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Seminars in Neurology Dec 2020Seizures affect the lives of 10% of the global population and result in epilepsy in 1 to 2% of people around the world. Current knowledge about etiology, diagnosis, and... (Review)
Review
Seizures affect the lives of 10% of the global population and result in epilepsy in 1 to 2% of people around the world. Current knowledge about etiology, diagnosis, and treatments for epilepsy is constantly evolving. As more is learned, appropriate and updated definitions and classification systems for seizures and epilepsy are of the utmost importance. Without proper definitions and classification, many individuals will be improperly diagnosed and incorrectly treated. It is also essential for research purposes to have proper definitions, so that appropriate populations can be identified and studied. Imprecise definitions, failure to use accepted terminology, or inappropriate use of terminology hamper our ability to study and advance the field of epilepsy. This article begins by discussing the pathophysiology and epidemiology of epilepsy, and then covers the accepted contemporary definitions and classifications of seizures and epilepsies.
Topics: Epilepsy; Humans; Seizures
PubMed: 33155183
DOI: 10.1055/s-0040-1718719 -
Pediatrics in Review Jul 2020Epilepsy is one of the most common neurologic disorders seen in children, with the highest incidence in the first year of life. Diagnostic accuracy can be challenging... (Review)
Review
Epilepsy is one of the most common neurologic disorders seen in children, with the highest incidence in the first year of life. Diagnostic accuracy can be challenging because many seizure mimics must be considered. Electroencephalography and neuroimaging can be critical in determining etiology and syndrome. Genetic testing is a high-yield endeavor, particularly in early-life epilepsies. Up to one-fourth of children with epilepsy will develop drug-resistant seizures. Comorbidities are very common in children with epilepsy, including intellectual disability in 25% and learning disability and attention-deficit/hyperactivity disorder in a significant minority. These comorbidities must be recognized and addressed as part of the child's overall care.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Comorbidity; Electroencephalography; Epilepsy; Humans; Infant; Neuroimaging; Physical Examination; Seizures
PubMed: 32611798
DOI: 10.1542/pir.2019-0134 -
Seminars in Neurology Apr 2020Neonates are exquisitely susceptible to seizures due to several physiologic factors and combination of risks that are uniquely associated with gestation, delivery, and... (Review)
Review
Neonates are exquisitely susceptible to seizures due to several physiologic factors and combination of risks that are uniquely associated with gestation, delivery, and the immediate postnatal period. Neonatal seizures can be challenging to identify; therefore, it is imperative that clinicians have a high degree of suspicion for seizures based on the clinical history or the presence of encephalopathy with or without paroxysmal abnormal movements. Acute symptomatic neonatal seizures are due to an acute brain injury, whereas neonatal-onset epilepsy may be related to underlying structural, metabolic, or genetic disorders. Though initial, acute treatment is similar, long-term treatment and prognosis varies greatly based on underlying seizure etiology. Early identification and treatment are likely important for long-term outcomes in acute symptomatic seizures, though additional studies are needed to understand optimal seizure control metrics and the ideal duration of treatment. Advances in genetic medicine are increasingly expanding our understanding of neonatal-onset epilepsies and will continue to open doors for personalized medicine to optimize outcomes in this fragile population.
Topics: Humans; Infant, Newborn; Infant, Newborn, Diseases; Seizures
PubMed: 32143234
DOI: 10.1055/s-0040-1702943 -
Current Neurology and Neuroscience... Sep 2022To review the mutual interactions between sleep and epilepsy, including mechanisms of epileptogenesis, the relationship between sleep apnea and epilepsy, and potential... (Review)
Review
PURPOSE OF REVIEW
To review the mutual interactions between sleep and epilepsy, including mechanisms of epileptogenesis, the relationship between sleep apnea and epilepsy, and potential strategies to treat seizures.
RECENT FINDINGS
Recent studies have highlighted the role of functional network systems underlying epileptiform activation in sleep in several epilepsy syndromes, including absence epilepsy, benign focal childhood epilepsy, and epileptic encephalopathy with spike-wave activation in sleep. Sleep disorders are common in epilepsy, and early recognition and treatment can improve seizure frequency and potentially reduce SUDEP risk. Additionally, epilepsy is associated with cyclical patterns, which has led to new treatment approaches including chronotherapy, seizure monitoring devices, and seizure forecasting. Adenosine kinase and orexin receptor antagonists are also promising new potential drug targets that could be used to treat seizures. Sleep and epilepsy have a bidirectional relationship that intersects with many aspects of clinical management. In this article, we identify new areas of research involving future therapeutic opportunities in the field of epilepsy.
Topics: Child; Electroencephalography; Epilepsies, Partial; Epilepsy; Humans; Seizures; Sleep; Sleep Wake Disorders
PubMed: 35802300
DOI: 10.1007/s11910-022-01219-1 -
Nature Reviews. Neurology Jun 2022The brain is a highly energy-demanding organ and requires bioenergetic adaptability to balance normal activity with pathophysiological fuelling of spontaneous recurrent... (Review)
Review
The brain is a highly energy-demanding organ and requires bioenergetic adaptability to balance normal activity with pathophysiological fuelling of spontaneous recurrent seizures, the hallmark feature of the epilepsies. Recurrent or prolonged seizures have long been known to permanently alter neuronal circuitry and to cause excitotoxic injury and aberrant inflammation. Furthermore, pathological changes in bioenergetics and metabolism are considered downstream consequences of epileptic seizures that begin at the synaptic level. However, as we highlight in this Review, evidence is also emerging that primary derangements in cellular or mitochondrial metabolism can result in seizure genesis and lead to spontaneous recurrent seizures. Basic and translational research indicates that the relationships between brain metabolism and epileptic seizures are complex and bidirectional, producing a vicious cycle that compounds the deleterious consequences of seizures. Metabolism-based treatments such as the high-fat, antiseizure ketogenic diet have become mainstream, and metabolic substrates and enzymes have become attractive molecular targets for seizure prevention and recovery. Moreover, given that metabolism is crucial for epigenetic as well as inflammatory changes, the idea that epileptogenesis can be both negatively and positively influenced by metabolic changes is rapidly gaining ground. Here, we review evidence that supports both pathophysiological and therapeutic roles for brain metabolism in epilepsy.
Topics: Brain; Energy Metabolism; Epilepsy; Humans; Seizures; Status Epilepticus
PubMed: 35361967
DOI: 10.1038/s41582-022-00651-8 -
Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures.Brain : a Journal of Neurology Aug 2020Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in... (Review)
Review
Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in early adulthood. Recent studies, however, show that 30% of children with absence seizures are pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions, including impairments in attention, cognition, memory and mood. In particular, attention deficits can be detected before the epilepsy diagnosis, may persist even when seizures are pharmacologically controlled and are aggravated by valproic acid monotherapy. New functional MRI-magnetoencephalography and functional MRI-EEG studies provide conclusive evidence that changes in blood oxygenation level-dependent signal amplitude and frequency in children with absence seizures can be detected in specific cortical networks at least 1 min before the start of a seizure, spike-wave discharges are not generalized at seizure onset and abnormal cortical network states remain during interictal periods. From a neurobiological perspective, recent electrical recordings and imaging of large neuronal ensembles with single-cell resolution in non-anaesthetized models show that, in contrast to the predominant opinion, cortical mechanisms, rather than an exclusively thalamic rhythmogenesis, are key in driving seizure ictogenesis and determining spike-wave frequency. Though synchronous ictal firing characterizes cortical and thalamic activity at the population level, individual cortico-thalamic and thalamocortical neurons are sparsely recruited to successive seizures and consecutive paroxysmal cycles within a seizure. New evidence strengthens previous findings on the essential role for basal ganglia networks in absence seizures, in particular the ictal increase in firing of substantia nigra GABAergic neurons. Thus, a key feature of thalamic ictogenesis is the powerful increase in the inhibition of thalamocortical neurons that originates at least from two sources, substantia nigra and thalamic reticular nucleus. This undoubtedly provides a major contribution to the ictal decrease in total firing and the ictal increase of T-type calcium channel-mediated burst firing of thalamocortical neurons, though the latter is not essential for seizure expression. Moreover, in some children and animal models with absence seizures, the ictal increase in thalamic inhibition is enhanced by the loss-of-function of the astrocytic GABA transporter GAT-1 that does not necessarily derive from a mutation in its gene. Together, these novel clinical and experimental findings bring about paradigm-shifting views of our understanding of absence seizures and demand careful choice of initial monotherapy and continuous neuropsychiatric evaluation of affected children. These issues are discussed here to focus future clinical and experimental research and help to identify novel therapeutic targets for treating both absence seizures and their comorbidities.
Topics: Adolescent; Animals; Child; Comorbidity; Humans; Seizures
PubMed: 32437558
DOI: 10.1093/brain/awaa072 -
Clinical Medicine (London, England) Jan 2021We present a practical overview of functional neurological disorder (FND), its epidemiology, assessment and diagnosis, diagnostic pitfalls, treatment, aetiology and... (Review)
Review
We present a practical overview of functional neurological disorder (FND), its epidemiology, assessment and diagnosis, diagnostic pitfalls, treatment, aetiology and mechanism. We present an update on functional limb weakness, tremor, dystonia and other abnormal movements, dissociative seizures, functional cognitive symptoms and urinary retention, and 'scan-negative' cauda equina syndrome. The diagnosis of FND should rest on clear positive evidence, typically from a combination of physical signs on examination or the nature of seizures. In treatment of FND, clear communication of the diagnosis and the involvement of the multidisciplinary team is beneficial. We recommend that patients with FND are referred to specialists with expertise in neurological diagnosis. FND is a common presentation in emergency and acute medical settings and there are many practical elements to making a positive diagnosis and communication which are useful for all physicians to be familiar with.
Topics: Conversion Disorder; Emergency Service, Hospital; General Practitioners; Humans; Nervous System Diseases; Seizures; Tremor
PubMed: 33479065
DOI: 10.7861/clinmed.2020-0987 -
Acta Neurologica Scandinavica Dec 2022Most seizures in critical ill patients are non-convulsive, and some patients may develop non-convulsive status epilepticus (NCSE), a state of continuous or repetitive... (Review)
Review
Most seizures in critical ill patients are non-convulsive, and some patients may develop non-convulsive status epilepticus (NCSE), a state of continuous or repetitive seizures without convulsions. With the growing use of continuous electroencephalogram (EEG) monitoring in neuro-intensive care units, non-convulsive seizure (NCS) and NCSE are increasingly diagnosed in patients with impaired consciousness, and progress has been made in identifying various EEG characteristics of NCS/NCSE. Epidemiological studies have contributed to a better understanding of etiologies and risk factors for NCS and NCSE. However, sufficient clinical trials about the treatment of NCS and NCSE are still lacking. The appropriate level of aggressiveness in the treatment of NCSE is still debated, particularly with regard to the use of anesthetics in patients with refractory NCSE. In this review, we summarize the EEG, clinical, epidemiological, diagnostic and therapeutic knowledge of NCS and NCSE in the neuro-intensive care setting in detail.
Topics: Humans; Status Epilepticus; Seizures; Electroencephalography; Intensive Care Units; Critical Care
PubMed: 36285875
DOI: 10.1111/ane.13718 -
Epileptic Disorders : International... Jun 2020Stroke is one of the commonest causes of seizures and epilepsy, mainly among the elderly and adults. This seminar paper aims to provide an updated overview of... (Review)
Review
Stroke is one of the commonest causes of seizures and epilepsy, mainly among the elderly and adults. This seminar paper aims to provide an updated overview of post-stroke seizures and post-stroke epilepsy (PSE) and offers clinical guidance to anyone involved in the treatment of patients with seizures and stroke. The distinction between acute symptomatic seizures occurring within seven days from stroke (early seizures) and unprovoked seizures occurring afterwards (late seizures) is crucial regarding their different risks of recurrence. A single late post-stroke seizure carries a risk of recurrence as high as 71.5% (95% confidence interval: 59.7-81.9) at ten years and is diagnostic of PSE. Several clinical and stroke characteristics are associated with increased risk of post-stroke seizures and PSE. So far, there is no evidence supporting the administration of antiepileptic drugs as primary prevention, and evidence regarding their use in PSE is scarce.
Topics: Epilepsy; Humans; Seizures; Stroke
PubMed: 32597766
DOI: 10.1684/epd.2020.1159 -
Continuum (Minneapolis, Minn.) Oct 2021This article discusses the evolving definitions of seizures and status epilepticus in the critical care environment and the role of critical care EEG in both diagnosing... (Review)
Review
PURPOSE OF REVIEW
This article discusses the evolving definitions of seizures and status epilepticus in the critical care environment and the role of critical care EEG in both diagnosing seizure activity and serving as a predictive biomarker of clinical trajectory.
RECENT FINDINGS
Initial screening EEG has been validated as a tool to predict which patients are at risk of future seizures. However, accepted definitions of seizures and nonconvulsive status epilepticus encourage a treatment trial when the diagnosis on EEG is indeterminate because of periodic or rhythmic patterns or uncertain clinical correlation. Similarly, recent data have demonstrated the diagnostic utility of intracranial EEG in increasing the yield of seizure detection. EEG has additionally been validated as a diagnostic biomarker of covert consciousness, a predictive biomarker of cerebral ischemia and impending neurologic deterioration, and a prognostic biomarker of coma recovery and status epilepticus resolution. A recent randomized trial concluded that patients allocated to continuous EEG had no difference in mortality than those undergoing intermittent EEG but could not demonstrate whether this lack of difference was because of studying heterogeneous conditions, examining a monitoring tool rather than a therapeutic approach, or examining an outcome measure (mortality) perhaps more strongly associated with early withdrawal of life-sustaining therapy than to a sustained response to pharmacotherapy.
SUMMARY
Seizures and status epilepticus are events of synchronous hypermetabolic activity that are either discrete and intermittent or, alternatively, continuous. Seizures and status epilepticus represent the far end of a continuum of ictal-interictal patterns that include lateralized rhythmic delta activity and periodic discharges, which not only predict future seizures but may be further classified as status epilepticus on the basis of intracranial EEG monitoring or a diagnostic trial of antiseizure medication therapy. In particularly challenging cases, neuroimaging or multimodality neuromonitoring may be a useful adjunct documenting metabolic crisis. Specialized uses of EEG as a prognostic biomarker have emerged in traumatic brain injury for predicting language function and covert consciousness, cardiac arrest for predicting coma recovery, and subarachnoid hemorrhage for predicting neurologic deterioration due to delayed cerebral ischemia.
Topics: Critical Care; Electroencephalography; Humans; Intensive Care Units; Seizures; Status Epilepticus
PubMed: 34618762
DOI: 10.1212/CON.0000000000001012