[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.

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.

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.

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.

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.

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.

Differential effects of early hippocampal pathology on episodic and semantic memory.

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.

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.

A novel susceptibility locus at 2p24 for generalised epilepsy with febrile seizures plus.

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 < 0.05) that 2p24 is a susceptibility locus for febrile seizures and epilepsy. Furthermore, we could reduce the candidate region to a 2.14 cM interval, localised between D2S1360 and D2S2342, based upon an ancestral haplotype. Identification of the disease gene at this locus will contribute to a better understanding of the complex genetic aetiology of febrile seizures and epilepsy.

Efficacy and safety of levetiracetam in clinical practice: results of the SKATE trial from Belgium and The Netherlands.

OBJECTIVE: Aim of the study was to assess the efficacy and safety of levetiracetam as add-on treatment in patients with partial-onset epilepsy in clinical practice. METHODS: In this observational, multi-centre study patients were treated with levetiracetam for 16 weeks. From a starting dose of 1000 mg/day, dose levels were adjusted at 2-weekly intervals in 1000-mg steps, to a maximum of 3000 mg/day, based on seizure control and tolerance. Analysis of efficacy was based on reduction in seizure frequency relative to baseline, 50% and 100% responder rates (for partial seizures and all seizure types combined) and percentage of patients using levetiracetam at the end of the study. Analysis of safety was based on occurrence of adverse events. RESULTS: The present analysis concerns the results of patients recruited in Belgium and The Netherlands. Of the 251 patients included in the study, 86.9% completed 16 weeks of treatment. Reduction in frequency of partial-onset seizures was 62.2%, with 19.3% of the patients becoming seizure free and 56.6% having a reduction in seizure frequency of > or = 50%. These percentages were more or less the same when calculated for all seizure types combined. Tolerance of levetiracetam treatment was good, with most adverse events being only mild to moderate in severity, and only 10.0% of the adverse events leading to discontinuation from the study. Asthenia, somnolence, dizziness and headache were the most frequently reported adverse events. CONCLUSION: Levetiracetam is effective and safe as add-on treatment for partial-onset seizures in clinical practice.

The amygdala and intractable temporal lobe epilepsy: a quantitative magnetic resonance imaging study.

OBJECTIVE: To establish a quantitative MRI technique using T2 relaxation time mapping to study systematically the amygdala in patients with intractable temporal lobe epilepsy (TLE). BACKGROUND: Identification of a focal abnormality on MRI in patients with intractable TLE is important, because outcome from surgery depends largely on the removal of the underlying pathology. Hippocampal sclerosis (HS) is the most common cause of intractable TLE, but epileptogenic lesions can be confined to the amygdala. METHODS: Twenty control subjects and 82 patients with intractable TLE were studied. Patients who had foreign tissue lesions visible on routine MRI were excluded. All subjects had a hippocampal T2 map and volumetry and an amygdala T2 (AT2) map. RESULTS: Forty-four of the 82 patients (54%) had an abnormal AT2, which was bilateral in 18. Forty-four patients (54%) had unilateral HS on MRI, 25 (57%) of whom had an abnormal AT2. Seven patients (8%) had bilateral HS, four of whom had an abnormal AT2. Thirty-one patients (38%) had normal quantitative hippocampal measures, 15 of whom had an abnormal AT2, which was bilateral in seven. Fluid attenuated inversion recovery (FLAIR) imaging, where appropriate, confirmed that the increased AT2 signal was due to parenchymal changes. Neuropathologic correlates of an increased AT2 included microdysgenesis in one and gliosis in three patients. Patients with an isolated AT2 abnormality were significantly older at the onset of habitual epilepsy and rarely had a history of febrile convulsions, in comparison with patients who had HS. An isolated AT2 abnormality correlated well with interictal EEG findings. CONCLUSIONS: The combination of AT2 mapping and FLAIR is a sensitive method to detect lesions that are not seen on routine MRI in the amygdalae of patients with intractable TLE. Further correlational studies will be required to define the role of this technique in the presurgical evaluation of patients with intractable TLE.

Etiology and early prognosis of newly diagnosed partial seizures in adults: a quantitative hippocampal MRI study.

Sixty-three adult patients with newly diagnosed partial seizures underwent MRI of the brain including hippocampal quantitation. Seventy-six percent of patients had normal MRI findings, 10% had hippocampal sclerosis (HS), and 14% had MRI abnormalities other than HS. Patients with HS had a worse early prognosis than patients with other MRI findings with respect to seizures. The extent of hippocampal damage appeared to be an important mediating factor in frequency of seizures, secondary generalization, and resistance to antiepileptic drug treatment. Because MRI provides prognostic information and can alter management for the individual patient, high-resolution MRI should be performed in all patients with newly diagnosed partial seizures.

Familial temporal lobe epilepsy with febrile seizures.

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.

Arachnoiditis ossificans with arachnoid cyst after cranial tuberculous meningitis.

A 34-year-old woman developed symptomatic arachnoiditis ossificans and an arachnoid cyst as a consequence of tuberculous meningitis adequately treated 20 years before. Surgical decompression of the cyst stopped the progression of her spastic paraparesis. Pathologic examination confirmed the presence of ossification of the arachnoid.

Self-injection ictal SPECT during partial seizures.

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.

Proton magnetic resonance spectroscopy in MRI-negative temporal lobe epilepsy.

OBJECTIVE: To determine the 1H MRS findings in patients with intractable temporal lobe epilepsy (TLE) who had no detectable abnormality on either qualitative or quantitative MRI. BACKGROUND: Previous work has indicated that approximately 20% of patients with TLE remain MRI negative after extensive qualitative and quantitative investigation. Single-voxel 1H MRS provides a means of identifying potentially diffuse disease. METHODS: Seven patients with intractable TLE, normal routine MRI, normal hippocampal volumes, and normal hippocampal and amygdala quantitative T2 values underwent single-voxel 1H MRS of the medial temporal lobes. The results are compared with those from 13 control subjects and 15 patients with evidence of hippocampal sclerosis (HS). RESULTS: The ratio N-acetylaspartate/(choline-creatine + phosphocreatine) was abnormally low in five of the seven MRI-negative patients. In two of these patients, the ratios were low bilaterally. The observed MRS ratios in the MRI-negative group with abnormal EEG were similar to those from temporal lobes ipsilateral to HS, suggesting the presence of widespread or diffuse disease of a similar degree in both groups. CONCLUSIONS: These results demonstrate that MRS can provide evidence of temporal lobe abnormalities in TLE patients who show no abnormality on extensive MRI investigation.

11C-flumazenil PET, volumetric MRI, and quantitative pathology in mesial temporal lobe epilepsy.

BACKGROUND: Using statistical parametric mapping and 11C-flumazenil (FMZ) PET we have previously shown reduction of central benzodiazepine receptor (cBZR) binding restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) due to hippocampal sclerosis (HS). The limited spatial resolution of PET, however, results in partial-volume averaging that affects quantitative analysis of cBZR density. METHOD: We determined hippocampal volume loss and reduction in cBZR binding using an MRI-based method for partial-volume effect correction of 11C-FMZ volume of distribution (FMZ-Vd) in 17 patients with refractory mTLE and an MRI diagnosis of HS that was subsequently histologically verified in all cases. Quantitative neuropathology was performed with assessment of neuron density in 14 of the 17 patients. Absolute FMZ-Vd and asymmetry indices (FMZ-AI) were compared before and after partial-volume effect correction with MRI-determined hippocampal volumes (HCV), hippocampal T2 measurements, and, if available, neuronal cell densities. RESULTS: Compared with 15 age-matched healthy volunteers, significant reductions of absolute hippocampal FMZ-Vd were found before correction for partial-volume effects in 11 of 17 patients (65%) and only abnormal FMZ-AI in the other six patients. After partial-volume effects correction all 17 patients (100%) showed both significant unilateral reduction of absolute FMZ-Vd and abnormal FMZ-AI. There was no correlation between corrected absolute FMZ-Vd and HCV or neuronal cell density. After correction for partial-volume effect we found a mean 38% reduction of FMZ-Vd in the sclerosed hippocampus, over and above the reduction of HCV. CONCLUSION: Correction for partial-volume effect allows absolute quantitation of FMZ-PET and increases its sensitivity for detecting abnormalities in TLE due to HS. The lack of correlation between cBZR binding and neuronal density implies that atrophy with neuron loss is not the sole determinant of reduced cBZR binding in patients with mTLE and hippocampal sclerosis.