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.

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.

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.

Individual prediction of change in delayed recall of prose passages after left-sided anterior temporal lobectomy.

Prognostic variables for individual memory outcome after left anterior temporal lobectomy (ATL) were studied in 27 patients with refractory temporal lobe epilepsy. The difference between pre- and postoperative performance in the delayed recall of two prose passages (Story A and B) from the Wechsler Memory Scale served as measure of postoperative memory change. Fifteen independent clinical, neuropsychological, and electrophysiological variables were submitted to a multiple linear regression analysis. Preoperative immediate and delayed recall of story content and right hemisphere Wada memory performance for pictorial and verbal items explained very well postoperative memory changes in recall of Story B. Delayed recall of Story B, but not of Story A, had high concurrent validity to other measures of memory. Patients who became seizure-free did not differ in memory change from patients who continued to have seizures after ATL. The variables age at epilepsy onset and probable age at temporal lobe damage provided complementary information for individual prediction but with less effectiveness than Wada test data. Our model confirmed that good preoperative memory functioning and impaired right hemispheric Wada memory performance for pictorial items predict a high risk of memory loss after left ATL. The analyses demonstrate that the combination of independent measures delivers more information than Wada test performance or any other variable alone. The suggested function can be used routinely to estimate the individual severity of verbal episodic memory impairment that might occur after left-sided ATL and offers a rational basis for the counseling of patients.

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.

Reorganization of memory functions after human temporal lobe damage.

Hemispheric (re-)organization of episodic memory functions after temporal lobe damage (TLD) was investigated by the intracarotid amobarbital procedure in patients suffering temporal lobe epilepsy. Memory of the speech-dominant left hemisphere was intact after right-sided TLD independent of the age at manifestation. In contrast, the right hemisphere mediated memory well only after early left-sided TLD. These findings suggest a predisposition of the speech-dominant left hemisphere for the encoding of episodic memory, and indicate that for left-sided TLD the right hemisphere may compensate memory encoding sufficiently only if the damage occurred within a critical period in childhood.

Hemispheric asymmetries in category-specific word retrieval.

We examined whether 53 adult non-aphasic patients with either left (22) or right temporal lobe lesions (31) demonstrate dissociable patterns of hemispheric asymmetries in category-specific word fluency tasks. The patients were asked to articulate as many appropriate words as possible within 60 or 90 s in response to six target categories. There was no effect of patient groups on the overall fluency. However, patients with a left-sided temporal lobe lesion were impaired retrieving words to 'initial letters' and to the category 'animals'. Right temporal lobe patients were impaired retrieving 'tools' and words referring to specific visual attributes. There were no fluency differences for 'food-supermarket goods' and 'flat interior'. We conclude that temporal lobe damage can result in category-specific impairments in word retrieval depending on the affected hemisphere.

Bilateral reductions of hippocampal volume, glucose metabolism, and wada hemispheric memory performance are related to the duration of mesial temporal lobe epilepsy.

In refractory temporal lobe epilepsy (TLE) temporal lobe structures and functions are continuously or intermittently affected by abnormal brain electrical events, noxious neurochemical agents, and metabolic disturbances. There is conflicting evidence regarding the relationship between the duration of refractory mesial TLE and quantitative measures of temporal lobe functions and volumes of the hippocampi. Twenty patients (aged 28 +/- 7 years, 14 males) with an initial precipitating injury before the age of 5 years were subjected to high-resolution magnetic resonance imaging, fluoro-2-deoxy-d-glucose positron-emission tomography (PET), and the Wada test. We investigated whether the duration of unilateral refractory TLE (12 left, 8 right) affects hippocampal volume, glucose metabolism, or Wada hemispheric memory performance. Ipsilateral to the epileptogenic zone the hippocampal volume, metabolism, and Wada hemispheric memory performance were reduced compared to the corresponding contralateral measures. The duration of epilepsy controlled for age at investigation, side of seizure origin, underlying cause, and sex were negatively correlated with ipsi- and contralateral hippocampal volume, hippocampal metabolism, and Wada hemispheric memory performance. Moreover, ipsilateral Wada hemispheric memory performance and contralateral hippocampal glucose metabolism were correlated with the frequency of habitual seizures. Refractory TLE seems to be associated with a slow but ongoing bilateral temporal lobe damage. These cross-sectional results require verification by longitudinal studies carried out over a period of more than two decades.

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.

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.

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.

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.

[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.

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.

[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.

Long term effects of refractory temporal lobe epilepsy on cognitive abilities: a cross sectional study.

OBJECTIVE: Intractable epilepsy is related to various transient and chronic brain electric and neurochemical disturbances. There is increasing evidence that chronic epilepsy induces secondary neuronal metabolic and structural decline. However, there is no convincing evidence that the cognitive abilities of patients deteriorate with increasing duration of intractable epilepsy. METHODS: To examine whether duration of refractory temporal lobe epilepsy (TLE) is related to generalised cognitive impairment, psychometric intelligence based on the full scale intelligence quotient (FSIQ, WAIS-R) was determined in 209 patients with unilateral TLE. For analyses of variance (ANOVA) patients were grouped into three categories: <15, 15-30, and >30 years of refractory TLE. RESULTS: An ANOVA and a multiple regression analysis showed that duration of TLE affects FSIQ. Patients with >30 years of TLE performed worse than patients with 15 or 30 years of TLE. The factors side of seizure origin and type of lesion on MRI did not reach significance. A second ANOVA including education as factor showed that in patients with higher educational attainment, the mean FSIQ was stable for a longer duration of TLE than in less educated patients. Retesting 6 months after anterior temporal lobectomy seizure free patients (n=85 of 127) had an higher FSIQ but showed a similar duration effect before and after anterior temporal lobectomy. The variables age at epilepsy onset, education, frequency of interictal epileptiform discharges, frequency of habitual and generalised seizures, serum concentration of antiepileptic drugs, and polypharmacy were statistically controlled. CONCLUSIONS: Psychometric intelligence of patients with a longer duration of refractory TLE were most severely impaired. Consequently, refractory TLE seems to be associated with slow but ongoing cognitive deterioration. It is assumed that epilepsy related noxious events and agents exhaust the compensatory capacity of brain functions. However, as in dementia and Alzheimer's disease, higher educational attainment as an indicator of higher brain reserve might delay the cognitive decline.