Voltage Gated Calcium Channels

Voltage-regulated or gated calcium channels affect neuronal excitability. As an action potential arrives at a nerve terminal, depolarization of the nerve terminal membrane causes entry of calcium through voltage-gated calcium channels with subsequent release of neurotransmitters. This is the classic paradigm for calcium-mediated neu-rotransmitter release and was the initial observation that demonstrated the importance of calcium in neuronal excitability, but little was understood about the...

Info

Rennie JM, Chorley G, Boylan GB, et al. Non-expert use of the cerebral function monitor for neonatal seizure detection. Arch Dis Child Fetal Neonatal Ed 2004 89 F37. Shellhaas, Venkat A, Clancy RR. Use of single channel EEG for neonatal seizure detection. Epilepsia 2006 47(suppl 4) 13-14. DeVries LS, Toet MC. Amplitude integrated electroencephalography in the full-term newborn. Clin Perinatol 2006 33(3) 619-632. Perlman JM. Intrapartum hypoxic-ischemic cerebral injury and subsequent cerebral...

Figure 233

Magnetoencephalography (MEG) studies from two patients with rolandic epilepsy (left two columns) and a patient with Panayiotopoulos syndrome (right two columns). In rolandic epilepsy, equivalent current dipoles of spikes are located and concentrated in the rolandic regions and have regular directions. In Panayiotopoulos syndrome, equivalent current dipoles of spikes are located and concentrated bilaterally in the rolandic regions and right occipital area. The directions of each equivalent...

Figure 235

Occipital paroxysms with fixation off sensitivity of an 11-year-old boy with idiopathic childhood occipital epilepsy. Occipital paroxysms occur immediately after and as long as fixation and central vision are eliminated by any means (eyes closed, darkness, plus 10 spherical lenses, Ganzfeld stimulation). Under these conditions, even in the presence of light, eye opening does not inhibit the occipital paroxysms. Conversely, occipital paroxysms are totally inhibited by fixation and central...

Brain Inflammation And Epilepsy

One of the most common inflammatory lesions encountered in corticectomies performed for intractable epilepsy is the chronic inflammatory reaction (often with a giant cell or granulomatous component) that is left by depth electrodes implanted for preoperative monitoring purposes within brain parenchyma. Leaving aside the obvious fact that any inflammatory disorder of the brain (especially viral encephalitides, e.g., caused by Herpes simplex) may be accompanied by seizure activity, evidence is...

Epileptic Channelopathy Syndromes

A first expectation, based on earlier studies of channel defects in hyperexcitability disorders of skeletal muscle (e.g., myotonia) and heart (long QT syndrome), would be that channel mutations leading to epilepsy would be associated with increases in Na+ or Ca2+ channel activity (since such activity leads to membrane depolarization) or with reductions in K+ or Cl channel activity (since these currents prevent membrane depolarization) (13, 14). As will be discussed subsequently, we have learned...

Table 114

Metabolic Disorders and Diagnostic Laboratory Tests Plasma, urine, and CSF amino acids Urine orotic acid Disorders of carbohydrate metabolism Fructose 1,6-diphosphase deficiency Propionic, methylmalonic, glutaric aciduria type I Multicarboxylase deficiency Plasma and urine biotin concentration Disorders of folic acid and vitamin B12 metabolism Plasma and urine homocystine and amino acids Carnitine transport defects Plasma acylcarnitine Plasma and CSF lactate Urine organic acids Plasma and urine...

Unverricht Lundborg Disease Confused With Battens

Treatment of these disorders may be distressingly difficult. Accurate diagnosis is the first step, as informed genetic counseling must be given. It is very important to distinguish MERRF, which may show maternal inheritance, from autosomal recessive disorders, such as Unverricht-Lundborg disease, Lafora disease, sialidoses, and the NCLs, and from rare dominant families with Kufs' disease. Genetic counseling may now be extended to prenatal diagnosis in some cases. Specific diagnosis also allows...

Acknowledgments

P. was supported by a Clinical Research Training Fellowship from the American Academy of Neurology. B. S. C. was supported by a K23 award from the NINDS. C. A. W. was supported by grants from the NINDS, the NLM Foundation, and the Marilyn and James Simons Foundation. C. A. W. is an Investigator of the Howard Hughes Medical Institute. Barkovich AJ. Congenital malformations of the brain and skull. In Pediatric Neuroimag-ing. Philadelphia Lippincott Williams and Wilkins, 2005 291-439. Guerrini...

Cockayne Syndrome

Cockayne syndrome is characterized by paucity of growth with developmental delay loss of subcutaneous fat cold, cyanosed extremities increased pigmented nevi and decreased scalp hair. With increasing cachexia the patient's distinctive facies, enophthalmos, and absent fat are prominent features. Mental retardation and microcephaly with ventriculomegaly and questionable normal-pressure hydrocephalus are present. Hyperto-nicity with various movement disorders and myoclonic jerks is present. Optic...

Earlyinfantile Epileptic Encephalopathy With Suppression Bursts Or Ohtahara Syndrome

Ohtahara syndrome was first described by Ohtahara and coworkers in 1976 (5) as the earliest form of an age-dependent epileptic encephalopathy, and it is characterized by frequent tonic spasms of early onset within the first few months of life and a S-B EEG pattern (6-8). Its evolutional change with age is specific (2, 3, 6, 9-12). The seizures are refractory to medications and the prognosis for neurological development is very poor. The age-dependent epileptic encephalopathy includes OS, West...

S

Benign epilepsy of childhood with centrotemporal EEG foci A genetic study. Epilepsia 1975 16 285-293. 27. Bjerre I, Corelius E. Benign familial neonatal convulsions. Acta Paediatr Scand 1968 57 557-561. 28. Brown JK. Convulsions in the newborn period. Dev Med Child Neuol 1973 15 823-846. 29. Dravet C, Bureau M. Roger J. Benign myoclonic epilepsy in infants. In Roger J, Dravet C, Bureau M, et al, eds. Epileptic Syndromes in Infancy, Childhood and Adolescence....

Treatment

All children with LKS and CSWS should have a formal neuropsychological evaluation to guide their educational program and track developmental changes. Children with LKS will, especially, require intensive speech and language therapy. These two syndromes are associated with significant neuropsychiatric comorbidities, and treatment for hyperactivity, attention deficit disorder, mood instability, behavior problems, and even an autistic picture may require referral to a psychopharmacologist and...

Figure

Epilepsy Diary

This axial T2 MR image from a child with intractable localization-related epilepsy shows right-sided hemimega-lencephaly. The entire right hemisphere is larger than the left, and there are abnormalities involving the gray and white matter (R right, L left). associated with epilepsy. As previously detailed in the section on Epidemiology, they are reported with varying frequency in series of children undergoing epilepsy surgery (17-19). The line between such nonneoplastic lesions as FCD and this...

Clinical Manifestations

The onset of LKS usually occurs in children older than 4 years (26), with a range of 3 to 10 years (27). LKS may first manifest as an apparent word deafness or a verbal auditory agnosia. Seizures and behavior disturbances, particularly attention deficits and hyperactivity, each occur in approximately two-thirds of children with LKS (5). The majority of cases are classified as idiopathic, although any pathologic process affecting the auditory cortex may cause LKS. Symptomatic cases have been...

Evaluation Of The First Seizure

There are two populations of children whose seizures are more likely to be associated with an identifiable insult to the brain those who have other neurologic signs or a history of abnormal development and those who have partial seizures that arise from a specific region of the cerebral cortex. However, in infants and young children, in particular, it is not unusual for a generalized seizure to be the first sign of an acute or chronic metabolic disorder or an infection of the brain or meninges....

Basic Mechanisms

Pathophysiology of Seizures and Epilepsy in the Immature Brain Cells, Synapses, and Circuits Libor Velisek and Solomon L. Moshe 1 2. Ion Channels, Membranes, and Molecules in Epilepsy and Neuronal Excitability Laxmikant S. Deshpande and Robert J. DeLorenzo 31 3. Channel Mutations in Epilepsy A Neurodevelopmental Perspective 4. Metabolic and Pharmacologic Consequences of Seizures Michael V. Johnston and John W. McDonald 65 5. Neuropathology Substrates of Epilepsy Caroline R. Houser and Harry V....

Identified gene defects in idiopathic epilepsies

Broadly these defects fall into two major categories (1) gene defects expressed in excitatory or inhibitory ion channels (Table 7-2) and (2) non-ion channel genes. It is of interest to note that despite the involvement of many channels, the net effect achieved is an increase in the excitability of the neuronal membrane and its ability to sustain repetitive firing. Mutations Affecting Ion Channel Genes Evidence linking channel defects with specific epilepsy phe-notype came with discovery of K...

Seizure Phenomena

The symptomatology of partial seizures depends greatly on the location of the seizure focus within the cerebral cortex. Although a given symptom may occur with seizures arising from different locations, the combined information from seizure symptomatology and electroencephalogram (EEG) findings enables one to determine the location of seizure focus. Simple partial seizures with motor manifestations may result from ictal onset within or propagation to the precentral and postcentral gyri of the...

Diagnostic Evaluation And Treatment

The diagnosis of infantile spasms is suggested on the basis of a good clinical history. Thorough general physical and neurological examinations must be performed. This should include a careful ophthalmic evaluation and close examination of the skin using a Wood's lamp to rule out such conditions as tuberous sclerosis. A routine EEG, recorded with the infant awake and asleep, is then obtained, which helps confirm the diagnosis. If the routine EEG does not reveal hypsarrhyth-mia and if the...

Figure 234

Multifocal Epilepsy

Interictal EEG variability in 11 children with Panayiotopoulos syndrome. Despite similar clinical features, EEG spikes are often located in different, often shifting, brain locations. EEG may show a single focus, but multifocal locations are more usual. Some interictal EEGs are similar to those seen in rolandic or idiopathic childhood occipital epilepsy. Brief generalized discharges may occur. Of particular interest are the clonedlike, repetitive, multifocal spike wave complexes these are as...

Conclusions

In this chapter we have indicated the role of EEG in evaluating children with known or suspected seizures. EEG is an important, perhaps the most important, adjunct to history and examination. But, as with any laboratory test, care and judgment must be used in relating EEG findings to other clinical data. Indeed, the full potential of EEG can be realized only when interpretations are placed in the full clinical context. EEG interpretation in infants and children is complicated by two important...

Etiology

Both acquired and inherited factors are implicated in the etiology of absence seizures, reflecting the heterogeneity of the patient population. Genetic factors predominate in children who match the syndromes of idiopathic generalized epilepsy. Alternatively, acquired disorders are frequently found in retarded children with abnormal neurologic findings, abnormal interictal EEGs, and atypical absence seizures. Typical absence seizures, both clinically and electrographi-cally, have been rarely...

Colin D Ferrie Douglas R Nordli Jr Chrysostomos P Panayiotopoulos

___ he International League Against I Epilepsy's ILAE's definition of a I benign epilepsy syndrome is A 4 syndrome characterized by epileptic seizures that are easily treated, or require no treatment, and remit without sequelae 1 . In approximately 60 of children with epilepsy seizures will cease, antiepileptic drugs AEDs can be withdrawn, and seizures will not recur 2 . This indicates that a majority of children with epilepsy have benign conditions. In its 2001 diagnostic scheme, the ILAE...

1

T is still common to use the concept of myoclonic epilepsy as a diagnosis in epilepsy, although the past decades have led to the indi-vidualization of numerous and highly different epileptic syndromes in this category. More important, perhaps, is the fact that myoclonias can be found in the most benign and in the most severe forms of epilepsy, particularly in young children. The clinician's job is to provide patient and family with the best possible treatment, and with a prognosis diagnosis of...

Sejal V Jain Lawrence D Morton

Eizures are time-limited paroxysmal events that result from abnormal, involuntary rhythmic neuronal discharges in the brain 1 . The term seizure appears to arise from a notion that patients were possessed or seized by spirits in old times. Age-adjusted incidence for first diagnosis of unprovoked seizure is 61 per 100,000 person-years 2 . Incidence of first nonfebrile seizure in children is 25,000 to 40,000 per year in the United States 3 . Although mortality directly related to seizure is low...

Modulating the Calcium Signal in Controlling Neuronal Excitability

The discovery of a calcium-binding protein, calmodulin CaM , was the first major breakthrough in understanding the molecular mechanisms that mediate calcium second messenger effects 139, 140 . Evidence now suggests that many of the effects of calcium on cell function are mediated by calmodulin 120, 121, 141-143 . Several important calcium-regulated processes are mediated by calmodulin and by a major calmodulin target enzyme system, calmodulin kinase II 144-146 . Evidence from several...

Longterm Monitoring

It is often desirable to record EEG activity for longer periods than conventional EEG recordings allow, so as to increase the likelihood of detecting epileptiform activity or capturing intermittent behavioral events. Two methods of long-term monitoring are now widely available they have greatly improved diagnostic accuracy and reliability of seizure classification. Both have value in providing continuous recordings through one or more complete wake-sleep cycles and in documenting ictal...

Douglas R Nordli Jr Timothy A Pedley

___ he electroencephalogram EEG is often the single most informative laboratory test in evaluating a children with seizures. At the most rudimentary level, it helps in differentiating epileptic from nonepileptic behavior. Because many conditions, including breathholding spells, movement disorders, syncope, cardiac arrhythmias, sleep disorders, migraine, and various psychiatric syndromes, may mimic epilepsy, EEG findings are often essential in making an accurate diagnosis. EEG, however, offers...

Distinguishing Pme From Other Epilepsies And Myoclonic Syndromes

It usually is not difficult to diagnose the syndrome of PME some years after onset with the distinctive diagnostic triad of myoclonic seizures, tonic-clonic seizures, and progressive neurologic decline. At the beginning of the illness, however, the clinical and EEG features may be similar to those of benign idiopathic generalized epilepsies, particularly mimicking juvenile myoclonic epilepsy. Initial response to therapy may be relatively favorable. However, seizures may become more frequent...

Genetic counseling issues in epilepsy

The issues relating to genetic counseling center around addressing the heritability of epilepsy, the risk of epilepsy in family members and offspring, and the value of genetic testing in epilepsy 10 . We have attempted to summarize the risk estimates in comparison to the general population risk in family relatives sibship and offspring Table 7-5 based on the data from epidemiologic studies in the literature presented in 102 . At the outset, it should be clarified that epilepsy is not a single...

References

The epidemiology of epilepsy in Rochester, Minnesota, 19351967. Epilepsia 1975 16 1-66. 2. Hauser W. The prevalence and incidence of convulsive disorders in children. Epilepsia 3. Hauser WA. Incidence and prevalence. In Engel J Jr, Pedley TA, eds. Epilepsy A Comprehensive Textbook. Philadelphia Lippincott-Raven Publishers, 1997 47-57. 4. Scher M. Neonatal seizures. In Wyllie E, ed. The Treatment of Epilepsy Principles and Practice. Baltimore Williams amp Wilkins, 1996...

Figure 173

Doose syndrome myoclonic-astatic epilepsy, MAE . A typical aspect of the EEG in a patient with MAE. Both segments generalized or diffuse EEG changes with irregular spike waves. Right segment a myoclonic-astatic episode, with myoclonias and atonia as shown on the polygraphic EMG leads . which increase during sleep. The presence of a regular, rhythmic theta activity at 4-7 Hz predominating over the vertex and central areas is considered fairly specific of MAE, but it is not present in all...

Prognosis

Contrary to previous reports that stated that up to one-third of patients with CPS became seizure-free 139 , our experience and that of others indicates that although some patients do become seizure free on medication, spontaneous remission that is, seizure free off medications is rare 140 . Pazzaglia and coworkers reported that good seizure control was achieved in 31 of patients with simple partial seizures, 37 of those with complex partial seizures, and 61 of those with secondarily...

Differential Diagnosis

Differential Diagnosis between OS and WS The age of onset of the two syndromes is different OS appears from the neonatal to early infantile periods and WS in middle infancy. Although the main seizure type is tonic spasms in both syndromes, tonic spasms in OS appear not only while awake but also during sleep, and not only in clusters. Partial seizures also occur in some OS cases but are rare in WS. Most cases with OS have severe cortical pathology, often displaying asymmetric lesions on...

Course And Prognosis

The average age of cessation of absence seizures is 10.5 years 12 however, some children continue to have absence seizures beyond puberty. Typical absence seizures generally have a favorable prognosis, with remission rates of approximately 80 7, 127-129 . An analysis of 52 patients with childhood absence by Loiseau and coworkers 130 demonstrated complete control in 95 of patients with absence seizures only and in 77 of patients with absence plus generalized tonic-clonic seizures. In contrast,...

Figure 172

Emg Myoclo

Dravet syndrome severe myoclonic epilepsy in infancy, SMEI . This child had a typical history, with early-onset simple febrile seizures. This plate illustrate one of the multiple aspects of clinical manifestations of SMEI. During a state of obtundation, the patient has both segmental, asynchronous, and diffuse myoclonias, as shown on the polygraphic EMG leads. The EEG shows global slowing, and predominantly multifocal sharp waves. seizures. Later, the background activity is variable, partly in...

Physical Examination

Head circumference should be measured. Presence of microcephaly could be secondary to congenital infections, hypoxia or maternal diseases, and drug and toxin exposure. Cranial malformations such as lissencephaly, cortical dysplasia, and heterotropia are primary causes of microcephaly 30-32 . Macrocephaly is associated with storage disorders and hydrocephalus 31 . Fundoscopic examination may show papilledema suggesting increased intracranial pressure or cherry red spot associated with storage...

Idiopathic Partial Epilepsies

Benign Partial Epilepsy in Infancy with Complex Partial Seizures This syndrome is characterized by complex partial seizures CPS occurring in clusters, age at onset mostly during the first year of life, a family history of benign infantile seizures in many cases, normal development prior to onset, no underlying disorders or neurological abnormalities, normal cranial computed tomography CT and magnetic resonance imaging MRI findings, normal interictal EEGs, excellent response to drug treatment,...

Table 211

Treatments for Children with Lennox-Gastaut Syndrome First-line treatments based on clinical experience or conventional wisdom Valproic acid Benzodiazepines Pyridoxine Suspected effective treatments based on open-label uncontrolled studies Adrenocorticotropic hormone-corticosteroids Intravenous immunoglobulin Vigabatrin Zonisamide Ketogenic diet Corpus callosotomy Vagus nerve stimulation Effective treatments based on double-blind, placebo-controlled studies Felbamate Lamotrigine Topiramate...

Functional Neuroimaging

Functional neuroimaging provides information complementary to structural MR imaging in the diagnosis of epilepsy. Positron emission tomography PET allows visualization of brain glucose metabolism with the use of positron-emitting ligands such as 2-deoxy-2- 18F fluoro-D-glucose FDG . Other ligands more specific to epilepsy have been developed, including nC flumazenil FMZ , which binds to GABAa receptors 70 , and alpha- 21C methyl-L-tryptophan AMT , which measures tryptophan metabolism 71 ....

Pathophysiology

The pathophysiology of LGS is not well known 14 , and there are no animal models 18 . A variety of possible pathophysiologies have been proposed including developmental, immunologic, and metabolic. One hypothesis is that there is excessive permeability in the excitatory interhemispheric pathways in the frontal areas at the time the anterior parts of the brain mature. This maturation commonly occurs around the age of onset of LGS and would allow for synchronization of both frontal lobes 18 ....

Febrile Seizures And Mesial Temporal Sclerosis

It remains controversial whether prolonged febrile seizures cause mesial temporal sclerosis MTS 39, 52 . Retrospective studies from tertiary epilepsy centers report that many adults with intractable mesial temporal lobe epilepsy had a history of prolonged or atypical febrile seizures in childhood 94-100 . However, both population-based studies and prospective studies of children with febrile seizures have failed to find this association 2, 8, 9, 13, 33, 38, 47 . In those studies that reported...

Eli M Mizrahi

He first four weeks of life are one of I the greatest periods of seizure hazard during childhood. The occurrence of seizures within this neonatal period is associated with significant morbidity and mortality. These seizures are often difficult to recognize clinically and treat effectively and can represent significant diagnostic and management challenges. In addition, despite their clinical importance, there are a number of unresolved issues concerning aspects of pathophysiology, mechanisms of...

Seizure Induced Structural Hippocampal Damage

Hippocampal Sclerosis

Studies in adult animals have shown that severe or repeated seizures can indeed induce hippocampal damage 268-274 . In the adult rats, kainic acid or pilocarpine administration or electric stimulation produce status epi-lepticus and hippocampal damage. This seizure-induced damage is more pronounced in CA3 and hilar cells than in CA1 145, 269, 273, 274 and is accompanied by sprouting of the mossy fibers of the granule cells in the dentate gyrus to the supragranular layers 275-281 . Later, after...

Figure 126

Electrodecremental event in a 7-month-old child characterized by transient flattening of background activity middle of figure . Such events frequently accompany the massive spasms of West syndrome. in relation to the ictal discharge 19 . Even short bursts of 3-Hz spike-wave activity produce some functional impairment that may go unrecognized clinically. Thus, childhood absence epilepsy is one instance in which follow-up EEGs are often necessary to gauge how effective treatment is clinical...

Disorders That Occur During Sleep

Benign neonatal sleep myoclonus is the most common quasi-epileptic disorder 19, 20 . It usually occurs during sleep and begins early in infancy, often in the first weeks or months of life however, it can be seen in older infants and even in young children. The disorder occurs during non-rapid eye movement NREM sleep. Rapid, forceful jerks may occur in the distal extremities, such as the hands or feet, or in the more proximal muscles, moving the entire limb or...

Lafora Disease

Lafora disease is characterized by the presence of Lafora bodies, which are polyglucosan inclusions found in neurons and in a variety of other sites, including the heart, skeletal muscle, liver, and sweat gland duct cells 35, 36 . Onset of Lafora disease is between the ages of 10 and 18 years, with a mean age of onset of 14 years. Clinical features are myoclonus, tonic-clonic seizures, and relentless cognitive decline. Focal seizures, particularly that arise from the occipital regions, occur in...

Withdrawing Aeds In Children With Epilepsy Who Have Been Seizure Free For 2 Or More Years

The available data indicate that children who are seizure free on medication for 2 or more years have a very high likelihood of remaining in remission on medication 39 . In selected populations, withdrawal may be feasible after an even shorter seizure-free interval 39-42 . How long should a child be maintained on medication before the attempt is made to withdraw it This decision will be influenced by a variety of factors, including the probability of remaining seizure free after withdrawal in a...

Benign Myoclonic Epilepsy In Infancy

Benign myoclonic epilepsy in infancy BMEI was individualized among the early-onset myoclonic epilepsies nearly 30 years ago 6 . BMEI stands out as the earliest form of idiopathic generalized epilepsy 7, 8 . It is easily recognizable, with solid clinical and electroencephalogram EEG features. Extensive experience with this syndrome has led to the description of clinical variants, which share its excellent overall prognosis. Its diagnostic criteria can be summarized as follows Onset in a normal...

Clinical Presentation And Classification Of Cerebral Cortical Malformations By Stages Of Cortical Development

The process of brain development, which follows a sequence that is under genetic regulation, provides a framework for understanding the variety of cerebral cortical malformations encountered in patients with pedi-atric epilepsy. The classification presented by Barkovich and colleagues has evolved to include an ever-expanding list of genetic etiologies for many cerebral malformations 1, 19, 66 . The importance of its emphasis on genetic causes cannot be overstated even when epilepsy is not the...

Laboratory Studies

Seizures provoked by metabolic abnormalities in an otherwise normal child are rare. Therefore, basic tests should be done based on clinical judgment per American Academy of Neurology AAN guidelines for evaluation of first unprovoked seizure 3 . If there is clinical suspicion of meningitis or encephalitis, lumbar puncture should be done per AAN guidelines for evaluation of first unprovoked seizure. Routine urinalysis is not recommended, but if there is clinical suspicion of recreational drug...

Imaging Modalities

Fetal ultrasound is a screening tool that has an established role in the diagnosis of cerebral malformations, congenital anomalies, and complex syndromes. In the postnatal period, ultrasound is often the initial study in a diagnostic workup for seizure activity. It has the benefits of being noninvasive and avoiding radiation exposure. Neonatal head ultrasound's primary role has traditionally been in the evaluation of the preterm newborn for diagnosis of parenchymal hemorrhage, germinal matrix...

Individual Syndromes

Juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures GTCS on awakening are the three syndromes of idiopathic generalized epilepsy of adolescent onset currently included in the ILAE classification. Childhood absence epilepsy is discussed in Chapter 22. JME is one of the most common forms of epilepsy seen in the adolescent population, and is one of the best-defined syndromes. Although there is some controversy, JME appears to represent a...

Epidemiology

LKS and CSWS are rare syndromes among the pediatric epilepsy syndromes. In a recent 20-year epidemiologic study of childhood epilepsy, Kramer and colleagues reported LKS and CSWS in 0.2 each, compared with West syndrome in 9 , myoclonic seizures in 2.2 , and Lennox-Gastaut syndrome in 1.5 24 . Ohtahara syndrome and myo-clonic astatic epilepsy also occurred in 0.2 each. In a review of LKS, Smith and Hoeppner 25 noted that only 81 cases had been reported between 1956 and 1980, whereas 117 cases...

Genetic Predisposition To Seizures And Epilepsies

Many forms of human epilepsy are genetically determined 203 . The mechanisms by which a multitude of genetic aberrations alter epileptogenicity are unclear. To date, there are several models of genetically determined epilepsy available in baboons, in rats, and many mutant mouse strains with epileptic disorders 42, 204 . The major advantage of gene mutation models is the occurrence of spontaneous seizures. The disadvantages may be that there may not be any obvious human correlate, or if there...

Evidence That Eaa Neurotransmitters Play A Role In Seizurerelated Injury

The link between excessive EAA neurotransmitter activity and epileptic brain injury was initially strengthened by Meldrum's pioneering studies in subhuman primates 9 . These studies showed that seizures alone could damage the brain and that the EAA analog kainic acid produced sustained seizures and brain injury with a regional his-tologic pattern resembling epileptic brain injury. Similar studies of selective injury in the hippocampus from kai-nic acid injection into the brain have been...

Historical Background

Early discussions on epilepsy rarely differentiated between epilepsies in childhood and those in adult life. The history of classification of the epilepsies might be defined in three major eras the philosophical era before the twentieth century, marked by patient observation and, to a large degree, philosophical speculation as to the nature of the disease the era of the localizationalists and pathologists, spanning roughly the first half of the twentieth century and the present molecular era,...

General Principles Of Therapy

Treatment Decisions in Childhood Seizures Shlomo Shinnar and Christine O'Dell 401 30. Comparative Anticonvulsant Profile and Proposed Mechanisms of Action of Antiepileptic Drugs H. Steve White and Karen S. Wilcox 413 31. Evidence-Based Medicine Issues Related to Drug Selection Tracy A. Glauser and Diego A. Morita 429 32. Combination Drug Therapy Monotherapy Versus Polytherapy 33. Adverse Effects of Antiepileptic Drugs L. James Willmore, James W. Wheless, and John M. Pellock 449 34. Status...

Sustained Repetitive Firing And Sodium cHannel Regulation

In studying SRF, several properties of neuronal excitability and seizure phenomenon have been recognized. Voltage-gated sodium channels are responsible for the rising phase of neuronal action potentials. Upon neuronal depolarization to action potential threshold, the sodium channel undergoes a conformational change that results in the channel opening for a few milliseconds from its closed resting , nonconducting state to permit sodium flux. The channel inactivates within a few milliseconds to...

Physiology

In vivo microelectrode studies show no evidence of inhibition in the paired-pulse paradigm in the cornu ammonis 1 CA1 area of the hippocampus prior to PN18 in rats, after which the intensity of inhibition steadily increases to reach adult levels by PN28. In contrast, already at PN14 the measures of excitation i.e., excitability and spike width are at fully mature levels 46 . These results indicate that in the rat hippocampus, excitatory processes are well established or fully mature within 2...

Preface

A s with the first and second editions, the goal of this third edition of Pediatric Epilepsy Diagnosis and Therapy is to assist all professionals involved in the care of pediat-ric patients with seizures and epilepsy. Our goal continues to be the perfect result no seizures, no side effects, and no stigma to limit these children from achieving their full potential. The scope and depth of coverage of this book remains unique in its field. We have again tried to balance discussions of practical...

Chromosomal Abnormalities And Congenital Brain Abnormalities

Chromosomal abnormalities, including trisomy 13 and 21, may result in infants and children with seizure activity. Approximately 20 percent of patients with fragile X syndrome have seizures generalized or partial with spikes similar to rolandic spikes, which are noted during sleep tracings 81, 82 . Five percent to 6 of children with Down syndrome trisomy 21 have seizures 83 . Infantile spasms may occur but are fairly responsive to therapy. Congenital malformations with neurologic deficits can...

Raman Sankar MD PhD

Professor and Chief, Pediatric Neurology Rubin Brown Distinguished Chair David Geffen School of Medicine Mattel Children's Hospital University of California, Los Angeles Los Angeles, California Compositor and Indexing Publication Services, Inc. Visit our website at www.demosmedpub.com 2008 Demos Medical Publishing, LLC. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic,...

Steve White Karen S Wilcox

Or the vast majority of people who I develop epilepsy, initial therapy consists of pharmacologic treatment with one or more of the established anticonvulsant drugs. These medications include phenytoin PHT , carbamazepine CBZ , valproate VPA , barbiturates such as phenobarbital PB , certain benzodiazepines BZDs , and ethosuximide ESM . For some patients, complete seizure control with this group of established antiepileptic drugs AEDs may not ever be achieved at doses that are devoid of various...

Classification Of Epileptic Seizures And The Epilepsies

Evolution of the Classification Schemes Classification is an ongoing process that is sequentially refined by addition of new information regarding seizures and the epilepsies. Our predecessors worked hard to lay down the foundations of our currently used classification schemes the 1981 International League Against Epilepsy ILAE classification of seizures and the 1989 ILAE classification of epilepsy syndromes 8, 9 . These classifications, intimately familiar to all epileptologists and many...

Figure 136

Flair Popcorn

Dysembryoplastic neuroepithelial tumor DNET . Horizontal post-contrast T1W image of a child with a DNET. The lesion is based in the cortical and subcortical region of the posterior insula on the left. The lesion has minimal mass effect and a cystlike appearance medially with a posterolateral nodule that follows gray matter signal black arrow . gelastic seizures as well as other types of partial and generalized seizures, including atypical absence and drop attacks 20 . Lesions usually are...

Table

Pros and Cons of Genetic Absence Models in Rats Absence Seizure Models in Genetically Prone Rats Spontaneous seizures Good electroclinical correlation to human absences Developmental discrepancy with the onset of human absence seizures Many spontaneous as well as engineered gene mutations were identified in mice and are now an important tool to study epilepsy syndromes, with the information well exceeding the extent of this chapter. Recently, several excellent reviews on this topic have been...

Symptomatic And Cryptogenic Partial Epilepsies In Infancy

Etiologies of symptomatic partial epilepsies in infants include focal cortical dysplasia FCD , pachygyria, poly-microgyria, low-grade dysplastic changes, heterotopic gray matter, schizencephaly, Sturge-Weber syndrome, tuberous sclerosis, hemimegalencephaly, with or without various neurocutaneous syndromes, dysembryoplastic neuroepithelial tumor, ganglioglioma, gangliocytoma, glialneuronal hamartoma, perinatal postnatal insult, and hippocampal sclerosis with or without cortical dysplasia 18,...

Diagnosing The Specific Type Of

Once the clinician is convinced that a patient has the PME syndrome, the critical question is to determine which specific disorder is present. This is essential for proper clinical and genetic counseling of the family see Treatment'' section . It is now possible to provide a specific diagnosis in life for the majority of patients with PME using clinical methods and minimally invasive investigations. An approach to this problem has been described previously. The clinician should first consider...

Developmental Changes In Glutamate Neurotoxicity

The immature brain is quite sensitive to neurotoxicity from glutamate and certain of its analogs 33, 60 . Olney discovered a number of years ago that feeding monosodium glutamate to neonatal mice produced characteristic lesions in the hypothalamus 33 . More recently, it has become clear that the receptors that mediate glutamate neurotoxicity respond differently in the immature brain compared with the adult brain. These observations have important implications for the EAA neurotransmitter...

The Gaba System Neuronal Excitability And Seizure Activity

Gamma-aminobutyric acid is the major inhibitory neu-rotransmitter in brain. It has been extensively characterized and plays a major role in regulating neuronal excitability by controlling chloride permeability 23-25 . Specific binding sites for GABA molecules have been identified in neuronal membrane. Although not all GABA receptors are linked to the chloride channel, a large proportion of these receptors are directly involved in regulating chloride channel function. The major inhibitory effect...

Ictal Clinical Manifestations

The repertoire of ictal manifestation of epilepsy in infants is limited. Seizures often begin with a change in facial expression or behavior, but the most striking feature is an arrest or marked reduction of behavioral motor activity, which was formerly called a hypomotor seizure 18 . Some authors consider seizures complex partial if nonconvulsive ictal phenomena are associated with disturbance of contact or unresponsiveness and focal or nongeneralized paroxysmal EEG discharges 15, 19 , but...

Exposure To Epileptogenic Stimuli Fever Infection Hypoxia During Development

Infants are exposed to a high risk of epileptogenic stimuli, represented by greater exposure to infectious agents that lead to fever and sometimes to cerebral infections. Neo-nates and infants may also often suffer from perinatal hypoxia ischemia. In susceptible subjects, these stimuli may induce seizures, and because of the higher susceptibility of the young brain to seizures, these seizures occur multiple times a day and may be difficult to control with currently available AEDs 239-245 ....

Potassium Channels

Potassium channels play a major role in regulating neuronal excitability. Although more than 20 types of potassium channels have been identified by biophysical studies, there are four major groups calcium-activated, voltage-gated, sodium-activated, and inwardly rectifying potassium channels. These different types of potassium channels are regulated by neuromodulators, ions, and second messenger systems. The opening of potassium channels has the effect of hyperpolarizing neurons or reversing...

Reza Behrouz Selim R Benbadis

Idiopathic generalized epilepsies IGEs are a distinct group of epi- lepsies, clearly defined in the 1989 International Classification of Epileptic Syndromes and Epilepsies. This classification established an important dichotomy between the idiopathic epilepsies on the one hand, and the symptomatic or cryp-togenic epilepsies on the other 1 . In prior versions of this classification, IGEs were referred to as primary generalized epilepsies, and symptomatic cryptogenic generalized epilepsies were...

Antiepileptic Drugs And Ketogenic Diet

Bourgeois and Raman Sankar Rajesh RamachandranNair and O. Carter Snead, III 543 Kevin Farrell and Aspasia Michoulas 557 42. Carbamazepine and Oxcarbazepine 43. Ethosuximide, Methsuximide, and Trimethadione Gregory L. Holmes and Philip L. Pearl 593 Raman Sankar and W. Donald Shields 611 49. Phenytoin and Related Drugs Dietz Rating, Nicole Wolf, and Thomas Bast 653 Shlomo Shinnar, Richard Civil, and Kenneth W. Sommerville 661 G nter Kr mer and Gabriele Wohlrab 699 55....

Sustained Repetitive Firing

Sustained high-frequency repetitive firing is an important property of vertebrate and invertebrate neurons that correlates with the excitability state of the neuron 6-10 . Many central nervous system CNS neurons exhibit SRF. Although no direct evidence has demonstrated the link between SRF and epilepsy, information from in vitro studies on isolated neurons may have some bearing on altered neuronal excitability and anticonvulsant action. Sustained repetitive firing is a nonsynaptic property of...

T

He International League Against Epilepsy ILAE defined a febrile seizure as a seizure in association with a febrile illness in the absence of a CNS infection or acute electrolyte imbalance in children older than 1 month of age without prior afebrile seizures 1 The temperature associated with the febrile illness must be greater than 38.4 C, although the temperature may not be evident until after the seizure. Prior epidemiological studies have used either one month 2-8 or 3 months 9,10 as the...

Drowsiness

r T r r r tmtt-t-v tVH .- VNS 'J 1 jj ,'A n v v,J S Benign myoclonic epilepsy in infancy BMEI . Two-year old female infant with onset before age 1 of myoclonic jerks, who remained untreated until this polygraphic-EEG evaluation at age 2, showing waking and drowsiness. Note the correlation between generalized, irregular spike wave discharges on the EEG and myoclonic jerks shown on the deltoid EMG leads. the reflex forms, or in patients with slightly later onset, after infancy. The jerks may...

Prakash Kotagal

He International Classification of Epilepsies and Epileptic Syndromes I 1 divides epilepsy, first, on the basis of whether the seizures are partial localization-related epilepsies or generalized generalized epilepsies and, second, by etiology idio-pathic, symptomatic, or cryptogenic epilepsy . Idiopathic epilepsies are defined by age-related onset, clinical and electroencephalographic characteristics, and a presumed genetic etiology. Symptomatic epilepsies comprise syndromes based on anatomic...

W Allen Hauser P Nina Banerjee

S a group, the convulsive disorders are among the most frequently occurring neurologic conditions 4 in children. In the United States approximately 5 of children and adolescents experience a seizure of some type by the age of 20 1 . This proportion may be very different in other cultures higher, for example, in Japanese and lower in Chinese or Asian Indians. The greatest proportion of these children experience convulsions only in association with a febrile illness. Only about a quarter of those...

Contributors

Distinguished Professor and Sally Reahard Chair Indiana University School of Nursing Indianapolis, Indiana Chapter 66 Quality of Life in Children with Epilepsy Department of Pediatric Neurology Lille University Hospital Pharmacology Laboratory Lille Medical School Lille, France Chapter 58 Inflammation, Epilepsy, and Anti-Inflammatory Therapies Assistant Professor Department of Human Services California State University Fullerton, California Chapter 68 Academic Deficits and Interventions in...

James J Riviello Jr Stavros Hadjiloizou

Epilepsy Diagnossis Ilae

___ he Landau-Kleffner syndrome I LKS and epilepsy with continuous spikewaves during slow-wave sleep 4 CSWS are recognized as specific epilepsy syndromes by the International League Against Epilepsy ILAE 1-3 . They were first classified as epilepsies and syndromes undetermined as to whether they are focal or generalized 2 . They are now classified as an epileptic encephalopathy, defined as disorders in which the epileptiform abnormalities may contribute to progressive dysfunction 3 . Other...