Epilepsy is a chronic disease of the brain characterized by an enduring (i.e., persisting) predisposition to generate seizures, unprovoked by any immediate central nervous system insult, and by the ...neurobiologic, cognitive, psychological, and social consequences of seizure recurrences. Epilepsy affects both sexes and all ages with worldwide distribution. The prevalence and the incidence of epilepsy are slightly higher in men compared to women and tend to peak in the elderly, reflecting the higher frequency of stroke, neurodegenerative diseases, and tumors in this age-group. Focal seizures are more common than generalized seizures both in children and in adults. The etiology of epilepsy varies according to the sociodemographic characteristics of the affected populations and the extent of the diagnostic workup, but a documented cause is still lacking in about 50% of cases from high-income countries (HIC). The overall prognosis of epilepsy is favorable in the majority of patients when measured by seizure freedom. Reports from low/middle-income countries (LMIC; where patients with epilepsy are largely untreated) give prevalence and remission rates that overlap those of HICs. As the incidence of epilepsy appears higher in most LMICs, the overlapping prevalence can be explained by misdiagnosis, acute symptomatic seizures and premature mortality. Studies have consistently shown that about one-half of cases tend to achieve prolonged seizure remission. However, more recent reports on the long-term prognosis of epilepsy have identified differing prognostic patterns, including early and late remission, a relapsing-remitting course, and even a worsening course (characterized by remission followed by relapse and unremitting seizures). Epilepsy per se carries a low mortality risk, but significant differences in mortality rates are expected when comparing incidence and prevalence studies, children and adults, and persons with idiopathic and symptomatic seizures. Sudden unexplained death is most frequent in people with generalized tonic-clonic seizures, nocturnal seizures, and drug refractory epilepsy.
Social functions are commonly impaired in people with epilepsy who are at increased risk of experiencing altered social cognition, communication problems, and interpersonal difficulties. Several ...factors are implicated, including developmental delay, seizure-related factors, somatic and psychiatric comorbidities, antiepileptic drugs (AEDs), and – not least – the effects of stigma. The variable interaction of all these factors can explain the differing pictures observed in the various epilepsy phenotypes but is also a source of interindividual variability depending on the strength of the effects of each factor on social cognition.
This article is part of the Special Issue "Epilepsy and social cognition across the lifespan.
•Social functions are commonly impaired in people with epilepsy.•Seizures and comorbidities alter social cognition and interpersonal relationships.•Public's stigma and negative attitudes towards epilepsy cause social maladjustment.•Poor and marginalized individuals most commonly incur in social difficulties.•Health providers should aim to prevent and care epilepsy and abate discrimination.
To illustrate the frequency and trends of the comorbidity of epilepsy and dementia and the effects of antiepileptic drugs (AEDs) on cognitive functions.
Although the mortality and incidence of ...epilepsy are decreasing overall, they are increasing in the elderly as a result of population growth and increased life expectancy. Alzheimer's disease and other dementias are among the commonest causes of seizures and epilepsy. Epilepsy can be also complicated by cognitive impairment, suggesting a bidirectional association. Although epilepsy with onset in the elderly can be the manifestation of a CNS disease/injury, the cause of cognitive impairment is multifactorial and includes static (genetic background, age at seizure onset, developmental and acquired cerebral lesions) and dynamic factors recurrent seizures, epileptiform discharges, type and number of AEDs and psychiatric comorbidities. Most AEDs, with special reference to first-generation drugs, have negative effects on cognitive functions; however, none was found to increase the risk of dementia.
A net increase in the burden of epilepsy, dementia and epilepsy-dementia comorbidity is expected. The growing use of second-generation AEDs might help reducing adverse cognitive effects. However, the fairly high cost of these drugs might delay their widespread use in resource-poor countries. VIDEO ABSTRACT: http://links.lww.com/CONR/A49.
...seizure recurrence with strong impact on one's health and quality of life cannot be excluded even after mild events, particularly in untreated patients, and one cannot exclude that future seizures ...have a greater impact on patient's and public safety. 7 The differences might be explained by the differing populations at risk (patients seen at the first seizure vs. patients with two or more seizures, the latter perhaps with more severe disease varieties) and by the length of follow-up (as poor treatment response proves to be a dynamic process when long-term follow-up is considered). The International League Against Epilepsy addressed this issue and concluded that in specific circumstances epilepsy can be diagnosed at the first seizure. 10 This definition helps reducing the diagnostic gap but requires that a comprehensive evaluation of the patient is performed and, for this reason, the diagnosis of epilepsy should be made by specialists who are well aware of the risk factors for seizure recurrence in a patient with a first seizure.
Antiepileptic drugs and the immune system Beghi, Ettore; Shorvon, Simon
Epilepsia (Copenhagen),
20/May , Volume:
52, Issue:
s3
Journal Article, Conference Proceeding
Peer reviewed
Open access
Summary
Data on the effects of antiepileptic drugs on the immune system are frequently inconsistent and sometimes conflicting because the effects of drugs cannot be separated from those of seizures, ...first‐generation drugs have been most intensively investigated, the patient’s genetic background, the mechanism of action and the pharmacokinetic profile of AEDs and the concurrent use of immunosuppressant drugs may act as confounders. Valproate, carbamazepine, phenytoin, vigabatrin, levetiracetam, and diazepam have been found to modulate the immune system activity by affecting humoral and cellular immunity. AEDs are associated with pharmacokinetic interactions (most frequently occurring with carbamazepine, phenytoin, phenobarbital and valproate). Hepatic metabolism is the primary site of interaction for both AEDs and immunotherapies (ACTH, dexamethasone, hydrocortisone, methylprednisolone, cyclophosphamide, methotrexate, rituximab), which entail induction or inhibition of drug effects. However, the clinical importance of these drug interactions is still far from defined. An important adverse effect of the action of AEDs on the immune system is antiepileptic hypersensitivity syndrome (AHS), a life‐threatening, idiosyncratic cutaneous reaction to aromatic AEDs resulting in end organ damage. Phenytoin, carbamazepine, phenobarbital, lamotrigine, oxcarbazepine, felbamate, and zonisamide have been implicated. The pathogenic mechanisms of AHS are incompletely understood.
To assess the worldwide variation of amyotrophic lateral sclerosis (ALS) incidence, we performed a systematic review and meta-analysis of population-based data published to date.
We reviewed Medline ...and Embase up to June 2015 and included all population-based studies of newly diagnosed ALS cases, using multiple sources for case ascertainment. ALS crude and standardized incidence (on age and sex using the US 2010 population) were calculated. Random effect meta-analysis and meta-regression were performed using the subcontinent as the main study level covariate. Sources of heterogeneity related to the characteristics of the study population and the study methodology were investigated.
Among 3216 records, 44 studies were selected, covering 45 geographical areas in 11 sub-continents. A total of 13 146 ALS cases and 825 million person-years of follow-up (PYFU) were co-nsidered. The overall pooled worldwide crude ALS incidence was at 1.75 (1.55-1.96)/100 000 PYFU; 1.68 (1.50-1.85)/100 000 PYFU after standardization. Heterogeneity was identified in ALS standardized incidence between North Europe 1.89 (1.46-2.32)/100 000 PYFU and East Asia 0.83 (0.42-1.24)/100 000 PYFU, China and Japan P = 0.001 or South Asia 0.73 (0.58-0.89)/100 000/PYFU Iran, P = 0.02. Conversely, homogeneous rates have been reported in populations from Europe, North America and New Zealand pooled ALS standardized incidence of 1.81 (1.66-1.97)/100 000 PYFU for those areas.
This review confirms a heterogeneous distribution worldwide of ALS, and sets the scene to sustain a collaborative study involving a wide international consortium to investigate the link between ancestry, environment and ALS incidence.
Summary
Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been ...published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population‐based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy‐associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals.
Summary
Objective
Information about the incidence of neonatal seizures (NS) is scarce. Previous studies relied primarily on a clinical diagnosis of seizures. This population‐based, retrospective ...study evaluated the incidence of electroencephalography (EEG)–confirmed seizures in neonates born in the province of Parma and the perinatal risk factors for mortality and epilepsy.
Methods
All neonates with suspected seizures or with medical conditions at high risk for seizures from the study area were recorded in the neonatal intensive care unit (NICU) of the Parma University Hospital. NS were EEG confirmed. Perinatal risk factors for mortality and epilepsy after NS were evaluated with Cox’s proportional hazards models.
Results
In a 13‐year period, 112 patients presented with NS: 102 newborns had electroclinical seizures (46 full‐term and 56 preterm), whereas 10 presented only electrical seizures. The incidence was 2.29/1000 live births (95% confidence interval CI 1.87‐2.72), with higher rates in preterm neonates (14.28/1000 in preterm vs 1.10/1000 in full‐term infants). The incidence increased with decreasing gestational age (31‐36 weeks of gestation: 5.01/1000, 28‐30: 54.9/1000, and <28: 85.6/1000) and with decreasing birth weight (≥2500 g: 1.19/1000, <1000 g: 127.57/1000). Twenty‐eight patients (25%) died, 16 (14.3%) had a diagnosis of epilepsy, 33 (29.5%) had cerebral palsy, and 39 (34.8%) had a developmental delay. Among the perinatal risk factors considered, the multivariate analysis showed an association between a 5‐minute Apgar score of 0‐7 and etiology with increased mortality and between female gender and status epilepticus with epilepsy.
Significance
The incidence of NS is inversely associated with gestational age and birth weight. The etiology and a low Apgar score are strongly related to mortality; female gender and status epilepticus are risk factors for the development of epilepsy.
Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and ...nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide.
The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were Alzheimer's disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, Parkinson's disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates.
In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5–23·9) in the EU and 41·1 million (36·7–45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09–1·14) in the EU and 1·97 million (1·95–2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3–17·1) of total DALYs and 19·5% (18·0–21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80–84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs.
Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries.
European Academy of Neurology.
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