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Evaluation and Management of First-Time Seizure in Adults
Abstract
First seizures are often perceived as devastating events by patients and their families due to the fear of having a life-long disease. One in 10 people experiences one or more seizures during their lifetime, while 1 in 26 people develops epilepsy. Acute symptomatic seizures are often related to a provoking factor or an acute brain insult and typically do not recur. Careful history and clinical examination should guide clinicians' management plans. Electroencephalography and brain imaging, preferably with epilepsy-specific magnetic resonance imaging, may help characterize both etiology and risk of seizure recurrence. Antiepileptic drugs should be initiated in patients with newly diagnosed epilepsy. In patients without an epilepsy diagnosis, the decision to prescribe drugs depends on individual risk factors for seizure recurrence and possible complications from seizures, which should be discussed with the patient. Counseling about driving and lifestyle modifications should be provided early, often at the first seizure encounter.
... Seizures represent a potentially devastating life event, carrying the risk of both physical and mental harm and exerting a detrimental influence on a patient's social well-being [1]. Diagnosing seizures can pose a challenge due to their diverse presentations and the potential overlap with conditions like syncope or encephalopathy, which may share similar symptoms such as confusion and tonic-clonic movements. ...
... Diagnosing seizures can pose a challenge due to their diverse presentations and the potential overlap with conditions like syncope or encephalopathy, which may share similar symptoms such as confusion and tonic-clonic movements. This difficulty is exacerbated when seizures go unwitnessed, requiring clinicians to rely on indicators like postictal confusion, incontinence, and lateral tongue biting as key signs of a generalised seizure event [1]. Accurate and timely diagnosis is important, as treatment is readily available and the consequences of uncontrolled seizures can be devastating and lifelong. ...
... Clozapine, a potent antipsychotic valued for its effectiveness in treating schizophrenia and schizoaffective disorder, is one medication known to have the potential to induce seizures as an adverse effect [7]. A comprehensive work-up is required to ascertain potential precipitants of seizures, as the long-term management of epileptic seizures is vastly different from non-epileptic seizures [1]. ...
Posterior shoulder dislocations are a recognised complication of generalised seizure episodes. Although less frequent, anterior shoulder dislocations are now being acknowledged as an emerging consequence. Particularly when they occur bilaterally, they can contribute to diagnosing a seizure disorder in a patient who shows no other signs during the post-ictal period. This article presents a case of bilateral anterior shoulder dislocations in an otherwise physically healthy young Sudanese gentleman following a generalised seizure episode on clozapine for a schizoaffective disorder.
The case aims to raise awareness of the occurrence of this phenomenon and emphasises the importance of timely diagnostic testing, seizure prophylaxis, and follow-up to minimise the risk of further seizure episodes and potential consequences. Additionally, there is a discussion regarding the utility of monitoring clozapine concentrations.
... Seizure is a common neurological symptom with a reported lifetime prevalence of up to 10%. Further, seizures constitute 1% of the reasons to visit the emergency department [1]. Importantly, a significant proportion of these patients have a first seizure. ...
... Virtually, any cerebral insult could cause a seizure. The possible etiologies of seizures are broad and include a wide range of pathologies, such as ischemic or hemorrhagic stroke, traumatic brain insult, brain abscess, meningitis, and cerebral venous thrombosis [1]. Neuroimaging studies are vital to evaluate the culprit of structural cerebral lesions. ...
Seizure is a prevalent symptom and is an important neurological complaint in the emergency department. Patients with first-time seizures require a thorough evaluation to determine the possible etiologies and identify any causative pathology. Further, neuroimaging studies are vital to identifying the structural culprits. We report the case of a 35-year-old man who was brought to the emergency department with abnormal repetitive shaking movements that were witnessed by his spouse. Before the event, he became dizzy and fell to the ground. During the episode, he was not aware of his surrounding. He developed uprolling of his eyes and had frothy secretions from the mouth. On physical examination, the patient was drowsy but fully oriented. There were no signs of focal neurological deficit. Routine laboratory investigations, including hematological and biochemical profiles, yielded normal results. He was referred to undergo magnetic resonance imaging of the brain. The scan demonstrated the presence of a well-circumscribed lesion in the left Sylvian fissure with high signal intensity on T1- and T2-weighted image with suppression on the fat-suppressed sequence and no post-contrast enhancement. The radiological impression was of Sylvian fissure lipoma. The lesion was successfully resected surgically and the patient had an uneventful recovery with no complaints at the follow-up visits. Sylvian fissure lipoma is among the rarest locations of intracranial lipoma. Despite this, physicians should remember this lesion when they encounter a brain lesion with high signal intensity on T1- and T2-weighted images. While the majority of cases are incidental, an intracranial lipoma can be an etiology of first-time seizures in adults.
... A seizure is a short-term change in regular electrical activity in the brain that leads to changes in perception, awareness, movement, or behavior (1). Seizures, broadly classified as febrile and non-febrile, account for approximately 1% of emergency department admissions (2). ...
... A seizure is a brief change in regular electrical activity in the brain resulting in alterations in awareness, perception, behavior, or movement [1]. It occurs in approximately 4 − 10% of children and accounts for 1% of all emergency department (ED) visits [2]. ...
Background
Electroencephalogram and neuroimaging in pediatric patients with new-onset afebrile seizures are performed to detect any underlying pathological severe condition that may require emergent neuro-intervention and guide prognosis. This study aims to determine the predictors of abnormal EEG and neuroimaging in children presenting to the emergency department with new-onset afebrile seizures.
Methods
This single-center cross-sectional study was conducted at a tertiary care hospital in Karachi, Pakistan, from July 01, 2019, to June 30, 2021. All patients aged one month to 18 years who presented with new-onset afebrile seizures were included. Demographic and clinical data were recorded, including age, gender, seizure type, duration of seizure, associated signs and symptoms, and disposition. Multivariable regression analysis was applied to determine the predictors of abnormal EEG and CT scan or MRI findings.
Results
Out of 201 participants, most patients were in the infantile age group (41.3%), with an equal gender distribution. The most common type of seizure was generalized onset 152 (75.6%). EEG was performed on a total of 126 patients (62.7%) and out of these patients, 67 patients (53.1%) had abnormal findings. In a multivariable analysis, the age group of 5 to 10 years and seizure duration of more than 5 min were significantly associated with higher odds of abnormal EEG findings. In contrast, only the focal onset of seizure was significantly associated with higher odds of abnormal neuroimaging findings.
Conclusion
The study emphasizes the need for a protocol regarding the performance of EEG and neuroimaging in children presenting to the ED with new-onset afebrile seizures that would aid emergency physicians in the direction of appropriate management, thus ensuring a better quality of patient care and outcomes.
Background:
The English community pharmacy New Medicine Service (NMS) significantly increases patient adherence to medicines, compared with normal practice. We examined the cost effectiveness of NMS compared with normal practice by combining adherence improvement and intervention costs with the effect of increased adherence on patient outcomes and healthcare costs.
Methods:
We developed Markov models for diseases targeted by the NMS (hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease, asthma and antiplatelet regimens) to assess the impact of patients' non-adherence. Clinical event probability, treatment pathway, resource use and costs were extracted from literature and costing tariffs. Incremental costs and outcomes associated with each disease were incorporated additively into a composite probabilistic model and combined with adherence rates and intervention costs from the trial. Costs per extra quality-adjusted life-year (QALY) were calculated from the perspective of NHS England, using a lifetime horizon.
Results:
NMS generated a mean of 0.05 (95% CI 0.00-0.13) more QALYs per patient, at a mean reduced cost of -£144 (95% CI -769 to 73). The NMS dominates normal practice with a probability of 0.78 [incremental cost-effectiveness ratio (ICER) -£3166 per QALY]. NMS has a 96.7% probability of cost effectiveness compared with normal practice at a willingness to pay of £20,000 per QALY. Sensitivity analysis demonstrated that targeting each disease with NMS has a probability over 0.90 of cost effectiveness compared with normal practice at a willingness to pay of £20,000 per QALY.
Conclusions:
Our study suggests that the NMS increased patient medicine adherence compared with normal practice, which translated into increased health gain at reduced overall cost.
Trial registration:
ClinicalTrials.gov Trial reference number NCT01635361 ( http://clinicaltrials.gov/ct2/show/NCT01635361 ). Current Controlled trials: Trial reference number ISRCTN 23560818 ( http://www.controlled-trials.com/ISRCTN23560818/ ; DOI 10.1186/ISRCTN23560818 ). UK Clinical Research Network (UKCRN) study 12494 ( http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12494 ).
Funding:
Department of Health Policy Research Programme.
The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) "partial" becomes "focal"; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types.
Nearly one-third of patients with focal epilepsy experience disabling seizures that are refractory to pharmacotherapy. Drug-resistant focal epilepsy is, however, potentially curable by surgery. Although lesions associated with the epileptic focus can often be accurately detected by MRI, in many patients conventional imaging based on visual evaluation is unable to pinpoint the surgical target. Patients with so-called cryptogenic epilepsy represent one of the greatest clinical challenges in many tertiary epilepsy centers. In recent years, it has become increasingly clear that epilepsies that are considered cryptogenic are not necessarily nonlesional, the primary histopathological substrate being subtle cortical dysplasia. This Review considers the application of new advances in brain imaging, such as MRI morphometry, computational modeling and diffusion tensor imaging. By revealing dysplastic lesions that previously eluded visual assessments, quantitative structural MRI methods such as these have clearly demonstrated an increased diagnostic yield of epileptic lesions, and have provided successful surgical options to an increasing number of patients with 'cryptogenic' epilepsy.
Epilepsy affects approximately 50 million people worldwide, with an annual incidence of 50 to 70 cases per 100,000 population. The condition can strike at any time of life, with an immediate impact on everyday activities and routine. Key to optimal management is swift referral to an epilepsy specialist, appropriate investigation, and timely institution of antiepileptic drug therapy. In the past 20 years, the explosion of 13 new agents into the marketplace has greatly increased the potential for therapeutic intervention. This article explores the rationale for treatment selection in adults with epilepsy.
To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for specific etiologies.
Systematic review of the literature and of epidemiologic studies.
An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well-defined epileptogenic drugs.
Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification.
Neurocysticercosis is a disease of poverty and underdevelopment. Little is known about the natural history of the infection in humans, but some of the mechanisms whereby the parasite remains silent and evades the host immune response are understood. Symptomatic neurocysticercosis usually results from host inflammatory response after parasite death, and the clinical manifestations can be diverse. There is no evidence that cysticidal treatment does more good than harm in addition to conventional antiepileptic treatment. Population control measures involving immunisation or mass treatment have not shown long term effectiveness.Epilepsy, similarly to neurocysticercosis, is a largely unrecognised but increasing burden on the welfare and economies of developing countries. The technology of drug treatment and psychosocial rehabilitation is well known but requires widespread and effective dissemination at low cost. There is little epidemiological data on risk factors for epilepsy in developing countries on which to base prevention strategies. The public health prioritisation of chronic disorders such as epilepsy remains a challenge for policy and practice in developing countries. For both neurocysticercosis and epilepsy, there is a dilemma about whether limited public resources would better be spent on general economic development, which would be expected to have a broad impact on the health and welfare of communities, or on specific programmes to help individual affected people with neurocysticercosis and epilepsy. Either approach requires detailed economic evaluation.
Over an 18-month period, all incident cases of neurological disorders were ascertained prospectively in an unselected urban population based in 13 general practices in the London area by a General Practice Linkage Scheme with the National Hospital for Neurology and Neurosurgery. In three of these practices, the lifetime prevalence of neurological disorders was also assessed. A population of 100 230 patients registered with participating general practices was followed prospectively for the onset of neurological disorders. Multiple methods of case finding were used to maintain accuracy. The age- and sex-adjusted incidence rates of neurological disorders were calculated. The lifetime prevalence of neurological disorders was surveyed in 27 658 of the patients. The age- and sex-adjusted incidence rates were calculated for major neurological conditions. [These are expressed as rates per 100 000 persons per annum, with 95% confidence intervals (CI) in parentheses]. The commonest of these were first cerebrovascular events, 205 (CI: 183, 230); shingles, 140 (CI: 104, 184); diabetic polyneuropathy, 54 (CI: 33, 83); compressive neuropathies, 49 (CI: 39, 61); epilepsy, 46 (CI: 36, 60); Parkinson's disease, 19 (CI: 12, 27); peripheral neuropathies, 15 (CI: 9, 23); CNS infections, 12 (CI: 5, 13); post-herpetic neuralgia, 11 (CI: 6, 17); and major neurological injuries, 10 (CI: 4, 11). Lifetime prevalence rates are also reported (expressed as rate per 1000 persons with 95% CI). The most prevalent conditions were: completed stroke, 9 (CI: 8, 11); transient ischaemic attacks, 5 (CI: 4, 6); active epilepsy, 4 (CI: 4, 5); congenital neurological deficit, 3 (CI: 3, 4); Parkinson's disease, 2 (CI: 1, 3); multiple sclerosis, 2 (CI: 2, 3); diabetic polyneuropathy, 2 (CI: 1, 3); compressive mononeuropathies, 2 (CI: 2, 3); and sub-arachnoid haemorrhage, 1 (CI: 0.8, 2). Overall, the onset of 625 neurological disorders was observed per 100 000 population annually. Six percent of the population had at some time had a neurological disorder. This is the first study of the incidence and lifetime prevalence of neurological disorders in recent times; we found that these disorders give rise to significant morbidity in the community.
Purpose of review:
Recognizing the cause of a first seizure and identifying the etiology of epilepsy are essential for management. A systematic approach to patients who present with a first seizure helps distinguish between an acute symptomatic seizure, a provoked or unprovoked seizure, and potential mimickers. Routine testing with EEG and MRI may reveal a predisposition for further seizures and help to establish the underlying epilepsy syndrome. An acquired etiology can be identified in 30% of patients with established epilepsy. The remaining 70% of patients have a presumably genetic etiology. Particularly in patients with specific epilepsy syndromes or suspicion for an autosomal dominant inheritance, genetic testing and counseling should be considered.
Recent findings:
Neuroimaging, autoimmune antibodies, and genetic testing have revolutionized our ability to investigate the etiology of many epilepsies. The new epilepsy classification distinguishes structural, metabolic, genetic, infectious, and immune-mediated etiologies, which often help determine prognosis and treatment.
Summary:
There is growing acceptance and demystification of the term epilepsy as the most common cause for recurrent seizures. The new classification of epilepsy does not stop with the recognition of particular epilepsy syndromes but aims to determine the underlying etiology. This can lead to earlier recognition of surgical candidates, a better understanding of many of the genetic epilepsies, and medical treatments aimed at the underlying mechanism causing the disease.
Purpose of review:
For patients living with epilepsy, quality of life is determined not only by seizure control but by mood, antiepileptic drug adverse effects, relationships, and access to education, employment, and transportation. This article reviews some of the most commonly encountered concerns associated with epilepsy, including mood disorders, driving, injuries, mortality, bone health, genetic burden, and impact on relationships.
Recent findings:
People with epilepsy are at increased risk for anxiety, depression, and suicide. Depression is underrecognized in patients with epilepsy, but effective validated screening tools are available for use. Mortality rates for people with epilepsy are 2 times higher than those of the general population, but much of this is attributable to underlying conditions rather than seizures. Sudden unexpected death in epilepsy (SUDEP) occurs in an estimated 1:1000 adults with epilepsy per year, and the risk can be reduced by improved observation and seizure control. An increased risk of injury, including fractures, is also present in patients with epilepsy. Reduced bone health leading to increased fracture risk is an important negative consequence of long-term use of antiepileptic medication. Seizures while driving can also cause accidents and injury. Despite the importance of driving for people with epilepsy, physicians are underperforming in providing counsel about driving.
Summary:
Optimal care of the patient with epilepsy includes addressing risks to emotional health, physical health including fractures and SUDEP, social health, and an independent lifestyle. Identification of and treatments to reduce these risks can do more to improve quality of life than a narrow clinical focus on seizure control alone.
Seizure- and epilepsy-related complications are a common cause of emergency medical evaluation, accounting for 5% of 911 calls and 1% of emergency department visits. Emergency physicians and neurologists must be able to recognize and treat seizure- and epilepsy-related emergencies. This review describes the emergency evaluation and management of new onset seizures, breakthrough seizures in patients with known epilepsy, status epilepticus, acute symptomatic seizures, and acute adverse effects of antiepileptic drugs.
Objective
To determine the frequency and yield of neuroimaging in patients with known seizure disorders presenting to the emergency department (ED) with recurrent (nonindex) seizures.
Methods
We reviewed 822 consecutive ED visits for nonindex seizures at the Oregon Health & Science University and the VA Portland Health Care System. For each visit, we abstracted details of the clinical presentation, whether neuroimaging was obtained, the results of neuroimaging, and the results of previous neuroimaging studies, when available. We determined whether ED neuroimaging led to an acute change in patient management (yield). Clinical factors associated with obtaining ED neuroimaging, and with the yield of neuroimaging, were evaluated by multivariate logistic regression.
Results
A majority (78%) of ED seizure visits were for nonindex seizures. Neuroimaging was obtained in 381 of 822 nonindex seizure visits (46%). Of these, 11 imaging studies (3%) led to an acute change in patient management, 8 (2%) after excluding false‐positive scans. Acute head trauma, prolonged alteration of consciousness, and a focal neurologic examination at presentation were associated with an increased yield of ED neuroimaging. Absent any of these 3 clinical factors the true positive yield of neuroimaging was zero.
Significance
ED neuroimaging was performed in nearly half of all patients presenting with nonindex seizures. A more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at presentation, could decrease imaging frequency with minimal loss of yield.
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.
Background:
Driving restrictions in epilepsy are intended to safeguard public and personal safety; however, these limitations inhibit socialization, restrict employment, and reduce self-esteem in patients with seizures. A large proportion of patients with seizures continue to drive, and factors leading to noncompliance with driving regulations are poorly understood. Thus, the patients' perspective on driving safety is not incorporated into the existing counseling tools on driving safety in epilepsy. The present study assessed social, economic, and psychological perceptions related to driving restrictions in patients with refractory and pharmacotherapy-controlled seizures at the single epilepsy center and identified impediments for safe driving.
Methods:
Data were obtained from an anonymous survey completed by 25 adult patients in the presurgical group (PG) with refractory epilepsy and 46 patients in the ambulatory group (AG) with confirmed epilepsy which did not meet criteria for refractoriness. The questionnaire (administered via Research Electronic Data Capture (REDCap)) addressed seizure and driving history, knowledge of driving restrictions, and social consequences of losing driving privileges.
Results:
Eighty-seven percent of all responders experienced seizures with alteration of awareness; however, 34% of patients continued to drive during the time when they were legally restricted, and 6% had accidents related to seizures. All responders reported their seizure status accurately to the treating physician, and 93% understood state-based driving restrictions. The median time from the last seizure was shorter, and the duration of last driving restriction was longer in the PG compared with the AG (1 vs. 20weeks, and 12 vs. 24weeks, respectively). Despite that, the proportions of patients driving at the time of survey were not significantly different between the two groups. Nearly 80% of all patients stated that driving restrictions reduced their quality of life, and 70% believed that these restrictions carry a social stigma. Employment was chosen to be the most affected by driving restrictions from a list of four social domains by the majority of patients in both groups. Notably, the employment rate was 26% higher in the AG compared with the PG. The lack of public transportation was regarded as a hurdle by more than 60% of patients in each group with greater than two-thirds of patients relying on other drivers for transportation.
Conclusions:
These findings suggest that patients with refractory and pharmacotherapy-controlled seizures are similarly likely to drive a vehicle, disregarding a practitioner's advice and state restrictions. The lack of public transportation is a shared constraint and likely leads to reduced compliance with driving regulations. Driving restrictions carry social stigma and limit the employment of patients with epilepsy, regardless of the refractory seizure status.
Epilepsy is surrounded by prejudice and stigma. Little is known about the perception of stigma by cohabiting relatives (CR) of people with epilepsy (PWE). The study investigated whether the Stigma Scale of Epilepsy (SSE) scores of 90 CR and 148 adult PWE were related to the PWE's clinical aspects and QOLIE-31 at a significance level of p<0.05. The SSE scores of the CR were equivalent to those of PWE dyads (ICC=0.385, p=0.001). Cohabiting relatives of PWE with depressive disorder perceived more stigma (t-test: p=0.038). Higher perceived stigma by PWE was significantly related to exclusively generalized seizures (p=0.005), longer disease duration (p=0.002), and higher perception of stigma by CR in the linear regression model. Both PWE and CR have high perception of stigma, which is related to clinical aspects. Higher perceptions of stigma by PWE and CR are associated with worse QoL in PWE.
Status epilepticus (SE) is a severe medical condition. To determine its epidemiology and outcome of SE, we performed a meta-analysis to investigate the etiology, incidence and mortality of SE. We searched PubMed and Embase between Jan 1, 2000, and Oct 31, 2016, with no regional restrictions, for observational studies of the etiology, incidence and mortality of SE. Forty-three studies were included in the meta-analysis. The pooled crude annual incidence rate, the pooled case fatality rate and the pooled crude annual mortality rate of SE were 12.6/100,000 (95% CI: 10.0–15.3), 14.9% (95% CI: 11.7–118.7) and 0.98/100,000 (95% CI: 0.74–1.22), respectively. Elderly subjects with SE had a higher case fatality rate (28.4% (95% CI: 17.7–42.3)) and crude annual incidence rate (27.1% (95% CI: 15.8–38.2)). The most important etiology-specific attributable fraction of patients with SE was acute symptomatic etiology (OR 0.411, 95% CI: 0.315–0.507). Age and economic income contributed to differences in SE incidence and short-term case fatality rate.
Objective:
Continuous EEG (cEEG) monitoring of critically ill patients has gained widespread use, but there is substantial reported variability in its use. We analyzed cEEG and antiseizure drug (ASD) usage at three high volume centers.
Methods:
We utilized a multicenter cEEG database used daily as a clinical reporting tool in three tertiary care sites (Emory Hospital, Brigham and Women's Hospital and Yale - New Haven Hospital). We compared the cEEG usage patterns, seizure frequency, detection of rhythmic/periodic patterns (RPP), and ASD use between the sites.
Results:
5792 cEEG sessions were analyzed. Indication for cEEG monitoring and recording duration were similar between the sites. Seizures detection rate was nearly identical between the three sites, ranging between 12.3% and 13.6%. Median time to first seizure and detection rate of RPPs were similar. There were significant differences in doses of levetiracetam, valproic acid, and lacosamide used between the three sites.
Conclusions:
There was remarkable uniformity in seizure detection rates within three high volume centers. In contrast, dose of ASD used frequently differed between the three sites.
Significance:
These large volume data are in line with recent guidelines regarding cEEG use. Difference in ASD use suggests discrepancies in how cEEG results influence patient management.
Importance
Approximately 8% to 10% of the population will experience a seizure during their lifetime. Only about 2% to 3% of patients go on to develop epilepsy. Understanding the underlying etiology leading to an accurate diagnosis is necessary to ensure appropriate treatment and that patients with low risk for recurrence are not treated unnecessarily.
Observations
Patients can present with new-onset seizure for a variety of reasons such as acute symptomatic seizures due to acute brain injury or metabolic derangements, or unprovoked seizures that are the initial manifestation of epilepsy. A patient history and physical examination may identify features more consistent with an epileptic event and laboratory studies and brain imaging can identify an acute insult contributing to the presentation. Patients diagnosed with first-time unprovoked seizure require electroencephalography and epilepsy protocol–specific magnetic resonance imaging of the brain, which includes thin-cut coronal slices to determine risk of recurrence and the need for long-term treatment. In patients who meet the criteria for diagnosis of epilepsy, a carefully selected antiepileptic medication with consideration of comorbidities, adverse effect profile, and type of epilepsy is essential along with appropriate counseling.
Conclusions and Relevance
Approximately 3% of the population will develop epilepsy but 2 to 3 times as many patients will experience a single seizure or seizure-like event. A diagnosis of epilepsy has significant medical, social, and emotional consequences. A careful patient history and physical examination, electroencephalography, and brain imaging are necessary to separate patients with acute symptomatic seizures, single unprovoked seizures, and nonepileptic events from those with new-onset epilepsy.
The initial evaluation of the patient with suspected epilepsy is multifaceted and includes a careful history, diagnostic evaluation (EEG and brain imaging) and prompt referral to an epilepsy specialist to clarify seizure types and epilepsy syndrome. Screening for mental health conditions also should be considered, along with neurocognitive testing when deficits of language, memory, learning, attention, or executive function are present or when MRI shows involvement of brain regions implicated in cognitive function. In this review, we examine the approach to the initial evaluation of those with new-onset unprovoked seizures and possible epilepsy.
People with epilepsy identify driving and employment among their major concerns. People with controlled seizures may be permitted to drive in every state in the United States, but people with uncontrolled seizures are restricted from licensure. Unemployment and underemployment for people with epilepsy are serious problems that depend on the frequency and type of seizure disorder and associated medical and psychological problems. Most jobs, with reasonable accommodation by employers, are suitable for people with epilepsy. Federal protections through the Americans with Disabilities Act confer civil rights protection by law on people with disabilities such as epilepsy.
Brain imaging has a crucial role in the presurgical assessment of patients with epilepsy. Structural imaging reveals most cerebral lesions underlying focal epilepsy. Advances in MRI acquisitions including diffusion-weighted imaging, post-acquisition image processing techniques, and quantification of imaging data are increasing the accuracy of lesion detection. Functional MRI can be used to identify areas of the cortex that are essential for language, motor function, and memory, and tractography can reveal white matter tracts that are vital for these functions, thus reducing the risk of epilepsy surgery causing new morbidities. PET, SPECT, simultaneous EEG and functional MRI, and electrical and magnetic source imaging can be used to infer the localisation of epileptic foci and assist in the design of intracranial EEG recording strategies. Progress in semi-automated methods to register imaging data into a common space is enabling the creation of multimodal three-dimensional patient-specific datasets. These techniques show promise for the demonstration of the complex relations between normal and abnormal structural and functional data and could be used to direct precise intracranial navigation and surgery for individual patients.
Purpose of review:
Assessment of the patient with a first seizure is a common and important neurologic issue. Less than 50% of patients who have a first unprovoked seizure have a second seizure; thus, the evaluation should focus on determining the patient's risk of seizure recurrence.
Recent findings:
A number of population studies, including some classic reports, have identified the relative risk factors for subsequent seizure recurrence. The 2014 update of the International League Against Epilepsy definition of epilepsy incorporates these findings, and in 2015, the American Academy of Neurology published a guideline that analyzed the available data.
Summary:
Provoked or acute symptomatic seizures do not confer increased risk for subsequent unprovoked seizure recurrence. Multiple seizures in a given 24-hour period do not increase the risk of seizure recurrence. Remote symptomatic seizures, an epileptiform EEG, a significant brain imaging abnormality, and nocturnal seizures are risk factors for seizure recurrence. Antiepileptic drug therapy delays the time to second seizure but may not influence long-term remission.
We conducted a randomized multicenter clinical trial on 397 patients ranging in age from 2 to 70 years to assess the effectiveness of treatment of the first unprovoked epileptic seizure. Subjects seen within 7 days after a first witnessed tonic-clonic seizure with or without partial onset were randomized to immediate treatment (car-bamazepine, phenytoin, phenobarbital, or sodium valproate) or to treatment with the same drugs only after seizure recurrence. We excluded individuals with acute symptomatic seizures, progressive neurologic disorders, or gross psychiatric illness. Thirty-six of 204 subjects randomized to treatment and 75 of 193 randomized to delayed treatment experienced seizure recurrence during follow-up. The cumulative time-dependent risk of relapse among treated subjects was 25% by 24 months. The corresponding figure for untreated subjects was 51%. The risk of relapse was 2.8 times higher (95% CI, 1.9 to 4.2) for untreated subjects. There were no interactions between age and EEG findings (the only predictors of risk of relapse) and treatment effects. We conclude that treatment of the first seizure with antiepileptic drugs leads to a significant reduction of the risk of relapse.
Aim:
To determine whether there is added benefit in detecting electrographic abnormalities from 16-24 hours of continuous video-EEG in adult medical/surgical ICU patients, compared to a 30-minute EEG.
Methods:
This was a prospectively enroled non-randomized study of 130 consecutive ICU patients for whom EEG was requested. For 117 patients, a 30-minute EEG was requested for altered mental state and/or suspected seizures; 83 patients continued with continuous video-EEG for 16-24 hours and 34 patients had only the 30-minute EEG. For 13 patients with prior seizures, continuous video-EEG was requested and was carried out for 16-24 hours. We gathered EEG data prospectively, and reviewed the medical records retrospectively to assess the impact of continuous video-EEG.
Results:
A total of 83 continuous video-EEG recordings were performed for 16-24 hours beyond 30 minutes of routine EEG. All were slow, and 34% showed epileptiform findings in the first 30 minutes, including 2% with seizures. Over 16-24 hours, 14% developed new or additional epileptiform abnormalities, including 6% with seizures. In 8%, treatment was changed based on continuous video-EEG. Among the 34 EEGs limited to 30 minutes, almost all were slow and 18% showed epileptiform activity, including 3% with seizures. Among the 13 patients with known seizures, continuous video-EEG was slow in all and 69% had epileptiform abnormalities in the first 30 minutes, including 31% with seizures. An additional 8% developed epileptiform abnormalities over 16-24 hours. In 46%, treatment was changed based on continuous video-EEG.
Conclusion:
This study indicates that if continuous video-EEG is not available, a 30-minute EEG in the ICU has a substantial diagnostic yield and will lead to the detection of the majority of epileptiform abnormalities. In a small percentage of patients, continuous video-EEG will lead to the detection of additional epileptiform abnormalities. In a sub-population, with a history of seizures prior to the initiation of EEG recording, the benefits of continuous video-EEG in monitoring seizure activity and influencing treatment may be greater.
The role of neuroimaging in the assessment of a firstever seizure has not been well-defined, in particular the utility of MRI when CT is normal. The results of neuroimaging (CT brain, MRI brain, or both) in 1, 013 adults with first-ever unprovoked seizure were correlated with clinical features and seizure outcome. Epileptogenic lesions were identified in 29%. Of patients with a normal CT who also had MRI, 12% had an epileptogenic lesion on MRI, the strongest independent predictor of which was a focal abnormality on EEG. Patients with an epileptogenic lesion had a higher risk of seizure recurrence, including when this was only evident on MRI.
Objectives
Patients with intractable epilepsy may benefit from epilepsy surgery especially if they have a radiologically demonstrable cerebral lesion. Dedicated magnetic resonance imaging (MRI) protocols as performed at epilepsy surgery centres can detect epileptogenic abnormalities with great sensitivity and specificity. However, many patients with epilepsy are investigated with standard MRI sequences by radiologist outside epilepsy centres (“non-experts”). This study was undertaken to compare standard MRI and epilepsy specific MRI findings in patients with focal epilepsy.
Methods
Comparison of results of standard MRI reported by “non-expert” radiologists, standard MRI evaluated by epilepsy “expert” radiologists, and epilepsy specific MRI read by “expert” radiologists in 123 consecutive patients undergoing epilepsy surgery evaluation between 1996 and 1999. Validation of radiological findings by correlation with postoperative histological examination.
Results
Sensitivity of “non-expert” reports of standard MRI reports for focal lesions was 39%, of “expert” reports of standard MRI 50%
,
and of epilepsy dedicated MRI 91%. Dedicated MRI showed focal lesions in 85% of patients with “non-lesional” standard MRI. The technical quality of standard MRI improved during the study period, but “non-expert” reporting did not. In particular, hippocampal sclerosis was missed in 86% of cases. Neuropathological diagnoses (n=90) were predicted correctly in 22% of “non-expert” standard MRI reports but by 89% of dedicated MRI reports.
Conclusions
Standard MRI failed to detect 57% of focal epileptogenic lesions. Patients without MRI lesion are less likely to be considered candidates for epilepsy surgery. Patients with refractory epilepsy should be referred to an MRI unit with epileptological experience at an early point.
Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy ( ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age‐dependent epilepsy syndrome but are now past the applicable age or who have remained seizure‐free for the last 10 years and off antiseizure medicines for at least the last 5 years. “Resolved” is not necessarily identical to the conventional view of “remission or “cure.” Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use.
A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .
Purpose
The demand for long term EEG monitoring is increasing with the emphasis on recording patients’ attacks. Outpatient ambulatory EEG is relatively inexpensive and widely available. The main disadvantage of the technique is the lack of video which can make interpretation of an ictus difficult. We investigated whether patients, if offered home video equipment, would take it, if this resulted in simultaneous EEG-video capture of an ictus and if interpretation of the recording was facilitated by the video.
Method
All ambulatory EEG patients, adults and children, were offered a camcorder to take home during a 17 month study period.
Results
130 patients/carers were offered a camcorder (93 adults, 37 children), 45 patients (35%) accepted; the main reason for not accepting were that attacks were considered too brief to record. An ictal event occurred in 34 patients (76%) with a camcorder; in 17 (50%) of these an attack was captured successfully on video. The main reasons for failure to capture events were that attacks were too brief, or that the camcorder was not operated successfully. Attacks were captured with greater success in children (14/23, 61%) than adults (3/11, 27%). Of the 17 video recordings, 14 (82%) were helpful in aiding interpretation of the ambulatory EEG.
Conclusion
In our study, home video facilities aided interpretation of ambulatory EEG recordings in approximately one third of patients. Technological advances and familiarity with portable recording devices will improve this figure and patients and their carers should be encouraged to use such facilities when available.
Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives' medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75-5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted 'prenatal/developmental cause' (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as 'idiopathic' or 'unknown cause'), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93-15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92-4.00) for focal epilepsy. In relatives of probands with focal epilepsy, standardized incidence ratios were 1.0 (95% confidence interval 0.00-2.19) for generalized epilepsy and 2.6 (95% confidence interval 1.19-4.26) for focal epilepsy. Epilepsy incidence was greater in offspring of female probands than in offspring of male probands, and this maternal effect was restricted to offspring of probands with focal epilepsy. The results suggest that risks for epilepsies of unknown and prenatal/developmental cause may be influenced by shared genetic mechanisms. They also suggest that some of the genetic influences on generalized and focal epilepsies are distinct. However, the similar increase in risk for focal epilepsy among relatives of probands with either generalized (2.5-fold) or focal epilepsy (2.6-fold) may reflect some coexisting shared genetic influences.
Objective:
To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies.
Methods:
A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003.
Results:
All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome.
Conclusions:
The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.
Approximately 1 in 26 people will develop epilepsy at some point in their lives. Although epilepsy is one of the nation's most common neurological disorders, public understanding is limited. A complex spectrum of disorders, epilepsy affects an estimated 2.2million people in the United States. Living with epilepsy is about more than just seizures; it is often defined in practical terms, such as challenges, uncertainties, and limitations in school, social situations, employment, driving, and independent living. People with epilepsy are also faced with health and community services that are fragmented, uncoordinated, and difficult to obtain. The Institute of Medicine's report (2012) [1], Epilepsy across the spectrum: promoting health and understanding, examines the public health dimensions of epilepsy with a focus on (a) public health surveillance and data collection and integration; (b) population and public health research; (c) health policy, health care, and human services; and (d) education for providers, people with epilepsy and their families, and the public. The report's recommendations range from the expansion of collaborative epilepsy surveillance efforts to the independent accreditation of epilepsy centers, to the coordination of public awareness efforts, and to the engagement of people with epilepsy and their families in education, dissemination, and advocacy activities. Given the current gaps in epilepsy knowledge, care, and education, there is an urgent need to take action-across multiple dimensions-to improve the lives of people with epilepsy and their families. The realistic, feasible, and action-oriented recommendations in this report can help enable short- and long-term improvements for people with epilepsy.
Purpose: We describe first unprovoked seizures and newly diagnosed epilepsies at initial presentation, with a special emphasis on epilepsy syndromes, in a large cohort recruited in the mid-1990s in France.
Methods: The French Foundation for Research on Epilepsy set up a network to conduct a prospective study of patients with newly diagnosed unprovoked seizures. Information was provided by 243 child or adult neurologists. Four neurologists classified each case according to the International League Against Epilepsy (ILAE) criteria. First-seizure patients and patients with previously undiagnosed seizures were compared.
Results: Between May 1, 1995, and June 30, 1996, 1,942 patients aged from 1 month to 95 years were identified: 926 (47.7%) with a single seizure and 1,016 (52.3%) with newly diagnosed epilepsy. All but 17 patients had EEGs. In the first-seizure and newly-diagnosed-epilepsy groups, neuroimaging studies were performed in 78.2 and 68.3% of patients, and medication prescribed in 54.1 and 89.6%, respectively. There were significant differences between the two groups with respect to age at onset and diagnosis, sex, etiology, several specific syndromes, as well as the type and presentation of initial seizure. In patients for whom the first seizure was convulsive, only sex, multiple seizures in a day or status epilepticus, and cryptogenic localization-related syndrome differed between the two groups.
Conclusions: Approximately half of patients who first came to attention for an unprovoked seizure already met epidemiologic criteria for epilepsy. There were significant differences between the types of patients with a first seizure and those with newly diagnosed epilepsy. One or several seizures at diagnosis did not influence the diagnostic assessment of the patients but had a strong influence on the initiation of treatment.
To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy.
Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: (A) early and sustained seizure freedom; (B) delayed but sustained seizure freedom; (C) fluctuation between periods of seizure freedom and relapse; and (D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year.
A total of 1,098 patients were included (median age 32 years, range 9-93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p < 0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen.
Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.
Adverse effects (AEs) are a major concern when starting antiepileptic drug (AED) treatment. This study quantified the extent to which AE reporting in people with new-onset seizures started on AEDs is attributable to the medication per se, and investigated variables contributing to AE reporting.
We pooled data from 2 large prospective studies, the Multicenter Study of Early Epilepsy and Single Seizures and the Northern Manhattan Study of incident unprovoked seizures, and compared adverse event profile (AEP) total and factor scores between adult cases prescribed AEDs for new-onset seizures and untreated controls, adjusting for several demographic and clinical variables. Differences in AEP scores were also tested across different AED monotherapies and controls, and between cases and controls grouped by number of seizures.
A total of 212 cases and 206 controls were identified. Most cases (94.2%) were taking low AED doses. AEP scores did not differ significantly between the 2 groups. Depression, female gender, symptomatic etiology, younger seizure onset age, ≥2 seizures, and history of febrile seizures were associated with higher AEP scores. There were no significant differences in AEP scores across different monotherapies and controls. AEP scores increased in both cases and controls with increasing number of seizures, the increment being more pronounced in cases.
When AED treatment is started at low doses following new-onset seizures, AE reporting does not differ from untreated individuals. Targeting specific factors affecting AE reporting could lead to improved tolerability of epilepsy treatment.
To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new-onset epilepsy.
Randomized, double-blind, 28-day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new-onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure.
At day 28, the estimated seizure-free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment-related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047).
This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new-onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new-onset epilepsy requiring rapid treatment initiation.
To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.
To compare mortality and subsequent unprovoked seizure risk in a population-based study of acute symptomatic seizure and first unprovoked seizure due to static brain lesions.
We ascertained all first episodes of acute symptomatic seizure and unprovoked seizure due to central nervous system (CNS) infection, stroke, and traumatic brain injury (TBI). Subjects were residents of Rochester, Minnesota, identified through the Rochester Epidemiology Project's records-linkage system between 1/1/55 and 12/31/84. Information was collected on age, gender, seizure type, etiology, status epilepticus (SE), 30-day and 10-year mortality, and subsequent episodes of unprovoked seizure.
Two hundred sixty-two individuals experienced a first acute symptomatic seizure and 148 individuals experienced a first unprovoked seizure, all due to static brain lesions. Individuals with a first acute symptomatic seizure were 8.9 times more likely to die within 30 days compared to those with a first unprovoked seizure [95% confidence intervals (CI) = 3.5-22.5] after adjustment for age, gender, and SE. Among 30-day survivors, the risk of 10-year mortality did not differ. Over the 10-year period, individuals with a first acute symptomatic seizure were 80% less likely to experience a subsequent unprovoked seizure compared with individuals with a first unprovoked seizure [adjusted rate ratio (RR) = 0.2, 95% CI = 0.2-0.4].
The prognosis of first acute symptomatic seizures differs from that of first unprovoked seizure when the etiology is stroke, TBI, and CNS infection. Acute symptomatic seizures have a higher early mortality and a lower risk for subsequent unprovoked seizure. These differences argue against the inclusion of acute symptomatic seizures as epilepsy.
An epidemiologic survey began on March 1, 1984, and ended on February 28, 1985. During this period, all neurologists and electroencephalographers of the department of Gironde, an administrative district of the French Southwest (1,128,164 residents in 1982) obtained information by questionnaire from all persons who had experienced an epileptic seizure for the first time in their lives. Recurrent, isolated, and situation‐related seizures were included. Febrile convulsions and neonatal seizures were excluded. The global incidence rate of diagnosed epileptic seizures was 71.3/100,000. The incidence rates per year and per 100,000 persons by type of epileptic syndrome were 1.7 for idiopathic and 13.6 for symptomatic localization‐related epilepsies, S.6 for idiopathic and 1.1 for symptomatic generalized epilepsies, 1.9 for undetermined epilepsies, 29.0 for situation‐related seizures, 18.3 for isolated seizures, and 0.3 for television epilepsies. Other epileptic syndromes were not represented. Using a classification of epileptic syndromes and not of epileptic seizures reduces difficulties in an epidemiologic survey. Diagnosis of an epileptic syndrome is time dependent, however, and at follow‐up some patients shift from one group to another.
RÉSUMÉ
Pendant un an (1 mars 1984 à 28 février 1985), tous les neuro‐logues et électroencéphalographistes de la Gironde (population du département en 1982: 1,128,164 personnes) ont recueilli des informations sur tous les habitants du département ayant eu pour la première fois de leur vie une crise épileptique pendant cette période. Les crises répétées, les crises uniques, et les crises contemporaries d'une affection aiguë ont été retenues. Les convulsions fébriles et les crises néonatales ont été exclues. II a été trouvé une incidence annuelle globale de 71.3/100,000 pour les crises diagnostiquées. Le taux d'incidence annuelle des divers syndromes a été pour 100,000 personnes, de 1.7 pour les épilepsies partielles idiopathiques, 13.6 pour les épilepsies partielles symptomatiques, 5.6 pour les épilepsies généralisées idiopathiques, 1.1 pour les épilepsies généralisées symptomatiques, 1.9 pour les épilepsies indéterminées, 29.0 pour les crises symptomatiques aiguës, 18.3 pour les crises isolées, et 0.3 pour les épilepsies de la télévision. Les autres syndromes épileptiques n'étaient pas représentés. Utiliser une classification des syndromes épileptiques et non des crises réduit les difficultés d'une enquête épidémiologique. Toutefois, l'inclusion dans un syndrome dépend du moment où est vu le patient, et des changements se produisent en cours d'évolution.
RESUMEN
El día 1 o de marzo de 1984 se inició un estudio epidemiológico que terminó el 28 de Febrero de 1985. Durante este periodo todos los neurólogos y electroencefalografistas del Departamento de Gironde, un distrito administrativo del Sudoeste de Francia (1.128.164 residentes en 1982), mediante un cuestionario obtuvieron información de todas las personas que habían experimentado un ataque epiléptico por primera vez en su vida. También se incluyeron los ataques recurrentes, los aislados y los relacionados con ciertas situaciones. Se excluyeron los ataques febriles y las convulsiones neonatales. La incidencia global del diagnóstico de ataques epilépticos fue 71.3/100.000. Las cifras de incidencia por años y por 100.000 personas y según los tipos de ataques epilépticos fueron: 1.7 idiopáticos y 13.6 para epilepsías sintomáticas en relación con la localización; 5.6 idiopáticas y 1.1 epilepsías generalizadas sintomáticas; 1.9 para epilepsías indeterminadas; 29.0 para ataques relacionados con ciertas situaciones; 18.3 para ataques aislados y 0.3 para epilepsias precipitadas por la televisión. Otros síndromes epilépticos no consiguieron representatión. Utilizando una clasificación de síndromes epilépticos y no de ataques epilépticos, reduce las dificultades de los estudios epidemiológicos. Sin embargo el diagnóstico de síndrome epiléptico depende del tiempo y durante el seguimiento algunos enfermos pueden cambiar de un grupo a otro.
ZUSAMMENFASSUNG
Zwischen dem 01. März 1984 und dem 28. Febr. 1985 wurde eine epidemiologische Umfrage durchgeführt. Während dieses Zeitraumes sammelten alle Neurologen und EEG‐Befunder aus dem Department Gironde, einem administrativen Distrikt in Süd‐west‐Frankreich (1,128,164 Einwohner 1982) mit Hilfe eines Fragebogens Informationen über alle Personen, die zum ersten Mai in ihrem Leben einen epileptischen Anfall erlitten. Wiederholte, isolierte und situative Anfälle wurden eingeschlossen. Fieberkrämpfe sowie Neugeborenenkrämpfe wurden ausgeschlossen. Die globale Inzidenz der diagnostizierten Anfälle betrug 71,3/100.000. Die Inzidenz pro Jahr und pro 100.000 Personen aufgeschlüsselt nach dem Epilepsiesyndrom betrugen: 1,7 für ideopathische und 13,6 für symptomatische partielle Epilepsien, 5,5 für idiopathische und 1,1 für symptomatische generalisierte Epilepsien, 1,9 für unklare Epilepsien, 29,0 für situative Anfälle, 18,3 für isolierte Anfälle und 0,3 für fotosensitive Epilepsien. Andere epileptische Syndrome waren nicht vertreten. Die Anwendung einer Klassifikation epileptischer Syndrome und nicht von epileptischen Anfällen reduzierte Schwierigkeiten der epidemiologischen Umfrage. Trotzdem ist die Diagnose eines epileptischen Syndroms zeitabhängig und in Nachuntersuchungen wechseln einige Patienten von einer Gruppe zu einer anderen.
We determined the incidence of seizures due to acute CNS insults for residents of Rochester, Minnesota, U.S.A., from 1935 through 1984. The age-adjusted incidence rates for 1955-1984, the period of most complete case ascertainment, was 39.0/100,000 person-years (United States 1970 population as standard). The age-adjusted incidence was considerably higher in men: 52.0 as compared with 29.5 in women. The 3.6% risk of experiencing an acute symptomatic seizure in an 80-year lifespan approaches that of developing epilepsy. The major causes of acute symptomatic seizures were traumatic brain injury, cerebrovascular disease, drug withdrawal, and CNS infections. Each type of acute symptomatic seizure has age, gender, and time period patterns that reflect the occurrence of the underlying cause.
In a prospective study, we have followed 347 children identified at the time of a first unprovoked seizure for a mean of 46 months. To date, 135 (39%) have experienced a seizure recurrence. In this study, we analyzed recurrence risk as a function of whether the child was asleep or awake at the time of the first seizure. The cumulative recurrence risks for children whose first seizure occurred in sleep was 28% at 0.5 years, 39% at 1 year, 53% at 2 years, and 55% at 4 years, compared with recurrence risks of 18%, 23%, 30%, and 35% at the same intervals in children whose first seizure occurred while awake (p < 0.001). The association of a first seizure during sleep with an increased recurrence risk was present primarily in children with idiopathic seizures. It occurred in both those with a normal and an abnormal EEG. On multivariable analysis, sleep state, etiology, and the EEG were statistically significant predictors of recurrence risk. In children who experienced a seizure recurrence, the recurrences occurred in the same sleep state in 73% of the cases (p < 0.0001). This was also true of subsequent recurrences. We conclude that the occurrence of a first seizure in sleep is associated with an increased risk of recurrence. Subsequent seizures, if they do occur, usually occur in the same sleep state as the initial seizure.
The incidence of epilepsy and of all unprovoked seizures was determined for residents of Rochester, Minnesota U.S.A. from 1935 through 1984. Age-adjusted incidence of epilepsy was 44 per 100,000 person-years. Incidence in males was significantly higher than in females and was high in the first year of life but highest in persons aged > or = 75 years. Sixty percent of new cases had epilepsy manifested by partial seizures, and two thirds had no clearly identified antecedent. Cerebrovascular disease was the most commonly identified antecedent, accounting for 11% of cases. Neurologic deficits from birth, mental retardation and/or cerebral palsy, observed in 8% of cases, was the next most frequently identified preexisting condition. The cumulative incidence of epilepsy through age 74 years was 3.1%. The age-adjusted incidence of all unprovoked seizures was 61 per 100,000 person-years. Age- and gender-specific incidence trends were similar to those of epilepsy, but a higher proportion of cases was of unknown etiology and was characterized by generalized onset seizures. The cumulative incidence of all unprovoked seizures was 4.1% through age 74 years. With time, the incidence of epilepsy and of unprovoked seizures decreased in children and increased in the elderly.
Patients with a single unprovoked seizure have about a 35 percent risk of recurrence in the subsequent five years. We studied the risk of recurrence after two unprovoked seizures.
We prospectively followed 204 patients with a first unprovoked seizure from the day of the initial seizure. Information was obtained from patients (and verified by a review of their medical records) about the dates and circumstances of any subsequent seizures. The risk of a second, third, and fourth seizure was estimated by the Kaplan-Meier method.
Of the 204 patients, 63 had a second seizure, 41 a third seizure, and 26 a fourth seizure. The mean age of the patients was 36 years, 10 percent were less than 16 years of age, 70 percent were male, 71 percent had epilepsy of unknown cause, and 66 percent had generalized seizures. The risk of a second unprovoked seizure was 33 percent. Among those with a second seizure, the risk of a third unprovoked seizure was 73 percent; among those with a third unprovoked seizure, the risk of a fourth was 76 percent. Most recurrences occurred within one year of the second or third seizure. The risk of a third seizure was higher in those with a presumed cause of epilepsy (relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.4).
Although only about one third of patients with a first unprovoked seizure will have further seizures within five years, about three quarters of those with two or three unprovoked seizures have further seizures within four years.
Prognosis and treatment of the first seizure depends on identification of a specific epilepsy syndrome, yet patients with first seizures are generally regarded as a homogeneous group. We studied whether it is possible to diagnose specific epilepsy syndromes promptly by use of standard clinical methods, electroencephalography (EEG) and magnetic resonance imaging (MRI).
300 consecutive adults and children presented with unexplained seizures. We systematically collected clinical data from patients and witnesses, and attempted to obtain an EEG within 24 h of the seizure. Where the EEG was negative, a sleep-deprived EEG was done. MRI was done electively.
A generalised or partial epilepsy syndrome was clinically diagnosed in 141 (47%) patients. Subsequent analysis showed that only three of these clinical diagnoses were incorrect. Addition of the EEG data enabled us to diagnose an epilepsy syndrome in 232 (77%) patients. EEG within 24 h was more useful in diagnosis of epileptiform abnormalities than later EEG (51 vs 34%). Neuroimaging showed 38 epileptogenic lesions, including 17 tumours. There were no lesions in patients for whom generalised epilepsy was confirmed by EEG. Our final diagnoses were: generalised epilepsy (23% of patients); partial epilepsy (58%); and unclassified (19%).
An epilepsy syndrome can be diagnosed in most first-seizure patients. Ideally, an EEG should be obtained within 24 h of the seizure followed by a sleep deprived EEG if necessary. MRI aids diagnosis and should be done for all patients except for those with idiopathic generalised epilepsies and for children with benign rolandic epilepsy.
Studies on the predictive value of the electroencephalogram (EEG) concerning the risk of seizure recurrence have shown contradictory results. We prospectively studied the predictive value of the standard EEG and EEG with sleep deprivation for seizure relapse in adult patients presenting with a first unprovoked seizure.
EEGs were performed on 157 adult patients within the first 48 hours of the first seizure. Additional EEGs with sleep deprivation were obtained in 60 cases. The standard EEG was abnormal in 70.7% and significantly associated with an increased risk of seizure recurrence [risk ratio 4.5, 95% confidence interval (CI) 1.8; 11.3, p=0.001]. Subgroup analysis revealed the highest recurrence rates for patients with focal epileptiform activity (risk ratio 2.2, CI 1.2; 4.2, p=0.01). EEGs with sleep deprivation were abnormal in 48.3% of all cases and revealed epileptiform discharges in 13.3% of the patients who had no epileptiform activity in the standard EEG.
Routine EEG revealed abnormalities in 60 of 94 patients who presented with normal neurologic status on admission. Further neuroradiological examinations detected previously unknown brain lesions in 19 of these cases, particularly cerebrovascular disease (CVD, n=7), brain tumors (n=6), and posttraumatic scars (n=4).
In conclusion, the EEG is important for the early detection of focal nonepileptic and epileptic abnormalities after a first unprovoked seizure in adult patients and may provide valuable information on previously unknown disorders, particularly CVD and cerebral tumors. The abnormal EEG is a highly significant predictor for seizure recurrence. An additional EEG with sleep deprivation is helpful in cases when standard EEG does not reveal epileptiform discharges.
To identify patients most likely to have seizures documented on continuous EEG (cEEG) monitoring and patients who require more prolonged cEEG to record the first seizure.
Five hundred seventy consecutive patients who underwent cEEG monitoring over a 6.5-year period were reviewed for the detection of subclinical seizures or evaluation of unexplained decrease in level of consciousness. Baseline demographic, clinical, and EEG findings were recorded and a multivariate logistic regression analysis performed to identify factors associated with 1) any EEG seizure activity and 2) first seizure detected after >24 hours of monitoring.
Seizures were detected in 19% (n = 110) of patients who underwent cEEG monitoring; the seizures were exclusively nonconvulsive in 92% (n = 101) of these patients. Among patients with seizures, 89% (n = 98) were in intensive care units at the time of monitoring. Electrographic seizures were associated with coma (odds ratio [OR] 7.7, 95% CI 4.2 to 14.2), age <18 years (OR 6.7, 95% CI 2.8 to 16.2), a history of epilepsy (OR 2.7, 95% CI 1.3 to 5.5), and convulsive seizures during the current illness prior to monitoring (OR 2.4, 95% CI 1.4 to 4.3). Seizures were detected within the first 24 hours of cEEG monitoring in 88% of all patients who would eventually have seizures detected by cEEG. In another 5% (n = 6), the first seizure was recorded on monitoring day 2, and in 7% (n = 8), the first seizure was detected after 48 hours of monitoring. Comatose patients were more likely to have their first seizure recorded after >24 hours of monitoring (20% vs 5% of noncomatose patients; OR 4.5, p = 0.018).
CEEG monitoring detected seizure activity in 19% of patients, and the seizures were almost always nonconvulsive. Coma, age <18 years, a history of epilepsy, and convulsive seizures prior to monitoring were risk factors for electrographic seizures. Comatose patients frequently required >24 hours of monitoring to detect the first electrographic seizure.
The relative risks and benefits of starting or withholding antiepileptic drug treatment in patients with few or infrequent seizures are unclear. We sought to compare policies of immediate versus deferred treatment in such patients and to assess the effects of these policies on short-term recurrence and long-term outcomes.
We undertook an unmasked, multicentre, randomised study of immediate and deferred antiepileptic drug treatment in 1847 patients with single seizures and early epilepsy. Outcomes comprised time to first, second, and fifth seizures; time to 2-year remission; no seizures between years 1 and 3 and between years 3 and 5 after randomisation; and quality of life. Analysis was by intention to treat.
404 patients invited to join the trial did not consent to randomisation; 722 were subsequently assigned immediate treatment with antiepileptic drugs and 721 were assigned deferred treatment. Immediate treatment increased time to first seizure (hazard ratio 1.4 [95% CI 1.2 to 1.7]), second seizure (1.3 [1.1 to 1.6]), and first tonic-clonic seizure (1.5 [1.2 to 1.8]). It also reduced the time to achieve 2-year remission of seizures (p=0.023). At 5-years follow-up, 76% of patients in the immediate treatment group and 77% of those in the deferred treatment group were seizure free between 3 and 5 years after randomisation (difference -0.2% [95% CI -5.8% to 5.5%]). The two policies did not differ with respect to quality of life outcomes or serious complications.
Immediate antiepileptic drug treatment reduces the occurrence of seizures in the next 1-2 years, but does not affect long-term remission in individuals with single or infrequent seizures.
No population-based incidence studies of epilepsy have studied syndrome classification from the outset. We prospectively studied the incidence of a single unprovoked seizure and epilepsy in the population of Iceland, and applied the syndrome classification endorsed by the International League Against Epilepsy to this population.
We used a nationwide surveillance system to prospectively identify all residents of Iceland who presented with a first diagnosis of a single unprovoked seizure or epilepsy between December 1995 and February 1999. All cases were classified by seizure type, cause or risk factors, and epilepsy syndrome.
The mean annual incidence of first unprovoked seizures was 56.8 per 100,000 person-years, 23.5 per 100,000 person-years for single unprovoked seizures, and 33.3 per 100,000 person-years for epilepsy (recurrent unprovoked seizures). Incidence was similar in males and females. Partial seizures occurred in 40% and a putative cause was identified in 33%. Age-specific incidence was highest in the first year of life (130 per 100,000 person-years) and in those 65 years and older (110.5 per 100,000 person-years). Using strict diagnostic criteria for epilepsy syndromes, 58% of cases fell into non-informative categories. Idiopathic epilepsy syndromes were identified in 14% of all cases.
Findings are consistent with incidence studies from developed countries. Although the epilepsy syndrome classification might be useful in tertiary epilepsy centers, it has limited practicality in population studies and for use by general neurologists.
Being a woman with epilepsy is not the same as being a man with epilepsy. Epilepsy affects sexual development, menstrual cycle, aspects of contraception, fertility, and reproduction.
Menstrual cycle, epilepsy, and fertility: The diagnosis of epilepsy and the use of antiepileptic drugs (AEDs) present women of childbearing age with many problems; both the disease and its treatment can alter the menstrual cycle and fertility.
Contraception in epilepsy: There are no contraindications to the use of nonhormonal methods of contraception in women with epilepsy (see Table 3 ). Nonenzyme‐inducing AEDs (valproate sodium, benzodiazepines, ethosuximide, and levetiracetam) do not show any interactions with the combined oral contraceptive pill. There are interactions between the COCP and hepatic microsomal‐inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [doses above 200 mg/day], and oxcarbazepine) and also lamotrigine.
Contraception—statements and recommendations
• There are no contraindications to the use of nonhormonal methods of contraception in women with epilepsy or the use of the Mirena coil (III)
• For women on nonenzyme‐inducing AEDs (valproate sodium, benzodiazepines, vigabatrin, gabapentin, tiagabine, levetiracetam, pregabalin), all current contraceptive methods are suitable (III)
• Hormonal forms of contraception are affected by enzyme‐inducing AEDs (phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate [>200 mg/day], and lamotrigine); women taking these forms of contraception should be counseled on their risks and benefits (C)
• For women on enzyme‐inducing AEDs wishing to take the COCP:
—Start with 50 μg/day ethinyl oestradiol dosage (C)
—If breakthrough bleeding occurs, increase the dose of ethinyl oestradiol to 75 or 100 μg/day or consider giving three packs of the pill without a break (“tricycling”) (C)
• Even on a higher‐dose COCP with normal cycles, full oral contraceptive efficacy cannot be guaranteed in women with epilepsy taking enzyme‐inducing AEDs (III)
• The progesterone only pill is likely to be ineffective in women taking enzyme‐induced AEDs (III)
Medroxyprogesterone injections appear to be effective (III)
• There are no contraindications to the Mirena coil (III)
• Levonorgestrel implants are contraindicated (III)
• If appropriate, the emergency contraceptive pill can be used in women with epilepsy after unprotected sexual intercourse (C); a higher dose may be needed in women taking enzyme‐inducing AEDs (C)
• Lamotrigine concentrations are lowered by the COCP (II)
AED, antiepileptic drug; COCP, combined oral contraceptive pill.
Sexuality: The majority of women with epilepsy appear to have normal sex lives, although in some women with epilepsy, both the desire and arousal phases may be inhibited.
Preconception counseling: Preconception counseling should be available to all women with epilepsy who are considering pregnancy. Women with epilepsy should be aware of a number of issues relating to future pregnancy, including methods and consequences of prenatal screening, genetics of their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K supplements, labor, breast feeding, and childcare.
Pregnancy: The lowest effective dose of the most appropriate AED should be used, aiming for monotherapy where possible. Recent pregnancy databases have suggested that valproate is significantly more teratogenic than carbamazepine, and the combination of valproate sodium and lamotrigine is particularly teratogenic. Most pregnancies are uneventful in women with epilepsy, and most babies are delivered healthy with no increased risk of obstetric complications in women.
Breast feeding: All women with epilepsy should be encouraged to breastfeed their babies. The AED concentration profiled in breast milk follows the plasma concentration curve. The total amount of drug transferred to infants via breast milk is usually much smaller than the amount transferred via the placenta during pregnancy. However, as drug elimination mechanisms are not fully developed in early infancy, repeated administration of a drug such as lamotrigine via breast milk may lead to accumulation in the infant.
The care of children of mothers with epilepsy: Although there is much anxiety about the possible risks to a child from the mother's epilepsy, there is little published evidence. The risk of the child being harmed depends on the type of seizure and its severity and frequency, and this risk is probably small if time is taken to train mothers and caregivers in safety precautions.
Menopause: During menopause, about 40% of women report worsening of their seizure disorder, 27% improve, and a third had no change. Hormone replacement therapy is significantly associated with an increase in seizure frequency during menopause, and this is more likely in women with a history of catamenial epilepsy.
Bone health: Women with epilepsy are at increased risk of fractures, osteoporosis, and osteomalacia.
We compared clinical features and prognosis of 72 adults with a first-ever seizure presentation comprising multiple discrete seizures within 24 hours to 425 patients presenting with a single seizure. Those presenting with multiple seizures were no more likely to have seizure recurrence, irrespective of etiology or treatment. Hence, a presentation with multiple seizures within 24 hours should be regarded as a single event, in keeping with the International League Against Epilepsy recommendations.