Sex differences in face recognition memory in patients with temporal lobe epilepsy, patients with generalized epilepsy, and healthy controls.

The influence of sex on face recognition memory was studied in 49 patients with temporal lobe epilepsy, 20 patients with generalized epilepsy, and 32 healthy controls. After learning 20 faces, serially presented for 5 seconds each, subjects had to recognize the 20 among 40 faces (including 20 new faces) immediately and 24 hours later. Women had better face recognition than men, with no significant differences between groups. Women's advantage was due mainly to superior delayed recognition. Taken together, the results suggest that sex has a similar impact on face recognition in patients with epilepsy and healthy controls, and that testing delayed face recognition raises sensitivity for sex differences. The influence of sex on face recognition in patients with epilepsy should be acknowledged when evaluating individuals or comparing groups.

Epilepsy increases vulnerability of long-term face recognition to proactive interference.

Proactive interference (PI) decreases short- and long-term memory in healthy subjects. Neurological patients exhibit a heightened PI effect on short-term memory. It is, however, not known if PI affects long-term memory in neurological patients. We analyzed whether epilepsy heightens the negative effect of PI on long-term face memory. PI was induced by a list of 20 faces learned 24 hours prior to a target list of 20 faces. We tested immediate and 24-hour recognition for both lists. Twelve healthy controls and 42 patients with generalized epilepsy or temporal lobe epilepsy (TLE) were studied. PI led to a decrease in 24-hour recognition in patients with generalized epilepsy and TLE but not in controls. Thus, PI may cause long-term memory disturbances in epilepsy patients. PI was also associated with decreased short-term memory, but only in right TLE. This confirms the dominant role of the right temporal lobe in short-term face memory.

Epilepsy: from consensus to daily practice.

Most clinicians would accept that epilepsy treatment should begin with monotherapy, and in the majority of cases this is the preferred drug maintenance option. The clinical choice of one antiepileptic drug (AED) over another should be based on firm evidence of efficacy and tolerability as evaluated in comparative monotherapy studies and pharmacokinetics. This paper presents the findings of evidence-based reviews of AED monotherapy in patients newly diagnosed with epilepsy. The main study was conducted in the United Kingdom and investigated the clinical evidence supporting AEDs used as first-line monotherapy. In this paper the general treatment recommendations will focus on valproate, one of the mainstay drugs used in the fight against epilepsy. Finally, with these recommendations in mind, the principles behind AED drug selection in clinical practice will be discussed. Factors for consideration that impact on AED decision-making include: seizure and syndrome diagnosis, AED tolerability profiles, patient characteristics and pharmacokinetic/pharmacodynamic AED interactions.

Effect of levetiracetam in patients with epilepsy and interictal epileptiform discharges.

The effect of acute treatment with the new antiepileptic drug (AED) levetiracetam (Keppra) on the frequency of interictal epileptiform discharges (IEDs) was evaluated in a double-blind, placebo-controlled, crossover study with therapeutic drug monitoring and serial electroencephalographic (EEG) observations. Acute (500 mg twice daily) and chronic (individualized, 500-1000 mg twice daily) doses of levetiracetam were administered as an add-on to current AED treatment. Efficacy was tested by measuring the frequency of IEDs in EEG recordings and the number of seizures. A single acute dose of levetiracetam induced a reduction of IEDs in eight out of ten patients. During the acute phase, an insufficient number of seizures occurred for analysis. During chronic treatment over 8 weeks, seven patients showed a reduction in seizure frequency (responder rate), and one patient remained seizure free. No correlation was seen between levetiracetam levels and IED frequency. Doses of levetiracetam of up to 2000 mg/day were well tolerated, and no interactions were seen with concomitant AEDs.

Cerebral hemodynamic response to generalized spike-wave discharges.

PURPOSE: Data in the literature concerning metabolic demand during generalized spike-wave activity (gSW) are conflicting. We investigated instantaneous changes in cerebral blood flow velocities (CBFV) in both middle cerebral arteries (MCAs) by transcranial Doppler sonography (TCD) during gSW paroxysms recorded by scalp EEG. METHODS: In 13 patients, CBFVs in both MCAs were averaged, time-locked to the occurrence of the gSW; respiratory rate (RR) and end-expiratory pco2 were measured in one patient. RESULTS: Nine patients showed significant changes in CBFV during gSW. Four had biphasic flow changes with an initial increase (p < 0.05) and a subsequent decrease (p < 0.01). This was partially paralleled by an increase in RR (p < 0.01) and a decrease in pco2 (p < 0.01). In three patients, an increase in CBFV that preceded the onset of gSW by several seconds was observed, followed by a decrease in CBFV. Two patients showed a significant decrease only of CBFV. Only gSWs of a median duration of >0.8 s were associated with significant changes in CBFV. CONCLUSIONS: We were able to demonstrate that gSWs of several seconds duration lead to cortical perfusion changes. We suggest that the initial increase of CBFV demonstrated in some patients reflects neuronal activation, whereas the subsequent decrease might in part be due to hyperventilation-induced hypocapnia.

PET and SPECT in medically non-refractory complex partial seizures. Temporal asymmetries of glucose consumption, benzodiazepine receptor density, and blood flow.

AIM: In contrast to medically refractory complex partial seizures (CPS), only limited knowledge exists on cerebral perfusion and metabolism in medically non-refractory CPS. The aim of this study was to investigate the frequency of temporal asymmetries in regional cerebral glucose consumption (rCMRGlc), regional cerebral blood flow (rCBF), and regional cerebral benzodiazepine receptor density (BRD) in this group of patients. METHODS: The study included 49 patients with medically non-refractory cryptogenic CPS (age: 36.0 +/- 16.1 years). rCMRGlc was studied with F-18-FDG-PET (FDG), rCBF with Tc-99m-ECD-SPECT (ECD), and BRD with l-123-iomazenil-SPECT (IMZ). All studies were performed interictally and within four weeks in each patient. Duration of epilepsy ranged from 0.1 to 42 years (median 4.0 years). SPECT was performed with the triple-headed SPECT camera Multispect 3, PET with the PET camera ECAT EXACT 47. Using linear profiles, glucose consumption, as well as uptake of ECD and IMZ, were measured in four temporal regions of interest (ROIs), and asymmetry indices were calculated (ASY). The results were compared to 95% confidence intervals determined in control subjects. RESULTS: Thirty-five of the 49 (71%) patients had at least one significantly elevated ASY; temporal rCMRGlc was asymmetrical in 41% of the patients, temporal BRD in 29%, and temporal rCBF in 24%. One patient had an asymmetry of all three variables, two of temporal rCMRGlc and BRD, three of temporal rCMRGlc and rCBF, and another four of rCBF and BRD. Fourteen patients had an isolated temporal asymmetry in rCMRGlc, seven in BRD, and four in rCBF. A discrepancy in lateralization between the three modalities was not observed. CONCLUSION: The majority of patients with medically non-refractory CPS have focal abnormalities of blood flow and metabolism in their temporal lobe. In this group of patients, FDG-PET demonstrates abnormalities with the highest frequency of the three modalities studied, followed by IMZ-SPECT, and ECD-SPECT.

The photic driving EEG response and photoreactive cerebral blood flow in the posterior cerebral artery in controls and in patients with epilepsy.

OBJECTIVES: Instantaneous changes in blood flow velocities during visual stimulation can be assessed by transcranial Doppler sonography (TCD). METHODS: We investigated the possible relationship between the characteristics of photic driving in the EEG elicited by repetitive intermittent photic stimulation and the photoreactive flow changes in the posterior and middle cerebral artery (PCA, MCA) of 25 normal controls and 25 patients with focal epilepsy. Cerebral blood flow velocities (CBFV) of the right PCA (P2 segment) and the left middle cerebral artery (MCA) were measured using a 2 Hz transcranial Doppler device. Simultaneously, scalp EEGs were recorded. RESULTS: During photic stimulation the mean CBFV increase was 20.4 +/- 9.5% in the PCA of the controls (n = 132 stimulations) and 16.0 +/- 10.8% in epileptic patients (n = 150 stimulations, P < 0.01). During those stimulation series with a good EEG driving response (n = 203), the mean increase of CBFV in the PCA was 19.7 +/- 10.0%, as opposed to 14.4 +/- 10.5% during the stimulations with a poor EEG response (n = 79, P < 0.01). A good photic driving response was associated with a higher increase of CBFV in the PCA than a poor one. The increase in CBFV of the PCA in normal controls was higher than in patients with focal epilepsy. CONCLUSIONS: This may indicate that epileptic patients have a reduced coupling between neuronal activation and blood flow.

Modified approach for the selective treatment of temporal lobe epilepsy: transsylvian-transcisternal mesial en bloc resection.

OBJECT: The authors propose a novel surgical approach for amygdalohippocampectomy (AH) in patients with temporal lobe epilepsy. Via a transsylvian-transcisternal route, the parahippocampal gyrus is directly exposed from its medial aspect, thus allowing a standardized en bloc resection of the temporomesial epileptogenic structures--the amygdala, anterior hippocampus, parahippocampal gyrus, and subiculum. Additional anatomical studies have been performed for standardization of this approach. METHODS: From 1990 to 1996, 32 patients presenting with medically intractable mesial temporal lobe epilepsy underwent AH via the transsylvian-transcisternal approach. Preoperative computerized tomography and magnetic resonance imaging revealed temporomesial lesions in 16 patients. Histopathological examination revealed cavernous malformations in seven patients, low-grade astrocytomas in four, hamartomas in three, and gangliogliomas in two patients. Specimens obtained in patients with no lesions were diagnosed as hippocampal sclerosis in all cases. No patient experienced permanent morbidity. Nine percent of the patients developed a temporary partial oculomotor nerve palsy. Only one patient developed a postoperative visual field deficit with a contralateral quadrantanopsia. With respect to seizure outcome, all patients benefited from surgery. At follow-up evaluation (mean 26.4 months), 80% of the patients were free from seizures (Engel Class I). Eight patients in this group were no longer receiving medication. Seventeen percent had experienced only one to several seizures since surgery (Engel Class II) and 3% reported a worthwhile improvement (Engel Class III). CONCLUSIONS: In contrast to previously described standard techniques for AH, the transsylvian-transcisternal approach presented in this study offers improved anatomical orientation and intraoperative control over the mesial temporal lobe and preserves the lateral as well as the laterobasal temporal lobe.

Measurement of temporal asymmetries of glucose consumption using linear profiles: reproducibility and comparison with visual analysis.

AIM: One approach to regionally analyze temporal glucose consumption consists in drawing linear profiles over the maximal values measured in the temporal cortical ribbon. The aim of our study was to test the reproducibility of this method and to compare its diagnostic performance to that of visual analysis in patients with complex partial seizures (CPS). METHODS: Regional cerebral glucose consumption (rCMRGIc) was measured interictally in 25 CPS patients and 10 controls using F-18-deoxyglucose and the positron emission tomography (PET) camera ECAT EXACT 47. The PET scans were visually analyzed for the occurrence of unilateral temporal hypometabolism. Furthermore, rCMRGIc was quantified on six contiguous coronal planes by manually tracing maximal values of temporal glucose consumption, thus creating line profiles of temporal glucose consumption for each side. Indices of asymmetry (ASY) were then calculated from these line profiles in four temporal regions and compared to the corresponding 95% confidence intervals of the control data. All analyses were performed by two observers independently from each other and without knowledge of the clinical findings. RESULTS: The agreement between the two observers with regard to focus lateralization was 96% (kappa = 0.93) on visual analysis and 100% (kappa = 1) on quantitative analysis. There was an excellent agreement with regard to focus lateralization between visual and quantitative evaluation (kappa = 0.8). CONCLUSION: Quantitation of local temporal rCMRGIc by using linear profile analysis is highly reproducible; for the lateralization of epileptogenic foci, however, this method does not possess significant advantages over the visual evaluation of the scans.

Spontaneous oscillations in cerebral blood flow velocities in middle cerebral arteries in control subjects and patients with epilepsy.

BACKGROUND AND PURPOSE: Cardiac arrhythmias mediated by the sympathetic nervous system have been implicated in sudden, unexplained deaths in patients with epilepsy. Cerebral blood flow velocities (CBFV) as measured by transcranial Doppler are characterized by slow spontaneous oscillations in part attributed to changes in sympathetic activity (M waves, 3 to 9 cycles per minute) and to discharges of monoaminergic neurons in the brain stem (B waves, 0.5 to 2 cycles per minute). This study was designed to compare spontaneous fluctuations of CBFV in patients with epilepsy with those in normal control subjects. METHODS: Simultaneous registrations of scalp electroencephalograms, with electrodes placed according to the 10-20 System, and transcranial Doppler recordings of both middle cerebral arteries were performed in 27 patients (9 with primary generalized epilepsy, 18 with focal epilepsy). Data analysis of CBFV was based on the envelope curves of the Doppler spectrum. A fast Fourier transformation over the 20-minute CBFV curve was performed, and the amplitudes of B and M waves were calculated and compared with those in 20 normal, age-matched control subjects. RESULTS: While the amplitudes of the B waves in both groups were similar, patients with epilepsy showed significantly increased M waves. Patients with focal epilepsy did not present asymmetries between the normal hemisphere and the side of the epileptic focus with respect to both M and B waves. CONCLUSIONS: Enhanced M waves in epileptic patients may reflect increased sympathetic activity even in the absence of seizures. This study provides further evidence for an autonomic dysfunction as a possible mechanism for sudden unexplained death in patients with epilepsy.

High-signal lesions in the midbrain on T1-weighted MRI in an HIV-infected patient.

In addition to opportunistic infections, neoplasms or cerebrovascular complications, metabolic encephalopathies are a classical cause of diffuse brain dysfunction in HIV infection and are frequent in the terminal stage. We report an HIV-infected patient with symmetrical, focally increased signal in the midbrain on proton density-and T1-weighted MRI without corresponding high signal on T2-weighted images or on CT. While the precise nature and cause of this uncommon finding is not fully understood, the available evidence suggests that these lesions might represent a novel metabolic encephalopathy.

Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child.

OBJECTIVE: To investigate the transfer of lamotrigine in pregnancy and during lactation from a mother on lamotrigine treatment to her child. METHODS: Concentrations of lamotrigine were measured by high-pressure liquid chromatography in umbilical cord serum and in serum samples of the mother and her child as well as in the mother's milk during the first five postpartum months. RESULTS: In the child lamotrigine serum concentrations (up to 2.8 micrograms ml-1) comparable to those usually achieved in active treatment with lamotrigine were found not only after birth, but also during lactation. A considerable amount of lamotrigine (2-5 mg per day) was excreted in breast milk. No adverse effects were seen in the child. CONCLUSION: The transfer of lamotrigine taking place during pregnancy and lactation should not be neglected. In this case the child should be thoroughly observed for potential adverse effects.

Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam.

The experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the "photosensitivity model", an early phase II study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13-38) were investigated during a 3 day period in 3 centres (France, The Netherlands, Germany), using the same standardised method. The subjects were either treated with a single oral dose of 250 mg, 500 mg, 750 mg or 1,000 mg. In addition, 4 patients took 250 mg b.i.d. for 3-5 days, after which they were re-examined. In 9 of 12 photosensitive patients (75%) a clear suppression (3 patients) or abolishment (6 patients) of IPS evoked photoparoxysmal EEG responses was found. This effect appeared to be dose-dependent, the higher the dose the greater the effect; complete abolishment was only seen at dosages of 750 mg and 1,000 mg, occurring at peak plasma levels and lasting between 6 and 30 h. There was no indication of pharmacokinetic interaction with concomitant antiepileptic drugs such as valproic acid, ethosuximide or phenobarbitone. No serious side-effects were seen and some patients reported enhancement of their mood. Two patients with myoclonic jerks noticed a clear reduction of their myoclonus, although this was not one of the objectives of the study. In conclusion, levetiracetam showed a clear antiepileptic effect in the photosensitivity model.

Persistent unihemispheric perceptual impairments in humans following focal seizures.

Perception has been linked to a highly coordinated activation of cortical regions whose functional organization and performance is subject to plastic changes. We tested whether chronic repetitive disturbances of the brain by focal epileptic activity have a long-standing detrimental effect on the perceptual performance in the affected hemisphere. Nine patients were examined who had a history of complex partial seizures but no structural cerebral damage on magnetic resonance imaging and no evidence of ongoing epileptic activity on scalp electroencephalography and who had clinically been without seizures for at least 3 days. The side of primary epileptic involvement was determined by seizure semiology (n = 2), focal electroencephalographic slowing (n = 3) or focal abnormality during single photon emission topography (SPECT) (n = 4). The computer controlled psychometric assessment of the somesthetic frequency discrimination revealed that the perception in the hand corresponding to the affected hemisphere was impaired relative to the contralateral hand (P < 0.01), and to the performance of a group of normal controls (P < 0.01). We conclude that mechanisms related to focal epileptic activity can result in regional perceptual decrements even when there is no clinical or surface-electroencephalographic evidence of epileptic discharges. This in turn suggests that somatosensory testing may be of help in localizing, or at least lateralizing an epileptic focus.

Reduced GABAA receptor density contralateral to a potentially epileptogenic MRI abnormality in a patient with complex partial seizures.

Imaging cerebral GABAA receptor density (GRD) with single-photon emission tomography (SPET) and iodine-123 iomazenil is highly accurate in lateralizing epileptogenic foci in patients with complex partial seizures of temporal origin. Limited knowledge exists on how iomazenil SPET compares with magnetic resonance imaging (MRI) in this regard. We present a patient with complex partial seizures in whom MRI had identified an arachnoid cyst anterior to the tip of the left temporal lobe. Contralaterally to this structural abnormality, interictal electroencephalography (EEG) performed after sleep deprivation disclosed an intermittent frontotemporal dysrhythmic focus with slow and sharp waves. On iomazenil SPET images GRD was significantly reduced in the right temporal lobe and thus contralaterally to the MRI abnormality, but ipsilaterally to the pathological EEG findings. These data suggest that iomazenil SPET may significantly contribute to the presurgical evaluation of epileptic patients even when MRI identifies potentially epileptogenic structural lesions.

Scalp topography and analysis of intracranial sources of face-evoked potentials.

Several reports have described that a positive vertex peak of an evoked potential varied in amplitude and latency specifically when images of faces were the eliciting stimulus. The scalp topography and the possible underlying dipole sources of this peak are the subject of this report. We presented black-and-white photographs of human faces, flowers and leaves to 16 healthy subjects and recorded the evoked brain potentials from 31 scalp electrodes. We found the previously described higher amplitude of the positive vertex peak when faces were the crucial stimulus, but the latency of this peak was the same (180 ms) for all three categories of stimulus. At the posterior temporal electrodes, the face waveforms showed a negative peak at 175 ms, which was only rudimentary in the waveforms elicited by the other stimuli. Since in most previous reports a mastoid reference was used, it is most likely that the previously described latency shift of the positive vertex peak associated with face stimuli was due to the interaction with this posterior temporal peak. The dipole analysis of the possible generators of the recorded potentials suggested the sequential activation of occipital, lateral temporal and mesio-temporal brain structures during the perception of a human face.

[Cardiac side effects and ECG changes with lamotrigine?--A clinical study]. / Kardiale Nebenwirkungen und EKG-Veränderungen unter Lamotrigin?--Eine klinische Untersuchung.

After a patient treated with lamotrigine (LTG) had suffered from thoracal pain and repolarisation deficiencies in the electrocardiogram (ECG), we prospectively investigated 20 patients with localization-related epilepsies to assess cardiovascular side effects of LTG. During the study, LTG was added to a stable dosage of one to three first line antiepileptic drugs (AED). Physical examinations and ECG recordings were performed regularly. Clinical cardial side effects did not occur. Only in single ECG traces of six patients non specific abnormalities were seen. Only in one patient, the abnormalities (supraventricular extrasystoles and a first grade atrioventricular block) unequivocally appeared initially under LTG. However, in the same patient two later ECG recordings under higher LTG dosages were normal. The statistical analysis of the ventricular activation times did not reveal any significant changes under LTG (p = 0.05) with the exception of an extended PQ time when comparing a patient group before LTG (n = 11) with another patient group under LTG (n = 11). Since this observation was not confirmed by the statistical analysis of a third patient group (n = 10) with ECG data prior to and under LTG, we believe that the statistically significant changes mentioned above were based mainly on structural differences between the patient groups and not on true LTG effects. Our results do not give evidence for an elevated risk of clinically relevant cardial side effects under LTG.

Noninvasive assessment of cerebral hemodynamics and tissue oxygenation during activation of brain cell function in human adults using near infrared spectroscopy.

Near Infrared Spectroscopy (NIRS) was employed to noninvasively and continuously (temporal resolution 0.5 s) assess changes in cerebral hemodynamics and oxygenation during various functional states of the adult human brain. During cognitive stimulation (performing calculations) a frontal increase in local cerebral blood volume and oxygenated hemoglobin concentration was observed in most (10 of 12) subjects. During visual stimulation (observing a picture) this was demonstrated in the occipital region in all three subjects. Deoxygenated hemoglobin either decreased, remained unchanged or slightly increased during these procedures. Epileptic patients were examined during spontaneously occurring complex-partial seizures. During these seizures extremely large increases in blood volume and oxygenated hemoglobin concentration were measured. In conclusion, this feasibility study indicates that NIRS might become a useful and simple bedside tool to assess brain function.