Seizure Syndrome
Description
School Nurse Intervention
Typical absence seizures
It is characterized by a black stare that takes approximately 10-20 minutes (Selekman, 2012). They are characterized with unresponsiveness. A child exhibits symptoms as eye fluttering, lip-smacking and pupillary dilation
The school nurse should stay with the child. He or she should not be restrained. The school nurse should equally place the hand of the child on the shoulder to prevent injuries.
Atypical absence seizures
The seizure is different from the typical absence in that it is not abrupt. It can last for 30 minutes (Selekman, 2012). It is associated with structural abnormalities of the brain. A child recovers from it gradually. Seizure Syndrome Chart Essay.
The school nurse should stay with the child. He or she should not be restrained. The school nurse should equally place the hand of the child on the shoulder to prevent injuries.
Tonic seizures
It is characterized by stiffening of the whole body. It has an abrupt start and end. The seizures take a few minutes
The student should be lowered to the floor and positioned well to prevent aspiration. Seizure Syndrome Chart Essay. The school nurse should not put anything into the child’s mouth. Besides, restraining the child should be avoided.
Clonic seizures
The seizures are characterized by the contraction of the muscles in a rhythmic pattern (Selekman, 2012). It impairs an individual’s consciousness. Cases of postictal confusions are not witnessed.
The student should be lowered to the floor and positioned well to prevent aspiration (Selekman, 2012). The school nurse should not put anything into the child’s mouth. Besides, restraining the child should be avoided
Tonic-clonic seizures
The seizures have an abrupt beginning, and an individual barely shows warning signs. It is characterized by a prodrome phase, which takes a few hours. The common symptoms include insomnia and irritability. Thetonic phase takes up to 30 seconds, and it is characterized by rhythmic jerking of the extreme body parts. The jerking can last up to 60 seconds.
The student should be lowered to the floor and positioned well to prevent aspiration. The school nurse should not put anything in the child’s mouth (Selekman, 2012). Besides, restraining the child should be avoided
Myoclonic seizures
They are characterized by sudden muscle jerks. It affects upper extremities and the shoulders. They may occur in clusters or individually. Seizure Syndrome Chart Essay.
The student should be lowered to the floor and positioned well to prevent aspiration. The school nurse should not put anything into the child’s mouth. Besides, restraining the child should be avoided
Atonic Seizures
It characterized by the loss of tone, which is sudden. An individual may show signs of limping.
The student should be lowered to the floor and positioned well to prevent aspiration. The school nurse should not put anything into the child’s mouth. Besides, restraining the child should be avoided
Akinetic Seizures
It is often termed as a drop attack. An individual falls to the ground and may recover immediately. An individual may incur great injuries from the seizure.
The student should be lowered to the floor and positioned well to prevent aspiration. The school nurse should not put anything into the child’s mouth. Besides, restraining the child should be avoided
Infantile Seizure
The seizures greatly depend on an individual’s age. It primarily occurs in infants below one year. They disappear before a child starts schooling.
Most of the seizures are managed by parents at home.
Simple Partial Seizures
It results as a result of the limited focus of one cerebral hemisphere. Seizure Syndrome Chart Essay/ An individual under the seizure attack is often alert and conscious of his or her surroundings. An individual is equally aware of what happens during the seizure attack
The school nurse should stay with the child. He or she should not be restrained. The school nurse should equally place the hand of the child on the shoulder to prevent injuries.
Complex Partial Seizures
They start from the limbic system and end up affecting the lobes of the brain. Unlike simple partial seizure, an individual is not conscious of his or her surroundings. It is characterized by memory loss and extreme confusion.
The school nurse is expected to remain with the child and avoid restraining him or her. The school nurse should equally speak gently to the child and guide him or her to prevent injuries.
School Health Considerations for the use of Diastat and Midazolam
The use of the two drugs can have adverse effects on individuals if not properly used. The school nurse is supposed on to insist on reading instruction before the two drugs are given to the students at the school. One of the precautions is that diastat not be given to children who have special eye condition such as acute narrow-angle glaucoma (Selekman, 2012). Midazolam, on the other hand, should not be given to children if they have allergies to cherries. It is associated with special side effects such as drowsiness or weakness for 1-2 days. It equally affects an individual’s thinking ability.
References
Selekman, J. (2012). School nursing: A comprehensive text. FA Davis Company.
Epilepsy is one of the most common and disabling neurologic conditions, yet we have an incomplete understanding of the detailed pathophysiology and, thus, treatment rationale for much of epilepsy. This article reviews the clinical aspects of seizures and epilepsy with the goal of providing neuroscientists an introduction to aspects that might be amenable to scientific investigation. Seizures and epilepsy are defined, diagnostic methods are reviewed, various clinical syndromes are discussed, and aspects of differential diagnosis, treatment, and prognosis are considered to enable neuroscientists to formulate basic and translational research questions. Seizure Syndrome Chart Essay.
This article provides an overview of seizures and epilepsy for neuroscientists. We focus on broad concepts, rather than clinical details, and raise questions related to mechanisms, epileptogenesis, and therapeutic approaches that might generate interest among basic researchers. Further information about differential diagnosis, drug doses, and clinical management are available from numerous resources (Engel and Pedley 2008; Duchowny et al. 2012; Engel 2013). Seizure Syndrome Chart Essay.
We first define seizures and epilepsy and summarize their classification, pathophysiology, and genetics. Diagnostic methods are then considered, including the importance of an accurate historical description of an event suspected to be a seizure and the appropriate use of ancillary/confirmative tests, such as electroencephalogram (EEG), neuroimaging, and genetic studies. These modalities enable the clinician to differentiate epilepsy from numerous clinical conditions that mimic seizures, but have a nonepileptic pathophysiological basis. Examples of epilepsy syndromes are then described, selected based on their frequency in the population or because they embody scientific questions that warrant elucidation. Finally, we provide an overview of treatment options and prognosis, including a consideration of conditions that accompany epilepsy (comorbidities) and complicate the daily lives of people with epilepsy. Subsequent articles in this collection explore the scientific basis of many of the clinical concepts introduced here.
DEFINITIONS AND EPIDEMIOLOGY
A “seizure” is a paroxysmal alteration of neurologic function caused by the excessive, hypersynchronous discharge of neurons in the brain. “Epileptic seizure” is used to distinguish a seizure caused by abnormal neuronal firing from a nonepileptic event, such as a psychogenic seizure. “Epilepsy” is the condition of recurrent, unprovoked seizures. Epilepsy has numerous causes, each reflecting underlying brain dysfunction (Shorvon et al. 2011). A seizure provoked by a reversible insult (e.g., fever, hypoglycemia) does not fall under the definition of epilepsy because it is a short-lived secondary condition, not a chronic state.
“Epilepsy syndrome” refers to a group of clinical characteristics that consistently occur together, with similar seizure type(s), age of onset, EEG findings, triggering factors, genetics, natural history, prognosis, and response to antiepileptic drugs (AEDs). The nonspecific term “seizure disorder” should be avoided.
Epilepsy is one of the most common neurologic conditions, with an incidence of approximately 50 new cases per year per 100,000 population (Hauser and Hersdorffer 1990). About 1% of the population suffers from epilepsy, and about one-third of patients have refractory epilepsy (i.e., seizures not controlled by two or more appropriately chosen antiepileptic medications or other therapies). Approximately 75% of epilepsy begins during childhood, reflecting the heightened susceptibility of the developing brain to seizures. Seizure Syndrome Chart Essay.
CLASSIFICATION OF SEIZURES AND EPILEPSIES
The most recent International League Against Epilepsy (ILAE) classification of epileptic seizures and epilepsies (epilepsy syndromes), published in 2010, revises past classifications using terminology and concepts appropriate for the modern era (Berg et al. 2010; Berg and Millichap 2013; Muro and Connolly 2014). Seizures are divided into three categories: generalized, focal (formerly called partial), and epileptic spasms. Focal seizures originate in neuronal networks limited to part of one cerebral hemisphere. Generalized seizures begin in bilateral distributed neuronal networks. A seizure can begin focally and later generalize. Seizures can originate in the cortex or in subcortical structures. Using a detailed history, EEG findings, and ancillary information, a physician can often categorize the seizure/epilepsy type, after which an appropriate diagnostic evaluation and treatment plan is formulated.
The main subtypes of generalized seizures are absence, generalized tonic–clonic (GTC), myoclonic, and atonic (Table 1). Absence seizures (formerly called petit mal) involve staring with unresponsiveness to external verbal stimuli, sometimes with eye blinking or head nodding. GTC seizures (formerly called grand mal) consist of bilateral symmetric convulsive movements (stiffening followed by jerking) of all limbs with impairment of consciousness. Seizure Syndrome Chart Essay. Myoclonic seizures consist of sudden, brief (“lightning-fast”) movements that are not associated with any obvious disturbance of consciousness. These brief involuntary muscle contractions may affect one or several muscles; therefore, myoclonic seizures can be generalized or focal. Atonic seizures involve the loss of body tone, often resulting in a head drop or fall.
Table 1.
Epileptic seizures
| Generalized seizures |
| Tonic–clonic |
| Absence |
| Typical |
| Atypical |
| Myoclonic |
| Atonic |
| Focal seizures |
| Epileptic spasms |
The clinical manifestations of a focal seizure depend on the area of cortex involved. For example, a focal seizure arising from the occipital lobe may present with visual phenomena; from the precentral gyrus, with rhythmic clonic or tonic motor activity; and from the postcentral gyrus, with sensory symptoms, such as paresthesias. When consciousness is impaired during a focal seizure, that is, the patient is unable to respond normally to verbal or tactile stimuli, the seizure is classified as dyscognitive (formerly called complex partial); seizures arising from the temporal lobe are often dyscognitive. Some seizures are preceded by an aura, which is a focal seizure wherein a patient retains awareness and describes motor, sensory, autonomic, or psychic symptoms. An aura precedes a focal dyscognitive or generalized seizure by seconds or minutes and is most often experienced by patients with temporal lobe epilepsy.
The origin of the third category of seizure type, epileptic spasms, is uncertain. Epileptic spasms are manifest by sudden extension or flexion of extremities, held for several seconds, and then recur in clusters. Epileptic spasms can occur at any age; when they begin in the first year of life, they comprise a syndrome called infantile spasms (IS) (West syndrome [WS]; see below).
Epilepsies (epilepsy syndromes) (Table 2) were previously classified according to their onset site (generalized or related to a specific cortical localization) and etiology, that is, whether the cause was known (symptomatic) or not known (idiopathic). Here, we use the 2010 revised guideline for classification of seizures and epilepsy (Berg et al. 2010).Seizure Syndrome Chart Essay. The updated system takes into account expanding knowledge of structural and genetic causes, and includes the ictal semiology (seizure type), syndrome diagnosis (if present), and degree of functional impairment. New classification schemes will continue to evolve as knowledge about epilepsy pathophysiology, and genetics emerges.
Table 2.
Examples of epilepsy syndromes according to age of onset
| Neonatal |
| Benign familial neonatal epilepsy (BFNE) |
| Infancy |
| West syndromea |
| Dravet syndromea |
| Childhood |
| Generalized epilepsy with febrile seizures plus (GEFS+) |
| Childhood absence epilepsy |
| Lennox–Gastaut syndromea |
| Landau–Kleffner syndromea |
| Adolescence and adulthood |
| Juvenile myoclonic epilepsy |
aConsidered an “epileptic encephalopathy,” whereby seizures themselves contribute to cognitive impairment.
PATHOPHYSIOLOGY AND GENETICS
A seizure can be conceptualized as occurring when there is distortion of the normal balance between excitation (E) and inhibition (I) in the brain (Stafstrom 2010). This E/I imbalance can result from an alteration at many levels of brain function, from genes and subcellular signaling cascades to widespread neuronal circuits. The factors that alter E/I balance can be genetic or acquired. Genetic pathologies leading to epilepsy can occur anywhere from the circuit level (e.g., abnormal synaptic connectivity in cortical dysplasia) to the receptor level (e.g., abnormal γ-aminobutyric acid [GABA] receptor subunits in Angelman syndrome) to abnormal ionic channel function (e.g., potassium channel mutations in benign familial neonatal epilepsy [BFNE]). Similarly, acquired cerebral insults can alter circuit function (e.g., structural alteration of hippocampal circuitry following prolonged febrile seizures or head trauma). The developing brain is particularly prone to seizures for a variety of physiological reasons (see Berkovic 2015). Even in the normal developing brain, excitatory synaptic function develops before inhibitory synaptic function, favoring enhanced excitation and seizure generation. In addition, early in life, the neurotransmitter GABA causes excitation rather than inhibition (Ben-Ari 2002; Pitkänen et al. 2015). These observations partly explain why the very young brain is especially susceptible to seizures. However, seizures cause less structural damage in the developing brain than in the adult brain (Holmes and Ben-Ari 1998).
There has been a recent explosion of new information about the genetic basis of epilepsy syndromes. Both monogenic and polygenic mutations can lead to epilepsy (Poduri and Lowenstein 2011). Many epilepsies have a complex genetic basis with multiple gene defects contributing to a state of altered cellular excitability, which underlies epilepsy. Seizure Syndrome Chart Essay. For example, copy number variants, which are de novo or inherited deletions or duplications >1 kb, are increasingly recognized as a source of genetic mutations in patients with epilepsy (Mullen et al. 2013; Olson et al. 2014). As genetics knowledge expands, there is hope that syndrome-specific therapeutic interventions can be designed (Thomas and Berkovic 2014).
DIAGNOSTIC EVALUATION
History and Examination
The history and neurologic examination are the cornerstones of the diagnosis of seizures and epilepsy, whereas laboratory evaluations serve as adjunctive tests. Important historical features include the clinical context in which the seizure occurred, including premonitory signs, details of the seizure itself, such as phenomenology, responsiveness, focal features, and the postictal state. Further inquiry centers on whether an epilepsy syndrome is present, guides the nature and extent of the evaluation, and determines treatment and prognosis.
The neurological examination assesses focal signs that might implicate or localize cerebral pathology. For example, increased tone on one side of the body could indicate pathology in the contralateral hemisphere, such as a cortical dysplasia. The general physical examination is also important to determine whether the patient has an underlying condition. For example, abnormal skin markings could indicate a neurocutaneous disorder in which epilepsy is common, such as tuberous sclerosis or neurofibromatosis.
EEG
An EEG is a recording of the brain’s electrical activity. It can detect abnormal electrical activity, such as focal spikes or waves (consistent with focal epilepsy), or diffuse bilateral spike waves (consistent with generalized epilepsy). A routine EEG will, preferably, include wakefulness, drowsiness, and sleep because the prevalence of epileptiform abnormalities varies in these different states of consciousness.Seizure Syndrome Chart Essay. Hyperventilation and photic stimulation are activation procedures performed during an EEG to increase the yield of epileptic activity. Having a patient hyperventilate for 3 min has a high yield of leading to an absence seizure, related to the seizure-provoking effect of alkalosis (Schuchmann et al. 2006). Photic stimulation may elicit paroxysmal epileptiform activity or even a generalized seizure in a person susceptible to generalized epilepsy (Verrotti et al. 2012). Simultaneous video-EEG monitoring for hours to days can increase the diagnostic yield or differentiate an epileptic seizure from a nonepileptic event. The EEG can be repeatedly normal in someone with epilepsy, especially if seizures begin in the frontal or temporal lobe. In such cases, intracranial EEG monitoring, usually in the context of presurgical evaluation, may be necessary to define a seizure focus. The diagnosis of epilepsy is based on clinical information and the EEG should be regarded as confirmatory, not diagnostic. The standard teaching is “treat the patient, not the EEG.” An exception to this guideline is absence epilepsy in which brief generalized bursts of spike-wave activity, even if not associated with obvious clinical changes, imply a high likelihood of absence seizure recurrences that can go unrecognized.
Neuroimaging
Computed tomography (CT) and magnetic resonance imaging (MRI) scans are important adjuncts to the clinical examination and EEG in the evaluation of a person with seizures. Neuroimaging techniques are especially sensitive for central nervous system (CNS) structural lesions. Focal neurologic findings on examination (e.g., unilateral weakness, asymmetric reflexes) mandate neuroimaging.
MRI is more likely to show an abnormality in a patient with focal seizures, abnormal neurologic findings, or focal discharges on EEG. MRI is more sensitive than CT and is therefore preferred, especially for the detection of cortical malformation, dysgenesis, or hippocampal sclerosis. Quantitative, computer-assisted volume analysis of the temporal lobes may detect asymmetries that are not readily apparent on visual analysis of the scan. CT is valuable in the acute setting to detect hemorrhage, calcification, or tumors. Seizure Syndrome Chart Essay.
Several new imaging techniques are available to aid in the assessment of epilepsy (Kim et al. 2010). MRI abnormalities can be correlated directly with EEG activity. Functional MRI (fMRI) takes advantage of blood oxygen level dependence (BOLD) to image neuronal activation and map interictal or ictal epileptiform activity and localize language and memory. Magnetic resonance (MR) spectroscopy measures the concentrations of a variety of neurochemicals in different brain regions and can sometimes assist in localizing a seizure focus. Positron emission tomography (PET) images the brain’s regional use of glucose with asymmetries suggesting areas of interictal or ictal abnormality. Single-photon emission-computed tomography (SPECT) compares local blood flow discrepancies, information that is most useful when recorded during a seizure. Magnetoencephalography (MEG) assesses the brain’s dynamic electromagnetic fields and can better localize epileptic dipoles, including those tangential to the scalp, which can be missed by conventional EEG (Caruso et al. 2013). These advanced modalities are used mainly in epilepsy centers for presurgical evaluations (Kay and Szaflarski 2014).
Metabolic Evaluation
The type of seizure and syndrome dictates the extent of the metabolic workup (Pearl 2009). For example, a child with IS or Lennox–Gastaut syndrome is more likely to have a metabolic or degenerative disorder than one presenting with simple partial seizures. In metabolic disorders, seizures are typically accompanied by other abnormalities, such as developmental delay, unexplained vomiting, or coma. In neonatal seizures, a metabolic evaluation is mandatory, including a screen of serum amino acids and urine organic acids, and blood lactate to screen for mitochondrial disease.Seizure Syndrome Chart Essay. In addition to its more common use to evaluate CNS infection, cerebrospinal fluid can be analyzed for glucose transporter defects (GLUT1 deficiency syndrome) (Pearson et al. 2013) and rare (but sometimes treatable) neurotransmitter defects (Pearl et al. 2007).
Genetic Testing
As the genetic basis of epilepsies becomes progressively unraveled, clinical testing will occupy an increasingly pivotal role in the clinic (Michelucci et al. 2012; Olson and Poduri 2014). At this point, genetic testing is available for several single genes, as well as complex genetic disorders (see Coulter and Steinhäuser 2015; Vezzani et al. 2015). A basic karyotype can be performed to evaluate for a chromosomal anomaly, especially in a patient with dysmorphic features. If a specific syndrome is suspected, an epilepsy panel of selected genes can be ordered (e.g., SCN1A for Dravet syndrome [DS]). Comparative genomic hybridization (CGH) microarray evaluates targeted chromosomal regions for copy number variants. When a genetic diagnosis is highly suspected, but other work up is unrevealing, the clinician can consider whole exome sequencing of the patient and parents, a technique with rapidly expanding clinical use, especially in epileptic encephalopathies of unknown etiology (Olson et al. 2014). Seizure Syndrome Chart Essay.
SELECTED EPILEPSY SYNDROMES
The most recent ILAE epilepsy classification dispenses with the dichotomies used in the 1989 classification (generalized vs. localization related, idiopathic vs. symptomatic) in favor of an organization according to pathogenesis (genetic vs. structural/metabolic/autoimmune) and age of onset (Berg et al. 2010). Examples of epilepsy syndromes are now provided. Details of epilepsy syndromes not described here can be found elsewhere (Engel and Pedley 2008; Nabbout and Dulac 2008).
Electroclinical Syndromes with Age-Related Onset
BFNE
BFNE is a neonatal epilepsy syndrome in which seizures begin in the first week of life. Seizures are focal clonic or focal tonic, often accompanied by apnea. They usually stop after a few days or weeks. Except for seizures, the infants are normal and evaluation fails to detect an etiology. The key to the diagnosis is a family history of newborn or infantile seizures that resolved. The prognosis of BFNE is good, although ∼10%–15% of affected infants continue to have seizures beyond the neonatal period, even into adulthood (Steinlein et al. 2007).
BFNE is the first epilepsy syndrome to be explained by a mutation in a voltage-gated ion channel gene. BFNE has been linked to two genes: KCNQ2 on chromosome 20q and KCNQ3 on chromosome 8q. These genes code for voltage-gated potassium channel subunits, which regulate the M-current, a muscarine-activated neuronal current that turns off potassium channels (Rogawski and Bazil 2008). The M-current stabilizes resting membrane potential; its dysfunction leads to increased neuronal excitability and seizures.Seizure Syndrome Chart Essay. It is not known why seizures in BFNE affect neonates and then resolve because the genetic defect is present throughout life.
WS
WS is characterized by the triad of epileptic spasms (usually during infancy, when it is called IS), an interictal EEG pattern called hypsarrhythmia, and intellectual disability. WS is an age-specific disorder, beginning primarily in the first year of life; the peak age of onset is between 4 and 6 mo. The duration of an epileptic spasm is intermediate between a myoclonic jerk (which is briefer) and a tonic seizure (which is more sustained). Spasms often occur in clusters of head nods, forceful flexion, or extension of the trunk and limbs. They frequently occur during sleep transitions, especially on awakening.
The interictal EEG pattern in WS is called hypsarrhythmia, a disorganized, “chaotic” pattern of very high voltage slow waves and spikes over multiple cortical areas. The classic ictal EEG pattern is a generalized slow wave followed by background voltage attenuation in all channels (“electrodecremental response”), accompanied by a clinical spasm.
Most cases of WS have an identifiable cause, such as hypoxia-ischemia, intracranial hemorrhage, CNS infection, developmental brain anomaly, or inborn metabolic error. Tuberous sclerosis complex (TSC) has an especially high incidence of IS (up to 50% of TSC patients).
Adrenocorticotrophic hormone (ACTH) and corticosteroids are the primary drugs used to treat IS. The anticonvulsant mechanism of ACTH is not known; it may work via the hypothalamic-pituitary axis or directly affect neuronal membrane excitability (Stafstrom et al. 2011). Vigabatrin, a GABA transaminase inhibitor, is highly effective for spasms in children with TSC. Infants with focal-onset spasms, such as those caused by cortical dysplasia, may benefit from resective surgery.
WS is an epileptic encephalopathy with a poor prognosis. At least two-thirds of affected children have intellectual disability. With age, the seizures often change from spasms to other seizure types, such as those seen in Lennox–Gastaut syndrome (see below). Several animal models of IS have been reported recently, raising hope that elucidating the pathophysiology of IS will lead to more efficacious treatments (Stafstrom 2009; Swann and Moshe 2012; Lado et al. 2013). Seizure Syndrome Chart Essay.
Febrile Seizures Plus
Children with febrile seizures plus (FS+) (formerly called generalized epilepsy with febrile seizures plus [GEFS+]) have febrile seizures beyond the age at which febrile seizures usually stop (∼5 yr). In addition, these children may develop additional afebrile seizure types, including GTC, absence, and myoclonic. Therefore, this syndrome differs from ordinary febrile seizures (see below) and represents a genetic predisposition to epilepsy. In FS+, the outcome is variable; seizures resolve in some children, but persist in others. In different families, genetic defects have been identified in neuronal sodium channels (Escayg et al. 2000) and GABA receptors (Macdonald et al. 2010). Many patients with FS+ have mutations in the α1 subunit of the voltage-gated sodium channel gene, SCN1A (Steinlein 2014).
DS
DS, previously called severe myoclonic epilepsy of infancy, is a rare epilepsy syndrome in which children present with seizures before 18 mo of age (Dravet et al. 2005). The initial seizure often occurs with a fever and has a hemiclonic semiology. Later, other seizure types occur and the child shows developmental regression. Seizures tend to be refractory to medications, although stiripentol has shown some efficacy; sodium channel blockers must be avoided.
About 70%–80% of patients with DS have a mutation in the SCN1A gene, mostly sporadic, with haploinsufficiency causing nonfunctional sodium channels. Therefore, the spectrum of SCN1A mutations in epilepsy spans from mild (FS+–missense mutations) to severe (DS–truncating mutations) (Escayg and Goldin 2010). The presence of SCN1A mutations in multiple epilepsy syndromes has generated considerable research interest. Mice with knockout of SCN1A replicate many clinical features of DS (Oakley et al. 2011). Seizure Syndrome Chart Essay. The cellular defect may be abnormal sodium channels in cortical interneurons, allowing increased firing of downstream excitatory pyramidal neurons, which are released from inhibitory control (Yu et al. 2006). Several laboratories are pursuing potential methods to remediate the effect of the SCN1Amutation (Liu et al. 2013; Lenck-Santini and Scott 2015).
Lennox–Gastaut Syndrome
Lennox–Gastaut syndrome (LGS) begins between the ages of 1 and 6 yr. Patients develop medically intractable seizures (up to hundreds per day), constituting an epileptic encephalopathy. LGS characteristics include: (1) slow spike-wave EEG pattern (1.5–2.5 Hz), (2) intellectual disability, and (3) multiple seizure types (e.g., tonic, GTC, atypical absence, atonic, tonic, myoclonic).
Tonic seizures consist of periods of sustained muscle contractions and are especially frequent during sleep. Atonic (astatic) seizures, or drop attacks, occur without warning and often result in head or face injuries. Atypical absences occur frequently in children with LGS. These have a gradual onset and cessation during which the child appears confused with behavioral arrest. It can be difficult to tell when one seizure ends and the next one begins because alertness and activity level may not improve between epileptiform bursts, which occur in long runs during wakefulness and even more frequently during sleep.
Children with LGS are already handicapped neurologically. The numerous LGS etiologies overlap those of WS and include hypoxic brain injury, cerebral dysgenesis, and neurocutaneous disorders. The encephalopathy in the majority of children with LGS is static, although a degenerative disorder, such as neuronal ceroid lipofuscinosis, can present as LGS.
Seizures in LGS patients are notoriously refractory to AEDs. Drug therapy is individualized to seizure type and frequency (Hancock and Cross 2013). Patients may benefit from valproate, clonazepam, lamotrigine, topiramate, rufinamide, lacosamide, clobazam, or felbamate. Because of the intractability of the seizures, there is a tendency to place patients on multiple AEDs. This polypharmaceutical approach often causes drug toxicity with somnolence, fatigue, nausea, ataxia, and rarely results in optimal seizure control. Seizure Syndrome Chart Essay.
Children with LGS have a poor neurologic prognosis. Over time, the atonic, myoclonic, and atypical absence seizures may decrease, but GTC seizures increase and partial seizures emerge. In addition to debilitating seizures, intellectual impairment hinders children with LGS from leading independent lives. The lack of an experimental model hinders progress in this disorder. One potentially informative animal model mimics atypical absence seizures (Cortez et al. 2001).
Landau–Kleffner Syndrome
Landau–Kleffner syndrome (LKS) (acquired epileptic aphasia) is a rare epilepsy in which a child loses previously acquired language abilities because of seizures or epileptiform abnormalities on EEG. In its pure form, LKS occurs in previously normal children with normal language development who gradually lose the ability to understand spoken language and produce speech (Landau and Kleffner 1957). More recently, the syndrome has expanded to include behavioral and cognitive deterioration, including autistic symptoms. Regression of social and language skills is frequently seen in children with autism, with or without accompanying seizures, so the differentiation of autism and LKS can be difficult. In LKS, compared with autism, social skills are better preserved. The pathophysiology of LKS is unknown. Imaging studies are generally negative although PET studies have shown bitemporal abnormalities, supporting the hypothesis that language-related brain regions are dysfunctional in LKS (Issa 2014).
EEG abnormalities in LKS may include generalized, focal, or multifocal spikes or spike waves. If focal, discharges commonly involve one or both temporal or perisylvian regions. One hypothesis is that the epileptiform discharges interfere with language production; alternatively, both the language dysfunction and EEG abnormalities might be independent consequences of the same underlying brain pathology. Successful treatment of the seizures or EEG discharges is not usually accompanied by language or behavioral improvement. The outcome is variable; some children recover completely, usually in adolescence, whereas others have persistent aphasia in adulthood. The seizures usually respond readily to AEDs (e.g., valproate, benzodiazepines), although the language impairment does not (Van Bogaert 2013). Treatment with steroids or subpial resection is controversial.
Childhood Absence Epilepsy (CAE)
Absence seizures, characterized by staring and diminished responsiveness, can be part of several epilepsy syndromes, including CAE and juvenile myoclonic epilepsy (JME). Note that “absence” refers to both a seizure type and an epilepsy syndrome. CAE onset is between 4 and 10 yr of age. The seizures start abruptly and, generally, last from 5 to 20 sec. When a seizure ends, the patient immediately resumes prior conversation or activity. Because absence seizures are brief and nonconvulsive, they can be easily missed or misdiagnosed.
The frequency of absence seizures varies from a few to hundreds per day. Stress and fatigue increase their frequency. Most children with typical absence seizures have a normal neurologic examination and intelligence, although school performance may be impaired if seizures are frequent. Seizure Syndrome Chart Essay.
The EEG background is normal, whereas the seizure itself is accompanied by generalized 3-Hz spike-wave complexes. This EEG abnormality is a marker for genetic susceptibility to absence epilepsy. Hyperventilation is a potent activator of absence seizures, and this simple test is used in the clinic to diagnose absence seizures and assess treatment effectiveness.
The pathophysiology of absence seizures involves altered function of thalamocortical circuits, with thalamic relay neurons firing abnormally owing to calcium channel dysfunction (Cain and Snutch 2013). Ethosuximide and valproic acid (VPA) are effective for treating absence seizures (Glauser-Menachem et al. 2013). Both drugs block low-threshold calcium currents in thalamic neurons (Coulter et al. 1989). CAE (and other genetic generalized epilepsies) has a complex genetic basis with only a few percent transmitted monogenically. The prognosis of CAE is good with ∼75% of children outgrowing the absence seizures during adolescence.
JME
JME is an epilepsy syndrome that typically begins in adolescence and consists of myoclonic or GTC seizures in an otherwise normal individual. The myoclonic jerks may cause the patient to drop or fling objects, especially in the morning. GTC seizures occur in as many as 90% of patients with JME, and the syndrome often presents with these. The myoclonic and GTC seizures often occur soon after awakening. Up to 35% of patients with JME also have absence seizures. Seizures are exacerbated by fatigue, sleep deprivation, and alcohol use.
The neurologic examination and intelligence are usually normal in JME. Multifactorial inheritance is presumed. Some studies have linked JME to chromosome 6p, a locus that appears to be dominantly inherited, but a responsible gene has not yet been identified, and this mutation accounts only for a small fraction of patients (Michelucci et al. 2012).
The interictal EEG in JME shows characteristic bursts of fast (3.5- to 6-Hz) spike-wave complexes. Photic stimulation may activate these epileptiform discharges. Valproate is the most effective AED, but, in females, other broad-spectrum AEDs are preferable (levetiracetam, lamotrigine). Long-term treatment is usually required.
Epilepsy Syndromes Caused by Structural/Metabolic/Autoimmune Causes
Epilepsy syndromes, previously called “symptomatic localization-related,” are those in which seizures arise in a focal brain region caused by an acquired or congenital lesion. Etiologies include tumor, scar (e.g., hippocampal sclerosis), cortical dysplasia, porencephalic cyst, and vascular malformation. The seizure semiology is related to the region of brain affected; seizures often begin focally and then generalize.Seizure Syndrome Chart Essay. The interictal EEG will show focal spikes, sharp waves, or slowing, related to the area of brain involved. If neuroimaging results, EEG evidence of seizure onset, and ancillary data (e.g., neuropsychological findings) align, surgical intervention is considered.
Temporal Lobe Epilepsy
The syndrome of mesial temporal sclerosis is a pertinent example of a structural lesion (hippocampal scarring), in which seizures often become intractable and for which surgery is a viable option (Thom et al. 2010; Bernhardt et al. 2013). Seizures originate in the medial temporal region with such manifestations as posturing, altered responsiveness, and memory/behavior change. Spread of seizure discharges beyond the hippocampus is common. Seizures often become intractable and affective comorbidities are frequent. When two medications fail, a surgical evaluation should be undertaken. Extensive laboratory investigation has been performed to understand the mechanisms of seizure genesis and spread. Impaired GABAergic inhibition, enhanced synaptic excitation via axonal sprouting, and changes in ion channel distribution and function have all been implicated in the pathophysiology of temporal lobe epilepsy, and genetic factors may also play a role (Liu et al. 1995; Buckmaster 2004; Dudek and Sutula 2007; Joshi et al. 2013). Seizure Syndrome Chart Essay.
