Synergistic GABA-Enhancing Therapy against Seizures in a Mouse Model of Dravet Syndrome

PubMed Central

Oakley, John C.; Cho, Alvin R.; Cheah, Christine S.; Scheuer, Todd

2013-01-01

Seizures remain uncontrolled in 30% of patients with epilepsy, even with concurrent use of multiple drugs, and uncontrolled seizures result in increased morbidity and mortality. An extreme example is Dravet syndrome (DS), an infantile-onset severe epilepsy caused by heterozygous loss of function mutations in SCN1A, the gene encoding the brain type-I voltage-gated sodium channel NaV1.1. Studies in Scn1a heterozygous knockout mice demonstrate reduced excitability of GABAergic interneurons, suggesting that enhancement of GABA signaling may improve seizure control and comorbidities. We studied the efficacy of two GABA-enhancing drugs, clonazepam and tiagabine, alone and in combination, against thermally evoked myoclonic and generalized tonic-clonic seizures. Clonazepam, a positive allosteric modulator of GABA-A receptors, protected against myoclonic and generalized tonic-clonic seizures. Tiagabine, a presynaptic GABA reuptake inhibitor, was protective against generalized tonic-clonic seizures but only minimally protective against myoclonic seizures and enhanced myoclonic seizure susceptibility at high doses. Combined therapy with clonazepam and tiagabine was synergistic against generalized tonic-clonic seizures but was additive against myoclonic seizures. Toxicity determined by rotorod testing was additive for combination therapy. The synergistic actions of clonazepam and tiagabine gave enhanced seizure protection and reduced toxicity, suggesting that combination therapy may be well tolerated and effective for seizures in DS. PMID:23424217

Post-traumatic seizure susceptibility is attenuated by hypothermia therapy

PubMed Central

Atkins, Coleen M.; Truettner, Jessie S.; Lotocki, George; Sanchez-Molano, Juliana; Kang, Yuan; Alonso, Ofelia F.; Sick, Thomas J.; Dietrich, W. Dalton; Bramlett, Helen M.

2010-01-01

Traumatic brain injury (TBI) is a major risk factor for the subsequent development of epilepsy. Currently, chronic seizures after brain injury are often poorly controlled by available anti-epileptic drugs. Hypothermia treatment, a modest reduction in brain temperature, reduces inflammation, activates pro-survival signaling pathways, and improves cognitive outcome after TBI. Given the well-known effect of therapeutic hypothermia to ameliorate pathological changes in the brain after TBI, we hypothesized that hypothermia therapy may attenuate the development of post-traumatic epilepsy and some of the pathomechanisms that underlie seizure formation. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury, and then were maintained at normothermic or moderate hypothermic temperatures for 4 hr. At 12 weeks after recovery, seizure susceptibility was assessed by challenging the animals with pentylenetetrazole (PTZ), a GABAA receptor antagonist. PTZ elicited a significant increase in seizure frequency in TBI normothermic animals as compared to sham surgery animals and this was significantly reduced in TBI hypothermic animals. Early hypothermia treatment did not rescue chronic dentate hilar neuronal loss, nor did it improve loss of doublecortin-labeled cells in the dentate gyrus post-seizure. However, mossy fiber sprouting was significantly attenuated by hypothermia therapy. These findings demonstrate that reductions in seizure susceptibility after TBI are improved with post-traumatic hypothermia and provide a new therapeutic avenue for the treatment of post-traumatic epilepsy. PMID:21044182

Toward Evidence-Based Transport of Evidence-Based Treatments: MST as an Example

ERIC Educational Resources Information Center

Schoenwald, Sonja K.

2008-01-01

This article describes the journey toward evidence-based transport and implementation in usual care settings of Multisystemic Therapy (MST) for youth with drug abuse and behavioral problems (Henggeler, Schoenwald, Borduin, Rowland, & Cunningham, 1998). Research and experience informing the design of the MST transport strategy, progress in…

Cognitive-behavioral therapy for psychogenic nonepileptic seizures: a pilot RCT.

PubMed

Goldstein, L H; Chalder, T; Chigwedere, C; Khondoker, M R; Moriarty, J; Toone, B K; Mellers, J D C

2010-06-15

To compare cognitive-behavioral therapy (CBT) and standard medical care (SMC) as treatments for psychogenic nonepileptic seizures (PNES). Our randomized controlled trial (RCT) compared CBT with SMC in an outpatient neuropsychiatric setting. Sixty-six PNES patients were randomized to either CBT (plus SMC) or SMC alone, scheduled to occur over 4 months. PNES diagnosis was established by video-EEG telemetry for most patients. Exclusion criteria included comorbid history of epilepsy, <2 PNES/month, and IQ <70. The primary outcome was seizure frequency at end of treatment and at 6-month follow-up. Secondary outcomes included 3 months of seizure freedom at 6-month follow-up, measures of psychosocial functioning, health service use, and employment. In an intention-to-treat analysis, seizure reduction following CBT was superior at treatment end (group x time interaction p < 0.0001; large to medium effect sizes). At follow-up, the CBT group tended to be more likely to have experienced 3 months of seizure freedom (odds ratio 3.125, p = 0.086). Both groups improved in some health service use measures and on the Work and Social Adjustment Scale. Mood and employment status showed no change. Our findings suggest that cognitive-behavioral therapy is more effective than standard medical care alone in reducing seizure frequency in PNES patients. This study provides Class III evidence that CBT in addition to SMC, as compared to SMC alone, significantly reduces seizure frequency in patients with PNES (change in median monthly seizure frequency: baseline to 6 months follow-up, CBT group, 12 to 1.5; SMC alone group, 8 to 5).

An evaluation of cognitive behavioral therapy as a treatment for dissociative seizures: a pilot study.

PubMed

Goldstein, Laura H; Deale, Alicia C; Mitchell-O'Malley, Sara J; Toone, Brian K; Mellers, John D C

2004-03-01

To evaluate in an open trial the effectiveness of cognitive behavioral therapy as a treatment of adults with dissociative seizures (i.e., "pseudoseizures"). Although suggestions have been made concerning the management of patients with dissociative seizures, no studies have previously evaluated the systematic use of cognitive behavioral therapy in the treatment of this disorder. Twenty patients diagnosed with dissociative seizures were offered treatment comprising 12 sessions of cognitive behavioral therapy. Principal outcome measures were dissociative seizure frequency and psychosocial functioning, including improvement in employment status and mood. Measures were administered before treatment, at the end of treatment, and at a 6-month follow-up. Treatment was completed by 16 patients (questionnaire measures were not available for 4 patients who discontinued treatment). Following treatment, there was a highly significant reduction in seizure frequency and an improvement in self-rated psychosocial functioning. These improvements were maintained at the 6-month follow-up. There was also a tendency for patients to have improved their employment status between the start of treatment and the 6-month follow-up period. In this open prospective trial, cognitive behavioral therapy was associated with a reduction in dissociative seizure frequency and an improvement in psychosocial functioning in adults with dissociative seizures.

Resolution of electroconvulsive therapy refractory major depressive disorder with unintentional hypoglycemic seizure: a case report.

PubMed

Rosenblat, Joshua D; Devarajan, Sivakumaran

2013-09-01

We report a 74-year-old white woman with type 1 diabetes and major depressive disorder refractory to multiple medications who received 15 electroconvulsive therapy treatments with minimal improvement. After an accidental hypoglycemic seizure, the patient's symptoms completely resolved. In conclusion, the present case reveals an instance where electroconvulsive therapy-induced seizures appeared to be minimally effective, whereas a single accidental hypoglycemia-induced seizure was incredibly effective for the resolutions of depressive symptoms. Although this case presents a single efficacious use of accidental insulin coma therapy, the applicability is limited because of the known risks of insulin coma therapy.

Gene therapy decreases seizures in a model of Incontinentia pigmenti.

PubMed

Dogbevia, Godwin K; Töllner, Kathrin; Körbelin, Jakob; Bröer, Sonja; Ridder, Dirk A; Grasshoff, Hanna; Brandt, Claudia; Wenzel, Jan; Straub, Beate K; Trepel, Martin; Löscher, Wolfgang; Schwaninger, Markus

2017-07-01

Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. In a mouse model of IP, we administered a single intravenous dose of the adeno-associated virus (AAV) vector, AAV-BR1-CAG-NEMO, delivering the Nemo gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood-brain barrier (BBB) were monitored. The endothelium-targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV-BR1-CAG-NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile. The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in IP. Ann Neurol 2017;82:93-104. © 2017 American Neurological Association.

Hormone Replacement Therapy: Will it affect seizure control and AED levels?

PubMed Central

Harden, Cynthia L.

2008-01-01

Interest in the years of reproductive changes for women with epilepsy (WWE), specifically perimenopause, menopause and postmenopause has been emerging in the epilepsy community. This article discusses evidence for changes in seizure frequency during perimenopause and postmenopause. Further, a catamenial epilepsy pattern during the reproductive years may be a hallmark for the observed seizure frequency change during these years; that is, an increase at perimenopause but a decrease at menopause. This finding implies that a subset of WWE are particularly susceptible to endogenous reproductive hormonal changes. An adverse effect on seizure frequency with the use of hormone replacement therapy (HRT) during postmenopause for WWE was reported in questionnaires, and was later borne out in a clinical trial. The laboratory counterpart of this human trial, HRT in ovariectomized rodent seizure models, shows that estrogen and progesterone are neuroprotective and do not uniformly increase seizure frequency. Possible reasons for the discrepancy between “the lab and the clinic” are presented. Strategies for managing HRT in symptomatic postmenopausal WWE using estrogenic and progestogenic compounds that may be less likely to promote seizures are discussed. PMID:18187348

Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

PubMed

Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

2014-01-01

Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

Lack of effect of naloxone on prolactin and seizures in electroconvulsive therapy.

PubMed

Sperling, M R; Melmed, S; McAllister, T; Price, T R

1989-01-01

Both opiate agonist and antagonist injection have been reported to modulate prolactin secretion, alter brain excitability and produce seizures, and modify the postictal state. We studied the effects of administration of high-dose naloxone, an opiate antagonist, on postictal prolactin levels, seizure duration, and postictal behavior, using patients undergoing electroconvulsive therapy (ECT) as a seizure model. Seven patients had 8 mg naloxone injected prior to one ECT treatment and saline injected prior to another treatment, with the order of injection randomized. Before ECT and 15 min after ECT, prolactin levels were drawn, and no blunting of the expected postictal prolactin elevation by naloxone injection was observed. We found no evidence that endogenous opiates trigger prolactin secretion during seizures. Seizure duration was also similar in saline and naloxone groups, and naloxone did not reverse postictal depression, as has been reported in an animal model.

Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea.

PubMed

Pornsriniyom, Darakul; Kim, Hu won; Bena, James; Andrews, Noah D; Moul, Douglas; Foldvary-Schaefer, Nancy

2014-08-01

Previous studies suggest that treatment for obstructive sleep apnea (OSA) in patients with epilepsy can improve seizure control. We investigated the effect of positive airway pressure (PAP) therapy on seizures in adults with epilepsy referred to the Cleveland Clinic for polysomnography (PSG) from 1997 to 2010. Seizure outcome at baseline and 1 year later was compared in patients with no OSA (apnea-hypopnea index [AHI] <5), patients with PAP-treated OSA, and patients with untreated OSA. One hundred thirty-two subjects (age: 40.2±13 (18-76) years, 65.4% female) were included. Seventy-six (57.6%) subjects had OSA; of these, 43 (56.6%) were on PAP therapy, and 33 (43.4%) were not on PAP therapy (either PAP-intolerant or refused therapy). Of the group with PAP-treated OSA, 83.7% were adherent (use ≥4 h/night at least 5 nights/week). The percentage of subjects with ≥50% seizure reduction and the mean percentage of seizure reduction were significantly greater in the group with PAP-treated OSA (73.9%; 58.5%) than in subjects with untreated OSA (14.3%; 17.0%). There were significantly more subjects with successful outcomes (with ≥50% seizure reduction or seizure-free at both baseline and follow-up) in the group with PAP-treated OSA (83.7%) than in the groups with no OSA (53.6%) and untreated OSA (39.4%). After adjusting for age, gender, body mass index, AHI, and epilepsy duration, we found that the odds of successful outcomes in subjects in the group with PAP-treated OSA were 9.9 and 3.91 times those of the groups with untreated OSA and no OSA, respectively. The group with PAP-treated OSA had 32.3 times the odds of having a ≥50% seizure reduction compared with the group with untreated OSA and 6.13 times compared with the group with no OSA. Positive airway pressure therapy appears to produce beneficial effects on seizures in adult patients with epilepsy and OSA. Copyright © 2014 Elsevier Inc. All rights reserved.

MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes.

PubMed

Ardestani, Amin; Paroni, Federico; Azizi, Zahra; Kaur, Supreet; Khobragade, Vrushali; Yuan, Ting; Frogne, Thomas; Tao, Wufan; Oberholzer, Jose; Pattou, Francois; Conte, Julie Kerr; Maedler, Kathrin

2014-04-01

Apoptotic cell death is a hallmark of the loss of insulin-producing beta cells in all forms of diabetes mellitus. Current treatments fail to halt the decline in functional beta cell mass, and strategies to prevent beta cell apoptosis and dysfunction are urgently needed. Here, we identified mammalian sterile 20-like kinase-1 (MST1) as a critical regulator of apoptotic beta cell death and function. Under diabetogenic conditions, MST1 was strongly activated in beta cells in human and mouse islets and specifically induced the mitochondrial-dependent pathway of apoptosis through upregulation of the BCL-2 homology-3 (BH3)-only protein BIM. MST1 directly phosphorylated the beta cell transcription factor PDX1 at T11, resulting in the latter's ubiquitination and degradation and thus in impaired insulin secretion. MST1 deficiency completely restored normoglycemia, beta cell function and survival in vitro and in vivo. We show MST1 as a proapoptotic kinase and key mediator of apoptotic signaling and beta cell dysfunction and suggest that it may serve as target for the development of new therapies for diabetes.

Population dose-response analysis of daily seizure count following vigabatrin therapy in adult and pediatric patients with refractory complex partial seizures.

PubMed

Nielsen, Jace C; Hutmacher, Matthew M; Wesche, David L; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G

2015-01-01

Vigabatrin is an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T) and is used as an adjunctive therapy for adult patients with refractory complex partial seizures (rCPS). The purpose of this investigation was to describe the relationship between vigabatrin dosage and daily seizure rate for adults and children with rCPS and identify relevant covariates that might impact seizure frequency. This population dose-response analysis used seizure-count data from three pediatric and two adult randomized controlled studies of rCPS patients. A negative binomial distribution model adequately described daily seizure data. Mean seizure rate decreased with time after first dose and was described using an asymptotic model. Vigabatrin drug effects were best characterized by a quadratic model using normalized dosage as the exposure metric. Normalized dosage was an estimated parameter that allowed for individualized changes in vigabatrin exposure based on body weight. Baseline seizure rate increased with decreasing age, but age had no impact on vigabatrin drug effects after dosage was normalized for body weight differences. Posterior predictive checks indicated the final model was capable of simulating data consistent with observed daily seizure counts. Total normalized vigabatrin dosages of 1, 3, and 6 g/day were predicted to reduce seizure rates 23.2%, 45.6%, and 48.5%, respectively. © 2014, The American College of Clinical Pharmacology.

Music-supported therapy (MST) in improving post-stroke patients' upper-limb motor function: a randomised controlled pilot study.

PubMed

Tong, Yanna; Forreider, Brian; Sun, Xinting; Geng, Xiaokun; Zhang, Weidong; Du, Huishan; Zhang, Tong; Ding, Yuchuan

2015-05-01

Music-supported therapy (MST) is a new approach for motor rehabilitation of stroke patients. Recently, many studies have demonstrated that MST improved the motor functions of post-stroke patients. However, the underlying mechanism for this effect is still unclear. It may result from repeated practice or repeated practice combined with musical stimulation. Currently, few studies have been designed to clarify this discrepancy. In this study, the application of "mute" musical instruments allowed for the study of music as an independent factor. Thirty-three post-stroke patients with no substantial previous musical training were included. Participants were assigned to either audible music group (MG) or mute music group (CG), permitting observation of music's independent effect. All subjects received the conventional rehabilitation treatments. Patients in MG (n = 15) received 20 extra sessions of audible musical instrument training over 4 weeks. Patients in CG (n = 18) received "mute" musical instrument training of the same protocol as that of MG. Wolf motor function test (WMFT) and Fugl-Meyer assessment (FMA) for upper limbs were utilised to evaluate motor functions of patients in both groups before and after the treatment. Three patients in CG dropped out. All participants in both groups showed significant improvements in motor functions of upper limbs after 4  weeks' treatment. However, significant differences in the WMFT were found between the two groups (WMFT-quality: P = 0.025; WMFT-time: P = 0.037), but not in the FMA (P = 0.448). In short, all participants showed significant improvement after 4 weeks' treatment, but subjects in MG demonstrated greater improvement than those in CG. This study supports that MST, when combined with conventional treatment, is effective for the recovery of motor skills in post-stroke patients. Additionally, it suggests that apart from the repetitive practices of MST, music may play a unique role in improving

Changes in Maternal Depression Are Associated with MST Outcomes for Adolescents with Co-Occurring Externalizing and Internalizing Problems

ERIC Educational Resources Information Center

Grimbos, Teresa; Granic, Isabela

2009-01-01

The efficacy of Multisystemic therapy (MST) in treating adolescent aggression has been established, however, not all youth and their families benefit from MST. One reason for this treatment variability could be the failure to distinguish between different aggressive subtypes with different risk factors, developmental prognoses and treatment needs.…

Lacosamide: a review of its use as adjunctive therapy in the management of partial-onset seizures.

PubMed

Hoy, Sheridan M

2013-12-01

Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a syrup or tablet) and as an intravenous infusion. It is believed to exert its antiepileptic effect by selectively enhancing the slow inactivation of voltage-gated sodium channels. Lacosamide is approved in several countries worldwide as an adjunctive therapy for the treatment of partial-onset seizures; however, prescribing regulations differ between countries. This article reviews the use of lacosamide as indicated in adults and adolescents (aged 16-18 years) in the EU, where it is approved in this patient population as an adjunctive therapy to other AEDs in the treatment of partial-onset seizures, with or without secondary generalization. In three randomized, double-blind, placebo-controlled, multicentre studies in adults and adolescents (aged 16-18 years) with partial-onset seizures, adjunctive therapy with oral lacosamide (administered for an initial titration period followed by 12 weeks' maintenance therapy) generally reduced the frequency of seizures to a significantly greater extent than placebo, with antiepileptic efficacy sustained following longer-term treatment (up to 8 years) in this patient population. Oral and intravenous lacosamide were generally well tolerated in clinical studies, with the majority of adverse events being mild or moderate in severity. Very common adverse reactions following adjunctive therapy with oral lacosamide included diplopia, dizziness, headache and nausea; the tolerability profile of intravenous lacosamide appeared consistent with that of oral lacosamide, although intravenous administration was associated with local adverse events, such as injection site discomfort or pain, irritation and erythema. Thus, oral and intravenous lacosamide as an adjunctive therapy to other AEDs provides a useful option in the treatment of patients with partial-onset seizures.

The efficacy of Life Review Therapy combined with Memory Specificity Training (LRT-MST) targeting cancer patients in palliative care: A randomized controlled trial.

PubMed

Kleijn, Gitta; Lissenberg-Witte, Birgit I; Bohlmeijer, Ernst T; Steunenberg, Bas; Knipscheer-Kuijpers, Kitty; Willemsen, Vincent; Becker, Annemarie; Smit, Egbert F; Eeltink, Corien M; Bruynzeel, Anna M E; van der Vorst, Maurice; de Bree, Remco; Leemans, C René; van den Brekel, Michiel W M; Cuijpers, Pim; Verdonck-de Leeuw, Irma M

2018-01-01

The aim of this study was to evaluate the efficacy of an intervention combining Life Review Therapy (LRT) and Memory Specificity Training (MST) (LRT-MST) to improve ego-integrity and despair among cancer patients in palliative care. In this multicentre randomized controlled trial, cancer patients in palliative care were randomized to the intervention group (LRT-MST; n = 55) or waiting-list control group (n = 52). LRT-MST is a 4-session home-based psychological intervention that aims to retrieve specific positive memories, to re-evaluate life events and to reconstruct the story of a patient's life, including the diagnosis of incurable cancer. Outcome measures were ego-integrity and despair (NEIS), psychological distress, anxiety and depression (HADS), quality of life (EORTC QLQ-C15-PAL), and specificity of the autobiographical memory (AMT). NEIS, HADS and EORTC QLQ-C15-PAL were assessed at baseline (T0), 1 month later (post-treatment; T1), and at 1 month follow-up (T2). AMT was assessed at T0 and T1. Linear mixed models (intention to treat) were used to assess group differences in changes over time. Independent samples t-tests were used to assess group differences at T0, T1, and T2, and effect sizes (ES) were calculated at T1 and T2. The course of ego-integrity (not despair) improved significantly over time (p = .007) in the intervention group compared to the waiting-list control group, with moderate, but insignificant, effect sizes at T1 (ES = .42) and T2 (ES = .48). Compliance rate was 69% and total dropout rate was 28%, both primarily related to disease progression and death. LRT-MST seems effective among cancer patients in palliative care to improve the course of ego-integrity.

Seizures and Teens: Surgery for Seizures--What's It All About?

ERIC Educational Resources Information Center

Duchowny, Michael S.; Dean, Patricia

2006-01-01

Nearly 1 out of 2 children and teens with seizures may need to take medications throughout their lives. At least 25% will develop a condition called refractory epilepsy--meaning that their seizures do not respond to medical therapy. For these children and teens, non-drug therapies such as brain surgery are available that may offer a chance to…

MST Filterability Tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poirier, M. R.; Burket, P. R.; Duignan, M. R.

2015-03-12

The Savannah River Site (SRS) is currently treating radioactive liquid waste with the Actinide Removal Process (ARP) and the Modular Caustic Side Solvent Extraction Unit (MCU). The low filter flux through the ARP has limited the rate at which radioactive liquid waste can be treated. Recent filter flux has averaged approximately 5 gallons per minute (gpm). Salt Batch 6 has had a lower processing rate and required frequent filter cleaning. Savannah River Remediation (SRR) has a desire to understand the causes of the low filter flux and to increase ARP/MCU throughput. In addition, at the time the testing started, SRRmore » was assessing the impact of replacing the 0.1 micron filter with a 0.5 micron filter. This report describes testing of MST filterability to investigate the impact of filter pore size and MST particle size on filter flux and testing of filter enhancers to attempt to increase filter flux. The authors constructed a laboratory-scale crossflow filter apparatus with two crossflow filters operating in parallel. One filter was a 0.1 micron Mott sintered SS filter and the other was a 0.5 micron Mott sintered SS filter. The authors also constructed a dead-end filtration apparatus to conduct screening tests with potential filter aids and body feeds, referred to as filter enhancers. The original baseline for ARP was 5.6 M sodium salt solution with a free hydroxide concentration of approximately 1.7 M.3 ARP has been operating with a sodium concentration of approximately 6.4 M and a free hydroxide concentration of approximately 2.5 M. SRNL conducted tests varying the concentration of sodium and free hydroxide to determine whether those changes had a significant effect on filter flux. The feed slurries for the MST filterability tests were composed of simple salts (NaOH, NaNO 2, and NaNO 3) and MST (0.2 – 4.8 g/L). The feed slurry for the filter enhancer tests contained simulated salt batch 6 supernate, MST, and filter enhancers.« less

Overview of MST Research

NASA Astrophysics Data System (ADS)

Chapman, B. E.

2017-10-01

MST progress in advancing the RFP for (1) fusion plasma confinement with ohmic heating and minimal external magnetization, (2) predictive capability in toroidal confinement physics, and (3) basic plasma physics is summarized. Validation of key plasma models is a program priority, which is enhanced by programmable power supplies (PPS) to maximize inductive capability. The existing PPS enables access to very low plasma current, down to Ip =0.02 MA. This greatly expands the Lundquist number range S =104 -108 and allows nonlinear, 3D MHD computation using NIMROD and DEBS with dimensionless parameters that overlap those of MST plasmas. A new, second PPS will allow simultaneous PPS control of the Bp and Bt circuits. The PPS also enables MST tokamak operation, thus far focused on disruptions and RMP suppression of runaway electrons. Gyrokinetic modeling with GENE predicts unstable TEM in improved-confinement RFP plasmas. Measured fluctuations have TEM properties including a density-gradient threshold larger than for tokamak plasmas. Turbulent energization of an electron tail occurs during sawtooth reconnection. Probe measurements hint that drift waves are also excited via the turbulent cascade in standard RFP plasmas. Exploration of basic plasma science frontiers in MST RFP and tokamak plasmas is proposed as part of WiPPL, a basic science user facility. Work supported by USDoE.

Dendritic cell MST1 inhibits Th17 differentiation

PubMed Central

Li, Chunxiao; Bi, Yujing; Li, Yan; Yang, Hui; Yu, Qing; Wang, Jian; Wang, Yu; Su, Huilin; Jia, Anna; Hu, Ying; Han, Linian; Zhang, Jiangyuan; Li, Simin; Tao, Wufan; Liu, Guangwei

2017-01-01

Although the differentiation of CD4+T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4+T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4+T cells, whereas ectopic MST1 expression in DCs inhibits it. Notably, MST1-mediated DC-dependent Th17 differentiation regulates experimental autoimmune encephalomyelitis and antifungal immunity. Mechanistically, MST1-deficient DCs promote IL-6 secretion and regulate the activation of IL-6 receptor α/β and STAT3 in CD4+T cells in the course of inducing Th17 differentiation. Activation of the p38 MAPK signal is responsible for IL-6 production in MST1-deficient DCs. Thus, our results define the DC MST1–p38MAPK signalling pathway in directing Th17 differentiation. PMID:28145433

Lacosamide adjunctive therapy for partial-onset seizures: a meta-analysis

PubMed Central

Newman, Jennifer J.; Deshpande, Santosh; Jones, Philip M.

2013-01-01

Background. The relative efficacy and safety of lacosamide as adjunctive therapy compared to other antiepileptic drugs has not been well established. Objective. To determine if lacosamide provides improved efficacy and safety, reduced length of hospital stay and improved quality of life compared with other anti-epileptic therapies for adults with partial-onset seizures. Data Sources. A systematic review of the medical literature using Medline (1946–Week 4, 2012), EMBASE (1980–Week 3, 2012), Cochrane Central Register of Controlled Trials (Issue 1 of 12, January 2012). Additional studies were identified (through to February 7, 2012) by searching bibliographies, the FDA drug approval files, clinical trial registries and major national and international neurology meeting abstracts. No restrictions on publication status or language were applied. Study Selection. Randomized controlled trials of lacosamide in adults with partial-onset seizures were included. Data Extraction. Study selection, extraction and risk of bias assessment were performed independently by two authors. Authors of studies were contacted for missing data. Data Synthesis. All pooled analyses used the random effects model. Results. Three trials (1311 patients) met inclusion criteria. Lacosamide increased the 50% responder rate compared to placebo (RR 1.68 [95% CI 1.36 to 2.08]; I2 = 0%). Discontinuation due to adverse events was statistically significantly higher in the lacosamide arm (RR3.13 [95% CI 1.94 to 5.06]; I2 = 0%). Individual adverse events (ataxia, dizziness, fatigue, and nausea) were also significantly higher in the lacosamide group. Limitations. All dosage arms from the included studies were pooled to make a single pair-wise comparison to placebo. Selective reporting of outcomes was found in all of the included RCTs. Conclusions. Lacosamide as adjunctive therapy in patients with partial-onset seizures increases the 50% responder rate but with significantly more adverse events compared to

Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP).

PubMed

Klein, Brian D; Jacobson, Catherine A; Metcalf, Cameron S; Smith, Misty D; Wilcox, Karen S; Hampson, Aidan J; Kehne, John H

2017-07-01

Cannabidiol (CBD) is a cannabinoid component of marijuana that has no significant activity at cannabinoid receptors or psychoactive effects. There is considerable interest in CBD as a therapy for epilepsy. Almost a third of epilepsy patients are not adequately controlled by clinically available anti-seizure drugs (ASDs). Initial studies appear to demonstrate that CBD preparations may be a useful treatment for pharmacoresistant epilepsy. The National Institute of Neurological Disorders and Stroke (NINDS) funded Epilepsy Therapy Screening Program (ETSP) investigated CBD in a battery of seizure models using a refocused screening protocol aimed at identifying pharmacotherapies to address the unmet need in pharmacoresistant epilepsy. Applying this new screening workflow, CBD was investigated in mouse 6 Hz 44 mA, maximal electroshock (MES), corneal kindling models and rat MES and lamotrigine-resistant amygdala kindling models. Following intraperitoneal (i.p.) pretreatment, CBD produced dose-dependent protection in the acute seizure models; mouse 6 Hz 44 mA (ED 50 164 mg/kg), mouse MES (ED 50 83.5 mg/kg) and rat MES (ED 50 88.9 mg/kg). In chronic models, CBD produced dose-dependent protection in the corneal kindled mouse (ED 50 119 mg/kg) but CBD (up to 300 mg/kg) was not protective in the lamotrigine-resistant amygdala kindled rat. Motor impairment assessed in conjunction with the acute seizure models showed that CBD exerted seizure protection at non-impairing doses. The ETSP investigation demonstrates that CBD exhibits anti-seizure properties in acute seizure models and the corneal kindled mouse. However, further preclinical and clinical studies are needed to determine the potential for CBD to address the unmet needs in pharmacoresistant epilepsy.

The effect of propofol-remifentanil anesthesia on selected seizure quality indices in electroconvulsive therapy.

PubMed

Dinwiddie, Stephen H; Glick, David B; Goldman, Morris B

2012-07-01

Use of a short-acting opiate to potentiate anesthetic induction agents has been shown to increase seizure duration in electroconvulsive therapy (ECT), but little is known of the effect of this combination on indices of seizure quality. To determine whether anesthetic modality affects commonly provided indices of seizure quality. Twenty-five subjects were given propofol 2 mg/kg body weight for their first ECT session, at which time seizure threshold was titrated. Subjects thereafter alternated between that anesthetic regimen or propofol 0.5 mg/kg plus remifentanil 1 mcg/kg. Linear mixed models with random subject effect, adjusting for electrode placement, electrical charge, and number of treatments, were fit to estimate effect of anesthesia on seizure duration and several standard seizure quality indices (average seizure energy, time to peak electroencephalography (EEG) power, maximum sustained power, interhemispheric coherence, early and midictal EEG amplitude, and maximum sustained interhemispheric EEG coherence). Propofol-remifentanil anesthesia significantly lengthened seizure duration and was associated with longer time to reach maximal EEG power and coherence as well as maximal degree of interhemispheric EEG coherence. No effect was seen on early ictal amplitude or average seizure energy index. Propofol-remifentanil anesthesia prolongs seizure duration and has a significant effect on some, but not all, measures of seizure quality. This effect may be of some benefit in cases where adequate seizures are otherwise difficult to elicit. Varying anesthetic technique may allow more precise investigation of the relationships between and relative impacts of commonly used seizure quality indices on clinical outcomes and ECT-related cognitive side effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Focal electrically administered seizure therapy: a novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction.

PubMed

Spellman, Timothy; Peterchev, Angel V; Lisanby, Sarah H

2009-07-01

Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication-resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified through scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of the 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These

Seizure Duration and Hemodynamic State During Electroconvulsive Therapy: Sodium Thiopental Versus Propofol.

PubMed

Jarineshin, Hashem; Kashani, Saeed; Fekrat, Fereydoon; Vatankhah, Majid; Golmirzaei, Javad; Alimolaee, Esmaeel; Zafarpour, Hamid

2015-06-12

General anesthesia is required for Electroconvulsive Therapy (ECT) and it is usually provided by a hypnotic agent. The seizure duration is important for the treatment, and it is usually accompanied by severe hemodynamic changes. The aim of this study was to compare the effects of sodium thiopental versus Propofol on seizure duration and hemodynamic variables during ECT. A number of 100 patient-sessions of ECT were included in this randomized clinical trial. The initial hemodynamic state of each patient was recorded. Anesthesia was induced by Sodium thiopental in the 1st group and with Propofol in 2nd group. All the patients received the muscle relaxant succinylcholine. The hemodynamic variables after seizure and seizure duration were recorded. The data were analyzed through SPSS 20 and independent t-test. P<0.05 was considered significant. The mean duration of seizure in the sodium thiopental group was significantly longer than the Propofol group (40.3±16.6 sec versus 32±11.3 sec) (P=0.001). There was no statistically significant difference between the mean energy level applied in the two groups (20.5±3.81 joules in the sodium thiopental versus 20.2±3.49 joules in the Propofol group). The mean systolic and diastolic blood pressure at all times after seizure and mean heart rate at 3 and 5 minutes after seizure were significantly lower in Propofol than sodium thiopental groups. Propofol provides a more stable hemodynamic state for the ECT procedures, and its use is highly preferred over sodium thiopental in patients with cardiovascular disease.

Gene therapy mediated seizure suppression in Genetic Generalised Epilepsy: Neuropeptide Y overexpression in a rat model.

PubMed

Powell, Kim L; Fitzgerald, Xavier; Shallue, Claire; Jovanovska, Valentina; Klugmann, Matthias; Von Jonquieres, Georg; O'Brien, Terence J; Morris, Margaret J

2018-05-01

Neuropeptide Y (NPY) is an important 36 amino acid peptide that is abundantly expressed in the mammalian CNS and is known to be an endogenous modulator of seizure activity, including in rat models of Genetic Generalised Epilepsy (GGE) with absence seizures. Studies have shown that viral-mediated "gene therapy" with overexpression of NPY in the hippocampus can suppress seizures in acquired epilepsy animal models. This study investigated whether NPY gene delivery to the thalamus or somatosensory cortex, using recombinant adeno-associated viral vector (rAAV), could produce sustained seizure suppression in the GAERS model of GGE with absence seizures. Three cohorts of GAERS were injected bilaterally into the thalamus (short term n = 14 and long term n = 8) or the somatosensory cortex (n = 26) with rAAV-NPY or rAAV-empty. EEG recordings were acquired weekly post-treatment and seizure expression was quantified. Anxiety levels were tested using elevated plus maze and open field test. NPY and NPY receptor mRNA and protein expression were evaluated using quantitative PCR, immunohistochemistry and immunofluorescence. Viral overexpression of human NPY in the thalamus and somatosensory cortex in GAERS significantly reduced the time spent in seizure activity and number of seizures, whereas seizure duration was only reduced after thalamic NPY overexpression. Human and rat NPY and rat Y2 receptor mRNA expression was significantly increased in the somatosensory cortex. NPY overexpression in the thalamus was observed in rAAV-NPY treated rats compared to controls in the long term cohort. No effect was observed on anxiety behaviour. We conclude that virally-mediated human NPY overexpression in the thalamus or somatosensory cortex produces sustained anti-epileptic effects in GAERS. NPY gene therapy may represent a novel approach for the treatment of patients with genetic generalised epilepsies. Copyright © 2018 Elsevier Inc. All rights reserved.

Genetic characterization drives personalized therapy for early-stage non-small-cell lung cancer (NSCLC) patients and survivors with metachronous second primary tumor (MST): A case report.

PubMed

Ding, Xingchen; Wang, Linlin; Liu, Xijun; Sun, Xindong; Yu, Jinming; Meng, Xue

2017-03-01

The pathogenesis and progression of lung cancer is a complicated process in which many genes take part. But molecular gene testing is typically only performed in advanced-stage non-squamous non-small-cell lung cancer (NSCLC). The value of tyrosine kinase inhibitors (TKI) administration is not widely recognized with respect to early-stage NSCLC. Here, we present a case of a man, heavy smoker who initially presented with stage IA lung adenocarcinoma (LADC). Three years after a lung lobectomy, he was diagnosed with advanced lung squamous cell carcinoma (SCC), according to laboratory, imaging, and pathological examinations. The case initially had an early-stage LADC with an L858R epidermal growth factor receptor (EGFR) mutation. A subsequent advanced SCC bearing EGFR L858R/T790M mutations occurred 3 years after surgery. The comprehensive therapy we utilized, including surgical resection for the early-stage lesion and GP chemotherapy and local radiotherapy as the first line therapy along with gefitinib maintenance treatment for the advanced metachronous second primary tumors (MST). The synthetical therapy, have resulted in our patient with remaining alive and progression free for 4.5 years. This case suggests that changes in molecular pathology should be monitored closely throughout cancer progression to guide personalized therapy and improve prognosis. We further review administration of TKI to early-stage NSCLC and to the metachronous second primary tumors (MST) in survivors.

Bravemind: Advancing the Virtual Iraq/Afghanistan PTSD Exposure Therapy for MST

DTIC Science & Technology

2015-06-01

threatened death, serious injury or sexual violation. Military Sexual Trauma (MST) has been recognized as a significant risk factor for the...development of PTSD. This has become an issue of grave concern within the military, as reports of sexual violations and assaults have been on the rise over the...far, the system was built and delivered and the RCT has commenced. 15. SUBJECT TERMS PTSD, Virtual Reality, Prolonged Exposure, Military Sexual

Seizure Duration and Hemodynamic State during Electroconvulsive Therapy: Sodium Thiopental versus Propofol

PubMed Central

Jarineshin, Hashem; Kashani, Saeed; Fekrat, Fereydoon; Vatankhah, Majid; Golmirzaei, Javad; Alimolaee, Esmaeel; Zafarpour, Hamid

2016-01-01

Introduction: General anesthesia is required for Electroconvulsive Therapy (ECT) and it is usually provided by a hypnotic agent. The seizure duration is important for the treatment, and it is usually accompanied by severe hemodynamic changes. The aim of this study was to compare the effects of sodium thiopental versus Propofol on seizure duration and hemodynamic variables during ECT. Methods: A number of 100 patient-sessions of ECT were included in this randomized clinical trial. The initial hemodynamic state of each patient was recorded. Anesthesia was induced by Sodium thiopental in the 1st group and with Propofol in 2nd group. All the patients received the muscle relaxant succinylcholine. The hemodynamic variables after seizure and seizure duration were recorded. The data were analyzed through SPSS 20 and independent t-test. P<0.05 was considered significant. Results: The mean duration of seizure in the sodium thiopental group was significantly longer than the Propofol group (40.3±16.6 sec versus 32±11.3 sec) (P=0.001). There was no statistically significant difference between the mean energy level applied in the two groups (20.5±3.81 joules in the sodium thiopental versus 20.2±3.49 joules in the Propofol group). The mean systolic and diastolic blood pressure at all times after seizure and mean heart rate at 3 and 5 minutes after seizure were significantly lower in Propofol than sodium thiopental groups. Discussion and Conclusion: Propofol provides a more stable hemodynamic state for the ECT procedures, and its use is highly preferred over sodium thiopental in patients with cardiovascular disease. PMID:26383207

Focal Electrically Administered Seizure Therapy (FEAST): A novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction

PubMed Central

Spellman, Timothy; Peterchev, Angel V.; Lisanby, Sarah H.

2009-01-01

Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified via scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These findings

Common and Specific Factors Approaches to Home-Based Treatment: I-FAST and MST

ERIC Educational Resources Information Center

Lee, Mo Yee; Greene, Gilbert J.; Fraser, J. Scott; Edwards, Shivani G.; Grove, David; Solovey, Andrew D.; Scott, Pamela

2013-01-01

Objectives: This study examined the treatment outcomes of integrated families and systems treatment (I-FAST), a moderated common factors approach, in reference to multisystemic therapy (MST), an established specific factor approach, for treating at risk children and adolescents and their families in an intensive community-based setting. Method:…

AWIWPCA STATES HELPING STATES CLL ON MST

EPA Science Inventory

Several Microbial Source Tracking (MST) tools are now being applied in the development of TMDL plans and in the evaluation of best management practices. However, due to the relatively recent development of MST most environmental managers and scientists have little training and ...

Seizures in Infants and Young Children.

ERIC Educational Resources Information Center

McBrien, Dianne M.; Bonthius, Daniel J.

2000-01-01

This article reviews the most frequent causes of seizure disorders in young children and the classification of different seizure types. It discusses current therapies, including alternatives to medication. Emergency response to seizures is covered a well as non-epileptic episodes that may resemble seizures. Epilepsy's potential impact on the…

Possible induction of West syndrome by oxcarbazepine therapy in a patient with complex partial seizures.

PubMed

Veerapandiyan, Aravindhan; Singh, Piyush; Mikati, Mohamad A

2012-03-01

Oxcarbazepine has been reported to precipitate myoclonic, generalised tonic-clonic, absence, and complex partial seizures, and carbamazepine to precipitate absences, myoclonic seizures and spasms. Here, we report a one-year, six-month-old girl with complex partial seizures who developed infantile spasms, developmental regression, and hypsarrhythmia during the two weeks directly following initiation of oxcarbazepine (14 mg/kg/day). All of these resolved within a few days after discontinuation of this medication. Although we cannot rule out that the above association may have been coincidental, or that the improvement may have been due to concurrent therapy, this case raises the possibility that oxcarbazepine, like carbamazepine, may precipitate infantile spasms and West syndrome.

Pretreatment With Caffeine Citrate to Increase Seizure Duration During Electroconvulsive Therapy: A Case Series.

PubMed

Pinkhasov, Aaron; Biglow, Michael; Chandra, Subhash; Pica, Tiffany

2016-04-01

Due to the shortage of parenteral caffeine and sodium benzoate, patients were pretreated with caffeine citrate to increase therapeutic seizure duration during electroconvulsive therapy (ECT). To date, no data are available on the use of caffeine citrate during ECT. This retrospective case series was done to demonstrate utilization of caffeine citrate as a substitute for caffeine and sodium benzoate in optimizing ECT. Medical records were reviewed to identify patients who received ECT and caffeine citrate. Physician notes were reviewed to determine the parameters of the ECT procedure, the seizure length, and the dose of caffeine citrate. Each chart was thoroughly studied to find the relationship between seizure duration and dose of caffeine citrate. Of the 12 ECT treatments utilizing caffeine citrate, 9 achieved at least 1 session lasting >30 seconds with an average seizure duration of 35 seconds. Increase in seizure duration ranged from -41% to 276% with an average increase of 48%. Only 3 treatment sessions utilizing caffeine citrate showed no increase in seizure duration. Doses ranged from 120 to 600 mg of both oral and parenteral caffeine citrate. Although increase in seizure duration was achieved for the majority of the ECT sessions, no dose-response correlation could be made. No significant adverse reactions were noted with the use of caffeine citrate during ECT. It was determined that, much like caffeine and sodium benzoate, caffeine citrate does increase the seizure duration. However, this response did vary due to many reasons including small sample size, concomitant medications, duration of illness, and number of ECTs they received in the past and how long ago they received the last ECT. Further research is required to elucidate the effect of these variables on seizure duration. © The Author(s) 2014.

The Telomerase Inhibitor MST-312 Interferes with Multiple Steps in the Herpes Simplex Virus Life Cycle.

PubMed

Haberichter, Jarod; Roberts, Scott; Abbasi, Imran; Dedthanou, Phonphanh; Pradhan, Prajakta; Nguyen, Marie L

2015-10-01

The life cycle of herpes simplex virus (HSV) has the potential to be further manipulated to yield novel, more effective therapeutic treatments. Recent research has demonstrated that HSV-1 can increase telomerase activity and that expression of the catalytic component of telomerase, telomerase reverse transcriptase (TERT), alters sensitivity to HSV-dependent apoptosis. Telomerase is a cellular enzyme that synthesizes nucleotide repeats at the ends of chromosomes (telomeres), which prevents shortening of the 3' ends of DNA with each cell division. Once telomeres reach a critical length, cells undergo senescence and apoptosis. Here, we used a cell-permeable, reversible inhibitor of the telomerase enzyme, MST-312, to investigate telomerase activity during HSV infection. Human mammary epithelial cells immortalized through TERT expression and human carcinoma HEp-2 cells were infected with the KOS1.1 strain of HSV-1 in the presence of MST-312. MST-312 treatment reduced the number of cells displaying a cytopathic effect and the accumulation of immediate early and late viral proteins. Moreover, the presence of 20 μM to 100 μM MST-312 during infection led to a 2.5- to 5.5-log10 decrease in viral titers. MST-312 also inhibited the replication of HSV-2 and a recent clinical isolate of HSV-1. Additionally, we determined that MST-312 has the largest impact on viral events that take place prior to 5 h postinfection (hpi). Furthermore, MST-312 treatment inhibited virus replication, as measured by adsorption assays and quantification of genome replication. Together, these findings demonstrate that MST-312 interferes with the HSV life cycle. Further investigation into the mechanism for MST-312 is warranted and may provide novel targets for HSV therapies. Herpes simplex virus (HSV) infections can lead to cold sores, blindness, and brain damage. Identification of host factors that are important for the virus life cycle may provide novel targets for HSV antivirals. One such factor

Nonepileptic seizures under levetiracetam therapy: a case report of forced normalization process.

PubMed

Anzellotti, Francesca; Franciotti, Raffaella; Zhuzhuni, Holta; D'Amico, Aurelio; Thomas, Astrid; Onofrj, Marco

2014-01-01

Nonepileptic seizures (NES) apparently look like epileptic seizures, but are not associated with ictal electrical discharges in the brain. NES constitute one of the most important differential diagnoses of epilepsy. They have been recognized as a distinctive clinical phenomenon for centuries, and video/electroencephalogram monitoring has allowed clinicians to make near-certain diagnoses. NES are supposedly unrelated to organic brain lesions, and despite the preponderance of a psychiatric/psychological context, they may have an iatrogenic origin. We report a patient with NES precipitated by levetiracetam therapy; in this case, NES was observed during the disappearance of epileptiform discharges from the routine video/electroencephalogram. We discuss the possible mechanisms underlying NES with regard to alternative psychoses associated with the phenomenon of the forced normalization process.

Nonepileptic seizures under levetiracetam therapy: a case report of forced normalization process

PubMed Central

Anzellotti, Francesca; Franciotti, Raffaella; Zhuzhuni, Holta; D’Amico, Aurelio; Thomas, Astrid; Onofrj, Marco

2014-01-01

Nonepileptic seizures (NES) apparently look like epileptic seizures, but are not associated with ictal electrical discharges in the brain. NES constitute one of the most important differential diagnoses of epilepsy. They have been recognized as a distinctive clinical phenomenon for centuries, and video/electroencephalogram monitoring has allowed clinicians to make near-certain diagnoses. NES are supposedly unrelated to organic brain lesions, and despite the preponderance of a psychiatric/psychological context, they may have an iatrogenic origin. We report a patient with NES precipitated by levetiracetam therapy; in this case, NES was observed during the disappearance of epileptiform discharges from the routine video/electroencephalogram. We discuss the possible mechanisms underlying NES with regard to alternative psychoses associated with the phenomenon of the forced normalization process. PMID:24926197

Risk factors and the outcome of therapy in patients with seizure after Carbamazepine poisoning: A two-year cross-sectional study

PubMed Central

Yaraghi, Ahmad; Eizadi-Mood, Nastaran; Salehi, Marzieh; Massoumi, Gholamreza; Zunic, Lejla; Sabzghabaee, Ali Mohammad

2015-01-01

Objective: We aimed to investigate the frequency of seizure after acute carbamazepine poisoning and the important risk factors related to the outcomes of therapy. Methods: In this two-year cross-sectional study conducted in a University Hospital in Iran, 114 patients with acute carbamazepine poisoning were divided into two groups of with seizure (n = 8) and without seizure (n = 106) after intoxication. Demographic data, average amount of drug ingestion, time elapsed from ingestion to hospital admission, history of seizure before poisoning, mental status, visual disturbances and nystagmus, duration of hospitalization, the outcomes of therapy, arterial blood gas values and serum biochemical indices were compared between the two groups. Findings: Patients with seizure had an estimated (Mean ± SD) ingestion of 14,300 ± 570 mg carbamazepine, which was significantly higher (P < 0.0001) than the seizure-free group (4600 ± 420 mg). The estimated average time between drug ingestion and hospital admission in patients with seizure and the seizure-free group were 515 ± 275 and 370 ± 46 minutes, respectively (P < 0.0001). In this study, 104 out of the total number of patients had recovered without any complication. Need for respiratory support, including airway support or intubation were the most recorded complication. One patient died after status epilepticus and aspiration pneumonia. Conclusion: The ingested amount of carbamazepine and the time elapsed from the ingestion of drug to hospital admission may influence the occurrence of seizure after acute carbamazepine poisoning; however, the outcome of supportive care in these patients seems to be positive. PMID:25710046

Automatic Detection of Seizures with Applications

NASA Technical Reports Server (NTRS)

Olsen, Dale E.; Harris, John C.; Cutchis, Protagoras N.; Cristion, John A.; Lesser, Ronald P.; Webber, W. Robert S.

1993-01-01

There are an estimated two million people with epilepsy in the United States. Many of these people do not respond to anti-epileptic drug therapy. Two devices can be developed to assist in the treatment of epilepsy. The first is a microcomputer-based system designed to process massive amounts of electroencephalogram (EEG) data collected during long-term monitoring of patients for the purpose of diagnosing seizures, assessing the effectiveness of medical therapy, or selecting patients for epilepsy surgery. Such a device would select and display important EEG events. Currently many such events are missed. A second device could be implanted and would detect seizures and initiate therapy. Both of these devices require a reliable seizure detection algorithm. A new algorithm is described. It is believed to represent an improvement over existing seizure detection algorithms because better signal features were selected and better standardization methods were used.

Hyponatraemia and seizures after ecstasy use

PubMed Central

Holmes, S.; Banerjee, A.; Alexander, W.

1999-01-01

A patient presented to our unit with seizures and profound hyponatraemia after ingestion of a single tablet of ecstasy. The seizures proved resistant to therapy and ventilation on the intensive care unit was required. Resolution of the seizures occurred on correction of the metabolic abnormalities. The pathogenesis of seizures and hyponatraemia after ecstasy use is discussed. Ecstasy use should be considered in any young patient presenting with unexplained seizures and attention should be directed towards electrolyte levels, particularly sodium.


Keywords: ecstasy; seizures; hyponatraemia PMID:10396584

Multiple subpial transection for intractable partial epilepsy: an international meta-analysis.

PubMed

Spencer, Susan S; Schramm, Johannes; Wyler, Allen; O'Connor, Michael; Orbach, Darren; Krauss, Gregory; Sperling, Michael; Devinsky, Orrin; Elger, Christian; Lesser, Ronald; Mulligan, Lisa; Westerveld, Michael

2002-02-01

Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome.

Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy.

PubMed

Ramgopal, Sriram; Thome-Souza, Sigride; Jackson, Michele; Kadish, Navah Ester; Sánchez Fernández, Iván; Klehm, Jacquelyn; Bosl, William; Reinsberger, Claus; Schachter, Steven; Loddenkemper, Tobias

2014-08-01

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy. Copyright © 2014. Published by Elsevier Inc.

[The influence of cognitive-behavioral therapy on the P300 potential in children with psychogenic nonepileptic seizures and tension headache].

PubMed

Stolarska-Weryńska, Urszula; Steczkowska, Małgorzata; Kaciński, Marek

2016-01-01

Explaining associations between neurophysiological and neuropsychological parameteres in children and improving the measurement methods would lead to a better understanding of the pathogenesis and course of psychosomatic disease. Goal: clinical assessment of the efficacy of cognitive-behavioral therapy in the treatment of psychogenic no- nepileptic seizures and tension type headaches in children. Determining the influence of cognitive behavioral therapy on the cognitive P300 potential and whether P300 parameters in children correlate with neuropsychological parameters. 20 children with nonepileptic psychogenic seizures and 30 children with tension type headaches, aged 11.3 - 17.11 years. The final diagnosis was made in the Paediatric Neurology Clinic. The P300 examination was performed before/after therapy, with/without hyperventilation. A fixed structure therapy was implemented (10 sessions, 90 minutes each), during two weeks of hospitalization or in an outpatient clinic (9 children with tension type headache). The psychological assessment comprised of temperament questionnaires, auditory and visual memory trials, executive function and attention trials, and in some cases also intelligence testing. More significant correlations were found in children with psychogenic seizures: attention parameters correlated negatively with reaction time, and this correlation tended to fade in the second examination, after psychotherapy. In children with tension type headache a statistically insignificant tendency was found of a positive correlation between those parameters. Medium P300 parameteres in this group were better. In 17/20 of children with psychogenic seizures a clinical improvement was observed, in 3 children the symptoms persisted in a 6 month follow up, but of a lower frequency. In 11/27 of chil- dren with tension headache the symptoms persisted, also with a lower frequency. cognitive-behavioral therapy is effective in the reduction of symptoms in many cases of

MST1, a key player, in enhancing fast skeletal muscle atrophy

PubMed Central

2013-01-01

Background Skeletal muscle undergoes rapid atrophy upon denervation and the underlying mechanisms are complicated. FOXO3a has been implicated as a major mediator of muscle atrophy, but how its subcellular location and activity is controlled during the pathogenesis of muscle atrophy remains largely unknown. MST1 (Mammalian Sterile 20-like kinase 1) is identified as a central component of the Hippo signaling pathway. MST1 has been shown to mediate phosphorylation of FOXO3a at Ser207. Whether this MST1-FOXO signaling cascade exerts any functional consequence on cellular homeostasis remains to be investigated. Result We identified that MST1 kinase was expressed widely in skeletal muscles and was dramatically up-regulated in fast- but not slow-dominant skeletal muscles immediately following denervation. The results of our histological and biochemical studies demonstrated that deletion of MST1 significantly attenuated denervation-induced skeletal muscle wasting and decreased expression of Atrogin-1 and LC3 genes in fast-dominant skeletal muscles from three- to five-month-old adult mice. Further studies indicated that MST1, but not MST2, remarkably increased FOXO3a phosphorylation level at Ser207 and promoted its nuclear translocation in atrophic fast-dominant muscles. Conclusions We have established that MST1 kinase plays an important role in regulating denervation-induced skeletal muscle atrophy. During the early stage of muscle atrophy, the up-regulated MST1 kinase promoted progression of neurogenic atrophy in fast-dominant skeletal muscles through activation of FOXO3a transcription factors. PMID:23374633

Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation

PubMed Central

Meng, Fansen; Zhou, Ruyuan; Wu, Shiying; Zhang, Qian; Jin, Qiuheng; Zhou, Yao; Plouffe, Steven W.; Liu, Shengduo; Song, Hai; Xia, Zongping; Zhao, Bin; Ye, Sheng; Feng, Xin-Hua; Guan, Kun-Liang; Zou, Jian

2016-01-01

Cytosolic RNA/DNA sensing elicits primary defense against viral pathogens. Interferon regulatory factor 3 (IRF3), a key signal mediator/transcriptional factor of the antiviral-sensing pathway, is indispensible for interferon production and antiviral defense. However, how the status of IRF3 activation is controlled remains elusive. Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1 (Mst1), but not Mst2, profoundly inhibited cytosolic nucleic acid sensing. Mst1 associated with IRF3 and directly phosphorylated IRF3 at Thr75 and Thr253. This Mst1-mediated phosphorylation abolished activated IRF3 homodimerization, its occupancy on chromatin, and subsequent IRF3-mediated transcriptional responses. In addition, Mst1 also impeded virus-induced activation of TANK-binding kinase 1 (TBK1), further attenuating IRF3 activation. As a result, Mst1 depletion or ablation enabled an enhanced antiviral response and defense in cells and mice. Therefore, the identification of Mst1 as a novel physiological negative regulator of IRF3 activation provides mechanistic insights into innate antiviral defense and potential antiviral prevention strategies. PMID:27125670

LEACHING OF TITANIUM FROM MONOSODIUM TITANATE AND MODIFIED MST

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor-Pashow, K.; Fondeur, F.; Fink, S.

2012-08-01

Analysis of a fouled coalescer and pre-filters from Actinide Removal Process/Modular Caustic Side Solvent Extraction Unit (ARP/MCU) operations showed evidence of Ti containing solids. Based on these results a series of tests were planned to examine the extent of Ti leaching from monosodium titanate (MST) and modified monosodium titanate (mMST) in various solutions. The solutions tested included a series of salt solutions with varying free hydroxide concentrations, two sodium hydroxide concentrations, 9 wt % and 15 wt %, nitric and oxalic acid solutions. Overall, the amount of Ti leached from the MST and mMST was much greater in the acidmore » solutions compared to the sodium hydroxide or salt solutions, which is consistent with the expected trend. The leaching data also showed that increasing hydroxide concentration, whether pure NaOH solution used for filter cleaning in ARP or the waste salt solution, increased the amount of Ti leached from both the MST and mMST. For the respective nominal contact times with the MST solids - for filter cleaning or the normal filter operation, the dissolved Ti concentrations are comparable suggesting either cause may contribute to the increased Ti fouling on the MCU coalescers. Tests showed that Ti containing solids could be precipitated from solution after the addition of scrub acid and a decrease in temperature similar to expected in MCU operations. FTIR analysis of these solids showed some similarity to the solids observed on the fouled coalescer and pre-filters. Although only a cursory study, this information suggests that the practice of increasing free hydroxide in feed solutions to MCU as a mitigation to aluminosilicate formation may be offset by the impact of formation of Ti solids in the overall process. Additional consideration of this finding from MCU and SWPF operation is warranted.« less

Intravenous theophylline is the most effective intervention to prolong EEG seizure duration in patients undergoing electroconvulsive therapy.

PubMed

Tzabazis, Alexander; Wiernik, Michaela E; Wielopolski, Jan; Sperling, Wolfgang; Ihmsen, Harald; Schmitt, Hubert J; Münster, Tino

2017-08-29

Seizure duration in electroconvulsive therapy (ECT) is positively related with patients' outcome. This study sought to investigate the impact of anesthetic management on seizure duration, and the impact of selected drugs (theophylline, remifentanil, S-ketamine) on seizure duration. Retrospective analysis of all patients undergoing ECT at our institution from January 2011 to April 2012 was performed based on electronic medical chart and review of existing quality improvement data. Patient data (N = 78), including gender, age, height, weight, and administered drugs, energy levels, and electroencephalic seizure duration were analyzed. Statistical analysis was performed using a generalized linear model. A total of 78 patients (male = 39, female = 39, age 51 ± 12 years) were included. Average number of session was 10 ± 6 (1-30). In our patient population, theophylline administration was the only parameter, which significantly prolonged seizure duration, whereas S-ketamine, remifentanil, thiopental, age, sex, session or energy level had no significant effect. Theophylline can be a useful adjunct for patients with inadequate seizure duration. If there is a concomitant beneficial effect on patients' outcome needs to be investigated in further studies.

Prolonged exposure therapy for the treatment of patients diagnosed with psychogenic non-epileptic seizures (PNES) and post-traumatic stress disorder (PTSD).

PubMed

Myers, Lorna; Vaidya-Mathur, Urmi; Lancman, Marcelo

2017-01-01

Although there is general consensus that psychogenic non-epileptic seizures (PNES) are treated with psychotherapy, the effectiveness of most psychotherapeutic modalities remains understudied. In this treatment series of 16 patients dually diagnosed with PNES and post-traumatic stress disorder (PTSD), we evaluated the effect of prolonged exposure therapy (PE) on reduction of PNES. Secondary measures included Beck Depression Inventory (BDI-II) and Post-Traumatic Disorder Diagnostic Scale (PDS). Subjects diagnosed with video EEG-confirmed PNES and PTSD confirmed through neuropsychological testing and clinical interview were treated with traditional PE psychotherapy with certain modifications for the PNES. Treatment was conducted over the course of 12-15 weekly sessions. Seizure frequency was noted in each session by examining the patients' seizure logs, and mood and PTSD symptomatology was assessed at baseline and on the final session. Eighteen subjects enrolled, and 16 (88.8%) completed the course of treatment. Thirteen of the 16 (81.25%) therapy completers reported no seizures by their final PE session, and the other three reported a decline in seizure frequency (Z=-3.233, p=0.001). Mean scores on scales of depression (M=-13.56, SD=12.27; t (15)=-4.420, p<0,001) and PTSD symptoms (M=-17.1875, SD=13.01; t (15)=-5.281, p<0.001) showed significant improvement from baseline to final session. Longitudinal seizure follow up in 14 patients revealed that gains made on the final session were maintained at follow-up (Z=-1.069 p=0.285). Prolonged exposure therapy for patients dually diagnosed with PNES and PTSD reduced the number of PNES and improved mood and post traumatic symptomatology. Follow-up revealed that gains made in seizure control on the last day of treatment were maintained over time. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Intravenous Carbamazepine for Adults With Seizures.

PubMed

Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

2018-03-01

To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

Bridging the Gap between Science and Practice: The Effective Nationwide Transport of MST Programs in Norway

ERIC Educational Resources Information Center

Ogden, Terje; Christensen, Bernadette; Sheidow, Ashli J.; Holth, Per

2008-01-01

The successful nationwide transport and evaluation of Multisystemic Therapy (MST) programs in Norway is described. This description is provided within the context of the nation's movement towards the adoption of evidence-based practices (EBPs) during the past decade, the conduct of a multisite randomized clinical trial to examine the effectiveness…

Reflex seizures in Rett syndrome.

PubMed

Roche Martínez, Ana; Alonso Colmenero, M Itziar; Gomes Pereira, Andreia; Sanmartí Vilaplana, Francesc X; Armstrong Morón, Judith; Pineda Marfa, Mercé

2011-12-01

Reflex seizures are a rare phenomenon among epileptic patients, in which an epileptic discharge is triggered by various kinds of stimuli (visual, auditory, tactile or gustatory). Epilepsy is common in Rett syndrome patients (up to 70%), but to the authors' knowledge, no pressure or eating-triggered seizures have yet been reported in Rett children. We describe three epileptic Rett patients with reflex seizures, triggered by food intake or proprioception. One patient with congenital Rett Sd. developed infantile epileptic spasms at around seven months and two patients with classic Rett Sd. presented with generalised tonic-clonic seizures at around five years. Reflex seizures appeared when the patients were teenagers. The congenital-Rett patient presented eating-triggered seizures at the beginning of almost every meal, demonstrated by EEG recording. Both classic Rett patients showed self-provoked pressure -triggered attacks, influenced by stress or excitement. Non-triggered seizures were controlled with carbamazepine or valproate, but reflex seizures did not respond to antiepileptic drugs. Risperidone partially improved self-provoked seizures. When reflex seizures are suspected, reproducing the trigger during EEG recording is fundamental; however, self-provoked seizures depend largely on the patient's will. Optimal therapy (though not always possible) consists of avoiding the trigger. Stress modifiers such as risperidone may help control self-provoked seizures.

Implementation of Evidence-Based Models in Social Work Practice: Practitioners' Perspectives on an MST Trial in Sweden

ERIC Educational Resources Information Center

Gustle, Lars-Henry; Hansson, Kjell; Sundell, Knut; Andree-Lofholm, Cecilia

2008-01-01

The implementation of new treatment methods in social work practice is warranted. Moreover, little is known about professionals' attitudes toward the introduction of evidence-based practices into their communities. Therefore, this article reports on the implementation of a Swedish research project that evaluated Multisystemic Therapy (MST). All…

Involvement of Mst1 in tumor necrosis factor-{alpha}-induced apoptosis of endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohtsubo, Hideki; Ichiki, Toshihiro; Imayama, Ikuyo

2008-03-07

Mammalian sterile 20-kinase 1 (Mst1), a member of the sterile-20 family protein kinase, plays an important role in the induction of apoptosis. However, little is know about the physiological activator of Mst1 and the role of Mst1 in endothelial cells (ECs). We examined whether Mst1 is involved in the tumor necrosis factor (TNF)-{alpha}-induced apoptosis of ECs. Western blot analysis revealed that TNF-{alpha} induced activation of caspase 3 and Mst1 in a time- and dose-dependent manner. TNF-{alpha}-induced Mst1 activation is almost completely prevented by pretreatment with Z-DEVD-FMK, a caspase 3 inhibitor. Nuclear staining with Hoechst 33258 and fluorescence-activated cell sorting ofmore » propidium iodide-stained cells showed that TNF-{alpha} induced apoptosis of EC. Diphenyleneiodonium, an inhibitor of NADPH oxidase, and N-acetylcysteine, a potent antioxidant, also inhibited TNF-{alpha}-induced activation of Mst1 and caspase 3, as well as apoptosis. Knockdown of Mst1 expression by short interfering RNA attenuated TNF-{alpha}-induced apoptosis but not cleavage of caspase 3. These results suggest that Mst1 plays an important role in the induction of TNF-{alpha}-induced apoptosis of EC. However, positive feedback mechanism between Mst1 and caspase 3, which was shown in the previous studies, was not observed. Inhibition of Mst1 function may be beneficial for maintaining the endothelial integrity and inhibition of atherogenesis.« less

Hypermethylation of MST1 in IgG4-related autoimmune pancreatitis and rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukuhara, Takataro; Tomiyama, Takashi; Yasuda, Kaneki

The serine/threonine kinase Mst1 plays important roles in the control of immune cell trafficking, proliferation, and differentiation. Previously, we reported that Mst1 was required for thymocyte selection and regulatory T-cell functions, thereby the prevention of autoimmunity in mice. In humans, MST1 null mutations cause T-cell immunodeficiency and hypergammaglobulinemia with autoantibody production. RASSF5C(RAPL) is an activator of MST1 and it is frequently methylated in some tumors. Herein, we investigated methylation of the promoter regions of MST1 and RASSF5C(RAPL) in leukocytes from patients with IgG4-related autoimmune pancreatitis (AIP) and rheumatoid arthritis (RA). Increased number of CpG methylation in the 5′ region ofmore » MST1 was detected in AIP patients with extrapancreatic lesions, whereas AIP patients without extrapancreatic lesions were similar to controls. In RA patients, we detected a slight increased CpG methylation in MST1, although the overall number of methylation sites was lower than that of AIP patients with extrapancreatic lesions. There were no significant changes of the methylation levels of the CpG islands in the 5′ region of RASSF5C(RAPL) in leukocytes from AIP and RA patients. Consistently, we found a significantly down-regulated expression of MST1 in regulatory T cells of AIP patients. Our results suggest that the decreased expression of MST1 in regulatory T cells due to hypermethylation of the promoter contributes to the pathogenesis of IgG4-related AIP. - Highlights: • Mst1 controls immune cells trafficking, cell proliferation and differentiation. • Autoimmune pancreatitis (AIP) is an idiopathic pancreatitis affecting multiple organs. • Decreased MST1 expression and increased CpG methylation of promoter of MST1 in AIP. • Slight increased CpG methylation of MST1 in rheumatoid arthritis patients. • MST1 contributes pathogenesis of IgG4-related AIP.« less

MST radar data-base management

NASA Technical Reports Server (NTRS)

Wickwar, V. B.

1983-01-01

Data management for Mesospheric-Stratospheric-Tropospheric, (MST) radars is addressed. An incoherent-scatter radar data base is discussed in terms of purpose, centralization, scope, and nature of the data base management system.

Lacosamide monotherapy for partial onset seizures.

PubMed

Lattanzi, Simona; Cagnetti, Claudia; Foschi, Nicoletta; Provinciali, Leandro; Silvestrini, Mauro

2015-04-01

To evaluate the 1-year efficacy and safety of oral lacosamide as conversion monotherapy in adult patients with partial onset seizures with or without generalization. We prospectively followed-up consecutive patients converted to lacosamide monotherapy after 1-year seizure freedom on lacosamide add-on therapy and withdrawal of the concurrent antiepileptic drug (AED). Seizure occurrence, treatment compliance and drug toxicity were assessed every 3 months up to 1 year. The study outcomes were the retention rate of lacosamide as single AED and the seizure freedom under lacosamide monotherapy at 1 year from withdrawal of background AED. The safety variable was the prevalence of lacosamide related adverse events (AEs). Among the 58 included patients, at 1 year from withdrawal of background medication, 37 (63.8%) retained lacosamide as single AED and 32 (55.2%) were free from seizure occurrence under lacosamide monotherapy throughout the entire follow-up. The history of less than three lifetime AEDs turned out to be significant predictor of seizure freedom (adjusted OR = 6.38, 95% CI 1.85-21.98, p = 0.003). Twelve (20.8%) subjects reported mild to moderate AEs, with the commonest being drowsiness, dizziness, and headache. Conversion to lacosamide monotherapy could be effective and well tolerated in selected adults patients with partial onset seizures who had achieved seizure freedom during lacosamide add-on therapy. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Treating seizures in Creutzfeldt-Jakob disease.

PubMed

Ng, Marcus C; Westover, M Brandon; Cole, Andrew J

2014-01-01

Seizures are known to occur in Creutzfeldt-Jakob disease (CJD). In the setting of a rapidly progressive condition with no effective therapy, determining appropriate treatment for seizures can be difficult if clinical morbidity is not obvious yet the electroencephalogram (EEG) demonstrates a worrisome pattern such as status epilepticus. Herein, we present the case of a 39-year-old man with CJD and electrographic seizures, discuss how this case challenges conventional definitions of seizures, and discuss a rational approach toward treatment. Coincidentally, our case is the first report of CJD in a patient with Stickler syndrome.

21. DETAIL OF AIR HANDLER 1 (MST AIRCONDITIONING SYSTEM) INTERIOR, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. DETAIL OF AIR HANDLER 1 (MST AIR-CONDITIONING SYSTEM) INTERIOR, SOUTHEAST CORNER, STATION 30, SLC-3W MST - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

22. DETAIL OF CHILLERS 1 AND 2 (MST AIRCONDITIONING SYSTEM) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. DETAIL OF CHILLERS 1 AND 2 (MST AIR-CONDITIONING SYSTEM) INTERIOR, NORTHEAST CORNER, STATION 30, SLC-3W MST - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Seizure prognosis of patients with low-grade tumors.

PubMed

Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

2012-09-01

Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

The effects of adjunctive topiramate therapy on seizure severity and health-related quality of life in patients with refractory epilepsy---a Canadian study.

PubMed

Baker, Gus A; Currie, Natalie G T; Light, Margaret J; Schneiderman, Jack H

2002-01-01

Although reduction in seizure frequency is the most common endpoint used to assess the antiepileptic efficacy, seizure frequency alone does not provide a complete picture of effectiveness, particularly in patients with refractory epilepsy. The aim of our study was to assess the effects of topiramate on seizure severity and health-related quality of life (HRQL), in addition to standard efficacy measures, in an open, multicentre, 6-month trial of patients with epilepsy uncontrolled on antiepileptic drugs other than topiramate. Two hundred and nine patients were enrolled and received topiramate for up to 6 months (initiated at 50 mg/day and titrated to a recommended dose of 200-400 mg/day) in addition to existing medication. The median reduction in seizure frequency from baseline to the post-titration period was 40.9% ( P< 0.0001). Patients also demonstrated a mean reduction in the Liverpool Seizure Severity Scale (LSSS) of 5.3 ( P< 0.0001), which was considered clinically significant. Statistically significant changes in HRQL were not observed with the SF-36, a generic measure. Tolerability of antiepileptic medication was good, with a low incidence of cognitive adverse events. The results indicate that topiramate significantly reduces seizure severity---an important aspect of HRQL---when administered as adjunctive therapy to anticonvulsant therapy. Copyright 2002 BEA Trading Ltd.

17. VIEW OF INTERIOR, EAST SIDE, DECK LEVEL OF MST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. VIEW OF INTERIOR, EAST SIDE, DECK LEVEL OF MST. NOTE CANVAS CURTAIN (RIGHT) USED TO COVER SOUTH SIDE OF MST BELOW LOWEST ENVIRONMENTAL DOORS. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

73. LIQUID NITROGEN PUMPING STATION ON WEST SIDE OF MST; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

73. LIQUID NITROGEN PUMPING STATION ON WEST SIDE OF MST; NITROGEN EXCHANGERS ON RIGHT. SOUTHWEST CORNER OF MST VISIBLE; ENVIRONMENTAL CURTAIN SWING AND PLATFORM EXTENDED. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Reversible MRI lesions after seizures.

PubMed

Aykut-Bingol, C; Tekin, S; Ince, D; Aktan, S

1997-06-01

After generalized or partial seizures, transient lesions may appear on magnetic resonance (MR) images. The mechanisms of MR changes might be a defect in cerebral autoregulation and blood-brain permeability. We report a patient with partial and secondary generalized tonic-clonic seizures. After her first seizure which was generalized tonic-clonic in nature, we detected multiple high signal intensities over the frontal cortical area on proton density images which were enhanced with gadolinium on T1-weighted images. The first and repeated EEGs showed no abnormalities or epileptic discharges. We started carbamezapine (600 mg/d) and excluded systemic diseases like vasculitis, infections, aetiological factors causing cerebrovascular diseases. In the follow-up, she was seizure free under antiepileptic therapy and no other neurological deficit. Repeated MR scans after 24 months from her first seizure revealed no pathologic signal intensities. Although the pathophysiology is unknown, recognition of reversible lesions helps diagnostic and therapeutic approaches to abnormal MR findings after seizures.

M Current-Based Therapies for Nerve Agent Seizures

DTIC Science & Technology

2012-07-01

2012.235820. Third goal was to test whether drugs that open M channels wouterminate status epilepticus induced by an organophosphate and cholinergic...agonist (Li/Pilocarpine). Two modelof organophasphate-induced seizures were characterized and published: Characterization of status epilepticus induced...terminates refractory status epilepticus in two models. . 15. SUBJECT TERMS- Seizures, status epilepticus Cholinergic, M Current, Synaptoic

Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy

PubMed Central

Rolston, John D.; Wright, Clinton W.; Hassnain, Kevin H.; Chang, Edward F.

2015-01-01

BACKGROUND: Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation do not achieve complete seizure freedom, and, therefore, previous studies of vagus nerve stimulation (VNS) therapy have focused instead on reduction of seizure frequency as a measure of treatment response. OBJECTIVE: To elucidate rates and predictors of seizure freedom with VNS. METHODS: We examined 5554 patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature including 2869 patients across 78 studies. RESULTS: Registry data revealed a progressive increase over time in seizure freedom after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50% reduction seizure frequency), with 5.1% of patients becoming seizure-free, while 63% of patients were responders at 24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by age of epilepsy onset >12 years (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.38-2.58), and predominantly generalized seizure type (OR, 1.36; 95% CI, 1.01-1.82), while overall response to VNS was predicted by nonlesional epilepsy (OR, 1.38; 95% CI, 1.06-1.81). Systematic literature review results were consistent with the registry analysis: At 0 to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure-free, while at last follow-up, 60.1% of individuals were responders, with 8.0% achieving seizure freedom. CONCLUSION: Response and seizure freedom rates increase over time with VNS therapy, although complete seizure freedom is achieved in a small percentage of patients. ABBREVIATIONS: AED, antiepileptic drug VNS, vagus nerve stimulation PMID:26645965

Neonatal Seizures: An Update on Mechanisms and Management

PubMed Central

Jensen, Frances E.

2010-01-01

The lifespan risk of seizures is highest in the neonatal period. Currently used therapies have limited efficacy. Although the treatment of neonatal seizures has not significantly changed in the last several decades, there has been substantial progress in understanding developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. Here we provide an overview of current approaches to the diagnosis and treatment of neonatal seizures, identifying some of the recent insights about the pathophysiology of neonatal seizures that may provide the foundation for better treatment. PMID:19944840

1. VIEW OF SOUTHEAST CORNER OF MOBILE SERVICE TOWER (MST). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. VIEW OF SOUTHEAST CORNER OF MOBILE SERVICE TOWER (MST). CABLE TRAY SHED IN FOREGROUND. MICROWAVE ANTENNAS AND AIR-CONDITIONING PORCH ON EAST SIDE OF MST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Optimizing therapy of seizures in neurosurgery.

PubMed

Michelucci, Roberto

2006-12-26

The use of antiepileptic drugs (AEDs) in the neurosurgical setting has a number of implications, including their possible role in the prevention of seizures after acute cerebral insults or brain tumors and the potential for toxicity and interactions when these agents are administered in association with radiotherapy or chemotherapy. This review discusses these controversial issues and draws the following conclusions. 1) AEDs should be prescribed on a short-term basis to prevent seizures occurring within the first week after a cerebral insult (trauma, neurosurgical procedure) but are ineffective to avoid true post-traumatic epilepsy or first seizures in patients with primary or secondary cerebral neoplasms. 2) The use of phenytoin and, to a lesser extent, phenobarbital and carbamazepine during cranial irradiation is associated with an increased risk for severe, potentially fatal, mucocutaneous reactions. In this context, new AEDs with a very low potential for allergic cutaneous reactions should be preferred. 3) Enzyme-inducing AEDs, such as phenytoin, phenobarbital, and carbamazepine, may increase the clearance and reduce the clinical efficacy of corticosteroids and anticancer agents that are also metabolized by the cytochrome P450 system. The newly developed AEDs that are devoid of hepatic metabolism, such as levetiracetam and gabapentin, are now recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents.

Lacosamide: A Review in Focal Seizures in Patients with Epilepsy.

PubMed

Scott, Lesley J

2015-12-01

Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a solution or tablets) and as an intravenous infusion for use as monotherapy (only in the USA) or adjunctive therapy for the treatment of focal seizures in adult and adolescent (aged ≥17 years in the USA) patients with epilepsy. As adjunctive therapy to other antiepileptic drugs (AEDs), lacosamide provided effective seizure control and was generally well tolerated in adults and adolescents (aged ≥16 years) in randomized clinical trials and in the real-world setting. In clinical trials, adjunctive lacosamide provided significantly greater reductions in 28-day seizure rates than adjunctive placebo, with these benefits maintained after up to 8 years of therapy in open-label extension studies. Moreover, patients were effectively switched from oral to short-term intravenous adjunctive therapy at the same dosage, which may be particularly beneficial in situations where oral therapy is not suitable. Conversion to lacosamide monotherapy was superior to a historical-control cohort in patients with focal seizures converting from previous AED therapy. In the absence of head-to-head comparisons with other AEDs, the exact position of lacosamide relative to other AEDs remains to be fully determined. In the meantime, oral and intravenous lacosamide provides a useful option as monotherapy (only in the USA) or adjunctive therapy for the treatment of focal seizures in adult and adolescent (aged ≥17 years in the USA) patients with epilepsy.

Multisystemic Therapy and Functional Family Therapy Compared on their Effectiveness Using the Propensity Score Method.

PubMed

Eeren, Hester V; Goossens, Lucas M A; Scholte, Ron H J; Busschbach, Jan J V; van der Rijken, Rachel E A

2018-01-09

Multisystemic Therapy (MST) and Functional Family Therapy (FFT) have overlapping target populations and treatment goals. In this study, these interventions were compared on their effectiveness using a quasi-experimental design. Between October, 2009 and June, 2014, outcome data were collected from 697 adolescents (mean age 15.3 (SD 1.48), 61.9% male) assigned to either MST or FFT (422 MST; 275 FFT). Data were gathered during Routine Outcome Monitoring. The primary outcome was externalizing problem behavior (Child Behavior Checklist and Youth Self Report). Secondary outcomes were the proportion of adolescents living at home, engaged in school or work, and who lacked police contact during treatment. Because of the non-random assignment, a propensity score method was used to control for observed pre-treatment differences. Because the risk-need-responsivity (RNR) model guided treatment assignment, effectiveness was also estimated in youth with and without a court order as an indicator of their risk level. Looking at the whole sample, no difference in effect was found with regard to externalizing problems. For adolescents without a court order, effects on externalizing problems were larger after MST. Because many more adolescents with a court order were assigned to MST compared to FFT, the propensity score method could not balance the treatment groups in this subsample. In conclusion, few differences between MST and FFT were found. In line with the RNR model, higher risk adolescents were assigned to the more intensive treatment, namely MST. In the group with lower risk adolescents, this more intensive treatment was more effective in reducing externalizing problems.

Pervanadate induces Mammalian Ste20 Kinase 3 (MST3) tyrosine phosphorylation but not activation.

PubMed

Kan, Wei-Chih; Lu, Te-Ling; Ling, Pin; Lee, Te-Hsiu; Cho, Chien-Yu; Huang, Chi-Ying F; Jeng, Wen-Yih; Weng, Yui-Ping; Chiang, Chun-Yen; Wu, Jin Bin; Lu, Te-Jung

2016-07-01

The yeast Ste20 (sterile) protein kinase, which is a serine/threonine kinase, responds to the stimulation of the G proteincoupled receptor (GPCR) pheromone receptor. Ste20 protein kinase serves as the critical component that links signaling from the GPCR/G proteins to the mitogen-activated protein kinase (MAPK) cascade in yeast. The yeast Ste20p functions as a MAP kinase kinase kinase kinase (MAP4K) in the pheromone response. Ste20-like kinases are structurally conserved from yeast to mammals. The mechanism by which MAP4K links GPCR to the MAPK pathway is less clearly defined in vertebrates. In addition to MAP4K, the tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Mammalian Ste20 Kinase 3 (MST3) has been categorized into the Ste20 family and has been reported to function in the regulation of cell polarity and migration. However, whether MST3 tyrosine phosphorylation regulates diverse signaling pathways is unknown. In this study, the tyrosine phosphatase inhibitor pervanadate was found to induce MST3 tyrosine phosphorylation in intact cells, and the activity of tyrosine-phosphorylated MST3 was measured. This tyrosine-directed phosphorylation was independent of MST3 activity. Parameters including protein conformation, Triton concentration and ionic concentration influenced the sensitivity of MST3 activity. Taken together, our data suggests that the serine/threonine kinase MST3 undergoes tyrosinedirected phosphorylation. The tyrosine-phosphorylated MST3 may create a docking site for the structurally conserved SH2/SH3 (Src Homology 2 and 3) domains within the Src oncoprotein. The unusual tyrosinephosphorylated MST3 may recruit MST3 to various signaling components. Copyright © 2016. Published by Elsevier Inc.

MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Teng, E-mail: tengyu33@yahoo.com; Ji, Jiang; Guo, Yong-li

2013-11-08

Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen speciesmore » (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.« less

Post-traumatic seizure disorder following acquired brain injury.

PubMed

Teasell, Robert; Bayona, Nestor; Lippert, Corbin; Villamere, James; Hellings, Chelsea

2007-02-01

The present study aimed to evaluate the effectiveness of prophylactic anticonvulsant pharmacological strategies for the prevention of seizure disorders following acquired brain injury (ABI) to provide guidance for clinical practice based on the best available evidence. A systematic review of the literature from 1980-2005 was conducted focusing on treatment interventions available for post-traumatic seizures following ABI. The evidence for the efficacy of a given intervention was ranked as strong (supported by at least two randomized controlled trials (RCTs), moderate (supported by a single RCT), or limited (supported by other types of studies in the absence of RCTs). Based on a previous meta-analysis and the findings of this review, there is strong evidence that prophylactic anticonvulsant therapy decreases the occurrence of early seizures but only within the first week post-injury. Moreover, the evidence indicates that prophylactic anticonvulsant therapy does not decrease the incidence of seizure onset more than one week post-injury. In children, there is moderate evidence that prophylactic phenytoin does not reduce the incidence of early or late seizures. The efficacy of anticonvulsants after the development of seizures has not been specifically studied in ABI. Prophylactic anti-convulsants are effective in reducing seizures in the first week post-injury in adults. However, they do not reduce the occurrence of seizures after the first week.

Controlled-release oxycodone-induced seizures.

PubMed

Klein, Moti; Rudich, Zvia; Gurevich, Boris; Lifshitz, Matityahu; Brill, Silviu; Lottan, Michael; Weksler, Natan

2005-11-01

The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.

Paternal Involvement in Multisystemic Therapy: Effects on Adolescent Outcomes and Maternal Depression

ERIC Educational Resources Information Center

Gervan, Shannon; Granic, Isabela; Solomon, Tracy; Blokland, Kirsten; Ferguson, Bruce

2012-01-01

The association between paternal involvement in therapy, adolescent outcomes and maternal depression was examined within the context of Multisystemic Therapy (MST), an empirically supported, family- and community-based treatment for antisocial adolescents. Ninety-nine families were recruited from five mental health agencies providing MST. We…

29. DETAIL OF OUTLET DUCTS FOR MST AIRCONDITIONING SYSTEM IN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

29. DETAIL OF OUTLET DUCTS FOR MST AIR-CONDITIONING SYSTEM IN NORTHWEST CORNER OF SLC-3W MST STATION 70.5 (LOWEST PAYLOAD SERVICE STATION). NOTE RING ATTACHMENT FOR PERSONNEL SAFETY HARNESS IN LEFT FOREGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

14. VIEW OF MST, FACING SOUTHEAST, AND LAUNCH PAD TAKEN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. VIEW OF MST, FACING SOUTHEAST, AND LAUNCH PAD TAKEN FROM NORTHEAST PHOTO TOWER WITH WINDOW OPEN. FEATURES LEFT TO RIGHT: SOUTH TELEVISION CAMERA TOWER, SOUTHWEST PHOTO TOWER, LAUNCHER, UMBILICAL MAST, MST, AND OXIDIZER APRON. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Budget impact analysis of adjunctive therapy with lacosamide for partial-onset epileptic seizures in Belgium.

PubMed

Simoens, Steven

2011-01-01

This study aims to compute the budget impact of lacosamide, a new adjunctive therapy for partial-onset seizures in epilepsy patients from 16 years of age who are uncontrolled and having previously used at least three anti-epileptic drugs from a Belgian healthcare payer perspective. The budget impact analysis compared the 'world with lacosamide' to the 'world without lacosamide' and calculated how a change in the mix of anti-epileptic drugs used to treat uncontrolled epilepsy would impact drug spending from 2008 to 2013. Data on the number of patients and on the market shares of anti-epileptic drugs were taken from Belgian sources and from the literature. Unit costs of anti-epileptic drugs originated from Belgian sources. The budget impact was calculated from two scenarios about the market uptake of lacosamide. The Belgian target population is expected to increase from 5333 patients in 2008 to 5522 patients in 2013. Assuming that the market share of lacosamide increases linearly over time and is taken evenly from all other anti-epileptic drugs (AEDs), the budget impact of adopting adjunctive therapy with lacosamide increases from €5249 (0.1% of reference drug budget) in 2008 to €242,700 (4.7% of reference drug budget) in 2013. Assuming that 10% of patients use standard AED therapy plus lacosamide, the budget impact of adopting adjunctive therapy with lacosamide is around €800,000-900,000 per year (or 16.7% of the reference drug budget). Adjunctive therapy with lacosamide would raise drug spending for this patient population by as much as 16.7% per year. However, this budget impact analysis did not consider the fact that lacosamide reduces costs of seizure management and withdrawal. The literature suggests that, if savings in other healthcare costs are taken into account, adjunctive therapy with lacosamide may be cost saving.

Spotlight on perampanel in the management of seizures: design, development and an update on place in therapy.

PubMed

Faulkner, Michele A

2017-01-01

Perampanel is a first-in-class antiepileptic medication approved for the treatment of partial (focal) seizures, and as adjunctive treatment for primarily generalized tonic-clonic seizures. The pharmacology, efficacy data, adverse-effect profile, pharmacokinetics and place in therapy are reviewed. Perampanel is indicated for use in patients with epilepsy who are 12 years of age or older. It is the first medication designed specifically to be a non-competitive antagonist at post-synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors. Efficacy in refractory seizures has been established, and ongoing efficacy demonstrated by post-marketing data. The drug is completely absorbed, and exhibits a half-life that allows for once-daily administration in doses up to 12 mg/day. Drug interactions are minimal, but increased doses may be necessary when given with strong inducers of cytochrome P450 enzymes, including when perampanel is co-administered with other antiepileptics that exhibit this property. The most common adverse effects noted in both clinical trials and post-marketing are dizziness and somnolence. Psychiatric and behavioral adverse events have been documented in both adult and pediatric patients, including those with no corresponding diagnostic history. Perampanel is a novel adjunctive antiepileptic medication that is an effective option for adolescents and adults with partial seizures, and primarily generalized tonic-clonic seizures uncontrolled with other medications.

Spotlight on perampanel in the management of seizures: design, development and an update on place in therapy

PubMed Central

Faulkner, Michele A

2017-01-01

Purpose Perampanel is a first-in-class antiepileptic medication approved for the treatment of partial (focal) seizures, and as adjunctive treatment for primarily generalized tonic–clonic seizures. The pharmacology, efficacy data, adverse-effect profile, pharmacokinetics and place in therapy are reviewed. Summary Perampanel is indicated for use in patients with epilepsy who are 12 years of age or older. It is the first medication designed specifically to be a non-competitive antagonist at post-synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors. Efficacy in refractory seizures has been established, and ongoing efficacy demonstrated by post-marketing data. The drug is completely absorbed, and exhibits a half-life that allows for once-daily administration in doses up to 12 mg/day. Drug interactions are minimal, but increased doses may be necessary when given with strong inducers of cytochrome P450 enzymes, including when perampanel is co-administered with other antiepileptics that exhibit this property. The most common adverse effects noted in both clinical trials and post-marketing are dizziness and somnolence. Psychiatric and behavioral adverse events have been documented in both adult and pediatric patients, including those with no corresponding diagnostic history. Conclusion Perampanel is a novel adjunctive antiepileptic medication that is an effective option for adolescents and adults with partial seizures, and primarily generalized tonic–clonic seizures uncontrolled with other medications. PMID:29042752

System aspects of the Indian MST radar facility

NASA Technical Reports Server (NTRS)

Viswanathan, G.

1986-01-01

One of the major objectives of the Indian Middle Atmosphere Program is to investigate the motions of the middle atmosphere on temporal and spatial scales and the interaction between the three height regions of the middle atmosphere. Realizing the fact that radar technique has proven to be a very powerful tool for the study of Earth atmosphere, the Indian Middle Atmosphere Program has recommended establishing a mesosphere-stratosphere-troposphere (MST) radar as a national facility for atmospheric research. The major landmarks in this attempt to setup the MST radar as a national facility are described.

Maximizing MST's inductive capability with a Bp programmable power supply

NASA Astrophysics Data System (ADS)

Chapman, B. E.; Holly, D. J.; Jacobson, C. M.; McCollam, K. J.; Morin, J. C.; Sarff, J. S.; Squitieri, A.

2016-10-01

A major goal of the MST program is the advancement of inductive control for the development of both the RFP's fusion potential and, synergistically, the predictive capability of fusion science. This entails programmable power supplies (PPS's) for the Bt and Bp circuits. A Bt PPS is already in place, allowing advanced RFP operation and the production of tokamak plasmas, and a Bp PPS prototype is under construction. To explore some of the new capabilities to be provided by the Bp PPS, the existing Bt PPS has been temporarily connected to the Bp circuit. One key result is new-found access to very low Ip (20 kA) and very low Lundquist number, S (104). At this low S, simulation of RFP plasmas with the MHD code NIMROD is readily achievable, and work toward validation of extended MHD models using NIMROD is underway with direct comparisons to these MST plasmas. The full Bp PPS will also provide higher Ip and S than presently possible, allowing MST to produce plasmas with S spanning as much as five orders of magnitude, a dramatic extension of MST's capability. In these initial tests, the PPS has also increased five-fold MST's Ip flattop duration, to about 100 ms. This, coupled with the recently demonstrated PPS ability to drive large-amplitude sinusoidal oscillations in Ip, will allow tests of extended-duration oscillating field current drive, the goal of which is ac sustainment of a quasi-dc plasma current. Work supported by US DOE.

Structural basis of the heterodimerization of the MST and RASSF SARAH domains in the Hippo signalling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, Eunha; Korea University, Seoul 136-701; Cheong, Hae-Kap

2014-07-01

The heterodimeric structure of the MST1 and RASSF5 SARAH domains is presented. A comparison of homodimeric and heterodimeric interactions provides a structural basis for the preferential association of the SARAH heterodimer. Despite recent progress in research on the Hippo signalling pathway, the structural information available in this area is extremely limited. Intriguingly, the homodimeric and heterodimeric interactions of mammalian sterile 20-like (MST) kinases through the so-called ‘SARAH’ (SAV/RASSF/HPO) domains play a critical role in cellular homeostasis, dictating the fate of the cell regarding cell proliferation or apoptosis. To understand the mechanism of the heterodimerization of SARAH domains, the three-dimensional structuresmore » of an MST1–RASSF5 SARAH heterodimer and an MST2 SARAH homodimer were determined by X-ray crystallography and were analysed together with that previously determined for the MST1 SARAH homodimer. While the structure of the MST2 homodimer resembled that of the MST1 homodimer, the MST1–RASSF5 heterodimer showed distinct structural features. Firstly, the six N-terminal residues (Asp432–Lys437), which correspond to the short N-terminal 3{sub 10}-helix h1 kinked from the h2 helix in the MST1 homodimer, were disordered. Furthermore, the MST1 SARAH domain in the MST1–RASSF5 complex showed a longer helical structure (Ser438–Lys480) than that in the MST1 homodimer (Val441–Lys480). Moreover, extensive polar and nonpolar contacts in the MST1–RASSF5 SARAH domain were identified which strengthen the interactions in the heterodimer in comparison to the interactions in the homodimer. Denaturation experiments performed using urea also indicated that the MST–RASSF heterodimers are substantially more stable than the MST homodimers. These findings provide structural insights into the role of the MST1–RASSF5 SARAH domain in apoptosis signalling.« less

The Clonic Phase of Seizures in Patients Treated with Electroconvulsive Therapy is Related to Age and Stimulus Intensity.

PubMed

Wang, Chao-Chih; Lin, Ching-Hung; Chiu, Yao-Chu; Tseng, Chih-Chieh

2013-01-01

Electroconvulsive therapy (ECT) is effective in the treatment of major depressive disorder and schizophrenia in patients who are drug-naïve or less-receptive to antipsychotic drugs. Several studies have discussed the correlation between patient characteristics, input-current volume, and seizure duration. According to the present principle of ECT guidelines, the therapeutic effect of ECT mostly correlates with seizure duration. As the tonic phase is different from the clonic phase with respect to brain function and activity, it is informative to analyze both the tonic and clonic phases. Thus, this study sought to clarify the relationship between the features of the two phases, and to re-examine and refine guidelines regarding ECT treatment. ECT-course data from 44 schizophrenia or bipolar I patients were recollected, including the number of treatments that they had received, their gender, age, and the association of these characteristics with motor seizure duration was analyzed. A two-factor correlation was employed to test the relationship between each of the two factors. The post-analysis results indicate that seizure duration and age are significantly correlated. Older patients had relatively short seizure durations after ECT-treatment. Notably, a negative correlation was only found between age and the clonic phase of the seizure, not between age and the tonic phase. Furthermore, this study also found an inverse relationship between ECT-intensity and the clonic phase, but not between ECT-intensity and the tonic phase. This study demonstrated that age and ECT-intensity are negatively correlated with seizure duration, particularly in the clonic phase. The present observations are not fully consistent with the basic guidelines of the APA-ECT practical manual. Accordingly, the predictions regarding the therapeutic effect of ECT can be based on both the seizure duration and the clonic phase.

A feasibility study of a new method for electrically producing seizures in man: focal electrically administered seizure therapy [FEAST].

PubMed

Nahas, Ziad; Short, Baron; Burns, Carol; Archer, Melanie; Schmidt, Matthew; Prudic, Joan; Nobler, Mitchell S; Devanand, D P; Fitzsimons, Linda; Lisanby, Sarah H; Payne, Nancy; Perera, Tarique; George, Mark S; Sackeim, Harold A

2013-05-01

Electroconvulsive therapy (ECT) remains the most effective acute treatment for severe major depression, but with significant risk of adverse cognitive effects. Unidirectional electrical stimulation with a novel electrode placement and geometry (Focal Electrically Administered Seizure Therapy (FEAST)) has been proposed as a means to initiate seizures in prefrontal cortex prior to secondary generalization. As such, it may have fewer cognitive side effects than traditional ECT. We report on its first human clinical application. Seventeen unmedicated depressed adults (5 men; 3 bipolar disorder; age 53 ± 16 years) were recruited after being referred for ECT. Open-label FEAST was administered with a modified spECTrum 5000Q device and a traditional ECT dosing regimen until patients clinically responded. Clinical and cognitive assessments were obtained at baseline, and end of course. Time to orientation recovery, a predictor of long-term amnestic effects, was assessed at each treatment. Nonresponders to FEAST were transitioned to conventional ECT. One patient withdrew from the study after a single titration session. After the course of FEAST (median 10 sessions), there was a 46.1 ± 35.5% improvement in Hamilton Rating Scale for Depression (HRSD24) scores compared to baseline (33.1 ± 6.8, 16.8 ± 10.9; P < 0.0001). Eight of 16 patients met response criteria (50% decrease in HRSD24) and 5/16 met remission criteria (HRSD24 ≤ 10). Patients achieved full re-orientation (4 of 5 items) in 5.5 ± 6.4 min (median = 3.6), timed from when their eyes first opened after treatment. In this feasibility study, FEAST produced clinically meaningful antidepressant improvement, with relatively short time to reorientation. Our preliminary work first in primates and now depressed adults demonstrates that FEAST is feasible, safe, well-tolerated and, if efficacy can be optimized, has potential to replace traditional ECT. Copyright © 2013 Elsevier Inc. All rights reserved.

Antenna induced range smearing in MST radars

NASA Technical Reports Server (NTRS)

Watkins, B. J.; Johnston, P. E.

1984-01-01

There is considerable interest in developing stratosphere troposphere (ST) and mesosphere stratosphere troposphere (MST) radars for higher resolution to study small-scale turbulent structures and waves. At present most ST and MST radars have resolutions of 150 meters or larger, and are not able to distinguish the thin (40 - 100 m) turbulent layers that are known to occur in the troposphere and stratosphere, and possibly in the mesosphere. However the antenna beam width and sidelobe level become important considerations for radars with superior height resolution. The objective of this paper is to point out that for radars with range resolutions of about 150 meters or less, there may be significant range smearing of the signals from mesospheric altitudes due to the finite beam width of the radar antenna. At both stratospheric and mesospheric heights the antenna sidelobe level for lear equally spaced phased arrays may also produce range aliased signals. To illustrate this effect the range smearing functions for two vertically directed antennas have been calculated, (1) an array of 32 coaxial-collinear strings each with 48 elements that simulates the vertical beam of the Poker Flat, Glaska, MST radar; and (2) a similar, but smaller, array of 16 coaxial-collinear strings each with 24 elements.

MST's Programmable Power Supplies: Bt Update, Bp Prototype

NASA Astrophysics Data System (ADS)

Holly, D. J.; Chapman, B. E.; McCollam, K. J.; Morin, J. C.; Thomas, M. A.

2013-10-01

MST's toroidal field programmable power supply (Bt PPS) has now been in operation for several years and has provided important new capabilities. One of the primary goals for the Bt PPS is the partial optimization of inductive current profile control, involving control of the poloidal electric field. The Bt PPS has achieved fluctuation reduction over MST's entire range of Ip. At the largest Ip, the Bt PPS achieves fluctuation reduction with a smaller poloidal electric field than the previous passive system, implying that substantially longer periods of current profile control may be possible. The Bt PPS has also been used to produce Ohmic tokamak plasmas in MST. With an applied toroidal field of 0.135 T, and q(a) > 2, the estimated energy confinement time is roughly consistent with neo-Alcator scaling. Driving q(a) < 2 with larger Ip, the confinement time degrades, but the discharge duration does not terminate prematurely. To fully optimize current profile control and to test MST operational limits, a PPS is also needed for the Bp circuit. Currently in prototype stage, the Bp PPS will feature a number of innovations to increase its flexibility and performance. Isolated charging, control, and monitor systems will eliminate charging relays, reduce coupling between modules, and minimize capacitor heating. Seven-level pulse width modulation will reduce output ripple and switching losses. Solid state shorting bars will eliminate shorting relays and minimize wiring. A balanced switching algorithm will minimize capacitive noise generation. Work supported by U. S. D. o. E.

Assessment of performing an MST strike in Tank 21H

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poirier, Michael R.

2014-09-29

Previous Savannah River National Laboratory (SRNL) tank mixing studies performed for the Small Column Ion Exchange (SCIX) project have shown that 3 Submersible Mixer Pumps (SMPs) installed in Tank 41 are sufficient to support actinide removal by MST sorption as well as subsequent resuspension and removal of settled solids. Savannah River Remediation (SRR) is pursuing MST addition into Tank 21 as part of the Large Tank Strike (LTS) project. The preliminary scope for LTS involves the use of three standard slurry pumps (installed in N, SE, and SW risers) in a Type IV tank. Due to the differences in tankmore » size, internal interferences, and pump design, a separate mixing evaluation is required to determine if the proposed configuration will allow for MST suspension and strontium and actinide sorption. The author performed the analysis by reviewing drawings for Tank 21 [W231023] and determining the required cleaning radius or zone of influence for the pumps. This requirement was compared with previous pilot-scale MST suspension data collected for SCIX that determined the cleaning radius, or zone of influence, as a function of pump operating parameters. The author also reviewed a previous Tank 50 mixing analysis that examined the ability of standard slurry pumps to suspend sludge particles. Based on a review of the pilot-scale SCIX mixing tests and Tank 50 pump operating experience, three standard slurry pumps should be able to suspend sludge and MST to effectively sorb strontium and actinides onto the MST. Using the SCIX data requires an assumption about the impact of cooling coils on slurry pump mixing. The basis for this assumption is described in this report. Using the Tank 50 operating experience shows three standard slurry pumps should be able to suspend solids if the shear strength of the settled solids is less than 160 Pa. Because Tank 21 does not contain cooling coils, the shear strength could be larger.« less

MST4 kinase phosphorylates ACAP4 protein to orchestrate apical membrane remodeling during gastric acid secretion.

PubMed

Yuan, Xiao; Yao, Phil Y; Jiang, Jiying; Zhang, Yin; Su, Zeqi; Yao, Wendy; Wang, Xueying; Gui, Ping; Mullen, McKay; Henry, Calmour; Ward, Tarsha; Wang, Wenwen; Brako, Larry; Tian, Ruijun; Zhao, Xuannv; Wang, Fengsong; Cao, Xinwang; Wang, Dongmei; Liu, Xing; Ding, Xia; Yao, Xuebiao

2017-09-29

Digestion in the stomach depends on acidification of the lumen. Histamine-elicited acid secretion is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. Our recent study revealed the functional role of PKA-MST4-ezrin signaling axis in histamine-elicited acid secretion. However, it remains uncharacterized how the PKA-MST4-ezrin signaling axis operates the insertion of H,K-ATPases into the apical plasma membranes of gastric parietal cells. Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr 545 Histamine stimulation activates MST4 and promotes MST4 interaction with ACAP4. ACAP4 physically interacts with MST4 and is a cognate substrate of MST4 during parietal cell activation. The phosphorylation site of ACAP4 by MST4 was mapped to Thr 545 by mass spectrometric analyses. Importantly, phosphorylation of Thr 545 is essential for acid secretion in parietal cells because either suppression of ACAP4 or overexpression of non-phosphorylatable ACAP4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, persistent overexpression of MST4 phosphorylation-deficient ACAP4 results in inhibition of gastric acid secretion and blockage of tubulovesicle fusion to the apical membranes. Significantly, phosphorylation of Thr 545 enables ACAP4 to interact with ezrin. Given the location of Thr 545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ACAP4 signaling cascade to polarized acid secretion in gastric parietal cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Overview of MST Research

NASA Astrophysics Data System (ADS)

Sarff, J. S.

2016-10-01

MST progress in advancing the RFP for (1) fusion plasma confinement with ohmic heating and minimal external magnetization, (2) predictive capability in toroidal confinement physics, and (3) basic plasma physics is summarized. Validation of key plasma models is a program priority. Programmable power supplies (PPS) are being developed to maximize inductive capability. Well-controlled flattops with current as low as 0.02 MA are produced with an existing PPS, and Ip <= 0.8 MA is anticipated with a second PPS under construction. The Lundquist number spans S =10(4 - 9) for 0.02-0.8 MA, allowing nonlinear MHD validation using NIMROD and DEBS at low S to be connected to highest S experiments. The PPS also enables MST tokamak operation for studying transients and runaway electron suppression with RMPs. Gyrokinetic modeling with GENE predicts unstable TEM in improved-confinement plasmas. Fluctuations are measured with TEM properties including a density-gradient threshold larger than for tokamak plasmas. Probe measurements hint that drift waves are also excited via the turbulent cascade in standard RFP plasmas. Turbulent energization of an electron tail occurs during sawtooth reconnection. New diagnostics are being developed to measure the energetic ion profile and transport from EP instabilities with NBI. Supported by US DoE and NSF.

Frequency of seizures and epilepsy in neurological HIV-infected patients.

PubMed

Kellinghaus, C; Engbring, C; Kovac, S; Möddel, G; Boesebeck, F; Fischera, M; Anneken, K; Klönne, K; Reichelt, D; Evers, S; Husstedt, I W

2008-01-01

Infection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy. The database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined. Of 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on

Alfentanil anesthetic augmentation lengthens seizure duration in electroconvulsive therapy with older people.

PubMed

D'Cunha, Craig; Plakiotis, Christos; O'Connor, Daniel W

2016-06-01

Electroconvulsive therapy (ECT) prescription rates rise with age, making it important that treatments be made as effective and safe as possible (Plakiotis et al., 2012). Older people are vulnerable to post-treatment confusion and to subsequent deficits in attention, new learning, and autobiographical memory (Gardner and O'Connor, 2008). Strategies to minimize cognitive side-effects include unilateral electrode placement and stimulus dose titration whereby electrical charge is individually calibrated to seizure threshold (Sackeim et al., 2000). It remains the case, however, that threshold levels typically rise over the treatment course, leading to an increase both in delivered charge and the risk of adverse sequelae.

The Development of MST Test Information for the Prediction of Test Performances

ERIC Educational Resources Information Center

Park, Ryoungsun; Kim, Jiseon; Chung, Hyewon; Dodd, Barbara G.

2017-01-01

The current study proposes novel methods to predict multistage testing (MST) performance without conducting simulations. This method, called MST test information, is based on analytic derivation of standard errors of ability estimates across theta levels. We compared standard errors derived analytically to the simulation results to demonstrate the…

Music-supported therapy in the rehabilitation of subacute stroke patients: a randomized controlled trial.

PubMed

Grau-Sánchez, Jennifer; Duarte, Esther; Ramos-Escobar, Neus; Sierpowska, Joanna; Rueda, Nohora; Redón, Susana; Veciana de Las Heras, Misericordia; Pedro, Jordi; Särkämö, Teppo; Rodríguez-Fornells, Antoni

2018-04-01

The effect of music-supported therapy (MST) as a tool to restore hemiparesis of the upper extremity after a stroke has not been appropriately contrasted with conventional therapy. The aim of this trial was to test the effectiveness of adding MST to a standard rehabilitation program in subacute stroke patients. A randomized controlled trial was conducted in which patients were randomized to MST or conventional therapy in addition to the rehabilitation program. The intensity and duration of the interventions were equated in both groups. Before and after 4 weeks of treatment, motor and cognitive functions, mood, and quality of life (QoL) of participants were evaluated. A follow-up at 3 months was conducted to examine the retention of motor gains. Both groups significantly improved their motor function, and no differences between groups were found. The only difference between groups was observed in the language domain for QoL. Importantly, an association was encountered between the capacity to experience pleasure from music activities and the motor improvement in the MST group. MST as an add-on treatment showed no superiority to conventional therapies for motor recovery. Importantly, patient's intrinsic motivation to engage in musical activities was associated with better motor improvement. © 2018 New York Academy of Sciences.

Dissociative seizures--a critical review and perspective.

PubMed

Schmutz, Matthias

2013-12-01

Dissociative seizures are commonly recognized as both a challenging and a poorly understood condition. Though research and publication activity is high, advances in knowledge and insight seem only moderate in recent years. This review focuses on some relevant problematic issues, which might account for a still unsatisfactory research state. A general tendency to deal with dissociative seizures as an assumed disorder in its own nosological right and not as a sole symptom of an underlying psychiatric disorder is most likely one of the major roots of the problem. Unfavorable impacts of this confusion pertaining to clinical management, therapy, and outcome of dissociative seizures are discussed. An alternative point of view, based on the immanent psychiatric and psychodynamic roots of dissociative seizures, is considered. © 2013.

Role of oxidative stress in epileptic seizures

PubMed Central

Shin, Eun-Joo; Jeong, Ji Hoon; Chung, Yoon Hee; Kim, Won-Ki; Ko, Kwang-Ho; Bach, Jae-Hyung; Hong, Jau-Shyong; Yoneda, Yukio; Kim, Hyoung-Chun

2013-01-01

Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. Therefore, antioxidant therapies aimed at reducing oxidative stress have received considerable attention in epilepsy treatment. However, much evidence suggests that oxidative stress does not always have the same pattern in all seizures models. Thus, this review provides an overview aimed at achieving a better understanding of this issue. We summarize work regarding seizure models (i.e., genetically epilepsy-prone rats, kainic acid, pilocarpine, pentylenetetrazol, and trimethyltin), oxidative stress as an etiologic factor in epileptic seizures (i.e., impairment of antioxidant systems, mitochondrial dysfunction, involvement of redox-active metals, arachidonic acid pathway activation, and aging), and antioxidant strategies for seizure treatment. Combined, this review highlights pharmacological mechanisms associated with oxidative stress in epileptic seizures and the potential for neuroprotection in epilepsy that targets oxidative stress and is supported by effective antioxidant treatment. PMID:21672578

Hydrogen sulfide ameliorates subarachnoid hemorrhage-induced neuronal apoptosis via the ROS-MST1 pathway

PubMed Central

Shi, Ligen; Lei, Jianwei; Xu, Hangzhe; Zheng, Jingwei; Wang, Yan; Peng, Yucong; Yu, Jun; Zhang, Jianmin

2017-01-01

Background Hydrogen sulfide (H2S) has shown a neuroprotective role in several cerebrovascular diseases. This study aimed to explore the underlying mechanisms of H2S in early brain injury after subarachnoid hemorrhage (SAH). Methods One hundred seventy-seven male Sprague-Dawley rats were employed in this study. Sodium hydrosulfide (NaHS), a donor of H2S, was injected intraperitoneally at 60 min after SAH was induced by endovascular perforation. Western blot analysis determined the expression of several proteins of interest, and an immunofluorescence assay was used to examine neuronal apoptosis. Results Exogenous NaHS markedly improved neurological scores, attenuated brain edema, and ameliorated neuronal apoptosis at 24 h after SAH induction. The underlying mechanisms of H2S in ameliorating neuronal apoptosis might be executed through inhibition of the activity of mammalian sterile 20-like kinase 1 (MST1) protein. Western blot analysis demonstrated that exogenous NaHS decreased cleaved MST1 (cl-MST1) while increasing full-length MST1 expression. This anti-apoptotic effect of H2S could be reversed by chelerythrine, which could activate MST1 via caspase-dependent cleavage. Conclusions Exogenous NaHS, as a donor of H2S, could ameliorate early brain injury after SAH by inhibiting neuronal apoptosis by reducing the activity of the MST1 protein. PMID:29088725

Sex and Hormonal influences on Seizures and Epilepsy

PubMed Central

Velíšková, Jana; DeSantis, Kara A.

2012-01-01

Epilepsy is the third most common chronic neurological disorder. Clinical and experimental evidence supports the role of sex and influence of sex hormones on seizures and epilepsy as well as alterations of the endocrine system and levels of sex hormones by epileptiform activity. Conversely, seizures are sensitive to changes in sex hormone levels, which in turn may affect the seizure-induced neuronal damage. The effects of reproductive hormones on neuronal excitability and seizure-induced damage are complex to contradictory and depend on different mechanisms, which have to be accounted for in data interpretation. Both estradiol and progesterone/allopregnanolone may have beneficial effects for patients with epilepsy. Individualized hormonal therapy should be considered as adjunctive treatment in patients with epilepsy to improve seizure control as well as quality of life. PMID:22504305

Intramuscular and rectal therapies of acute seizures.

PubMed

Leppik, Ilo E; Patel, Sima I

2015-08-01

The intramuscular (IM) and rectal routes are alternative routes of delivery for antiepileptic drugs (AEDs) when the intravenous route is not practical or possible. For treatment of acute seizures, the AED used should have a short time to maximum concentration (Tmax). Some AEDs have preparations that may be given intramuscularly. These include the benzodiazepines (diazepam, lorazepam, and midazolam) and others (fosphenytoin, levetiracetam). Although phenytoin and valproate have parenteral preparations, these should not be given intramuscularly. A recent study of prehospital treatment of status epilepticus evaluated a midazolam (MDZ) autoinjector delivering IM drug compared to IV lorazepam (LZP). Seizures were absent on arrival to the emergency department in 73.4% of the IM MDZ compared to a 63.4% response in LZP-treated subjects (p < 0.001 for superiority). Almost all AEDs have been evaluated for rectal administration as solutions, gels, and suppositories. In a placebo-controlled study, diazepam (DZP) was administered at home by caregivers in doses that ranged from 0.2 to 0.5 mg/kg. Diazepam was superior to placebo in reduced seizure frequency in children (p < 0.001) and in adults (p = 0.02) and time to recurrent seizures after an initial treatment (p < 0.001). Thus, at this time, only MZD given intramuscularly and DZP given rectally appear to have the properties required for rapid enough absorption to be useful when intravenous routes are not possible. Some drugs cannot be administered rectally owing to factors such as poor absorption or poor solubility in aqueous solutions. The relative rectal bioavailability of gabapentin, oxcarbazepine, and phenytoin is so low that the current formulations are not considered to be suitable for administration by this route. When administered as a solution, diazepam is rapidly absorbed rectally, reaching the Tmax within 5-20 min in children. By contrast, rectal administration of lorazepam is relatively slow, with a Tmax of 1-2h

Combined Diazepam and MK-801 Therapy Provides Synergistic Protection from Tetramethylenedisulfotetramine-induced Tonic-Clonic Seizures and Lethality in Mice

PubMed Central

Shakarjian, Michael P.; Ali, Mahil S.; Velíšková, Jana; Stanton, Patric K.; Heck, Diane E.; Velíšek, Libor

2015-01-01

The synthetic rodenticide, tetramethylenedisulfotetramine (TMDT), is a persistent and highly lethal GABA-gated Cl− channel blocker. TMDT is clandestinely produced, remains popular in mainland China, and causes numerous unintentional and deliberate poisonings worldwide. TMDT is odorless, tasteless, and easy to manufacture, features that make it a potential weapon of terrorism. There is no effective treatment. We previously characterized the effects of TMDT in C57BL/6 mice and surveyed efficacies of GABAergic and glutamatergic anticonvulsant treatments. At 0.4 mg/kg i.p., TMDT produced neurotoxic symptomatology consisting of twitches, clonic and tonic-clonic seizures, often progressing to status epilepticus and death. If administered immediately after the occurrence of the first clonic seizure, the benzodiazepine diazepam (DZP) effectively prevented all subsequent seizure symptoms, whereas the NMDA receptor antagonist dizocilpine (MK-801) primarily prevented tonic-clonic seizures. The latter agent, however, appeared to be more effective at preventing delayed death. The present study further explored these phenomena, and characterized the therapeutic actions of DZP and MK-801 as combinations. Joint treatment with both DZP and MK-801 displayed synergistic protection against tonic-clonic seizures and 24 hour lethality as determined by isobolographic analysis. Clonic seizures, however, remained poorly controlled. A modification of the treatment regimen, where DZP was followed 10 min later by MK-801, yielded a reduction in both types of seizures and improved overall outcome. Simultaneous monitoring of subjects via EEG and videography confirmed effectiveness of this sequential regimen. We conclude that TMDT blockage at GABAA receptors involves early activation of NMDA receptors, which contribute to persistent ictogenic activity. Our data predict that a sequential combination treatment with DZP followed by MK-801 will be superior to either individual therapy with, or

Intraoperative Seizures: Anesthetic and Antiepileptic Drugs.

PubMed

Uribe, Alberto; Zuleta-Alarcon, Alix; Kassem, Mahmoud; Sandhu, Gurneet S; Bergese, Sergio D

2017-01-01

Epilepsy is a common condition with up to 1% prevalence in the general population. In the perioperative course of neurologic surgery patients, the use of prophylactic and therapeutic antiepileptic drugs is a common practice. Nonetheless, there is limited evidence supporting the use of prophylactic antiepileptics to prevent perioperative seizures and there are no guidelines for which anesthetic technique is preferred. To discuss the seizurogenic potential of anesthetic drugs and to discuss intraoperative seizures in neurosurgical patients. We performed a search of the literature available in PubMed and Ovid MEDLINE. We also included articles identified in the review of the references of these articles. The incidence of seizures is heterogenic among neurosurgical patients. Seizure prophylaxis is widely administered despite limited available evidence of its effectiveness. In epileptic patients, the recommendation is to continue antiepileptic drugs in the perioperative setting. In these patients, anesthesiologists may also limit the use of medications that alter the seizure threshold and avoid medications that pose significant pharmacological interaction with antiepileptic drugs. In conclusion, a knowledgeable multidisciplinary perioperative team is essential to avoid, identify and treat intraoperative seizures competently. In patients with a history of epilepsy it is recommended to continue antiepileptic therapy. Therefore, clinical judgment should guide the decision of administering seizure prophylaxis in neurosurgery patients according to an individual assessment of potential risk for seizures. Furthermore, there is a need for randomized controlled trials that support new protocols and/or guidelines for anesthetic and perioperative regimens to prevent and treat intraoperative seizures. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multisystemic Therapy Effects on Attempted Suicide by Youths Presenting Psychiatric Emergencies

ERIC Educational Resources Information Center

Huey, Stanley J.; Henggeler, Scott W.; Rowland, Melisa D.; Halliday-Boykins, Colleen A.; Cunningham, Phillippe B.; Pickrel, Susan G.; Edwards, James

2004-01-01

Objective: To evaluate the efficacy of multisystemic therapy (MST) in reducing attempted suicide among predominantly African American youths referred for emergency psychiatric hospitalization. Method: Youths presenting psychiatric emergencies were randomly assigned to MST or hospitalization. Indices of attempted suicide, suicidal ideation,…

Electron Thermal Transport due to Magnetic Diffusion in the MST RFP

NASA Astrophysics Data System (ADS)

Reusch, J. A.; Anderson, J. K.; den Hartog, D. J.; Forest, C. B.; Kasten, C. P.; Schnack, D. D.; Stephens, H. D.

2011-10-01

Comparison of measurements made in the MST RFP to the results from extensive nonlinear resistive MHD simulations has provided two key observations. First, trapped particles reduce electron thermal diffusion; inclusion of this effect is required for quantitative agreement of simulation to measurement. Second, the structure and evolution of long-wavelength temperature fluctuations measured in MST shows remarkable qualitative similarity to fluctuations appearing in a finite-pressure simulation. These simulations were run at parameters matching those of 400 kA discharges in MST (S ~ 4 ×106). In a zero β simulation, the measured χe is compared to the thermal diffusion due to parallel losses along diffusing magnetic field lines, χst =v∥Dmag . Agreement is only found if the reduction in χst due to trapped particles is taken into account. In a second simulation, the pressure field was evolved self consistently assuming Ohmic heating and anisotropic thermal conduction. Fluctuations in the simulated temperature are very similar in character and time evolution to temperature fluctuations measured in MST. This includes m = 1 , n = 6 fluctuations that flatten the temperature profile as well as m = 1 , n = 5 fluctuations that generate hot island structures near the core shortly after sawtooth crashes. This work supported by the US DOE and NSF.

Electromagnetic Field Modeling of Transcranial Electric and Magnetic Stimulation: Targeting, Individualization, and Safety of Convulsive and Subconvulsive Applications

NASA Astrophysics Data System (ADS)

Deng, Zhi-De

The proliferation of noninvasive transcranial electric and magnetic brain stimulation techniques and applications in recent years has led to important insights into brain function and pathophysiology of brain-based disorders. Transcranial electric and magnetic stimulation encompasses a wide spectrum of methods that have developed into therapeutic interventions for a variety of neurological and psychiatric disorders. Although these methods are at different stages of development, the physical principle underlying these techniques is the similar. Namely, an electromagnetic field is induced in the brain either via current injection through scalp electrodes or via electromagnetic induction. The induced electric field modulates the neuronal transmembrane potentials and, thereby, neuronal excitability or activity. Therefore, knowledge of the induced electric field distribution is key in the design and interpretation of basic research and clinical studies. This work aims to delineate the fundamental physical limitations, tradeoffs, and technological feasibility constraints associated with transcranial electric and magnetic stimulation, in order to inform the development of technologies that deliver safer, and more spatially, temporally, and patient specific stimulation. Part I of this dissertation expounds on the issue of spatial targeting of the electric field. Contrasting electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) configurations that differ markedly in efficacy, side effects, and seizure induction efficiency could advance our understanding of the principles linking treatment parameters and therapeutic outcome and could provide a means of testing hypotheses of the mechanisms of therapeutic action. Using the finite element method, we systematically compare the electric field characteristics of existing forms of ECT and MST. We introduce a method of incorporating a modality-specific neural activation threshold in the electric field models that can

Overview of results from the MST reversed field pinch experiment

NASA Astrophysics Data System (ADS)

Sarff, J. S.; Almagri, A. F.; Anderson, J. K.; Borchardt, M.; Carmody, D.; Caspary, K.; Chapman, B. E.; Den Hartog, D. J.; Duff, J.; Eilerman, S.; Falkowski, A.; Forest, C. B.; Goetz, J. A.; Holly, D. J.; Kim, J.-H.; King, J.; Ko, J.; Koliner, J.; Kumar, S.; Lee, J. D.; Liu, D.; Magee, R.; McCollam, K. J.; McGarry, M.; Mirnov, V. V.; Nornberg, M. D.; Nonn, P. D.; Oliva, S. P.; Parke, E.; Reusch, J. A.; Sauppe, J. P.; Seltzman, A.; Sovinec, C. R.; Stephens, H.; Stone, D.; Theucks, D.; Thomas, M.; Triana, J.; Terry, P. W.; Waksman, J.; Bergerson, W. F.; Brower, D. L.; Ding, W. X.; Lin, L.; Demers, D. R.; Fimognari, P.; Titus, J.; Auriemma, F.; Cappello, S.; Franz, P.; Innocente, P.; Lorenzini, R.; Martines, E.; Momo, B.; Piovesan, P.; Puiatti, M.; Spolaore, M.; Terranova, D.; Zanca, P.; Belykh, V.; Davydenko, V. I.; Deichuli, P.; Ivanov, A. A.; Polosatkin, S.; Stupishin, N. V.; Spong, D.; Craig, D.; Harvey, R. W.; Cianciosa, M.; Hanson, J. D.

2013-10-01

An overview of recent results from the MST programme on physics important for the advancement of the reversed field pinch (RFP) as well as for improved understanding of toroidal magnetic confinement more generally is reported. Evidence for the classical confinement of ions in the RFP is provided by analysis of impurity ions and energetic ions created by 1 MW neutral beam injection (NBI). The first appearance of energetic-particle-driven modes by NBI in a RFP plasma is described. MST plasmas robustly access the quasi-single-helicity state that has commonalities to the stellarator and ‘snake’ formation in tokamaks. In MST the dominant mode grows to 8% of the axisymmetric field strength, while the remaining modes are reduced. Predictive capability for tearing mode behaviour has been improved through nonlinear, 3D, resistive magnetohydrodynamic computation using the measured resistivity profile and Lundquist number, which reproduces the sawtooth cycle dynamics. Experimental evidence and computational analysis indicates two-fluid effects, e.g., Hall physics and gyro-viscosity, are needed to understand the coupling of parallel momentum transport and current profile relaxation. Large Reynolds and Maxwell stresses, plus separately measured kinetic stress, indicate an intricate momentum balance and a possible origin for MST's intrinsic plasma rotation. Gyrokinetic analysis indicates that micro-tearing modes can be unstable at high beta, with a critical gradient for the electron temperature that is larger than for tokamak plasmas by roughly the aspect ratio.

Robust MST-Based Clustering Algorithm.

PubMed

Liu, Qidong; Zhang, Ruisheng; Zhao, Zhili; Wang, Zhenghai; Jiao, Mengyao; Wang, Guangjing

2018-06-01

Minimax similarity stresses the connectedness of points via mediating elements rather than favoring high mutual similarity. The grouping principle yields superior clustering results when mining arbitrarily-shaped clusters in data. However, it is not robust against noises and outliers in the data. There are two main problems with the grouping principle: first, a single object that is far away from all other objects defines a separate cluster, and second, two connected clusters would be regarded as two parts of one cluster. In order to solve such problems, we propose robust minimum spanning tree (MST)-based clustering algorithm in this letter. First, we separate the connected objects by applying a density-based coarsening phase, resulting in a low-rank matrix in which the element denotes the supernode by combining a set of nodes. Then a greedy method is presented to partition those supernodes through working on the low-rank matrix. Instead of removing the longest edges from MST, our algorithm groups the data set based on the minimax similarity. Finally, the assignment of all data points can be achieved through their corresponding supernodes. Experimental results on many synthetic and real-world data sets show that our algorithm consistently outperforms compared clustering algorithms.

The debate: Treatment after the first seizure - The CONTRA.

PubMed

Steinhoff, Bernhard J

2017-07-01

In many instances antiepileptic drug (AED) treatment of epilepsy patients is sustained for a long time and is even a lifelong therapy. Chronic drug treatment naturally means the potential burden of adverse effects. The prognosis to remain seizure-free is good after a first seizure even without AEDs. Therefore one has to consider the possibility that freedom from seizures when AED treatment has been initiated after the first seizure may not in fact be the result of the AED treatment. On the other hand seizure-free patients without severe side effects most probably will not consider discontinuing AEDs. Therefore in these cases it will not be possible to discover whether AEDs are really necessary to maintain freedom from seizures. Furthermore it has been shown that the long-term prognosis is independent of whether AED treatment started after the first or a following seizure. Therefore in most instances AED treatment after a first seizure should be avoided. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vališ, Karel, E-mail: karel.valis@biomed.cas.cz; Faculty of Science, Charles University, Prague; Talacko, Pavel

The general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. We have found that two key regulators of glycolysis, C-MYC and GLUT1, are targets of the Hippo signaling pathway in human leukemia cells. Our results revealed that activation of MST1 by the natural compound shikonin inhibited the expression of GLUT1 and C-MYC. Furthermore, RNAi experiments confirmed the regulation of GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis. Surprisingly, YAP1 was found to positively regulate C-MYC mRNA levels in complexmore » with TEAD1, while it negatively regulates C-MYC levels in cooperation with MST1. Hence, YAP1 serves as a rheostat for C-MYC, which is regulated by MST1. In addition, depletion of MST1 stimulates lactate production, whereas the specific depletion of TEAD1 has an opposite effect. The inhibition of lactate production and cellular proliferation induced by shikonin also depends on the Hippo pathway activity. Finally, a bioinformatic analysis revealed conserved TEAD-binding motifs in the C-MYC and GLUT1 promoters providing another molecular data supporting our observations. In summary, regulation of glucose metabolism could serve as a new tumor suppressor mechanism orchestrated by the Hippo signaling pathway. - Highlights: • Shikonin inhibits C-MYC and GLUT1 expression in MST1 and YAP1 dependent manner. • YAP1-TEAD1 interaction activates C-MYC and GLUT1 expression. • MST1 in cooperation with YAP1 inhibits C-MYC and GLUT1 expression. • MST1-YAP1-TEAD1 axis regulates lactate production by leukemic cells. • MST1 and YAP1 proteins block proliferation of leukemic cells.« less

The MST/Hippo Pathway and Cell Death: A Non-Canonical Affair

PubMed Central

Fallahi, Emma; O’Driscoll, Niamh A.; Matallanas, David

2016-01-01

The MST/Hippo signalling pathway was first described over a decade ago in Drosophila melanogaster and the core of the pathway is evolutionary conserved in mammals. The mammalian MST/Hippo pathway regulates organ size, cell proliferation and cell death. In addition, it has been shown to play a central role in the regulation of cellular homeostasis and it is commonly deregulated in human tumours. The delineation of the canonical pathway resembles the behaviour of the Hippo pathway in the fly where the activation of the core kinases of the pathway prevents the proliferative signal mediated by the key effector of the pathway YAP. Nevertheless, several lines of evidence support the idea that the mammalian MST/Hippo pathway has acquired new features during evolution, including different regulators and effectors, crosstalk with other essential signalling pathways involved in cellular homeostasis and the ability to actively trigger cell death. Here we describe the current knowledge of the mechanisms that mediate MST/Hippo dependent cell death, especially apoptosis. We include evidence for the existence of complex signalling networks where the core proteins of the pathway play a central role in controlling the balance between survival and cell death. Finally, we discuss the possible involvement of these signalling networks in several human diseases such as cancer, diabetes and neurodegenerative disorders. PMID:27322327

Precipitating factors and therapeutic outcome in epilepsy with generalized tonic-clonic seizures.

PubMed

Bauer, J; Saher, M S; Burr, W; Elger, C E

2000-10-01

The aim of the study was to evaluate the influence of precipitating factors and therapy on the outcome of epilepsy with generalized tonic-clonic seizures. Retrospective analysis of data from 34 patients (mean age at seizure onset 19 years; mean duration of follow-up 9.2 years) suffering from epilepsy of either cryptogenic or remote symptomatic (n = 19), or idiopathic (n = 15) etiology. The total number of seizures in all patients was 146. Without treatment 97 seizures manifested during 90.5 years without treatment (1.07 seizures/year), during treatment with carbamazepine or valproate 49 seizures occurred within 224 years (0.2 seizures/year). The frequency of seizures was significantly lower during treatment. Precipitating factors were found in relation to 31% of seizures in patients with remote symptomatic or cryptogenic epilepsy, and for 51% of seizures in patients with idiopathic epilepsy. There was a low frequency of seizures in patients with generalized tonic-clonic seizures. Precipitating factors are common. Antiepileptic drug treatment is effective.

PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Sujin; Kang, Jeong Gu; Lee, Ju Hee

2014-01-24

Highlights: • PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at Thr{sup 387}. • Overexpression of PHLPP1 sensitizes contact inhibition. • Tumor cells with suppressed PHLPP1 expression are refractory to apoptosis and highly proliferative. • Loss or down-regulation of PHLPP1 may drive tumor development and progression. - Abstract: Contact inhibition has been largely elusive despite that a loss of contact inhibition is a critical event for cancer development and progression. Here, we report that PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr{sup 387} of Mst1. Yap1 was localized predominantlymore » in the nucleus but marginally in the cytoplasm in HeLa cells under sparse conditions, whereas the functional protein was more directed to sequestration in the cytoplasm under dense environments. Furthermore, loss of PHLPP1 resulted in a failure of the apoptotic control. It is interesting that down-regulated expression of PHLPP1 appears to mimic the loss of contact inhibition, a hallmark of cancer.« less

Early pediatric antiepileptic drug nonadherence is related to lower long-term seizure freedom.

PubMed

Modi, Avani C; Rausch, Joseph R; Glauser, Tracy A

2014-02-25

To examine the relationship between previously identified nonadherence trajectories during the first 6 months of antiepileptic drug (AED) therapy and long-term seizure-free rates (defined as ≥1 year of seizure freedom at the 4 years postdiagnosis milestone) in a cohort of children with newly diagnosed epilepsy. A prospective longitudinal observational study of AED adherence and seizure freedom in a consecutive cohort of 124 children (ages 2-12 years) with newly diagnosed epilepsy was conducted. The association between previously identified AED adherence trajectories (i.e., near-perfect adherence [e.g., average adherence = 96.8%] vs nonadherent) and seizure freedom for ≥1 year at the 4 years postdiagnosis milestone was determined. Children who exhibited nonadherence to AED therapy in the first 6 months of treatment were 3.24 times more likely not to have achieved ≥1 year of seizure freedom at the 4 years postdiagnosis milestone compared to children in the near-perfect adherence group (χ² = 5.13; p = 0.02). Specifically, at the 4 years postdiagnosis milestone, only 12% of children in the near-perfect adherence group were continuing to experience seizures compared to 31% of children in the nonadherent group. Children with epilepsy who achieved near-perfect adherence during the first 6 months of therapy experienced a higher rate of seizure freedom 4 years postdiagnosis compared with those children who demonstrated early nonadherence. This suggests that adherence intervention early in the course of treatment could play a role in improving long-term seizure freedom rates in children with epilepsy.

Evidence-based guideline: Management of an unprovoked first seizure in adults

PubMed Central

Krumholz, Allan; Wiebe, Samuel; Gronseth, Gary S.; Gloss, David S.; Sanchez, Ana M.; Kabir, Arif A.; Liferidge, Aisha T.; Martello, Justin P.; Kanner, Andres M.; Shinnar, Shlomo; Hopp, Jennifer L.; French, Jacqueline A.

2015-01-01

Objective: To provide evidence-based recommendations for treatment of adults with an unprovoked first seizure. Methods: We defined relevant questions and systematically reviewed published studies according to the American Academy of Neurology's classification of evidence criteria; we based recommendations on evidence level. Results and recommendations: Adults with an unprovoked first seizure should be informed that their seizure recurrence risk is greatest early within the first 2 years (21%–45%) (Level A), and clinical variables associated with increased risk may include a prior brain insult (Level A), an EEG with epileptiform abnormalities (Level A), a significant brain-imaging abnormality (Level B), and a nocturnal seizure (Level B). Immediate antiepileptic drug (AED) therapy, as compared with delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B) but may not improve quality of life (Level C). Over a longer term (>3 years), immediate AED treatment is unlikely to improve prognosis as measured by sustained seizure remission (Level B). Patients should be advised that risk of AED adverse events (AEs) may range from 7% to 31% (Level B) and that these AEs are likely predominantly mild and reversible. Clinicians' recommendations whether to initiate immediate AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy, consider educated patient preferences, and advise that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce seizure risk over the subsequent 2 years. PMID:25901057

Anticonvulsant effect of xenon on neonatal asphyxial seizures.

PubMed

Azzopardi, Denis; Robertson, Nicola J; Kapetanakis, Andrew; Griffiths, James; Rennie, Janet M; Mathieson, Sean R; Edwards, A David

2013-09-01

Xenon, a monoatomic gas with very high tissue solubility, is a non-competitive inhibitor of N-methyl-D-aspartate (NMDA) glutamate receptor, has antiapoptotic effects and is neuroprotective following hypoxic ischaemic injury in animals. Xenon may be expected to have anticonvulsant effects through glutamate receptor blockade, but this has not previously been demonstrated clinically. We examined seizure activity on the real time and amplitude integrated EEG records of 14 full-term infants with perinatal asphyxial encephalopathy treated within 12 h of birth with 30% inhaled xenon for 24 h combined with 72 h of moderate systemic hypothermia. Seizures were identified on 5 of 14 infants. Seizures stopped during xenon therapy but recurred within a few minutes of withdrawing xenon and stopped again after xenon was restarted. Our data show that subanaesthetic levels of xenon may have an anticonvulsant effect. Inhaled xenon may be a valuable new therapy in this hard-to-treat population.

Simulation of MST tokamak discharges with resonant magnetic perturbations

NASA Astrophysics Data System (ADS)

Cornille, B. S.; Sovinec, C. R.; Chapman, B. E.; Dubois, A.; McCollam, K. J.; Munaretto, S.

2016-10-01

Nonlinear MHD modeling of MST tokamak plasmas with an applied resonant magnetic perturbation (RMP) reveals degradation of flux surfaces that may account for the experimentally observed suppression of runaway electrons with the RMP. Runaway electrons are routinely generated in MST tokamak discharges with low plasma density. When an m = 3 RMP is applied these electrons are strongly suppressed, while an m = 1 RMP of comparable amplitude has little effect. The computations are performed using the NIMROD code and use reconstructed equilibrium states of MST tokamak plasmas with q (0) < 1 and q (a) = 2.2 . Linear computations show that the (1 , 1) -kink and (2 , 2) -tearing modes are unstable, and nonlinear simulations produce sawtoothing with a period of approximately 0.5 ms, which is comparable to the period of MHD activity observed experimentally. Adding an m = 3 RMP in the computation degrades flux surfaces in the outer region of the plasma, while no degradation occurs with an m = 1 RMP. The outer flux surface degradation with the m = 3 RMP, combined with the sawtooth-induced distortion of flux surfaces in the core, may account for the observed suppression of runaway electrons. Work supported by DOE Grant DE-FC02-08ER54975.

Long-Read Single Molecule Sequencing to Resolve Tandem Gene Copies: The Mst77Y Region on the Drosophila melanogaster Y Chromosome

PubMed Central

Krsticevic, Flavia J.; Schrago, Carlos G.; Carvalho, A. Bernardo

2015-01-01

The autosomal gene Mst77F of Drosophila melanogaster is essential for male fertility. In 2010, Krsticevic et al. (Genetics 184: 295−307) found 18 Y-linked copies of Mst77F (“Mst77Y”), which collectively account for 20% of the functional Mst77F-like mRNA. The Mst77Y genes were severely misassembled in the then-available genome assembly and were identified by cloning and sequencing polymerase chain reaction products. The genomic structure of the Mst77Y region and the possible existence of additional copies remained unknown. The recent publication of two long-read assemblies of D. melanogaster prompted us to reinvestigate this challenging region of the Y chromosome. We found that the Illumina Synthetic Long Reads assembly failed in the Mst77Y region, most likely because of its tandem duplication structure. The PacBio MHAP assembly of the Mst77Y region seems to be very accurate, as revealed by comparisons with the previously found Mst77Y genes, a bacterial artificial chromosome sequence, and Illumina reads of the same strain. We found that the Mst77Y region spans 96 kb and originated from a 3.4-kb transposition from chromosome 3L to the Y chromosome, followed by tandem duplications inside the Y chromosome and invasion of transposable elements, which account for 48% of its length. Twelve of the 18 Mst77Y genes found in 2010 were confirmed in the PacBio assembly, the remaining six being polymerase chain reaction−induced artifacts. There are several identical copies of some Mst77Y genes, coincidentally bringing the total copy number to 18. Besides providing a detailed picture of the Mst77Y region, our results highlight the utility of PacBio technology in assembling difficult genomic regions such as tandemly repeated genes. PMID:25858959

Chemical–genetic attenuation of focal neocortical seizures

PubMed Central

Kätzel, Dennis; Nicholson, Elizabeth; Schorge, Stephanie; Walker, Matthew C.; Kullmann, Dimitri M.

2014-01-01

Focal epilepsy is commonly pharmacoresistant, and resective surgery is often contraindicated by proximity to eloquent cortex. Many patients have no effective treatment options. Gene therapy allows cell-type specific inhibition of neuronal excitability, but on-demand seizure suppression has only been achieved with optogenetics, which requires invasive light delivery. Here we test a combined chemical–genetic approach to achieve localized suppression of neuronal excitability in a seizure focus, using viral expression of the modified muscarinic receptor hM4Di. hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO). Systemic administration of CNO suppresses focal seizures evoked by two different chemoconvulsants, pilocarpine and picrotoxin. CNO also has a robust anti-seizure effect in a chronic model of focal neocortical epilepsy. Chemical–genetic seizure attenuation holds promise as a novel approach to treat intractable focal epilepsy while minimizing disruption of normal circuit function in untransduced brain regions or in the absence of the specific ligand. PMID:24866701

Does remifentanil improve ECT seizure quality?

PubMed

Gálvez, Verònica; Tor, Phern-Chern; Bassa, Adriana; Hadzi-Pavlovic, Dusan; MacPherson, Ross; Marroquin-Harris, Mincho; Loo, Colleen K

2016-12-01

Studies have reported that co-adjuvant remifentanil can enhance electroconvulsive therapy (ECT) seizure quality, putatively by allowing a reduction in the dosage of the main anaesthetic agents, as the latter have anticonvulsant properties. However, whether remifentanil also has direct effects on ECT seizure quality, and by implication, treatment efficacy, is unknown. This is the first study examining the effect of adjuvant remifentanil on ECT seizure quality when the dose of conventional anaesthesia remained unchanged. A total of 96 ECT sessions (from 36 patients) were retrospectively analysed. Subjects received ECT with and without remifentanil (1 µg/kg), while the dose of thiopentone (3-5 mg/kg) or propofol (1-2 mg/kg) was unchanged. Seizure quality indices (time to slow wave activity or TSLOW, amplitude, regularity, stereotypy, post-ictal suppression) and duration were assessed through a structured rating scale by a single trained blinded rater. Linear mixed-effects models with random subject effects analysed the effect of remifentanil on seizure parameters, controlling for other variables that can affect seizure quality or duration. Remifentanil was given in 47.9 % of the ECT sessions. Co-adjuvant remifentanil had no effects on any of the seizure quality parameters analysed [TSLOW (E = -0.21, p > 0.1), amplitude (E = 0.08, p > 0.5), regularity (E = -0.05, p > 0.5), stereotypy (E = -0.02, p > 0.5), suppression (E = -0.3, p > 0.05)] or on seizure duration (E = -0.25, p > 0.1). While adjuvant remifentanil may be a useful strategy for reducing anaesthetic dosage in ECT, present evidence suggests that remifentanil does not have intrinsic properties that enhance ECT seizures.

Focal seizure symptoms in idiopathic generalized epilepsies.

PubMed

Seneviratne, Udaya; Woo, Jia J; Boston, Ray C; Cook, Mark; D'Souza, Wendyl

2015-08-18

We sought to study the frequency and prognostic value of focal seizure symptoms (FSS) in idiopathic generalized epilepsies (IGE) using a validated tool: Epilepsy Diagnostic Interview Questionnaire and Partial Seizure Symptom Definitions. Participants with IGE were recruited from epilepsy clinics at 2 tertiary hospitals. The diagnosis was validated and classified into syndromes according to the International League Against Epilepsy criteria by 2 epileptologists independently with discordance resolved by consensus. The Epilepsy Diagnostic Interview Questionnaire utilizes both open- and closed-ended questions to elicit FSS in association with generalized tonic-clonic seizures, myoclonus, and absences. The elicited FSS were classified according to the Partial Seizure Symptom Definitions. Regression analysis was conducted to examine the relationship between the duration of seizure freedom and FSS. A total of 135 patients were studied, of whom 70 (51.9%) reported FSS. Those symptoms occurred in association with generalized tonic-clonic seizures (53.1%) as well as myoclonus and absences (58%). FSS were reported with similar frequency in juvenile absence epilepsy (62.5%) and juvenile myoclonic epilepsy (60%), and with a lesser frequency in generalized epilepsy with tonic-clonic seizures only (39.5%) and childhood absence epilepsy (33.3%). A strong relationship between FSS and duration of seizure freedom was found (regression coefficient -0.665, p = 0.037). FSS are frequently reported by patients with IGE. A shorter duration of seizure freedom is associated with FSS. Recognition of the presence of FSS in IGE is important to avoid misdiagnosis and delayed diagnosis as well as to choose appropriate antiepileptic drug therapy. © 2015 American Academy of Neurology.

Seizure clustering.

PubMed

Haut, Sheryl R

2006-02-01

Seizure clusters, also known as repetitive or serial seizures, occur commonly in epilepsy. Clustering implies that the occurrence of one seizure may influence the probability of a subsequent seizure; thus, the investigation of the clustering phenomenon yields insights into both specific mechanisms of seizure clustering and more general concepts of seizure occurrence. Seizure clustering has been defined clinically as a number of seizures per unit time and, statistically, as a deviation from a random distribution, or interseizure interval dependence. This review explores the pathophysiology, epidemiology, and clinical implications of clustering, as well as other periodic patterns of seizure occurrence. Risk factors for experiencing clusters and potential precipitants of clustering are also addressed.

Lacosamide in patients with gliomas and uncontrolled seizures: results from an observational study.

PubMed

Rudà, Roberta; Pellerino, Alessia; Franchino, Federica; Bertolotti, Cinzia; Bruno, Francesco; Mo, Francesca; Migliore, Enrica; Ciccone, Gianni; Soffietti, Riccardo

2018-01-01

To report the efficacy and tolerability of lacosamide as an add-on treatment in patients with gliomas and uncontrolled seizures despite conventional antiepileptic drugs (AEDs). We conducted an observational study on 71 patients to describe patterns of response to lacosamide and the association between clinico-pathological factors and seizure control. We observed at 3, 6 and 9 months a seizure reduction ≥ 50% in 74.6, 76 and 86.2% of patients and a seizure freedom in 42.2, 43 and 50%, respectively. The median number of seizures in the 3 months before treatment was 13, and decreased to 3 between baseline and 6 months, and to 0.5 between 6 and 9 months. The best seizure response was observed at 3 months (62%). Sixty per cent of patients displayed the maximum seizure control with doses of lacosamide of 100-250 mg/day, while 21% needed doses up to 400 mg/day. Seizure reduction ≥ 50% and seizure freedom were higher in patients who received lacosamide as first add-on compared to those who received a later adjunctive therapy. A reduction ≥ 50% of seizures was observed in a proportion of patients with progressive disease on MRI. Age > 45 years (OR 0.11, 95% CI 0.02-0.63, p = 0.013) was a significant predictor of seizure freedom at 9 months on multivariate analysis. The study suggests that lacosamide, when added to any baseline AEDs, is effective in obtaining a high seizure reduction and seizure freedom regardless of the tumor activity and response to antineoplastic therapies.

Vagus nerve stimulation magnet activation for seizures: a critical review.

PubMed

Fisher, R S; Eggleston, K S; Wright, C W

2015-01-01

Some patients receiving VNS Therapy report benefit from manually activating the generator with a handheld magnet at the time of a seizure. A review of 20 studies comprising 859 subjects identified patients who reported on-demand magnet mode stimulation to be beneficial. Benefit was reported in a weighted average of 45% of patients (range 0-89%) using the magnet, with seizure cessation claimed in a weighted average of 28% (range 15-67%). In addition to seizure termination, patients sometimes reported decreased intensity or duration of seizures or the post-ictal period. One study reported an isolated instance of worsening with magnet stimulation (Arch Pediatr Adolesc Med, 157, 2003 and 560). All of the reviewed studies assessed adjunctive magnet use. No studies were designed to provide Level I evidence of efficacy of magnet-induced stimulation. Retrospective analysis of one pivotal randomized trial of VNS therapy showed significantly more seizures terminated or improved in the active stimulation group vs the control group. Prospective, controlled studies would be required to isolate the effect and benefit of magnet mode stimulation and to document that the magnet-induced stimulation is the proximate cause of seizure reduction. Manual application of the magnet to initiate stimulation is not always practical because many patients are immobilized or unaware of their seizures, asleep or not in reach of the magnet. Algorithms based on changes in heart rate at or near the onset of the seizure provide a methodology for automated responsive stimulation. Because literature indicates additional benefits from on-demand magnet mode stimulation, a potential role exists for automatic activation of stimulation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Forecasting seizures in dogs with naturally occurring epilepsy.

PubMed

Howbert, J Jeffry; Patterson, Edward E; Stead, S Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W Douglas; Litt, Brian; Worrell, Gregory A

2014-01-01

Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-70 Hz), and high-gamma (70-180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring.

Dissociation of spontaneous seizures and brainstem seizure thresholds in mice exposed to eight flurothyl-induced generalized seizures.

PubMed

Kadiyala, Sridhar B; Ferland, Russell J

2017-03-01

C57BL/6J mice exposed to eight flurothyl-induced generalized clonic seizures exhibit a change in seizure phenotype following a 28-day incubation period and subsequent flurothyl rechallenge. Mice now develop a complex seizure semiology originating in the forebrain and propagating into the brainstem seizure network (a forebrain→brainstem seizure). In contrast, this phenotype change does not occur in seizure-sensitive DBA/2J mice. The underlying mechanism(s) was the focus of these studies. DBA2/J mice were exposed to eight flurothyl-induced seizures (1/day) followed by 24-hour video-electroencephalographic recordings for 28-days. Forebrain and brainstem seizure thresholds were determined in C57BL/6J and DBA/2J mice following one or eight flurothyl-induced seizures, or after eight flurothyl-induced seizures, a 28-day incubation period, and final flurothyl rechallenge. Similar to C57BL/6J mice, DBA2/J mice expressed spontaneous seizures. However, unlike C57BL/6J mice, DBA2/J mice continued to have spontaneous seizures without remission. Because DBA2/J mice do not express forebrain→brainstem seizures following flurothyl rechallenge after a 28-day incubation period, this indicated that spontaneous seizures were not sufficient for the evolution of forebrain→brainstem seizures. Therefore, we determined whether brainstem seizure thresholds were changing during this repeated-flurothyl model and whether this could account for the expression of forebrain→brainstem seizures. Brainstem seizure thresholds were not different between C57BL/6J and DBA/2J mice on day one or on the last induction seizure trial (day eight). However, brainstem seizure thresholds did differ significantly on flurothyl rechallenge (day 28) with DBA/2J mice showing no lowering of their brainstem seizure thresholds. These results demonstrated that DBA/2J mice exposed to the repeated-flurothyl model develop spontaneous seizures without evidence of seizure remission and provide a new model of

Inherited MST1 deficiency underlies susceptibility to EV-HPV infections.

PubMed

Crequer, Amandine; Picard, Capucine; Patin, Etienne; D'Amico, Aurelia; Abhyankar, Avinash; Munzer, Martine; Debré, Marianne; Zhang, Shen-Ying; de Saint-Basile, Geneviève; Fischer, Alain; Abel, Laurent; Orth, Gérard; Casanova, Jean-Laurent; Jouanguy, Emmanuelle

2012-01-01

Epidermodysplasia verruciformis (EV) is characterized by persistent cutaneous lesions caused by a specific group of related human papillomavirus genotypes (EV-HPVs) in otherwise healthy individuals. Autosomal recessive (AR) EVER1 and EVER2 deficiencies account for two thirds of known cases of EV. AR RHOH deficiency has recently been described in two siblings with EV-HPV infections as well as other infectious and tumoral manifestations. We report here the whole-exome based discovery of AR MST1 deficiency in a 19-year-old patient with a T-cell deficiency associated with EV-HPV, bacterial and fungal infections. MST1 deficiency has recently been described in seven patients from three unrelated kindreds with profound T-cell deficiency and various viral and bacterial infections. The patient was also homozygous for a rare ERCC3 variation. Our findings broaden the clinical range of infections seen in MST1 deficiency and provide a new genetic etiology of susceptibility to EV-HPV infections. Together with the recent discovery of RHOH deficiency, they suggest that T cells are involved in the control of EV-HPVs, at least in some individuals.

Inherited MST1 Deficiency Underlies Susceptibility to EV-HPV Infections

PubMed Central

Crequer, Amandine; Picard, Capucine; Patin, Etienne; D’Amico, Aurelia; Abhyankar, Avinash; Munzer, Martine; Debré, Marianne; Zhang, Shen-Ying; de Saint-Basile, Geneviève; Fischer, Alain

2012-01-01

Epidermodysplasia verruciformis (EV) is characterized by persistent cutaneous lesions caused by a specific group of related human papillomavirus genotypes (EV-HPVs) in otherwise healthy individuals. Autosomal recessive (AR) EVER1 and EVER2 deficiencies account for two thirds of known cases of EV. AR RHOH deficiency has recently been described in two siblings with EV-HPV infections as well as other infectious and tumoral manifestations. We report here the whole-exome based discovery of AR MST1 deficiency in a 19-year-old patient with a T-cell deficiency associated with EV-HPV, bacterial and fungal infections. MST1 deficiency has recently been described in seven patients from three unrelated kindreds with profound T-cell deficiency and various viral and bacterial infections. The patient was also homozygous for a rare ERCC3 variation. Our findings broaden the clinical range of infections seen in MST1 deficiency and provide a new genetic etiology of susceptibility to EV-HPV infections. Together with the recent discovery of RHOH deficiency, they suggest that T cells are involved in the control of EV-HPVs, at least in some individuals. PMID:22952854

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis

PubMed Central

Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

2006-01-01

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2–0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the Ih current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes. PMID:16819552

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

PubMed

Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

2006-07-01

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

[Seizures in neurofibromatosis. What is the risk?].

PubMed

Drouet, A

2011-12-01

The prevalence and the type of seizures associated with neurofibromatosis 1 (NF1) and 2 (NF2) are not adequately characterized. NF1 has a birth incidence of one in 2500, and NF2 one in 25000. Seizures are an occasional complication in NF1 patients and there is no data for NF2 patients. Central nervous system tumors are always suspected, since NF1 and NF2 are caused by mutations in tumor suppressor gene controlling cell proliferation and differentiation. The aim of this article is to provide a synthetic overview about epilepsy associated with NF1 and NF2 based on published studies. In NF1, the type of seizures and their response to therapy are reported, the heterogeneity of etiology is also discussed. For NF2 patients, no specific data are available; the current knowledge comes from series of NF2 patients for which seizures has revealed the disease or from isolated case reports of tumors associated with seizures. Cryptogenic epilepsy without anatomic defect is likely to be related to NF1, while seizures seem to be secondary to leptomeningeal tumors (meningioma, meningioangiomatosis) in NF2 patients. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Multisystemic Therapy for Child Non-Externalizing Psychological and Health Problems: A Preliminary Review

ERIC Educational Resources Information Center

Pane, Heather T.; White, Rachel S.; Nadorff, Michael R.; Grills-Taquechel, Amie; Stanley, Melinda A.

2013-01-01

Multisystemic therapy (MST) is effective for decreasing or preventing delinquency and other externalizing behaviors and increasing prosocial or adaptive behaviors. The purpose of this project was to review the literature examining the efficacy of MST for other child psychological and health problems reflecting non-externalizing behaviors,…

Seizure precipitants (triggering factors) in patients with epilepsy.

PubMed

Ferlisi, Monica; Shorvon, Simon

2014-04-01

adult epilepsy clinic population: (a) to identify the frequency of seizure precipitants (triggering factors) and their relative frequency in those with psychiatric disorders, and in those in remission or with active epilepsy, differences in frequency with regard to gender, seizure duration, number of drugs taken; (b) to determine which precipitants patients most commonly report; and (c) to identify differences in the distribution of precipitants among generalized, temporal, and extratemporal epilepsies. Consecutive patients attending a tertiary-care epilepsy clinic were prospectively and an open personal interview to identify and characterize seizure precipitants. Information about the epilepsy and clinical characteristics of patients was collected during the interview and from medical records. Of 104 patients, 97% cited at least one precipitant. Stress, sleep deprivation, and fatigue were the most frequently reported precipitants. Patients with psychological comorbidities reported a greater percentage of seizures with seizure precipitants. Patients with idiopathic generalized epilepsy seemed to be more sensitive to seizures during awakening and sleep deprivation, patients with extratemporal epilepsy reported more frequent seizures during sleep. There were no differences in frequency or type of seizure precipitants with regard to gender, seizure duration or frequency, and the number of antiepileptic drugs taken. The findings may have implications for the better management of epilepsy by increasing a focus on nonpharmacological therapy. The implications of the findings for nosology and causation of epilepsy are also briefly discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Cell Polarity Kinase MST4 Cooperates with cAMP-dependent Kinase to Orchestrate Histamine-stimulated Acid Secretion in Gastric Parietal Cells*

PubMed Central

Jiang, Hao; Wang, Wenwen; Zhang, Yin; Yao, William W.; Jiang, Jiying; Qin, Bo; Yao, Wendy Y.; Liu, Fusheng; Wu, Huihui; Ward, Tarsha L.; Chen, Chun Wei; Liu, Lifang; Ding, Xia; Liu, Xing; Yao, Xuebiao

2015-01-01

The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin, whose phosphorylation at Ser-66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which this signaling pathway operates in gastric acid secretion. Here we show that PKA cooperates with MST4 to orchestrate histamine-elicited acid secretion by phosphorylating ezrin at Ser-66 and Thr-567. Histamine stimulation activates PKA, which phosphorylates MST4 at Thr-178 and then promotes MST4 kinase activity. Interestingly, activated MST4 then phosphorylates ezrin prephosphorylated by PKA. Importantly, MST4 is important for acid secretion in parietal cells because either suppression of MST4 or overexpression of non-phosphorylatable MST4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, overexpressing MST4 phosphorylation-deficient ezrin results in an inhibition of gastric acid secretion. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ezrin signaling cascade to polarized epithelial secretion in gastric parietal cells. PMID:26405038

Naloxone fails to prolong seizure length in ECT.

PubMed

Rasmussen, K G; Pandurangi, A K

1999-12-01

Electroconvulsive shock (ECS) in animals has been shown to enhance endogenous opiate systems. The anticonvulsant effects of ECS are also partially blocked by the opiate receptor antagonist naloxone, leading some investigators to postulate that the anticonvulsant effects of ECS are mediated by activation of endogenous opiates. If such a phenomenon occurs in humans, then naloxone might prolong seizure length in electroconvulsive therapy (ECT). In the present study, nine patients were given 2.0 mg intravenous (i.v.) naloxone 2 minutes prior to one-half of their ECT treatments. Motor seizure length was measured via the cuff technique. EEG tracings were read by an investigator blind to naloxone status. There was no difference between the two groups in either EEG or nonblindly evaluated motor seizure length. It is concluded that a dose of 2 mg naloxone does not effectively increase seizure length in ECT.

Neuromodulation for mood and memory: from the engineering bench to the patient bedside

PubMed Central

Deng, Zhi-De; McClintock, Shawn M.; Oey, Nicodemus E.; Luber, Bruce; Lisanby, Sarah H.

2014-01-01

Brain stimulation, in the form of electroconvulsive therapy (ECT), has long been a gold standard treatment for depression, but today, the field of neuromodulation is rapidly changing with the advent of newer and more precise tools to alter neuroplasticity and to treat brain-based disorders. Now there are new means to induce focal seizures, as with magnetic seizure therapy (MST), or modifications to ECT. There are also surgical approaches to target brain circuits via implanted stimulators placed in the brain or on cranial nerves. Finally, there are noninvasive subconvulsive approaches for the transcranial application of either electric or magnetic fields. Collectively, these tools have transformed the face of neurotherapeutics and informed our understanding of the brain basis of complex neurobehavioral conditions. PMID:25222617

Studying Filamentary Currents with Thomson Scattering on MST

NASA Astrophysics Data System (ADS)

den Hartog, D. J.; Young, W. C.; Kubala, S. Z.

2016-10-01

The MST reversed-field pinch plasma generates bursts of toroidally localized magnetic activity associated with m = 0 modes resonant at the reversal surface near the plasma edge. Previously, using data from an array of edge magnetic probes, these bursts were connected to poloidal current filaments. Now the MST Thomson scattering diagnostic is being used to measure the net drift in the electron distribution due to these currents. An additional long-wavelength spectral bin has been added to several Thomson scattering polychromators, in addition to 5-7 pre-existing short wavelength spectral bins, to improve discrimination between shifted vs. broadened spectra. The bursts are examined in plasma conditions that display spontaneous periods of low tearing-mode activity, with higher confinement and higher temperatures that improve Thomson scattering measurement performance. This work is supported by the U.S. Department of Energy and the National Science Foundation.

Bursts of seizures in long-term recordings of human focal epilepsy

PubMed Central

Karoly, Philippa J.; Nurse, Ewan S.; Freestone, Dean R.; Ung, Hoameng; Cook, Mark J.; Boston, Ray

2017-01-01

Summary Objective We report on temporally clustered seizures detected from continuous long-term ambulatory human electroencephalographic data. The objective was to investigate short-term seizure clustering, which we have termed bursting, and consider implications for patient care, seizure prediction, and evaluating therapies. Methods Chronic ambulatory intracranial EEG data collected for the purpose of seizure prediction were annotated to identify seizure events. A detection algorithm was used to identify bursts of events. Burst events were compared to non-burst events to evaluate event dispersion, duration and dynamics. Results Bursts of seizures were present in six of fifteen patients, and detections were consistent over long term monitoring (> 2 years). Seizures within bursts are highly overdispersed compared to non-burst seizures. There was a complicated relationship between bursts and clinical seizures, although bursts were associated with multi-modal distributions of seizure duration, and poorer predictive outcomes. For three subjects, bursts demonstrated distinctive pre-ictal dynamics compared to clinical seizures. Significance We have previously hypothesized that there are distinct physiological pathways underlying short and long duration seizures. Here we show that burst seizures fall almost exclusively within the short population of seizure durations; however, a short duration was not sufficient to induce or imply bursting. We can therefore conclude that in addition to distinct mechanisms underlying seizure duration, there are separate factors regulating bursts of seizures. We show that bursts were a robust phenomenon in our patient cohort, which were consistent with overdispersed seizure rates, suggesting long-memory dynamics. PMID:28084639

Seizures

MedlinePlus

... Your Child Has a Seizure Print en español Crisis convulsivas (convulsiones) Seizures are caused by a sudden surge of electrical activity in the brain. A seizure usually affects how a person looks or acts for a ...

Forecasting Seizures in Dogs with Naturally Occurring Epilepsy

PubMed Central

Stead, S. Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H.; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W. Douglas; Litt, Brian; Worrell, Gregory A.

2014-01-01

Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), low-gamma (30–70 Hz), and high-gamma (70–180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring. PMID:24416133

Mechanisms of morphine enhancement of spontaneous seizure activity.

PubMed

Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam

2007-12-01

High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

Functional Neuroimaging of Spike-Wave Seizures

PubMed Central

Motelow, Joshua E.; Blumenfeld, Hal

2013-01-01

Generalized spike-wave seizures are typically brief events associated with dynamic changes in brain physiology, metabolism, and behavior. Functional magnetic resonance imaging (fMRI) provides a relatively high spatio-temporal resolution method for imaging cortical-subcortical network activity during spike-wave seizures. Patients with spike-wave seizures often have episodes of staring and unresponsiveness which interfere with normal behavior. Results from human fMRI studies suggest that spike-wave seizures disrupt specific networks in the thalamus and fronto-parietal association cortex which are critical for normal attentive consciousness. However, the neuronal activity underlying imaging changes seen during fMRI is not well understood, particularly in abnormal conditions such as seizures. Animal models have begun to provide important fundamental insights into the neuronal basis for fMRI changes during spike-wave activity. Work from these models including both fMRI and direct neuronal recordings suggest that, like in humans, specific cortical-subcortical networks are involved in spike-wave, while other regions are spared. Regions showing fMRI increases demonstrate correlated increases in neuronal activity in animal models. The mechanisms of fMRI decreases in spike-wave will require further investigation. A better understanding of the specific brain regions involved in generating spike-wave seizures may help guide efforts to develop targeted therapies aimed at preventing or reversing abnormal excitability in these brain regions, ultimately leading to a cure for this disorder. PMID:18839093

Absence seizure

MedlinePlus

Seizure - petit mal; Seizure - absence; Petit mal seizure; Epilepsy - absence seizure ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

28. VIEW SOUTH FROM SLC3W MST STATION 63. FOREGROUND LEFT: ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. VIEW SOUTH FROM SLC-3W MST STATION 63. FOREGROUND LEFT: THEODOLITE SHELTER (BLDG. 786) CENTER LEFT TO RIGHT: GLOBAL POSITIONING SYSTEM AZIMUTH STATION (BLDG. 775), PYROTECHNIC SHED (BLDG. 757), PORTABLE GUARD SHED, METEOROLOGICAL SHED (BLDG. 756), METEOROLOGICAL TOWER. BACKGROUND CENTER TO RIGHT: STORAGE SHED (BLDG. 776), LIQUID OXYGEN APRON, SLC-3E MST, TOP OF SLC-3E FUEL STORAGE TANK. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Antiepileptic effects of levetiracetam in a rodent neonatal seizure model.

PubMed

Talos, Delia M; Chang, Meayoung; Kosaras, Bela; Fitzgerald, Erin; Murphy, Andrew; Folkerth, Rebecca Dunn; Jensen, Frances E

2013-01-01

Neonatal seizures can result in chronic epilepsy and long-term behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used off-label for the therapy of neonatal seizures. Preclinical data regarding the acute or long-term efficacy of LEV are lacking. We tested the anticonvulsant efficacy of LEV in a rat model of hypoxia-induced neonatal seizures. In addition, we evaluated the protective effects of postnatal day (P)10 LEV treatment on later-life kainic acid (KA)-induced seizure susceptibility and seizure-induced neuronal injury. Western blot and immunohistochemistry were used to assess the developmental regulation of SV2A in the rat and human brain. LEV pretreatment at P10 significantly decreased the cumulative duration of behavioral and electrographic seizures at both 25 and 50 mg/kg. At P40, KA-induced seizures and neuronal loss were significantly diminished in rats previously treated with LEV. LEV target SV2A is present in both neonatal rat and human brain and increases steadily to adulthood. LEV suppressed acute seizures induced by perinatal hypoxia and diminished later-life seizure susceptibility and seizure-induced neuronal injury, providing evidence for disease modification. These results support consideration of a clinical trial of LEV in neonatal seizures.

Emulating the Visual Receptive Field Properties of MST Neurons with a Template Model of Heading Estimation

NASA Technical Reports Server (NTRS)

Perrone, John A.; Stone, Leland S.

1997-01-01

We have previously proposed a computational neural-network model by which the complex patterns of retinal image motion generated during locomotion (optic flow) can be processed by specialized detectors acting as templates for specific instances of self-motion. The detectors in this template model respond to global optic flow by sampling image motion over a large portion of the visual field through networks of local motion sensors with properties similar to neurons found in the middle temporal (MT) area of primate extrastriate visual cortex. The model detectors were designed to extract self-translation (heading), self-rotation, as well as the scene layout (relative distances) ahead of a moving observer, and are arranged in cortical-like heading maps to perform this function. Heading estimation from optic flow has been postulated by some to be implemented within the medial superior temporal (MST) area. Others have questioned whether MST neurons can fulfill this role because some of their receptive-field properties appear inconsistent with a role in heading estimation. To resolve this issue, we systematically compared MST single-unit responses with the outputs of model detectors under matched stimulus conditions. We found that the basic physiological properties of MST neurons can be explained by the template model. We conclude that MST neurons are well suited to support heading estimation and that the template model provides an explicit set of testable hypotheses which can guide future exploration of MST and adjacent areas within the primate superior temporal sulcus.

Urinary urge seizure semiology localization by intracranial monitoring.

PubMed

Rengarajan, Ronak; Shamim, Sadat

2018-01-01

Seizures may present with many different symptom complexes. Seizure semiologies have localization value when contemplating surgical therapies. Epilepsy presenting as a desire to micturate is exceedingly rare, with only a handful of published cases. We present a patient who had initially unexplained childhood urinary urge that progressed into lapses of memory and confusion that was eventually diagnosed as epilepsy in adulthood. Due to refractoriness to medical management, our patient's epileptic focus was localized through both noninvasive and invasive subdural electrode arrays to the nondominant medial temporal lobe and successfully treated with an amygdalohippocampectomy. Only one other case of ictal urinary urgency seizures has been recorded with intracranial electroencephalogram monitoring in the literature.

Urinary urge seizure semiology localization by intracranial monitoring

PubMed Central

Rengarajan, Ronak; Shamim, Sadat

2018-01-01

ABSTRACT Seizures may present with many different symptom complexes. Seizure semiologies have localization value when contemplating surgical therapies. Epilepsy presenting as a desire to micturate is exceedingly rare, with only a handful of published cases. We present a patient who had initially unexplained childhood urinary urge that progressed into lapses of memory and confusion that was eventually diagnosed as epilepsy in adulthood. Due to refractoriness to medical management, our patient's epileptic focus was localized through both noninvasive and invasive subdural electrode arrays to the nondominant medial temporal lobe and successfully treated with an amygdalohippocampectomy. Only one other case of ictal urinary urgency seizures has been recorded with intracranial electroencephalogram monitoring in the literature. PMID:29686574

Seizure ending signs in patients with dyscognitive focal seizures.

PubMed

Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

2015-09-01

Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

[Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

PubMed

Sokić, D; Janković, S M

1994-01-01

Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

Effects of the addition of remifentanil to propofol anesthesia on seizure length and postictal suppression index in electroconvulsive therapy.

PubMed

Porter, Richard; Booth, David; Gray, Hamish; Frampton, Chris

2008-09-01

Propofol is a widely used anesthetic agent for electroconvulsive therapy (ECT). However, there are concerns that its anticonvulsant effect may interfere with the efficacy of ECT. We aimed to investigate the effects on seizure activity of the addition of the opiate remifentanil to propofol anesthesia for ECT. A retrospective analysis of 633 treatments in 73 patients was conducted. At each treatment, patients had received anesthesia with propofol alone or propofol plus remifentanil, depending on which anesthetist was providing anesthesia. Analysis of variance was performed to examine the effects of the anesthetic used, the electrode placement, the dose of electricity administered, and the stage in the course of treatment. Dependent variables were electroencephalogram seizure length and postictal suppression index (PSI). Addition of remifentanil resulted in a small but significantly lower dose of propofol being used to induce unconsciousness. Addition of remifentanil affected seizure length, mainly related to an effect when placement was right unilateral (F = 5.70; P = 0.017). There was also a significantly increased PSI (F = 4.3; P = 0.039), which was not dependent on dose or on placement. The data suggest that addition of remifentanil to propofol anesthesia significantly alters seizure indices. This may be secondary to a reduction in the amount of propofol required or to an independent effect of remifentanil. The increase in PSI in particular suggests that addition of remifentanil may improve clinical response. However, this can only be examined in a randomized controlled trial.

Use of an image-guided robotic radiosurgery system for the treatment of canine nonlymphomatous nasal tumors.

PubMed

Glasser, Seth A; Charney, Sarah; Dervisis, Nikolaos G; Witten, Matthew R; Ettinger, Susan; Berg, Jason; Joseph, Richard

2014-01-01

An image-guided robotic stereotactic radiosurgery (SRS) system can be used to deliver curative-intent radiation in either single fraction or hypofractionated doses. Medical records for 19 dogs with nonlymphomatous nasal tumors treated with hypofractionated image-guided robotic stereotactic body radiotherapy (SBRT), either with or without adjunctive treatment, were retrospectively analyzed for survival and prognostic factors. Median survival time (MST) was evaluated using Kaplan-Meier survival curves. Age, breed, tumor type, stage, tumor size, prescribed radiation dose, and heterogeneity index were analyzed for prognostic significance. Dogs were treated with three consecutive-day, 8-12 gray (Gy) fractions of image-guided robotic SBRT. Overall MST was 399 days. No significant prognostic factors were identified. Acute side effects were rare and mild. Late side effects included one dog with an oronasal fistula and six dogs with seizures. In three of six dogs, seizures were a presenting complaint prior to SBRT. The cause of seizures in the remaining three dogs could not be definitively determined due to lack of follow-up computed tomography (CT) imaging. The seizures could have been related to either progression of disease or late radiation effect. Results indicate that image-guided robotic SBRT, either with or without adjunctive therapy, for canine nonlymphomatous nasal tumors provides comparable survival times (STs) to daily fractionated megavoltage radiation with fewer required fractions and fewer acute side effects.

A Role for MST Neurons in Heading Estimation

NASA Technical Reports Server (NTRS)

Stone, L. S.; Perrone, J. A.

1994-01-01

A template model of human visual self-motion perception, which uses neurophysiologically realistic "heading detectors", is consistent with numerous human psychophysical results including the failure of humans to estimate their heading (direction of forward translation) accurately under certain visual conditions. We tested the model detectors with stimuli used by others in single-unit studies. The detectors showed emergent properties similar to those of MST neurons: (1) Sensitivity to non-preferred flow; Each detector is tuned to a specific combination of flow components and its response is systematically reduced by the addition of nonpreferred flow, and (2) Position invariance; The detectors maintain their apparent preference for particular flow components over large regions of their receptive fields. It has been argued that this latter property is incompatible with MST playing a role in heading perception. The model however demonstrates how neurons with the above response properties could still support accurate heading estimation within extrastriate cortical maps.

Seizures and Teens: Stress, Sleep, & Seizures

ERIC Educational Resources Information Center

Shafer, Patricia Osborne

2007-01-01

Most parents are used to erratic sleep patterns and mood swings in their teenagers. When these occur in an adolescent with seizures, however, the parent may wonder if sleep and mood problems are related to seizures. Sorting out the cause and effects of sleep in an adolescent with seizures can be confusing. Since stress can be a contributor to both…

Termination of seizure clusters is related to the duration of focal seizures.

PubMed

Ferastraoaru, Victor; Schulze-Bonhage, Andreas; Lipton, Richard B; Dümpelmann, Matthias; Legatt, Alan D; Blumberg, Julie; Haut, Sheryl R

2016-06-01

Clustered seizures are characterized by shorter than usual interseizure intervals and pose increased morbidity risk. This study examines the characteristics of seizures that cluster, with special attention to the final seizure in a cluster. This is a retrospective analysis of long-term inpatient monitoring data from the EPILEPSIAE project. Patients underwent presurgical evaluation from 2002 to 2009. Seizure clusters were defined by the occurrence of at least two consecutive seizures with interseizure intervals of <4 h. Other definitions of seizure clustering were examined in a sensitivity analysis. Seizures were classified into three contextually defined groups: isolated seizures (not meeting clustering criteria), terminal seizure (last seizure in a cluster), and intracluster seizures (any other seizures within a cluster). Seizure characteristics were compared among the three groups in terms of duration, type (focal seizures remaining restricted to one hemisphere vs. evolving bilaterally), seizure origin, and localization concordance among pairs of consecutive seizures. Among 92 subjects, 77 (83%) had at least one seizure cluster. The intracluster seizures were significantly shorter than the last seizure in a cluster (p = 0.011), whereas the last seizure in a cluster resembled the isolated seizures in terms of duration. Although focal only (unilateral), seizures were shorter than seizures that evolved bilaterally and there was no correlation between the seizure type and the seizure position in relation to a cluster (p = 0.762). Frontal and temporal lobe seizures were more likely to cluster compared with other localizations (p = 0.009). Seizure pairs that are part of a cluster were more likely to have a concordant origin than were isolated seizures. Results were similar for the 2 h definition of clustering, but not for the 8 h definition of clustering. We demonstrated that intracluster seizures are short relative to isolated seizures and terminal seizures. Frontal

Emulating the visual receptive-field properties of MST neurons with a template model of heading estimation

NASA Technical Reports Server (NTRS)

Perrone, J. A.; Stone, L. S.

1998-01-01

We have proposed previously a computational neural-network model by which the complex patterns of retinal image motion generated during locomotion (optic flow) can be processed by specialized detectors acting as templates for specific instances of self-motion. The detectors in this template model respond to global optic flow by sampling image motion over a large portion of the visual field through networks of local motion sensors with properties similar to those of neurons found in the middle temporal (MT) area of primate extrastriate visual cortex. These detectors, arranged within cortical-like maps, were designed to extract self-translation (heading) and self-rotation, as well as the scene layout (relative distances) ahead of a moving observer. We then postulated that heading from optic flow is directly encoded by individual neurons acting as heading detectors within the medial superior temporal (MST) area. Others have questioned whether individual MST neurons can perform this function because some of their receptive-field properties seem inconsistent with this role. To resolve this issue, we systematically compared MST responses with those of detectors from two different configurations of the model under matched stimulus conditions. We found that the characteristic physiological properties of MST neurons can be explained by the template model. We conclude that MST neurons are well suited to support self-motion estimation via a direct encoding of heading and that the template model provides an explicit set of testable hypotheses that can guide future exploration of MST and adjacent areas within the superior temporal sulcus.

The involvement of audio-motor coupling in the music-supported therapy applied to stroke patients.

PubMed

Rodriguez-Fornells, Antoni; Rojo, Nuria; Amengual, Julià L; Ripollés, Pablo; Altenmüller, Eckart; Münte, Thomas F

2012-04-01

Music-supported therapy (MST) has been developed recently to improve the use of the affected upper extremity after stroke. MST uses musical instruments, an electronic piano and an electronic drum set emitting piano sounds, to retrain fine and gross movements of the paretic upper extremity. In this paper, we first describe the rationale underlying MST, and we review the previous studies conducted on acute and chronic stroke patients using this new neurorehabilitation approach. Second, we address the neural mechanisms involved in the motor movement improvements observed in acute and chronic stroke patients. Third, we provide some recent studies on the involvement of auditory-motor coupling in the MST in chronic stroke patients using functional neuroimaging. Finally, these ideas are discussed and focused on understanding the dynamics involved in the neural circuit underlying audio-motor coupling and how functional connectivity could help to explain the neuroplastic changes observed after therapy in stroke patients. © 2012 New York Academy of Sciences.

Identifying seizure clusters in patients with psychogenic nonepileptic seizures.

PubMed

Baird, Grayson L; Harlow, Lisa L; Machan, Jason T; Thomas, Dave; LaFrance, W C

2017-08-01

The present study explored how seizure clusters may be defined for those with psychogenic nonepileptic seizures (PNES), a topic for which there is a paucity of literature. The sample was drawn from a multisite randomized clinical trial for PNES; seizure data are from participants' seizure diaries. Three possible cluster definitions were examined: 1) common clinical definition, where ≥3 seizures in a day is considered a cluster, along with two novel statistical definitions, where ≥3 seizures in a day are considered a cluster if the observed number of seizures statistically exceeds what would be expected relative to a patient's: 1) average seizure rate prior to the trial, 2) observed seizure rate for the previous seven days. Prevalence of clusters was 62-68% depending on cluster definition used, and occurrence rate of clusters was 6-19% depending on cluster definition. Based on these data, clusters seem to be common in patients with PNES, and more research is needed to identify if clusters are related to triggers and outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Measuring power loss due to radiation and charge exchange in MST

NASA Astrophysics Data System (ADS)

Waksman, Jeff; Chapman, Brett; Fiksel, Gennady; Nonn, Paul

2008-11-01

An array of photodiode-pyrobolometer pairs will be placed on MST to measure the spatial structure of the radiated power and charge exchange. Photodiodes (XUV detectors) measure photonic radiated power from about 10eV to 10keV, while pyrobolometers (thermal detectors) measure both photonic radiated power and power carried by charge-exchange neutrals. Compared to other thermal detectors, pyrobolometers have very good time resolution. To accurately calibrate the individual detectors, an electron gun producing a modulated square wave output has been set up to carefully calibrate each new pyrobolometer to be placed on MST. When viewing the MST plasma, subtraction of the data from the photodiode-pyrobolometer pairs allows one to determine the net power loss due to charge-exchange neutrals. These measurements are important in the calculation of ion energy balance, and it is potentially important in understanding the difference in the temperatures reached by majority and impurity ions during magnetic-reconnection ion-heating events. Since toroidal and poloidal asymmetries in charge exchange are possible, a distributed array of detector pairs will facilitate a better estimate of global power loss. Work supported by the U.S.D.O.E. .

Bearing Witness: Personal and Poetic Descriptions of Seizure Therapy.

PubMed

Fink, Max

2016-03-01

Many voices comment on personal experience with induced seizures. The encouraging voices of professionals are contrasted with those in theater and film that stigmatize the treatments. The negative images have done much to support restrictive legislation.

Prevalence of seizures in children infected with human immunodeficiency virus.

PubMed

Samia, Pauline; Petersen, Reneva; Walker, Kathleen G; Eley, Brian; Wilmshurst, Jo M

2013-03-01

A retrospective study of 354 human immunodeficiency virus (HIV)-infected patients identified a subgroup of 27 children with seizures (7.6%, 95% confidence interval: 5.1%-10.9%). Of the total group, 13% (n = 46) had identifiable neurologic deficits and 30% (n = 107) had developmental delay. Both observations were significantly more frequent in the subgroup of patients with seizures (P < .001). The median age of patients with seizures was 20 months (range, 8-87 months) and the median baseline CD4 percentage was 13.5% (interquartile range, 8%-23%). Seizures were treated with sodium valproate (n = 11), phenobarbital (n = 3), diazepam (n = 2), lamotrigine (n = 1), and carbamazepine (n = 1). Combination therapy was required for 5 children. Suboptimal valproic acid levels were recorded for 3 patients. When resources are available, antiepileptic drug level monitoring is advised for children who require both antiepileptic and antiretroviral medications to facilitate optimal seizure management.

Modeling Seizure Self-Prediction: An E-Diary Study

PubMed Central

Haut, Sheryl R.; Hall, Charles B.; Borkowski, Thomas; Tennen, Howard; Lipton, Richard B.

2013-01-01

Purpose A subset of patients with epilepsy successfully self-predicted seizures in a paper diary study. We conducted an e-diary study to ensure that prediction precedes seizures, and to characterize the prodromal features and time windows that underlie self-prediction. Methods Subjects 18 or older with LRE and ≥3 seizures/month maintained an e-diary, reporting AM/PM data daily, including mood, premonitory symptoms, and all seizures. Self-prediction was rated by, “How likely are you to experience a seizure [time frame]”? Five choices ranged from almost certain (>95% chance) to very unlikely. Relative odds of seizure (OR) within time frames was examined using Poisson models with log normal random effects to adjust for multiple observations. Key Findings Nineteen subjects reported 244 eligible seizures. OR for prediction choices within 6hrs was as high as 9.31 (1.92,45.23) for “almost certain”. Prediction was most robust within 6hrs of diary entry, and remained significant up to 12hrs. For 9 best predictors, average sensitivity was 50%. Older age contributed to successful self-prediction, and self-prediction appeared to be driven by mood and premonitory symptoms. In multivariate modeling of seizure occurrence, self-prediction (2.84; 1.68,4.81), favorable change in mood (0.82; 0.67,0.99) and number of premonitory symptoms (1,11; 1.00,1.24) were significant. Significance Some persons with epilepsy can self-predict seizures. In these individuals, the odds of a seizure following a positive prediction are high. Predictions were robust, not attributable to recall bias, and were related to self awareness of mood and premonitory features. The 6-hour prediction window is suitable for the development of pre-emptive therapy. PMID:24111898

Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures.

PubMed

Töllner, Kathrin; Twele, Friederike; Löscher, Wolfgang

2016-04-01

Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy therapy, so that development of more effective AEDs is an unmet clinical need. Several rat and mouse models of epilepsy with spontaneous difficult-to-treat seizures exist, but because testing of antiseizure drug efficacy is extremely laborious in such models, they are only rarely used in the development of novel AEDs. Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy. In the present study, we compared the effects of five AEDs (valproate, phenobarbital, diazepam, lamotrigine, levetiracetam) on the pentylenetetrazole (PTZ) seizure threshold in mice that were made epileptic by pilocarpine. Experiments were started 6 weeks after a pilocarpine-induced status epilepticus. At this time, control seizure threshold was significantly lower in epileptic than in nonepileptic animals. Unexpectedly, only one AED (valproate) was less effective to increase seizure threshold in epileptic vs. nonepileptic mice, and this difference was restricted to doses of 200 and 300 mg/kg, whereas the difference disappeared at 400mg/kg. All other AEDs exerted similar seizure threshold increases in epileptic and nonepileptic mice. Thus, induction of acute seizures with PTZ in mice pretreated with pilocarpine does not provide an effective and valuable surrogate method to screen drugs for antiseizure efficacy in a model of difficult-to-treat chronic epilepsy as previously suggested from experiments with this approach in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Electron Bernstein Wave Studies in MST

NASA Astrophysics Data System (ADS)

Seltzman, Andrew; Anderson, Jay; Forest, Cary; Nonn, Paul; Thomas, Mark; Almagri, Abdulgader; Chapman, Brett; Dubois, Ami; Goetz, John; McCollam, Karsten

2015-11-01

The RFP plasma is inaccessible to ECRH, requiring the electron Bernstein wave (EBW) for edge localized heating and current drive. MST is capable of generating RFPs or overdense tokamaks with Bt(0) ~ 0.08-0.14T in which a 5.55 GHz RF source (450kW, 2ms pulse) can heat at fundamental and harmonic EC resonances. The design of a suitable antenna is challenging in the RFP due to a magnetic field geometry that requires a low-field-side launch. The small vacuum gap between the close-fitting conducting shell and plasma leads to substantial antenna-plasma interaction. A minimized port hole size is required to limit error fields. Even so the port hole induced magnetic field perturbation in the antenna near-field that affects the mode conversion process and introduces EC resonances. A 5cm diameter cylindrical antenna centered in 5cm and 11cm diameter portholes is used. A multi-chord time-resolved x-ray detector and GENRAY ray tracing verifies EBW heating at higher harmonics in an MST tokamak with 10-40keV detected x-ray energies. Evidence of RF-induced emission from absorption at higher harmonics (4th / 5th) in low current RFP discharges has been observed. Simultaneous reflected power changes correspond to termination of x-ray emission indicating power limits. Work supported by USDOE.

M Current-Based Therapies for Nerve Agent Seizures

DTIC Science & Technology

2013-07-01

Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS Seizures, status epilepticus Cholinergic, M Current...Channel openers in cholinergic overstimulation-induced status epilepticus . Body: We proposed to study the effects of organophosphates and muscarinic...test whether drugs that open M channels would terminate status epilepticus induced by an organophosphate and cholinergic agonist (Li/Pilocarpine). Two

Economic Impact of Multisystemic Therapy for Child Abuse and Neglect.

PubMed

Dopp, Alex R; Schaeffer, Cindy M; Swenson, Cynthia Cupit; Powell, Jennifer S

2018-04-04

This study evaluated the economics of Multisystemic Therapy for Child Abuse and Neglect (MST-CAN) by applying the Washington State Institute for Public Policy (WSIPP) cost-benefit model to data from a randomized effectiveness trial with 86 families (Swenson et al. in JFP 24:497-507, 2010b). The net benefit of MST-CAN, versus enhanced outpatient treatment, was $26,655 per family at 16 months post-baseline. Stated differently, every dollar spent on MST-CAN recovered $3.31 in savings to participants, taxpayers, and society at large. Policymakers and public service agencies should consider these findings when making investments into interventions for high-need families involved with child protective services.

Seizure outcomes in non-resective epilepsy surgery: An update

PubMed Central

Englot, Dario J.; Birk, Harjus; Chang, Edward F.

2016-01-01

In approximately 30% of patients with epilepsy, seizures are refractory to medical therapy, leading to significant morbidity and increased mortality. Substantial evidence has demonstrated the benefit of surgical resection in patients with drug-resistant focal epilepsy, and in the present journal, we recently reviewed seizure outcomes in resective epilepsy surgery. However, not all patients are candidates for or amenable to open surgical resection for epilepsy. Fortunately, several non-resective surgical options are now available at various epilepsy centers, including novel therapies which have been pioneered in recent years. Ablative procedures such as stereotactic laser ablation and stereotactic radiosurgery offer minimally invasive alternatives to open surgery with relatively favorable seizure outcomes, particularly in patients with mesial temporal lobe epilepsy. For certain individuals who are not candidates for ablation or resection, palliative neuromodulation procedures such as vagus nerve stimulation, deep brain stimulation, or responsive neurostimulation may result in a significant decrease in seizure frequency and improved quality of life. Finally, disconnection procedures such as multiple subpial transections and corpus callosotomy continue to play a role in select patients with an eloquent epileptogenic zone or intractable atonic seizures, respectively. Overall, open surgical resection remains the gold standard treatment for drug-resistant epilepsy, although it is significantly under-utilized. While non-resective epilepsy procedures have not replaced the need for resection, there is hope that these additional surgical options will increase the number of patients who receive treatment for this devastating disorder - particularly individuals who are not candidates for or who have failed resection. PMID:27206422

Suppression of high-energy electrons generated in both disrupting and sustained MST tokamak plasmas

NASA Astrophysics Data System (ADS)

Pandya, M. D.; Chapman, B. E.; Munaretto, S.; Cornille, B. S.; McCollam, K. J.; Sovinec, C. R.; Dubois, A. M.; Almagri, A. F.; Goetz, J. A.

2017-10-01

High-energy electrons appearing during MST tokamak plasma disruptions are rapidly lost from the plasma due apparently to internal MHD activity. Work has just recently begun on generating and diagnosing disruptions in MST tokamak plasmas. Initial measurements show the characteristic drop in central temperature and density preceding a quench of the plasma current. This corresponds to a burst of dominantly n=1 MHD activity, which is accompanied by a short-lived burst of high-energy electrons. The short-lived nature of these electrons is suspected to be due to stochastic transport associated with the increased MHD. Earlier work shows that runaway electrons generated in low density, sustained plasmas are suppressed by a sufficiently large m=3 RMP in plasmas with q(a) <3. RMPs of various poloidal mode number can be generated with an array of saddle coils wound around the vertical insulated gap in MST's thick conducting shell. With an m=3 RMP, the degree of runaway suppression increases with RMP amplitude, while an m=1 RMP has little effect on the runaways. Nonlinear MHD modeling with NIMROD of these MST plasmas indicates increased stochasticity with an m=3 RMP, while no such increase in stochasticity is observed with an m=1 RMP. Work supported by US DOE.

Program of the Antarctic Syowa MST/IS radar (PANSY)

NASA Astrophysics Data System (ADS)

Sato, K.; Tsutsumi, M.; Sato, T.; Saito, A.; Tomikawa, Y.; Aso, T.; Yamanouchi, T.; Ejiri, M.

We have been promoting a project to introduce the first MST Mesosphere-Stratosphere-Troposphere IS Incoherent Scatter radar which is a VHF pulse Doppler radar in the Antarctic to Syowa Station 39E 69S Program of the Antarctic Syowa MST IS Radar PANSY as an important station observing the earth s environment with the aim to catch the climate change signals that the Antarctic atmosphere shows This radar consists of about 1000 crossed Yagi antennas having a peak power of 500kW which allows us to observe the Antarctic atmosphere with fine resolution and good accuracy in a wide height range of 1-500 km The interaction of the neutral atmosphere with the ionosphere and magnetosphere as well as the global-scale atmospheric circulation including the low and middle latitude regions are also targets of PANSY The observation data with high resolution and good accuracy obtained by the PANSY radar are also valuable from the viewpoint of certification of the reality of phenomena simulated by high-resolution numerical models The scientific importance of PANSY is discussed and resolved by international research organizations of IUGG URSI SCAR SCOSTEP and SPARC and documented in a report by Council of Science and Technology Policy in Japan One major issue for the operation of the MST IS radar at an isolated place such as Syowa Station is the reduction of power consumption We have developed a new power-efficient transmitter class-E amplifier and successfully reduced the needed power consumption to an acceptable

Stimulation of the nervous system for the management of seizures: current and future developments.

PubMed

Murphy, Jerome V; Patil, Arunangelo

2003-01-01

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for

Absence Seizure (Petit Mal Seizure)

MedlinePlus

... people have many episodes daily, which interfere with school or daily activities. A child may have absence seizures for some time before an adult notices the seizures, because they're so brief. A decline in a child's learning ability may be the first sign of this ...

Seizures presenting as incessant laughter: a case of gelastic epilepsy.

PubMed

Holmes, Christina M; Goldman, Mitchell J

2012-12-01

Gelastic seizures are defined as seizure activity manifesting as laughter inappropriate to the situation, with supporting evidence on electroencephalogram or magnetic resonance imaging. Gelastic seizures are most commonly reported in patients with hypothalamic hamartomas causing precocious puberty. The differential diagnosis of incessant laughter is important to recognize in the Emergency Department, as some conditions warrant immediate treatment and others require further diagnostic work-up with implications for the entire family. The background and pathophysiology of gelastic epilepsy will be discussed. The case of a previously healthy girl with acute onset of incessant laughter is reported. This patient was diagnosed with a clinical case of gelastic seizures. This case illustrates the importance of recognizing this form of seizures for accurate treatment and follow-up. This case report illustrates the importance of a broad differential for a patient presenting emergently with uncontrollable laughter. Gelastic epilepsy is relatively rare but requires further work-up and often may require chronic therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Psychological interventions for psychogenic non-epileptic seizures: A meta-analysis.

PubMed

Carlson, Perri; Nicholson Perry, Kathryn

2017-02-01

The aim of this meta-analysis is to evaluate and synthesize the available evidence from the previous 20 years regarding the utility of psychological interventions in the management of psychogenic non-epileptic seizures (PNES). Studies were retrieved from MEDLINE via OvidSP and PsychINFO. Selection criteria included controlled and before-after non-controlled studies including case series, using seizure frequency as an outcome measurement. Studies were required to assess one or more types of psychological intervention for the treatment of PNES in adults. Data from 13 eligible studies was pooled to examine the effectiveness of psychological interventions in treating PNES on two primary outcomes: seizure reduction of 50% or more and seizure freedom. A meta-analysis was conducted with data extracted from 228 participants with PNES. Interventions reviewed in the analysis included CBT, psychodynamic therapy, paradoxical intention therapy, mindfulness and psychoeducation and eclectic interventions. Meta-analysis synthesized data from 13 studies with a total of 228 participants with PNES, of varied gender and age. Results showed 47% of people with PNES are seizure free upon completion of a psychological intervention. Additional meta-analysis synthesized data from 10 studies with a total of 137 participants with PNES. This analysis found 82% of people with PNES who complete psychological treatment experience a reduction in seizures of at least 50%. The studies identified for this analysis were diverse in nature and quality. The findings highlight the potential for psychological interventions as a favorable alternative to the current lack of treatment options offered to people with PNES. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Biomarkers related with seizure risk in glioma patients: A systematic review.

PubMed

Zhou, Xing-Wang; Wang, Xiang; Yang, Yuan; Luo, Jie-Wen; Dong, Hui; Liu, Yan-Hui; Mao, Qing

2016-12-01

Increasing evidence indicates that genetic biomarkers play important roles in the development of glioma-associated seizures. Thus, we performed a systematic review to summarise biomarkers that are associated with seizures in glioma patients. An electronic literature search of public databases (PubMed, Embase and Medline) was performed using the keywords glioma, seizure and epilepsy. A totall of 26 eligible studies with 2224 cases were included in this systematic review of publications to 20 June, 2016. Genetic biomarkers such as isocitrate dehydrogenase 1 (IDH1) mutations, low expression of excitatory amino acid transporter 2 (EAAT2), high xCT expression, overexpression of adenosine kinase (ADK) and low expression of very large G-protein-coupled receptor-1 (VLGR1) are primarily involved in synaptic transmission, whereas BRAF mutations, epidermal growth factor receptor (EGFR) amplification, miR-196b expression and low ki-67 expression are associated with regulation of cell proliferation. However, there is limited evidence regarding the roles of RAD50 interactor 1 (RINT1) and olig2 in epileptogenesis among glioma patients. Glioma-related seizure was related to the dysfunction of tumor microenvironment. Our findings may provide new mechanistic insights into targeted therapy for glioma-related seizures and may result in the development of multi-target therapies. Copyright © 2016 Elsevier B.V. All rights reserved.

What Works for Whom? Gender Differences in Intake Characteristics and Treatment Outcomes Following Multisystemic Therapy

ERIC Educational Resources Information Center

Ogden, Terje; Hagen, Kristine Amlund

2009-01-01

Aims of the study: We investigated whether girls and boys had similar referral symptoms and background characteristics at intake to Multisystemic Therapy (MST) and whether adolescent girls with serious behavior problems benefited as much from MST treatment as did boys. We also examined gender differences in rate of co-morbidity at intake and…

A Randomized Controlled Trial of Multisystemic Therapy and a Statutory Therapeutic Intervention for Young Offenders

ERIC Educational Resources Information Center

Butler, Stephen; Baruch, Geoffrey; Hickey, Nicole; Fonagy, Peter

2011-01-01

Objective: To evaluate whether Multisystemic Therapy (MST) is more effective in reducing youth offending and out-of-home placement in a large, ethnically diverse, urban U.K. sample than an equally comprehensive management protocol; and to determine whether MST leads to broader improvements in youth sociality and in mediators believed to be…

Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients.

PubMed

Bumb, Jan Malte; Aksay, Suna Su; Janke, Christoph; Kranaster, Laura; Geisel, Olga; Gass, Peter; Hellweg, Rainer; Sartorius, Alexander

2015-04-01

Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.

Proton MR spectroscopy in patients with acute temporal lobe seizures.

PubMed

Castillo, M; Smith, J K; Kwock, L

2001-01-01

Decreases in N-acetyl aspartate (NAA) as seen by proton MR spectroscopy are found in hippocampal sclerosis, and elevated levels of lipids/lactate have been observed after electroconvulsive therapy. Our purpose was to determine whether increased levels of lipids/lactate are found in patients with acute seizures of hippocampal origin. Seventeen patients with known temporal lobe epilepsy underwent proton MR spectroscopy of the mesial temporal lobes within 24 hours of their last seizure. Four of them were restudied when they were seizure-free. Five healthy individuals were used as control subjects. All MR spectroscopy studies were obtained using a single-voxel technique with TEs of 135 and 270. The relationship between the presence of lipids/lactate and seizures was tested using Fisher's exact test. Mean and standard deviations for NAA/creatine (Cr) were obtained in the hippocampi in patients with seizures on initial and follow-up studies and these values were compared with those in the control subjects. Seizure lateralization was obtained in 15 patients. Of the 17 seizure locations that involved hippocampi, 16 showed lipids/lactate by proton MR spectroscopy. Of the 13 hippocampi not directly affected by seizures, 10 showed no lipids/lactate and three showed lipids/lactate. The relationship between lipids/lactate and seizure location was confirmed. A comparison of NAA/Cr ratios for the involved hippocampi with those in control subjects showed significant differences on initial MR spectroscopy; however, no significant difference was found between acute and follow-up NAA/Cr ratios in hippocampi affected by seizures. Lipids/lactate were present in the hippocampi of patients with acute seizures and decreased when the patients were seizure-free. Thus, lipids/lactate may be a sensitive marker for acute temporal lobe seizures.

10. PARTIAL VIEW OF SOUTH FACE OF MST AND BRIDGE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. PARTIAL VIEW OF SOUTH FACE OF MST AND BRIDGE CRANE MOVED TO ITS SOUTHERN LIMIT - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

11. PARTIAL VIEW OF NORTH FACE OF MST AND BRIDGE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. PARTIAL VIEW OF NORTH FACE OF MST AND BRIDGE CRANE MOVED TO ITS NORTHERN LIMIT - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Partial (focal) seizure

MedlinePlus

... Jacksonian seizure; Seizure - partial (focal); Temporal lobe seizure; Epilepsy - partial seizures ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

Febrile seizures

MedlinePlus

... proper care. Occasionally, a provider will prescribe a medicine called diazepam to prevent or treat febrile seizures that occur more than once. However, no drug is completely effective in preventing febrile seizures. Alternative Names Seizure - fever induced; Febrile convulsions Patient Instructions ...

Seizures and Teens: Sorting Out Seizures--Part Two

ERIC Educational Resources Information Center

Devinsky, Orrin

2006-01-01

In adolescents, diagnosing seizures can be challenging and can lead to many pitfalls. Because seizures are episodic and unpredictable events, they usually do not occur in the doctor's office. Thus, a diagnosis of epilepsy is usually based on information presented by the person with seizures and their family. Together with results of diagnostic…

Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet.

PubMed

Taub, Katherine S; Kessler, Sudha Kilaru; Bergqvist, A G Christina

2014-04-01

Few studies have examined the long-term sustainability of complete seizure freedom on the ketogenic diet (KD). The purpose of this study was to describe the risk of seizure recurrence in children who achieved at least 1 month of seizure freedom on the KD, and to assess clinical features associated with sustained seizure freedom. Records of patients initiated on the KD at The Children's Hospital of Philadelphia (CHOP) from 1991 to 2009 were reviewed. Subjects who attained seizure freedom for at least 1 month within 2 years were included in the study. Seizure frequency was recorded based on caregiver-reported seizure diaries as unchanged, improved, or worse compared to baseline. Those patients with seizure freedom ≥1 year were compared to those with seizure freedom <1 year in terms of demographics, age of seizure onset, number of antiepileptic drugs (AEDs) prior to KD, and epilepsy classification. Of 276 patients initiated on the KD, 65 patients (24%) attained seizure freedom for a minimum of 1 month. The majority of these patients had daily seizures. The median time to seizure freedom after KD initiation was 1.5 months. Seizures recurred in 53 patients (82%), with a median time to seizure recurrence of 3 months. However, seizure frequency after initial recurrence remained far less than baseline. No clinical features were identified as risk factors for seizure recurrence. Seizure recurrence on the KD after 1 month of seizure freedom most often occurred as occasional breakthrough seizures and not a return to baseline seizure frequency. This study provides evidence to support the continued use of the KD in patients with initial seizure freedom even after breakthrough seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Transtracheal oxygen therapy.

PubMed

Christopher, Kent L; Schwartz, Michael D

2011-02-01

Transtracheal oxygen therapy (TTO) has been used for long-term oxygen therapy for nearly 30 years. Numerous investigators have explored the potential benefits of TTO. Those results are reviewed in this article. TTO is best viewed not as a catheter but as a program for care. This article discusses patient selection for TTO. Publications evaluating complications are reviewed. In the past, a modified Seldinger technique (MST) was used for the creation of the tracheocutaneous fistula. The rather long program required for tract maturation with MST was labor-intensive and required substantial patient education and monitoring, particularly during the immature tract phase. Minor complications were not infrequent. More recently, the Lipkin method has been used to create a surgical tract under conscious sedation with topical anesthesia. The procedure is safe and well tolerated. Transtracheal oxygen is initiated the day following the procedure. Similarly, the tract matures in 7 to 10 days rather than the 6 to 8 weeks with MST. More rapid healing time and superior tract characteristics substantially reduce complications. The TTO program tailored for the Lipkin procedure is shortened, streamlined, and much less labor-intensive. Optimal outcomes with the TTO program require a committed pulmonologist, respiratory therapist, nurse, and surgeon (for the Lipkin procedure). This article discusses new directions in the use of transtracheal gas delivery, including the management of obstructive sleep apnea. Preliminary investigations regarding transtracheal augmented ventilation are presented. These include nocturnal use in severe chronic lung disease and liberation from prolonged mechanical ventilation.

Different ketogenesis strategies lead to disparate seizure outcomes.

PubMed

Dolce, Alison; Santos, Polan; Chen, Weiran; Hoke, Ahmet; Hartman, Adam L

2018-07-01

Despite the introduction of new medicines to treat epilepsy over the last 50 years, the number of patients with poorly-controlled seizures remains unchanged. Metabolism-based therapies are an underutilized treatment option for this population. We hypothesized that two different means of systemic ketosis, the ketogenic diet and intermittent fasting, would differ in their acute seizure test profiles and mitochondrial respiration. Male NIH Swiss mice (aged 3-4 weeks) were fed for 12-13 days using one of four diet regimens: ketogenic diet (KD), control diet matched to KD for protein content and micronutrients (CD), or CD with intermittent fasting (24 h feed/24 h fast) (CD-IF), tested post-feed or post-fast. Mice were subject to the 6 Hz threshold test or, in separate cohorts, after injection of kainic acid in doses based on their weight (Cohort I) or a uniform dose regardless of weight (Cohort II). Mitochondrial respiration was tested in brain tissue isolated from similarly-fed seizure-naïve mice. KD mice were protected against 6 Hz-induced seizures but had more severe seizure scores in the kainic acid test (Cohorts I & II), the opposite of CD-IF mice. No differences were noted in mitochondrial respiration between diet regimens. KD and CD-IF do not share identical antiseizure mechanisms. These differences were not explained by differences in mitochondrial respiration. Nevertheless, both KD and CD-IF regimens protected against different types of seizures, suggesting that mechanisms underlying CD-IF seizure protection should be explored further. Published by Elsevier B.V.

Music-supported therapy induces plasticity in the sensorimotor cortex in chronic stroke: a single-case study using multimodal imaging (fMRI-TMS).

PubMed

Rojo, Nuria; Amengual, Julian; Juncadella, Montserrat; Rubio, Francisco; Camara, Estela; Marco-Pallares, Josep; Schneider, Sabine; Veciana, Misericordia; Montero, Jordi; Mohammadi, Bahram; Altenmüller, Eckart; Grau, Carles; Münte, Thomas F; Rodriguez-Fornells, Antoni

2011-01-01

Music-Supported Therapy (MST) has been developed recently in order to improve the use of the affected upper extremity after stroke. This study investigated the neuroplastic mechanisms underlying effectiveness in a patient with chronic stroke. MST uses musical instruments, a midi piano and an electronic drum set emitting piano sounds, to retrain fine and gross movements of the paretic upper extremity. Data are presented from a patient with a chronic stroke (20 months post-stroke) with residual right-sided hemiparesis who took part in 20 MST sessions over the course of 4 weeks. Post-therapy, a marked improvement of movement quality, assessed by 3D movement analysis, was observed. Moreover, functional magnetic resonance imaging (fMRI) of a sequential hand movement revealed distinct therapy-related changes in the form of a reduction of excess contralateral and ipsilateral activations. This was accompanied by changes in cortical excitability evidenced by transcranial magnetic stimulation (TMS). Functional MRI in a music listening task suggests that one of the effects of MST is the task-dependent coupling of auditory and motor cortical areas. The MST appears to be a useful neurorehabilitation tool in patients with chronic stroke and leads to neural reorganization in the sensorimotor cortex.

Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures.

PubMed

Faught, E; Ayala, R; Montouris, G G; Leppik, I E

2001-11-27

Zonisamide is a sulfonamide antiepilepsy drug with sodium and calcium channel-blocking actions. Experience in Japan and a previous European double-blind study have demonstrated its efficacy against partial-onset seizures. A randomized, double-blind, placebo-controlled trial enrolling 203 patients was conducted at 20 United States sites to assess zonisamide efficacy and dose response as adjunctive therapy for refractory partial-onset seizures. Zonisamide dosages were elevated by 100 mg/d each week. The study design allowed parallel comparisons with placebo for three dosages and a final crossover to 400 mg/d of zonisamide for all patients. The primary efficacy comparison was change in seizure frequency from a 4-week placebo baseline to weeks 8 through 12 on blinded therapy. At 400 mg/d, zonisamide reduced the median frequency of all seizures by 40.5% from baseline, compared with a 9% reduction (p = 0.0009) with placebo treatment, and produced a > or =50% seizure reduction (responder rate) in 42% of patients. A dosage of 100 mg/d produced a 20.5% reduction in median seizure frequency (p = 0.038 compared with placebo) and a dosage of 200 mg/d produced a 24.7% reduction in median seizure frequency (p = 0.004 compared with placebo). Dropouts from adverse events (10%) did not differ from placebo (8.2%, NS). The only adverse event differing significantly from placebo was weight loss, though somnolence, anorexia, and ataxia were slightly more common with zonisamide treatment. Serum zonisamide concentrations rose with increasing dose. Zonisamide is effective and well tolerated as an adjunctive agent for refractory partial-onset seizures. The minimal effective dosage was 100 mg/d, but 400 mg/d was the most effective dosage.

Automated seizure detection systems and their effectiveness for each type of seizure.

PubMed

Ulate-Campos, A; Coughlin, F; Gaínza-Lein, M; Fernández, I Sánchez; Pearl, P L; Loddenkemper, T

2016-08-01

Epilepsy affects almost 1% of the population and most of the approximately 20-30% of patients with refractory epilepsy have one or more seizures per month. Seizure detection devices allow an objective assessment of seizure frequency and a treatment tailored to the individual patient. A rapid recognition and treatment of seizures through closed-loop systems could potentially decrease morbidity and mortality in epilepsy. However, no single detection device can detect all seizure types. Therefore, the choice of a seizure detection device should consider the patient-specific seizure semiologies. This review of the literature evaluates seizure detection devices and their effectiveness for different seizure types. Our aim is to summarize current evidence, offer suggestions on how to select the most suitable seizure detection device for each patient and provide guidance to physicians, families and researchers when choosing or designing seizure detection devices. Further, this review will guide future prospective validation studies. Copyright © 2016. Published by Elsevier Ltd.

Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man.

PubMed

Youssef, Nagy A; Sidhom, Emad

2017-11-01

Current pulse amplitude used in clinical ECT may be higher than needed. Reducing pulse amplitude may improve focality of the electric field and thus cognitive adverse effects. Here we examine the feasibility, safety, and whether Low Pulse Amplitude Seizure Therapy (LAP-ST, 0.5-0.6A) minimizes cognitive adverse effects while retaining efficacy. Patients with treatment-resistant primary mood (depressive episodes) or psychotic disorders who were clinically indicated to undergo ECT were offered to be enrolled in an open-label study. The study consisted of a full acute course of LAP-ST under standard anesthesia and muscle relaxation. The primary outcome was feasibility of seizure induction. Clinical outcome measures were: time to reorientation (TRO), Mini Mental State Examination, Montgomery Aberg Depression Scale, and Brief Psychiatric Rating Scale, and Clinical Global Impression Scale. Twenty-two patients consented for enrollment in the study. LAP-ST was feasible, and all patients had seizures in the first session. Participants had a quick orientation with median TRO of 4.5min. Treatment was efficacious for both depressive and psychotic symptoms. Relatively small sample size, non-blinded, and no randomization was performed in this initial proof of concept study. This first human preliminary data of a full course of focal LAP-ST demonstrates that seizure induction is feasible. These results, although preliminary, suggest that the LAP-ST compared to the standard ECT techniques may result in less cognitive side effects, but comparable efficacy. Larger studies are needed to replicate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

The temporal relation between seizure onset and arousal-awakening in temporal lobe seizures.

PubMed

Gumusyayla, Sadiye; Erdal, Abidin; Tezer, F Irsel; Saygi, Serap

2016-07-01

Our main aim was to determine the time interval between the seizure onsets and arousal-awakening related to these seizures in patients with temporal lobe epilepsy (TLE) and to discuss the role of lateralization on arousal-awakening mechanisms. Thirty-three TLE patients who underwent video-EEG monitoring with simultaneous polysomnography (PSG) and had recorded nocturnal seizures were retrospectively examined. These TLE patients had 64 seizures during sleep. The onsets of seizures and arousal-awakening related to these seizures were marked according to clinical and electrophysiological features. The time interval between the seizure onset and arousal-awakening related to the seizure was compared in patients with right- or left-sided temporal lobe seizures. In our TLE patients nocturnal seizures mostly followed arousal-awakening (64%). The time interval between the seizure onset and arousal-awakening related to the seizure was significantly shorter in patients with left-sided temporal lobe seizures (p=0.01). Video-EEG monitoring and PSG with scalp electrodes in our TLE patients showed that nocturnal seizures mostly followed arousal-awakening, and it was more pronounced in those with left-sided seizures. Arousal-awakening might be a signal for subsequent seizures in patients with TLE. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

4. VIEW OF NORTH FACE OF MST. NOTE: ENVIRONMENTAL DOOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. VIEW OF NORTH FACE OF MST. NOTE: ENVIRONMENTAL DOOR ON THE LOWER EAST SIDE OF THE NORTH FACE IS MISSING. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

A Stochastic Framework for Evaluating Seizure Prediction Algorithms Using Hidden Markov Models

PubMed Central

Wong, Stephen; Gardner, Andrew B.; Krieger, Abba M.; Litt, Brian

2007-01-01

Responsive, implantable stimulation devices to treat epilepsy are now in clinical trials. New evidence suggests that these devices may be more effective when they deliver therapy before seizure onset. Despite years of effort, prospective seizure prediction, which could improve device performance, remains elusive. In large part, this is explained by lack of agreement on a statistical framework for modeling seizure generation and a method for validating algorithm performance. We present a novel stochastic framework based on a three-state hidden Markov model (HMM) (representing interictal, preictal, and seizure states) with the feature that periods of increased seizure probability can transition back to the interictal state. This notion reflects clinical experience and may enhance interpretation of published seizure prediction studies. Our model accommodates clipped EEG segments and formalizes intuitive notions regarding statistical validation. We derive equations for type I and type II errors as a function of the number of seizures, duration of interictal data, and prediction horizon length and we demonstrate the model’s utility with a novel seizure detection algorithm that appeared to predicted seizure onset. We propose this framework as a vital tool for designing and validating prediction algorithms and for facilitating collaborative research in this area. PMID:17021032

Effect of local therapy on locoregional recurrence in postmenopausal women with breast cancer in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

PubMed

van Hezewijk, Marjan; Bastiaannet, Esther; Putter, Hein; Scholten, Astrid N; Liefers, Gerrit-Jan; Rea, Daniel; Hasenburg, Annette; Paridaens, Robert; Hozumi, Yasuo; Markopoulos, Christos; Seynaeve, Caroline; Jones, Stephen E; Marijnen, Corrie A M; van de Velde, Cornelis J H

2013-08-01

The TEAM trial investigated the efficacy and safety of adjuvant endocrine therapy consisting of either exemestane or the sequence of tamoxifen followed by exemestane in postmenopausal hormone-sensitive breast cancer. The present analyses explored the association between locoregional therapy and recurrence (LRR) in this population. Between 2001 and 2006, 9779 patients were randomized. Local treatment was breast conserving surgery plus radiotherapy (BCS+RT), mastectomy without radiotherapy (MST-only), or mastectomy plus radiotherapy (MST+RT). Patients with unknown data on surgery, radiotherapy, tumor or nodal stage (n=199), and patients treated by lumpectomy without radiotherapy (n=349) were excluded. After a median follow-up of 5.2 years, 270 LRRs occurred (2.9%) among 9231 patients. The 5-years actuarial incidence of LRR was 4.2% (95% CI 3.3-4.9%) for MST-only, 3.4% (95% CI 2.4-4.2%) for MST+RT and 1.9% (95% CI 1.5-2.3%) for BCS+RT. After adjustment for prognostic factors, the hazard ratio (HR, reference BCS+RT) for LRR remained significantly higher for MST-only (HR 1.53; 95% CI 1.10-2.11), not for MST+RT (HR 0.78; 95% CI 0.50-1.22). This explorative analysis showed a higher LRR risk after MST-only than after BCS+RT, even after adjustment for prognostic factors. As this effect was not seen for MST+RT versus BCS+RT, it might be explained by the beneficial effects of radiation treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Epilepsy and Other Seizure Disorders in Children: Drug Management

ERIC Educational Resources Information Center

Thomas, John A.; Knotts, Glenn R.

1976-01-01

A teacher can be valuable in aiding the recognition of seizure patterns in children and in providing further insight into possible side effects of anticonvulsant therapy, which might occur to the child in the classroom. (JD)

Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission.

PubMed

Kadiyala, Sridhar B; Yannix, Joshua Q; Nalwalk, Julia W; Papandrea, Dominick; Beyer, Barbara S; Herron, Bruce J; Ferland, Russell J

2016-07-13

The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7-12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure-ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with anticonvulsant medication

Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures.

PubMed

Porter, R J; Partiot, A; Sachdeo, R; Nohria, V; Alves, W M

2007-04-10

To evaluate the efficacy and safety of retigabine 600, 900, and 1,200 mg/day administered three times daily as adjunctive therapy in patients with partial-onset seizures. A multicenter, randomized, double-blind, placebo-controlled trial was performed. After an 8-week baseline phase, patients were randomized to a 16-week double-blind treatment period (8-week forced titration and 8-week maintenance) followed by either tapering or entry into an open-label extension study. Primary efficacy was the percentage change from baseline in monthly seizure frequency and compared across treatment arms. Secondary efficacy comparisons included the proportion of patients experiencing >/=50% reduction in seizure frequency (responder rate), emergence of new seizure types, and physician assessment of global clinical improvement. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluations. Efficacy analyses were performed on the intent-to-treat population. Of the 399 randomized patients, 279 (69.9%) completed the double-blind treatment period. The median percent change in monthly total partial seizure frequency from baseline was -23% for 600 mg/day, -29% for 900 mg/day, and -35% for 1,200 mg/day vs -13% for placebo (p < 0.001 for overall difference across all treatment arms). Responder rates for retigabine were 23% for 600 mg/day, 32% for 900 mg/day (p = 0.021), and 33% for 1,200 mg/day (p = 0.016), vs 16% for placebo. The most common treatment-emergent AEs were somnolence, dizziness, confusion, speech disorder, vertigo, tremor, amnesia, abnormal thinking, abnormal gait, paresthesia, and diplopia. Adjunctive therapy with retigabine is well tolerated and reduces the frequency of partial-onset seizures in a dose-dependent manner.

A Role for MST Neurons in Heading Estimation

NASA Technical Reports Server (NTRS)

Stone, Leland Scott; Perrone, J. A.; Wade, Charles E. (Technical Monitor)

1994-01-01

A template model of human visual self-motion perception (Perrone, JOSA, 1992; Perrone & Stone, Vis. Res., in press), which uses neurophysiologically realistic "heading detectors", is consistent with numerous human psychophysical results (Warren & Hannon, Nature, 1988; Stone & Perrone, Neuro. Abstr., 1991) including the failure of humans to estimate their heading (direction of forward translation) accurately under certain visual conditions (Royden et al., Nature, 1992). We tested the model detectors with stimuli used by others in- single-unit studies. The detectors showed emergent properties similar to those of MST neurons: 1) Sensitivity to non-preferred flow. Each detector is tuned to a specific combination of flow components and its response is systematically reduced by the addition of nonpreferred flow (Orban et al., PNAS, 1992), and 2) Position invariance. The detectors maintain their apparent preference for particular flow components over large regions of their receptive fields (e.g. Duffy & Wurtz, J. Neurophys., 1991; Graziano et al., J. Neurosci., 1994). It has been argued that this latter property is incompatible with MST playing a role in heading perception. The model however demonstrates how neurons with the above response properties could still support accurate heading estimation within extrastriate cortical maps.

Measuring viscosity with a resonant magnetic perturbation in the MST RFP

NASA Astrophysics Data System (ADS)

Fridström, Richard; Munaretto, Stefano; Frassinetti, Lorenzo; Chapman, Brett; Brunsell, Per; Sarff, John; MST Team

2016-10-01

Application of an m = 1 resonant magnetic perturbation (RMP) causes braking and locking of naturally rotating m = 1 tearing modes (TMs) in the MST RFP. The experimental TM dynamics are replicated by a theoretical model including the interaction between the RMP and multiple TMs [Fridström PoP 23, 062504 (2016)]. The viscosity is the only free parameter in the model, and it is chosen such that model TM velocity evolution matches that of the experiment. The model does not depend on the means by which the natural rotation is generated. The chosen value of the viscosity, about 40 m2/s, is consistent with separate measurements in MST using a biased probe to temporarily spin up the plasma. This viscosity is about 100 times larger than the classical prediction, likely due to magnetic stochasticity in the core of these plasmas. Viscosity is a key parameter in visco-resistive MHD codes like NIMROD. The validation of these codes requires measurement of the viscosity over a broad parameter range, which will now be possible with the RMP technique that, unlike the biased probe, is not limited to low-energy-density plasmas. Estimation with the RMP technique of the viscosity in several MST discharges suggests that the viscosity decreases as the electron beta increases. Work supported by USDOE.

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

PubMed

Robinson, Emily J; Goldstein, Laura H; McCrone, Paul; Perdue, Iain; Chalder, Trudie; Mellers, John D C; Richardson, Mark P; Murray, Joanna; Reuber, Markus; Medford, Nick; Stone, Jon; Carson, Alan; Landau, Sabine

2017-06-06

Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014).

Lacosamide: A Review in Focal-Onset Seizures in Patients with Epilepsy.

PubMed

Hoy, Sheridan M

2018-05-01

Lacosamide (Vimpat ® ) is a functionalized amino acid (available orally and intravenously) approved in the EU and the USA for use as monotherapy and adjunctive therapy for the treatment of focal-onset seizures in adults, adolescents and children aged ≥ 4 years with epilepsy. In adults and adolescents (aged ≥ 16 years), oral lacosamide as adjunctive therapy to other antiepileptic drugs was generally effective in reducing seizure frequency during short-term (up to 18 weeks) treatment, with efficacy sustained over the longer-term (up to 8 years). Moreover, patients were effectively switched from adjunctive oral lacosamide to the same dosage of intravenous lacosamide. Oral lacosamide was an effective conversion to monotherapy agent in this patient population and as monotherapy demonstrated noninferiority to carbamazepine controlled release in terms of seizure freedom. Antiepileptic benefits were maintained during longer-term (≤ 2 years) monotherapy. The antiepileptic efficacy of lacosamide in children aged ≥ 4 years has been extrapolated from data from adults and adolescents, with a similar response expected provided paediatric dosage adaptations are used and safety is demonstrated. Indeed, preliminary data demonstrated the efficacy of short-term (16 weeks) adjunctive lacosamide in patients aged ≥ 4 to < 17 years. Oral lacosamide was generally well tolerated over the short- and longer-term when administered as adjunctive therapy, a conversion to monotherapy agent and monotherapy in adults and adolescents and when administered as adjunctive therapy in children aged ≥ 4 years. Thus, lacosamide is a useful option for the management of focal-onset seizures across a broad age range, starting as early as 4 years of age.

Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission

PubMed Central

Kadiyala, Sridhar B.; Yannix, Joshua Q.; Nalwalk, Julia W.; Papandrea, Dominick; Beyer, Barbara S.; Herron, Bruce J.

2016-01-01

The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7–12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. SIGNIFICANCE STATEMENT Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure–ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with

Seizures

MedlinePlus

... wake up between them. Seizures can have many causes, including medicines, high fevers, head injuries and certain diseases. People who have recurring seizures due to a brain disorder have epilepsy. NIH: National Institute of Neurological Disorders and Stroke

Deep Recurrent Neural Networks for seizure detection and early seizure detection systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talathi, S. S.

Epilepsy is common neurological diseases, affecting about 0.6-0.8 % of world population. Epileptic patients suffer from chronic unprovoked seizures, which can result in broad spectrum of debilitating medical and social consequences. Since seizures, in general, occur infrequently and are unpredictable, automated seizure detection systems are recommended to screen for seizures during long-term electroencephalogram (EEG) recordings. In addition, systems for early seizure detection can lead to the development of new types of intervention systems that are designed to control or shorten the duration of seizure events. In this article, we investigate the utility of recurrent neural networks (RNNs) in designing seizuremore » detection and early seizure detection systems. We propose a deep learning framework via the use of Gated Recurrent Unit (GRU) RNNs for seizure detection. We use publicly available data in order to evaluate our method and demonstrate very promising evaluation results with overall accuracy close to 100 %. We also systematically investigate the application of our method for early seizure warning systems. Our method can detect about 98% of seizure events within the first 5 seconds of the overall epileptic seizure duration.« less

Morin impedes Yap nuclear translocation and fosters apoptosis through suppression of Wnt/β-catenin and NF-κB signaling in Mst1 overexpressed HepG2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perumal, NaveenKumar; Perumal, MadanKumar; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Recent clinical and experimental evidences strongly acclaim Yes-associated protein (Yap), a key oncogenic driver in liver carcinogenesis, as a therapeutic target. Of the known multiple schemes to inhibit Yap activity, activation of Mammalian Sterile 20-like Kinase 1 (Mst1), an upstream regulator of Yap, appears to be a promising one. In this study, we hypothesize that morin, a bioflavonoid, mediates its anti-cancer effect through the activation of Mst1/hippo signaling in liver cancer cells. To test this hypothesis, both full length Mst1 (F-Mst1) and kinase active N-terminal Mst1 (N-Mst1)-overexpressed HepG2 cells were used. Exposure of F-Mst1 overexpressed HepG2 cells to morin activatedmore » Mst1 by caspase-3 cleavage and thereby inhibited Yap nuclear translocation and fostered apoptosis. Morin suppressed NF-κB p65 and Wnt/β-catenin signaling through Mst1 activation via cleavage and phosphorylation, leading to cell death. Annexin-V/PI staining further confirmed the induction of apoptosis in morin treated F-Mst1 overexpressed cells. The present study shows that morin targets cell survival molecules such as NF-κB p65 and β-catenin through activation of hippo signaling. Therefore, morin could be considered as a potential anti-cancer agent against liver cancer. - Highlights: • Morin induced cytotoxicity in cultured HepG2 cells. • Morin activated hippo pathway via Mst1 activation in transfected HepG2 cells. • Morin suppressed Wnt/β-catenin signaling and induced G0/G1 cell cycle arrest. • Morin inhibited NF-κB signaling through Mst1 activation in transfected HepG2 cells. • Morin potentiates apoptosis through Mst1-JNK-caspase mediated mechanism in HepG2 cells.« less

Seizures and the natural history of World Health Organization Grade II gliomas: a review.

PubMed

Smits, Anja; Duffau, Hugues

2011-05-01

The majority of adults with low-grade gliomas have seizures. Despite the frequency of seizures as initial symptoms and symptoms of later disease, seizures in relation to the natural course of low-grade gliomas have received little attention. In this review, we provide an update of the literature on the prognostic impact of preoperative seizures and discuss the tumor- and treatment-related factors affecting seizure control at later stages of the disease. Seizures occur most frequently at disease presentation and predict a more favorable outcome. Initial seizures are correlated with tumor location and possibly indirectly to the molecular profile of the tumor. About 50% of all patients with seizures at presentation continue to have seizures before surgery. Maximal tumor resection, including resection of epileptic foci, is a valuable strategy for improving seizure control. In addition, radiotherapy and chemotherapy, as single therapies or in combination with surgery, have shown beneficial effects in terms of seizure reduction. Recurrent seizures after macroscopically complete tumor resection may be a marker for accelerated tumor growth. Recurrent seizures after an initial transient stabilization after radiotherapy and/or chemotherapy may be a marker for anaplastic tumor transformation. Preoperative seizures likely reflect, apart from tumor location, intrinsic tumor properties as well. Change in seizure control in individual patients is frequently associated with altered tumor behavior. Including seizures and seizure control as clinical parameters is recommended in future trials of low-grade gliomas to further establish the prognostic value of these symptoms and to identify the factors affecting seizure control.

The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, M.K.; Wright, L.K.M.; Stone, M.F.

2012-03-15

Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min followingmore » seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY

Treating acute seizures with benzodiazepines: does seizure duration matter?

PubMed

Naylor, David E

2014-10-01

Several clinical trials have shown improved seizure control and outcome by early initiation of treatment with benzodiazepines, before arrival in the emergency department and before intravenous access can be established. Here, evidence is provided and reviewed for rapid treatment of acute seizures in order to avoid the development of benzodiazepine pharmacoresistance and the emergence of self-sustaining status epilepticus. Alterations in the physiology, pharmacology, and postsynaptic level of GABA-A receptors can develop within minutes to an hour and hinder the ability of synaptic inhibition to stop seizures while also impairing the efficacy of GABAergic agents, such as benzodiazepines, to boost impaired inhibition. In addition, heightened excitatory transmission further exacerbates the inhibitory/excitatory balance and makes seizure control even more resistant to treatment. The acute increase in the surface expression of NMDA receptors during prolonged seizures also may cause excitotoxic injury, cell death, and other pathological expressions and re-arrangements of receptor subunits that all contribute to long-term sequelae such as cognitive impairment and chronic epilepsy. In conclusion, a short window of opportunity exists when seizures are maximally controlled by first-line benzodiazepine treatment. After that, multiple pathological mechanisms quickly become engaged that make seizures increasingly more difficult to control with high risk for long-term harm.

Antisense reduction of tau in adult mice protects against seizures.

PubMed

DeVos, Sarah L; Goncharoff, Dustin K; Chen, Guo; Kebodeaux, Carey S; Yamada, Kaoru; Stewart, Floy R; Schuler, Dorothy R; Maloney, Susan E; Wozniak, David F; Rigo, Frank; Bennett, C Frank; Cirrito, John R; Holtzman, David M; Miller, Timothy M

2013-07-31

Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS--brain and spinal cord tissue, interstitial fluid, and CSF--while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability.

An independent randomized clinical trial of multisystemic therapy with non-court-referred adolescents with serious conduct problems.

PubMed

Weiss, Bahr; Han, Susan; Harris, Vicki; Catron, Thomas; Ngo, Victoria K; Caron, Annalise; Gallop, Robert; Guth, Carol

2013-12-01

Adolescent conduct problems exact serious social as well as personal costs, and effective treatments are essential. One of the most widely disseminated and effective programs for the treatment of serious conduct problems in adolescents is Multisystemic Therapy (MST). However, most evaluations of MST have involved the developers of MST. The purpose of the present study was to conduct an independent evaluation of MST, with non-court-referred adolescents with conduct problems. Participants were 164 adolescents ages 11-18 years who were recruited from self-contained behavior intervention classrooms in public schools. Adolescents and their families were randomly assigned to receive MST or services as usual. Outcome measures assessed conduct problems, school functioning, and court records of criminal behavior. Participants were followed for 18 months after baseline using parent, adolescent, and teacher reports; arrest data were collected for 2.5 years postbaseline. Two of 4 primary outcome measures focused on externalizing problems showed significant treatment effects favoring MST. Several secondary and intervention targets pertaining to family functioning and parent psychopathology showed positive effects of MST, and no negative effects were identified. Results provide some further support for the effectiveness of MST, although smaller effect sizes than previous studies also suggest the complexity of successful dissemination, particularly to non-court-referred populations.

Serotonin neurones have anti-convulsant effects and reduce seizure-induced mortality

PubMed Central

Buchanan, Gordon F; Murray, Nicholas M; Hajek, Michael A; Richerson, George B

2014-01-01

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Defects in central control of breathing are important contributors to the pathophysiology of SUDEP, and serotonin (5-HT) system dysfunction may be involved. Here we examined the effect of 5-HT neurone elimination or 5-HT reduction on seizure risk and seizure-induced mortality. Adult Lmx1bf/f/p mice, which lack >99% of 5-HT neurones in the CNS, and littermate controls (Lmx1bf/f) were subjected to acute seizure induction by maximal electroshock (MES) or pilocarpine, variably including electroencephalography, electrocardiography, plethysmography, mechanical ventilation or pharmacological therapy. Lmx1bf/f/p mice had a lower seizure threshold and increased seizure-induced mortality. Breathing ceased during most seizures without recovery, whereas cardiac activity persisted for up to 9 min before terminal arrest. The mortality rate of mice of both genotypes was reduced by mechanical ventilation during the seizure or 5-HT2A receptor agonist pretreatment. The selective serotonin reuptake inhibitor citalopram reduced mortality of Lmx1bf/f but not of Lmx1bf/f/p mice. In C57BL/6N mice, reduction of 5-HT synthesis with para-chlorophenylalanine increased MES-induced seizure severity but not mortality. We conclude that 5-HT neurones raise seizure threshold and decrease seizure-related mortality. Death ensued from respiratory failure, followed by terminal asystole. Given that SUDEP often occurs in association with generalised seizures, some mechanisms causing death in our model might be shared with those leading to SUDEP. This model may help determine the relationship between seizures, 5-HT system dysfunction, breathing and death, which may lead to novel ways to prevent SUDEP. PMID:25107926

42. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM MST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

42. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM MST BASE. LAUNCHER IS BEHIND UMBILICAL MAST AND RAIL SYSTEM IS PARALLEL TO MAST ON RIGHT AND LEFT. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

3. VIEW OF NORTHEAST CORNER OF MST. NOTE: ENVIRONMENTAL DOOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. VIEW OF NORTHEAST CORNER OF MST. NOTE: ENVIRONMENTAL DOOR ON THE LOWER EAST SIDE OF THE NORTH FACE IS MISSING. NORTH CAMERA TOWER IN FOREGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Multistimulation group therapy in Alzheimer's disease promotes changes in brain functioning.

PubMed

Baglio, Francesca; Griffanti, Ludovica; Saibene, Francesca Lea; Ricci, Cristian; Alberoni, Margherita; Critelli, Raffaella; Villanelli, Fabiana; Fioravanti, Raffaella; Mantovani, Federica; D'amico, Alessandra; Cabinio, Monia; Preti, Maria Giulia; Nemni, Raffaello; Farina, Elisabetta

2015-01-01

Background. The growing social emergency represented by Alzheimer's disease (AD) and the lack of medical treatments able to modify the disease course have kindled the interest in nonpharmacological therapies. Objective. We introduced a novel nonpharmacological approach for people with AD (PWA) named Multidimensional Stimulation group Therapy (MST) to improve PWA condition in different disease domains: cognition, behavior, and motor functioning. Methods. Enrolling 60 PWA in a mild to moderate stage of the disease, we evaluated the efficacy of MST with a randomized-controlled study. Neuropsychological and neurobehavioral measures and functional magnetic resonance imaging (fMRI) data were considered as outcome measures. Results. The following significant intervention-related changes were observed: reduction in Neuropsychiatric Inventory scale score, improvement in language and memory subscales of Alzheimer's Disease Assessment Scale-Cognitive subscale, and increased fMRI activations in temporal brain areas, right insular cortex, and thalamus. Conclusions. Cognitive-behavioral and fMRI results support the notion that MST has significant effects in improving PWA cognitive-behavioral status by restoring neural functioning. © The Author(s) 2014.

Neonatal seizures triple the risk of a remote seizure after perinatal ischemic stroke.

PubMed

Fox, Christine K; Glass, Hannah C; Sidney, Stephen; Smith, Sabrina E; Fullerton, Heather J

2016-06-07

To determine incidence rates and risk factors of remote seizure after perinatal arterial ischemic stroke. We retrospectively identified a population-based cohort of children with perinatal arterial ischemic stroke (presenting acutely or in a delayed fashion) from a large Northern Californian integrated health care system. We determined incidence and predictors of a remote seizure (unprovoked seizure after neonatal period, defined as 28 days of life) by survival analyses, and measured epilepsy severity in those with active epilepsy (≥1 remote seizure and maintenance anticonvulsant treatment) at last follow-up. Among 87 children with perinatal stroke, 40 (46%) had a seizure in the neonatal period. During a median follow-up of 7.1 years (interquartile range 3.2-10.5), 37 children had ≥1 remote seizure. Remote seizure risk was highest during the first year of life, with a 20% (95% confidence interval [CI] 13%-30%) cumulative incidence by 1 year of age, 46% (CI 35%-58%) by 5 years, and 54% (CI 41%-67%) by 10 years. Neonatal seizures increased the risk of a remote seizure (hazard ratio 2.8, CI 1.3-5.8). Children with neonatal seizures had a 69% (CI 48%-87%) cumulative incidence of remote seizure by age 10 years. Among the 24 children with active epilepsy at last follow-up, 8 (33%) were having monthly seizures despite an anticonvulsant and 7 (29%) were on more than one anticonvulsant. Remote seizures and epilepsy, including medically refractory epilepsy, are common after perinatal stroke. Neonatal seizures are associated with nearly 3-fold increased remote seizure risk. © 2016 American Academy of Neurology.

Intraoperative seizures and seizures outcome in patients underwent awake craniotomy.

PubMed

Yuan, Yang; Peizhi, Zhou; Xiang, Wang; Yanhui, Liu; Ruofei, Liang; Shu, Jiang; Qing, Mao

2016-11-25

Awake craniotomies (AC) could reduce neurological deficits compared with patients under general anesthesia, however, intraoperative seizure is a major reason causing awake surgery failure. The purpose of the study was to give a comprehensive overview the published articles focused on seizure incidence in awake craniotomy. Bibliographic searches of the EMBASE, MEDLINE,were performed to identify articles and conference abstracts that investigated the intraoperative seizure frequency of patients underwent AC. Twenty-five studies were included in this meta-analysis. Among the 25 included studies, one was randomized controlled trials and 5 of them were comparable studies. The pooled data suggested the general intraoperative seizure(IOS) rate for patients with AC was 8%(fixed effect model), sub-group analysis identified IOS rate for glioma patients was 8% and low grade patients was 10%. The pooled data showed early seizure rates of AC patients was 11% and late seizure rates was 35%. This systematic review and meta-analysis shows that awake craniotomy is a safe technique with relatively low intraoperative seizure occurrence. However, few RCTs were available, and the acquisition of further evidence through high-quality RCTs is highly recommended.

Validation of MHD Models using MST RFP Plasmas

NASA Astrophysics Data System (ADS)

Jacobson, C. M.; Chapman, B. E.; den Hartog, D. J.; McCollam, K. J.; Sarff, J. S.; Sovinec, C. R.

2017-10-01

Rigorous validation of computational models used in fusion energy sciences over a large parameter space and across multiple magnetic configurations can increase confidence in their ability to predict the performance of future devices. MST is a well diagnosed reversed-field pinch (RFP) capable of operation with plasma current ranging from 60 kA to 500 kA. The resulting Lundquist number S, a key parameter in resistive magnetohydrodynamics (MHD), ranges from 4 ×104 to 8 ×106 for standard RFP plasmas and provides substantial overlap with MHD RFP simulations. MST RFP plasmas are simulated using both DEBS, a nonlinear single-fluid visco-resistive MHD code, and NIMROD, a nonlinear extended MHD code, with S ranging from 104 to 105 for single-fluid runs, and the magnetic Prandtl number Pm = 1 . Validation metric comparisons are presented, focusing on how normalized magnetic fluctuations at the edge b scale with S. Preliminary results for the dominant n = 6 mode are b S - 0 . 20 +/- 0 . 02 for single-fluid NIMROD, b S - 0 . 25 +/- 0 . 05 for DEBS, and b S - 0 . 20 +/- 0 . 02 for experimental measurements, however there is a significant discrepancy in mode amplitudes. Preliminary two-fluid NIMROD results are also presented. Work supported by US DOE.

Evidence for Consolidation of Neuronal Assemblies after Seizures in Humans

PubMed Central

Stead, Matt; Bower, Regina S.; Kucewicz, Michal T.; Sulc, Vlastimil; Cimbalnik, Jan; Brinkmann, Benjamin H.; Vasoli, Vincent M.; St. Louis, Erik K.; Meyer, Fredric B.; Marsh, W. Richard; Worrell, Gregory A.

2015-01-01

The establishment of memories involves reactivation of waking neuronal activity patterns and strengthening of associated neural circuits during slow-wave sleep (SWS), a process known as “cellular consolidation” (Dudai and Morris, 2013). Reactivation of neural activity patterns during waking behaviors that occurs on a timescale of seconds to minutes is thought to constitute memory recall (O'Keefe and Nadel, 1978), whereas consolidation of memory traces may be revealed and served by correlated firing (reactivation) that appears during sleep under conditions suitable for synaptic modification (Buhry et al., 2011). Although reactivation has been observed in human neuronal recordings (Gelbard-Sagiv et al., 2008; Miller et al., 2013), reactivation during sleep has not, likely because data are difficult to obtain and the effect is subtle. Seizures, however, provide intense and synchronous, yet sparse activation (Bower et al., 2012) that could produce a stronger consolidation effect if seizures activate learning-related mechanisms similar to those activated by learned tasks. Continuous wide-bandwidth recordings from patients undergoing intracranial monitoring for drug-resistant epilepsy revealed reactivation of seizure-related neuronal activity during subsequent SWS, but not wakefulness. Those neuronal assemblies that were most strongly activated during seizures showed the largest correlation changes, suggesting that consolidation selectively strengthened neuronal circuits activated by seizures. These results suggest that seizures “hijack” physiological learning mechanisms and also suggest a novel epilepsy therapy targeting neuronal dynamics during post-seizure sleep. PMID:25609617

Genetic (idiopathic) epilepsy with photosensitive seizures includes features of both focal and generalized seizures.

PubMed

Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian

2018-04-19

Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

Seizure development after stroke.

PubMed

Misirli, H; Ozge, A; Somay, G; Erdoğan, N; Erkal, H; Erenoğlu, N Y

2006-12-01

Although there have been many studies on seizures following stroke, there is still much we do not know about them. In this study, we evaluated the characteristics of seizures in stroke patients. There were 2267 patients with a first-ever stroke, and after excluding 387 patients, 1880 were available for analysis. Of these 1880 patients, we evaluated 200 patients with seizures and 400 patients without seizures. We investigated the seizures according to age, gender, stroke type, the aetiology of ischaemic stroke and the localisation of the lesion. The seizures were classified as early onset and late onset and the seizure type as partial, generalised or secondarily generalised. Seizures occurred in 200 (10.6%) of 1880 strokes. The number of patients with seizures were 138 (10.6%) in ischaemic stroke group and 62 (10.7%) in haemorrhagic stroke group. Patients with ischaemic strokes had 41 embolic (29.7%) and 97 thrombotic (70.3%) origin, and these were not statistically significant in comparison with controls. Cortical involvement for the development of seizures was the most important risk factor (odds ratios = 4.25, p < 0.01). It was concluded that embolic strokes, being younger than 65 years old, and cortical localisation of stroke were important risks for developing seizures.

21. STATION 70.5 OF MST, WEST SIDE. AIRCONDITIONING DUCT AT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. STATION 70.5 OF MST, WEST SIDE. AIR-CONDITIONING DUCT AT TOP; POWER BOX ON RIGHT; WINCH ON LEFT. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

22. DOOR CONTROL BOX AT STATION 70.5 OF MST FOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. DOOR CONTROL BOX AT STATION 70.5 OF MST FOR CONTROL OF SOUTH DOORS. NITROGEN PRESSURE REGULATOR ON LEFT. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Real-time detection, quantification, warning, and control of epileptic seizures: the foundations for a scientific epileptology.

PubMed

Osorio, I; Frei, M G

2009-11-01

Substantive advances in clinical epileptology may be realized through the judicious use of real-time automated seizure detection, quantification, warning, and delivery of therapy in subjects with pharmacoresistant seizures. Materialization of these objectives is likely to elevate epileptology to the level of a mature clinical science.

What is the standard approach to assessment of an unprovoked seizure in an adult?: HONG KONG.

PubMed

Kwan, Patrick

2012-12-01

Since Hong Kong is highly urbanized and acute public hospitals have been established across the city, most patients with unprovoked seizures not already receiving antiepileptic drug (AED) therapy, particularly convulsive seizures, will be admitted as emergency for assessment. A thorough history is taken from the patient and any witnesses to the seizure. This includes the circumstance of the seizures, detailed symptoms and signs experienced by the patient and witnessed by others before, during, and after the seizure, any potential precipitating factors, history of previous seizures (that the patient might have overlooked), and history of previous brain insults that might have increased the risk of epilepsy later in life, including gestational and birth history, history of childhood febrile seizure, significant head trauma, any family history of epilepsy or seizures, comorbidities, current medications, drug and alcohol abuse, and social history including employment, driving, and living circumstances. A detailed physical and neurologic examination is performed.

Gaseous signalling molecule SO2 via Hippo-MST pathway to improve myocardial fibrosis of diabetic rats

PubMed Central

Liu, Maojun; Liu, Shengquan; Tan, Wenting; Tang, Fen; Long, Junrong; Li, Zining; Liang, Biao; Chu, Chun; Yang, Jun

2017-01-01

Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)-generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo-MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague-Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L-Aspartic acid β-hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra-peritoneal injection of STZ (40 mg/kg) Following model establishment, intra-peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo-MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis-associated protein B-cell lymphoma associated protein X, caspase-3 and caspase-9 were upregulated, and Bcl-2 expression was downregulated. The expression of ERS and Hippo-MST pathway-associated proteins

Gaseous signalling molecule SO2 via Hippo‑MST pathway to improve myocardial fibrosis of diabetic rats.

PubMed

Liu, Maojun; Liu, Shengquan; Tan, Wenting; Tang, Fen; Long, Junrong; Li, Zining; Liang, Biao; Chu, Chun; Yang, Jun

2017-12-01

Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)‑generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo‑MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague‑Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L‑Aspartic acid β‑hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra‑peritoneal injection of STZ (40 mg/kg) Following model establishment, intra‑peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo‑MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis‑associated protein B‑cell lymphoma associated protein X, caspase‑3 and caspase‑9 were upregulated, and Bcl‑2 expression was downregulated. The expression of ERS and Hippo‑MST

Athletes with seizure disorders.

PubMed

Knowles, Byron Don; Pleacher, Michael D

2012-01-01

Individuals with seizure disorders have long been restricted from participation in certain sporting activities. Those with seizure disorders are more likely than their peers to have a sedentary lifestyle and to develop obesity. Regular participation in physical activity can improve both physical and psychosocial outcomes for persons with seizure disorders. Seizure activity often is reduced among those patients who regularly engage in aerobic activity. Recent literature indicates that the diagnosis of seizure disorders remains highly stigmatizing in the adolescent population. Persons with seizure disorders may be more accepted by peer groups if they are allowed to participate in sports and recreational activities. Persons with seizure disorders are encouraged to participate in regular aerobic activities. They may participate in team sports and contact or collision activities provided that they utilize appropriate protective equipment. There seems to be no increased risk of injury or increasing seizure activity as the result of such participation. Persons with seizure disorders still are discouraged from participating in scuba diving and skydiving. The benefits of participation in regular sporting activity far outweigh any risk to the athlete with a seizure disorder who chooses to participate in sports.

Soman increases neuronal COX-2 levels: possible link between seizures and protracted neuronal damage.

PubMed

Angoa-Pérez, Mariana; Kreipke, Christian W; Thomas, David M; Van Shura, Kerry E; Lyman, Megan; McDonough, John H; Kuhn, Donald M

2010-12-01

Nerve agent-induced seizures cause neuronal damage in brain limbic and cortical circuits leading to persistent behavioral and cognitive deficits. Without aggressive anticholinergic and benzodiazepine therapy, seizures can be prolonged and neuronal damage progresses for extended periods of time. The objective of this study was to determine the effects of the nerve agent soman on expression of cyclooxygenase-2 (COX-2), the initial enzyme in the biosynthetic pathway of the proinflammatory prostaglandins and a factor that has been implicated in seizure initiation and propagation. Rats were exposed to a toxic dose of soman and scored behaviorally for seizure intensity. Expression of COX-2 was determined throughout brain from 4h to 7 days after exposure by immunohistochemistry and immunoblotting. Microglial activation and astrogliosis were assessed microscopically over the same time-course. Soman increased COX-2 expression in brain regions known to be damaged by nerve agents (e.g., hippocampus, amygdala, piriform cortex and thalamus). COX-2 expression was induced in neurons, and not in microglia or astrocytes, and remained elevated through 7 days. The magnitude of COX-2 induction was correlated with seizure intensity. COX-1 expression was not changed by soman. Increased expression of neuronal COX-2 by soman is a late-developing response relative to other signs of acute physiological distress caused by nerve agents. COX-2-mediated production of prostaglandins is a consequence of the seizure-induced neuronal damage, even after survival of the initial cholinergic crisis is assured. COX-2 inhibitors should be considered as adjunct therapy in nerve agent poisoning to minimize nerve agent-induced seizure activity. Published by Elsevier B.V.

Seizure Disorders in Pregnancy

MedlinePlus

... If I have a seizure disorder, can it cause problems during pregnancy? • What risks are associated with having a seizure ... If I have a seizure disorder, can it cause problems during pregnancy? Seizure disorders can affect pregnancy in several ways: • ...

Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response.

PubMed

Nora, Tommi; Heinonen, Hanna; Tenhunen, Mirja; Rainesalo, Sirpa; Järvenpää, Soila; Lehtimäki, Kai; Peltola, Jukka

2018-01-01

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

Neutral dynamics and ion energy transport in MST plasma

NASA Astrophysics Data System (ADS)

Xing, Zichuan; Nornberg, Mark; den Hartog, Daniel; Kumar, Santosh; Anderson, Jay

2015-11-01

Neutral dynamics can have a significant effect on ion energy transport through charge exchange collisions. Whereas previously charge exchange was considered a direct loss mechanism in MST plasmas, new analysis indicates that significant thermal charge exchange neutrals are reionized. Further, the temperatures of the neutral species in the core of the plasma are suspected to be much higher than room temperature, which has a large effect on ion energy losses due to charge exchange. The DEGAS2 Monte Carlo simulation code is applied to the MST reversed field pinch experiment to estimate the density and temperature profile of the neutral species. The result is then used to further examine the effect of the neutral species on ion energy transport in improved confinement plasmas. This enables the development of a model that accounts for collisional equilibration between species, classical convective and conductive energy transport, and energy loss due to charge exchange collisions. The goal is to quantify classical, stochastic, and anomalous ion heating and transport in RFP plasmas. Work supported by the US DOE. DEGAS2 is provided by PPPL and STRAHL is provided by Ralph Dux of the Max-Planck-Institut fur Plasmaphysik.

Terminology and global standardization of endoscopic information: Minimal Standard Terminology (MST).

PubMed

Fujino, Masayuki A; Bito, Shigeru; Takei, Kazuko; Mizuno, Shigeto; Yokoi, Hideto

2006-01-01

Since 1994, following the leading efforts by the European Society for Gastrointestinal Endoscopy, Organisation Mondiale d'Endoscopie Digestive (OMED) has succeeded in compiling minimal number of terms required for computer generation of digestive endoscopy reports nicknamed MST (Minimal Standard Terminology). Though with some insufficiencies, and though developed only for digestive endoscopy, MST has been the only available terminology that is globally standardized in medicine. By utilizing the merits of a unified, structured terminology that can be used in multiple languages we can utilize the data stored in different languages as a common database. For this purpose, a standing, terminology-managing organization that manages and maintains and, when required, expands the terminology on a global level, is absolutely necessary. Unfortunately, however, the organization that performs version control of MST (OMED terminology, standardization and data processing committee) is currently suspending its activity. Medical practice of the world demands more and more specialization, with resultant needs for information exchange among specialized territories. As the cooperation between endoscopy and pathology has become currently the most important problem in the Endoscopy Working Group of Integrating Healthcare Enterprise-Japan (IHE-J,) the cooperation among different specialties is essential. There are DICOM or HL7 standards as the protocols for storage, and exchange (communication) of the data, but there is yet no organization that manages the terminology itself astride different specialties. We hereby propose to establish, within IEEE, for example, a system that promotes standardization of the terminology that can transversely describe a patient, and that can control different societies and groups, as far as the terminology is concerned.

Brivaracetam: An Adjunctive Treatment for Partial-Onset Seizures.

PubMed

Kappes, John A; Hayes, William J; Strain, Joe D; Farver, Debra K

2017-07-01

Brivaracetam is an analogue of levetiracetam that is Food and Drug Administration-approved for adjunctive treatment of partial-onset seizures in patients 16 years and older. In placebo-controlled trials adjunct brivaracetam demonstrated efficacy in reducing the frequency of seizures. The most commonly reported adverse effects are somnolence, dizziness, and fatigue. Clinical trials have evaluated brivaracetam for safety and efficacy in adjunctive treatment of partial-onset seizures in patients 16 years and older for up to 16 weeks. Brivaracetam's mechanism is similar to that of levetiracetam but with greater receptor binding affinity on synaptic vesicle protein 2A and inhibitory effects on sodium channels. Clinically significant differences between these agents are undetermined. Brivaracetam is available as oral tablets, oral solution, and intravenous solution. The Food and Drug Administration-approved dose is 50 mg twice daily, and titration is not required. Brivaracetam does not need dose adjustment for renal impairment and has minimal drug-drug interactions. Current limitations of brivaracetam include lack of head-to-head trials, limited long-term safety and efficacy data, and cost. Overall, brivaracetam is a viable adjunct therapeutic option for refractory partial-onset seizures in those who have failed conventional therapies. © 2017, The American College of Clinical Pharmacology.

Acute postoperative seizures as predictors of seizure outcomes after epilepsy surgery.

PubMed

Giridharan, Nisha; Horn, Paul S; Greiner, Hansel M; Holland, Katherine D; Mangano, Francesco T; Arya, Ravindra

2016-11-01

This meta-analysis was performed to determine if acute postoperative seizures (APOS) predict epilepsy surgery outcomes. Additionally, we estimated pooled prevalence for APOS and explored if certain APOS characteristics predict surgical outcomes. A systematic literature search was performed for studies reporting seizure outcomes after epilepsy surgery in patients with and without APOS. APOS were defined as seizure(s) occurring within 30days of surgery. After data extraction, pooled Mantel-Haenszel odds ratio (OR) with 95% confidence intervals (CI) was calculated for 1-year seizure-free outcome in patients with and without APOS using random-effects meta-analysis. Sub-group meta-analysis for pediatric studies, time of occurrence, and APOS semiology were also performed. A meta-regression was performed to explore source(s) of heterogeneity. Seventeen studies were included in the final synthesis. Pooled prevalence of APOS was found to be 22.58%. A significantly higher proportion of patients without APOS within 30days of surgery (73.49%) were seizure-free at ≥1-year (OR 4.20, 95% CI 2.97-5.93, p<0.0001) compared to those with APOS (38.96%). Among the pediatric studies (n=6) 77.14% of patients without APOS were seizure-free at ≥1-year, compared to 35.94% of those with APOS (OR 5.71, 95% CI 3.32-9.80, p<0.0001). Patients having APOS within 24h of surgery and APOS semiology different from habitual pre-surgical seizures were more likely to achieve seizure-free outcomes, but these results failed to achieve statistical significance. APOS reliably predict 1-year seizure outcomes after epilepsy surgery. This information should help counsel patients and families. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetics of reflex seizures and epilepsies in humans and animals.

PubMed

Italiano, Domenico; Striano, Pasquale; Russo, Emilio; Leo, Antonio; Spina, Edoardo; Zara, Federico; Striano, Salvatore; Gambardella, Antonio; Labate, Angelo; Gasparini, Sara; Lamberti, Marco; De Sarro, Giovambattista; Aguglia, Umberto; Ferlazzo, Edoardo

2016-03-01

patients with symptomatic epilepsies but have also been reported in the setting chromosomal disorders or genetically inherited lysosomal storage diseases. The genetic background of reflex seizures and epilepsies is heterogeneous and mostly unknown with no major gene identified in humans. The benefits offered by next-generation sequencing technologies should be merged with increasing information on animal models that represent an useful tool to study the mechanism underlying epileptogenesis. Finally, we expect that genetic studies will lead to a better understanding of the multiple factors involved in the pathophysiology of reflex seizures, and eventually to develop preventive strategies focused on seizure control and therapy optimization. Copyright © 2016 Elsevier B.V. All rights reserved.

Concurrent Electroconvulsive Therapy and Bupropion Treatment.

PubMed

Takala, Christopher R; Leung, Jonathan G; Murphy, Lauren L; Geske, Jennifer R; Palmer, Brian A

2017-09-01

Bupropion is associated with a dose-dependent increased risk of seizures. Use of concomitant bupropion and electroconvulsive therapy (ECT) remains controversial because of an increased risk of prolonged seizures. This is the first systematic evaluation of the effect of bupropion on ECT. A case group (n = 119), patients treated with concomitant ECT and bupropion, was compared with an age and gender frequency-matched control group (n = 261), treated with only ECT. Electroconvulsive therapy treatment data including seizure length, number of treatments, and concurrent medications were extracted. Longitudinal mixed models examined ECT versus ECT + bupropion group differences over the course of treatments measured by seizure duration (electroencephalogram [EEG] and motor). Multivariable models examined the total number of treatments and first and last seizure duration. All models considered group differences with ECT treatment measures adjusted for age, gender, benzodiazepine treatment, lead placement, and setting. Electroconvulsive therapy treatment with bupropion led to shorter motor seizure duration (0.047) and EEG seizure duration (P = 0.001). The number of ECT treatments (7.3 vs 7.0 treatments; P = 0.23), respectively, or the probability of a prolonged seizure (P = 0.15) was not significantly different. Benzodiazepine use was significantly more common in control subjects (P = 0.01). This is a retrospective analysis limited in part by unavailable variables (seizure threshold, nature of EEG and motor seizure monitoring, type of ECT device, dosing and formulation of bupropion, and duration of the current depressive illness). This study revealed a significantly shorter duration in seizure length with ECT + concomitant bupropion, but not in the number of required treatments in those treated compared with ECT without bupropion. There remains a critical need to reevaluate the efficacy of concomitant use of psychotropic medications + ECT.

Efficacy of multisystemic therapy in youths aged 10-17 with severe antisocial behaviour and emotional disorders: systematic review.

PubMed

Tan, Jia Xuan; Fajardo, Maria Lourdes Restrepo

2017-11-01

Antisocial behaviour and conduct disorders are the most common behavioural and mental health problems in children and young people globally. An efficacious intervention is needed to manage these antisocial behaviours that have costly consequences. Multisystemic Therapy (MST), an intensive home-based intervention for youths with psychosocial and behavioural problems, is recommended under National Institute for Health and Clinical Excellence guidelines for conduct disorder. However, reviews on the efficacy of MST are mixed. To review randomised controlled trials (RCTs) reporting efficacy of MST among youths presenting with antisocial behaviour and emotional disorder respectively. A systematic map term to subject heading search was conducted in PsycINFO, Embase, and Ovid Medline databases for articles up to November 2015. RCTs comparing MST vs.treatment as usual (TAU) in youths presenting with antisocial behaviour and emotional disorder were included. 12 RCTs ( n  = 1425) reported efficacy of MST vs. TAU in youths presenting with antisocial behaviour and emotional disorder. Clinically significant treatment effects of MST showed a reduction of antisocial behaviour which includes delinquency. MST, vs. psychiatric hospitalisation, was associated with a reduction of suicidal attempts in youths presenting with psychiatric emergencies. 4 studies showed that MST was less costly than TAU in the short term, with further analysis required for long-term cost-effectiveness. MST is an efficacious intervention for severe antisocial behaviours in reduction of delinquency and should be included in clinical practices. MST was shown to have a positive effect on emotional disorder but further research is needed to evaluate the efficacy of MST with emotional disorder. Further analysis is required to assess the services utilized for long-term cost effectiveness.

CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study

PubMed Central

2013-01-01

Background 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is effective and safe to suppress febrile seizures in children. Methods The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents. Prospect The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an

Neurodevelopmental comorbidities and seizure control 24 months after a first unprovoked seizure in children.

PubMed

Jason, Eva Åndell; Tomson, Torbjörn; Carlsson, Sofia; Tedroff, Kristina; Åmark, Per

2018-07-01

To follow children with newly diagnosed unprovoked seizures to determine (1) whether the prevalence of neurodevelopmental comorbidities and cerebral palsy (CP) changed after the initial seizure, and (2) the association between studied comorbidities and seizures 13-24 months after seizure onset or initiation of treatment. Analyses were based on 750 children (28 days-18 years) with a first unprovoked seizure (index) included in a population-based Incidence Registry in Stockholm between 2001 and 2006. The children were followed for two years and their medical records were examined for a priori defined neurodevelopmental/psychiatric comorbidities and CP and seizure frequency. Baseline information was collected from medical records from before, and up to six months after, the index seizure. Odds ratios (OR) of repeated seizures 13-24 months after the first seizure or after initiation of anti-epileptic drug treatment was calculated by logistic regression and adjusted for age and sex. At baseline, 32% of the children had neurodevelopmental/psychiatric comorbidities or CP compared to 35%, 24 months later. Children with such comorbidities more often experienced seizures 13-24 months after the index seizure (OR 2.87, CI 2.07-3.99) with the highest OR in those with CP or attention deficit hyperactivity disorder (ADHD). Children diagnosed at age <1 year exhibited the highest prevalence of comorbidities as well as OR for repeated seizures. A combination of young age and comorbidity was associated with an OR for repeated seizures of 5.12 (CI 3.03-8.65). Among the children without comorbidities 76% were seizure free 13-24 months after the index seizure or after initiation of AED treatment compared to 53% of children with comorbidities. This study indicates that neurodevelopmental comorbidities and CP in children with epilepsy tend to be present already at seizure onset and that such comorbidities are strong indicators of poor outcome regarding seizure control with or without

Adeno-Associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

ERIC Educational Resources Information Center

Woldbye, David P. D.; Angehagen, Mikael; Gotzsche, Casper R.; Elbrond-Bek, Heidi; Sorensen, Andreas T.; Christiansen, Soren H.; Olesen, Mikkel V.; Nikitidou, Litsa; Hansen, Thomas v. O.; Kanter-Schlifke, Irene; Kokaia, Merab

2010-01-01

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is…

Ion Heating Anisotropy during Dynamo Activity in the MST RFP

NASA Astrophysics Data System (ADS)

den Hartog, D. J.; Chapman, J. T.; Craig, D.; Fiksel, G.; Fontana, P. W.

1999-11-01

MHD dynamo activity is large in the MST Reversed-Field Pinch during sawtooth crashes, and small otherwise. During a sawtooth crash, ion temperature increases rapidly to a level several times as high as the temperature between sawteeth, which itself can be larger than the electron temperature. Several theories have been developed to explain this ion heating, some indicating a possible asymmetry in perpendicular to parallel heating [C. G. Gimblett, Europhys. Lett. 11, 541 (1990); Z. Yoshida, Nucl. Fusion 31, 386 (1991); N. Mattor, P. W. Terry, and S. C. Prager, Comments Plasma Phys. Controlled Fusion 15, 65 (1992)]. In standard MST discharges, impurity ion temperature measured perpendicular to the magnetic field (T_⊥) is higher than impurity ion temperature parallel to the magnetic field (T_allel) during a sawtooth crash. Throughout the rest of the sawtooth cycle, T_⊥ <= T_allel. This is in contrast to results obtained on the EXTRAP-T2 RFP which showed T_⊥ < T_allel throughout the discharge [K. Sasaki et al., Plasma Phys. Control. Fusion 39, 333 (1997)

Correlation between prescribed daily dose, seizure freedom and defined daily dose in antiepileptic drug treatment.

PubMed

Horváth, László; Fekete, Klára; Márton, Sándor; Fekete, István

2017-04-01

Background Although defined daily doses (DDD) for antiepileptic drugs (AED) have been assigned only in combination therapy, based on the literature, most patients take them in monotherapy. Furthermore, discrepancies between DDD and prescribed daily dose (PDD) were observed. Objective First, to determine PDDs of AEDs and to reveal PDD/DDD ratio among seizure free versus not seizure free patients in everyday clinical practice. Second, to test the applicability of 75% cut-off of DDD to achieve seizure freedom. Furthermore, to find out what factors might influence PDD. Setting Outpatient data files at a Hungarian university hospital were studied. Methods A retrospective, 20-year cross-sectional database was compiled from 1282 epileptic outpatients' files. Main outcome measure Seizure freedom and PDD were used as outcome measures. Results The mean DDD% of all prescribed AEDs increased steadily from monotherapy, through bitherapy towards polytherapy (p < 0.0001). Most seizure free patients took AEDs in doses in the range of ≤75% of DDDs in monotherapy and bitherapy. Older AEDs (carbamazepine and valproate) were given in a significantly higher mean dose in bitherapy in the seizure free group. Among the newer types, only levetiracetam and lamotrigine had a significantly higher DDD% in mono-, bi-, and polytherapy. Confirmed by logistic regression analysis, gender, age, type of epilepsy, and number of AEDs had a significant impact on the value of 75% DDD. Conclusion No significant unfavourable impact of the lower ratio of PDD/DDD on the outcome of achieving seizure freedom has been confirmed. As a measure of seizure freedom, 75% of DDD may be used, although individual therapy must be emphasised. Precisely quantified DDD would provide a more accurate calculation of other derived values.

AMPA GluA1-flip targeted oligonucleotide therapy reduces neonatal seizures and hyperexcitability

PubMed Central

Lykens, Nicole M.; Reddi, Jyoti M.

2017-01-01

Glutamate-activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs) mediate the majority of excitatory neurotransmission in brain and thus are major drug targets for diseases associated with hyperexcitability or neurotoxicity. Due to the critical nature of AMPA-Rs in normal brain function, typical AMPA-R antagonists have deleterious effects on cognition and motor function, highlighting the need for more precise modulators. A dramatic increase in the flip isoform of alternatively spliced AMPA-R GluA1 subunits occurs post-seizure in humans and animal models. GluA1-flip produces higher gain AMPA channels than GluA1-flop, increasing network excitability and seizure susceptibility. Splice modulating oligonucleotides (SMOs) bind to pre-mRNA to influence alternative splicing, a strategy that can be exploited to develop more selective drugs across therapeutic areas. We developed a novel SMO, GR1, which potently and specifically decreased GluA1-flip expression throughout the brain of neonatal mice lasting at least 60 days after single intracerebroventricular injection. GR1 treatment reduced AMPA-R mediated excitatory postsynaptic currents at hippocampal CA1 synapses, without affecting long-term potentiation or long-term depression, cellular models of memory, or impairing GluA1-dependent cognition or motor function in mice. Importantly, GR1 demonstrated anti-seizure properties and reduced post-seizure hyperexcitability in neonatal mice, highlighting its drug candidate potential for treating epilepsies and other neurological diseases involving network hyperexcitability. PMID:28178321

Limbic Encephalitis Manifesting as Selective Amnesia and Seizure-like Activity: A Case Report

PubMed Central

Kim, So-Yeon; Um, Yoo Hyun; Lim, Sung Chul

2018-01-01

Limbic encephalitis (LE) is characterized by short-term memory loss, disorientation, agitation, seizures, and histopathological evidence of medial temporal lobe inflammation. Leucine-rich, glioma inactivated 1 (LGI-1) is an auto-antigen associated with LE. We report a 37-year-old male patient with LGI-1-related LE who presented with recurrent episodes of selective amnesia, seizure-like activity, confusion, and personality change. His symptoms were significantly improved with steroid therapy. Thorough differential diagnosis with consideration for autoimmune encephalitis should be in patients with presentation of symptoms, such as memory impairment, personality change and seizure-like activity, especially when other neurological diagnoses are excluded. PMID:29397673

Febrile Seizures

MedlinePlus

... seizures in infants and children, doctors sometimes perform tests to be sure that the seizures are not caused by an underlying or more serious health condition. For example, meningitis, an infection of the membranes surrounding the ...

EEG analysis of seizure patterns using visibility graphs for detection of generalized seizures.

PubMed

Wang, Lei; Long, Xi; Arends, Johan B A M; Aarts, Ronald M

2017-10-01

The traditional EEG features in the time and frequency domain show limited seizure detection performance in the epileptic population with intellectual disability (ID). In addition, the influence of EEG seizure patterns on detection performance was less studied. A single-channel EEG signal can be mapped into visibility graphs (VGS), including basic visibility graph (VG), horizontal VG (HVG), and difference VG (DVG). These graphs were used to characterize different EEG seizure patterns. To demonstrate its effectiveness in identifying EEG seizure patterns and detecting generalized seizures, EEG recordings of 615h on one EEG channel from 29 epileptic patients with ID were analyzed. A novel feature set with discriminative power for seizure detection was obtained by using the VGS method. The degree distributions (DDs) of DVG can clearly distinguish EEG of each seizure pattern. The degree entropy and power-law degree power in DVG were proposed here for the first time, and they show significant difference between seizure and non-seizure EEG. The connecting structure measured by HVG can better distinguish seizure EEG from background than those by VG and DVG. A traditional EEG feature set based on frequency analysis was used here as a benchmark feature set. With a support vector machine (SVM) classifier, the seizure detection performance of the benchmark feature set (sensitivity of 24%, FD t /h of 1.8s) can be improved by combining our proposed VGS features extracted from one EEG channel (sensitivity of 38%, FD t /h of 1.4s). The proposed VGS-based features can help improve seizure detection for ID patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Retention, dosing, tolerability and patient reported seizure outcome of Zonisamide as only add-on treatment under real-life conditions in adult patients with partial onset seizures: Results of the observational study ZOOM.

PubMed

Hamer, Hajo; Baulac, Michel; McMurray, Rob; Kockelmann, Edgar

2016-01-01

Zonisamide is licensed for adjunctive therapy for partial-onset seizures with or without secondary generalisation in patients 6 years and older and as monotherapy for the treatment of partial seizures in adult patients with newly diagnosed epilepsy, and shows a favourable pharmacokinetic profile with low interaction potential with other drugs. The aim of the present study was to gather real-life data on retention and modalities of zonisamide use when administered as only add-on treatment to a current AED monotherapy in adult patients with partial-onset seizures. This multicenter observational study was performed in 4 European countries and comprised three visits: baseline, and after 3 and 6 months. Data on patients' retention, reported efficacy, tolerability and safety, and quality of life was collected. Of 100 included patients, 93 could be evaluated. After 6 months, the retention rate of zonisamide add-on therapy was 82.8%. At this time, a reduction of seizure frequency of at least 50% was observed in 79.7% of patients, with 43.6% reporting seizure freedom over the last 3 months of the study period. Adverse events were reported by 19.4% of patients, with fatigue, agitation, dizziness, and headache being most frequent. Approximately 25% of patients were older than 60 years, many of whom suffered from late-onset epilepsy. Compared to younger patients, these patients showed considerable differences with regard to their antiepileptic drug regimen at baseline, and slightly higher responder and retention rates at 6 months. Despite limitations due to the non-interventional open-label design and the low sample size, the results show that zonisamide as only add-on therapy is well retained, indicating effectiveness in the majority of patients under real-life conditions. Copyright © 2015. Published by Elsevier Ltd.

Management of seizures in the elderly: a survey of UK geriatricians.

PubMed Central

Stolarek, I H; Brodie, A F; Brodie, M J

1995-01-01

The incidence and prevalence of epilepsy increase substantially with old age. Despite this, the investigation and management of this patient population remains a grey area. Four hundred and eleven (53%) consultant geriatricians responded to a questionnaire exploring their approach to seizures in the elderly in order to establish an overview of current clinical practice. Between one and five patients presenting with seizures, predominantly aged between 75-85 years, were reviewed monthly. Seventy per cent of geriatricians undertook to investigate the patients themselves with biochemical and haematological profiles performed by most. Electroencephalography and computerized tomographic scanning were routinely requested by a quarter of responders. Only 58% would themselves initiate therapy with antiepileptic drugs, with 16% of consultants starting treatment following the first seizure, 59% after a second and 5% after a third. Phenytoin was first choice for generalized tonic-clonic seizures with carbamazepine preferred for partial seizures. If good control was not obtained, 67% would substitute another first line drug, while 27% would add in a second. Less than 3% would use the new anticonvulsants lamotrigine or vigabatrin. Sixty per cent monitored anticonvulsant concentrations in patients with poor control or suspected toxicity. A wide variability was seen in the current approach to seizures in the elderly, which reflects a lack of established practice. Epilepsy clinics for the elderly would encourage structured research into the many unanswered questions affecting the care of older people with seizures. PMID:8786590

Seizure semiology: an important clinical clue to the diagnosis of autoimmune epilepsy.

PubMed

Lv, Rui-Juan; Ren, Hai-Tao; Guan, Hong-Zhi; Cui, Tao; Shao, Xiao-Qiu

2018-02-01

The purpose of this study is to analyze the seizure semiologic characteristics of patients with autoimmune epilepsy (AE) and describe the investigation characteristics of AE using a larger sample size. This observational retrospective case series study was conducted from a tertiary epilepsy center between May 2014 and March 2017. Cases of new-onset seizures were selected based on laboratory evidence of autoimmunity. At the same time, typical mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) were recruited as the control group from the subjects who underwent presurgical evaluation during the same period. A total of 61 patients with AE were identified. Specific autoimmune antibodies were detected in 39 patients (63.93%), including anti-VGKC in 23 patients (37.70%), anti-NMDA-R in 9 patients (14.75%), anti-GABA B -R in 6 patients (9.84%), and anti-amphiphysin in 1 patient (1.64%). Regarding the seizure semiology, no significant differences were noted between AE patients with autoantibody and patients with suspected AE without antibody. Compared to typical MTLE patients with HS, both AE patients with autoantibody and patients with suspected AE without antibody had the same seizure semiologic characteristics, including more frequent SPS or CPS, shorter seizure duration, rare postictal confusion, and common sleeping SGTC seizures. This study highlights important seizure semiologic characteristics of AE. Patients with autoimmune epilepsy had special seizure semiologic characteristics. For patients with autoimmune epilepsy presenting with new-onset seizures in isolation or with a seizure-predominant neurological disorder, the special seizure semiologic characteristics may remind us to test neuronal nuclear/cytoplasmic antibodies early and initiate immunomodulatory therapies as soon as possible. Furthermore, the absence of neural-specific autoantibodies does not rule out AE.

Leaving tissue associated with infrequent intracranial EEG seizure onsets is compatible with post-operative seizure freedom

PubMed Central

Huang, Cyrus; Marsh, Eric D.; Ziskind, Daniela M.; Celix, Juanita M.; Peltzer, Bradley; Brown, Merritt W.; Storm, Phillip B.; Litt, Brian; Porter, Brenda E.

2013-01-01

Identify seizure onset electrodes that need to be resected for seizure freedom in children undergoing intracranial electroencephalography recording for treatment of medically refractory epilepsy. All children undergoing intracranial electroencephalography subdural grid electrode placement at the Children’s Hospital of Philadelphia from 2002-2008 were asked to enroll. We utilized intraoperative pictures to determine the location of the electrodes and define the resection cavity. A total of 15 patients had surgical fields that allowed for complete identification of the electrodes over the area of resection. Eight of 15 patients were seizure free after a follow up of 1.7 to 8 yr. Only one seizure-free patient had complete resection of all seizure onset associated tissue. Seizure free patients had resection of 64.1% of the seizure onset electrode associated tissue, compared to 35.2% in the not seizure free patients (p=0.05). Resection of tissue associated with infrequent seizure onsets did not appear to be important for seizure freedom. Resecting ≥ 90% of the electrodes from the predominant seizure contacts predicted post-operative seizure freedom (p=0.007). The best predictor of seizure freedom was resecting ≥ 90% of tissue involved in majority of a patient’s seizures. Resection of tissue under infrequent seizure onset electrodes was not necessary for seizure freedom. PMID:24563805

DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2

PubMed Central

Kwan, Julian; Sczaniecka, Anna; Heidary Arash, Emad; Nguyen, Liem; Chen, Chia-Chun; Ratkovic, Srdjana; Klezovitch, Olga; Attisano, Liliana; McNeill, Helen; Emili, Andrew; Vasioukhin, Valeri

2016-01-01

Disruption of apical–basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation. Affinity purification/mass spectrometry revealed a critical role of DLG5 in the formation of protein assemblies containing core Hippo kinases mammalian ste20 homologs 1/2 (MST1/2) and Par-1 polarity proteins microtubule affinity-regulating kinases 1/2/3 (MARK1/2/3). Consistent with this finding, Hippo signaling is markedly hyperactive in mammalian Dlg5−/− tissues and cells in vivo and ex vivo and in Drosophila upon dlg5 knockdown. Conditional deletion of Mst1/2 fully rescued the phenotypes of brain-specific Dlg5 knockout mice. Dlg5 also interacts genetically with Hippo effectors Yap1/Taz. Mechanistically, we show that DLG5 inhibits the association between MST1/2 and large tumor suppressor homologs 1/2 (LATS1/2), uses its scaffolding function to link MST1/2 with MARK3, and inhibits MST1/2 kinase activity. These data reveal a direct connection between cell polarity proteins and Hippo, which is essential for proper development of multicellular organisms. PMID:28087714

The economics of data acquisition computers for ST and MST radars

NASA Technical Reports Server (NTRS)

Watkins, B. J.

1983-01-01

Some low cost options for data acquisition computers for ST (stratosphere, troposphere) and MST (mesosphere, stratosphere, troposphere) are presented. The particular equipment discussed reflects choices made by the University of Alaska group but of course many other options exist. The low cost microprocessor and array processor approach presented here has several advantages because of its modularity. An inexpensive system may be configured for a minimum performance ST radar, whereas a multiprocessor and/or a multiarray processor system may be used for a higher performance MST radar. This modularity is important for a network of radars because the initial cost is minimized while future upgrades will still be possible at minimal expense. This modularity also aids in lowering the cost of software development because system expansions should rquire little software changes. The functions of the radar computer will be to obtain Doppler spectra in near real time with some minor analysis such as vector wind determination.

Probing RFP Density Limits and the Interaction of Pellet Fueling and NBI Heating on MST

NASA Astrophysics Data System (ADS)

Caspary, K. J.; Chapman, B. E.; Anderson, J. K.; Limbach, S. T.; Oliva, S. P.; Sarff, J. S.; Waksman, J.; Combs, S. K.; Foust, C. R.

2013-10-01

Pellet fueling on MST has previously achieved Greenwald fractions of up to 1.5 in 200 kA improved confinement discharges. Additionally, pellet fueling to densities above the Greenwald limit in 200 kA standard discharges resulted in early termination of the plasma, but pellet size was insufficient to exceed the limit for higher current discharges. To this end, the pellet injector on MST has been upgraded to increase the maximum fueling capability by increasing the size of the pellet guide tubes, which constrain the lateral motion of the pellet in flight, to accommodate pellets of up to 4.0 mm in diameter. These 4.0 mm pellets are capable of triggering density limit terminations for MST's peak current of 600 kA. An unexpected improvement in the pellet speed and mass control was also observed compared to the smaller diameter pellets. Exploring the effect of increased density on NBI particle and heat deposition shows that for MST's 1 MW tangential NBI, core deposition of 25 keV neutrals is optimized for densities of 2-3 × 1019 m-3. This is key for beta limit studies in pellet fueled discharges with improved confinement where maximum NBI heating is desired. An observed toroidal deflection of pellets injected into NBI heated discharges is consistent with asymmetric ablation due to the fast ion population. In 200 kA improved confinement plasmas with NBI heating, pellet fueling has achieved a Greenwald fraction of 2.0. Work supported by US DoE.

Sensor integration of multiple tripolar concentric ring electrodes improves pentylenetetrazole-induced seizure onset detection in rats.

PubMed

Makeyev, Oleksandr; Ding, Quan; Kay, Steven M; Besio, Walter G

2012-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via tripolar concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole. We developed a system to detect seizures and automatically trigger the stimulation and evaluated the system on the electrographic activity from rats. In this preliminary study we propose and validate a novel seizure onset detection algorithm based on exponentially embedded family. Unlike the previously proposed approach it integrates the data from multiple electrodes allowing an improvement of the detector performance.

Economic evaluation of multisystemic therapy for young people at risk for continuing criminal activity in the UK.

PubMed

Cary, Maria; Butler, Stephen; Baruch, Geoffrey; Hickey, Nicole; Byford, Sarah

2013-01-01

To evaluate whether multisystemic therapy (MST) is more cost-effective than statutory interventions that are currently available for young offenders in England. A cost-offset evaluation of MST based on data from a randomised controlled trial conducted in North London, England, comparing MST with usual services provided by two youth offending teams (YOT). Service costs were compared to cost savings in terms of rates of criminal re-offending. 108 adolescents, aged 11-17 years, were randomly allocated to MST+YOT (n = 56) or YOT alone (n = 52). Reductions in offending were evident in both groups, but were higher in the MST+YOT group. At 18-month follow-up, the MST+YOT group cost less in terms of criminal activity (£9,425 versus £11,715, p = 0.456). The MST+YOT group were significantly cheaper in terms of YOT services than the YOT group (£3,402 versus £4,619, p = 0.006), but more expensive including the cost of MST, although not significantly so (£5,687 versus £4,619, p = 0.195). The net benefit per young person for the 18-month follow-up was estimated to be £1,222 (95% CI -£5,838 to £8,283). The results reported in this study support the finding that MST+YOT has scope for cost-savings when compared to YOT alone. However, the limitations of the study in terms of method of economic evaluation, outcome measures used and data quality support the need for further research.

Blast TBI Models, Neuropathology, and Implications for Seizure Risk

PubMed Central

Kovacs, S. Krisztian; Leonessa, Fabio; Ling, Geoffrey S. F.

2014-01-01

Traumatic brain injury (TBI) due to explosive blast exposure is a leading combat casualty. It is also implicated as a key contributor to war related mental health diseases. A clinically important consequence of all types of TBI is a high risk for development of seizures and epilepsy. Seizures have been reported in patients who have suffered blast injuries in the Global War on Terror but the exact prevalence is unknown. The occurrence of seizures supports the contention that explosive blast leads to both cellular and structural brain pathology. Unfortunately, the exact mechanism by which explosions cause brain injury is unclear, which complicates development of meaningful therapies and mitigation strategies. To help improve understanding, detailed neuropathological analysis is needed. For this, histopathological techniques are extremely valuable and indispensable. In the following we will review the pathological results, including those from immunohistochemical and special staining approaches, from recent preclinical explosive blast studies. PMID:24782820

Epidemiology of early stages of epilepsy: Risk of seizure recurrence after a first seizure.

PubMed

Rizvi, Syed; Ladino, Lady Diana; Hernandez-Ronquillo, Lizbeth; Téllez-Zenteno, José F

2017-07-01

A single unprovoked seizure is a frequent phenomenon in the general population and the rate of seizure recurrence can vary widely. Individual risk prognostication is crucial in predicting patient outcomes and guiding treatment decisions. In this article, we review the most important risk factors associated with an increased likelihood of seizure recurrence after a single unprovoked seizure. In summary, the presence of focal seizure, nocturnal seizure, history of prior brain injury, family history of epilepsy, abnormal neurological exam, epileptiform discharges on electroencephalography and neuroimaging abnormalities, portend increased risk of seizure recurrence. Elucidation of these risk factors in patient assessment will augment clinical decision-making and may help determine the appropriateness of instituting anti-epilepsy treatment. We also discuss the Canadian model of single seizure clinics and the potential use to assess these patients. Copyright © 2017. Published by Elsevier Ltd.

36. 1,000POUND CHAIN HOIST AT STATION 124 OF MST, WEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

36. 1,000-POUND CHAIN HOIST AT STATION 124 OF MST, WEST SIDE. (ITS ONLY USE WAS INSTALLATION OF ELEVATOR MOTOR.) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Suppression of runaway electrons with a resonant magnetic perturbation in MST tokamak plasmas

NASA Astrophysics Data System (ADS)

Munaretto, Stefano; Chapman, B. E.; Almagri, A. F.; Cornille, B. S.; Dubois, A. M.; Goetz, J. A.; McCollam, K. J.; Sovinec, C. R.

2016-10-01

Runaway electrons generated in MST tokamak plasmas are now being probed with resonant magnetic perturbations (RMP's). An RMP with m =3 strongly suppresses the runaway electrons. Initial modeling of these plasmas with NIMROD shows the degradation of flux surfaces with an m =3 RMP, which may account for the runaway electron suppression. These MST tokamak plasmas have Bt =0.14 T, Ip =50kA, and q(a) =2.2, with a bulk electron density and temperature of 5x1017 m-3 and 150 eV. Runaway electrons are detected via x-ray emission. The RMP is produced by a poloidal array of 32 saddle coils at the narrow vertical insulated cut in MST's thick conducting shell. Each RMP has a single m but a broad n spectrum. A sufficiently strong m =3 RMP completely suppresses the runaway electrons, while a comparable m =1 RMP has little effect. The impact of the RMP's on the magnetic topology of these plasmas is being studied with the nonlinear MHD code, NIMROD. With an m =3 RMP, stochasticity is introduced in the outer third of the plasma. No such change is observed with the m =1 RMP. NIMROD also predicts regularly occurring sawtooth oscillations with a period comparable to MHD activity observed in the experiment. Work supported by USDOE.

Afebrile seizure subsequent to initial febrile seizure.

PubMed

Fallah, Razieh; Razieh, Fallah; Akhavan Karbasi, Sedighah; Sedighah, Akhavan Karbasi; Golestan, Motahhareh; Motahhareh, Golestan

2012-05-01

Febrile seizure (FS) is the most common paediatric neurological problem. The purpose of this study was to determine the frequency of afebrile seizures subsequent to FS in children with initial FS and to evaluate its risk factors. A prospective study was conducted on all children (age 6 months to 6 years) referred with initial FS to the Shahid Sadoughi Hospital, Yazd, Iran, between August 2004 and March 2006, who were followed up for at least 15 months for the occurrence of subsequent afebrile seizures. 161 boys and 120 girls (mean age 2.12 ± 1.33 years) were followed up for 34.1 ± 7.8 months. 87 (31%) patients had complex FS and 19 (6.7%) patients had subsequent afebrile seizure, with a mean occurrence time of 10.6 ± 6.4 months. Univariate analysis using chi-square test showed that initial FS within one hour of developing fever (p = 0.0001), neurodevelopmental delay (p = 0.0001), family history of epilepsy (p = 0.0001), recurrent FS (p = 0.003) and focal FS (p = 0.04) were risk factors for subsequent afebrile seizure. On multivariate analysis, neurodevelopmental delay (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.3-3.4), initial FS within one hour of developing fever (OR 1.7, 95% CI 1.2-2.1) and family history of epilepsy (OR 1.5, 95% CI 1.1-1.9) were significant factors. Special attention should be paid to children with FS during history-taking and developmental assessments to identify high-risk patients and those who might need prophylactic anticonvulsants.

Validation of Extended MHD Models using MST RFP Plasmas

NASA Astrophysics Data System (ADS)

Jacobson, C. M.; Chapman, B. E.; Craig, D.; McCollam, K. J.; Sovinec, C. R.

2016-10-01

Significant effort has been devoted to improvement of computational models used in fusion energy sciences. Rigorous validation of these models is necessary in order to increase confidence in their ability to predict the performance of future devices. MST is a well diagnosed reversed-field pinch (RFP) capable of operation over a wide range of parameters. In particular, the Lundquist number S, a key parameter in resistive magnetohydrodynamics (MHD), can be varied over a wide range and provide substantial overlap with MHD RFP simulations. MST RFP plasmas are simulated using both DEBS, a nonlinear single-fluid visco-resistive MHD code, and NIMROD, a nonlinear extended MHD code, with S ranging from 104 to 5 ×104 for single-fluid runs, with the magnetic Prandtl number Pm = 1 . Experiments with plasma current IP ranging from 60 kA to 500 kA result in S from 4 ×104 to 8 ×106 . Validation metric comparisons are presented, focusing on how magnetic fluctuations b scale with S. Single-fluid NIMROD results give S b - 0.21 , and experiments give S b - 0.28 for the dominant m = 1 , n = 6 mode. Preliminary two-fluid NIMROD results are also presented. Work supported by US DOE.

Effects of Multisystemic Therapy through Midlife: A 21.9-Year Follow-Up to a Randomized Clinical Trial with Serious and Violent Juvenile Offenders

ERIC Educational Resources Information Center

Sawyer, Aaron M.; Borduin, Charles M.

2011-01-01

Objective: Although current evidence suggests that the positive effects of multisystemic therapy (MST) on serious crime reach as far as young adulthood, the longer term impact of MST on criminal and noncriminal outcomes in midlife has not been evaluated. In the present study, the authors examined a broad range of criminal and civil court outcomes…

Further developments of EISCAT as an MST radar

NASA Technical Reports Server (NTRS)

Rottger, J.

1984-01-01

The principal capabilities of EISCAT as an MST radar were described. Since the VHF transmitter of the EISCAT system is not yet delivered, only the UHF system could be used for radar experiments. Considerable developments in the year 1983 have now strongly improved the reliability of the operations. Most of the experiments were and will be done to investigate the high latitude ionosphere and thermosphere, but some time was also devoted to observations of the lower and middle atmosphere, particularly during the MAP/WINE compaign.

18. VIEW OF EAST SIDE INTERIOR OF MST AT STATIONS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. VIEW OF EAST SIDE INTERIOR OF MST AT STATIONS 3 AND 12, FACING WEST. COMPRESSED AIR TANK AND GENERATOR AT STATION 3. CURTAIN FOR NORTH ENVIRONMENTAL DOOR VISIBLE ON LEFT SIDE OF PHOTOGRAPH; RAIL VISIBLE AT BOTTOM OF PHOTOGRAPH. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide

PubMed Central

Hanaoka, Kenjiro; Sasakura, Kiyoshi; Suwanai, Yusuke; Toma-Fukai, Sachiko; Shimamoto, Kazuhito; Takano, Yoko; Shibuya, Norihiro; Terai, Takuya; Komatsu, Toru; Ueno, Tasuku; Ogasawara, Yuki; Tsuchiya, Yukihiro; Watanabe, Yasuo; Kimura, Hideo; Wang, Chao; Uchiyama, Masanobu; Kojima, Hirotatsu; Okabe, Takayoshi; Urano, Yasuteru; Shimizu, Toshiyuki; Nagano, Tetsuo

2017-01-01

Very recent studies indicate that sulfur atoms with oxidation state 0 or −1, called sulfane sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1. Most of the identified inhibitors had similar aromatic ring-carbonyl-S-pyrimidone structures. Among them, compound 3 showed very high selectivity for 3MST over other H2S/sulfane sulfur-producing enzymes and rhodanese. The X-ray crystal structures of 3MST complexes with two of the inhibitors revealed that their target is a persulfurated cysteine residue located in the active site of 3MST. Precise theoretical calculations indicated the presence of a strong long-range electrostatic interaction between the persulfur anion of the persulfurated cysteine residue and the positively charged carbonyl carbon of the pyrimidone moiety of the inhibitor. Our results also provide the experimental support for the idea that the 3MST-catalyzed reaction with 3-mercaptopyruvate proceeds via a ping-pong mechanism. PMID:28079151

Predicting early positive change in multisystemic therapy with youth exhibiting antisocial behaviors.

PubMed

Tiernan, Kristine; Foster, Sharon L; Cunningham, Phillippe B; Brennan, Patricia; Whitmore, Elizabeth

2015-03-01

This study examined individual and family characteristics that predicted early positive change in the context of Multisystemic Therapy (MST). Families (n = 185; 65% male; average youth age 15 years) receiving MST in community settings completed assessments at the outset of treatment and 6-12 weeks into treatment. Early positive changes in youth antisocial behavior were assessed using the caregiver report on the Child Behavior Checklist Externalizing Behaviors subscale and youth report on the Self-Report Delinquency Scale. Overall, families showed significant positive changes by 6-12 weeks into treatment; these early changes were maintained into midtreatment 6-12 weeks later. Families who exhibited clinically significant gains early in treatment were more likely to terminate treatment successfully compared with those who did not show these gains. Low youth internalizing behaviors and absence of youth drug use predicted early positive changes in MST. High levels of parental monitoring and low levels of affiliation with deviant peers (mechanisms known to be associated with MST success) were also associated with early positive change. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Epilepsy or seizures - discharge

MedlinePlus

... this page: //medlineplus.gov/ency/patientinstructions/000128.htm Epilepsy or seizures - discharge To use the sharing features on this page, please enable JavaScript. You have epilepsy . People with epilepsy have seizures. A seizure is ...

Manipulating the content of dynamic natural scenes to characterize response in human MT/MST.

PubMed

Durant, Szonya; Wall, Matthew B; Zanker, Johannes M

2011-09-09

Optic flow is one of the most important sources of information for enabling human navigation through the world. A striking finding from single-cell studies in monkeys is the rapid saturation of response of MT/MST areas with the density of optic flow type motion information. These results are reflected psychophysically in human perception in the saturation of motion aftereffects. We began by comparing responses to natural optic flow scenes in human visual brain areas to responses to the same scenes with inverted contrast (photo negative). This changes scene familiarity while preserving local motion signals. This manipulation had no effect; however, the response was only correlated with the density of local motion (calculated by a motion correlation model) in V1, not in MT/MST. To further investigate this, we manipulated the visible proportion of natural dynamic scenes and found that areas MT and MST did not increase in response over a 16-fold increase in the amount of information presented, i.e., response had saturated. This makes sense in light of the sparseness of motion information in natural scenes, suggesting that the human brain is well adapted to exploit a small amount of dynamic signal and extract information important for survival.

Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

PubMed

Wright, Samantha; Wallace, Eli; Hwang, Youngdeok; Maganti, Rama

2016-02-01

This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies. Copyright © 2015 Elsevier Inc. All rights reserved.

Time course of motor gains induced by music-supported therapy after stroke: An exploratory case study.

PubMed

Grau-Sánchez, Jennifer; Ramos, Neus; Duarte, Esther; Särkämö, Teppo; Rodríguez-Fornells, Antoni

2017-09-01

Previous studies have shown that Music-Supported Therapy (MST) can improve the motor function and promote functional neuroplastic changes in motor areas; however, the time course of motor gains across MST sessions and treatment periods remain unknown. The aim of this study was to explore the progression of the rehabilitation of motor deficits in a chronic stroke patient for a period of 7 months. A reversal design (ABAB) was implemented in a chronic stroke patient where no treatment was provided in the A periods and MST was applied in the B periods. Each period comprised of 4 weeks and an extensive evaluation of the motor function using clinical motor tests and 3D movement analysis was performed weekly. During the MST periods, a keyboard task was recorded daily. A follow-up evaluation was performed 3 months after the second MST treatment. Improvements were observed during the first sessions in the keyboard task but clinical gains were noticeable only at the end of the first treatment and during the second treatment period. These gains were maintained in the follow-up evaluation. This is the first study examining the pattern of motor recovery progression in MST, evidencing that gradual and continuous motor improvements are possible with the repeated application of MST training. Fast-acquisition in specific motor abilities was observed at the beginning of the MST training but generalization of these improvements to other motor tasks took place at the end or when another treatment period was provided. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Mediators of change for multisystemic therapy with juvenile sexual offenders.

PubMed

Henggeler, Scott W; Letourneau, Elizabeth J; Chapman, Jason E; Borduin, Charles M; Schewe, Paul A; McCart, Michael R

2009-06-01

The mediators of favorable multisystemic therapy (MST) outcomes achieved at 12 months postrecruitment were examined within the context of a randomized effectiveness trial with 127 juvenile sexual offenders and their caregivers. Outcome measures assessed youth delinquency, substance use, externalizing symptoms, and deviant sexual interest/risk behaviors; hypothesized mediators included measures of parenting and peer relations. Data were collected at pretreatment, 6 months postrecruitment, and 12 months postrecruitment. Consistent with the MST theory of change and the small extant literature in this area of research, analyses showed that favorable MST effects on youth antisocial behavior and deviant sexual interest/risk behaviors were mediated by increased caregiver follow-through on discipline practices as well as decreased caregiver disapproval of and concern about the youth's bad friends during the follow-up. These findings have important implications for the community-based treatment of juvenile sexual offenders. Copyright 2009 APA

Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

PubMed Central

Hashmi, Mubashira; Saleem, Feroza; Mustafa, Muhammad Shahid; Sheerani, Mughis; Ehtesham, Zeeshan; Siddiqui, Khurram

2010-01-01

Lafora disease is one of the rare, most fatal progressive myoclonic epilepsies reported. We present a case of a teenager with intractable seizures and progressive mental decline, diagnosed as Lafora body disease on axillary skin biopsy. He was admitted with status epilepticus with refractory myoclonic and generalised tonic clonic seizures. Despite on maximum doses of multiple antiepileptic drugs and infusions of propofol and midazolam, his seizures were refractory to all forms of medical therapy tried. Levetiracetam (LEV), a pyrrolidine derivative, was introduced; he showed a prompt response and was weaned off successfully from infusions of anticonvulsants and mechanical ventilation within 48 h of introduction of LEV, followed by an almost seizure-free status. PMID:22791845

MiR-183 regulates milk fat metabolism via MST1 in goat mammary epithelial cells.

PubMed

Chen, Zhi; Shi, HuaiPing; Sun, Shuang; Luo, Jun; Zhang, Wei; Hou, Yu; Loor, Juan J

2018-03-10

The nutritional value of goat milk largely depends on its fatty acid content and composition. MicroRNAs (miRNAs) are a class of RNA molecules 18-25nt in length that regulate gene expression and play crucial roles in several biological processes, including fatty acid metabolism. In this study, we analyzed the correlation between differentially expressed miRNAs in goat mammary tissue and the fatty acid composition of goat milk by using Pearson correlations. Results revealed that levels of miR-183 were highly and positively correlated with the fatty acid content in the milk. In addition, we demonstrated that overexpression of miR-183 inhibits milk fat metabolism and inhibition of miR-183 promotes milk fat metabolism. Using Western blot, we demonstrate that MST1, one of the major elements of the Hippo signaling pathway, is a target of miR-183. Immunofluorescence assays revealed that miR-183 targets MST1 in the cytoplasm. In summary, data indicate that miR-183 inhibits the metabolism of milk fat by targeting the MST1 gene in the cytoplasm in goat mammary epithelial cells. Copyright © 2017 Elsevier B.V. All rights reserved.

COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): a multicentre randomised controlled trial protocol.

PubMed

Goldstein, Laura H; Mellers, John D C; Landau, Sabine; Stone, Jon; Carson, Alan; Medford, Nick; Reuber, Markus; Richardson, Mark; McCrone, Paul; Murray, Joanna; Chalder, Trudie

2015-06-27

The evidence base for the effectiveness of psychological interventions for patients with dissociative non-epileptic seizures (DS) is currently extremely limited, although data from two small pilot randomised controlled trials (RCTs), including from our group, suggest that Cognitive Behavioural Therapy (CBT) may be effective in reducing DS occurrence and may improve aspects of psychological status and psychosocial functioning. The study is a multicentre, pragmatic parallel group RCT to evaluate the clinical and cost-effectiveness of specifically-tailored CBT plus standardised medical care (SMC) vs SMC alone in reducing DS frequency and improving psychological and health-related outcomes. In the initial screening phase, patients with DS will receive their diagnosis from a neurologist/epilepsy specialist. If patients are eligible and interested following the provision of study information and a booklet about DS, they will consent to provide demographic information and fortnightly data about their seizures, and agree to see a psychiatrist three months later. We aim to recruit ~500 patients to this screening stage. After a review three months later by a psychiatrist, those patients who have continued to have DS in the previous eight weeks and who meet further eligibility criteria will be told about the trial comparing CBT + SMC vs SMC alone. If they are interested in participating, they will be given a further booklet on DS and study information. A research worker will see them to obtain their informed consent to take part in the RCT. We aim to randomise 298 people (149 to each arm). In addition to a baseline assessment, data will be collected at 6 and 12 months post randomisation. Our primary outcome is monthly seizure frequency in the preceding month. Secondary outcomes include seizure severity, measures of seizure freedom and reduction, psychological distress and psychosocial functioning, quality of life, health service use, cost effectiveness and adverse

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

PubMed

Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

2016-03-01

Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. Copyright © 2016 Elsevier Inc. All rights reserved.

Placement and Delinquency Outcomes Among System-Involved Youth Referred to Multisystemic Therapy: A Propensity Score Matching Analysis.

PubMed

Vidal, Sarah; Steeger, Christine M; Caron, Colleen; Lasher, Leanne; Connell, Christian M

2017-11-01

Multisystemic therapy (MST) was developed to help youth with serious social, emotional, and behavioral problems. Research on the efficacy and effectiveness of MST has shown positive outcomes in different domains of development and functioning among various populations of youth. Nonetheless, even with a large body of literature investigating the treatment effects of MST, few studies have focused on the effectiveness of MST through large-scale dissemination efforts. Utilizing a large sample of youth involved in a statewide dissemination of MST (n = 740; 43% females; 14% Black; 29% Hispanic; 49% White; M age  = 14.9 years), propensity score matching was employed to account for baseline differences between the treatment (n = 577) and comparison (n = 163) groups. Treatment effects were examined based on three outcomes: out-of-home placement, adjudication, and placement in a juvenile training school over a 6-year period. Significant group differences remained after adjusting for baseline differences, with youth who received MST experiencing better outcomes in offending rates than youth who did not have an opportunity to complete MST due to non-clinical or administrative reasons. Survival analyses revealed rates of all three outcomes were approximately 40% lower among the treatment group. Overall, this study adds to the body of literature supporting the long-term effectiveness of MST in reducing offending among high-risk youth. The findings underscore the potential benefits of taking evidence-based programs such as MST to scale to improve the well-being and functioning of high-risk youth. However, strategies to effectively deliver the program in mental health service settings, and to address the specific needs of high-risk youth are necessary.

Fibromyalgia and seizures.

PubMed

Tatum, William O; Langston, Michael E; Acton, Emily K

2016-06-01

The purpose of this case-matched study was to determine how frequently fibromyalgia is associated with different paroxysmal neurological disorders and explore the utility of fibromyalgia as a predictor for the diagnosis of psychogenic non-epileptic seizures. The billing diagnosis codes of 1,730 new, non-selected patient encounters were reviewed over a three-year period for an epileptologist in a neurology clinic to identify all patients with historical diagnoses of fibromyalgia. The frequency with which epileptic seizures, psychogenic non-epileptic seizures, and physiological non-epileptic events were comorbid with fibromyalgia was assessed. Age and gender case-matched controls were used for a between-group comparison. Wilcoxon tests were used to analyse interval data, and Chi-square was used to analyse categorical data (p<0.05). Fibromyalgia was retrospectively identified in 95/1,730 (5.5%) patients in this cohort. Females represented 95% of the fibromyalgia sample (age: 53 years; 95% CI: 57, 51). Forty-three percent of those with fibromyalgia had a non-paroxysmal, neurological primary clinical diagnosis, most commonly chronic pain. Paroxysmal events were present in 57% of fibromyalgia patients and 54% of case-matched controls. Among patients with fibromyalgia and paroxysmal disorders, 11% had epileptic seizures, 74% had psychogenic non-epileptic seizures, and 15% had physiological non-epileptic events, compared to case-matched controls with 37% epileptic seizures, 51% psychogenic non-epileptic events, and 12% physiological non-epileptic events (p = 0.009). Fibromyalgia was shown to be a predictor for the diagnosis of psychogenic non-epileptic seizures in patients with undifferentiated paroxysmal spells. However, our results suggest that the specificity and sensitivity of fibromyalgia as a marker for psychogenic non-epileptic seizures in a mixed general neurological population of patients is less than previously described.

On Quantitative Biomarkers of VNS Therapy Using EEG and ECG Signals.

PubMed

Ravan, Maryam; Sabesan, Shivkumar; D'Cruz, O'Neill

2017-02-01

The goal of this work is to objectively evaluate the effectiveness of neuromodulation therapies, specifically, Vagus nerve stimulation (VNS) in reducing the severity of seizures in patients with medically refractory epilepsy. Using novel quantitative features obtained from combination of electroencephalographic (EEG) and electrocardiographic (ECG) signals around seizure events in 16 patients who underwent implantation of closed-loop VNS therapy system, namely AspireSR, we evaluated if automated delivery of VNS at the time of seizure onset reduces the severity of seizures by reducing EEG spatial synchronization as well as the duration and magnitude of heart rate increase. Unsupervised classification was subsequently applied to test the discriminative ability and validity of these features to measure responsiveness to VNS therapy. Results of application of this methodology to compare 105 pre-VNS treatment and 107 post-VNS treatment seizures revealed that seizures that were acutely stimulated using VNS had a reduced ictal spread as well as reduced impact on cardiovascular function compared to the ones that occurred prior to any treatment. Furthermore, application of an unsupervised fuzzy-c-mean classifier to evaluate the ability of the combined EEG-ECG based features to classify pre and post-treatment seizures achieved a classification accuracy of 85.85%. These results indicate the importance of timely delivery of VNS to reduce seizure severity and thus help achieve better seizure control for patients with epilepsy. The proposed set of quantitative features could be used as potential biomarkers for predicting long-term response to VNS therapy.

Epileptic seizures in Neuro-Behcet disease: why some patients develop seizure and others not?

PubMed

Kutlu, Gulnihal; Semercioglu, Sencer; Ucler, Serap; Erdal, Abidin; Inan, Levent E

2015-03-01

Behcet disease (BD) is a chronic relapsing inflammatory disorder. Neuro BD (NBD) is seen in approximately 5% of all patients. The aim of this study is to investigate the frequency, type and prognosis of epileptic seizures in different forms of NBD. All files of 42 patients with NBD were evaluated between 2006 and 2012, retrospectively. The demographic data, the presentation of NBD, clinical findings including seizures, EEG and neuroimaging findings were reviewed. The mean age of patients was 35.02±8.43 years. Thirty (71.4%) patients were male; the remaining 12 of them were female. Twenty-four patients had brainstem lesions; 16 patients had cerebral venous thrombosis. Spinal cord involvement was seen in two patients. Seven patients had epileptic seizures (six partial onset seizures with or without secondary generalization). Six of them had cerebral sinus thrombosis (CVT). Four patients had a seizure as the first symptom of the thrombosis. One patient had late onset seizure due to chronic venous infarct. The other patient with seizure had brainstem involvement. The remaining was diagnosed as epilepsy before the determination of NBD. CVT seen in BD seems to be the main risk factor for epileptic seizures in patients with NBD. The prognosis is usually good especially in patients with CVT. Epileptic seizures in patients with brainstem involvement may be an indicator for poor prognosis. Superior sagittal thrombosis or cortical infarct would be predictor of seizures occurrence because of the high ratio in patients with seizures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

2015-08-01

The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

Do reflex seizures and spontaneous seizures form a continuum? - triggering factors and possible common mechanisms.

PubMed

Irmen, Friederike; Wehner, Tim; Lemieux, Louis

2015-02-01

Recent changes in the understanding and classification of reflex seizures have fuelled a debate on triggering mechanisms of seizures and their conceptual organization. Previous studies and patient reports have listed extrinsic and intrinsic triggers, albeit their multifactorial and dynamic nature is poorly understood. This paper aims to review literature on extrinsic and intrinsic seizure triggers and to discuss common mechanisms among them. Among self-reported seizure triggers, emotional stress is most frequently named. Reflex seizures are typically associated with extrinsic sensory triggers; however, intrinsic cognitive or proprioceptive triggers have also been assessed. The identification of a trigger underlying a seizure may be more difficult if it is intrinsic and complex, and if triggering mechanisms are multifactorial. Therefore, since observability of triggers varies and triggers are also found in non-reflex seizures, the present concept of reflex seizures may be questioned. We suggest the possibility of a conceptual continuum between reflex and spontaneous seizures rather than a dichotomy and discuss evidence to the notion that to some extent most seizures might be triggered. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures

PubMed Central

Mumoli, Laura; Palleria, Caterina; Gasparini, Sara; Citraro, Rita; Labate, Angelo; Ferlazzo, Edoardo; Gambardella, Antonio; De Sarro, Giovambattista; Russo, Emilio

2015-01-01

Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10–30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca2+ channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%–11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical

Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures.

PubMed

Mumoli, Laura; Palleria, Caterina; Gasparini, Sara; Citraro, Rita; Labate, Angelo; Ferlazzo, Edoardo; Gambardella, Antonio; De Sarro, Giovambattista; Russo, Emilio

2015-01-01

Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10-30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca(2+) channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%-11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical

Increase in MST activity correlates with visual motion learning: A functional MRI study of perceptual learning

PubMed Central

Larcombe, Stephanie J.; Kennard, Chris

2017-01-01

Abstract Repeated practice of a specific task can improve visual performance, but the neural mechanisms underlying this improvement in performance are not yet well understood. Here we trained healthy participants on a visual motion task daily for 5 days in one visual hemifield. Before and after training, we used functional magnetic resonance imaging (fMRI) to measure the change in neural activity. We also imaged a control group of participants on two occasions who did not receive any task training. While in the MRI scanner, all participants completed the motion task in the trained and untrained visual hemifields separately. Following training, participants improved their ability to discriminate motion direction in the trained hemifield and, to a lesser extent, in the untrained hemifield. The amount of task learning correlated positively with the change in activity in the medial superior temporal (MST) area. MST is the anterior portion of the human motion complex (hMT+). MST changes were localized to the hemisphere contralateral to the region of the visual field, where perceptual training was delivered. Visual areas V2 and V3a showed an increase in activity between the first and second scan in the training group, but this was not correlated with performance. The contralateral anterior hippocampus and bilateral dorsolateral prefrontal cortex (DLPFC) and frontal pole showed changes in neural activity that also correlated with the amount of task learning. These findings emphasize the importance of MST in perceptual learning of a visual motion task. Hum Brain Mapp 39:145–156, 2018. © 2017 Wiley Periodicals, Inc. PMID:28963815

Morphine potentiates seizures induced by GABA antagonists and attenuates seizures induced by electroshock in the rat.

PubMed

Foote, F; Gale, K

1983-11-25

In a naloxone-reversible, dose-dependent manner, morphine (10-50 mg/kg i.p.) protected against seizures induced by maximal electroshock and increased the incidence and severity of seizures induced by bicuculline, in rats. Morphine also potentiated seizures induced by isoniazid and by picrotoxin. Thus, opiate activity influences the expression of seizures in contrasting ways depending upon the mode of seizure induction. Since morphine consistently potentiated seizures induced by interference with GABA transmission, it appears that GABAergic systems may be of particular significance for the elucidation of the varied effects of morphine on seizure susceptibility.

Seizure-related factors and non-verbal intelligence in children with epilepsy. A population-based study from Western Norway.

PubMed

Høie, B; Mykletun, A; Sommerfelt, K; Bjørnaes, H; Skeidsvoll, H; Waaler, P E

2005-06-01

To study the relationship between seizure-related factors, non-verbal intelligence, and socio-economic status (SES) in a population-based sample of children with epilepsy. The latest ILAE International classifications of epileptic seizures and syndromes were used to classify seizure types and epileptic syndromes in all 6-12 year old children (N=198) with epilepsy in Hordaland County, Norway. The children had neuropediatric and EEG examinations. Of the 198 patients, demographic characteristics were collected on 183 who participated in psychological studies including Raven matrices. 126 healthy controls underwent the same testing. Severe non-verbal problems (SNVP) were defined as a Raven score at or <10th percentile. Children with epilepsy were highly over-represented in the lowest Raven percentile group, whereas controls were highly over-represented in the higher percentile groups. SNVP were present in 43% of children with epilepsy and 3% of controls. These problems were especially common in children with remote symptomatic epilepsy aetiology, undetermined epilepsy syndromes, myoclonic seizures, early seizure debut, high seizure frequency and in children with polytherapy. Seizure-related characteristics that were not usually associated with SNVP were idiopathic epilepsies, localization related (LR) cryptogenic epilepsies, absence and simple partial seizures, and a late debut of epilepsy. Adjusting for socio-economic status factors did not significantly change results. In childhood epilepsy various seizure-related factors, but not SES factors, were associated with the presence or absence of SNVP. Such deficits may be especially common in children with remote symptomatic epilepsy aetiology and in complex and therapy resistant epilepsies. Low frequencies of SNVP may be found in children with idiopathic and LR cryptogenic epilepsy syndromes, simple partial or absence seizures and a late epilepsy debut. Our study contributes to an overall picture of cognitive function

Ipsiversive ictal eye deviation in inferioposterior temporal lobe epilepsy-Two SEEG cases report.

PubMed

Zhang, Wei; Liu, Xingzhou; Zuo, Lijun; Guo, Qiang; Chen, Qi; Wang, Yongjun

2017-02-21

Versive seizure characterized by conjugate eye movement during epileptic seizure has been considered commonly as one of the most valuable semiological signs for epilepsy localization, especially for frontal lobe epilepsy. However, the lateralizing and localizing significance of ictaleye deviation has been questioned by clinical observation of a series of focal epilepsy studies, including frontal, central, temporal, parietal and occipital epilepsy. Two epileptic cases characterized by ipsiversive eye deviation as initial clinical sign during the habitual epileptic seizures are presented in this paper. The localization of the epileptogenic zone of both of the cases has been confirmed as inferioposterior temporal region by the findings of ictalstereoelectroencephalography (SEEG) and a good result after epileptic surgery. Detailed analysis of the exact position of the key contacts of the SEEG electrodes identified the overlap between the location of the epileptogenic zone and human MT/MST complex, which play a crucial role in the control of smooth pursuit eye movement. Ipsiversive eye deviation could be the initial clinical sign of inferioposterior temporal lobe epilepsy and attribute to the involvement of human MT/MST complex, especially human MST whichwas located on the anterior/dorsal bank of the anterior occipital sulcus (AOS).

Delayed seizures after intracerebral haemorrhage

PubMed Central

Rattani, Abbas; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand

2016-01-01

Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5–1

EDITORIAL: MST Best Paper Award for 2003

NASA Astrophysics Data System (ADS)

Gill, Patrick

2004-09-01

For the last 12 years, Measurement Science and Technology has awarded a Best Paper prize. The Editorial Board of the journal believes that such a prize is an opportunity to thank authors for submitting their work, and serves as an integral part of the on-going quality review of the journal. An Editorial Board working party, comprising Patrick Gill (Chairman), Ralph Tatam and David Birch, was convened to determine a single contributed paper describing new and significant work, well aligned with the measurement scope of the journal, and presented in clear and rigorous form. They received a number of recommendations from the Editorial and International Advisory Board Members, and they would like to record their thanks to the Members for these recommendations, as they form an all-important first stage in the assessment process. There were responses from some 12 Board Members. In total, there were 31 papers nominated. To aid the process, additional information in the form of the 2003 MST papers top rated by referees, and the top papers ranked by most electronic accesses, was accessed. Reviews, and papers which included a Board Member as an author, were automatically excluded. From the totality of nominations and working party deliberations, there emerged a clear winner. Thus the paper recommended by the working party for the MST Best Paper Award for 2003 is: 'Extension of the torsional crystal viscometer to measurements in the time domain' by Richard F Hafer and Arno Laesecke, 14 663-673 (2003) This paper describes a significant advance in viscosity measurement using torsional vibration in piezoelectric rods. The method reported here demonstrates the use of free-decay time-domain measurements as opposed to the more established steady-state forced-mode resonance technique. The time domain technique is faster and more sensitive, with the potential for improved accuracy due to the lack of large time constants necessary for the interpretation of forced mode data. It offers

Evaluation of levetiracetam effects on pilocarpine-induced seizures: cholinergic muscarinic system involvement.

PubMed

Oliveira, A A; Nogueira, C R A; Nascimento, V S; Aguiar, L M V; Freitas, R M; Sousa, F C F; Viana, G S B; Fonteles, M M F

2005-09-16

Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy for partial seizures. It displays a unique pharmacological profile against experimental models of seizures, including pilocarpine-induced seizures in rodents. Aiming to clarify if anticonvulsant activity of LEV occurs due to cholinergic alterations, adult male mice received LEV injections before cholinergic agonists' administration. Pretreatment with LEV (30-200 mg/kg, i.p.) increased the latencies of seizures, but decreased status epilepticus and death on the seizure model induced by pilocarpine, 400 mg/kg, s.c. (P400). LEV (LEV200, 200 mg/kg, i.p.) pretreatment also reduced the intensity of tremors induced by oxotremorine (0.5 mg/kg, i.p). [3H]-N-methylscopolamine-binding assays in mice hippocampus showed that LEV200 pretreatment reverts the downregulation on muscarinic acetylcholine receptors (mAChR), induced by P400 administration, bringing back these density values to control ones (0.9% NaCl, i.p.). However, subtype-specific-binding assays revealed that P400- and LEV-alone treatments result in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of LEV on the inhibitory M2 mAChR subtype, observed in this work, could contribute to explain the reduction on oxotremorine-induced tremors and the delay on pilocarpine-induced seizures, by an increase in the attenuation of neuronal activity mediated by the M1 receptors.

Seizures induced by music.

PubMed

Ogunyemi, A O; Breen, H

1993-01-01

Musicogenic epilepsy is a rare disorder. Much remains to be learned about the electroclinical features. This report describes a patient who has been followed at our institution for 17 years, and was investigated with long-term telemetered simultaneous video-EEG recordings. She began to have seizures at the age of 10 years. She experienced complex partial seizures, often preceded by elementary auditory hallucination and complex auditory illusion. The seizures occurred in relation to singing, listening to music or thinking about music. She also had occasional generalized tonic clonic seizures during sleep. There was no significant antecedent history. The family history was negative for epilepsy. The physical examination was unremarkable. CT and MRI scans of the brain were normal. During long-term simultaneous video-EEG recordings, clinical and electrographic seizure activities were recorded in association with singing and listening to music. Mathematical calculation, copying or viewing geometric patterns and playing the game of chess failed to evoke seizures.

Animal Models of Seizures and Epilepsy: Past, Present, and Future Role for the Discovery of Antiseizure Drugs.

PubMed

Löscher, Wolfgang

2017-07-01

The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. Except for some early treatments, including bromides and phenobarbital, the antiseizure activity of all clinically used drugs was, for the most part, defined by acute seizure models in rodents using the maximal electroshock and subcutaneous pentylenetetrazole seizure tests and the electrically kindled rat. Unfortunately, the clinical evidence to date would suggest that none of these models, albeit useful, are likely to identify those therapeutics that will effectively manage patients with drug resistant seizures. Over the last 30 years, a number of animal models have been developed that display varying degrees of pharmacoresistance, such as the phenytoin- or lamotrigine-resistant kindled rat, the 6-Hz mouse model of partial seizures, the intrahippocampal kainate model in mice, or rats in which spontaneous recurrent seizures develops after inducing status epilepticus by chemical or electrical stimulation. As such, these models can be used to study mechanisms of drug resistance and may provide a unique opportunity for identifying a truly novel antiseizure drug (ASD), but thus far clinical evidence for this hope is lacking. Although animal models of drug resistant seizures are now included in ASD discovery approaches such as the ETSP (epilepsy therapy screening program), it is important to note that no single model has been validated for use to identify potential compounds for as yet drug resistant seizures, but rather a battery of such models should be employed, thus enhancing the sensitivity to discover novel, highly effective ASDs. The present review describes the previous and current approaches used in the search for new ASDs and offers some insight into future directions incorporating new and emerging animal models of therapy resistance.

An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold

PubMed Central

Chiavegato, Angela; Zonta, Micaela; Cammarota, Mario; Brondi, Marco; Vetri, Francesco; Uva, Laura; Pozzan, Tullio; de Curtis, Marco; Ratto, Gian Michele; Carmignoto, Giorgio

2010-01-01

Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic acid (NMDA) in rat entorhinal cortex slices. We found that a Ca2+ elevation in astrocytes correlates with both the initial development and the maintenance of a focal, seizure-like discharge. A delayed astrocyte activation during ictal discharges was also observed in other models (including the whole in vitro isolated guinea pig brain) in which the site of generation of seizure activity cannot be precisely monitored. In contrast, interictal discharges were not associated with Ca2+ changes in astrocytes. Selective inhibition or stimulation of astrocyte Ca2+ signalling blocked or enhanced, respectively, ictal discharges, but did not affect interictal discharge generation. Our data reveal that neurons engage astrocytes in a recurrent excitatory loop (possibly involving gliotransmission) that promotes seizure ignition and sustains the ictal discharge. This neuron–astrocyte interaction may represent a novel target to develop effective therapeutic strategies to control seizures. PMID:20405049

Targeting deficiencies in mitochondrial respiratory complex I and functional uncoupling exerts anti-seizure effects in a genetic model of temporal lobe epilepsy and in a model of acute temporal lobe seizures.

PubMed

Simeone, Kristina A; Matthews, Stephanie A; Samson, Kaeli K; Simeone, Timothy A

2014-01-01

Mitochondria actively participate in neurotransmission by providing energy (ATP) and maintaining normative concentrations of reactive oxygen species (ROS) in both presynaptic and postsynaptic elements. In human and animal epilepsies, ATP-producing respiratory rates driven by mitochondrial respiratory complex (MRC) I are reduced, antioxidant systems are attenuated and oxidative damage is increased. We report that MRCI-driven respiration and functional uncoupling (an inducible antioxidant mechanism) are reduced and levels of H2O2 are elevated in mitochondria isolated from KO mice. Experimental impairment of MRCI in WT hippocampal slices via rotenone reduces paired-pulse ratios (PPRs) at mossy fiber-CA3 synapses (resembling KO PPRs), and exacerbates seizure-like events in vitro. Daily treatment with AATP [a combination therapy composed of ascorbic acid (AA), alpha-tocopherol (T), sodium pyruvate (P) designed to synergistically target mitochondrial impairments] improved mitochondrial functions, mossy fiber PPRs, and reduced seizure burden index (SBI) scores and seizure incidence in KO mice. AATP pretreatment reduced severity of KA-induced seizures resulting in 100% protection from the severe tonic-clonic seizures in WT mice. These data suggest that restoration of bioenergetic homeostasis in the brain may represent a viable anti-seizure target for temporal lobe epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

Seizures and epilepsy in Alzheimer's disease.

PubMed

Friedman, Daniel; Honig, Lawrence S; Scarmeas, Nikolaos

2012-04-01

Many studies have shown that patients with Alzheimer's disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome, and progression vary widely between studies. We performed a literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG) studies, and treatment responses. Finally, we consider limitations and methodological issues. There is considerable variability in the reported prevalence and incidence of seizures in patients with AD-with reported lifetime prevalence rates of 1.5-64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. We conclude that the literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps. © 2011 Blackwell Publishing Ltd.

Mitochondria Are Critical for BDNF-Mediated Synaptic and Vascular Plasticity of Hippocampus following Repeated Electroconvulsive Seizures.

PubMed

Chen, Fenghua; Ardalan, Maryam; Elfving, Betina; Wegener, Gregers; Madsen, Torsten M; Nyengaard, Jens R

2018-03-01

Electroconvulsive therapy is a fast-acting and efficient treatment of depression used in the clinic. The underlying mechanism of its therapeutic effect is still unclear. However, recovery of synaptic connections and synaptic remodeling is thought to play a critical role for the clinical efficacy obtained from a rapid antidepressant response. Here, we investigated the relationship between synaptic changes and concomitant nonneuronal changes in microvasculature and mitochondria and its relationship to brain-derived neurotrophic factor level changes after repeated electroconvulsive seizures, an animal model of electroconvulsive therapy. Electroconvulsive seizures or sham treatment was given daily for 10 days to rats displaying a genetically driven phenotype modelling clinical depression: the Flinders Sensitive and Resistant Line rats. Stereological principles were employed to quantify numbers of synapses and mitochondria, and the length of microvessels in the hippocampus. The brain-derived neurotrophic factor protein levels were quantified with immunohistochemistry. In untreated controls, a lower number of synapses and mitochondria was accompanied by shorter microvessels of the hippocampus in "depressive" phenotype (Flinders Sensitive Line) compared with the "nondepressed" phenotype (Flinders Resistant Line). Electroconvulsive seizure administration significantly increased the number of synapses and mitochondria, and length of microvessels both in Flinders Sensitive Line-electroconvulsive seizures and Flinders Resistant Line-electroconvulsive seizures rats. In addition, the amount of brain-derived neurotrophic factor protein was significantly increased in Flinders Sensitive Line and Flinders Resistant Line rats after electroconvulsive seizures. Furthermore, there was a significant positive correlation between brain-derived neurotrophic factor level and mitochondria/synapses. Our results indicate that rapid and efficient therapeutic effect of electroconvulsive seizures

Seizures and Teens: Using Technology to Develop Seizure Preparedness

ERIC Educational Resources Information Center

Shafer, Patricia O.; Schachter, Steven C.

2007-01-01

Most people learn about seizures from their doctors, but others know only what they have seen on television. Unfortunately, visits to doctor's office aren't long enough to learn all that is needed, and often times, doctors and nurses aren't available to teach this information. Seizures are often represented inaccurately and too dramatically on…

mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia

PubMed Central

Yang, Guo-Shuai; Zhou, Xiao-Yan; An, Xue-Fang; Liu, Xuan-Jun; Zhang, Yan-Jun; Yu, Dan

2018-01-01

Stroke is considered an underlying etiology of the development of seizures. Stroke leads to glucose and oxygen deficiency in neurons, resulting in brain dysfunction and injury. Mild hypothermia is a therapeutic strategy to inhibit stroke-induced seizures, which may be associated with the regulation of energy metabolism of the brain. Mammalian target of rapamycin (mTOR) signaling and solute carrier family 2, facilitated glucose transporter member (GLUT)-1 are critical for energy metabolism. Furthermore, mTOR overactivation and GLUT-1 deficiency are associated with genetically acquired seizures. It has been hypothesized that mTOR and GLUT-1 may additionally be involved in seizures elicited by stroke. The present study established global cerebral ischemia (GCI) models of rats. Convulsive seizure behaviors frequently occurred during the first and the second days following GCI, which were accompanied with seizure discharge reflected in the EEG monitor. Expression of phosphor (p)-mTOR and GLUT-1 were upregulated in the cerebral cortex and hippocampus, as evidenced by immunohistochemistry and western blot analyses. Mild hypothermia and/or rapamycin (mTOR inhibitor) treatments reduced the number of epileptic attacks, seizure severity scores and seizure discharges, thereby alleviating seizures induced by GCI. Mild hypothermia and/or rapamycin treatments reduced phosphorylation levels of mTOR and the downstream effecter p70S6 in neurons, and the amount of GLUT-1 in the cytomembrane of neurons. The present study revealed that mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia. The role of GLUT-1 in stroke-elicited seizures appears to be different from the role in seizures induced by other reasons. Further studies are necessary in order to elucidate the exact function of GLUT-1 in stroke-elicited seizures. PMID:29484389

Increase in MST activity correlates with visual motion learning: A functional MRI study of perceptual learning.

PubMed

Larcombe, Stephanie J; Kennard, Chris; Bridge, Holly

2018-01-01

Repeated practice of a specific task can improve visual performance, but the neural mechanisms underlying this improvement in performance are not yet well understood. Here we trained healthy participants on a visual motion task daily for 5 days in one visual hemifield. Before and after training, we used functional magnetic resonance imaging (fMRI) to measure the change in neural activity. We also imaged a control group of participants on two occasions who did not receive any task training. While in the MRI scanner, all participants completed the motion task in the trained and untrained visual hemifields separately. Following training, participants improved their ability to discriminate motion direction in the trained hemifield and, to a lesser extent, in the untrained hemifield. The amount of task learning correlated positively with the change in activity in the medial superior temporal (MST) area. MST is the anterior portion of the human motion complex (hMT+). MST changes were localized to the hemisphere contralateral to the region of the visual field, where perceptual training was delivered. Visual areas V2 and V3a showed an increase in activity between the first and second scan in the training group, but this was not correlated with performance. The contralateral anterior hippocampus and bilateral dorsolateral prefrontal cortex (DLPFC) and frontal pole showed changes in neural activity that also correlated with the amount of task learning. These findings emphasize the importance of MST in perceptual learning of a visual motion task. Hum Brain Mapp 39:145-156, 2018. © 2017 Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Multisystemic Therapy Improves the Patient-Provider Relationship in Families of Adolescents with Poorly Controlled Insulin Dependent Diabetes

PubMed Central

Carcone, April Idalski; Ellis, Deborah A.; Chen, Xinguang; Naar-King, Sylvie; Cunningham, Phillippe B.; Moltz, Kathleen

2015-01-01

Objective The purpose of this study was to determine if Multisystemic Therapy (MST), an intensive, home and community-based family treatment, significantly improved patient-provider relationships in families where youth had chronic poor glycemic control. Methods One hundred forty-six adolescents with type 1 or 2 diabetes in chronic poor glycemic control (HbA1c ≥ 8%) and their primary caregivers were randomly assigned to MST or a telephone support condition. Caregiver perceptions of their relationship with the diabetes multidisciplinary medical team were assessed at baseline and treatment termination with the Measure of Process of Care-20. Results At treatment termination, MST families reported significant improvement on the Coordinated and Comprehensive Care scale and marginally significant improvement on the Respectful and Supportive Care scale. Improvements on the Enabling and Partnership and Providing Specific Information scales were not significant. Conclusions Results suggest MST improves the ability of the families and the diabetes treatment providers to work together. PMID:25940767

Drosophila as a model for intractable epilepsy: gilgamesh suppresses seizures in para(bss1) heterozygote flies.

PubMed

Howlett, Iris C; Rusan, Zeid M; Parker, Louise; Tanouye, Mark A

2013-08-07

Intractable epilepsies, that is, seizure disorders that do not respond to currently available therapies, are difficult, often tragic, neurological disorders. Na(+) channelopathies have been implicated in some intractable epilepsies, including Dravet syndrome (Dravet 1978), but little progress has been forthcoming in therapeutics. Here we examine a Drosophila model for intractable epilepsy, the Na(+) channel gain-of-function mutant para(bss1) that resembles Dravet syndrome in some aspects (parker et al. 2011a). In particular, we identify second-site mutations that interact with para(bss1), seizure enhancers, and seizure suppressors. We describe one seizure-enhancer mutation named charlatan (chn). The chn gene normally encodes an Neuron-Restrictive Silencer Factor/RE1-Silencing Transcription factor transcriptional repressor of neuronal-specific genes. We identify a second-site seizure-suppressor mutation, gilgamesh (gish), that reduces the severity of several seizure-like phenotypes of para(bss1)/+ heterozygotes. The gish gene normally encodes the Drosophila ortholog of casein kinase CK1g3, a member of the CK1 family of serine-threonine kinases. We suggest that CK1g3 is an unexpected but promising new target for seizure therapeutics.

A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures.

PubMed

Steinhoff, Bernhard J; Eckhardt, Klaus; Doty, Pamela; De Backer, Marc; Brunnert, Marcus; Schulze-Bonhage, Andreas

2016-05-01

This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were

Seizure disorders in 43 cattle.

PubMed

D'Angelo, A; Bellino, C; Bertone, I; Cagnotti, G; Iulini, B; Miniscalco, B; Casalone, C; Gianella, P; Cagnasso, A

2015-01-01

Large animals have a relatively high seizure threshold, and in most cases seizures are acquired. No published case series have described this syndrome in cattle. To describe clinical findings and outcomes in cattle referred to the Veterinary Teaching Hospital of the University of Turin (Italy) because of seizures. Client-owned cattle with documented evidence of seizures. Medical records of cattle with episodes of seizures reported between January 2002 and February 2014 were reviewed. Evidence of seizures was identified based on the evaluation of seizure episodes by the referring veterinarian or 1 of the authors. Animals were recruited if physical and neurologic examinations were performed and if diagnostic laboratory test results were available. Forty-three of 49 cases fulfilled the inclusion criteria. The mean age was 8 months. Thirty-one animals were male and 12 were female. Piedmontese breed accounted for 39/43 (91%) animals. Seizures were etiologically classified as reactive in 30 patients (70%) and secondary or structural in 13 (30%). Thirty-six animals survived, 2 died naturally, and 5 were euthanized for reasons of animal welfare. The definitive cause of reactive seizures was diagnosed as hypomagnesemia (n = 2), hypocalcemia (n = 12), and hypomagnesemia-hypocalcemia (n = 16). The cause of structural seizures was diagnosed as cerebrocortical necrosis (n = 8), inflammatory diseases (n = 4), and lead (Pb) intoxication (n = 1). The study results indicate that seizures largely are reported in beef cattle and that the cause can be identified and successfully treated in most cases. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Frontal Lobe Seizures

MedlinePlus

... cause of frontal lobe epilepsy remains unknown. Complications Status epilepticus. Frontal lobe seizures tend to occur in clusters and may provoke a dangerous condition called status epilepticus — in which seizure activity lasts much longer than ...

Feasibility of recording high frequency oscillations with tripolar concentric ring electrodes during pentylenetetrazole-induced seizures in rats.

PubMed

Makeyev, Oleksandr; Liu, Xiang; Wang, Liling; Zhu, Zhenghan; Taveras, Aristides; Troiano, Derek; Medvedev, Andrei V; Besio, Walter G

2012-01-01

As epilepsy remains a refractory condition in about 30% of patients with complex partial seizures, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via novel tripolar concentric ring electrodes (TCREs) on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ). We developed a close-loop system to detect seizures and automatically trigger the stimulation and evaluated its effect on the electrographic activity recorded by TCREs in rats. In our previous work the detectors of seizure onset were based on seizure-induced changes in signal power in the frequency range up to 100 Hz, while in this preliminary study we assess the feasibility of recording high frequency oscillations (HFOs) in the range up to 300 Hz noninvasively with scalp TCREs during PTZ-induced seizures. Grand average power spectral density estimate and generalized likelihood ratio tests were used to compare power of electrographic activity at different stages of seizure development in a group of rats (n= 8). The results suggest that TCREs have the ability to record HFOs from the scalp as well as that scalp-recorded HFOs can potentially be used as features for seizure onset detection.

The ROME (Retrospective Observational Multicenter study on Eslicarbazepine) study: Efficacy and behavioural effects of Eslicarbazepine acetate as adjunctive therapy for adults with partial onset seizures in real life.

PubMed

Assenza, G; Mecarelli, O; Lanzone, J; Assenza, F; Tombini, M; Di Lazzaro, V; Pulitano, P

2018-05-01

Eslicarbazepine acetate (ESL) is a third-generation member of the dibenzazepine family approved in 2009 by the European Medicines Agency with the indication of adjunctive therapy in adult people with partial-onset seizures (PPOS). We aimed at assessing the ESL impact on seizure frequency and quality of life in PPOS with a particular attention to sleepiness and depression. We evaluated 50 adult PPOS (>18 years; 48 ± 14 years-old; 23 males) treated with adjunctive ESL for ≥2months with a retrospective multi-centric design. Clinical files of the last 2 years were reviewed checking for monthly seizure frequency, treatment retention rate, adverse drug reactions (ADRs), concomitant anti-epileptic drugs and behavioural scales for sleepiness (Stanford Sleepiness Scale, SSS, and Epworth Sleepiness Scale, ESS), depression (Beck Depression Inventory-II, BDI) and overall quality of life (QOLIE-31). At the end of 96 ± 28 days of ESL treatment, the mean seizure reduction was 56%; 60% of patients had seizure reduction above 50%, with a 31% of the whole population becoming seizure free. We reported 16 ADRs with 4 hyponatremia. Retention rate was 76%. Patient reported less sleepiness after ESL (SSS, p = 0.031; ESS, p = 0.0000002). Before ESL, 38% of patients had pathologic BDI scores, which normalized in most of them (73%) after ESL (BDI improvement, p = 0.000012). These scores resulted in an amelioration of quality of life (QOLIE-31, p = 0.000002). ESL is a safe and effective anti-epileptic drug in a real life scenario, with an excellent behavioural profile for the overall quality of life and, in particular, for sleepiness and depression. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Slow Spatial Recruitment of Neocortex during Secondarily Generalized Seizures and Its Relation to Surgical Outcome

PubMed Central

Martinet, Louis-Emmanuel; Ahmed, Omar J.; Lepage, Kyle Q.; Cash, Sydney S.

2015-01-01

Understanding the spatiotemporal dynamics of brain activity is crucial for inferring the underlying synaptic and nonsynaptic mechanisms of brain dysfunction. Focal seizures with secondary generalization are traditionally considered to begin in a limited spatial region and spread to connected areas, which can include both pathological and normal brain tissue. The mechanisms underlying this spread are important to our understanding of seizures and to improve therapies for surgical intervention. Here we study the properties of seizure recruitment—how electrical brain activity transitions to large voltage fluctuations characteristic of spike-and-wave seizures. We do so using invasive subdural electrode arrays from a population of 16 patients with pharmacoresistant epilepsy. We find an average delay of ∼30 s for a broad area of cortex (8 × 8 cm) to be recruited into the seizure, at an estimated speed of ∼4 mm/s. The spatiotemporal characteristics of recruitment reveal two categories of patients: one in which seizure recruitment of neighboring cortical regions follows a spatially organized pattern consistent from seizure to seizure, and a second group without consistent spatial organization of activity during recruitment. The consistent, organized recruitment correlates with a more regular, compared with small-world, connectivity pattern in simulation and successful surgical treatment of epilepsy. We propose that an improved understanding of how the seizure recruits brain regions into large amplitude voltage fluctuations provides novel information to improve surgical treatment of epilepsy and highlights the slow spread of massive local activity across a vast extent of cortex during seizure. PMID:26109670

Spatial Attention Reduces Burstiness in Macaque Visual Cortical Area MST

PubMed Central

Xue, Cheng; Kaping, Daniel; Ray, Sonia Baloni; Krishna, B. Suresh; Treue, Stefan

2017-01-01

Abstract Visual attention modulates the firing rate of neurons in many primate cortical areas. In V4, a cortical area in the ventral visual pathway, spatial attention has also been shown to reduce the tendency of neurons to fire closely separated spikes (burstiness). A recent model proposes that a single mechanism accounts for both the firing rate enhancement and the burstiness reduction in V4, but this has not been empirically tested. It is also unclear if the burstiness reduction by spatial attention is found in other visual areas and for other attentional types. We therefore recorded from single neurons in the medial superior temporal area (MST), a key motion-processing area along the dorsal visual pathway, of two rhesus monkeys while they performed a task engaging both spatial and feature-based attention. We show that in MST, spatial attention is associated with a clear reduction in burstiness that is independent of the concurrent enhancement of firing rate. In contrast, feature-based attention enhances firing rate but is not associated with a significant reduction in burstiness. These results establish burstiness reduction as a widespread effect of spatial attention. They also suggest that in contrast to the recently proposed model, the effects of spatial attention on burstiness and firing rate emerge from different mechanisms. PMID:28365773

Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does not alter performance of automated seizure detection.

PubMed

Mathieson, Sean R; Livingstone, Vicki; Low, Evonne; Pressler, Ronit; Rennie, Janet M; Boylan, Geraldine B

2016-10-01

Phenobarbital increases electroclinical uncoupling and our preliminary observations suggest it may also affect electrographic seizure morphology. This may alter the performance of a novel seizure detection algorithm (SDA) developed by our group. The objectives of this study were to compare the morphology of seizures before and after phenobarbital administration in neonates and to determine the effect of any changes on automated seizure detection rates. The EEGs of 18 term neonates with seizures both pre- and post-phenobarbital (524 seizures) administration were studied. Ten features of seizures were manually quantified and summary measures for each neonate were statistically compared between pre- and post-phenobarbital seizures. SDA seizure detection rates were also compared. Post-phenobarbital seizures showed significantly lower amplitude (p<0.001) and involved fewer EEG channels at the peak of seizure (p<0.05). No other features or SDA detection rates showed a statistical difference. These findings show that phenobarbital reduces both the amplitude and propagation of seizures which may help to explain electroclinical uncoupling of seizures. The seizure detection rate of the algorithm was unaffected by these changes. The results suggest that users should not need to adjust the SDA sensitivity threshold after phenobarbital administration. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The prevalence of thyrotoxicosis-related seizures.

PubMed

Song, Tae-Jin; Kim, Sun-Jung; Kim, Gyu Sik; Choi, Young-Chul; Kim, Won-Joo

2010-09-01

Central nervous system dysfunction, such as hyperexcitation, irritability, and disturbance of consciousness, may occur in patients with thyrotoxicosis. There are also a few case reports of seizures attributed to thyrotoxicosis. The objective of the present study was to determine the prevalence of seizures that appeared to be related to the thyrotoxic state in patients with thyrotoxicosis. We retrospectively determined the prevalence and clinical features of seizures in 3382 patients with hyperthyroidism. Among patients with seizures, we excluded those with other causes of seizures or a history of epilepsy. We did not exclude two patients in whom later work-up showed an abnormal magnetic resonance imaging, as their seizures resolved after they became euthyroid. Among the 3382 patients with hyperthyroidism, there were seven patients (0.2%) with seizures who met our criteria. Primary generalized tonic-clonic seizures occurred in four patients (57%), complex partial seizures with secondary generalized tonic-clonic seizures occurred in two patients (29%), and one patient had a focal seizure (14%). The initial electroencephalography (EEG) was normal in two patients (29%), had generalized slow activity in four patients (57%), and had diffuse generalized beta activity in one patient (14%). On magnetic resonance imaging, one patient had diffuse brain atrophy, and one had an old basal ganglia infarct. After the patients became euthyroid, the EEG was repeated and was normal in all patients. During follow-up periods ranging from 18 to 24 months, none of the patients had seizures. Hyperthyroidism is the precipitating cause of seizures in a small percentage of these patients. In these patients, the prognosis is good if they become euthyroid. The prevalence of thyrotoxicosis-related seizures reported here can be used in conjunction with the prevalence of thyrotoxicosis in the population to estimate the prevalence of thyrotoxicosis-related seizures in populations.

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

PubMed Central

Eitan, Renana; Lerer, Bernard

2006-01-01

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT. Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability. PMID:16889109

Overview of MST Research

NASA Astrophysics Data System (ADS)

Sarff, J. S.; MST Team

2011-10-01

MST progress in advancing the RFP for (1) fusion plasma confinement with minimal external magnetization, (2) toroidal confinement physics, and (3) basic plasma physics is summarized. New tools and diagnostics are accessing physics barely studied in the RFP. Several diagnostic advances are important for ITER/burning plasma. A 1 MW neutral beam injector operates routinely for fast ion, heating, and transport investigations. Energetic ions are also created spontaneously by tearing mode reconnection, reminiscent of astrophysical plasmas. Classical confinement of impurity ions is measured in reduced-tearing plasmas. Fast ion slowing-down is also classical. Alfven-eigenmode-like activity occurs with NBI, but apparently not TAE. Stellarator-like helical structure appears in the core of high current plasmas, with improved confinement characteristics. FIR interferometry, Thomson scattering, and HIBP diagnostics are beginning to explore microturbulence scales, an opportunity to exploit the RFP's high beta and strong magnetic shear parameter space. A programmable power supply for the toroidal field flexibly explores scenarios from advanced inductive profile control to low current tokamak operation. A 1 MW 5.5 GHz source for electron Bernstein wave injection is nearly complete to investigate heating and current drive in over-dense plasmas. Supported by DOE and NSF.

Mediators of Change for Multisystemic Therapy with Juvenile Sexual Offenders

ERIC Educational Resources Information Center

Henggeler, Scott W.; Letourneau, Elizabeth J.; Chapman, Jason E.; Borduin, Charles M.; Schewe, Paul A.; McCart, Michael R.

2009-01-01

The mediators of favorable multisystemic therapy (MST) outcomes achieved at 12 months postrecruitment were examined within the context of a randomized effectiveness trial with 127 juvenile sexual offenders and their caregivers. Outcome measures assessed youth delinquency, substance use, externalizing symptoms, and deviant sexual interest/risk…

NKCC1 up-regulation contributes to early post-traumatic seizures and increased post-traumatic seizure susceptibility.

PubMed

Wang, Fushun; Wang, Xiaowei; Shapiro, Lee A; Cotrina, Maria L; Liu, Weimin; Wang, Ernest W; Gu, Simeng; Wang, Wei; He, Xiaosheng; Nedergaard, Maiken; Huang, Jason H

2017-04-01

Traumatic brain injury (TBI) is not only a leading cause for morbidity and mortality in young adults (Bruns and Hauser, Epilepsia 44(Suppl 10):210, 2003), but also a leading cause of seizures. Understanding the seizure-inducing mechanisms of TBI is of the utmost importance, because these seizures are often resistant to traditional first- and second-line anti-seizure treatments. The early post-traumatic seizures, in turn, are a contributing factor to ongoing neuropathology, and it is critically important to control these seizures. Many of the available anti-seizure drugs target gamma-aminobutyric acid (GABA A ) receptors. The inhibitory activity of GABA A receptor activation depends on low intracellular Cl - , which is achieved by the opposing regulation of Na + -K + -Cl - cotransporter 1 (NKCC1) and K + -Cl - -cotransporter 2 (KCC2). Up-regulation of NKCC1 in neurons has been shown to be involved in neonatal seizures and in ammonia toxicity-induced seizures. Here, we report that TBI-induced up-regulation of NKCC1 and increased intracellular Cl - concentration. Genetic deletion of NKCC1 or pharmacological inhibition of NKCC1 with bumetanide suppresses TBI-induced seizures. TGFβ expression was also increased after TBI and competitive antagonism of TGFβ reduced NKKC1 expression, ameliorated reactive astrocytosis, and inhibited seizures. Thus, TGFβ might be an important pathway involved in NKCC1 up-regulation after TBI. Our findings identify neuronal up-regulation of NKCC1 and its mediation by TGFβ, as a potential and important mechanism in the early post-traumatic seizures, and demonstrate the therapeutic potential of blocking this pathway.

Is the first seizure epilepsy--and when?

PubMed

Lawn, Nicholas; Chan, Josephine; Lee, Judy; Dunne, John

2015-09-01

Epilepsy has recently been redefined to include a single unprovoked seizure if the probability of recurrence is ≥60% over the following 10 years. This definition is based on the estimated risk of a third seizure after two unprovoked seizures, using the lower-limit 95% confidence interval (CI) at 4 years, and does not account for the initially high recurrence rate after first-ever seizure that rapidly falls with increasing duration of seizure freedom. We analyzed long-term outcomes after the first-ever seizure, and the influence of duration of seizure freedom on the likelihood of seizure recurrence, and their relevance to the new definition of epilepsy. Prospective analysis of 798 adults with a first-ever unprovoked seizure seen at a hospital-based first seizure clinic between 2000 and 2011. The likelihood of seizure recurrence was analyzed according to the duration of seizure freedom, etiology, electroencephalography (EEG), and neuroimaging findings. The likelihood of seizure recurrence at 10 years was ≥60% in patients with epileptiform abnormalities on EEG or neuroimaging abnormalities, therefore, meeting the new definition of epilepsy. However, the risk of recurrence was highly time dependent; after a brief period (≤12 weeks) of seizure freedom, no patient group continued to fulfill the new definition of epilepsy. Of 407 patients who had a second seizure, the likelihood of a third seizure at 4 years was 68% (95% CI 63-73%) and at 10 years was 85% (95% CI 79-91%). The duration of seizure freedom following first-ever seizure substantially influences the risk of recurrence, with none of our patients fulfilling the new definition of epilepsy after a short period of seizure freedom. When a threshold was applied based on the 10-year risk of a third seizure from our data, no first-seizure patient group ever had epilepsy. These data may be utilized in a definition of epilepsy after a first-ever seizure. Wiley Periodicals, Inc. © 2015 International League Against

Seizure Prediction and its Applications

PubMed Central

Iasemidis, Leon D.

2011-01-01

Epilepsy is characterized by intermittent, paroxysmal, hypersynchronous electrical activity, that may remain localized and/or spread and severely disrupt the brain’s normal multi-task and multi-processing function. Epileptic seizures are the hallmarks of such activity and had been considered unpredictable. It is only recently that research on the dynamics of seizure generation by analysis of the brain’s electrographic activity (EEG) has shed ample light on the predictability of seizures, and illuminated the way to automatic, prospective, long-term prediction of seizures. The ability to issue warnings in real time of impending seizures (e.g., tens of minutes prior to seizure occurrence in the case of focal epilepsy), may lead to novel diagnostic tools and treatments for epilepsy. Applications may range from a simple warning to the patient, in order to avert seizure-associated injuries, to intervention by automatic timely administration of an appropriate stimulus, for example of a chemical nature like an anti-epileptic drug (AED), electromagnetic nature like vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial direct current (TDC) or transcranial magnetic stimulation (TMS), and/or of another nature (e.g., ultrasonic, cryogenic, biofeedback operant conditioning). It is thus expected that seizure prediction could readily become an integral part of the treatment of epilepsy through neuromodulation, especially in the new generation of closed-loop seizure control systems. PMID:21939848

Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.

PubMed

Khan, Raja B; Morris, E Brannon; Pui, Ching-Hon; Hudson, Melissa M; Zhou, Yinmei; Cheng, Cheng; Ledet, Davonna S; Howard, Scott C

2014-06-01

Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate. © The Author(s) 2013.

Diazepam prophylaxis of contrast media-induced seizures during computed tomography of patients with brain metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pagani, J.J.; Hayman, L.A.; Bigelow, R.H.

1983-04-01

The effect of 5 mg of intravenous diazepam (Valium) on contrast media-associated seizer incidence was studied in a randomized controlled trial involving 284 patients with known or suspected brain metastases undergoing cerebral computed tomography. Of these patients, 188 were found to have brain metastases, and it is estimated that for this subgroup prophylactic diazepam reduces the risk of contrast-assocated seizure by a factor of 0.26. Seizures occurred in three of 96 patients with metastases on diazepam and in 14 of 92 patients with metastases but without diazepam. Factors related to increased risk of contrast media-associated seizures are: (1) prior seizuremore » history due to brain metatases and/or prior contrast, (2) progressive cerebral metastases, and (3) prior or concurrent brain antineoplastic therapy. Factors not related to an increased risk of these seizures are: (1) contrast media dosage, chemical composition, or osmolarity, (2) computed tomographic appearance of metastases, and (3) type of primary malignancy. Concomitant therapeutic levels of diphenylhydantoin (Dilantin) do not protect completely against contrast media-associated seizures. Pathophysiology of contrast media-associated seizures is discussed in view of the risk factors determined by this study.« less

Improving staff response to seizures on the epilepsy monitoring unit with online EEG seizure detection algorithms.

PubMed

Rommens, Nicole; Geertsema, Evelien; Jansen Holleboom, Lisanne; Cox, Fieke; Visser, Gerhard

2018-05-11

User safety and the quality of diagnostics on the epilepsy monitoring unit (EMU) depend on reaction to seizures. Online seizure detection might improve this. While good sensitivity and specificity is reported, the added value above staff response is unclear. We ascertained the added value of two electroencephalograph (EEG) seizure detection algorithms in terms of additional detected seizures or faster detection time. EEG-video seizure recordings of people admitted to an EMU over one year were included, with a maximum of two seizures per subject. All recordings were retrospectively analyzed using Encevis EpiScan and BESA Epilepsy. Detection sensitivity and latency of the algorithms were compared to staff responses. False positive rates were estimated on 30 uninterrupted recordings (roughly 24 h per subject) of consecutive subjects admitted to the EMU. EEG-video recordings used included 188 seizures. The response rate of staff was 67%, of Encevis 67%, and of BESA Epilepsy 65%. Of the 62 seizures missed by staff, 66% were recognized by Encevis and 39% by BESA Epilepsy. The median latency was 31 s (staff), 10 s (Encevis), and 14 s (BESA Epilepsy). After correcting for walking time from the observation room to the subject, both algorithms detected faster than staff in 65% of detected seizures. The full recordings included 617 h of EEG. Encevis had a median false positive rate of 4.9 per 24 h and BESA Epilepsy of 2.1 per 24 h. EEG-video seizure detection algorithms may improve reaction to seizures by improving the total number of seizures detected and the speed of detection. The false positive rate is feasible for use in a clinical situation. Implementation of these algorithms might result in faster diagnostic testing and better observation during seizures. Copyright © 2018. Published by Elsevier Inc.

Comparing maximum autonomic activity of psychogenic non-epileptic seizures and epileptic seizures using heart rate variability.

PubMed

Jeppesen, Jesper; Beniczky, Sándor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders

2016-04-01

The semiology of psychogenic non-epileptic seizures (PNES) can resemble epileptic seizures, and differentiation between epileptic seizures with no EEG-correlate and PNES can be challenging even for trained experts. Therefore, there has been a search for a quantitative measure, other than EEG and semiology that could distinguish PNES from epileptic seizures. We used ECG to measure heart rate variability (HRV) in order to compare maximum autonomic activity of epileptic seizures and PNES. These comparisons could potentially serve as biomarkers for distinguishing these types of clinical episodes. Forty-nine epileptic seizures from 17 patients and 24 PNES from 7 patients with analyzable ECG were recorded during long-term video-EEG monitoring. Moving windows of 100 R-R intervals throughout each seizure were used to find maximum values of Cardiac Sympathetic Index (CSI) (sympathetic tonus) and minimum values of Cardiac Vagal Index (CVI), Root-Mean-Square-of-Successive-Differences (RMSSD) and HF-power (parasympathetic tonus). In addition, non-seizure recordings of each patient were used to compare HRV-parameters between the groups. The maximum CSI for epilepsy seizures were higher than PNES (P=0.015). The minimum CVI, minimum RMSSD and HF-power did not show significant difference between epileptic seizures and PNES (P=0.762; P=0.152; P=0.818). There were no statistical difference of non-seizure HRV-parameters between the PNES and epilepsy patients. We found the maximum sympathetic activity accompanying the epileptic seizures to be higher, than that during the PNES. However, the great variation of autonomic response within both groups makes it difficult to use these HRV-measures as a sole measurement in distinguishing epileptic seizures from PNES. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Development of lacosamide for the treatment of partial-onset seizures

PubMed Central

Doty, Pamela; Hebert, David; Mathy, Francois-Xavier; Byrnes, William; Zackheim, James; Simontacchi, Kelly

2013-01-01

Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug–drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic–clonic seizures in those with idiopathic generalized epilepsy. PMID:23859801

Music supported therapy promotes motor plasticity in individuals with chronic stroke.

PubMed

Ripollés, P; Rojo, N; Grau-Sánchez, J; Amengual, J L; Càmara, E; Marco-Pallarés, J; Juncadella, M; Vaquero, L; Rubio, F; Duarte, E; Garrido, C; Altenmüller, E; Münte, T F; Rodríguez-Fornells, A

2016-12-01

Novel rehabilitation interventions have improved motor recovery by induction of neural plasticity in individuals with stroke. Of these, Music-supported therapy (MST) is based on music training designed to restore motor deficits. Music training requires multimodal processing, involving the integration and co-operation of visual, motor, auditory, affective and cognitive systems. The main objective of this study was to assess, in a group of 20 individuals suffering from chronic stroke, the motor, cognitive, emotional and neuroplastic effects of MST. Using functional magnetic resonance imaging (fMRI) we observed a clear restitution of both activity and connectivity among auditory-motor regions of the affected hemisphere. Importantly, no differences were observed in this functional network in a healthy control group, ruling out possible confounds such as repeated imaging testing. Moreover, this increase in activity and connectivity between auditory and motor regions was accompanied by a functional improvement of the paretic hand. The present results confirm MST as a viable intervention to improve motor function in chronic stroke individuals.

Dopey's seizure.

PubMed

Dan, B; Christiaens, F

1999-06-01

Angelman syndrome is a neurogenetic condition namely characterized by developmental delay, virtual absence of expressive verbal language, peculiar organization of movement, seizures and happy demeanor. This syndrome has been recognized since 1965, but it seems that Walt Disney presented an original depiction of it in his first full-length animated film, including myoclonic jerks and an apparently generalized tonic-clonic seizure. Copyright 1999 BEA Trading Ltd.

Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia.

PubMed

Nemes, Ashley D; O'Dwyer, Rebecca; Najm, Imad M; Ying, Zhong; Gonzalez-Martinez, Jorge; Alexopoulos, Andreas V

2017-10-01

Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA A ) antagonist used to provoke generalized seizures as a "second hit." LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Early and late postoperative seizure outcome in 97 patients with supratentorial meningioma and preoperative seizures: a retrospective study.

PubMed

Zheng, Zhe; Chen, Peng; Fu, Weiming; Zhu, Junming; Zhang, Hong; Shi, Jian; Zhang, Jianmin

2013-08-01

We identified factors associated with early and late postoperative seizure control in patients with supratentorial meningioma plus preoperative seizures. In this retrospective study, univariate analysis and multivariate logistic regression analysis compared 24 clinical variables according to the occurrence of early (≤1 week) or late (>1 week) postoperative seizures. Sixty-two of 97 patients (63.9 %) were seizure free for the entire postoperative follow-up period (29.5 ± 11.8 months), while 13 patients (13.4 %) still had frequent seizures at the end of follow-up. Fourteen of 97 patients (14.4 %) experienced early postoperative seizures, and emergence of new postoperative neurological deficits was the only significant risk factor (odds ratio = 7.377). Thirty-three patients (34.0 %) experienced late postoperative seizures at some time during follow-up, including 12 of 14 patients with early postoperative seizures. Associated risk factors for late postoperative seizures included tumor progression (odds ratio = 7.012) and new permanent postoperative neurological deficits (odds ratio = 4.327). Occurrence of postoperative seizures in patients with supratentorial meningioma and preoperative seizure was associated with new postoperative neurological deficits. Reduced cerebral or vascular injury during surgery may lead to fewer postoperative neurological deficits and better seizure outcome.

Seizures and Teens: The Practical Aspects of Managing Seizure Medications

ERIC Educational Resources Information Center

Shafer, Patricia Osborne; Israel, Beth

2007-01-01

Medications are the primary treatment for epilepsy, yet many teens and their families have problems managing seizure medicines. Fear of side effects, difficulties remembering to take medicines and figuring out how to take them are common challenges. Unfortunately, not taking medicine as prescribed can lead to breakthrough seizures, which in turn…

MST Pellet Injector Upgrades to Probe Beta and Density Limits and Impurity Particle Transport

NASA Astrophysics Data System (ADS)

Caspary, K. J.; Chapman, B. E.; Anderson, J. K.; Kumar, S. T. A.; Limbach, S. T.; Oliva, S. P.; Sarff, J. S.; Waksman, J.; Combs, S. K.; Foust, C. R.

2012-10-01

Upgrades to the pellet injector on MST will allow for significantly increased fueling capability enabling density limit studies for previously unavailable density regimes. Thus far, Greenwald fractions of 1.2 and 1.5 have been achieved in 500 kA and 200 kA improved confinement plasmas, respectively. The size of the pellet guide tubes, which constrain the lateral motion of the pellet in flight, was increased to accommodate pellets of up to 4.0 mm in diameter, capable of fueling to Greenwald fractions > 2.0 for MST's peak current of 600 kA. Exploring the effect of increased density on NBI deposition shows that for MST's NBI, core deposition of 25 keV neutrals is optimized for densities of 2 -- 3 x 10^19 m-3. This is key for beta limit studies in pellet fueled discharges with improved confinement where maximum NBI heating is desired. In addition, a modification to the injector has allowed operation using alternative pellet fuels with triple points significantly higher than that of deuterium (18.7 K). A small flow of helium into the pellet formation vacuum chamber introduces a controllable heat source capable of elevating the operating temperature of the injector. Injection of methane pellets with a triple point of 90.7 K results in a 12-fold increase in the core carbon impurity density. The flow rate is easily adjusted to optimize injector operating temperature for other fuel gases as well. Work supported by US DoE.

An Open and Shut Case: The Interaction of Magnesium with MST Enzymes

PubMed Central

2016-01-01

The shikimate pathway of bacteria, fungi, and plants generates chorismate, which is drawn into biosynthetic pathways that form aromatic amino acids and other important metabolites, including folates, menaquinone, and siderophores. Many of the pathways initiated at this branch point transform chorismate using an MST enzyme. The MST enzymes (menaquinone, siderophore, and tryptophan biosynthetic enzymes) are structurally homologous and magnesium-dependent, and all perform similar chemical permutations to chorismate by nucleophilic addition (hydroxyl or amine) at the 2-position of the ring, inducing displacement of the 4-hydroxyl. The isomerase enzymes release isochorismate or aminodeoxychorismate as the product, while the synthase enzymes also have lyase activity that displaces pyruvate to form either salicylate or anthranilate. This has led to the hypothesis that the isomerase and lyase activities performed by the MST enzymes are functionally conserved. Here we have developed tailored pre-steady-state approaches to establish the kinetic mechanisms of the isochorismate and salicylate synthase enzymes of siderophore biosynthesis. Our data are centered on the role of magnesium ions, which inhibit the isochorismate synthase enzymes but not the salicylate synthase enzymes. Prior structural data have suggested that binding of the metal ion occludes access or egress of substrates. Our kinetic data indicate that for the production of isochorismate, a high magnesium ion concentration suppresses the rate of release of product, accounting for the observed inhibition and establishing the basis of the ordered-addition kinetic mechanism. Moreover, we show that isochorismate is channeled through the synthase reaction as an intermediate that is retained in the active site by the magnesium ion. Indeed, the lyase-active enzyme has 3 orders of magnitude higher affinity for the isochorismate complex relative to the chorismate complex. Apparent negative-feedback inhibition by ferrous

Utility of laboratory studies in seizures of children older than one month of age.

PubMed

Karbasi, S Akhavan; Mosadegh, M Modares; Fallah, R

2009-08-01

Seizure is the most common paediatric neurological disease which occurs in ten percent of children. In approaching a convulsive patient, finding the causes of seizure is essential, and the patient's history as well as the physical examination are important. The role of routine laboratory tests for children's seizures (except neonates) is undetermined, but checking for serum sodium, glucose, calcium and urea routinely has been advised. The purpose of this study was to determine the diagnostic efficacy of these serum chemistry tests in the seizures of children older than one month of age. In this descriptive, retrospective study, medical records of 302 hospitalised children with seizure were reviewed. Results of laboratory tests, like sodium, calcium, blood glucose and urea levels, pertinent history and physical examination, and the change in patient management based on serum chemistry test results, were analysed. All the children in the study were classified as having seizure with or without fever. In 302 hospitalised children with seizure, about ten percent of 938 tests were abnormal. 27.7 percent of these abnormal results were seen in 1-12-month-old infants. Only 11 percent of abnormal tests (1.3 percent of total tests) might have caused a seizure. Also, 0.2 percent of the results could not be predicted from the history or physical examination, which was conducted in patients younger than one year of age. Routine determination of serum chemistry values in seizures of children does not contribute to therapy, and are costly and time-consuming. It may not be helpful and informative unless the patient is less than one year of age.

Photogenic partial seizures.

PubMed

Hennessy, M J; Binnie, C D

2000-01-01

To establish the incidence and symptoms of partial seizures in a cohort of patients investigated on account of known sensitivity to intermittent photic stimulation and/or precipitation of seizures by environmental visual stimuli such as television (TV) screens or computer monitors. We report 43 consecutive patients with epilepsy, who had exhibited a significant EEG photoparoxysmal response or who had seizures precipitated by environmental visual stimuli and underwent detailed assessment of their photosensitivity in the EEG laboratory, during which all were questioned concerning their ictal symptoms. All patients were considered on clinical grounds to have an idiopathic epilepsy syndrome. Twenty-eight (65%) patients reported visually precipitated attacks occurring initially with maintained consciousness, in some instances evolving to a period of confusion or to a secondarily generalized seizure. Visual symptoms were most commonly reported and included positive symptoms such as coloured circles or spots, but also blindness and subjective symptoms such as "eyes going funny." Other symptoms described included nonspecific cephalic sensations, deja-vu, auditory hallucinations, nausea, and vomiting. No patient reported any clear spontaneous partial seizures, and there were no grounds for supposing that any had partial epilepsy excepting the ictal phenomenology of some or all of the visually induced attacks. These findings provide clinical support for the physiological studies that indicate that the trigger mechanism for human photosensitivity involves binocularly innervated cells located in the visual cortex. Thus the visual cortex is the seat of the primary epileptogenic process, and the photically triggered discharges and seizures may be regarded as partial with secondary generalization.

How long do most seizures last? A systematic comparison of seizures recorded in the epilepsy monitoring unit.

PubMed

Jenssen, Sigmund; Gracely, Edward J; Sperling, Michael R

2006-09-01

More information is needed regarding how long seizures typically last, since this influences treatment decisions. Seizure type and other factors could influence seizure duration. Data were collected from a random sample of patients being evaluated with continuous video and scalp EEG. Seizure duration was defined as time from early sign of seizure (clinical or EEG) until the end of seizure on EEG. Seizures were categorized as simple partial (SPS), complex partial (CPS), secondarily generalized tonic-clonic (SGTCS), primary generalized tonic-clonic (PGTCS) and tonic (TS). SGTCS were divided into a complex partial part (SGTCS/CP) and a tonic-clonic part (SGTCS/TC). Median and longest duration of each seizure type in each individual were used. Comparisons of seizure types, first and last seizure, area of onset, and state of onset were performed. Five hundred seventy-nine seizures were recorded in 159 adult patients. Seizures with partial onset spreading to both hemispheres had the longest duration. SGTCS were unlikely to last more than 660 s, CPS more than 600 s, and SPS more than 240 s. PGTCS and TS had shorter durations, but the number of subjects with those two types was small. CPS did not differ in duration according to sleep state at onset nor side of origin. A working definition of status epilepticus in adults with cryptogenic or symptomatic epilepsy can be drawn from these data for purposes of future epidemiologic research. More information is needed for the idiopathic epilepsies and in children.

Fluctuation reduction and enhanced confinement in the MST reversed-field pinch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Brett Edward

1997-10-01

Plasmas with a factor of ≥3 improvement in energy confinement have been achieved in the MST reversed-field pinch (RFP). These plasmas occur spontaneously, following sawtooth crashes, subject to constraints on, eg, toroidal magnetic field reversal and wall conditioning. Possible contributors to the improved confinement include a reduction of core-resonant, global magnetic fluctuations and a reduction of electrostatic fluctuations over the entire plasma edge. One feature of these plasmas is a region of strong ExB flow shear in the edge. Never before observed in conjunction with enhanced confinement in the RFP, such shear is common in enhanced confinement discharges in tokamaks and stellarators. Another feature of these plasmas is a new type of discrete dynamo event. Like sawtooth crashes, a common form of discrete dynamo, these events correspond to bursts of edge parallel current. The reduction of electrostatic fluctuations in these plasmas occurs within and beyond the region of strong ExB flow shear, similar to what is observed in tokamaks and stellarators. However, the reductions in the MST include fluctuations whose correlation lengths are larger than the width of the shear region. The reduction of the global magnetic fluctuations is most likely due to flattening of the μ=μ 0more » $$\\vec{J}$$∙$$\\vec{B}$$/B 2 profile. Flattening can occur, eg, due to the new type of discrete dynamo event and reduced edge resistivity. Enhanced confinement plasmas are also achieved in the MST when auxiliary current is applied to flatten the μ profile and reduce magnetic fluctuations. Unexpectedly, these plasmas also exhibit a region (broader than in the case above) of strong ExB flow shear in the edge, an edge-wide reduction of electrostatic fluctuations, and the new type of discrete dynamo event. Auxiliary current drive has historically been viewed as the principal route to fusion reactor viability for the RFP.« less

Characteristics of seizure-induced signal changes on MRI in patients with first seizures.

PubMed

Kim, Si Eun; Lee, Byung In; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Park, Kang Min; Kim, Hyung Chan; Lee, Joonwon; Bae, Soo-Young; Lee, Dongah; Kim, Sung Eun

2017-05-01

The aim of this study was to investigate the predictive factors and identify the characteristics of the seizure-induced signal changes on MRI (SCM) in patients with first seizures. We conducted a retrospective study of patients with first seizures from March 2010 to August 2014. The inclusion criteria for this study were patients with 1) first seizures, and 2) MRI and EEG performed within 24h of the first seizures. The definition of SCM was hyper-intensities in the brain not applying to cerebral arterial territories. Multivariate logistic regression was performed with or without SCM as a dependent variable. Of 431 patients with seizures visiting the ER, 69 patients met the inclusion criteria. Of 69 patients, 11 patients (15.9%) had SCM. Epileptiform discharge on EEG (OR 29.7, 95% CI 1.79-493.37, p=0.018) was an independently significant variable predicting the presence of SCM in patients with first seizures. In addition, the topography of SCM was as follows; i) ipsilateral hippocampus, thalamus and cerebral cortex (5/11), ii) unilateral cortex (4/11), iii) ipsilateral thalamus and cerebral cortex (1/11), iv) bilateral hippocampus (1/11). Moreover, 6 out of 7 patients who underwent both perfusion CT and MRI exhibited unilateral cortical hyperperfusion with ipsilateral thalamic involvement reflecting unrestricted vascular territories. There is an association between epileptiform discharges and SCM. Additionally, the involvement of the unilateral cortex and ipsilateral thalamus in SCM and its hyperperfusion state could be helpful in differentiating the consequences of epileptic seizures from other pathologies. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Electroencephalography after a single unprovoked seizure.

PubMed

Debicki, Derek B

2017-07-01

Electroencephalography (EEG) is an essential diagnostic tool in the evaluation of seizure disorders. In particular, EEG is used as an additional investigation for a single unprovoked seizure. Epileptiform abnormalities are related to seizure disorders and have been shown to predict recurrent unprovoked seizures (i.e., a clinical definition of epilepsy). Thus, the identification of epileptiform abnormalities after a single unprovoked seizure can inform treatment options. The current review addresses the relationship between EEG abnormalities and seizure recurrence. This review also addresses factors that are found to improve the yield of recording epileptiform abnormalities including timing of EEG relative to the new-onset seizure, use of repeat studies, use of sleep deprivation and prolonged recordings. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Hyponatraemia and Moduretic-grand mal seizures: a review.

PubMed Central

Johnston, C; Webb, L; Daley, J; Spathis, G S

1989-01-01

Three cases are presented which emphasize the importance of hyponatraemia as a cause of grand mal seizures. The combination of hydrochlorothiazide and amiloride appears to increase the risk of hyponatraemia. We discuss the aetiology and treatment of hyponatraemia and review the necessity for such combination therapy. We recommend caution in prescribing diuretics and preparations such as Moduretic should be used only in those few patients shown to need potassium supplementation. PMID:2506346

Influence of vigilance state on physiological consequences of seizures and seizure-induced death in mice.

PubMed

Hajek, Michael A; Buchanan, Gordon F

2016-05-01

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP occurs more commonly during nighttime sleep. The details of why SUDEP occurs at night are not well understood. Understanding why SUDEP occurs at night during sleep might help to better understand why SUDEP occurs at all and hasten development of preventive strategies. Here we aimed to understand circumstances causing seizures that occur during sleep to result in death. Groups of 12 adult male mice were instrumented for EEG, EMG, and EKG recording and subjected to seizure induction via maximal electroshock (MES) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Seizure inductions were performed with concomitant EEG, EMG, and EKG recording and breathing assessment via whole body plethysmography. Seizures induced via MES during sleep were associated with more profound respiratory suppression and were more likely to result in death. Despite REM sleep being a time when seizures do not typically occur spontaneously, when seizures were forced to occur during REM sleep, they were invariably fatal in this model. An examination of baseline breathing revealed that mice that died following a seizure had increased baseline respiratory rate variability compared with those that did not die. These data demonstrate that sleep, especially REM sleep, can be a dangerous time for a seizure to occur. These data also demonstrate that there may be baseline respiratory abnormalities that can predict which individuals have higher risk for seizure-induced death.

Predicting Epileptic Seizures in Advance

PubMed Central

Moghim, Negin; Corne, David W.

2014-01-01

Epilepsy is the second most common neurological disorder, affecting 0.6–0.8% of the world's population. In this neurological disorder, abnormal activity of the brain causes seizures, the nature of which tend to be sudden. Antiepileptic Drugs (AEDs) are used as long-term therapeutic solutions that control the condition. Of those treated with AEDs, 35% become resistant to medication. The unpredictable nature of seizures poses risks for the individual with epilepsy. It is clearly desirable to find more effective ways of preventing seizures for such patients. The automatic detection of oncoming seizures, before their actual onset, can facilitate timely intervention and hence minimize these risks. In addition, advance prediction of seizures can enrich our understanding of the epileptic brain. In this study, drawing on the body of work behind automatic seizure detection and prediction from digitised Invasive Electroencephalography (EEG) data, a prediction algorithm, ASPPR (Advance Seizure Prediction via Pre-ictal Relabeling), is described. ASPPR facilitates the learning of predictive models targeted at recognizing patterns in EEG activity that are in a specific time window in advance of a seizure. It then exploits advanced machine learning coupled with the design and selection of appropriate features from EEG signals. Results, from evaluating ASPPR independently on 21 different patients, suggest that seizures for many patients can be predicted up to 20 minutes in advance of their onset. Compared to benchmark performance represented by a mean S1-Score (harmonic mean of Sensitivity and Specificity) of 90.6% for predicting seizure onset between 0 and 5 minutes in advance, ASPPR achieves mean S1-Scores of: 96.30% for prediction between 1 and 6 minutes in advance, 96.13% for prediction between 8 and 13 minutes in advance, 94.5% for prediction between 14 and 19 minutes in advance, and 94.2% for prediction between 20 and 25 minutes in advance. PMID:24911316

Audiogenic reflex seizures in cats

PubMed Central

Lowrie, Mark; Bessant, Claire; Harvey, Robert J; Sparkes, Andrew; Garosi, Laurent

2015-01-01

Objectives This study aimed to characterise feline audiogenic reflex seizures (FARS). Methods An online questionnaire was developed to capture information from owners with cats suffering from FARS. This was collated with the medical records from the primary veterinarian. Ninety-six cats were included. Results Myoclonic seizures were one of the cardinal signs of this syndrome (90/96), frequently occurring prior to generalised tonic–clonic seizures (GTCSs) in this population. Other features include a late onset (median 15 years) and absence seizures (6/96), with most seizures triggered by high-frequency sounds amid occasional spontaneous seizures (up to 20%). Half the population (48/96) had hearing impairment or were deaf. One-third of cats (35/96) had concurrent diseases, most likely reflecting the age distribution. Birmans were strongly represented (30/96). Levetiracetam gave good seizure control. The course of the epilepsy was non-progressive in the majority (68/96), with an improvement over time in some (23/96). Only 33/96 and 11/90 owners, respectively, felt the GTCSs and myoclonic seizures affected their cat’s quality of life (QoL). Despite this, many owners (50/96) reported a slow decline in their cat’s health, becoming less responsive (43/50), not jumping (41/50), becoming uncoordinated or weak in the pelvic limbs (24/50) and exhibiting dramatic weight loss (39/50). These signs were exclusively reported in cats experiencing seizures for >2 years, with 42/50 owners stating these signs affected their cat’s QoL. Conclusions and relevance In gathering data on audiogenic seizures in cats, we have identified a new epilepsy syndrome named FARS with a geriatric onset. Further studies are warranted to investigate potential genetic predispositions to this condition. PMID:25916687

Quality of life, mood and seizure control in patients with brain tumor related epilepsy treated with lacosamide as add-on therapy: A prospective explorative study with a historical control group.

PubMed

Maschio, Marta; Zarabla, Alessia; Maialetti, Andrea; Fabi, Alessandra; Vidiri, Antonello; Villani, Veronica; Giannarelli, Diana

2017-08-01

Brain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated. Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n=19) treated with Levetiracetam as an add-on. We recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3months and at 6months. This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28-70) with uncontrolled partial-onset seizures treated with LEV as add-on. The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency. Twelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400mg/die (mean final dose 300mg/die). Four patients dropped out due to poor

RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

PubMed Central

Catenacci, Daniel VT; Cervantes, Gustavo; Yala, Soheil; Nelson, Erik A; El-Hashani, Essam; Kanteti, Rajani; El Dinali, Mohamed; Hasina, Rifat; Brägelmann, Johannes; Seiwert, Tanguy; Sanicola, Michele; Henderson, Les; Grushko, Tatyana A; Olopade, Olufunmilayo; Karrison, Theodore; Bang, Yung-Jue; Ho Kim, Woo; Tretiakova, Maria; Vokes, Everett; Frank, David A; Kindler, Hedy L; Huet, Heather

2011-01-01

RON (MST1R) is one of two members of the MET receptor tyrosine kinase family, along with parent receptor MET. RON has a putative role in several cancers, but its expression and function is poorly characterized in gastroesophageal adenocarcinoma. A recognized functional role of MET tyrosine kinase in gastroesophageal cancer has led to early phase clinical trials using MET inhibitors, with unimpressive results. Therefore, the role of RON in gastroesophageal cancer, as well as its role in cooperative signaling with MET and as a mechanism of resistance to MET inhibition, was studied in gastroesophageal tissues and cell lines. By IHC, RON was highly overexpressed in 74% of gastroesophageal samples (n = 94) and overexpression was prognostic of poor survival (p = 0.008); RON and MET co-expression occurred in 43% of samples and was prognostic of worst survival (p = 0.03). High MST1R gene copy number by quantitative polymerase chain reaction and confirmed by fluorescence in situ hybridization and/or array comparative genomic hybridization, was seen in 35.5% (16/45) of cases. High MST1R gene copy number correlated with poor survival (p = 0.01), and was associated with high MET and ERBB2 gene copy number. a novel somatic MST1R juxtamembrane mutation R1018G was found in 11% of samples. RON signaling was functional in cell lines, activating downstream effector STAT3, and resulted in increased viability over controls. RON and MET co-stimulation assays led to enhanced malignant phenotypes over stimulation of either receptor alone. Growth inhibition as evidenced by viability and apoptosis assays was optimal using novel blocking monoclonal antibodies to both ROn and MET, versus either alone. SU11274, a classic MET small molecule tyrosine kinase inhibitor, blocked signaling of both receptors and proved synergistic when combined with STAT3 inhibition (combination index <1). These preclinical studies define RON as an important novel prognostic marker and therapeutic target for

Pre-seizure architecture of the local connections of the epileptic focus examined via graph-theory.

PubMed

Vecchio, Fabrizio; Miraglia, Francesca; Vollono, Catello; Fuggetta, Filomena; Bramanti, Placido; Cioni, Beatrice; Rossini, Paolo Maria

2016-10-01

Epilepsy is characterized by unpredictable and sudden paroxysmal neuronal firing occurrences and sometimes evolving in clinically evident seizure. To predict seizure event, small-world characteristic in nine minutes before seizure, divided in three 3-min periods (T0, T1, T2) were investigated. Intracerebral recordings were obtained from 10 patients with drug resistant focal epilepsy examined by means of stereotactically implanted electrodes; analysis was focused in a period of low spiking (Baseline) and during two seizures. Networks' architecture is undirected and weighted. Electrodes' contacts close to epileptic focus are the vertices, edges are weighted by mscohere (=magnitude squared coherence). Differences were observed between Baseline and T1 and between Baseline and T2 in theta band; and between Baseline and T1, Baseline and T2, and near-significant difference between T0 and T2 in Alpha 2 band. Moreover, an intra-band index was computed for small worldness as difference between Theta and Alpha 2. It was found a growing index trend from Baseline to T2. Cortical network features a specific pre-seizure architecture which could predict the incoming epileptic seizure. Through this study future researches could investigate brain connectivity modifications approximating a clinical seizure also in order to address a preventive therapy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Seizures and Teens: When Seizures Aren't the Only Problem

ERIC Educational Resources Information Center

Kanner, Andres M.; Shafer, Patricia O.

2006-01-01

Some teenagers with epilepsy only have to deal with seizures, which can be tough enough, but for other teens, seizures are not the only problem. Parents and caregivers often report changes in their teens' abilities to think clearly, learn in school, or remain focused in class. Mood and other behavioral problems may also be seen. It is critical…

Recent advances in drug therapy for epilepsy.

PubMed Central

Bruni, J.

1979-01-01

Recent advances in drug therapy for epilepsy have contributed to the reduction in the proportion of persons whose epilepsy is uncontrolled. New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses. Carbamazepine has recently been introduced for the treatment of generalized tonic-clonic and partial seizures. Clonazepam has been found of particular benefit in the treatment of absence and myoclonic seizures. Valproic acid is a promising antiepileptic drug with broad-spectrum activity, and is particularly useful in the treatment of absence and myoclonic seizures, although further clinical experience is required before it can supplant ethosuximide as the preferred drug for the treatment of absence seizures. Monitoring of the plasma concentration of antiepileptic drugs has added greatly to the achievement of optimal drug therapy and the prevention of toxic effects. PMID:371777

Seizure clusters: characteristics and treatment.

PubMed

Haut, Sheryl R

2015-04-01

Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.

Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients Undergoing Surgery for Metastatic Brain Tumors.

PubMed

Wu, Adela; Weingart, Jon D; Gallia, Gary L; Lim, Michael; Brem, Henry; Bettegowda, Chetan; Chaichana, Kaisorn L

2017-08-01

Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined. Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively. Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases. The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures.

PubMed

Wang, Z; Chen, Y; Lü, Y; Chen, X; Cheng, L; Mi, X; Xu, X; Deng, W; Zhang, Y; Wang, N; Li, J; Li, Y; Wang, X

2015-08-06

JNK-interacting protein 3 (JIP3), also known as JNK stress-activated protein kinase-associated protein 1 (JSAP1), is a scaffold protein mainly involved in the regulation of the pro-apoptotic signaling cascade mediated by c-Jun N-terminal kinase (JNK). Overexpression of JIP3 in neurons in vitro has been reported to lead to accelerated activation of JNK and enhanced apoptosis response to cellular stress. However, the occurrence and the functional significance of stress-induced modulations of JIP3 levels in vivo remain elusive. In this study, we investigated the expression of JIP3 in temporal lobe epilepsy (TLE) and in a kainic acid (KA)-induced mouse model of epileptic seizures, and determined whether down-regulation of JIP3 can decrease susceptibility to seizures and neuron damage induced by KA. We found that JIP3 was markedly increased in TLE patients and a mouse model of epileptic seizures; mice underexpressing JIP3 through lentivirus bearing LV-Letm1-RNAi showed decreased susceptibility, delayed first seizure and decreased seizure duration response to the epileptogenic properties of KA. Subsequently, a decreased activation of JNK following seizure induction was observed in mice underexpressing JIP3, which also exhibited less neuronal apoptosis in the CA3 region of the hippocampus, as assessed three days after KA administration. We also found that mice underexpressing JIP3 exhibited a delayed pentylenetetrazole (PTZ)-induced kindling seizure process. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Social context, parental monitoring, and multisystemic therapy outcomes.

PubMed

Robinson, Brittany A; Winiarski, D Anne; Brennan, Patricia A; Foster, Sharon L; Cunningham, Phillippe B; Whitmore, Elizabeth A

2015-03-01

Multisystemic therapy (MST) and other evidence-based treatments targeting juvenile delinquency have been well substantiated in the literature. Although these treatments have been demonstrated to be effective overall at reducing juvenile delinquency, it is well known that they do not benefit all treated youth. Research has yet to examine the potential influence of contextual factors, such as socioeconomic status (SES) and neighborhood characteristics, on treatment outcomes, particularly as they influence parental monitoring, which is often a focus of interventions targeting juvenile delinquency. A primary goal of these treatments is to help parents develop the requisite skills to adequately monitor and discipline their children; however, this goal may be compromised by contextual factors affecting parental effectiveness and, ultimately, treatment efficacy. The objective of this study was to explore the role of SES and neighborhood factors in moderating the effects of parental monitoring across treatment. Using hierarchical linear modeling (HLM), we analyzed these contextual and family predictors of response to MST treatment within a sample of 185 youth (65.4% male) ages 12-18 (M = 15.35; SD = 1.28). Neighborhood factors interacted with parental monitoring, such that monitoring predicted decreases in externalizing behavior only for youth residing in better neighborhoods. In contrast, SES was unrelated to changes in externalizing behaviors in response to MST. Taken together, these results demonstrate a need for further understanding the potential role of the youth's larger social context in predicting MST outcomes. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Does electroconvulsive therapy cause epilepsy?

PubMed

Ray, Anindya Kumar

2013-09-01

Electroconvulsive therapy (ECT) has been mentioned as a risk factor for epilepsy in some texts. This observation is based on isolated case reports and 2 studies done in 1980s. Since 1983, no study was done on this topic. The objective of the current study was to find out the incidence of spontaneous seizures after ECT. The study was done in Central Institute of Psychiatry, India. It was a retrospective cohort study where files of the patients receiving unmodified ECT during 1990 to 1995 were reviewed over approximately the next 10 years. Patients having the risk factors for spontaneous seizures like past and family history of seizure, substance abuse, and organicity were excluded from the study group. For minimizing the confounding effect of concurrent psychotropic drugs, an age-, sex-, and diagnosis-matched control group was selected. This group consisted of patients admitted during the same time and treated with similar drugs but no ECT. No report of spontaneous seizure was found in the study group of 619 patients. One patient who was excluded from the study group due to suspected neurosyphilis developed recurrent seizures 1 month after ECT. Two patients in the control group had single occasion convulsion with no further recurrence even with continuation of similar drugs. Electroconvulsive therapy has not been found to cause epilepsy. Patient's underlying organic condition may influence development of seizures.

Rates and predictors of seizure freedom in resective epilepsy surgery: an update

PubMed Central

Englot, Dario J.; Chang, Edward F.

2017-01-01

Epilepsy is a debilitating neurological disorder affecting approximately 1 % of the world’s population. Drug-resistant focal epilepsies are potentially surgically remediable. Although epilepsy surgery is dramatically underutilized among medically refractory patients, there is an expanding collection of evidence supporting its efficacy which may soon compel a paradigm shift. Of note is that a recent randomized controlled trial demonstrated that early resection leads to considerably better seizure outcomes than continued medical therapy in patients with pharmacoresistant temporal lobe epilepsy. In the present review, we provide a timely update of seizure freedom rates and predictors in resective epilepsy surgery, organized by the distinct pathological entities most commonly observed. Class I evidence, meta-analyses, and individual observational case series are considered, including the experiences of both our institution and others. Overall, resective epilepsy surgery leads to seizure freedom in approximately two thirds of patients with intractable temporal lobe epilepsy and about one half of individuals with focal neocortical epilepsy, although only the former observation is supported by class I evidence. Two common modifiable predictors of postoperative seizure freedom are early operative intervention and, in the case of a discrete lesion, gross total resection. Evidence-based practice guidelines recommend that epilepsy patients who continue to have seizures after trialing two or more medication regimens should be referred to a comprehensive epilepsy center for multidisciplinary evaluation, including surgical consideration. PMID:24497269

Setting the scene: definition of prolonged seizures, acute repetitive seizures, and status epilepticus. Do we know why seizures stop?

PubMed

Cross, J Helen

2014-10-01

Status epilepticus is recognised as an acute emergency requiring urgent intervention. The optimal timing of such an intervention during a prolonged seizure, and the reasons for such, have provided much discussion. For operational purposes, a definition of a prolonged seizure of ≥5 minutes requiring intervention appears justified. However, a definition of status epilepticus of ≥30 minutes should stand, with the proportion of seizures proceeding to this clinical state remaining small. The reasons for this may be inherent to an individual, but an understanding of the mechanisms underlying the predisposition may lead to improved management pathways in the future.

Within-Intervention Change: Mediators of Intervention Effects during Multisystemic Therapy

ERIC Educational Resources Information Center

Dekovic, Maja; Asscher, Jessica J.; Manders, Willeke A.; Prins, Pier J. M.; van der Laan, Peter

2012-01-01

Objective: The present study tested the hypothesis that improvements in parental sense of competence during multisystemic therapy (MST) lead to positive changes in parenting, which in turn lead to a decrease of adolescent externalizing problems. Mediational models were tested separately for 3 dimensions of parenting (positive discipline, inept…

Spatial Attention Reduces Burstiness in Macaque Visual Cortical Area MST.

PubMed

Xue, Cheng; Kaping, Daniel; Ray, Sonia Baloni; Krishna, B Suresh; Treue, Stefan

2017-01-01

Visual attention modulates the firing rate of neurons in many primate cortical areas. In V4, a cortical area in the ventral visual pathway, spatial attention has also been shown to reduce the tendency of neurons to fire closely separated spikes (burstiness). A recent model proposes that a single mechanism accounts for both the firing rate enhancement and the burstiness reduction in V4, but this has not been empirically tested. It is also unclear if the burstiness reduction by spatial attention is found in other visual areas and for other attentional types. We therefore recorded from single neurons in the medial superior temporal area (MST), a key motion-processing area along the dorsal visual pathway, of two rhesus monkeys while they performed a task engaging both spatial and feature-based attention. We show that in MST, spatial attention is associated with a clear reduction in burstiness that is independent of the concurrent enhancement of firing rate. In contrast, feature-based attention enhances firing rate but is not associated with a significant reduction in burstiness. These results establish burstiness reduction as a widespread effect of spatial attention. They also suggest that in contrast to the recently proposed model, the effects of spatial attention on burstiness and firing rate emerge from different mechanisms. © The Author 2016. Published by Oxford University Press.

Two-fluid Magnetic Relaxation in the MST Reversed Field Pinch

NASA Astrophysics Data System (ADS)

Triana, Joseph; Almagri, Af; McCollam, Kj; Sarff, Js; Sovinec, Cr

2016-10-01

Recent measurements and extended MHD simulations expose the importance of two-fluid physics in the relaxation and self-organization of the current and momentum profiles in RFP plasmas. A hallmark of relaxation is that the inductive electric field is not balanced by resistive dissipation, prompting the study of fluctuation-induced emfs in the generalized Ohm's law, E- ηJ =- +/ne, the two terms on the right known as the MHD and Hall dynamo terms, respectively. The Hall emf is measured in the outer half of the MST plasma minor radius using an armored deep-insertion probe. The emf matches previous measurements in the edge (r/a>0.8) but in the new region examined (0.8>r/a>0.6) it is much larger than E- ηJ, implying the MHD dynamo must also be large and oppositely directed. Recent nonlinear simulations that include two-fluid effects using the extended-MHD NIMROD code show complex radial structure for the emf terms, but the size of the measured Hall emf is much larger than predicted by the simulations. In the two-fluid model, the Hall dynamo couples to the parallel momentum as the mean-field Maxwell stress. The simulations predict relaxation of the parallel flow profiles that is also qualitatively consistent with measurements in MST plasmas. Work supported by US DoE and NSF.

Seizures and Epilepsy in Alzheimer’s Disease

PubMed Central

Friedman, Daniel; Honig, Lawrence S.; Scarmeas, Nikolaos

2013-01-01

Introduction Many studies have shown that patients with Alzheimer’s disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome and progression vary widely between studies. Methods Literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG)studies, and treatment responses. Finally, we consider limitations and methodological issues. Results There is considerable variability in the reported prevalence and incidence of seizures in patients with AD - with reported lifetime prevalence rates of 1.5 - 64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. Conclusions The literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps. PMID:22070283

Generalized onset seizures with focal evolution (GOFE) - A unique seizure type in the setting of generalized epilepsy.

PubMed

Linane, Avriel; Lagrange, Andre H; Fu, Cary; Abou-Khalil, Bassel

2016-01-01

We report clinical and electrographic features of generalized onset seizures with focal evolution (GOFE) and present arguments for the inclusion of this seizure type in the seizure classification. The adult and pediatric Epilepsy Monitoring Unit databases at Vanderbilt Medical Center and Children's Hospital were screened to identify generalized onset seizures with focal evolution. We reviewed medical records for epilepsy characteristics, epilepsy risk factors, MRI abnormalities, neurologic examination, antiepileptic medications before and after diagnosis, and response to medications. We also reviewed ictal and interictal EEG tracings, as well as video-recorded semiology. Ten patients were identified, 7 males and 3 females. All of the patients developed generalized epilepsy in childhood or adolescence (ages 3-15years). Generalized onset seizures with focal evolution developed years after onset in 9 patients, with a semiology concerning for focal seizures or nonepileptic events. Ictal discharges had a generalized onset on EEG, described as either generalized spike-and-wave and/or polyspike-and-wave discharges, or generalized fast activity. This electrographic activity then evolved to focal rhythmic activity most commonly localized to one temporal or frontal region; five patients had multiple seizures evolving to focal activity in different regions of both hemispheres. The predominant interictal epileptiform activity included generalized spike-and-wave and/or polyspike-and-wave discharges in all patients. Taking into consideration all clinical and EEG data, six patients were classified with genetic (idiopathic) generalized epilepsy, and four were classified with structural/metabolic (symptomatic) generalized epilepsy. All of the patients had modifications to their medications following discharge, with three becoming seizure-free and five responding with >50% reduction in seizure frequency. Generalized onset seizures may occasionally have focal evolution with semiology

Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei

PubMed Central

Feng, Li; Motelow, Joshua E.; Ma, Chanthia; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro

2017-01-01

The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal

Intraoperative seizures during craniotomy under general anesthesia.

PubMed

Howe, John; Lu, Xiaoying; Thompson, Zoe; Peterson, Gordon W; Losey, Travis E

2016-05-01

An acute symptomatic seizure is a clinical seizure occurring at the time of or in close temporal association with a brain insult. We report an acute symptomatic seizure occurring during a surgical procedure in a patient who did not have a prior history of epilepsy and who did not have a lesion associated with an increased risk of epilepsy. To characterize the incidence and clinical features of intraoperative seizures during craniotomy under general anesthesia, we reviewed cases where continuous EEG was acquired during craniotomy. Records of 400 consecutive cases with propofol as general anesthesia during craniotomy were reviewed. Demographic data, indication for surgery, clinical history, history of prior seizures, duration of surgery and duration of burst suppression were recorded. Cases where seizures were observed were analyzed in detail. Two out of 400 patients experienced intraoperative seizures, including one patient who appeared to have an acute symptomatic seizure related to the surgical procedure itself and a second patient who experienced two seizures likely related to an underlying diagnosis of epilepsy. This is the first report of an acute symptomatic seizure secondary to a neurosurgical procedure. Overall, 0.5% of patients monitored experienced seizures, indicating that intraoperative seizures are rare, and EEG monitoring during craniotomies is of low yield in detecting seizures. Copyright © 2016. Published by Elsevier Ltd.

Mammalian Sterile 20-like Kinase 1 (Mst1) Enhances the Stability of Forkhead Box P3 (Foxp3) and the Function of Regulatory T Cells by Modulating Foxp3 Acetylation.

PubMed

Li, Jiang; Du, Xingrong; Shi, Hao; Deng, Kejing; Chi, Hongbo; Tao, Wufan

2015-12-25

Regulatory T cells (Tregs) play crucial roles in maintaining immune tolerance. The transcription factor Foxp3 is a critical regulator of Treg development and function, and its expression is regulated at both transcriptional and post-translational levels. Acetylation by lysine acetyl transferases/lysine deacetylases is one of the main post-translational modifications of Foxp3, which regulate Foxp3's stability and transcriptional activity. However, the mechanism(s) by which the activities of these lysine acetyl transferases/lysine deacetylases are regulated to preserve proper Foxp3 acetylation during Treg development and maintenance of Treg function remains to be determined. Here we report that Mst1 can enhance Foxp3 stability, its transcriptional activity, and Treg function by modulating the Foxp3 protein at the post-translational level. We discovered that Mst1 could increase the acetylation of Foxp3 by inhibiting Sirt1 activity, which requires the Mst1 kinase activity. We also found that Mst1 could attenuate Sirt1-mediated deacetylation of Foxp3 through directly interacting with Foxp3 to prevent or interfere the interaction between Sirt1 and Foxp3. Therefore, Mst1 can regulate Foxp3 stability in kinase-dependent and kinase-independent manners. Finally, we showed that treatment of Mst1(-/-) Tregs with Ex-527, a Sirt1-specific inhibitor, partially restored the suppressive function of Mst1(-/-) Tregs. Our studies reveal a novel mechanism by which Mst1 enhances Foxp3 expression and Treg function at the post-translational level. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats.

PubMed

Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G

2013-05-01

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect.

[Reflex seizures, cinema and television].

PubMed

Olivares-Romero, Jesús

2015-12-16

In movies and television series are few references to seizures or reflex epilepsy even though in real life are an important subgroup of total epileptic syndromes. It has performed a search on the topic, identified 25 films in which they appear reflex seizures. Most seizures observed are tonic-clonic and visual stimuli are the most numerous, corresponding all with flashing lights. The emotions are the main stimuli in higher level processes. In most cases it is not possible to know if a character suffers a reflex epilepsy or suffer reflex seizures in the context of another epileptic syndrome. The main conclusion is that, in the movies, the reflex seizures are merely a visual reinforcing and anecdotal element without significant influence on the plot.

Pretreatment seizure semiology in childhood absence epilepsy.

PubMed

Kessler, Sudha Kilaru; Shinnar, Shlomo; Cnaan, Avital; Dlugos, Dennis; Conry, Joan; Hirtz, Deborah G; Hu, Fengming; Liu, Chunyan; Mizrahi, Eli M; Moshé, Solomon L; Clark, Peggy; Glauser, Tracy A

2017-08-15

To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes. For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit. Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%-84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern. Almost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome. © 2017 American Academy of Neurology.

19 CFR 162.22 - Seizure of conveyances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Seizure of conveyances. 162.22 Section 162.22... TREASURY (CONTINUED) INSPECTION, SEARCH, AND SEIZURE Seizures § 162.22 Seizure of conveyances. (a) General applicability. If it shall appear to any officer authorized to board conveyances and make seizures that there...

[Peptidergic nootropic therapy in cerebral palsy associated with epilepsy].

PubMed

Kholin, A A; Zavadenko, N N; Il Ina, E S; Kolpakchi, L M; Fedonyuk, I D; Bembeeva, R C; Esipova, E S

To assess the efficacy and safety of сortexin in the treatment of children with cerebral palsy (CP) combined with epilepsy. Eighty-four patients (55 boys and 29 girls), aged from 1 to 11 years, with CP combined with epilepsy received cortexin together with antiepileptic drugs (AEDs). Cortexin was administered in doses of 5-10 mg depending on the patient's age and body weight intramuscularly during hospitalization. Cortexin as add-on to AEDs reduced for more than two times the number of seizures, along with improvement of motor function, in 31 (36.9%) patients. The improvement of motor function, but without a significant decrease in epileptic seizures, was achieved in 15 (17.8%) of the patients. Reduction of epileptic seizures frequency (>2 times), but without a significant effect on motor function, was observed in 14 cases (16.7%). Twenty-three patients (27.4%) did not respond the therapy. The aggravation of epileptic seizures during cortexin therapy was observed in only 1 girl with West syndrome (1.2%), and this was significantly lower than the probability of seizures aggravation on AED. Polypeptide nootropic medication cortexin demonstrated efficacy and safety as adjunctive therapy in children with CP combined with epilepsy.

The effects of music-supported therapy on motor, cognitive, and psychosocial functions in chronic stroke.

PubMed

Fujioka, Takako; Dawson, Deirdre R; Wright, Rebecca; Honjo, Kie; Chen, Joyce L; Chen, J Jean; Black, Sandra E; Stuss, Donald T; Ross, Bernhard

2018-05-24

Neuroplasticity accompanying learning is a key mediator of stroke rehabilitation. Training in playing music in healthy populations and patients with movement disorders requires resources within motor, sensory, cognitive, and affective systems, and coordination among these systems. We investigated effects of music-supported therapy (MST) in chronic stroke on motor, cognitive, and psychosocial functions compared to conventional physical training (GRASP). Twenty-eight adults with unilateral arm and hand impairment were randomly assigned to MST (n = 14) and GRASP (n = 14) and received 30 h of training over a 10-week period. The assessment was conducted at four time points: before intervention, after 5 weeks, after 10 weeks, and 3 months after training completion. As for two of our three primary outcome measures concerning motor function, all patients slightly improved in Chedoke-McMaster Stroke Assessment hand score, while the time to complete Action Research Arm Test became shorter in the MST group. The third primary outcome measure for well-being, Stroke Impact Scale, was improved for emotion and social communication earlier in MST and coincided with the improved executive function for task switching and music rhythm perception. The results confirmed previous findings and expanded the potential usage of MST for enhancing quality of life in community-dwelling chronic-stage survivors. © 2018 New York Academy of Sciences.

Glycolysis in energy metabolism during seizures.

PubMed

Yang, Heng; Wu, Jiongxing; Guo, Ren; Peng, Yufen; Zheng, Wen; Liu, Ding; Song, Zhi

2013-05-15

Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment.

Anti-proliferative effects, cell cycle G2/M phase arrest and blocking of chromosome segregation by probimane and MST-16 in human tumor cell lines

PubMed Central

Lu, Da Yong; Huang, Min; Xu, Cheng Hui; Yang, Wei Yi; Hu, Chao Xin; Lin, Li Ping; Tong, Lin Jiang; Li, Mei Hong; Lu, Wei; Zhang, Xiong Wen; Ding, Jian

2005-01-01

Background Anticancer bisdioxopiperazines, including ICRF-154, razoxane (Raz, ICRF-159) and ICRF-193, are a family of anticancer agents developed in the UK, especially targeting metastases of neoplasms. Two other bisdioxopiperazine derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Cytotoxic activities and mechanisms of Raz (+)-steroisomer (ICRF-187, dexrazoxane), Pro and MST-16 against tumor cells were evaluated by MTT colorimetry, flow cytometry and karyotyping. Results Pro was cytotoxic to human tumor cell lines in vitro (IC50<50 μM for 48 h). Four human tumor cell lines (SCG-7901, K562, A549 and HL60) were susceptible to Pro at low inhibitory concentrations (IC50 values < 10 μM for 48 h). Although the IC50 against HeLa cell line of vincristine (VCR, 4.56 μM), doxorubicin (Dox, 1.12 μM) and 5-fluoruouracil (5-Fu, 0.232 μM) are lower than Pro (5.12 μM), ICRF-187 (129 μM) and MST-16 (26.4 μM), VCR, Dox and 5-Fu shows a low dose-related – high cytotoxic activity. Time-response studies showed that the cytotoxic effects of Pro are increased for 3 days in human tumor cells, whereas VCR, Dox and 5-Fu showed decreased cytotoxic action after 24 h. Cell cycle G2/M phase arrest and chromosome segregation blocking by Pro and MST-16 were noted. Although there was similar effects of Pro and MST-16 on chromosome segregation blocking action and cell cycle G2/M phase arrest at 1- 4 μM, cytotoxicity of Pro against tumor cells was higher than that of MST-16 in vitro by a factor of 3- 10 folds. Our data show that Pro may be more effective against lung cancer and leukemia while ICRF-187 and MST-16 shows similar IC50 values only against leukemia. Conclusion It suggests that Pro has a wider spectrum of cytotoxic effects against human tumor cells than other bisdioxopiperazines, especially against solid tumors, and with a single cytotoxic pathway of Pro and MST-16 affecting

Runaway electrons and mitigation studies in MST tokamak plasmas

NASA Astrophysics Data System (ADS)

Goetz, J. A.; Chapman, B. E.; Almagri, A. F.; Cornille, B. S.; Dubois, A.; McCollam, K. J.; Munaretto, S.; Sovinec, C. R.

2016-10-01

Studies of runaway electrons generated in low-density MST tokamak plasmas are being undertaken. The plasmas have Bt <= 0.14 T, Ip <= 50 kA, q (a) = 2.2 , and an electron density and temperature of about 5 ×1017m-3 and 150 eV. Runaway electrons are detected via x-ray bremsstrahlung emission. The density and electric field thresholds for production and suppression have been previously explored with variations in gas puffing for density control. Runaway electrons are now being probed with resonant magnetic perturbations (RMP's). An m = 3 RMP strongly suppresses the runaway electrons and initial NIMROD modeling shows that this may be due to degradation of flux surfaces. The RMP is produced by a poloidal array of 32 saddle coils at the narrow vertical insulated cut in MST's thick conducting shell, with each RMP having a single m but a broad n spectrum. While a sufficiently strong m = 3 RMP suppresses the runaway electrons, an RMP with m = 1 and comparable amplitude has little effect. The impact of the RMP's on the magnetic topology of these plasmas is being studied with the nonlinear MHD code NIMROD. With an m = 3 RMP, stochasticity is introduced in the outer third of the plasma but no such flux surface degradation is observed with an m = 1 RMP. NIMROD also predicts regularly occurring MHD activity similar to that observed in the experiment. These studies have also been done in q (a) = 2.7 plasmas and analysis and modeling is ongoing. This work supported by USDoE.

Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures.

PubMed

Awad, Patricia N; Sanon, Nathalie T; Chattopadhyaya, Bidisha; Carriço, Josianne Nunes; Ouardouz, Mohamed; Gagné, Jonathan; Duss, Sandra; Wolf, Daniele; Desgent, Sébastien; Cancedda, Laura; Carmant, Lionel; Di Cristo, Graziella

2016-07-01

Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling and chemical-induced seizure models.

PubMed

Shannon, Harlan E; Yang, Lijuan

2004-01-01

Neuropeptide Y (NPY) administered exogenously is anticonvulsant, and, NPY null mutant mice are more susceptible to kainate-induced seizures. In order to better understand the potential role of NPY in epileptogenesis, the present studies investigated the development of amygdala kindling, post-kindling seizure thresholds, and anticonvulsant effects of carbamazepine and levetiracetam in 129S6/SvEv NPY(+/+) and NPY(-/-) mice. In addition, susceptibility to pilocarpine- and kainate-induced seizures was compared in NPY(+/+) and (-/-) mice. The rate of amygdala kindling development did not differ in the NPY(-/-) and NPY(+/+) mice either when kindling stimuli were presented once daily for at least 20 days, or, 12 times daily for 2 days. However, during kindling development, the NPY(-/-) mice had higher seizure severity scores and longer afterdischarge durations than the NPY(+/+) mice. Post-kindling, the NPY(-/-) mice had markedly lower afterdischarge thresholds and longer afterdischarge durations than NPY (+/+) mice. Carbamazepine and levetiracetam increased the seizure thresholds of both NPY (-/-) and (+/+) mice. In addition, NPY (-/-) mice had lower thresholds for both kainate- and pilocarpine-induced seizures. The present results in amygdala kindling and chemical seizure models suggest that NPY may play a more prominent role in determining seizure thresholds and severity of seizures than in events leading to epileptogenesis. In addition, a lack of NPY does not appear to confer drug-resistance in that carbamazepine and levetiracetam were anticonvulsant in both wild type (WT) and NPY null mutant mice.

Children with New Onset Seizures: A Prospective Study of Parent Variables, Child Behavior Problems, and Seizure Occurrence

PubMed Central

Austin, Joan K.; Haber, Linda C.; Dunn, David W.; Shore, Cheryl P.; Johnson, Cynthia S.; Perkins, Susan M.

2015-01-01

Objective Parent variables (stigma, mood, unmet needs for information and support, and worry) are associated with behavioral difficulties in children with seizures, however, it is not known how this relationship is influenced by additional seizures. This study followed children (ages 4 – 14 years) and their parents over a 24-month period (with data collected at baseline, 6, 12, and 24 months) and investigated the effect of an additional seizure on the relationship between parenting variables and child behavior difficulties. Methods The sample was parents of 196 children (104 girls and 92 boys) with a first seizure within the past 6 weeks. Child mean age at baseline was 8 years, 3 months (SD 3 years). Data were analyzed using t-tests, chi-square tests, and repeated measures analyses of covariance. Results Relationships between parent variables, additional seizures, and child behavior problems were consistent across time. Several associations between parent variables and child behavior problems were stronger in the additional seizure group than in the no additional seizures group. Conclusions Findings suggest that interventions that assist families to respond constructively to the reactions of others regarding their child's seizure condition and to address their needs for information and support could help families of children with continuing seizures to have an improved quality of life. PMID:26520879

How do doctors in training react to seizures?

PubMed

Seneviratne, Udaya; Ma, Henry; Phan, Thanh G

2016-01-01

There are scant data on how doctors approach seizures in the acute setting. We sought to study (a) exposure to seizure disorders as well as relevant training and (b) reactions to seizures in the acute setting, among medical residents undergoing physician training. The exposure to and training on seizure disorders were assessed using a structured questionnaire first. Then, they were tested with 20 videos consisting of 10 epileptic seizures (ESs) and 10 psychogenic nonepileptic seizures (PNESs). After each video, we asked three questions to test (a) the diagnosis and the practice of administration of benzodiazepines to terminate the seizure, (b) the estimation of seizure duration, and (c) the practice of intubation. The accuracy of diagnosis was measured by the area under the summary receiver operating characteristics curve (AUC). The difference between true seizure duration and estimated duration was evaluated using paired-sample t-test. A total of 48 trainees participated in the study. The majority witnessed seizures in movies (37, 77.1%) and television (35, 72.9%). Only 12 (25%) received bedside teaching on seizure disorders. Their diagnostic accuracy of seizures was very poor (AUC=0.54). Participants significantly underestimated the duration of seizures. Thirty-five doctors made an illogical decision to intubate but not to terminate the seizure with intravenous benzodiazepine. The diagnostic accuracy of seizures is poor among trainees, and their estimates of seizure duration are unreliable. Our study highlights potential pitfalls in the acute management of seizures and the need for more training on seizure disorders. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Misdiagnosis of gastroesophageal reflux disease as epileptic seizures in children.

PubMed

Bayram, Ayşe Kaçar; Canpolat, Mehmet; Karacabey, Neslihan; Gumus, Hakan; Kumandas, Sefer; Doğanay, Selim; Arslan, Duran; Per, Hüseyin

2016-03-01

Gastroesophageal reflux disease (GERD) can mimic epileptic seizure, and may be misdiagnosed as epilepsy. On the other hand, GERD can be more commonly seen in children with neurological disorders such as cerebral palsy (CP); this co-incidence may complicate the management of patients by mimicking refractory seizures. The purpose of our study was to evaluate the clinical features, definite diagnoses and treatment approaches of the patients with clinically suspected GERD who were referred to the division of pediatric neurology with a suspected diagnosis of epileptic seizure. We also aimed to investigate the occurrence of GERD in children with epilepsy and/or CP. Fifty-seven children who had a final diagnosis of GERD but were initially suspected of having epileptic seizures were assessed prospectively. All patients were assigned to 3 groups according to definite diagnoses as follows: patients with only GERD who were misdiagnosed as having epileptic seizure (group 1: n=16; 28.1%), those with comorbidity of epilepsy and GERD (group 2: n=21; 36.8%), and those with the coexistence of GERD with epilepsy and CP (group 3: n=20; 35.1%). Five patients (8.8%) did not respond to anti-reflux treatment and laparoscopic reflux surgery was performed. The positive effect of GERD therapy on paroxysmal nonepileptic events was observed in 51/57 (89.5%) patients. GERD is one of the important causes of paroxysmal nonepileptic events. In addition, GERD must be kept in mind at the initial diagnosis and also in the long-term management of patients with neurological disorders such as epilepsy and CP. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Quantitative Simulations of MST Visual Receptive Field Properties Using a Template Model of Heading Estimation

NASA Technical Reports Server (NTRS)

Stone, Leland S.; Perrone, J. A.

1997-01-01

We previously developed a template model of primate visual self-motion processing that proposes a specific set of projections from MT-like local motion sensors onto output units to estimate heading and relative depth from optic flow. At the time, we showed that that the model output units have emergent properties similar to those of MSTd neurons, although there was little physiological evidence to test the model more directly. We have now systematically examined the properties of the model using stimulus paradigms used by others in recent single-unit studies of MST: 1) 2-D bell-shaped heading tuning. Most MSTd neurons and model output units show bell-shaped heading tuning. Furthermore, we found that most model output units and the finely-sampled example neuron in the Duffy-Wurtz study are well fit by a 2D gaussian (sigma approx. 35deg, r approx. 0.9). The bandwidth of model and real units can explain why Lappe et al. found apparent sigmoidal tuning using a restricted range of stimuli (+/-40deg). 2) Spiral Tuning and Invariance. Graziano et al. found that many MST neurons appear tuned to a specific combination of rotation and expansion (spiral flow) and that this tuning changes little for approx. 10deg shifts in stimulus placement. Simulations of model output units under the same conditions quantitatively replicate this result. We conclude that a template architecture may underlie MT inputs to MST.

Resolving cognitive dissonance by acquisition of self-organizational skills may decrease drug-resistant seizures - A case report.

PubMed

Michaelis, Rosa; Andrews, Donna J; Reiter, Joel M; von Schoen-Angerer, Tido

2014-01-01

A recent review of psychobehavioral therapy for epilepsy recommends case reports as a research design to explore specific psychological mediators of psychobehavioral interventions for epilepsy that address the bidirectional relationship between psychological states and seizures. The report was prepared according to the consensus-based CARE guidelines for standardized clinical case reporting. This is a case of a 16-year-old male individual with a diagnosed seizure disorder and learning disability who continued to have daytime and nighttime seizures on a regular basis despite exhausting of available conventional treatment options. A psychological assessment led to the working hypothesis that cognitive dissonance between fear of failure and high expectations of self had led to a "broken" self-image and active avoidance of responsibility that resulted in intense emotional distress which correlated with the occurrence of seizures. This working hypothesis resulted in a treatment plan that employed the acquisition of self-organizational skills and relaxation techniques as the main therapeutic strategy. Motivational strategies were employed to facilitate the regulation of lifestyle-related seizure precipitants. In this case, the acquisition of self-organizational skills and the development of seizure interruption techniques correlated with a clinically significant decrease of seizures. Methodological limitations of the interpretation of the presented data are discussed.

AMPA Receptor antagonist NBQX attenuates later-life epileptic seizures and autistic-like social deficits following neonatal seizures

PubMed Central

Lippman-Bell, Jocelyn J.; Rakhade, Sanjay N.; Klein, Peter M.; Obeid, Makram; Jackson, Michele C.; Joseph, Annelise; Jensen, Frances E.

2013-01-01

Summary Purpose To determine whether AMPA receptor (AMPAR) antagonist NBQX can prevent early mTOR pathway activation and long-term sequelae following neonatal seizures in rats, including later-life spontaneous recurrent seizures, CA3 mossy fiber sprouting, and autistic-like social deficits. Methods Long-Evans rats experienced hypoxia-induced neonatal seizures (HS) at postnatal day (P)10. NBQX (20 mg/kg) was administered immediately following HS (every 12h x 4 doses). 12h post-HS, we assessed mTOR activation marker phosphorylated p70-S6 kinase (p-p70S6K) in hippocampus and cortex of vehicle (HS+V) or NBQX-treated post-HS rats (HS+N) versus littermate controls (C+V). Spontaneous seizure activity was compared between groups by epidural cortical electroencephalography (EEG) at P70-100. Aberrant mossy fiber sprouting was measured using Timm staining. Finally, we assessed behavior between P30-38. Key findings Post-seizure NBQX treatment significantly attenuated seizure-induced increases in p-P70S6K in the hippocampus (p<0.01) and cortex (p<0.001). While spontaneous recurrent seizures increased in adulthood in HS+V rats compared to controls (3.22±1seizures/hour; p=0.03), NBQX significantly attenuated later-life seizures (0.14±0.1 seizures/hour; p=0.046). HS+N rats showed less aberrant mossy fiber sprouting (115±8.0%) than vehicle-treated post-HS rats (174±10%, p=0.004), compared to controls (normalized to 100%). Finally, NBQX treatment prevented alterations in later-life social behavior; post-HS rats showed significantly decreased preference for a novel over a familiar rat (71.0±12 sec) compared to controls (99.0±15.6 sec; p<0.01), while HS+N rats showed social novelty preference similar to controls (114.3±14.1 sec). Significance Brief NBQX administration during the 48 hours post-seizure in P10 Long-Evans rats suppresses transient mTOR pathway activation and attenuates spontaneous recurrent seizures, social preference deficits and mossy fiber sprouting observed in

Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei.

PubMed

Feng, Li; Motelow, Joshua E; Ma, Chanthia; Biche, William; McCafferty, Cian; Smith, Nicholas; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro; Blumenfeld, Hal

2017-11-22

The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal

19 CFR 145.59 - Seizures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Seizures. 145.59 Section 145.59 Customs Duties U.S...) MAIL IMPORTATIONS Restricted and Prohibited Merchandise § 145.59 Seizures. (a) Articles prohibited and... handled by the Postal Service as specified in §§ 145.51 and 145.52. (b) Notification of seizure or...

Ketogenic diet therapy for epilepsy during pregnancy: A case series.

PubMed

van der Louw, Elles J T M; Williams, Tanya J; Henry-Barron, Bobbie J; Olieman, Joanne F; Duvekot, Johannes J; Vermeulen, Marijn J; Bannink, Natalja; Williams, Monique; Neuteboom, Rinze F; Kossoff, Eric H; Catsman-Berrevoets, Coriene E; Cervenka, Mackenzie C

2017-02-01

Evaluation of ketogenic diet (KD) therapies for seizure control during pregnancy when safety and appropriate management become considerations. Until now, no information has been available on seizure reduction and human pregnancy related outcomes in women treated with KD therapies. We describe two cases of pregnant women with epilepsy treated with KD therapy either as monotherapy (Case 1) or as adjunctive therapy (Case 2). Case 1: A 27 year old woman, gravida1, started the classic KD with medium chain triglyceride (MCT) emulsion and 75g carbohydrate-restriction, later reduced to 47g. Glucose levels were 4-6mmol/L and blood ketone levels ranged from 0.2 to 1.4mmol/L. Seizure frequency decreased and seizure-free days increased. Mild side effects included intolerance to MCT, reduced serum carnitine and vitamin levels, and mild hyperlipidemia. Fetal and neonatal growth was normal as was growth and development at 12 months. Case 2: A 36 year-old nulliparous woman was treated with a 20 gram carbohydrate-restricted Modified Atkins Diet (MAD) and lamotrigine, resulting in reduction of seizure frequency to once per month prior to pregnancy. Once pregnant, carbohydrates were increased to 30g. When seizures increased, lamotrigine dose was doubled. Urine ketones trended down during second trimester. A male was born with bilateral ear deformities of unknown significance. The child had a normal neurodevelopment at eight months. Non-pharmacological epilepsy therapies like KD and MAD may be effective during human pregnancy. However, safety still has to be established. Further monitoring to identify potential long term side effects is warranted. Copyright © 2017 British Epilepsy Association. All rights reserved.

Dynamics of absence seizures

NASA Astrophysics Data System (ADS)

Deeba, Farah; Sanz-Leon, Paula; Robinson, Peter

A neural field model of the corticothalamic system is used to investigate the dynamics of absence seizures in the presence of temporally varying connection strength between the cerebral cortex and thalamus. Variation of connection strength from cortex to thalamus drives the system into seizure once a threshold is passed and a supercritical Hopf bifurcation occurs. The dynamics and spectral characteristics of the resulting seizures are explored as functions of maximum connection strength, time above threshold, and ramp rate. The results enable spectral and temporal characteristics of seizures to be related to underlying physiological variations via nonlinear dynamics and neural field theory. Notably, this analysis adds to neural field modeling of a wide variety of brain activity phenomena and measurements in recent years. Australian Research Council Grants FL1401000225 and CE140100007.

Genes, Seizures & Epilepsy

ERIC Educational Resources Information Center

Goldman, Alica M.

2006-01-01

The chance that someone will develop any disease is influenced by heredity and environment. Epilepsy is not an exception. Everybody inherits a unique degree of susceptibility to seizures. About 3 percent of the United States population is prone to seizures and will get epilepsy at some point of their lives (1). Two thirds of the people with…

Nonlinear analysis of EEG for epileptic seizures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hively, L.M.; Clapp, N.E.; Daw, C.S.

1995-04-01

We apply chaotic time series analysis (CTSA) to human electroencephalogram (EEG) data. Three epoches were examined: epileptic seizure, non-seizure, and transition from non-seizure to seizure. The CTSA tools were applied to four forms of these data: raw EEG data (e-data), artifact data (f-data) via application of a quadratic zero-phase filter of the raw data, artifact-filtered data (g- data) and that was the residual after subtracting f-data from e-data, and a low-pass-filtered version (h-data) of g-data. Two different seizures were analyzed for the same patient. Several nonlinear measures uniquely indicate an epileptic seizure in both cases, including an abrupt decrease inmore » the time per wave cycle in f-data, an abrupt increase in the Kolmogorov entropy and in the correlation dimension for e-h data, and an abrupt increase in the correlation dimension for e-h data. The transition from normal to seizure state also is characterized by distinctly different trends in the nonlinear measures for each seizure and may be potential seizure predictors for this patient. Surrogate analysis of e-data shows that statistically significant nonlinear structure is present during the non-seizure, transition , and seizure epoches.« less

Measurements of Impurity Particle Transport Associated with Drift-Wave Turbulence in MST