Automatic seizure detection and seizure pattern morphology.

OBJECTIVE: We studied the influence of seizure pattern morphology on detection rate and detection delay of an automatic seizure detection system. We correlated seizure pattern morphology with seizure onset zone and assessed the influence of seizure onset zone on the performance of the seizure detection system. METHODS: We analyzed 10.000 hours of EEG in 129 patients, 193 seizures in 67 patients were included in the final analysis. Seizure pattern morphologies were classified as rhythmic activity (alpha, theta and delta), paroxysmal fast activity, suppression of activity, repetitive epileptiform and arrhythmic activity. The seizure detection system EpiScan was compared with visual analysis. RESULTS: Detection rates were significantly higher for rhythmic and repetitive epileptiform activities than for paroxysmal fast activity. Seizure patterns significantly correlated with seizure onset zone. Detection rate was significantly higher in temporal lobe (TL) seizures than in frontal lobe (FL) seizures. Detection delay tended to be shorter in seizures with rhythmic alpha or theta activity. TL seizures were significantly more often detected within 10 seconds than FL seizures. CONCLUSIONS: Seizure morphology is critical for optimization of automatic seizure detection algorithms. SIGNIFICANCE: This study is unique in exploring the influence of seizure pattern morphology on automatic seizure detection and can help future research on seizure detection in epilepsy.

Imaging visuospatial memory in temporal lobe epilepsy-Results of an fMRI study.

PURPOSE: Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland's Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE. METHODS: We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC). RESULTS: Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE. CONCLUSION: While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.

Increased expression of GABAA receptor subunits associated with tonic inhibition in patients with temporal lobe epilepsy.

Epilepsy animal models indicate pronounced changes in the expression and rearrangement of GABAA receptor subunits in the hippocampus and in para-hippocampal areas, including widespread downregulation of the subunits α5 and δ, and upregulation of α4, subunits that mediate tonic inhibition of GABA. In this case-control study, we investigated changes in the expression of subunits α4, α5 and δ in hippocampal specimens of drug resistant temporal lobe epilepsy patients who underwent epilepsy surgery. Using in situ hybridization, immunohistochemistry and α5-specific receptor autoradiography, we characterized expression of the receptor subunits in specimens from patients with and without Ammon's horn sclerosis compared to post-mortem controls. Expression of the α5-subunit was abundant throughout all subfields of the hippocampus, including the dentate gyrus, sectors CA1 and CA3, the subiculum and pre- and parasubiculum. Significant but weaker expression was detected for subunits α4 and δ notably in the granule cell/molecular layer of control specimens, but was faint in the other parts of the hippocampus. Expression of all three subunits was similarly altered in sclerotic and non-sclerotic specimens. Respective mRNA levels were increased by about 50-80% in the granule cell layer compared with post-mortem controls. Subunit α5 mRNA levels and immunoreactivities were also increased in the sector CA3 and in the subiculum. Autoradiography for α5-containing receptors using [3H]L-655,708 as ligand showed significantly increased binding in the molecular layer of the dentate gyrus in non-sclerotic specimens. Increased expression of the α5 and δ subunits is in contrast to the previously observed downregulation of these subunits in different epilepsy models, whereas increased expression of α4 in temporal lobe epilepsy patients is consistent with that in the rodent models. Our findings indicate increased tonic inhibition likely representing an endogenous anticonvulsive mechanism in temporal lobe epilepsy.

The impact of hippocampal impairment on task-positive and task-negative language networks in temporal lobe epilepsy.

OBJECTIVE: To study hippocampal integration within task-positive and task-negative language networks and the impact of a diseased left and right hippocampus on the language connectome in temporal lobe epilepsy (TLE). METHODS: We used functional magnetic resonance imaging (fMRI) to study a homogenous group of 32 patients with TLE (17 left) and 14 healthy controls during a verb-generation task. We performed functional connectivity analysis and quantified alterations within the language connectome and evaluated disruptions of the functional dissociation along the anterior-posterior axis of the hippocampi. RESULTS: Connectivity analysis revealed significant differences between left and right TLE compared to healthy controls. Left TLE showed widespread impairment of task-positive language networks, while right TLE showed less pronounced alterations. Particularly right TLE showed altered connectivity for cortical regions that were part of the default mode network (DMN). Left TLE showed a disturbed functional dissociation pattern along the left hippocampus to left and right inferior frontal language regions, while left and right TLE revealed an altered dissociation pattern along the right hippocampus to regions associated with the DMN. CONCLUSIONS: Our results showed an impaired hippocampal integration into active language and the default mode networks, which both may contribute to language impairment in TLE. SIGNIFICANCE: Our results emphasize the direct role of the left hippocampus in language processing, and the potential role of the right hippocampus as a modulator between DMN and task-positive networks.

Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study.

Background: IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features. Methods: We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD. Results: A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD. Conclusion: Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.

Language network reorganization before and after temporal lobe epilepsy surgery.

OBJECTIVE: Epilepsy surgery is the recommended treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). This method offers a good chance of seizure freedom but carries a considerable risk of postoperative language impairment. The extremely variable neurocognitive profiles in surgical epilepsy patients cannot be fully explained by extent of resection, fiber integrity, or current task-based functional MRI (fMRI). In this study, the authors aimed to investigate pathology- and surgery-triggered language organization in TLE by using fMRI activation and network analysis as well as considering structural and neuropsychological measures. METHODS: Twenty-eight patients with unilateral TLE (16 right, 12 left) underwent T1-weighted imaging, diffusion tensor imaging, and task-based language fMRI pre- and postoperatively (n = 15 anterior temporal lobectomy, n = 11 selective amygdalohippocampectomy, n = 2 focal resection). Twenty-two healthy subjects served as the control cohort. Functional connectivity, activation maps, and laterality indices for language dominance were analyzed from fMRI data. Postoperative fractional anisotropy values of 7 major tracts were calculated. Naming, semantic, and phonematic verbal fluency scores before and after surgery were correlated with imaging parameters. RESULTS: fMRI network analysis revealed widespread, bihemispheric alterations in language architecture that were not captured by activation analysis. These network changes were found preoperatively and proceeded after surgery with characteristic patterns in the left and right TLEs. Ipsilesional fronto-temporal connectivity decreased in both left and right TLE. In left TLE specifically, preoperative atypical language dominance predicted better postoperative verbal fluency and naming function. In right TLE, left frontal language dominance correlated with good semantic verbal fluency before and after surgery, and left fronto-temporal language laterality predicted good naming outcome. Ongoing seizures after surgery (Engel classes ID-IV) were associated with naming deterioration irrespective of seizure side. Functional findings were not explained by the extent of resection or integrity of major white matter tracts. CONCLUSIONS: Functional connectivity analysis contributes unique insight into bihemispheric remodeling processes of language networks after epilepsy surgery, with characteristic findings in left and right TLE. Presurgical contralateral language recruitment is associated with better postsurgical language outcome in left and right TLE.

Presurgical epilepsy evaluation and epilepsy surgery.

With a prevalence of 0.8 to 1.2%, epilepsy represents one of the most frequent chronic neurological disorders; 30 to 40% of patients suffer from drug-resistant epilepsy (that is, seizures cannot be controlled adequately with antiepileptic drugs). Epilepsy surgery represents a valuable treatment option for 10 to 50% of these patients. Epilepsy surgery aims to control seizures by resection of the epileptogenic tissue while avoiding neuropsychological and other neurological deficits by sparing essential brain areas. The most common histopathological findings in epilepsy surgery specimens are hippocampal sclerosis in adults and focal cortical dysplasia in children. Whereas presurgical evaluations and surgeries in patients with mesial temporal sclerosis and benign tumors recently decreased in most centers, non-lesional patients, patients requiring intracranial recordings, and neocortical resections increased. Recent developments in neurophysiological techniques (high-density electroencephalography [EEG], magnetoencephalography, electrical and magnetic source imaging, EEG-functional magnetic resonance imaging [EEG-fMRI], and recording of pathological high-frequency oscillations), structural magnetic resonance imaging (MRI) (ultra-high-field imaging at 7 Tesla, novel imaging acquisition protocols, and advanced image analysis [post-processing] techniques), functional imaging (positron emission tomography and single-photon emission computed tomography co-registered to MRI), and fMRI significantly improved non-invasive presurgical evaluation and have opened the option of epilepsy surgery to patients previously not considered surgical candidates. Technical improvements of resective surgery techniques facilitate successful and safe operations in highly delicate brain areas like the perisylvian area in operculoinsular epilepsy. Novel less-invasive surgical techniques include stereotactic radiosurgery, MR-guided laser interstitial thermal therapy, and stereotactic intracerebral EEG-guided radiofrequency thermocoagulation.

Video-EEG.

Indications for video-EEG monitoring (VEM) include differential diagnosis of paroxysmal events including epileptic seizures, organic nonepileptic seizures, and psychogenic nonepileptic seizures; classification of seizure types and electroclinical syndromes; quantification of seizures and of interictal and ictal epileptiform discharges; and presurgical evaluation in medically refractory epilepsy patients. Standardized questionnaires and examinations should be used on admission to the epilepsy monitoring unit (EMU). Patients should be provided with comprehensive information concerning purpose and procedures during VEM and need to sign informed consents. Staff working in the EMU needs to be properly trained in the management of seizures and periictal testing according to written protocols as well as in cardiopulmonary resuscitation. Minimum staffing ratios of dedicated healthcare professionals to patients have been recommended. Antiepileptic drug tapering/withdrawal needs to be individualized for each patient. EEG recordings have to be performed according to established guidelines. Cardiorespiratory monitoring including continuous ECG monitoring and continuous measurement of oxygen saturation is strongly recommended. Patient safety is of utmost importance during VEM. Indicators for reporting quality and safety have been developed. Standardized ictal testing protocols and standardized computer-based organized reporting should further improve standards of VEM and training of EMU staff, and facilitate data exchange and collaborations between EMUs.

Epidemiology and pathophysiology of autonomic seizures: a systematic review.

PURPOSE: To review the epidemiology and pathophysiology of autonomic symptoms and signs during epileptic seizures. METHODS: We performed a systematic literature search on the following autonomic symptoms and signs during epileptic seizures: cardiovascular changes, respiratory manifestations, gastrointestinal symptoms, cutaneous manifestations, sexual and genital manifestations, and urinary symptoms. RESULTS: Autonomic symptoms and signs can represent the predominant symptom at the onset of a focal seizure, which would then lead to the seizure being classified as a focal onset autonomic seizure. Conversely, clinically relevant autonomic symptoms and signs frequently accompany seizures of focal, generalized, and/or unknown onset, but the seizure is regardless classified according to other, more relevant features. Autonomic symptoms and signs do not represent mere reactions to motor activity or other behavioral seizure manifestations, but rather they are generated by epileptic discharges affecting the central autonomic network. We have reviewed the localizing and lateralizing information currently available on the seizure onset zone and on seizure propagation pathways as provided by systematic analysis of specific autonomic seizure symptoms and signs. We present data on how autonomic seizure symptoms and signs are useful for gaining a better understanding of the anatomical and functional organization of the central autonomic network. Finally, we discuss the differential diagnosis of focal autonomic seizures with autonomic symptoms and signs representing the sole seizure manifestation versus various non-epileptic conditions. CONCLUSIONS: Autonomic seizure symptoms and signs are relevant in clinical epileptology and open a unique window on the functional organization and pathophysiology of the central autonomic network.

Automated Long-Term EEG Review: Fast and Precise Analysis in Critical Care Patients.

Background: Ongoing or recurrent seizure activity without prominent motor features is a common burden in neurological critical care patients and people with epilepsy during ICU stays. Continuous EEG (CEEG) is the gold standard for detecting ongoing ictal EEG patterns and monitoring functional brain activity. However CEEG review is very demanding and time consuming. The purpose of the present multirater, EEG expert reviewer study, is to test and assess the clinical feasibility of an automatic EEG pattern detection method (Neurotrend). Methods: Four board certified EEG reviewers used Neurotrend to annotate 76 CEEG datasets à 6 h (in total 456 h of EEG) for rhythmic and periodic EEG patterns (RPP), unequivocal ictal EEG patterns and burst suppression. All reviewers had a predefined time limit of 5 min (± 2 min) per CEEG dataset and were compared to a predefined gold standard (conventional EEG review with unlimited time). Subanalysis of specific features of RPP was conducted as well. We used Gwet's AC1 and AC2 coefficients to calculate interrater agreement (IRA) and multirater agreement (MRA). Also, we determined individual performance measures for unequivocal ictal EEG patterns and burst suppression. Bonferroni-Holmes correction for multiple testing was applied to all statistical tests. Results: Mean review time was 3.3 min (± 1.9 min) per CEEG dataset. We found substantial IRA for unequivocal ictal EEG patterns (0.61-0.79; mean sensitivity 86.8%; mean specificity 82.2%, p < 0.001) and burst suppression (0.68-0.71; mean sensitivity 96.7%; mean specificity 76.9% p < 0.001). Two reviewers showed substantial IRA for RPP (0.68-0.72), whereas the other two showed moderate agreement (0.45-0.54), compared to the gold standard (p < 0.001). MRA showed almost perfect agreement for burst suppression (0.86) and moderate agreement for RPP (0.54) and unequivocal ictal EEG patterns (0.57). Conclusions: We demonstrated the clinical feasibility of an automatic critical care EEG pattern detection method on two levels: (1) reasonable high agreement compared to the gold standard, (2) reasonable short review times compared to previously reported EEG review times with conventional EEG analysis.

Automatic ictal onset source localization in presurgical epilepsy evaluation.

OBJECTIVE: To test the diagnostic accuracy of a new automatic algorithm for ictal onset source localization (IOSL) during routine presurgical epilepsy evaluation following STARD (Standards for Reporting of Diagnostic Accuracy) criteria. METHODS: We included 28 consecutive patients with refractory focal epilepsy (25 patients with temporal lobe epilepsy (TLE) and 3 with extratemporal epilepsy) who underwent resective epilepsy surgery. Ictal EEG patterns were analyzed with a novel automatic IOSL algorithm. IOSL source localizations on a sublobar level were validated by comparison with actual resection sites and seizure free outcome 2 years after surgery. RESULTS: Sensitivity of IOSL was 92.3% (TLE: 92.3%); specificity 60% (TLE: 50%); positive predictive value 66.7% (TLE: 66.7%); and negative predictive value 90% (TLE: 85.7%). The likelihood ratio was more than ten times higher for concordant IOSL results as compared to discordant results (p = 0.013). CONCLUSIONS: We demonstrated the clinical feasibility of our IOSL approach yielding reasonable high performance measures on a sublobar level. SIGNIFICANCE: Our IOSL method may contribute to a correct localization of the seizure onset zone in temporal lobe epilepsy and can readily be used in standard epilepsy monitoring settings. Further studies are needed for validation in extratemporal epilepsy.

Mesial temporal lobe epilepsy: long-term seizure outcome of patients primarily treated with transsylvian selective amygdalohippocampectomy.

OBJECTIVE The aim of this study was to present long-term seizure outcome data in a consecutive series of patients with refractory mesial temporal lobe epilepsy primarily treated with transsylvian selective amygdalohippocampectomy (SAHE). METHODS The authors retrospectively analyzed prospectively collected data for all patients who had undergone resective surgery for medically refractory epilepsy at their institution between July 1994 and December 2014. Seizure outcome was assessed according to the International League Against Epilepsy (ILAE) and the Engel classifications. RESULTS The authors performed an SAHE in 158 patients (78 males, 80 females; 73 right side, 85 left side) with a mean age of 37.1 ± 10.0 years at surgery. Four patients lost to follow-up and 1 patient who committed suicide were excluded from analysis. The mean follow-up period was 9.7 years. At the last available follow-up (or before reoperation), 68 patients (44.4%) had achieved an outcome classified as ILAE Class 1a, 46 patients (30.1%) Class 1, 6 patients (3.9%) Class 2, 16 patients (10.4%) Class 3, 15 patients (9.8%) Class 4, and 2 patients (1.3%) Class 5. These outcomes correspond to Engel Class I in 78.4% of the patients, Engel Class II in 10.5%, Engel Class III in 8.5%, and Engel Class IV in 2.0%. Eleven patients underwent a second surgery (anterior temporal lobectomy) after a mean of 4.4 years from the SAHE (left side in 6 patients, right side in 5). Eight (72.7%) of these 11 patients achieved seizure freedom. The overall ILEA seizure outcome since (re)operation after a mean follow-up of 10.0 years was Class 1a in 72 patients (47.0%), Class 1 in 50 patients (32.6%), Class 2 in 7 patients (4.6%), Class 3 in 15 patients (9.8%), Class 4 in 8 patients (5.2%), and Class 5 in 1 patient (0.6%). These outcomes correspond to an Engel Class I outcome in 84.3% of the patients. CONCLUSIONS A satisfactory long-term seizure outcome following transsylvian SAHE was demonstrated in a selected group of patients with refractory temporal lobe epilepsy.

Rhythmic and periodic EEG patterns of 'ictal-interictal uncertainty' in critically ill neurological patients.

OBJECTIVES: To study periodic and rhythmic EEG patterns classified according to Standardized Critical Care EEG Terminology (SCCET) of the American Clinical Neurophysiology Society and their relationship to electrographic seizures. METHODS: We classified 655 routine EEGs in 371 consecutive critically ill neurological patients into (1) normal EEGs or EEGs with non-specific abnormalities or interictal epileptiform discharges, (2) EEGs containing unequivocal ictal EEG patterns, and (3) EEGs showing rhythmic and periodic EEG patterns of 'ictal-interictal uncertainty' (RPPIIIU) according to SCCET. RESULTS: 313 patients (84.4%) showed normal EEGs, non-specific or interictal abnormalities, 14 patients (3.8%) had EEGs with at least one electrographic seizure, and 44 patients (11.8%) at least one EEG containing RPPIIIU, but no EEG with electrographic seizures. Electrographic seizures occurred in 11 of 55 patients (20%) with RPPIIIU, but only in 3 of 316 patients (0.9%) without RPPIIIU (p⩽0.001). Conversely, we observed RPPIIIU in 11 of 14 patients (78.6%) with electrographic seizures, but only in 44 of 357 patients (12.3%) without electrographic seizures (p⩽0.001). CONCLUSIONS: On routine-EEG in critically ill neurological patients RPPIIIU occur 3 times more frequently than electrographic seizures and are highly predictive for electrographic seizures. SIGNIFICANCE: RPPIIIU can serve as an indication for continuous EEG recordings.

Progressive Dopamine Transporter Binding Loss in Autopsy-Confirmed Corticobasal Degeneration.

BACKGROUND: Corticobasal degeneration (CBD) is characterized by neuronal and glial deposition of 4-repeat tau in the frontal and parietal cerebral cortex, white matter and striatum. There is neuronal loss in affected cortical regions and in the substantia nigra (SN). Recent single photon emission tomography (SPECT) studies have reported normal striatal dopamine transporter (DAT) binding in individual patients with CBD. OBJECTIVE: To study the pattern and course of DAT binding loss in CBD. METHODS: We retrospectively analyzed DAT SPECT studies in two patients presenting with a corticobasal syndrome in whom a diagnosis of CBD was later confirmed pathologically. RESULTS: Baseline scans at 1.5 years after symptom onset revealed only mild abnormalities (reduced uptake in one putamen). Follow up scans at 4.5 years (Case 1) and 5 years (Case 2) after symptom onset showed a marked decline of striatal DAT binding. In both cases, there was a 37% binding reduction from the age-expected striatal binding value. Asymmetry of striatal DAT binding had increased from mild in the first SPECT studies to moderate at the time of their final imaging. CONCLUSION: CBD patients can have delayed neuronal loss in the SN. Follow up DAT imaging may be of value in patients with possible CBD and a normal baseline scan.

Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts.

Dopamine transporter imaging is widely used for the differential diagnosis of parkinsonism. Only limited data are available on the relationship between striatal dopamine transporter binding and dopaminergic cell loss in the substantia nigra (SN). We analyzed postmortem SN cell counts in patients who had previously undergone dopamine transporter single-photon emission computed tomography (SPECT). Pathological diagnoses included Parkinson's disease (n = 1), dementia with Lewy bodies (n = 2), multiple system atrophy (n = 1), corticobasal degeneration (n = 2), atypical parkinsonism with multiple pathological conditions (n = 1), Alzheimer's disease (n = 1), and Creutzfeldt-Jakob disease (n = 1). [(12) (3) I]ß-CIT SPECT had been performed in all subjects using a standardized protocol on the same triple-head gamma camera. The density of neuromelanin-containing and tyrosine hydroxylase-positive substantia nigra neurons/mm(2) was evaluated in paraffin-embedded tissue sections by morphometric methods. Mean disease duration at the time of dopamine transporter imaging was 2.3 years, and the mean interval from imaging to death was 29.3 months (range, 4-68 months). Visual analysis of dopamine transporter images showed reduced striatal uptake in all seven patients with neurodegenerative parkinsonism, but not in Alzheimer's and Creutzfeldt-Jakob disease cases. Averaged [(right+left)/2] striatal uptake was highly correlated with averaged SN cell counts (rs = 0.98, P < 0.0005 for neuromelanin- and rs = 0.96, P < 0.0005 for tyrosine hydroxylase-positive cells). Similar strong correlations were found in separate analyses for the right and left sides. Striatal dopamine transporter binding highly correlated with postmortem SN cell counts, confirming the validity of dopamine transporter imaging as an excellent in vivo marker of nigrostriatal dopaminergic degeneration.

Automatic ictal HFO detection for determination of initial seizure spread.

High-frequency oscillations (HFOs) are a reliable indicator for the epileptic seizure onset zone (SOZ) in ECoG recordings. We propose a novel method for the automatic detection of ictal HFOs in the ripple band (80-250 Hz) based on CFAR matched sub-space filtering. This allows to track the early propagation of ictal HFOs, revealing initial and follow-up epileptic activity on the electrodes. We apply this methodology to two seizures from one patient suffering from focal epilepsy. The electrodes identified are in very good accordance with the visual HFO analysis by clinicians. Furthermore the electrodes with initial HFO activity are correlated well with the SOZ (conventional v-activity).

Influence analysis for high-dimensional time series with an application to epileptic seizure onset zone detection.

Granger causality is a useful concept for studying causal relations in networks. However, numerical problems occur when applying the corresponding methodology to high-dimensional time series showing co-movement, e.g. EEG recordings or economic data. In order to deal with these shortcomings, we propose a novel method for the causal analysis of such multivariate time series based on Granger causality and factor models. We present the theoretical background, successfully assess our methodology with the help of simulated data and show a potential application in EEG analysis of epileptic seizures.

Dopamine D2 receptor SPECT in corticobasal syndrome and autopsy-confirmed corticobasal degeneration.

BACKGROUND: Corticobasal degeneration (CBD) is a rare neurodegenerative disorder characterized by tau-positive neuronal and glial lesions in the cortex and striatum with neuronal loss in cortical regions and in the substantia nigra. Striatal dopamine D2 receptor binding in autopsy-confirmed CBD has not been studied before. METHODS: We performed D2 receptor single photon emission computerized tomography using (123)I-IBZM in nine patients with a clinically diagnosed corticobasal syndrome (CBS) and on ten healthy controls. Two of the patients subsequently came to autopsy and were diagnosed with CBD. RESULTS: Overall striatal D2 receptor binding was preserved in 8/9 patients, but more asymmetric than in controls. Overall striatal binding in pathologically confirmed CBD was reduced in one case and normal in the other, and was lower contralateral to the clinically more affected side in both. CONCLUSION: This first study on D2 receptor imaging in autopsy-confirmed CBD demonstrates that loss of postsynaptic striatal neurons in CBD is a variable finding. Given the heterogeneity of our findings in pathology-confirmed cases, D2 receptor imaging seems to be of little practical value in the diagnostic workup of patients with CBS.

Preoperative depressive symptoms are not predictors of postoperative seizure control in patients with mesial temporal lobe epilepsy and hippocampal sclerosis.

Retrospective data analysis was performed in a sample of 45 consecutive patients who underwent epilepsy surgery for medically refractory mTLE-HS. Beck Depression Inventory (BDI) was used preoperatively to detect actual depressive symptoms and label patients into those "with depressive symptoms" or "without depressive symptoms". Postoperative seizure outcome one, two, and three years after surgery was classified into "complete seizure freedom" versus "presence of auras and/or seizures". Postoperative seizure outcomes were compared in patients with and without depressive symptoms, and no significant difference of postoperative seizure outcome was found. However, there was a non-significant trend for patients with preoperative depressive symptoms to experience a postoperative running down phenomenon more frequently than nondepressed patients. Depressive symptoms, identified by the BDI, do not seem to have a predictive value for postoperative seizure outcome in this highly selected patient population with mTLE-HS, but may be positive predictors for experiencing a postoperative running down phenomenon.