EEG-fMRI study of the interictal epileptic activity in patients with partial epilepsy

PURPOSE: To investigate Blood Oxygen Level Dependent (BOLD) responses to interictal epileptic discharges (IEDs) during EEG-correlated functional MRI (EEG-fMRI) in patients with partial epilepsy. METHODS: We studied eight patients who had a diagnosis of partial epilepsy and active spiking on routine scalp EEG recording. Sessions of continuous EEG-fMRI were recorded, and spikes (identified after online artifact removal) were used as events in the fMRI analysis. Regions of BOLD signal change in response to interictal epileptic discharge were assessed and epileptogenic zone localization was electroclinically identified. RESULTS: Eight patients with partial epilepsy were recruited (6 males, 2 females, mean age 18.5, mean onset age range 0.5-29). Two who underwent EEG-fMRI were excluded from further analysis: one due to absence of epileptic discharges, the other due to excessive head motion. Eight sessions of EEG-fMRI scanning in 6 patients were obtained: 6 with activation and deactivation, one with activation only, and one with deactivation only. Focal activations corresponding to electroclinical localization occurred in 7 sessions, 5 of which were maximal. CONCLUSIONS: Maximally activated areas detected by EEG-fMRI in patients with partial epilepsy appear to be concordant with epileptogenic areas as defined by electroclinical localization data. In most patients with focal epilepsy, positive BOLD responses seem to be mainly in epileptogenic zones and the corresponding contralateral areas. Responses to deactivation seem less associated with IEDs. So EEG-fMRI is a useful tool to study the pathophysiological mechanisms of epilepsy and may assist in presurgical evaluation of epilepsy.     

Ictal and interictal SPECT findings in childhood absence epilepsy.

The purpose of this study was to investigate the informative value of single photon emission tomography (SPECT) in relation to the pathophysiological functioning of the brain during absence seizures and the origin of ictal discharges in idiopathic generalized epilepsies (IGEs). Six patients with childhood absence epilepsy (CAE) were selected for the study and two consecutive SPECT sessions were performed concomitant with EEG recordings revealing normal results and during hyperventilation (HV) studies where the ictal discharges were induced either alone or accompanied by clinical absence seizures. All six patients had ictal discharges in their EEGs during HV and two of them also had clinical absences. SPECT findings during HV revealed an overall increase in the cerebral blood flow (CBF) with significantly higher values as compared to the baseline data. There was no indication for any focal origin in either the interictal or the ictal SPECT findings. Results of the study were supportive for the concept of subcortical origin for the absence seizures and they were also promising for the diagnostic value of ictal SPECT in epileptic cases with undetermined origin as to whether they were localization-related or generalized.     

A magnetization transfer imaging study in patients with temporal lobe epilepsy and interictal psychosis.

BACKGROUND: Findings from previous neuropathological and neuroimaging studies in patients with epilepsy and interictal psychosis have been inconclusive, and both focal and widespread brain abnormalities have been reported. Thus, further investigation with advanced in vivo magnetic resonance imaging (MRI) techniques, such as magnetization transfer imaging, capable of detecting more subtle brain abnormalities, is warranted. METHODS: Twenty patients with temporal lobe epilepsy and interictal psychosis were compared with 20 nonpsychotic patients. Patients were matched with respect to conventional MRI findings. Each group comprised of 10 patients with hippocampal sclerosis (6 left, 4 right) and 10 patients without focal lesions on MRI. A voxel-based analysis was used for the group comparisons. RESULTS: Voxel-based analysis revealed significant reductions of magnetization transfer ratio (an index of signal loss derived from magnetization transfer imaging) in the left superior and middle temporal gyri in the psychotic patients for the subgroup of patients with no focal lesions on MRI. There were no significant volumetric differences between the psychotic and nonpsychotic patients. CONCLUSIONS: Focal cortical magnetization transfer ratio abnormalities in the left temporal lobe unrelated to volume changes can be demonstrated in some temporal lobe epilepsy patients with interictal psychosis. Our findings might reflect subtle neuropathological abnormalities that are undetected by conventional MRI.     

Predictive variables of interictal psychosis in epilepsy

OBJECTIVE: To evaluate which variables predict interictal psychosis in epilepsy. METHODS: The authors reviewed the biological backgrounds, clinical characteristics, and EEG findings in 246 patients with epilepsy and interictal psychosis and in 658 control patients with epilepsy and no psychotic history. With a logistic regression approach, the significance of each variable for the development of interictal psychosis was evaluated. RESULTS: There are significant differences in family history of psychosis, age at onset of epilepsy, type of epilepsy, lateralization of epileptiform discharges, and level of intelligence between patients with interictal psychosis and those without it. Subsequent logistic regression analysis with all variables demonstrated that family history of psychosis, age at onset of epilepsy, type of seizures, and level of intelligence significantly correlated with psychosis. CONCLUSIONS: A family history of psychosis, earlier age at onset of epilepsy, complex partial seizures or generalized tonic clonic seizures, and borderline intellectual functioning were the most important predictors for development of interictal psychosis.     

The interictal behavior syndrome of temporal lobe epilepsy.

A distinct syndrome of interictal behavior changes occurs in many patients with temporal lobe epilepsy. These changes include alterations in sexual behavior, religiosity, and a tendency toward extensive, and in some cases compulsive, writing and drawing. The concomitants of abnormal limbic acitivity therefore include behavior alterations as well as manifest seizures. The demonstration of interictal spike activity in temporal structures provides a pathophysiologic basis for this syndrome. The constellation of behavioral changes may be of great diagnostic value. In addition, it provides an example of a human behavioral syndrome assocaited with dysfunction at specific anatomic loci. The behavior syndrome of temporal lobe epilepsy may prove to be a useful model in studies on the neural substrates for behavior.     

Intensive monitoring of interictal psychosis in epilepsy

Ten epileptic patients developed interictal psychosis while being treated in hospital for seizure control. They were subjected to intensive behavioral, video-electroencephalographic, and serum anticonvulsant monitoring for an average of 7.1 weeks in a specialized epilepsy unit. In 9 patients, the interictal psychosis was indistinguishable from acute schizophrenia. Only 5 of these patients had complex partial seizures; the other 4 showed evidence of generalized epilepsies. Thus a “unique” association between schizophreniform psychosis and complex partial seizures, noted by previous authors, could not be confirmed. Only 1 patient showed normalization of the electroencephalogram during psychosis and an inverse relationship between psychosis and seizure frequency. In most cases the emergence of psychosis could not be explained. Interictal psychosis in epilepsy appears to be a spectrum of disorders that may be multifactorially determined.     

Factors affecting interictal spike discharges in adults with epilepsy.

We investigated various factors affecting interictal spike discharges (ISDs) in standard interictal EEGs of 203 consecutive cases with seizure(s). 94 EEGs (46%) showed ISDs. Yield was maximum (68%) when recordings were done within 2 days of a seizure; beyond this period, incidence of ISD did not change with time from the last seizure. EEGs of patients having greater than 12 seizures/year were more likely to contain ISD (68%) than the records of cases with less than 12 attacks/year (37-41%; P less than 0.001). Age and neurological status at the time of EEG, etiology and anticonvulsants did not influence the frequency of ISD. Analysis of serial EEGs (n = 512) from the study group showed that if initial 3 EEGs lacked ISD, yield from further standard EEGs is small.     

Computerized spectral analysis of the interictal EEG in epilepsy

Eight seizure patients without encephalopathy, frequent seizures, brain lesion, or medication intoxication had significant slowing of alpha-frequency activity, as compared to nonepileptic controls, that was evident in compressed spectral analysis but not in standard EEG. Those patients with cognitive or behavioral problems or taking more than one antiepileptic medication had a greater degree of slowing. Differences between seizure patients with and without cognitive or behavioral symptoms, and between specific antiepileptic drugs, were suggested but could not be assigned significance due to small numbers. The findings suggest that interictal changes in brain function that are not revealed by standard EEG may relate to observed changes in interictal behavior and cognition, and that computerized spectral analysis of the interictal EEG may be of value in the assessment of seizure patients before and during therapy.     

Sleep-EEG modulation of interictal epileptiform discharges in adult partial epilepsy: a spectral analysis study.

INTRODUCTION: In order to define accurately the relationship between EEG components (spindles, delta and theta frequencies) and the occurrence of interictal epileptiform discharges (IED) during sleep in partial epilepsy, a correlation study between spike overnight distribution and EEG spectral power time series was performed. METHODS: Eighteen patients (mean age: 24.7+/-5.5 years) affected by partial epilepsy underwent continuous EEG-polysomnography. The temporal series of Slow Wave Activity (SWA), Sigma Activity (SA) and Theta Band (TB), derived from spectral analysis, were obtained from a spike-free and pathologic alteration-free derivation, contralateral to the most active lead, where the IED count was performed. Relationships between SA, SWA and TB and time series of IED were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significantly higher correlation between IED and SWA in 12 subjects; a significantly higher correlation between IED and SA in three subjects and a significant correlation with TB in three cases. CONCLUSIONS: Data suggest that in most adult patients with partial epilepsy IED production during sleep is facilitated by the action of synchronizing mechanisms which are active during NREM sleep and lead to the appearance of EEG delta waves. Nevertheless evidence is given of two smaller groups of patients. In one of them IED are more sensitive to the promoting action of the spindle generating mechanism, active during stage 2 of NREM sleep. In the other one the promoting action of TB, characterizing EEG during stage 1 and REM sleep, is evident.     

Ictal chronology and interictal spikes predict perfusion patterns in temporal lobe epilepsy: a multivariate study.

Typical (TPP) and atypical (APP) perfusion patterns (PP) may be seen in ictal SPECT of patients with temporal lobe epilepsy (TLE). APP may pose problem in the lateralization of the epileptogenic zone (EZ). We aimed to investigate predictive variables for the occurrence of TPP and APP. Fifty-one TLE patients were submitted to successful anterior-mesial temporal lobectomy. Univariate (UVA) and multivariate (MVA) analysis were performed upon clinical data, distribution of interictal spikes, and ictal chronology of seizures. From MVA, a final predictive model (FPM) was determined to better predict TPP and APP. Forty patients showed TPP (78.5%) and 11 patients APP (21.5%). Accuracy of ictal SPECT was higher in the unilateral (UIS) than in the bilateral (BIS) interictal spikes group (P = 0.05). FPM showed that patients exhibiting BIS, with shorter proportion of the electrographic seizure occurring after completion of tracer injection, and longer clinical than EEG seizure duration had more APP (P = 0.003). Generalized tonic-clonic seizures did not result in more APP. We concluded that analysis of ictal SPECT in TLE requires the knowledge of TPP and APP, the distribution of interictal spikes on temporal lobes and the ictal chronology of seizures. BIS showed that beyond a more complex epileptogenicity and seizure propagation, they may also lead to APP.     

发作间期SPECT在癫痫外科中的临床应用

目的 探讨发作间期SPECT在顽固性癫痫患者术前致痫灶定位的临床应用价值。方法 本组57例患者，男43例，女14例，年龄3～40岁，病程1～24年。所有患者术前均行了EEG检查和CT／MRI检查，同时行发作间期SPECT检查。根据发作间期SPECT的结果，并结合EEG和CT／MRI检查结果对患者进行手术，术中将发作间期SPECT结果与ECoG监测进行对比，术后通过3年以上的随访，观察手术疗效。结果 SPECT与ECoG监测进行对比，发作间期SPECT对致痫灶的定侧率为94．74％，定位率为56．14％。术后3年以上随访显示手术的有效率为77．20％，优良率为52．63％。结论 发作间期SPECT在术前致痫灶定位上有一定的价值，但需结合EEG和CT／MRI，同时术中还应在ECoG监测下进行手术，以提高癫痫外科的疗效。     

A neuropsychological study of patients with temporal lobe epilepsy and chronic interictal psychosis

PURPOSE: To characterize the pattern of cognitive deficits in patients with temporal lobe epilepsy (TLE) and interictal (schizophrenia-like) psychosis and to examine the relationship between neuropsychological deficits and Magnetization transfer imaging. METHODS: Twenty patients with TLE and interictal psychosis were compared to 20 non-psychotic TLE patients. Patients were matched with respect to premorbid IQ, age and conventional MRI findings. A battery of neuropsychological tests was administered. The neuropsychological tests which showed significant group differences were used for correlational analysis with magnetization transfer ratio (MTR) which provides a quantitative measure of macromolecular structural integrity. RESULTS: Patients with interictal psychosis were significantly more impaired on executive and semantic memory tasks than the non-psychotic TLE group. Vocabulary test scores correlated significantly with MTR reduction in the left fusiform gyrus in the psychotic but not the non-psychotic group. DISCUSSION: In this study, patients with TLE and interictal psychosis were more cognitively impaired than non-psychotic TLE patients. Our findings suggest that the cognitive deterioration in these patients may occur as the illness progresses and the causes for this are probably multifactorial. Our study also provides further evidence that MTR may be useful in investigating structural correlates of cognitive impairment.     

An interictal study of partial epilepsy using positron emission tomography and the oxygen - 15 inhalation technique.

Data from ten patients with complex partial seizures who underwent positron emission tomography using the 15-0 inhalation technique are presented. Decreased flow and metabolism are noted in the hemisphere ipsilateral to the EEG focus, but, in patients with unilateral foci, bilateral changes in temporal cortex are detected. Other areas maximally affected include the basal ganglia, and the cerebellum. The possible role of anticonvulsant drugs in these findings is discussed.     

Ictal and interictal ECD-SPECT for focus localization in epilepsy

Forty-one ECD (Technetium-99m-ethyl cysteinate dimer) SPECT investigations were undertaken in the course of a presurgical diagnostic work-up in 23 patients with pharmacoresistant focal epilepsy. In 21 patients, both an ictal and interictal SPECT were conducted. In the patients receiving ictal SPECT the tracer was injected between 7 and 30 s after the seizure onset. Of the interictal SPECTs 17 of 23 showed focal hypoperfusion which was consistent in 17 cases (74%) with the area of the electrophysiological focus (EF) and 6 patients had a normal interictal SPECT. Of the ictal SPECTs 18 of 21 (86%) showed regional hyperperfusion, 18 of them in the same location as the EF. Ictal SPECT showed a hypoperfusion similar to that in interictal SPECT in another 3 patients. In these cases seizure duration was short (28–54 s), so that the tracer reached the brain postictally. Our results show that ictal ECD-SPECT is an effective method for demonstrating an epileptogenic focus. Possible reasons for false-negative ictal SPECT results are discussed.     

Structural brain abnormalities in patients with schizophrenia, epilepsy, and epilepsy with chronic interictal psychosis.

Chronic interictal psychotic syndromes, often resembling schizophrenia, develop in some patients with epilepsy. Although widespread brain abnormalities are recognized as characteristic of schizophrenia, prevailing but controversial hypotheses on the co-occurrence of epilepsy and psychosis implicate left temporal lobe pathology. In this study, quantitative MRI methods were used to address the regional specificity of structural brain abnormalities in patients with epilepsy plus chronic interictal psychosis (E+PSY, n=9) relative to three comparison groups: unilateral temporal lobe epilepsy without chronic psychosis (TLE, n=18), schizophrenia (SCZ, n=46), and healthy control subjects (HC, n=57). Brain measures, derived from a coronal spin-echo MRI sequence, were adjusted for age and cerebral volume. Relative to HC, all patient groups had ventricular enlargement and smaller temporal lobe, frontoparietal, and superior temporal gyrus gray matter volumes, with the extent of these abnormalities greatest in E+PSY. Only TLE had temporal lobe white matter deficits, as well as smaller hippocampi, which were ipsilateral to the seizure focus. Structural brain abnormalities in E+PSY are not restricted to the left temporal lobe. The confluence of cortical gray matter deficits in E+PSY and SCZ suggests salience to chronic psychosis.     

Activation of interictal spiking in mesiotemporal lobe epilepsy by propofol-induced sleep.

The objective of this study was to test whether low-dose propofol increases the number of interictal spikes in patients with mesiotemporal lobe epilepsy, and to determine whether this is the result of intrinsic properties and is restricted to the primary epileptogenic focus. Controlled infusion of propofol in step-up/-down target concentrations of 0, 0.3, 0.6, and 0.8 mg/L was administered to 10 patients during a 3.5-hour daytime EEG registration. The number of spikes were counted and related to propofol concentration and sleep level. Results were compared with a spontaneous, nocturnal first sleep cycle in 9 of 10 patients. All patients entered nonrapid eye movement 1 sleep during propofol administration, and 8 reached nonrapid eye movement 2 sleep. In 7 patients who showed spikes, spikes were related to sleep (P < 0.05) and not to increasing (P = 0.1) or decreasing (P = 0.5) propofol concentration. Six of nine patients showed more spikes during spontaneous (nocturnal) sleep than during propofol-induced sleep. Contralateral spiking was not suppressed selectively. Low-dose propofol is a safe means of increasing spiking in these patients because it induces sleep. There were no signs of an intrinsic epileptogenicity of propofol or a selective effect on ipsilateral spikes. Controlled sleep induction will increase the yield of interictal spikes during short interictal recordings such as in magnetoencephalography.