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The Lancet. Neurology Jul 2017People with epilepsy who became seizure-free while taking antiepileptic drugs might consider discontinuing their medication, with the possibility of increased quality of... (Meta-Analysis)
Meta-Analysis Review
Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis.
BACKGROUND
People with epilepsy who became seizure-free while taking antiepileptic drugs might consider discontinuing their medication, with the possibility of increased quality of life because of the elimination of adverse events. The risk with this action, however, is seizure recurrence. The objectives of our study were to identify predictors of seizure recurrence and long-term seizure outcomes and to produce nomograms for estimation of individualised outcomes.
METHODS
We did a systematic review and meta-analysis, and identified eligible articles and candidate predictors, using PubMed and Embase databases with a last update on Nov 6, 2014. Eligible articles had to report on cohorts of patients with epilepsy who were seizure-free and had started withdrawal of antiepileptic drugs; articles also had to contain information regarding seizure recurrences during and after withdrawal. We excluded surgical cohorts, reports with fewer than 30 patients, and reports on acute symptomatic seizures because these topics were beyond the scope of our objective. Risk of bias was assessed using the Quality in Prognosis Studies system. Data analysis was based on individual participant data. Survival curves and proportional hazards were computed. The strongest predictors were selected with backward selection. Models were converted to nomograms and a web-based tool to determine individual risks.
FINDINGS
We identified 45 studies with 7082 patients; ten studies (22%) with 1769 patients (25%) were included in the meta-analysis. Median follow-up was 5·3 years (IQR 3·0-10·0, maximum 23 years). Prospective and retrospective studies and randomised controlled trials were included, covering non-selected and selected populations of both children and adults. Relapse occurred in 812 (46%) of 1769 patients; 136 (9%) of 1455 for whom data were available had seizures in their last year of follow-up, suggesting enduring seizure control was not regained by this timepoint. Independent predictors of seizure recurrence were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, age at onset of epilepsy, history of febrile seizures, number of seizures before remission, absence of a self-limiting epilepsy syndrome, developmental delay, and epileptiform abnormality on electroencephalogram (EEG) before withdrawal. Independent predictors of seizures in the last year of follow-up were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, number of antiepileptic drugs before withdrawal, female sex, family history of epilepsy, number of seizures before remission, focal seizures, and epileptiform abnormality on EEG before withdrawal. Adjusted concordance statistics were 0·65 (95% CI 0·65-0·66) for predicting seizure recurrence and 0·71 (0·70-0·71) for predicting long-term seizure freedom. Validation was stable across the individual study populations.
INTERPRETATION
We present evidence-based nomograms with robust performance across populations of children and adults. The nomograms facilitate prediction of outcomes following drug withdrawal for the individual patient, including both the risk of relapse and the chance of long-term freedom from seizures. The main limitations were the absence of a control group continuing antiepileptic drug treatment and a consistent definition of long-term seizure freedom.
FUNDING
Epilepsiefonds.
Topics: Adult; Anticonvulsants; Child; Humans; Outcome Assessment, Health Care; Recurrence; Remission Induction; Seizures
PubMed: 28483337
DOI: 10.1016/S1474-4422(17)30114-X -
Epileptic Disorders : International... Feb 2022Acute symptomatic seizures occurring in close temporal relationship with an acute CNS insult are distinct from epilepsy and occur frequently in clinical practice. The... (Review)
Review
Acute symptomatic seizures occurring in close temporal relationship with an acute CNS insult are distinct from epilepsy and occur frequently in clinical practice. The aim of this educational review is to provide information on the most important aspects related to acute symptomatic seizures that will allow clinicians to accurately distinguish acute symptomatic seizures from epilepsy in their patients. We explain the definition of acute symptomatic seizures and we illustrate how acute symptomatic seizures differ from epilepsy. We describe acute symptomatic seizures in the context of their various underlying aetiologies and we discuss the approach to the management of patients with acute symptomatic seizures.
Topics: Diagnosis, Differential; Epilepsy; Humans; Seizures
PubMed: 34789447
DOI: 10.1684/epd.2021.1376 -
Epilepsia Apr 2017This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the...
This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor-onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic-clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic-atonic, myoclonic-tonic-clonic, tonic, or tonic-clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic-clonic, epileptic spasms, or behavior arrest. This "users' manual" for the ILAE 2017 seizure classification will assist the adoption of the new system.
Topics: Awareness; Electroencephalography; Humans; International Agencies; Seizures; Terminology as Topic
PubMed: 28276064
DOI: 10.1111/epi.13671 -
Geriatrie Et Psychologie... Mar 2019Non-convulsive status epilepticus (NCSE) is common in the elderly. It most often corresponds to prolonged focal seizures with impaired contact ("complex partial status... (Review)
Review
Non-convulsive status epilepticus (NCSE) is common in the elderly. It most often corresponds to prolonged focal seizures with impaired contact ("complex partial status epilepticus"). A form of de novo absence status epilepticus, much rarer, can also meet. The identified risk factors for NCSE onset are: a precession by a generalized tonic-clonic seizure, a known history of epilepsy, female gender, and known brain injury (especially a stroke sequelae). The presence of one of these risk factors combined with a confusional picture of unknown origin should lead us to think of the diagnosis of NCSE. As the clinic is often not very suggestive (stupor, confusion, even coma), the diagnosis will be based on the EEG with criteria now accepted (so-called Salzburg EEG criteria). The treatment is based first on the injection of benzodiazepines and in the second line on intravenous or oral or gastric tube administration of antiepileptic drugs. It is not recommended to resort to an intubation-ventilation (except need out treatment of the state of evil: respiratory distress, multi-organ failure…). The prognosis is generally poor with about 30% mortality.
Topics: Aged; Aged, 80 and over; Anticonvulsants; Electroencephalography; Female; Humans; Male; Risk Factors; Status Epilepticus
PubMed: 30916648
DOI: 10.1684/pnv.2019.0782 -
Arquivos de Neuro-psiquiatria May 2022Status epilepticus (SE) is a frequent neurological emergency associated with high morbidity and mortality. According to the new ILAE 2015 definition, SE results either...
Status epilepticus (SE) is a frequent neurological emergency associated with high morbidity and mortality. According to the new ILAE 2015 definition, SE results either from the failure of the mechanisms responsible for seizure termination or initiation, leading to abnormally prolonged seizures. The definition has different time points for convulsive, focal and absence SE. Time is brain. There are changes in synaptic receptors leading to a more proconvulsant state and increased risk of brain lesion and sequelae with long duration. Management of SE must include three pillars: stop seizures, stabilize patients to avoid secondary lesions and treat underlying causes. Convulsive SE is defined after 5 minutes and is a major emergency. Benzodiazepines are the initial treatment, and should be given fast and an adequate dose. Phenytoin/fosphenytoin, levetiracetam and valproic acid are evidence choices for second line treatment. If SE persists, anesthetic drugs are probably the best option for third line treatment, despite lack of evidence. Midazolam is usually the best initial choice and barbiturates should be considered for refractory cases. Nonconvulsive status epilepticus has a similar initial approach, with benzodiazepines and second line intravenous (IV) agents, but after that, aggressiveness should be balanced considering risk of lesion due to seizures and medical complications caused by aggressive treatment. Usually, the best approach is the use of sequential IV antiepileptic drugs (oral/tube are options if IV options are not available). EEG monitoring is crucial for diagnosis of nonconvulsive SE, after initial control of convulsive SE and treatment control. Institutional protocols are advised to improve care.
Topics: Anticonvulsants; Benzodiazepines; Humans; Levetiracetam; Seizures; Status Epilepticus
PubMed: 35976303
DOI: 10.1590/0004-282X-ANP-2022-S113 -
Neurology Jul 2018To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy with second- and third-generation antiepileptic...
Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.
OBJECTIVE
To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy with second- and third-generation antiepileptic drugs (AEDs).
METHODS
The 2004 AAN criteria were used to systematically review literature (January 2003-November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength.
RESULTS
Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy.
RECOMMENDATIONS
Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years of age with new-onset focal epilepsy. Unless there are compelling adverse effect-related concerns, ethosuximide or valproic acid should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.
Topics: Adult; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Humans; Seizures
PubMed: 29898971
DOI: 10.1212/WNL.0000000000005755 -
Brain and Nerve = Shinkei Kenkyu No... May 2023Antiseizure drugs (ASDs) should be selected depending on the drug's efficacy for the seizure types. The seizure types are roughly classified into focal onset and...
Antiseizure drugs (ASDs) should be selected depending on the drug's efficacy for the seizure types. The seizure types are roughly classified into focal onset and generalized onset (generalized tonic-clonic, absence, and generalized myoclonic) seizures. Due care should be taken when selecting an ASD for patients with comorbidities and women of child-bearing age. If seizures persist after 2 or more trials with an appropriate ASD at optimal doses, the patients should be referred to epileptologists.
Topics: Humans; Female; Seizures; Anticonvulsants
PubMed: 37194513
DOI: 10.11477/mf.1416202359 -
European Journal of Paediatric... Jul 2021CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic...
CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.
Topics: Ataxia; Calcium Channels; Child, Preschool; Epilepsy; Female; Humans; Male; Seizures; Spinocerebellar Ataxias
PubMed: 34102571
DOI: 10.1016/j.ejpn.2021.05.010 -
Handbook of Clinical Neurology 2020More than one-third of patients with meningiomas will experience seizures at some point in their disease. Despite this, meningioma-associated epilepsy remains... (Review)
Review
More than one-third of patients with meningiomas will experience seizures at some point in their disease. Despite this, meningioma-associated epilepsy remains significantly understudied, as most investigations focus on tumor progression, extent of resection, and survival. Due to the impact of epilepsy on the patient's quality of life, identifying predictors of preoperative seizures and postoperative seizure freedom is critical. In this chapter, we review previously reported rates and predictors of seizures in meningioma and discuss surgical and medical treatment options. Preoperative epilepsy occurs in approximately 30% of meningioma patients with peritumoral edema on neuroimaging being one of the most significant predictor of seizures. Other associated factors include age <18, male gender, the absence of headache, and non-skull base tumor location. Following tumor resection, approximately 70% of individuals with preoperative epilepsy achieve seizure freedom. Variables associated with persistent seizures include a history of preoperative epilepsy, peritumoral edema, skull base tumor location, tumor progression, and epileptiform discharges on postoperative electroencephalogram. In addition, after surgery, approximately 10% of meningioma patients without preoperative epilepsy experience new seizures. Variables associated with new postoperative seizures include tumor progression, prior radiation exposure, and gross total tumor resection. Both pre- and postoperative meningioma-related seizures are often responsive to antiepileptic drugs (AEDs), although AED prophylaxis in the absence of seizures is not recommended. AED selection is based on current guidelines for treating focal seizures with additional considerations including efficacy in tumor-related epilepsy, toxicities, and potential drug-drug interactions. Continued investigation into medical and surgical strategies for preventing and alleviating epilepsy in meningioma is warranted.
Topics: Anticonvulsants; Humans; Meningeal Neoplasms; Meningioma; Neurosurgical Procedures; Seizures
PubMed: 32586490
DOI: 10.1016/B978-0-12-822198-3.00053-7 -
Emergency Medicine Clinics of North... Feb 2021Functional or psychogenic seizures have proved a diagnostic and therapeutic challenge for centuries. Functional seizures can look and feel similar to epileptic seizures... (Review)
Review
Functional or psychogenic seizures have proved a diagnostic and therapeutic challenge for centuries. Functional seizures can look and feel similar to epileptic seizures but are instead a common and highly disabling form of functional neurologic disorder, or conversion disorder. Consistent with the biopsychosocial model of mental illness, functional seizures are caused by biological, psychological, and social factors unrelated to epileptic discharges. People with functional seizures do not consciously fake their symptoms. Functional seizures can be differentiated from epileptic seizures through the clinical history, features of the seizures themselves, and electroencephalography findings. Psychotherapy is effective in treating functional seizures.
Topics: Conversion Disorder; Emergency Service, Hospital; Humans; Seizures
PubMed: 33218653
DOI: 10.1016/j.emc.2020.09.007