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.

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.

Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice.

PubMed

Zarnowska, Iwona; Luszczki, Jarogniew J; Zarnowski, Tomasz; Wlaz, Piotr; Czuczwar, Stanislaw J; Gasior, Maciej

2017-04-01

Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.

Anesthetic considerations for pediatric electroconvulsive therapy.

PubMed

Franklin, Andrew D; Sobey, Jenna H; Stickles, Eric T

2017-05-01

Electroconvulsive therapy is being used more frequently in the treatment of many chronic and acute psychiatric illnesses in children. The most common psychiatric indications for pediatric electroconvulsive therapy are refractory depression, bipolar disorder, schizophrenia, catatonia, and autism. In addition, a relatively new indication is the treatment of pediatric refractory status epilepticus. The anesthesiologist may be called upon to assist in the care of this challenging and vulnerable patient population. Unique factors for pediatric electroconvulsive therapy include the potential need for preoperative anxiolytic and inhalational induction of anesthesia, which must be weighed against the detrimental effects of anesthetic agents on the evoked seizure quality required for a successful treatment. Dexmedetomidine is likely the most appropriate preoperative anxiolytic as oral benzodiazepines are relatively contraindicated. Methohexital, though becoming less available at many institutions, remains the gold standard for induction of anesthesia for pediatric electroconvulsive therapy though ketamine, propofol, and sevoflurane are becoming increasingly viable options. Proper planning and communication between the multidisciplinary teams involved in the care of children presenting for electroconvulsive therapy treatments is vital to mitigating risks and achieving the greatest therapeutic benefit. © 2017 John Wiley & Sons Ltd.

Differential neurophysiological effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS) in non-human primates.

PubMed

Cycowicz, Yael M; Luber, Bruce; Spellman, Timothy; Lisanby, Sarah H

2008-07-01

Magnetic seizure therapy (MST) is under development as a means of reducing the side effects of electroconvulsive therapy (ECT) through enhanced control over patterns of seizure induction and spread. We previously reported that chronic treatment with MST resulted in less impairment in cognitive function than electroconvulsive shock (ECS) in a non-human primate model of convulsive therapy. Here we present quantitative analyses of ictal expression and post-ictal suppression following ECS, MST, and anesthesia-alone sham in the same model to test whether differential neurophysiological characteristics of the seizures could be identified. Rhesus monkeys received 4 weeks of daily treatment with ECS, MST, and anesthesia-alone sham in a counterbalanced order separated by a recovery period. Both ECS and MST were given bilaterally at 2.5 x seizure threshold. Neurophysiological characteristics were derived from two scalp EEG electrode recording sites during and immediately following the ictal period, and were compared to sham treatment. EEG power within four frequencies (delta, theta, alpha and beta) was calculated. Our results support earlier findings from intracerebral electrode recordings demonstrating that MST- and ECS- induced seizures elicit differential patterns of EEG activation. Specifically, we found that ECS shows significantly more marked ictal expression, and more intense post-ictal suppression than MST in the theta, alpha, and beta frequency bands (Ps < .05). However, the ECS and MST were indistinguishable in the delta frequency band during both ictal and post-ictal periods. These results demonstrate that magnetic seizure induction can result in seizures that differ in some neurophysiological respects compared with ECS, but that these modalities share some aspects of seizure expression. The clinical significance of these similarities and differences awaits clinical correlation.

Anaesthesia for electroconvulsive therapy - new tricks for old drugs: a systematic review.

PubMed

Stripp, Tobias Kvist; Jorgensen, Martin Balslev; Olsen, Niels Vidiendal

2018-04-01

The objective of this review is to investigate existing literature in order to delineate whether the use of anaesthesia and timing of seizure induction in a new and optimised way may improve the efficacy of electroconvulsive therapy (ECT). PubMed/MEDLINE was searched for existing literature, last search on 24 June 2015. Relevant clinical studies on human subjects involving choice of anaesthetic, ventilation and bispectral index (BIS) monitoring in the ECT setting were considered. The references of relevant studies were likewise considered. Propofol yields the shortest seizures, etomidate and ketamine the longest. Etomidate and ketamine+propofol 1 : 1 seems to yield the seizures with best quality. Seizure quality is improved when induction of ECT is delayed until the effect of the anaesthetic has waned - possibly monitored with BIS values. Manual hyperventilation with 100% O2 may increase the pO2/pCO2-ratio, which may be correlated with better seizure quality. Etomidate or a 1 : 1 ketamine and propofol combination may be the best method to achieve general anaesthesia in the ECT setting. There is a need for large randomised prospective studies comparing the effect of methohexital, thiopental, propofol, ketamine, propofol+ketamine 1 : 1 and etomidate in the ECT treatment of major depressed patients. These studies should investigate safety and side effects, and most importantly have antidepressant efficacy and cognitive side effects as outcome measures instead of seizure quality.

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.

Beta-blocking agents during electroconvulsive therapy: a review.

PubMed

Boere, E; Birkenhäger, T K; Groenland, T H N; van den Broek, W W

2014-07-01

Electroconvulsive therapy (ECT) is associated with at least transient episodes of hypertension and tachycardia. Beta-blocking agents may be indicated to prevent cardiovascular complications and may shorten seizure duration. This review evaluates studies that used beta-blocking agents during ECT to determine which agent has the most favourable outcomes on cardiovascular variables and seizure duration. A Medline database search was made using the combined keywords 'adrenergic beta-antagonists' and 'electroconvulsive therapy'. The search was restricted to double-blind randomized controlled trials and yielded 29 original studies. With the use of esmolol, significant attenuating effects were found on cardiovascular parameters in the first 5 min after stimulation; its shortening effects on seizure duration may be dose-related. With the use of labetalol, findings on cardiovascular effects were inconsistent during the first minutes after stimulation but were significant after 5 min and thereafter; seizure duration was scarcely studied. Landiolol attenuates heart rate but with inconsistent findings regarding arterial pressure (AP); seizure duration was mostly unaffected. Esmolol appears to be effective in reducing the cardiovascular response, although seizure duration may be affected with higher dosages. Landiolol can be considered a suitable alternative, but effects on AP need further investigation. Labetalol has been studied to a lesser extent and may have prolonged cardiovascular effects. The included studies varied in design, methodology, and the amount of exact data provided in the publications. Further study of beta-blocking agents in ECT is clearly necessary. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Heart rate changes during electroconvulsive therapy

PubMed Central

2013-01-01

Background This observational study documented heart rate over the entire course of electrically induced seizures and aimed to evaluate the effects of stimulus electrode placement, patients' age, stimulus dose, and additional predictors. Method In 119 consecutive patients with 64 right unilateral (RUL) and 55 bifrontal (BF) electroconvulsive treatments, heart rate graphs based on beat-to-beat measurements were plotted up to durations of 130 s. Results In RUL stimulation, the initial drop in heart rate lasted for 12.5 ± 2.6 s (mean ± standard deviation). This depended on stimulus train duration, age, and baseline heart rate. In seizures induced with BF electrode placement, a sympathetic response was observed within the first few seconds of the stimulation phase (median 3.5 s). This was also the case with subconvulsive stimulations. The mean peak heart rate in all 119 treatments amounted to 135 ± 20 bpm and depended on baseline heart rate and seizure duration; electrode placement, charge dose, and age were insignificant in regression analysis. A marked decline in heart rate in connection with seizure cessation occurred in 71% of treatments. Conclusions A significant independent effect of stimulus electrode positioning on cardiac action was evident only in the initial phase of the seizures. Electrical stimulation rather than the seizure causes the initial heart rate increase in BF treatments. The data reveal no rationale for setting the stimulus doses as a function of intraictal peak heart rates (‘benchmark method’). The marked decline in heart rate at the end of most seizures is probably mediated by a baroreceptor reflex. PMID:23764036

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.

Effect of stimulus intensity and number of treatments on ECS-related seizure duration and retrograde amnesia in rats.

PubMed

Andrade, Chittaranjan; Thyagarajan, S; Vinod, P S; Srikanth, S N; Rao, N S K; Chandra, J Suresh

2002-12-01

Animal models are frequently used to generate and test hypotheses about amnesia resulting from electroconvulsive therapy (ECT). Although many predictors of ECT-induced amnesia are known, their relative effects have been inadequately researched in the context of the animal models. We sought to determine the relative retrograde amnestic effects of electroconvulsive shock (ECS) stimulus intensity (dose) and number on strong memories in rats. We also sought to identify dose-dependent ceiling amnestic effects, if any. Adult rats (n = 144) were overtrained in a passive avoidance task using a step down apparatus. The rats were then randomized in a factorial design to receive one, two, or three once-daily bilateral ECS at 0-mC (sham ECS), 30-mC, 60-mC, 120-mC, or 180-mC doses. Recall of the pre-ECS training was assessed 1 day after the last ECS. Retrograde amnesia was observed only in rats that received 3 ECS; dose-dependent amnestic effects did not emerge. Higher stimulus intensity was associated with a small (13%) but significant increase in motor seizure duration, but only at the first ECS; stimulus intensity did not influence the attenuation of seizure duration across repeated occasions of ECS. With bilateral ECS, the number of ECSs administered is a more important variable than the ECS dose in weakening a strong, recently acquired, noxious memory; this finding may have important clinical implications. Higher stimulus intensity marginally increases motor seizure duration at the first ECS but does not influence the decrease in seizure duration across repeated ECSs.

Electroconvulsive Therapy. Consensus Development Conference Statement, Vol. 5, No. 11.

ERIC Educational Resources Information Center

National Institutes of Health (DHHS), Bethesda, MD.

Electroconvulsive therapy (ECT), a treatment for severe mental illness in which a brief application of electric stimulus is used to produce a generalized seizure, has been in use for over 45 years. Controversies still exist today concerning the use of ECT. In 1985, the National Institutes of Health and the National Institute of Mental Health held…

Is Electroconvulsive Therapy a Treatment for Depression Following Traumatic Brain Injury?

PubMed Central

Srienc, Anja; Sarai, Simrat; Xiong, Yee; Lippmann, Steven

2018-01-01

Traumatic brain injury (TBI) can be caused by blunt or penetrating injury to the head. The pathophysiological evolution of TBI involves complex biochemical and genetic changes. Common sequelae of TBI include seizures and psychiatric disorders, particularly depression. In considering pharmacologic interventions for treating post-TBI depression, it is important to remember that TBI patients have a higher risk of seizures; therefore, the benefits of prescribing medications that lower the seizure threshold need to be weighed against the risk of seizures. When post-TBI depression is refractory to pharmacotherapy, electroconvulsive therapy (ECT) could provide an alternative therapeutic strategy. Data remain sparse on using ECT in this seizure-prone population, but three case reports demonstrated good outcomes. Currently, not enough evidence exists to provide clinical recommendations for using ECT for treating post-TBI depression, and more research is needed to generate guidelines on how best to treat depression in TBI patients. However, the preliminary data on using ECT in patients with TBI are promising. If proven safe, ECT could be a powerful tool to treat post-TBI depression. PMID:29707426

Is Electroconvulsive Therapy a Treatment for Depression Following Traumatic Brain Injury?

PubMed

Srienc, Anja; Narang, Puneet; Sarai, Simrat; Xiong, Yee; Lippmann, Steven

2018-04-01

Traumatic brain injury (TBI) can be caused by blunt or penetrating injury to the head. The pathophysiological evolution of TBI involves complex biochemical and genetic changes. Common sequelae of TBI include seizures and psychiatric disorders, particularly depression. In considering pharmacologic interventions for treating post-TBI depression, it is important to remember that TBI patients have a higher risk of seizures; therefore, the benefits of prescribing medications that lower the seizure threshold need to be weighed against the risk of seizures. When post-TBI depression is refractory to pharmacotherapy, electroconvulsive therapy (ECT) could provide an alternative therapeutic strategy. Data remain sparse on using ECT in this seizure-prone population, but three case reports demonstrated good outcomes. Currently, not enough evidence exists to provide clinical recommendations for using ECT for treating post-TBI depression, and more research is needed to generate guidelines on how best to treat depression in TBI patients. However, the preliminary data on using ECT in patients with TBI are promising. If proven safe, ECT could be a powerful tool to treat post-TBI depression.

Protocolized hyperventilation enhances electroconvulsive therapy.

PubMed

de Arriba-Arnau, Aida; Dalmau, Antonia; Soria, Virginia; Salvat-Pujol, Neus; Ribes, Carmina; Sánchez-Allueva, Ana; Menchón, José Manuel; Urretavizcaya, Mikel

2017-08-01

Hyperventilation is recommended in electroconvulsive therapy (ECT) to enhance seizures and to increase patients' safety. However, more evidence is needed regarding its effects and the optimum method of application. This prospective study involving 21 subjects compared two procedures, protocolized hyperventilation (PHV) and hyperventilation as usual (HVau), applied to the same patient in two consecutive sessions. Transcutaneous partial pressure of carbon dioxide (TcPCO 2 ) was measured throughout all sessions. Ventilation parameters, hemodynamic measures, seizure characteristics, and side effects were also explored. PHV resulted in lower TcPCO 2 after hyperventilation (p=.008) and over the whole session (p=.035). The lowest TcPCO 2 was achieved after voluntary hyperventilation. Changes in TcPCO 2 from baseline showed differences between HVau and PHV at each session time-point (all p<.05). Between- and within-subjects factors were statistically significant in a general linear model. Seizure duration was greater in PHV sessions (p=.028), without differences in other seizure quality parameters or adverse effects. Correlations were found between hypocapnia induction and seizure quality indexes. Secondary outcomes could be underpowered. PHV produces hypocapnia before the stimulus, modifies patients' TcPCO 2 values throughout the ECT session and lengthens seizure duration. Voluntary hyperventilation is the most important part of the PHV procedure with respect to achieving hypocapnia. A specific ventilation approach, CO 2 quantification and monitoring may be advisable in ECT. PHV is easy to apply in daily clinical practice and does not imply added costs. Ventilation management has promising effects in terms of optimizing ECT technique. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial.

PubMed

Salehi, B; Mohammadbeigi, A; Kamali, A R; Taheri-Nejad, M R; Moshiri, I

2015-01-01

Electroconvulsive therapy (ECT) is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD). In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2 nd , 4 th , 6 th , and 8 th ECT. Depression was assessed by Hamilton depression scale. The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain at the injection site, short-term delirium, and long-term delirium were higher in ketamine group (P > 0.05). But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05). The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05). Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD.

Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial

PubMed Central

Salehi, B.; Mohammadbeigi, A.; Kamali, A. R.; Taheri-Nejad, M. R.; Moshiri, I.

2015-01-01

Background: Electroconvulsive therapy (ECT) is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD). Materials and Methods: In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2nd, 4th, 6th, and 8th ECT. Depression was assessed by Hamilton depression scale. Results: The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain at the injection site, short-term delirium, and long-term delirium were higher in ketamine group (P > 0.05). But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05). The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05). Conclusion: Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD. PMID:26440233

Caffeine Sodium Benzoate for Electroconvulsive Therapy Augmentation.

PubMed

Bozymski, Kevin M; Potter, Teresa G; Venkatachalam, Vasu; Pandurangi, Ananda K; Crouse, Ericka L

2018-05-15

Because of an ongoing manufacturer shortage of injectable caffeine sodium benzoate (CSB), patients at our health system were given CSB compounded in-house to increase seizure response during electroconvulsive therapy (ECT). Therefore, we aimed to evaluate its effectiveness and safety as an ECT augmentation agent. Medical records of patients who received compounded CSB at Virginia Commonwealth University Health System were reviewed to identify adults receiving it as part of an index ECT treatment course between June 2012 and December 2016. The primary outcome was change in electroencephalogram seizure duration from pre-caffeine session to initial caffeine session. Data were also collected on demographics, motor seizure duration, maximum heart rate, mean arterial pressure, and concurrent medication use for these sessions and the last caffeine session. Seven-one patients were included in the study, predominantly white females with a mean age of 58.6 years. The most common indication for ECT was major depressive disorder resistant to pharmacotherapy (71.8%), followed by catatonia associated with another mental disorder (19.7%). Electroencephalogram seizure duration increased by 24.1 seconds on average with first CSB use (P < 0.0001), allowing 24 more patients overall to achieve goal of at least 30 seconds (P < 0.0001). No clinically significant changes in maximum heart rate or mean arterial pressure were observed, nor did any patients require an abortive agent for prolonged seizure. Five patients (7%) discontinued CSB prematurely: 4 related to adverse effects and 1 secondary to ineffectiveness. We confirm results of prior studies of the utility of CSB and add that compounded CSB is effective for ECT augmentation, maintaining effectiveness throughout the index course with minimal safety concerns.

Feasibility Study of Pharmacological Treatment to Reduce Morbidity and Mortality After Brain Injury

DTIC Science & Technology

1991-04-02

1976). Long-term effects of electroconvulsive shock therapy on synthesis, turnover and uptake of brain monoamines. Psvchopharmacol. 49: 179-185. 30...tissue, and relieving concomitant effects, such as hemorrhage, edema, or elevated intracranial pressure. These therapies have not resulted in...and antagonists, and 3) electroconvulsive seizures on funztional recovery from hemiplegia. In addition, the extent of cortical neci otic cavitation was

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

PubMed Central

Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. PMID:28910337

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.

PubMed

van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.

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.

Electroconvulsive therapy can benefit from controlled hyperventilation using a laryngeal mask.

PubMed

Haeck, Martina; Gillmann, Benjamin; Janouschek, Hildegard; Grözinger, Michael

2011-11-01

Hypocapnia through hyperventilation is a well-known procedure in electroconvulsive therapy (ECT) to enhance seizure activity. However, it has mostly been applied in an uncontrolled manner. Originally intended for a better management of the supraglottic airway, laryngeal masks are more suited to monitor levels of CO(2) during hyperventilation than face masks and thereby provide for the possibility of controlled hyperventilation (CHV). The impact of CHV was retrospectively studied in 114 consecutive patients; 65 of them had received ECT with CHV and 49 had received ECT with uncontrolled hyperventilation (UHV) directly prior to the time period when the laryneal mask was introduced to the ECT treatment procedure. The CO(2) level in the CHV group was aimed at 30 mmHg or below. CHV considerably enhanced the seizure activity leading to changes in clinically determined parameters of the treatment course: the necessity for increasing the electric charge, for re-stimulations (trend) and for bilateral stimulations was lower in the CHV group as compared to the UHV group. The improvement in the Global Assessment of Functioning Scores was not different in both groups. CHV was associated with a higher amount of prolonged seizures, with a reduced number of delirious symptoms after treatments and an attenuating effect on heart rate. Concluding, CHV can help to maintain the applied electric charge low without worsening the clinical outcome. Therefore, it is a helpful technical improvement. However, it should be used carefully with regard to prolonged seizures.

Antidepressant effects, of magnetic seizure therapy and electroconvulsive therapy, in treatment-resistant depression.

PubMed

Kayser, Sarah; Bewernick, Bettina H; Grubert, Christiane; Hadrysiewicz, Barbara L; Axmacher, Nikolai; Schlaepfer, Thomas E

2011-05-01

Major depression is a common mental health problem and associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide. Electroconvulsive therapy (ECT) is highly efficacious in treatment-resistant depressive disorders, but cognitive side effects are frequently associated with the treatment. Magnetic seizure therapy (MST) is a form of convulsive therapy, using magnetic fields in order to induce therapeutic seizures. First studies suggested that cognitive side effects of MST, including postictal recovery time, are more benign than those resulting from ECT treatment. In this open-label study we tested the hypothesis that MST is associated with clinically significant antidepressant effects in treatment-resistant depression (TRD) as an add-on therapy to a controlled pharmacotherapy. Twenty patients suffering from TRD were randomly assigned to receive either MST or ECT starting from July 2006 until November 2008. Primary outcome measure was antidepressant response assessed by Montgomery Åsberg Depression Scale. Secondary outcome measures included Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Beck Depression Inventory and 90-Item Symptom Checklist. Antidepressant response (improvement of 50% in MADRS ratings) was statistically significant and of similar size in both treatment groups. Cognitive side effects were observed in neither group. Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression. Thus, MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials. Copyright © 2010 Elsevier Ltd. All rights reserved.

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

PubMed

Radman, Thomas; Lisanby, Sarah H

2017-04-01

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

A Randomized Controlled Trial of Brief and Ultrabrief Pulse Right Unilateral Electroconvulsive Therapy

PubMed Central

Katalinic, Natalie; Smith, Deirdre J.; Ingram, Anna; Dowling, Nathan; Martin, Donel; Addison, Kerryn; Hadzi-Pavlovic, Dusan; Simpson, Brett; Schweitzer,, Isaac

2015-01-01

Background: Some studies suggest better overall outcomes when right unilateral electroconvulsive therapy (RUL ECT) is given with an ultrabrief, rather than brief, pulse width. Methods: The aim of the study was to test if ultrabrief-pulse RUL ECT results in less cognitive side effects than brief- pulse RUL ECT, when given at doses which achieve comparable efficacy. One hundred and two participants were assigned to receive ultrabrief (at 8 times seizure threshold) or brief (at 5 times seizure threshold) pulse RUL ECT in a double-blind, randomized controlled trial. Blinded raters assessed mood and cognitive functioning over the ECT course. Results: Efficacy outcomes were not found to be significantly different. The ultrabrief group showed less cognitive impairment immediately after a single session of ECT, and over the treatment course (autobiographical memory, orientation). Conclusions: In summary, when ultrabrief RUL ECT was given at a higher dosage than brief RUL ECT (8 versus 5 times seizure threshold), efficacy was comparable while cognitive impairment was less. PMID:25522389

Individualized Anesthetic Management for Patients Undergoing Electroconvulsive Therapy: A Review of Current Practice.

PubMed

Bryson, Ethan O; Aloysi, Amy S; Farber, Kate G; Kellner, Charles H

2017-06-01

Electroconvulsive therapy (ECT) remains an indispensable treatment for severe psychiatric illness. It is practiced extensively in the United States and around the world, yet there is little guidance for anesthesiologists involved with this common practice. Communication between the anesthesiologist and the proceduralist is particularly important for ECT, because the choice of anesthetic and management of physiologic sequelae of the therapeutic seizure can directly impact both the efficacy and safety of the treatment. In this review, we examine the literature on anesthetic management for ECT. A casual or "one-size-fits-all" approach may lead to less-than-optimal outcomes; customizing the anesthetic management for each patient is essential and can significantly increase treatment success rate and patient satisfaction.

Post-electroconvulsive therapy recovery and reorientation time with methohexital and ketamine: a randomized, longitudinal cross-over design trial

PubMed Central

Yen, Tony; Khafaja, Mohamad; Lam, Nicholas; Crumbacher, James; Schrader, Ronald; Rask, John; Billstrand, Mary; Rothfork, Jacob; Abbott, Christopher C.

2014-01-01

Objectives Methohexital, a barbiturate anesthetic commonly used for electroconvulsive therapy (ECT), possesses dose-dependent anticonvulsant properties, and its use can interfere with effective seizure therapy in patients with high seizure thresholds. Ketamine, a NMDA-antagonist with epileptogenic properties not broadly used for ECT inductions, is a commonly used induction agent for general anesthesia. Recent studies suggest that the use of ketamine is effective in allowing successful ECT treatment in patients with high seizure thresholds without an increase in side-effects. In this preliminary study, we directly compared the recovery and re-orientation times of subjects receiving ketamine and methohexital for ECTs. Methods Twenty patients were randomized in a cross-over design to receive methohexital and ketamine for ECT inductions in alternating fashion for six trials. Primary outcome measures were recovery time (voluntary movement, respiratory effort, blood pressure, consciousness, and O2 saturation) and re-orientation time. Secondary outcome measures were individual recovery variables, side-effect occurrence, and seizure duration. Results: Overall recovery time was not significantly different between the two treatment arms (F(1,17) = 0.72, P = 0.41). Re-orientation time was faster in the methohexital arm (F(1,17) = 9.23, P = 0.007). Conclusion Ketamine inductions resulted in higher number of side-effects, higher subject dropout rates, and a longer reorientation time with respect to methohexital inductions. No significant difference in post-anesthesia recovery time was found between the ketamine and methohexital arms. Intolerability to ketamine affected a significant proportion of subjects, and suggests that ketamine should remain as an alternative or adjunctive agent for patients with high seizure thresholds. PMID:24755722

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.

Propofol interruption of ECT seizure to reduce side-effects: a pilot study.

PubMed

Warnell, Ronald L; Swartz, Conrad M; Thomson, Alice

2010-01-30

Fifteen depressed subjects received six bitemporal electroconvulsive therapy (ECT) treatments under etomidate anesthesia. They were randomized to blindly either receive propofol 0.5mg/kg 15s post-stimulus or not. Propofol infusion significantly prevented long seizures, and prevented cognitive decrements in most neuropsychological tests, several significantly. Propofol interruption may clinically help reduce ECT side-effects.

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.

Electroconvulsive seizures (ECS) do not prevent LPS-induced behavioral alterations and microglial activation.

PubMed

van Buel, E M; Bosker, F J; van Drunen, J; Strijker, J; Douwenga, W; Klein, H C; Eisel, U L M

2015-12-12

Long-term neuroimmune activation is a common finding in major depressive disorder (MDD). Literature suggests a dual effect of electroconvulsive therapy (ECT), a highly effective treatment strategy for MDD, on neuroimmune parameters: while ECT acutely increases inflammatory parameters, such as serum levels of pro-inflammatory cytokines, there is evidence to suggest that repeated ECT sessions eventually result in downregulation of the inflammatory response. We hypothesized that this might be due to ECT-induced attenuation of microglial activity upon inflammatory stimuli in the brain. Adult male C57Bl/6J mice received a series of ten electroconvulsive seizures (ECS) or sham shocks, followed by an intracerebroventricular (i.c.v.) lipopolysaccharide (LPS) or phosphate-buffered saline (PBS) injection. Brains were extracted and immunohistochemically stained for the microglial marker ionized calcium-binding adaptor molecule 1 (Iba1). In addition, a sucrose preference test and an open-field test were performed to quantify behavioral alterations. LPS induced a short-term reduction in sucrose preference, which normalized within 3 days. In addition, LPS reduced the distance walked in the open field and induced alterations in grooming and rearing behavior. ECS did not affect any of these parameters. Phenotypical analysis of microglia demonstrated an LPS-induced increase in microglial activity ranging from 84 to 213 % in different hippocampal regions (CA3 213 %; CA1 84 %; dentate gyrus 131 %; and hilus 123 %). ECS-induced alterations in microglial activity were insignificant, ranging from -2.6 to 14.3 % in PBS-injected mice and from -20.2 to 6.6 % in LPS-injected mice. We were unable to demonstrate an effect of ECS on LPS-induced microglial activity or behavioral alterations.

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-08-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800-900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112-174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST.

Clinically favourable effects of ketamine as an anaesthetic for electroconvulsive therapy: a retrospective study.

PubMed

Kranaster, Laura; Kammerer-Ciernioch, Jutta; Hoyer, Carolin; Sartorius, Alexander

2011-12-01

In a retrospective chart review, we examined the effects of ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, as electroconvulsive therapy (ECT) anaesthetic in patients suffering from therapy-resistant depression. We included 42 patients who received ECT treatment with either ketamine (n = 16) or the barbiturate thiopental (n = 26). We analysed the number of sessions until completion of ECT treatment (used as a surrogate parameter for outcome), psychopathology as assessed by pre- and post-ECT Mini-Mental State Examination (MMSE) and Hamilton Rating Scale for Depression (HAM-D) scores as well as ECT and seizure parameters (stimulation dose, seizure duration and concordance, urapidil dosage for post-seizure blood pressure management). The ketamine group needed significantly fewer ECT sessions and had significantly lower HAM-D and higher MMSE scores afterwards. As expected, the ketamine group needed more urapidil for blood pressure control. Taking into account the limits inherent in a retrospective study design and the rather small sample size, our results nonetheless point towards synergistic effects of ECT and ketamine anaesthesia, less cognitive side effects and good tolerability of ketamine.

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

Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Lee, Won H; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2017-05-01

Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

Controlling stimulation strength and focality in electroconvulsive therapy via current amplitude and electrode size and spacing: comparison with magnetic seizure therapy.

PubMed

Deng, Zhi-De; Lisanby, Sarah H; Peterchev, Angel V

2013-12-01

Understanding the relationship between the stimulus parameters of electroconvulsive therapy (ECT) and the electric field characteristics could guide studies on improving risk/benefit ratio. We aimed to determine the effect of current amplitude and electrode size and spacing on the ECT electric field characteristics, compare ECT focality with magnetic seizure therapy (MST), and evaluate stimulus individualization by current amplitude adjustment. Electroconvulsive therapy and double-cone-coil MST electric field was simulated in a 5-shell spherical human head model. A range of ECT electrode diameters (2-5 cm), spacing (1-25 cm), and current amplitudes (0-900 mA) was explored. The head model parameters were varied to examine the stimulus current adjustment required to compensate for interindividual anatomical differences. By reducing the electrode size, spacing, and current, the ECT electric field can be more focal and superficial without increasing scalp current density. By appropriately adjusting the electrode configuration and current, the ECT electric field characteristics can be made to approximate those of MST within 15%. Most electric field characteristics in ECT are more sensitive to head anatomy variation than in MST, especially for close electrode spacing. Nevertheless, ECT current amplitude adjustment of less than 70% can compensate for interindividual anatomical variability. The strength and focality of ECT can be varied over a wide range by adjusting the electrode size, spacing, and current. If desirable, ECT can be made as focal as MST while using simpler stimulation equipment. Current amplitude individualization can compensate for interindividual anatomical variability.

Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

NASA Astrophysics Data System (ADS)

Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

2011-02-01

We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

Randomized controlled trial of the cognitive side-effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS).

PubMed

Moscrip, Tammy D; Terrace, Herbert S; Sackeim, Harold A; Lisanby, Sarah H

2006-02-01

Magnetic seizure therapy (MST) is under development as a means of improving the cognitive side-effect profile of electroconvulsive therapy (ECT) by inducing more spatially delimited seizures that spare cortical regions involved in memory. We tested whether MST had a cognitive side-effect profile distinct from electroconvulsive shock (ECS) in a non-human primate model, using the Columbia University Primate Cognitive Profile, which has been shown to be sensitive to the cognitive effects of ECS. Using a within-subject cross-over design, daily ECS, MST, and sham (anaesthesia-only) interventions were administered in 5-wk blocks. Rhesus macaques (n = 2) were trained on a long-term memory task, an anterograde learning and memory task, and a combined anterograde and retrograde task where learning and memory were evaluated for new and previously learned 3-item lists. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-h retention interval. Overall, monkeys were least accurate following ECS (p's < 0.05) compared to sham and MST. This effect was most marked for long-term memory of a constant target, short-term memory of a variable target and recall of previously learned 3-item lists. Monkeys were slowest to complete all tasks following ECS (p's = 0.0001). Time to task completion following MST did not differ from sham. These findings suggest that MST results in a more benign acute cognitive side-effect profile than ECS in this model, consistent with initial observations with human MST.

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

PubMed Central

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-01-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800–900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112–174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST. PMID:25920013

Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures.

PubMed

Chrościńska-Krawczyk, Magdalena; Ratnaraj, Neville; Patsalos, Philip N; Czuczwar, Stanisław J

2009-01-01

Caffeine has been reported to be proconvulsant and to reduce the anticonvulsant efficacy of a variety of antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproate and topiramate) in animal models of epilepsy and to increase seizure frequency in patients with epilepsy. Using the mouse maximal electroshock model, the present study was undertaken so as to ascertain whether caffeine affects the anticonvulsant efficacy of the new antiepileptic drugs lamotrigine, oxcarbazepine and tiagabine. The results indicate that neither acute nor chronic caffeine administration (up to 46.2 mg/kg) affected the ED(50) values of oxcarbazepine or lamotrigine against maximal electroshock. Similarly, caffeine did not modify the tiagabine electroconvulsive threshold. Furthermore, caffeine had no effect on oxcarbazepine, lamotrigine and tiagabine associated adverse effects such as impairment of motor coordination (measured by the chimney test) or long-term memory (measured by the passive avoidance task). Concurrent plasma concentration measurements revealed no significant effect on lamotrigine and oxcarbazepine concentrations. For tiagabine, however, chronic caffeine (4 mg/kg) administration was associated with an increase in tiagabine concentrations. In conclusion, caffeine did not impair the anticonvulsant effects of lamotrigine, oxcarbazepine, or tiagabine as assessed by electroconvulsions in mice. Also, caffeine was without effect upon the adverse potential of the studied antiepileptic drugs. Thus caffeine may not necessarily adversely affect the efficacy of all antiepileptic drugs and this is an important observation.

Bilateral ECT induces bilateral increases in regional cortical thickness.

PubMed

van Eijndhoven, P; Mulders, P; Kwekkeboom, L; van Oostrom, I; van Beek, M; Janzing, J; Schene, A; Tendolkar, I

2016-08-23

Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from severe or treatment-resistant major depressive disorder (MDD). Unfortunately its underlying neurobiological mechanisms are still unclear. One line of evidence indicates that the seizures produced by ECT induce or stimulate neuroplasticity effects. Although these seizures also affect the cortex, the effect of ECT on cortical thickness is not investigated until now. We acquired structural magnetic resonance imaging data in 19 treatment-resistant MDD patients before and after a bilateral ECT course, and 16 healthy controls at 2 time points, and compared changes in cortical thickness between the groups. Our results reveal that ECT induces significant, bilateral increases in cortical thickness, including the temporal pole, inferior and middle temporal cortex and the insula. The pattern of increased cortical thickness was predominant in regions that are associated with seizure onset in ECT. Post hoc analyses showed that the increase in thickness of the insular cortex was larger in responders than in non-responders, which may point to a specific relationship of this region with treatment effects of ECT.

Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: A finite element simulation study

PubMed Central

Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

2014-01-01

We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced maximum electric field in the brain of 2.1–2.5 V/cm and 1.1–2.2 V/cm, corresponding to 6.2–7.2 times and 1.2–2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much higher with ECT (up to 100%) than MST (up to 8.2%). MST with the double cone coil was the most focal and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800–900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects. PMID:21248385

Differential Effects of High Dose Magnetic Seizure Therapy (MST) and Electroconvulsive Shock (ECS) on Cognitive Function

PubMed Central

Spellman, Timothy; McClintock, Shawn M.; Terrace, Herbert; Luber, Bruce; Husain, Mustafa M.; Lisanby, Sarah H.

2008-01-01

Background Magnetic seizure therapy (MST) is under investigation as an alternative form of convulsive therapy that induces more focal seizures and spares cortical regions involved in memory. Using a newly expanded version of the Columbia University Primate Cognitive Profile, we compared the cognitive effects of high-dose MST delivered at 100 Hz (6X seizure threshold) with electroconvulsive shock (ECS) delivered at 2.5X seizure threshold. Methods Daily high-dose MST, ECS, and Sham (anesthesia-only) were administered for 4 weeks each in a within-subject cross-over design. Rhesus macaques (n = 3) were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval. Results Subjects were slower to complete criterion tasks (p’s<0.0001) following ECS, compared to sham and high-dose MST. Moreover, time to task-completion following high-dose MST did not differ from sham. Out of 6 measures of accuracy, treatment effects were found in 4; in all of these, ECS, but not MST, fared worse than Sham. On all accuracy and time to completion measurements, subjects performed as well as following high-dose MST as did subjects from a previous study on moderate-dose MST. Conclusion These findings provide evidence that high-dose MST results in benign acute cognitive side-effect profile relative to ECS, and are in line with our previous studies. PMID:18262171

Comparison of anesthetics in electroconvulsive therapy: an effective treatment with the use of propofol, etomidate, and thiopental.

PubMed

Zahavi, Guy Sender; Dannon, Pinhas

2014-01-01

Electroconvulsive therapy (ECT) is considered to be one of the most effective treatments in psychiatry. Currently, three medications for anesthesia are used routinely during ECT: propofol, etomidate, and thiopental. The objective of this study was to evaluate the effects of the anesthetics used in ECT on seizure threshold and duration, hemodynamics, recovery from ECT, and immediate side effects. Our study is a retrospective cohort study, in which a comparison was made between three groups of patients who underwent ECT and were anesthetized with propofol, etomidate, or thiopental. The main effect compared was treatment dose and seizure duration. All patients were chosen as responders to ECT. Data were gathered about 91 patients (39 were anesthetized with thiopental, 29 with etomidate, and 23 with propofol). Patients in the thiopental group received a lower electrical dose compared to the propofol and etomidate group (mean of 459 mC compared to 807 mC and 701 mC, respectively, P<0.001). Motor seizure duration was longer in the thiopental group compared to propofol and etomidate (mean of 40 seconds compared to 21 seconds and 23 seconds, respectively, P=0.018). Seizure duration recorded by electroencephalography was similar in the thiopental and etomidate groups and lower in the propofol group (mean of 57 seconds in both groups compared to 45 seconds, respectively, P=0.038). Patients who were anesthetized with thiopental received a lower electrical treatment dose without an unwanted decrease in seizure duration. Thiopental might be the anesthetic of choice when it is congruent with other medical considerations.

SCN3A deficiency associated with increased seizure susceptibility

PubMed Central

Lamar, Tyra; Vanoye, Carlos G.; Calhoun, Jeffrey; Wong, Jennifer C.; Dutton, Stacey B.B.; Jorge, Benjamin S.; Velinov, Milen; Escayg, Andrew; Kearney, Jennifer A.

2017-01-01

Mutations in voltage-gated sodium channels expressed highly in the brain (SCN1A, SCN2A, SCN3A, and SCN8A) are responsible for an increasing number of epilepsy syndromes. In particular, mutations in the SCN3A gene, encoding the pore-forming Nav1.3 α subunit, have been identified in patients with focal epilepsy. Biophysical characterization of epilepsy-associated SCN3A variants suggests that both gain- and loss-of-function SCN3A mutations may lead to increased seizure susceptibility. In this report, we identified a novel SCN3A variant (L247P) by whole exome sequencing of a child with focal epilepsy, developmental delay, and autonomic nervous system dysfunction. Voltage clamp analysis showed no detectable sodium current in a heterologous expression system expressing the SCN3A-L247P variant. Furthermore, cell surface biotinylation demonstrated a reduction in the amount of SCN3A-L247P at the cell surface, suggesting the SCN3A-L247P variant is a trafficking-deficient mutant. To further explore the possible clinical consequences of reduced SCN3A activity, we investigated the effect of a hypomorphic Scn3a allele (Scn3aHyp) on seizure susceptibility and behavior using a gene trap mouse line. Heterozygous Scn3a mutant mice (Scn3a+/Hyp) did not exhibit spontaneous seizures nor were they susceptible to hyperthermia-induced seizures. However, they displayed increased susceptibility to electroconvulsive (6 Hz) and chemiconvulsive (flurothyl and kainic acid) induced seizures. Scn3a+/Hyp mice also exhibited deficits in locomotor activity and motor learning. Taken together, these results provide evidence that loss-of-function of SCN3A caused by reduced protein expression or deficient trafficking to the plasma membrane may contribute to increased seizure susceptibility. PMID:28235671

The seizure, not electricity, is essential in convulsive therapy: the flurothyl experience.

PubMed

Fink, Max

2014-06-01

For more than 50 years, research in convulsive therapy has been focused on the impact of electricity and seizures on memory and not on brain chemistry or neurophysiology. Brief pulse and ultra-brief pulse currents replaced sinusoidal currents. Electrode placements were varied, energy dosing was altered, and electricity was replaced by magnetic currents. The published experiences and archival records of seizures induced by camphor, pentylenetetrazol, and flurothyl are reviewed and compared with the changes induced by electricity. The clinical efficacy of chemically induced seizures is equal to that of electrical inductions. Seizure durations are longer, and impairment of cognition and memory is less. Electroconvulsive therapy replaced chemical treatments for ease of use, not for greater efficacy or safety. The brain seizure, not the method of induction, is the essential element in the efficacy of convulsive therapy. Seizure induction with chemicals avoids the direct effects of electricity on brain functions with lesser effects on cognition. Reexamination of chemical inductions of seizures as replacements for electricity is encouraged.

The dose-response ratio in electroconvulsive therapy a preliminary study.

PubMed

Price, T R; Mackenzie, T B; Tucker, G J; Culver, C

1978-09-01

To investigate pretreatment patient variables that might correlate with dose-response characteristics of electroconvulsive therapy (ECT) and treatment outcomes, 14 patients were assessed on a daily basis, before and during treatment, using self-report affective scales, three simple paper-and-pencil tests of cognitive function,and finger-tapping speed. From these data, dose-response ratios and treatment outcome measures were derived. The dose-response ratio of ECT was found to correlate with age--the younger the patient, the more favorable the ratio. This finding is discussed in terms of the known relationships between brain monoamine oxidase levels and age, and the established relationship between seizure duration and treatment efficacy. The dose-response ratio over the first two electroconvulsive treatments as well as lesser degrees of initial congnitive and greater degrees of initial affective impairment correlated strongly with greater overall affective improvement. Some clinical and research implications of these findings are discussed.

Assessment of the anticonvulsant potency of various benzylamide derivatives in the mouse maximal electroshock-induced seizure threshold model.

PubMed

Świąder, Mariusz J; Paruszewski, Ryszard; Łuszczki, Jarogniew J

2016-04-01

The aim of this study was to assess the anticonvulsant potency of 6 various benzylamide derivatives [i.e., nicotinic acid benzylamide (Nic-BZA), picolinic acid 2-fluoro-benzylamide (2F-Pic-BZA), picolinic acid benzylamide (Pic-BZA), (RS)-methyl-alanine-benzylamide (Me-Ala-BZA), isonicotinic acid benzylamide (Iso-Nic-BZA), and (R)-N-methyl-proline-benzylamide (Me-Pro-BZA)] in the threshold for maximal electroshock (MEST)-induced seizures in mice. Electroconvulsions (seizure activity) were produced in mice by means of a current (sine-wave, 50Hz, 500V, strength from 4 to 18mA, ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Nic-BZA, 2F-Pic-BZA, Pic-BZA, Me-Ala-BZA, Iso-Nic-BZA, and Me-Pro-BZA administered systemically (ip) in a dose-dependent manner increase the threshold for maximal electroconvulsions in mice. Linear regression analysis of Nic-BZA, 2F-Pic-BZA, Pic-BZA, MeAla-BZA, IsoNic-BZA, and Me-Pro-BZA doses and their corresponding threshold increases allowed determining threshold increasing doses by 20% (TID20 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 values in the MEST test for Nic-BZA, 2F-Pic-BZA, Pic-BZA, Me-Ala-BZA, Iso-Nic-BZA, and Me-Pro-BZA were 7.45mg/kg, 7.72mg/kg, 8.74mg/kg, 15.11mg/kg, 21.95mg/kg and 28.06mg/kg, respectively. The studied benzylamide derivatives can be arranged with respect to their anticonvulsant potency in the MEST test as follows: Nic-BZA>2F-Pic-BZA>Pic-BZA>Me-Ala-BZA>Iso-Nic-BZA>Me-Pro-BZA. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Incidence and risk factors for oxygen desaturation during recovery from modified electroconvulsive therapy: A prospective observational study.

PubMed

Surve, Rohini; Bansal, Sonia; Sriganesh, Kamath; Subbakrishna, Doddaballapur Kumaraswamy; Thirthalli, Jagadisha; Umamaheswara Rao, Ganne Sesha

2015-01-01

Electroconvulsive therapy (ECT) is an established modality of treatment for severe psychiatric illnesses. Among the various complications associated with ECT, oxygen desaturation is often under reported. None of the previous studies has evaluated the predictive factors for oxygen desaturation during ECT. The objective of this study was to evaluate the incidence of oxygen desaturation during recovery from anesthesia for modified ECT and evaluate its risk factors in a large sample. All patients aged above 15 years who were prescribed a modified ECT for their psychiatric illness over 1 year were prospectively included in this observational study. The association between age, body mass index (BMI), doses of thiopentone and suxamethonium, stimulus current, ECT session number, pre- and post-ECT heart rate and mean arterial pressure, seizure duration, and pre- and post ECT oxygen saturation, was systematically studied. The incidence of oxygen desaturation was 29% (93/316 patients). Seizure duration and BMI were found to be significantly correlated with post ECT desaturation. In this prospective observational study, the incidence of oxygen desaturation during recovery from anesthesia for ECT was high. The study identified obesity and duration of seizure as the independent predictors of this complication. This knowledge is likely to help in identifying and optimizing such patients before subsequent ECT sessions.

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.

S -ketamine compared to etomidate during electroconvulsive therapy in major depression.

PubMed

Zavorotnyy, Maxim; Kluge, Ina; Ahrens, Kathrin; Wohltmann, Thomas; Köhnlein, Benjamin; Dietsche, Patricia; Dannlowski, Udo; Kircher, Tilo; Konrad, Carsten

2017-12-01

Objective of the study was to compare two commonly used anesthetic drugs, S-ketamine and etomidate, regarding their influence on seizure characteristics, safety aspects, and outcome of electroconvulsive therapy (ECT) in major depression. Treatment data of 60 patients who underwent a total number of 13 ECTs (median) because of the severe or treatment-resistant major depressive disorder (DSM-IV) were analyzed. Etomidate, mean dosage (SD) = 0.25 (0.04) mg/kg, was used for anesthesia in 29 participants; 31 patients received S-ketamine, mean dosage (SD) = 0.96 (0.26) mg/kg. Right unilateral brief pulse ECTs were performed. The number of ECTs was individually adjusted to clinical needs, mean (SD) = 13.0 (4.3). Seizure characteristics, adverse events, and the clinical global impression (CGI) scores were compared between the both groups during ECT series. In the S-ketamine group, a lower initial seizure threshold (p = 0.014), stimulation charge (p < 0.001), higher postictal suppression (p < 0.001), EEG ictal amplitude (p = 0.04), EEG coherence (p < 0.001) and maximum heart rate (p = 0.015) were measured. Etomidate was associated with more frequent abortive seizures (p = 0.02) and restimulations (p = 0.01). The CGI scores, the number of sessions within an ECT series, and the incidence of adverse events did not differ between groups. Due to its lower initial seizure threshold, S-ketamine might hold a potential to become a clinically favorable anesthetic agent during ECT. However, the current findings should be interpreted with caution, and further prospective randomized clinical trials are required. Also, specific adverse effects profile of S-ketamine, especially with regard to the cardiovascular risk, needs to be taken into account.

A retrospective comparison of the effects of propofol and etomidate on stimulus variables and efficacy of electroconvulsive therapy in depressed inpatients.

PubMed

Graveland, Pieternella E; Wierdsma, André I; van den Broek, Walter W; Birkenhäger, Tom K

2013-08-01

To compare the effects of propofol and etomidate on the stimulus variables and efficacy of electroconvulsive therapy (ECT) in depressed inpatients. This retrospective study included 54 inpatients (aged 18-75 years) who met the DSM-IV criteria for major depression and were treated with bilateral ECT. For the first part of the study, the primary outcome was the mean stimulus charge per ECT session. For the second part, the main outcome measure was the proportion of patients achieving full remission. Propofol-treated patients showed a higher mean stimulus charge (etomidate = 227.58 ± 130.44, propofol = 544.91 ± 237.56, p<0.001) despite the lack of a significant difference in starting threshold doses. The propofol group had shorter mean electroencephalogram (etomidate = 69.41 ± 22.50, propofol = 42.95 ± 22.26, p<0.001) seizure duration and motor (etomidate = 46.11 ± 14.38, propofol = 22.89 ± 7.13, p<0.001) seizure duration and a higher mean number of inadequate seizures (etomidate = 0.12 ± 0.15, propofol = 0.47 ± 0.26, p<0.001). No significant differences were found between the groups for the effects of the anesthetics on the efficacy of ECT. Our study is limited by a retrospective design and the small number of patients treated with propofol restricted the sample size. Anesthesia with propofol has a significant reducing effect on seizure duration during the course of ECT which results in more inadequate seizures, despite the use of a higher mean stimulus charge. Regarding the possible effect of the anesthetics on ECT, randomized clinical trials with sufficient power to detect differences are warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictors of Seizure Threshold in Right Unilateral Ultrabrief Electroconvulsive Therapy: Role of Concomitant Medications and Anaesthesia Used.

PubMed

Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Smith, Deidre; Loo, Colleen K

2015-01-01

An individualized approach to maximize electroconvulsive therapy (ECT) efficacy and minimize cognitive side effects is to treat patients relative to their seizure threshold (ST). However, although Right Unilateral-Ultrabrief (0.3 ms) (RUL-UB) ECT is increasingly used in clinical settings as an effective form of ECT with minimal cognitive effects, there is sparse data regarding predictors of ST. To analyze the relationship between ST and clinical and demographic factors in a sample of patients treated with RUL-UB ECT. Clinical, demographic and ECT data from 179 patients in ECT research studies were examined. Seizure threshold was titrated at the first ECT session. ECT was performed with a Thymatron(®) or Mecta(®) device, with thiopentone (2.5-5 mg/kg) or propofol (1-2 mg/kg) anaesthesia. Medications taken at the time of ST titration were documented. The association between ST and candidate predictor variables was examined with regression analysis. Multiple regression analyses showed that 34% of the variance in ST (P < 0.001) could be predicted. Older age (R(2) = 0.194, P < 0.001), propofol (vs thiopentone) (R(2) = 0.029, P ≤ 0.01) and higher anaesthetic dose (mg in propofol equivalents) (R(2) = 0.029, P < 0.05) were found to be predictors of higher initial ST. Treatment with lithium (R(2) = 0.043, P < 0.01) and study site (R(2) = 0.019, P < 0.05) significantly predicted lower initial ST. Empirical titration is recommended for accurate determination of ST in patients receiving RUL-UB ECT. Novel findings of this study are that propofol anaesthesia resulted in higher ST than thiopentone and concomitant treatment with lithium treatment lowered ST. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of small-dose dexmedetomidine on hyperdynamic responses to electroconvulsive therapy.

PubMed

Li, Xiang; Tan, Fang; Jian, Chao-Jun; Guo, Na; Zhong, Zhi-Yong; Hei, Zi-Qing; Zhou, Shao-Li

2017-08-01

Acute hemodynamic responses to electroconvulsive therapy (ECT) may increase the risk of cardiovascular complications in vulnerable patients. The aim of the current study was to assess the effect of small-dose dexmedetomidine on hyperdynamic responses to ECT. Seventy-eight patients were enrolled and randomly allocated to receive either 0.2 μg/kg dexmedetomidine (Dex group, n = 39) or saline (Control group, n = 39) prior to ECT. Heart rate (HR) and mean arterial pressure (MAP) were recorded immediately after the administration of dexmedetomidine (T1), and 0, 1, 3, 5 and 10 min after the electrical stimuli ended (T2, T3, T4, T5 and T6). In addition, the peak HR after ECT, seizure duration, recovery time, and incidence rates of post-ECT adverse effects (agitation, headache and nausea) were also recorded. HR and MAP in the Dex group were significantly lower than those in the Control group from T2 to T5. In addition, peak HR was significantly lower in the Dex group compared with that in the Control group. Seizure length and time to spontaneous breathing, eye opening, and obeying commands in the Dex group were similar to those in the Control group. The incidence rates of post-ECT agitation and headache in the Dex group were significantly lower than that in the Control group. The administration of 0.2 μg/kg dexmedetomidine to patients receiving ECT leads to a significant reduction in HR, MAP, and peak HR responses to ECT without altering seizure duration or delaying recovery. Furthermore, dexmedetomidine effectively reduced the incidence rates of post-ECT adverse effects such as agitation and headache. Copyright © 2017. Published by Elsevier Taiwan LLC.

Effects of electrical stimulus composition on cardiac electrophysiology in a rodent model of electroconvulsive therapy.

PubMed

Singh, Nagendra Madan; Sathyaprabha, T N; Thirthalli, Jagadisha; Andrade, Chittaranjan

2018-01-01

No electroconvulsive therapy (ECT) study on humans or in animal models has so far examined whether differently composed electrical stimuli exert different cardiac electrophysiological effects at constant electrical dose. The subject is important because cardiac electrophysiological changes may provide indirect information about ECT seizure quality as modulated by stimulus composition. Adult female Wistar rats ( n = 20/group) received fixed, moderately suprathreshold (18 mC) electrical stimuli. This stimulus in each of eight groups was formed by varying pulse amplitude, pulse width, pulse frequency, and stimulus duration. The electrocardiogram was recorded, and time and frequency domain variables were examined in 30 s epochs in preictal (30 s before electroconvulsive shock [ECS]), early postictal (starting 15 s after stimulation), and late postictal (5 h after ECS) periods. Alpha for statistical significance was set at P < 0.01 to adjust for multiple hypothesis testing. Cardiac electrophysiological indices in the eight groups did not differ significantly at baseline. At both early and late postictal time points, almost no analysis yielded statistically significant differences between groups for four time domain variables, including heart rate and standard deviation of R-R intervals, and for six frequency domain variables, including low-frequency power, high-frequency power, and total power. Cardiac electrophysiological measures may not be helpful to identify differences in seizure quality that are driven by differences in the composition of electrical stimuli at constant, moderately suprathreshold electrical dose. The generalization of this conclusion to threshold electrical doses and to human contexts requires a study.

Is prolongation of corrected QT interval associated with seizures induced by electroconvulsive therapy reduced by atropine sulfate?

PubMed

Suzuki, Yoko; Miyajima, Miho; Ohta, Katsuya; Yoshida, Noriko; Omoya, Rie; Fujiwara, Mayo; Watanabe, Takafumi; Okumura, Masaki; Yamazaki, Hiroaki; Shintaku, Masayuki; Murata, Issei; Ozaki, Shigeru; Sasaki, Takeshi; Nakamura, Mitsuru; Suwa, Hiroshi; Sasano, Tetsuo; Kawara, Tokuhiro; Matsuura, Masato; Matsushima, Eisuke

2017-11-01

Electrocardiogram abnormalities have been reported during electroconvulsive therapy (ECT). A corrected QT interval (QTc) prolongation indicates delayed ventricular repolarization, which can trigger ventricular arrhythmias such as torsade de pointes (TdP). We examined the QTc changes during generalized tonic-clonic seizures induced by ECT, and the effects of atropine sulfate on these QTc changes. We analyzed heart rate, QT interval, and QTc in 32 patients with depression who underwent ECT (25 women, 67.4 ± 8.7 years of age). The QTc from -30 to 0 seconds prestimulation was used as baseline, which was compared with QTc at 20-30 seconds and 140-150 seconds poststimulus onset. QTc was significantly prolonged at 20-30 seconds poststimulus, then significantly decreased at 140-150 seconds poststimulus, compared with baseline. QTc prolongation induced by ECT was significantly decreased by atropine sulfate. These data suggest that the risk of TdP may be enhanced by ECT. Further, the risk of cardiac ventricular arrhythmias, including TdP, may be reduced by administration of atropine sulfate. © 2017 Wiley Periodicals, Inc.

Pre-electroconvulsive shock administration of calcium channel blockers reduces retrograde amnesia induced by ECS.

PubMed

Sushma, M; Sudha, S; Guido, S

2004-11-01

Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats. The groups (Gr 1-7) of adult, male Wistar rats received true ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; ip) and other groups (Gr 8-14) received sham ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; i.p). The anti-amnestic activity of CCBs were evaluated using the passive avoidance paradigm in rats. Results showed that, the baseline latencies for all the groups did not differ significantly. Rats receiving true ECS produced significantly lower latencies. There was increase in the post ECS step through latencies of the rats administered CCBs before ECS. Therefore, pre-ECS administration of calcium channel blockers might reduce retrograde amnesia produced by ECS without altering seizure duration.

Effects of the concurrent use of a reduced dose of propofol with divided supplemental remifentanil and moderate hyperventilation on duration and morphology of electroconvulsive therapy-induced electroencephalographic seizure activity: A randomized controlled trial.

PubMed

Nishikawa, Kohki; Yamakage, Michiaki

2017-02-01

The clinical adequacy of electroconvulsive therapy (ECT) depends on not only seizure duration but also seizure amplitude and postictal suppression. The objective of this study was to evaluate the effects of combination of a reduced dose of propofol and moderate hyperventilation on seizure duration and electrical stimulus requirement for adequate ictal amplitude and postictal suppression. Prospective, randomized, controlled trial. Operating room at a municipal hospital. Sixty ASA physical status I or II patients scheduled to receive a total of >300 ECT treatments. Patients were randomly assigned to have the three interventions: the use of a standard dose (1mg/kg) of propofol and normoventilation (ETCO 2 of 40-45mmHg) (group P/N), the use of a reduced dose (0.5mg/kg) of propofol with divided remifentanil injections and normoventilation (group RP/N), and the use of a reduced dose of propofol with divided remifentanil injections and moderate hyperventilation (ETCO 2 of 30-35mmHg) (group RP/H). Patients in groups RP/N and RP/H received remifentanil 1μg/kg followed by propofol 0.5mg/kg for unconsciousness and thereafter remifentanil 1μg/kg immediately before the electrical stimulus. Patients in group RP/H had significantly longer durations of electroencephalographic (EEG) seizures in the early phase of the ECT course (P<0.05) and lower intensities of electrical stimulus in the late phase of the ECT course (P<0.05) than those in groups P/N and RP/N. A reduced dose of propofol combined with divided supplemental remifentanil under moderate hyperventilation during ECT may contribute to reduced electrical dosage due to the ability of its augmentation of seizure amplitude and postictal suppression in the late phase of the ECT course. Copyright © 2016 Elsevier Inc. All rights reserved.

Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity

PubMed Central

Jang, Sung-Soo; Royston, Sara E.; Lee, Gunhee; Wang, Shuwei; Chung, Hee Jung

2016-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Pathologic accumulation of soluble amyloid-β (Aβ) oligomers impairs synaptic plasticity and causes epileptic seizures, both of which contribute to cognitive dysfunction in AD. However, whether seizures could regulate Aβ-induced synaptic weakening remains unclear. Here we show that a single episode of electroconvulsive seizures (ECS) increased protein expression of membrane-associated STriatal-Enriched protein tyrosine Phosphatase (STEP61) and decreased tyrosine-phosphorylation of its substrates N-methyl D-aspartate receptor (NMDAR) subunit GluN2B and extracellular signal regulated kinase 1/2 (ERK1/2) in the rat hippocampus at 2 days following a single ECS. Interestingly, a significant decrease in ERK1/2 expression and an increase in APP and Aβ levels were observed at 3-4 days following a single ECS when STEP61 level returned to the baseline. Given that pathologic levels of Aβ increase STEP61 activity and STEP61-mediated dephosphorylation of GluN2B and ERK1/2 leads to NMDAR internalization and ERK1/2 inactivation, we propose that upregulation of STEP61 and downregulation of GluN2B and ERK1/2 phosphorylation mediate compensatory weakening of synaptic strength in response to acute enhancement of hippocampal network activity, whereas delayed decrease in ERK1/2 expression and increase in APP and Aβ expression may contribute to the maintenance of this synaptic weakening. PMID:27127657

Effects of electrical stimulus composition on cardiac electrophysiology in a rodent model of electroconvulsive therapy

PubMed Central

Singh, Nagendra Madan; Sathyaprabha, T. N.; Thirthalli, Jagadisha; Andrade, Chittaranjan

2018-01-01

Background: No electroconvulsive therapy (ECT) study on humans or in animal models has so far examined whether differently composed electrical stimuli exert different cardiac electrophysiological effects at constant electrical dose. The subject is important because cardiac electrophysiological changes may provide indirect information about ECT seizure quality as modulated by stimulus composition. Materials and Methods: Adult female Wistar rats (n = 20/group) received fixed, moderately suprathreshold (18 mC) electrical stimuli. This stimulus in each of eight groups was formed by varying pulse amplitude, pulse width, pulse frequency, and stimulus duration. The electrocardiogram was recorded, and time and frequency domain variables were examined in 30 s epochs in preictal (30 s before electroconvulsive shock [ECS]), early postictal (starting 15 s after stimulation), and late postictal (5 h after ECS) periods. Alpha for statistical significance was set at P < 0.01 to adjust for multiple hypothesis testing. Results: Cardiac electrophysiological indices in the eight groups did not differ significantly at baseline. At both early and late postictal time points, almost no analysis yielded statistically significant differences between groups for four time domain variables, including heart rate and standard deviation of R-R intervals, and for six frequency domain variables, including low-frequency power, high-frequency power, and total power. Conclusions: Cardiac electrophysiological measures may not be helpful to identify differences in seizure quality that are driven by differences in the composition of electrical stimuli at constant, moderately suprathreshold electrical dose. The generalization of this conclusion to threshold electrical doses and to human contexts requires a study. PMID:29736058

Effects of stimulus intensity on the efficacy and safety of twice-weekly, bilateral electroconvulsive therapy (ECT) combined with antipsychotics in acute mania: a randomised controlled trial.

PubMed

Mohan, Titus S P; Tharyan, Prathap; Alexander, Jacob; Raveendran, Nirmal S

2009-03-01

To examine differences in speed of improvement and remission in people with mania undergoing bilateral, brief-pulse, twice-weekly electroconvulsive therapy (ECT) at stimulus intensities administered just above and 2.5 times their individually titrated seizure threshold. Consecutive, eligible subjects with mania, prescribed ECT, were randomised to receive treatments at stimulus doses either just above or 2.5 times their individually titrated seizure thresholds. Main outcomes were the speed of improvement and remission as measured by the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions-Improvement scale (CGI-I) and cognitive side effects assessed by the Mini-Mental State Exam, the Wechsler Memory Scale, and a scale for autobiographical memory. A total of 24/26 subjects (92.3%) given threshold ECT and 22/24 subjects (91.7%) given suprathreshold ECT were significantly improved [CGI = 2; odds ratio (OR) = 1.1, 95% confidence interval (CI): 0.1-8.4; p = 1.0] at the end of ECT. A total of 88% of the sample had remitted [YMRS < 10; threshold 23/26 (88.5%) versus suprathreshold 21/24 (87.5%)], with no significant differences between interventions (OR = 1.1, 95% CI: 0.2- 6.0; p = 1.0). The interventions did not differ significantly in the time or number of ECT treatments required for improvement or remission. Both interventions were equally safe. Bilateral, twice-weekly ECT delivered at stimulus intensities just above individually titrated seizure threshold was as effective and safe as ECT administered at stimulus intensities 2.5 times seizure threshold in rapidly resolving the symptoms of acute mania.

Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression.

PubMed

Zhong, Xiaomei; He, Hongbo; Zhang, Chunping; Wang, Zhijie; Jiang, Miaoling; Li, Qirong; Zhang, Minling; Huang, Xiong

2016-09-01

Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects. Ninety TRD patients (36 males, 54 females; average age, 30.6 years old) were randomly assigned to receive either ketamine (0.8mg/kg) (n=30), subanesthetic ketamine (0.5mg/kg) plus propofol (0.5mg/kg) (n=30) or propofol (0.8mg/kg) (n=30) as an anesthetic and underwent 8 ECT sessions. The primary outcome measures were the 17-item Hamilton Depression Rating Scale (HDRS-17), cognitive assessments and seizure parameters. The ketamine group had an earlier improvement in HDRS-17, longer seizure duration, lower electric quantity, a higher remission rate, and a lower degree of executive cognitive impairment compared to the ketamine+propofol and propofol groups. The ketamine+propofol group showed earlier improvement in the HDRS-17, a longer seizure duration and a different seizure energy index when compared to the propofol group. The postoperative dissociative side effect was not assessed. Both anesthetic and subanesthetic concentrations of ketamine have rapid mood enhancing actions in ECT for TRD, while anesthetic concentrations results in larger magnitudes of antidepression and cognitive protection. ECT with ketamine anesthesia might be an optimized therapy for patients with TRD. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model

PubMed Central

Lee, Won Hee; Lisanby, Sarah H.; Laine, Andrew F.; Peterchev, Angel V.

2017-01-01

Background This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST). Methods The electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes. Results The standard ECT configurations and current amplitude of 800–900 mA produced the strongest overall stimulation with median of 1.8–2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST. Conclusions The relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio. PMID:27318858

High but not low ECS stimulus intensity augments apomorphine-stimulated dopamine postsynaptic receptor functioning in rats.

PubMed

Andrade, Chittaranjan; Srinivasamurthy, Gurunath M; Vishwasenani, A; Prakash, G Sai; Srihari, B S; Chandra, J Suresh

2002-06-01

Clinical research shows that the antidepressant and cognitive adverse effects of electroconvulsive therapy are both dependent on the administered electrical stimulus intensity (dose); however, dose-dependent neurotransmitter system changes in the brain, which might underlie the therapeutic or adverse effects, remain to be demonstrated. We used a behavioral model to examine dose-related effects of electroconvulsive shock (ECS) on dopamine postsynaptic receptor functioning in the rat brain. In a factorially designed study, rats (n = 100) were treated with five once-daily ECSs at three levels (sham ECS, 30 mC ECS, and 120 mC ECS), and with drug at two levels (saline, and 1 mg/kg s.c. apomorphine). Motility was assessed in the small open field. Apomorphine-elicited, dopamine postsynaptic receptor-mediated hypermotility was significantly increased by 120 mC ECS but not by 30 mC ECS. An additional but unrelated finding was that, while the ECS seizure duration expectedly decreased across time, no dose-dependent effects were observed. ECS-induced dopamine postsynaptic receptor up-regulation may depend on the intensity of the administered electrical stimulus.

Electroconvulsive therapy: Part I. A perspective on the evolution and current practice of ECT.

PubMed

Payne, Nancy A; Prudic, Joan

2009-09-01

The concept of inducing convulsions, mainly through chemical means, to promote mental wellness has existed since the 16th century. In 1938, Italian scientists first applied electrically induced therapeutic seizures. Although electroconvulsive therapy (ECT) is employed in the treatment of several psychiatric disorders, it is most frequently used today to treat severe depressive episodes and remains the most effective treatment available for those disorders. Despite this, ECT continues to be the most stigmatized treatment available in psychiatry, resulting in restrictions on and reduced accessibility to a helpful and potentially life-saving treatment. The psychiatric and psychosocial ramifications of this stigmatization may include the exacerbation of the increasingly serious, global health problem of major depressive disorders as well as serious consequences for individual patients who may not be offered, or may refuse, a potentially beneficial treatment. The goal of this first article in this two-part series is to provide an overview of ECT's historical development and discuss the current state of knowledge about ECT, including technical aspects of delivery, patient selection, its side-effect profile, and factors that may contribute to underuse of ECT.

USSR and Eastern Europe Scientific Abstracts, Biomedical and Behavioral Sciences, Number 67.

DTIC Science & Technology

1977-03-30

and Ecological Problems 14 Molecular Biology 23 Pharmacology. 25 Physiology. 27 Public Health 46 Radiobiology 48 Therapy . 49 BEHAVIORAL...normalizing metabolic processes be included in the complex therapy . USSR UDC 612.3 616.3 DIGESTIBILITY OF VEGETARIAN FISH MEAT PROTEINS BY PROTEOLYTIC...inactivation of one hemisphere, arising after unilateral electroconvulsive seizure, a study was made of the intelli- gibility of phonemes (vowels and

Bitemporal v. high-dose right unilateral electroconvulsive therapy for depression: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Kolshus, E; Jelovac, A; McLoughlin, D M

2017-02-01

Brief-pulse electroconvulsive therapy (ECT) is the most acutely effective treatment for severe depression though concerns persist about cognitive side-effects. While bitemporal electrode placement is the most commonly used form worldwide, right unilateral ECT causes less cognitive side-effects though historically it has been deemed less effective. Several randomized trials have now compared high-dose (>5× seizure threshold) unilateral ECT with moderate-dose (1.0-2.5× seizure threshold) bitemporal ECT to investigate if it is as effective as bitemporal ECT but still has less cognitive side-effects. We aimed to systematically review these trials and meta-analyse clinical and cognitive outcomes where appropriate. We searched PubMed, PsycINFO, Web of Science, Cochrane Library and EMBASE for randomized trials comparing these forms of ECT using the terms 'electroconvulsive' OR 'electroshock' AND 'trial'. Seven trials (n = 792) met inclusion criteria. Bitemporal ECT did not differ from high-dose unilateral ECT on depression rating change scores [Hedges's g = -0.03, 95% confidence interval (CI) -0.17 to 0.11], remission (RR 1.06, 95% CI 0.93-1.20), or relapse at 12 months (RR 1.42, 95% CI 0.90-2.23). There was an advantage for unilateral ECT on reorientation time after individual ECT sessions (mean difference in minutes = -8.28, 95% CI -12.86 to -3.70) and retrograde autobiographical memory (Hedges's g = -0.46, 95% CI -0.87 to -0.04) after completing an ECT course. There were no differences for general cognition, category fluency and delayed visual and verbal memory. High-dose unilateral ECT does not differ from moderate-dose bitemporal ECT in antidepressant efficacy but has some cognitive advantages.

[Ketamine as anesthetic agent in electroconvulsion therapy].

PubMed

Janke, C; Bumb, J M; Aksay, S S; Thiel, M; Kranaster, L; Sartorius, A

2015-05-01

Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment for severe psychiatric disorders. Ketamine is known as a core medication in anesthesiology and has recently gained interest in ECT practice as there are three potential advantages: (1) ketamine has no anticonvulsive actions, (2) according to recent studies ketamine could possess a unique intrinsic antidepressive potential and (3) ketamine may exhibit neuroprotective properties, which again might reduce the risk of cognitive side effects associated with ECT. The use of ketamine in psychiatric patients has been controversially discussed due to its dose-dependent psychotropic and psychotomimetic effects. This study was carried out to test if the occurrence of side effects is comparable and if seizure quality is better with ketamine when compared to thiopental. This retrospective study analyzed a total of 199 patients who received ketamine anesthesia for a total of 2178 ECT sessions. This cohort was compared to patients who were treated with thiopental for 1004 ECT sessions. A repeated measurement multiple logistic regression analysis revealed significant advantages in the ketamine group for seizure concordance and postictal suppression (both are surrogates for central inhibition). S-ketamin also necessitated the use of a higher dose of urapidil and a higher maximum postictal heart frequency. Clinically relevant psychiatric side effects were rare in both groups. No psychiatric side effects occurred in the subgroup of patients with schizophrenia (ketamine: n = 30). The mean dose of S-ketamine used increased in the first years but stabilized at 63 mg per patient in 2014. From these experiences it can be concluded that S-ketamine can be recommended at least as a safe alternative to barbiturates.

A New Type of ECT Stimuli: Burst Stimulus ECT.

PubMed

Aksay, S S; Bumb, J M; Janke, C; Kranaster, L; Sartorius, A

2015-11-01

Pulse width in electroconvulsive therapy has significant influence on effectiveness and side effects. While shorter pulses are beneficial for cognitive performance, there is still a debate about a negative impact on ECT efficacy at least for ultra-brief pulse durations. We report a first patient treated with burst stimulus ECT, i. e., with 4 consecutive 250-µs pulses, separated by another 250 µs. Within the same patient we compared 6 classical vs. 6 burst stimulus ECT sessions. In all cases a typical tonic-clonic seizure was observed. Seizure parameters like concordance, coherence and mid-ictal amplitude increased numerically, but not significantly with burst ECT. The time needed to show a reorientation was significantly shortened with burst stimuli (30 min vs. 14 min, p=0.007). In conclusion we present the first case of ECT in a single patient comparing "classical" single stimulus pulses vs. burst stimulus ECT. The new burst stimulus was better tolerated regarding reorientation time after the treatment, while parameters of seizure quality remained basically unchanged. Whether burst stimulus ECT has the potential to improve ECT quality by reducing side effects without losing efficacy has to be investigated in clinical trials. © Georg Thieme Verlag KG Stuttgart · New York.

A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and electroconvulsive therapy in persistent depression.

PubMed

Fitzgerald, Paul B; Hoy, Kate E; Elliot, David; McQueen, Susan; Wambeek, Lenore E; Chen, Leo; Clinton, Anne Maree; Downey, Glenn; Daskalakis, Zafiris J

2018-05-01

Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment. Thirty-seven patients completed a course of at least nine ECT or MST treatments in a randomized double-blind protocol. Assessments of depression severity and cognition were performed before and after treatment. No difference in the antidepressant effectiveness between the treatments was seen across any of the clinical outcome measures, although the overall response rates in both groups were quite low. In regards to cognition, following MST there were significant improvements in tests of psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in cognitive performance. Following ECT there was significant improvement in only one of the cognitive inhibition tasks. With respect to the between-group comparisons, the MST group showed a significantly greater improvement on psychomotor speed than ECT. MST showed similar efficacy to right unilateral ECT in patients with treatment-resistant depression without cognitive side effects but in a sample that was only of sufficient size to demonstrate relatively large differences in response between the two groups. Future research should aim to optimize the methods of MST administration and compare its efficacy to ECT in large randomized controlled trials. © 2018 Wiley Periodicals, Inc.

Somatic Treatments for Mood Disorders

PubMed Central

Rosa, Moacyr A; Lisanby, Sarah H

2012-01-01

Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation. PMID:21976043

Effect of etomidate versus thiopental on major depressive disorder in electroconvulsive therapy, a randomized double-blind controlled clinical trial.

PubMed

Abdollahi, Mohammad Hassan; Izadi, Amir; Hajiesmaeili, Mohammad Reza; Ghanizadeh, Ahmad; Dastjerdi, Ghasem; Hosseini, Habib Allah; Ghiamat, Mohammad Mehdi; Abbasi, Hamid Reza

2012-03-01

Although the therapeutic effect of electroconvulsive therapy (ECT) on major depressive disorder is widely investigated, there is a gap in literature regarding the possible effects of the medications used for induction of anesthesia in ECT. To the best of the authors' knowledge, this study is the first randomized double-blind clinical trial comparing the effect of etomidate and sodium thiopental on the depression symptoms in patients who have received ECT. The participants of this study are 60 adult patients with major depressive disorder who were referred for ECT. They were randomly allocated into 1 of the 2 groups. One group received etomidate, and the other group received sodium thiopental, as medication for induction of anesthesia. All the patients received bilateral ECT. The outcomes measures included the Beck Depression Inventory score, seizure duration, and recovery duration after induction of anesthesia. The sex ratio and mean age were not different between the 2 groups. Linear regression analysis showed that etomidate decreased the depression score more than did sodium thiopental. Seizure duration in all of the sessions in the etomidate group was significantly higher than that of sodium thiopental group. In conclusion, etomidate may improve major depressive disorder more than sodium thiopental in patients who are receiving ECT.

Do ictal EEG characteristics predict treatment outcomes in schizophrenic patients undergoing electroconvulsive therapy?

PubMed

Simsek, Gulnihal Gokce; Zincir, Selma; Gulec, Huseyin; Eksioglu, Sevgin; Semiz, Umit Basar; Kurtulmus, Yasemin Sipka

2015-08-01

The aim of this study is to investigate the relationship between features of electroencephalography (EEG), including seizure time, energy threshold level and post-ictal suppression time, and clinical variables, including treatment outcomes and side-effects, among schizophrenia inpatients undergoing electroconvulsive therapy (ECT). This is a naturalistic follow-up study on schizophrenia patients, diagnosed using DSM-IV-TR criteria, treated by a psychosis inpatient service. All participants completed the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning (GAF) scale, the Frontal Assessment Battery (FAB) and a Data Collection Form. Assessments were made before treatment, during ECT and after treatment. Statistically significant improvements in both clinical and cognitive outcome were noted after ECT in all patients. Predictors of improvement were sought by evaluating electrophysiological variables measured at three time points (after the third, fifth and seventh ECT sessions). Logistic regression analysis showed that clinical outcome/improvement did not differ by seizure duration, threshold energy level or post-ictal suppression time. We found that ictal EEG parameters measured at several ECT sessions did not predict clinical recovery/outcomes. This may be because our centre defensively engages in "very specific patient selection" when ECT is contemplated. ECT does not cause short-term cognitive functional impairment and indeed improves cognition, because symptoms of the schizophrenic episode are alleviated.

Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures

PubMed Central

LaFrance, W.C.; Leaver, K.; Stopa, E.G.; Papandonatos, G.D.; Blum, A.S.

2010-01-01

Objective: Neurotrophins promote neurogenesis and help regulate synaptic reorganization. Their dysregulation has been implicated in a number of neurologic and psychiatric disorders. Previous studies have shown decreased levels of brain-derived neurotrophic factor (BDNF) in the serum of patients with psychiatric disorders such as major depressive disorder (MDD) and conversion disorder (CD). In human patients with temporal lobe epilepsy, there is an increase in both BDNF mRNA and protein levels in surgically resected hippocampi compared to controls. One study of children with epilepsy has found normal to increased serum BDNF levels compared to controls. Serum BDNF levels have not been investigated in adult patients with epileptic seizures (ES). We hypothesized that BDNF would differentiate between ES and psychogenic nonepileptic seizures (PNES). Methods: We assessed serum BDNF immunoreactivity in 15 patients with ES, 12 patients with PNES, and 17 healthy volunteers. Serum BDNF levels were measured using an enzyme-linked immunoassay. Results: Healthy controls showed higher BDNF levels (4,289 ± 1,810 pg/mL) compared to patients with PNES (1,033 ± 435 pg/mL) (p < 0.001). However, unexpectedly, healthy controls also showed higher levels of BDNF compared to patients with ES without comorbid MDD (977 ± 565 pg/mL) (p < 0.001). Conclusions: Unlike children, adults with epilepsy appear to have decreased levels of serum BDNF. Reduced serum BDNF levels can be used to differentiate adult patients with ES or PNES from healthy controls. Further human studies are needed to better understand the pathophysiology explaining the decreased serum BDNF levels found in epilepsy and in PNES. GLOSSARY AED = antiepileptic drug; BDI-II = Beck Depression Inventory II; BDNF = brain-derived neurotrophic factor; CD = conversion disorder; ECS = electroconvulsive seizure; ES = epileptic seizure; GTC = generalized tonic-clonic seizure; HC = healthy control; MDD = major depressive disorder; PNES = psychogenic nonepileptic seizure; PRL = prolactin; RIH = Rhode Island Hospital. PMID:20921514

Differential plastic changes in synthesis and binding in the mouse somatostatin system after electroconvulsive stimulation.

PubMed

Olesen, Mikkel Vestergaard; Gøtzsche, Casper René; Christiansen, Søren Hofman; Woldbye, David Paul Drucker

2018-03-21

Electroconvulsive therapy (ECT) is regularly used to treat patients with severe major depression, but the mechanisms underlying the beneficial effects remain uncertain. Electroconvulsive stimulation (ECS) regulates diverse neurotransmitter systems and induces anticonvulsant effects, properties implicated in mediating therapeutic effects of ECT. Somatostatin (SST) is a candidate for mediating these effects because it is upregulated by ECS and exerts seizure-suppressant effects. However, little is known about how ECS might affect the SST receptor system. The present study examined effects of single and repeated ECS on the synthesis of SST receptors (SSTR1-4) and SST, and SST receptor binding ([125I]LTT-SST28) in mouse hippocampal regions and piriform/parietal cortices. A complex pattern of plastic changes was observed. In the dentate gyrus, SST and SSTR1 expression and the number of hilar SST immunoreactive cells were significantly increased at 1 week after repeated ECS while SSTR2 expression was downregulated by single ECS, and SSTR3 mRNA and SST binding were elevated 24 h after repeated ECS. In hippocampal CA1 and parietal/piriform cortices, we found elevated SST mRNA levels 1 week after repeated ECS and elevated SST binding after single ECS and 24 h after repeated ECS. In hippocampal CA3, repeated ECS increased SST expression 1 week after and SST binding 24 h after. In the parietal cortex, SSTR2 mRNA expression was downregulated after single ECS while SSTR4 mRNA expression was upregulated 24 h after repeated ECS. Considering the known anticonvulsant effects of SST, it is likely that these ECS-induced neuroplastic changes in the SST system could participate in modulating neuronal excitability and potentially contribute to therapeutic effects of ECT.

Propofol for ECT anesthesia a review of the literature.

PubMed

Rasmussen, Keith G

2014-09-01

Propofol is a commonly used anesthetic drug for electroconvulsive therapy (ECT), as evidenced by the frequency with which its use is reported in ECT literature. Concerns have been raised over its propensity to be associated with shortened seizure duration vis-à-vis other anesthetic drugs, thus limiting its use in some settings. However, in the surgical anesthesia literature, propofol has shown distinct advantages such as improved hemodynamics and postanesthesia recovery. Given the capricious availability of standard barbiturate anesthetics in some countries, propofol use has probably increased. Thus, a review of its profile for a number of outcome measures in ECT is appropriate. Herein, the author reviews the extensive literature for propofol in ECT, focusing on 5 outcome measures: seizure duration, hemodynamics, postanesthesia recovery, cognitive adverse effects, and therapeutic efficacy. Results indicate that propofol is indeed robustly associated with shorter seizures than other anesthetics but that antidepressant efficacy does not seem to be compromised. Heart rate and blood pressure changes are not as high with propofol, and postanesthesia recovery may be quicker with propofol as well. Not enough data are available regarding cognitive adverse effects to make definitive conclusions, but so far, there does not seem to be a worsened cognitive profile when it is used in ECT. Propofol seems to be an acceptable anesthetic for ECT with advantages for some situations. Using the lowest effective anesthetic dosage minimizes its effect on seizure elicitation and duration.

Electroconvulsive Therapy Part I: A Perspective on the Evolution and Current Practice of ECT

PubMed Central

Payne, Nancy A.; Prudic, Joan

2010-01-01

The concept of inducing convulsions, mainly through chemical means, to promote mental wellness has existed since the 16th century. In 1938, Italian scientists first applied electrically induced therapeutic seizures. Although electroconvulsive therapy (ECT) is employed in the treatment of several psychiatric disorders, it is most frequently used today to treat severe depressive episodes and remains the most effective treatment available for those disorders. Despite this, ECT continues to be the most stigmatized treatment available in psychiatry, resulting in restrictions on and reduced accessibility to a helpful and potentially life-saving treatment. The psychiatric and psychosocial ramifications of this stigmatization may include the exacerbation of the increasingly serious, global health problem of major depressive disorders as well as serious consequences for individual patients who may not be offered, or may refuse, a potentially beneficial treatment. The goal of this first article in this two-part series is to provide an overview of ECT's historical development and discuss the current state of knowledge about ECT, including technical aspects of delivery, patient selection, its side-effect profile, and factors that may contribute to underuse of ECT. PMID:19820553

Bispectral index monitoring during electroconvulsive therapy under propofol anaesthesia.

PubMed

Gunawardane, P O; Murphy, P A; Sleigh, J W

2002-02-01

The accuracy of the bispectral index (BIS) as a monitor of consciousness has not been well studied in patients who have abnormal electroencephalograms (EEG). We studied the changes in BIS, its subparameters, and spectral entropy of the EEG during 18 electroconvulsive treatments under propofol and succinylcholine anaesthesia. A single bifrontal EEG, and second subocular channel (for eye movement estimation) was recorded. The median (interquartile range) BIS value at re-awakening was only 57 (47-78)--thus more than a quarter of the patients woke at BIS values of less than 50. The changes in spectral entropy values were similar: 0.84 (0.68-0.99) at the start, 0.65 (0.42-0.88) at the point of loss-of-consciousness, 0.63 (0.47-0.79) during the seizures, and 0.58 (0.31-0.85) at awakening. Post-ictal slow-wave activity in the EEG (acting via the SynchFastSlow subparameter) may cause low BIS values that do not correspond to the patient's clinical level of consciousness. This may be important in the interpretation of the BIS in other groups of patients who have increased delta-band power in their EEG.

A systematic review and meta-analysis of randomized controlled trials of adjunctive ketamine in electroconvulsive therapy: efficacy and tolerability.

PubMed

McGirr, Alexander; Berlim, Marcelo T; Bond, David J; Neufeld, Nicholas H; Chan, Peter Y; Yatham, Lakshmi N; Lam, Raymond W

2015-03-01

Electroconvulsive therapy (ECT) remains one of the most effective tools in the psychiatric treatment armamentarium, particularly for refractory depression. Yet, there remains a subset of patients who do not respond to ECT or for whom clinically adequate seizures cannot be elicited, for whom ketamine has emerged as a putative augmentation agent. We searched EMBASE, PsycINFO, CENTRAL, and MEDLINE from 1962 to April 2014 to identify randomized controlled trials evaluating ketamine in ECT (PROSPERO #CRD42014009035). Clinical remission, response, and change in depressive symptom scores were extracted by two independent raters. Adverse events were recorded. Drop-outs were assessed as a proxy for acceptability. Meta-analyses employed a random effects model. Data were synthesized from 5 RCTs, representing a total of 182 patients with major depressive episodes (n = 165 Major Depressive Disorder, n = 17 Bipolar Disorder). ECT with ketamine augmentation was not associated with higher rates of clinical remission (Risk Difference (RD) = 0.00; 95%CI = -0.08 to 0.10), response (RD = -0.01; 95%CI = -0.11 to 0.08), or improvements in depressive symptoms (SMD = 0.38; 95%CI = -0.41 to 1.17). Ketamine augmentation was associated with higher rates of confusion/disorientation/prolonged delirium (OR = 6.59, 95%CI: 1.28-33.82, NNH = 3), but not agitation, hypertension or affective switches. Our meta-analysis of randomized controlled trials of ketamine augmentation in the ECT setting suggests a lack of clinical efficacy, and an increased likelihood of confusion. Individuals for whom adequate seizures or therapeutic response cannot be obtained have not been studied using randomized controlled designs. Additional research is required to address the role of ketamine in this population. Copyright © 2015 Elsevier Ltd. All rights reserved.

A critical examination of bifrontal electroconvulsive therapy: clinical efficacy, cognitive side effects, and directions for future research.

PubMed

Crowley, Kevin; Pickle, Jody; Dale, Roman; Fattal, Omar

2008-12-01

Bifrontal (BF) electroconvulsive therapy (ECT), although researched less extensively than bitemporal (BT) or right unilateral (RUL) ECT, has been suggested to be comparable to the other 2 electrode placements with respect to clinical efficacy while resulting in less cognitive impairment than BT ECT. Imaging studies have indicated that seizures induced by BF ECT affect the brain differently than BT or RUL ECT, in that BF ECT increases cerebral blood flow in the frontal lobes more intensely than either of the other 2 placements. Therefore, it is possible that the cognitive impairment manifested after a course of BF ECT could also be different than the impairment seen with BT and RUL ECT. Research conducted on cognitive impairment from BF ECT to date has been inadequate due to the use of nonspecific cognitive measures (such as the Mini-Mental Status Examination) or an inordinate focus on memory functioning (which is believed to be mostly subsumed in the temporal lobes). Because BF ECT increases cerebral blood flow in the frontal lobes more intensely than either of the other placements, research must instead focus on investigating the possible effects of BF ECT on executive functioning, which is believed to be subsumed in the frontal lobes. This is especially important because of the established relationship between executive dysfunction and depression and also because of the increasing popularity of BF ECT.

Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy.

PubMed

Hoirisch-Clapauch, Silvia; Mezzasalma, Marco A U; Nardi, Antonio E

2014-02-01

Electroconvulsive therapy is an important treatment option for major depressive disorders, acute mania, mood disorders with psychotic features, and catatonia. Several hypotheses have been proposed as electroconvulsive therapy's mechanism of action. Our hypothesis involves many converging pathways facilitated by increased synthesis and release of tissue-plasminogen activator. Human and animal experiments have shown that tissue-plasminogen activator participates in many mechanisms of action of electroconvulsive therapy or its animal variant, electroconvulsive stimulus, including improved N-methyl-D-aspartate receptor-mediated signaling, activation of both brain-derived neurotrophic factor and vascular endothelial growth factor, increased bioavailability of zinc, purinergic release, and increased mobility of dendritic spines. As a result, tissue-plasminogen activator helps promote neurogenesis in limbic structures, modulates synaptic transmission and plasticity, improves cognitive function, and mediates antidepressant effects. Notably, electroconvulsive therapy seems to influence tissue-plasminogen activator metabolism. For example, electroconvulsive stimulus increases the expression of glutamate decarboxylase 65 isoform in γ-aminobutyric acid-releasing neurons, which enhances the release of tissue-plasminogen activator, and the expression of p11, a protein involved in plasminogen and tissue-plasminogen activator assembling. This paper reviews how electroconvulsive therapy correlates with tissue-plasminogen activator. We suggest that interventions aiming at increasing tissue-plasminogen activator levels or its bioavailability - such as daily aerobic exercises together with a carbohydrate-restricted diet, or normalization of homocysteine levels - be evaluated in controlled studies assessing response and remission duration in patients who undergo electroconvulsive therapy.

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors.

PubMed

Martin, Donel M; Gálvez, Verònica; Loo, Colleen K

2015-06-19

Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview - Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview - Short Form scores following right unilateral electroconvulsive therapy. Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for patients with lower baseline cognitive status or older age. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors

PubMed Central

Gálvez, Verònica; Loo, Colleen K.

2015-01-01

Background: Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. Methods: Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview – Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. Results: Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview – Short Form scores following right unilateral electroconvulsive therapy. Conclusions: Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for patients with lower baseline cognitive status or older age. PMID:26091817

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

High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy: A Prospective, Observational Cohort Study.

PubMed

Duma, Andreas; Pal, Swatilika; Johnston, Joshua; Helwani, Mohammad A; Bhat, Adithya; Gill, Bali; Rosenkvist, Jessica; Cartmill, Christopher; Brown, Frank; Miller, J Philip; Scott, Mitchell G; Sanchez-Conde, Francisco; Jarvis, Michael; Farber, Nuri B; Zorumski, Charles F; Conway, Charles; Nagele, Peter

2017-04-01

While electroconvulsive therapy is widely regarded as a lifesaving and safe procedure, evidence regarding its effects on myocardial cell injury is sparse. The objective of this investigation was to determine the incidence and magnitude of new cardiac troponin elevation after electroconvulsive therapy using a novel high-sensitivity cardiac troponin I assay. This was a prospective cohort study in adult patients undergoing electroconvulsive therapy in a single academic center (up to three electroconvulsive therapy treatments per patient). The primary outcome was new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy, defined as an increase of high-sensitivity cardiac troponin I greater than 100% after electroconvulsive therapy compared to baseline with at least one value above the limit of quantification (10 ng/l). Twelve-lead electrocardiogram and high-sensitivity cardiac troponin I values were obtained before and 15 to 30 min after electroconvulsive therapy; in a subset of patients, an additional 2-h high-sensitivity cardiac troponin I value was obtained. The final study population was 100 patients and a total of 245 electroconvulsive therapy treatment sessions. Eight patients (8 of 100; 8%) experienced new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy with a cumulative incidence of 3.7% (9 of 245 treatments; one patient had two high-sensitivity cardiac troponin I elevations), two of whom had a non-ST-elevation myocardial infarction (incidence 2 of 245; 0.8%). Median high-sensitivity cardiac troponin I concentrations did not increase significantly after electroconvulsive therapy. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of electroconvulsive therapy treatments. Electroconvulsive therapy appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with preexisting cardiovascular risk factors, however, may develop new cardiac troponin elevation after electroconvulsive therapy, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia.

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.

[Electroconvulsive therapy and level of evidence: From causality to dose-effect relationship].

PubMed

Micoulaud-Franchi, J-A; Quilès, C; Cermolacce, M; Belzeaux, R; Adida, M; Fakra, E; Azorin, J-M

2016-12-01

The first objective of this article is to summarize the history of electroconvulsive therapy (ECT) in psychiatry in order to highlight the transition from clinical level of evidence based on phenomenological descriptions to controlled trial establishing causal relationship. The second objective is to apply the criteria of causation for ECT, to focus on the dose-effect relationship criteria, and thus to analyze the conditions of application of these criteria for ECT. A literature review exploring the use of electricity, ECT and electroencephalography (EEG) in psychiatry was conducted. The publications were identified from the Pubmed and GoogleScholar electronic databases. The scientific literature search of international articles was performed in July 2016. In 1784, a Royal commission established in France by King Louis XVI tested Mesmer's claims concerning animal magnetism. By doing that, the commission, including such prominent scientists as the chemist Anton Lavoisier and the scientist and researcher on electricity and therapeutics Benjamin Franklin, played a central role in establishing the criteria needed to assess the level of evidence of electrical therapeutics in psychiatry. Surprisingly, it is possible to identify the classical Bradford Hill criteria of causation in the report of the commission, except the dose-effect relationship criteria. Since then, it has been conducted blinded randomized controlled trials that confirmed the effectiveness of ECT against ECT placebos for the treatment of psychiatric disorders. At present, the dose-effect relationship criteria can be analyzed through an EEG quality assessment of ECT-induced seizures. EEG quality assessment includes several indices: TSLOW (time to onset of seizure activity ≤5Hz, seconds), peak mid-ictal amplitude (mm), regularity (intensity or morphology of the seizure (0-6)), stereotypy (global seizure patterning, 0-3) and post-ictal suppression (0-3). A manual rating sheet is needed to score theses indices. Such manual rating with example of EEG segments recording is proposed in this article. Additional studies are needed to validate this manual, to better establish the dose-response relationship for the ECT, and thus strengthen the position of the EEG as a central element for clinical good practice for ECT. © L’Encéphale, Paris, 2016.

Electroconvulsive therapy and nursing care.

PubMed

Kavanagh, Adam; McLoughlin, Declan M

Modified electroconvulsive therapy (ECT) is a controlled medical procedure in which a seizure is induced in an anaesthetized patient to produce a therapeutic effect. ECT is the most acutely effective treatment available for affective disorders and is more effective than antidepressant drugs. Although in use for 70 years, ECT continues to attract controversy and there is considerable stigma associated with its use that often overshadows the empirical evidence for its effectiveness. One way to overcome this is for health professionals to be educated about contemporary ECT practice. Patients need to make informed decisions when consenting to ECT and this process can be influenced by preconceived ideas and scientific fact. It is, therefore, essential that nurses possess sufficient information to help patients make rational and informed treatment decisions and be able to care for both the clinical and psychological needs of patients treated with ECT. This review outlines the nursing role in ECT and summarizes the main aspects of contemporary ECT practice relevant to general and psychiatric nursing practice.

A national survey of electroconvulsive therapy use in the Russian Federation.

PubMed

Nelson, Alexander I

2005-09-01

A survey of electroconvulsive therapy (ECT) throughout Russia was undertaken to understand the range of ECT usage and knowledge. A survey form was distributed by mail to 1648 Russian doctors and institutions expected to deal with ECT. A total of 114 replies were received. They indicated that ECT is available to 22.4% of the country's population. In available regions, ECT is given to 1.43% of hospital admissions and 0.54 per 10,000 persons per year. ECT is used in Russian psychiatry, neurology, and addictionology. Outdated ECT instruments are used in more than one third of sites, and EEG and seizure quality are virtually never monitored. Fewer than 20% of ECTs are modified with anesthesia. There is no system or expectation for ECT training or privileging, there is no national organization that aims to advance ECT practice, and ECT research is haphazard. Nevertheless, most respondents are enthusiastic and positive about ECT, and most institutions are eager to adopt modern ECT methods.

Maintenance ECT as a therapeutic approach to medication-refractory epilepsy in an adult with mental retardation: case report and review of literature.

PubMed

Shah, Nilesh; Pande, Nikhil; Bhat, Tushar; Murke, Mukund; Andrade, Chittaranjan

2012-06-01

Electroconvulsive therapy (ECT) raises the seizure threshold. This physiological change may benefit patients with seizure disorders. Whereas ECT has recently been used to terminate medication-refractory status epilepticus, there is little current literature on its planned administration as a specific maintenance treatment for medication-refractory epilepsy. We used maintenance ECT to treat an 18-year-old man with a long-standing generalized tonic-clonic seizure disorder who had shown poor response to several antiepileptic drugs administered in combination with antiepileptic medication compliance confirmed through drug level monitoring. A total of 52 ECTs were administered across nearly 20 months at a mean frequency of once in nearly 12 days. From the very outset, ECT dramatically decreased the frequency of spontaneous seizures from approximately 6 to 24 per week at baseline to approximately 1 to 2 per week after ECT initiation. The efficacy of maintenance ECT in spontaneous seizure prophylaxis was greater when the ECT treatment interval was narrower. Improvement with ECT was associated with improved behavior and improved psychosocial functioning on clinical report. No cognitive or other adverse effects were reported or clinically ascertained. The ECT charge administered at the last 10 treatment sessions was 1434 millicoulombs. This is probably the highest electrical stimulus dose recorded in literature. Maintenance ECT may reduce the frequency of breakthrough seizures in patients with seizure disorder that is inadequately responsive to antiepileptic medication regimes. Very high ECT seizure thresholds may be observed when many antiepileptic drugs are concurrently administered in high doses.

Position statement and guidelines on unmodified electroconvulsive therapy

PubMed Central

Andrade, Chittaranjan; Shah, N.; Tharyan, P.; Reddy, M. S.; Thirunavukarasu, M.; Kallivayalil, R. A.; Nagpal, R.; Bohra, N. K.; Sharma, A.; Mohandas, E.

2012-01-01

Background: In modern day psychiatric practice, it is assumed as a matter of fact that when electroconvulsive therapy (ECT) is administered, it will be administered under anesthesia and with succinylcholine (or its equivalent) modification. Yet, as surveys indicate, there is considerable practice of unmodified ECT in developing countries and, to a small extent, in the developed world, as well. Materials and Methods: This document examines historical and recent literature on the geographical practice, physiology, efficacy, and adverse effects of unmodified ECT. Particular attention is paid to musculoskeletal risks. Results: Although almost all the research is of poor methodological quality, there is a good reason to accept that unmodified ECT is associated with a wide range of adverse consequences, important among which are musculoskeletal complications, pre-ECT anxiety, and post-ECT confusion. However, it appears from recent data that these risks are not as large as historically portrayed. Possibly explanations are suggested, with seizure modification using parenteral benzodiazepines as a special possibility. Conclusions: Under exceptional circumstances, if ECT is strongly indicated and seizure modification with succinylcholine is not feasible, unmodified ECT, especially benzodiazepine-modified ECT, may be a viable option. A detailed set of recommendations for such use of unmodified ECT is proposed along with necessary checks and balances. This document has been approved by the Indian Psychatric Society, the Indian Association of Biological Psychiatry, and the Indian Association of Private Psychiatry (which commissioned the preparation of the document). PMID:22988318

Electroconvulsive therapy in adolescents: a retrospective study from north India.

PubMed

Grover, Sandeep; Malhotra, Savita; Varma, Sannidhya; Chakrabarti, Subho; Avasthi, Ajit; Mattoo, Surendra K

2013-06-01

There are minimal data on the use of electroconvulsive therapy (ECT) in adolescents from India. The present study aimed to evaluate the clinical profile and effectiveness of ECT in adolescents (aged 13-18 years). A retrospective chart review was carried out to identify adolescents (aged 13-18 years) who had received ECT during the period 1999-2011. During the study period, 39 such patients received ECT; complete records of 25 patients were available. Details regarding their sociodemographic, clinical, and treatment data were extracted from these records for the present study. During the study period, 658 patients received ECT, of which 39 were aged 18 or younger (5.9%). Schizophrenia (n = 14; 56%) was the commonest diagnosis for which ECT was used in adolescents, followed by depression (n = 3; 12%). Catatonic symptoms (n = 17; 68%) were the most common symptoms among these subjects. Electroconvulsive therapy was considered as a treatment of choice taking the clinical picture account in about three fourths of the patients (n = 19; 76%). The mean (SD) numbers of ECTs administered per patient were 10.1 (4.87) (range, 2-21). The mean (SD) response rate to ECT was 76% (23.3%) (range, 31%-100%). Response rates according to diagnosis were the following: 76.3% for schizophrenia, 87.2% for depression, 81.8% for psychosis (not otherwise specified), and 77.7% for acute and transient psychosis. Response rate in patients with catatonia was 91.6%. Prolonged seizures, nausea and vomiting, and headache were reported in 2 cases each. Electroconvulsive therapy is used less frequently in children and adolescents compared to the older patients. This study shows that ECT is effective in the treatment of severe psychiatric disorders in adolescents and is associated with the same frequency of adverse effects as the adults.

The Anaesthetic-ECT Time Interval in Electroconvulsive Therapy Practice--Is It Time to Time?

PubMed

Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Wark, Harry; Harper, Simon; Leyden, John; Loo, Colleen K

2016-01-01

Because most common intravenous anaesthetics used in ECT have anticonvulsant properties, their plasma-brain concentration at the time of seizure induction might affect seizure expression. The quality of ECT seizure expression has been repeatedly associated with efficacy outcomes. The time interval between the anaesthetic bolus injection and the ECT stimulus (anaesthetic-ECT time interval) will determine the anaesthetic plasma-brain concentration when the ECT stimulus is administered. The aim of this study was to examine the effect of the anaesthetic-ECT time interval on ECT seizure quality and duration. The anaesthetic-ECT time interval was recorded in 771 ECT sessions (84 patients). Right unilateral brief pulse ECT was applied. Anaesthesia given was propofol (1-2 mg/kg) and succinylcholine (0.5-1.0 mg/kg). Seizure quality indices (slow wave onset, amplitude, regularity, stereotypy and post-ictal suppression) and duration were rated through a structured rating scale by a single blinded trained rater. Linear Mixed Effects Models analysed the effect of the anaesthetic-ECT time interval on seizure quality indices, controlling for propofol dose (mg), ECT charge (mC), ECT session number, days between ECT, age (years), initial seizure threshold (mC) and concurrent medication. Longer anaesthetic-ECT time intervals lead to significantly higher quality seizures (p < 0.001 for amplitude, regularity, stereotypy and post-ictal suppression). These results suggest that the anaesthetic-ECT time interval is an important factor to consider in ECT practice. This time interval should be extended to as long as practically possible to facilitate the production of better quality seizures. Close collaboration between the anaesthetist and the psychiatrist is essential. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of age and anticonvulsants on seizure threshold during bilateral electroconvulsive therapy with brief-pulse stimulus: A chart-based analysis

PubMed Central

Nitturkar, Abhishek R.; Sinha, Preeti; Bagewadi, Virupakshappa I.; Thirthalli, Jagadisha

2016-01-01

Background: Efficacy and adverse effects of electroconvulsive therapy (ECT) depend on the extent to which the electrical stimulus exceeds patients' seizure thresholds (STs). Titration method of estimating ST is recommended. Age and co-prescribed anticonvulsants (ACs) are known to affect ST. Literature on ST in bilateral ECT (BLECT) is sparse. Objective: To explore the clinical and demographic determinants of ST in a clinically representative sample of patients prescribed with BLECT. Materials and Methods: ECT records of 640 patients who received BLECT in 2011 in an academic psychiatric setting were studied. Demographic, clinical, pharmacological, and ECT details were analyzed. As per the standard practice, during the 1st ECT session, ST was determined by titration method, starting with 30 milli-Coulombs (mC) and increasing by 30 mC and thence in steps of 60 mC. Increase in ST over up to 6th session of ECT was noted. Receiver operating characteristic curve was used to find age cut-off with high specificity for ST ≥120 mC. The associations of ST and increase in ST with the age cut-off and other clinical factors were assessed using Chi-square test and logistic regression analysis. Results: The mean age was 30.98 years (+11.23 years) and mean ST at 1st ECT session was 130.36 mC (+51.96 mC). There was significantly high positive correlation (r = 0.37, P < 0.001) between age and ST. Cut-off age of 45 years had high specificity: Only 4.6% of those older than 45 years had ST <120 mC. Higher proportion of patients on AC had ST ≥120 mC. These associations were seen even after controlling for potential confounds of each other using logistic regression analysis. The results were similar for increase in ST over the course of ECT. Sex, diagnosis, use of antipsychotics, antidepressants, lithium, and benzodiazepines (BZPs) had no effect on ST or its increase. Conclusions: For BLECT using brief-pulse stimulus, ST depends on age and use of AC. For patients above the age of 45 years, ST estimation may be started at 120 mC with least risk of using unduly higher stimulus. Other medications including BZPs have little influence on ST. PMID:27385853

Effect of age and anticonvulsants on seizure threshold during bilateral electroconvulsive therapy with brief-pulse stimulus: A chart-based analysis.

PubMed

Nitturkar, Abhishek R; Sinha, Preeti; Bagewadi, Virupakshappa I; Thirthalli, Jagadisha

2016-01-01

Efficacy and adverse effects of electroconvulsive therapy (ECT) depend on the extent to which the electrical stimulus exceeds patients' seizure thresholds (STs). Titration method of estimating ST is recommended. Age and co-prescribed anticonvulsants (ACs) are known to affect ST. Literature on ST in bilateral ECT (BLECT) is sparse. To explore the clinical and demographic determinants of ST in a clinically representative sample of patients prescribed with BLECT. ECT records of 640 patients who received BLECT in 2011 in an academic psychiatric setting were studied. Demographic, clinical, pharmacological, and ECT details were analyzed. As per the standard practice, during the 1(st) ECT session, ST was determined by titration method, starting with 30 milli-Coulombs (mC) and increasing by 30 mC and thence in steps of 60 mC. Increase in ST over up to 6(th) session of ECT was noted. Receiver operating characteristic curve was used to find age cut-off with high specificity for ST ≥120 mC. The associations of ST and increase in ST with the age cut-off and other clinical factors were assessed using Chi-square test and logistic regression analysis. The mean age was 30.98 years (+11.23 years) and mean ST at 1(st) ECT session was 130.36 mC (+51.96 mC). There was significantly high positive correlation (r = 0.37, P < 0.001) between age and ST. Cut-off age of 45 years had high specificity: Only 4.6% of those older than 45 years had ST <120 mC. Higher proportion of patients on AC had ST ≥120 mC. These associations were seen even after controlling for potential confounds of each other using logistic regression analysis. The results were similar for increase in ST over the course of ECT. Sex, diagnosis, use of antipsychotics, antidepressants, lithium, and benzodiazepines (BZPs) had no effect on ST or its increase. For BLECT using brief-pulse stimulus, ST depends on age and use of AC. For patients above the age of 45 years, ST estimation may be started at 120 mC with least risk of using unduly higher stimulus. Other medications including BZPs have little influence on ST.

Opiate-like electroencephalographic and behavioral effects of electroconvulsive shock in rats.

PubMed

Tortella, F C; Cowan, A; Belenky, G L; Holaday, J W

1981-12-03

Rats were studied (a) after a single transauricular electroshock (acute ECS) and (b) following 10 consecutive once-daily shocks (chronic ECS). ECS produced a generalized convulsion marked by a polyspike EEG seizure. The seizure was followed by a period of postictal depression (PID) characterized by EEG high-voltage synchrony, EMG quietening, and an associated stuporous behavior in the rat. Acute ECS produced a maximal of 33 +/- 8 (S.E.) percent above control in the EEG voltage output during postictus, with the PID lasting 2680 +/- 658 sec. Chronic ECS resulted in a significant enhancement of these acute responses. Pretreating rats with naloxone (0.3-10 mg/kg s.c.) antagonized the postictal effects of acute ECS, but not of chronic ECS. These naloxone-sensitive postictal EEG and behavioral changes appear to reflect a release of endogenous opioid peptides during ictus, a finding consistent with the hypothesis that electroshock activates opioid systems.

The use of ECT and MST in treating depression.

PubMed

Allan, Charlotte L; Ebmeier, Klaus P

2011-10-01

Electroconvulsive therapy (ECT) has been used clinically since 1938. Its most common use is in the treatment of depression: first line treatment where rapid recovery is a priority, but more frequently as an effective treatment for patients who do not respond to pharmacological and psychological approaches. Whilst it is widely hailed as an effective treatment, concerns about its effect on cognition remain. The development of magnetic seizure therapy (MST) over the past decade has attempted to devise a therapy with comparable efficacy to ECT, but without the associated cognitive side effects. The rationale for this is that MST uses magnetic fields to induce seizures in the cortex, without electrical stimulation of brain structures involved with memory. MST has been used successfully in the treatment of depression, yet there is a dearth of literature in comparison with ECT. We present a systematic review of the literature on ECT (from 2009-2011) and MST (from 2001-2011).

A comparison of RUL ultrabrief pulse (0.3 ms) ECT and standard RUL ECT.

PubMed

Loo, Colleen K; Sainsbury, Kirby; Sheehan, Patrick; Lyndon, Bill

2008-11-01

An important goal in electroconvulsive therapy (ECT) research is to minimize associated cognitive side-effects while maintaining its high efficacy. This study explored the use of a novel approach, right unilateral (RUL) ECT with an ultrabrief pulsewidth (0.3 ms) (RUL-UB), in comparison with standard RUL ECT. Seventy-four depressed in-patients received RUL-UB ECT at six times seizure threshold, and 22 patients received standard RUL ECT (1.0 ms pulsewidth) at five times seizure threshold. Formal, prospective evaluations of mood and cognitive functioning over the treatment course were done by a rater blinded to treatment condition. Efficacy was maintained using the ultrabrief pulsewidth, with equivalent numbers of responders and remitters to the standard RUL ECT group, although the speed of response was slower. Cognitive outcomes were superior in the RUL-UB ECT group, particularly in the retention of verbal and visual information, as well as in retrograde autobiographical memory.

Effects of electroconvulsive therapy and magnetic seizure therapy on acute memory retrieval.

PubMed

Polster, Julia D; Kayser, Sarah; Bewernick, Bettina H; Hurlemann, René; Schlaepfer, Thomas E

2015-03-01

Electroconvulsive therapy (ECT) is currently the most effective treatment for severe depression. However, it is frequently associated with negative cognitive side effects. Magnetic seizure therapy (MST) depicts an alternative, although experimental, convulsive treatment for major depression. Initial results suggest comparable antidepressant effects accompanied by a better side effect profile. However, no studies up to now have addressed acute retrieval disruption after MST in comparison to ECT. Therefore, we intended to broaden insight into the side effect profile of MST compared to ECT by examining the disruption of acute verbal memory processes after treatment. Twenty depressed patients were randomly assigned to either MST (10 patients) or ECT (10 patients) treatment. On 2 treatment days and 2 treatment-free days, the patients memorized words using a controlled learning paradigm derived from the Batchelder and Riefer storage retrieval model. Four hours after memorization, the patients were asked to retrieve words freely (delayed recall) and a second time with the help of an additional cue constructed out of a hypernymic category (cued recall). By comparing memory performance on treatment days to control days, treatment-induced memory disruption was evaluated. After ECT, delayed recall was disturbed, whereas after MST, it was not. However, this difference in performance was no longer apparent upon cue application (cued recall). This study demonstrates that ECT-induced acute memory disruption measured by delayed recall is absent after MST, confirming its superior side effect profile. We hope that confirming advantages of MST over ECT will improve therapy options for patients with severe depression.

Low-dose right unilateral electroconvulsive therapy (ECT): effectiveness of the first treatment.

PubMed

Lapidus, Kyle A B; Shin, Joseph S W; Pasculli, Rosa M; Briggs, Mimi C; Popeo, Dennis M; Kellner, Charles H

2013-06-01

Electroconvulsive therapy (ECT) is a widely used, highly effective antidepressant treatment. Except for the most severely ill patients, right unilateral (RUL) electrode placement is the most frequent initial treatment choice. In current practice, RUL ECT is administered at several multiples of seizure threshold (ST) based on reports that lower stimulus intensity results in lower response/remission rates. Many patients, as part of an initial dose titration to determine ST, will receive a single treatment with low-dose RUL ECT and subsequent treatments with a stimulus at a multiple of ST. To assess response to the first ECT. A retrospective analysis of charts from clinical practice at Mount Sinai Medical Center was performed. A single treatment with low-dose (presumably near ST) RUL ECT had a significant and immediate antidepressant effect in our sample of patients with major depression. We determined that this response is similar to that of patients receiving a single initial treatment with high-dose RUL ECT (at a multiple of ST). These data suggest, contrary to commonly held belief, that RUL ECT may be effective at a low stimulus dose. This argues against restimulating at 6 times ST in the initial session, based on the belief that the near-threshold seizure has no antidepressant efficacy. Our findings suggest a need for further investigation of cases in which low-dose RUL ECT may be an effective antidepressant treatment. Further prospective studies, including larger numbers of patients who receive randomized treatment with low- or high-dose RUL with longer follow-up, are indicated.

Nitroprusside and ECS-induced retrograde amnesia.

PubMed

Sudha, S; Andrade, C; Anand, A; Guido, S; Venkataraman, B V

2001-03-01

Previous research found that the administration of verapamil and felodipine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. This study examined whether sodium nitroprusside, an antihypertensive drug that does not affect calcium channels, has a similar action. Adult male Sprague-Dawley rats received nitroprusside (0.5 mg/kg ip) or saline 3 minutes before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after ECS using a passive avoidance task. Nitroprusside was associated with increased seizure duration in ECS-treated rats, and with enhanced recall in both true and sham ECS groups. The latter finding suggests that nitroprusside nonspecifically improves cognitive functions, and does not support the hypothesis that ECS-induced cognitive impairment is a result of blood-brain barrier breach. Nitric oxide mechanisms may underlie the benefits purveyed by nitroprusside.

Effect of propofol versus sodium thiopental on electroconvulsive therapy in major depressive disorder: a randomized double-blind controlled clinical trial.

PubMed

Purtuloğlu, Tark; Özdemir, Barbaros; Erdem, Murat; Deniz, Süleyman; Balkç, Adem; Ünlü, Gazi; Öznur, Taner

2013-03-01

To compare propofol and sodium thiopental as anesthetic agents for electroconvulsive therapy (ECT) in major depression with respect to clinical effect. Participants were composed of 96 patients with depression who were administered either propofol or sodium thiopental as an anesthetic agent for bilateral ECT. The Hamilton Depression Rating Scale was administered at baseline and after 6 treatments. Algorithm-based charge dosing was used. There was a statistically significant difference between the groups regarding postintervention Hamilton Depression Rating Scale score. The preintervention mean (SD) scores in the propofol group and the sodium thiopental group were 37.3 (2.2) and 36.7 (1.2), respectively. The postintervention mean (SD) scores in the propofol group and the sodium thiopental group were 10.7 (1.8) and 13.4 (3.3), respectively. No correlation was found between clinical response and age, weight, and body mass index. There was no association between the groups' seizure time and duration of recovery. In conclusion, propofol may improve major depressive disorder more than sodium thiopental in patients who are receiving ECT.

Multifactorial Determinants of the Neurocognitive Effects of Electroconvulsive Therapy

PubMed Central

McClintock, Shawn M.; Choi, Jimmy; Deng, Zhi-De; Appelbaum, Lawrence G.; Krystal, Andrew D.; Lisanby, Sarah H.

2014-01-01

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper is to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the utility of this important and widely used intervention tool for neuropsychiatric diseases. PMID:24820942

Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.

PubMed

McClintock, Shawn M; Choi, Jimmy; Deng, Zhi-De; Appelbaum, Lawrence G; Krystal, Andrew D; Lisanby, Sarah H

2014-06-01

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.

Electric field characteristics of electroconvulsive therapy with individualized current amplitude: a preclinical study.

PubMed

Lee, Won Hee; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2013-01-01

This study examines the characteristics of the electric field induced in the brain by electroconvulsive therapy (ECT) with individualized current amplitude. The electric field induced by bilateral (BL), bifrontal (BF), right unilateral (RUL), and frontomedial (FM) ECT electrode configurations was computed in anatomically realistic finite element models of four nonhuman primates (NHPs). We generated maps of the electric field strength relative to an empirical neural activation threshold, and determined the stimulation strength and focality at fixed current amplitude and at individualized current amplitudes corresponding to seizure threshold (ST) measured in the anesthetized NHPs. The results show less variation in brain volume stimulated above threshold with individualized current amplitudes (16-36%) compared to fixed current amplitude (30-62%). Further, the stimulated brain volume at amplitude-titrated ST is substantially lower than that for ECT with conventional fixed current amplitudes. Thus individualizing the ECT stimulus current could compensate for individual anatomical variability and result in more focal and uniform electric field exposure across different subjects compared to the standard clinical practice of using high, fixed current for all patients.

Orchestrated Regulation of Nogo Receptors, Lotus, AMPA Receptors and BDNF in an ECT Model Suggests Opening and Closure of a Window of Synaptic Plasticity

PubMed Central

Nordgren, Max; Karlsson, Tobias; Svensson, Maria; Koczy, Josefin; Josephson, Anna; Olson, Lars; Tingström, Anders; Brené, Stefan

2013-01-01

Electroconvulsive therapy (ECT) is an efficient and relatively fast acting treatment for depression. However, one severe side effect of the treatment is retrograde amnesia, which in certain cases can be long-term. The mechanisms behind the antidepressant effect and the amnesia are not well understood. We hypothesized that ECT causes transient downregulation of key molecules needed to stabilize synaptic structure and to prevent Ca2+ influx, and a simultaneous increase in neurotrophic factors, thus providing a short time window of increased structural synaptic plasticity. Here we followed regulation of NgR1, NgR3, LOTUS, BDNF, and AMPA subunits GluR1 and GluR2 flip and flop mRNA levels in hippocampus at 2, 4, 12, 24, and 72 hours after a single episode of induced electroconvulsive seizures (ECS) in rats. NgR1 and LOTUS mRNA levels were transiently downregulated in the dentate gyrus 2, 4, 12 and 4, 12, 24 h after ECS treatment, respectively. GluR2 flip, flop and GluR1 flop were downregulated at 4 h. GluR2 flip remained downregulated at 12 h. In contrast, BDNF, NgR3 and GluR1 flip mRNA levels were upregulated. Thus, ECS treatment induces a transient regulation of factors important for neuronal plasticity. Our data provide correlations between ECS treatment and molecular events compatible with the hypothesis that both effects and side effects of ECT may be caused by structural synaptic rearrangements. PMID:24244357

Orchestrated regulation of Nogo receptors, LOTUS, AMPA receptors and BDNF in an ECT model suggests opening and closure of a window of synaptic plasticity.

PubMed

Nordgren, Max; Karlsson, Tobias; Svensson, Maria; Koczy, Josefin; Josephson, Anna; Olson, Lars; Tingström, Anders; Brené, Stefan

2013-01-01

Electroconvulsive therapy (ECT) is an efficient and relatively fast acting treatment for depression. However, one severe side effect of the treatment is retrograde amnesia, which in certain cases can be long-term. The mechanisms behind the antidepressant effect and the amnesia are not well understood. We hypothesized that ECT causes transient downregulation of key molecules needed to stabilize synaptic structure and to prevent Ca2+ influx, and a simultaneous increase in neurotrophic factors, thus providing a short time window of increased structural synaptic plasticity. Here we followed regulation of NgR1, NgR3, LOTUS, BDNF, and AMPA subunits GluR1 and GluR2 flip and flop mRNA levels in hippocampus at 2, 4, 12, 24, and 72 hours after a single episode of induced electroconvulsive seizures (ECS) in rats. NgR1 and LOTUS mRNA levels were transiently downregulated in the dentate gyrus 2, 4, 12 and 4, 12, 24 h after ECS treatment, respectively. GluR2 flip, flop and GluR1 flop were downregulated at 4 h. GluR2 flip remained downregulated at 12 h. In contrast, BDNF, NgR3 and GluR1 flip mRNA levels were upregulated. Thus, ECS treatment induces a transient regulation of factors important for neuronal plasticity. Our data provide correlations between ECS treatment and molecular events compatible with the hypothesis that both effects and side effects of ECT may be caused by structural synaptic rearrangements.

Electroconvulsive therapy (ECT) in Parkinson's disease: ECS and dopamine enhancement.

PubMed

Cumper, Samantha K; Ahle, Gabriella M; Liebman, Lauren S; Kellner, Charles H

2014-06-01

In addition to its effects in major psychiatric illness, electroconvulsive therapy (ECT) is known to have a beneficial effect on the core motor symptoms of Parkinson's disease (PD). This effect is believed to be mediated via dopamine in the striatum. Electroconvulsive shock (ECS), the animal analogue of ECT, is the model in which investigators have sought to elucidate the specific dopaminergic mechanisms by which ECT exerts its therapeutic effect in PD. Electroconvulsive shock has been given to intact animals as well as to animals with neurotoxic lesions that create parkinsonism. In this paper, we selectively review the electroconvulsive shock literature on dopamine in the striatum. Electroconvulsive shock, and by extension, ECT, is associated with increased dopamine release and modulation of dopamine receptors. Better understanding of how ECT works to enhance dopaminergic systems in the brain could help to make it a more accepted treatment for PD.

Additive interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and clobazam in the mouse maximal electroshock-induced tonic seizure model--an isobolographic analysis for parallel dose-response relationship curves.

PubMed

Andres-Mach, Marta; Haratym-Maj, Agnieszka; Zagaja, Mirosław; Luszczki, Jarogniew J

2014-01-01

The aim of this study was to characterize the anticonvulsant effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ) in combination with clobazam (CLB) in the mouse maximal electroshock-induced seizure (MES) model. The anticonvulsant interaction profile between 1-MeTHIQ and CLB in the mouse MES model was determined using an isobolographic analysis for parallel dose-response relationship curves. Electroconvulsions were produced in albino Swiss mice by a current (sine wave, 25 mA, 500 V, 50 Hz, 0.2-second stimulus duration) delivered via auricular electrodes by a Hugo Sachs generator. There was an additive effect of the combination of 1-MeTHIQ with CLB (at the fixed ratios of 1:3, 1:1 and 3:1) in the mouse MES-induced tonic seizure model. The additive interaction of the combination of 1-MeTHIQ with CLB (at fixed-ratios of 1:3, 1:1 and 3:1) in the mouse MES model seems to be pharmacodynamic in nature and worth of considering in further clinical practice. © 2014 S. Karger AG, Basel.

Nonconvulsive Status Epilepticus After Electroconvulsive Therapy: A Review of Literature.

PubMed

Aftab, Awais; VanDercar, Ashley; Alkhachroum, Ayham; LaGrotta, Christine; Gao, Keming

The clinical presentation and risk factors of nonconvulsive status epilepticus (NCSE) in the context of electroconvulsive therapy (ECT) are poorly understood, and guidance regarding diagnosis and management remains scarce. In this article, we identify case reports of ECT-induced NCSE from literature, and discuss the presentation, diagnosis, and management of these cases in the context of what is known about NCSE from the neurology literature. A literature search on PubMed for case reports of NCSE after ECT. We identified 13 cases for this review. Diagnosis in all cases was based on clinical features and electroencephalogram (EEG) findings. Clinical presentation was altered mental status or unresponsiveness, with subtle motor phenomena in some cases. All cases had nonspecific risk factors that have been associated with prolonged seizures and convulsions, such as recent discontinuation/reduction of benzodiazepines or anticonvulsants, and concurrent use of antipsychotics and antidepressants. All patients were treated with either benzodiazepines or antiepileptic agents. Outcomes in these post-ECT NCSE cases were generally favorable. Although rare, post-ECT NCSE should be kept in mind by physicians when confusion or unresponsiveness develops and continues after ECT; multilead EEG is gold standard for diagnosis. An intravenous (IV) antiepileptic drug (AED) challenge can help clarify the diagnosis. Initial treatment is recommended with IV benzodiazepines, with a repeat dose if necessary. If seizures persist, IV AEDs are warranted. NCSE refractory to this treatment should be treated with a scheduled IV or oral AED. Serial multilead EEGs should be used to monitor resolution of symptoms. NCSE after ECT is a rare but recognizable clinical event. A high clinical suspicion and low threshold for EEG is necessary for prompt diagnosis. Copyright © 2018 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

BDNF restores the expression of Jun and Fos inducible transcription factors in the rat brain following repetitive electroconvulsive seizures.

PubMed

Hsieh, T F; Simler, S; Vergnes, M; Gass, P; Marescaux, C; Wiegand, S J; Zimmermann, M; Herdegen, T

1998-01-01

The expression of inducible transcription factors was studied following repetitive electroconvulsive seizures (ECS), c-Fos, c-Jun, JunB, and JunD immunoreactivities were investigated following a single (1 x ECS) or repetitive ECS evoked once per day for 4, 5, or 10 days (4 x ECS, 5 x ECS, or 10 x ECS). Animals were killed 3 or 12 h following the last ECS. Three hours after 1 x ECS, c-Fos was expressed throughout the cortex and hippocampus. After 5 x ECS and 10 x ECS, c-Fos was reexpressed in the CA4 area, but was completely absent in the other hippocampal areas and cortex. In these areas, c-Fos became only reinducible when the time lag between two ECS stimuli was 5 days. In contrast to c-Fos, intense JunB expression was inducible in the cortex and hippocampus, but not CA4 subfield, after 1 x ECS, 5 x ECS, and 10 x ECS. Repetitive ECS did not effect c-Jun and JunD expression. In a second model of systemic excitation of the brain, repetitive daily injection of kainic acid for 4 days completely failed to express c-Fos, c-Jun, and JunB after the last application whereas injection of kainic acid once per week did not alter the strong expressions compared to a single application of kainic acid. In order to study the maintenance of c-Fos expression during repetitive seizures, brain-derived neurotrophic factor (BDNF) was applied in parallel for 5 or 10 days via miniosmotic pumps and permanent cannula targeted at the hippocampus or the parietal cortex. Infusion of BDNF completely reinduced c-Fos expression during 5 x ECS or 10 x ECS in the cortex ipsilaterally to the cannula and, to a less extent, also increased the expression of c-Jun and JunB when compared to saline-treated controls. BDNF had no effect on the expression patterns in the hippocampus. ECS with or without BDNF infusion did not change the expression patterns of the constitutive transcription factors ATF-2, CREB, and SRF. These data demonstrate that various transcription factors substantially differ in their response to acute and chronic neural stimulation. Repetitive pathophysiological excitation decreases the transcriptional actions of neurons over days in the adult brain, and this decrement can be prevented by BDNF restoring the neuroplasticity at the level of gene transcription.

Comparison of the effect of intravenous anesthetics used for anesthesia during electroconvulsive therapy on the hemodynamic safety and the course of ECT.

PubMed

Wojdacz, Rafał; Święcicki, Łukasz; Antosik-Wójcińska, Anna

2017-12-30

Electroconvulsive therapy (ECT) is the treatment method widely used in psychiatric disorders such as depression, bipolar disorder, schizophrenia and schizoaffective disorder. The advantage of ECT is therapeutic response that occurs significantly earlier than during pharmacotherapy. Initially ECTwas used without anesthesia. Then, in the 1950s procedures with general anesthesia were introduced to reduce the complications that may occur during a seizure caused by ECT, such as broken bones, teeth, tendon rupture, muscle damage. Currently, in general anesthesia for ECTseveral medications are used interchangeably: thiopental, propofol, etomidate and ketamine. In different resorts and different countries different anestethics are used, the choice is determined mainly by the experience of each resort and a kind of tradition. The authors provide an overview of objective data showing how various anesthetics affect the quality of ECT and the presence of any hemodynamic complications after ETC. Selection of articles included in this paper was made by searching Medline and PubMed databases using specific keywords: electroconvulsive therapy, general anesthesia, the risks and benefits of thiopental, ketamine, propofol and etomidate. The results of this review are inconclusive when it comes to the effect of intravenous anesthetics on the quality of the ECT treatment and side effects relating to respiratory and cardiovascular system. On this basis it is impossible to determine which of intravenous anesthetics is most advantageous from the point of view of the patient. To develop the optimum scheme of anesthesia for ECT, it is necessary to conduct further, methodologically correct studies.

Predictors of readmission after successful electroconvulsive therapy for depression: a chart review study.

PubMed

Uchida, Takahito; Kishimoto, Taishiro; Koreki, Akihiro; Nakao, Shigetsugu; Owada, Ai; Koizumi, Teruki; Saito, Atsuyuki; Sato, Minako; Sawada, Shinya; Matsuzaki, Ryuta; Petrides, Georgios; Mimura, Masaru

2016-11-01

The study aimed to identify the predictors for readmission after a successful electroconvulsive therapy (ECT) course. Medical charts of patients who received ECT for major depressive episodes were reviewed. Patients' demographic characteristics and treatment parameters, such as ECT charge, seizure duration, the number of ECT sessions and pharmacotherapy, were extracted. We compared differences between those who were readmitted after successful ECT within 6 and 12 months, versus those not readmitted. We also conducted a multivariate logistic regression analysis to identify the predictors for readmission. Out of 51 patients who were discharged after ECT, 27 patients met the inclusion criteria and were included in the analysis. Eight patients were readmitted within 6 months after discharge, and four more patients were readmitted during the next 6-month follow up. Comparing patients who were and were not readmitted, we found no significant differences between groups, including ECT parameters such as the number of ECT sessions, average charge and final charge. No predictors for readmission were found through multivariate analysis. Although patients who require higher ECT charge and more sessions seem to be prone to readmission, our dataset suggested that none of these types of ECT parameters were risk factors for readmission.

Magnetic Seizure Therapy for Unipolar and Bipolar Depression: A Systematic Review

PubMed Central

Cretaz, Eric; Brunoni, André R.

2015-01-01

Objective. Magnetic seizure therapy (MST) is a novel, experimental therapeutic intervention, which combines therapeutic aspects of electroconvulsive therapy (ECT) and transcranial magnetic stimulation, in order to achieve the efficacy of the former with the safety of the latter. MST might prove to be a valuable tool in the treatment of mood disorders, such as major depressive disorder (MDD) and bipolar disorder. Our aim is to review current literature on MST. Methods. OVID and MEDLINE databases were used to systematically search for clinical studies on MST. The terms “magnetic seizure therapy,” “depression,” and “bipolar” were employed. Results. Out of 74 studies, 8 met eligibility criteria. There was considerable variability in the methods employed and samples sizes were small, limiting the generalization of the results. All studies focused on depressive episodes, but few included patients with bipolar disorder. The studies found reported significant antidepressant effects, with remission rates ranging from 30% to 40%. No significant cognitive side effects related to MST were found, with a better cognitive profile when compared to ECT. Conclusion. MST was effective in reducing depressive symptoms in mood disorders, with generally less side effects than ECT. No study focused on comparing MST to ECT on bipolar depression specifically. PMID:26075100

Inflammation and Improvement of Depression Following Electroconvulsive Therapy in Treatment-Resistant Depression.

PubMed

Kruse, Jennifer L; Congdon, Eliza; Olmstead, Richard; Njau, Stephanie; Breen, Elizabeth C; Narr, Katherine L; Espinoza, Randall; Irwin, Michael R

Electroconvulsive therapy (ECT) is the most robust acute treatment for severe major depressive disorder, yet clinical response is variable. Inflammation is associated with depression, especially in women, and levels of C-reactive protein (CRP) and interleukin (IL)-6 predict response to antidepressant medications. This study evaluated whether markers of inflammation predicted response to electroconvulsive therapy (ECT) in patients with treatment-resistant depression and to what extent this association differed between men and women. In patients (N = 29) who had a current major depressive episode diagnosed using DSM-IV-TR criteria and were scheduled to undergo ECT at an academic referral center, levels of CRP, IL-6, IL-8, and tumor necrosis factor-α and severity of depressive symptoms (Montgomery-Asberg Depression Rating Scale [MADRS]) were prospectively evaluated before ECT treatment, after the second ECT session, and again at the completion of the index treatment series. Data were collected between December 2011 and December 2014. The primary outcome was end-of-treatment MADRS score. In multivariate analyses, higher levels of IL-6 at baseline, but not other inflammatory markers or clinical variables, were associated with lower end-of-treatment MADRS score (P = .01). When stratified by sex, IL-6 remained a significant predictor of end-of-treatment MADRS for women (P = .02) but not men (P = .1), and CRP emerged as a significant predictor for women (P = .04) but not men (P = .66). CRP and IL-6 increased from baseline to the second ECT session (P values < .01) and returned to baseline levels at end of treatment; these changes did not relate to MADRS score over the course of ECT. Levels of IL-6 prior to ECT treatment may be useful in identifying those depressed patients most likely to benefit from ECT treatment. In contrast, acute changes in IL-6 and CRP may reflect spikes in inflammatory response related to the initiation of seizure therapy, but not mood. Assessment of pretreatment inflammatory biomarkers, especially in women, might be useful in guiding treatment decision-making in treatment-resistant depression. © Copyright 2018 Physicians Postgraduate Press, Inc.

[Clinical analysis of safety and effectiveness of electroconvulsive therapy].

PubMed

Dabrowski, Marek; Parnowski, Tadeusz

2012-01-01

The aim of the study was to assess efficacy and safety of electroconvulsive therapy. 43 patients included into the study were hospitalised in The Institute of Psychiatry and Neurology and received all together over 400 bilateral electroconvulsive procedures. Most of the patients (N = 25) were qualified for electroconvulsive therapy due to treatment resistant depression (58.1%). Six patients: 2 with catatonia and 4 with depression had life saving indications for electroconvulsive therapy. Three patients (7%) were excluded from electroconvulsive therapy, following 1 or 2 electroconvulsive procedures. Forty patients continued electroconvulsive therapy. There were no complications and serious adverse events in patients who continued electroconvulsive therapy. Generally, electroconvulsive therapy was well tolerated and treatment had been cut down in only one case due to adverse events and high risk related to the procedure. Transient cardiac arrhythmias (10% of patients) were the most often occurring adverse events and patients (35%) mostly reported headaches. We observed remission in 22 patients (58%) and improvement in 14 patients (35%) following electroconvulsive treatment. Only 4 patients (10%) had no benefit after a series of electroconvulsive procedures. Electroconvulsive treatment was most effective in patients with catatonia (80% patients had full recovery) and in depressive patients with bipolar disorder (73% patients had full recovery). Electroconvulsive procedures were safe and effective. Electroconvulsive treatment was most effective in catatonic patients with schizophrenia and in depressive patients with bipolar disorder.

Images in electroconvulsive therapy: ECS dose-dependently increases cell proliferation in the subgranular region of the rat hippocampus.

PubMed

Smitha, Jangama S M; Roopa, Ravindranath; Sagar, B K Chandrasekhar; Kutty, Bindu M; Andrade, Chittaranjan

2014-09-01

Stress and depression are associated with impaired neuroplasticity in the hippocampus; there is a decrease in neurogenesis, which is hypothesized to decrease the adaptative competence of the organism. Representative light microscopy images are presented which show that 6 once-daily electroconvulsive shocks (ECS), dose-dependently increased new cell formation in the subgranular region of the hippocampus in healthy adult male Wistar rats (10 sections per rat, 3 rats in each of sham ECS, 10 mC, and 40 mC groups). These neuroplasticity changes, demonstrated 1 month after the last ECS, may explain a part of the mechanism of action of electroconvulsive therapy in conditions such as depression.

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 suggest that current directionality, polarity, and electrode configuration influence the efficiency of seizure induction with ECT. Unidirectional stimulation and novel electrode configurations such as FEAST are two approaches to lowering seizure threshold. Furthermore, the impact of FEAST on ictal and post-ictal expression appeared to be polarity-dependent. Future studies may examine whether these differences in seizure threshold and expression have clinical significance for patients receiving ECT. PMID:19225453

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 findings suggest that current directionality, polarity, and electrode configuration influence the efficiency of seizure induction with ECT. Unidirectional stimulation and novel electrode configurations such as FEAST are two approaches to lowering seizure threshold. Furthermore, the impact of FEAST on ictal and post-ictal expression appeared to be polarity dependent. Future studies may examine whether these differences in seizure threshold and expression have clinical significance for patients receiving ECT.

Electroconvulsive therapy in the continuation and maintenance treatment of depression: Systematic review and meta-analyses.

PubMed

Elias, Alby; Phutane, Vivek H; Clarke, Sandy; Prudic, Joan

2018-05-01

Acute course of electroconvulsive therapy is effective in inducing remission from depression, but recurrence rate is unacceptably high following termination of electroconvulsive therapy despite continued pharmacotherapy. Continuation electroconvulsive therapy and maintenance electroconvulsive therapy have been studied for their efficacy in preventing relapse and recurrence of depression. The purpose of this meta-analysis was to examine the efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy in preventing relapse and recurrence of depression in comparison to antidepressant pharmacotherapy alone. We searched MEDLINE, Embase, PsycINFO, clinicaltrials.gov and Cochrane register of controlled trials from the database inception to December 2016 without restriction on language or publication status for randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. Two independent Cochrane reviewers extracted the data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. The risk of bias was assessed using four domains of the Cochrane Collaboration Risk of Bias Tool. Outcomes were pooled using random effect model. The primary outcome was relapse or recurrence of depression. Five studies involving 436 patients were included in the meta-analysis. Analysis of the pooled data showed that continuation electroconvulsive therapy and maintenance electroconvulsive therapy, both with pharmacotherapy, were associated with significantly fewer relapses and recurrences than pharmacotherapy alone at 6 months and 1 year after a successful acute course of electroconvulsive therapy (risk ratio = 0.64, 95% confidence interval = [0.41, 0.98], p = 0.04, risk ratio = 0.46, 95% confidence interval = [0.21, 0.98], p = 0.05, respectively). There was insufficient data to perform a meta-analysis of stand-alone continuation electroconvulsive therapy or maintenance electroconvulsive therapy beyond 1 year. There are only a few randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. The preliminary and limited evidence suggests the modest efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy with concomitant pharmacotherapy in preventing relapse and recurrence of depressive episodes for 1 year after the remission of index episode with the acute course of electroconvulsive therapy.

General Anaesthesia Protocols for Patients Undergoing Electroconvulsive Therapy

PubMed Central

Narayanan, Aravind; Lal, Chandar; Al-Sinawi, Hamed

2017-01-01

Objectives This study aimed to review general anaesthesia protocols for patients undergoing electroconvulsive therapy (ECT) at a tertiary care hospital in Oman, particularly with regards to clinical profile, potential drug interactions and patient outcomes. Methods This retrospective study took place at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman. The electronic medical records of patients undergoing ECT at SQUH between January 2010 and December 2014 were reviewed for demographic characteristics and therapy details. Results A total of 504 modified ECT sessions were performed on 57 patients during the study period. All of the patients underwent a uniform general anaesthetic regimen consisting of propofol and succinylcholine; however, they received different doses between sessions, as determined by the treating anaesthesiologist. Variations in drug doses between sessions in the same patient could not be attributed to any particular factor. Self-limiting tachycardia and hypertension were periprocedural complications noted among all patients. One patient developed aspiration pneumonitis (1.8%). Conclusion All patients undergoing ECT received a general anaesthetic regimen including propofol and succinylcholine. However, the interplay of anaesthetic drugs with ECT efficacy could not be established due to a lack of comprehensive data, particularly with respect to seizure duration. In addition, the impact of concurrent antipsychotic therapy on anaesthetic dose and subsequent complications could not be determined. PMID:28417028

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study.

PubMed

Cunningham, Miles G; Yadollahikhales, Golnaz; Vitaliano, Gordana; van Horne, Craig

2016-11-15

Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression. The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. Five years after initiating DBS, during a routine battery change, an apparent electrical event occurred that triggered the rapid onset of severe depression. Anti-seizure and antidepressant medications were ineffective, and the patient was offered a course of electroconvulsive therapy (ECT), which resulted in complete reversal of her depressive episode. Parkinson's syndrome can be seen after a single closed head injury event. Post-traumatic parkinsonism is responsive to DBS; however, DBS has been associated with an infrequent occurrence of dramatic disruption in mood. ECT is a therapeutic option for patients who develop intractable depressive illness associated with DBS.

NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

PubMed Central

Rothan, Hussin A.; Amini, Elham; Faraj, Fadihl L.; Golpich, Mojtaba; Teoh, Teow Chong; Gholami, Khadijeh; Yusof, Rohana

2017-01-01

N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants. PMID:28358047

Possible neurologic effects of aspartame, a widely used food additive.

PubMed Central

Maher, T J; Wurtman, R J

1987-01-01

The artificial sweetener aspartame (L-aspartyl-L-phenylalanyl-methyl ester), is consumed, primarily in beverages, by a very large number of Americans, causing significant elevations in plasma and, probably, brain phenylalanine levels. Anecdotal reports suggest that some people suffer neurologic or behavioral reactions in association with aspartame consumption. Since phenylalanine can be neurotoxic and can affect the synthesis of inhibitory monoamine neurotransmitters, the phenylalanine in aspartame could conceiveably mediate neurologic effects. If mice are given aspartame in doses that elevate plasma phenylalanine levels more than those of tyrosine (which probably occurs after any aspartame dose in humans), the frequency of seizures following the administration of an epileptogenic drug, pentylenetetrazole, is enhanced. This effect is simulated by equimolar phenylalanine and blocked by concurrent administration of valine, which blocks phenylalanine's entry into the brain. Aspartame also potentiates the induction of seizures by inhaled fluorothyl or by electroconvulsive shock. Perhaps regulations concerning the sale of food additives should be modified to require the reporting of adverse reactions and the continuing conduct of mandated safety research. PMID:3319565

A prospective comparative study of interaction between lithium and modified electroconvulsive therapy.

PubMed

Thirthalli, Jagadisha; Harish, Thippeswamy; Gangadhar, Bangalore N

2011-03-01

To compare patients on lithium and those not on lithium with regard to adverse effects while receiving ECT. Inpatients with schizophrenia, non-organic psychosis, mania and depression, who were prescribed ECTs either on (n=27) or not (n=28) on lithium were studied. Clinicians blind to lithium-status recorded seizure parameters, interaction with succinyl choline, cardiovascular response, recovery from ECT and immediate post-ECT complications. The lithium group showed no significant difference in terms of seizure variables, apnea time, and recovery from anaesthesia when compared to the non-lithium group. Average maximum heart rate, average maximum systolic blood pressure and average maximum rate pressure product were significantly lower in patients who had combined lithium and ECT. In lithium patients the average time to post-ECT recovery was directly correlated with serum lithium level. Though concurrent lithium is by and large safe during ECT, it benefits to maintain serum lithium level at lower end of therapeutic range. However, the findings can be applied to relatively young patients with no risk factors for ECT-complications.

Electroconvulsive treatment--more than electricity?: An Odyssey of facilities.

PubMed

Berg, John E

2009-12-01

To investigate whether the practice of electroconvulsive treatment (ECT) today is done in a comparable way in different hospitals on several continents. During visits to the ECT facilities of 14 hospitals on 3 continents, comparisons were made, and responsible health professionals were interviewed using a semistructured guide. It is emphasized that the present article is not the result of a well-structured research, but of reflections after observing a lack of homogeneity among facilities. A total of more than 18,000 modified ECT sessions were given per year in the 14 hospitals. The opinion of the public and regulatory bodies on ECT strongly influences the possibility of giving ECT to patients. Indications for ECT are wider than the cases of depression in most facilities visited. A psychiatrist gives ECT in all but 1 facility. Anesthesia is given by an anesthesiologist in all but 1 facility. A mouthpiece was not used in 2 (or 3) facilities, although the rationale was the same as in facilities using mouthpieces. No facility gave unmodified ECT. Holding on to the patient during seizures was judged unnecessary in 12 of 14 facilities. In severe mental illness, the practice of using ECT seems to have its merit also in cases with debilitating illnesses other than unipolar and bipolar depression. Giving ECT may be done by qualified or specially certified nurses, but the giving of anesthesia should be the realm of the anesthesiologist. Mouthpieces are judged by some facilities to be a superfluous device. The holding of patients during seizure can be omitted. Some of the facilities visited give ECT to a huge number of patients each year. They differ in the practice of ECT and could be the focus of comparative research. Despite the differences observed, and procedures that could be altered, giving ECT in a modified way effectively relieves suffering in the patients.

The Incidence and Predictors of Headache and Myalgia in Patients After Electroconvulsive Therapy (ECT)

PubMed Central

Haghighi, Mohammad; Sedighinejad, Abbas; Naderi Nabi, Bahram; Emiralavi, Cyrus; Biazar, Gelareh; Mirmozaffari, Kaveh; Zahedan, Cyrus; Jafari, Mehdi

2016-01-01

Background: Electroconvulsive therapy (ECT) is a safe and effective mode of therapy for a wide variety of psychiatric disorders. However, it is associated with some disturbing side effects, such as nausea and vomiting, dental and tongue injury, confusion, dizziness, headache, and myalgia. Objectives: The present study focused on the evaluation of myalgia and headache and their predictors after ECT. Patients and Methods: A prospective analytical descriptive study was conducted from October 2014 to January 2015, in an academic hospital in northern Iran. Before sampling, the study was approved by the ethics committee of Guilan University of Medical Sciences. 621 patients with psychiatric disorders who were referred to Shafa hospital enrolled in the study. They were evaluated based on a verbal rating scale (4 point scales) 6 hours after ECT, regarding headache and myalgia side effects. Results: 6 hours after ECT, 126 patients (21.9%) reported headaches, and 56 patients (9%) reported myalgia. The presence of headache or myalgia 6 hours after ECT was not correlated to the duration of convulsion, treatment sessions, sex, or age. But myalgia at 2 hours after treatment was correlated with sex (0.04). Sex, age, duration of seizure, and treatment sessions were not predictors of headache and myalgia 6 hours after ECT (log regression, enter mode). The intensity and frequency of headaches decreased during 6 hours after ECT (P = 0.0001 and P = 0.0001, respectively), and myalgia frequency decreased (P = 0.062) but the intensity increased (P = 0.87). Conclusions: The results of the present study demonstrate that headache after ECT procedures was more common than myalgia, but it was mild, tolerable, and decreased within 6 hours of the treatment. It is also notable that we did not found any predictors for post-ECT headache and myalgia. PMID:27761416

The Incidence and Predictors of Headache and Myalgia in Patients After Electroconvulsive Therapy (ECT).

PubMed

Haghighi, Mohammad; Sedighinejad, Abbas; Naderi Nabi, Bahram; Emiralavi, Cyrus; Biazar, Gelareh; Mirmozaffari, Kaveh; Zahedan, Cyrus; Jafari, Mehdi

2016-06-01

Electroconvulsive therapy (ECT) is a safe and effective mode of therapy for a wide variety of psychiatric disorders. However, it is associated with some disturbing side effects, such as nausea and vomiting, dental and tongue injury, confusion, dizziness, headache, and myalgia. The present study focused on the evaluation of myalgia and headache and their predictors after ECT. A prospective analytical descriptive study was conducted from October 2014 to January 2015, in an academic hospital in northern Iran. Before sampling, the study was approved by the ethics committee of Guilan University of Medical Sciences. 621 patients with psychiatric disorders who were referred to Shafa hospital enrolled in the study. They were evaluated based on a verbal rating scale (4 point scales) 6 hours after ECT, regarding headache and myalgia side effects. 6 hours after ECT, 126 patients (21.9%) reported headaches, and 56 patients (9%) reported myalgia. The presence of headache or myalgia 6 hours after ECT was not correlated to the duration of convulsion, treatment sessions, sex, or age. But myalgia at 2 hours after treatment was correlated with sex (0.04). Sex, age, duration of seizure, and treatment sessions were not predictors of headache and myalgia 6 hours after ECT (log regression, enter mode). The intensity and frequency of headaches decreased during 6 hours after ECT (P = 0.0001 and P = 0.0001, respectively), and myalgia frequency decreased (P = 0.062) but the intensity increased (P = 0.87). The results of the present study demonstrate that headache after ECT procedures was more common than myalgia, but it was mild, tolerable, and decreased within 6 hours of the treatment. It is also notable that we did not found any predictors for post-ECT headache and myalgia.

Expanded Safety and Efficacy Data for a New Method of Performing Electroconvulsive Therapy

PubMed Central

Sahlem, Gregory L.; Short, E. Baron; Kerns, Suzanne; Snipes, Jon; DeVries, William; Fox, James B.; Burns, Carol; Schmidt, Matthew; Nahas, Ziad H.; George, Mark S.; Sackeim, Harold A.

2016-01-01

Objective Electroconvulsive therapy (ECT) is the most rapid and effective antidepressant treatment but with concerns about cognitive adverse effects. A new form of ECT, focal electrically administered seizure therapy (FEAST), was designed to increase the focality of stimulation and better match stimulus parameters with neurophysiology. We recently reported on the safety and feasibility of FEAST in a cohort (n = 17) of depressed patients. We now report on the safety, feasibility, preliminary efficacy, and cognitive effects of FEAST in a new cohort. Methods Open-label FEAST was administered to 20 depressed adults (6 men; 3 with bipolar disorder; age 49.1 ± 10.6 years). Clinical and cognitive assessments were obtained at baseline and end of course. Time to orientation recovery was assessed at each treatment. Nonresponders switched to conventional ECT. Results Participants tolerated the treatment well with no dropouts. Five patients (25%) transitioned from FEAST to conventional ECT due to inadequate response. After FEAST (mean, 9.3 ± 3.5 sessions; range, 4–14), there was a 58.1% ± 36.0% improvement in Hamilton Rating Scale for Depression scores compared with that in the baseline (P < 0.0001); 13 (65%) of 20 patients met response criteria, and 11 (55%) of 20 met remission criteria. Patients achieved reorientation (4 of 5 items) in 4.4 ± 3.0 minutes (median, 4.5 minutes), timed from eyes opening. There was no deterioration in neuropsychological measures. Conclusions These findings provide further support for the safety and efficacy of FEAST. The remission and response rates were in the range found using conventional ECT, and the time to reorientation may be quicker. However, without a randomized comparison group, conclusions are tentative. PMID:27379790

ECT Has Greater Efficacy Than Fluoxetine in Alleviating the Burden of Illness for Patients with Major Depressive Disorder: A Taiwanese Pooled Analysis

PubMed Central

Huang, Chun-Jen; Chen, Cheng-Chung

2018-01-01

Abstract Background The burden of major depressive disorder includes suffering due to symptom severity, functional impairment, and quality of life deficits. The aim of this study was to compare the differences between electroconvulsive therapy and pharmacotherapy in reducing such burdens. Methods This was a pooled analysis study including 2 open-label trials for major depressive disorder inpatients receiving either standard bitemporal and modified electroconvulsive therapy with a maximum of 12 sessions or 20 mg/d of fluoxetine for 6 weeks. Symptom severity, functioning, and quality of life were assessed using the 17-item Hamilton Rating Scale for Depression, the Modified Work and Social Adjustment Scale, and SF-36. Side effects following treatment, including subjective memory impairment, nausea/vomiting, and headache, were recorded. The differences between these 2 groups in 17-item Hamilton Rating Scale for Depression, Modified Work and Social Adjustment Scale, quality of life, side effects, and time to response (at least a 50% reduction of 17-item Hamilton Rating Scale for Depression) and remission (17-item Hamilton Rating Scale for Depression ≤7) following treatment were analyzed. Results Electroconvulsive therapy (n=116) showed a significantly greater reduction in 17-item Hamilton Rating Scale for Depression, Modified Work and Social Adjustment Scale, and quality of life deficits and had significantly shorter time to response/remission than fluoxetine (n=126). However, the electroconvulsive therapy group was more likely to experience subjective memory impairment and headache. Conclusions Compared with fluoxetine, electroconvulsive therapy was more effective in alleviating the burden of major depressive disorder and had a substantially increased speed of response/remission in the acute phase. Increased education and information about electroconvulsive therapy for clinicians, patients, and their families and the general public is warranted. PMID:29228200

Electroconvulsive therapy-induced persistent retrograde amnesia: could it be minimised by ketamine or other pharmacological approaches?

PubMed

Gregory-Roberts, Emily M; Naismith, Sharon L; Cullen, Karen M; Hickie, Ian B

2010-10-01

Certain pharmacological agents administered during electroconvulsive therapy may have the potential to prevent persistent retrograde amnesia induced during electroconvulsive therapy. This review examines mechanisms for electroconvulsive therapy-induced retrograde amnesia, and evaluates the suitability of the anaesthetic ketamine for preventing this amnestic outcome. A review of human studies, animal models and theoretical models in light of memory dysfunction following electroconvulsive therapy was conducted. MEDLINE was searched from 1950 to April 2009 using the MeSH terms "electroconvulsive therapy", "memory", "memory short term", "memory disorders", "excitatory amino acid antagonists", and "ketamine". PREMEDLINE was searched using the terms "electroconvulsive therapy", "amnesia" and "ketamine". Additional keyword and reference list searches were performed. No language, date constraints or article type constraints were used. Disruption of long term potentiation as a mechanism for electroconvulsive therapy-induced retrograde amnesia is well supported. Based on this putative mechanism, an N-methyl-D-aspartate receptor antagonist would appear suitable for preventing the retrograde amnesia. Available evidence in animals and humans supports the prediction that ketamine, an anaesthetic agent and N-methyl-D-aspartate receptor antagonist, could effectively prevent electroconvulsive therapy-induced persistent retrograde amnesia. Whilst there are concerns about the use of ketamine with electroconvulsive therapy, such as possible psychotomimetic effects, on balance this anaesthetic agent may improve or hasten clinical response to electroconvulsive therapy. A clinical trial is warranted to determine if ketamine anaesthesia during electroconvulsive therapy can lessen persistent retrograde amnesia and improve therapeutic response. Electroconvulsive therapy with ketamine anaesthesia may provide effective antidepressant action with minimal side effects. Copyright 2009 Elsevier B.V. All rights reserved.

Effectiveness of electroconvulsive therapy in patients with treatment resistant schizophrenia: A retrospective study.

PubMed

Grover, Sandeep; Chakrabarti, Subho; Hazari, Nandita; Avasthi, Ajit

2017-03-01

This study aimed to evaluate the effectiveness of electroconvulsive therapy (ECT) among patients with treatment resistant schizophrenia (TRS). Records of patients who had received ECT were reviewed to identify patients with TRS who were administered ECT in combination with clozapine. Socio-demographic, clinical data and ECT details were extracted. The most common diagnosis was of paranoid schizophrenia (49%) followed by undifferentiated schizophrenia (36%). A-fifth (22%) of the patients were judged to have poor response to clozapine. The mean number of ECTs given were 13.97 (SD-7.67) and mean clozapine dose was 287.5mgs/day (SD-100.1). About two-thirds (63%) of the patients showed >30% reduction in scores on different symptom-rating scales with combined use of clozapine and ECT. Among clozapine non-responders, approximately 69% responded to the combination. Post-ECT rise in blood pressure was the most common side effect (16.9%) followed by prolonged seizures (7%). Long-term follow-up data was available for 47 out of the 59 patients. More than two-third (N=34; 72%) followed-up for an average of 30 months (SD 32.3; range: 1-120), maintained well with continued clozapine treatment. To conclude, results of this study further endorse the effectiveness, safety and long-term benefits of the clozapine-ECT combination in TRS and clozapine-refractory schizophrenia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

The Clinical and Service Outcomes of Unilateral and Bilateral ECT Electrode Placements in Australian Aged Psychiatry Services.

PubMed

D'Cunha, Craig; Plakiotis, Christos; Macfarlane, Stephen; Moss, Francine; Reddy, Murali; Singh, Dhiren; Tofler, David; White, Erica; O'Connor, Daniel W

2016-03-01

The aim of the study was to determine whether depressed aged inpatients treated with brief pulse unilateral electroconvulsive therapy (ECT) differed from those treated with bilateral (bitemporal or bifrontal) ECT with respect to numbers of treatments, length of hospital admission, changes in scores on depression and cognitive scales, and serious adverse effects. An audit of routinely collected data regarding 221 acute ECT courses in 7 public aged psychiatry services in Victoria, Australia. Patients given unilateral, bifrontal, and bitemporal treatments were similar with respect to personal, clinical, and treatment characteristics. Most treatments were administered in line with local clinical guidelines and were rated as effective. Psychiatrists preferred unilateral ECT in the first instance with stimulus dosing based on patients' seizure thresholds. Approximately a quarter of unilateral courses were switched later to bitemporal placement, most probably because of insufficient progress. Bilateral treatments were associated with a larger number of treatments, less improvement in scores on mood and cognitive scales, and more refusals to continue treatment than unilateral-only ECT. Brief pulse unilateral ECT proved more effective than bitemporal and bifrontal ECT for most aged patients, especially when coupled with stimulus dosing based on seizure threshold.

Ictal EEG fractal dimension in ECT predicts outcome at 2 weeks in schizophrenia.

PubMed

Abhishekh, Hulegar A; Thirthalli, Jagadisha; Manjegowda, Anusha; Phutane, Vivek H; Muralidharan, Kesavan; Gangadhar, Bangalore N

2013-09-30

Studies of electroconvulsive therapy (ECT) have found an association between ictal electroencephalographic (EEG) measures and clinical outcome in depression. Such studies are lacking in schizophrenia. Consenting schizophrenia patients receiving ECT were assessed using the Brief Psychiatric Rating Scale (BPRS) before and 2 weeks after the start of ECT. The patients' seizure was monitored using EEG. In 26 patients, completely artifact-free EEG derived from the left frontal-pole (FP1) channel and electrocardiography (ECG) were available. The fractal dimension (FD) was computed to assess 4-s EEG epochs, and the maximal value from the earliest ECT session (2nd, 3rd or 4th) was used for analysis. There was a significant inverse correlation between the maximum FD and the total score following 6th ECT. An inverse Inverse correlation was also observed between the maximum FD and the total number of ECTs administered as well as the maximum heart rate (HR) and BPRS scores following 6th ECT. In patients with schizophrenia greater intensity of seizures (higher FD) during initial sessions of ECT is associated with better response at the end of 2 weeks. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The use of ketamine in ECT anaesthesia: A systematic review and critical commentary on efficacy, cognitive, safety and seizure outcomes.

PubMed

Gálvez, Verònica; McGuirk, Lucy; Loo, Colleen K

2017-09-01

This review will discuss ECT efficacy and cognitive outcomes when using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into account important moderator variables that have often not been considered to date. It will also include information on safety and other ECT outcomes (seizure threshold and quality). A systematic search through MEDLINE, PubMed, PsychINFO, Cochrane Databases and reference lists from retrieved articles was performed. Search terms were: "ketamine" and "Electroconvulsive Therapy", from 1995 to September 2016. Meta-analyses, randomised controlled trials, open-label and retrospective studies published in English of depressed samples receiving ECT with ketamine anaesthesia were included (n = 24). Studies were heterogeneous in the clinical populations included and ECT treatment and anaesthetic methods. Frequently, studies did not report on ECT factors (i.e., pulse-width, treatment schedule). Findings regarding efficacy were mixed. Tolerance from repeated use may explain why several studies found that ketamine enhanced efficacy early in the ECT course but not at the end. The majority of studies did not comprehensively examine cognition and adverse effects were not systematically studied. Only a minority of the studies reported on seizure threshold and expression. The routine use of ketamine anaesthesia for ECT in clinical settings cannot yet be recommended based on published data. Larger randomised controlled trials, taking into account moderator variables, specifically reporting on ECT parameters and systematically assessing outcomes are encouraged.

21 CFR 882.5940 - Electroconvulsive therapy device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electroconvulsive therapy device. 882.5940 Section 882.5940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Electroconvulsive therapy device. (a) Identification. An electroconvulsive therapy device is a device used for...

21 CFR 882.5940 - Electroconvulsive therapy device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electroconvulsive therapy device. 882.5940 Section 882.5940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Electroconvulsive therapy device. (a) Identification. An electroconvulsive therapy device is a device used for...

21 CFR 882.5940 - Electroconvulsive therapy device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electroconvulsive therapy device. 882.5940 Section 882.5940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Electroconvulsive therapy device. (a) Identification. An electroconvulsive therapy device is a device used for...

21 CFR 882.5940 - Electroconvulsive therapy device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electroconvulsive therapy device. 882.5940 Section 882.5940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Electroconvulsive therapy device. (a) Identification. An electroconvulsive therapy device is a device used for...

21 CFR 882.5940 - Electroconvulsive therapy device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electroconvulsive therapy device. 882.5940 Section 882.5940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Electroconvulsive therapy device. (a) Identification. An electroconvulsive therapy device is a device used for...

Delays in accessing electroconvulsive therapy: a comparison between two urban and two rural populations in Australia.

PubMed

Johnston, Natalie E

2015-10-01

A comparison of the timing, rates and characteristics of electroconvulsive therapy use between urban and rural populations. The medical records of patients who received an acute course of electroconvulsive therapy at two rural and two urban psychiatric hospitals in New South Wales (NSW), Australia, in 2010 were reviewed retrospectively. Main outcome measures were the time from symptom onset, diagnosis and admission to commencing electroconvulsive therapy. Rates of use of electroconvulsive therapy were also compared between rural and urban hospitals using NSW statewide data. There was a significant delay in the time it took for rural patients to receive electroconvulsive therapy compared with urban patients when measured both from the time of symptom onset and from when they received a diagnosis. There were corresponding delays in the time taken for rural patients to be admitted to hospital compared with urban patients. There was no difference in the time it took to commence electroconvulsive therapy once a patient was admitted to hospital. NSW statewide urban-rural comparisons showed rates of electroconvulsive therapy treatment were significantly higher in urban hospitals. Patients in rural areas receive electroconvulsive therapy later in their acute illness due to delays in being admitted to hospital. The rate of use of electroconvulsive therapy also differs geographically. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Brain-derived-neurotrophic-factor (BDNF) stress response in rats bred for learned helplessness.

PubMed

Vollmayr, B; Faust, H; Lewicka, S; Henn, F A

2001-07-01

Stress-induced elevation of glucocorticoids is accompanied by structural changes and neuronal damage in certain brain areas. This includes reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus which can be prevented by chronic electroconvulsive seizures and antidepressant drug treatment. In the last years we have bred two strains of rats, one which reacts with congenital helplessness to stress (cLH), and one which congenitally does not acquire helplessness when stressed (cNLH). After being selectively bred for more than 40 generations these strains have lost their behavioural plasticity including their sensitivity to antidepressant treatment. We show here that in cLH rats, acute immobilization stress does not induce a reduction of BDNF expression in the hippocampus which is observed in Sprague--Dawley and cNLH rats. All animals tested exhibited elevated corticosterone levels when stressed, an indication, that in cLH rats regulation of BDNF expression in the hippocampal formation is uncoupled from corticosterone increase induced through stress. This may explain the lack of adaptive responses in this strain.

ECT Has Greater Efficacy Than Fluoxetine in Alleviating the Burden of Illness for Patients with Major Depressive Disorder: A Taiwanese Pooled Analysis.

PubMed

Lin, Ching-Hua; Huang, Chun-Jen; Chen, Cheng-Chung

2018-01-01

The burden of major depressive disorder includes suffering due to symptom severity, functional impairment, and quality of life deficits. The aim of this study was to compare the differences between electroconvulsive therapy and pharmacotherapy in reducing such burdens. This was a pooled analysis study including 2 open-label trials for major depressive disorder inpatients receiving either standard bitemporal and modified electroconvulsive therapy with a maximum of 12 sessions or 20 mg/d of fluoxetine for 6 weeks. Symptom severity, functioning, and quality of life were assessed using the 17-item Hamilton Rating Scale for Depression, the Modified Work and Social Adjustment Scale, and SF-36. Side effects following treatment, including subjective memory impairment, nausea/vomiting, and headache, were recorded. The differences between these 2 groups in 17-item Hamilton Rating Scale for Depression, Modified Work and Social Adjustment Scale, quality of life, side effects, and time to response (at least a 50% reduction of 17-item Hamilton Rating Scale for Depression) and remission (17-item Hamilton Rating Scale for Depression ≤7) following treatment were analyzed. Electroconvulsive therapy (n=116) showed a significantly greater reduction in 17-item Hamilton Rating Scale for Depression, Modified Work and Social Adjustment Scale, and quality of life deficits and had significantly shorter time to response/remission than fluoxetine (n=126). However, the electroconvulsive therapy group was more likely to experience subjective memory impairment and headache. Compared with fluoxetine, electroconvulsive therapy was more effective in alleviating the burden of major depressive disorder and had a substantially increased speed of response/remission in the acute phase. Increased education and information about electroconvulsive therapy for clinicians, patients, and their families and the general public is warranted. © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

Effect of sildenafil on the activity of some antidepressant drugs and electroconvulsive shock treatment in the forced swim test in mice.

PubMed

Socała, Katarzyna; Nieoczym, Dorota; Wyska, Elżbieta; Wlaź, Piotr

2017-04-01

Sildenafil, a potent and selective inhibitor of phosphodiesterase type 5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. It is often taken by patients suffering from depression and receiving antidepressant drug treatment. However, its influence on the efficacy of antidepressant treatment was not sufficiently studied. Therefore, the aim of the present study was to investigate the influence of sildenafil on the anti-immobility action of several antidepressant drugs (i.e., sertraline, fluvoxamine, citalopram, maprotiline, trazodone, and agomelatine) as well as on antidepressant-like effect of electroconvulsive stimulations in the forced swim test in mice. The obtained results showed that acute sildenafil treatment enhanced the antidepressant-like activity of all of the studied drugs. The observed effects were not due to the increase in locomotor activity. The interactions between sildenafil and sertraline, maprotiline, and trazodone were pharmacodynamic in nature, as sildenafil did not affect concentrations of these drugs neither in serum nor in brain tissue. Increased concentrations of fluvoxamine, citalopram, and agomelatine in brain tissue evoked by sildenafil co-administration suggest that pharmacokinetic interactions between sildenafil and these drugs are very likely. Sildenafil injected acutely did not alter the antidepressant-like efficacy of electroconvulsive stimulations in mice, as assessed in the forced swim test. Interestingly, repeated (14 days) administration of sildenafil decreased the anti-immobility action of the electroconvulsive stimulations. In conclusion, the present study shows that sildenafil may alter the effectiveness of antidepressant treatment. Further studies are warranted to better characterize the influence of sildenafil on the activity of antidepressant drugs and electroconvulsive therapy.

Review of electroconvulsive therapy practice from a tertiary Child and Adolescent Psychiatry Centre.

PubMed

Jacob, Preeti; Gogi, Prabhu Kiran Vishwanath; Srinath, Shoba; Thirthalli, Jagadisha; Girimaji, Satish; Seshadri, Shekhar; Sagar, John Vijay

2014-12-01

The use of electroconvulsive therapy (ECT) in children and adolescents is a controversial issue. This study was done to examine the pattern and practice as well as the outcome of electroconvulsive therapy administered to children and adolescents admitted to a tertiary care centre. A 10 year retrospective chart review of all children and adolescents (up to 16 years of age) admitted in the Child and Adolescent Psychiatry Centre, National Institute of Mental Health and Neurosciences (NIMHANS) who had received at least 1 session of ECT was done. Information regarding diagnosis, reasons for prescribing electroconvulsive therapy, details regarding the procedure and outcome variables was collected from the records. Clinical Global Impressions (CGI) scale rating of the severity of illness and improvement seen were done by 2 trained psychiatrists independently. 22 children and adolescents received electroconvulsive therapy over 10 years. There were an equal number of boys and girls. All received modified ECT. Most patients who received electroconvulsive therapy were severely ill. Catatonic symptoms 54.5% (12) were the most common reason for prescribing electroconvulsive therapy. It was efficacious in 77.3% (17) of the patients. Electroconvulsive therapy was relatively safe, and most experienced no acute side effects. 68.2% (15) who were on follow up and did not experience any long term side effects due to the electroconvulsive therapy. Electroconvulsive therapy has a place in the acute management of severe childhood psychiatric disorders. Further long term prospective studies are required. Copyright © 2014 Elsevier B.V. All rights reserved.

The Relationship between Symptom Relief and Psychosocial Functional Improvement during Acute Electroconvulsive Therapy for Patients with Major Depressive Disorder.

PubMed

Lin, Ching-Hua; Yang, Wei-Cheng

2017-07-01

We aimed to compare the degree of symptom relief to psychosocial functional (abbreviated as "functional") improvement and explore the relationships between symptom relief and functional improvement during acute electroconvulsive therapy for patients with major depressive disorder. Major depressive disorder inpatients (n=130) requiring electroconvulsive therapy were recruited. Electroconvulsive therapy was generally performed for a maximum of 12 treatments. Symptom severity, using the 17-item Hamilton Depression Rating Scale, and psychosocial functioning (abbreviated as "functioning"), using the Modified Work and Social Adjustment Scale, were assessed before electroconvulsive therapy, after every 3 electroconvulsive therapy treatments, and after the final electroconvulsive therapy. Both 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale scores were converted to T-score units to compare the degrees of changes between depressive symptoms and functioning after electroconvulsive therapy. Structural equation modeling was used to test the relationships between 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale during acute electroconvulsive therapy. One hundred sixteen patients who completed at least the first 3 electroconvulsive therapy treatments entered the analysis. Reduction of 17-item Hamilton Depression Rating Scale T-scores was significantly greater than that of Modified Work and Social Adjustment Scale T-scores at assessments 2, 3, 4, and 5. The model analyzed by structural equation modeling satisfied all indices of goodness-of-fit (chi-square = 32.882, P =.107, TLI = 0.92, CFI = 0.984, RMSEA = 0.057). The 17-item Hamilton Depression Rating Scale change did not predict subsequent Modified Work and Social Adjustment Scale change. Functioning improved less than depressive symptoms during acute electroconvulsive therapy. Symptom reduction did not predict subsequent functional improvement. Depressive symptoms and functional impairment are distinct domains and should be assessed independently to accurately reflect the effectiveness of electroconvulsive therapy. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Efficacy and safety of electroconvulsive therapy in the first trimester of pregnancy: a case of severe manic catatonia.

PubMed

Pinna, Martina; Manchia, Mirko; Pillai, Gianluca; Salis, Piergiorgio; Minnai, Gian Paolo

2015-08-01

Electroconvulsive therapy (ECT) is an appropriate, albeit often neglected, option for managing severe or life-threatening psychiatric symptoms during pregnancy. We report on the rapid effectiveness and safety of ECT during the first trimester of pregnancy in a 28-year-old woman with severe catatonia. Catatonic symptoms were assessed using the Catatonia Rating Scale (CRS). The patient was treated with unilateral ECT using left anterior right temporal (LART) placement. Seizure quality and duration were monitored by a two-lead electroencephalograph (EEG) and by one-lead electromyography (EMG). During each ECT session, the fetal heart rate was monitored with electrocardiogram (ECG). After the second ECT treatment (day 13 of hospitalization), we observed remission of the catatonic symptoms, as shown by the drop in the CRS score from 22 to 0. No cognitive abnormalities were reported and no gynecological complications were detected (e.g. vaginal bleeding, abdominal pain, or uterine contraction). The patient delivered at term a healthy male neonate who presented normal growth as well as normal psychomotor development. This case highlights the effectiveness of ECT in treating severe catatonic mania during the first 3 months of pregnancy. In addition, ECT proved to be a safe therapeutic option, since neither mother nor infant experienced any adverse event. We suggest that ECT might be considered as a valid and safe option in the therapeutic decision-making process when catatonic symptoms manifest during pregnancy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Some considerations of the tolerability of ketamine for ECT anesthesia: a case series and review of the literature.

PubMed

Rasmussen, Keith G; Ritter, Matthew J

2014-12-01

Most anesthetic agents used for electroconvulsive therapy (ECT) have few intrinsic adverse effects. Ketamine, however, is well known to be associated with a variety of adverse effects including nausea, dizziness, and psychotomimetic phenomena. Over the past several decades, there have been numerous reports on the use of ketamine for ECT anesthesia, with varied assessments on how prominent these adverse effects are in the ECT situation. Ketamine has received a resurgence of interest as an ECT anesthetic of late owing to its established independent antidepressant effects and to theoretical reasons why it might lessen the cognitive adverse effects of ECT. In this case series, the author reviews the experience with 14 patients who had undergone ECT who were switched to ketamine as anesthetic from methohexital at the preference of the treating anesthesiologist. All 14 patients spontaneously reported a strong preference not to be given ketamine again due to bothersome adverse effects. The latter consisted of either vestibular-type symptoms (nausea/vomiting, dizziness, and vertigo) or psychotomimetic effects (dissociative phenomena). It is concluded that ketamine is not free of adverse effects when used as an ECT anesthetic. Electroconvulsive therapy clinicians should be vigilant about assessing for these effects when ketamine is used, and consideration should be given to using a benzodiazepine such as diazepam or midazolam at seizure termination when ketamine anesthesia is used to prevent bothersome adverse effects seen upon awakening.

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

Low medical morbidity and mortality after acute courses of electroconvulsive therapy in a population-based sample.

PubMed

Blumberger, D M; Seitz, D P; Herrmann, N; Kirkham, J G; Ng, R; Reimer, C; Kurdyak, P; Gruneir, A; Rapoport, M J; Daskalakis, Z J; Mulsant, B H; Vigod, S N

2017-12-01

To determine event rates for specific medical events and mortality among individuals receiving electroconvulsive therapy (ECT). Population-based cohort study using health administrative data of acute ECT treatments delivered in Ontario, Canada, from 2003 to 2011. We measured the following medical event rates, per 10 000 ECT treatments, up to 7 and 30 days post-treatment: stroke, seizure, acute myocardial infarction, arrhythmia, pneumonia, pulmonary embolus, deep vein thrombosis, gastrointestinal bleeding, falls, hip fracture, and mortality. A total of 135 831 ECT treatments were delivered to 8810 unique patients. Overall medical event rates were 9.1 and 16.8 per 10 000 ECT treatments respectively. The most common medical events were falls (2.7 and 5.5 per 10 000 ECT treatments) and pneumonia (1.8 and 3.8 per 10 000 ECT treatments). Fewer than six deaths occurred on the day of an ECT treatment. This corresponded to a mortality rate of less than 0.4 per 10 000 treatments. Deaths within 7 and 30 days of an ECT treatment, excluding deaths due to external causes (e.g., accidental and intentional causes of death), were 1.0 and 2.4 per 10 000 ECT treatments respectively. Morbidity and mortality events after ECT treatments were relatively low, supporting ECT as a low-risk medical procedure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Randomized comparison of ultra-brief bifrontal and unilateral electroconvulsive therapy for major depression: cognitive side-effects.

PubMed

Sienaert, P; Vansteelandt, K; Demyttenaere, K; Peuskens, J

2010-04-01

The cognitive side-effects of bifrontal (BF) and right unilateral (UL) ultra-brief pulse (0.3 ms) electroconvulsive therapy (ECT) were compared, in the treatment of patients with a depressive episode. Neuropsychological functioning in patients with a medication refractory depressive episode, that were treated with a course of BF ultra-brief ECT at 1.5 times seizure threshold (ST) or UL ultra-brief ECT at 6 times ST, by random assignment, was assessed before treatment, and 1 and 6 weeks after the treatment course, by a blinded rater. Of the 64 patients that were included, 32 (50%) received BF ECT, and 32 (50%) received UL ECT, by random assignment. Neuropsychological testing 1 and 6 weeks after treatment was performed by 30 (93.75%) and 19 (59.37%) patients, respectively, in the BF-group and 29 (90.62%) and 20 (62.50%), respectively, in the UL-group. There was no deterioration in any of the neuropsychological measures. Patients rated their memory as clearly improved after treatment. There were no significant differences between the patients given BF ECT and those given UL ECT. Ultrabrief pulse ECT, used either in combination with a UL electrode position and a stimulus of 6 times ST, or a BF electrode position with a stimulus of 1.5 times ST, are effective antidepressant techniques, that do not have a deleterious effect on cognitive function. Copyright 2009 Elsevier B.V. All rights reserved.

Safety of the electroconvulsive therapy and amisulpride combination.

PubMed

Takács, Rozália; Iványi, Zsolt; Ungvari, Gabor S; Gazdag, Gábor

2013-03-01

Electroconvulsive therapy is frequently considered when pharmacotherapy is ineffective. In such cases the combination of the two treatment modalities are commonly used. Amisulpiride, a second generation antipsychotic drug is used in the treatment of schizophrenia and psychotic depression. When amisulpiride is ineffective as a monotherapy, combination with ECT could be an option to enhance its efficacy. To the best of our knowledge, to date there have been no data about the safety of this combination. Medical notes of all patients who were given ECT while on amisulpiride were selected from the archives of the Department of Psychiatry, Semmelweis University Medical School, Budapest, covering a 10-year period. A randomly selected matched control group was formed from patients who underwent ECT but were not taking amisulpiride. Patients in both groups also received a variety of psychotropic drugs other than amisulpide. Side effects were compared between the two groups of patients. Twenty patients received amisulpride with ECT. The most common side effects were headache, hypertension, tachycardia, nausea, dizziness, confusion, psychomotor agitation, sialorrhea, and prolonged seizure activity. All adverse effects resolved within 24 hours. No side effects of any kind were observed in 7 and 8 cases in the study and control groups, respectively. This was the first study that examined the safety of amisulpride-ECT combination in schizophrenia. Comparing the side-effects between the study and control groups, no significant differences were detected in terms of their types or frequency. The amisulpiride-ECT combination appears to be a safe treatment option.

Use of Electroconvulsive Therapy in Adolescents With Treatment-Resistant Depressive Disorders: A Case Series.

PubMed

Zhand, Naista; Courtney, Darren B; Flament, Martine F

2015-12-01

This study presents a comprehensive case series of adolescents who received electroconvulsive therapy (ECT) for treatment-resistant depression. Conducting a chart review, we identified 13 adolescents who had ECT for treatment of depression over a 5-year interval (2008-2013) at a Canadian tertiary care psychiatric hospital. Details about participants' clinical profile, index course of ECT, outcome, side effects, and comorbidities were extracted and analyzed. Thirteen adolescents aged 15 to 18 years, received a mean of 14 (SD, 4.5) ECT sessions per patient. Based on the Beck Depression Inventory-II at baseline and after treatment with ECT, a reliable improvement was observed in 10 patients, with 3 achieving full recovery. Through mixed effects linear modeling, we found a decrease of 0.96 points (95% CI, -1.31 to -0.67, P < 0.001) on the Beck Depression Inventory-II total score for every ECT treatment received. The Montreal Cognitive Assessment was used for monitoring of cognitive function throughout the treatment. Adverse effects included transient subjective cognitive impairment (n = 11), headache (n = 10), muscular pain (n = 9), prolonged seizure (n = 3), and nausea and/or vomiting (n = 3). A clinically significant improvement was observed for 10 (77%) adolescents receiving ECT for treatment-resistant depression. These observations suggest that ECT is a potential treatment option for refractory depression in selected adolescents. More data are needed to draw conclusions about efficacy and possible predictors of treatment response.

Neuropsychological Effects of Neuromodulation Techniques for Treatment-Resistant Depression: A Review

PubMed Central

Moreines, Jared L.; McClintock, Shawn M.; Holtzheimer, Paul E.

2010-01-01

Electroconvulsive therapy (ECT) and ablative neurosurgical procedures are established interventions for treatment-resistant depression (TRD), but their use may be limited in part by neuropsychological adverse effects. Additional neuromodulation strategies are being developed that aim to match or exceed the efficacy of ECT/ablative surgery with a better neurocognitive side effect profile. In this review, we briefly discuss the neurocognitive effects of ECT and ablative neurosurgical procedures, then synthesize the available neurocognitive information for emerging neuromodulation therapies including repetitive transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, vagus nerve stimulation, and deep brain stimulation. The available evidence suggests these procedures may be more cognitively benign relative to ECT or ablative neurosurgical procedures, though further research is clearly needed to fully evaluate the neurocognitive effects, both positive and negative, of these novel neuromodulation interventions. PMID:21255751

Electroconvulsive Therapy in Women: A Retrospective Study from a Mental Health Hospital in Turkey.

PubMed

Özdemir, Armağan; Poyraz, Cana Aksoy; Erten, Evrim; Çırakoğlu, Emre; Tomruk, Nesrin

2016-12-01

The aim was to evaluate the clinical profile and effectiveness of ECT in women. A retrospective chart review was carried out to identify female patients who had received ECT during the period September 2013-February 2015. Details regarding their sociodemographic, clinical, and treatment data were extracted from these records for the present study. The total number of patients, admitted to our psychiatry inpatient clinic during the survey period, was 802. During this period, 26 (3.24 %) female patients received ECT. Patients who received ECT were mostly in age group of 25-44 years (76.9 %). Twenty percent of patients were in the postpartum period. Psychotic disorders (46.1 %) was the most common diagnosis for which ECT was used, followed by bipolar affective disorder, current episode manic (19.2 %). At the end of ECT courses, 70 % of the patients showed good response with a CGI-I of 1 or 2, and 30 % showed minimal response with a CGI-I score of 3. The most common side effects were post-ECT confusion (15.4 %) and prolonged seizure (11.5 %). This rate of prolonged seizure was higher the rates reported in the literature. The bronchospasm related with remifentanil, post-ECT bradycardia, hypertensive crisis and oligohydramnios were also reported in one case each. ECT is a safe and effective treatment option in women with severe psychiatric disorders and disorders in the perinatal/postpartum period are a major area of ECT use. The female gender may be a contributing factor for the higher rates of prolonged seizure.

Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study.

PubMed

Rocha, Renan Boeira; Dondossola, Eduardo Ronconi; Grande, Antônio José; Colonetti, Tamy; Ceretta, Luciane Bisognin; Passos, Ives C; Quevedo, Joao; da Rosa, Maria Inês

2016-12-01

We performed a systematic review and meta-analysis to estimate brain-derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT). A comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: "major depressive disorder", "unipolar depression", "brain-derived neurotrophic factor", and "electroconvulsive therapy". A total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17-0.96). Additionally, we found significant heterogeneity between studies (I 2  = 73%). Our findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effectiveness of an Educational Intervention on Medical Students' Knowledge About and Attitude Towards Electroconvulsive Therapy.

PubMed

Solomon, Susan; Simiyon, Manjula; Vedachalam, Ahalya

2016-04-01

This study was done to determine the effectiveness of a lecture and exposure to electroconvulsive therapy (ECT) followed by interaction with patient, on medical students' knowledge about and attitude towards electroconvulsive therapy. A questionnaire was administered to second year medical students to determine their baseline knowledge about and attitude towards electroconvulsive therapy. Following this, they underwent two educational interventions, a lecture on ECT and exposure to the procedure and interaction with the patient and relative, and their knowledge and attitude were reassessed after each intervention using the same questionnaire. Eighty-one students completed all the three assessments. Students' knowledge about ECT at baseline was minimal (mean 3.58 out of 12). Their knowledge increased significantly after the lecture (mean 10.3), and there was further increase following exposure to the procedure and subsequent interaction with the patient and relative (mean 11.1). At baseline, students had an overall negative attitude towards ECT. There was significant improvement on all attitude items following the lecture. Exposure to the procedure resulted in further improvement in attitude regarding whether ECT is a cruel treatment and has to be used as a last resort. Exposure to ECT in lecture and clinical scenarios followed by interaction with the patient should be included in the undergraduate medical curriculum to improve students' knowledge and attitude about this safe, effective, and potentially lifesaving treatment modality.

Severe anorexia nervosa, co-occurring major depressive disorder and electroconvulsive therapy as maintenance treatment: a case report.

PubMed

Poutanen, Outi; Huuhka, Kaija; Perko, Kaisa

2009-12-21

It is difficult to treat patients who, in addition to having severe anorexia nervosa, also have severe symptoms of major depressive disorder and a tendency for impulsive acting out behaviour. Our case report considers the feasibility of maintenance electroconvulsive therapy in such complicated cases. This is a case report of a woman with anorexia nervosa and co-morbid severe major depressive disorder who was treated with electroconvulsive therapy as a maintenance treatment. The maintenance electroconvulsive therapy was conducted without immediate complications. It had a positive effect on the patient's depressive symptoms and lability and her general wellbeing, although some cognitive deficits were observed. The maintenance electroconvulsive therapy seemed to support recovery in a case of refractory anorexia nervosa and a tendency for labile mood. The symptoms of co-occurring major depressive disorder were partly relieved and maintenance electroconvulsive therapy had some positive effect on weight gain.

Electroconvulsive therapy in Parkinson's disease.

PubMed

Calderón-Fajardo, Humberto; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Ramírez-Bermudez, Jesús; Ruiz-Chow, Ángel; Rodríguez-Violante, Mayela

2015-10-01

Purpose To analyze the effectiveness of electroconvulsive therapy for the management of depression and/or psychosis refractory to drug therapy in patients with Parkinson disease.Methods A retrospective study was carried out including patients treated with electroconvulsive therapy during the period between 2002 and 2013. A review of the literature was performed.Results A total of 27 patients were included. In regards to the neuropsychiatric diagnosis, 14 patients had major depression, 12 patients had both psychosis and depression, and only one patient had isolated psychosis. The mean number of electroconvulsive therapy sessions was 12 ± 2.8. After electroconvulsive therapy, all patients showed a statistically significant improvement in the Brief Psychiatric Rating scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points) independent of the presence of psychosis, depression or both.Conclusion Electroconvulsive therapy is effective for the treatment of refractory neuropsychiatric symptoms in Parkinson's disease.

Does a single session of electroconvulsive therapy alter the neural response to emotional faces in depression? A randomised sham-controlled functional magnetic resonance imaging study.

PubMed

Miskowiak, Kamilla W; Kessing, Lars V; Ott, Caroline V; Macoveanu, Julian; Harmer, Catherine J; Jørgensen, Anders; Revsbech, Rasmus; Jensen, Hans M; Paulson, Olaf B; Siebner, Hartwig R; Jørgensen, Martin B

2017-09-01

Negative neurocognitive bias is a core feature of major depressive disorder that is reversed by pharmacological and psychological treatments. This double-blind functional magnetic resonance imaging study investigated for the first time whether electroconvulsive therapy modulates negative neurocognitive bias in major depressive disorder. Patients with major depressive disorder were randomised to one active ( n=15) or sham electroconvulsive therapy ( n=12). The following day they underwent whole-brain functional magnetic resonance imaging at 3T while viewing emotional faces and performed facial expression recognition and dot-probe tasks. A single electroconvulsive therapy session had no effect on amygdala response to emotional faces. Whole-brain analysis revealed no effects of electroconvulsive therapy versus sham therapy after family-wise error correction at the cluster level, using a cluster-forming threshold of Z>3.1 ( p<0.001) to secure family-wise error <5%. Groups showed no differences in behavioural measures, mood and medication. Exploratory cluster-corrected whole-brain analysis ( Z>2.3; p<0.01) revealed electroconvulsive therapy-induced changes in parahippocampal and superior frontal responses to fearful versus happy faces as well as in fear-specific functional connectivity between amygdala and occipito-temporal regions. Across all patients, greater fear-specific amygdala - occipital coupling correlated with lower fear vigilance. Despite no statistically significant shift in neural response to faces after a single electroconvulsive therapy session, the observed trend changes after a single electroconvulsive therapy session point to an early shift in emotional processing that may contribute to antidepressant effects of electroconvulsive therapy.

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.

Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study

PubMed Central

Ryan, K M; Glaviano, A; O'Donovan, S M; Kolshus, E; Dunne, R; Kavanagh, A; Jelovac, A; Noone, M; Tucker, G M; Dunn, M J; McLoughlin, D M

2017-01-01

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression. PMID:28350398

Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study.

PubMed

Ryan, K M; Glaviano, A; O'Donovan, S M; Kolshus, E; Dunne, R; Kavanagh, A; Jelovac, A; Noone, M; Tucker, G M; Dunn, M J; McLoughlin, D M

2017-03-28

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

Electroconvulsive Therapy in Schizophrenia in China: A National Survey.

PubMed

Li, Qian; Su, Yun-Ai; Xiang, Yu-Tao; Shu, Liang; Yu, Xin; Ungvari, Gabor S; Seiner, Stephen J; Chiu, Helen F K; Ning, Yu-Ping; Wang, Gao-Hua; Zhang, Ke-Rang; Li, Tao; Sun, Li-Zhong; Shi, Jian-Guo; Chen, Xian-Sheng; Mei, Qi-Yi; Li, Ke-Qing; Si, Tian-Mei

2017-06-01

Little is known about electroconvulsive therapy (ECT) use in the treatment of schizophrenia in China. This study examined the frequency of ECT use, its trend between 2006 and 2012, and its independent demographic and clinical correlates in a nationwide survey in China. A total of 5162 inpatients in 45 Chinese psychiatric hospitals/centers were interviewed (2696 in 2006 and 2466 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Electroconvulsive therapy was used in 6.1% of the whole sample; 4.7% in 2006 and 7.7% in 2012 (P < 0.001) with wide interprovince variations. Multiple logistic regression analyses of the whole sample revealed that patients receiving ECT were more likely to be women, receive second-generation antipsychotics, treated in tertiary referral centers (level III hospitals), had a shorter illness duration, and more positive and depressive symptoms (R = 0.181; P < 0.001). Electroconvulsive therapy for schizophrenia has increased between 2006 and 2012 in China. Its percentage was higher than the figures reported in most other countries. Reasons for the substantial variations in the frequency of ECT across different provinces in China require further investigations.

Delayed onset and prolonged interictal delirium following electroconvulsive therapy.

PubMed

Selvaraj, Arun G; Praharaj, Samir Kumar

2012-09-01

Electroconvulsive therapy is safe and effective in the treatment of depression in older individuals. Minor cognitive side effects of electroconvulsive therapy include acute postictal confusion and reversible short-term memory deficits. However, interictal delirium is uncommon in absence of risk factors. Herein, we report the case a depressed male patient without any known risk factors who developed interictal delirium 2 days after his sixth electroconvulsive therapy session. Interictal delirium improved with treatment within 1 week. © 2012 The Authors. Psychogeriatrics © 2012 Japanese Psychogeriatric Society.

Electroconvulsive therapy: Promoting awareness among primary care physicians.

PubMed

Sicher, Sarah; Gedzior, Joanna

2016-04-01

This article aims to promote awareness among primary care providers and support electroconvulsive therapy as a generally well-tolerated, effective therapeutic modality to treat specific psychiatric conditions in appropriately selected patients. There seem to be several potential barriers to treatment with electroconvulsive therapy including stigma, lack of providers who preform it, and lack of awareness among providers referring patients who may be appropriate candidates. The article provides a brief overview of electroconvulsive therapy principles and topics and includes a case report to illustrate clinical utility. The article proposes the concept that a potential way to overcome barriers to treatment with electroconvulsive therapy may be to promote education and awareness of it as a viable treatment modality among primary care providers. © The Author(s) 2016.

Updates in Refractory Status Epilepticus

PubMed Central

Mahulikar, Advait; Suchdev, Kushak; Shah, Aashit

2018-01-01

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status. PMID:29854452

Evaluation of pro-convulsant risk in the rat: spontaneous and provoked convulsions.

PubMed

Esneault, Elise; Peyon, Guillaume; Froger-Colléaux, Christelle; Castagné, Vincent

2015-01-01

The aim of the present study was to evaluate the utility of different tests performed in the absence or presence of factors promoting seizures in order to evaluate the pro-convulsant effects of drugs. We studied the effects of theophylline in the rat since this is a well-known pro-convulsant substance in humans. The occurrence of spontaneous convulsions following administration of theophylline was evaluated by observation in the Irwin Test and by measuring brain activity using video-EEG recording in conscious telemetered animals. Theophylline was also tested in the electroconvulsive shock (ECS) threshold and pentylenetetrazole (PTZ)-induced convulsions tests, two commonly used models of provoked convulsions. In the Irwin test, theophylline induced convulsions in 1 out of 6 rats at 128 mg/kg. Paroxysmal/seizure activity was also observed by video-EEG recording in 4 out of the 12 animals tested at 128 mg/kg, in presence of clonic convulsions in 3 out of the 4 rats. Paroxysmal activity was observed in two rats in the absence of clear behavioral symptoms, indicating that some precursor signs can be detected using video-EEG. Clear pro-convulsant activity was shown over the dose-range 32-128 mg/kg in the ECS threshold and PTZ-induced convulsions tests. Evaluation of spontaneous convulsions provides information on the therapeutic window of a drug and the translational value of the approach is increased by the use of video-EEG. Tests based on provoked convulsions further complement the evaluation since they try to mimic high risk situations. Measurement of both spontaneous and provoked convulsions improves the evaluation of the pro-convulsant risk of novel pharmacological substances. Copyright © 2014 Elsevier Inc. All rights reserved.

Effectiveness and risks of combining antipsychotic drugs with electroconvulsive treatment.

PubMed

Sanz-Fuentenebro, Francisco Javier; Vidal Navarro, Ignacio; Ballesteros Sanz, Daniel; Verdura Vizcaíno, Ernesto

2011-01-01

The simultaneous application of electroconvulsive therapy (ECT) and psychotropic drugs is based on sparse data. Despite this, and the restrictive approach of the Guidelines and Consensus is widespread in the usual care, it is widely practiced in routine clinical. We reviewed the results of search on the topic in MEDLINE, PsychINFO, EMBASE and Cochrane, and the main guidelines on the subject and analyzed for drug groups. Except some reservation with regard to classical MAOIs, antidepressants are safe and effective enhancers of the TEC. It is desirable to discontinuation of BZD whenever clinically possible before the course of ECT for risk of interference, if not possible will have to use proper technique to ensure effective incentives. It is advisable to stop or reduce the dose of lithium prior to ECT based on a cost-benefit analysis of the risk of relapse, if maintained will be adjusted lower levels and cognitive effects minimizing techniques. The combination with "classic" and "atypical" antipsychotics power positive clinical effects and the risk of combined use is low. The positive data are collected with clozapine and ECT-resistant psychosis, with little presence of effects of the decrease of seizure threshold by clozapine, and important effect of empowerment, but of limited duration. Although it is strictly necessary to identify situations in terms of drugs, patient and ECT technique, and care necessary to develop tests that provide methodologically sound data, the combined use of ECT and psychotropic drugs in general presents an acceptable risk level and efficacy data by encouraging empowerment. Copyright © 2010 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

Electroconvulsive therapy-related cognitive impairment and choice of anesthesia: the tipping point.

PubMed

Sedighinejad, Abbas; Nabi, Bahram Naderi; Haghighi, Mohammad; Farzam, Alieh; Sayyah, Zahra; Kabiri, Majid; Soleimani, Robabeh; Alavi, Cyrus Emir

2015-06-01

Electroconvulsive therapy (ECT) is among the most effective treatments of several life-threatening psychiatric disorder. Despite effective therapy, ECT-induced seizure could cause several adverse effects including cognitive disorders and memory impairment. Drugs such as thiopental, which have been prescribed for anesthesia required for ECT, are known as drugs with cognitive effects. This pilot randomized clinical trial tried to assess the feasibility of using a lower dose of thiopental in combination with remifentanil instead of a higher challenging dose of a single drug with cognitive side effects such as thiopental. We evaluated post-ECT cognitive impairment in patients who received remifentanil-thiopental compared with thiopental-placebo group. One hundred twenty patients with psychiatric disorders between the ages of 18 and 60 years were enrolled. The patients were randomized into 2 groups who received either thiopental sodium (4 mg/kg) and remifentanil (1 μg/kg) or thiopental sodium (3 mg/kg, placebo). The psychiatric patients were examined using mini-mental state examination in terms of the cognitive deficits before ECT as well as 5 and 24 hours after ECT. Statistical analyses were done using Statistical Package for the Social Sciences version 16. Unpaired t test, χ2 test, and analysis of variance were used to determine the association of variables. All the patients completed the trial. There were no reports of adverse effects. In terms of depth of anesthesia measured by bispectral index, no significant difference was observed. Regarding mini-mental state examination scores, the difference was not statistically significant. Depth of anesthesia was similar between the groups.

Electroconvulsive therapy with S-ketamine anesthesia for catatonia in coexisting depression and dementia.

PubMed

Litvan, Zsuzsa; Bauer, Martin; Kasper, Siegfried; Frey, Richard

2017-07-01

Information on efficacy and safety of electroconvulsive therapy in patients with dementia is sparse. The current case report describes a patient suffering from severe depression and dementia who received electroconvulsive therapy with S-ketamine anesthesia at our psychiatric intensive care unit for the treatment of her therapy-resistant catatonic stupor. The patient's condition improved remarkably through the treatment. By the end of 16 electroconvulsive therapy sessions, her catatonic symptoms remitted entirely, her affect was brighter and she performed markedly better at the cognitive testing.

The depiction of electroconvulsive therapy in Hindi cinema.

PubMed

Andrade, Chittaranjan; Shah, Nilesh; Venkatesh, Basappa K

2010-03-01

There is little literature on the depiction of electroconvulsive therapy (ECT) in movies. In India, Hindi cinema is an important source of public information and misinformation about ECT. We identified depictions of ECT in Hindi cinema through inquiries with e-communities, video libraries, and other sources. We also searched the PubMed database using search terms related to ECT and movies. Between 1967 and 2008, 13 Hindi movies contained referrals to or depictions of ECT. By and large, the depictions were inaccurate, distorted, and dramatized. Electroconvulsive therapy was administered to punish, to obliterate identity, to induce insanity, and for other rarely clinically valid indications. Electroconvulsive therapy was almost always administered by force. Premedication was rare. Genuine ECT devices were uncommonly used. Electroconvulsive therapy stimulation almost invariably appeared to cause pain. Multiple shocks were frequently delivered in the same session. The convulsions were usually bizarre. The treatment caused mental disturbance, amnesia, weakness, and even a zombielike state, thought not mortality; clinical improvement was rare. There was no pattern of increasing accuracy of depiction of ECT with recency of movie release. We examine the extent to which the identified inaccuracies are practically important and offer reasons for the inaccuracies. Although the inaccuracies are a cause for concern, we suggest that because Hindi cinema is generally hyperbolic, the public may be willing to distinguish real life from reel life when facing clinical decisions about ECT. Nevertheless, considering the potential for harm in the dissemination of misinformation, filmmakers should exhibit a greater sense of ethics when creating impressions that might adversely influence health.

Electroconvulsive therapy for depression in a patient with an Inspire hypoglossal nerve stimulator device for obstructive sleep apnea: A case report.

PubMed

Mingo, Katie; Kominsky, Alan

2018-04-19

METHODS: This is a case report of a patient who underwent placement and initiation of a hypoglossal nerve stimulator device in the context of receiving electroconvulsive therapy for bipolar depression between February and September 2016. To our knowledge, this has not yet been reported in the literature. Outcome measurements included successful device activation and successful device use throughout electroconvulsive therapy. The patient underwent successful device implantation, activation, and use without disruption throughout electroconvulsive therapy sessions. No special device deactivation was required during electroconvulsive therapy sessions. Obstructive sleep apnea is a common disorder that causes significant reduction in quality of life and is an independent risk factor for multiple comorbidities. Electroconvulsive therapy is an established treatment for medication-refractory depression with minimal risk in most patient populations. This is the first report in the literature of a patient undergoing ECT for bipolar depression with recent activation of Inspire hypoglossal nerve stimulator who had no disruption in the function of his implanted device. Copyright © 2018. Published by Elsevier Inc.

Assessment of the Combined Treatment with Umbelliferone and Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice.

PubMed

Zagaja, Mirosław; Andres-Mach, Marta; Skalicka-Woźniak, Krystyna; Rękas, Anna R; Kondrat-Wróbel, Maria W; Gleńsk, Michał; Łuszczki, Jarogniew J

2015-01-01

The aim of this study was to determine the effects of umbelliferone (7-hydroxycoumarin; UMB) on the anticonvulsant potency of four classical antiepileptic drugs (carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB) and valproate (VPA)) in the mouse maximal electroshock-induced seizure (MES) model. UMB administered systemically intraperitoneally (ip) in a dose of 150 mg/kg significantly elevated the threshold for maximal electroconvulsions (p < 0.05) in mice. Moreover, UMB (150 mg/kg) co-administered with PB and VPA significantly enhanced the anticonvulsant potency of these drugs by reducing their median effective doses (ED50 values) from 35.39 to 21.78 mg/kg (p < 0.01) for PB, and from 281.4 to 215.5 mg/kg (p < 0.01) for VPA. In contrast, UMB (150 mg/kg, ip) had no significant effect on the antiseizure activity of CBZ and PHT in the mouse MES model. Neither total brain PB, nor total brain VPA concentrations were altered after ip administration of UMB, indicating a pharmacodynamic nature of interactions between the tested drugs. The selective potentiation of the anticonvulsant potency of PB and VPA by UMB, and lack of any pharmacokinetic interactions between drugs, make the combinations of UMB with PB or VPA worthy of consideration for epileptic patients who are refractory to standard antiepileptic treatment. © 2015 S. Karger AG, Basel.

Speed of response in ultrabrief and brief pulse width right unilateral ECT.

PubMed

Loo, Colleen K; Garfield, Joshua B B; Katalinic, Natalie; Schweitzer, Isaac; Hadzi-Pavlovic, Dusan

2013-05-01

Ultrabrief pulse width stimulation electroconvulsive therapy (ECT) results in less cognitive side-effects than brief pulse ECT, but recent work suggests that more treatment sessions may be required to achieve similar efficacy. In this retrospective analysis of subjects pooled from three research studies, time to improvement was analysed in 150 depressed subjects who received right unilateral ECT with a brief pulse width (at five times seizure threshold) or ultrabrief pulse width (at six times seizure threshold). Multivariate Cox regression analyses compared the number of treatments required for 50% reduction in depression scores (i.e. speed of response) in these two samples. The analyses controlled for clinical, demographic and treatment variables that differed between the samples or that were found to be significant predictors of speed of response in univariate analyses. In the multivariate analysis, older age predicted faster speed of response. There was a non-significant trend for faster time to 50% improvement with brief pulse ECT (p = 0.067). Remission rates were higher after brief pulse ECT than ultrabrief pulse ECT (p = 0.007) but response rates were similar. This study, the largest of its kind reported to date, suggests that fewer treatments may be needed to attain response with brief than ultrabrief pulse ECT and that remission rates are higher with brief pulse ECT. Further research with a larger randomized and blinded study is recommended.

A report on mood and cognitive outcomes with right unilateral ultrabrief pulsewidth (0.3 ms) ECT and retrospective comparison with standard pulsewidth right unilateral ECT.

PubMed

Loo, Colleen; Sheehan, Patrick; Pigot, Melissa; Lyndon, William

2007-11-01

Electroconvulsive therapy (ECT) is a highly effective treatment for depression but its use is limited by the risk of cognitive side effects. This study explored the potential of a novel approach, ultrabrief pulsewidth (0.3 ms) right unilateral (RUL-UB) ECT, to minimise cognitive effects while preserving efficacy. Mood and neuropsychological functioning were objectively rated in 30 patients over a course of RUL-UB ECT at 6 times seizure threshold. Results (mood outcomes, ECT treatment parameters) were compared with a retrospectively assessed group of 30 age and gender matched patients who received RUL ECT (1.0 ms pulsewidth, 3.5 times seizure threshold) at the same hospital. Six treatments of RUL-UB ECT resulted in relatively few cognitive side effects, compared to reports of previous studies. The number of responders did not differ between groups but significantly more treatments were required in the RUL-UB group, suggesting a slower speed of response. Patients were not randomised to the two forms of ECT and data was obtained retrospectively in the RUL ECT comparison group. This study suggests that RUL-UB ECT can be effective in treating depression while incurring lesser cognitive side effects than a commonly used form of RUL ECT, but a greater number of treatments may be required for response.

Neural Response After a Single ECT Session During Retrieval of Emotional Self-Referent Words in Depression: A Randomized, Sham-Controlled fMRI Study.

PubMed

Miskowiak, Kamilla W; Macoveanu, Julian; Jørgensen, Martin B; Støttrup, Mette M; Ott, Caroline V; Jensen, Hans M; Jørgensen, Anders; Harmer, J; Paulson, Olaf B; Kessing, Lars V; Siebner, Hartwig R

2018-03-01

Negative neurocognitive bias is a core feature of depression that is reversed by antidepressant drug treatment. However, it is unclear whether modulation of neurocognitive bias is a common mechanism of distinct biological treatments. This randomized controlled functional magnetic resonance imaging study explored the effects of a single electroconvulsive therapy session on self-referent emotional processing. Twenty-nine patients with treatment-resistant major depressive disorder were randomized to one active or sham electroconvulsive therapy session at the beginning of their electroconvulsive therapy course in a double-blind, between-groups design. The following day, patients were given a self-referential emotional word categorization test and a free recall test. This was followed by an incidental word recognition task during whole-brain functional magnetic resonance imaging at 3T. Mood was assessed at baseline, on the functional magnetic resonance imaging day, and after 6 electroconvulsive therapy sessions. Data were complete and analyzed for 25 patients (electroconvulsive therapy: n = 14, sham: n = 11). The functional magnetic resonance imaging data were analyzed using the FMRIB Software Library randomize algorithm, and the Threshold-Free Cluster Enhancement method was used to identify significant clusters (corrected at P < .05). A single electroconvulsive therapy session had no effect on hippocampal activity during retrieval of emotional words. However, electroconvulsive therapy reduced the retrieval-specific neural response for positive words in the left frontopolar cortex. This effect occurred in the absence of differences between groups in behavioral performance or mood symptoms. The observed effect of electroconvulsive therapy on prefrontal response may reflect early facilitation of memory for positive self-referent information, which could contribute to improvements in depressive symptoms including feelings of self-worth with repeated treatments.

Altered Serum Levels of Matrix Metalloproteinase-2, -9 in Response to Electroconvulsive Therapy for Mood Disorders.

PubMed

Shibasaki, Chiyo; Takebayashi, Minoru; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Yamawaki, Shigeto

2016-09-01

Inflammatory processes could underlie mood disorders. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMP) are inflammation-related molecules. The current study sought an association between mood disorders and systemic levels of MMPs and TIMPs. Serum was obtained from patients with mood disorders (n=21) and patients with schizophrenia (n=13) scheduled to undergo electroconvulsive therapy. Serum was also obtained from healthy controls (n=40). Clinical symptoms were assessed by the Hamilton Rating Score for Depression and the Brief Psychiatric Rating Scale. Serum levels of MMPs and TIMPs were quantified by ELISA. The serum levels of MMP-2 in mood disorder patients, but not in schizophrenia patients, prior to the first electroconvulsive therapy session (baseline) was significantly lower than that of healthy controls. At baseline, levels of MMP-9 and TIMP-2, -1 were not different between patients with mood disorder and schizophrenia and healthy controls. After a course of electroconvulsive therapy, MMP-2 levels were significantly increased in mood disorder patients, but MMP-9 levels were significantly decreased in both mood disorder and schizophrenia patients. In mood disorder patients, there was a significant negative correlation between depressive symptoms and serum levels of MMP-2 and a positive correlation between depressive symptoms and MMP-9. In addition, alterations of serum levels of MMP-2 and MMP-9 were significantly correlated each other and were associated with certain depressive symptoms. A change in inflammatory homeostasis, as indicated by MMP-2 and MMP-9, could be related to mood disorders, and these markers appear to be sensitive to electroconvulsive therapy. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT)

PubMed Central

Shibasaki, Chiyo; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Takebayashi, Minoru

2018-01-01

Abstract Background Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Methods Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Results Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. Conclusion The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients. PMID:29025075

Electroconvulsive Therapy Intervention for Parkinson's Disease.

PubMed

Narang, Puneet; Glowacki, Anna; Lippmann, Steven

2015-01-01

Electroconvulsive therapy is an established means to improve function in a variety of psychiatric and neurologic conditions, particularly for patients who remain treatment-refractory. Parkinson's disease is a neurodegenerative disorder that sometimes does not respond well to conventional pharmacotherapies. Reports have indicated that electroconvulsive therapy may be an effective and safe treatment for those patients with Parkinson's disease who are not optimally responding to first-line treatments. Despite these reports, however, electroconvulsive therapy is not often used by clinicians in patients with treatment-resistant Parkinson's disease, perhaps due to stigma, lack of knowledge regarding its safety and efficacy, and/or inability to predict the duration of therapeutic benefit. Our objective was to determine if the available literature on ECT supports it as a safe and effective treatment option in patients with treatment-refractory Parkinson's disease. Motoric improvement induced by electroconvulsive therapy has been documented for decades in persons with Parkinson's disease. Efficacy and safety are reported following electroconvulsive therapy in people with Parkinson's disease who have sub-optimal response to medicines or experience the "on/off" phenomenon to L-dopa. Electroconvulsive therapy is an effective option for acute and maintenance treatment of Parkinson's disease in select patients. Inability to predict how long the beneficial effects of ECT therapy will last in patients with Parkinson's disease may be a reason why this treatment is underutilized by clinicians. More research is warranted to clarify parameters for application and duration of therapeutic benefit in individuals with difficult-to-treat Parkinson's disease.

Electroconvulsive Therapy During Pregnancy.

PubMed

Thyen, Aubrey; Narang, Puneet; Sarai, Simrat; Tegin, Gulay; Lippmann, Steven

2017-07-13

Women often experience worsening mood disorder symptoms during pregnancy. Women with mood disorders have an increased risk for suboptimal prenatal care, inadequate weight gain, and more substance abuse during pregnancy. It is often difficult to balance pharmacotherapy risks to a developing fetus versus not medicinally treating maternal mental health conditions. Electroconvulsive therapy (ECT) is a rapid and effective treatment option that can be an appropriate intervention in some women during pregnancy. This report presents an overview of ECT in pregnancy and the case of a 28-year-old pregnant woman with bipolar mania who responded well to ECT. © Copyright 2017 Physicians Postgraduate Press, Inc.

A Systematic Review and Meta-Analysis of Brief Versus Ultrabrief Right Unilateral Electroconvulsive Therapy for Depression.

PubMed

Tor, Phern-Chern; Bautovich, Alison; Wang, Min-Jung; Martin, Donel; Harvey, Samuel B; Loo, Colleen

2015-09-01

Electroconvulsive therapy (ECT) is an effective depression treatment, but it has potential cognitive side effects. Ultrabrief pulse (UBP) right unilateral (RUL) ECT is an increasingly used treatment option that can potentially combine efficacy with lesser cognitive side effects. However, current trials are underpowered or have conflicting results. A systematic review and meta-analysis was conducted to evaluate the relative efficacy and cognitive effects of brief pulse (BP) and UBP RUL ECT. MEDLINE, EMBASE, PsycINFO, CENTRAL, DARE, and the International Clinical Trials Registry Platform were searched with the search terms ECT, electroconvulsive therapy, electroconvulsive shock, electroconvulsive shock therapy, electrical stimulation, electroconvulsive combined with brief, ultra*, pulse, and trial in English, all fields including title, abstract, subject heading, and full text up to June 20, 2013, for studies comparing BP and UBP RUL ECT in depressed patients that reported formalized mood ratings for depression. Six studies met the inclusion criteria, comprising a total of 689 patients. Efficacy, cognitive, response, and remission outcomes were extracted from each publication or obtained directly from authors. BP RUL ECT was significantly more efficacious in treating depression than UBP RUL ECT (standardized mean difference = 0.25; 95% CI, 0.08–0.41; P = .004) but showed significantly more cognitive side effects in all cognitive domains examined (global cognition, anterograde learning and recall, retrograde memory) (P < .01). The mean number of treatment sessions given was 8.7 for BP ECT and 9.6 for UBP ECT (P < .001). UBP had a lower remission rate (OR = 0.71; 95% CI, 0.51–0.99; P = .045), with a number needed to treat of 12.1. BP compared with UBP RUL ECT was slightly more efficacious in treating depression and required fewer treatment sessions, but led to greater cognitive side effects. The decision of whether to use BP or UBP RUL ECT should be made on an individual patient basis and should be based on a careful weighing of the relative priorities of efficacy versus minimization of cognitive impairment.

Near-infrared spectroscopy of the human brain during electroconvulsive therapy

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Fabbri, Francesco; Nadgir, Shalini; Henry, Michael E.; Renshaw, Perry F.; Franceschini, Maria-Angela

2003-07-01

We report non-invasive, bilateral measurements of cerebral oxygenation performed with near-infrared spectroscopy (NIRS) on ten patients undergoing right unilateral electro-convulsive therapy (ECT). Right unilateral ECT consists of delivering an electrical current through the right brain hemisphere to induce a seizure, which is associated with significant changes in systemic and regional physiological parameters. In this work, we have examined the regional cerebral oxygenation (StO2) measured with NIRS on the right and left sides of the frontal brain region, and the systemic arterial oxygenation (SaO2) measured with pulse oximetry. On the ten patients examined, we have found that the decrease in the cerebral oxygenation on the side ipsilateral to the ECT electrical discharge (ΔStO2(ipsi)) is consistently stronger than the decrease on the contralateral side (ΔStO2(contra)). The average and standard deviation for the ipsilateral and contralateral oxygenation changes across the ten patients are ΔStO2(ipsi) = -22 +/- 10% and ΔStO2(contra) = -6 +/- 10%, respectively. By contrast, we observed two distinct behaviors in the arterial saturation; in five patients, SaO2 did not significantly change during the ECT procedure, and in three patients, SaO2 decreased by -16+/- 6%, an intermediate value with respect to the changes observed in StO2(ipsi) and StO2(contra) (we do not have the SaO2 recording in the remaining two patients for technical reasons). These results indicate that NIRS monitoring of the cerebral oxygenation during ECT has the potential of being a valuable addition to the standard monitoring of arterial saturation with pulse oximetry.

Retrograde Amnesia in Rats, Produced by Electron Beam Exposure.

DTIC Science & Technology

1983-02-01

radiation. Am J Physiol 215:803-806, 1968. 6. Cronholm, B., and L. Molander. Memory disturbances after electroconvulsive therapy : conditions one month after...stimuli have been demonstrated to be effective in producing RA: e.g., electroconvulsive shock (ECS) (14,19); hypoxia (9); and drugs (3,7). Preliminary...effect argues against ionization as a mechanism of CNS activation. Current induction via electroconvulsive shock (ECS) is known to produce RA (14,19

Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT).

PubMed

Shibasaki, Chiyo; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Takebayashi, Minoru

2018-03-01

Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Electroconvulsive Therapy Intervention for Parkinson’s Disease

PubMed Central

Glowacki, Anna; Lippmann, Steven

2015-01-01

Background: Electroconvulsive therapy is an established means to improve function in a variety of psychiatric and neurologic conditions, particularly for patients who remain treatment-refractory. Parkinson’s disease is a neurodegenerative disorder that sometimes does not respond well to conventional pharmacotherapies. Reports have indicated that electroconvulsive therapy may be an effective and safe treatment for those patients with Parkinson’s disease who are not optimally responding to first-line treatments. Despite these reports, however, electroconvulsive therapy is not often used by clinicians in patients with treatment-resistant Parkinson’s disease, perhaps due to stigma, lack of knowledge regarding its safety and efficacy, and/or inability to predict the duration of therapeutic benefit. Objective: Our objective was to determine if the available literature on ECT supports it as a safe and effective treatment option in patients with treatment-refractory Parkinson’s disease. Conclusion: Motoric improvement induced by electroconvulsive therapy has been documented for decades in persons with Parkinson’s disease. Efficacy and safety are reported following electroconvulsive therapy in people with Parkinson’s disease who have sub-optimal response to medicines or experience the “on/off” phenomenon to L-dopa. Electroconvulsive therapy is an effective option for acute and maintenance treatment of Parkinson’s disease in select patients. Inability to predict how long the beneficial effects of ECT therapy will last in patients with Parkinson’s disease may be a reason why this treatment is underutilized by clinicians. More research is warranted to clarify parameters for application and duration of therapeutic benefit in individuals with difficult-to-treat Parkinson’s disease. PMID:26634178

Transient anosmia during acute phase electroconvulsive therapy: a report of 2 cases.

PubMed

Upshaw, William N; Hubbard, Jacqueline D; Ali, Sadia; Fernandez, Jamie Winderbaum

2013-12-01

Treatment-resistant psychiatric illness poses a clinical challenge to psychiatrists in both inpatient and outpatient settings. Although electroconvulsive therapy is a relatively safe option for the treatment of these patients, initiation of this treatment requires a conscientious discussion of the risks and benefits of the procedure to obtain informed consent. The 2 cases presented here describe transient anosmia, a seldom reported but potentially significant adverse effect of electroconvulsive therapy.

Brain Stimulation in Alzheimer's Disease.

PubMed

Chang, Chun-Hung; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Brain stimulation techniques can modulate cognitive functions in many neuropsychiatric diseases. Pilot studies have shown promising effects of brain stimulations on Alzheimer's disease (AD). Brain stimulations can be categorized into non-invasive brain stimulation (NIBS) and invasive brain stimulation (IBS). IBS includes deep brain stimulation (DBS), and invasive vagus nerve stimulation (VNS), whereas NIBS includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), electroconvulsive treatment (ECT), magnetic seizure therapy (MST), cranial electrostimulation (CES), and non-invasive VNS. We reviewed the cutting-edge research on these brain stimulation techniques and discussed their therapeutic effects on AD. Both IBS and NIBS may have potential to be developed as novel treatments for AD; however, mixed findings may result from different study designs, patients selection, population, or samples sizes. Therefore, the efficacy of NIBS and IBS in AD remains uncertain, and needs to be further investigated. Moreover, more standardized study designs with larger sample sizes and longitudinal follow-up are warranted for establishing a structural guide for future studies and clinical application.

Electroconvulsive stimulation (ECS) increases the expression of neuropeptide Y (NPY) in rat brains in a model of neuropathic pain: a quantitative real-time polymerase chain reaction (RT-PCR) study.

PubMed

Okabe, Tadashi; Sato, Chiyo; Matsumoto, Keisuke; Ozawa, Hitoshi; Sakamoto, Atsuhiro

2009-11-01

Electroconvulsive shock therapy (ECT) has been widely used as an effective and established treatment for refractory depression and schizophrenia. Some reports have shown that ECT is also effective for treating refractory neuropathic pain. In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from day 2 after surgery. An electroconvulsive shock (ECS) was administered to rodents once daily for 6 days on days 7-12 after CCI operation using a pulse generator. Thermal and mechanical stimulation tests were performed to assess pain thresholds. Real-time polymerase chain reaction was used to measure the gene expression levels for 5HT(1A)R, 5HT(2A)R, neuropeptide Y (NPY), and GABAA(alpha1)R in the brain. After ECS, the latency to withdrawal from thermal stimulation was significantly increased; however, pain withdrawal thresholds in response to mechanical stimulation were not significantly changed. Expression ratios of NPY were significantly greater after ECS. Symptoms of neuropathic pain improved and expression of NPY in the brain was increased in CCI model rats after ECS, suggesting that changes in the expression of NPY in the brain may be related to the mechanism of action of ECT in treating neuropathic pain.

Decreased Cognitive Functioning After Electroconvulsive Therapy Is Related to Increased Hippocampal Volume: Exploring the Role of Brain Plasticity.

PubMed

van Oostrom, Iris; van Eijndhoven, Philip; Butterbrod, Elke; van Beek, Maria H; Janzing, Joost; Donders, Rogier; Schene, Aart; Tendolkar, Indira

2018-06-01

Electroconvulsive therapy (ECT) is still the most effective treatment of severe and therapy-refractory major depressive disorder. Cognitive side effects are the major disadvantage of ECT. Cognitive deficits are generally temporary in nature and may be mediated by the hippocampus. Recent studies have shown a temporary increase in hippocampal volume and a temporary decrease in cognitive functioning post-ECT compared with pre-ECT. This study investigates whether these volumetric changes are related to changes in cognitive functioning after ECT. Nineteen medication-free patients with treatment-resistant major depressive disorder underwent a whole-brain magnetic resonance imaging scan and a neuropsychological examination (including the Rey auditory verbal learning task, Wechsler Memory Scale Visual Reproduction, fluency, Trail Making Task) within 1 week before and within 1 week after the course of ECT. Electroconvulsive therapy was administered twice a week bitemporally with a brief pulse. A matched healthy control group (n = 18) received the same neuropsychological examination and at a similar interval to that of the patients. Hippocampal volumes increased significantly from pretreatment to posttreatment in patients. Mean performance on cognitive tasks declined, or remained stable, whereas performance in controls generally improved because of retesting effects. The increase in hippocampal volume was related to changes in cognitive performance, indicating that this increase co-occurred with a decrease in cognitive functioning. Our findings tentatively suggest that the temporal increase in hippocampal volume after treatment, which may result from neurotrophic processes and is thought to be crucial for the antidepressive effect, is also related to the temporary cognitive side effects of ECT.

Interactions between ACE inhibitors and classical antiepileptic drugs in the mouse maximal electroshock seizures.

PubMed

Łukawski, Krzysztof; Jakubus, Tomasz; Janowska, Agnieszka; Czuczwar, Stanisław J

2011-11-01

This study evaluated the effect of two angiotensin-converting enzyme (ACE) inhibitors, enalapril and cilazapril, commonly used antihypertensive drugs, on the protective efficacy of the classical antiepileptics - carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and phenobarbital (PB). For this purpose, we used the maximal electroshock seizure (MES) test in mice. Additionally, adverse effects of combined treatment with ACE inhibitors and antiepileptic drugs in the passive avoidance task and chimney test were assessed. All drugs were administered intraperitoneally. Neither enalapril (10, 20 and 30 mg/kg) nor cilazapril (5, 10 and 20mg/kg) affected the threshold for electroconvulsions. Enalapril (30 mg/kg) but not cilazapril (20mg/kg), enhanced the protective action of VPA, decreasing its ED(50) value from 249.5 to 164.9 mg/kg (p<0.01). Free plasma (non-protein-bound) and total brain concentrations of VPA were not significantly influenced by enalapril. Therefore, the observed interaction could be pharmacodynamic in nature. The combinations of ACE inhibitors with other antiepileptics (CBZ, PHT, and PB) were ineffective in that their ED(50) values against MES were not significantly changed. Enalapril and cilazapril remained ineffective as regards memory retention in the passive avoidance task or motor performance in the chimney test. The current study suggests that there are no negative interactions between the studied ACE inhibitors and classical antiepileptic drugs. Enalapril was even documented to enhance the anticonvulsant activity of VPA. Copyright © 2011 Elsevier Inc. All rights reserved.

Bio-heat transfer model of electroconvulsive therapy: Effect of biological properties on induced temperature variation.

PubMed

de Oliveira, Marilia M; Wen, Paul; Ahfock, Tony

2016-08-01

A realistic human head model consisting of six tissue layers was modelled to investigate the behavior of temperature profile and magnitude when applying electroconvulsive therapy stimulation and different biological properties. The thermo-electrical model was constructed with the use of bio-heat transfer equation and Laplace equation. Three different electrode montages were analyzed as well as the influence of blood perfusion, metabolic heat and electric and thermal conductivity in the scalp. Also, the effect of including the fat layer was investigated. The results showed that temperature increase is inversely proportional to electrical and thermal conductivity increase. Furthermore, the inclusion of blood perfusion slightly drops the peak temperature. Finally, the inclusion of fat is highly recommended in order to acquire more realistic results from the thermo-electrical models.

Recurrent Aspiration in a Patient With Gastric Band Undergoing Electroconvulsive Therapy.

PubMed

Lubit, Elana B; Fetterman, Tammy Cohen; Ying, Patrick

2016-06-01

We report a case of a 33-year-old woman with depression and suicidal ideation, treated successfully with electroconvulsive therapy (ECT) in the past. Since her previous course of ECT, she underwent gastric banding, a bariatric surgical procedure associated with increased risk of gastric regurgitation. Despite increasingly stringent measures to minimize the risk of regurgitation and aspiration during ECT, she had several episodes of regurgitation, the last of which precipitated an acute illness consistent with aspiration pneumonitis. We took additional precautions after each event, until she had no further episodes of regurgitation. We discuss the risk posed by the gastric band, the measures we implemented to minimize that risk, and our recommendations for assessment and management of post-gastric banding patients who present for ECT.

Tics as signs of catatonia: electroconvulsive therapy response in 2 men.

PubMed

Dhossche, Dirk M; Reti, Irving M; Shettar, Shashidhar M; Wachtel, Lee E

2010-12-01

Tics have rarely been described in catatonia although tics are sudden and nonrhythmic variants of stereotypic or repetitive movement abnormalities that are considered cardinal symptoms of catatonia. We describe 2 men with tics and self-injurious behavior, who met criteria for catatonia. One patient met criteria for autism. We reported 2 new cases and performed a literature review using PubMed to identify other cases of tics that were treated with electroconvulsive therapy. Tics along with other catatonic symptoms and self-injurious behavior responded to electroconvulsive therapy in 2 men. Eight other patients with tics that were treated with electroconvulsive therapy were found in the literature. Catatonia was recognized in 4 of the 8 patients. Two patients met criteria for autism. Tics, with or without self-injurious behavior, may be signs of catatonia. Patients with tics or Tourette syndrome warrant assessment for catatonia. If catatonia is present, electroconvulsive therapy provides a safe but rarely used alternative to pharmacotherapy, psychosurgery, or invasive brain stimulation in the treatment of tics and Tourette syndrome. © 2010 Lippincott Williams & Wilkins, Inc.

British nurses' attitudes to electroconvulsive therapy, 1945-2000.

PubMed

Adams, John

2015-10-01

The aim of the study was to collect and analyse historical material on nurses' attitudes to electroconvulsive therapy in Britain between 1945-2000. Electroconvulsive therapy became widely used in Britain from the late 1940s onwards and remains in current use, but became one of the main targets of the 'antipsychiatry' movement of the 1960s and 1970s. A cultural history design was used to recreate the perspectives of mental health nurses in the period under review. A range of primary sources including journal articles, textbooks and oral history sources were combined to create a coherent historical account. The controversy surrounding electroconvulsive therapy created a deep-seated ambivalence towards it among mental health nurses. While a sizeable minority were critical of its use and may have taken steps to avoid involvement with it, most acquiesced in providing the treatment. Recorded incidents of outright refusal to participate are few. Mental health nurses' views on electroconvulsive therapy are reflective of the profession's growing knowledge of the use of evidence in debating whether particular therapies should be used. © 2015 John Wiley & Sons Ltd.

Electroconvulsive Therapy Practice in New Zealand.

PubMed

Fisher, Mark Wilkinson; Morrison, John; Jones, Paul Anthony

2017-06-01

The aim of this study was to describe the contemporary practice of electroconvulsive therapy (ECT) in New Zealand. A 53-item questionnaire was sent to all services providing ECT as of December 2015. Electroconvulsive therapy was provided by 16 services covering 15 district health boards funded by the New Zealand government. No private facilities provided ECT. All services providing ECT responded to an online survey questionnaire. Rates of ECT utilization were low relative to similar countries. Survey results indicated ECT was practiced to an overall good standard. Several resource and logistical issues potentially contributing to low ECT utilization were identified. Electroconvulsive therapy in New Zealand is provided using modern equipment and practices. However, overall rates of utilization remain low, perhaps as a result of controversy surrounding ECT and some resourcing issues.

Catatonia after deep brain stimulation successfully treated with lorazepam and right unilateral electroconvulsive therapy: a case report.

PubMed

Quinn, Davin K; Rees, Caleb; Brodsky, Aaron; Deligtisch, Amanda; Evans, Daniel; Khafaja, Mohamad; Abbott, Christopher C

2014-09-01

The presence of a deep brain stimulator (DBS) in a patient who develops neuropsychiatric symptoms poses unique diagnostic challenges and questions for the treating psychiatrist. Catatonia has been described only once, during DBS implantation, but has not been reported in a successfully implanted DBS patient. We present a case of a patient with bipolar disorder and renal transplant who developed catatonia after DBS for essential tremor. The patient was successfully treated for catatonia with lorazepam and electroconvulsive therapy after careful diagnostic workup. Electroconvulsive therapy has been successfully used with DBS in a handful of cases, and certain precautions may help reduce potential risk. Catatonia is a rare occurrence after DBS but when present may be safely treated with standard therapies such as lorazepam and electroconvulsive therapy.

Is electroconvulsive therapy safe in the presence of an intracranial metallic object?: case report and review of the literature.

PubMed

Mortier, Philippe; Sienaert, Pascal; Bouckaert, Filip

2013-09-01

Little is known about the use of electroconvulsive therapy (ECT) in patients with intracranial metallic objects. Theoretically, electric current might cause heating of the metal and damage of the surrounding brain tissue. Moreover, intracranial foreign objects increase the risk for epileptic phenomena and could thus complicate the treatment course. The case of a man with intracranial bullet fragments as a result of a headshot, treated with ECT for mania, is presented. We conducted a PubMed literature search for other relevant cases. In our patient, ECT was completed without complication. Electroconvulsive therapy was safely administered in 22 published cases of patients with intracranial metallic objects. After carefully weighing benefits and risks in each individual case, psychiatrists should not be reluctant to use ECT in patients with intracranial metallic objects. Apart from avoiding empirical dosage titration to minimize the exposure to current, positioning the electrodes to avoid the electric current of heating the metal, and continuing antiepileptic agents in high-risk patients, no precautions need to be considered.

Electroconvulsive Therapy in the Elderly: New Findings in Geriatric Depression.

PubMed

Geduldig, Emma T; Kellner, Charles H

2016-04-01

This paper reviews recent research on the use of electroconvulsive therapy (ECT) in elderly depressed patients. The PubMed database was searched for literature published within the past 4 years, using the search terms: "electroconvulsive elderly," "electroconvulsive geriatric," "ECT and elderly," and "ECT elderly cognition." The studies in this review indicate excellent efficacy for ECT in geriatric patients. Adverse cognitive effects of ECT in this population are usually transient and not typically severe. In addition, continuation/maintenance ECT (C/M-ECT) may be a favorable strategy for relapse prevention in the elderly after a successful acute course of ECT. ECT is an important treatment option for depressed geriatric patients with severe and/or treatment-resistant illness. New data add to the evidence demonstrating that ECT is a highly effective, safe, and well-tolerated antidepressant treatment option for geriatric patients.

Overgeneral memory predicts stability of short-term outcome of electroconvulsive therapy for depression.

PubMed

Raes, Filip; Sienaert, Pascal; Demyttenaere, Koen; Peuskens, Joseph; Williams, J Mark G; Hermans, Dirk

2008-03-01

To investigate the predictive value of overgeneral memory (OGM) for outcome of electroconvulsive therapy (ECT) for depression. The Autobiographical Memory Test was used to measure OGM in 25 patients with depression before ECT. The Hamilton Rating Scale for Depression (HRSD) was administered weekly to 1 week posttreatment. Overgeneral memory did not predict HRSD scores from the last ECT treatment, but did predict HRSD change scores from the last treatment to 1-week follow-up: patients high in OGM experienced a relatively greater increase in HRSD scores after the last treatment. Results further extend the status of OGM as a predictor of an unfavorable course of depression to a previously unstudied ECT population.

Increasing Epilepsy Awareness in Schools: A Seizure Smart Schools Project.

PubMed

Brook, Heather A; Hiltz, Cynthia M; Kopplin, Vicki L; Lindeke, Linda L

2015-08-01

A high prevalence of epilepsy diagnoses and seizure events among students was identified at a large Midwestern school district. In partnership with the Epilepsy Foundation of Minnesota (EFMN), a quality improvement project was conducted to provide education and resources to staff caring for school children with seizures. School nurses (N = 26) were trained as seizure management educators and instructed staff in 21 schools on seizure awareness and response. School nurses utilized new seizure management resources, a procedural guideline, and care plan updates. The majority of school nurses rated the resources and training interventions as "very helpful." School nurse confidence in managing students with seizures increased, seizure action plan use increased, and 88% of children's records with new seizure diagnoses had completed documentation. School nurses played vital roles in increasing seizure awareness as educators and care managers. EFMN is using this project as an exemplar for expanding its Seizure Smart Schools program. © The Author(s) 2015.

Reducing the risk of burns during electroconvulsive therapy.

PubMed

2011-10-01

Poor contact between electroconvulsive therapy (ECT) electrodes and the skin can result in patient burns during ECT treatment. Proper site preparation and electrode application are essential to ensure adequate contact and to reduce the risk of burns.

A Case of Treatment- resistant Depression and Body Dysmorphic Disorder: The Role of Electroconvulsive Therapy Revisited.

PubMed

Mahato, Ram S; San Gabriel, Maria Chona P; Longshore, Carrol T; Schnur, David B

2016-01-01

Body dysmorphic disorder is a common, often disabling condition, and is frequently comorbid with major depressive disorder. Selective serotonin reuptake inhibitors constitute first line set of somatic interventions but the management of refractory patients remains challenging. Electroconvulsive therapy, an often highly beneficial treatment for medication resistant-depression, is not considered an effective therapeutic alternative for treatment refractory body dysmorphic disorder. Here we present a 50-year-old woman with body dysmorphic disorder and comorbid major depressive disorder who remained incapacitated and suicidal despite several trials with selective serotonin reuptake inhibitors and antipsychotic medication. Depressive and dysmorphic symptoms appeared to resolve with electroconvulsive therapy, and remission was sustained for two months. Electroconvulsive therapy has an important place in the management of treatment- resistant depression associated with body dysmorphic disorder, and, in select cases, may be effective for dysmorphic symptoms as well.

Response to Electroconvulsive Therapy in Patients With Autism Spectrum Disorder and Intractable Challenging Behaviors Associated With Symptoms of Catatonia.

PubMed

Sajith, Sreedharan Geetha; Liew, Siew Fai; Tor, Phern Chern

2017-03-01

There are several reports of electroconvulsive therapy (ECT) used in autism spectrum disorder (ASD) in the context of catatonic symptoms. We describe response to ECT in two adults with ASD and intellectual disability with intractable aggression and self-injurious behaviors associated with catatonic symptoms who had not responded to standard interventions. Unilateral ECT at a frequency of 3 times a week was given followed by weekly maintenance ECT. Patients' catatonic symptoms included episodes of agitation and echophenomena. Electroconvulsive therapy resulted in significant improvement in their behavior problems but 1 patient relapsed when the ECT was discontinued or frequency of treatment reduced. The second patient required 2 courses of ECT before improvement which was maintained on weekly ECT. Electroconvulsive therapy could be a potentially beneficial intervention in patients with ASD and severe challenging behaviors associated with catatonic symptoms including agitated or excited forms of catatonia.

Grey matter volume increase following electroconvulsive therapy in patients with late life depression: a longitudinal MRI study

PubMed Central

Bouckaert, Filip; De Winter, François-Laurent; Emsell, Louise; Dols, Annemieke; Rhebergen, Didi; Wampers, Martien; Sunaert, Stefan; Stek, Max; Sienaert, Pascal; Vandenbulcke, Mathieu

2016-01-01

Background The evidence on the mechanisms of action of electroconvulsive therapy (ECT) has grown over the past decades. Recent studies show an ECT-related increase in hippocampal, amygdala and subgenual cortex volume. We examined grey matter volume changes following ECT using voxel-based morphometry (VBM) whole brain analysis in patients with severe late life depression (LLD). Methods Elderly patients with unipolar depression were treated twice weekly with right unilateral ECT until remission on the Montgomery–Åsberg Depression Rating Scale (MADRS) was achieved. Cognition (Mini Mental State Examination) and psychomotor changes (CORE Assessment) were monitored at baseline and 1 week after the last session of ECT. We performed 3 T structural MRI at both time points. We used the VBM8 toolbox in SPM8 to study grey matter volume changes. Paired t tests were used to compare pre- and post-ECT grey matter volume (voxel-level family-wise error threshold p < 0.05) and to assess clinical response. Results Twenty-eight patients (mean age 71.9 ± 7.8 yr, 8 men) participated in our study. Patients received a mean of 11.2 ± 4 sessions of ECT. The remission rate was 78.6%. Cognition, psychomotor agitation and psychomotor retardation improved significantly (p < 0.001). Right- hemispheric grey matter volume was increased in the caudate nucleus, medial temporal lobe (including hippocampus and amygdala), insula and posterior superior temporal regions but did not correlate with MADRS score. Grey matter volume increase in the caudate nucleus region correlated significantly with total CORE Assessment score (r = 0.63; p < 0.001). Limitations Not all participants were medication-free. Conclusion Electroconvulsive therapy in patients with LLD is associated with significant grey matter volume increase, which is most pronounced ipsilateral to the stimulation side. PMID:26395813

Dynamic Cross-Entropy.

PubMed

Aur, Dorian; Vila-Rodriguez, Fidel

2017-01-01

Complexity measures for time series have been used in many applications to quantify the regularity of one dimensional time series, however many dynamical systems are spatially distributed multidimensional systems. We introduced Dynamic Cross-Entropy (DCE) a novel multidimensional complexity measure that quantifies the degree of regularity of EEG signals in selected frequency bands. Time series generated by discrete logistic equations with varying control parameter r are used to test DCE measures. Sliding window DCE analyses are able to reveal specific period doubling bifurcations that lead to chaos. A similar behavior can be observed in seizures triggered by electroconvulsive therapy (ECT). Sample entropy data show the level of signal complexity in different phases of the ictal ECT. The transition to irregular activity is preceded by the occurrence of cyclic regular behavior. A significant increase of DCE values in successive order from high frequencies in gamma to low frequencies in delta band reveals several phase transitions into less ordered states, possible chaos in the human brain. To our knowledge there are no reliable techniques able to reveal the transition to chaos in case of multidimensional times series. In addition, DCE based on sample entropy appears to be robust to EEG artifacts compared to DCE based on Shannon entropy. The applied technique may offer new approaches to better understand nonlinear brain activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Electroconvulsive therapy for lycanthropy and Cotard syndrome: a case report.

PubMed

Grover, Sandeep; Shah, Ruchita; Ghosh, Abhishek

2010-12-01

We present a case of psychotic depression presenting with lycanthropy (being converted to a pig) and Cotard syndrome simultaneously and treated with electroconvulsive therapy. A 37-year-old female patient developed psychotic depression after a stressor (a possibility of having a malignancy). As her depression worsened, she developed delusional belief of self being metamorphosed to a pig and her children also being metamorphosed into pig. In addition, she had the delusional belief that her own body and body of her children was rotting away. She was treated with electroconvulsive therapy along with venlafaxine and olanzapine, with which she improved completely.

Comparing ECT data of two different inpatient clinics: propofol or thiopental?

PubMed

Yazici, Esra; Bosgelmez, Sukriye; Tas, Halil Ibrahim; Karabulut, Umit; Yazici, Ahmet Bulent; Yildiz, Mustafa; Kirpinar, Ismet

2013-10-01

This study compares the data of (modified) electroconvulsive theraphy (ECT) applications from two different inpatient clinics in Turkey: Kocaeli Derince Training and Research Hospital (Clinic-I) and Kocaeli University (Clinic-II). Recorded files of patients from the two clinics were compared in terms of ECT indications, number and duration of seizures, and anesthetic agents used (propofol vs. thiopental). ECT applications occurring between January 2011 and January 2013 were included in the study. A total of 86 patients (9.5% of the inpatients) received ECT in Clinic-I and 103 patients (21.1% of the inpatients) in Clinic-II during the period studied. The yearly ECT rate (treated person rate per 10,000 per year) was 0.59/10,000 for Kocaeli (Turkey) as a whole. The overall number of ECT applications was 539 in Clinic-I and 999 in Clinic-II, and the average number of ECT sessions for each patient was 6.4 ± 2.33 in Clinic-I and 9.69 ± 4.66 in Clinic-II. The majority of indications were depressive disorders and insufficient response to medicine. Patients in the clinic which utilized thiopental as the anesthetic agent experienced more cardiovascular and respiratory side effects than the one which used propofol. The number of ECT sessions required was greater for patients with schizoaffective disorder than for others. The administration of ECT was considered to be a reliable method of treatment in these clinics. With respect to specific anesthetic agents, propofol was found to have less hemodynamic side effects and shorter seizure durations than thiopental.

Repeated seizures induce long-term increase in hippocampal benzodiazepine receptors.

PubMed Central

McNamara, J O; Peper, A M; Patrone, V

1980-01-01

Repeated seizures, whether induced by kindling or electroshock, caused a long-lasting (at least 24 hr) increase of [3H]diazepam binding in hippocampal membranes of Sprague-Dawley rats. Scatchard analyses demonstrated that increased numbers of binding sites accounted for the increase. Neither repeated hypoxia nor repeated administration of electrical current without inducing seizures caused an increase of [3H]diazepam binding. Regardless of the method used for seizure induction, the response was graded in that large numbers of seizures were required to induce significant increases, whereas fewer seizures induced only slight increases. We suggest that the receptor increases imply a heightened response to benzodiazepines and more powerful hippocampal recurrent inhibition. PMID:6930682

Electroconvulsive Therapy (ECT) and Race: A Report of ECT Use and Sociodemographic Trends in Texas.

PubMed

Williams, Julie; Chiu, Lawrence; Livingston, Robin

2017-06-01

Minimal research on race and other sociodemographic disparities in patients receiving electroconvulsive therapy (ECT) exists. One previously noted national trend reveals whites receiving ECT disproportionately more than other races. The aim of this study is to determine whether a county ECT program demonstrates similar disparities observed at the state and national levels. This study examined 21 years of ECT data, between 1993 and 2014, provided by the Texas Department of State Health Services, focusing on race, sex, age, and payer source and 2.5 years of the same variables from a Harris County hospital ECT program. In addition, population demographic data for Harris County and the state of Texas during the same period were obtained from the Department of State Health Services Web site. Despite an overall decrease in the population of whites countywide and statewide, whites continue to use more ECT than African Americans, Latinos, and Asians in both Harris County and Texas. However, the rates of ECT use in minorities increased overall. Both countywide and statewide, ECT was used more than twice as often in women than men. Statewide, elderly patients (>65 years old) saw decreases in ECT use, and there was an increase in private third-party payer source. Electroconvulsive therapy remains underused among African Americans, Latinos, and Asians. Hypotheses and areas for future study include cultural beliefs, stigma, patient and provider knowledge of ECT, and access to care. Despite this, the general use of ECT in Texas has increased overall, and minority use is slowly on the rise.

Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study.

PubMed

Bjoerke-Bertheussen, Jeanette; Schoeyen, Helle; Andreassen, Ole A; Malt, Ulrik F; Oedegaard, Ketil J; Morken, Gunnar; Sundet, Kjetil; Vaaler, Arne E; Auestad, Bjoern; Kessler, Ute

2017-12-21

Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form. Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085). This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution. ClinicalTrials.gov: NCT00664976. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Electroconvulsive therapy after maxillofacial metallic implants.

PubMed

Freeman, G Mark; Perry, Matthew T; Manatt, George S; Cristancho, Pilar

2014-03-01

A growing body of literature suggests that electroconvulsive therapy (ECT) can be safely utilized in patients with craniofacial metallic implants. Here we provide radiographic images and the clinical course of a 49-year-old woman with both maxillary and mandibular metallic implants who safely received ECT.

Electroconvulsive Therapy and Suicide.

ERIC Educational Resources Information Center

Tanney, Bryan L.

1986-01-01

When the effectiveness and mortality-morbidity of electroconvulsive therapy (ECT) are compared with those of drug therapies, it appears that ECT is an effective and preferred treatment strategy. It remains underutilized as a modality of suicide prevention. Addresses controversies that presently limit the use of this treatment. (Author/ABB)

Maintenance electroconvulsive therapy for depression with catatonia in a young woman with Down syndrome.

PubMed

Torr, Jennifer; D'Abrera, Juan Carlos

2014-12-01

To describe and discuss the use of maintenance electroconvulsive therapy (ECT) in a young woman with Down syndrome and depression with catatonia. Clinical case report. A 23-year-old woman with Down syndrome (mosaic type) and a 4-year history of depressed mood triggered by adverse life events presented with mutism, psychomotor retardation, and compromised oral intake. Multiple trials of antidepressant medications were either ineffective or complicated by adverse reactions. She improved rapidly with a course of bilateral ECT but required maintenance ECT to sustain recovery. A series of premorbid, morbid, and post-treatment drawings by the young woman highlight the efficacy of treatment. Electroconvulsive therapy was found to be a safe and effective treatment for life-threatening mental illness in a young woman with Down syndrome who had failed multiple trials of antidepressant medications. This case highlights the importance of considering catatonia as a diagnosis in persons with Down syndrome and the effectiveness of electroconvulsive treatment.

Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

NASA Astrophysics Data System (ADS)

Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

1998-12-01

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

Efficacy and cognitive side effects after brief pulse and ultrabrief pulse right unilateral electroconvulsive therapy for major depression: a randomized, double-blind, controlled study.

PubMed

Spaans, Harm-Pieter; Verwijk, Esmée; Comijs, Hannie C; Kok, Rob M; Sienaert, Pascal; Bouckaert, Filip; Fannes, Katrien; Vandepoel, Koen; Scherder, Erik J A; Stek, Max L; Kho, King H

2013-11-01

To compare the efficacy and cognitive side effects of high-dose unilateral brief pulse electroconvulsive therapy (ECT) with those of high-dose unilateral ultrabrief pulse ECT in the treatment of major depression. From April 2007 until March 2011, we conducted a prospective, double-blind, randomized multicenter trial in 3 tertiary psychiatric hospitals. All patients with a depressive disorder according to DSM-IV criteria were eligible. Depression severity was assessed with the Montgomery-Asberg Depression Rating Scale; primary efficacy outcomes were response, defined as a score decrease ≥ 60% from baseline, and remission, defined as a score < 10 at 2 consecutive weekly assessments. Total scores on the Autobiographical Memory Interview and Amsterdam Media Questionnaire were the primary outcome measures for retrograde amnesia. Other cognitive domains included category fluency (semantic memory) and letter fluency (lexical memory). Patients received twice-weekly unilateral brief pulse (1.0 millisecond) or ultrabrief pulse (0.3-0.4 millisecond) ECT 8 times seizure threshold until remission, for a maximum of 6 weeks. Of the 116 patients, 75% (n = 87) completed the study. Among completers, 68.4% (26/58) of those in the brief pulse group achieved remission versus 49.0% (24/49) of those in the ultrabrief pulse group (P = .019), and the brief pulse group needed fewer treatment sessions to achieve remission: mean (SD) of 7.1 (2.6) versus 9.2 (2.3) sessions (P = .008). No significant group differences were found in the evaluation of the cognitive assessments. The efficacy and speed of remission seen with high-dose brief pulse right unilateral ECT twice weekly were superior to those seen with high-dose ultrabrief pulse right unilateral ECT, with equal cognitive side effects as defined by retrograde amnesia, semantic memory, and lexical memory. Netherlands National Trial Register number: NTR1304. © Copyright 2013 Physicians Postgraduate Press, Inc.

A randomized, double-blind, placebo-controlled trial on the role of preemptive analgesia with acetaminophen [paracetamol] in reducing headache following electroconvulsive therapy [ECT].

PubMed

Isuru, Amila; Rodrigo, Asiri; Wijesinghe, Chamara; Ediriweera, Dileepa; Premadasa, Shan; Wijesekara, Carmel; Kuruppuarachchi, Lalith

2017-07-28

Electroconvulsive therapy (ECT) is a safe and efficient treatment for several severe psychiatric disorders, but its use is limited by side effects. Post-ECT headache is one of the commonest side effects. Preemptive analgesia is effective in post-surgical pain management. The most commonly used analgesic is acetaminophen (paracetamol). However, acetaminophen as a preemptive analgesic for post-ECT headache has not been studied adequately. This study was conducted to compare the incidence and severity of post-ECT headache in patients who were administered acetaminophen pre-ECT with a placebo group. This study was a randomised, double-blind, placebo-controlled trial. Sixty-three patients received 1 g acetaminophen and 63 patients received a placebo identical to acetaminophen. The incidence and severity of headache 2 h before and after ECT were compared between placebo and acetaminophen groups. The severity was measured using a visual analog scale. Generalised linear models were used to evaluate variables associated with post ECT headache. Demographic and clinical variables of placebo and acetaminophen groups were comparable except for the energy level used to induce a seizure. Higher proportion of the placebo group (71.4%) experienced post-ECT headache when compared to the acetaminophen group (p < 0.001). The median pain score for headache was 0 (Inter quartile range: 0-2) in acetaminophen group whereas the score was 2 (IQR: 0-4) in placebo group (P < 0.001). Model fitting showed that the administration of acetaminophen is associated with less post-ECT headache (odds ratio = 0.23, 95% CI: 0.11-0.48, P < 0.001). A significant reduction was seen in both the incidence and severity of post-ECT headache with preemptive analgesia with acetaminophen. Ethical approval was granted by an Ethic review committee, University of Kelaniya, Sri Lanka (P/166/10/2015) and the trial was registered in the Sri Lanka Clinical Trials Registry ( SLCTR/2015/27 ).

Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

PubMed

Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

2014-10-03

Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

Is electroconvulsive therapy during pregnancy safe?

PubMed

Jiménez-Cornejo, Magdalena; Zamorano-Levi, Natalia; Jeria, Álvaro

2016-12-07

Therapeutic options for psychiatric conditions are limited during pregnancy because many drugs are restricted or contraindicated. Electroconvulsive therapy constitutes an alternative, however there is controversy over its safety. Using the Epistemonikos database, which is maintained by searching multiple databases, we found five systematic reviews, including 81 studies overall describing case series or individual cases. Data were extracted from the identified reviews and summary tables of the results were prepared using the GRADE method. We concluded it is not clear what are the risks associated with electroconvulsive therapy during pregnancy because the certainty of the existing evidence is very low. Likewise, existing systematic reviews and international clinical guidelines differ in their conclusions and recommendations.

Seizure Correlates with Prolonged Hospital Stay, Increased Costs, and Increased Mortality in Nontraumatic Subdural Hematoma.

PubMed

Joseph, Jacob R; Smith, Brandon W; Williamson, Craig A; Park, Paul

2016-08-01

Nontraumatic subdural hematoma (NTSDH) is a common neurosurgical disease process, with mortality reported as high as 13%. Seizure has a known association with NTSDH, although patient outcomes have not previously been well studied in this population. The purpose of this study was to examine the relationship between in-hospital seizure and inpatient outcomes in NTSDH. Using the University HealthSystem Consortium (UHC) database, we performed a retrospective cohort study of adults with a principal diagnosis of NTSDH (International Classification of Diseases, Ninth Revision code 43.21) between 2011 and 2015. Patients with in-hospital seizure (International Classification of Diseases, Ninth Revision codes 34500-34591, 78033, 78039) were compared with those without. Patients with a history of seizure before arrival were excluded. Patient demographics, hospital length of stay (LOS), intensive care unit stay, in-hospital mortality, and direct costs were recorded. A total 16,928 patients with NTSDH were identified. Mean age was 69.2 years, and 64.7% were male. In-hospital seizure was documented in 744 (4.40%) patients. Hospital LOS was 17.64 days in patients with seizure and 6.26 days in those without (P < 0.0001). Mean intensive care unit stay increased from 3.36 days without seizure to 9.36 days with seizure. In-hospital mortality was 9.19% in patients without seizure and 16.13% in those with seizure (P < 0.0001). Direct costs were $12,781 in patients without seizure and $38,110 in those with seizure (P < 0.0001). Seizure in patients with NTSDH correlates with significantly increased total LOS and increased mortality. Direct costs are similarly increased. Further studies accounting for effects of illness severity are necessary to validate these results. Copyright © 2016 Elsevier Inc. All rights reserved.

Propofol ameliorates electroconvulsive shock-induced learning and memory impairment by regulation of synaptic metaplasticity via autophosphorylation of CaMKIIa at Thr 305 in stressed rats.

PubMed

Ren, Li; Zhang, Fan; Min, Su; Hao, Xuechao; Qin, Peipei; Zhu, Xianlin

2016-06-30

Electroconvulsive therapy (ECT) is an effective treatment for depression, but it can induce learning and memory impairment. Our previous study found propofol (γ-aminobutyric acid (GABA) receptor agonist) could ameliorate electroconvulsive shock (ECS, an analog of ECT to animals)-induced cognitive impairment, however, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of propofol on metaplasticity and autophosphorylation of CaMKIIa in stressed rats receiving ECS. Depressive-like behavior and learning and memory function were assessed by sucrose preference test and Morris water test respectively. LTP were tested by electrophysiological experiment, the expression of CaMKIIa, p-T305-CaMKII in hippocampus and CaMKIIα in hippocampal PSD fraction were evaluated by western blot. Results suggested ECS raised the baseline fEPSP and impaired the subsequent LTP, increased the expression of p-T305-CaMKII and decreased the expression of CaMKIIα in hippocampal PSD fraction, leading to cognitive dysfunction in stressed rats. Propofol could down-regulate the baseline fEPSP and reversed the impairment of LTP partly, decreased the expression of p-T305-CaMKII and increased the expression of CaMKIIα in hippocampal PSD fraction and alleviated ECS-induced learning and memory impairment. In conclusion, propofol ameliorates ECS-induced learning and memory impairment, possibly by regulation of synaptic metaplasticity via p-T305-CaMKII. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Electroconvulsive shock increases preproenkephalin messenger RNA abundance in rat hypothalamus.

PubMed Central

Yoshikawa, K; Hong, J S; Sabol, S L

1985-01-01

Daily administration of electroconvulsive shock (ECS) to rats for 10 days increased the content of [Met5]enkephalin in the hypothalamus and the striatum by 64% and 45%, respectively. The effect of ECS on the relative abundance of mRNA coding for the enkephalin precursor preproenkephalin was investigated. Analysis by cell-free translation of polyadenylylated RNA and immunoprecipitation of preproenkephalin revealed ECS-elicited increases of 79% and 14% in preproenkephalin mRNA activity in the hypothalamus and striatum, respectively. ECS treatment did not affect the general translational activity of total polyadenylylated RNA from these brain regions. A 32P-labeled probe prepared from a rat preproenkephalin cDNA clone hybridized with an apparently single species of polyadenylylated RNA of approximately equal to 1450 nucleotides from both hypothalamus and striatum. Dot-blot hybridization of polyadenylylated RNA with the rat probe indicated that ECS elicits a 76% increase in the preproenkephalin mRNA abundance in the hypothalamus and no significant change in the striatum. These results suggest that ECS treatment leads to enhanced biosynthesis of the enkephalin precursor in hypothalamic neurons. Images PMID:2578669

Brief Report: Electroconvulsive Therapy for Malignant Catatonia in an Autistic Adolescent

ERIC Educational Resources Information Center

Wachtel, Lee Elizabeth; Griffin, Margaret Merrie; Dhossche, Dirk Marcel; Reti, Irving Michael

2010-01-01

A 14-year-old male with autism and mild mental retardation developed malignant catatonia characterized by classic symptoms of catatonia, bradycardia and hypothermia. Bilateral electroconvulsive therapy and lorazepam were required for resolution. The case expands the occurrence of catatonia in autism into its malignant variant.

Electroconvulsive Therapy: A Primer for Mental Health Counselors.

ERIC Educational Resources Information Center

Leinbaugh, Tracy C.

2001-01-01

Electroconvulsive therapy is the treatment of choice for severe depressive episodes. Although little definitive research exists to explain its effectiveness, since its development in 1938 it has proven effective for the treatment of depression with psychotic features and suicidal ideation. Explains the procedure and discusses implications for the…

Achieving Competency in Electroconvulsive Therapy: A Model Curriculum

ERIC Educational Resources Information Center

Dolenc, Tamara J.; Philbrick, Kemuel L.

2007-01-01

Objective: This article illustrates a model electroconvulsive therapy (ECT) curriculum with specific parameters of both practice-based learning and medical knowledge. Method: The authors review the recommendations of the APA Task Force on ECT as they relate to training in ECT in psychiatry residency programs, and discuss diverse educational…

Research on electroconvulsive therapy in India: An overview

PubMed Central

Gangadhar, Bangalore N.; Phutane, Vivek H.; Thirthalli, Jagadisha

2010-01-01

The contribution of researchers from India in the field of electroconvulsive therapy (ECT) has been substantial. Over 250 papers have been published by authors from India in the past five decades on this issue; about half of these have appeared in the Indian Journal of Psychiatry. This article summarizes the papers on ECT research that have appeared in the Journal. A bulk of these articles has focused on establishing the efficacy in different disorders. Considerable numbers of papers describe refinement in the ECT procedure, including anesthetic modification, ECT machine and EEG monitoring. Papers on neurobiology of ECT and long-term follow-up of ECT-treated patients form a minority. Despite the decline in the use of ECT across the globe, papers on ECT have only increased in the recent decades in the Journal. PMID:21836706

Electroconvulsive therapy-induced Wolff-Parkinson-White syndrome: a case report.

PubMed

Enomoto, Shingo; Yoshino, Aihide; Takase, Bonpei; Kuwahara, Tatsuro; Tatsuzawa, Yasutaka; Nomura, Soichiro

2013-01-01

Wolff-Parkinson-White (WPW) syndrome is characterized by premature ventricular excitation due to the presence of an abnormal accessory pathway. Electrocardiography (ECG) of patients with WPW syndrome portrays a short PR interval and a wide QRS interval with a delta wave. Herein, we report the case of a patient with schizophrenia who developed a wide QRS interval with a delta wave immediately following electroconvulsive therapy (ECT). Initially, the delta wave disappeared within 2 days after ECT. However, the duration of the delta wave increased exponentially to 4 months when ECT was repeated. Although the patient's cardiocirculatory dynamics remained normal, we continued to monitor her ECG until the delta wave disappeared because WPW syndrome can lead to serious arrhythmia. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of Electroconvulsive Therapy on Cognitive Functions of Rats with Depression-Like Disorders Induced by Ultrasound Exposure.

PubMed

Ushakova, V M; Zubkov, E A; Morozova, A Y; Gorlova, A V; Pavlov, D A; Inozemtsev, A N; Chekhonin, V P

2017-09-01

We studied the effect of electroconvulsive therapy on cognitive functions in rats with depression-like disorder caused by exposure to ultrasound of varying frequency (20-45 kHz). Object recognition and Morris water-maze tests revealed no negative effects of the therapy on memory. Moreover, positive effect of therapy was demonstrated that manifested in amelioration of memory disturbances in depression-like disorders in these behavioral tests. The results of this study do not support the idea about side effects of electroconvulsive therapy, in particular, development of transient amnesia, and are a prerequisite for a more thorough study of internal mechanisms of the effect of the therapy on cognitive sphere.

Postictal ventricular tachycardia after electroconvulsive therapy treatment associated with a lithium-duloxetine combination.

PubMed

Heinz, Boeker; Lorenzo, Perniola; Markus, Risch; Holger, Himmighoffen; Beatrix, Roemer; Erich, Seifritz; Alain, Borgeat

2013-09-01

This report addresses the dilemma of continuing lithium prophylaxis and antidepressant therapy in view of cardiovascular adverse effects under electroconvulsive therapy (ECT) in patients with a long history of recurrent affective disorders. A severely depressed 48-year-old woman who had been treated with lithium for 18 years developed a ventricular tachycardia during ECT. Possible interaction with succinylcholine was taken into account, and rocuronium was used as an alternative muscle relaxant. Electroconvulsive therapy was continued without adverse effects after reduction of lithium and withdrawal from duloxetine. Systemic studies on cardiac adverse effects of serotonin and norepinephrine reuptake inhibitors and serotonin and norepinephrine reuptake inhibitor-lithium combinations during ECT are needed.

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

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.

Impact on Psychiatric Interns of Watching Live Electroconvulsive Treatment

ERIC Educational Resources Information Center

Gazdag, Gabor; Sebestyen, Gabor; Ungvari, Gabor S.; Tolna, Judit

2009-01-01

Objective: Watching a live electroconvulsive treatment (ECT) has both positive and negative effects on spectators. The authors aim to survey the attitude change towards ECT in interns after watching a live ECT session. Methods: A 23-item questionnaire was administered to 66 interns before and after watching ECT. Results: In five statements, the…

Practice Parameter for Use of Electroconvulsive Therapy with Adolescents

ERIC Educational Resources Information Center

Ghaziuddin, Neera; Kutcher, Stanley P.; Knapp, Penelope

2004-01-01

Electroconvulsive therapy (ECT) may be an effective treatment for adolescents with severe mood disorders and other Axis I psychiatric disorders when more conservative treatments have been unsuccessful. ECT may be considered when there is a lack of response to two or more trials of pharmacotherapy or when the severity of symptoms precludes waiting…

Teaching Electroconvulsive Therapy to Medical Students: Effects of Instructional Method on Knowledge and Attitudes

ERIC Educational Resources Information Center

Warnell, Ronald L.; Duk, Anthony D.; Christison, George W.; Haviland, Mark G.

2005-01-01

Objective: To compare the effects of learning about electroconvulsive therapy (ECT) via live observation to learning via an instructional videotape. Method: During their psychiatry clerkship, 122 medical students were randomized using these two educational methods, and their ECT knowledge and attitudes were assessed during the first and last weeks…

A case of Todd's Palsy following unilateral electroconvulsive therapy

PubMed Central

Bell, Christine; Lepping, Peter; Clifford, John; Gardner-Thorpe, Catherine

2012-01-01

This case describes a woman undergoing unilateral electroconvulsive therapy (ECT) who developed a Todd's Palsy following the treatment, and which resolved when converted to bilateral ECT. We go on to hypothesize that this rare side effect may be an indication of the need to switch laterality during a course of ECT. PMID:22988330

Electroconvulsive Therapy in Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report and Review of the Literature.

PubMed

Coffey, M Justin; Cooper, Joseph J

2016-12-01

There is a growing scientific literature describing the neuropsychiatric symptoms of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, including the use of electroconvulsive therapy (ECT) to treat those symptoms. We sought to consolidate this literature into a review that highlights its relevance to ECT practitioners. We performed a PubMed search using the terms electroconvulsive therapy and encephalitis, autoimmune encephalitis, or anti-NMDA receptor encephalitis. We reviewed all relevant studies in detail, cross-referenced all bibliographies, and collected key clinical information related to the practice of ECT. We identified 6 studies offering patient-level descriptions of the use of ECT in patients with anti-NMDA receptor encephalitis. In all cases ECT was used to target symptoms of catatonia. Electroconvulsive therapy was delivered safely and effectively irrespective of the timing of diagnosis, tumor removal, or immunotherapy. There are no controlled data on the use of ECT in anti-NMDA receptor encephalitis. Further investigation is needed to determine whether ECT has a disease-modifying effect on this form of autoimmune encephalitis.

Treatment-resistant, five-year long, postpartum-onset Capgras episode resolving after electroconvulsive therapy.

PubMed

Rapinesi, Chiara; Kotzalidis, Georgios D; Del Casale, Antonio; Ferri, Vittoria Rachele; Di Pietro, Simone; Scatena, Paola; Serata, Daniele; Danese, Emanuela; Sani, Gabriele; Koukopoulos, Alexia E; Angeletti, Gloria; Girardi, Paolo

2015-01-01

Postpartum psychosis, which rarely presents with Capgras syndrome (delusional misidentification), requires rapid symptom resolution. First-line drugs have important drawbacks, such as delayed onset of clinical response and secretion in breast milk. In this report, we report successful treatment of a treatment-resistant woman presenting with treatment-resistant Capgras syndrome, with onset during postpartum. A 36-year-old woman had presented with Capgras syndrome during postpartum. For more than five years, she believed her son and other family members were substituted by impostors. All adequately administrated treatments were unsuccessful. We suggested electroconvulsive therapy to overcome treatment resistance. After six electroconvulsive therapy sessions, delusions of doubles subsided and other symptoms improved. She was discharged two weeks later with a mood stabilizer and low-dose atypical antipychotic combination and is well at the one-and-a-half-year follow-up. Electroconvulsive therapy followed by a mood stabilizer-antipsychotic drug combination showed rapid, permanent, and effective control of long-standing Capgras syndrome in a young woman. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Impedance testing on cochlear implants after electroconvulsive therapy.

PubMed

McRackan, Theodore R; Rivas, Alejandro; Hedley-Williams, Andrea; Raj, Vidya; Dietrich, Mary S; Clark, Nathaniel K; Labadie, Robert F

2014-12-01

Cochlear implants (CI) are neural prostheses that restore hearing to individuals with profound sensorineural hearing loss. The surgically implanted component consists of an electrode array, which is threaded into the cochlea, and an electronic processor, which is buried under the skin behind the ear. The Food and Drug Administration and CI manufacturers contend that electroconvulsive therapy (ECT) is contraindicated in CI recipients owing to risk of damage to the implant and/or the patient. We hypothesized that ECT does no electrical damage to CIs. Ten functional CIs were implanted in 5 fresh cadaveric human heads. Each head then received a consecutive series of 12 unilateral ECT sessions applying maximum full pulse-width energy settings. Electroconvulsive therapy was delivered contralaterally to 5 CIs and ipsilaterally to 5 CIs. Electrical integrity testing (impedance testing) of the electrode array was performed before and after CI insertion, and after the first, third, fifth, seventh, ninth, and 12th ECT sessions. Electroconvulsive therapy was performed by a staff psychiatrist experienced with the technique. Explanted CIs were sent back to the manufacturer for further integrity testing. No electrical damage was identified during impedance testing. Overall, there were statistically significant decreases in impedances (consistent with no electrical damage) when comparing pre-ECT impedance values to those after 12 sessions. There was no statistically significant difference (P > 0.05) in impedance values comparing ipsilateral to contralateral ECT. Manufacturer testing revealed no other electrical damage to the CIs. Electroconvulsive therapy does not seem to cause any detectable electrical injury to CIs.

Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model.

PubMed

Luszczki, Jarogniew J; Czernecki, Remigiusz; Wojtal, Katarzyna; Borowicz, Kinga K; Czuczwar, Stanislaw J

2008-11-01

Accumulating evidence indicates that agmatine (AGM--an endogenous neuromodulator/neurotransmitter in the brain) exerts the anticonvulsant action in various in vivo experiments. Therefore, the aim of this study was to assess the influence of AGM on the protective action of numerous conventional and newer antiepileptic drugs [carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), topiramate (TPM) and valproate (VPA)] in the mouse maximal electroshock seizure (MES) model. Results indicate that AGM (up to 100 mg/kg, i.p., 45 min before the test) neither altered the threshold for electroconvulsions nor protected the animals against MES-induced seizures in mice. Moreover, AGM (100 mg/kg, i.p.) significantly enhanced the anticonvulsant effects of PB and VPA in the MES test by reducing their ED50 values from 22.54 to 16.82 mg/kg (P < 0.01) for PB, and from 256.1 to 210.6 mg/kg (P < 0.05) for VPA, respectively. In contrast, AGM at 100 mg/kg (i.p.) had no significant effect on the antielectroshock action of the remaining drugs tested (CBZ, LTG, OXC, PHT, and TPM) in mice. Estimation of total brain PB and VPA concentrations revealed that the observed interactions between AGM and PB or VPA in the MES test were pharmacodynamic in nature because neither total brain PB, nor total brain VPA concentrations were altered after i.p. administration of AGM at 100 mg/kg. Moreover, none of the examined combinations of AGM (100 mg/kg) with CBZ, LTG, OXC, PB, PHT, TPM, and VPA (at their ED50 values from the MES test) affected motor coordination in the chimney test, long-term memory in the passive avoidance task, and muscular strength in the grip-strength test in mice, indicating no acute adverse effects in animals. In conclusion, one can ascertain that the selective potentiation of the antielectroshock action of PB and VPA by AGM, lack of any pharmacokinetic interactions between drugs and no acute adverse effects, make the combinations of AGM with PB or VPA of pivotal importance for epileptic patients. It seems that modulation of AGM concentration in the brain may occur favorable in further clinical practice.

Clinical usefulness and economic implications of continuation/maintenance electroconvulsive therapy in a Spanish National Health System public hospital: A case series.

PubMed

Rodriguez-Jimenez, Roberto; Bagney, Alexandra; Torio, Iosune; Caballero, Montserrat; Ruiz, Pedro; Rivas, Francisco de Paula Jose; Jimenez-Arriero, Miguel Angel

2015-01-01

Continuation/maintenance electroconvulsive therapy has been shown to be effective for prevention of relapse in affective and psychotic disorders. However, there is a limited nubber of studies that investigate clinical management, associated costs, and perceived quality variables. A series of 8 cases included during the first 18 months of the Continuation/Maintenance Electroconvulsive Therapy Program of the Psychiatry Department at 12 de Octubre University Hospital is presented. Clinical variables (Clinical Global Impression-Improvement Scale, length of hospitalization, number of Emergency Department visits, number of urgent admissions) before and after inclusion in the continuation/maintenance electroconvulsive therapy program were compared for each patient, as well as associated costs and perceived quality. After inclusion in the program, 50.0% of patients reported feeling « much better » and 37.5% « moderately better » in the Clinical Global Impression-Improvement Scale. In addition, after inclusion in the continuation/maintenance electroconvulsive therapy program, patients were hospitalized for a total of 349 days, visited the Emergency Department on 3 occasions, and had 2 urgent admissions, compared to 690 days of hospitalization (P = .012), 26 Emergency Department visits (P = .011) and 22 urgent admissions (P = .010) during the same period before inclusion in the program. Associated direct costs per day of admission were reduced to 50.6% of the previous costs, and costs associated with Emergency Department visits were reduced to 11.5% of the previous costs. As regards perceived quality, 87.5% of patients assessed the care and treatment received as being « very satisfactory », and 12.5% as « satisfactory ». This continuation/maintenance electroconvulsive therapy program has shown to be clinically useful and to have a favourable economic impact, as well as high perceived quality. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry.

PubMed

Herzog, Andrew G; Mandle, Hannah B; Cahill, Kaitlyn E; Fowler, Kristen M; Hauser, W Allen

2016-07-01

The aim of this study was to determine whether categories of contraception differ in their impact on seizures in women with epilepsy and whether the impact varies by antiepileptic drug category. Retrospective survey data came from 2712 contraceptive experiences reported by 1144 women with epilepsy. We compared risk ratios for reports of increase and decrease in seizure frequency on hormonal versus nonhormonal contraception, stratified by antiepileptic drug categories. More women with epilepsy reported a change in seizures on hormonal (28.2%) than on nonhormonal contraception (9.7%) (p<0.0001). The risk ratio for seizure increase on hormonal (18.7%) versus nonhormonal contraception (4.2%) was 4.47 (p<0.0001). The risk ratio for seizure decrease on hormonal (9.5%) versus nonhormonal contraception (5.5%) was 1.71, p<0.0001. On hormonal contraception, the risk ratio for seizure increase was greater than for decrease (1.98, p<0.0001). In comparison to combined pills, both hormonal patch and progestin-only pills had greater risk ratios for seizure increase. Depomedroxyprogesterone was the only hormonal method with a greater risk ratio for seizure decrease than combined pills. Seizure increase was greater for hormonal than nonhormonal contraception for each antiepileptic drug category (p<0.001). On hormonal contraception, relative to the non-enzyme-inducing antiepileptic drug category which had the lowest rate, each of the other categories had significantly greater risks for seizure increase, especially the enzyme-inhibiting (valproate) category (risk ratio=2.53, p=0.0002). The findings provide community-based, epidemiological survey evidence that contraceptive methods may differ in their impact on seizures and that this impact may vary by antiepileptic drug category. Copyright © 2016. Published by Elsevier Inc.

Use of ECT in Nepal: A One Year Study From the Country's Largest Psychiatric Facility.

PubMed

Subedi, Sandip; Aich, Tapas Kumar; Sharma, Niru

2016-02-01

Electro-Convulsive Therapy (ECT) refers to the electrical stimulation of the brain to produce seizures for therapeutic purpose. Since the development of ECT, it's use has been consistent. Inspite of the common use, data pertaining to the use of ECT in Nepal is lacking. This study was undertaken with the aim of exploring the clinico-demographic profile of patients treated with ECT in the largest psychiatry facility in the country. It is a retrospective descriptive study of patients who were treated with ECT after admission in the inpatient psychiatry unit of Universal College of Medical Sciences Teaching Hospital, Bhairahawa, Nepal during a period of one year (August 2012 to July 2013). Out of 1095 patients admitted during the specified period, 81 (7.39%) patients received ECT. About 44.44% of the patients belonged to 20-29 years age group. Female patients constituted more than half of the subjects (55.56%). Review of diagnostic profile showed that majority of patients receiving ECT were suffering from Schizophrenia (44.4%), followed by Bipolar Affective Disorder/Mania (29.6%), Depressive disorder (11.1%), Acute and Transient Psychotic Disorder (6.2%), Post-partum Psychosis (3.7%) and substance induced mood/psychotic disorders (3.7%). A significant majority of subjects (75.3%) received about 5-7 ECT treatments. The mean seizure duration after ECT treatment was 31.13±5.79 seconds. No any major complications were noted during ECT treatment. This study suggests that ECT, use, as a treatment modality is common in young adults and females with Schizophrenia being the most common indication. Direct ECT is safe when used judiciously.

Use of ECT in Nepal: A One Year Study From the Country’s Largest Psychiatric Facility

PubMed Central

Aich, Tapas Kumar; Sharma, Niru

2016-01-01

Introduction Electro-Convulsive Therapy (ECT) refers to the electrical stimulation of the brain to produce seizures for therapeutic purpose. Since the development of ECT, it’s use has been consistent. Inspite of the common use, data pertaining to the use of ECT in Nepal is lacking. Aim This study was undertaken with the aim of exploring the clinico-demographic profile of patients treated with ECT in the largest psychiatry facility in the country. Materials and Methods It is a retrospective descriptive study of patients who were treated with ECT after admission in the inpatient psychiatry unit of Universal College of Medical Sciences Teaching Hospital, Bhairahawa, Nepal during a period of one year (August 2012 to July 2013). Results Out of 1095 patients admitted during the specified period, 81 (7.39%) patients received ECT. About 44.44% of the patients belonged to 20-29 years age group. Female patients constituted more than half of the subjects (55.56%). Review of diagnostic profile showed that majority of patients receiving ECT were suffering from Schizophrenia (44.4%), followed by Bipolar Affective Disorder/Mania (29.6%), Depressive disorder (11.1%), Acute and Transient Psychotic Disorder (6.2%), Post-partum Psychosis (3.7%) and substance induced mood/psychotic disorders (3.7%). A significant majority of subjects (75.3%) received about 5-7 ECT treatments. The mean seizure duration after ECT treatment was 31.13±5.79 seconds. No any major complications were noted during ECT treatment. Conclusion This study suggests that ECT, use, as a treatment modality is common in young adults and females with Schizophrenia being the most common indication. Direct ECT is safe when used judiciously. PMID:27042563

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.

Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis.

PubMed

Vespa, Paul M; Miller, Chad; McArthur, David; Eliseo, Mathew; Etchepare, Maria; Hirt, Daniel; Glenn, Thomas C; Martin, Neil; Hovda, David

2007-12-01

To determine whether nonconvulsive electrographic post-traumatic seizures result in increases in intracranial pressure and microdialysis lactate/pyruvate ratio. Prospective monitoring with retrospective data analysis. Single center academic neurologic intensive care unit. Twenty moderate to severe traumatic brain injury patients (Glasgow Coma Score 3-13). Continuous electroencephalography and cerebral microdialysis were performed for 7 days after injury. Ten patients had seizures and were compared with a matched cohort of traumatic brain injury patients without seizures. The seizures were repetitive and constituted status epilepticus in seven of ten patients. Using a within-subject design, post-traumatic seizures resulted in episodic increases in intracranial pressure (22.4 +/- 7 vs. 12.8 +/- 4.3 mm Hg; p < .001) and an episodic increase in lactate/pyruvate ratio (49.4 +/- 16 vs. 23.8 +/- 7.6; p < .001) in the seizure group. Using a between-subjects comparison, the seizure group demonstrated a higher mean intracranial pressure (17.6 +/- 6.5 vs. 12.2 +/- 4.2 mm Hg; p < .001), a higher mean lactate/pyruvate ratio (38.6 +/- 18 vs. 27 +/- 9; p < .001) compared with nonseizure patients. The intracranial pressure and lactate/pyruvate ratio remained elevated beyond postinjury hour 100 in the seizure group but not the nonseizure group (p < .02). Post-traumatic seizures result in episodic as well as long-lasting increases in intracranial pressure and microdialysis lactate/pyruvate ratio. These data suggest that post-traumatic seizures represent a therapeutic target for patients with traumatic brain injury.

Electroconvulsive therapy for manic state with mixed and psychotic features in a teenager with bipolar disorder and comorbid episodic obsessive-compulsive disorder: a case report.

PubMed

Rask, Olof; Suneson, Klara; Holmström, Eva; Bäckström, Beata; Johansson, Björn Axel

2017-12-12

Comorbidity of bipolar disorder and obsessive-compulsive disorder is common in adolescence. Obsessive-compulsive disorder symptoms may be episodic and secondary to alterations in mood, and display specific features. Management of pediatric bipolar disorder-obsessive-compulsive disorder is challenging, as pharmacotherapy of obsessive-compulsive disorder may induce or exacerbate manic episodes and there is limited evidence of treatment efficacy. Electroconvulsive therapy is sparsely used in children and adolescents, but is documented to be a safe and efficacious intervention in adults with bipolar disorder. In view of the severity of symptoms in juvenile mania, studies on treatment strategies are warranted. We report a case of an adolescent with bipolar disorder-obsessive-compulsive disorder who was successfully treated with electroconvulsive therapy during an episode of severe mania. A 16-year-old girl of Middle East origin first presented to us with depressed mood, irritability, and increased obsessive-compulsive disorder symptoms, which were initially interpreted in the context of acute stress secondary to migration. She had been diagnosed with bipolar disorder and obsessive-compulsive disorder in her previous home country, but had difficulties in accounting for earlier psychiatric history. During hospitalization her mood switched to a manic state with mixed and psychotic features, at times showing aggression toward others. Interruption in her lithium treatment for a short period and possibly the introduction of an atypical antipsychotic could in part have been triggering factors. After 8 weeks of in-patient care and psychotropic drug trials, electroconvulsive therapy was initiated and administered every second or third day for 4 weeks, with marked positive response. No apparent side effects were reported. This case demonstrates the need for a detailed medical history, taking special note of periodicity and character of obsessive-compulsive disorder symptoms, in adolescents with mood disorders. When treating culturally diverse patients, extra consideration should be taken. Special concerns in the pharmacological treatment to avoid the patient's condition from worsening must be addressed, including giving priority to mood stabilization before obsessive-compulsive disorder symptoms. There are potential benefits in considering electroconvulsive therapy in young patients with severe mania where first-line treatment options have failed.

Oral Health in Electroconvulsive Therapy: A Neglected Topic.

PubMed

Muzyka, Brian C; Glass, Magdalena; Glass, Oliver M

2017-03-01

Psychiatric medications may have serious and untoward adverse effects such as blurred vision, restlessness, agranulocytosis, muscle rigidity, and tremors. When compared to medications, electroconvulsive therapy (ECT) is becoming a more acceptable treatment due to its efficacy, tolerability, and minimal adverse effect profile. Oral trauma can be an ECT-related adverse effect. We reviewed the published literature on oral health and dental protection in patients undergoing ECT, and found that there are deficits in all guidelines on dental protection during ECT. Dental assessment and treatment before and after ECT is warranted. Given the increased risk of poor oral health in psychiatric patients, and the continued evolution of ECT as a mainstay treatment, it is important that studies be conducted to determine the optimal method of oral protection. If adequate care can be ensured, the risks of ECT-induced oral trauma will be minimized.

Summary of the Practice Parameter for the Use of Electroconvulsive Therapy with Adolescents

ERIC Educational Resources Information Center

Ghaziuddin, N.; Kutcher, S. P.; Knapp, P.

2004-01-01

Electroconvulsive therapy (ECT) may be an effective treatment for adolescents with severe mood disorders and other Axis I psychiatric disorders when more conservative treatments have been unsuccessful. ECT may be considered when there is a lack of response to two or more trials of pharmacotherapy or when the severity of symptoms precludes waiting…

Electroconvulsive therapy for depression in Parkinson's disease: systematic review of evidence and recommendations.

PubMed

Borisovskaya, Anna; Bryson, William Culbertson; Buchholz, Jonathan; Samii, Ali; Borson, Soo

2016-04-01

We performed a systematic review of evidence regarding treatment of depression in Parkinson's disease (PD) utilizing electroconvulsive therapy. The search led to the inclusion of 43 articles, mainly case reports or case series, with the largest number of patients totaling 19. The analysis included 116 patients with depression and PD; depression improved in 93.1%. Where motor symptoms' severity was reported, 83% of patients improved. Cognition did not worsen in the majority (94%). Many patients experienced delirium or transient confusion, sometimes necessitating discontinuation of electroconvulsive therapy (ECT). Little is known about maintenance ECT in this population. ECT can benefit patients suffering from PD and depression. We recommend an algorithm for treatment of depression in PD, utilizing ECT sooner rather than later.

DOPAMINE POSTSYNAPTIC RECEPTOR EFFECTS OF RESTRICTED SCHEDULES OF ELECTROCONVULSIVE SHOCK

PubMed Central

Andrade, Chittaranjan; Gangadhar, B.N.; Meena, M.; Pradhan, N.

1990-01-01

SUMMMARY Little work is available on the acute and time-dependant dopaminergic effects of single electroconvulsive shock (ECS) and multiple ECS despite the posited clinical utility of such schedules of electroconvulsive therapy (ECT) administration and the posited role of dopaminergic mechanisms in iieuropsychiatric disorders. In this study, using the apomorphine-induced motility-alteration behavioural paradigm, single session multiple ECS was found to produce no significant effect while single ECS behaviourally downregulated dopamine postsynaptic receptor functioning one week after the ECS, which effect was also seen (albeit to a lesser extent) a further week later. These findings indicate a possible application of restricted schedules of ECT to dopamine postsynaptic receptor supersensitivity syndromes. Lines for future research are suggested. PMID:21927479

Differential impact of antiepileptic drugs on the effects of contraceptive methods on seizures: Interim findings of the epilepsy birth control registry.

PubMed

Herzog, Andrew G

2015-05-01

To present the interim findings of the Epilepsy Birth Control Registry (EBCR) regarding the impact of various contraceptive methods on seizures, stratified by antiepileptic drug (AED) type. This is an observational study that reports interim findings on the first 750 subjects. There are significantly greater relative risks (RR) for both seizure increase and decrease with hormonal contraception (HC) than with non-hormonal contraception (NHC). The rates of HC experiences associated with seizure increase (21.0%) are greater than with NHC (3.9%) (RR=5.39 [95% CI=3.77-7.73, p<0.0001]). The rates of HC experiences associated with seizure decrease (10.3%) are greater than with NHC (5.6%) (RR=1.85 [95% CI=1.30-2.62, p=0.0006]). While differences can reflect biological effects or reporting bias, the finding of a greater RR for seizure increase with hormonal patch than with combined oral contraceptive, perhaps related to the delivery of substantially higher concentrations of hormones, and a greater RR for seizure decrease with depomedroxyprogesterone, known to reduce seizure frequency when used in dosages which produce amenorrhea, support biological effects. All AED categories showed significantly higher frequencies of reports of seizure increase when combined with HC than with NHC. RR for seizure increase with HC was higher with valproate than with any other AED category. There were no significant differences among AEDs for seizure decrease with HC at this juncture of the study. Overall, NEIAEDs had the most favorable profile with regard to reports of seizure increase and decrease when used with HC. Interim EBCR findings suggest that contraception category and interactions between contraception category and AED category are predictive factors for changes in seizure frequency in WWE. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Tranexamic acid-associated seizures: Causes and treatment.

PubMed

Lecker, Irene; Wang, Dian-Shi; Whissell, Paul D; Avramescu, Sinziana; Mazer, C David; Orser, Beverley A

2016-01-01

Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients. © 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Tranexamic acid–associated seizures: Causes and treatment

PubMed Central

Lecker, Irene; Wang, Dian‐Shi; Whissell, Paul D.; Avramescu, Sinziana; Mazer, C. David

2015-01-01

Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in‐hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid–associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid–associated seizures and by translating scientific findings into therapeutic interventions for patients. ANN NEUROL 2016;79:18–26 PMID:26580862

Seizure Termination by Acidosis Depends on ASIC1a

PubMed Central

Ziemann, Adam E.; Schnizler, Mikael K.; Albert, Gregory W.; Severson, Meryl A.; Howard, Matthew A.; Welsh, Michael J.; Wemmie, John A.

2008-01-01

SUMMARY Most seizures stop spontaneously. However, the molecular mechanisms remain unknown. Earlier observations that seizures reduce brain pH and that acidosis inhibits seizures indicated that acidosis halts epileptic activity. Because acid–sensing ion channel–1a (ASIC1a) shows exquisite sensitivity to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a to terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant–induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, also required ASIC1a to interrupt tonic–clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. These findings identify ASIC1a as a key element in seizure termination when brain pH falls. The results suggest a molecular mechanism for how the brain stops seizures and suggest new therapeutic strategies. PMID:18536711

Catatonia in Autism: A Distinct Subtype?

ERIC Educational Resources Information Center

Ghaziuddin, M.; Quinlan, P.; Ghaziuddin, N.

2005-01-01

Catatonia is a life-threatening disorder characterized by motor abnormalities, mutism, and disturbances of behaviour, which is increasingly being diagnosed in persons with autism. In this report, we describe the presentation and course of catatonia in an adolescent with autism who responded to electroconvulsive therapy (ECT). The illness started…

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.

NBQX, a highly selective competitive antagonist of AMPA and KA ionotropic glutamate receptors, increases seizures and mortality following picornavirus infection

PubMed Central

Libbey, Jane E.; Hanak, Tyler J.; Doty, Daniel J.; Wilcox, Karen S.; Fujinami, Robert S.

2016-01-01

Seizures occur due to an imbalance between excitation and inhibition, with the balance tipping towards excitation, and glutamate is the predominant excitatory neurotransmitter in the central nervous system of mammals. Since upregulation of expression and/or function of glutamate receptors can contribute to seizures we determined the effects of three antagonists, NBQX, GYKI-52466 and MK 801, of the various ionotropic glutamate receptors, AMPA, NMDA and KA, on acute seizure development in the Theiler’s murine encephalomyelitis virus (TMEV)-induced seizure model. We found that only NBQX had an effect on acute seizure development, resulting in a significantly higher number of mice experiencing seizures, an increase in the number of seizures per mouse, a greater cumulative seizure score per mouse and a significantly higher mortality rate among the mice. Although NBQX has previously been shown to be a potent anticonvulsant in animal seizure models, seizures induced by electrical stimulation, drug administration or as a result of genetic predisposition may differ greatly in terms of mechanism of seizure development from our virus-induced seizure model, which could explain the opposite, proconvulsant effect of NBQX observed in the TMEV-induced seizure model. PMID:27072529

Cellular responses to recurrent pentylenetetrazole-induced seizures in the adult zebrafish brain

PubMed Central

Duy, Phan Q; Berberoglu, Michael A; Beattie, Christine E; Hall, Charles W

2017-01-01

A seizure is a sustained increase in brain electrical activity that can result in loss of consciousness and injury. Understanding how the brain responds to seizures is important for development of new treatment strategies for epilepsy, a neurological condition characterized by recurrent and unprovoked seizures. Pharmacological induction of seizures in rodent models results in a myriad of cellular alterations, including inflammation, angiogenesis, and adult neurogenesis. The purpose of this study is to investigate the cellular responses to recurrent pentylenetetrazole seizures in the adult zebrafish brain. We subjected zebrafish to five once daily pentylenetetrazole induced seizures and characterized the cellular consequences of these seizures. In response to recurrent seizures, we found histologic evidence of vasodilatation, perivascular leukocyte egress and leukocyte proliferation suggesting seizure-induced acute CNS inflammation. We also found evidence of increased proliferation, neurogenesis, and reactive gliosis. Collectively, our results suggest that the cellular responses to seizures in the adult zebrafish brain are similar to those observed in mammalian brains. PMID:28238851

Alterations of network synchrony after epileptic seizures: An analysis of post-ictal intracranial recordings in pediatric epilepsy patients.

PubMed

Tomlinson, Samuel B; Khambhati, Ankit N; Bermudez, Camilo; Kamens, Rebecca M; Heuer, Gregory G; Porter, Brenda E; Marsh, Eric D

2018-07-01

Post-ictal EEG alterations have been identified in studies of intracranial recordings, but the clinical significance of post-ictal EEG activity is undetermined. The purpose of this study was to examine the relationship between peri-ictal EEG activity, surgical outcome, and extent of seizure propagation in a sample of pediatric epilepsy patients. Intracranial EEG recordings were obtained from 19 patients (mean age = 11.4 years, range = 3-20 years) with 57 seizures used for analysis (mean = 3.0 seizures per patient). For each seizure, 3-min segments were extracted from adjacent pre-ictal and post-ictal epochs. To compare physiology of the epileptic network between epochs, we calculated the relative delta power (Δ) using discrete Fourier transformation and constructed functional networks based on broadband connectivity (conn). We investigated differences between the pre-ictal (Δ pre , conn pre ) and post-ictal (Δ post , conn post ) segments in focal-network (i.e., confined to seizure onset zone) versus distributed-network (i.e., diffuse ictal propagation) seizures. Distributed-network (DN) seizures exhibited increased post-ictal delta power and global EEG connectivity compared to focal-network (FN) seizures. Following DN seizures, patients with seizure-free outcomes exhibited a 14.7% mean increase in delta power and an 8.3% mean increase in global connectivity compared to pre-ictal baseline, which was dramatically less than values observed among seizure-persistent patients (29.6% and 47.1%, respectively). Post-ictal differences between DN and FN seizures correlate with post-operative seizure persistence. We hypothesize that post-ictal deactivation of subcortical nuclei recruited during seizure propagation may account for this result while lending insights into mechanisms of post-operative seizure recurrence. Copyright © 2018 Elsevier B.V. All rights reserved.

[Contemporary place of the electroconvulsive therapy. Part 2. Clinical aspect].

PubMed

Zyssi, Tomasz; Rachel, Wojciech; Datka, Wojciech; Hese, Robert T; Gorczyca, Piotr; Szwajca, Krzysztof; Piekoszewski, Wojciech; Zięba, Andrzej

2015-01-01

Electroconvulsive therapy (ECT) is an important method of biological treatment in serious psychic disturbances. Similarly to drug therapy it is marked by a determined schematics of applying including the list of indications, contraindications, procedures of the performance, as well as the list of adverse invents. Applying defined schemas allows for minimizing the risk and influences the final effectiveness of therapy.

Mental Health Service Career Ladder

DTIC Science & Technology

1994-01-01

suicide risk patients 54 H315 Adjust or inspect refrigerators for proper temperatures 54 1372 Participate in rehashes of therapy sessions 53 H320...included biofeedback (paragraph 13c), electroconvulsive therapy (ECT) (paragraph 13h), and combat/disaster casualty management (paragraph 13m). Two other...focused on identifying marital and family counseling factors and determining the purpose and procedures for administering electroconvulsive therapy (ECT

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.

Combined use of clozapine and ECT: a review.

PubMed

Grover, Sandeep; Hazari, Nandita; Kate, Natasha

2015-06-01

This paper aims to review the available evidence for the use of clozapine and electroconvulsive therapy (ECT) in combination. Electronic searches were carried out to identify reports describing the combined use of clozapine and ECT. Forty reports including 208 patients were identified. The majority of reports were in the form of case reports and case series, with few retrospective and open-label studies. The majority of patients were aged between 18 and 65 years and diagnosed with schizophrenia or schizoaffective disorder. Most of the patients refractory to clozapine were started on ECT as an augmentation therapy; however, in some reports, both ECT and clozapine were started concurrently, and in few cases clozapine was started after ECT. In terms of effectiveness, 37.5-100% patients improved in short-term, and sustained long-term improvement (3 weeks to 24 months) was described in few studies. In terms of the side-effect profile, five patients each had delirium and tachycardia and only four patients were described to have prolonged seizures. Overall, the combination was considered effective and safe. There is evidence for the effectiveness and safety of the clozapine-ECT combination and it should be used in patients with treatment-resistant schizophrenia who do not respond to clozapine.

Glutamate receptor 1 phosphorylation at serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability after early life seizures.

PubMed

Rakhade, Sanjay N; Fitzgerald, Erin F; Klein, Peter M; Zhou, Chengwen; Sun, Hongyu; Huganir, Richard L; Hunganir, Richard L; Jensen, Frances E

2012-12-05

Neonatal seizures can lead to later life epilepsy and neurobehavioral deficits, and there are no treatments to prevent these sequelae. We showed previously that hypoxia-induced seizures in a neonatal rat model induce rapid phosphorylation of serine-831 (S831) and Serine 845 (S845) sites of the AMPA receptor GluR1 subunit and later neuronal hyperexcitability and epilepsy, suggesting that seizure-induced posttranslational modifications may represent a novel therapeutic target. To unambiguously assess the contribution of these sites, we examined seizure susceptibility in wild-type mice versus transgenic knock-in mice with deficits in GluR1 S831 and S845 phosphorylation [GluR1 double-phosphomutant (GluR1 DPM) mice]. Phosphorylation of the GluR1 S831 and S845 sites was significantly increased in the hippocampus and cortex after a single episode of pentyleneterazol-induced seizures in postnatal day 7 (P7) wild-type mouse pups and that transgenic knock-in mice have a higher threshold and longer latencies to seizures. Like the rat, hypoxic seizures in P9 C57BL/6N wild-type mice resulted in transient increases in GluR1 S831 and GluR1 S845 phosphorylation in cortex and were associated with enhanced seizure susceptibility to later-life kainic-acid-induced seizures. In contrast, later-life seizure susceptibility after hypoxia-induced seizures was attenuated in GluR1 DPM mice, supporting a role for posttranslational modifications in seizure-induced network excitability. Finally, human hippocampal samples from neonatal seizure autopsy cases also showed an increase in GluR1 S831 and S845, supporting the validation of this potential therapeutic target in human tissue.

Glutamate receptor 1 phosphorylation at Serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability following early life seizures

PubMed Central

Rakhade, S.N.; Fitzgerald, E.F.; Klein, P.M.; Zhou, C.; Sun, H; Huganir, R.L.; Jensen, F.E.

2012-01-01

Neonatal seizures can lead to later life epilepsy and neurobehavioral deficits, and there are no treatments to prevent these sequelae. We previously showed that hypoxia-induced seizures in a neonatal rat model induce rapid phosphorylation of S831 and S845 sites of the AMPA receptor GluR1 subunit and later neuronal hyperexcitability and epilepsy, suggesting that seizure-induced post-translational modifications may represent a novel therapeutic target. To unambiguously assess the contribution of these sites, we examined seizure susceptibility in wild type mice versus transgenic knock-in mice with deficits in GluR1 S831 and S845 phosphorylation (GluR1 double phosphomutant (GluR1DPM) mice). Phosphorylation of the GluR1 S831 and S845 sites was significantly increased in the hippocampus and cortex following a single episode of pentyleneterazol (PTZ) induced seizures in postnatal day 9 (P9) wild type mouse pups, and that transgenic knock-in mice have a higher threshold and longer latencies to seizures. Like the rat, hypoxic seizures in P9 C57BL/6N wild type mice resulted in transient increases in GluR1 S831 and GluR1 S845 phosphorylation in cortex, and were associated with enhanced seizure susceptibility to later-life kainic acid induced seizures. In contrast, later-life seizure susceptibility following hypoxia-induced seizures was attenuated in GluR1 DPM mice, supporting a role for post-translational modifications in seizure-induced network excitability. Finally, human hippocampal samples from neonatal seizure autopsy cases also showed an increase in GluR1 S831 and S845, supporting the validation of this potential therapeutic target in human tissue. PMID:23223299

NBQX, a highly selective competitive antagonist of AMPA and KA ionotropic glutamate receptors, increases seizures and mortality following picornavirus infection.

PubMed

Libbey, Jane E; Hanak, Tyler J; Doty, Daniel J; Wilcox, Karen S; Fujinami, Robert S

2016-06-01

Seizures occur due to an imbalance between excitation and inhibition, with the balance tipping towards excitation, and glutamate is the predominant excitatory neurotransmitter in the central nervous system of mammals. Since upregulation of expression and/or function of glutamate receptors can contribute to seizures we determined the effects of three antagonists, NBQX, GYKI-52466 and MK 801, of the various ionotropic glutamate receptors, AMPA, NMDA and KA, on acute seizure development in the Theiler's murine encephalomyelitis virus (TMEV)-induced seizure model. We found that only NBQX had an effect on acute seizure development, resulting in a significantly higher number of mice experiencing seizures, an increase in the number of seizures per mouse, a greater cumulative seizure score per mouse and a significantly higher mortality rate among the mice. Although NBQX has previously been shown to be a potent anticonvulsant in animal seizure models, seizures induced by electrical stimulation, drug administration or as a result of genetic predisposition may differ greatly in terms of mechanism of seizure development from our virus-induced seizure model, which could explain the opposite, proconvulsant effect of NBQX observed in the TMEV-induced seizure model. Copyright © 2016 Elsevier Inc. All rights reserved.

A new model to study sleep deprivation-induced seizure.

PubMed

Lucey, Brendan P; Leahy, Averi; Rosas, Regine; Shaw, Paul J

2015-05-01

A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation. Seizure activity was evaluated in an adult bang-sensitive seizure mutant, stress sensitive B (sesB(9ed4)), and in an adult temperature sensitive seizure mutant seizure (sei(ts1)) under baseline and following 12 h of sleep deprivation. The long-term effect of sleep deprivation on young, immature sesB(9ed4) flies was also assessed. Laboratory. Drosophila melanogaster. Sleep deprivation. Sleep deprivation increased seizure susceptibility in adult sesB(9ed4)/+ and sei(ts1) mutant flies. Sleep deprivation also increased seizure susceptibility when sesB was disrupted using RNAi. The effect of sleep deprivation on seizure activity was reduced when sesB(9ed4)/+ flies were given the anti-seizure drug, valproic acid. In contrast to adult flies, sleep deprivation during early fly development resulted in chronic seizure susceptibility when sesB(9ed4)/+ became adults. These findings show that Drosophila is a model organism for investigating the relationship between sleep and seizure activity. © 2015 Associated Professional Sleep Societies, LLC.

Unit Activity of Hippocampal Interneurons before Spontaneous Seizures in an Animal Model of Temporal Lobe Epilepsy

PubMed Central

Toyoda, Izumi; Fujita, Satoshi; Thamattoor, Ajoy K.

2015-01-01

Mechanisms of seizure initiation are unclear. To evaluate the possible roles of inhibitory neurons, unit recordings were obtained in the dentate gyrus, CA3, CA1, and subiculum of epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Most interneurons in the dentate gyrus, CA1, and subiculum increased their firing rate before seizures, and did so with significant consistency from seizure to seizure. Identification of CA1 interneuron subtypes based on firing characteristics during theta and sharp waves suggested that a parvalbumin-positive basket cell and putative bistratified cells, but not oriens lacunosum moleculare cells, were activated preictally. Preictal changes occurred much earlier than those described by most previous in vitro studies. Preictal activation of interneurons began earliest (>4 min before seizure onset), increased most, was most prevalent in the subiculum, and was minimal in CA3. Preictal inactivation of interneurons was most common in CA1 (27% of interneurons) and included a putative ivy cell and parvalbumin-positive basket cell. Increased or decreased preictal activity correlated with whether interneurons fired faster or slower, respectively, during theta activity. Theta waves were more likely to occur before seizure onset, and increased preictal firing of subicular interneurons correlated with theta activity. Preictal changes by other hippocampal interneurons were largely independent of theta waves. Within seconds of seizure onset, many interneurons displayed a brief pause in firing and a later, longer drop that was associated with reduced action potential amplitude. These findings suggest that many interneurons inactivate during seizures, most increase their activity preictally, but some fail to do so at the critical time before seizure onset. PMID:25904809

Electroconvulsive therapy-induced brain functional connectivity predicts therapeutic efficacy in patients with schizophrenia: a multivariate pattern recognition study.

PubMed

Li, Peng; Jing, Ri-Xing; Zhao, Rong-Jiang; Ding, Zeng-Bo; Shi, Le; Sun, Hong-Qiang; Lin, Xiao; Fan, Teng-Teng; Dong, Wen-Tian; Fan, Yong; Lu, Lin

2017-05-11

Previous studies suggested that electroconvulsive therapy can influence regional metabolism and dopamine signaling, thereby alleviating symptoms of schizophrenia. It remains unclear what patients may benefit more from the treatment. The present study sought to identify biomarkers that predict the electroconvulsive therapy response in individual patients. Thirty-four schizophrenia patients and 34 controls were included in this study. Patients were scanned prior to treatment and after 6 weeks of treatment with antipsychotics only (n = 16) or a combination of antipsychotics and electroconvulsive therapy (n = 13). Subject-specific intrinsic connectivity networks were computed for each subject using a group information-guided independent component analysis technique. Classifiers were built to distinguish patients from controls and quantify brain states based on intrinsic connectivity networks. A general linear model was built on the classification scores of first scan (referred to as baseline classification scores) to predict treatment response. Classifiers built on the default mode network, the temporal lobe network, the language network, the corticostriatal network, the frontal-parietal network, and the cerebellum achieved a cross-validated classification accuracy of 83.82%, with specificity of 91.18% and sensitivity of 76.47%. After the electroconvulsive therapy, psychosis symptoms of the patients were relieved and classification scores of the patients were decreased. Moreover, the baseline classification scores were predictive for the treatment outcome. Schizophrenia patients exhibited functional deviations in multiple intrinsic connectivity networks which were able to distinguish patients from healthy controls at an individual level. Patients with lower classification scores prior to treatment had better treatment outcome, indicating that the baseline classification scores before treatment is a good predictor for treatment outcome. CONNECTIVITY NETWORKS REVEAL GOOD CANDIDATES FOR BRAIN STIMULATION: Connectivity patterns in the brain may help identify patients with schizophrenia most likely to benefit from electroconvulsive therapy. A team led by Lin Lu from Peking University, China, and Yong Fan from the University of Pennsylvania, USA, took functional magnetic resonance imaging (MRI) scans of 34 people with schizophrenia and 34 control individuals without mental illness. Those with schizophrenia were scanned before and after treatment; some received antipsychotics alone, others received medication plus electroconvulsive therapy. The researchers created organizational brain maps known as "intrinsic connectivity networks" for each individual, and showed that the neuroimaging pattern could discriminate between people with and without schizophrenia. For the schizophrenia patients, the connectivity networks taken prior to treatment also helped predict who would benefit from the brain-stimulation procedure. Such a biomarker could prove a useful diagnostic tool for clinicians.

Influence of Val108/158Met COMT Gene Polymorphism on the Efficacy of Modified Electroconvulsive Therapy in Patients with Treatment Resistant Depression.

PubMed

Lin, Zhaoyu; He, Hongbo; Zhang, Chunping; Wang, Zhijie; Jiang, Miaoling; Li, Qirong; Lan, Xiaochang; Zhang, Minling; Huang, Xiong

2015-04-01

Depression is a common emotional disorder associated with increased risk of suicide and rate of disability. In this double-blinded control study, we tested the efficacy of modified electroconvulsive therapy (MECT) in patients with treatment resistant depression (TRD) using the Hamilton Depression Rating Scale for Depression (HAMD). The total scores of HAMD were found to be significantly decreased after the treatment. The genotyping of catechol-O-methyltransferase (COMT) was carried out with polymerase chain reaction-based testing. Our results demonstrated that frequency of mutant COMT alleles in TRD patients was significantly higher than that of the controls indicating a correlation of the enzyme genotype to the occurrence of TRD. Moreover, the patients homozygous for wild-type COMT gene (G/G) were evidenced to be more sensitive to MECT treatment than those with an heterozygous mutant genotype (A/G).

Electroconvulsive therapy: a life course approach for recurrent depressive disorder

PubMed Central

Carney, Sarah; Sami, Musa Basseer; Clark, Victoria; Kuruvilla, Kompancariel Kuruvilla

2015-01-01

We describe the case of an 89-year-old woman (deceased) with a 60-year history of recurrent depressive disorder treated with electroconvulsive therapy (ECT). It is estimated that she received up to 400 ECTs over her life course as her symptoms would not respond to oral medication. Despite extensive exposure to ECT, there was only minimal cognitive impairment and an excellent safety record, even in later life, as she became increasingly frail from multiple comorbidities. Over the years, there has been a drive to reduce the frequency of ECT administration. However, this case illustrates how in some patients ECT may be vital for acute episodes of severe depression as well as for maintenance therapy. This case report adds to observational evidence that maintenance ECT may be an underused treatment for recurrent depression and also recommends that greater emphasis be given to incorporating carers’ views when planning individualised treatment approaches. PMID:26009602

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.

Focal BOLD-fMRI changes in bicuculline-induced tonic-clonic seizures in the rat

PubMed Central

DeSalvo, Matthew N.; Schridde, Ulrich; Mishra, Asht M.; Motelow, Joshua E.; Purcaro, Michael J.; Danielson, Nathan; Bai, Xiaoxiao; Hyder, Fahmeed; Blumenfeld, Hal

2010-01-01

Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG) these changes can be characterized with high spatiotemporal resolution. We studied BOLD changes in anesthetized Wistar rats during bicuculline-induced tonic-clonic seizures. Bicuculline, a GABAA receptor antagonist, was injected systemically and seizure activity was observed on EEG as high amplitude, high-frequency polyspike discharges followed by clonic paroxysmal activity of lower frequency, with mean electrographic seizure duration of 349 s. Our aim was to characterize the spatial localization, direction, and timing of BOLD signal changes during the pre-ictal, ictal and post-ictal periods. Group analysis was performed across seizures using paired t-maps of BOLD signal superimposed on high resolution anatomical images. Regional analysis was then performed using volumes of interest to quantify BOLD timecourses. In the pre-ictal period we found focal BOLD increases in specific areas of somatosensory cortex (S1, S2) and thalamus several seconds before seizure onset. During seizures we observed BOLD increases in cortex, brainstem and thalamus and BOLD decreases in the hippocampus. The largest ictal BOLD increases remained in the focal regions of somatosensory cortex showing pre-ictal increases. During the post-ictal period we observed widespread BOLD decreases. These findings support a model in which “generalized” tonic-clonic seizures begin with focal changes before electrographic seizure onset, which progress to non-uniform changes during seizures, possibly shedding light on the etiology and pathophysiology of similar seizures in humans. PMID:20079442

Intraperitoneal administration of docosahexaenoic acid for 14days increases serum unesterified DHA and seizure latency in the maximal pentylenetetrazol model.

PubMed

Trépanier, Marc-Olivier; Lim, Joonbum; Lai, Terence K Y; Cho, Hye Jin; Domenichiello, Anthony F; Chen, Chuck T; Taha, Ameer Y; Bazinet, Richard P; Burnham, W M

2014-04-01

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) which has been shown to raise seizure thresholds following acute administration in rats. The aims of the present experiment were the following: 1) to test whether subchronic DHA administration raises seizure threshold in the maximal pentylenetetrazol (PTZ) model 24h following the last injection and 2) to determine whether the increase in seizure threshold is correlated with an increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.) injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested) subset of animals, blood was collected, and brains were excised following high-energy, head-focused microwave fixation. Lipid analysis was performed on serum and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were combined since they did not differ significantly from each other. In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3-fold as compared to vehicle-injected animals. This increase in seizure latency was associated with an increase in serum unesterified DHA. Total brain DHA and brain unesterified DHA concentrations, however, did not differ significantly in the treatment and control groups. An increase in serum unesterified DHA concentration reflecting increased flux of DHA to the brain appears to explain changes in seizure threshold, independent of changes in brain DHA concentrations. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Ictal electroencephalograms in neonatal seizures: characteristics and associations.

PubMed

Nagarajan, Lakshmi; Ghosh, Soumya; Palumbo, Linda

2011-07-01

The characteristics of ictal electroencephalograms in 160 neonatal seizures of 43 babies were correlated with mortality and neurodevelopmental outcomes. Neonatal seizures are focal at onset, most frequently temporal, and often occur during sleep. Twenty-one percent of babies with seizures died, and 76% of survivors manifested neurodevelopmental impairment during 2-6-year follow-up. A low-amplitude ictal electroencephalogram discharge was associated with increased mortality, and a frequency of <2 Hz with increased morbidity. Status epilepticus, ictal fractions, multiple foci, and bihemispheric involvement did not influence outcomes. Of 160 seizures, 99 exhibited no associated clinical features (electrographic seizures). Neonatal seizures with clinical correlates (electroclinical seizures) exhibited a higher amplitude and frequency of ictal electroencephalogram discharge than electrographic seizures. During electroclinical seizures, the ictal electroencephalogram was more likely to involve larger areas of the brain and to cross the midline. Mortality and morbidity were similar in babies with electroclinical and electrographic seizures, emphasizing the need to diagnose and treat both types. Ictal electroencephalogram topography has implications for electrode application during limited-channel, amplitude-integrated electroencephalograms. We recommend temporal and paracentral electrodes. Video electroencephalograms are important in diagnosing neonatal seizures and providing useful information regarding ictal electroencephalogram characteristics. Copyright © 2011 Elsevier Inc. All rights reserved.

Periictal activity in cooled asphyxiated neonates with seizures.

PubMed

Major, Philippe; Lortie, Anne; Dehaes, Mathieu; Lodygensky, Gregory Anton; Gallagher, Anne; Carmant, Lionel; Birca, Ala

2017-04-01

Seizures are common in critically ill neonates. Both seizures and antiepileptic treatments may lead to short term complications and worsen the outcomes. Predicting the risks of seizure reoccurrence could enable individual treatment regimens and better outcomes. We aimed to identify EEG signatures of seizure reoccurrence by investigating periictal electrographic features and spectral power characteristics in hypothermic neonates with hypoxic-ischemic encephalopathy (HIE) with or without reoccurrence of seizures on rewarming. We recruited five consecutive HIE neonates, submitted to continuous EEG monitoring, with high seizure burden (>20% per hour) while undergoing therapeutic hypothermia. Two of them had reoccurrence of seizures on rewarming. We performed quantitative analysis of fifteen artifact-free consecutive seizures to appreciate spectral power changes between the interictal, preictal and ictal periods, separately for each patient. Visual analysis allowed description of electrographic features associated with ictal events. Every patient demonstrated a significant increase in overall spectral power from the interictal to preictal and ictal periods (p<0.01). Alpha power increase was more pronounced in the two patients with reoccurrence of seizures on rewarming and significant when comparing both interictal-to-preictal and interictal-to-ictal periods. This alpha activity increase could be also appreciated using visual analysis and distinguished neonates with and without seizure reoccurrence. This distinct alpha activity preceding ictal onset could represent a biomarker of propensity for seizure reoccurrence in neonates. Future studies should be performed to confirm whether quantitative periictal characteristics and electrographic features allow predicting the risks of seizure reoccurrence in HIE neonates and other critically ill patients. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Rapamycin down-regulates KCC2 expression and increases seizure susceptibility to convulsants in immature rats

PubMed Central

Huang, Xiaoxing; McMahon, John; Yang, Jun; Shin, Damian; Huang, Yunfei

2012-01-01

Summary Seizure susceptibility to neurological insults, including chemical convulsants, is age-dependent and most likely reflective of overall differences in brain excitability. The molecular and cellular mechanisms underlying development-dependent seizure susceptibility remain to be fully understood. Because the mTOR pathway regulates neurite outgrowth, synaptic plasticity and cell survival, thereby influencing brain development, we tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes seizure susceptibility to neurological insults. We found that inhibition of mTOR by rapamycin in immature rats (3 to 4 weeks old) increases the severity of seizures induced by pilocarpine, including lengthening the total seizure duration and reducing the latency to the onset of seizures. Rapamycin also reduces the minimal dose of pentylenetetrazol (PTZ) necessary to induce clonic seizures. However, in mature rats, rapamycin does not significantly change the seizure sensitivity to pilocarpine and PTZ. Likewise, kainate sensitivity was not significantly affected by rapamycin treatment in either mature or immature rats. Additionally, rapamycin treatment down-regulates the expression of potassium-chloride cotransporter 2 (KCC2) in the thalamus and to a lesser degree in the hippocampus. Pharmacological inhibition of thalamic mTOR or KCC2 increases susceptibility to pilocarpine-induced seizure in immature rats. Thus, our study suggests a role for the mTOR pathway in age-dependent seizure susceptibility. PMID:22613737

Do oral contraceptives increase epileptic seizures?

PubMed

Reddy, Doodipala Samba

2017-02-01

Hormonal contraceptives are used by over 100 million people worldwide. Recently, there has been an emerging interest in studying the potential impact of oral contraceptives (OCs) on certain neurological conditions. It has been suspected for some time that hormonal birth control increases seizure activity in women with epilepsy, but there is little supportive data. Areas covered: Literature from PubMed and online sources was analyzed with respect to hormonal contraception and epilepsy or seizures. New evidence indicates that OCs can cause an increase in seizures in women with epilepsy. The epilepsy birth control registry, which surveyed women with epilepsy, found that those using hormonal contraceptives self-reported 4.5 times more seizures than those that did not use such contraceptives. A preclinical study confirmed these outcomes wherein epileptic animals given ethinyl estradiol, the primary component of OCs, had more frequent seizures that are more likely to be resistant. Expert commentary: OC pills may increase seizures in women with epilepsy and such refractory seizures are more likely to cause neuronal damage in the brain. Thus, women of child bearing age with epilepsy should consider using non-hormonal forms of birth control to avoid risks from OC pills. Additional research into the mechanisms and prospective clinical investigation are needed.

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

Propofol alleviates electroconvulsive shock-induced memory impairment by modulating proBDNF/mBDNF ratio in depressive rats.

PubMed

Zhang, Fan; Luo, Jie; Min, Su; Ren, Li; Qin, Peipei

2016-07-01

This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear. Recent evidence has found that mBDNF and its precursor proBDNF are related to depression and cognitive function; they elicit opposite effects on cellular functions. Chronic unpredicted mild stress is widely used to induce depressive behaviors in rodents. This study found that the depression resulted in an increased expression of PAI-1 and upregulation of the proBDNF/mBDNF ratio, together with a decreased level of tPA, long-term potentiation (LTP) impairment, and cognitive decline. The proBDNF/mBDNF ratio was further upregulated after the ECS treatment in depressive rats, resulting in the deterioration of cognitive function and hippocampal LTP. Propofol alone did not reverse the changes in depressive rats, but when co-administered with ECS, it improved the cognitive function, alleviated the impairment of LTP, downregulated the proBDNF/mBDNF ratio, and increased the tPA expression. The results of this study suggest that propofol ameliorates cognitive decline induced by ECT, which was partly by modulating the proBDNF/mBDNF ratio and reversing the excessive changes in hippocampal synaptic plasticity, providing a new evidence for involving the proBDNF/mBDNF system in the progression and treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

The practice of electroconvulsive therapy in Greece.

PubMed

Kaliora, Styliani C; Braga, Raphael J; Petrides, Georgios; Chatzimanolis, John; Papadimitriou, George N; Zervas, Iannis M

2013-09-01

To describe the practice of electroconvulsive therapy (ECT) in Greece. A survey was conducted during the academic year 2008-2009. Electroconvulsive therapy use was investigated for 2007. All civilian institutions providing inpatient care were included. Centers that provided ECT completed a 57-item questionnaire. Centers that did not offer ECT completed a 13-item questionnaire. Fifty-five (82.1%) of 67 institutions responded. Electroconvulsive therapy was offered in 18 hospitals. Only 2 of 10 university hospitals offered ECT. Overall, 137 patients were treated with 1271 sessions in 2007. Only 1.47% discontinued treatment owing to adverse events. There were no deaths. Schizophrenia was the most common diagnosis (41.3%) among those receiving ECT, followed by major depression (28.9%), bipolar depression (9.1%), catatonia (4.1%), suicidal ideation (3.3%), and schizoaffective disorder (2.5%). Physicians considered major depression (93.8%), catatonia (86.5%), schizophrenia (56.3%), and mania (50%) the most appropriate indications. Written informed consent was required in 77.8% of the institutions, whereas the rest required verbal consent. Bilateral ECT was the preferred electrode placement (88.9%). Modified ECT was used exclusively. Propofol was the preferred anesthetic (44.4%), followed by thiopental (38.9%). Seven (38.9%) of 18 hospitals used a fixed stimulus dose at first treatment. Five (27.8%) of 18 hospitals used the half-age method. Continuation/maintenance ECT was used in 33.3% of the hospitals. Outpatient ECT was seldom used. Lack of training, difficult access to anesthesiology, billing issues, and stigma were cited as the main impediments to the practice of ECT. Electroconvulsive therapy is practiced in moderate numbers in Greece and almost exclusively on an inpatient basis. Lack of training and lack of availability of anesthesiologists were cited as the most common obstacles to providing ECT.

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.

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.

Electroconvulsive therapy for depression following acute coronary syndromes: a concern for the anesthesiologist.

PubMed

Pourafkari, Nosratollah; Pourafkari, Leili; Nader, Nader D

2016-06-01

The prevalence of depression in patients with cardiovascular disease is higher than general population and especially following an acute coronary syndrome (ACS), a significant number of patients report a wide spectrum of behavioral and mood changes attributable to clinical depression. Treatment of depression following ACS event is particularly challenging since most of the therapeutic modalities are associated with increasing the systemic sympathetic tone from neurogenic or pharmacologic sources. Increased activity of the adrenergic and catecholamine activity may further deter the myocardial oxygen supply and demand therefore treating depression should be carefully evaluated for its risk benefit ratio. Electroconvulsive therapy (ECT) is recommended for patients with severe depression, in whom behavioral and pharmacologic treatments have failed. Patients who refuse to take medications or present with any psychological emergency such as harming self or others, are also candidates for ECT. ECT is also associated with sudden surges of catecholamines and may cause recurrent myocardial ischemia and fatal dysrhythmias in patients convalescing from an ACS event. Herein, we provide an overview and practical guidelines for management of patients presented for ECT following ACS. Published by Elsevier Inc.

Pseudocholinesterase levels in patients under electroconvulsive therapy

PubMed Central

Küçükosman, Gamze; Pişkin, Özcan; Hancı, Volkan; Okyay, Rahşan D.; Ayoğlu, Hilal; Yurtlu, Bülent S.; Akın, Mehmet; Turan, Işıl

2018-01-01

Objectives: In this study, we aimed to retrospectively assess the correlation of pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This retrospective study was conducted at Bülent Ecevit University Hospital, Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were retrospectively scanned to evaluate PChE values before ECT and other file information. Results: There was no difference between gender in terms of PChE levels. Correlation analysis determined a weakly positive correlation between age (p=0.013; correlation coefficient [cc]: 0.178) and body weight (p<0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender, weight or psychiatric diagnosis, and PChE levels. Conclusion: Neuromuscular blockage is a significant factor that increases patient safety, while increasing the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and the pharmacological properties of the neuromuscular blocker should be considered. We think that in situations with delayed recovery of ECT cases without identified PChE levels, low PChE levels must be considered. PMID:29332117

Weather as a risk factor for epileptic seizures: A case-crossover study.

PubMed

Rakers, Florian; Walther, Mario; Schiffner, Rene; Rupprecht, Sven; Rasche, Marius; Kockler, Michael; Witte, Otto W; Schlattmann, Peter; Schwab, Matthias

2017-07-01

Most epileptic seizures occur unexpectedly and independently of known risk factors. We aimed to evaluate the clinical significance of patients' perception that weather is a risk factor for epileptic seizures. Using a hospital-based, bidirectional case-crossover study, 604 adult patients admitted to a large university hospital in Central Germany for an unprovoked epileptic seizure between 2003 and 2010 were recruited. The effect of atmospheric pressure, relative air humidity, and ambient temperature on the onset of epileptic seizures under temperate climate conditions was estimated. We found a close-to-linear negative correlation between atmospheric pressure and seizure risk. For every 10.7 hPa lower atmospheric pressure, seizure risk increased in the entire study population by 14% (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.01-1.28). In patients with less severe epilepsy treated with one antiepileptic medication, seizure risk increased by 36% (1.36, 1.09-1.67). A high relative air humidity of >80% increased seizure risk in the entire study population by up to 48% (OR 1.48, 95% CI 1.11-1.96) 3 days after exposure in a J-shaped association. High ambient temperatures of >20°C decreased seizure risk by 46% in the overall study population (OR 0.54, 95% CI 0.32-0.90) and in subgroups, with the greatest effects observed in male patients (OR 0.33, 95% CI 0.14-0.74). Low atmospheric pressure and high relative air humidity are associated with an increased risk for epileptic seizures, whereas high ambient temperatures seem to decrease seizure risk. Weather-dependent seizure risk may be accentuated in patients with less severe epilepsy. Our results require further replication across different climate regions and cohorts before reliable clinical recommendations can be made. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study.

PubMed

Harden, Cynthia L; Herzog, Andrew G; Nikolov, Blagovest G; Koppel, Barbara S; Christos, Paul J; Fowler, Kristen; Labar, Douglas R; Hauser, W Allen

2006-09-01

Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of postmenopausal women with epilepsy was associated with an increase in seizure frequency. This was a randomized, double-blind, placebo-controlled trial of the effect of HRT on seizure frequency in postmenopausal women with epilepsy, taking stable doses of antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3-month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or CEE/MPA) daily, or double-dose CEE/MPA daily for a 3-month treatment period. Twenty-one subjects were randomized after completing baseline. The subjects' ages ranged from 45 to 62 years (mean, 53 years; SD, +/-5), and the number of AEDs used ranged from none to three (median, one). Five (71%) of seven subjects taking double-dose CEE/MPA had a worsening seizure frequency of at least one seizure type, compared with four (50%) of eight taking single-dose CEE/MPA and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency of the subject's most severe seizure type was associated with increasing CEE/MPA dose (p = 0.008). An increase in complex partial seizure frequency also was associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking lamotrigine had a decrease in lamotrigine levels of 25-30% while taking CEE/MPA. CEE/MPA is associated with a dose-related increase in seizure frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine levels.

Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

PubMed

Cleary, Ryan T; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M; Li, Yijun; Rotenberg, Alexander; Talos, Delia M; Kahle, Kristopher T; Jackson, Michele; Rakhade, Sanjay N; Berry, Gerard T; Berry, Gerard; Jensen, Frances E

2013-01-01

Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

Bumetanide Enhances Phenobarbital Efficacy in a Rat Model of Hypoxic Neonatal Seizures

PubMed Central

Cleary, Ryan T.; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M.; Li, Yijun; Rotenberg, Alexander; Talos, Delia M.; Kahle, Kristopher T.; Jackson, Michele; Rakhade, Sanjay N.; Berry, Gerard; Jensen, Frances E.

2013-01-01

Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na+-K+-2 Cl− cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures. PMID:23536761

Incidence of seizure exacerbation and seizures reported as adverse events during adjunctive treatment with eslicarbazepine acetate: A pooled analysis of three Phase III controlled trials.

PubMed

Carreño, Mar; Benbadis, Selim; Rocha, Francisco; Blum, David; Cheng, Hailong

2017-12-01

To investigate whether adjunctive eslicarbazepine acetate (ESL) could lead to exacerbation of seizures in some patients. Post-hoc analysis of data pooled from three Phase III trials of adjunctive ESL (studies 301, 302, and 304) for refractory partial-onset seizures (POS). Following an 8-week baseline period, patients were randomized to receive placebo or ESL 400, 800, or 1,200 mg once daily (2-week titration, 12-week maintenance, 2-4 week tapering-off periods). Patient seizure diary data and seizure treatment-emergent adverse event (TEAE) reports were pooled for analysis. The modified intent-to-treat and safety populations comprised 1,410 patients and 1,447 patients, respectively. Titration period : Compared with placebo (32/21%), significantly smaller proportions of patients taking ESL 800 mg (20/15%) and 1,200 mg (22/12%) had a ≥25/≥50% increase in standardized seizure frequency (SSF) from baseline; there was no significant difference between placebo and ESL 400 mg. Maintenance period : Compared with placebo (20%), significantly smaller proportions of patients taking ESL (400 mg, 12%; 800 mg, 12%; 1,200 mg, 14%) had an increase in SSF ≥25%. When evaluating ≥50% increases in SSF, only ESL 800 mg (7%) was significantly different from placebo (12%). Some patients had no secondarily generalized tonic-clonic (sGTC) seizures during baseline but had ≥1 sGTC seizure during maintenance treatment (placebo, 11%; ESL 400 mg, 5%; 800 mg, 10%; 1,200 mg, 5%). Fewer patients had a ≥25% increase in sGTC seizure frequency with ESL (400 mg, 11%; 800 mg, 9%; 1,200 mg, 14%) versus placebo (19%). The incidence of seizures reported as TEAEs was low in all treatment groups; incidences were generally lower with ESL versus placebo. Tapering-off period : Similar proportions of patients taking ESL and placebo had a ≥25/≥50% increase in SSF. Seizure TEAE incidence was numerically higher with ESL versus placebo. Treatment with adjunctive ESL does not appear to aggravate POS or sGTC seizures.

A New Model to Study Sleep Deprivation-Induced Seizure

PubMed Central

Lucey, Brendan P.; Leahy, Averi; Rosas, Regine; Shaw, Paul J.

2015-01-01

Background and Study Objectives: A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation. Design: Seizure activity was evaluated in an adult bang-sensitive seizure mutant, stress sensitive B (sesB9ed4), and in an adult temperature sensitive seizure mutant seizure (seits1) under baseline and following 12 h of sleep deprivation. The long-term effect of sleep deprivation on young, immature sesB9ed4 flies was also assessed. Setting: Laboratory. Participants: Drosophila melanogaster. Interventions: Sleep deprivation. Measurements and Results: Sleep deprivation increased seizure susceptibility in adult sesB9ed4/+ and seits1 mutant flies. Sleep deprivation also increased seizure susceptibility when sesB was disrupted using RNAi. The effect of sleep deprivation on seizure activity was reduced when sesB9ed4/+ flies were given the anti-seizure drug, valproic acid. In contrast to adult flies, sleep deprivation during early fly development resulted in chronic seizure susceptibility when sesB9ed4/+ became adults. Conclusions: These findings show that Drosophila is a model organism for investigating the relationship between sleep and seizure activity. Citation: Lucey BP, Leahy A, Rosas R, Shaw PJ. A new model to study sleep deprivation-induced seizure. SLEEP 2015;38(5):777–785. PMID:25515102

Effects of propofol and dizocilpine maleate on the cognitive abilities and the hyperphosphorylation of Tau protein of rats after the electroconvulsive therapy.

PubMed

Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Li, Ping; Liu, Xiao-bin

2012-08-01

To explore the effects of propofol and dizocilpine maleate (MK-801) on the cognitive abilities the hyperphosphorylation of Tau protein of rats after the electroconvulsive therapy. Two intervention factors including electroconvulsive shock therapy (ECT) (two levels: not applied and one treatment course) and drug intervention (three levels: intravenous saline,intravenous MK-801, and intravenous propofol). The morris water maze test started within 1 day after ECT to evaluate the learning-memory. The glutamate level in the hippocampus of rats was determined by high-performance liquid chromatography. The Tau protein that includes Tau5 (total Tau protein), PHF-1 (pSer(396/404)), AT8 (pSer(199/202)), and 12E8 (pSer(262)) in the hippocampus of rats was determined using Western blotting. Propofol, MK-801, and ECT could induce the impairment of learning-memory in depressed rats. The electroconvulsive shock significantly up-regulated the glutamate level, which was reduces by the propofol. The ECT up-regulated the hyperphosphorylation of Tau protein in the hippocampus of depressed rats, which was reduced by propofol and MK-801. Both propofol and MK-801 could protect against the impairment of learning-memory and reduce the hyperphosphorylation of Tau protein induced by ECT in depressed rats.

Seizure Risk in Patients with Attention-Deficit-Hyperactivity Disorder Treated with Atomoxetine

ERIC Educational Resources Information Center

Wernicke, Joachim F.; Holdridge, Karen Chilcott; Jin, Ling; Edison, Timothy; Zhang, Shuyu; Bangs, Mark E.; Allen, Albert J.; Ball, Susan; Dunn, David

2007-01-01

The comorbidity of seizures, epilepsy, and attention-deficit-hyperactivity disorder (ADHD) prompted the examination of whether atomoxetine use for ADHD is associated with an increased risk of seizures. Seizures and seizure-related symptoms were reviewed from two independent Eli Lilly and Company databases: the atomoxetine clinical trials database…

Seizure activity results in calcium- and mitochondria-independent ROS production via NADPH and xanthine oxidase activation

PubMed Central

Kovac, S; Domijan, A-M; Walker, M C; Abramov, A Y

2014-01-01

Seizure activity has been proposed to result in the generation of reactive oxygen species (ROS), which then contribute to seizure-induced neuronal damage and eventually cell death. Although the mechanisms of seizure-induced ROS generation are unclear, mitochondria and cellular calcium overload have been proposed to have a crucial role. We aim to determine the sources of seizure-induced ROS and their contribution to seizure-induced cell death. Using live cell imaging techniques in glioneuronal cultures, we show that prolonged seizure-like activity increases ROS production in an NMDA receptor-dependent manner. Unexpectedly, however, mitochondria did not contribute to ROS production during seizure-like activity. ROS were generated primarily by NADPH oxidase and later by xanthine oxidase (XO) activity in a calcium-independent manner. This calcium-independent neuronal ROS production was accompanied by an increase in intracellular [Na+] through NMDA receptor activation. Inhibition of NADPH or XO markedly reduced seizure-like activity-induced neuronal apoptosis. These findings demonstrate a critical role for ROS in seizure-induced neuronal cell death and identify novel therapeutic targets. PMID:25275601

Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice.

PubMed

Salat, Kinga; Moniczewski, Andrzej; Salat, Robert; Janaszek, Monika; Filipek, Barbara; Malawska, Barbara; Wieckowski, Krzysztof

2012-03-01

Recently we have shown that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride (LPP1) is an antinociceptive and local anesthetic agent in rodents. Below an extended study of the pharmacological activity of LPP1 is described. In vitro LPP1 has no affinity for GABA(A), opioidergic μ and serotonergic 5-HT(1A) receptors. The total antioxidant capacity of LPP1 (1-10mM) measured as ABTS radical cation-scavenging activity showed that LPP1 has dose-dependent antioxidant properties in vitro. Low plasma concentration of this compound detected by means of HPLC method 30min after its intraperitoneal administration suggests a rapid conversion to metabolite(s) which may be responsible for its analgesic and anticonvulsant activities in vivo. In vivo the compound's influence on the electroconvulsive threshold and its activity in the maximal electroshock seizure test (MES) were evaluated. The results demonstrated that LPP1 had an anticonvulsant activity in the MES model (ED(50)=112mg/kg) and at a dose of 50mg/kg was able to elevate the electroconvulsive threshold for 8mA as compared to the vehicle-treated mice. The analgesic activity of LPP1 was investigated in the acetic acid-induced writhing test in two groups of mice: animals with sensory C-fibers ablated, and mice with C-fibers unimpaired. It proved the potent activity of this compound in both groups (approximately 85% as compared to the vehicle-treated mice). The adverse effects of LPP1 were evaluated as acute toxicity (LD(50)=747.8mg/kg) and motor coordination impairments in the rotarod and chimney tests. The results from these tests show that LPP1 at doses higher than 100mg/kg is likely to impair the motor performance of experimental animals. Concluding, LPP1 is an analgesic and anticonvulsant compound which has antioxidant properties in vitro. Further studies are necessary to assess whether the antioxidant activity and the receptor profiling demonstrated in vitro can be confirmed for its metabolite(s) that are formed in vivo. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of Federal drug law enforcement on the supply of heroin in Australia.

PubMed

Smithson, Michael; McFadden, Michael; Mwesigye, Sue-Ellen

2005-08-01

To conduct an empirical investigation of the efficacy of law enforcement in reducing heroin supply in Australia. Specifically, this paper addresses the question of whether heroin purity levels in the Australian Capital Territory (ACT) could be predicted by heroin seizures at the national level by the Australian Federal Police (AFP) in the preceding year. We considered two forms of evidence. First, a Bayesian Markov Chain Monte Carlo (MCMC) change-point model was used to discover (a) if there was a substantial increase in heroin seizures by the AFP, (b) when the increase began and (c) whether it occurred after increased funding to the Australian Federal Police for the purpose of drug law enforcement. Second, standard time-series methods were used to ascertain whether fluctuations in heroin seizure weights or the frequency of large-scale seizures after the aforementioned changes in seizure levels predicted fluctuations in heroin purity levels in the ACT after autocorrelation had been removed from the purity series. A Bayesian MCMC change-point model supported the hypothesis that heroin seizures rapidly increased about a year before the estimated decline in heroin purity and after the increased funding of AFP. The autoregression models suggested that 10-20% of the variance in the residuals of the heroin purity series was predicted by appropriately lagged residuals of the seizure-number and log-weight series, after autocorrelation had been removed. The overall results are consistent with the hypothesis that large-scale heroin seizures by the AFP reduce street-level heroin supply a year or so later, although the short-term dynamics suggest an 'opponent' response to residual fluctuations in seizures. To our knowledge, this is first time a connection has been identified between large-scale heroin seizures and street-level supply.

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.

High-frequency oscillations mirror disease activity in patients with epilepsy.

PubMed

Zijlmans, M; Jacobs, J; Zelmann, R; Dubeau, F; Gotman, J

2009-03-17

High-frequency oscillations (HFOs) can be recorded in epileptic patients with clinical intracranial EEG. HFOs have been associated with seizure genesis because they occur in the seizure focus and during seizure onset. HFOs are also found interictally, partly co-occurring with epileptic spikes. We studied how HFOs are influenced by antiepileptic medication and seizure occurrence, to improve understanding of the pathophysiology and clinical meaning of HFOs. Intracerebral depth EEG was partly sampled at 2,000 Hz in 42 patients with intractable focal epilepsy. Patients with five or more usable nights of recording were selected. A sample of slow-wave sleep from each night was analyzed, and HFOs (ripples: 80-250 Hz, fast ripples: 250-500 Hz) and spikes were identified on all artifact-free channels. The HFOs and spikes were compared before and after seizures with stable medication dose and during medication reduction with no intervening seizures. Twelve patients with five to eight nights were included. After seizures, there was an increase in spikes, whereas HFO rates remained the same. Medication reduction was followed by an increase in HFO rates and mean duration. Contrary to spikes, high-frequency oscillations (HFOs) do not increase after seizures, but do so after medication reduction, similarly to seizures. This implies that spikes and HFOs have different pathophysiologic mechanisms and that HFOs are more tightly linked to seizures than spikes. HFOs seem to play an important role in seizure genesis and can be a useful clinical marker for disease activity.

Synchronization analysis of voltage-sensitive dye imaging during focal seizures in the rat neocortex

NASA Astrophysics Data System (ADS)

Takeshita, Daisuke; Bahar, Sonya

2011-12-01

Seizures are often assumed to result from an excess of synchronized neural activity. However, various recent studies have suggested that this is not necessarily the case. We investigate synchronization during focal neocortical seizures induced by injection of 4-aminopyridine (4AP) in the rat neocortex in vivo. Neocortical activity is monitored by field potential recording and by the fluorescence of the voltage-sensitive dye RH-1691. After removal of artifacts, the voltage-sensitive dye (VSD) signal is analyzed using the nonlinear dynamics-based technique of stochastic phase synchronization in order to determine the degree of synchronization within the neocortex during the development and spread of each seizure event. Results show a large, statistically significant increase in synchronization during seizure activity. Synchrony is typically greater between closer pixel pairs during a seizure event; the entire seizure region is synchronized almost exactly in phase. This study represents, to our knowledge, the first application of synchronization analysis methods to mammalian VSD imaging in vivo. Our observations indicate a clear increase in synchronization in this model of focal neocortical seizures across a large area of the neocortex; a sharp increase in synchronization during seizure events was observed in all 37 seizures imaged. The results are consistent with a recent computational study which simulates the effect of 4AP in a neocortical neuron model.

Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling

PubMed Central

Feng, Bo; Tang, Yangshun; Chen, Bin; Xu, Cenglin; Wang, Yi; Dai, Yunjian; Wu, Dengchang; Zhu, Junmin; Wang, Shuang; Zhou, Yudong; Shi, Liyun; Hu, Weiwei; Zhang, Xia; Chen, Zhong

2016-01-01

It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS. PMID:26902320

A minimum of 3 months of dietary fish oil supplementation is required to raise amygdaloid afterdischarge seizure thresholds in rats--implications for treating complex partial seizures.

PubMed

Taha, Ameer Y; Trepanier, Marc-Olivier; Ciobanu, Flaviu A; Taha, Nadeen M; Ahmed, Muaz; Zeng, Qiudi; Cheuk, Waiyin I; Ip, Bryan; Filo, Elvis; Scott, Brian W; Burnham, W M; Bazinet, Richard P

2013-04-01

Complex partial seizures, which typically originate in limbic structures such as the amygdala, are often resistant to antiseizure medications. Our goal was to investigate the effects of chronic dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) derived from fish oil on seizure thresholds in the amygdala, as well as on blood and brain PUFA levels. The acute effects of injected n-3 PUFAs--eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--were also tested in the maximal pentylenetetrazol (PTZ) seizure model. In amygdala-implanted subjects, fish oil supplementation significantly increased amygdaloid afterdischarge thresholds, as compared with controls at 3, 5, and 7 months after the start of supplementation. Fish oil supplementation also increased serum EPA and DHA concentrations. DHA concentration in the pyriform-amygdala area increased in the fish-oil treated group by 17-34%, but this effect did not reach statistical significance (P=0.065). DHA significantly increased the latency to seizure onset in the PTZ seizure model, whereas EPA had no significant effect. These observations suggest that chronic dietary fish oil supplementation can raise focal amygdaloid seizure thresholds and that this effect is likely mediated by DHA rather than by EPA. Copyright © 2012 Elsevier Inc. All rights reserved.

Dynamic, cell type-specific roles for GABAergic interneurons in a mouse model of optogenetically inducible seizures

PubMed Central

Khoshkhoo, Sattar; Vogt, Daniel; Sohal, Vikaas S.

2016-01-01

SUMMARY GABAergic interneurons play critical roles in seizures, but it remains unknown whether these vary across interneuron subtypes or evolve during a seizure. This uncertainty stems from the unpredictable timing of seizures in most models, which limits neuronal imaging or manipulations around the seizure onset. Here, we describe a mouse model for optogenetic seizure induction. Combining this with calcium imaging, we find that seizure onset rapidly recruits parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptitde (VIP)-expressing interneurons, whereas excitatory neurons are recruited several seconds later. Optogenetically inhibiting VIP interneurons consistently increased seizure threshold and reduced seizure duration. Inhibiting PV+ and SOM+ interneurons had mixed effects on seizure initiation, but consistently reduced seizure duration. Thus, while their roles may evolve during seizures, PV+ and SOM+ interneurons ultimately help maintain ongoing seizures. These results show how an optogenetically-induced seizure model can be leveraged to pinpoint a new target for seizure control: VIP interneurons. PMID:28041880

Epileptic seizures as condensed sleep: an analysis of network dynamics from electroencephalogram signals.

PubMed

Gast, Heidemarie; Müller, Markus; Rummel, Christian; Roth, Corinne; Mathis, Johannes; Schindler, Kaspar; Bassetti, Claudio L

2014-06-01

Both deepening sleep and evolving epileptic seizures are associated with increasing slow-wave activity. Larger-scale functional networks derived from electroencephalogram indicate that in both transitions dramatic changes of communication between brain areas occur. During seizures these changes seem to be 'condensed', because they evolve more rapidly than during deepening sleep. Here we set out to assess quantitatively functional network dynamics derived from electroencephalogram signals during seizures and normal sleep. Functional networks were derived from electroencephalogram signals from wakefulness, light and deep sleep of 12 volunteers, and from pre-seizure, seizure and post-seizure time periods of 10 patients suffering from focal onset pharmaco-resistant epilepsy. Nodes of the functional network represented electrical signals recorded by single electrodes and were linked if there was non-random cross-correlation between the two corresponding electroencephalogram signals. Network dynamics were then characterized by the evolution of global efficiency, which measures ease of information transmission. Global efficiency was compared with relative delta power. Global efficiency significantly decreased both between light and deep sleep, and between pre-seizure, seizure and post-seizure time periods. The decrease of global efficiency was due to a loss of functional links. While global efficiency decreased significantly, relative delta power increased except between the time periods wakefulness and light sleep, and pre-seizure and seizure. Our results demonstrate that both epileptic seizures and deepening sleep are characterized by dramatic fragmentation of larger-scale functional networks, and further support the similarities between sleep and seizures. © 2013 European Sleep Research Society.

Increased hair cortisol and antecedent somatic complaints in children with a first epileptic seizure.

PubMed

Stavropoulos, Ioannis; Pervanidou, Panagiota; Gnardellis, Charalampos; Loli, Nomiki; Theodorou, Virginia; Mantzou, Aimilia; Soukou, Faye; Sinani, Olga; Chrousos, George P

2017-03-01

Stress is the most frequent seizure-precipitating factor reported by patients with epilepsy, while stressful life events may increase seizure susceptibility in humans. In this study, we investigated the relations between both biological and behavioral measures of stress in children with a first epileptic seizure (hereafter called seizure). We hypothesized that hair cortisol, a biomarker of chronic stress reflecting approximately 3months of preceding exposure, might be increased in children with a first seizure. We also employed standardized questionnaires to examine presence of stress-related behavioral markers. This was a cross-sectional clinical study investigating stress-related parameters in children with a first seizure (First Epileptic Seizure Group (FESG), n=22) in comparison to healthy children without seizures (Control Group, n=29). Within 24h after a first seizure, hair samples were collected from children for the determination of cortisol. In parallel, perceived stress and anxiety and depressive symptoms were examined with appropriate self- and parent-completed questionnaires, and history of stressful life events during the past year was recorded. Emotional and behavioral problems were also assessed by parent-reported validated and widely-used questionnaires. Higher hair cortisol measurements were observed in the FESG than control children (7.5 versus 5.0pg/mg respectively, p=0.001). The former were more likely to complain of somatic problems than the latter (59.8 vs. 55.4 according to DSM-oriented Scale, p=0.021); however, there were no differences in perceived stress and anxiety or depressive symptoms between the two groups. Using ROC analysis of hair cortisol measurements for predicting disease status, the maximum sensitivity and specificity were observed for a cut-off point of 5.25pg/mg. Increased hair cortisol indicates chronic hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis prior to the first seizure. This might have contributed to the epileptogenesis process and may help explain the higher incidence of antecedent somatic complaints in the first seizure group. Copyright © 2016 Elsevier Inc. All rights reserved.

Earlier tachycardia onset in right than left mesial temporal lobe seizures.

PubMed

Kato, Kazuhiro; Jin, Kazutaka; Itabashi, Hisashi; Iwasaki, Masaki; Kakisaka, Yosuke; Aoki, Masashi; Nakasato, Nobukazu

2014-10-07

To clarify whether the presence and timing of peri-ictal heart rate (HR) change is a seizure lateralizing sign in patients with mesial temporal lobe epilepsy (mTLE). Long-term video EEGs were retrospectively reviewed in 21 patients, 7 men and 14 women aged 13 to 67 years, diagnosed as mTLE with MRI lesions in the mesial temporal structures (hippocampal sclerosis in 20 cases, amygdala hypertrophy in 1 case). Seventy-seven partial seizures without secondary generalization were extracted. Peri-ictal HR change was compared between 29 right seizures (9 patients) and 48 left seizures (12 patients). HR abruptly increased in all 29 right seizures and 42 of 48 left seizures. Onset time of HR increase in relation to ictal EEG onset was significantly earlier in right seizures than in left seizures (mean ± SD, -11.5 ± 14.8 vs 9.2 ± 21.7 seconds; p < 0.0001). Time of maximum HR was also significantly earlier in right seizures than in left seizures (36.0 ± 18.1 vs 58.0 ± 28.7 seconds; p < 0.0001). Maximum HR changes from baseline showed no significant difference between right and left seizures (47.5 ± 19.1 vs 40.8 ± 20.0/min). Significantly earlier tachycardia in right than left mTLE seizures supports previous hypotheses that the right cerebral hemisphere is dominant in the sympathetic network. No HR change, or delayed tachycardia possibly due to seizure propagation to the right hemisphere, may be a useful lateralizing sign of left mTLE seizures. © 2014 American Academy of Neurology.

Electroconvulsive therapy (ECT) for catatonia in a patient with schizophrenia and synthetic cannabinoid abuse: a case report.

PubMed

Leibu, Evan; Garakani, Amir; McGonigle, Daniel P; Liebman, Lauren S; Loh, Daniella; Bryson, Ethan O; Kellner, Charles H

2013-12-01

We present the case of a young man with a long-standing history of schizophrenia who presented with severe and life-threatening catatonia in the setting of synthetic cannabis use who was successfully treated with electroconvulsive therapy. To our knowledge, this is the first reported case of severe and persistent catatonia in the setting of synthetic cannabis use and the first documented successful treatment.

Is Maintenance Electroconvulsive Therapy Always an Elective Procedure?: Weighing Medical Versus Psychiatric Risk.

PubMed

Rosenthal, Isobel A; Kellner, Charles H

2018-03-01

Because of the severe nature of psychiatric illness, electroconvulsive therapy (ECT) is not always an "elective procedure." The pre-ECT medical evaluation, although important, should not be an impediment to timely ECT. We argue that an arbitrary regulation requiring new assessments every 30 days may be unduly burdensome and unnecessary. The small medical risk of treatment should be weighed against the potential psychiatric risk (including suicide) of delayed treatment.

Cotard's syndrome with schizophreniform disorder can be successfully treated with electroconvulsive therapy: case report

PubMed Central

Caliyurt, Okan; Vardar, Erdal; Tuglu, Cengiz

2004-01-01

We report a case of Cotard's syndrome associated with psychotic symptoms. A 27-year-old man was admitted to hospital with the diagnosis of schizophreniform disorder. His presenting symptoms, which had started 1 month before hospital admission, were somatic delusions of gastrointestinal and cardiovascular malfunction and the absence of a stomach, which resulted in a decrease in weight from 75 kg to 63 kg in 1 month. Cranial computed tomographic images showed dilatation of the lateral and third ventricles, whereas magnetic resonance imaging revealed central atrophy and lateral ventricle dilatation. Single- photon emission computed tomography demonstrated left temporal, left frontal and left parietal hypoperfusion. The patient did not respond to antipsychotic therapies, but he was successfully treated with electroconvulsive therapy. This report emphasizes that Cotard's syndrome may be accompanied by lesions of the left hemisphere and that electroconvulsive therapy could be the first-line therapy in such patients with psychotic disorder. PMID:15069468

Convulsions may alter the specificity of kappa-opiate receptors.

PubMed

Mansour, A; Valenstein, E S

1986-06-01

Morphine, a mu-opiate agonist, and ethylketazocine, a kappa-opiate agonist, produce distinct behavioral, pharmacologic, and biochemical effects. In the mouse, large doses of morphine produce convulsions that are usually lethal and that cannot be blocked by naltrexone, whereas ethylketazocine produces nonlethal clonic convulsions that can be blocked by naltrexone. Moreover, mice made tolerant to morphine failed to show cross-tolerance to ethylketazocine, suggesting that the convulsions induced by these drugs are not mediated via a common opioid mechanism. Following a series of electroconvulsive shocks, both morphine and ethylketazocine produced clonic convulsions that were not lethal and that could be blocked by naltrexone. Furthermore, electroconvulsive shock-treated animals made tolerant to morphine-induced convulsions showed cross-tolerance to ethylketazocine. These data suggest that electroconvulsive shock may alter kappa-opioid systems in such a way as to allow mu-agonists to be functional at these sites.

Is electroconvulsive therapy effective as augmentation in clozapine-resistant schizophrenia?

PubMed

Kittsteiner Manubens, Lucas; Lobos Urbina, Diego; Aceituno, David

2016-10-14

Clozapine is considered to be the most effective antipsychotic drug for patients with treatment resistant schizophrenia, but up to a third of the patients do not respond to this treatment. Various strategies have been tried to augment the effect of clozapine in non-responders, one of these strategies being electroconvulsive therapy. However, its efficacy and safety are not yet clear. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 55 studies, among them six randomized controlled trials addressing clozapine-resistant schizophrenia. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded electroconvulsive therapy probably augments response to clozapine in patients with treatment resistant schizophrenia, but it is not possible to determine if it leads to cognitive adverse effects because the certainty of the evidence is very low.

Electroconvulsive therapy and its different indications

PubMed Central

Baghai, Thomas C.; Möller, Hans-Jürgen

2008-01-01

In spite of recent developments in the pharmacotherapy of depressive disorders, the delay until clinical improvement can be achieved, and the considerable rate of nonresponse and nonremission, are major problems which remain unresolved. Electroconvulsive therapy (ECT) is a nonpharmacoloqic bioloqical treatment which has been proven to be a highly effective treatment option, predominantly for depression, but also for schizophrenia and other indications. Though there is a lack of controlled investigations on long-term treatments, ECT can also be used for relapse prevention during maintenance therapies. The safety and tolerabitity of electroconvulsive treatment have been enhanced by the use of modified stimulation techniques and by progress in modern anesthesia. Thus, today a safe treatment can also be offered to patients with higher somatic risks, ECT still represents an important option, especially in the therapy of treatmentresistant psychiatric disorders after medication treatment failures. Earlier consideration of ECT may reduce the rate of chronic and difficult-to-treat psychiatric disorders. PMID:18472488

Recurrent spontaneous motor seizures after repeated low-dose systemic treatment with kainate: assessment of a rat model of temporal lobe epilepsy.

PubMed

Hellier, J L; Patrylo, P R; Buckmaster, P S; Dudek, F E

1998-06-01

Human temporal lobe epilepsy is associated with complex partial seizures that can produce secondarily generalized seizures and motor convulsions. In some patients with temporal lobe epilepsy, the seizures and convulsions occur following a latent period after an initial injury and may progressively increase in frequency for much of the patient's life. Available animal models of temporal lobe epilepsy are produced by acute treatments that often have high mortality rates and/or are associated with a low proportion of animals developing spontaneous chronic motor seizures. In this study, rats were given multiple low-dose intraperitoneal (i.p.) injections of kainate in order to minimize the mortality rate usually associated with single high-dose injections. We tested the hypothesis that these kainate-treated rats consistently develop a chronic epileptic state (i.e. long-term occurrence of spontaneous, generalized seizures and motor convulsions) following a latent period after the initial treatment. Kainate (5 mg/kg per h, i.p.) was administered to rats every hour for several hours so that class III-V seizures were elicited for > or = 3 h, while control rats were treated similarly with saline. This treatment protocol had a relatively low mortality rate (15%). After acute treatment, rats were observed for the occurrence of motor seizures for 6-8 h/week. Nearly all of the kainate-treated rats (97%) had two or more spontaneous motor seizures months after treatment. With this observation protocol, the average latency for the first spontaneous motor seizure was 77+/-38 (+/-S.D.) days after treatment. Although variability was observed between rats, seizure frequency initially increased with time after treatment, and nearly all of the kainate-treated rats (91%) had spontaneous motor seizures until the time of euthanasia (i.e. 5-22 months after treatment). Therefore, multiple low-dose injections of kainate, which cause recurrent motor seizures for > or = 3 h, lead to the development of a chronic epileptic state that is characterized by (i) a latent period before the onset of chronic motor seizures, and (ii) a high but variable seizure frequency that initially increases with time after the first chronic seizure. This modification of the kainate-treatment protocol is efficient and relatively simple, and the properties of the chronic epileptic state appear similar to severe human temporal lobe epilepsy. Furthermore, the observation that seizure frequency initially increased as a function of time after kainate treatment supports the hypothesis that temporal lobe epilepsy can be a progressive syndrome.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

PubMed Central

Giacobbe, Peter; Kennedy, Sidney H.; Blumberger, Daniel M.; Daskalakis, Zafiris J.; Downar, Jonathan; Modirrousta, Mandana; Patry, Simon; Vila-Rodriguez, Fidel; Lam, Raymond W.; MacQueen, Glenda M.; Parikh, Sagar V.; Ravindran, Arun V.

2016-01-01

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Neurostimulation Treatments” is the fourth of six sections of the 2016 guidelines. Results: Evidence-informed responses were developed for 31 questions for 6 neurostimulation modalities: 1) transcranial direct current stimulation (tDCS), 2) repetitive transcranial magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain stimulation (DBS). Most of the neurostimulation treatments have been investigated in patients with varying degrees of treatment resistance. Conclusions: There is increasing evidence for efficacy, tolerability, and safety of neurostimulation treatments. rTMS is now a first-line recommendation for patients with MDD who have failed at least 1 antidepressant. ECT remains a second-line treatment for patients with treatment-resistant depression, although in some situations, it may be considered first line. Third-line recommendations include tDCS and VNS. MST and DBS are still considered investigational treatments. PMID:27486154

Reduced expression of IA channels is associated with post-ischemic seizures.

PubMed

Lei, Zhigang; Zhang, Hui; Liang, Yanling; Xu, Zao C

2016-08-01

Post-stroke seizures are considered as a major cause of epilepsy in adults. The pathophysiologic mechanisms resulting in post-stroke seizures are not fully understood. The present study attempted to reveal a new mechanism underlying neuronal hyperexcitability responsible to the seizure development after ischemic stroke. Transient global ischemia was produced in adult Wistar rats using the 4-vessel occlusion (4-VO) method. The spontaneous behavioral seizures were defined by the Racine scale III-V. The neuronal death in the brain was determined by hematoxylin-eosin staining. The expression levels of A-type potassium channels were analyzed by immunohistochemical staining and western blotting. We found that the incidence of spontaneous behavioral seizures increased according to the severity of ischemia with 0% after 15-min ischemia and ∼50% after 25-min ischemia. All behavioral seizures occurred with 48h after ischemia. Morphological analysis indicated that brain damage was not correlated with behavioral seizures. Immunohistochemical staining showed that the expression levels of the A-type potassium channel subunit Kv4.2 was significantly reduced in ischemic brains with behavioral seizures, but not in ischemic brains without seizures. In addition, rats failing to develop spontaneous behavioral seizures within 2days after ischemia were more sensitive to bicuculline-induced seizures at 2 months after ischemia than control rats. Meanwhile, Kv4.2 expression was decreased in brain at 2 months after ischemia. Our results demonstrated the reduction of Kv4.2 expression might contribute to the development of post-ischemic seizures and long-term increased seizure susceptibility after ischemia. The mechanisms underlying post-stroke seizures and epilepsy is unknown so far. The down-regulation of IA channels may explained the abnormal neuronal hyperexcitability responsible for the seizure development after ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in Non-Convulsive Seizures in a Rat Model of Post-Traumatic Epilepsy.

PubMed

Campbell, John N; Gandhi, Anandh; Singh, Baljinderjit; Churn, Severn B

2014-01-01

Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later.

Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in Non-Convulsive Seizures in a Rat Model of Post-Traumatic Epilepsy

PubMed Central

Campbell, John N.; Gandhi, Anandh; Singh, Baljinderjit; Churn, Severn B.

2014-01-01

Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later. PMID:25580467

Seizure-Related Regulation of GABAA Receptors in Spontaneously Epileptic Rats

PubMed Central

González, Marco I.; Grabenstatter, Heidi L.; del Rio, Christian Cea; Del Angel, Yasmin Cruz; Carlsen, Jessica; Laoprasert, Rick; White, Andrew M.; Huntsman, Molly M.; Brooks-Kayal, Amy

2015-01-01

In this study, we analyzed the impact that spontaneous seizures might have on the plasma membrane expression, composition and function of GABAA receptors (GABAARs). For this, tissue of chronically epileptic rats was collected within 3 hours of seizure occurrence (≤3 hours group) or at least 24 hours after seizure occurrence (≥24 hours group). A retrospective analysis of seizure frequency revealed that selecting animals on the bases of seizure proximity also grouped animals in terms of overall seizure burden with a higher seizure burden observed in the ≤3 hours group. A biochemical analysis showed that although animals with more frequent/recent seizures (≤3 hours group) had similar levels of GABAAR at the plasma membrane they showed deficits in inhibitory neurotransmission. In contrast, tissue obtained from animals experiencing infrequent seizures (≥24 hours group) had increased plasma membrane levels of GABAAR and showed no deficit in inhibitory function. Together, our findings offer an initial insight into the molecular changes that might help to explain how alterations in GABAAR function can be associated with differential seizure burden. Our findings also suggest that increased plasma membrane levels of GABAAR might act as a compensatory mechanism to more effectively maintain inhibitory function, repress hyperexcitability and reduce seizure burden. This study is an initial step towards a fuller characterization of the molecular events that trigger alterations in GABAergic neurotransmission during chronic epilepsy. PMID:25769812

Rapidly Learned Identification of Epileptic Seizures from Sonified EEG

PubMed Central

Loui, Psyche; Koplin-Green, Matan; Frick, Mark; Massone, Michael

2014-01-01

Sonification refers to a process by which data are converted into sound, providing an auditory alternative to visual display. Currently, the prevalent method for diagnosing seizures in epilepsy is by visually reading a patient’s electroencephalogram (EEG). However, sonification of the EEG data provides certain advantages due to the nature of human auditory perception. We hypothesized that human listeners will be able to identify seizures from EEGs using the auditory modality alone, and that accuracy of seizure identification will increase after a short training session. Here, we describe an algorithm that we have used to sonify EEGs of both seizure and non-seizure activity, followed by a training study in which subjects listened to short clips of sonified EEGs and determined whether each clip was of seizure or normal activity, both before and after a short training session. Results show that before training subjects performed at chance level in differentiating seizures from non-seizures, but there was a significant improvement of accuracy after the training session. After training, subjects successfully distinguished seizures from non-seizures using the auditory modality alone. Further analyses using signal detection theory demonstrated improvement in sensitivity and reduction in response bias as a result of training. This study demonstrates the potential of sonified EEGs to be used for the detection of seizures. Future studies will attempt to increase accuracy using novel training and sonification modifications, with the goals of managing, predicting, and ultimately controlling seizures using sonification as a possible biofeedback-based intervention for epilepsy. PMID:25352802

Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study.

PubMed

Sokoloff, Max D; Plegue, Melissa A; Chervin, Ronald D; Barks, John D E; Shellhaas, Renée A

2015-07-01

Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures. In neonates monitored with video-electroencephalography, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 s. Mean rSO2 was extracted for 1-h blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of three times the duration of the seizure before and after the ictal pattern, as well as during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction. For 20 neonates (estimated gestational age: 39.6 ± 1.5 wk), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (P = 0.005), and fractional tissue oxygen extraction declined (P = 0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and postictal phases (baseline 81.2 vs. ictal 77.7 vs. postictal 79.4; P = 0.004). Fractional tissue oxygen extraction was highest during seizures (P = 0.002). Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact.

Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study

PubMed Central

Sokoloff, Max D.; Plegue, Melissa A.; Chervin, Ronald D.; Barks, John D.E.; Shellhaas, Renée A.

2014-01-01

Background Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically-ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures. Methods In neonates monitored with video-EEG, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 seconds. Mean rSO2 was extracted for 1-hour blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of 3-times the duration of the seizure before and after the ictal pattern, and during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction (FTOE). Results For 20 neonates (EGA 39.6±1.5 weeks), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (p=0.005), and FTOE declined (p=0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and post-ictal phases (baseline 81.2 vs. ictal 77.7 vs. post-ictal 79.4; p=0.004). FTOE was highest during seizures (p=0.002). Conclusions Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact. PMID:25812123

Dynamic timecourse of typical childhood absence seizures: EEG, behavior and fMRI

PubMed Central

Bai, X; Vestal, M; Berman, R; Negishi, M; Spann, M; Vega, C; Desalvo, M; Novotny, EJ; Constable, RT; Blumenfeld, H

2010-01-01

Absence seizures are 5–10 second episodes of impaired consciousness accompanied by 3–4Hz generalized spike-and-wave discharge on electroencephalography (EEG). The timecourse of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from 9 pediatric patients. We investigated behavior concurrently using a continuous performance task (CPT) or simpler repetitive tapping task (RTT). EEG time-frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5s before seizure onset, followed by profound fMRI decreases continuing >20s after seizure end. This timecourse differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long lasting sequence of fMRI changes in absence seizures, which are not detectible by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior. PMID:20427649

Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy.

PubMed

Patel, Dipan C; Wallis, Glenna; Dahle, E Jill; McElroy, Pallavi B; Thomson, Kyle E; Tesi, Raymond J; Szymkowski, David E; West, Peter J; Smeal, Roy M; Patel, Manisha; Fujinami, Robert S; White, H Steve; Wilcox, Karen S

2017-01-01

Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler's murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures. We found a significant increase in both mRNA and protein levels of TNFα and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the hippocampus, a brain region most likely involved in seizure initiation, after TMEV infection, which suggests that TNFα signaling, predominantly through TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal cell-surface glutamate receptor expression was also observed during acute seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no effect on acute seizures, several lines of genetically modified animals deficient in either TNFα or TNFRs had robust changes in seizure incidence and severity after TMEV infection. TNFR2 -/- mice were highly susceptible to developing acute seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects during the acute seizure period. Taken together, the present results suggest that inflammation in the hippocampus, caused predominantly by TNFα signaling, contributes to hyperexcitability and acute seizures after TMEV infection. Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated effects of TNFα may provide antiseizure and disease-modifying effects after central nervous system infection.

Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy

PubMed Central

Patel, Dipan C.; Wallis, Glenna; Dahle, E. Jill; McElroy, Pallavi B.; Thomson, Kyle E.; West, Peter J.; Smeal, Roy M.; Patel, Manisha; Fujinami, Robert S.; White, H. Steve

2017-01-01

Abstract Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler’s murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures. We found a significant increase in both mRNA and protein levels of TNFα and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the hippocampus, a brain region most likely involved in seizure initiation, after TMEV infection, which suggests that TNFα signaling, predominantly through TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal cell-surface glutamate receptor expression was also observed during acute seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no effect on acute seizures, several lines of genetically modified animals deficient in either TNFα or TNFRs had robust changes in seizure incidence and severity after TMEV infection. TNFR2–/– mice were highly susceptible to developing acute seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects during the acute seizure period. Taken together, the present results suggest that inflammation in the hippocampus, caused predominantly by TNFα signaling, contributes to hyperexcitability and acute seizures after TMEV infection. Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated effects of TNFα may provide antiseizure and disease-modifying effects after central nervous system infection. PMID:28497109

Brain State Is a Major Factor in Preseizure Hippocampal Network Activity and Influences Success of Seizure Intervention

PubMed Central

Ewell, Laura A.; Liang, Liang; Armstrong, Caren; Soltész, Ivan; Leutgeb, Stefan

2015-01-01

Neural dynamics preceding seizures are of interest because they may shed light on mechanisms of seizure generation and could be predictive. In healthy animals, hippocampal network activity is shaped by behavioral brain state and, in epilepsy, seizures selectively emerge during specific brain states. To determine the degree to which changes in network dynamics before seizure are pathological or reflect ongoing fluctuations in brain state, dorsal hippocampal neurons were recorded during spontaneous seizures in a rat model of temporal lobe epilepsy. Seizures emerged from all brain states, but with a greater likelihood after REM sleep, potentially due to an observed increase in baseline excitability during periods of REM compared with other brains states also characterized by sustained theta oscillations. When comparing the firing patterns of the same neurons across brain states associated with and without seizures, activity dynamics before seizures followed patterns typical of the ongoing brain state, or brain state transitions, and did not differ until the onset of the electrographic seizure. Next, we tested whether disparate activity patterns during distinct brain states would influence the effectiveness of optogenetic curtailment of hippocampal seizures in a mouse model of temporal lobe epilepsy. Optogenetic curtailment was significantly more effective for seizures preceded by non-theta states compared with seizures that emerged from theta states. Our results indicate that consideration of behavioral brain state preceding a seizure is important for the appropriate interpretation of network dynamics leading up to a seizure and for designing effective seizure intervention. SIGNIFICANCE STATEMENT Hippocampal single-unit activity is strongly shaped by behavioral brain state, yet this relationship has been largely ignored when studying activity dynamics before spontaneous seizures in medial temporal lobe epilepsy. In light of the increased attention on using single-unit activity for the prediction of seizure onset and closed-loop seizure intervention, we show a need for monitoring brain state to interpret correctly whether changes in neural activity before seizure onset is pathological or normal. Moreover, we also find that the brain state preceding a seizure determines the success of therapeutic interventions to curtail seizure duration. Together, these findings suggest that seizure prediction and intervention will be more successful if tailored for the specific brain states from which seizures emerge. PMID:26609157

The effect of dorsal hippocampal administration of nicotinic and muscarinic cholinergic ligands on pentylenetetrazol-induced generalized seizures in rats.

PubMed

Gholami, Morteza; Saboory, Ehsan; Zare, Samad; Roshan-Milani, Shiva; Hajizadeh-Moghaddam, Akbar

2012-10-01

In the present study, the effects of intrahippocampal injections of cholinergic ligands on pentylenetetrazol (PTZ)-induced seizures were investigated in rats. The rats were assigned to 1 of the following 9 groups: saline, nicotine (0.5 or 1 μg), atropine (0.25 or 1 μg), oxotremorine-M (0.1 or 1 μg), or mecamylamine (2 or 8 μg). Cholinergic ligands were administered via intrahippocampal infusion 30 min before seizure induction (intraperitoneal injection of 80 mg/kg PTZ). Results show that antagonists caused nonsignificant increases in the latency of tonic-clonic seizures, significant decreases in the duration of tonic-clonic seizures, significant decreases in the latency of death, and increases in mortality rate. Agonists led to increases in the duration of tonic-clonic seizures, decreases in the latency of death, and decreases in mortality rate. These results provide compelling evidence that cholinergic ligands show modulatory effects on a PTZ model of acute seizure in the rat hippocampus. Copyright © 2012 Elsevier Inc. All rights reserved.

Seizure burden is independently associated with short term outcome in critically ill children

PubMed Central

Payne, Eric T.; Zhao, Xiu Yan; Frndova, Helena; McBain, Kristin; Sharma, Rohit; Hutchison, James S.

2014-01-01

Seizures are common among critically ill children, but their relationship to outcome remains unclear. We sought to quantify the relationship between electrographic seizure burden and short-term neurological outcome, while controlling for diagnosis and illness severity. Furthermore, we sought to determine whether there is a seizure burden threshold above which there is an increased probability of neurological decline. We prospectively evaluated all infants and children admitted to our paediatric and cardiac intensive care units who underwent clinically ordered continuous video-electroencephalography monitoring over a 3-year period. Seizure burden was quantified by calculating the maximum percentage of any hour that was occupied by electrographic seizures. Outcome measures included neurological decline, defined as a worsening Paediatric Cerebral Performance Category score between hospital admission and discharge, and in-hospital mortality. Two hundred and fifty-nine subjects were evaluated (51% male) with a median age of 2.2 years (interquartile range: 0.3 days–9.7 years). The median duration of continuous video-electroencephalography monitoring was 37 h (interquartile range: 21–56 h). Seizures occurred in 93 subjects (36%, 95% confidence interval = 30–42%), with 23 (9%, 95% confidence interval = 5–12%) experiencing status epilepticus. Neurological decline was observed in 174 subjects (67%), who had a mean maximum seizure burden of 15.7% per hour, compared to 1.8% per hour for those without neurological decline (P < 0.0001). Above a maximum seizure burden threshold of 20% per hour (12 min), both the probability and magnitude of neurological decline rose sharply (P < 0.0001) across all diagnostic categories. On multivariable analysis adjusting for diagnosis and illness severity, the odds of neurological decline increased by 1.13 (95% confidence interval = 1.05–1.21, P = 0.0016) for every 1% increase in maximum hourly seizure burden. Seizure burden was not associated with mortality (odds ratio: 1.003, 95% confidence interval: 0.99–1.02, P = 0.613). We conclude that in this cohort of critically ill children, increasing seizure burden was independently associated with a greater probability and magnitude of neurological decline. Our observation that a seizure burden of more than 12 min in a given hour was strongly associated with neurological decline suggests that early antiepileptic drug management is warranted in this population, and identifies this seizure burden threshold as a potential therapeutic target. These findings support the hypothesis that electrographic seizures independently contribute to brain injury and worsen outcome. Our results motivate and inform the design of future studies to determine whether more aggressive seizure treatment can improve outcome. PMID:24595203

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

PubMed

Boon, Paul; Vonck, Kristl; van Rijckevorsel, Kenou; El Tahry, Riem; Elger, Christian E; Mullatti, Nandini; Schulze-Bonhage, Andreas; Wagner, Louis; Diehl, Beate; Hamer, Hajo; Reuber, Markus; Kostov, Hrisimir; Legros, Benjamin; Noachtar, Soheyl; Weber, Yvonne G; Coenen, Volker A; Rooijakkers, Herbert; Schijns, Olaf E M G; Selway, Richard; Van Roost, Dirk; Eggleston, Katherine S; Van Grunderbeek, Wim; Jayewardene, Amara K; McGuire, Ryan M

2015-11-01

This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Exploring the capability of wireless near infrared spectroscopy as a portable seizure detection device for epilepsy patients.

PubMed

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

2015-03-01

Near infrared spectroscopy (NIRS) has proved useful in measuring significant hemodynamic changes in the brain during epileptic seizures. The advance of NIRS-technology into wireless and portable devices raises the possibility of using the NIRS-technology for portable seizure detection. This study used NIRS to measure changes in oxygenated (HbO), deoxygenated (HbR), and total hemoglobin (HbT) at left and right side of the frontal lobe in 33 patients with epilepsy undergoing long-term video-EEG monitoring. Fifteen patients had 34 focal seizures (20 temporal-, 11 frontal-, 2 parietal-lobe, one unspecific) recorded and analyzed with NIRS. Twelve parameters consisting of maximum increase and decrease changes of HbO, HbR and HbT during seizures (1 min before- to 3 min after seizure-onset) for left and right side, were compared with the patients' own non-seizure periods (a 2-h period and a 30-min exercise-period). In both non-seizure periods 4 min moving windows with maximum overlapping were applied to find non-seizure maxima of the 12 parameters. Detection was defined as positive when seizure maximum change exceeded non-seizure maximum change. When analyzing the 12 parameters separately the positive seizure detection was in the range of 6-24%. The increase in hemodynamics was in general better at detecting seizures (15-24%) than the decrease in hemodynamics (6-18%) (P=0.02). NIRS did not seem to be a suitable technology for generic seizure detection given the device, settings, and methods used in this study. There are still several challenges to overcome before the NIRS-technology can be used as a home-monitoring seizure detection device. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Chronic catatonic schizophrenia treated successfully with right unilateral ultrabrief pulse electroconvulsive therapy: case report.

PubMed

Cupina, Denise; Patil, Sachin; Loo, Colleen

2013-06-01

Catatonia is a syndrome with prominent motor and behavioral symptoms commonly seen in acutely ill psychiatric patients. Catatonic symptoms have been considered as positive predictors of response to electroconvulsive therapy (ECT); however, few studies so far have addressed the role of ECT treatment technique in schizophrenia. We present the case of a 41-year-old woman with chronic catatonic schizophrenia who was treated successfully with a course of ultrabrief right unilateral ECT.

Placebo Controlled Study of Repetitive Transcranial Magnetic Stimulation for the Treatment of Parkinson’s Disease

DTIC Science & Technology

2004-03-01

References Aarsland D., Larsen J.P., Waage 0., Langeveld J.H. Maintenance electroconvulsive therapy for Parkinson’s disease. Convuls Ther. 1997; 13: 274-277...following electroconvulsive therapy . 1: Psychopharmacology (Berl). 1982; 76: 371-376. Belmaker R.H., Grisaru N. Magnetic stimulation of the brain in...rTMS might have any long-lasting therapeutic effects (weeks or months) in persons with PD who are already receiving optimal available therapy

50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

PubMed

Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

2016-02-01

The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Salivary Alpha-Amylase Activity Levels in Catatonic Schizophrenia Decrease after Electroconvulsive Therapy.

PubMed

Kanayama, Misako; Miyaoka, Tsuyoshi; Araki, Tomoko; Hayashida, Maiko; Hashioka, Sadayuki; Horiguchi, Jun

2018-01-01

Dysfunction of the autonomic nervous system (ANS) in schizophrenia has been detected by electrophysiological methods, but the underlying mechanisms remain unknown. Several studies have suggested that measuring salivary alpha-amylase activity levels is useful for evaluating the ANS activity and that sAA levels increase in schizophrenia and correlate with Brief Psychiatric Rating Scale (BPRS) scores. However, no study has examined the relationship between sAA activity levels and symptoms of schizophrenia with catatonic state. We present the case of a 59-year-old female with persistent catatonic schizophrenia treated by electroconvulsive therapy. We evaluated the ANS activity by measuring sAA activity levels before and after ECT, and we evaluated her symptoms using the BPRS and Bush-Francis Catatonia Rating Scale (BFCRS). ECT was highly effective and BPRS and BFCRS scores substantially decreased. sAA activity levels decreased from 125 kU/l to 33 kU/l. sAA activity levels could be a potential biomarker of schizophrenia with catatonic state.

Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain.

PubMed

Imran, Imran; Hillert, Markus H; Klein, Jochen

2015-12-01

The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). Twenty-four hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase in glucose and a prominent, five-fold increase in lactate during seizures. Lactate release was because of neuronal activation as it was strongly reduced by infusion of tetrodotoxin, administration of atropine or when seizures were terminated by diazepam or ketamine. In ex vivo assays, mitochondrial function as measured by respirometry was not affected by 90 min of seizures. Extracellular levels of choline, however, increased two-fold and glycerol levels 10-fold, which indicate cellular phospholipid breakdown during seizures. Within 60 min of pilocarpine administration, hydroxylation of salicylate increased two-fold and formation of isoprostanes 20-fold, revealing significant oxidative stress in hippocampal tissue. Increases in lactate, glycerol and isoprostanes were abrogated, and increases in choline were completely prevented, when hippocampal probes were perfused with calcium-free solution. Similarly, administration of pregabalin (100 mg/kg i.p.), a calcium channel ligand, 15 min prior to pilocarpine strongly attenuated parameters of membrane damage and oxidative stress. We conclude that seizure development in a rat model of status epilepticus is accompanied by increases in extracellular lactate, choline and glycerol, and by oxidative stress, while mitochondrial function remains intact for at least 90 min. Membrane damage depends on calcium influx and can be prevented by treatment with pregabalin. Status epilepticus (SE) was induced in rats by lithium-pilocarpine ('Pilo') administration, and extracellular metabolites were measured by microdialysis. Seizures caused several-fold increases in lactate levels which were attenuated by diazepam ('Diaz'), ketamine, atropine and tetrodotoxin (TTX). Indicators of oxidative stress and membrane damage were also increased during seizures. Omission of calcium and pregabalin, a calcium channel blocker, reduced cellular damage induced by SE. © 2015 International Society for Neurochemistry.

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.

Implacable images: why epileptiform events continue to be featured in film and television.

PubMed

Kerson, Toba Schwaber; Kerson, Lawrence A

2006-06-01

Epileptiform events have been portrayed in film since 1900 and on television since the 1950's. Over time, portrayals have not reflected medicine's understanding of epilepsy. At present, it is unlikely that individuals who do not have a close relationship with someone with a seizure-disorder will witness a seizure. Because fictive and often incorrect images appear increasingly, many think of them as accurate depictions. The research addresses three questions in relation to these images: How do directors use the images? Why do uses of seizures in visual media not reflect contemporary scientific knowledge? Why have they persisted and increased in use? Data consist of material from 192 films and television episodes. The general category of seizures includes seizures in characters said to have epilepsy or some other condition, seizures related to drug or alcohol use, pseudoseizures and feigned seizures, and, a category in which, for example, someone is described as "having a fit." The research demonstrates how epileptiform events drive the narrative, support the genre, evoke specific emotional reactions, accentuate traits of characters with seizures, highlight qualities of other characters through their responses to the seizures, act as catalysts for actions, and enhance the voyeuristic experience of the audience. Twenty video sequences are included in the manuscript. The authors conclude that the visual experience of seizures remains so enthralling that its use is most likely to increase particularly on television, and that as the public has less experience with real seizures, depictions in film will continue to be more concerned with what the image can do for the show and less interested in accurate portrayals. Ways to influence depictions are suggested.

Transition dynamics of generalized multiple epileptic seizures associated with thalamic reticular nucleus excitability: A computational study

NASA Astrophysics Data System (ADS)

Liu, Suyu; Wang, Qingyun

2017-11-01

Presently, we improve a computational framework of thalamocortical circuits related to the Taylor's model to investigate the relationship between thalamic reticular nucleus (RE) excitability and epilepsy. By using bifurcation analysis, we explore the RE's excitability dynamics mechanism in the processes of seizure generation, development and transition. Results show that the seizure-free state, absence seizures, clonic seizures and tonic seizures can be formed as the RE excitability is changed in this established model. Importantly, it is verified that physiological changing GABAA inhibition in RE can elicit absence seizures and clonic seizures and the pathological transitions between these two seizures. Furthermore, when the level of AMPA connection is decreased or increased, this proposed model embraces absence seizures and clonic seizures, and tonic seizures, respectively. Except that, bifurcation mechanisms of dynamical transition of different seizures are analyzed in detail. In addition, hybrid regulations of the reticular nucleus excitability for epileptic seizures are proven to be valid within the suitable levels of AMPA and GABAA connection. Hopefully, the obtained results could be helpful for effective control of epileptic activities with additional pharmacological interference.

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 and temporal lobe seizures are more likely to cluster. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

RECURRENT NEONATAL SEIZURES RESULT IN LONG-TERM INCREASE OF NEURONAL NETWORK EXCITABILITY IN THE RAT NEOCORTEX

PubMed Central

Isaeva, Elena; Isaev, Dmytro; Savrasova, Alina; Khazipov, Rustem; Holmes, Gregory L.

2011-01-01

Neonatal seizures are associated with a high likelihood of adverse neurological outcomes, including mental retardation, behavioral disorders, and epilepsy. Early seizures typically involve the neocortex, and post-neonatal epilepsy is often of neocortical origin. However, our understanding of the consequences of neonatal seizures for neocortical function is limited. In the present study, we show that neonatal seizures induced by flurothyl result in markedly enhanced susceptibility of the neocortex to seizure-like activity. This change occurs in young rats studied weeks after the last induced seizure and in adult rats studied months after the initial seizures. Neonatal seizures resulted in reductions in the amplitude of spontaneous inhibitory postsynaptic currents and the frequency of miniature inhibitory postsynaptic currents, and significant increases in the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and in the frequency of miniature excitatory postsynaptic currents (mEPSCs) in pyramidal cells of layer 2/3 of the somatosensory cortex. The selective N-methyl-d-aspartate (NMDA) receptor antagonist d-2-amino-5-phosphon-ovalerate eliminated the differences in amplitude and frequency of sEPSCs and mEPSCs in the control and flurothyl groups, suggesting that NMDA receptors contribute significantly to the enhanced excitability seen in slices from rats that experienced recurrent neonatal seizures. Taken together, our results suggest that recurrent seizures in infancy result in a persistent enhancement of neocortical excitability. PMID:20384780

Predictors of seizure occurrence in children undergoing pre-surgical monitoring.

PubMed

Harini, Chellamani; Singh, Kanwaljit; Takeoka, Masanori; Parulkar, Isha; Bergin, Ann Marie; Loddenkemper, Tobias; Kothare, Sanjeev V

2013-10-01

Long-Term-Monitoring (LTM) is a valuable tool for seizure localization/lateralization among children with refractory-epilepsy undergoing pre-surgical-monitoring. The aim of this study was to examine the factors predicting occurrence of single/multiple seizures in children undergoing pre-surgical monitoring in the LTM unit. Chart review was done on 95 consecutive admissions on 92 children (40 females) admitted to the LTM-unit for pre-surgical workup. Relationship between occurrence of multiple (≥ 3) seizures and factors such as home seizure-frequency, demographics, MRI-lesions/seizure-type and localization/AED usage/neurological-exam/epilepsy-duration was evaluated by logistic-regression and survival-analysis. Home seizure-frequency was further categorized into low (up-to 1/month), medium (up-to 1/week) and high (>1/week) and relationship of these categories to the occurrence of multiple seizures was evaluated. Mean length of stay was 5.24 days in all 3 groups. Home seizure frequency was the only factor predicting the occurrence of single/multiple seizures in children undergoing presurgical workup. Other factors (age/sex/MRI-lesions/seizure-type and localization/AED-usage/neurological-exam/epilepsy-duration) did not affect occurrence of single/multiple seizures or time-to-occurrence of first/second seizure. Analysis of the home-seizure frequency categories revealed that 98% admissions in high-frequency, 94% in the medium, and 77% in low-frequency group had at-least 1 seizure recorded during the monitoring. Odds of first-seizure increased in high vs. low-frequency group (p=0.01). Eighty-nine percent admissions in high-frequency, 78% in medium frequency, versus 50% in low-frequency group had ≥ 3 seizures. The odds of having ≥ 3 seizures increased in high-frequency (p=0.0005) and in medium-frequency (p=0.007), compared to low-frequency group. Mean time-to-first-seizure was 2.7 days in low-frequency, 2.1 days in medium, and 2 days in high-frequency group. Time-to-first-seizure in high and medium-frequency was less than in low-frequency group (p<0.0014 and p=0.038). Majority of the admissions (92%) admitted to the LTM-unit for pre-surgical workup had at-least one seizure during a mean length of stay of 5.24 days. Home seizure-frequency was the only predictor influencing occurrence of single/multiple seizures in the LTM unit. Patients with low seizure-frequency are at risk for completing the monitoring with less than the optimum number (<3) of seizures captured. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Development of hypersynchrony in the cortical network during chemoconvulsant-induced epileptic seizures in vivo.

PubMed

Cymerblit-Sabba, Adi; Schiller, Yitzhak

2012-03-01

The prevailing view of epileptic seizures is that they are caused by increased hypersynchronous activity in the cortical network. However, this view is based mostly on electroencephalography (EEG) recordings that do not directly monitor neuronal synchronization of action potential firing. In this study, we used multielectrode single-unit recordings from the hippocampus to investigate firing of individual CA1 neurons and directly monitor synchronization of action potential firing between neurons during the different ictal phases of chemoconvulsant-induced epileptic seizures in vivo. During the early phase of seizures manifesting as low-amplitude rhythmic β-electrocorticography (ECoG) activity, the firing frequency of most neurons markedly increased. To our surprise, the average overall neuronal synchronization as measured by the cross-correlation function was reduced compared with control conditions with ~60% of neuronal pairs showing no significant correlated firing. However, correlated firing was not uniform and a minority of neuronal pairs showed a high degree of correlated firing. Moreover, during the early phase of seizures, correlated firing between 9.8 ± 5.1% of all stably recorded pairs increased compared with control conditions. As seizures progressed and high-frequency ECoG polyspikes developed, the firing frequency of neurons further increased and enhanced correlated firing was observed between virtually all neuronal pairs. These findings indicated that epileptic seizures represented a hyperactive state with widespread increase in action potential firing. Hypersynchrony also characterized seizures. However, it initially developed in a small subset of neurons and gradually spread to involve the entire cortical network only in the later more intense ictal phases.

Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

PubMed

Gidal, Barry E; Wechsler, Robert T; Sankar, Raman; Montouris, Georgia D; White, H Steve; Cloyd, James C; Kane, Mary Clare; Peng, Guangbin; Tworek, David M; Shen, Vivienne; Isojarvi, Jouko

2016-10-25

To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg -1 ·d -1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg -1 ·d -1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. NCT00518713 and NCT01160770. This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. © 2016 American Academy of Neurology.

Deconstructing tolerance with clobazam

PubMed Central

Wechsler, Robert T.; Sankar, Raman; Montouris, Georgia D.; White, H. Steve; Cloyd, James C.; Kane, Mary Clare; Peng, Guangbin; Tworek, David M.; Shen, Vivienne; Isojarvi, Jouko

2016-01-01

Objective: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Methods: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg−1·d−1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg−1·d−1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Results: Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Conclusions: Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. ClinicalTrials.gov identifier: NCT00518713 and NCT01160770. Classification of evidence: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. PMID:27683846

Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression: a longitudinal neuroimaging study

PubMed Central

Cano, M; Martínez-Zalacaín, I; Bernabéu-Sanz, Á; Contreras-Rodríguez, O; Hernández-Ribas, R; Via, E; de Arriba-Arnau, A; Gálvez, V; Urretavizcaya, M; Pujol, J; Menchón, J M; Cardoner, N; Soriano-Mas, C

2017-01-01

Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement. We assessed 12 patients with treatment-resistant depression (TRD) at four time points (pre-treatment, after the first ECT session, after the ninth ECT session and 15 days after ECT course completion) and 10 healthy participants at two time points, 5 weeks apart. Patients with TRD showed bilateral medial temporal lobe (MTL) and perigenual anterior cingulate cortex volume increases. Left MTL volume increase was associated with (i) a hippocampal N-acetylaspartate concentration decrease, (ii) a hippocampal Glutamate+Glutamine concentration increase and (iii) significant clinical improvement. The observed findings are, in part, compatible with both neuroplastic and neuroinflammatory changes induced by ECT. We postulate that such phenomena may be interrelated, therefore reconciling the neuroplasticity and neuroinflammatory hypotheses of ECT action. PMID:28170003

Treatment resistant non-catatonic mutism in schizophrenia responding to a combination of continuation electroconvulsive therapy and neuroleptics

PubMed Central

Grover, Sandeep; Dutt, Alakananda; Chakrabarty, Kaustav; Kumar, Vineet

2012-01-01

Non-catatonic mutism in schizophrenia has been described less frequently in literature. We describe the case of a young male who presented with non-catatonic mutism, secondary to first rank symptoms, which was refractory to adequate antipsychotic trials (quetiapine, risperidone, aripiprazole, ziprasidone, and trifluperazine) and responded to a combination of electroconvulsive therapy (ECT) and neuroleptics partially. However, when the ECT was continued in the continuation phase, the patient started speaking. PMID:23766583

A case of catatonia in a 14-year-old girl with schizophrenia treated with electroconvulsive therapy.

PubMed

Häßler, Frank; Reis, Olaf; Weirich, Steffen; Höppner, Jacqueline; Pohl, Birgit; Buchmann, Johannes

2013-01-01

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

Somatic symptom disorder treated with electroconvulsive therapy.

PubMed

Borisovskaya, Anna; Augsburger, Jay Alan

2017-05-01

Somatic symptom disorder (SSD) is a challenging condition to treat with chronic pain, a common and disabling symptom. We present a patient who received electroconvulsive therapy (ECT) for SSD with significant improvement in pain and gastrointestinal symptoms. We also present a brief literature review of similar cases treated with ECT. Preliminary evidence suggests that ECT should be considered for treatment of SSD comorbid with major depressive disorder, when standard treatments fail. Further research is needed to clarify whether ECT can be used for SSD without associated depression.

[Risk of long-lasting negative cognitive consequences after electroconvulsive therapy].

PubMed

Svendsen, Anne Marie; Miskowiak, Kamilla; Vinberg, Maj

2013-10-28

This case study describes a patient who had a unipolar depression and experienced long-lasting cognitive problems after electroconvulsive therapy (ECT). Neuropsychological testing revealed lower scores on measures of learning, memory and sustained attention. These results stress the importance of informing patients who have ECT of the potential cognitive consequences of this treatment as it may influence the patients' functional capabilities. Prospective studies are needed since we do not have sufficient knowledge regarding the 3-5% of these patients who experience sustained cognitive problems.

Evaluation of nonmemory cognitive parameters in psychiatric patients' pre- and post-electroconvulsive therapy: An observational study.

PubMed

Prakash, Jyoti; Srivastava, Kalpana; Manandhar, Pradeep; Saha, Amitabh

2015-01-01

Possibility of cognitive side effects has made electroconvulsive therapy (ECT) questionable. Variable deficits have been debated in memory cognition. Pattern of changes in nonmemory cognition pre- and post-ECT is not clear. Forty patients undergoing ECT were studied on nonmemory cognitive parameters before ECT, after a course of ECT, and after 4 weeks of last. ECT. Nonmemory cognition improved during the course of ECT and over 4 weeks of ECT. ECT does not affect the nonmemory cognition adversely.

Improving relapse prevention after successful electroconvulsive therapy for patients with severe depression: completed audit cycle involving 102 full electroconvulsive therapy courses in West Sussex, United kingdom.

PubMed

Atiku, Leonard; Gorst-Unsworth, Caroline; Khan, Barkath Ulla; Huq, Fuad; Gordon, Jackie

2015-03-01

The aim of this study was to determine whether current guidance or consensus regarding continuation pharmacotherapy after successful electroconvulsive therapy (ECT) was being followed by referring clinicians in West Sussex, United Kingdom. A complete audit cycle examining psychotropic medication after successful ECT for patients with severe depression was performed. Clinical and ECT records (electronic and paper) were reviewed, and relapse rates in the 4 commonly prescribed psychotropic medication groups were compared. The pattern of relapse in the 4 groups was similar for both audits 1 and 2. Taking the 102 patients as a whole, the lowest relapse rates were recorded for patients taking a combination of an antidepressant and lithium (16% relapsed within 6 months of successful ECT). Patients taking a combination of antipsychotic and antidepressants fared the worst with 75% relapse rate. This was followed by those taking a combination of antidepressant and a mood stabilizer (other than lithium) (69%). Patients taking antidepressant(s) only were associated with a relapse rate of 60%. Audit 2 demonstrated that clinicians did not change their prescribing practices for their patients after successful ECT despite the efforts made in widely disseminating the results of audit 1. In particular, there was no increase in the use of lithium. Not all psychotropic medication prescribing for patients receiving ECT for depression followed available and current guidance or consensus. More needs to be done to understand the reasons for the reluctance to use lithium if relapse rates after ECT are to improve.

Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro.

PubMed

Meller, R; Schindler, C K; Chu, X P; Xiong, Z G; Cameron, J A; Simon, R P; Henshall, D C

2003-05-01

Seizure-induced neuronal death may involve engagement of the BCL-2 family of apoptosis-regulating proteins. In the present study we examined the activation of proapoptotic BAD in cultured hippocampal neurons following seizures induced by removal of chronic glutamatergic transmission blockade. Kynurenic acid withdrawal elicited an increase in seizure-like electrical activity, which was inhibited by blockers of AMPA (CNQX) and NMDA (MK801 and AP5) receptor function. However, only NMDA receptor antagonists inhibited calcium entry as assessed by fura-2, and cell death of hippocampal neurons. Seizures increased proteolysis of caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) of cells. Seizure-like activity induced dephosphorylation of BAD and the disruption of its constitutive interaction with 14-3-3 proteins. In turn, BAD dimerized with antiapoptotic BCL-Xl after seizures. However, the absence of neuroprotective effects of pathway intervention suggests that BAD may perform a reinforcement rather than instigator role in cell death following seizures in vitro.

Effect of combined treatment with diuretics and gabapentin on convulsive threshold in mice.

PubMed

Łukawski, Krzysztof; Swiderska, Grajyna; Czuczwar, Stanisław J

2013-01-01

Research data show that diuretics can have anticonvulsant properties. This study examined effects of ethacrynic acid, a loop diuretic, and hydrochlorothiazide, a thiazide-type diuretic, on the anticonvulsant activity of gabapentin, a newer antiepileptic drug, in the maximal electroshock seizure threshold test in mice. Diuretics were administered intraperitoneally (ip.) both acutely (single dose) and chronically (once daily for seven days). Electroconvulsions were produced by an alternating current (50 Hz, 500 V, 0.2 s stimulus duration) delivered via ear-clip electrodes by a generator. Additionally, the influence of combined treatment with the diuretics and gabapentin on motor performance in the chimney test has been assessed. In the current study, ethacrynic acid at the chronic dose of 12.5 mg/kg and the single dose of 100 mg/kg did not affect the anticonvulsant activity of gabapentin. Similarly, hydrochlorothiazide (100 mg/kg), both in acute and chronic experiments, had no effect on the gabapentin action. On the other hand, in the chimney test, the combined treatment with ethacrynic acid (100 mg/kg) and gabapentin (50 mg/kg) significantly impaired motor performance in mice. Based on the current preclinical findings, it can be suggested that the diuretics should not affect the anticonvulsant action of gabapentin in epileptic patients. However, the combination of ethacrynic acid with gabapentin may cause neurotoxicity.

Pseudocholinesterase levels in patients under electroconvulsive therapy.

PubMed

Küçükosman, Gamze; Pişkin, Özcan; Hancı, Volkan; Okyay, Rahşan D; Ayoğlu, Hilal; Yurtlu, Bülent S; Akın, Mehmet; Turan, Işıl Ö

2018-01-01

In this study, we aimed to retrospectively assess the correlation of pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This retrospective study was conducted at Bülent Ecevit University Hospital, Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were retrospectively scanned to evaluate PChE values before ECT and other file information.  Results: There was no difference between gender in terms of PChE levels. Correlation analysis determined a weakly positive correlation between age (p=0.013; correlation coefficient [cc]: 0.178) and body weight (p less than 0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender, weight or psychiatric diagnosis, and PChE levels.  Conclusion: Neuromuscular blockage is a significant factor that increases patient safety, while increasing the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and the pharmacological properties of the neuromuscular blocker should be considered. We think that in situations with delayed recovery of ECT cases without identified PChE levels, low PChE levels must be considered.

Bitemporal Versus High-Dose Unilateral Twice-Weekly Electroconvulsive Therapy for Depression (EFFECT-Dep): A Pragmatic, Randomized, Non-Inferiority Trial.

PubMed

Semkovska, Maria; Landau, Sabine; Dunne, Ross; Kolshus, Erik; Kavanagh, Adam; Jelovac, Ana; Noone, Martha; Carton, Mary; Lambe, Sinead; McHugh, Caroline; McLoughlin, Declan M

2016-04-01

ECT is the most effective treatment for severe depression. Previous efficacy studies, using thrice-weekly brief-pulse ECT, reported that high-dose (6× seizure threshold) right unilateral ECT is similar to bitemporal ECT but may have fewer cognitive side effects. The authors aimed to assess the effectiveness and cognitive side effects of twice-weekly moderate-dose (1.5× seizure threshold) bitemporal ECT with high-dose unilateral ECT in real-world practice. This was a pragmatic, patient- and rater-blinded, noninferiority trial of patients with major depression (N=138; 63% female; age=56.7 years [SD=14.8]) in a national ECT service with a 6-month follow-up. Participants were independently randomly assigned to bitemporal or high-dose unilateral ECT. The primary outcome was change in the 24-item Hamilton Depression Rating Scale (HAM-D) score after the ECT course; the prespecified noninferiority margin was 4.0 points. Secondary outcomes included response and remission rates, relapse status after 6 months, and cognition. Of the eligible patients, 69 were assigned to bitemporal ECT and 69 to unilateral ECT. High-dose unilateral ECT was noninferior to bitemporal ECT regarding the 24-item HAM-D scores after the ECT course (mean difference=1.08 points in favor of unilateral ECT [95% CI=-1.67 to 3.84]). There were no significant differences for response and remission or 6-month relapse status. Recovery of orientation was quicker following unilateral ECT (median=19.1 minutes versus 26.4 minutes). Bitemporal ECT was associated with a lower percent recall of autobiographical information (odds ratio=0.66) that persisted for 6 months. Twice-weekly high-dose unilateral ECT is not inferior to bitemporal ECT for depression and may be preferable because of its better cognitive side-effect profile.

Opiate receptor binding in the brain of the seizure sensitive Mongolian gerbil (Meriones unguiculatus).

PubMed

Lee, R J; Olsen, R W; Lomax, P; McCabe, R T; Wamsley, J K

1984-12-01

Opiate receptor binding was studied in seizure sensitive (SS) and seizure resistant (SR) strains of the Mongolian gerbil. Cryostat sections of the brain were labeled with [3H]-dihydromorphine, subjected to autoradiography and analysed by microdensitometry. SS gerbils, prior to seizure induction, demonstrated overall greater brain opiate binding when compared to SR animals. Immediately following a seizure, binding in the interpeduncular nucleus fell to levels found in SR animals. The increased opiate binding in the SS (pre-seizure) compared to SR gerbils could reflect a deficit of endogenous ligand which could underlie the seizure diathesis in the gerbil.

MANAGEMENT OF A REEVE'S MUNTJAC ( MUNTIACUS REEVESI) WITH SEIZURES USING LEVETIRACETAM.

PubMed

Blatt, Emily R; Seeley, Kathryn E; Lovett, Mathew C; Junge, Randall E

2017-12-01

This report describes the diagnosis and management of idiopathic epilepsy in a 4-yr-old intact female Reeve's muntjac ( Muntiacus reevesi). The patient was initially witnessed to have isolated paroxysmal events consistent with epileptic seizures (altered consciousness, lateral recumbency, tonic/clonic movement of limbs) lasting less than 3 min with an immediate return to normal consciousness. The seizure frequency increased to >3 seizures within 24 hr and phenobarbital 3 mg/kg orally every 12 hr was started. Because of continued epileptic seizures and low serum phenobarbital levels, the dose was increased until significant elevations of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. Levetiracetam 40 mg/kg orally every 12 hr was initiated and the phenobarbital was weaned and discontinued. One breakthrough seizure has been witnessed in the 10 mo since starting levetiracetam.

Do drug seizures predict drug-related emergency department presentations or arrests for drug use and possession?

PubMed

Wan, Wai-Yin; Weatherburn, Don; Wardlaw, Grant; Sarafidis, Vasilis; Sara, Grant

2016-01-01

Direct evidence of the effect of drug seizures on drug use and drug-related harm is fairly sparse. The aim of this study was to see whether seizures of heroin, cocaine and ATS predict the number of people arrested for use and possession of these drugs and the number overdosing on them. We examined the effect of seizure frequency and seizure weight on arrests for drug use and possession and on the frequency of drug overdose with autoregressive distributed lag (ARDL) models. Granger causality tests were used to test for simultaneity. Over the short term (i.e. up to 4 months), increases in the intensity of high-level drug law enforcement (as measured by seizure weight and frequency) directed at ATS, cocaine and heroin did not appear to have any suppression effect on emergency department (ED) presentations relating to ATS, cocaine and heroin, or on arrests for use and/or possession of these drugs. A significant negative contemporaneous relationship was found between the heroin seizure weight and arrests for use and/or possession of heroin. However no evidence emerged of a contemporaneous or lagged relationship between heroin seizures and heroin ED presentations. The balance of evidence suggests that, in the Australian context, increases in the monthly seizure frequency and quantity of ATS, cocaine and heroin are signals of increased rather than reduced supply. Copyright © 2015 Elsevier B.V. All rights reserved.

The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.

PubMed

Zamani, Gholam Reza; Mohammadi, Mahmoud; Ashrafi, Mahmoud Reza; Karimi, Parviz; Mahmoudi, Maryam; Badv, Reza Shervin; Tavassoli, Ali Reza; Azizi Malamiri, Reza

2016-12-01

More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P < 0.001), median total cholesterol was significantly increased (from 180 to 285 mg/dl, P < 0.001), median serum low-density lipoprotein (LDL) was significantly increased (from 91 to 175 mg/dl, P < 0.001), and median serum high-density lipoprotein (HDL) was significantly increased (from 51 to 58 mg/dl, P < 0.001). Results of this study indicate that a classic ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.

Dopamine D1 vs D5 receptor-dependent induction of seizures in relation to DARPP-32, ERK1/2 and GluR1-AMPA signalling

PubMed Central

O’Sullivan, Gerard J.; Dunleavy, Mark; Hakansson, Kerstin; Clementi, Mario; Kinsella, Anthony; Croke, David T.; Drago, John; Fienberg, Allen A.; Greengard, Paul; Sibley, David R.; Fisone, Gilberto; Henshall, David C.; Waddington, John L.

2013-01-01

Summary Recent reports have shown that the selective dopamine D1-like agonist SKF 83822 [which stimulates adenylate cyclase, but not phospholipase C] induces prominent behavioral seizures in mice, whereas its benzazepine congener SKF 83959 [which stimulates phospholipase C, but not adenylate cyclase] does not. To investigate the relative involvement of D1 vs D5 receptors in mediating seizures, ethological behavioral topography and cortical EEGs were recorded in D1, D5 and DARPP-32 knockout mice in response to a convulsant dose of SKF 83822. SKF 83822-induced behavioral and EEG seizures were gene dose-dependently abolished in D1 knockouts. In both heterozygous and homozygous D5 knockouts, the latency to first seizure was significantly increased and total EEG seizures were reduced relative to wild-types. The majority (60%) of homozygous DARPP-32 knockouts did not have seizures; of those having seizures (40%), the latency to first seizure was significantly increased and the number of high amplitude, high frequency polyspike EEG events was reduced. In addition, immunoblotting was performed to investigate downstream intracellular signalling mechanisms at D1-like receptors following challenge with SKF 83822 and SKF 83959. In wild-types administered SKF 83822, levels of ERK1/2 and GluR1 AMPA receptor phosphorylation increased two-fold in both the striatum and hippocampus; in striatal slices DARPP-32 phosphorylation at Thr34 increased five-fold relative to vehicle-treated controls. These findings indicate that D1, and to a lesser extent D5, receptor coupling to DARPP-32, ERK1/2 and glutamatergic signalling is involved in mediating the convulsant effects of SKF 83822. PMID:18367215

Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

PubMed Central

Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

2014-01-01

Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

Detection of convulsive seizures using surface electromyography.

PubMed

Beniczky, Sándor; Conradsen, Isa; Wolf, Peter

2018-06-01

Bilateral (generalized) tonic-clonic seizures (TCS) increase the risk of sudden unexpected death in epilepsy (SUDEP), especially when patients are unattended. In sleep, TCS often remain unnoticed, which can result in suboptimal treatment decisions. There is a need for automated detection of these major epileptic seizures, using wearable devices. Quantitative surface electromyography (EMG) changes are specific for TCS and characterized by a dynamic evolution of low- and high-frequency signal components. Algorithms targeting increase in high-frequency EMG signals constitute biomarkers of TCS; they can be used both for seizure detection and for differentiating TCS from convulsive nonepileptic seizures. Two large-scale, blinded, prospective studies demonstrated the accuracy of wearable EMG devices for detecting TCS with high sensitivity (76%-100%). The rate of false alarms (0.7-2.5/24 h) needs further improvement. This article summarizes the pathophysiology of muscle activation during convulsive seizures and reviews the published evidence on the accuracy of EMG-based seizure detection. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Seizure Suppression by High Temperature via cAMP Modulation in Drosophila.

PubMed

Saras, Arunesh; Tanouye, Mark A

2016-10-13

Bang-sensitive (BS) Drosophila mutants display characteristic seizure-like activity (SLA) and paralysis after mechanical shock . After high-frequency electrical stimulation (HFS) of the brain, they generate robust seizures at very low threshold voltage. Here we report an important phenomenon, which effectively suppresses SLA in BS mutants. High temperature causes seizure suppression in all BS mutants (para bss1 , eas, sda) examined in this study. This effect is fully reversible and flies show complete recovery from BS paralysis once the temperature effect is nullified. High temperature induces an increase in seizure threshold after a brief pulse of heat shock (HS). By genetic screening, we identified the involvement of cAMP in the suppression of seizures by high temperature. We propose that HS induces adenylyl cyclase which in turn increases cAMP concentration which eventually suppresses seizures in mutant flies. In summary, we describe an unusual phenomenon, where high temperature can suppress SLA in flies by modulating cAMP concentration. Copyright © 2016 Saras and Tanouye.

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.

Decreasing adverse outcomes of unmodified electroconvulsive therapy: suggestions and possibilities.

PubMed

Gallegos, Jesus; Vaidya, Punit; D'Agati, Douglas; Jayaram, Geetha; Nguyen, Thai; Tripathi, Adarsh; Trivedi, Jitendra K; Reti, Irving M

2012-06-01

Electroconvulsive therapy (ECT) is far and away the most effective treatment for depression and quite effective for a range of other psychiatric conditions that are unresponsive to medication. Electroconvulsive therapy in the developed world has been administered with anesthesia, muscle relaxants, and ventilation since the mid-1950s following 20 years of unmodified treatment. However, in much of the developing world, ECT continues to be administered unmodified because of lack of resources. We review the efficacy of unmodified compared with modified treatment. We also review the potential drawbacks of unmodified treatment including fear and anxiety, worse postictal confusion, fracture risk, and the negative effects of unmodified treatment on how ECT is perceived in the general community. Finally, we consider potential solutions in developing countries to minimize adverse outcomes of unmodified treatment by pretreating patients either with low-dose benzodiazepines or sedating, but not anesthetizing, dosages of anesthetic agents. Randomized controlled trials are necessary before either of these options could be considered an acceptable alternative to completely unmodified treatment when modified treatment is unavailable.

The effect of acute aripiprazole treatment on chemically and electrically induced seizures in mice: The role of nitric oxide.

PubMed

Shafaroodi, Hamed; Oveisi, Simin; Hosseini, Mahsa; Niknahad, Hossein; Moezi, Leila

2015-07-01

Aripiprazole is an antipsychotic drug which acts through dopamine and serotonin receptors. Aripiprazole was noted to have antiseizure effects in a study on mice, while it induced seizures in a few human case reports. Dopaminergic and serotonergic systems relate to nitric oxide, and aripiprazole also has effects on dopamine and serotonin receptors. This study investigated the effects of aripiprazole on seizures and the potential role of nitric oxide in the process. The following three models were examined to explore the role of aripiprazole on seizures in mice: 1 - pentylenetetrazole administered intravenously, 2 - pentylenetetrazole administered intraperitoneally, and 3 - electroshock. Aripiprazole administration delayed clonic seizure in intravenous and intraperitoneal pentylenetetrazole models. In the electroshock-induced seizure model, tonic seizure and mortality protection percent were increased after aripiprazole administration. In intraperitoneal administration of pentylenetetrazole, aripiprazole effects on clonic seizure latency were significantly decreased when l-NAME - a nonselective nitric oxide synthase (NOS) inhibitor, 7-nitroindazole - a selective neuronal NOS (nNOS) inhibitor, or aminoguanidine - a selective inducible NOS (iNOS) inhibitor was injected before aripiprazole administration. In the intravenous pentylenetetrazole method, administration of l-NAME or aminoguanidine inhibited aripiprazole effects on clonic seizure threshold. Aminoguanidine or l-NAME administration decreased aripiprazole-induced protection against tonic seizures and death in the electroshock model. In both intravenous and intraperitoneal seizure models, aripiprazole and l-arginine coadministration delayed the onset of clonic seizures. Moreover, it increased protection against tonic seizures and death in intraperitoneal pentylenetetrazole and electroshock models. In conclusion, the release of nitric oxide via iNOS or nNOS may be involved in anticonvulsant properties of aripiprazole. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Enhanced susceptibility to seizures modulated by high interleukin-1β levels during early life malnutrition.

PubMed

Simão, Fabrício; Habekost Oliveira, Victória; Lahorgue Nunes, Magda

2016-10-01

Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin-1β (IL-1β) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL-1β, IL-1R1, PSD-95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL-1β and IL-1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL-1β in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL-1β and IL-1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD-95 and synapsin expression in the hippocampus. We suggest that malnutrition-induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150-1159, 2016. © 2016 Wiley Periodicals, Inc.

SEIZURE ACTIVITY INVOLVED IN THE UP-REGULATION OF BDNF mRNA EXPRESSION BY ACTIVATION OF CENTRAL MU OPIOID RECEPTORS

PubMed Central

ZHANG, H. N.; KO, M. C.

2009-01-01

Chemical-induced seizures up-regulated brain-derived neurotrophic factor (BDNF) mRNA expression. Intracerebroventricular (i.c.v.) administration of endogenous opioids preferentially activating μ opioid receptor (MOR) could also increase BDNF mRNA expression. The aim of this study was to determine to what extent i.c.v. administration of synthetic MOR-selective agonists in rats can modulate both seizure activity and up-regulation of BDNF mRNA expression. Effects and potencies of i.c.v. administration of morphine and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), were directly investigated by scoring behavioral seizures and measuring BDNF mRNA expression. In addition, effects of the opioid receptor antagonist naloxone and antiepileptic drugs, diazepam, phenobarbital, and valproate, on i.c.v. MOR agonist-induced behavioral seizures and up-regulation of BDNF mRNA expression were determined. A single i.c.v. administration of morphine (10–100 μg) or DAMGO (0.15–1.5 μg) dose-dependently elicited behavioral seizures and increased BDNF mRNA expression in the widespread brain regions. However, subcutaneous administration of MOR agonists neither produced behavioral seizures nor increased BDNF mRNA expression. Pretreatment with naloxone 1 mg/kg significantly reduced behavioral seizure scores and the up-regulation of BDNF mRNA expression elicited by i.c.v. morphine or DAMGO. Similarly, diazepam 10 mg/kg and phenobarbital 40 mg/kg significantly blocked i.c.v. MOR agonist-induced actions. Pretreatment with valproate 300 mg/kg only attenuated behavioral seizures, but it did not affect morphine-induced increase of BDNF mRNA expression. This study provides supporting evidence that seizure activity plays an important role in the up-regulation of BDNF mRNA expression elicited by central MOR activation and that decreased inhibitory action of GABAergic system through the modulation on GABA receptor synaptic function by central MOR activation is involved in its regulation of BDNF mRNA expression. PMID:19303919

Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

PubMed

Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

2015-03-01

An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

The relationship between seizures, interictal spikes and antiepileptic drugs.

PubMed

Goncharova, Irina I; Alkawadri, Rafeed; Gaspard, Nicolas; Duckrow, Robert B; Spencer, Dennis D; Hirsch, Lawrence J; Spencer, Susan S; Zaveri, Hitten P

2016-09-01

A considerable decrease in spike rate accompanies antiepileptic drug (AED) taper during intracranial EEG (icEEG) monitoring. Since spike rate during icEEG monitoring can be influenced by surgery to place intracranial electrodes, we studied spike rate during long-term scalp EEG monitoring to further test this observation. We analyzed spike rate, seizure occurrence and AED taper in 130 consecutive patients over an average of 8.9days (range 5-17days). We observed a significant relationship between time to the first seizure, spike rate, AED taper and seizure occurrence (F (3,126)=19.77, p<0.0001). A high spike rate was related to a longer time to the first seizure. Further, in a subset of 79 patients who experienced seizures on or after day 4 of monitoring, spike rate decreased initially from an on- to off-AEDs epoch (from 505.0 to 382.3 spikes per hour, p<0.00001), and increased thereafter with the occurrence of seizures. There is an interplay between seizures, spikes and AEDs such that spike rate decreases with AED taper and increases after seizure occurrence. The direct relationship between spike rate and AEDs and between spike rate and time to the first seizure suggests that spikes are a marker of inhibition rather than excitation. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Treatment of Adults With Treatment-Resistant Depression: Electroconvulsive Therapy Plus Antidepressant or Electroconvulsive Therapy Alone? Evidence From an Indirect Comparison Meta-Analysis

PubMed Central

Song, Guo-Min; Tian, Xu; Shuai, Ting; Yi, Li-Juan; Zeng, Zi; Liu, Shuang; Zhou, Jian-Guo; Wang, Yan

2015-01-01

Abstract Electroconvulsive therapy (ECT) and antidepressant are the effective treatment alternatives for patients with treatment-resistant depression (TRD); however, the effects and safety of the ECT plus antidepressant relative to ECT alone remain controversial. We decide to assess the potential of ECT plus antidepressant compared with ECT alone by undertaking an indirect comparison meta-analysis. Databases from PubMed, ISI Web of Science, CENTRAL, Clinicaltrials.gov, EMBASE, CBM (China Biomediccal Literatures Database), and CNKI (China National Knowledge Infrastructure) were searched for relevant studies through November 21, 2014. Literature was screened, data were extracted and methodological quality of the eligible trial was assessed by 2 independent reviewers accordingly. Then, head-to-head and indirect comparison meta-analyses were carried out. A total of 17 studies which including 13 studies regarding ECT plus antidepressant versus antidepressant alone and 4 studies concerning ECT versus antidepressant alone containing a total of 1098 patients were incorporated into this meta-analysis. The head-to-head comparison suggested that response rate can be improved in the ECT plus antidepressant (RR, 1.82; 95% CI, 1.55–2.14) and ECT alone group (RR, 2.24, 95% CI, 1.51–3.33) compared with antidepressant alone, respectively; adverse complications including memory deterioration and somatization were not significantly increased except incidence of memory deterioration in ECT plus antidepressant in the 4th weeks after treatment (RR, 0.09, 95% CI, 0.02–0.49). Indirect comparison meta-analysis showed that no significant differences were detected in response rate and memory deterioration between ECT plus antidepressant and ECT alone. However, ECT plus antidepressant increased the incidence of memory deterioration relative to ECT alone. With present evidence, the regime of ECT plus antidepressant should not be preferentially recommended to treat the patients with TRD relative to ECT alone. PMID:26131818

Anticonvulsant serotonergic and deep brain stimulation in anterior thalamus.

PubMed

Mirski, Marek A; Ziai, Wendy C; Chiang, Jason; Hinich, Melvin; Sherman, David

2009-01-01

Anterior thalamus (AN) has been shown to mediate seizures in both focal and generalized models. Specific regional increase in AN serotonergic activity was observed following AN-DBS in our pentylenetetrazol (PTZ) rodent model of acute seizures, and this increase may inhibit seizures and contribute to the mechanism of anticonvulsant DBS. Anesthetized rats with AN-directed dialysis cannula with scalp/depth EEG were infused with PTZ at 5.5mg/(kg min) until an EEG seizure occurred. Eight experimental groups of AN-dialysis infusion were evaluated: controls (dialysate-only), 10 and 100 microM serotonin 5-HT(7) agonist 5-carboxamidotryptamine (5-CT), 1, 10 and 100 microM serotonin antagonist methysergide (METH), AN-DBS, and 100 microM METH+AN-DBS. Latency for seizures in control animals was 3,120+/-770 s (S.D.); AN-DBS delayed onset to 5018+/-1100 (p<0.01). AN-directed 5-CT increased latency in dose-dependent fashion: 3890+/-430 and 4247+/-528 (p<0.05). Methysergide had an unexpected protective effect at low-dose (3908+/-550, p<0.05) but not at 100 microM (2687+/-1079). The anticonvulsant action of AN-DBS was blocked by prior dialysis using 100 microM METH. Surface EEG burst count and nonlinear analysis (H-Statistic) noted significant (p<0.05) increased pre-ictal epileptiform bursts in 5-CT, methysergide, but not DBS group compared to control. Increased serotonergic activity in AN raised PTZ seizure threshold, similar to DBS, but without preventing cortical bursting. 5-Carboxamidotryptamine, a 5-HT(7) agonist, demonstrated dose-dependent seizure inhibition. Methysergide proved to have an inverse, dose-dependent agonist property, antagonizing the action of AN-DBS at the highest dose. Anticonvulsant AN-DBS may in part act to selectively alter serotonin neurotransmission to raise seizure threshold.

Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy.

PubMed

Rempe, Ralf G; Hartz, Anika M S; Soldner, Emma L B; Sokola, Brent S; Alluri, Satya R; Abner, Erin L; Kryscio, Richard J; Pekcec, Anton; Schlichtiger, Juli; Bauer, Björn

2018-05-02

The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamate ex vivo and used an in vivo / ex vivo approach of isolated brain capillaries from female Wistar rats that experienced status epilepticus as an acute seizure model. We found that exposing isolated rat brain capillaries to glutamate increased MMP-2 and MMP-9 protein and activity levels, and decreased tight junction protein levels, which resulted in barrier leakage. We confirmed these findings in vivo in rats after status epilepticus and in brain capillaries from male mice lacking cytosolic phospholipase A 2 Together, our data support the hypothesis that glutamate released during seizures signals an increase in MMP-2 and MMP-9 protein expression and activity levels, resulting in blood-brain barrier leakage. SIGNIFICANCE STATEMENT The mechanism leading to seizure-mediated blood-brain barrier dysfunction in epilepsy is poorly understood. In the present study, we focused on defining this mechanism in the brain capillary endothelium. We demonstrate that seizures trigger a pathway that involves glutamate signaling through cytosolic phospholipase A 2 , which increases MMP levels and decreases tight junction protein expression levels, resulting in barrier leakage. These findings may provide potential therapeutic avenues within the blood-brain barrier to limit barrier dysfunction in epilepsy and decrease seizure burden. Copyright © 2018 the authors 0270-6474/18/384301-15$15.00/0.

Why do seizures occur when they do? Situations perceived to be associated with increased or decreased seizure likelihood in people with epilepsy and intellectual disability

PubMed Central

Illingworth, Josephine L.; Watson, Peter; Ring, Howard

2014-01-01

Seizure precipitants are commonly reported in the general population of people with epilepsy. However, there has been little research in this area in people with epilepsy and intellectual disability (ID). We conducted a survey of the situations associated with increased or decreased seizure likelihood in this population. The aim of the research was to identify situations of increased seizure likelihood (SISLs) and situations of decreased seizure likelihood (SDSLs) reported by carers of people with an ID and epilepsy. Three study groups were investigated: two groups comprising individuals with ID associated with a specific genetic diagnosis – Rett syndrome or fragile X syndrome – and one group consisting of individuals with a range of other etiologies. Responses relating to 100 people were received: 44 relating to people with Rett syndrome, 25 to people with fragile X syndrome, and 31 to people whose ID had some other etiologies. Ninety-eight percent of the respondents reported at least one SISL, and 60% reported at least one SDSL. Having more seizure types and greater seizure frequency were associated with a higher number of SISLs reported. The most commonly reported SISLs and SDSLs for each of the three groups are presented. The most common SISL overall was illness, which was reported as an SISL by 71% of the respondents. There was less consensus with regard to SDSLs. These findings provide a greater understanding of when seizures occur in those with ID and epilepsy, with possible implications for adjunctive behavioral management of seizures in those with treatment-refractory epilepsy. PMID:25218091

Why do seizures occur when they do? Situations perceived to be associated with increased or decreased seizure likelihood in people with epilepsy and intellectual disability.

PubMed

Illingworth, Josephine L; Watson, Peter; Ring, Howard

2014-10-01

Seizure precipitants are commonly reported in the general population of people with epilepsy. However, there has been little research in this area in people with epilepsy and intellectual disability (ID). We conducted a survey of the situations associated with increased or decreased seizure likelihood in this population. The aim of the research was to identify situations of increased seizure likelihood (SISLs) and situations of decreased seizure likelihood (SDSLs) reported by carers of people with an ID and epilepsy. Three study groups were investigated: two groups comprising individuals with ID associated with a specific genetic diagnosis - Rett syndrome or fragile X syndrome - and one group consisting of individuals with a range of other etiologies. Responses relating to 100 people were received: 44 relating to people with Rett syndrome, 25 to people with fragile X syndrome, and 31 to people whose ID had some other etiologies. Ninety-eight percent of the respondents reported at least one SISL, and 60% reported at least one SDSL. Having more seizure types and greater seizure frequency were associated with a higher number of SISLs reported. The most commonly reported SISLs and SDSLs for each of the three groups are presented. The most common SISL overall was illness, which was reported as an SISL by 71% of the respondents. There was less consensus with regard to SDSLs. These findings provide a greater understanding of when seizures occur in those with ID and epilepsy, with possible implications for adjunctive behavioral management of seizures in those with treatment-refractory epilepsy. Copyright © 2014. Published by Elsevier Inc.

Heart rate changes in partial seizures: analysis of influencing factors among refractory patients

PubMed Central

2014-01-01

Background We analyzed the frequency of heart rate (HR) changes related to seizures, and we sought to identify the influencing factors of these changes during partial seizures, to summarize the regularity of the HR changes and gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function. To date, detailed information on influencing factors of HR changes related to seizures by multiple linear regression analysis remains scarce. Methods Using video-electroencephalograph (EEG)-electrocardiograph (ECG) recordings, we retrospectively assessed the changes in the HR of 81 patients during a total of 181 seizures, including 27 simple partial seizures (SPS), 110 complex partial seizures (CPS) and 44 complex partial seizures secondarily generalized (CPS-G). The epileptogenic focus and the seizure type, age, gender, and sleep/wakefulness state of each patient were evaluated during and after the seizure onset. The HR changes were evaluated in the stage of epilepsy as time varies. Results Of the 181 seizures from 81 patients with ictal ECGs, 152 seizures (83.98%) from 74 patients were accompanied by ictal tachycardia (IT). And only 1 patient was accompanied by ictal bradycardia (IB). A patient has both IT and IB. We observed that HR difference was independently correlated with side, type and sleep/wakefulness state. In this analysis, the HR changes were related to the side, gender, seizure type, and sleep/wakefulness state. Right focus, male, sleep, and CPS-G showed more significant increases than that were observed in left, female, wakefulness, SPS and CPS. HR increases rapidly within 10 seconds before seizure onset and ictus, and typically slows to normal with seizure offset. Conclusion CPS-G, sleep and right focus led to higher ictal HR. The HR in the stage of epilepsy has regularly been observed to change to become time-varying. The risk factors of ictal HR need to be controlled along with sleep, CPS-G and right focus. Our study first explains that the HR in seizures has a regular evolution varying with time. Our study might help to further clarify the basic mechanisms of interactions between heart and brain, making seizure detection and closed-loop systems a possible therapeutic alternative in refractory patients. PMID:24950859

Increased seizure latency and decreased severity of pentylenetetrazol-induced seizures in mice after essential oil administration.

PubMed

Koutroumanidou, Eleni; Kimbaris, Athanasios; Kortsaris, Alexandros; Bezirtzoglou, Eugenia; Polissiou, Moschos; Charalabopoulos, Konstantinos; Pagonopoulou, Olga

2013-01-01

The effect of pretreatment with essential oils (EOs) from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ-) induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p.) injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil). After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures). Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects.

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.

Quantitative analysis of seizure frequency 1 week and 6, 12, and 24 months after surgery of epilepsy.

PubMed

Lüders, H; Murphy, D; Awad, I; Wyllie, E; Dinner, D S; Morris, H H; Rothner, A D

1994-01-01

We made quantitative analysis of seizure frequency 1 week and 6, 12, and 24 months after seizure surgery. Seizure recurrence was significantly higher when seizures occurred in the first postoperative week. Seizure recurrence increased progressively with longer follow-ups, but the 6 month postoperative follow-up period was an excellent index of long-term outcome. In operative follow-up studies, seizure frequency should be reported at fixed follow-up periods, e.g., at 6 months and 1, 2, 5, and 10 years. Meaningful comparison of outcomes between different studies is possible only when reports include outcome at fixed postoperative follow-up periods (as opposed to ranges of follow-up periods).

Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae.

PubMed

Barbalho, Patrícia Gonçalves; Lopes-Cendes, Iscia; Maurer-Morelli, Claudia Vianna

2016-03-09

It has been demonstrated that the zebrafish model of pentylenetetrazole (PTZ)-evoked seizures and the well-established rodent models of epilepsy are similar pertaining to behavior, electrographic features, and c-fos expression. Although this zebrafish model is suitable for studying seizures, to date, inflammatory response after seizures has not been investigated using this model. Because a relationship between epilepsy and inflammation has been established, in the present study we investigated the transcript levels of the proinflammatory cytokines interleukin-1 beta (il1b) and cyclooxygenase-2 (cox2a and cox2b) after PTZ-induced seizures in the brain of zebrafish 7 days post fertilization. Furthermore, we exposed the fish to the nonsteroidal anti-inflammatory drug indomethacin prior to PTZ, and we measured its effect on seizure latency, number of seizure behaviors, and mRNA expression of il1b, cox2b, and c-fos. We used quantitative real-time PCR to assess the mRNA expression of il1b, cox2a, cox2b, and c-fos, and visual inspection was used to monitor seizure latency and the number of seizure-like behaviors. We found a short-term upregulation of il1b, and we revealed that cox2b, but not cox2a, was induced after seizures. Indomethacin treatment prior to PTZ-induced seizures downregulated the mRNA expression of il1b, cox2b, and c-fos. Moreover, we observed that in larvae exposed to indomethacin, seizure latency increased and the number of seizure-like behaviors decreased. This is the first study showing that il1b and cox-2 transcripts are upregulated following PTZ-induced seizures in zebrafish. In addition, we demonstrated the anticonvulsant effect of indomethacin based on (1) the inhibition of PTZ-induced c-fos transcription, (2) increase in seizure latency, and (3) decrease in the number of seizure-like behaviors. Furthermore, anti-inflammatory effect of indomethacin is clearly demonstrated by the downregulation of the mRNA expression of il1b and cox2b. Our results are supported by previous evidences suggesting that zebrafish is a suitable alternative for studying inflammation, seizures, and the effect of anti-inflammatory compounds on seizure suppression.

A Phase-Locked Loop Epilepsy Network Emulator.

PubMed

Watson, P D; Horecka, K M; Cohen, N J; Ratnam, R

2016-10-15

Most seizure forecasting employs statistical learning techniques that lack a representation of the network interactions that give rise to seizures. We present an epilepsy network emulator (ENE) that uses a network of interconnected phase-locked loops (PLLs) to model synchronous, circuit-level oscillations between electrocorticography (ECoG) electrodes. Using ECoG data from a canine-epilepsy model (Davis et al. 2011) and a physiological entropy measure (approximate entropy or ApEn, Pincus 1995), we demonstrate the entropy of the emulator phases increases dramatically during ictal periods across all ECoG recording sites and across all animals in the sample. Further, this increase precedes the observable voltage spikes that characterize seizure activity in the ECoG data. These results suggest that the ENE is sensitive to phase-domain information in the neural circuits measured by ECoG and that an increase in the entropy of this measure coincides with increasing likelihood of seizure activity. Understanding this unpredictable phase-domain electrical activity present in ECoG recordings may provide a target for seizure detection and feedback control.

Tranexamic Acid in cardiac surgery and postoperative seizures: a case report series.

PubMed

Bell, David; Marasco, Silvana; Almeida, Aubrey; Rowland, Michael

2010-08-01

With the recent withdrawal of the antifibrinolytic aprotinin from the market, tranexamic acid (TxA) has become more widely used. This change has led to increasing concern about the side-effect profile of TxA, particularly the incidence of postoperative seizures. In this case series, we describe 7 patients over an 18-month period who had open-chamber cardiac surgery and developed seizures in the postoperative period. This incidence is increased compared with that of a cohort of patients in the previous 36 months who did not receive TxA (0.66% versus 0%; P < .05). The exact mechanism of TxA-induced seizures is thought to be via inhibition of gamma-aminobutyric acid receptors in neurons. Data from the neurosurgical literature show a well-established link between this antifibrinolytic and seizures. There is now increasing awareness of this association in cardiac surgery, particularly when high TxA doses are used.

Association of Periodic and Rhythmic Electroencephalographic Patterns With Seizures in Critically Ill Patients.

PubMed

Rodriguez Ruiz, Andres; Vlachy, Jan; Lee, Jong Woo; Gilmore, Emily J; Ayer, Turgay; Haider, Hiba Arif; Gaspard, Nicolas; Ehrenberg, J Andrew; Tolchin, Benjamin; Fantaneanu, Tadeu A; Fernandez, Andres; Hirsch, Lawrence J; LaRoche, Suzette

2017-02-01

Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear. To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures. We reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures. Continuous electroencephalography. Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures. Of the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P < .001). Generalized periodic discharges (GPDs) and lateralized rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.5-2 Hz: GPDs, 24%,OR, 2.31, P = .02; LRDA, 24%, OR, 1.79, P = .05; ≥ 2 Hz: GPDs, 32%, OR, 3.30, P < .001; LRDA, 40%, OR, 3.98, P < .001) as was the association with Plus (GPDs, 28%, OR, 3.57, P < .001; LRDA, 40%, P < .001). There was no difference in seizure incidence in patients with generalized rhythmic delta activity compared with no periodic or rhythmic pattern (13%, OR, 1.18, P = .26). Higher prevalence of LPDs and GPDs also conferred increased seizure risk (37% frequent vs 45% abundant/continuous, OR, 1.64, P = .03 for difference; 8% rare/occasional vs 15% frequent, OR, 2.71, P = .03, vs 23% abundant/continuous, OR, 1.95, P = .04). Patterns associated with stimulation did not show an additional risk for seizures from the underlying pattern risk (P > .10). In this study, LPDs, LRDA, and GPDs were associated with seizures while generalized rhythmic delta activity was not. Lateralized periodic discharges were associated with seizures at all frequencies with and without Plus modifier, but LRDA and GPDs were associated with seizures when the frequency was 1.5 Hz or faster or when associated with a Plus modifier. Increased pattern prevalence was associated with increased risk for seizures in LPDs and GPDs. Stimulus-induced patterns were not associated with such risk. These findings highlight the importance of detailed electroencephalographic interpretation using standardized nomenclature for seizure risk stratification and clinical decision making.

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.

Acute administration of ginger (Zingiber officinale rhizomes) extract on timed intravenous pentylenetetrazol infusion seizure model in mice.

PubMed

Hosseini, Abdolkarim; Mirazi, Naser

2014-03-01

Zingiber officinale (Zingiberaceae) or ginger, which is used in traditional medicine has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied. The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice. The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100mg/kg) were administered intraperitonal (i.p.), 2 and 24h before induction of PTZ. Phenobarbital sodium (30mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints (myoclonic, generalized clonus and forelimb tonic extension phase) was recorded. The results showed that the ginger extract has anticonvulsant effects in all the experimental treatment groups of seizure tested as it significantly increased the seizure threshold. Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100mg/kg (p<0.001) and significantly prevented generalized clonic (p<0.001) and increased the threshold for the forelimb tonic extension (p<0.01) seizure 2 and 24h before induction of PTZ compared with control group. Based on the results the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory system, antioxidant mechanisms, oxidative stress and calcium channel inhibition. Copyright © 2014 Elsevier B.V. All rights reserved.

Study on localization of epileptic focus based on causality analysis

NASA Astrophysics Data System (ADS)

Shan, Shaojie; Li, Hanjun; Tang, Xiaoying

2018-05-01

In this paper, we considered that the ECoG signal contain abundant pathological information, which can be used for the localization of epileptic focus before epileptic seizures in 1-2 mins. In order to validate this hypothesis, cutting the ECoG into three stages: before seizure, seizure and after seizure, then through using Granger causality algorithm, PSI causality algorithm, Transfer Entropy causality algorithm at different stages of epilepsy ECoG, we were able to do the causality analysis of ECoG data. The results have shown that there is significant difference with the causality value of the epileptic focus area in before seizure, seizure and after seizure. An increase is in the causality value of each channel during epileptic seizure. After epileptic seizure, the causality between the channels showed a downward trend, but the difference was not obvious. The difference of the causality provides a reliable technical method to assist the clinical diagnosis of epileptic focus.

Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

PubMed

Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

2016-06-01

Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative sensitivity of quantitative EEG (QEEG) spectrograms for detecting seizure subtypes.

PubMed

Goenka, Ajay; Boro, Alexis; Yozawitz, Elissa

2018-02-01

To assess the sensitivity of Persyst version 12 QEEG spectrograms to detect focal, focal with secondarily generalized, and generalized onset seizures. A cohort of 562 seizures from 58 patients was analyzed. Successive recordings with 2 or more seizures during continuous EEG monitoring for clinical indications in the ICU or EMU between July 2016 and January 2017 were included. Patient ages ranged from 5 to 64 years (mean = 36 years). There were 125 focal seizures, 187 secondarily generalized and 250 generalized seizures from 58 patients analyzed. Seizures were identified and classified independently by two epileptologists. A correlate to the seizure pattern in the raw EEG was sought in the QEEG spectrograms in 4-6 h EEG epochs surrounding the identified seizures. A given spectrogram was interpreted as indicating a seizure, if at the time of a seizure it showed a visually significant departure from the pre-event baseline. Sensitivities for seizure detection using each spectrogram were determined for each seizure subtype. Overall sensitivities of the QEEG spectrograms for detecting seizures ranged from 43% to 72%, with highest sensitivity (402/562,72%) by the seizure detection trend. The asymmetry spectrogram had the highest sensitivity for detecting focal seizures (117/125,94%). The FFT spectrogram was most sensitive for detecting secondarily generalized seizures (158/187, 84%). The seizure detection trend was the most sensitive for generalized onset seizures (197/250,79%). Our study suggests that different seizure types have specific patterns in the Persyst QEEG spectrograms. Identifying these patterns in the EEG can significantly increase the sensitivity for seizure identification. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study.

PubMed

Stefanidou, Maria; Das, Rohit R; Beiser, Alexa S; Sundar, Banu; Kelly-Hayes, Margaret; Kase, Carlos S; Devinsky, Orrin; Seshadri, Sudha; Friedman, Daniel

2017-04-01

We examined the incidence of seizures following ischemic stroke in a community-based sample. All subjects with incident ischemic strokes in the Framingham Original and Offspring cohorts between 1982 and 2003 were identified and followed for up to 20 years to determine incidence of seizures. Seizure-type was based on the 2010 International League Against Epilepsy (ILAE) classification. Disability was stratified into mild/none, moderate and severe, based on post-stroke neurological deficit documentation according to the Framingham Heart Study (FHS) protocol and functional status was determined using the Barthel Index. An initial ischemic stroke occurred in 469 subjects in the cohort and seizures occurred in 25 (5.3%) of these subjects. Seizure incidence was similar in both large artery atherosclerosis (LAA) (6.8%) and cardio-embolic (CE) (6.2%) strokes. No seizures occurred following lacunar strokes. The predominant seizure type was focal seizure with or without evolution to bilateral convulsive seizure. One third of participants had seizures within the first 24h from stroke onset and half of all seizures occurred within the first 30days. On multivariate analysis, moderate and severe disability following stroke was associated with increased risk of incident seizure. Seizures occurred in approximately 5% of subjects after an ischemic stroke. One third of these seizures occurred in the first 24h after stroke and none followed lacunar strokes. Focal seizures with or without evolution in bilateral convulsive seizures were the most common seizure type. Moderate and severe disability was predictive of incident seizures. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Speed of antidepressant response to electroconvulsive therapy in bipolar disorder vs. major depressive disorder.

PubMed

Agarkar, Smita; Hurt, Stephen W; Young, Robert C

2018-07-01

We reviewed studies that reported speed of antidepressant response to electroconvulsive therapy (ECT) in both bipolar depression (BPD) and major depressive disorder (MDD). We identified English language reports allowing this comparison. Ten studies met our criteria. Four reported significantly faster response in BPD and in one there was trend for faster response. None reported evidence for slower response in BPD. The findings support further study of speed of response to ECT in BPD. Copyright © 2018 Elsevier B.V. All rights reserved.

Electroconvulsive therapy (ECT) in literature: Sylvia Plath's The Bell Jar.

PubMed

Kellner, Charles H

2013-01-01

Sylvia Plath's well-known novel, The Bell Jar, recounts her experience of a severe depressive episode. In the novel, the protagonist is treated with electroconvulsive therapy (ECT), as was Plath in life. The first ECT is given in the now-obsolete "unmodified" form, without general anesthesia. Later in the story, she receives ECT again, this time with full general anesthesia and muscle relaxation, as is the standard of care today. This chapter examines how the novelistic descriptions of the treatment compare with actual clinical practice. © 2013 Elsevier B.V. All rights reserved.

Use of Orally Disintegrating Olanzapine During Electroconvulsive Therapy for Prevention of Postictal Agitation.

PubMed

Hermida, Adriana P; Janjua, A Umair; Tang, Yilang; Syre, Sharyn R; Job, Gregory; McDonald, William M

2016-11-01

A major medical problem for patients undergoing electroconvulsive therapy (ECT) is the occurrence of postictal agitation (PIA). This phenomenon is associated with confusion and disorientation that can have severe clinical implications for the safety of the patient and health care professionals. Many different pharmacological strategies have been used to prevent PIA. We present data on 40 patients who suffered from PIA after a course of ECT and evaluate the prophylactic use of orally disintegrating olanzapine in the prevention of PIA in subsequent ECT treatments.

Electroconvulsive therapy in pregnancy - A review.

PubMed

Spodniaková, B; Halmo, M; Nosáľová, P

2015-01-01

Most major psychiatric illnesses are resistant to psychotropic drugs that are approved for use during pregnancy. Maternal illness and related medications may have adverse impacts on the foetus. Electroconvulsive therapy (ECT) might be an effective and safe option for treating several psychiatric disorders in pregnant women. This study evaluates the use of ECT for treating major psychoses during pregnancy and presents an assessment of risks faced by both mother and foetus. Based on our analysis we present recommendations for safe and effective treatment of psychiatric diseases via ECT in pregnant women.

[Information about electroconvulsive therapy on the internet].

PubMed

Degraeve, G; Van Heeringen, C; Audenaert, K

2006-01-01

This article aims to provide a quantitative and qualitative assessment of the information about electroconvulsive therapy that is currently available on the internet. We carried out a quantitative assessment by entering five search terms into eight (meta)search engines. We achieved our qualitative assessment by visiting the first twenty websites generated by each search on one of the search engines, in particular Google (www.google.com), and by scoring these websites with an adapted Sandvik-score. We conclude that the scored websites are technically sound but are incomplete as far as content is concerned.

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.

Do antipsychotic drugs increase seizure frequency in epilepsy patients?

PubMed

Okazaki, Mitsutoshi; Adachi, Naoto; Akanuma, Nozomi; Hara, Koichiro; Ito, Masumi; Kato, Masaaki; Onuma, Teiichi

2014-11-01

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

TASK channel deletion reduces sensitivity to local anesthetic-induced seizures

PubMed Central

Du, Guizhi; Chen, Xiangdong; Todorovic, Marko S.; Shu, Shaofang; Kapur, Jaideep; Bayliss, Douglas A.

2011-01-01

Background Local anesthetics (LAs) are typically used for regional anesthesia but can be given systemically to mitigate postoperative pain, supplement general anesthesia or prevent cardiac arrhythmias. However, systemic application or inadvertent intravenous injection can be associated with substantial toxicity, including seizure induction. The molecular basis for this toxic action remains unclear. Methods We characterized effects of different LAs on homomeric and heteromeric K+ channels containing TASK-1 (K2P3.1, KCNK3) and TASK-3 (K2P9.1, KCNK9) subunits in a mammalian expression system. In addition, we used TASK-1/TASK-3 knockout mice to test the possibility that TASK channels contribute to LA-evoked seizures. Results LAs inhibited homomeric and heteromeric TASK channels in a range relevant for seizure induction; channels containing TASK-1 subunits were most sensitive and IC50 values indicated a rank order potency of bupivacaine > ropivacaine ⟫ lidocaine. LAs induced tonic-clonic seizures in mice with the same rank order potency, but higher LA doses were required to evoke seizures in TASK knockout mice. For bupivacaine, which produced the longest seizure times, seizure duration was significantly shorter in TASK knockout mice; bupivacaine-induced seizures were associated with an increase in electroencephalogram power at frequencies <5 Hz in both wild type and TASK knockout mice. Conclusions These data suggest that increased neuronal excitability associated with TASK channel inhibition by LAs contributes to seizure induction. Since all LAs were capable of evoking seizures in TASK channel deleted mice, albeit at higher doses, the results imply that other molecular targets must also be involved in this toxic action. PMID:21946151

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

Recording the adult zebrafish cerebral field potential during pentylenetetrazole seizures

PubMed Central

Pineda, Ricardo; Beattie, Christine E.; Hall, Charles W.

2017-01-01

Although the zebrafish is increasingly used as a model organism to study epilepsy, no standard electrophysiological technique for recording electrographic seizures in adult fish exists. The purpose of this paper is to introduce a readily implementable technique for recording pentylenetetrazole seizures in the adult zebrafish. We find that we can consistently record a high quality field potential over the zebrafish cerebrum using an amplification of 5000 V/V and bandpass filtering at corner frequencies of 1.6 and 16 Hz. The cerebral field potential recordings show consistent features in the baseline, pre-seizure, seizure and post-seizure time periods that can be easily recognized by visual inspection as is the case with human and rodent electroencephalogram. Furthermore, numerical analysis of the field potential at the time of seizure onset reveals an increase in the total power, bandwidth and peak frequency in the power spectrum, as is also the case with human and rodent electroencephalogram. The techniques presented herein stand to advance the utility of the adult zebrafish in the study of epilepsy by affording an equivalent to the electroencephalogram used in mammalian models and human patients. PMID:21689682

The Inhibitory Effects of Npas4 on Seizures in Pilocarpine-Induced Epileptic Rats

PubMed Central

Guo, Jiamei; Yang, Guang; Long, Xianghua; Hu, Rong; Shen, Wenjing; Wang, Xuefeng; Zeng, Kebin

2014-01-01

To explore the effects of neuronal Per-Arnt-Sim domain protein 4 (Npas4) on seizures in pilocarpine-induced epileptic rats, Npas4 expression was detected by double-label immunofluorescence, immunohistochemistry, and Western blotting in the brains of pilocarpine-induced epileptic model rats at 6 h, 24 h, 72 h, 7 d, 14 d, 30 d, and 60 d after status epilepticus. Npas4 was localized primarily in the nucleus and in the cytoplasm of neurons. The Npas4 protein levels increased in the acute phase of seizures (between 6 h and 72 h) and decreased in the chronic phases (between 7 d and 60 d) in the rat model. Npas4 expression was knocked down by specific siRNA interference. Then, the animals were treated with pilocarpine, and the effects on seizures were evaluated on the 7th day. The onset latencies of pilocarpine-induced seizures were decreased, while the seizure frequency, duration and attack rate increased in these rats. Our study indicates that Npas4 inhibits seizure attacks in pilocarpine-induced epileptic rats. PMID:25536221

The inhibitory effects of Npas4 on seizures in pilocarpine-induced epileptic rats.

PubMed

Wang, Dan; Ren, Min; Guo, Jiamei; Yang, Guang; Long, Xianghua; Hu, Rong; Shen, Wenjing; Wang, Xuefeng; Zeng, Kebin

2014-01-01

To explore the effects of neuronal Per-Arnt-Sim domain protein 4 (Npas4) on seizures in pilocarpine-induced epileptic rats, Npas4 expression was detected by double-label immunofluorescence, immunohistochemistry, and Western blotting in the brains of pilocarpine-induced epileptic model rats at 6 h, 24 h, 72 h, 7 d, 14 d, 30 d, and 60 d after status epilepticus. Npas4 was localized primarily in the nucleus and in the cytoplasm of neurons. The Npas4 protein levels increased in the acute phase of seizures (between 6 h and 72 h) and decreased in the chronic phases (between 7 d and 60 d) in the rat model. Npas4 expression was knocked down by specific siRNA interference. Then, the animals were treated with pilocarpine, and the effects on seizures were evaluated on the 7th day. The onset latencies of pilocarpine-induced seizures were decreased, while the seizure frequency, duration and attack rate increased in these rats. Our study indicates that Npas4 inhibits seizure attacks in pilocarpine-induced epileptic rats.

Efficacy of right unilateral ultrabrief pulse width ECT: a preliminary report.

PubMed

Magid, Michelle; Truong, Liz; Trevino, Kenneth; Husain, Mustafa

2013-12-01

Ultrabrief (right unilateral) electroconvulsive therapy (UB-RU ECT) is a newer form of ECT, which uses a shorter pulse width than the standard ECT (0.3 vs 1.0 millisecond, respectively). As a result, the use of UB ECT may provide a means of further decreasing ECT-related cognitive adverse effects. In 2011, the University of Texas Southwestern Department of ECT in Austin adopted a UB ECT protocol. The purpose of this study was to perform a preliminary evaluation of the effectiveness and efficiency of UB-RU ECT. This study also examined whether sex, age, or diagnosis affected response rates. This retrospective chart review identified 62 patients treated with the UB ECT protocol. An analysis of ECT response rates and demographic characteristics was conducted based on the data from clinical evaluations and Patient Health Questionnaire 9. Sixty-eight percent of patients in the study responded to ECT; 55% responded to UB pulse width RU ECT with another 13% responding when switched to standard pulse width bilateral ECT. The mean number of treatments in an index ECT series was 12.5. There was no statistically significant difference in response rates between bipolar and unipolar depressed patients. Men required progression to bilateral treatment more than women. This UB ECT protocol demonstrated a similar response rate when compared to standard ECT protocols; however, an increase in the number of treatments was required. Ultrabrief protocols are a viable option for both bipolar and unipolar depression. In men, UB ECT protocols may be less advantageous due to a need to overcome a potentially higher seizure threshold in men; however, additional research is needed to confirm this finding.

High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy.

PubMed

Depositario-Cabacar, Dewi T; Peters, Jurriaan M; Pong, Amanda W; Roth, Julie; Rotenberg, Alexander; Riviello, James J; Takeoka, Masanori

2010-07-01

We review our experience with high-dose intravenous levetiracetam (IV-LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures-while on chronic antiepileptic drugs-that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV-LEV of 150 mg/kg/day or greater, with a mean dose of 228 +/- 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure-free in two, >/=80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV-LEV was well tolerated in all children without complications.

The impact of antidepressants on seizure frequency and depressive and anxiety disorders of patients with epilepsy: Is it worth investigating?

PubMed

Ribot, Ramses; Ouyang, Bichun; Kanner, Andres M

2017-05-01

Depression and anxiety disorders in patients with epilepsy (PWE) remain under-recognized and under-treated, despite being the most common psychiatric co-morbidities. Selective serotonin re-uptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are considered first-line treatment for primary depression and anxiety disorders. We performed this study to investigate if SSRIs and SNRIs could affect the seizure frequency of PWE and to assess whether such effect is independent of the response of the mood and anxiety disorders to these drugs. This was a retrospective study of 100 consecutive PWE who were started on an SSRI or SNRI for the treatment of a depressive and/or anxiety disorder. Every patient underwent a psychiatric evaluation by one of the investigators using a semi-structured interview who also managed the pharmacologic treatment in all the patients. Patients were excluded if they had a diagnosis of psychogenic non-epileptic seizures or if they had undergone epilepsy surgery or the implant of the vagal nerve stimulator six months before and after the start of the antidepressant therapy. The final analysis was conducted in 84 patients. For each type of seizure, an average and maximal monthly seizure frequency during the six months preceding and following the start of psychotropic drugs was extracted from the medical records. We identified the number of patients whose seizure frequency during treatment with antidepressants: (i) shifted from a <1/month to a ≥1 seizure/month and vice-versa, (ii) increased beyond maximal/monthly baseline frequency, and (iii) patients who developed de-novo generalized tonic-clonic (GTC) seizures. None of the patients with a baseline seizure frequency <1seizure/month went on to have ≥1seizure/month after initiating treatment with antidepressants, had an increase in frequency beyond baseline maximal counts or developed de-novo-GTC seizures. Furthermore, there was no seizure recurrence among patients that had been seizure-free. Among the patients with a baseline seizure frequency ≥1/month, 27.5% had a reduction in seizure frequency to <1/month, which suggested a positive effect of SSRI/SNRI on seizure frequency (p=0.001, McNemar test). Among the patients with a baseline seizure frequency ≥1seizure/month, 48% exhibited a >50% reduction in seizure frequency after the start of treatment with SSRIs or SNRIs. A therapeutic response to SSRIs and SNRIs was found in 73% of patients. The change in seizure frequency was independent of the improvement in psychiatric symptomatology. In this retrospective observational study, SSRIs or SNRIs did not appear to worsen seizure frequency. Also, in patients with frequent seizures, SSRIs and SNRIs may be associated with a possible decrease in seizure frequency. Furthermore, these drugs appear to yield good therapeutic response of psychiatric symptoms independently of seizure frequency. It is pivotal to replicate these data in prospective, double-blind, placebo-controlled trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Indispensable Amino Acid-Deficient Diets Induce Seizures in Ketogenic Diet-Fed Rodents, Demonstrating a Role for Amino Acid Balance in Dietary Treatments for Epilepsy.

PubMed

Gietzen, Dorothy W; Lindström, Sarah H; Sharp, James W; Teh, Pok Swee; Donovan, Michael J

2018-03-01

Low protein amounts are used in ketogenic diets (KDs), where an essential (indispensable) amino acid (IAA) can become limiting. Because the chemically sensitive, seizurogenic, anterior piriform cortex (APC) is excited by IAA limitation, an imbalanced KD could exacerbate seizure activity. We questioned whether dietary IAA depletion worsens seizure activity in rodents fed KDs. In a series of 6 trials, male rats or gerbils of both sexes (6-8/group) were given either control diets (CDs) appropriate for each trial, a KD, or a threonine-devoid (ThrDev) diet for ≥7 d, and tested for seizures using various stimuli. Microchip analysis of rat APCs was also used to determine if changes in transcripts for structures relevant to seizurogenesis are affected by a ThrDev diet. Glutamate release was measured in microdialysis samples from APCs during the first meal after 7 d on a CD or a ThrDev diet. Adult rats showed increased susceptibility to seizures in both chemical (58%) and electroshock (doubled) testing after 7 d on a ThrDev diet compared with CD (each trial, P ≤ 0.05). Seizure-prone Mongolian gerbils had fewer seizures after receiving a KD, but exacerbated seizures (68%) after 1 meal of KD minus Thr (KD-T compared with CD, P < 0.05). In kindled rats fed KD-T, both counts (19%) and severities (77%) of seizures were significantly elevated (KD-T compared with CD, P < 0.05). Gene transcript changes were consistent with enhanced seizure susceptibility (7-21 net-fold increases, P = 0.045-0.001) and glutamate release into the APC was increased acutely (4-fold at 20 min, 2.6-fold at 60 min, P < 0.05) after 7 d on a ThrDev diet. Seizure severity in rats and gerbils was reduced after KDs and exacerbated by ThrDev, both in KD- and CD-fed animals, consistent with the mechanistic studies. We suggest that a complete protein profile in KDs may improve IAA balance in the APC, thereby lowering the risk of seizures.

Age-dependent long-term structural and functional effects of early life seizures: evidence for a hippocampal critical period influencing plasticity in adulthood

PubMed Central

Meyerand, M.E.; Sutula, T.

2015-01-01

Neural activity promotes circuit formation in developing systems and during critical periods permanently modifies circuit organization and functional properties. These observations suggest that excessive neural activity, as occurs during seizures, might influence developing neural circuitry with long-term outcomes that depend on age at the time of seizures. We systematically examined long-term structural and functional consequences of seizures induced in rats by kainic acid, pentylenetetrazol, and hyperthermia across postnatal ages from birth through postnatal day 90 in adulthood (P90). Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and electrophysiological methods at ≥P95 following seizures induced from P1 to P90 demonstrated consistent patterns of gross atrophy, microstructural abnormalities in the corpus callosum and hippocampus, and functional alterations in hippocampal circuitry at ≥P95 that were independent of the method of seizure induction and varied systematically as a function of age at the time of seizures. Three distinct epochs were observed in which seizures resulted in distinct long-term structural and functional outcomes at ≥P95. Seizures prior to P20 resulted in DTI abnormalities in corpus callosum and hippocampus in the absence of gross cerebral atrophy, and increased paired pulse inhibition (PPI) in the dentate gyrus at ≥P95. Seizures after P30 induced a different pattern of DTI abnormalities in the fimbria and hippocampus accompanied by gross cerebral atrophy with increases in lateral ventricular volume, as well as increased PPI in the dentate gyrus at ≥P95. In contrast, seizures between P20-P30 did not result in cerebral atrophy or significant imaging abnormalities in the hippocampus or white matter, but irreversibly decreased PPI in the dentate gyrus compared to normal adult controls. These age-specific long-term structural and functional outcomes identify P20-P30 as a potential critical period in hippocampal development defined by distinctive long-term structural and functional properties in adult hippocampal circuitry, including loss of capacity for seizure-induced plasticity in adulthood that could influence epileptogenesis and other hippocampal – dependent behaviors and functional properties. PMID:25555928

Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

PubMed Central

Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

2015-01-01

There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure threshold. Taken together these findings indicate that early-life seizures alter the development of oscillations and result in autistic-like behaviors. The altered communication between these brain regions could reflect the physiological underpinnings underlying social cognitive deficits seen in autism spectrum disorders. PMID:25766676

COMPARING STIMULANT EFFECTS IN YOUTH WITH ADHD SYMPTOMS AND EPILEPSY

PubMed Central

Gonzalez-Heydrich, Joseph; Hsin, Olivia; Gumlak, Sarah; Kimball, Kara; Rober, Ashley; Azeem, Muhammad W.; Hickory, Meredith; Mrakotsky, Christine; Torres, Alcy; Mezzacappa, Enrico; Bourgeois, Blaise; Biederman, Joseph

2014-01-01

To retrospectively examine response to stimulant treatment in patients with epilepsy and ADHD symptoms as predicted by seizure freedom for six months, use of methylphenidate (MPH) versus amphetamine (AMP) preparations, and cognitive level, medical records were searched for patients under age 18 with epilepsy and ADHD symptoms treated with MPH or AMP (n = 36, age 10.4±3.5; 67% male). “Responders” had a CGI-Improvement score of ≤2 and did not stop medication due to adverse effects. “Worsened” patients discontinued medication due to agitation/emotional lability. Seizure freedom did not predict treatment response. Lower cognitive level was associated with increased rate of worsening (p=0.048). No patients who were seizure-free at start of the medication trial experienced an increase in seizures. Of the patients having seizures at the start of trial, one patient on MPH and two on AMP had increased seizures during the trial. Seizures returned to baseline frequency or less after stimulant discontinuation or anticonvulsant adjustment. MPH was associated with a higher response rate, with 12 of 19 given MPH 0.62±0.28mg/kg/day compared to 4 of 17 given AMP 0.37±0.26mg/kg/day responding (p=0.03). MPH treatment and higher cognitive level were associated with improved treatment outcome while seizure freedom had no clear effect. Confidence in these findings is limited by the study’s small, open label, and uncontrolled nature. PMID:24907495

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 Epilepsy.

Multiscale Entropy of Electroencephalogram as a Potential Predictor for the Prognosis of Neonatal Seizures.

PubMed

Lu, Wen-Yu; Chen, Jyun-Yu; Chang, Chi-Feng; Weng, Wen-Chin; Lee, Wang-Tso; Shieh, Jiann-Shing

2015-01-01

Increasing animal studies supported the harmful effects of prolonged or frequent neonatal seizures in developing brain, including increased risk of later epilepsy. Various nonlinear analytic measures had been applied to investigate the change of brain complexity with age. This study focuses on clarifying the relationship between later epilepsy and the changes of electroencephalogram (EEG) complexity in neonatal seizures. EEG signals from 19 channels of the whole brain from 32 neonates below 2 months old were acquired. The neonates were classified into 3 groups: 9 were normal controls, 9 were neonatal seizures without later epilepsy, and 14 were neonatal seizures with later epilepsy. Sample entropy (SamEn), multiscale entropy (MSE) and complexity index (CI) were analyzed. Although there was no significant change in SamEn, the CI values showed significantly decreased over Channels C3, C4, and Cz in patients with neonatal seizures and later epilepsy compared with control group. More multifocal epileptiform discharges in EEG, more abnormal neuroimaging findings, and higher incidence of future developmental delay were noted in the group with later epilepsy. Decreased MSE and CI values in patients with neonatal seizures and later epilepsy may reflect the mixed effects of acute insults, underlying brain immaturity, and prolonged seizures-related injuries. The analysis of MSE and CI can therefore provide a quantifiable and accurate way to decrypt the mystery of neonatal seizures, and could be a promising predictor.

Prenatal corticosteroid exposure alters early developmental seizures and behavior

PubMed Central

Velíšek, Libor

2011-01-01

In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hydrocortisone (2× 10 mg/kg), betamethasone (2× 0.4 mg/kg) or vehicle. On postnatal day (P)15, seizures were induced by flurothyl or kainic acid (3.5 or 5.0 mg/kg). Horizontal bar holding was determined prior to seizures and again on P17. Performance in the elevated plus maze was assessed on P20-22. Prenatal exposure to betamethasone decreased postnatal susceptibility to flurothyl-induced clonic seizures but not to kainic acid-induced seizures. Prenatal hydrocortisone decreased postnatal weight but did not affect seizure susceptibility. Hydrocortisone alone did not affect performance in behavioral tests except for improving horizontal bar holding on P17. A combination of prenatal hydrocortisone and postnatal seizures resulted in increased anxiety. Prenatal exposure to mineralocorticoid receptor blocker canrenoic acid did not attenuate, but surprisingly amplified the effects of hydrocortisone on body weight and significantly worsened horizontal bar performance. Thus, prenatal exposure to excess corticosteroids alters postnatal seizure susceptibility and behaviors. Specific effects may depend on corticosteroid species. PMID:21429712

[Cardiac safety of electroconvulsive therapy in an elderly patient--a case report].

PubMed

Karakuła-Juchnowicz, Hanna; Próchnicki, Michał; Kiciński, Paweł; Olajossy, Marcin; Pelczarska-Jamroga, Agnieszka; Dzikowski, Michał; Jaroszyński, Andrzej

2015-10-01

Since electroconvulsive therapy (ECT) was introduced as treatment for psychiatric disorders in 1938, it has remained one of the most effective therapeutic methods. ECT is often used as a "treatment of last resort" when other methods fail, and a life-saving procedure in acute clinical states when a rapid therapeutic effect is needed. Mortality associated with ECT is lower, compared to the treatment with tricyclic antidepressants, and comparable to that observed in so-called minor surgery. In the literature, cases of effective and safe electroconvulsive therapy have been described in patients of advanced age, with a burden of many somatic disorders. However, cases of acute cardiac episodes have also been reported during ECT. The qualification of patients for ECT and the selection of a group of patients at the highest risk of cardiovascular complications remains a serious clinical problem. An assessment of the predictive value of parameters of standard electrocardiogram (ECG), which is a simple, cheap and easily available procedure, deserves special attention. This paper reports a case of a 74-year-old male patient treated with ECT for a severe depressive episode, in the context of cardiologic safety. Both every single ECT session and the full course were assessed to examine their impact on levels of troponin T, which is a basic marker of cardiac damage, and selected ECG parameters (QTc, QRS). In the presented case ECT demonstrated its high general and cardiac safety with no negative effect on cardiac troponin (TnT) levels, corrected QT interval (QTc) duration, or other measured ECG parameters despite initially increased troponin levels, the patient's advanced age, the burden of a severe somatic disease and its treatment (anticancer therapy). © 2015 MEDPRESS.

Safety and utility of acute electroconvulsive therapy for agitation and aggression in dementia.

PubMed

Acharya, Deepa; Harper, David G; Achtyes, Eric D; Seiner, Stephen J; Mahdasian, Jack A; Nykamp, Louis J; Adkison, Lesley; Van der Schuur White, Lori; McClintock, Shawn M; Ujkaj, Manjola; Davidoff, Donald A; Forester, Brent P

2015-03-01

Agitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. Twenty-three participants admitted to McLean Hospital (Belmont, MA, USA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI, USA), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory-Short Form, Neuropsychiatric Inventory-Nursing Home Version, Cornell Scale for Depression in Dementia, and the Clinical Global Impression Scale at baseline, during, and after the ECT course. Regression analyses revealed a significant decrease from baseline to discharge on the Cohen-Mansfield Agitation Inventory (F(4,8) = 13.3; p = 0.006) and Neuropsychiatric Inventory (F(4,31) = 14.6; p < 0.001). There was no statistically significant change in scores on the Cornell Scale for Depression in Dementia. The Clinical Global Impression scores on average changed from a rating of "markedly agitated/aggressive" at baseline to "borderline agitated/aggressive" at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants because of recurrence of agitation and for three participants because of adverse events. Electroconvulsive therapy may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. Copyright © 2014 John Wiley & Sons, Ltd.

Blood serum concentrations of kynurenic acid in patients diagnosed with recurrent depressive disorder, depression in bipolar disorder, and schizoaffective disorder treated with electroconvulsive therapy.

PubMed

Olajossy, Marcin; Olajossy, Bartosz; Wnuk, Sebastian; Potembska, Emilia; Urbańska, Ewa

2017-06-18

The aim of the present study was to compare blood serum kynurenic acid (KYNA) concentrations measured before ECT and after 1, 6 and 12 electroconvulsive treatment (ECT) sessions in patients with diagnoses of recurrent depressive disorder (RDD), depression in bipolar disorder (DBD) and schizoaffective disorder (SAD). The study group comprised of 50 patients with ICD-10 diagnoses of RDD, DBD and SAD. Blood serum KYNA concentrations were determined and clinical assessment was performed using the MADRS and the GAF scale. Significant differences were found in blood serum KYNA levels between RDD, DBD and SAD patients treated with electroconvulsive therapy and healthy controls: 1) KYNA concentrations in DBD patients measured before ECT and after 12 ECT sessions were significantly lower than in the control group; 2) KYNA concentrations in the serum of RDD patients measured before ECT and after one and 12 ECT sessions were significantly lower than in the control group, while those measured after 6 ECT session did not differ significantly from KYNA concentrations in healthy controls; 3) higher pre-treatment blood serum concentrations of KYNA in DBD patients correlated with a higher number of illness phases and poorer general functioning before treatment; 4) significant relationships were found between higher blood serum concentrations of KYNA in RDD patients after 1 ECT session and male gender, and between higher KYNA concentrations after 6 ECT sessions and increased depression and poorer functioning before treatment in those patients. Results show that KYNA concentrations in all diagnostic groups were lower before ECT (not statistically significant for the SAD group) and that there were no significant changes in those concentrations (compared with the baseline) during ECT.

Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABAA receptors

PubMed Central

Shakarjian, Michael P.; Velíšková, Jana; Stanton, Patric K.; Velíšek, Libor

2012-01-01

Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic-clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic-clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic-clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABAA receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists are more likely to be effective in treating TMDT poisoning. PMID:23022509

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

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 maintenance, but its precise seizure-associated functions are not known. We recorded neuronal activity in three different thalamic regions and found divergent activity patterns, which may respectively participate in seizure propagation, impaired level of conscious arousal, and altered relay of information to the cortex during focal limbic seizures. These very different activity patterns within the thalamus may help explain why focal temporal lobe seizures often disrupt widespread network function, and can help guide future treatments aimed at restoring normal thalamocortical network activity and cognition. Copyright © 2017 the authors 0270-6474/17/3711441-14$15.00/0.

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 maintenance, but its precise seizure-associated functions are not known. We recorded neuronal activity in three different thalamic regions and found divergent activity patterns, which may respectively participate in seizure propagation, impaired level of conscious arousal, and altered relay of information to the cortex during focal limbic seizures. These very different activity patterns within the thalamus may help explain why focal temporal lobe seizures often disrupt widespread network function, and can help guide future treatments aimed at restoring normal thalamocortical network activity and cognition. PMID:29066556

Increased glial glutamate transporter EAAT2 expression reduces epileptogenic processes following pilocarpine-induced status epilepticus

PubMed Central

Kong, Qiongman; Takahashi, Kou; Schulte, Delanie; Stouffer, Nathan; Lin, Yuchen; Lin, Chien-liang Glenn

2013-01-01

Several lines of evidence indicate that glutamate plays a crucial role in the initiation of seizures and their propagation; abnormal glutamate release causes synchronous firing of large populations of neurons, leading to seizures. In the present study, we investigated whether enhanced glutamate uptake by increased glial glutamate transporter EAAT2, the major glutamate transporter, could prevent seizure activity and reduce epileptogenic processes. EAAT2 transgenic mice, which have a 1.5-2 fold increase in EAAT2 protein levels as compared to their non-transgenic counterparts, were tested in a pilocarpine-induced status epilepticus (SE) model. Several striking phenomena were observed in EAAT2 transgenic mice compared with their non-transgenic littermates. First, the post-SE mortality rate and chronic seizure frequency were significantly decreased. Second, neuronal degeneration in hippocampal subfields after SE were significantly reduced. Third, the SE-induced neurogenesis and mossy fiber sprouting were significantly decreased. The severity of cell loss in epileptic mice was positively correlated with that of mossy fiber sprouting and chronic seizure frequency. Our results suggest that increased EAAT2 expression can protect mice against SE-induced death, neuropathological changes, and chronic seizure development. This study suggests that enhancing EAAT2 protein expression is a potential therapeutic approach. PMID:22513140

Febrile seizures after 2009 influenza A (H1N1) vaccination and infection: a nationwide registry-based study.

PubMed

Bakken, Inger Johanne; Aaberg, Kari Modalsli; Ghaderi, Sara; Gunnes, Nina; Trogstad, Lill; Magnus, Per; Håberg, Siri Eldevik

2015-11-09

During the 2009 influenza A (H1N1) pandemic, a monovalent pandemic strain vaccine containing the oil-in-water adjuvant AS03 (Pandemrix®) was offered to the Norwegian population. The coverage among children reached 54%. Our aim was to estimate the risk of febrile seizure in children after exposure to pandemic influenza vaccination or infection. The study population comprised 226,889 children born 2006-2009 resident in Norway per October 1st, 2009. Febrile seizure episodes were defined by emergency hospital admissions / emergency outpatient hospital care with International Classification of Diseases, Version 10, codes R56.0 or R56.8. The self-controlled case series method was applied to estimate incidence rate ratios (IRRs) in pre-defined risk periods compared to the background period. The total observation window was ± 180 days from exposure day. Among 113,068 vaccinated children, 656 (0.6%) had at least one febrile seizure episode. The IRR of febrile seizures 1-3 days after vaccination was 2.00 (95% confidence interval [CI]: 1.15-3.51). In the period 4-7 days after vaccination, no increased risk was observed. Among the 8172 children diagnosed with pandemic influenza, 84 (1.0%) had at least one febrile seizure episode. The IRR of febrile seizures on the same day as a diagnosis of influenza was 116.70 (95% CI: 62.81-216.90). In the period 1-3 days after a diagnosis of influenza, a tenfold increased risk was observed (IRR 10.12, 95% CI: 3.82 - 26.82). In this large population-based study with precise timing of exposures and outcomes, we found a twofold increased risk of febrile seizures 1-3 days after pandemic influenza vaccination. However, we found that pandemic influenza infection was associated with a much stronger increase in risk of febrile seizures.

Does comorbid alcohol and substance abuse affect electroconvulsive therapy outcome in the treatment of mood disorders?

PubMed

Moss, Lori; Vaidya, Nutan

2014-03-01

Antidepressant medications remain the principal agents used to treat patients with mood disorders, although 30% to 40% of these patients do not improve. One of the factors associated with poor medication response is alcohol and substance abuse. Persons with mood disorders are at the greatest risk for suicide, and alcoholism is a significant additional risk factor. Electroconvulsive therapy (ECT) is shown to be the most effective treatment for major depression especially when associated with psychosis, catatonia, and suicide intent. However, similar to most antidepressant trials, patients with depression and comorbid alcohol and substance abuse are excluded from ECT efficacy studies. Through a retrospective chart review, we compared response to ECT in patients with mood disorder and comorbid alcohol and drug abuse to those with mood disorder only. From 2004 to 2010, 80 patients with mood disorder received ECT. Fifty of these had comorbid alcohol or drug abuse. Using a 10-item psychopathology scale, we compared pre- and post-ECT symptom severity between the 2 groups. Outcome was determined by measuring a decrease in the pre-ECT and post-ECT score using Wilcoxon rank tests, with statistical significance at P = 0.05. There was no difference between the 2 groups in most demographics, ECT medication, or seizure quality. There was no difference in ECT outcome between those with comorbid alcohol abuse and those without based on percent decrease in pre- and post-ECT symptom scores (abuse: mean [SD], 0.89 [0.2] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 1332; P = 0.086). When we compared those who met the criteria for alcohol or drug dependence (19 patients) with those with no abuse, there was a trend for the dependence group to not do as well (dependence: mean [SD], 0.83 [0.25] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 405; P = 0.053). Those with combined drug and alcohol abuse (18 patients) did have a significantly worse outcome (combined: mean [SD], 0.82 [0.25] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 372; P = 0.033). Our results indicate that comorbid alcohol and drug abuse may influence the response to ECT in the treatment of mood disorders. Based on our results, patients with comorbid dependence and combined drug and alcohol abuse showed symptom improvement but did not do as well as those with nonabuse.

Seizure Freedom Rates and Prognostic Indicators After Resection of Gangliogliomas: A Review.

PubMed

Bonney, Phillip A; Glenn, Chad A; Ebeling, Peter A; Conner, Andrew K; Boettcher, Lillian B; Cameron, Drew M; Battiste, James D; Sughrue, Michael E

2015-12-01

Gangliogliomas are rare tumors that comprise up to 40% of lesional epilepsy. Seizure control represents an important quality-of-life determinant in patients with these tumors. Here we present results of a literature review addressing rates of seizure freedom in in patients with gangliogliomas. Across studies, seizure freedom occurred in 63%-100% of patients. Many studies included follow-up times of greater than 5 years, suggesting that the responses are durable. We discuss potential prognostic factors associated with seizure freedom, including the duration of epilepsy, patient age, frequency and semiology of seizures, tumor location, extent of surgical resection, and operative strategy, including surgical approach and use of invasive monitoring. Although significant differences in study populations and treatments preclude meta-analysis, we discuss prognostic factors identified in individual studies. Increased extent of resection, lesser duration of epilepsy, and younger age at surgery have been associated with increased seizure freedom rates in at least 2 studies each. Although all studies were retrospective in nature and are consequently limited by the weaknesses inherent to such investigations, the literature suggests that surgery is able to relieve most ganglioglioma patients--regardless of patient demographics, tumor characteristics, and operative variables--of seizures. Copyright © 2015 Elsevier Inc. All rights reserved.

Repeated electroconvulsive shock (ECS) alters the phosphorylation of glutamate receptor subunits in the rat hippocampus.

PubMed

Fumagalli, Fabio; Pasini, Matteo; Sartorius, Alexander; Scherer, Rosine; Racagni, Giorgio; Riva, Marco A; Gass, Peter

2010-10-01

Glutamate and its receptors are involved in the pathophysiology of mood disorders and have recently emerged as potential targets for the pharmacotherapy of depression. In rats, we investigated plasticity changes of the glutamatergic system evoked by electroconvulsive shock (ECS), which represents the most effective therapy for patients who are refractory to antidepressants. Chronic ECS produced a marked increase in the phosphorylation of the regulatory NMDA receptor subunit NR2B (Ser1303) and the AMPA receptor subunit GluR-A (Ser831) in the hippocampus, with no effects on the obligatory subunit NR1. No effects were found on total receptor subunit expression levels. We suggest that, at least in part, ECS exerts its clinical activity through the modulation of the glutamatergic synapses, via potentiation of AMPA currents mediated by GluR-A (Ser831) phosphorylation, and a reduction of NMDA receptor activity through the phosphorylation of NR2B (Ser1303), presumably uncoupling NR2B from its signalling partner CaMKII. These effects functionally resemble the recently described antidepressant effects of ketamine.

Sociodemographic characterization of ECT utilization in Hawaii.

PubMed

Ona, Celia M; Onoye, Jane M; Goebert, Deborah; Hishinuma, Earl; Bumanglag, R Janine; Takeshita, Junji; Carlton, Barry; Fukuda, Michael

2014-03-01

Minimal research has been done on sociodemographic differences in utilization of electroconvulsive therapy (ECT) for refractory depression, especially among Asian Americans and Pacific Islanders. This study examined sociodemographic and diagnostic variables using retrospective data from Hawaii, an island state with predominantly Asian Americans and Pacific Islanders. Retrospective data were obtained from an inpatient and outpatient database of ECT patients from 2008 to 2010 at a tertiary care community hospital on O'ahu, Hawaii. There was a significant increase in overall ECT utilization from 2008 to 2009, with utilization remaining stable from 2009 to 2010. European Americans (41%) and Japanese Americans (29%) have relatively higher rates of receiving ECT, and Filipino Americans and Native Hawaiians have relatively lower rates in comparison with their population demographics. Japanese Americans received significantly more ECT procedures than European Americans. Electroconvulsive therapy is underutilized by certain sociodemographic groups that may benefit most from the treatment. There are significant differences in ECT usage based on ethnicity. Such differences may be related to help-seeking behavior, economic differences, and/or attitudes regarding mental illness. Further research is needed to elucidate the reasons for differences in utilization.

Epilepsy phenotypes in siblings with Norrie disease.

PubMed

Okumura, Akihisa; Arai, Eisuke; Kitamura, Yuri; Abe, Shinpei; Ikeno, Mitsuru; Fujimaki, Takuro; Yamamoto, Toshiyuki; Shimizu, Toshiaki

2015-11-01

Norrie disease is an X-linked recessive disorder that is characterized by congenital blindness. Although epileptic seizures are observed in some patients with Norrie disease, little is known about this phenomenon. Here, we report the manifestation of epilepsy in siblings with Norrie disease to increase our knowledge of epilepsy in this condition. Three brothers with congenital blindness were diagnosed with Norrie disease after genetic analyses indicated the deletion of exon 2 of the NDP gene. The eldest brother had suffered from epileptic seizures since the age of 11years, and his seizures were resistant to antiepileptic drugs. Although the second brother had no epileptic seizures, the youngest sibling had experiences epileptic seizures since the age of 8years. His seizures were controlled using lamotrigine and levetiracetam. An electroencephalography (EEG) revealed epileptiform discharges in the occipital areas in all three brothers. A study of these patients will increase our knowledge of epilepsy in patients with Norrie disease. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups.

PubMed

Laorden, M L; Miralles, F S; Puig, M M

1988-03-01

The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.

Differences in cortical vs. subcortical GABAergic signaling: a candidate mechanism of electroclinical dissociation of neonatal seizures

PubMed Central

Glykys, J.; Dzhala, V.I.; Kuchibhotla, K.V.; Feng, G.; Kuner, T.; Augustine, G.; Bacskai, BJ.; Staley, KJ.

2010-01-01

Electroclinical dissociation of neonatal seizures refers to electrographic seizure activity that is not clinically manifest. Dissociation increases after treatment with Phenobarbital, which increases the GABAA receptor (GABAAR) conductance. The effects of GABAAR activation depend on the intracellular Cl− concentration ([Cl−]i) that is determined by the inward Cl− transporter NKCC1 and the outward Cl− transporter KCC2. Differential maturation of Cl− transport observed in cortical vs. subcortical regions should alter the efficacy of GABA-mediated inhibition. In perinatal rat pups, most thalamic neurons maintained low [Cl−]i, and were inhibited by GABA. Phenobarbital suppressed thalamic seizure activity. Most neocortical neurons maintained higher [Cl−]i, and were excited by GABAAR activation. Phenobarbital had insignificant anticonvulsant responses in the neocortex until NKCC1 was blocked. Regional differences in the ontogeny of Cl− transport may thus explain why seizure activity in the cortex is not suppressed by anticonvulsants that block the transmission of seizure activity through subcortical networks. PMID:19755108

Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.

PubMed

Belcastro, Vincenzo; Caraballo, Roberto Horacio; Romeo, Antonino; Striano, Pasquale

2013-12-01

Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

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.

Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures.

PubMed

Klein, Nicola P; Fireman, Bruce; Yih, W Katherine; Lewis, Edwin; Kulldorff, Martin; Ray, Paula; Baxter, Roger; Hambidge, Simon; Nordin, James; Naleway, Allison; Belongia, Edward A; Lieu, Tracy; Baggs, James; Weintraub, Eric

2010-07-01

In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine. Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses. MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6). Among 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.

Suppressing cAMP response element-binding protein transcription shortens the duration of status epilepticus and decreases the number of spontaneous seizures in the pilocarpine model of epilepsy.

PubMed

Zhu, Xinjian; Dubey, Deepti; Bermudez, Camilo; Porter, Brenda E

2015-12-01

Current epilepsy therapies directed at altering the function of neurotransmitter receptors or ion channels, or release of synaptic vesicles fail to prevent seizures in approximately 30% of patients. A better understanding of the molecular mechanism underlying epilepsy is needed to provide new therapeutic targets. The activity of cyclic AMP (cAMP) response element-binding protein (CREB), a major transcription factor promoting CRE-mediated transcription, increases following a prolonged seizure called status epilepticus. It is also increased in the seizure focus of patients with medically intractable focal epilepsy. Herein we explored the effect of acute suppression of CREB activity on status epilepticus and spontaneous seizures in a chronic epilepsy model. Pilocarpine chemoconvulsant was used to induce status epilepticus. To suppress CREB activity, a transgenic mouse line expressing an inducible dominant negative mutant of CREB (CREB(IR) ) with a serine to alanine 133 substitution was used. Status epilepticus and spontaneous seizures of transgenic and wild-type mice were analyzed using video-electroencephalography (EEG) to assess the effect of CREB suppression on seizures. Our findings indicate that activation of CREB(IR) shortens the duration of status epilepticus. The frequency of spontaneous seizures decreased in mice with chronic epilepsy during CREB(IR) induction; however, the duration of the spontaneous seizures was unchanged. Of interest, we found significantly reduced levels of phospho-CREB Ser133 upon activation of CREB(IR) , supporting prior work suggesting that binding to the CRE site is important for CREB phosphorylation. Our results suggest that CRE transcription supports seizure activity both during status epilepticus and in spontaneous seizures. Thus, blocking of CRE transcription is a novel target for the treatment of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Increased cortical extracellular adenosine correlates with seizure termination.

PubMed

Van Gompel, Jamie J; Bower, Mark R; Worrell, Gregory A; Stead, Matt; Chang, Su-Youne; Goerss, Stephan J; Kim, Inyong; Bennet, Kevin E; Meyer, Fredric B; Marsh, W Richard; Blaha, Charles D; Lee, Kendall H

2014-02-01

Seizures are currently defined by their electrographic features. However, neuronal networks are intrinsically dependent on neurotransmitters of which little is known regarding their periictal dynamics. Evidence supports adenosine as having a prominent role in seizure termination, as its administration can terminate and reduce seizures in animal models. Furthermore, microdialysis studies in humans suggest that adenosine is elevated periictally, but the relationship to the seizure is obscured by its temporal measurement limitations. Because electrochemical techniques can provide vastly superior temporal resolution, we test the hypothesis that extracellular adenosine concentrations rise during seizure termination in an animal model and humans using electrochemistry. White farm swine (n = 45) were used in an acute cortical model of epilepsy, and 10 human epilepsy patients were studied during intraoperative electrocorticography (ECoG). Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS)-based fast scan cyclic voltammetry (FSCV) and fixed potential amperometry were obtained utilizing an adenosine-specific triangular waveform or biosensors, respectively. Simultaneous ECoG and electrochemistry demonstrated an average adenosine increase of 260% compared to baseline, at 7.5 ± 16.9 s with amperometry (n = 75 events) and 2.6 ± 11.2 s with FSCV (n = 15 events) prior to electrographic seizure termination. In agreement with these animal data, adenosine elevation prior to seizure termination in a human patient utilizing FSCV was also seen. Simultaneous ECoG and electrochemical recording supports the hypothesis that adenosine rises prior to seizure termination, suggesting that adenosine itself may be responsible for seizure termination. Future work using intraoperative WINCS-based FSCV recording may help to elucidate the precise relationship between adenosine and seizure termination. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Dynamics of convulsive seizure termination and postictal generalized EEG suppression

PubMed Central

Bauer, Prisca R.; Thijs, Roland D.; Lamberts, Robert J.; Velis, Demetrios N.; Visser, Gerhard H.; Tolner, Else A.; Sander, Josemir W.; Lopes da Silva, Fernando H.; Kalitzin, Stiliyan N.

2017-01-01

Abstract It is not fully understood how seizures terminate and why some seizures are followed by a period of complete brain activity suppression, postictal generalized EEG suppression. This is clinically relevant as there is a potential association between postictal generalized EEG suppression, cardiorespiratory arrest and sudden death following a seizure. We combined human encephalographic seizure data with data of a computational model of seizures to elucidate the neuronal network dynamics underlying seizure termination and the postictal generalized EEG suppression state. A multi-unit computational neural mass model of epileptic seizure termination and postictal recovery was developed. The model provided three predictions that were validated in EEG recordings of 48 convulsive seizures from 48 subjects with refractory focal epilepsy (20 females, age range 15–61 years). The duration of ictal and postictal generalized EEG suppression periods in human EEG followed a gamma probability distribution indicative of a deterministic process (shape parameter 2.6 and 1.5, respectively) as predicted by the model. In the model and in humans, the time between two clonic bursts increased exponentially from the start of the clonic phase of the seizure. The terminal interclonic interval, calculated using the projected terminal value of the log-linear fit of the clonic frequency decrease was correlated with the presence and duration of postictal suppression. The projected terminal interclonic interval explained 41% of the variation in postictal generalized EEG suppression duration (P < 0.02). Conversely, postictal generalized EEG suppression duration explained 34% of the variation in the last interclonic interval duration. Our findings suggest that postictal generalized EEG suppression is a separate brain state and that seizure termination is a plastic and autonomous process, reflected in increased duration of interclonic intervals that determine the duration of postictal generalized EEG suppression. PMID:28073789

Postpartum electroconvulsive therapy: a systematic review and case report.

PubMed

Gressier, Florence; Rotenberg, Samuel; Cazas, Odile; Hardy, Patrick

2015-01-01

Postpartum depression can have devastating consequences on the mother and child. Prompt treatment is challenging. Whereas electroconvulsive therapy (ECT) is considered to be an effective treatment modality in severe depression and brings about rapid clinical improvement, little is known about ECT during the postpartum period. We systematically reviewed the literature on the use of ECT during the postpartum period using PubMed, Institute for Scientific Information Web of Knowledge and PsycINFO databases until September 2014, using the search terms "electroconvulsive therapy" or "ECT" and "postpartum". Then, we described the successful treatment with ECT and the joint mother-baby hospitalization of a woman with severe depression. Eight case reports and 8 studies were identified. All of the studies reported that ECT is effective in the postpartum period. It is well tolerated, provides a fast response and allows for breastfeeding. In addition, our case report showed the benefits of the hospitalization of the mother-baby unit. Combined ECT and joint mother-baby hospitalization could be a valuable treatment by targeting both the mother-infant relationship and the maternal depressive symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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.

A Phase-Locked Loop Epilepsy Network Emulator

PubMed Central

Watson, P.D.; Horecka, K. M.; Cohen, N.J.; Ratnam, R.

2015-01-01

Most seizure forecasting employs statistical learning techniques that lack a representation of the network interactions that give rise to seizures. We present an epilepsy network emulator (ENE) that uses a network of interconnected phase-locked loops (PLLs) to model synchronous, circuit-level oscillations between electrocorticography (ECoG) electrodes. Using ECoG data from a canine-epilepsy model (Davis et al. 2011) and a physiological entropy measure (approximate entropy or ApEn, Pincus 1995), we demonstrate the entropy of the emulator phases increases dramatically during ictal periods across all ECoG recording sites and across all animals in the sample. Further, this increase precedes the observable voltage spikes that characterize seizure activity in the ECoG data. These results suggest that the ENE is sensitive to phase-domain information in the neural circuits measured by ECoG and that an increase in the entropy of this measure coincides with increasing likelihood of seizure activity. Understanding this unpredictable phase-domain electrical activity present in ECoG recordings may provide a target for seizure detection and feedback control. PMID:26664133

Transient serotonin syndrome by concurrent use of electroconvulsive therapy and selective serotonin reuptake inhibitor: a case report and review of the literature.

PubMed

Okamoto, Nagahisa; Sakamoto, Kota; Yamada, Maki

2012-01-01

The serotonin syndrome, which is characterized by psychiatric, autonomic nervous and neurological symptoms, is considered to be caused by excessive stimulation of the 5-HT1A and 5-HT2 receptors in the gray matter and spinal cord of the central nervous system, after the start of dosing or increase of the dose of a serotoninergic drug. There have been hardly any reports of induction of serotonin syndrome by electroconvulsive therapy (ECT) in combination with antidepressant. We present the case of a female patient with major depressive disorder (MDD) who developed transient serotonin syndrome soon after the first session of ECT in combination with paroxetine. Paroxetine was discontinued, and her psychiatric, autonomic nervous and neurological symptoms were gradually relieved and disappeared within 2 days. We performed the second ECT session 5 days after the initial session and performed 12 sessions of ECT without any changes in the procedure of ECT and anesthesia, but no symptoms of SS were observed. Finally, her MDD remitted. ECT might cause transiently increased blood-brain barrier (BBB) permeability and enhance the transmissivity of the antidepressant in BBB. Therefore, it is necessary to pay attention to rare side effect of serotonin syndrome by ECT in combination with antidepressant.

Polymicrogyria-associated epilepsy: a multi-center phenotypic study from the Epilepsy Phenome/Genome Project

PubMed Central

Shain, Catherine; Ramgopal, Sriram; Fallil, Zianka; Parulkar, Isha; Alongi, Richard; Knowlton, Robert; Poduri, Annapurna

2013-01-01

Purpose Polymicrogyria (PMG) is an epileptogenic malformation of cortical development. We describe the clinical epilepsy and imaging features of a large cohort with PMG-related epilepsy. Methods Participants were recruited through the Epilepsy Phenome/Genome Project, a multi-center collaborative effort to collect detailed phenotypic data on individuals with epilepsy. We reviewed phenotypic data from participants with epilepsy and PMG. Key Findings We identified 87 participants, 43 female and 44 male, with PMG and epilepsy. Median age of seizure onset was 3 years (range <1 month-37 years). Most presented with focal epilepsy (87.4%), some in combination with seizures generalized from onset (23.0%). Focal seizures with dyscognitive features were most common (54.3%). Of those presenting with generalized seizure types, infantile spasms were most prevalent (45.2%). The most common topographic pattern was perisylvian PMG (77.0%), of which the majority was bilateral (56.7%). Generalized PMG presented with an earlier age of seizure onset (median age of 8 months) and an increased prevalence of developmental delay prior to seizure onset (57.1%). Of the focal, unilateral and asymmetric bilateral groups where PMG was more involved in one hemisphere, the majority (71.4%) of participants had seizures that lateralized to the same hemisphere as the PMG or the hemisphere with greater involvement. Significance Participants with PMG had both focal and generalized onset of seizures. Our data confirm the involvement of known topographic patterns of PMG and suggest that more extensive distributions of PMG present with an earlier age of seizure onset and increased prevalence of developmental delay prior to seizure onset. PMID:23750890

Characterization of Early Partial Seizure Onset: Frequency, Complexity and Entropy

PubMed Central

Jouny, Christophe C.; Bergey, Gregory K.

2011-01-01

Objective A clear classification of partial seizures onset features is not yet established. Complexity and entropy have been very widely used to describe dynamical systems, but a systematic evaluation of these measures to characterize partial seizures has never been performed. Methods Eighteen different measures including power in frequency bands up to 300Hz, Gabor atom density (GAD), Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample entropy, and permutation entropy, were selected to test sensitivity to partial seizure onset. Intracranial recordings from forty-five patients with mesial temporal, neocortical temporal and neocortical extratemporal seizure foci were included (331 partial seizures). Results GAD, Lempel-Ziv complexity, HFD, high frequency activity, and sample entropy were the most reliable measures to assess early seizure onset. Conclusions Increases in complexity and occurrence of high-frequency components appear to be commonly associated with early stages of partial seizure evolution from all regions. The type of measure (frequency-based, complexity or entropy) does not predict the efficiency of the method to detect seizure onset. Significance Differences between measures such as GAD and HFD highlight the multimodal nature of partial seizure onsets. Improved methods for early seizure detection may be achieved from a better understanding of these underlying dynamics. PMID:21872526

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: a dissociation of hippocampal Fos from seizure activity

PubMed Central

Kadiyala, Sridhar B.; Papandrea, Dominick; Tuz, Karina; Anderson, Tara M.; Jayakumar, Sachidhanand; Herron, Bruce J.; Ferland, Russell J.

2014-01-01

Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2’s seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ~85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype in B6 mice is highly correlated with bilateral Fos expression in the VMH and was not observed in D2 mice, which always express clonic-forebrain seizures upon flurothyl retest. Overall, these results illustrate specific differences in protein and RNA expression in different inbred strains following seizures that precede the reorganizational events that affect seizure susceptibility and changes in seizure semiology over time. PMID:25524858

Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity.

PubMed

Kadiyala, Sridhar B; Papandrea, Dominick; Tuz, Karina; Anderson, Tara M; Jayakumar, Sachidhanand; Herron, Bruce J; Ferland, Russell J

2015-01-01

Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2's seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ∼85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype in B6 mice is highly correlated with bilateral Fos expression in the VMH and was not observed in D2 mice, which always express clonic-forebrain seizures upon flurothyl retest. Overall, these results illustrate specific differences in protein and RNA expression in different inbred strains following seizures that precede the reorganizational events that affect seizure susceptibility and changes in seizure semiology over time. Copyright © 2014 Elsevier B.V. All rights reserved.

Tonic Seizure Status Epilepticus Triggered by Valproate in a Child with Doose Syndrome.

PubMed

Grande-Martín, Alberto; Pardal-Fernández, José Manuel; Carrascosa-Romero, María Carmen; De Cabo, Carlos

2016-06-01

Antiepileptic drugs may occasionally increase seizure frequency or eliciting de novo seizure occurrence; the underlying mechanism of these effects is not known. The potential adverse effects of valproic acid in myoclonic astatic epilepsy have been noted by experienced clinicians in various different regions of the world, but this important observation has not been sufficiently reported. We present the case of tonic status epilepticus in an 8-year-old boy with Doose syndrome related to valproic acid. Valproic acid, such as others antiepileptic drugs, is liable to produce paradoxical effects such as the atypical seizures we report. We emphasize the importance for the management of acute seizures in an intensive care unit setting and increase awareness of the acute toxic effects of antiepileptic drugs. Georg Thieme Verlag KG Stuttgart · New York.

Seizures after Onyx embolization for the treatment of cerebral arteriovenous malformation.

PubMed

de Los Reyes, K; Patel, A; Doshi, A; Egorova, N; Panov, F; Bederson, J B; Frontera, J A

2011-09-01

Onyx embolization of cerebral arteriovenous malformations (AVM) has become increasingly common. We explored the risk of seizures after Onyx use.A retrospective review was conducted of 20 patients with supratentorial brain arteriovenous malformation (AVM) who received Onyx embolization between 2006 and 2009. Baseline demographics, clinical history, seizure history, AVM characteristics and treatment were compared between those who developed post-onyx seizure and those who did not. MRIs were reviewed for edema following Onyx treatment.Of 20 patients who underwent Onyx embolization, the initial AVM presentation was hemorrhage in 40% (N=8). The median number of embolizations was two (range 1-4) and the median final obliteration amount was 90% (range 50-100%). A history of seizure was present in 50% (N=10) of patients pre-embolization and 12 (60%) patients received seizure medications (treatment or prophylaxis) prior to embolization. Seizur post-Onyx embolization occurred in 45% (N=9). The median time to seizur post-Onyx was seven days (range 0.3-210). Four patients (20%) with seizures post-Onyx had no seizure history. Two of these patients (10%) had no other identifiable cause for seizure other than recent Onyx embolization. Seizures in these two patients occurred within 24 hours of Onyx administration. Among patients with post-Onyx seizures, there was a trend toward larger AVM size (P=0.091) and lower percent obliteration (P=0.062). Peri-AVM edema was present in 75% of MRIs performed within one month of Onyx treatment and may represent a possible etiology for seizures.New onset seizures post-Onyx embolization are not uncommon. Further study of seizure prevention is warranted.

EFFECTS OF CHRONIC ANTIDEPRESSANT DRUG ADMINISTRATION AND ELECTROCONVULSIVE SHOCK ON ACTIVITY OF DOPAMINERGIC NEURONS IN THE VENTRAL TEGMENTUM

PubMed Central

West, Charles Hutchison Keesor; Weiss, Jay Michael

2010-01-01

Increasing attention is now focused on reduced dopaminergic neurotransmission in the forebrain as participating in depression. The present paper assessed whether effective antidepressant (AD) treatments might counteract, or compensate for, such a change by altering the neuronal activity of dopaminergic neurons in the ventral tegmental area (VTA-DA neurons), the cell bodies of the mesocorticolimbic dopaminergic system. Eight AD drugs or vehicle were administered to rats for 14 days via subcutaneously-implanted minipumps, at which time single-unit electrophysiological activity of VTA-DA neurons was recorded under anesthesia. Also, animals received a series of five electroconvulsive shocks (ECS) or control procedures, after which VTA-DA activity was measured either three or five days after the last ECS. Results showed that the chronic administration of all AD drugs tested except for the monoamine oxidase inhibitor increased the spontaneous firing rate of VTA-DA neurons, while effects on “burst” firing activity were found to be considerably less notable or consistent. ECS increased both spontaneous firing rate and burst firing of VTA-DA neurons. It is suggested that the effects observed are consistent with reports of increased dopamine release in regions to which VTA neurons project after effective AD treatment. However, it is further suggested that changes in VTA-DA neuronal activity in response to AD treatment should be most appropriately assessed under conditions associated with depression, such as stressful conditions. PMID:20482941

Truly enthralling: epileptiform events in film and on television--why they persist and what we can do about them.

PubMed

Kerson, Toba Schwaber; Kerson, Lawrence A

2008-01-01

Seizures and epilepsy have been portrayed in film since 1900 and on television since the 1950s, but unlike many other conditions, their depictions have not improved with increased scientific understanding. At this time, most individuals who are under 45 years of age will never witness a seizure. Thus, their information about what seizures are comes from depictions in film and on television. Because especially on television these fictive and often erroneous images are increasing, many think of them as accurate. The research addresses three questions in relation to these images: How do directors use the images? Why do uses of seizures in visual media not reflect contemporary scientific knowledge? Why have they persisted and increased in use? Data consist of material from 242 films and television episodes. The general category of seizures includes seizures in characters said to have epilepsy or some other condition, seizures related to alcohol/drug use, feigned or pseudoseizures, and a "throwaway" category. The research demonstrates how epileptiform events drive the narrative, support the genre, evoke emotional reactions, highlight traits of characters with seizures, accentuate traits of other characters through their responses, act as catalysts for action, and enhance voyeuristic experience. Through connecting categories, we explain a basic social process (Glaser, 2007). The conclusion is that these images are so enthralling that their use is likely to persist. The authors suggest that advocates acknowledge this and then find ways to have more continuing characters with correctly depicted epilepsy be part of television series as a way of exploring the truly enthralling dimensions of the condition.

Epilepsy-related injuries.

PubMed

Wirrell, Elaine C

2006-01-01

Only one prospective, controlled study has compared the risk of accidental injury in persons with epilepsy to controls without seizures. A mildly increased risk in the epilepsy group was found, predominantly due to injuries that result directly from a seizure. With regard to injury type, this study found significantly higher rates of only head and soft tissue injury; however, most injuries were minor. Several retrospective, population-based studies have suggested increased rates of more serious injury types. Submersion injury has a high mortality; the risk of submersion in children with epilepsy is 7.5-13.9 fold higher than in the general population. The risk of fracture is elevated approximately twofold, either resulting directly from seizure-induced injury or predisposed by drug-induced reduction in bone mineral density. Burns due to seizures account for between 1.6% and 3.7% of burn unit admissions. The risk of motor vehicle accidents in drivers with epilepsy also appears increased, albeit marginally. Several factors predispose to a higher risk of injury among those with epilepsy. Seizures resulting in falls increase the risk of concussion and other injuries. Higher seizure frequency, lack of a prolonged seizure-free interval, comorbid attention deficit disorder, or cognitive handicap may also increase the risk of injury. While some restrictions are necessary to protect the safety of the person with epilepsy, undue limitations may further limit achievement of independence. Given the high morbidity and mortality of submersion injury, those with active epilepsy should bathe or swim only with supervision; however, showering is a reasonable option. Appropriate vitamin D and calcium supplementation and periodic measurement of bone mineral density in those at risk for osteopenia are recommended.

Role of Steroids in Hyperexcitatory Adverse and Anesthetic Effects of Sevoflurane in Neonatal Rats.

PubMed

Zhang, Jiaqiang; Xu, Changqing; Puentes, Dyanet L; Seubert, Christoph N; Gravenstein, Nikolaus; Martynyuk, Anatoly E

2016-01-01

Recent studies have demonstrated that long-term developmental effects of neonatal anesthesia were more prominent in males. We tested whether steroids, in general, and sex steroids, in particular, are involved in the mediation of sevoflurane-caused paradoxical cortical seizures during the early postnatal period. Cortical electroencephalograms, hippocampal synaptic activity, serum levels of steroids and the loss of the righting reflex (LORR), a marker of anesthetic effect, were measured on postnatal days 4-6 in Sprague Dawley rats of both genders exposed to 2.1% sevoflurane. Episodes of seizures, persistent spikes in electroencephalograms and increases in serum corticosterone were similar in both genders. In the order of increasing potency, the corticosteroid receptor antagonist RU 28318, the estradiol receptor antagonist ICI 182780 and the estradiol synthesis inhibitor formestane decreased sevoflurane-induced seizures. Exogenous estradiol increased sevoflurane-caused seizures, spikes and serum levels of corticosterone. These estradiol-enhanced seizures and spikes were depressed by ICI 182780 and the NKCC1 inhibitor, bumetanide, while RU 28318 decreased seizures only. In hippocampal CA1 neurons, estradiol increased the amplitude, rise time and area under the curve of gamma-aminobutyric acid type A receptor (GABAAR)-mediated miniature postsynaptic currents. Exogenous estradiol shortened, while ICI 182780 and formestane lengthened the time needed for sevoflurane to induce LORR. These findings provide evidence for gender-independent acute electroencephalographic effects of sevoflurane at this age. Corticosterone and estradiol are involved in the mediation of sevoflurane-induced seizures. Estradiol, but not corticosterone, also contributes to sevoflurane-caused spikes, by enhancing GABAAR-mediated excitation in the cortex. By increasing GABAAR-mediated inhibition in more mature caudal regions of the brain, estradiol contributes to sevoflurane-induced LORR. © 2015 S. Karger AG, Basel.

Early Post Traumatic Seizures in Military Personnel Result in Long Term Disability

DTIC Science & Technology

2013-10-01

contusional versus non-contusional). The seizures occurred repeatedly in nearly ¼ of patients are 1/3 of those with seizures had status epilepticus . In...a seizure or status epilepticus occurs within the initial 3 days. Electrographic epileptiform activity will be categorized as follows: Type of...increases of 50% above the baseline value of any of these quantitative measures. A standardized protocol to treat status epilepticus as well as dosage

Idiopathic burning mouth syndrome: a common treatment-refractory somatoform condition responsive to ECT.

PubMed

McGirr, Alexander; Davis, Lindsay; Vila-Rodriguez, Fidel

2014-04-30

Somatic symptom disorders are common causes of disability and suffering, and can pose significant management challenges. Idiopathic burning mouth syndrome is a challenging somatic symptom disorder with relatively high prevalence, particularly among post-menopausal women. Here, we present the case of a woman with severe treatment refractory idiopathic burning mouth syndrome and comorbid major depressive disorder, who was successfully treated with bitemporal electroconvulsive therapy. This case highlights the potential effectiveness of electroconvulsive therapy in idiopathic burning mouth syndrome when other treatment options have been exhausted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Historical essay: electroconvulsive therapy, memory, and self in America.

PubMed

Hirshbein, Laura

2012-01-01

Electroconvulsive Therapy (ECT) practitioners and anti-ECT activists have divergent interpretations of both the treatment and its history. Despite claims by ECT opponents that practitioners do not acknowledge memory side effects, the published literature on the procedure demonstrates psychiatrists' awareness of this issue. And though current ECT practitioners claim that memory side effects were mostly the result of outmoded methods, investigators continue to publish studies that indicate ongoing memory problems. This article explores the conflict between pro- and anti-ECT groups around the issue of memory side effects in the broader context of changes in American psychiatry and society.

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

Probability of detection of clinical seizures using heart rate changes.

PubMed

Osorio, Ivan; Manly, B F J

2015-08-01

Heart rate-based seizure detection is a viable complement or alternative to ECoG/EEG. This study investigates the role of various biological factors on the probability of clinical seizure detection using heart rate. Regression models were applied to 266 clinical seizures recorded from 72 subjects to investigate if factors such as age, gender, years with epilepsy, etiology, seizure site origin, seizure class, and data collection centers, among others, shape the probability of EKG-based seizure detection. Clinical seizure detection probability based on heart rate changes, is significantly (p<0.001) shaped by patients' age and gender, seizure class, and years with epilepsy. The probability of detecting clinical seizures (>0.8 in the majority of subjects) using heart rate is highest for complex partial seizures, increases with a patient's years with epilepsy, is lower for females than for males and is unrelated to the side of hemisphere origin. Clinical seizure detection probability using heart rate is multi-factorially dependent and sufficiently high (>0.8) in most cases to be clinically useful. Knowledge of the role that these factors play in shaping said probability will enhance its applicability and usefulness. Heart rate is a reliable and practical signal for extra-cerebral detection of clinical seizures originating from or spreading to central autonomic network structures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Longitudinal changes in seizure outcomes after resection of cerebral cavernous malformations in patients presenting with seizures: a long-term follow-up of 46 patients.

PubMed

Kim, Jiha; Kim, Chi Heon; Chung, Chun Kee

2014-08-01

Seizure is the most common presentation in patients with cerebral cavernous malformations (CCMs). Although many articles have documented seizure outcomes after resection of CCM, few have conducted long-term follow-ups; thus, the fluctuating seizure outcomes have been neglected. The purpose of this study is to describe long-term postoperative seizure outcomes in patients with CCM and to compare seizure outcomes between patients with sporadic seizures and those with chronic seizures. Forty-six patients with CCM presenting with seizures underwent surgery. The male-to-female ratio was 1:1, and the average age at initial seizure onset was 27.6 years. The mean preoperative seizure duration was 42.7 months. Patients were divided into two groups: a chronic group (N = 20) and a sporadic group (N = 26) according to seizure frequency and duration. The mean postoperative follow-up duration was 96.3 months, and the postoperative seizure outcomes were checked annually based upon Engel's classification. After the first year of follow-up, 80.8 % of the sporadic group and 75.0 % of the chronic group were evaluated as Engel class I. These rates increased to 100.0 % and 90.0 %, respectively, at the eighth year of follow-up. Overall, 29 (63.0 %) of the 46 patients experienced changes in seizure outcomes over the follow-up period. Despite their delayed improvements, the chronic group showed less favorable outcomes throughout follow-up (p = 0.025). Long-term follow-up is indispensable for accurately assessing postoperative seizure outcomes because these outcomes change continuously. We recommend earlier surgery to achieve seizure-free status in patients with CCM. However, even in the chronic group, surgery is recommended, considering the overall delayed improvement.

Physiological reactivity to spontaneously occurring seizure activity in dogs with epilepsy and their carers.

PubMed

Packer, R M A; Volk, H A; Fowkes, R C

2017-08-01

There is a complex bidirectional relationship between stress and epilepsy. Stressful stimuli and subsequent cortisol release act as a trigger for seizure activity in some individuals with epilepsy, and seizure activity itself may act as a stressor to the affected individual. Epilepsy is the most common chronic neurological condition in domestic dogs and requires chronic management by their human carers, impacting upon the quality of life of both dog and carer. Seizures occur unpredictably and may be stressful for carers to witness and manage. In the present study we investigated the role of seizure activity as a stressor, measuring the effect of spontaneously occurring seizure activity in dogs with epilepsy upon their own cortisol levels and that of their carers. Furthermore, we tested whether individual differences in HPA reactivity were associated with owner personality characteristics and the quality of the dog-carer relationship. Saliva samples were obtained from sixteen dog-carer dyads in the home setting 20 and 40minute post-seizure, and at time-matched points on the following (non-seizure) day. Significant differences in cortisol levels were found in dogs at 40minute post-seizure (265.1% increase), and at 20minute post-seizure in their carers (40.5% increase). No associations were found between cortisol reactivity and the strength of the dog-carer bond. Carers with higher neuroticism scores exhibited higher cortisol levels at both post-seizure sampling points. As there was a gender bias in the carer sample (15/16 were female), and there are known sex differences in cortisol reactivity in response to psychological stress, the conclusions of this study may be limited to female carers. These findings are the first to objectively demonstrate the acutely stressful effects of seizures in dogs with epilepsy and their carers. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose?

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

Lagard, Camille, E-mail: camille.lagard@gmail.com

Poisoning with opioid analgesics including tramadol represents a challenge. Tramadol may induce respiratory depression, seizures and serotonin syndrome, possibly worsened when in combination to benzodiazepines. Our objectives were to investigate tramadol-related neurotoxicity, consequences of diazepam/tramadol combination, and mechanisms of drug-drug interactions in rats. Median lethal-doses were determined using Dixon–Bruce's up-and-down method. Sedation, seizures, electroencephalography and plethysmography parameters were studied. Concentrations of tramadol and its metabolites were measured using liquid-chromatography-high-resolution-mass-spectrometry. Plasma, platelet and brain monoamines were measured using liquid-chromatography coupled to fluorimetry. Median lethal-doses of tramadol and diazepam/tramadol combination did not significantly differ, although time-to-death was longer with combination (P =more » 0.04). Tramadol induced dose-dependent sedation (P < 0.05), early-onset seizures (P < 0.001) and increase in inspiratory (P < 0.01) and expiratory times (P < 0.05). The diazepam/tramadol combination abolished seizures but significantly enhanced sedation (P < 0.01) and respiratory depression (P < 0.05) by reducing tidal volume (P < 0.05) in addition to tramadol-related increase in respiratory times, suggesting a pharmacodynamic mechanism of interaction. Plasma M1 and M5 metabolites were mildly increased, contributing additionally to tramadol-related respiratory depression. Tramadol-induced early-onset increase in brain concentrations of serotonin and norepinephrine was not significantly altered by the diazepam/tramadol combination. Interestingly neither pretreatment with cyproheptadine (a serotonin-receptor antagonist) nor a benserazide/5-hydroxytryptophane combination (enhancing brain serotonin) reduced tramadol-induced seizures. Our study shows that diazepam/tramadol combination does not worsen tramadol-induced fatality risk but alters its toxicity pattern with enhanced respiratory depression but abolished seizures. Drug-drug interaction is mainly pharmacodynamic but increased plasma M1 and M5 metabolites may also contribute to enhancing respiratory depression. Tramadol-induced seizures are independent of brain serotonin. - Highlights: • Diazepam does not alter tramadol-induced median lethal dose but delays death onset. • Diazepam/tramadol combination worsens respiratory depression but prevents seizures. • Diazepam/tramadol-induced respiratory effects results from a pharmacodynamic drug-drug interaction. • Tramadol increases brain serotonin and norepinephrine that is not altered by diazepam. • Tramadol-induced seizures are independent of brain serotonin.« less

Safety and efficacy of caffeine-augmented ECT in elderly depressives: a retrospective study.

PubMed

Kelsey, M C; Grossberg, G T

1995-07-01

Prior studies have shown that in younger depressives undergoing ECT whose seizure durations declined despite maximum settings on three different ECT devices, pretreatment with caffeine lengthened seizures and resulted in clinical improvement. Caffeine (half life, 140-270 minutes) was well tolerated even in patients with pre-existing cardiovascular disease. The purpose of this retrospective study was to determine the safety and efficacy of caffeine augmented ECT in elderly depressed patients. The charts of 14 elderly depressives (average age 75.6, range 59-83; 2 males, 12 females) who received caffeine-augmented ECT were reviewed. Patients pre- and post-ECT medications, blood pressure, pulse, and seizure times (cuff and EEG) for each ECT performed were noted. The following conclusions were drawn from our study: (1) Caffeine definitely increases the seizure length and was useful in our setting when the energy settings could not be increased anymore. (2) Caffeine augmentation inconsistently causes an increase in pulse rate, on average, in the elderly. (3) Caffeine inconsistently produces an increase in mean arterial pressure. (4) Caffeine did not consistently produce an increase in the maximum rate-pressure product. We conclude from this study that caffeine-augmented ECT is safe and effective in increasing seizure duration in the elderly. However, more research needs to be done to determine optimal dosing and tolerability.

Human seizures self-terminate across spatial scales via a critical transition.

PubMed

Kramer, Mark A; Truccolo, Wilson; Eden, Uri T; Lepage, Kyle Q; Hochberg, Leigh R; Eskandar, Emad N; Madsen, Joseph R; Lee, Jong W; Maheshwari, Atul; Halgren, Eric; Chu, Catherine J; Cash, Sydney S

2012-12-18

Why seizures spontaneously terminate remains an unanswered fundamental question of epileptology. Here we present evidence that seizures self-terminate via a discontinuous critical transition or bifurcation. We show that human brain electrical activity at various spatial scales exhibits common dynamical signatures of an impending critical transition--slowing, increased correlation, and flickering--in the approach to seizure termination. In contrast, prolonged seizures (status epilepticus) repeatedly approach, but do not cross, the critical transition. To support these results, we implement a computational model that demonstrates that alternative stable attractors, representing the ictal and postictal states, emulate the observed dynamics. These results suggest that self-terminating seizures end through a common dynamical mechanism. This description constrains the specific biophysical mechanisms underlying seizure termination, suggests a dynamical understanding of status epilepticus, and demonstrates an accessible system for studying critical transitions in nature.

Understanding the burden of idiopathic generalized epilepsy in the United States, Europe, and Brazil: An analysis from the National Health and Wellness Survey.

PubMed

Gupta, Shaloo; Kwan, Patrick; Faught, Edward; Tsong, Wan; Forsythe, Anna; Ryvlin, Phillipe

2016-02-01

The aim of this study was to understand the current burden of primary generalized tonic-clonic seizures (PGTCS) associated with idiopathic generalized epilepsy (IGE) as a function of seizure frequency. We analyzed data for (IGE) as a proxy measure of PGTCS. Little is known about the quality of life (QoL), health utility, productivity, healthcare resource utilization (HRU), and cost burden of PGTCS or IGE. Patients were identified from the US (2011, 2012, & 2013), 5EU (2011 & 2013), and Brazil (2011 & 2012) National Health and Wellness Survey, a nationally representative, internet-based survey of adults (18+ years). Patients that self-reported a diagnosis of IGE were categorized into seizure frequencies of: ≥1 seizure per week, 1-3 seizures per month, 1-4 seizures per year, or <1 seizure per year. QoL was measured using the SF-36v2 Mental (MCS) and Physical Component Summary (PCS) scores, health utilities with the SF-6D, productivity with the Work Productivity and Activity Impairment (WPAI) questionnaire, and HRU as reported in the past six months. Unit costs were estimated from the literature and multiplied against HRU values to calculate direct costs and WPAI values to calculate indirect costs. Generalized linear regression was utilized to examine the relationship between seizure frequency and each measure of burden with adjustment for covariates. Out of the general population surveyed, IGE was self-reported in 782 of 176,093 (US), 172 of 30,000 (UK), 106 of 30,001 (Germany), 87 of 30,000 (France), 31 of 12,011 (Spain), 22 of 17,500 (Italy), and 34 of 24,000 (Brazil). Persistent seizures (≥1 per year) were reported in over 40% of patients with IGE (10-15% with ≥1 seizure per week, 10-15% with 1-3 seizures per month, 20-25% with 1-4 seizures per year). Over 75% were treated with antiepileptic drugs (AEDs). Compared with those having <1 seizure per year (reference group), patients in the two most frequent seizure categories reported worse MCS and PCS scores. Patients in the three highest seizure frequency groups consistently reported worse health utility scores, and greater presenteeism (attending work while not physically or mentally capable of working), overall work impairment, activity impairment, HRU, indirect costs, and direct costs than the reference group. Despite the availability of AEDs during the year surveyed, a substantial number of patients experienced persistent seizures. Increasing seizure frequency was clearly associated with worse outcomes. The burden of PGTCS and IGE may be proportionally reduced by newer AEDs which may increase the proportion of seizure-free patients or shift more patients into lower seizure frequency categories. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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 vehicle-treated adult rats after early-life seizures. These results suggest that acute AMPAR antagonist treatment during the latent period immediately following neonatal HS can modify seizure-induced activation of mTOR, reduce the frequency of later-life seizures, and protect against CA3 mossy fiber sprouting and autistic-like social deficits. PMID:24117347

Effect of epileptic seizures on the cerebrospinal fluid--A systematic retrospective analysis.

PubMed

Tumani, Hayrettin; Jobs, Catherine; Brettschneider, Johannes; Hoppner, Anselm C; Kerling, Frank; Fauser, Susanne

2015-08-01

Analyses of the cerebrospinal fluid (CSF) are obligatory when epileptic seizures manifest for the first time in order to exclude life-threatening causes or treatable diseases such as acute infections or autoimmune encephalitis. However, there are only few systematic investigations on the effect of seizures themselves on CSF parameters and the significance of these parameters in differential diagnosis. CSF samples of 309 patients with epileptic and 10 with psychogenic seizures were retrospectively analyzed. CSF samples were collected between 1999 and 2008. Cell counts, the albumin quotient, lactate and Tau-protein levels were determined. Findings were correlated with seizure types, seizure etiology (symptomatic, cryptogenic, occasional seizure), and seizure duration. Pathological findings were only observed in patients with epileptic but not with psychogenic seizures. The lactate concentration was elevated in 14%, the albumin quotient in 34%, and the Tau protein level in 36% of CSF samples. Cell counts were only slightly elevated in 6% of patients. Different seizure types influenced all parameters except for the cell count: In status epilepticus highest, in simple partial seizures lowest values were seen. Symptomatic partial and generalized epileptic seizures had significantly higher Tau-protein levels than cryptogenic partial seizures. In patients with repetitive and occasional epileptic seizures, higher Tau-protein levels were seen than in those with psychogenic seizures. Duration of epileptic seizures was positively correlated with the albumin quotient, lactate and Tau-protein levels. High variability of investigated CSF parameters within each subgroup rendered a clear separation between epileptic and psychogenic seizures impossible. Elevated cell counts are infrequently observed in patients with epileptic seizures and should therefore not uncritically be interpreted as a postictal phenomenon. However, blood-CSF barrier disruption, increased glucose metabolism and elevation of neuronal damage markers are observed in considerable percentages of patients and depend on many factors such as etiology, seizure type and duration. Copyright © 2015 Elsevier B.V. All rights reserved.

The SAFARI Score to Assess the Risk of Convulsive Seizure During Admission for Aneurysmal Subarachnoid Hemorrhage.

PubMed

Jaja, Blessing N R; Schweizer, Tom A; Claassen, Jan; Le Roux, Peter; Mayer, Stephan A; Macdonald, R Loch

2018-06-01

Seizure is a significant complication in patients under acute admission for aneurysmal SAH and could result in poor outcomes. Treatment strategies to optimize management will benefit from methods to better identify at-risk patients. To develop and validate a risk score for convulsive seizure during acute admission for SAH. A risk score was developed in 1500 patients from a single tertiary hospital and externally validated in 852 patients. Candidate predictors were identified by systematic review of the literature and were included in a backward stepwise logistic regression model with in-hospital seizure as a dependent variable. The risk score was assessed for discrimination using the area under the receiver operator characteristics curve (AUC) and for calibration using a goodness-of-fit test. The SAFARI score, based on 4 items (age ≥ 60 yr, seizure occurrence before hospitalization, ruptured aneurysm in the anterior circulation, and hydrocephalus requiring cerebrospinal fluid diversion), had AUC = 0.77, 95% confidence interval (CI): 0.73-0.82 in the development cohort. The validation cohort had AUC = 0.65, 95% CI 0.56-0.73. A calibrated increase in the risk of seizure was noted with increasing SAFARI score points. The SAFARI score is a simple tool that adequately stratified SAH patients according to their risk for seizure using a few readily derived predictor items. It may contribute to a more individualized management of seizure following SAH.

Use of anticonvulsants as prophylaxis for seizures in patients on clozapine.

PubMed

Caetano, Dorgival

2014-02-01

The aim of this study is to conduct a critical review of the literature regarding the use of anticonvulsants in the prophylaxis of clozapine-induced seizures, to examine the relationship of the latter with clozapine daily dose, serum concentration and other factors than dosage that effect clozapine blood concentration, and to make recommendations for the management of clozapine-induced seizures. A systematic review of English-language MEDLINE articles was undertaken. Clozapine-induced seizures may occur at any dose; the risk increases with dose and goes up to 4% at ≥ 600 mg/day. Some authors have advocated that patients on that dose regimen have anticonvulsant added as a primary prophylactic measure. The author discusses the pitfalls of this recommendation and highlights that seizures are better predicted from serum concentration (1300 ng/ml) rather than dose alone, and that serum concentration is strongly influenced by sex, age, smoking habit, drug-drug interactions and variations in the 1A2, 2D6 and 3A4 genotypes. Anticonvulsants are not recommended as a primary prophylaxis for clozapine-induced seizures. When deemed necessary as secondary prophylaxis, the clinician's choice should consider drug-drug interactions that may increase/decrease clozapine serum concentration and lead to more side effects, including neutropenia/agranulocytosis and seizures, or compromise therapeutic response. Recommendations for primary and secondary prophylaxis of clozapine related-seizures are provided.

Seizures after Onyx Embolization for the Treatment of Cerebral Arteriovenous Malformation

PubMed Central

de los Reyes, K.; Patel, A.; Doshi, A.; Egorova, N.; Panov, F.; Bederson, J.B.; Frontera, J.A.

2011-01-01

Summary Onyx embolization of cerebral arteriovenous malformations (AVM) has become increasingly common. We explored the risk of seizures after Onyx use. A retrospective review was conducted of 20 patients with supratentorial brain arteriovenous malformation (AVM) who received Onyx embolization between 2006 and 2009. Baseline demographics, clinical history, seizure history, AVM characteristics and treatment were compared between those who developed post-onyx seizure and those who did not. MRIs were reviewed for edema following Onyx treatment. Of 20 patients who underwent Onyx embolization, the initial AVM presentation was hemorrhage in 40% (N=8). The median number of embolizations was two (range 1-4) and the median final obliteration amount was 90% (range 50-100%). A history of seizure was present in 50% (N=10) of patients pre-embolization and 12 (60%) patients received seizure medications (treatment or prophylaxis) prior to embolization. Seizur post-Onyx embolization occurred in 45% (N=9). The median time to seizur post-Onyx was seven days (range 0.3-210). Four patients (20%) with seizures post-Onyx had no seizure history. Two of these patients (10%) had no other identifiable cause for seizure other than recent Onyx embolization. Seizures in these two patients occurred within 24 hours of Onyx administration. Among patients with post-Onyx seizures, there was a trend toward larger AVM size (P=0.091) and lower percent obliteration (P=0.062). Peri-AVM edema was present in 75% of MRIs performed within one month of Onyx treatment and may represent a possible etiology for seizures. New onset seizures post-Onyx embolization are not uncommon. Further study of seizure prevention is warranted. PMID:22005695

Human seizures couple across spatial scales through travelling wave dynamics

NASA Astrophysics Data System (ADS)

Martinet, L.-E.; Fiddyment, G.; Madsen, J. R.; Eskandar, E. N.; Truccolo, W.; Eden, U. T.; Cash, S. S.; Kramer, M. A.

2017-04-01

Epilepsy--the propensity toward recurrent, unprovoked seizures--is a devastating disease affecting 65 million people worldwide. Understanding and treating this disease remains a challenge, as seizures manifest through mechanisms and features that span spatial and temporal scales. Here we address this challenge through the analysis and modelling of human brain voltage activity recorded simultaneously across microscopic and macroscopic spatial scales. We show that during seizure large-scale neural populations spanning centimetres of cortex coordinate with small neural groups spanning cortical columns, and provide evidence that rapidly propagating waves of activity underlie this increased inter-scale coupling. We develop a corresponding computational model to propose specific mechanisms--namely, the effects of an increased extracellular potassium concentration diffusing in space--that support the observed spatiotemporal dynamics. Understanding the multi-scale, spatiotemporal dynamics of human seizures--and connecting these dynamics to specific biological mechanisms--promises new insights to treat this devastating disease.

Decreased subcortical cholinergic arousal in focal seizures

PubMed Central

Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal

2015-01-01

SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258

Perampanel and Challenging Behaviour in Intellectual Disability and Epilepsy: A Management Dilemma

PubMed Central

Choudry, Ansar

2014-01-01

We describe a case of a patient with a diagnosis of moderate learning disability with challenging behaviour and treatment refractory epilepsy. Antiepileptics can increase challenging behaviour; however, antipsychotics can provoke seizures. This results in a difficult balance for patient care. Due to worsening seizures, the patient was prescribed perampanel. This increased her aggression and agitation resulting in admission. We trialled four antipsychotic drugs to reduce her challenging behaviour, two of which worsened her seizures. It was necessary to continue antiepileptic medication to maintain adequate seizure control. However, the resulting uncontrolled challenging behaviour persisted, meaning she was unable to return to her family home on discharge. This case emphasises the difficult scenario clinician's encounter when balancing the use of antipsychotics and antiepileptics. The case demonstrates the significant functional loss due to challenging behaviour, balanced against controlling life threatening seizures. PMID:25580340

Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

PubMed Central

Huang, Li-Tung

2014-01-01

Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

Non-pharmacological biological treatment approaches to difficult-to-treat depression.

PubMed

Fitzgerald, Paul B

2013-09-16

There has been substantial recent interest in novel brain stimulation treatments for difficult-to-treat depression. Electroconvulsive therapy (ECT) is a well established, effective treatment for severe depression. ECT's problematic side-effect profile and questions regarding optimal administration methods continue to be investigated. Magnetic seizure therapy, although very early in development, shows promise, with potentially similar efficacy to ECT but fewer side effects. Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) are clinically available in some countries. Limited research suggests VNS has potentially long-lasting antidepressant effects in a small group of patients. Considerable research supports the efficacy of rTMS. Both techniques require further study of optimal treatment parameters. Transcranial direct current stimulation may provide a low-cost antidepressant option if its efficacy is substantiated in larger samples. Deep brain stimulation is likely to remain reserved for patients with the most severe and difficult-to-treat depression, requiring further exploration of administration methods and its role in depression therapy. New and innovative forms of brain stimulation, including low-intensity ultrasound, low-field magnetic stimulation and epidural stimulation of the cortical surface, are in early stages of exploration and are yet to move into the clinical domain. Ongoing work is required to define which brain stimulation treatments are likely to be most useful, and in which patient groups. Clinical service development of brain stimulation treatments will likely be inconsistent and variable.

What was learned: studies by the consortium for research in ECT (CORE) 1997-2011.

PubMed

Fink, M

2014-06-01

To review the findings of the four-hospital collaborative studies of electroconvulsive therapy (ECT) in unipolar depressed patients known as CORE between 1997 and 2011. Unipolar depressed patients were treated with bilateral ECT, and on remission were randomly assigned to a fixed schedule continuation ECT or to combined lithium and nortriptyline for 6 months. A second study compared three electrode placements in unipolar and bipolar depressed patients. Nineteen published reports were reviewed. The findings are compared with those of a parallel multi-hospital study of ECT led by a Columbia University Collaboration (CUC) team that studied right unilateral ECT in a similar population with similar inclusion/exclusion and remission criteria. Successful ECT was followed by placebo, nortriptyline alone, or combined lithium, and nortriptyline. Relapse rates after remission were similar with fixed schedule ECT as with medications. Predictors of outcome (psychosis, suicide risk, polarity, melancholia, atypical depression, age) and technical aspects (electrode placement, seizure threshold, speed of response) are discussed, The findings offer criteria to optimize the selection of patients, the technique, and outcome of ECT for unipolar and bipolar depressed patients. Continuation ECT is an effective alternative to continuation treatment with lithium and nortriptyline. Bilateral electrode placement is more efficient than alternative placements. ECT relieves both bipolar and unipolar depression. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of undernourishment, recurrent seizures and enriched environment during early life in hippocampal morphology.

PubMed

Alvarez, Paula Steffen; Simão, Fabrício; Hemb, Marta; Xavier, Léder Leal; Nunes, Magda Lahorgue

2014-04-01

It has been recently shown that enriched environment led to a significant benefit in learning and retention of visual-spatial memory, being able to reverse the cognitive impairment generated by undernourishment and recurrent seizures. We investigated the hippocampal morphological effects of recurrent seizures and undernourishment early in life in Wistar rats and the possible benefits produced by the enriched environment in these conditions. The morphological parameters stereologically evaluated were hippocampal volume, thickness of pyramidal stratum of the CA1 subfield and neuronal and glial densities in the same subfield. Male Wistar rats were divided into eight groups including nourished, nourished+enriched environment, nourished+recurrent seizures, nourished+recurrent seizures+enriched environment, undernourished, undernourished+enriched environment, undernourished+recurrent seizures and undernourished+recurrent seizures+enriched environment. Undernourishment model consisted in nutritional deprivation regimen from post-natal day 2 (P2) to P15. From P8 to P10, recurrent seizures group were induced by flurothyl three times per day. Enriched environment groups were exposed between P21 and P51. Our main findings were: (1) animals submitted to the enriched environment showed an increased hippocampal volume; (2) enriched environment promotes increases in the thickness of the pyramidal layer in hippocampal CA1 subfield in animals nourished and undernourished with recurrent seizures; (3) undernourishment during early development decreased neuronal density in CA1 and CA3 subfields. Our findings show that these three conditions induces important changes in hippocampal morphology, the most deleterious changes are induced by undernourishment and recurrent seizures, while more beneficial morphological changes are produced by enriched environment. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Acute anticonvulsant effects of capric acid in seizure tests in mice.

PubMed

Wlaź, Piotr; Socała, Katarzyna; Nieoczym, Dorota; Żarnowski, Tomasz; Żarnowska, Iwona; Czuczwar, Stanisław J; Gasior, Maciej

2015-03-03

Capric acid (CA10) is a 10-carbon medium-chain fatty acid abundant in the medium-chain triglyceride ketogenic diet (MCT KD). The purpose of this study was to characterize acute anticonvulsant effects of CA10 across several seizure tests in mice. Anticonvulsant effects of orally (p.o.) administered CA10 were assessed in the maximal electroshock seizure threshold (MEST), 6-Hz seizure threshold, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests in mice. Acute effects of CA10 on motor coordination were assessed in the grip and chimney tests. Plasma and brain concentrations of CA10 were measured. Co-administration studies with CA10 and another abundant medium-chain fatty acid, caprylic acid (CA8) were performed. CA10 showed significant and dose-dependent anticonvulsant properties by increasing seizure thresholds in the 6-Hz and MEST seizure tests; it was ineffective in the i.v. PTZ seizure test. At higher doses than those effective in the 6-Hz and MEST seizure tests, CA10 impaired motor performance in the grip and chimney tests. An enhanced anticonvulsant response in the 6-Hz seizure test was produced when CA8 and CA10 were co-administered. An acute p.o. administration of CA10 resulted in dose-proportional increases in its plasma and brain concentrations. CA10 exerted acute anticonvulsant effects at doses that produce plasma exposures comparable to those reported in epileptic patients on the MCT KD. An enhanced anticonvulsant effect is observed when CA10 and the other main constituent of the MCT KD, CA8, were co-administered. Thus, acute anticonvulsant properties of CA10 and CA8 may influence the overall clinical efficacy of the MCT KD. Copyright © 2014. Published by Elsevier Inc.

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

Picrotoxin-induced seizures modified by morphine and opiate antagonists.

PubMed

Thomas, J; Nores, W L; Kenigs, V; Olson, G A; Olson, R D

1993-07-01

The effects of naloxone, Tyr-MIF-1, and MIF-1 on morphine-mediated changes in susceptibility to picrotoxin-induced seizures were studied. Rats were pretreated with naloxone, MIF-1, Tyr-MIF-1, or saline. At 15-min intervals, they received a second pretreatment of morphine or saline and then were tested for seizures following a convulsant dose of picrotoxin. Several parameters of specific categories of seizures were scored. Morphine increased the number of focal seizure episodes, duration of postseizure akinesis, and incidence of generalized clonic seizures. Naloxone tended to block the morphine-mediated changes in susceptibility. Tyr-MIF-1 had effects similar to naloxone on duration of postseizure immobility but tended to potentiate the effects of morphine on focal seizure episodes. The effects of morphine and the opiate antagonists on focal seizure episodes and postseizure duration suggest the general involvement of several types of opiate receptors in these picrotoxin-induced behaviors. However, the observation of antagonistic effects for Tyr-MIF-1 on immobility but agonistic effects for focal seizures suggests that the type of effect exerted by opiate agents may depend upon other neuronal variables.

Delivery of electroconvulsive therapy in Canada: a first national survey report on usage, treatment practice, and facilities.

PubMed

Martin, Barry A; Delva, Nicholas John; Graf, Peter; Gosselin, Caroline; Enns, Murray W; Gilron, Ian; Jewell, Mark; Lawson, James Stuart; Milev, Roumen; Patry, Simon; Chan, Peter K Y

2015-06-01

The aims of this study were to document electroconvulsive therapy use in Canada with respect to treatment facilities and caseloads based on a survey of practice (Canadian Electroconvulsive Therapy Survey/Enquete Canadienne Sur Les Electrochocs-CANECTS/ECANEC) and to consider these findings in the context of guideline recommendations. All 1273 registered hospitals in Canada were contacted, and 175 sites were identified as providing electroconvulsive therapy; these sites were invited to complete a comprehensive questionnaire. The survey period was calendar year 2006 or fiscal year 2006/2007. National usage rates were estimated from the responses. Sixty-one percent of the sites completed the questionnaire; a further 10% provided caseload data. Seventy were identified as general; 31, as university teaching; and 21, as provincial psychiatric/other single specialty (psychiatric) hospitals. Caseload volumes ranged from a mean of fewer than 2 to greater than 30 treatments per week. Estimated national usage during the 1-year survey period was 7340 to 8083 patients (2.32-2.56 per 10,000 population) and 66,791 to 67,424 treatments (2.11-2.13 per 1000 population). The diagnostic indications, admission status, and protocols for course end points are described. The usage rates are in keeping with earlier Canadian data and with those from other jurisdictions. The difficulty obtaining caseload data from individual hospitals is indicative of the need for standardized data collection to support both clinical research and quality assurance. The wide variation in protocols for number of treatments per course indicates a need for better informed clinical guidelines. The broad range of caseload volumes suggests the need to review the economies of scale in the field.

Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial.

PubMed

Brakemeier, Eva-Lotta; Merkl, Angela; Wilbertz, Gregor; Quante, Arnim; Regen, Francesca; Bührsch, Nicole; van Hall, Franziska; Kischkel, Eva; Danker-Hopfe, Heidi; Anghelescu, Ion; Heuser, Isabella; Kathmann, Norbert; Bajbouj, Malek

2014-08-01

Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

High-fat diets and seizure control in myoclonic-astatic epilepsy: a single center's experience.

PubMed

Simard-Tremblay, Elisabeth; Berry, Patricia; Owens, Aaron; Cook, William Byron; Sittner, Haley R; Mazzanti, Marta; Huber, Jennifer; Warner, Molly; Shurtleff, Hillary; Saneto, Russell P

2015-02-01

To determine the efficacy of the Modified Atkins Diet (MAD) and Ketogenic Diet (KD) in seizure control within a population of myoclonic-astatic epilepsy (MAE) patients. This was a retrospective, single center study evaluating the seizure control by high fat diets. Seizure diaries kept by the parents performed seizure counts. All patients met the clinical criteria for MAE. Nine patients met the clinical criteria. We found that both the MAD and KD were efficacious in complete seizure control and allowed other medications to be stopped in seven patients. Two patients had greater than 90% seizure control without medications, one on the KD and the other on the MAD. Seizure freedom has ranged from 13 to 36 months, and during this time four patients have been fully weaned off of diet management. One patient was found to have a mutation in SLC2A1. Our results suggest that strictly defined MAE patients respond to the MAD with prolonged seizure control. Some patients may require the KD for seizure freedom, suggesting a common pathway of increased requirement for fats. Once controlled, those fully responsive to the Diet(s) could be weaned off traditional seizure medications and in many, subsequently off the MAD or KD. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Disruption of Endocytosis with the Dynamin Mutant shibirets1 Suppresses Seizures in Drosophila

PubMed Central

Kroll, Jason R.; Wong, Karen G.; Siddiqui, Faria M.; Tanouye, Mark A.

2015-01-01

One challenge in modern medicine is to control epilepsies that do not respond to currently available medications. Since seizures consist of coordinated and high-frequency neural activity, our goal was to disrupt neurotransmission with a synaptic transmission mutant and evaluate its ability to suppress seizures. We found that the mutant shibire, encoding dynamin, suppresses seizure-like activity in multiple seizure–sensitive Drosophila genotypes, one of which resembles human intractable epilepsy in several aspects. Because of the requirement of dynamin in endocytosis, increased temperature in the shits1 mutant causes impairment of synaptic vesicle recycling and is associated with suppression of the seizure-like activity. Additionally, we identified the giant fiber neuron as critical in the seizure circuit and sufficient to suppress seizures. Overall, our results implicate mutant dynamin as an effective seizure suppressor, suggesting that targeting or limiting the availability of synaptic vesicles could be an effective and general method of controlling epilepsy disorders. PMID:26341658