Seizure Activity In Patients Research Articles

Seizure source imaging by means of FINE spatio-temporal dipole localization and directed transfer function in partial epilepsy patients

ObjectiveTo investigate the usage of a high-density EEG recording system and source imaging technique for localizing seizure activity in patients with medically intractable partial epilepsy. MethodsHigh-density, 76-channel scalp EEG signals were recorded in 10 patients with partial epilepsy. The patients underwent routine clinical pre-surgical evaluation and all had resective surgery with seizure free outcome. After applying a FINE (first principle vectors) spatio–temporal source localization and DTF (directed transfer function) connectivity analysis approach, ictal sources were imaged. Effects of number of scalp EEG electrodes on the seizure localization were also assessed using 76, 64, 48, 32, and 21 electrodes, respectively. ResultsSurgical resections were used to assess the source imaging results. Results from the 76-channel EEG in the 10 patients showed high correlation with the surgically resected brain regions. The localization of seizure onset zone from 76-channel EEG showed improved source detection accuracy compared to other EEG configurations with fewer electrodes. ConclusionsFINE together with DTF was able to localize seizure onset zones of partial epilepsy patients. High-density EEG recording can help achieve improved seizure source imaging. SignificanceThe present results suggest the promise of high-density EEG and electrical source imaging for noninvasively localizing seizure onset zones.

Delayed Seizure Associated with Paclitaxel‐Cremophor EL in a Patient with Early‐Stage Breast Cancer

Paclitaxel, a microtubule stabilizer, is an effective agent for treating cancer of the breast, ovary, head and neck, and lung. Because paclitaxel is insoluble in water, it is formulated with the micelle-forming Cremophor EL. Neurologic toxicity is well described with both the drug and this carrier, with most toxicities manifesting as peripheral neuropathy, motor neuropathy, autonomic neuropathy, and myopathy. Toxic effects on the central nervous system, such as seizures or encephalopathy, have been rarely reported; however, the seizures reported were closely related to the time of infusion. We describe a 41-year-old woman with no history of seizures who was treated with paclitaxel for breast cancer. Four days after the drug was infused, she developed a generalized tonic-clonic seizure that could not be attributed to other causes. The patient was treated with phenytoin and was able to complete her adjuvant chemotherapy with nab-paclitaxel without further events. Her condition was neurologically stable without phenytoin for the next 6 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible association (score of 3) between the delayed seizure and paclitaxel or its solvent, Cremophor EL. Clinicians should be aware of the potential for seizure activity in patients who receive paclitaxel formulated with Cremophor EL.

Systemic Cooling to Treat Status Epilepticus: An Old Idea Becomes a Hot Topic

Hypothermia for Refractory Status Epilepticus. Corry JJ, Dhar R, Murphy T, Diringer MN. Neurocrit Care 2008;9(2): 189–197. INTRODUCTION: Status epilepticus (SE) can be refractory to conventional anticonvulsants, requiring anesthetic doses of medications to suppress seizures. This approach carries significant morbidity, is associated with a high fatality rate, and may not always control SE. Hypothermia has been shown to suppress epileptiform activity experimentally, but has not previously been used as a primary modality to control SE in humans. METHODS: Four patients with SE refractory to benzodiazepine and/or barbiturate infusions were treated with hypothermia (target temperature: 31–35°C) using an endovascular cooling system. All received continuous EEG monitoring, three were on midazolam infusions and one had recurrent seizures on weaning from pentobarbital. RESULTS: Therapeutic hypothermia was successful in aborting seizure activity in all four patients, allowing midazolam infusions to be discontinued; three achieved a burst-suppression pattern on EEG. After controlled rewarming, two patients remained seizure-free, and all four demonstrated a marked reduction in seizure frequency. Adverse events included shivering, coagulopathy without bleeding, and venous thromboembolism. Two death occurred, neither directly related to hypothermia; however, immunosuppression related to the use of barbiturates and hypothermia may have contributed to an episode of fatal sepsis in one patient. CONCLUSIONS: Hypothermia was able to suppress seizure activity in patients with SE refractory to traditional therapies with minimal morbidity. It appears promising as an alternative or an adjunct to anesthetic doses of other agents, but requires further study to better evaluate its safety and efficacy.

Perilesional brain oedema and seizure activity in patients with calcified neurocysticercosis: a prospective cohort and nested case–control study

Cysticercosis due to Taenia solium is a cause of adult-acquired seizures and epilepsy even in patients with only calcified larval cysts. Transient perilesional brain oedema is seen around the calcified foci but its importance, association with seizures, incidence, and pathophysiology are unknown. 110 patients with only calcified lesions and a history of seizures or severe headaches were followed prospectively in a cohort design to assess the incidence of seizure relapse. In a nested case-control substudy, perilesional oedema was assessed by MRI at the time of seizure in symptomatic patients and in matched asymptomatic controls taken from the study population. Between November, 1999, and December, 2006, 29 patients had an incident seizure during a median follow up of 32.33 (SD 19.99) months, with an estimated 5-year seizure incidence of 36% (95% CI 25% to 49%). 24 of 29 (83%) patients with seizure relapse had an MRI evaluation within 5 days of the event; perilesional oedema was seen in 12 patients (50%) compared with two (9%) of 23 asymptomatic matched controls. Perilesional oedema is common and associated with episodic seizure activity in patients with calcified neurocysticercosis. Our findings are probably representative of symptomatic patients in regions where T solium neurocysticercosis is endemic and suggest a unique and possibly preventable cause of seizures in this population.

Hypothermia for Refractory Status Epilepticus

Status epilepticus (SE) can be refractory to conventional anticonvulsants, requiring anesthetic doses of medications to suppress seizures. This approach carries significant morbidity, is associated with a high fatality rate, and may not always control SE. Hypothermia has been shown to suppress epileptiform activity experimentally, but has not previously been used as a primary modality to control SE in humans. Four patients with SE refractory to benzodiazepine and/or barbiturate infusions were treated with hypothermia (target temperature: 31-35 degrees C) using an endovascular cooling system. All received continuous EEG monitoring, three were on midazolam infusions and one had recurrent seizures on weaning from pentobarbital. Therapeutic hypothermia was successful in aborting seizure activity in all four patients, allowing midazolam infusions to be discontinued; three achieved a burst-suppression pattern on EEG. After controlled rewarming, two patients remained seizure-free, and all four demonstrated a marked reduction in seizure frequency. Adverse events included shivering, coagulopathy without bleeding, and venous thromboembolism. Two death occurred, neither directly related to hypothermia; however, immunosuppression related to the use of barbiturates and hypothermia may have contributed to an episode of fatal sepsis in one patient. Hypothermia was able to suppress seizure activity in patients with SE refractory to traditional therapies with minimal morbidity. It appears promising as an alternative or an adjunct to anesthetic doses of other agents, but requires further study to better evaluate its safety and efficacy.

Absence of electroencephalographic seizure activity in patients treated for head injury with an intracranial pressure–targeted therapy

The authors prospectively studied the occurrence of clinical and nonclinical electroencephalographically verified seizures during treatment with an intracranial pressure (ICP)-targeted protocol in patients with traumatic brain injury (TBI). All patients treated for TBI at the Department of Neurosurgery, University Hospital Umeå, Sweden, were eligible for the study. The inclusion was consecutive and based on the availability of the electroencephalographic (EEG) monitoring equipment. Patients were included irrespective of pupil size, pupil reaction, or level of consciousness as long as their first measured cerebral perfusion pressure was > 10 mm Hg. The patients were treated in a protocol-guided manner with an ICP-targeted treatment based on the Lund concept. The patients were continuously sedated with midazolam, fentanyl, propofol, or thiopental, or combinations thereof. Five-lead continuous EEG monitoring was performed with the electrodes at F3, F4, P3, P4, and a midline reference. Sensitivity was set at 100 muV per cm and filter settings 0.5-70 Hz. Amplitude-integrated EEG recording and relative band power trends were displayed. The trends were analyzed offline by trained clinical neurophysiologists. Forty-seven patients (mean age 40 years) were studied. Their median Glasgow Coma Scale score at the time of sedation and intubation was 6 (range 3-15). In 8.5% of the patients clinical seizures were observed before sedation and intubation. Continuous EEG monitoring was performed for a total of 7334 hours. During this time neither EEG nor clinical seizures were observed. Our protocol-guided ICP targeted treatment seems to protect patients with severe TBI from clinical and subclinical seizures and thus reduces the risk of secondary brain injury.

Influence of aminophylline on the anticonvulsive action of gabapentin in the mouse maximal electroshock seizure threshold model

Accumulating evidence indicates that aminophylline [theophylline(2) x ethylenediamine] markedly attenuates the anticonvulsant action of conventional antiepileptic drugs in experimental animal models of epilepsy and evokes severe seizure activity in patients treated with this methylxanthine. The objective of this study was to determine the influence of acute (single) and chronic (twice daily for 14 consecutive days) treatments with aminophylline on the anticonvulsant potential of gabapentin (a second-generation antiepileptic drug) in the mouse maximal electroshock seizure threshold model. Additionally, the effects of acute and chronic administration of aminophylline on the adverse effect potential of gabapentin in terms of motor coordination impairment were assessed in the chimney test. To evaluate pharmacokinetic characteristics of interaction between drugs, total brain concentrations of gabapentin and theophylline were estimated with high-pressure liquid chromatography and fluorescence polarization immunoassay, respectively. Results indicated that gabapentin (at doses of 75 and 100 mg/kg, i.p.) increased the threshold for electroconvulsions in mice. Aminophylline in non-convulsive doses of 50 and 100 mg/kg (i.p.), both in acute and chronic experiments, did not attenuate the anticonvulsant potential of gabapentin in the maximal electroshock seizure threshold test in mice. Similarly, aminophylline at a dose of 100 mg/kg had no impact on the adverse effect potential of gabapentin in the chimney test. Pharmacokinetic evaluation of total brain concentrations of gabapentin and theophylline revealed no significant changes in total brain concentrations of the drugs after both, acute and chronic applications of aminophylline in combination with gabapentin. The data show that aminophylline did not alter the ability of gabapentin to protect mice against seizures induced by electroconvulsive shock. The observed interaction between gabapentin and aminophylline in both acute and chronic experiments was pharmacodynamic in nature.

Retrospective analysis of the efficacy and tolerability of levetiracetam in patients with metastatic brain tumors

Seizures are a common complication of metastatic brain tumors (MBT), affecting approximately 27-50% of all patients during the course of their illness. Treatment of tumor-induced seizures is often inadequate with traditional antiepileptic drugs (AED) due to a variety of factors, including activation of glutamatergic NMDA receptors, alterations of neuronal input pathways, and tumor growth. Levetiracetam (LEV) is a 2nd generation non-enzyme inducing AED with a novel mechanism of action, binding to neuronal synaptic vesicle protein SV2A, that has been previously shown to reduce seizure activity in patients with primary brain tumors. Due to its unique mechanism of action, it has been postulated that LEV may also be effective in controlling seizures from MBT. A retrospective chart review was performed of all Neuro-Oncology Center patients with MBT who had received LEV for seizure control. Thirteen patients were reviewed with a median age of 55.1 years (range: 34-70). Six patients had breast cancer, five had lung cancer, and two had melanoma. LEV was used as an add-on AED in seven patients (54%) and as monotherapy in six patients (46%), with a median dose of 1,000 mg/day (range: 500-3,000). The baseline median seizure frequency was one ictal event every other day. After the addition of LEV, the median seizure frequency was reduced to 0 per week. The seizure frequency was reduced to less than 50% of the pre-LEV baseline in 100% of patients (P=0.0002, Sign test), with 10 patients (77%; confidence interval: 46-95%) noting complete seizure control. The most common adverse event was somnolence and headache, noted in 3 of 13 patients (23%). LEV was very effective and well tolerated in MBT patients with seizures and should be considered for add-on therapy or as a substitute AED for monotherapy.

Anesthesia for Caffeine Augmentation in Electroconvulsive Therapy: A case report

The efficacy of electroconvulsive therapy (ECT) in depression is dependent on the duration of seizure. Over a course of ECT, progressive reduction in the duration of the induced seizure is common. Caffeine pretreatment is reported to prolong seizure activity in patients experiencing inadequate seizure activity although maximal electrical stimulus for ECT is applied. The side effects of caffeine are anxiety, psychomotor agitation, prolonged seizures, enhanced hemodynamic changes and arrythmias. Caffeine is generally well tolerated by most patients, but it should be used with caution for those medically fragile patients, i.e., with preexisting cardiac disease. We describe here a case of anesthesia for ECT with caffeine augmentation. A 61-year-old man was diagnosed of major depression. Caffeine pretreatment with ECT was scheduled after antidepressants and 3 ECTs failed. Hypertension and tachyarrythmia were treated with esmolol.

Prophylactic phenytoin does not improve cerebral edema or survival in acute liver failure—a controlled clinical trial

Background/Aims Seizure activity in patients with acute liver failure (ALF) may increase cerebral oxygen requirements and worsen cerebral edema. Recently, prophylactic phenytoin has been recommended to suppress sub-clinical seizure activity evident on electroencephalographic monitoring. To determine the clinical utility of prophylactic phenytoin therapy in patients with ALF. Methods Forty two patients with ALF were randomized. Twenty two patients were given prophylactic phenytoin and 22 patients acted as controls. The baseline clinical and biochemical features were similar in the two groups and patients with ≥2 poor prognostic variables were equally represented. Results Sixteen patients in the phenytoin group, and 15 in the control group developed cerebral edema ( P=0.38). Mechanical ventilation was required in 10 and 12 patients in the phenytoin and control groups, respectively, ( P=0.77). Seizures occurred in 5 (22.7%) control patients and 5 (25%) phenytoin treated patients ( P=0.86). Fourteen (70%) patients randomized to phenytoin and 15 (68.2%) control patients died ( P=0.89). Conclusions Seizure was common in patients with ALF. Prophylactic use of phenytoin did not prevent cerebral edema, seizures or need for mechanical ventilation, and did not improve survival.

Propofol-related myoclonic seizures

Propofol is a popular agent for induction and maintenance of anaesthesia, as well as an excellent sedative agent widely used in ambulatory anaesthesia. Although involuntary movements due to propofol are well known, the occurrence of propofol-related seizure activity in patients with no previous history of epilepsy is less well highlighted. These seizures may occur at all stages of anaesthesia: induction, maintenance, emergence as well as early and late recovery. The cause of these seizures is as yet unknown. The occurrence of seizures with propofol may raise cautions on its use, especially in ambulatory anaesthesia.

Epilepsy in Patients with Multiple Sclerosis: Radiological‐Clinical Correlations

To determine potential mechanisms of epilepsy in patients with multiple sclerosis (MS). Among 402 patients with clinically and radiologically defined MS, including de novo cases, presenting to the Neurology Service, University Hospital of Dijon, we identified 17 with epileptic seizures (4.25%). Among them, the percentage with partial seizures (50%) was greater than that in the reference population. In most of the patients with MS, plaques were localized in the frontal region, associated with frontal and callosal atrophy, a frontal syndrome, and severe disability status (as assessed by a standard scale). Magnetic resonance imaging (MRI) showed numerous subcortical plaques. Seizures generally were well controlled with antiepileptic drugs (AEDs). Our data suggest that the subcortical plaques of MS underlie seizure activity in patients with MS and epilepsy.

Adverse effects of opioid agonists and agonist-antagonists in anaesthesia.

The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific kappa-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available kappa-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing. Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy. Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain. The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.

Acute hemodynamic responses to electroconvulsive therapy are not related to the duration of seizure activity

Study Objective: To test the hypothesis that the magnitude of the acute hemodynamic response to electroconvulsive therapy (ECT) is related to the duration of the seizure activity in patients receiving different dosages of intravenous (IV) lidocaine. Design: Randomized, double-blind, placebo-controlled, cross-over study. Setting: University-affiliated hospital. Patients: 21 ASA physical status I, II, and III patients undergoing four consecutive maintenance ECT treatments for chronic depression. Interventions: Patients received lidocaine 50 mg, 100 mg, 200 mg IV, or saline prior to induction of anesthesia via a standardized anesthetic technique. Measurements and Main Results: Noninvasive blood pressure (BP) and heart rate (HR), as well as the duration of motor and electroencephalographic (EEG) seizure, were measured. The duration of motor and EEG seizures (means ± SD) were 37 ± 13 sec and 64 ± 21 sec, 25 ± 11 sec and 52 ± 43 sec, 17 ± 12 sec and 32 ± 17 sec, 1 ± 3 sec and 18 ± 10 sec in the saline, lidocaine 50 mg, 100 mg, 200 mg groups, respectively. Although the duration of seizure activity was decreased in a dose-related fashion after lidocaine pretreatment, the peak increases in BP and HR were similar in the lidocaine and saline treatment groups. Conclusions: Despite producing dose-related decreases in the duration of both motor and EEG seizure activity, lidocaine failed to attenuate the acute hemodynamic response to ECT. Thus, the acute hemodynamic response to ECT is not related to the duration of seizure activity.

Reversible, reproducible reduction of brain water apparent diffusion coefficient by cortical electroshocks.

Rat brains were imaged after cortical electroshock pulse trains (1 ms pulses at 100 Hz) of varying durations (0.1-10 s), with diffusion-weighted echo planar imaging sequences at 2.0 T. The apparent water diffusion coefficient (ADC) decreased after either single or repeat electroshock trains. ADC reductions were observed within 6 s after the first shock. The size of the affected area of the brain increased in subsequent images during the 1st min after a 10-pulse (0.1 s) train, and also increased with the duration of electroshock trains. ADC reduction was reproducible in extent and time course after single 10-shock trains and was reversible. In the affected pixels the mean ADC reduction was 4% for a single shock train (0.1 s), and 7-8% for trains repeated once a minute, independent of electroshock train duration. The results indicate that neuronal activity associated with electrostimulation may be monitored with water diffusion measurements, and they may be useful for measuring the severity of seizure activity in patients with medically intractable epilepsy.

Cyclic Decrease in Mixed Venous Oxygen Saturation for the Early Diagnosis of Seizure Complications After Cardiac Surgery

Cyclic Decrease in Mixed Venous Oxygen Saturation for the Early Diagnosis of Seizure Complications After Cardiac Surgery

Fentanyl-induced electrocorticographic seizures in patients with complex partial epilepsy.

Although electrical seizure activity in response to opioids such as fentanyl has been well described in animals, scalp electroencephalographic (EEG) recordings have failed to demonstrate epileptiform activity following narcotic administration in humans. The purpose of this study was to determine whether fentanyl is capable of evoking electrical seizure activity in patients with complex partial (temporal lobe) seizures. Nine patients were studied in whom recording electrode arrays had been placed in the bitemporal epidural space several days earlier to determine which temporal lobe gave rise to their seizures. The symptomatic temporal lobe was localized by correlating clinical and electrical seizure activity obtained during continuous simultaneous videotape and epidural EEG monitoring. In each patient, clinical seizures and electrical seizure activity were consistently demonstrated to arise unilaterally from one temporal lobe (four on the right, five on the left). During fentanyl induction of anesthesia in preparation for secondary craniotomy for anterior temporal lobectomy, eight of the nine patients exhibited electrical seizure activity at fentanyl doses ranging from 17.7 to 35.71 micrograms.kg-1 (mean 25.75 micrograms.kg-1). More importantly, four of these eight seizures occurred initially in the "healthy" temporal lobe contralateral to the surgically resected lobe from which the clinical seizures had been shown to arise. These findings indicate that, in patients with complex partial seizures, moderate doses of fentanyl can evoke electrical seizure activity. The results of this study could have important implications for neurosurgical centers where electrocorticography is used during surgery for the purpose of determining the extent of the resection.

The Effect of L-Carnitine-Supplemented Total Parenteral Nutrition on Tissue Amino Acid Concentrations in Piglets

Miniature piglets underwent total parenteral nutrition (TPN) with and without L-carnitine supplementation during a 7-day period. Thereafter the tissue amino acid concentrations of liver, heart, skeletal muscle and brain were determined and compared to those of orally fed animals. The altered tissue amino acid concentrations during TPN without carnitine returned to normal when L-carnitine was supplemented. The most striking changes of tissue concentrations showed taurine in liver, muscle and brain and ethanolamine in heart and brain. In muscle the branched-chain amino acids were increased when L-carnitine was added to the TPN regime. Ethanolamine changes were discussed with respect to the position of this amino acid in the synthesis of phospholipids. The marked decrease of brain taurine concentrations after carnitine-free TPN was accompanied by reduced values for GABA. Both the substances function as inhibitory transmitters in the brain and should be considered when seizure activity in patients with systemic carnitine deficiency is discussed.

Myoclonus Induced by Metoclopramide Therapy

Metoclopramide hydrochloride is increasingly used as an antiemetic agent. Clinical and experimental studies have demonstrated dopamine antagonism, and extrapyramidal side effects have been reported in patients given the drug for gastrointestinal disorders. Multifocal myoclonic jerking developed in our patient after he received metoclopramide therapy for gastroparesis due to renal failure. He had had no previous neurologic symptoms, and no evidence of CNS abnormality was found; the myoclonic jerking subsided when metoclopramide therapy was discontinued. Multifocal myoclonus must be differentiated from seizure activity in patients with renal failure and other metabolic encephalopathies. Metoclopramide clearance is reduced in renal failure, and myoclonus or other neurologic complications may be precipitated in such patients by usual doses of this drug.

Ketamine and Epilepsy

In an investigation of the effects of ketamine on the electroencephalogram (EEG) of healthy human volunteers free of epileptic disorders and those with a history of active epilepsy, the authors conclude: 1. Ketamine does NOT induce seizure discharges in the EEG of patients without epilepsy, nor does the drug cause EEG alterations indicative of seizure activity in patients with a history of epilepsy but with a normal EEG; while it is possible that under ketamine an abnormal EEG may worsen, such development is uncommon. 2. They found no evidence that ketamine is likely to precipitate generalized convulsions, even in patients with both a history of epilepsy and an abnormal EEG, but, on the contrary, that there is evidence that ketamine is capable of suppressing or virtually eliminating seizure or seizure-like EEG discharges in epileptic patients during clinical seizures. 3. Although the authors found nothing to suggest that ketamine precipitates generalized convulsions in an epileptic patient, due caution should be exercised with this drug, as with any general anesthetic agent, in anesthesia for patients with epileptic disorders.