Management Of Seizures In Patients Research Articles

Management of seizures in patients with primary mitochondrial diseases: consensus statement from the InterERNs Mitochondrial Working Group.

Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy. A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement. A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in POLG disease, vigabatrin in patients with γ-aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted. These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug-related adverse events in individuals living with PMD-related epilepsy.

Clinical management of seizures in patients with meningiomas: Efficacy of surgical resection for seizure control and patient-tailored postoperative anti-epileptic drug management.

Meningiomas are the most common primary intracranial tumor. They are slow growing and often incidentally found tumors that arise from the arachnoid villi. As they grow, they have a greater likelihood of becoming symptomatic with seizures being one of the most clinically significant symptoms. Seizures are more likely to present as a symptom of larger meningiomas and meningiomas that compress cortical areas particularly those in non-skull base locations. These seizures are often managed medically, utilizing the same anti-seizure medications that are used to treat other causes of epilepsy. We discuss common anti-seizure medications used including valproate, phenobarbital, carbamazepine, phenytoin, lacosamide, lamotrigine, levetiracetam and topiramate and their common adverse effects. The goal of pharmacotherapy for seizure control is to maximize seizure control while minimizing the adverse effects of the medication. The decision to provide medical management is dependent on individual seizure history and plans for surgical treatment. Patients who did not require seizure prophylaxis before surgery are commonly prescribed seizure prophylaxis postoperatively. Symptomatic meningiomas not controlled by medical management alone are commonly evaluated for surgical resection. The efficacy of surgical resection in providing seizure freedom is dependent on several features of the tumor including tumor size, the extent of the peritumoral edema, the number of tumors, sinus infiltration and the degree of resection.

Effects of psychiatric comorbidities in persons with epilepsy on recurrent emergency department visits

BackgroundCoexisting mental health disorders in persons with epilepsy present as substantial burdens to patients and healthcare systems. Study design and methodsIn this retrospective study, we reviewed 160 patients presenting to a safety net hospital Emergency Department (ED) with seizures to investigate whether differences in clinical workup, follow-ups, and ED visit recurrence existed between epilepsy patients with epilepsy with and without a coexisting psychiatric disorder. ResultsPatients with epilepsy with a psychiatric comorbidity had more subsequent ED visits (45 % vs 26 %, p = 0.01) and fewer outpatient follow-up opportunities (74 % vs 87 %, p = 0.042) compared to patients with epilepsy without psychiatric comorbidities, highlighting a healthcare gap that needs to be addressed. InterpretationOur findings suggest a need for ED providers to shift their clinical practice in favor of offering more outpatient follow-up opportunities, to ensure long-term management of seizures in patients with epilepsy with comorbid psychiatric disorders.

The high incidence and risk factors of levetiracetam and lacosamide-related skin rashes in glioma patients

ObjectiveAntiseizure drug (ASD)-induced skin rash remains the main side effect of seizure management in patients with glioma. New generations of ASDs, such as levetiracetam (LEV) and lacosamide (LCM) are associated with less frequent skin rashes than conventional ASDs. However, there are few reports regarding the incidence of skin rashes by LEV and LCM in patients with glioma. Therefore, the aim of this study was to investigate the incidence and risk factors of LEV- and LCM-associated skin rashes in patients with glioma. MethodsWe compared the incidence of ASD-associated skin rash between 353 patients with glioma and 125 patients with meningioma, who received LEV or LCM and underwent surgery between 2017 and 2019 at our institution. Furthermore, to evaluate the association between potential risk factors and ASD-associated skin rashes, univariate and multivariate analyses were performed. ResultsThe incidence of ASD-associated skin rash in patients with glioma was higher (11 %) than in those with meningiomas (1.6 %). The multivariate regression analysis showed that adjuvant treatment with radiotherapy (p = 0.023) and a history of drug allergy (p = 0.023) were significant risk factors for ASD-associated skin rash. The rate of ASD-related skin rashes in patients with glioma was also higher than the previously reported rates of 1–3 % in patients with epilepsy. ConclusionOur results indicate that adjuvant treatment with radiotherapy and a history of drug allergy correlated with a high incidence of ASD-related skin rashes in patients with glioma who receive LEV and LCM. Patients with these two factors should be carefully checked for skin rashes.

Pharmacological management of seizures in patients with COVID-19: a systematic review

Background: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to exhibit neurological symptoms such as seizures and impaired consciousness. Our study reviews reported cases to assess the pharmacological approach to managing seizures in SARS-CoV-2 patients and associated outcomes. Methods: A systematic review of case reports on the incidence of seizures following coronavirus disease 2019 (COVID-19) among patients that reported use of antiepileptic drugs (AEDs) in management was performed by using the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines. Databases used included EMBASE, PubMed, SCOPUS, and Google Scholar. Data was presented as qualitative and descriptive data. Results: In total, 67 articles were selected for full-text assessment, of which 19 were included in the final review. Patients had a median age of 54 years, most of whom were male. Remdisivir, dexamethasone, Laminavir, hydroxychloroquine, azithromycin, and Lopinavir-ritonavir were common agents used in the management of COVID-19. Most patients presented with either generalized tonic-clonic seizures or status epilepticus. Most patients received levetiracetam as drug choice or as part of their regimen. Other AEDs commonly prescribed included midazolam and sodium valproate. Some patients received no antiepileptic drug therapy. Most of the patients who died had more than one comorbidity. Also, most of the patients who died received COVID-19 treatment drugs. None of the patients who received midazolam as drug choice or as part of their regimen developed recurrent seizures in contrast to patients who received levetiracetam and sodium valproate as drug choice or as part of their regimen. Interestingly, none of the patients who received no AEDs suffered recurrent seizures or died. Conclusions: Standard guidelines for managing seizures in COVID-19 patients may be required. A limitation of this review is that it involved the use of case reports with no controls and a small number of patients.

Management of epilepsy in brain tumors.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy

ABSTRACTEpilepsy, commonly encountered by patients with brain tumors, is often refractory to standard therapies. Our aim was to examine the safety and efficacy of pharmaceutical grade cannabidiol (CBD; Epidiolex; Greenwich Biosciences) in those patients with epilepsy with concomitant tumors enrolled in The University of Alabama at Birmingham CBD Program (NCT02700412 and NCT02695537). Of the three patients with refractory seizures and a history of a primary brain tumor, two had improvement in seizure frequency and all three had improvement in seizure severity. These pilot results suggest that CBD should be further studied for the treatment of brain tumor-related epilepsy.

Cause of death in patients with poststroke epilepsy: Results from a nationwide cohort study.

The risk of death is increased for persons with epilepsy. The literature on causes of death in epilepsy is based mainly on cohorts with epilepsy of mixed aetiologies. For clinical purposes and improved understanding of mortality in different epilepsies, more information is needed on mortality in epilepsies of specific causes. In poststroke epilepsy (PSE), seizures occur in a setting of vascular disease and high mortality rates. The extent to which epilepsy contributes to mortality in this patient group is poorly understood. We therefore aimed to describe causes of death (COD) in PSE on a national scale. A previously identified cohort of 7740 patients with epilepsy or seizures after a stroke in 2005–2010 was investigated. A total of 4167 deaths occurred before the end of 2014. The standardized mortality ratio for the study cohort was 3.56 (95% CI: 3.45–3.67). The main underlying causes of death were disorders of the circulatory system (60%) followed by neoplasms (12%). Diseases of the nervous system were the sixth leading underlying COD (3%), and epilepsy or status epilepticus was considered the underlying COD in approximately a similar proportion of cases as neurodegenerative disorders (0.9% and 1.1%, respectively). Epilepsy was considered a contributing COD in 14% of cases. Our findings highlight the importance of optimal management of vascular morbidity in patients with PSE. The large proportion of patients with epilepsy as a contributing COD indicate the need of high ambitions also regarding the management of seizures in patients with PSE.

Treatment of Seizures and Postanoxic Status Epilepticus.

Seizures are a common occurrence following cardiac arrest and may occur both during targeted temperature management and after rewarming. Postanoxic seizures may be nonconvulsive and very difficult to diagnose without electroencephalography (EEG) or associated with prominent myoclonus. Importantly, to date no randomized controlled trials are available to guide the management of seizures in patients with cardiac arrest. Seizure prophylaxis is not recommended, and when seizures are diagnosed they are typically treated the same as seizures in other patients with acute brain injury. Electroencephalographic abnormalities that are highly epileptiform, but do not fulfill classic seizure criteria, also known as the ictal-interictal continuum, occur frequently and there is no consensus on how to treat these. Several EEG patterns have been associated with poor outcome in retrospective studies. Increasing evidence has emerged that patients may have a favorable outcome, even with status myoclonus and malignant EEG patterns, if aggressive management is pursued.

P18.08 * A MULTICENTRIC, OBSERVATIONAL, NON INTERVENTIONAL STUDY OF EFFICACY AND SAFETY OF LACOSAMIDE FOR THE TREATMENT OF EPILEPTIC SEIZURES IN PATIENTS WITH BRAIN TUMORS

INTRODUCTION: Epileptic seizures are common in oncologic patients. Seizures could be the initial symptom of a brain tumor in 20-40% of the cases and 40% of the patients with brain tumors will have a seizure throught the diseqse. Management of these complications is crucial in the treatment of brain tumors. The ideal antiepileptic drug (AED) would be that one which could ensure a high and proved efficacy, wide security, low interactions, easy and quick to titrate and available in i.v. formulation. Until today there is a scarce number of publications on the use of lacosamide (LCM) in patients with btain tumors, although there is some experience in routine clinical practice that has previously shown a very promising profile of efficacy and safety. This study tries to compile some of these experiences in Spain. OBJECTIVES: To evaluate the efficacy of LCM in the management of seizures in patients with brain tumors. Secondary objectives were the evaluation of safety and tolerability of LCM . DESIGN: Multicentric, observational, non-interventional retrospective study. Patients who suffered at least 1 convulsive episode and at least treated with 1 dose of LCM were recruited. RESULTS: 37 patients with brain tumor suffering seizures were recruited in 6 centers all over the country, and 24 of them (64.9%) could be followed-up until the end of the study (after 6 months). Of these 37 patients, 26 (70%) were male, the age was 54.14 ± 14 years. 28 patients had one lesion and 9 had several lesions, 7 of them were metastatic. The average of total number of seizures from the onset of LCM treatment to the last visit performed shows a statistically significant change from the initiation of LCM treatment, showing a reduction of -16.8 ± 41'7 seizures. (p <000.1) The reason for withdrawing from the study was death by cancer in 7 of all the 37 initially included (53.85%), being a lack of LCM efficacy in 2 patients. A total of 12 more patients needed a LCM modification of treatment, 9 due to lack of efficacy, 3 due to adverse events. CONCLUSIONS: In a retrospective, non-interventional study with brain tumor patients, LCM has shown to be effective and safe in the management of seizures in neurooncological patients.

A Review of the Use of Antiepileptic Drugs in High-Grade Central Nervous System Tumors

Seizures are a common complication in patients with central nervous system (CNS) tumors. Optimal management is unclear with no defined guidelines and pharmacological management poses many controversies. Due to a hypothesized lack of consistency, we aimed to retrospectively review seizure management in patients with high-grade CNS tumors in our institution. The medical records of patients with high-grade CNS tumors referred to the specialist palliative medicine service in our institution from January-June 2008 were retrospectively reviewed. Seizure incidence, antiepileptic drug (AED) choice, neurology input, medication interactions, and appropriate drug level monitoring were assessed. Twenty-seven patients were included for analysis. Fifteen (56%) were female. The mean age was 58.8 years (range 31-82 years). Three (11%) patients presented with seizures and 8 (30%) developed seizures subsequently. Eight (73% of those with seizures) were on monotherapy AED. Six different agents were used as first-line agents. Phenytoin was the most common AED used (n = 4). Three (27%) patients were on combination AEDs. Five (45.5%) patients had been seen by neurology and 6 (54.5%) had appropriate drug level monitoring performed. Six (55%) patients had potential AED-non-AED interactions. None of the patients had instructions documented in the clinical notes against driving. Seizure management in patients with CNS tumors is not consistent and remains very much a neglected area. Appropriate choice of AED is crucial. Physicians should be aware of potential drug interactions. Ownership and regular follow-up of this group is required to ensure optimum patient management.

Mechanisms of action of antiepileptic drugs

Epilepsy affects up to 1% of the general population and causes substantial disability. The management of seizures in patients with epilepsy relies heavily on antiepileptic drugs (AEDs). Phenobarbital, phenytoin, carbamazepine and valproic acid have been the primary medications used to treat epilepsy for several decades. Since 1993 several AEDs have been approved by the US FDA for use in epilepsy. The choice of the AED is based primarily on the seizure type, spectrum of clinical activity, side effect profile and patient characteristics such as age, comorbidities and concurrent medical treatments. Those AEDs with broad-spectrum activity are often found to exert an action at more than one molecular target. This article will review the proposed mechanisms of action of marketed AEDs in the US and discuss the future of AEDs in development.

Seizures in patients with glioma treated with phenytoin and levetiracetam

Second-generation antiepileptic drugs (AEDs) are increasingly used in the care of patients with glioma. There is little data on how this practice compares with the use of traditional AEDs in this population. This noninferiority analysis compares seizure outcomes and side effects in patients with glioma treated with phenytoin and levetiracetam monotherapy. The authors retrospectively reviewed the records of 500 consecutive patients with glioma who were treated in clinical trials from 2001 to 2008 at 3 Mayo Clinic campuses. To be eligible for the study, these patients had to have had at least 1 clinical seizure and to have undergone follow-up for at least 6 months. Seizure outcomes, defined by the occurrence of a second seizure, time to second seizure, and seizure frequency, along with AED side effects, were compared between cohorts treated with phenytoin or levetiracetam Seventy-six patients were identified, 25 treated with phenytoin and 51 with levetiracetam. Sixty-four percent of the patients had a Grade 4 astrocytoma. There was no difference in seizure outcome between the phenytoin and levetiracetam groups when comparing time to second seizure (p=0.584), second seizure rates (p=0.561), and average seizures per month (p=0.776). When adjusting for age, sex, type of seizure, type of glioma, and dosage using univariate and multivariate models, there were no differences between the treatment groups and none of these covariates were statistically significant for explaining the second seizure rates between treatment groups (all p values>0.05). The incidence of side effects in the levetiracetam group was 6% versus 20% in the phenytoin group (p=0.106). Additionally, 36% of the patients in the phenytoin group had dose adjustments unrelated to breakthrough seizures compared with only 10% in the levetiracetam group (p=0.010) In this study, patients with glioma treated with levetiracetam and phenytoin had similar seizure control. Patients treated with levetiracetam experienced fewer side effects and required fewer nonseizure-related dose adjustments than patients treated with phenytoin. Levetiracetam is a safe, effective, and preferred alternative for seizure management in patients with glioma.

Seizures in patients with glioma treated with phenytoin and levetiracetam

e13020 Background: Seizures are common in patients with glioma. Phenytoin, traditionally used for these patients, can be associated with intolerable side effects and potentially alters the metabolism of chemotherapeutic agents. Levetiracetam has more favorable pharmacokinetics facilitating ease of use with fewer side effects and is nonenzyme inducing. We compare seizure outcomes and side effects in patients with glioma treated with phenytoin and levetiracetam monotherapy. Methods: Retrospective analysis of consecutive patients with glioma. Subjects had at least one clinical seizure and had to be followed for 6 months. Seizure outcomes and side effects were compared between cohorts treated with phenytoin or levetiracetam. Seizure outcomes were measured by time to second seizure and seizure frequency. Results: 76 patients (34 female) with pathologically proven glioma and seizures were identified, 25 treated with phenytoin and 51 with levetiracetam. 64% had grade 4 astrocytoma. There was no difference in seizure outcome between the phenytoin and levetiracetam groups when comparing time to second seizure (p = 0.584), second seizure rates (p = 0.462), and average seizures per month (p = 0.776). When adjusting for age, gender, type of seizure, type of glioma, and dosage using univariate and multivariate models there were no differences between the treatment groups and none of these covariates were statistically significant for explaining the second seizure rates between treatment groups (all p values &gt;0.05). The incidence of side effects in the levetiracetam group was 5.9% versus 20% in the phenytoin group (p = 0.106). Additionally, 36.0% of the patients in the phenytoin group had dose adjustments not related to breakthrough seizures compared to only 9.8% in the levetiracetam group (p = 0.010). Conclusions: In this study, glioma patients treated with levetiracetam had similar seizure control as patients treated with phenytoin. Patients treated with levetiracetam experienced fewer side effects and required fewer non seizure related dose adjustments than patients treated with phenytoin. Levetiracetam is a safe, effective, and preferred alternative for seizure management in patients with glioma. No significant financial relationships to disclose.

Perspectives on interactions between antiepileptic drugs (AEDs) and antimicrobial agents

In the treatment of seizures and epilepsy associated with central nervous system (CNS) infections, drug-drug interactions may significantly and unexpectedly impact outcome not only of epilepsy but also of the infectious disorders in both emergent and chronic care situations. A case is described in whom, the administration of the antimicrobial agent, meropenem presumably reduced serum valproate concentrations resulting in impaired seizure control. Other situations are reviewed in which interactions between antiepileptic drugs (AEDs) and antimicrobial agents may be of clinical significance. These include: (1) seizure management in individuals with neurocysticercosis, (2) management of seizures in patients with lobar tuberculomas, (3) management of seizures due to cerebral abscess, and (4) management of seizures in HIV-seropositive individuals.

Diabetic hyperglycemia is associated with the severity of epileptic seizures in adults

Epileptic seizures in diabetic hyperglycemia (DH) patients are not uncommon in clinical practice. Although there have been reports suggesting an association, most were limited case studies. The role of DH in the severity and recurrence of epileptic seizures remains unclear. We thus conducted a prospective comparative study of newly diagnosed unprovoked seizures in adult patients, with and without DH, from 2000 to 2004. Seizure semiology and severity were studied and all subjects were followed-up for 2 years to evaluate seizure recurrence. Forty-one patients in the DH and 70 patients in the non-DH group were recruited. Seizure clustering in initial presentation (63%) and in recurrence (78.6%) in the DH group was significantly higher than that in the non-DH group (38.5 and 41.4%) (p<0.05). In the DH group, the HbA1c at first seizure was significantly higher in patients with seizure recurrence than in those without (11.8% vs. 8.6%, p<0.05). Patients with poor glycemic control (HbA1c >9%) had significantly higher risk of seizure recurrence (44.8% vs. 8.3%) and clustering (79.3% vs. 25%) (p<0.05). In conclusion, DH might aggravate epileptic seizures. Severe seizures might be associated with recurrent seizures in patients with DH. DH should be investigated in adult patients with newly diagnosed epileptic seizures and aggressive blood sugar control might benefit seizure management in patients with DH.

Seizures in elderly patients with dementia: epidemiology and management.

Epileptic seizures occur in patients with dementia at a higher prevalence than among healthy elderly individuals. The incidence of seizures among patients with dementia varies with the aetiology of the dementing illness. In patients with Alzheimer's disease (the most common form of dementia), approximately 10-22% have at least one unprovoked seizure. Seizures usually occur in later stages of Alzheimer's disease, on average, > or =6 years into the course of the disease. Seizures in Alzheimer's disease are more likely to occur with early-onset disease, particularly if there is a familial presenilin I mutation. The incidence of seizures in other dementing diseases is less clear. There are special considerations regarding the management of seizures in the elderly with dementia. First, the presence of cognitive impairment may impede an accurate diagnosis of seizures. Clinicians may also mistake seizure manifestations for symptoms of the underlying dementia. Second, since most dementia patients are elderly, there are pharmacokinetic changes with aging that affect the use of antiepileptic drugs. Third, antiepileptic drugs have potential cognitive adverse effects that may worsen dementia. Although few studies are available, extrapolations from research in young people and elderly patients without dementia provide several recommendations for the management of seizures in patients with dementia: exclude symptomatic causes of seizures before committing to antiepileptic drug therapy; treat after a first seizure if there is evidence of focal neurological involvement or a risk of recurrent seizures; use antiepileptic drugs with minimal cognitive adverse effects, such as carbamazepine, valproic acid, gabapentin and lamotrigine; and use the lowest possible dosage and monitor antiepileptic drug levels, where possible.

Using the New Antiepilepsy Drugs in Children

New epilepsy treatment options are becoming available to physicians and may help provide safe and effective seizure management in patients for whom traditional drug therapies have been unsuccessful. Presented here is a brief discussion on the screening models used to test drugs for efficacy against various seizure types and the mechanisms of action and pharmacology of antiepilepsy drugs. This is followed by a more detailed review of the clinical pharmacology of the latest three antiepilepsy drugs introduced to the United States: levetiracetam, oxcarbazepine, and zonisamide. All three appear to have advantages over some traditional antiepilepsy drugs and with more clinical experience may replace them in certain seizure types or epilepsy syndromes.