Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using noninvasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (N30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2- dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25–90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue

Higher evening antiepileptic drug dose for nocturnal and early-morning seizures

We describe 17 children with nocturnal or early-morning seizures who were switched to a proportionally higher evening dose of antiepileptic drugs and were retrospectively reviewed for seizure outcome and side effects. Of 10 children with unknown etiology, clinical presentation was consistent with nocturnal frontal lobe epilepsy (NFLE) in 5 and benign epilepsy with centrotemporal spikes (BECTS) in 3. After a mean follow-up of 5.3 months, 15 patients were classified as responders: 11 of these became seizure free (5 NFLE, 1 BECTS, 5 with structural lesions) and 4 (2 BECTS, 2 with structural lesions) experienced 75-90% reductions in seizures. Among two nonresponders, seizures in one had failed to resolve with epilepsy surgery. Nine subjects (53%) received monotherapy after dose modification, and none presented with worsening of seizures. Two complained of transient side effects (fatigue/somnolence). Differential dosing led to seizure freedom in 64.7% (11/17) of patients, and 88.2% (15/17) experienced >= 50% reductions in seizures. (C) 2010 Elsevier Inc. All rights reserved.

UBE2A Deficiency Syndrome: Mild to Severe Intellectual Disability Accompanied by Seizures, Absent Speech, Urogenital, and Skin Anomalies in Male Patients

We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present inpatients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck. (C) 2010 Wiley-Liss, Inc.

The non-coding RNA BC1 is down-regulated in the hippocampus of Wistar Audiogenic Rat (WAR) strain after audiogenic kindling

The aim of this study was to identify molecular pathways involved in audiogenic seizures in the epilepsy-prone Wistar Audiogenic Rat (WAR). For this, we used a suppression-subtractive hybridization (SSH) library from the hippocampus of WARs coupled to microarray comparative gene expression analysis, followed by Northern blot validation of individual genes. We discovered that the levels of the non-protein coding (npc) RNA BC1 were significantly reduced in the hippocampus of WARs submitted to repeated audiogenic seizures (audiogenic kindling) when compared to Wistar resistant rats and to both naive WARs and Wistars. By quantitative in situ hybridization, we verified lower levels of BC1 RNA in the GD-hilus and significant signal ratio reduction in the stratum radiatum and stratum pyramidale of hippocampal CA3 subfield of audiogenic kindled animals. Functional results recently obtained in a BC1-/- mouse model and our current data are supportive of a potential disruption in signaling pathways, upstream of BC1, associated with the seizure susceptibility of WARs. (C) 2010 Elsevier B.V. All rights reserved.

Correlation between the fighting rates of REM sleep-deprived rats and susceptibility to the 'wild running' of audiogenic seizures

Sleep-deprived rats exhibit defensive fighting as well as explosive flights very similar to the wild-running of audiogenic seizures. In order to determine why sleep deprivation is a common factor that facilitates both panic and convulsive manifestations, the present study was undertaken to investigate whether rats that display sleep deprivation-induced fighting (SDIF) are the same as those that are susceptible to audiogenic wild-running (WR). Twenty-eight male adult Wistar rats were divided into two groups assigned to two e-sleep deprivation for 5 days and had their SDIF evaluated in social experimental schemes. In the first, 18 subjects were submitted to REM grouping. After 1 week for recovery, their susceptibility to WR was tested in an acoustic stimulation trial ( 104 dB, 200 Hz, 60 S). Rats that did not present WR received a lactate infusion and were tested again by acoustic stimulation 40 min later. In the second experimental scheme, 10 subjects were initially evaluated for WR susceptibility and the number of SDIF was recorded in social grouping after I week. Three categories of WR-susceptibility were determined: WR-sensitive rats, intermediate WR-sensitive rats and WR-insensitive rats. T'he number of SDIF in each category was significantly different and there was a high positive correlation (r=0.89; Spearman test) between the number of SDIF and the level of WR-susceptibility. We conclude that the reasons why sleep deprivation exerts facilitatory effects on both panic and convulsive manifestations are due to overlappings of neural pathways responsible for both behavioral patterns and for the property of sleep deprivation to increase neuronal excitability. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Porencephaly and cortical dysplasia as cause of seizures in a dog

Background: Seizures are a common problem in small animal neurology and it may be related to underlying diseases. Porencephaly is an extremely rare disorder, and in Veterinary Medicine it affects more often ruminants, with only few reports in dogs.Case presentation: A one-year-old intact male Shih-Tzu dog was referred to Veterinary University Hospital with history of abnormal gait and generalized tonic-clonic seizures. Signs included hypermetria, abnormal nystagmus and increased myotatic reflexes. At necropsy, during the brain analysis, a cleft was observed in the left parietal and occipital lobes, creating a communication between the subarachnoid space and the left lateral ventricle, consistent with porencephaly; and also a focal atrophy of the caudal paravermal and vermal portions of the cerebellum. Furthermore, the histological examination showed cortical and cerebellar neuronal dysplasia.Conclusions: Reports of seizures due to porencephaly are rare in dogs. In this case, the dog presented a group of brain abnormalities which per se or in assemblage could result in seizure manifestation.

NATRIURESIS, NOT SEIZURES, INDUCED BY CHOLINERGIC STIMULATION OF THE LOCUS-CERULEUS IS AFFECTED BY FOREBRAIN LESIONS AND WATER-DEPRIVATION

Two groups of rats with electrolytic lesions of the medial and upper septal area (MUL) or, alternatively, of the anteroventral portion of the third ventricle (AV3V) and a third group of sham-operated rats were water loaded and received three carbachol injections into the locus coeruleus according to the following schedule: 1) prelesion, 2) on the second postlesion day and 3) on the seventh postlesion day. Both MUL and AV3V lesions inhibited the carbachol-induced natriuresis on the second postlesion day. Recovery was almost complete after MUL but not after AV3V lesion on the seventh day. Water deprivation also reduced the carbachol-induced natriuresis but passive hydration of AV3V animals did not avoid the impairment induced by the lesion. Transient seizure phenomena such as clonic convulsions, salivation and analgesia subsequent to carbachol injection were not altered by the lesions.

Alterations of cell-mediated immune response in children with febrile seizures

The aim of the present investigation was to study the distribution of T-cell subsets in peripheral blood defined by monoclonal antibodies and by the lymphocyte proliferative response to phytohemagglutinin (PHA) in 30 children with febrile seizures and in 14 age-matched control subjects. Frequent respiratory, urinary and dermatologic infections were observed in 22 patients. The immunologic parameters showed that 64% of the patients presented an increased number of CD8+ cells and a low helper/suppressor ratio was observed in 60% of the patients. In addition, the proliferative response of lymphocytes to PHA was impaired in the patients It was observed the presence of inhibitory activity on lymphocyte function in the plasma of 33% of children with febrile seizures. These results suggest that patients with febrile seizures have an impairment of cellular immunity that may be connected with this epileptic syndrome and explain the infections observed.

Effect of the classic ketogenic diet on the treatment of refractory epileptic seizures

Objective The ketogenic diet is used as a therapeutic alternative for the treatment of epilepsy in patients with refractory epilepsy. It simulates biochemical changes typical of fasting. The present study verified the nutritional impact of the ketogenic diet on children with refractory epilepsy. Methods Nutritional status data (dietary, biochemical and anthropometric measurements), seizure frequency, and adverse events were collected from the medical records and during outpatient clinic visits of children over a period of 36 months. Results Of the 29 children who initiated the ketogenic diet, 75.8% presented fewer seizures after one month of treatment. After six months, 48.3% of the patients had at least a 90.0% decrease in seizure frequency, and 50.0% of these patients presented total seizure remission. At 12 months, eight patients continued to show positive results, and seven of these children remained on the ketogenic diet for 24 months. There was an improvement of the nutritional status at 24 months, especially in terms of weight, which culminated with the recovery of proper weight-for-height. There were no significant changes in biochemical indices (total cholesterol and components, triglycerides, albumin, total protein, creatinine, glycemia, serum aspartate transaminase and serum alanine transaminase). Serum cholesterol levels increased significantly in the first month, fell in the following six months, and remained within the normal limits thereafter. Conclusion In conclusion, patients on the classic ketogenic diet for at least 24 months gained weight. Moreover, approximately one third of the patients achieved significant reduction in seizure frequency, and some patients achieved total remission.

The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls

Introduction: Impairments in facial emotion recognition (PER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the alpha 1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Material and methods: Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a PER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. Results: The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Limitations: Sample size. Conclusion: The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. (C) 2012 Elsevier B.V. All rights reserved.

Seizures in Primary Antiphospholipid Syndrome: The Relevance of Smoking to Stroke

Objectives. To evaluate the frequency of seizures in primary antiphospholipid syndrome (PAPS) and their possible clinical and laboratory associations. Methods. Eighty-eight PAPS patients (Sydney's criteria) were analyzed by a standard interview, physical examination and review of medical charts. Risk factors for seizures, clinical manifestations, associated comorbidities, and antiphospholipid antibodies were evaluated. Results. Nine (10.2%) patients with seizures were identified, 77.8% had convulsions onset after PAPS diagnosis. Mean age, gender, and race were comparable in groups with or without seizures. Interestingly, a higher frequency of current smoking (44.4 versus 10.1%, P = 0.019) was observed in the first group. Stroke, Sneddon's syndrome, and livedo reticularis were more frequent in PAPS patients with seizures than those without seizures, although not statistically significant (P > 0.05). Comparison between patients with seizures onset after PAPS diagnosis (n = 7) and those without convulsions (n = 79) demonstrated a higher frequency of current smoking (42.9 versus 10%, P = 0.042) and stroke in the first group (71.4 versus 30.4%, P = 0.041). Regression analysis confirmed that smoking (P = 0.030) and stroke (P = 0.042) were independently associated to seizures. Conclusion. About 10.2% of PAPS patients had convulsions, predominantly after PAPS diagnosis, and seizures were associated to current smoking and stroke.

Wavelet analysis of heart rate variability related to nocturnal frontal lobe epilepsy seizures

Introduction: Nocturnal frontal lobe epilepsy (NFLE) is a distinct syndrome of partial epilepsy whose clinical features comprise a spectrum of paroxysmal motor manifestations of variable duration and complexity, arising from sleep. Cardiovascular changes during NFLE seizures have previously been observed, however the extent of these modifications and their relationship with seizure onset has not been analyzed in detail. Objective: Aim of present study is to evaluate NFLE seizure related changes in heart rate (HR) and in sympathetic/parasympathetic balance through wavelet analysis of HR variability (HRV). Methods: We evaluated the whole night digitally recorded video-polysomnography (VPSG) of 9 patients diagnosed with NFLE with no history of cardiac disorders and normal cardiac examinations. Events with features of NFLE seizures were selected independently by three examiners and included in the study only if a consensus was reached. Heart rate was evaluated by measuring the interval between two consecutive R-waves of QRS complexes (RRi). RRi series were digitally calculated for a period of 20 minutes, including the seizures and resampled at 10 Hz using cubic spline interpolation. A multiresolution analysis was performed (Daubechies-16 form), and the squared level specific amplitude coefficients were summed across appropriate decomposition levels in order to compute total band powers in bands of interest (LF: 0.039062 - 0.156248, HF: 0.156248 - 0.624992). A general linear model was then applied to estimate changes in RRi, LF and HF powers during three different period (Basal) (30 sec, at least 30 sec before seizure onset, during which no movements occurred and autonomic conditions resulted stationary); pre-seizure period (preSP) (10 sec preceding seizure onset) and seizure period (SP) corresponding to the clinical manifestations. For one of the patients (patient 9) three seizures associated with ictal asystole were recorded, hence he was treated separately. Results: Group analysis performed on 8 patients (41 seizures) showed that RRi remained unchanged during the preSP, while a significant tachycardia was observed in the SP. A significant increase in the LF component was instead observed during both the preSP and the SP (p<0.001) while HF component decreased only in the SP (p<0.001). For patient 9 during the preSP and in the first part of SP a significant tachycardia was observed associated with an increased sympathetic activity (increased LF absolute values and LF%). In the second part of the SP a progressive decrease in HR that gradually exceeded basal values occurred before IA. Bradycardia was associated with an increase in parasympathetic activity (increased HF absolute values and HF%) contrasted by a further increase in LF until the occurrence of IA. Conclusions: These data suggest that changes in autonomic balance toward a sympathetic prevalence always preceded clinical seizure onset in NFLE, even when HR changes were not yet evident, confirming that wavelet analysis is a sensitive technique to detect sudden variations of autonomic balance occurring during transient phenomena. Finally we demonstrated that epileptic asystole is associated with a parasympathetic hypertonus counteracted by a marked sympathetic activation.