[Non convulsive status epilepticus in a man with chronic alcohol dependence]. / Niet-convulsieve status epilepticus bij een man met chronische alcoholafhankelijkheid.

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.

Sleep in children with refractory epilepsy and epileptic encephalopathies: A systematic review of literature.

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.

Fast responses to images of animate and inanimate objects in the nonhuman primate amygdala.

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.

The impact of global hemodynamics, oxygen and carbon dioxide on epileptiform EEG activity in comatose survivors of out-of-hospital cardiac arrest.

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 48h (TWA-MAP48), the percentage of time with a MAP below 65 and above 85mmHg and the percentage of time with normoxia, hypoxia (<70mmHg), hyperoxia (>150mmHg), normocapnia, hypocapnia (<35mmHg) and hypercapnia (>45mmHg) 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 65mmHg or above 85mmHg, 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<65mmHg (OR: 0.96, CI 95% 0.94-0.98). 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.

Clinical predictors and differential diagnosis of posterior reversible encephalopathy syndrome.

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.

Callosotopy: leg motor connections illustrated by fiber dissection.

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.

Voxel-based comparison of state-of-the-art reconstruction algorithms for 18F-FDG PET brain imaging using simulated and clinical data.

UNLABELLED: The resolution of a PET scanner (2.5-4.5mm for brain imaging) is similar to the thickness of the cortex in the (human) brain (2.5mm 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.

Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect.

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.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

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.

Removing muscle and eye artifacts using blind source separation techniques in ictal EEG source imaging.

OBJECTIVE: The contamination of muscle and eye artifacts during an ictal period of the EEG significantly distorts source estimation algorithms. Recent blind source separation (BSS) techniques based on canonical correlation (BSS-CCA) and independent component analysis with spatial constraints (SCICA) have shown much promise in the removal of these artifacts. In this study we want to use BSS-CCA and SCICA as a preprocessing step before the source estimation during the ictal period. METHODS: Both the contaminated and cleaned ictal EEG were subjected to the RAP-MUSIC algorithm. This is a multiple dipole source estimation technique based on the separation of the EEG in signal and noise subspace. The source estimates were compared with the subtracted ictal SPECT (iSPECT) coregistered to magnetic resonance imaging (SISCOM) by means of the euclidean distance between the iSPECT activations and the dipole location estimates. SISCOM results in an image denoting the ictal onset zone with a propagation. RESULTS: We applied the artifact removal and the source estimation on 8 patients. Qualitatively, we can see that 5 out of 8 patients show an improvement of the dipoles. The dipoles are nearer to or have tighter clusters near the iSPECT activation. From the median of the distance measure, we could appreciate that 5 out of 8 patients show improvement. CONCLUSIONS: The results show that BSS-CCA and SCICA can be applied to remove artifacts, but the results should be interpreted with care. The results of the source estimation can be misleading due to excessive noise or modeling errors. Therefore, the accuracy of the source estimation can be increased by preprocessing the ictal EEG segment by BSS-CCA and SCICA. SIGNIFICANCE: This is a pilot study where EEG source localization in the presurgical evaluation can be made more reliable, if preprocessing techniques such as BSS-CCA and SCICA are used prior to EEG source analysis on ictal episodes.

Detection of inter-hemispheric metabolic asymmetries in FDG-PET images using prior anatomical information.

[(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.

Canonical decomposition of ictal scalp EEG reliably detects the seizure onset zone.

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.

Familial occipitotemporal lobe epilepsy and migraine with visual aura: linkage to chromosome 9q.

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.