D. R. Fish

Identification of EEG events in the MR scanner: the problem of pulse artifact and a method for its subtraction.

Triggering functional MRI (fMRI) image acquisition immediately after an EEG event can provide information on the location of the event generator. However, EEG artifact associated with pulsatile blood flow in a subject inside the scanner may obscure EEG events. This pulse artifact (PA) has been widely recognized as a significant problem, although its characteristics are unpredictable. We have investigated the amplitude, distribution on the scalp, and frequency of occurrence of this artifact. This showed large interindividual variations in amplitude, although PA is normally largest in the frontal region. In five of six subjects, PA was greater than 50 microV in at least one of the temporal, parasagittal, and central channels analyzed. Therefore, we developed and validated a method for removing PA. This subtracts an averaged PA waveform calculated for each electrode during the previous 10 s. Particular attention has been given to reliable ECG peak detection and ensuring that the average PA waveform is free of other EEG artifacts. Comparison of frequency spectra for EEG recorded outside and inside the scanner, with and without PA subtraction, showed a clear reduction in artifact after PA subtraction for all four frequency ranges analyzed. As further validation, lateralized epileptiform spikes were added to recordings from inside and outside the scanner: PA subtraction significantly increased the proportion of these spikes that were correctly identified and decreased the number of false spike detections. We conclude that in some subjects, EEG/fMRI studies will be feasible only using PA subtraction.

Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy.

OBJECTIVE--To record non-invasively ictal cardiorespiratory variables. METHODS--Techniques employed in polysomnography were used in patients with epilepsy undergoing EEG-video recording at a telemetry unit. RESULTS--Apnoea (> 10, range > 10-63, mean 24 s) was seen in 20 of 47 clinical seizures (three secondary generalised, 16 complex partial, and one tonic) and 10 of 17 patients. Apnoea was central in 10 patients, but obstructive apnoea was also recorded in three of 10. Oxyhaemoglobin saturation (SpO2) dropped to less than 85% in 10 seizures (six patients). An increase in heart rate was common (91% of seizures). Bradycardia/sinus arrest was documented in four patients (mean maximum RR interval 5.36, range 2.8-8.6 s) but always in the context of a change in respiratory pattern. CONCLUSION--Ictal apnoea was often seen. The occurrence of bradycardia in association with apnoea suggests the involvement of cardiorespiratory reflexes. Similar mechanisms may operate in cases of sudden death in epilepsy.

Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder

We describe a distinctive epilepsy syndrome in six families, which is the first partial epilepsy syndrome to follow single gene inheritance. The predominant seizure pattern had frontal lobe seizure semiology with clusters of brief motor attacks occurring in sleep. Onset was usually in childhood, often persisting through adult life. Misdiagnosis as night terrors, nightmares, hysteria, or paroxysmal nocturnal dystonia was common, and the inheritance pattern was often not appreciated. This autosomal dominant epilepsy syndrome is ideal for identification of partial epilepsy genes.

The clinical features and prognosis of pseudoseizures diagnosed using video‐EEG telemetry

A total of 110 patients underwent diagnostic evaluation for attacks of uncertain origin by means of video-EEG telemetry and had a diagnosis of pseudoseizures confirmed. Eighty-six patients (78%) were female, mean age of onset 25 years, and mean duration of attacks was 3 years. Many of the patients had erroneously been thought to be suffering from epilepsy. The attacks could be divided into two broad categories: attacks of collapse (one-third) and attacks with prominent motor activity (two-thirds). In some patients, the attacks were associated with incontinence and injury. The differential diagnosis and clinical features of the attacks are described. Additional psychiatric features were present in 52 (47%) patients. Follow-up (for a median 5 years; range, 1 to 14 years) showed that 40% of these patients stopped having pseudoseizures. This favorable outcome was associated with being female, leading an independent life, a formal psychological approach to therapy and counseling, and the absence of coexisting epilepsy, but not with the duration of pseudoepilepsy, prior episodes of pseudostatus, the coexistence of overt psychiatric disease, or the clinical features of the attacks.

Event-Related fMRI with Simultaneous and Continuous EEG: Description of the Method and Initial Case Report

We report on the initial imaging findings with a new technique for the simultaneous and continuous acquisition of functional MRI data and EEG recording. Thirty-seven stereotyped interictal epileptiform discharges (spikes) were identified on EEG recorded continuously during the fMRI acquisition on a patient with epilepsy. Localization of the BOLD activation associated with the EEG events was consistent with previous findings and EEG source modeling. The time course of activation was comparable with the physiological hemodynamic response function (HRF). The new methodology could lead to novel and important applications in many areas of neuroscience.

Functional magnetic resonance imaging of human absence seizures

We studied a patient with idiopathic generalized epilepsy and frequent absences, using electroencephalogram‐correlated functional magnetic resonance imaging. Four prolonged runs of generalized spike‐wave discharge occurred during a 35‐minute experiment. Time‐locked activation was observed bilaterally within the thalami in conjunction with widespread but symmetrical cortical deactivation with a frontal maximum. We demonstrate the reciprocal participation of focal thalamic and widespread cortical networks during human absence seizures and suggest reductions in cortical blood flow, in response to synchronized electroencephalogram activity. Ann Neurol 2003;53:663–667

Sudden Death in Epilepsy: A Study of Incidence in a Young Cohort with Epilepsy and Learning Difficulty

Summary: Sudden death, often seizure related, may occur in patients with epilepsy. Population‐based incidence is probably on the order of 1:1,000/year. The incidence is much higher in selected groups, however. We wished to establish the incidence of sudden unexpected death (SUD) in a young cohort with severe epilepsy and learning difficulties. The study cohort included 310 pupils with epilepsy enrolled at a special residential school between April 1970 and April 1993. The follow‐up period totaling 4,135 person‐years included a period of residence at the school as well as time after leaving. Age and sex standardized overall mortality ratio was 15.9 [95% confidence interval (CI) 10.6–23.0], with 20 of 28 deaths considered epilepsy related. An incidence of sudden death cases of 1:295/year was noted. All 14 sudden deaths occurred when the pupils were not under the close supervision of the school and most were unwitnessed, which has implications for prevention.

Hemodynamic correlates of epileptiform discharges: an EEG-fMRI study of 63 patients with focal epilepsy.

Using continuous EEG-correlated fMRI, we investigated the Blood Oxygen Level Dependent (BOLD) signal correlates of interictal epileptic discharges (IEDs) in 63 consecutively recruited patients with focal epilepsy. Semi-automated spike detection and advanced modeling strategies are introduced to account for different EEG event types, and to minimize false activations from uncontrolled motion. We show that: (1) significant hemodynamic correlates were detectable in over 68% of patients in whom discharges were captured and were highly, but not entirely, concordant with site(s) of presumed seizure generation where known; (2) deactivations were less concordant and may non-specifically reflect the consequential or downstream effects of IEDs on brain activity; (3) a striking pattern of retrosplenial deactivation was observed in 7 cases mainly with focal discharges; (4) the basic hemodynamic response to IEDs is physiological; (5) incorporating information about different types of IEDs, their durations and saturation effects resulted in more powerful models for the detection of fMRI correlates; (6) focal activations were more likely when there was good electroclinical localization, frequent stereotyped spikes, less head motion and less background EEG abnormality, but were also seen in patients in whom the electroclinical focus localization was uncertain. These findings provide important new information on the optimal use and interpretation of EEG-fMRI in focal epilepsy and suggest a possible role for EEG-fMRI in providing new targets for invasive EEG monitoring.

Frequency and characteristics of dual pathology in patients with lesional epilepsy

We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (521, vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5-or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions. Further clarification of this issue would improve our understanding of the pathogenesis of mesial temporal sclerosis and lead to more efficient planning of surgical treatment for lesional epilepsy.

EEG-fMRI of idiopathic and secondarily generalized epilepsies

We used simultaneous EEG and functional MRI (EEG-fMRI) to study generalized spike wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE). Recent studies have demonstrated thalamic and cortical fMRI signal changes in association with GSW in idiopathic generalized epilepsy (IGE). We report on a large cohort of patients that included both IGE and SGE, and give a functional interpretation of our findings. Forty-six patients with GSW were studied with EEG-fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in 25 of 36 individual patients who had GSW during EEG-fMRI. This was seen in thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%), and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were predominantly positive and cortical changes predominantly negative. Group analysis showed a negative BOLD response in the cortex in the IGE group and to a lesser extent a positive response in thalamus. Thalamic activation was consistent with its known role in GSW, and its detection in individual cases with EEG-fMRI may in part be related to the number and duration of GSW epochs recorded. The spatial distribution of the cortical fMRI response to GSW in both IGE and SGE involved areas of association cortex that are most active during conscious rest. Reduction of activity in these regions during GSW is consistent with the clinical manifestation of absence seizures.