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Objective: We sought to determine which combination of clinical and electroencephalography (EEG) characteristics differentiate between an antiseizure medication (ASM)–resistant vs ASM‐responsive outcome for patients with idiopathic generalized epilepsy (IGE). Methods: This was a case‐control study of ASM‐resistant cases and ASM‐responsive controls with IGE treated at five epilepsy centers in the United States and Australia between 2002 and 2018. We recorded clinical characteristics and findings from the first available EEG study for each patient. We then compared characteristics of cases vs controls using multivariable logistic regression to develop a predictive model of ASM‐resistant IGE. Results: We identified 118 ASM‐resistant cases and 114 ASM‐responsive controls with IGE. First, we confirmed our recent finding that catamenial epilepsy is associated with ASM‐resistant IGE (odds ratio [OR] 3.53, 95% confidence interval [CI] 1.32–10.41, for all study subjects) after covariate adjustment. Other independent factors seen with ASM resistance include certain seizure‐type combinations (absence, myoclonic, and generalized tonic‐clonic seizures [OR 7.06, 95% CI 2.55–20.96]; absence and generalized tonic‐clonic seizures [OR 4.45, 95% CI 1.84–11.34]), as well as EEG markers of increased generalized spike‐wave discharges (GSWs) in sleep (OR 3.43, 95% CI 1.12–11.36 for frequent and OR 7.21, 95% CI 1.50–54.07 for abundant discharges in sleep) and the presence of generalized polyspike trains (GPTs; OR 5.49, 95% CI 1.27–38.69). The discriminative ability of our final multivariable model, as measured by area under the receiver‐operating characteristic curve, was 0.80. Significance: Multiple clinical and EEG characteristics independently predict ASM resistance in IGE. To improve understanding of a patient's prognosis, clinicians could consider asking about specific seizure‐type combinations and track whether they experience catamenial epilepsy. Obtaining prolonged EEG studies to record the burden of GSWs in sleep and assessing for the presence of GPTs may provide additional predictive value. [ABSTRACT FROM AUTHOR]

This paper summarizes and focuses on the National General Practice Study of Epilepsy with emphasis on epilepsy prognosis after initial diagnosis. [ABSTRACT FROM AUTHOR]

The article reports on a study which conducted a randomized, single-center trial comparing the efficacy and tolerability of therapeutic substitution on failed antiepileptic drug (AED) monotherapy. The researchers have substituted therapies with the new epilepsy drug levetiractam. It compares result outcomes of the new drug against the initial treatment with first-generation antiepileptic agents using carbamazepine and valproic acid.

ALTHOUGH OVERT CONVULSIVE STATUS EPILEPTICUS HAS deservedly received wide spread attention due to systemic complications, nonconvulsive status epilepticus (NCSE) has become increasingly recognized in both comatose and noncomatose patients. As such, the ideal medication for nonconvulsive status should be intravenous, relatively free of drug interactions, and non-sedating. Lacosamide, already approved for adjunctive partial seizures in adults, meets the above three criteria, suggesting a potential role in the treatment of nonconvulsive status. The authors of this paper report on their experience with intravenous lacosamide in the treatment of NCSE The records of all patients with refractory nonconvulsive status epilepticus were reviewed at University Hospitals Case Medical Center (Cleveland). Four patients were identified who were treated with lacosamide and underwent continuous video EEG monitoring. EEG traces were blindly reviewed to confirm onset and offset of nonconvulsive status. Both general and neurologic examinations were performed before and after administration of intravenous lacosamide. All four patients were found to have medically resistant focal NCSE despite treatment with varying doses and combinations of lorazepam, levetiracetam, fosphenytoin, and enteral pregabalin. Intravenous lacosamide was administered between 3 and 50 hours after known diagnosis of NCSE. Side effects were recorded by patient-reported diary. Pre- and post-PR intervals were calculated after infusion of lacosamide. Patient #1 presented with new onset prolonged convulsion and subsequent depressed mental status despite 2 mg of lorazepam and 1,000 mg fosphenytoin. Continuous electroencephalographic recording (cEEG) reveale nearly continuous left hemispheric ictal activity. An additional 2 g of levetiracetam and enteric 300 mg pregbalin were administered. Ictai activity persisted nearly hours later, prompting intravenous infusion with low-dose (50 mg) lacosamide. There was electrographic cessation of ictal activity nearly 30 minutes after intravenous fusion. The patient returned to baseline neurologic status with eventual 100 mg twice daily maintenance dosing of lacosamide. No seizure recurrence occurred during subsequent 48 hour cEEG recoring. Patient #2 presented with new onset symptomatic right hemispheric seizures in the setting of an acute right subdural hemorrhage. Two milligrams of lorazepam and three grams of intravenous levetiracetam were administered without seizure cessation. Subsequently, 100 mg of iv lacosamide was infused with reduction of electrograpic seizures from 5 per hour to 1 every 2 hours. Intravenous maintenance lacosamide was escalated to 200 mg twice daily with improvement in seizure frequency to 3 per day. Patient #3 presented initially with new onset seizures and electroclinical correlate in the setting of atypical recurrent right fronto-parietal meningioma. Seizures characterized initially by focal facial clonic movements, vocalizations, and excessive salivation. Low-dose levetiracetam was initiated at 500 mg twice daily. Electroclical seizures were replaced with electrographic seizures (recorded on cEEG) without clinical correlate from the right frontocentral region. Ictal activity persisted despite 4 mg of intravenous lorazepam and further escalation of levetiracetam to 4 grams per day. After a 15-minute infusion of 100 mg of intravenous lacosamide, complete cessation of ictal activity was noted. Patient #4 presented with left hemibody clonic movements in the setting of a remote right sided hemorrhagic stroke. The patient was given rapid sequence lorazepa (6 mg), followed by fosphenytoin load, and increase in maintenance levetiracetam. Intravenous lacosamide was added after failure to control seizures, with cessation of ictal events within 2 hours of intravenous lacosamide infusion. The patient remained seizure-free on adjunctive maintenance lacosamide of 100 mg bid. [ABSTRACT FROM AUTHOR]

MESIAL TEMPORAL LOBE EPILEPSY WITH MESIAL TEMporal sclerosis is the most surgically remediable epilepsy syndrome, with reported success rates of nearly 70%. However, in recent years, novel approaches to reduce the invasiveness--and perhaps the cognitive deficits--of open surgery have become increasingly important. One prior study of 20 patients who were treated with radiosurgery reported no significant declines in memory or IQ during a two-year follow up period. This study by Barbaro and colleagues presents the second paper regarding long-term data on cognitive outcome, paving the road to a potential phase 3 trial comparing temporal lobectomy to focused radiosurgery. Patients were included in this prospective study if they met criteria for unilateral mesial temporal lobe epilepsy as defined by ictal video EEG criteria, magnetic resonance imaging (MRI) (unilateral asymmetric increased hippocampal T2 signal or hippocampal atrophy), neuropsychological evaluations, and intracarotid sodium amytal (WADA) tests. All patients had an average of at least three complex partial seizures per month over a three-month baseline period. All participants were then randomized to treatment with either 20 Gy (low dose) or 24 Gy (high dose) of radiosurgery (50% isodose volume from 5.5-7.5 mL) targeted at the amygdala, anterior 2 cm of hippocampus, and parahippocampal gyms. After treatment, patients were examined every three months for 36 months with quantification and review of seizures by way of patient-documented seizure diaries. Seizure freedom was defined as no complex partial seizures with or without auras between months 24 and 36. MRIs were performed at 12 and 24 months, or more frequently if clinically warranted, along with visual field examinations at baseline and at 24 months. Neuropsychological testing was also performed at baseline and at 12 mad 24 months. Patients were categorized as significant improvement, no change, or significant impairment based on indices of the California Verbal Learning Test and Wechsler Memory Scale Revised. Thirty patients met final inclusion criteria and were randomized to either high-dose ( 13 patients) or low-dose (17 patients/radiosurgery. Both groups showed significant reduction in complex partial seizures from baseline at approximately one year after treatment. Between months 24 and 36, the average seizure remission rate was 67% for both groups. Ten out of 13 patients in the high-dose group (76.9%) and 10 out of 17 patients (58.8%) in the low-dose group were seizure-free, However, the difference in remission rate between treatment groups was not statistically significant due to the small numbers in each group. Sixty-one percent of the high- dose group and 53% of the low-dose group required transient use of steroids for brain edema. One patient in the high-dose ,group eventually reqiured temporal lobectomy for refractory edema. Twenty-six out of 30 patients completed assessments of verbal memory. Verbal memory impairment was seen in 25% of patients with dominant hemisphere treatment and 7% of patients with non-dominant treatment. Significant improvement in at least one test was seen in 16% of dominant-treated and 7% of non-dominant-treated radiosurgery patients. [ABSTRACT FROM AUTHOR]

In this multicenter, observational study, the authors assessed the prevalence of neuropsychiatric side effects from medications in subjects with tumor-related epilepsy. Levetiracetam was found to have the highest prevalence of such side effects. [ABSTRACT FROM AUTHOR]

In this prospective study, the authors use brain imaging criteria to determine whether acute febrile status results in acute hippocampal injury and potentially chronic hippocampal sclerosis. [ABSTRACT FROM AUTHOR]

Drug-resistant epilepsy affects nearly a third of epilepsy patients and is defined as failure of two or more maximally tolerated, adequately chosen, anti-epileptic agents. The recommended clinical practice (2003 American Academy of Neurology Practice Parameter) is to consider referral for potential epilepsy surgery in pharmacoresistant epilepsy. However, the literature is scarce regarding the natural history of incident (new-onset) drug-resistant epilepsy. In this observational, population-based study, the authors aim to answer two questions, mainly the proportion of patients with drug-resistant epilepsy that become seizure free and the clinical features that predict seizure freedom. Children under the age of 16 who met International League Against Epilepsy criteria for epilepsy (two or more unprovoked seizures) within the catchment area of University of Turku, Finland, up until the year 1964 were study eligible. Further inclusion criteria were well-documented and adequate anti-epileptic regimen trials, drug resistance (failure of one or two appropriate drugs used singly or in combination without seizure remission at the 2-year mark), and at least 10-year follow-up from time of epilepsy onset. One hundred two patients ultimately met study criteria. Outcome variables, including time to and duration of seizure remission, were defined as the following: 1-year remission ever, 2-year remission ever, 2-year terminal remission, 5-year remission ever, or 5-year terminal remission. Terminal remission was the remission at the end of follow up. Remote symptomatic epilepsy was defined as major neurological impairment or history of major neurologic insult. Of the 102 patients, 98 had focal seizures (68 symptomatic and 30 idiopathic/cryptogenic), one had generalized convulsive seizures, and three had unclassified seizures. At the conclusion of the 40.5 year median follow-up, 82% of patients entered one or more 1-year remissions, 79% one or more 2-year remissions, 69% one or more 5-year remissions, and 51% with 5-year terminal remission. On multivariate analysis, only idiopathic/cryptogenic seizure etiology proved to be a significant predictor of seizure freedom. [ABSTRACT FROM AUTHOR]

SINCE THE INITIAL 1998 LANDMARK VETERAN'S ADMINISTRATION (VA) study, intravenous benzodiazepines have been first-line treatment for status epilepticus (SE). However, the VA cooperative study, like many others to follow, only studies an intravenous route of administration of acute abortive agents. Over time, the medical community became increasingly aware that untreated prolonged convulsive SE has the potential to become refractory. Out of these clinical observations, the operational definition of SE has grown to include seizure activity of 5 minutes or greater duration. This timely article by Silbergleit et al is the first large-scale, randomized, blinded study to compare the traditional intravenous vs intramuscular route of benzodiazepine administration for prehospital seizure cessation. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) involved 79 centers nationwide and a total of 448 subjects assigned to active treatment with intramuscular midazolam and 445 assigned to active treatment with intravenous lorazepam. Patients met criteria for inclusion if convulsive seizures of longer than 5 minutes in duration were noted. Both patients and emergency medical personnel were blinded and randomized to treatment via the use of investigational autoinjectors and prefilled syringes with either 10 mg intramuscular midazolam followed by intravenous placebo, or intramuscular placebo followed by 4 mg of intravenous lorazepam. A timestamped voice recorder in the prefilled study kit allowed paramedics to record orally when intramuscular treatment was administered, when intravenous access was gained, when intravenous study drug was administered, and when convulsions clinically stopped. Rescue therapy, as dictated by local paramedic protocol, was used for patients who were still convulsing 10 minutes after the last study medication was administered or if convulsions resumed after transient cessation. The primary outcome of this study was clinical seizure cessation without the need for rescue therapy before emergency room arrival. In particular, the authors' primary aim was to demonstrate noninferiority of intramuscular midazolam vs intravenous lorazepam in prehospital treatment of convulsive seizures. Secondary outcome measures included time from study box opening to seizure cessation, time from initiation of study drug to termination of seizures, frequency and duration of hospitalization to the intensive care unit, frequency of endotracheal intubation, and seizure recurrence. Seizures were successfully aborted in 73.4% and 63.4% in the intramuscular vs intravenous treatment groups respectively. The median time to active treatment in the intramuscular group was 1.2 minutes vs 4.8 minutes in the intravenous group. However, the actual onset of action (termination of seizures) was more immediate in the intravenous group vs the intramuscular group (1.6 vs 3.3 minutes). The secondary endpoints of frequency of intubation, recurrent seizures, and duration and frequency of hospitalization were similar in both treatment groups. [ABSTRACT FROM AUTHOR]

THE MOST SEVERE FORM OF CARBAMAZEPINE HYPERSENSItivity reactions is Stevens-Johnson Syndrome (SJS), characterized by a blistering rash involving the mucous membranes and systemic inflammatory side effects. The most extreme form, toxic epidermal necrolysis (TEN), involves even greater epidermal detachment. Both syndromes carry a high risk of mortality and are the focus of two recent studies from Taiwan and the UK. Previous reports have confirmed the association of SJS and TEN with HLA-B*1502 allele in individuals of Han Chinese descent. In this first paper from Taiwan, the authors prospectively screened patients, by using HLA-B*1502 genotyping, to identify subjects at risk for SJS-TEN before starting clinical treatment with carbamazepine. The second paper from the UK presents data implicating the HLA variant, HLA-A*3101, in the full range of carbamazepine-associated hypersensitivity reactions. Chen et al screened patients from 23 hospitals in Taiwan and identified 4877 subjects who were carbamazepine candidates (epilepsy, neuralgia, neuropathic pain, tinnitus, bipolar or psychiatric disorders). Patients with a previous history of carbamazepine allergy, bone marrow transplant, and non-Han Chinese descent were excluded. Patients were told to defer taking carbamazepine until results of genetic testing were complete. All individuals had an initial screening visit. Only HLA-B*1502 positive individuals were asked to return for a second office visit to communicate test results and offer alternative treatments. Weekly telephone interviews with all subjects were conducted over the next 2 months. Any clinical suspicion of adverse drug reaction prompted an immediate hospital evaluation by a staff dermatologist. Based on an 8% historical prevalence of the HLA-B*1502 allele in the Taiwanese population, the authors determined that 4419 subjects would render a power of 99% to detect a reduction in the historical incidence of carbamazepine-induced SJS-TEN from 0.25% to 0.03%. In Taiwan, 4855 patients underwent genotyping; 7.7% (372) were found to be HLA-B*1502 positive and advised not to take carbamazepine and 215 were given alternative treatment (gabapentin, lamotrigine, naproxen, imipramine, or prednisolone). Among all 4855 subjects, 211 (4.3%) developed mild transient rash and pruritis and five were HLA-B*1502 positive. Seven patients had more severe cutaneous symptoms. Three patients had maculopapular eruption, two with hypersensitivity syndrome, and two patients were noted with urticaria. One patient with urticaria was HLA-B*1502 positive and had taken oxcarbazepine before study enrollment. No cases of SJS-TEN were noted in any subjects during the 2-month follow-up. McCormack et al recruited subjects from either the Liverpool collaborators or the EPIGEN consortium. Subjects were divided into three categories: 1) hypersensitivity syndrome defined as the presence of rash or liver involvement within 3 months of initiation of carbamazepine treatment, accompanied by two of the following: prolonged recovery phase despite drug withdrawal, fever, or involvement of other internal organs (liver, kidney, lung, central nervous system, heart, muscle, thyroid, or lymphoid system); 2) maculopapular exanthema, defined as rash without systemic symptoms; and 3) SJS-TEN defined as skin detachment between 10-30% of body surface area with target skin lesions. Both population and clinical controls (those with epilepsy taking carbamazepine for 3 months or greater without clinical or biochemical hypersensitivity) were used. Single-nucleotide polymorphisms and imputation with high-resolution confirmation sequence-based HLA typing was performed to test for HLA allele association and clinical disease. Follow-up genotyping confirmed the HLA-A*3101 as a risk factor for the following: hypersensitivity syndrome with an odds ratio of 12.41 (27 subjects vs 257 controls without adverse drug reactions), maculopapular exanthema with an odds ratio of 8.33 (106 subjects vs 257 controls), and SJS-TEN with an odds ratio of 25.93 (12 subjects vs 257 controls). Overall, the presence of the HLA-A*3101 allele increased the risk of carbamazepine induced hypersensitivity reactions from 5% to 26%, whereas its absence reduced the risk from 5% to 3.8%. [ABSTRACT FROM AUTHOR]

THE DECISION TO UNDERGO SURGERY FOR REFRACTORY epilepsy often involves discussion of immediate operative risks such as infection, bleeding, and injury to eloquent areas of cortex. However, risk of premature mortality may not be emphasized. The authors in this study tried to answer the question: "Does surgery in medically refractory patients influence mortality?" In this single institution, prospective study, both medical and surgical cohorts were followed from the time of initial presurgical evaluation or surgery, until the time of death or date last known to be alive. Surgical patients were assigned to six groups. Groups 1 and 2 had no seizures, or only simple partial seizures (auras). Groups 3-6 had increasingly more frequent seizures. In the 641 nonsurgical patients, 40 deaths occurred. A little over half the deaths were attributable to SUDEP (sudden unexplained death in epilepsy). One death was due to drowning, and another was due to status epilepticus. SUDEP, drowning, and status epilepticus were classified as epilepsy-related deaths. The maximum duration of follow up was 15.4 years. In the 561 surgical patients, 19 deaths occurred. Two patient deaths were due to SUDEP in the surgical group. The maximum follow-up for the surgical group was 17.4 years. Of the patients in the surgical cohort at post operative year one, four deaths occurred in groups 1 and 2 (no seizures or simple partial seizures only). Nine deaths occurred in groups 3-6. Non-operated patients were nearly 2.5 times as likely to die during follow up as those who had surgery and were 4.5 times more likely to die from an epilepsy-related cause. Surgical patients in group 3-6 were four times as likely to die as those in group 1 or 2. [ABSTRACT FROM AUTHOR]

SEIZURES MAY OCCUR AS THE INITIAL PRESENTATION OR LATER in the medical course of a primary brain tumor. The treatment of central nervous system glioma patients is multimodal, requiring the use of anti-epileptic agents, systemic steroids, and chemotherapeutics. Thus, anti-seizure medications such as levetiracetam with no clinically relevant drug interactions and lack of hepatic P-450 induction or inhibitory effects is very desirable. Although levetiracetam has been used extensively in both the United States and Europe in glioma patients, few long-term studies assessing the efficacy of the medication are available. The authors of this study present the clinical treatment response of newly diagnosed glioma patients with epilepsy. Only newly diagnosed glioma and epilepsy patients were included in this clinical prospective trial. Patients previously on anti-epileptic agents or prior diagnosis of glioma were excluded. Epilepsy was defined as either recurrent clinical seizures with or without interictal epileptiform abnormalities (IEAs) on electroencephalogram recording, single focal or convulsive seizure with associated IEAs, single convulsion and history of prior episodes suggestive of focal seizures with or without IEAs, or seizures occurring de novo during medical follow up with or without IEAs. Patients were then treated with initial dosages of either 500 mg bid (< 70 years of age) or 250 mg bid (>70 years of age) of levetiracetam. At subsequent follow up visits (every 1-3 months), seizure recurrence and causative factors were assessed. Seizure recurrence was categorized as either daily, weekly, monthly, rare (< 1 seizure per month), or no seizures. Cause of seizure recurrence was categorized as follows: 1. radiographic tumor recurrence after prior radiographic response; 2. malignant (radiographic or pathologic) tumor progression; 3. subtherapeutic anticonvulsant levels in the absence of clear tumor progression and cessation of seizures with dose increase; 4. refractory seizures that occurred despite optimal therapeutic anticonvulsant levels and absence of tumor recurrence; or 5. radiotherapy induced seizures. Seizures secondary to causes 1-3 were treated with levetiracetam dose increase. Condition 4, refractory seizures, was treated with add on treatment with either oxcarbazepine, topiramate, or valproic acid. Radiotherapy induced seizures were treated only with corticosteroids. All patients were categorized based on the extent of neurosurgical resection (neurosurgeon report and post contract CT scan) as partial (< 50%), subtotal (50%-80%) or total tumor removal. Out of the 176 consecutive newly diagnosed glioma patients in the nearly three-year study, 82 patients had epilepsy and met study criteria. In 75 of 82 patients (91%), epilepsy was the presenting symptom and nearly two thirds of enrolled patients had grade IV glioma; 75 of 82 patients were seizure-free at the last evaluation either with monotherapy with levetiracetam (73 patients), topiramate (1 patient), or valproic acid (1 patient). The mean follow-up time was 13.1 months. Levetiracetam was stopped in the above two patients receiving topiramate and valproic acid monotherapy due to intolerable side effects. In the 7 of 82 drugresistant patients, all patients were either grade III or IV. [ABSTRACT FROM AUTHOR]

DEFINITIVE CRITERIA FOR SUDDEN UNEXPECTED DEATH in epilepsy (SUDEP) exclude death due to trauma, drowning, and status epilepticus. Death can occur with or without evidence of a seizure, can be witnessed or unwitnessed, and occurs without evidence of toxicological or structural abnormality on subsequent postmortem examination. The main risk factor for SUDEP has been poor seizure control, suggesting that in many cases SUDEP is indeed a seizure-related event. Due to the inherent difficulty of formally studying a relatively rare and oftentimes unwitnessed phenomenon, the pathophysiology of SUDEP has not been fully elucidated. The prevailing theory is that seizure-related cardio-respiratory autonomic dysfunction contributes to SUDEP. Heart rate variability indicates the heart's ability to respond to various environmental and physiologic stimuli. Decreased heart rate variability (HRV) has been postulated as a mechanism involved in autonomic dysfunction leading to SUDEP. The authors of this study analyzed whether decreased HRV exists in early and late postictal states. Thirty-one patients and 31 seizures (one seizure per patient) were included in this retrospective study after fulfilling criteria for medication-resistant partial epilepsy (failure of greater than two anti-epileptic agents). Nine generalized tonic-clonic seizures (GTCS), 15 complex partial seizures (CPS), and seven simple focal motor seizures were included in the study. All included patients had a normal baseline EKG and prior evaluation with long-term EEG with synchronized six-lead continuous EKG monitoring. In a blinded fashion, one investigator reviewed seizure onsets and offsets while the second investigator analyzed four separate, 300-second EKG epochs (baseline epoch 30 minutes before seizure onset, preictal epoch five minutes before seizure onset, postictal epoch 10 minutes after seizure offset, late postictal epoch defined as six hours after seizure onset). Measured heart rate variability indices include the following: RRI (mean interbeat interval of normal beats in milliseconds and mean heart rate (HR) on the entire 300-second-long epoch), SDNN (standard deviation of normal-to-normal RRI), coefficient of variation (CV) (SDNN divided by the RR expressed in percent), RMSSD (root mean square of successive RR differences). To minimize the influence of HR on the HRV, CV was used. The RMSSD index represents the parasympathetic activity found from the analysis of adjacent RR intervals. The results of the study showed elevation in HR both immediately after seizures and return to baseline six hours postictally. Early postictal HR elevation was higher after GTCS compared to both CPS and simple focal seizures. The authors found a long-lasting, decreased postictal HRV up to six hours after the seizures. [ABSTRACT FROM AUTHOR]

CHILDHOOD OCCIPITAL EPILEPSY--GASTAUT TYPE (COE-G) represents one of a few' idiopathic focal types of epilepsy. The prevalence of this syndrome among all epilepsies is less than 1%. This unique syndrome presents with primarily visual symptoms with without ictal and or post-ictal headache. Attenuation occipital spike and wave discharges with eye opening a characteristic electrographic hallmark of this disorder. Historically COE-G responds well to first generation anti-epileptic agents such as carbamazepine and valproic acid. However, long-term data regarding treatment this rare syndrome with second-generation anti-epileptic agents such as levetiracetam is limited. Since the advent of several new anti-epileptic agents in the mid 1990s, renewed interest in finding optimal anti-epileptic medication regimens with potentially fewer side effects emerged. The authors of this study present both clinical and electrographic outcomes of new-onset COE-G treated with levetiracetam monotherapy. Patients were included in this prospective, multicenter, open-label trial if they met criteria for COE-G as defined by the International League Against Epilepsy. Inclusion criteria were as follows: visual seizures (elementary or complex visual hallucinations, illusions, partial or complete transient visual loss, or ictal eye or deviation), occipital spike and wave discharges on electroencephalography (EEG), and normal neurologic examination and brain imaging. Patients were excluded in the setting of intellectual impairment/abnormal neurologic examination, recurrent psychosis or major affective disorder, use of central nervous system-influencing medication less than one month prior to commencing study, metabolic derangements, acute infection or neoplasms, progressive medical illness, and previous treatment any other anti-epileptic agents. Twelve patients met final criteria for study inclusion. EEG was performed for 60 minutes during the awake sleep states. Patients were initiated with levetiracetam mg orally each evening, with target maintenance therapy after four weeks ranging from 20 mg/kg/day 45 mg/kg/day based on clinical reporting of seizures. Seizures were recorded by patients or parents (legal guardians) along with any observed adverse events daily charting system. Patients were examined by physician investigators and underwent routine EEG testing 12, and 18 months. In addition, laboratory assessment complete blood counts, basic metabolic profile, hepatic profile, urinalysis, and EKG were performed. At the six-month mark, 11 out of 12 patients were seizure-free, and EEG normalized in six patients. At the 12-month mark, all patients were seizure-free. Four patients had persistent interictal abnormalities. Further. at the 18-month evaluation, all 12 patients remained seizure-free, and only two patients had less prominent occipital interictal abnormalities. Two patients reported transient dizziness and somnolence with introduction levetiracetam. [ABSTRACT FROM AUTHOR]

HISTORICALLY, THE GOLD STANDARD IN ESTABLISHING or refuting a diagnosis of epilepsy or seizures has been the electroencephalogram. Advances in neurophysiology, including digital long-term monitoring, have helped increase the yield of capturing and characterizing paroxysmal symptoms. In response to this ever-growing technology, the International League Against Epilepsy (ILAE) released a 2007 position paper outlining the recommended applications for long-term recording, including detection, characterization, and quantification of electroclinical seizures in epilepsy, differentiation of epileptic and nonepileptic events, and identification of subclinical seizures in comatose patients. In this article, the authors scrutinize their own database of long-term monitoring cases over a consecutive one-year period and report their findings in the context of the established guidelines. From 2005-2005, 364 patients at the Gowers Center were retrospectively identified and met criteria for inclusion into the study. Patients who had been previously monitored at the center were excluded. Patients were admitted to the unit for either inpatient ambulatory EEG or inpatient video EEG. Both the admitting and discharge diagnoses were recorded for each case. The reason for admission was divided into three distinct categories: diagnostic clarification, medication changes, and presurgical evaluation. For those admitted for diagnostic clarification, pre- and post-admission diagnoses were compared. Patients were then stratified into one of three categories after long-term monitoring: no change in diagnosis, refinement in diagnosis, and change in diagnosis. All epilepsy diagnoses were classified as focal, idiopathic generalized, or symptomatic/cryptogenic generalized according to the International Classification of Epileptic Seizures and Epileptic Syndromes (ILAE) guidelines. Of the 364 patients, 230 patients were referred for diagnostic clarification (63%), 75 (21%) for medication changes, and 59 (16%) for presurgical evaluation. Of the 230 patients, 58% of patients had a change in diagnosis and 13% had a refinement in diagnosis. Slightly fewer than one third of patients had no change in diagnosis. In the no-change subgroup, 75% of the patients had an inconclusive study for either lack of habitual events or uninformative interictal data. In those with a change of diagnosis, long-term monitoring helped distinguish between epileptic and non-epileptic events in 73 out of 133 patients (55%) and between focal and generalized epilepsies in 47 out of 133 patients (35%). In the 29 patients who had a refinement in diagnosis, seizure focus was lateralized to the frontal lobe in 59% of the patients. The mean duration of video telemetry (VT) and inpatient ambulatory EEG (aEEG) in those patients with change in diagnosis was 69.9 and 59.7 hours. In those patients where monitoring led to a refinement in diagnosis, mean duration of monitoring was 54.5 and 33.8 hours respectively. [ABSTRACT FROM AUTHOR]

ACUTE SYMPTOMATIC SEIZURES ARE A KNOWN COMPLICATION of central nervous system (CNS) infections. Traditionally, however, meningitides have been considered a medical and not neurological condition until focal neurologic signs or clinical seizures complicate the picture. In addition, use of continuous electroencephalography (cEEG) monitoring was not in wide practice until about a decade ago, when a landmark paper in 2000 by Towne and colleagues found an 8% incidence of nonconvulsive status epilepticus in a prospective study of patients with unexplained coma. Since then, physicians have noted that both electrographic seizures and nonconvulsive status epilepticus are under-recognized causes of coma. Interest in critically ill subpopulations such as those with CNS infections has grown. However, the true prevalence of electrographic seizures remains largely a mystery in this patient population. Hence, the authors of this study define and characterize the EEG findings in these critically ill patients. Over a one-year time period, all patients with CNS infections who underwent cEEG were retrospectively identified. Inclusion criteria were a diagnosis of primary CNS infection and accompanying elevation of the cerebrospinal fluid (CSF) white blood cell count (>4 /microliter) with or without characteristic imaging abnormalities. Exclusion criteria included postoperative neurosurgical infections and noninfectious causes of CSF pleocytosis. Infections were further subdivided into viral, bacterial, and fungal/parasitic based on appropriate CSF findings, including positive polymerase chain reaction (PCR), culture, antigen detection, and lymphocytic (viral infections) or neutrophilic (bacterial infections) pleocytosis. Imaging characteristics were used to help classify the cases. A total of 1,078 patients with a diagnosis of primary CNS infection were retrospectively identified at the Columbia University Medical Center. Seventy-five patients (7%) underwent cEEG, and 42 patients met full criteria for the study. In the study group, 64% of infections were viral, 8% bacterial, and 7% either fungal or parasitic. Fourteen of 42 patients had confirmed electrographic seizures, and 11 of these patients had accompanying periodic epileptiform discharges (PEDs). PEDs were recorded in 40% of patients. Overall, nearly half (48%) of patients had either electrographic seizures or PEDs. PEDs and viral etiology were independently associated with electrographic seizures. Clinical outcome was assessed in nearly all study patients (40 of 42 patients). Twenty-one patients had poor neurological outcome as assessed by a Glasgow outcome scale of 1-3. After adjustment for neurologic status, both PEDs and electrographic seizures were associated with poor outcome. [ABSTRACT FROM AUTHOR]

HISTORICALLY, THE BENZODIAZEPINES AND PHENYTOIN have been used as first-line therapy in aborting status epilepticus (SE). The rationale for use of these two agents mainly rests on the 1998 results of the Veterans Affairs Cooperative Trial. The greatest response rate was seen in those patients who received benzodiazepines in addition to phenytoin (PHT), rather than PHT alone. Although the intravenous formulation of valproic acid (VPA) was officially approved by the FDA in 1996, the agent was not included in the Veterans Affairs Cooperative Trial and still has not received approval by the FDA for use in SE. Nevertheless, despite the lack of FDA approval, IV VPA continues to be used off-label by clinicians. Therefore, papers such as this one by Gilad et al are critical in defining the exact role of VPA in both acute repetitive seizures (ARS) and SE. Seventy-four adult patients with either ARS or SE older than age 18 were included in this open-label study. Patients with baseline abnormal liver function tests or previous toxic serum levels of VPA were excluded from the study. For this study, SE was defined as greater than 30 minutes of continuous seizure activity or two or more sequential seizures without clinical recovery. ARS was defined as two or more repetitive seizures with clinical recovery between seizures during a 5- to 6-hour period. The primary endpoint was cessation of clinical seizure activity within 20 minutes of either VPA or PHT infusion, without rescue medication intervention. The secondary endpoint was assessment of infusion tolerability over the subsequent 24 hours. The IV VPA patient group received 30 mg/kg given over 20 minutes. The PHT patient group received an infusion of 18 mg/kg also given over 20 minutes. Patients were treated randomly in the emergency room in a 2:1 ratio of either VPA or PHT infusion. If seizure control was not achieved by infusion of the first study drug, then patients were treated with the other study drug. Patients who failed both study drug infusions were then treated with IV midazolam at a dosage of 0.2 mg/kg and were then subsequently transferred to the intensive care unit. Electroencephalography was performed in select cases of clinically suspected nonconvulsive status where patients did not regain consciousness. Forty-nine patients were treated with IV VPA and 25 patients were treated with PHT. Nearly two-thirds of patients in the study experienced breakthrough seizures secondary to subtherapeutic anti-epileptic drug levels or non-compliance. Post-stroke epilepsy made up approximately 25% of patients. Twelve percent of both the IV VPA and IV PHT groups required rescue medication. No significant side effects were found in the VPA group. One patient in the PHT group (no prior cardiac history) experienced ventricular premature beats during the infusion, one experienced vertigo, and one was noted to develop hyponatremia. [ABSTRACT FROM AUTHOR]

The ketogenic diet was beneficial in children with medically refractory epilepsy in this randomized controlled trial. [ABSTRACT FROM AUTHOR]

Since the advent of continuous EEG monitoring (cEEG), medical awareness of electrographic seizures has increased. In a previous retrospective study by Claassen and colleagues, nearly 20% of critically ill patients monitored for unexplained mental status had subclinical seizures. A separate observational study by Vespa and coworkers suggested that seizures after intraparenchymal hemorrhage, particularly lobar hemorrhage, are not uncommon and are associated with poor outcome. Thus, clinical evidence that electrographic seizures do occur with regular frequency in this subpopulation has emerged. This recent retrospective study by Claassen et al aims to determine the frequency and electrographic and radiologic variables associated with subclinical seizures and periodic discharges in patients with intracerebral hemorrhage (ICH). Over a six-year period, 102 patients with nontraumatic spontaneous ICH who underwent cEEG were retrospectively identified. Patients with ICH with unexplained mental status or suspicion of seizures underwent cEEG at the clinical discretion of the treating physician. Inclusion criteria included age older than 17 and cEEG duration of at least 12 hours. Patients with ICH secondary to trauma or aneurysmal bleed were excluded. Patients with a decreased level of consciousness and lobar hemorrhage or signs of increased intracranial pressure were loaded with 20 mg/kg of fosphenytoin, followed by maintenance phenytoin. Clinical, radiographic, and electrographic data were retrospectively obtained on each of the 102 study patients. Clinical data recorded by a study neurologist included: vitals signs/laboratory testing (admission blood pressure, serum glucose, toxicology screen), admission neurologic status, and hemorrhage etiology (hypertension, vascular malformation, amyloid angiopathy, anticoagulation, unknown, other). Four radiologic features were assessed: change in ICH volume, midline shift between baseline admission CT scan and follow up CT (at 24 hours, 48-72 hours, and between days 3-7), ICH location (deep versus lobar), and closest distance in mm of the ICH from the cortical surface. The presence of the following were determined: convulsive and electrographic seizures, PEDs (periodic epileptiform discharges), GPDs (generalized periodic discharges bilaterally synchronous with no consistent laterality), BIPLEDs (bilateral independent PLEDs), triphasic waves, FIRDA (frontal intermittent rhythmic delta activity), burst-suppression activity, reactivity to external stimuli, stage II sleep transients (K-complexes, sleep spindles), and SIRPIDs (stimulus induced rhythmic, periodic, or ictal discharges). A total of 31% of patients with ICH experienced a seizure (either clinical or electrographic) between hemorrhage onset and hospital discharge. Of the patients, 18% had electrographic seizures, of which 56% were detected within one hour of cEEG initiation. Nonconvulsive status epilepticus (NCSE) occurred in 39% of patients with electrographic seizures. Electrographic seizures were more frequent in those with PEDs (59%) versus those without PEDs (9%), in those with PLEDs than those without (77% versus 9%, respectively), and in those with focal SIRPIDs than those without (77% versus 14%, respectively). An increase in ICH volume of 30% or more between admission and 24-hour follow-up CT scan was associated with electrographic seizures. PEDs were significantly less frequently seen in patients with ICH located 1 mm or deeper from the cortical surface (8% of hemorrhages 1 mm or deeper versus 29% of hemorrhages within 1 mm of cortex). The only electrographic variable associated with poor outcome (a rating of 1-2 on the Glasgow outcome scale) was the presence of any periodic epileptiform discharge. In addition, ICH volumes > 60 mL and lower systolic blood pressure on admission also were associated with poor outcome. [ABSTRACT FROM AUTHOR]

THE OCCURRENCE OF PLEDS DURING A ROUTINE electroencephalographic study is not a new concept. In fact, the relevance of this elusive discharge has been the focus of interest over the last 2 decades, particularly since the advent of higher resolution imaging techniques. This recent retrospective study performed at the Cleveland Clinic aims to answer whether PLED morphology has any association with lesion location. Over a 4-year period, 106 patients with PLEDs were retrospectively identified from an EEG database. These 106 patients were then classified into one of 5 groups based upon corresponding imaging (CT and/or MRI) characteristics: normal, acute cortical, acute subcortical, chronic cortical, and chronic subcortical. Classification of imaging abnormalities prioritized acute over chronic changes, and cortical over subcortical changes. This stratification of data based on neuroimaging constituted part I of the study. In part II of the study, raw EEG data was scored quantitatively and/or qualitatively by a senior epileptologist, blinded to the neuroimaging findings in 95/106 patients where the original, complete EEG record was available. The selected 30 seconds of artifact free EEG was then scored, based on the following characteristics: inter-PLED interval (repetition rate), duration of complex, amplitude, prominent polarity, morphology (number of sharp phases and total number of phases), distribution, degree of intervening slow rhythms (subjective estimate) and reactivity. Of the 95 patients, 35 patient EEG records were excluded due to greater than one independent PLED population (eg. BIPLED), unsustained PLEDS (< 20 seconds during the recording), and physician disagreement with the original EEG classification. EEGs associated with normal neuroimaging were also excluded. Of the remaining 60 records, 49 of the records were associated with a cortical lesion (group A) and 11 records with a subcortical lesion (group B). The results of part I of the study showed that acute cortical lesions were the most common abnormality (40.5%). However, subcortical lesions (both acute and chronic combined) were not infrequent (23.6%). In part II of the study, the electrographic characteristics of group A (cortical) and group B(subcortical ) were compared. Overall, the duration of a typical cortical PLED (sharp or spike-and-slow wave discharge) was longer (mean 574 msec) than a subcortical one (mean 420 msec). Cortical PLEDSs were also more variable in morphology (mean of 2.367 in group A vs. mean of 1.727 in group B). However, repetition rate and degree of intervening background slowing between successive PLEDs was not statistically significant between the 2 groups. [ABSTRACT FROM AUTHOR]

In this 20-year, retrospective study, the authors summarize surgical trends in three major German epilepsy centers and identified a declining prevalence of epilepsy surgery from 1998 to 2008. [ABSTRACT FROM AUTHOR]

This 5-year retrospective observational study describes the epilepsy encountered in patients with amnestic mild cognitive impairment and early Alzheimer's disease. [ABSTRACT FROM AUTHOR]