The three pillars in treating antibody-mediated encephalitis.

The rapid initiation of immunotherapy has a decisive impact on the course of the disease in patients with antibody-mediated encephalitis (AE). The importance of treating AE with antiseizure medication and antipsychotics is discussed controversially; however, standardized procedures should be ensured, especially for the initiation of treatment in severe disease. Recommendations and guidelines for further interventions in refractory courses are needed. In this review, we contrast the three mainstays of treatment options in patients with AE and attempt to highlight the importance of 1) antiseizure therapy, 2) antipsychotic therapy, and 3) immunotherapy/tumor resection from today's perspective.

Voxel-Based Morphometry-from Hype to Hope. A Study on Hippocampal Atrophy in Mesial Temporal Lobe Epilepsy.

BACKGROUND AND PURPOSE: Automated volumetry of the hippocampus is considered useful to assist the diagnosis of hippocampal sclerosis in temporal lobe epilepsy. However, voxel-based morphometry is rarely used for individual subjects because of high rates of false-positives. We investigated whether an approach with high dimensional warping to the template and nonparametric statistics would be useful to detect hippocampal atrophy in patients with hippocampal sclerosis. MATERIALS AND METHODS: We performed single-subject voxel-based morphometry with nonparametric statistics within the framework of Statistical Parametric Mapping to compare MRI from 26 well-characterized patients with temporal lobe epilepsy individually against a group of 110 healthy controls. The following statistical threshold was used: P < .05 corrected for multiple comparisons with family-wise error over the region of interest right and left hippocampus. RESULTS: The sensitivity for the detection of atrophy related to hippocampal sclerosis was 0.92 (95% CI, 0.67-0.99) for the right hippocampus and 0.60 (0.31-0.83) for the left, and the specificity for volume changes was 0.98 (0.93-0.99). All clusters of decreased hippocampal volumes were correctly lateralized to the seizure focus. Hippocampal volume decrease was in accordance with neuronal cell loss on histology reports. CONCLUSIONS: Nonparametric voxel-based morphometry is sensitive and specific for hippocampal atrophy in patients with mesial temporal lobe epilepsy and may be useful in clinical practice.

Lesion-Specific Language Network Alterations in Temporal Lobe Epilepsy.

BACKGROUND AND PURPOSE: Temporal lobe epilepsy, structural or nonlesional, may negatively affect language function. However, little is known about the lesion-specific influence on language networks. We hypothesized that different epileptogenic lesions are related to distinct alterations in the functional language connectome detected by fMRI. MATERIALS AND METHODS: One hundred one patients with epilepsy due to mesiotemporal sclerosis (21 left, 22 right), low-grade mesiotemporal tumors (12 left), or nonlesional temporal lobe epilepsy (22 left, 24 right) and 22 healthy subjects performed 3T task-based language fMRI. Task-based activation maps (laterality indices) and functional connectivity analysis (global and connectivity strengths between language areas) were correlated with language scores. RESULTS: Laterality indices based on fMRI activation maps failed to discriminate among patient groups. Functional connectivity analysis revealed the most extended language network alterations in left mesiotemporal sclerosis (involving the left temporal pole, left inferior frontal gyrus, and bilateral premotor areas). The other patient groups showed less extended but also predominantly ipsilesional network changes compared with healthy controls. Left-to-right hippocampal connectivity strength correlated positively with naming function (P = .01), and connectivity strength between the left Wernicke area and the left hippocampus was linked to verbal fluency scores (P = .01) across all groups. CONCLUSIONS: Different pathologies underlying temporal lobe epilepsy are related to distinct alterations of the functional language connectome visualized by fMRI functional connectivity analysis. Network analysis allows new insights into language organization and provides possible imaging biomarkers for language function. These imaging findings emphasize the importance of a personalized treatment strategy in patients with epilepsy.

Prospective multi-center study of an automatic online seizure detection system for epilepsy monitoring units.

OBJECTIVE: A method for automatic detection of epileptic seizures in long-term scalp-EEG recordings called EpiScan will be presented. EpiScan is used as alarm device to notify medical staff of epilepsy monitoring units (EMUs) in case of a seizure. METHODS: A prospective multi-center study was performed in three EMUs including 205 patients. A comparison between EpiScan and the Persyst seizure detector on the prospective data will be presented. In addition, the detection results of EpiScan on retrospective EEG data of 310 patients and the public available CHB-MIT dataset will be shown. RESULTS: A detection sensitivity of 81% was reached for unequivocal electrographic seizures with false alarm rate of only 7 per day. No statistical significant differences in the detection sensitivities could be found between the centers. The comparison to the Persyst seizure detector showed a lower false alarm rate of EpiScan but the difference was not of statistical significance. CONCLUSIONS: The automatic seizure detection method EpiScan showed high sensitivity and low false alarm rate in a prospective multi-center study on a large number of patients. SIGNIFICANCE: The application as seizure alarm device in EMUs becomes feasible and will raise the efficiency of video-EEG monitoring and the safety levels of patients.

Postictal psychosis in temporal lobe epilepsy: a case-control study.

BACKGROUND AND PURPOSE: To investigate the prevalence of postictal psychosis (PP) in patients with temporal lobe epilepsy (TLE) and to estimate the predictive value of various variables for the development of PP. METHODS: By retrospectively reviewing the charts of all patients evaluated with video-electroencephalogram (EEG)-monitoring at our unit between January 1995 and February 2012, we identified 684 patients with TLE, of which 48 patients had a history of PP. Patients with TLE and PP were compared with 200 controls (patients with TLE without a psychotic history) on demographic, clinical, EEG and magnetic resonance imaging (MRI) variables. RESULTS: The prevalence of PP in our TLE sample was 7.0%. Aggressive behaviour during PP was present in 22.9% of the sample. Univariate analysis revealed that PP was significantly associated with early age at epilepsy onset (P = 0.007), longer duration of epilepsy (P = 0.002), presence of ictal fear (P = 0.005), impaired intellectual function (P = 0.045), and bilateral ictal and interictal epileptiform activity (both P < 0.0001). Using logistic regression analysis, ictal fear [odds ratio (OR) 2.88; P = 0.015] and bilateral interictal EEG activity (OR 6.40; P < 0.0001) were predictive of PP development. No association of PP with MRI pathology or epilepsy-relevant aetiological factors was found. CONCLUSIONS: PP is a frequent and potentially dangerous complication within the course of TLE. Bilateral or widespread functional central nervous system disturbances rather than distinct structural brain alterations or certain predisposing aetiologies of epilepsy appear to be a risk factor for the development of PP. Ictal fear may be a predictive clinical variable of PP in TLE.

Organization of receptive language-specific cortex before and after left temporal lobectomy.

OBJECTIVE: To examine brain activation associated with receptive language in patients with left temporal lobe epilepsy (TLE) before and after an anterior temporal lobectomy using magnetoencephalography (MEG), and to evaluate which patients were most likely to show a change in the lateralization and localization of the mechanisms supporting receptive language and if such changes were associated with neuropsychological function. METHODS: Twelve patients with left TLE underwent preoperative Wada testing, and pre- and postoperative neuropsychological testing and MEG language mapping. The anatomic location of receptive language-related activity sources observed with MEG was determined by coregistering MEG data with structural MRI scans. Language laterality indices were calculated based on the number of reproducible activity sources in each hemisphere. The proximity of language-specific activity sources to Wernicke's area was also examined. RESULTS: Although the small sample size precluded formal statistical analyses, patients with atypical (bilateral) hemispheric dominance preoperatively were more likely than patients with typical (left-hemisphere) dominance to show evidence of increased right hemisphere participation in language functions after surgery. Patients with left hemispheric dominance preoperatively were more likely to show intrahemispheric changes involving a slight inferior shift of the putative location of Wernicke's area. Patients with bilateral representation tended to perform worse on neuropsychological test measures obtained both pre- and postoperatively. CONCLUSION: Interhemispheric functional reorganization of language-specific areas may occur in patients undergoing left anterior temporal lobectomy. Intrahemispheric reorganization may take place even when the resection does not directly impinge upon Wernicke's area.

Spatio-temporal cortical dynamics of phonemic and semantic fluency.

Hemodynamic brain imaging and lesion studies have suggested differential involvement of expressive language-related cortical regions based on the phonemic versus semantic characteristics of verbal cues. The aims of this study were: 1) to elucidate the relative timing of the activity of inferior frontal and anterior insular versus motor and supplementary motor cortex during a fluency task and 2) to assess potential differences in the location or timing of activity in anterior and posterior language areas based on letter versus category cues. Using magnetic source imaging (MSI), we found significantly earlier onset latencies and a greater number of activity sources in motor and supplementary motor compared with inferior frontal and anterior insular regions. We also observed greater left versus right hemispheric asymmetry of activation for letter compared with category cues. This study provides new insights into cortico-cortical interactions during expressive language tasks.

Reorganization of language-specific cortex in patients with lesions or mesial temporal epilepsy.

OBJECTIVE: To examine brain activation profiles for receptive language function, using magnetoencephalography (MEG), in patients with left hemisphere space-occupying lesions and patients with left temporal lobe epilepsy due to mesial temporal sclerosis (MTS) and to evaluate whether cross- and intrahemispheric plasticity for language varied as a function of lesion type or location. METHODS: Twenty-one patients with MTS and 23 lesional patients underwent preoperative language mapping while performing a word recognition task. The anatomic location of late activity sources was determined by co-registering MEG coordinates onto structural MRI scans. A language laterality index was calculated based on the number of activity sources in each hemisphere. The location of language-specific activity was examined in relation to its proximity or overlap with Wernicke's area. RESULTS: A higher incidence of atypical language lateralization was noted among patients with MTS than lesional patients (43 vs 13%). The majority of MTS patients with early seizure onset (before age 5) showed atypical language lateralization. In contrast, the precise location of receptive language-specific cortex within the dominant hemisphere was found to be atypical (outside of Wernicke's area) in 30% of lesional patients and only 14% of MTS patients. CONCLUSIONS: There is an increased probability of a partial or total displacement of key components of the brain mechanism responsible for receptive language function to the nondominant hemisphere in mesial temporal sclerosis patients. Early onset of seizures is strongly associated with atypical language lateralization. Lesions in the dominant hemisphere tend to result in an intrahemispheric reorganization of linguistic function.

Does magnetoencephalography add to scalp video-EEG as a diagnostic tool in epilepsy surgery?

OBJECTIVE: The authors evaluated the sensitivity and selectivity of interictal magnetoencephalography (MEG) versus prolonged ictal and interictal scalp video-electroencephalography (V-EEG) in order to identify patient groups that would benefit from preoperative MEG testing. METHODS: The authors evaluated 113 consecutive patients with medically refractory epilepsy who underwent surgery. The epileptogenic region predicted by interictal and ictal V-EEG and MEG was defined in relation to the resected area as perfectly overlapping with the resected area, partially overlapping, or nonoverlapping. RESULTS: The sensitivity of a 30-minute interictal MEG study for detecting clinically significant epileptiform activity was 79.2%. Using MEG, we were able to localize the resected region in a greater proportion of patients (72.3%) than with noninvasive V-EEG (40%). MEG contributed to the localization of the resected region in 58.8% of the patients with a nonlocalizing V-EEG study and 72.8% of the patients for whom V-EEG only partially identified the resected zone. Overall, MEG and V-EEG results were equivalent in 32.3% of the cases, and additional localization information was obtained using MEG in 40% of the patients. CONCLUSION: MEG is most useful for presurgical planning in patients who have either partially or nonlocalizing V-EEG results.

Combining ictal surface-electroencephalography and seizure semiology improves patient lateralization in temporal lobe epilepsy.

PURPOSE: The study goal was to assess the concordance of ictal surface-EEG and seizure semiology data in lateralizing intractable temporal lobe epilepsy (TLE) and to examine the benefits of the combined use of these two methods. METHODS: We independently analyzed the ictal recordings and clinical symptoms associated with 262 seizures recorded in 59 TLE patients. Each seizure was lateralized on the basis of (i) its associated ictal surface-EEG pattern according to a predefined lateralization protocol and (ii) its associated ictal and postictal seizure semiology according to strictly defined clinical criteria. Individual patients were also lateralized based on these data. RESULTS: Ictal surface-EEG findings lateralized 62.6% of seizures and 64.4% of patients. Seizure semiology findings lateralized 46.2% of seizures and 78.0% of patients. There was a high degree of concordance between lateralizations based on these two methods, for both individual seizures and individual patients. Combination of the information from the two methods allowed for lateralization in a greater proportion of both seizures (79.8%) and patients (94.9%). Combined EEG-seizure lateralization was concordant with the side of operation in 33 of 34 patients who underwent successful surgery (Engel's surgical outcome class I/II). CONCLUSIONS: In TLE, there is a high agreement between the lateralization of individual seizures and patients, which is based on ictal surface-EEG findings and seizure semiology. Furthermore, combination of these two methods improves the lateralization of individual seizures and patients. Thus, standardized combined EEG-seizure analysis is a valuable noninvasive tool in the presurgical evaluation of TLE.

Magnetoencephalography in focal epilepsy.

The introduction of whole-head magnetoencephalographic (MEG) systems facilitating simultaneous recording from the entire brain surface has led to a major breakthrough in the MEG evaluation of epilepsy patients. MEG localizations estimates of the interictal spike zone showed excellent agreement with invasive electrical recordings and were useful to clarify the spatial relationship of the irritative zone and structural lesions. MEG appears to be especially useful for study of patients with neocortical epilepsy, and helped to guide the placement of subdural grid electrodes in patients with nonlesional epilepsies. MEG could differentiate between patients with mesial and lateral temporal seizure onset. Spike propagation in the temporal lobe and the spatio-temporal organization of the interictal spike complex could be studied noninvasively. MEG was useful to delineate essential brain regions before surgical procedures adjacent to the central fissure. MEG appears to be more sensitive than scalp EEG for detection of epileptic discharges arising from the lateral neocortex, whereas only highly synchronized discharges arising from mesial temporal structures could be recorded. A major limitation of MEG has been the recording of seizures because long-term recordings cannot be performed on a routine basis with the available technology. Because MEG and EEG yield both complementary and confirmatory information, combined MEG-EEG recordings in conjunction with advanced source modeling techniques should improve the noninvasive evaluation of epilepsy patients and further reduce the need for invasive procedures.

Ictal urinary urge indicates seizure onset in the nondominant temporal lobe.

The authors describe six patients with medically refractory temporal lobe epilepsy whose seizures were characterized by an aura of ictal urinary urge. All seizures originated in the nondominant temporal lobe as evidenced from interictal spikes, ictal EEG, and MRI. Ictal SPECT, which was obtained in two patients, showed a hyperperfusion of the insular cortex, indicating a critical role of the insula for the generation of this symptom. Ictal urinary urge represents a new lateralizing sign indicating a seizure onset in the nondominant temporal lobe.

Neuromagnetic recordings in temporal lobe epilepsy.

The introduction of whole-head magnetoencephalography (MEG) systems facilitating simultaneous recording from the entire brain surface has established MEG as a clinically feasible method for the evaluation of patients with temporal lobe epilepsy (TLE). In mesial TLE, two types of MEG spike dipoles could be identified: an anterior vertical and an anterior horizontal dipole. Dipole orientations can be used to attribute spike activity to temporal lobe subcompartments. Whereas the anterior vertical dipole is compatible with epileptic activity in the mediobasal temporal lobe, the anterior horizontal dipole can be explained by epileptic activity of the temporal tip cortex. In nonlesional TLE, medial and lateral vertical dipoles were found which could distinguish between medial and lateral temporal seizure onset zones as evidenced from invasive recordings. In lesional TLE, MEG could clarify the spatial relationship of the structural lesion to the irritative zone. Evaluation of patients with persistent seizures after epilepsy surgery may represent another clinical important application of MEG because magnetic fields are less influenced than electric fields by the prior operation. Simultaneous MEG and invasive EEG recordings indicate that epileptic activity restricted to mesial temporal structures cannot reliably be detected on MEG and that an extended cortical area of at least 6 to 8 cm2 involving also the basal temporal lobe is necessary to produce a reproducible MEG signal. In lateral neocortical TLE MEG seems to be more sensitive than scalp-EEG which further underlines the potential role of MEG for the study of nonlesional TLE. Whole-head MEG therefore can be regarded as a valuable and clinically relevant noninvasive method for the evaluation of patients with TLE.

Regional cerebral blood flow during temporal lobe seizures associated with ictal vomiting: an ictal SPECT study in two patients.

PURPOSE: Ictal vomiting represents a rare clinical manifestation during seizures originating from the temporal lobes of the nondominant hemisphere. The precise anatomic structures responsible for generation of ictal vomiting remain to be clarified. Ictal single photon emission computed tomography (SPECT), which allows one to visualize the three-dimensional dynamic changes of regional cerebral blood flow (rCBF) associated with the ongoing epileptic activity, should be useful to study the brain areas activated during ictal vomiting. METHODS: We performed ictal Tc-HMPAO SPECT scans in two patients with mesial temporal lobe epilepsy (MTLE) whose seizures were characterized by ictal retching and vomiting. MTLE was documented by typical clinical seizure semiology, interictal and ictal EEG findings, hippocampal atrophy on magnetic resonance imaging (MRI) scan, and a seizure-free outcome after selective amydalohippocampectomy. In both patients, seizures originated in the nondominant temporal lobe. We obtained accurate anatomic reference of rCBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. We used ictal SPECT studies in 10 patients with MTLE who had seizures without ictal vomiting as controls. RESULTS: In the two patients with ictal vomiting, we found a significant hyperperfusion of the nondominant temporal lobe (inferior, medial, and lateral superior) and of the occipital region on ictal SPECT. In patients without ictal vomiting, on the contrary, these brain regions never were hyperperfused simultaneously. CONCLUSIONS: Ictal SPECT provides further evidence that activation of a complex cortical network, including the medial and lateral superior aspects of the temporal lobe, and maybe the occipital lobes, is responsible for the generation of ictal vomiting.

A case of startle epilepsy and SSMA seizures documented with subdural recordings.

PURPOSE: To study the mechanisms of startle-induced supplementary sensorimotor area (SSMA) seizures. METHODS: We present a patient investigated with indwelling subdural grid electrodes covering both the SSMA and the dorsolateral frontal lobe. RESULTS: We found a simultaneous seizure onset in the right dorsolateral premotor cortex and the right SSMA. High-resolution magnetic resonance imaging (MRI) showed a small subcortical lesion adjacent to the right SSMA. The patient became seizure free after resection of the lesion and the ictal-onset zone. CONCLUSIONS: We conclude that an extended region of abnormally excitable tissue within the frontal lobe could facilitate the generation of startle-induced seizures. We speculate that a widespread epileptogenic zone could help to explain why some patients with SSMA or dorsolateral frontal lobe seizures are more likely to have startle-induced seizures.

Clinical symptoms in psychogenic seizures.

PURPOSE: To develop a classification system of psychogenic seizures based on characteristic clinical symptom clusters and sequences in order to facilitate the correct differential diagnosis of epileptic seizures. METHODS: We analysed the symptoms: clonic movements, hypermotor movements, trembling and tonic posturing of the upper/lower extremities, pelvic thrusting, stiffening of the body, version, side-to-side-head movements, non-versive head-turning and falling to the floor. We did this in a series of 16 patients with psychogenic seizures documented with prolonged video EEG monitoring. Nine patients (7 with frontal lobe epilepsy and 2 with primary generalised epilepsy with tonic, clonic seizures) served as a control group. RESULTS: We classified psychogenic seizures into 3 groups, namely (1) atonic psychogenic seizures, (2) psychogenic motor seizures and (3) psychogenic hypermotor seizures characterised by (1) falling to the ground, (2) trembling in the upper/lower extremities and (3) pelvic thrusting in combination with beating and kicking. While version exclusively occurred in epileptic seizures (incidence = 20%) and side-to-side head movements were only observed during psychogenic seizures (incidence = 8%), all other analysed symptoms were observed in both psychogenic and epileptic seizures. CONCLUSION: Our classification scheme should be useful in terms of permitting a more comprehensive clinical assessment of psychogenic seizures and their underlying psychiatric disorders. Furthermore, the differential diagnosis of psychogenic seizures should be considerably improved.

Health-related quality of life (HRQOL), activity of daily living (ADL) and depressive mood disorder in temporal lobe epilepsy patients.

We determined the interrelations of chronological age, age at seizure onset, duration of seizure disorder, cognitive functioning (IQ), scales of activities of daily living, depressive mood disorder and measures of health-related quality of life (HRQOL). Furthermore, we investigated the association of the laterality of seizure onset zone and absence/presence of hippocampal atrophy and/or sclerosis (HA/HS) with measures of HRQOL, activities of daily living (ADL) and depressive mood disorder. In the setting of pre-surgical epilepsy evaluation, a sample of 56 patients with temporal lobe epilepsy (TLE) was studied using the Bonner Skalen für Epilepsie (BPSE) and the depression inventory D-S of von Zerssen. Patients reported high levels of dependency on others and poor coping capabilities. Our data also showed specific ADL-behaviour suggesting social withdrawal and isolation. Our results indicate emotional impairment as a major problem in TLE, because 45% of our patients scored in the depressive range of the D-S depression scale. Depression score was found to be a powerful predictor of self-reported quality of life after adjusting for seizure-related variables, demographic variables and cognitive functioning (IQ). The only scale showing a significant laterality effect was ADL-home. No relationship between the dependent measures of HRQOL, ADL-social, ADL-cultural, depressive mood disorder and laterality of the epileptogenic zone or absence/presence of HA/HS was found. HRQOL and depressive mood disorder are strongly interrelated indicating that patients with depressive symptoms report lower quality of life and specific patterns of ADL. HRQOL, ADL and depressive mood disorder are largely independent of biological markers such as laterality of seizure onset zone and absence/presence of HA/HS in TLE.

Genital automatisms in complex partial seizures.

OBJECTIVE: To determine which brain region is responsible for the generation of sexual automatisms. METHODS: Ninety consecutive patients with medically refractory focal epilepsy (74 with temporal lobe and 16 with frontal lobe epilepsy) referred to an epilepsy monitoring unit were studied. The occurrence of the following sexual automatisms was assessed during prolonged video-EEG monitoring: 1) repeatedly grabbing or fondling the genitals and 2) pelvic or truncal thrusting or similar movements. RESULTS: Five patients repeatedly fondled or grabbed their genitals during or immediately after some of their seizures. All five had temporal lobe epilepsy, as evidenced from prolonged video-EEG monitoring, high-resolution MRI, and good to excellent outcome after epilepsy surgery. Sexual automatisms did not occur with frontal lobe epilepsy. CONCLUSION: Sexual automatisms cannot be related exclusively to frontal lobe seizures. As previously proposed, apparently sexual hypermotoric pelvic or truncal movements are common in frontal lobe seizures, but this study suggests that discrete genital automatisms, like fondling and grabbing the genitals, are more common in seizures evolving from the temporal lobe.

Postictal nose wiping: a lateralizing sign in temporal lobe complex partial seizures.

We report postictal nose wiping as a postictal symptom of localizing and lateralizing significance in focal epilepsy. We reviewed videotapes of 444 focal seizures in 101 patients who underwent prolonged video and EEG monitoring during presurgical epilepsy evaluation, and observed postictal nose wiping in 51.3% of 76 patients with temporal lobe epilepsy. The hand used to perform postictal nose wiping was ipsilateral to the side of seizure origin in 86.5% of all seizures and in 97.3% of all patients. We conclude that postictal nose wiping is a common, easily assessed symptom after focal seizures of temporal lobe origin that provides reliable lateralizing information on the side of seizure onset.