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Children with epilepsy have more sleep disorders compared to healthy children. The bidirectional interaction between epilepsy and sleep is not completely understood. However, disruption of sleep architecture during childhood may have consequences for cognitive development. As children with drug-refractory epilepsy often have intellectual disability, sleep disruption could be an important contributing factor in severity of their cognitive impairment. To better understand these interactions, sleep architecture in children with drug-refractory epilepsy and epileptic encephalopathies should be investigated. In this review, we conducted a systematic literature search on this topic. Articles that investigated sleep macro- and/or microstructure by means of electroencephalogram/polysomnography were included, as well as articles that used validated questionnaires. Sixteen articles were reviewed, eight of which used polysomnography. Only 2 articles examined sleep in children with epileptic encephalopathies. Consistent findings on measures of sleep architecture were a reduction in REM percentage and an increase in sleep fragmentation when comparing drug-refractory patients with non-refractory and healthy subjects. The findings on slow wave sleep were less clear. Studies with questionnaires unambiguously confirmed subjectively more sleep problems in children with drug-refractory epilepsy. This is the first review of literature in this patient population. More good quality sleep studies in children with drug-refractory epilepsy are warranted. The use of wearables in the home setting together with automatic sleep staging could provide more insights.

We describe a 48-year-old man who experienced a sudden, pervasive change of mental status following a generalized tonic-clonic seizure. In the absence of typical epileptic phenomena, diagnosis of non convulsive status epilepticus (NCSE) was delayed. Diagnosis depends upon clinical presentation, EEG findings and, in difficult cases, the effects of a trial with antiepileptic drugs (AEDs). In this case report the diagnosis of NCSE was made ‘a posteriori’ based upon symptom remission and EEG normalization following introduction of AEDs. We discuss epidemiology, clinical manifestations, morbidity, mortality and prognosis of NCSE.

BackgroundElectroconvulsive therapy (ECT) applies electric currents to the brain to induce seizures for therapeutic purposes. ECT increases gray matter (GM) volume, predominantly in the medial temporal lobe (MTL). The contribution of induced seizures to this volume change remains unclear.MethodsT1-weighted structural MRI was acquired from thirty patients with late-life depression (mean age 72.5±7.9 years, 19 female), before and one week after one course of right unilateral ECT. Whole brain voxel-/deformation-/surface-based morphometry analyses were conducted to identify tissue-specific (GM, white matter: WM), and cerebrospinal fluid (CSF) and cerebral morphometry changes following ECT. Whole-brain voxel-wise electric field (EF) strength was estimated to investigate the association of EF distribution and regional brain volume change. The association between percentage volume change in the right MTL and ECT-related parameters (seizure duration, EF, and number of ECT sessions) was investigated using multiple regression.ResultsECT induced widespread GM volume expansion with corresponding contraction in adjacent CSF compartments, and limited WM change. The regional EF was strongly correlated with the distance from the electrodes, but not with regional volume change. The largest volume expansion was identified in the right MTL, and this was correlated with the total seizure duration.ConclusionsRight unilateral ECT induces widespread, bilateral regional volume expansion and contraction, with the largest change in the right MTL. This dynamic volume change cannot be explained by the effect of electrical stimulation alone and is related to the cumulative effect of ECT-induced seizures.

Visual information reaches the amygdala through the various stages of the ventral visual stream. There is, however, evidence that a fast subcortical pathway for the processing of emotional visual input exists. To explore the presence of this pathway in primates, we recorded local field potentials in the amygdala of four rhesus monkeys during a passive fixation task showing images of ten object categories. Additionally, in one of the monkeys we also obtained multi-unit spiking activity during the same task. We observed remarkably fast medium and high gamma responses in the amygdala of the four monkeys. These responses were selective for the different stimulus categories, showed within-category selectivity, and peaked as early as 60 ms after stimulus onset. Multi-unit responses in the amygdala were lagging the gamma responses by about 40 ms. Thus, these observations add further evidence that selective visual information reaches the amygdala of nonhuman primates through a very fast route. ispartof: SCIENTIFIC REPORTS vol:10 issue:1 ispartof: location:England status: published

Aim To study the association between global hemodynamics, blood gases, epileptiform EEG activity and survival after out-of-hospital CA (0HCA). Methods We retrospectively analyzed 195 comatose post-CA patients. At least one EEG recording per patient was evaluated to diagnose epileptiform EEG activity. Refractory epileptiform EEG activity was defined as persisting epileptic activity on EEG despite the use of 2 or more anti-epileptics. The time weighted average mean arterial pressure 48 h (TWA-MAP48), the percentage of time with a MAP below 65 and above 85 mmHg and the percentage of time with normoxia, hypoxia ( 150 mmHg), normocapnia, hypocapnia ( 45 mmHg) were calculated. Results We observed epileptiform EEG activity in 57 patients (29%). A shockable rhythm was associated with a decreased likelihood of epileptic activity on the EEG (OR: 0.41, 95%CI 0.22–0.79). We did not identify an association between the TWA-MAP48, the percentage of time with MAP below 65 mmHg or above 85 mmHg, blood gas variables and the risk of post-CA epileptiform EEG activity. The presence of epileptiform activity decreased the likelihood of survival independently (OR: 0.10, 95% CI: 0.04–0.24). Interestingly, survival rates of patients in whom the epileptiform EEG resolved (n = 20), were similar compared to patients without epileptiform activity on EEG (60% vs 67%,p = 0.617). Other independent predictors of survival were presence of basic life support (BLS) (OR:5.08, 95% CI 1.98–13.98), presence of a shockable rhythm (OR: 7.03, 95% CI: 3.18–16.55), average PaO2 (OR = 0.93, CI 95% 0.90–0.96) and% time MAP Conclusion Epileptiform EEG activity in post-CA patients is independently and inversely associated with survival and this effect is mainly driven by patients in whom this pattern is refractory over time despite treatment with anti-epileptic drugs. We did not identify an association between hemodynamic factors, blood gas variables and epileptiform EEG activity after CA, although both hypotension, hypoxia and epileptic EEG activity were predictors of survival.

The aim of our study is to determine the clinical predictors and the differential diagnosis of posterior reversible encephalopathy syndrome (PRES) in patients presenting with acute neurological symptoms and risk factors for PRES. Using the diagnostic algorithm for PRES from Fugate and Rabinstein (Lancet Neurol 14(9):914–925, 1), we carried out a retrospective study on 220 patients, presenting with acute neurological symptoms such as seizures, encephalopathy, headache, visual disturbances or other focal neurological signs that appear in the clinical setting of risk factors such as hypertension/blood pressure fluctuations, chemotherapy, renal failure, autoimmune disorders, or eclampsia, in whom imaging of the brain was performed to exclude PRES. Seventeen percent of patients had a radiologically confirmed diagnosis of PRES. Univariable logistic regression showed a significant association between PRES and epileptic seizures, encephalopathy, hypertension, chemotherapy and renal failure. Multivariable logistic regression of acute neurological symptoms and risk factors showed a significant association of epileptic seizures, encephalopathy, visual disturbances, hypertension and chemotherapy with PRES. Using these variables to predict PRES yielded a discriminative ability (AUC) equal to 0.793. Diagnoses when PRES was not confirmed included primary or secondary headaches (26%), toxic-metabolic encephalopathy (21%), vascular pathology (12%) and other less frequent disorders. Epileptic seizures, encephalopathy, visual disturbances, hypertension, renal failure and chemotherapy were the best clinical predictors of PRES, while headache, immune suppression and autoimmune disease were not useful for the clinical diagnosis of PRES in our study. Electronic supplementary material The online version of this article (doi:10.1007/s13760-017-0750-6) contains supplementary material, which is available to authorized users.

Global anterograde amnesia is described in three patients with brain injuries that occurred in one case at birth, in another by age 4, and in the third at age 9. Magnetic resonance techniques revealed bilateral hippocampal pathology in all three cases. Remarkably, despite their pronounced amnesia for the episodes of everyday life, all three patients attended mainstream schools and attained levels of speech and language competence, literacy, and factual knowledge that are within the low average to average range. The findings provide support for the view that the episodic and semantic components of cognitive memory are partly dissociable, with only the episodic component being fully dependent on the hippocampus.

Objective: Mutations in SLC2A1 , encoding the glucose transporter type 1 (GLUT1), cause a broad spectrum of neurologic disorders including classic GLUT1 deficiency syndrome, paroxysmal exercise-induced dyskinesia (PED, DYT18), and absence epilepsy. A large German/Dutch pedigree has formerly been described as paroxysmal choreoathetosis/spasticity (DYT9) and linked close to but not including the SLC2A1 locus on chromosome 1p. We tested whether 1) progressive spastic paraparesis, in addition to PED, as described in DYT9, and 2) autosomal dominant forms of hereditary spastic paraparesis (HSP) without PED are caused by SLC2A1 defects. Methods: The German/Dutch family and an Australian monozygotic twin pair were clinically (re-)investigated, and 139 index cases with dominant or sporadic HSP in which relevant dominant genes were partially excluded were identified from databanks. SLC2A1 was sequenced in all cases in this observational study and the functional effects of identified sequence variations were tested in glucose uptake and protein expression assays. Results: We identified causative mutations in SLC2A1 in both families, which were absent in 400 control chromosomes, cosegregated with the affection status, and decreased glucose uptake in functional assays. In the 139 index patients with HSP without paroxysmal dyskinesias, we only identified one sequence variation, which, however, neither decreased glucose uptake nor altered protein expression. Conclusions: This study shows that DYT9 and DYT18 are allelic disorders and enlarges the spectrum of GLUT1 phenotypes, now also including slowly progressive spastic paraparesis combined with PED. SLC2A1 mutations were excluded as a cause of HSP without PED in our cohort.

[(18)F] FDG positron emission tomography (PET) is commonly used to highlight brain regions with abnormal metabolism. Correct interpretation of FDG images is important for investigation of diseases. When the FDG uptake is compared between hemispheres, confusion can arise because it might be difficult to determine whether an observed asymmetry is physiological and due to normal anatomical variation or pathological. In this paper we propose a new method, which calculates an anatomy-corrected asymmetry index (ACAI), to highlight inter-hemispheric metabolic asymmetry in FDG images without the influence of anatomical asymmetry. Using prior anatomical information from MRI, the ACAI method only takes into account voxels that belong to a certain anatomical class. For the evaluation of detection performance, this method is applied on homogeneous brain phantoms and realistic analytical simulated FDG-PET images with known asymmetries. Results from these simulations demonstrated the validity of ACAI and its potential perspective in the future.

Objective: To map the disease-causing locus in a large Belgian family with occipitotemporal lobe epilepsy associated with migraine with visual aura and to describe the clinical, electrophysiologic, and imaging characteristics. Methods: DNA samples from 21 family members were obtained and an 8 cM density genome-wide scan was performed. The authors interviewed 21 individuals and performed interictal EEG in 14 and brain MRI in 13 individuals. Results: Nine at risk family members and one deceased individual had epilepsy with occipital and temporal lobe symptomatology, variable age at onset, usually good prognosis, no epileptic EEG features, and normal brain MRI. Five of the 10 patients had a history of migraine with aura (p = 0.0026). Seizures and migraine attacks occurred as separate episodes in all but one patient. Three patients described light flashes both as epileptic and migraine aura. Epilepsy and migraine started at the same age in three patients and remitted simultaneously in two. The epileptic phenotype had a dominant mode of inheritance with a reduced penetrance of 75%. A conclusive two-point lod score of 3.3 was obtained for marker D9S257 at recombination fraction zero. Haplotype analysis defined a candidate region of 9.95 cM (5.96 Mb) between markers GATA152H04 and D9S253 located at chromosome 9q21-q22 based upon recombinations in affected individuals. Conclusions: The clinical association in this family of occipitotemporal lobe epilepsy and migraine with visual aura and the conclusive linkage of the occipitotemporal lobe epilepsy/migraine with aura trait to a single locus suggests a common monogenic gene defect.

© 2015 EURASIP. The ultimate goal of the EEG-fMRI analysis in refractory focal epilepsy is the precise localization of the epileptogenic zone (EZ) to facilitate successful surgery. Many studies have shown that simultaneous GLM-based EEG-correlated fMRI analysis can identify fMRI voxels which covary with the timing of interictal spikes assessed on EEG. However, this type of analysis often does not reveal a single focus but an extensive epileptic network. In this paper we investigate whether parallel independent component analysis (ICA), a data-driven, symmetric integration approach can disentangle this network. We assume that ICA of EEG and ICA of fMRI will reveal different temporal and spatial aspects of this network, respectively. We hypothesize that by matching these different epilepsy-related EEG and fMRI components, we can get a deeper insight in the neural processes this extensive network represents. We tested parallel ICA on 12 refractory epilepsy patients who underwent full presurgical evaluation and showed concordant data (excluding EEG-fMRI) pointing to a single epileptic focus. Our results show that parallel ICA has an added value, as it can help the interpretation of the GLM results and pinpoint the EZ. Furthermore, it might help to understand how the various aspects of epileptic activity are reflected in EEG and fMRI. ispartof: pages:429-433 ispartof: Proc. of the 22nd European Signal Processing Conference 2014 pages:429-433 ispartof: 22nd European Signal Processing Conference 2015 location:Nice, France date:Sep - Sep 2015 status: published

Precise anatomical knowledge of the structure of the corpus callosum is important in split-brain research and during neurosurgical procedures sectioning the callosum. According to the classic literature, commissural fibers connecting the motor cortex are situated in the anterior part of the corpus callosum. On the other hand, more recent imaging studies using diffusion tensor imaging indicate a more posterior topography of callosal fibers connecting motor areas. Topographical knowledge is especially critical when performing disconnective callosotomies in epilepsy patients who experience sudden loss of leg motor control, so-called epileptic drop attacks. In the current study, we aim to precisely delineate the topography of the leg motor connections of the corpus callosum. Of 20 hemispheres obtained at autopsy, 16 were dissected according to Klingler's fiber dissection technique to study the course and topography of callosal fibers connecting the most medial part of the precentral gyrus. Fibers originating from the anterior bank of the central sulcus were invariably found to be located in the isthmus of the corpus callosum, and no leg motor fibers were found in the anterior part of the callosum. The current results suggest that the disconnection of the pre-splenial fibers, located in the posterior one-third of the corpus callosum, is paramount in obtaining a good outcome after callosotomy.

The electroencephalogram (EEG) is often contaminated by muscle artifacts. In this paper, a new method for muscle artifact removal in EEG is presented, based on canonical correlation analysis (CCA) as a blind source separation (BSS) technique. This method is demonstrated on a synthetic data set. The method outperformed a low-pass filter with different cutoff frequencies and an independent component analysis (ICA)-based technique for muscle artifact removal. In addition, the method is applied on a real ictal EEG recording contaminated with muscle artifacts. The proposed method removed successfully the muscle artifact without altering the recorded underlying ictal activity.

BACKGROUND: The pathophysiological role of the extensive interictal cerebral hypometabolism in complex partial seizures (CPS) in refractory mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) is poorly understood. Our aim was to study ictal-interictal SPECT perfusion versus interictal fluorodeoxyglucose (FDG)-PET metabolic patterns. METHODS: Eleven adults with refractory unilateral mTLE-HS, who were rendered seizure free after epilepsy surgery, were included. All had an interictal FDG-PET and an interictal and ictal perfusion SPECT scan. FDG-PET data were reconstructed using an anatomy-based reconstruction algorithm, which corrected for partial volume effects, and analyzed semi-quantitatively after normalization to white matter activity. Using Statistical Parametric Mapping (SPM), we compared interictal metabolism of the patient group with a control group. We correlated metabolic with ictal perfusion changes in the patient group. RESULTS: Global cerebral grey matter glucose metabolism in patients was decreased 10-25% compared with control subjects. Interictal PET hypometabolism and ictal SPECT hypoperfusion were maximal in the ipsilateral frontal lobe. Ictal frontal lobe hypoperfusion was associated with crossed cerebellar diaschisis. The ipsilateral temporal lobe showed maximal ictal hyperperfusion and interictal hypometabolism, which was relatively mild compared with the degree of hypometabolism affecting the frontal lobes. CONCLUSION: Interictal hypometabolism in mTLE-HS was greatest in the ipsilateral frontal lobe and represented a seizure-related dynamic process in view of further ictal decreases. Crossed cerebellar diaschisis suggested that there is a strong ipsilateral frontal lobe inhibition during CPS. We speculate that surround inhibition in the frontal lobe is a dynamic defense mechanism against seizure propagation, and may be responsible for functional deficits observed in mTLE. ispartof: NeuroImage vol:32 issue:2 pages:684-695 ispartof: location:United States status: published

To prospectively assess the safety and efficacy of levetiracetam in patients with uncontrolled focal epilepsy, in a common practice-based setting.In this phase IV, open-label, 16-week community-based study, adult patients with focal seizures initially received levetiracetam 1,000 mg/day. Throughout the study, the dose was adjusted in increments of 1,000 mg (maximum 3,000 mg/day) to achieve seizure control and maintain tolerability. The outcome parameters were the percentage reduction in partial and total seizure frequency per week from historical baseline, global evaluation scale (GES), and adverse events (AE).Seven hundred and thirty-one patients were included in this analysis and 84.4% completed the study. The median percent reduction in all seizures was 47.8%, and 49.3% for all partial seizures. The 50% responder rate was 49%, and the seizure-free rate was 17.2% for all partial seizures. Approximately 60% of patients showed moderate to marked improvement on the GES. The majority of AE were of mild to moderate severity; the most commonly reported being asthenia, somnolence, headache, and dizziness.Levetiracetam is both efficacious and safe as an add-on therapy in patients with refractory epilepsy treated by clinicians in their daily practice.

The resolution of a PET scanner (2.5–4.5 mm for brain imaging) is similar to the thickness of the cortex in the (human) brain (2.5 mm on average), hampering accurate activity distribution reconstruction. Many techniques to compensate for the limited resolution during or post-reconstruction have been proposed in the past and have been shown to improve the quantitative accuracy. In this study, state-of-the-art reconstruction techniques are compared on a voxel-basis for quantification accuracy and group analysis using both simulated and measured data of healthy volunteers and patients with epilepsy. Methods Maximum a posteriori (MAP) reconstructions using either a segmentation-based or a segmentation-less anatomical prior were compared to maximum likelihood expectation maximization (MLEM) reconstruction with resolution recovery. As anatomical information, a spatially aligned 3D T1-weighted magnetic resonance image was used. Firstly, the algorithms were compared using normal brain images to detect systematic bias with respect to the true activity distribution, as well as systematic differences between two methods. Secondly, it was verified whether the algorithms yielded similar results in a group comparison study. Results Significant differences were observed between the reconstructed and the true activity, with the largest errors when using (post-smoothed) MLEM. Only 5–10% underestimation in cortical gray matter voxel activity was found for both MAP reconstructions. Higher errors were observed at GM edges. MAP with the segmentation-based prior also resulted in a significant bias in the subcortical regions due to segmentation inaccuracies, while MAP with the anatomical prior which does not need segmentation did not. Significant differences in reconstructed activity were also found between the algorithms at similar locations (mainly in gray matter edge voxels and in cerebrospinal fluid voxels) in the simulated as well as in the clinical data sets. Nevertheless, when comparing two groups, very similar regions of significant hypometabolism were detected by all algorithms. Conclusion Including anatomical a priori information during reconstruction in combination with resolution modeling yielded accurate gray matter activity estimates, and a significant improvement in quantification accuracy was found when compared to post-smoothed MLEM reconstruction with resolution modeling. AsymBowsher provided the most accurate subcortical GM activity estimates. It is also reassuring that the differences found between the algorithms did not hamper the detection of hypometabolic regions in the gray matter when performing a voxel-based group comparison. Nevertheless, the size of the detected clusters differed. More elaborated and application-specific studies are required to decide which algorithm is best for a group analysis.

Removing artifacts and background electroencephalography (EEG) from multichannel interictal and ictal EEG has become a major research topic in EEG signal processing in recent years. We applied for this purpose a recently developed subspace-based method for modeling the common dynamics in multichannel signals. When the epileptiform activity is common in the majority of channels and the artifacts appear only in a few channels the proposed method can be used to remove the latter. The performance of the method was tested on simulated data for different noise levels. For high noise levels the method was still able to identify the common dynamics. In addition, the method was applied to real life EEG recordings containing interictal and ictal activity contaminated with muscle artifact. The muscle artifacts were removed successfully. For both the synthetic data and the analyzed real life data the results were compared with the results obtained with principal component analysis (PCA). In both cases, the proposed method performed better than PCA.

We analysed the CACNA1A gene, located on chromosome 19p13, in three unrelated families and one sporadic case with episodic ataxia type 2 (EA-2). In two of the families and the sporadic patient, novel truncating mutations, which disrupt the reading frame and result in a premature stop of the CACNA1A protein, were identified in exons 14, 16 and 26. In the remaining family, a novel missense mutation (H253Y) was found. Of the twenty two EA-2 mutations identified thus far, including those of the present study, seventeen are truncating mutations and five are missense mutations, all resulting in an EA-2 clinical phenotype.

By using [ 11 C]flumaxenil-positron emission tomography ([ 11 C]FMZ-PET, we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [ 11 C]FMZPET and ex vivo binding using [ 3 H]FMZ autoradiography. We applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [ 11 C]FMZ volume of distribution ([ ll c]FMZ V d ) obtained in 10 patients with refractory mTLE due to unilateral, histologically verified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of receptor availability ([ 3 H]FMZ B max ). After correction for partial volume elect, [ 11 C]FMZ V d in the body of the epileptogenic hippocampus was reduced by a mean of 42.1% compared with normal controls. [ 3 H]FMZ B max , determined autoradiographically from the same hippocampal tissue, was reduced by a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining neurons in HS can be reliably detected in vivo by using [ 11 C]FMZPET after correction for partial volume effect.

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.

The aims of this study were to examine the relationships of hippocampal T2 (HCT2) relaxation time and magnetic resonance (MR)-based hippocampal volume (HCV) to neuronal (ND) and glial cell densities (GD) of hippocampal neuronal cell layers, and to obtain a better clinicopathological definition of hippocampal sclerosis (HS) and end folium sclerosis (EFS). Fifty-three hippocampi with HS, 6 with EFS, and 6 control hippocampi were studied. Pathologically, the HS group had a significantly higher logarithm (log) GD/ND than the controls in all hippocampal subregions, and than the EFS group in all subregions except the granule cell layer of the dentate gyrus (GCDG). The EFS group had a significantly higher log GD/ND than the control group only in the GCDG. Clinical correlations suggested that EFS may be the consequence of temporal lobe seizures and not an epileptogenic entity. Hippocampal atrophy in HS was associated with neuronal cell depletion and concomitant gliosis in the cornu Ammonis (CA) 1, CA2, CA3, and hilus. An increased HCT2 was associated with damage in the CA1 and also the hilus and has a different neuropathological basis than HCV loss. MR-based HCV measurement and HCT2 mapping, therefore, give complementary information in the presurgical evaluation of temporal lobe epilepsy and longitudinal studies.

We objectively delineated the extent of abnormalities in central benzodiazepine receptor (cBZR) binding using [11C]flumazenil (FMZ)-PET and high resolution volumetric MRI in 12 patients with mesial temporal lobe epilepsy (mTLE) associated with unilateral hippocampal sclerosis, who underwent presurgical evaluation and subsequent temporal lobe surgery. We compared parametric 3D-images of regional cerebral [11C]FMZ volume of distribution (Vd) obtained from individuals and groups of patients with [11C]FMZ-Vd from a group of 17 healthy controls using statistical parametric mapping (SPM). The [12C]FMZ-Vd was significantly reduced (P < 0.001) in the affected hippocampus in the group of 12 patients with unilateral hippocampal sclerosis. Analysis of individual patients reflected the group finding and there was no significant abnormality of cBZR binding outside the hippocampus in any patient. We conclude that SPM is an useful objective method for detecting changes in regional cerebral [11C]FMZ binding and that in patients with mTLE and unilateral hippocampal sclerosis reduction of cBZR binding is restricted to the area of hippocampal sclerosis with no abnormalities being detected in the temporal neocortex or elsewhere in the neocortex.

Objectives: To evaluate and compare T2 relaxometry and volumetrics of hippocampus in the presurgical evaluation of patients with intractable temporal lobe epilepsy (TLE), and to correlate these quantitative MRI measures with the pathology of the resected hippocampus. Patients: Forty patients with intractable TLE who underwent presurgical evaluation and subsequent temporal lobe surgery. Main outcome measures: Hippocampal T2 (HCT2), volumes of hippocampi and hippocampal volume ratio (HCVR) (volume of hippocampus with higher HCT2 divided by volume of hippocampus with lower HCT2), and qualitative pathology. Results: Thirty-two patients had hippocampal sclerosis, three patients had end-folium sclerosis, one patient had amygdala sclerosis, and four patients had a foreign tissue lesion in the temporal lobe. HCT (2) ratio (R/L) correlated inversely with the ratio of hippocampal volumes (R/L) (r equals minus 0.91; p less than 0.0001). A high T2 signal in an atrophic hippocampus was characteristic of hippocampal sclerosis. All patients with hippocampal sclerosis had an HCVR below control values, and only one of these had an HCT2 in the normal range. HCVR produced one false-positive result. The patients with end-folium sclerosis had normal HCT2 and HCVR. The patient with amygdala sclerosis had a normal hippocampus on qualitative and quantitative assessment. Of the four patients with a lesion, one had a mildly increased HCT2 and one had mild volume asymmetry. Hippocampal volume asymmetry could be reliably detected on visual inspection of the MRI with an HCVR of 0.85 or less, and an increase of HCT2 with a T2 of 115 msec or higher. Conclusion: Quantitative MRI combining HCT2 and HCVR is a reliable method for diagnosing hippocampal sclerosis noninvasively. End-folium sclerosis and amygdala sclerosis should be considered in patients with intractable TLE and negative findings on MRI studies, including quantitative measures of the hippocampus.NEUROLOGY 1995;45: 2233-2240

The authors report an HIV-seropositive patient with syphilitic perioptic neuritis as an initial and isolated manifestation of neurosyphilis. Cerebrospinal fluid was within normal limits. Visual evoked potentials (VEP's) showed a marked delay to medium spatial frequency grating stimuli (4.6 cycles per degree) but not to a coarse stimulus (2.3 cycles per degree) suggesting selective vulnerability of optic nerve fibers. The VEP normalized after treatment corresponding with improvement of the perioptic neuritis.

Background: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. Objectives: To determine the clinical–neurological spectrum and associated mutation loads in an extended m.14487T>C family. Methods: A genotype–phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Results: Heteroplasmic m.14487T>C levels (36–52% in leucocytes, 97–99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99–100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. Interpretation: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

When patients with epilepsy cannot be helped with medication, they stay one week in an epilepsy monitoring unit in order to localise the part of the brain that is causing the seizures. The electroencephalogram (EEG) is then recorded over several days as it is the direct measurement of electrical brain activity. We developed a method to extract localising information out of the EEG, even at low signal-to-noise ratios or when the ictal EEGs are severely contaminated. In this survey-paper, we write a manual how to apply the method and illustrate it.

Long-term electroencephalographic (EEG) recordings are important in the presurgical evaluation of refractory partial epilepsy for the delineation of the ictal onset zones. In this paper, we introduce a new concept for an automatic, fast, and objective localisation of the ictal onset zone in ictal EEG recordings. Canonical decomposition of ictal EEG decomposes the EEG in atoms. One or more atoms are related to the seizure activity. A single dipole was then fitted to model the potential distribution of each epileptic atom. In this study, we performed a simulation study in order to estimate the dipole localisation error. Ictal dipole localisation was very accurate, even at low signal-to-noise ratios, was not affected by seizure activity frequency or frequency changes, and was minimally affected by the waveform and depth of the ictal onset zone location. Ictal dipole localisation error using 21 electrodes was around 10.0 mm and improved more than tenfold in the range of 0.5–1.0 mm using 148 channels. In conclusion, our simulation study of canonical decomposition of ictal scalp EEG allowed a robust and accurate localisation of the ictal onset zone.

Long-term electroencephalographic (EEG) recordings are important in the presurgical evaluation of refractory partial epilepsy for the delineation of the ictal onset zones. In this paper we introduce a new concept for an automatic, fast and objective localisation of the ictal onset zone in ictal EEG recordings and show with a simulation study that canonical decomposition of ictal scalp EEG allows a robust and accurate localisation of the ictal onset zone.

Muscle artifacts and eye movement artifacts distort the EEG and make EEG dipole source localization near the ictal onset of the seizure very difficult and unreliable. Recently, two algorithms to remove these artifacts have been developed and validated. In our study we want to investigate if the multiple dipole model can be used in ictal EEG source localization. Furthermore, we want to investigate whether the use of the dipole model returns better interpretable results when artifacts are suppressed. The EEG dipole source localization was done by using the RAP-MUSIC algorithm. We used the relative residual energy as a goodness of fit for the dipole model. We found that in the unfiltered EEG the relative residual energy was very high, indicating that EEG dipole source localization is heavily affected by the noise. By removing the artifacts, we obtain a lower relative residual energy, which suggests that the multiple dipole model becomes an adequate model for EEG dipole source localization during ictal period.

Long-term electroencephalographic (EEG) recordings are important in the presurgical evaluation of refractory partial epilepsy for the delineation of the irritative and ictal onset zones. In this paper we introduce a new algorithm for an automatic, fast and objective localizing of the ictal onset zone in ictal EEG recordings. We extracted the potential distribution of the ictal activity from EEG using the higher order canonical decomposition method, also referred to as the CP model. The CP model decomposes in a unique way a higher order tensor in a minimal sum of rank-1 'atoms'. We showed that only one atom is related to the seizure activity. Simulation experiments demonstrated that the method correctly extracted the potential distribution of the ictal activity even with low signal-to-noise ratios. In 37 ictal EEGs, the CP method correctly localized the seizure onset zone in 34 (92%) and visual assessment in 21 cases (57%) (p=0.00024). The CP method is a fast method to delineate the ictal onset zone in ictal EEGs and is more sensitive than visual interpretation of the ictal EEGs.

Subtraction of ictal and interictal SPECT perfusion images of the brain has the potential of locating the epileptogenic region. This region generally shows large differences between both images. However, differences can also be induced by noise in the projection data. We hypothesized that the extent, besides the intensity, of observed clusters of voxels in thresholded subtraction images, is an important parameter in the classification of clusters into real perfusion differences and noise induced differences. To test this hypothesis, we performed a number of simulation experiments. Using a Monte Carlo approach, we constructed cumulative distribution functions (CDF) of the excess height (i.e. the largest difference in a cluster) and the cluster extent under the condition of no perfusion change (i.e. only noise induced clusters). The reproducibility of the CDF curves was shown using measured patient data. Furthermore, a 3D brain software phantom experiment was used to examine the detection and classification of an induced region of hyperperfusion. We assigned to every observed cluster a probability, derived from the CDF curves, for excess height and extent. For different probability thresholds, sensitivity and specificity of the detection of the induced hyperperfusion based on its probability for excess height and cluster extent was measured. These measurements were combined in receiver operating characteristic (ROC) curves. These ROC curves showed a better performance when using classification based on cluster extent. We conclude that the cluster extent is an important parameter in the characterization of clusters in thresholded subtraction of perfusion SPECT images of the brain.

Generalised epilepsy with febrile seizures plus (GEFS+) is a clinically and genetically heterogeneous epilepsy syndrome. Using positional cloning strategies, mutations in SCN1B, SCN1A, and GABRG2 have been identified as genetic causes of GEFS+. In the present study, we describe a large four generation family with GEFS+ in which we performed a 10 cM density genome-wide scan. We obtained conclusive evidence for a novel GEFS+ locus on chromosome 2p24 with a maximum two point logarithm of the odds (LOD) score of 4.22 for marker D2S305 at zero recombination. Fine mapping and haplotype segregation analysis in this family delineated a candidate region of 3.24 cM, corresponding to a physical distance of 4.2 Mb. Linkage to 2p24 was confirmed (p = 0.007) in a collection of 50 nuclear and multiplex families with febrile seizures and epilepsy. Transmission disequilibrium testing and association studies provided further evidence (p

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Idiopathic epilepsies have a genetic basis and are characterised by the absence of an overt underlying neurological abnormality. Most idiopathic epilepsies are complex diseases with considerable clinical and genetic heterogeneity and an unclear inheritance pattern because of genetic and environmental factors. Families in which the disease segregates as an autosomal dominant trait with reduced disease penetrance have been identified occasionally. In some of these families, a single gene defect was identified as the cause of epilepsy. To date, mutations in 13 genes have been identified for distinct epilepsy types. Most genes encode subunits of ion channels.1,2 In addition, the gene remains to be identified for 21 mapped loci for epilepsy, which highlights the genetic heterogeneity of the idiopathic epilepsy syndromes.3,4 Familial temporal lobe epilepsy (MIM 608096) was first described by Berkovic et al . and was recognised as a distinct epileptic syndrome by the International League Against Epilepsy.5 It is defined by familial occurrence of simple partial seizures, complex partial seizures, and secondarily generalised seizures of temporal lobe origin.6 Two genetically distinct autosomal dominant familial temporal lobe epilepsy syndromes have been reported. Autosomal dominant lateral temporal lobe epilepsy (MIM 600512), or autosomal dominant partial epilepsy with auditory features, was described first by Ottman et al . ,7 and recently, mutations in the leucine rich glioma inactivated 1 ( LGI1 ) gene on chromosome 10q24 were identified.8,9 Auras that present as auditory and visual hallucinations are a clinical hallmark of this syndrome. The other variant of familial temporal lobe epilepsy is characterised clinically by onset in teenage years or early adulthood, absence of antecedent factors, low frequency of deja vu, and a usually good prognosis. This variant, which still can be heterogeneous genetically, is not mapped yet. In a large family with febrile seizures …

The localizing value of ictal single-photon emission computed tomography (SPECT) performed with cerebral blood flow agents in patients with epilepsy is based on cerebral metabolic and perfusion coupling. Ictal hyperperfusion is used to localize the epileptogenic zone noninvasively, and is particularly useful in magnetic resonance (MR)-negative partial epilepsy and focal cortical dysplasias. Subtraction ictal SPECT coregistered with MRI (SISCOM) improves the localization of the area of hyperperfusion. Ictal SPECT should always be interpreted in the context of a full presurgical evaluation. Early ictal SPECT injections minimize the problem of seizure propagation and of nonlocalization due to an early switch from ictal hyperperfusion to postictal hypoperfusion during brief extratemporal seizures. The degree of thresholding of SISCOM images affects the sensitivity and specificity of ictal SPECT. Ictal hypoperfusion may reflect ictal inhibition or deactivation. Postictal and interictal SPECT studies are less useful to localize the ictal-onset zone. Statistical parametric mapping analysis of groups of selected ictal-interictal difference images has the potential to demonstrate the evolution of cortical, subcortical, and cerebellar perfusion changes during a particular seizure type, to study seizure-gating mechanisms, and to provide new insights into the pathophysiology of seizures.

The present paper reports on the application of the Hilbert transform to biological time series of the brain electrical activity of epilepsy patients. The Hilbert transform will be used to estimate the instantaneous frequency, the instantaneous amplitude and the phase synchronization of scalp EEG recordings. As a fourth measure derived from the Hilbert transform we will define a measure of rhythmicity. The purpose of this paper is to combine the time evolution of these four measures to come to a characterization of the dynamics present in, and between, different EEG channels. By applying these measures to scalp EEG recordings of patients with Mesial Temporal Lobe Epilepsy we will show that they are useful for off-line analysis of large amounts of EEG data. Because all these measures are derived from the fast Hilbert transform it is also possible to use them as an analysis tool for online monitoring.

Positron emission tomography (PET) of the cerebral glucose metabolism has shown to be useful in the presurgical evaluation of patients with epilepsy. Between seizures, PET images using fluorodeoxyglucose (FDG) show a decreased glucose metabolism in areas of the gray matter (GM) tissue that are associated with the epileptogenic region. However, detection of subtle hypo-metabolic regions is limited by noise in the projection data and the relatively small thickness of the GM tissue compared to the spatial resolution of the PET system. Therefore, we present an iterative maximum-a-posteriori based reconstruction algorithm, dedicated to the detection of hypo-metabolic regions in FDG-PET images of the brain of epilepsy patients. Anatomical information, derived from magnetic resonance imaging data, and pathophysiological knowledge was included in the reconstruction algorithm. Two Monte Carlo based brain software phantom experiments were used to examine the performance of the algorithm. In the first experiment, we used perfect, and in the second, imperfect anatomical knowledge during the reconstruction process. In both experiments, we measured signal-to-noise ratio (SNR), root mean squared (rms) bias and rms standard deviation. For both experiments, bias was reduced at matched noise levels, when compared to post-smoothed maximum-likelihood expectation-maximization (ML-EM) and maximum a posteriori reconstruction without anatomical priors. The SNR was similar to that of ML-EM with optimal post-smoothing, although the parameters of the prior distributions were not optimized. We can conclude that the use of anatomical information combined with prior information about the underlying pathology is very promising for the detection of subtle hypo-metabolic regions in the brain of patients with epilepsy.

We examined a 36-year-old right-handed woman. Her mother’s pregnancy and the patient’s birth and early development were normal. At the age of 4 years, she had simple febrile convulsions. Her mother, who had migraine, had an isolated, unprovoked epileptic seizure at the time of her menarche, while watching television. The first afebrile seizure of our patient was at the age of 12 years, also at her menarche, while watching television. This complex partial status epilepticus (CPSE) started with visual hallucinations and illusions characterized by palinopsia, polyopia, tunnel vision, and flashing lights, and lasted for more than an hour. She was treated with valproate for 6 months. Since that time she experienced monthly left-sided migraine headaches. In around 20% of migraine headaches she experienced an aura characterized by flashing lights, which were similar to those of her seizures. She remained seizure free until 1995, at the age of 28 years. Interictal EEG remained normal. She then had a second episode of occipital lobe CPSE that lasted for 1 hour and ended with a secondarily generalized tonic-clonic seizure. The first MRI …

Status epilepticus (SE) is a common neurological emergency. In around 10 percent, the etiology of SE is not clear, i.e. cryptogenic SE.To describe six young adult patients with de novo cryptogenic multifocal febrile SE with poor outcome.Retrospective chart review.We describe six patients who presented with de novo SE. All were young adults with an unremarkable previous medical history. In all except one, the family history for epilepsy was negative. All had a febrile illness in the week preceding SE. Investigations were unable to reveal the underlying etiology. SE proved refractory to conventional antiepileptic drug treatment (AED) and anesthesia was required to control seizures. Seizures during SE or ensuing epilepsy were multifocal. Brain pathology in four patients was normal in two and showed changes secondary to seizures in two. Outcome was poor in all cases: one patient died during the course of SE, another patient remained with severe mental and physical disability as well as refractory epileptic seizures, the other four developed refractory multifocal epilepsy. One of these patients died a sudden unexpected death in epilepsy (SUDEP) and one drowned during a seizure.Six patients were reviewed who presented with de novo cryptogenic multifocal refractory febrile SE. The possible etiologies are discussed. Based on the similarities in these cases, a distinct refractory SE syndrome might be assumed. Further prospective studies will, however, be required to validate this hypothesis as well as to elucidate its etiology and optimize treatment.

Cerebral perfusion changes reliably reflect changes in neuronal activity. Our aim was to obtain new insights into the pathophysiology of complex partial seizures (CPS) in patients with hippocampal sclerosis (HS) using interictal and ictal single photon emission computed tomography (SPECT). We studied 24 patients with refractory temporal lobe epilepsy (TLE) associated with HS. All had an interictal and ictal SPECT with early injection during a CPS. Images were normalized and co-registered. Using statistical parametric mapping (SPM99), brain regions with significant ictal perfusion changes were determined. To assess possible interrelationships between these regions, Pearson correlation coefficients were calculated. The temporal lobe ipsilateral to the seizure focus, the border of the ipsilateral middle frontal and precentral gyrus, both occipital lobes and two small regions in the contralateral postcentral gyrus showed ictal hyperperfusion. The frontal lobes, contralateral posterior cerebellum and ipsilateral precuneus showed hypoperfusion. Further exploratory analysis suggested an association between ipsilateral temporal lobe hyperperfusion and ipsilateral frontal lobe hypoperfusion, and an inverse association between seizure duration and hyperperfusion in the ipsilateral anterior cerebellum and contralateral postcentral gyrus. We conclude that there is a network of perfusion changes during CPS in patients with HS. Studying a particular seizure type in patients with HS with peri-ictal SPECT performed during a defined time window will allow further analysis of the cerebral network activities, and excitatory, inhibitory and gating mechanisms during seizures associated with HS. ispartof: Brain vol:126 issue:Pt 5 pages:1103-11 ispartof: location:England status: published

We analysed the CACNA1A gene, located on chromosome 19p13, in three unrelated families and one sporadic case with episodic ataxia type 2 (EA-2). In two of the families and the sporadic patient, novel truncating mutations, which disrupt the reading frame and result in a premature stop of the CACNA1A protein, were identified in exons 14, 16 and 26. In the remaining family, a novel missense mutation (H253Y) was found. Of the twenty two EA-2 mutations identified thus far, including those of the present study, seventeen are truncating mutations and five are missense mutations, all resulting in an EA-2 clinical phenotype.

Described are the clinical, EEG, MR, and genetic characteristics of 106 members of a family with autosomal dominant temporal lobe epilepsy (TLE) and febrile seizures (FS), with 22 affected individuals. Eleven patients had a history of FS, and 10 patients had TLE. EEG showed epileptic activity in five. None had hippocampal sclerosis. There was no evidence for linkage to 13 candidate loci. This large family with autosomal dominant TLE has a distinct phenotype and shows no linkage to known candidate regions for familial partial epilepsy and FS.

Article abstract The authors compared ictal SPECT injection performed by medical personnel with self-injection ictal SPECT in six patients with refractory temporal lobe epilepsy. Self-injection was safe and started faster. Self-injection subtraction ictal SPECT coregistered to MRI (SISCOM) was localizing in three patients who had a complex partial seizure, but only one of three patients who had a simple partial seizure, which may limit its usefulness in clinical practice. The localizing information of self-injection was better in three patients, and obviated the need for depth-EEG studies in one patient.