Association between structural abnormalities and fMRI response in the amygdala in patients with temporal lobe epilepsy.

OBJECTIVE: The goal of this study was to investigate whether dysplastic amygdalae show an impaired response as revealed by functional MRI (fMRI). METHODS: A fearful face fMRI paradigm using video sequences, as we have recently applied, was used in 25 patients with temporal lobe epilepsy (TLE): 24 had mesial TLE (14 right-, nine left-sided, one bilateral); one left lateral neocortical TLE. T1-, T2-weighted and fluid attenuated inversion recovery (FLAIR) MRI sequences were assessed for the detection and categorisation of structural amygdalar abnormalities according to size and MR signal intensity. Of the 25 patients, five patients had probable dysplastic amygdala (pDA): two right- and three left-sided. RESULTS: A fearful face paradigm led to significant amygdalar activation in all but one patient (p<0.05). In 15 (60%) of the patients amygdalar activation was found contralateral and in four (16%) ipsilateral to the side of seizure onset. Bilateral amygdalar activation was registered in five (20%) patients. In two patients with right-sided and one with left-sided pDA, fMRI activation was observed only in the contralateral amygdala. In two out of three patients with left-sided pDA we found significant ipsilateral amygdalar fMRI-responses. CONCLUSION: Unilateral pDA does not necessarily affect the amygdalar fMRI BOLD-response.

The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

[Neuropsychological outcome following intrauterine exposure to valproate]. / Neuropsychologisches Outcome nach intrauteriner Valproat-Exposition: Eine Stellungnahme der Deutschen Gesellschaft für Epileptologie.

A number of recent studies suggest a link between in utero exposure to valproate (VPA) and low IQ and behavioural disorders in children of mothers with epilepsy. In this review, a commission of the German Section of the International League Against Epilepsy discusses the evidence in the literature and practical recommendations for the use of VPA in women of childbearing potential. It is concluded that despite methodological shortcomings--largely due to the complexity of the problem and small case numbers in prospective studies--the existing data are sufficiently alarming to require great caution in the use of VPA in women who could become pregnant. The underlying mechanisms of how antiepileptic drugs may lead to neurodevelopmental problems are unclear. Further prospective studies are urgently needed to clarify this clinically important issue, and a collaborative study is suggested based on the international network established by the European Registry of Antiepileptic Drugs and Pregnancy.

Amygdala fMRI lateralizes temporal lobe epilepsy.

OBJECTIVE: To characterize the clinical value of an fMRI task activating the amygdala in controls and patients with mesial temporal lobe epilepsy (MTLE). METHODS: A fearful face fMRI paradigm using video sequences was developed and investigated in 17 patients with epilepsy (12 had MTLE [6 right- and 6 left-sided]) and 17 healthy control subjects. Reproducibility was demonstrated by reimaging 12 of the control subjects. In addition, parahippocampal activation was measured using Roland's Hometown Walking Task within the same session in all patients and in nine of the control subjects. RESULTS: A fearful face paradigm led to significant amygdala activation (p < 0.001) in all subjects. Amygdala activation was bilateral in control subjects and clearly lateralized in patients with MTLE. Dissociated amygdala and parahippocampal activation was found in three MTLE patients. A combination of results from both fMRI paradigms improved the lateralization of the side of seizure onset in patients with MTLE. CONCLUSIONS: fMRI activation of the amygdala evoked by an animated fearful face paradigm is strong, reproducible, and specific in individual subjects. The combination of the fearful face paradigm and Roland's Hometown Walking Task provides a more reliable presurgical mapping of mesial temporal lobe structures.

Epileptic activity influences the lateralization of mesiotemporal fMRI activity.

OBJECTIVE: To identify clinical factors contributing to the lateralization of mesiotemporal memory functions in epilepsy by using memory-activated fMRI. METHODS: Sixty patients aged 16 to 63 years with mesial temporal lobe epilepsy (MTLE) and 20 patients aged 16 to 60 years with extratemporal epilepsy (ETE) due to circumscribed epileptogenic lesions who consecutively underwent presurgical evaluation including continuous video-EEG monitoring and structural MRI examinations were examined. During memory fMRI, the activation condition consisted of retrieval from long-term memory induced by self-paced performance of an imaginative walk through the patient's hometown. On the basis of a previous study, memory lateralization was defined as typical if larger fMRI activation was in the mesiotemporal structures contralateral to the epileptic focus. RESULTS: There were 45 patients with MTLE who had typical memory lateralization (75%), whereas only 9 patients (45%) with ETE exhibited typical memory lateralization (p = 0.013). In MTLE patients, bilateral independent epileptiform discharges occurred more often in the atypical group than in patients with typical memory lateralization (p = 0.015). CONCLUSIONS: The fMRI lateralization of mesiotemporal visuospatial memory functions in patients with mesiotemporal lobe epilepsy (MTLE) is asymmetric: The larger activation usually appears contralateral to the side of the epileptogenic region. These findings occur more often in MTLE; in patients with extratemporal epilepsy, such type of asymmetry is not characteristic. In MTLE patients with bilateral independent epileptiform discharges, this type of asymmetry is also less frequent.

Bilateral mesial temporal lobe epilepsy: comparison of scalp EEG and hippocampal MRI-T2 relaxometry.

OBJECTIVE: Bilateral hippocampal abnormality is frequent in mesial temporal lobe sclerosis and might affect outcome in epilepsy surgery. The objective of this study was to compare the lateralization of interictal and ictal scalp EEG with MRI T2 relaxometry. MATERIAL AND METHODS: Forty-nine consecutive patients with intractable mesial temporal lobe epilepsy (MTLE) were studied with scalp EEG/video monitoring and MRI T2 relaxometry. RESULTS: Bilateral prolongation of hippocampal T2 time was significantly associated with following bitemporal scalp EEG changes: (i) in ictal EEG left and right temporal EEG seizure onsets in different seizures, or, after regionalized EEG onset, evolution of an independent ictal EEG over the contralateral temporal lobe (left and right temporal asynchronous frequencies or lateralization switch; P = 0.002); (ii) in interictal EEG both left and right temporal interictal slowing (P = 0.007). Bitemporal T2 changes were not, however, associated with bitemporal interictal epileptiform discharges (IED). Lateralization of bilateral asymmetric or unilateral abnormal T2 findings were associated with initial regionalization of the ictal EEG in all but one patient (P < 0.005), with lateralization of IED in all patients (P < 0.005), and with scalp EEG slowing in 28 (82,4%) of 34 patients (P = 0.007). CONCLUSION: Our data suggest that EEG seizure propagation is more closely related to hippocampal T2 abnormalities than IED. Interictal and ictal scalp EEG, including the recognition of ictal propagation patterns, and MRI T2 relaxometry can help to identify patients with bitemporal damage in MTLE. Further studies are needed to estimate the impact of bilateral EEG and MRI abnormal findings on the surgical outcome.

Language lateralization by Wada test and fMRI in 100 patients with epilepsy.

Comparing the determination of language dominance using fMRI with results of the Wada test in 100 patients with different localization-related epilepsies, the authors found 91% concordance between both tests. The overall rate of false categorization by fMRI was 9%, ranging from 3% in left-sided temporal lobe epilepsy (TLE) to 25% in left-sided extratemporal epilepsy. Language fMRI might reduce the necessity of the Wada test for language lateralization, especially in TLE.

Epileptic activity influences the speech organization in medial temporal lobe epilepsy.

Factors influencing atypical speech lateralization have theoretical importance in understanding the organization and reorganization of higher cognitive functions, as well as having practical implications, especially in brain surgery and neurorehabilitation. Atypical (right-sided or bilateral) language representation is more frequent in focal epilepsy than in healthy people. This difference is thought to be related to early childhood brain injuries localized in the neighbourhood of speech centres. The effect of epileptic activity on speech lateralization has not been investigated, although much data suggest that epileptic activity may interfere with higher brain functions. It can only be evaluated in a homogeneous human population with epilepsy having the same lesion type in the same localization. For these reasons, we investigated 184 patients with medial temporal lobe epilepsy (MTLE) due to unilateral hippocampal sclerosis (HS), but without other epileptogenic lesions. All patients underwent comprehensive presurgical evaluation. In MTLE, the influence of age at the time of brain damage, i.e. the initial precipitating injury (IPI), could be evaluated separately from the other timing factors. Of 100 patients in whom a Wada test was performed, left-sided speech occurred in 76% of the left-sided and in 100% of the right-sided MTLE patients (P < 0.05). For further evaluation, we included only the 83 left-sided MTLE patients. The mean age at seizure onset was 10.1 +/- 7.8 years (range 1-37 years); the mean age at evaluation was 35.7 +/- 9.8 years. Based on the Wada test, left-sided speech was present in 63 patients, while in 20 (24%) patients the Wada test revealed atypical speech dominance. We found that atypical speech representation in left MTLE was associated with higher spiking frequency (P < 0.05) and with sensory auras representing an ictal involvement of the lateral temporal structures (P < 0.01). Psychic auras suggesting limbic seizure spread showed a significant association with left-sided speech dominance in left MTLE (P < 0.05). Neither age at epilepsy onset, nor age at IPI was associated with atypical speech in left MTLE. Conclusively, we found that in patients with focal epilepsy, not only the known factors, i.e. the age at which the brain injury occurred and its localization, but also the epileptic activity itself, i.e. interictal discharges and seizure spread, may influence speech reorganization. Our findings also suggest that not only structural elements but also functional factors have an effect on the language organization of the brain.

Spatiotemporal relationship between seizure activity and interictal spikes in temporal lobe epilepsy.

PURPOSE: To analyze the spatio-temporal relationship between seizure propagation and interictal epileptiform discharges (IEDs) in patients with bitemporal epilepsy. METHODS: We investigated 18 adult patients with intractable temporal lobe epilepsy (TLE) who had undergone continuous video-EEG monitoring during presurgical evaluation. Only those patients were selected who had independent IEDs over both temporal lobes. Two authors evaluated the ictal and interictal EEG data independently. RESULTS: We analyzed 52 lateralized seizures of 18 patients. Thirty-one seizures showed ipsilateral seizure spread exclusively, whereas in 21 seizures the contralateral hemisphere was also involved. In lateralized seizures without contralateral propagation, we found that spikes ipsilateral to the seizure onset occurred postictally in a greater ratio than preictally (P<0.001). In lateralized seizures with contralateral propagation, we found no significant changes in the postictal spike distribution. CONCLUSIONS: Our findings showed that the lateralization of IEDs may depend on the brain areas involved by the preceding seizures, suggesting that spikes can be influenced by the seizure activity, and are not independent signs of epileptogenicity.

Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study.

BACKGROUND AND PURPOSE: It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry) influences the blood oxygenation level dependent (BOLD) contrast changes induced by neuronal activation and measured by functional MRI (fMRI). We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE). MATERIAL AND METHODS: Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL) activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. RESULTS: In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P < 0.001). Activation over the supposedly normal MTL, i.e. contralateral to the seizure onset of TLE patients, was smaller than the averaged MTL activation in healthy controls (P < 0.005). Age, duration of epilepsy, side of seizure onset, and intelligence were not correlated to the extent of the significant BOLD-response over both MTL in patients with TLE. CONCLUSIONS: In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

Memory fMRI lateralizes temporal lobe epilepsy.

BACKGROUND: The assessment of mesial temporal lobe (MTL) function is important for the diagnosis and treatment of temporal lobe epilepsy (TLE) and other brain diseases. Declarative memory depends on the integrity of the MTL region. OBJECTIVE: To investigate hemispheric asymmetries of MTL activity in patients with symptomatic TLE. METHODS: With use of blood oxygenation level-dependent fMRI, hemispheric asymmetries in MTL activation of 30 individual patients with refractory symptomatic TLE and 17 healthy control subjects were studied. Activation was induced by a task employing mental navigation and recall of landmarks based on the retrieval of individually familiar visuospatial knowledge. RESULTS: The study demonstrated that the memory task used reliably activated MTL structures in individual control subjects and patients with refractory TLE including children, older subjects, and patients with low formal IQ. Interhemispheric differences in MTL activation lateralized the side of seizure onset in 90% of patients with symptomatic unilateral TLE. In contrast, healthy control subjects did not show a systematic asymmetry of MTL activation. Correlations between MTL activation and neuropsychological measures suggest that the fMRI-detectable MTL changes were specifically related to memory rather than to memory-independent visuospatial abilities. CONCLUSION: fMRI of memory-induced MTL activation lateralizes the side of seizure onset in patients with refractory symptomatic TLE and may provide complementary information for presurgical evaluation.

Seizures accelerate forgetting in patients with left-sided temporal lobe epilepsy.

Ten patients with refractory temporal lobe epilepsy performed a word-position association learning task every 24 hours during video EEG monitoring. On 55 occasions recall performance was tested 30 minutes and 24 hours after the initial learning phase. Patients with left- but not right-sided temporal lobe epilepsy exhibited impaired retention of word position if a seizure had occurred during the preceding 24-hour interval. Seizures may impair the consolidation of memory in patients with left-sided temporal lobe epilepsy beyond the chronic memory deficits caused by the underlying pathology.

Lack of aura experience correlates with bitemporal dysfunction in mesial temporal lobe epilepsy.

UNLABELLED: The diagnostic value of lack of aura experience in patients with temporal lobe epilepsy (TLE) is unclear. PURPOSE: To evaluate possible factors of bitemporal dysfunction in patients with mesial TLE who did not experience an aura in electroencephalography EEG/video monitoring for epilepsy surgery. METHODS: Ictal scalp EEG propagation patterns of 347 seizures of 58 patients with mesial temporal lobe sclerosis or non-lesional mesial TLE, interictal epileptiform discharges (IED), presence of unilateral mesial temporal lobe sclerosis in visual magnetic resonance imaging (MRI) analysis, prose memory performance, history or not of an aura, and postictal memory or absence of an aura were analyzed. The ictal EEG was categorized as follows. EEG seizure: (a) remaining regionalized, (b) non-lateralized, (c) showing later switch of lateralization or bitemporal asynchronous ictal patterns. RESULTS: Absent aura in monitoring was significantly correlated with absence of unitemporal MRI sclerosis (P=0.004), bitemporal IED (P=0.008), and propagation of the ictal EEG to the contralateral temporal lobe (P=0.001). Other historical data and interictal prose memory performance were not significantly correlated with absent aura. Ten of 11 patients without aura in monitoring also had absent or rare auras in their history. CONCLUSIONS: Lack of aura experience strongly correlates with indicators of bitemporal dysfunction such as bitemporal interictal sharp waves and bitemporal ictal propagation in scalp EEG, and absence of lateralized MRI sclerosis in patients with mesial TLE. The fact that absent auras are not correlated with episodic memory suggests a transient memory deficit, probably because of rapid propagation to the contralateral mesial temporal lobe.

Lateralizing value of unilateral motor and somatosensory manifestations in frontal lobe seizures.

PURPOSE: To evaluate the lateralizing value of unilateral somatosensory aura, unilateral tonic posturing, head version, non-forced head turning, ictal cloni, dystonic posturing, and postictal nose wiping in seizures originating in the frontal lobe. METHODS: We included patients who had consecutively undergone presurgical evaluation with ictal video-EEG monitoring at our institution, had had resective epilepsy surgery involving the frontal lobe, and had remained seizure-free >1 year after operation. Twenty-seven patients aged 1-42 years (mean 18) met the inclusion criteria. Fifteen patients had right-sided, 12 patients had left-sided epileptogenic regions. Seizures recorded during EEG-video monitoring were re-evaluated by two investigators in order to identify lateralization signs in frontal lobe seizures. One of the investigators was blind to patients' clinical data. RESULTS: We analyzed 153 seizures of 27 patients. The most common unilateral phenomenon was the unilateral tonic posturing occurring in 48% of all the patients and in 25% of all seizures. Somatosensory aura and head version appeared exclusively contralateral whereas clonus occurred in 92% and unilateral tonic posturing in 89% of seizures contralateral to the epileptogenic region. Ictal non-forced head turning and postictal nose wiping showed no lateralizing significance. Dystonic posturing did not occur. CONCLUSIONS: Somatosensory aura, head version, ictal cloni, and tonic posturing are reliable lateralizing signs in frontal seizures. These signs may help in identifying the epileptogenic region during presurgical evaluation of patients suffering from frontal lobe epilepsy.

[Neuropsychological diagnosis in patients with epilepsy]. / Neuropsychologische Diagnostik bei Patienten mit Epilepsie.

Patients with epilepsy are at higher risk to demonstrate cognitive impairment compared with the normal population. A variety of interacting epilepsy related factors (e.g. lesion, epileptic activity, and antiepileptic medication) may influence the cognitive profile of patients. Neuropsychological tests provide information about the individual quality, severity, and dynamics of attentional, perceptual, mnestic, cognitive, mental speed, and psychomotor speed impairments. The interpretation of test data has to consider the etiology, the localisation of an underlying pathology, the frequency and severity of seizure activity, status epilepticus, the frequency and distribution of epilepsy typical discharges, antiepileptic drugs, the age at seizure onset, the duration of epilepsy, education, and possible effects of epilepsy surgery. Longitudinal studies allow the description of natural courses and of therapeutic effects including side-effects. Especially patients who are confronted with high professional and educational cognitive demands and who are at considerable risk of side effects may benefit from neuropsychological diagnostics prior to and following therapy decisions.

Are ictal vocalisations related to the lateralisation of frontal lobe epilepsy?

The purpose was to analyse whether non-speech vocalisations in seizures originating in the frontal lobe do have lateralising value. Patients were included who had undergone presurgical evaluation with ictal video-EEG monitoring at the Epilepsy Centre, had had resective epilepsy surgery involving the frontal lobe, and who had remained seizure free>1 year postoperatively. Twenty seven patients aged 1-42 years (mean 18) met the inclusion criteria. Age at epilepsy onset ranged from 1 month to 41 years (mean 7.1 years). All selected patients had a unilateral MRI detected lesion within the frontal lobe. Fifteen patients had right sided, 12 patients had left sided epileptogenic zones. Seizures recorded during EEG-video monitoring were re-evaluated to identify the occurrence of ictal vocalisations. Pure ictal vocalisations were distinguished from ictal sound productions due to motor or vegetative seizure activity (for example, cloni or respiratory sounds). Pure ictal vocalisation occurred in 11 patients of whom nine had a left frontal epileptogenic zone (p<0.01). It is concluded that ictal vocalisation could be an additional lateralising sign in frontal lobe epilepsy. The results suggest that not only speech, but vocalisation at a subverbal level also shows a left hemispheric dominance in humans.

Amplitude envelope correlation detects coupling among incoherent brain signals.

Cognitive processing involves gamma-activation over broad cortical regions. Phase coupling of these activities has rarely been reported for areas far apart. Other forms of coupling are generally not detected by conventional measures. Here, we use amplitude envelope correlation (AEC), which can detect signal coupling without phase coherence, even among different frequencies. We apply it to subdural recordings from humans performing a visual delayed match-to-sample task and systematically compare it with spectral amplitude and coherence. The different measures often show divergent results. In particular, AEC reveals y-coupling completely missed by coherence. We argue that coherence and AEC are adapted to different cortical mechanisms of short- and long-range interactions, respectively.

EEG predicts surgical outcome in lesional frontal lobe epilepsy.

BACKGROUND: Because of the relatively poor results of frontal lobe epilepsy (FLE) surgery, identification of prognostic factors for surgical outcome is of great importance. METHODS: To identify predictive factors for FLE surgery, we analyzed the data of 61 patients (mean age at surgery 19.2) who had undergone presurgical evaluation and resective surgery in the frontal lobe. Postoperative follow-up ranged from 0.5 to 5 years (mean 1.78). Fifty-nine patients had MRI-detectable lesions. Histopathologic examination showed dysplasia (57.4%), tumor (16.4%), or other lesions (26.2%). Thirty postoperatively seizure-free patients were compared with 31 non-seizure-free patients with respect to clinical history, seizure semiology, EEG and neuroimaging data, resected area, and postoperative data including histopathology. RESULTS: Three preoperative and two postoperative variables were related to poor outcome: generalized epileptiform discharges, generalized slowing, use of intracranial electrodes, incomplete resection detected by MRI, and postoperative epileptiform discharges. The only preoperative factor associated with seizure-free outcome was the absence of generalized EEG signs. Multivariate analysis showed that only the absence of generalized EEG signs predicts the outcome independently. Moreover, the occurrence of a somatosensory aura, secondarily generalized seizures, and negative MRI was identified as additional independent risk factors for poor surgical results. CONCLUSIONS: The absence of generalized EEG signs is the most predictive variable for a seizure-free outcome in FLE surgery. Furthermore, nonlesional MRI, somatosensory aura, and secondarily generalized seizures are risk factors for poor surgical results.