) EEG. Subgroup analysis of ictal waveforms showed greater concordance for ictal spiking, compared with rhythmic activity, paroxysmal fast activity, or obscured onset. Median distances from the dipole and maximum distributed source to a centroid of seizure onset zone electrodes were 30.0 and 32.5 mm, respectively, and the median distances from dipole and maximum distributed source to nearest seizure onset zone electrode were 22.8 and 21.7, respectively. There were significantly shorter distances in ictal spiking. There were shorter distances in patients with Engel Class 1 outcome from surgical resection compared to patients with worse outcomes. For the subgroup of 26 high-density EEG patients, EEG source localization had a significantly higher concordance (92% versus 65%), sensitivity (57% versus 35%) and positive predictive value (60% versus 36%) compared with epileptologist localization. Our study demonstrates good concordance between ictal and interictal source imaging and intracranial EEG. Temporal lobe discharges have higher concordance rates than extratemporal discharges. Importantly, this study shows that source imaging has greater agreement with intracranial EEG than visual review alone, supporting its role in surgical planning.

Frequent sleep-related bitemporal focal seizures in transient epileptic amnesia syndrome: Evidence from ictal video-EEG.

Two patients who shared similar presenting clinical features of anterograde and retrograde autobiographical amnesia typical of transient epileptic amnesia (TEA) underwent prolonged video electroencephalogram (VEEG) monitoring and were found to have sleep-activated epileptiform activity and frequent subclinical bitemporal seizures predominantly during sleep. Case 1 is a 59-year-old woman whose presenting complaint was memory impairment. Over 18 months, she had three distinct 8-h-long episodes of confusion and disorientation with persistent anterograde and retrograde autobiographical amnesia. VEEG recorded frequent interictal bitemporal sharp waves confined to sleep, and 14 subclinical seizures, also mostly during sleep. Case 2 is a 50-year-old woman with known focal epilepsy also presented with memory complaints. Over the course of 1 year, she had two discrete 2-h-long episodes of amnesia, with ongoing anterograde and retrograde autobiographical amnesia. VEEG recorded independent bitemporal sharp waves, and 14 subclinical seizures during sleep and drowsiness. Memory impairment improved in both patients with successful treatment of their seizures. Although the etiology of accelerated long-term forgetting (ALF) and remote memory impairment (RMI) in transient epileptic amnesia (TEA) is unknown, these cases suggest frequent sleep-related seizures may contribute, and they highlight the importance of video-EEG monitoring.

Routine vs extended outpatient EEG for the detection of interictal epileptiform discharges.

OBJECTIVE: To compare the yield of epileptiform abnormalities on 30-minute recordings with those greater than 45 minutes. METHODS: We performed a prospective observational cross-sectional study of all outpatient routine EEGs comparing the rate of interictal epileptiform discharges (IEDs) and clinical events during the initial 30 minutes (routine) with those occurring in the remaining 30-60 minutes (extended). A relative increase of 10% was considered clinically significant. RESULTS: EEGs from 1,803 patients were included; overall EEG duration was 59.4 minutes (SD ±6.5). Of 426 patients with IEDs at any time during the EEG, 81 (19.1%, 95% confidence interval 15.6-23) occurred only after the initial 30 minutes. The rate of late IEDs was not associated with age, indication, IED type, or sleep deprivation. Longer recording times also increased event capture rate by approximately 30%. CONCLUSIONS: The yield of IED and event detection is increased in extended outpatient EEGs compared to 30-minute studies.

Autoimmune epilepsy: clinical characteristics and response to immunotherapy.

OBJECTIVE: To describe clinical characteristics and immunotherapy responses in patients with autoimmune epilepsy. DESIGN: Observational, retrospective case series. SETTING: Mayo Clinic Health System. PATIENTS: Thirty-two patients with an exclusive (n=11) or predominant (n=21) seizure presentation in whom an autoimmune etiology was suspected (on the basis of neural autoantibody [91%], inflammatory cerebrospinal fluid [31%], or magnetic resonance imaging suggesting inflammation [63%]) were studied. All had partial seizures: 81% had failed treatment with 2 or more antiepileptic drugs and had daily seizures and 38% had seizure semiologies that were multifocal or changed with time. Head magnetic resonance imaging was normal in 15 (47%) at onset. Electroencephalogram abnormalities included interictal epileptiform discharges in 20; electrographic seizures in 15; and focal slowing in 13. Neural autoantibodies included voltage-gated potassium channel complex in 56% (leucine-rich, glioma-inactivated 1 specific, 14; contactin-associated proteinlike 2 specific, 1); glutamic acid decarboxylase 65 in 22%; collapsin response- mediator protein 5 in 6%; and Ma2, N-methyl-D-aspartate receptor, and ganglionic acetylcholine receptor in 1 patient each. INTERVENTION: Immunotherapy with intravenous methylprednisolone; intravenous immune globulin; and combinations of intravenous methylprednisolone, intravenous immune globulin, plasmapheresis, or cyclophosphamide. MAIN OUTCOME MEASURE: Seizure frequency. RESULTS: After a median interval of 17 months (range, 3-72 months), 22 of 27 (81%) reported improvement postimmunotherapy; 18 were seizure free. The median time from seizure onset to initiating immunotherapy was 4 months for responders and 22 months for nonresponders (P<.05). All voltage-gated potassium channel complex antibody-positive patients reported initial or lasting benefit (P<.05). One voltage-gated potassium channel complex antibody-positive patient was seizure free after thyroid cancer resection; another responded to antiepileptic drug change alone. CONCLUSION: When clinical and serological clues suggest an autoimmune basis for medically intractable epilepsy, early-initiated immunotherapy may improve seizure outcome.

Influence of subtraction ictal SPECT on surgical management in focal epilepsy of indeterminate localization: a prospective study.

The impact of functional imaging tests on the decision-making and planning process for epilepsy surgery has never been prospectively assessed. We prospectively evaluated 50 consecutively eligible patients whose noninvasive evaluations showed nonlocalized findings and determined how their SISCOM (subtraction ictal SPECT [single photon emission computed tomography] co-registered to MRI [magnetic resonance imaging]) data altered consensus decisions for epilepsy surgery. At an epilepsy surgery conference where each patient was discussed, consensus decisions were documented after a standardized presentation of data from the noninvasive evaluation (SISCOM findings initially were excluded). Consensus decisions were again documented after presentation of SISCOM data. Consensus decisions changed for 10 of 32 patients (31%) with localizing SISCOM results, whereas the decision changed in only 1 of 18 patients (6%) with nonlocalizing SISCOM results (P<.05). Changes in consensus decisions were as follows: (1) intracranial electrode implantation (IEI) was obviated and resective surgery was recommended (n=2); (2) resective surgery or further evaluation for patients initially not considered surgical candidates (n=2); (3) IEI in patients for whom it was not recommended initially (n=3); (4) increased IEI coverage (n=3); and (5) antiepileptic drug trial or vagal nerve stimulation was recommended instead of IEI (n=1). For some patients whose noninvasive evaluations did not clearly localize a surgical focus, SISCOM data can have a major impact on decisions to recommend resective epilepsy surgery or IEI.

Ictal source analysis: localization and imaging of causal interactions in humans.

We propose a new integrative approach to characterize the structure of seizures in the space, time, and frequency domains. Such characterization leads to a new technical development of ictal source analysis for the presurgical evaluation of epilepsy patients. The present new ictal source analysis method consists of three parts. First, a three-dimensional source scanning procedure is performed by a spatio-temporal FINE source localization method to locate the multiple sources responsible for the time evolving ictal rhythms at their onsets. Next, the dynamic behavior of the sources is modeled by a multivariate autoregressive process (MVAR). Lastly, the causal interaction patterns among the sources as a function of frequency are estimated from the MVAR modeling of the source temporal dynamics. The causal interaction patterns indicate the dynamic communications between sources, which are useful in distinguishing the primary sources responsible for the ictal onset from the secondary sources caused by the ictal propagation. The present ictal analysis strategy has been applied to a number of seizures from five epilepsy patients, and their results are consistent with observations from either MRI lesions or SPECT scans, which indicate its effectiveness. Each step of the ictal source analysis is statistically evaluated in order to guarantee the confidence in the results.

3D source localization of interictal spikes in epilepsy patients with MRI lesions.

The present study aims to accurately localize epileptogenic regions which are responsible for epileptic activities in epilepsy patients by means of a new subspace source localization approach, i.e. first principle vectors (FINE), using scalp EEG recordings. Computer simulations were first performed to assess source localization accuracy of FINE in the clinical electrode set-up. The source localization results from FINE were compared with the results from a classic subspace source localization approach, i.e. MUSIC, and their differences were tested statistically using the paired t-test. Other factors influencing the source localization accuracy were assessed statistically by ANOVA. The interictal epileptiform spike data from three adult epilepsy patients with medically intractable partial epilepsy and well-defined symptomatic MRI lesions were then studied using both FINE and MUSIC. The comparison between the electrical sources estimated by the subspace source localization approaches and MRI lesions was made through the coregistration between the EEG recordings and MRI scans. The accuracy of estimations made by FINE and MUSIC was also evaluated and compared by R(2) statistic, which was used to indicate the goodness-of-fit of the estimated sources to the scalp EEG recordings. The three-concentric-spheres head volume conductor model was built for each patient with three spheres of different radii which takes the individual head size and skull thickness into consideration. The results from computer simulations indicate that the improvement of source spatial resolvability and localization accuracy of FINE as compared with MUSIC is significant when simulated sources are closely spaced, deep, or signal-to-noise ratio is low in a clinical electrode set-up. The interictal electrical generators estimated by FINE and MUSIC are in concordance with the patients' structural abnormality, i.e. MRI lesions, in all three patients. The higher R(2) values achieved by FINE than MUSIC indicate that FINE provides a more satisfactory fitting of the scalp potential measurements than MUSIC in all patients. The present results suggest that FINE provides a useful brain source imaging technique, from clinical EEG recordings, for identifying and localizing epileptogenic regions in epilepsy patients with focal partial seizures. The present study may lead to the establishment of a high-resolution source localization technique from scalp-recorded EEGs for aiding presurgical planning in epilepsy patients.

Spectral analysis of slow modulation of EEG amplitude and cardiovascular variables in subjects with postural tachycardia syndrome.

OBJECTIVE: Previous studies have reported slow (<0.5 Hz) modulation of electroencephalographic (EEG) background amplitude and suggested that this reflects periodic neuronal activity in the brainstem, such as may be recorded from cardiovascular and respiratory centers in animals. We searched for a relationship between EEG amplitude modulation and modulation of simultaneously recorded cardiovascular variables and attempted to determine whether this relationship was altered in subjects with postural tachycardia syndrome (POTS). METHODS: We recorded EEG, blood flow velocity in the middle cerebral artery (MCA), heart rate, respirations, and blood pressure from subjects with POTS and controls during head-up tilt. Time-frequency analysis of 0.512-s epochs of EEG was performed to determine peak alpha amplitude. Spectra were divided into 3 bands: ultraslow, middle, and respiratory. RESULTS: EEG alpha amplitude modulation in all frequency bands was reduced in POTS subjects while supine. EEG modulation decreased in controls with head-up tilt but not in POTS subjects. Heart rate modulation in the respiratory frequency band decreased with head-up tilt and was significantly less (P<0.02) in ultraslow and respiratory frequency bands in POTS subjects after head-up tilt. Blood pressure and MCA flow velocity modulation in middle and respiratory bands increased with head-up tilt to a greater degree in POTS subjects. Blood pressure and MCA flow velocity modulation frequencies were moderately correlated, but correlations between EEG and cardiovascular variable modulation frequencies were generally low, being highest in the respiratory band but not statistically significant. CONCLUSION: There are subtle differences in EEG amplitude modulation in subjects with POTS. Altered EEG amplitude modulation in POTS may reflect altered brainstem physiology in this disorder.

Use of principal component analysis in the frequency domain for mapping electroencephalographic activities: comparison with phase-encoded Fourier spectral analysis.

Principal component analysis (PCA) can separate multichannel electroencephalographic (EEG) epochs into linearly independent (temporally and spatially noncorrelated) components. Results of PCA include component time-series waveforms and factors representing the contribution of each component to each electrode; these factors may be displayed as contour maps representing the topographic distribution of each component. However, PCA often does not achieve the most useful separation of components. PCA may be performed in the frequency domain to potentially improve results. After inspecting principal components of the frequency spectra, spectral values in a selected frequency range are multiplied by a chosen factor to emphasize (or de-emphasize) these frequencies and PCA is redone, promoting the separation of different frequencies into different components. Phase-encoded Fourier spectral analysis (PEFSA) uses multichannel complex Fourier spectra (amplitude and phase) to obtain positive or negative (phase-encoded) potentials at each electrode for any selected frequency. These may be displayed as a contour map representing the topographic distribution of the selected frequency. Applying both techniques, we found that EEG activities of differing frequency were readily separated by PEFSA, while standard PCA often mixed activities with different frequencies into a single component. However, frequency-domain PCA gave a component whose spatial distribution well matched PEFSA results. PCA is superior to PEFSA for separating activities with overlapping frequencies but differing spatial distributions. Preservation of phase information is an advantage of PEFSA and PCA over topographic maps that represent only amplitude (or power) at a given frequency. PCA or PEFSA maps can serve as a starting point for source localization.

Abnormal corticomuscular coherence is associated with the small amplitude cortical myoclonus in Parkinson's disease.

Coherence is the degree of time-locked correlation between two signals as a function of frequency. The purpose of this study was to test the following hypotheses: (1) corticomuscular coherence is abnormally increased in those Parkinson's disease (PD) patients with small amplitude cortical myoclonus, and (2) corticomuscular coherence peaks around the time of the myoclonus electromyographic (EMG) discharge. We studied Parkinson's disease patients with and without myoclonus and controls. The data were digitally collected and processed off-line with EMG rectification, creation of 511-msec epochs, Fast-Fourier transform, and coherence analysis. In the 12 to 30 Hz frequency band, but not at 30 to 60 Hz or above, coherence peaks were observed in the PD subjects with myoclonus that were significantly greater than in the control subjects (P < 0.001) and in PD subjects without myoclonus (P < 0.001). The abnormal coherence values are evidence for abnormal rhythmic activity in cortical motor areas in those Parkinson's disease patients with myoclonus. In combination with previous findings on back-averaging, our results show that this myoclonus occurs when neuronal populations are driven to an extreme amount of synchronous activity with higher corticomuscular coherence values. These results have mechanistic implications for cortical dysfunction in Parkinson's disease and for cortical myoclonus in general.

A general method for remontaging based on a singular value decomposition algorithm.

The authors developed a general mathematic algorithm to convert any montage (referential, bipolar, or Laplacian) to any other by linear transformation. Input and output montages are described by matrices, and singular value decomposition is used to find the linear transformation. An error signal can be calculated from the input data to monitor remontaging validity. This algorithm also identifies output channels that cannot be obtained from the specified input. The authors tested this algorithm using an instrument that retrieves digitally encoded EEG data from videotape and produces signals in referential or bipolar form. They obtained good agreement when they compared referential and Laplacian data derived from bipolar output with the same montages calculated from referential output for the same EEG segment.

Role and limitations of routine and ambulatory scalp electroencephalography in diagnosing and managing seizures.

The scalp electroencephalogram (EEG) is the cornerstone in the diagnosis and treatment of seizure disorders. The EEG, with its excellent temporal resolution, provides a direct measurement of cortical electrophysiology, revealing, for example, the presence of interictal epileptiform discharges that identify regions of an epileptogenic brain. We define the EEG characteristics of focal and generalized epileptiform discharges and provide evidence for their varying diagnostic importance in different patient populations. Identification of nonepileptiform EEG transients, such as wicket waves, small sharp spikes,rhythmic temporal theta activity, and 14- and 6-Hz positive bursts, that can be confused for epileptiform transients is emphasized. A final point is that the clinician must interpret EEG findings within the overall clinical context.