CHAPTER

3
Seizures and Epilepsy
Paul R. Carney and James D. Geyer

DEFINITIONS AND EPIDEMIOLOGY

A general simplied denition of a seizure is a sudden temporary change in brain function caused by an abnormal rhythmic electrical discharge. Epilepsy is, simply put, a state of recurrent seizure activity. The mechanism whereby a seizure turns into epilepsy, a process known as epileptogenesis, is controversial. Seizures are common in humans, with an incidence of approximately 80/100,000 per year and an overall risk of epilepsy of 1% to 3%.1 Status epilepticus is a less common form of severe prolonged seizure activity with a high morbidity and mortality.

PATHOGENESIS
Seizures arise secondary to a number of etiologies. Idiopathic seizures, or cryptogenic seizures, are fairly common. Contrary to what many patients and families might think, the inability to nd a cause for the seizure is not necessary bad. In fact, this may portend a somewhat better prognosis for long-term seizure control. Febrile seizures are common in children and are covered in detail in Chapter 4. Trauma contributes to the risk of seizures in two fairly distinct fashions. Early posttraumatic seizures are typically associated with intracranial hemorrhage, focal neurological decits, posttraumatic amnesia exceeding 24 hours, and linear skull fractures. Late posttraumatic seizures are also associated with intracranial hemorrhage and posttraumatic amnesia exceeding 24 hours, but are usually seen in patients with depressed skull fractures and with the injury after age 16 years.24 A number of congenital malformations increase the risk for epilepsy. Disorders associated with migrational

disorders and structural anomalies often increase the risk of subsequent seizures. The genetic diseases listed in Table 3-1 also increase the risk of epilepsy whether or not they are associated with structural malformations.57 Infections are also common causes of seizure activity in the pediatric population. Meningitis and encephalitis can result in seizures either related to the fever or to the direct effects of the infection. These are covered in detail in the chapters on infectious disease. Bacterial infections can result in meningitis, encephalitis, and abscess formation. Herpes simplex virus (HSV) is a well known cause of seizures and can be catastrophic.8 Other viral infections including cytomegalovirus (CMV) infection and various viral encephalitides can result in seizures. Fungal infections and toxoplasmosis also raise the risk of developing seizures. A wide array of toxic and metabolic disorders can result in seizures. These derangements can cause seizures to occur de novo but can also worsen a preexisting epilepsy. The common metabolic and toxic causes of seizures are listed in Table 3-2.

Table 3-1. Genetic Causes of Epilepsy

Amino acidurias Channelopathies Lysosomal storage diseases Phakomatosestuberous sclerosis, von HippelLindau disease, neurobromatosis Phenylketonuria (PKU) SturgeWeber syndrome

CHAPTER 3 Seizures and Epilepsy

31

Table 3-2. Toxic/Metabolic Causes of Seizures

Drug Intoxication Amphetamines Cocaine Lidocaine Theophylline Tricyclic antidepressants Drug withdrawal Antiepileptic drugs (AEDs) Barbiturates Benzodiazepines Ethanol Electrolytehypo/hypernatremia, hypo/hyperglycemia, hypocalcemia, hypomagnesemia Heavy metalslead, mercury Hyperosmolarity Hypoxia Liver failure Porphyria Pyridoxine deciency Thyroid storm Uremia (usually following 3 days of anuria)

Generalized seizures are the other major seizure type. In this category of epilepsy, the seizure affects the entire cortex electrically. Several subtypes of generalized seizures have also been identied, including absence epilepsy with 3-Hz spike and wave activity, generalized tonic-clonic seizures, juvenile myoclonic epilepsy, and progressive myoclonic epilepsy. The Revised International Classification of Epilepsies, Epileptic Syndromes and Related Seizure Disorders divides the generalized epilepsies as follows10: Primary generalized epilepsy Symptomatic generalized epilepsy Cryptogenic epilepsy A number of seizures and epilepsies may be very difcult to categorize. The Revised International Classication of Epilepsies, Epileptic Syndromes and Related Seizure Disorders groups these disorders in the undetermined category. These seizures may be divided as follows10: Both focal and generalized Situation-related epilepsy Febrile convulsions Isolated seizure Isolated status epilepticus Toxic/metabolic In each of these cases, the electroencephalographic (EEG) findings may be different. The EEG serves as a vitally important tool in the correct diagnosis of the various epilepsy subtypes and syndromes.

Cerebral ischemia is a common cause of seizures in the neonate and in the older adult but is relatively uncommon in the older pediatric population. Seizures usually occur in the more slowly growing tumors. Tumors located in the supratentorial region cause seizures more frequently than do cerebellar or brainstem tumors.

DIAGNOSIS
Seizure Types
Generalized tonic-clonic seizures
Generalized tonic-clonic seizures typically have no preceding aura but may have a prodrome of apathy or irritability. During the tonic phase, the jaw snaps shut followed by 10 to 15 seconds or longer of tonic spasms, apnea, and cyanosis. The clonic phase usually consists of 1 to 2 minutes of rhythmic generalized muscle contractions and increased blood pressure. The postictal phase lasts for minutes to hours, with confusion, somnolence, and possibly agitation. The ictal EEG usually consists of generalized spike and wave or polyspike activity. The interictal EEG is highly variable with a normal background in some patients and slowing present in others. Generalized seizures are rare in newborns. Generalized seizures occur most frequently in children secondary to fevers and metabolic derangements.

CLINICAL PRESENTATION
Epilepsy is divided into several categories with signicant differences in the characteristics of the electrical discharges as well as the clinical manifestations. Localizationrelated epilepsy or partial epilepsy has a primary focus from which the electrical discharges arise. Complex partial seizures occur with alteration of awareness while simple partial seizures have no alteration of awareness. Jacksonian motor seizures, Rolandic epilepsy, temporal lobe epilepsy, and frontal lobe epilepsy are all examples of partial epilepsy. The Revised International Classication of Epilepsies, Epileptic Syndromes and Related Seizure Disorders divides the localization-related epilepsies as follows:10 Idiopathic localization-related epilepsy Symptomatic or secondary localization-related epilepsy Cryptogenic localization-related epilepsy

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Section 2: Common Pediatric Neurologic Problems

Absence seizures
Absence seizures typically have no preceding aura or prodrome. An absence seizure usually lasts for only several seconds to minutes. There is a sudden interruption of consciousness, staring, 3-Hz blinking, and less frequently automatisms. There is no postictal confusion.11 The ictal EEG usually consists of 3-Hz generalized spike and wave activity with some slowing of the discharge frequency during the seizure. The interictal EEG usually has a normal background. Atypical absence seizures have generalized spike and wave activity but usually have a frequency less than 3 Hz.12 Absence seizures typically start between ages 4 and 10 years and resolve by age 20 years. Atypical absence epilepsy usually occurs in children who are neurologically or developmentally abnormal.13
Table 3-3. Progressive Myoclonic Epilepsies
Dentorubral-pallidoluysian atrophy Juvenile neuroaxonal atrophy Lafora disease Late infantile and juvenile GM2 gangliosidosis Myoclonic epilepsy and ragged red bers (MERRF) Neuronal ceroid lipofuscinosis (NCL) (also known as Batten disease) Noninfantile Gaucher disease Sialidosis UnverrichtLundborg disease (Baltic myoclonus)

Febrile seizures
Febrile seizures occur with a prodromal fever. A simple febrile seizure occurs as a brief generalized tonic clonic seizure occurring after the onset of fever. A complicated febrile seizure has prolonged seizure activity or focal seizure activity. Febrile seizures are covered in detail in Chapter 4.

Juvenile myoclonic epilepsy

The seizures associated with juvenile myoclonic epilepsy typically have no preceding aura but may have a prodrome of morning myoclonus. The seizures may consist of generalized tonic-clonic activity; however, absence seizures may also occur. The postictal phase is variable depending on the seizure type.11 The ictal EEG usually consists of generalized polyspike and slow wave activity. The interictal EEG is typically unremarkable.12 The age of onset of juvenile myoclonic epilepsy is typically 10 to 20 years. Patients are usually developmentally and neurologically normal.13

sharp waves alternate with a suppressed EEG.17 The clinical features of West syndrome include infantile spasms and mental retardation, which varies according to the etiology of the spasms. Aicardi syndrome is an X-linked disorder present from birth that is associated with infantile spasms. The seizures are described as infantile spasms, but alternating hemiconvulsions may also be seen. The clinical features of Aicardi syndrome include coloboma, chorioretinal lacunae, agenesis of the corpus callosum, vertebral anomalies, and seizures.18

LennoxGastaut syndrome
LennoxGastaut syndrome typically begins between 1 and 10 years of age. There are multiple seizure types, associated with variable degrees of mental retardation. The EEG reveals a slow spike wave complex with a frequency of 1 to 2.5 Hz, multifocal spikes, and generalized paroxysmal fast activity (GPFA).19

Progressive myoclonic epilepsy

The family of disorders known as the progressive myoclonic epilepsies (Table 3-3) consists of a number of loosely related disorders. These epilepsy subtypes are quite rare and have complex presentations and diagnostic ndings. Most of these disorders have a genetic basis, though sporadic cases have occurred in some cases (Table 3-4). The EEG associated with these disorders is variable. The background is often slow. The seizures are typically generalized.11

Partial seizures: localization-related epilepsy

Jacksonian motor seizures are simple partial seizures with no alteration of consciousness. These seizures begin with tonic contractions of the face, ngers, or feet and transform into clonic movements that march to other muscle groups on the ipsilateral hemibody. There is no alteration in consciousness, but postictal aphasia may occur if the primary epileptogenic zone involves the dominant hemisphere. Simple partial seizures may involve autonomic (Table 3-5), sensory, motor, or psychic functions.

Infantile spasms
West syndrome typically begins between 3 months and 3 years of age.1416 The seizures associated with West syndrome consist of a jack-knifing movement and myoclonus. The EEG consists of a hypsarrhythmia pattern with bursts of asynchronous slow waves; spikes and

Complex partial seizures

Benign Rolandic epilepsy. Benign Rolandic epilepsy usually begins between ages 5 and 10 years and is transmitted in an autosomal dominant pattern with variable penetrance. It is fairly common, with an incidence of

CHAPTER 3 Seizures and Epilepsy

33

Table 3-4. Distinguishing Characteristics of the Progressive Myoclonic Epilepsies Clinical Features
Ch o r e a Dentorubral-pallidoluysian atrophy Juvenile neuroaxonal dystrophy Juvenile Gaucher disease Deafness Biotin-responsive encephalopathy MERRF Sialidosis type II F o ca l O c c i p i t a l S p i k e s MERRF UnverrichtLundborg disease Little or No D ement i a Biotin-responsive encephalopathy Noninfantile Gaucher disease Myoclonusnal failure Sialidosis type I UnverrichtLundborg disease S ev e r e D e m e n t i a GM2 gangliosidosis Juvenile neuroaxonal dystrophy Lafora disease Late infantile NCL S ev e r e M y o c l o n u s Laforas disease MERRF Sialidosis

Table 3-5. Possible Autonomic Seizure Clinical Features

Abdominal sensations Apnea Arrhythmia Chest pain Cyanosis Erythema Flushing Genital sensations Hyperventilation Incontinence Miosis Perspiration Vomiting

The interictal EEG consists of central and midtemporal high-amplitude spike and wave with a characteristic dipole. The ictal EEG usually consists of a focal central or mid-temporal ictal onset, with the possibility of secondary generalization.23,24 Temporal lobe epilepsy. Temporal lobe epilepsy accounts for approximately 70% of partial seizures. Many patients have a prior history of febrile seizures or head trauma. A prodrome consisting of lethargy is common. Auras are also common but not universal and include an array of ndings such as dj vu. The ictal findings or semiology include oral or motor automatisms, alteration of consciousness, head and eye deviation, contralateral twitching or tonicclonic movements, and posturing. Right temporal lobe seizures are often hypermobile. Left temporal lobe seizures often result in behavior arrest. Versive head movements are relatively common, and 90% of patients with versive head movements had a primary epileptogenic zone in the contralateral hemisphere. Ipsiversive movements are less common but occur most commonly in patients with temporal foci. The postictal phase consists of minutes to hours of confusion and somnolence.2430 Frontal lobe epilepsy. Frontal lobe epilepsy accounts for approximately 20% of partial seizures. A prodrome is rare. Auras are unusual. The seizures typically consist of combinations of behavior alteration and automatisms of very brief duration. Frontal seizures often have atypical presentations and vary widely depending on the region of the frontal lobe from which the seizures arise (Table 3-6). Postictal confusion is rare.3136

Genetics
Au tosomal D o m i n a nt Dentatorubral-pallidoluysian atrophy Kuf disease

Geography
Ca n a d a Myoclonusrenal failure Fi n l a n d Santavori disease UnverrichtLundborg disease Japan Dentatorubral pallidoluysian atrophy Sialidosis type II S we d e n Gaucher disease

Maternal Inheritance
MERRF

21/100,000 children.20 The clinical features include a single nocturnal seizure with clonic movement of the mouth and gurgling. Secondary generalization is common. Alteration in consciousness, aura, and postictal confusion are rare. The seizures resolve by age 16 years.21, 22

34

Section 2: Common Pediatric Neurologic Problems

Table 3-6. Frequency of Aura Types by Location Temporal (%)

10 5 50 10 10 15 10 15 5 10 10

cases. The outcome for overall language and cognitive function depends in part on how early the syndrome is recognized and treated, but over 2/3 of children are left with signicant language or behavioral decits.47
Occipital (%)
0 5 5 5 10 5 10 15 0 50 0

Aura Type
Auditory Cephalic Epigastric General Gustatory None Olfactory Psychical Somatosensory Visual Vertiginous

Frontal (%)
0 15 15 15 0 40 0 5 15 5 2

Rasmussen encephalitis. Rasmussen encephalitis is a syndrome of diffuse lymphocytic inltration of the brain associated with partial seizures and progressive neurological deterioration with hemiparesis. This disorder typically affects children 1 to 14 years old. The syndrome is associated with perivascular cufng on pathologic sections, and antibodies to the glutamate subunit GluR3 are commonly identied. The disorder is usually unilateral. Rasmussen encephalitis is very difcult to treat and frequently requires surgical management with hemispherectomy.

EVALUATION
As with many facets of neurology, the history is the most important diagnostic tool and should include information on each of the items in Table 3-7. The history should be obtained from family and eyewitnesses, if possible. Many patients are unable to provide accurate descriptions of the seizure and the postictal period. MRI of the head with temporal lobe protocol (thin coronal slices through hippocampi) is the preferred imaging modality for most patients. The MRI sequences are much more sensitive to the causes of epilepsy than is CT imaging. CT can, however, be of help in the emergency department setting. EEG is a vital component of the evaluation to categorize the seizure type and assist with planning of the treatment strategy. The need for laboratory testing is highly variable depending on the history. Initial evaluation with uid balance prole (FBP), Ca++,

Occipital lobe epilepsy. Occipital lobe epilepsy is rare, accounting for less than 10% of partial seizures. Prodromes are rare with occipital lobe seizures and auras are unusual. As with the frontal lobe seizures, the seizure characteristics are dependent on the area of the occipital lobe involved. When the striate cortex is involved, there are typically elemental visual hallucinations. Involvement of the lateral occipital lobe results in twinkling, pulsing lights. Seizures arising from the temporo-occipital are usually associated with formed visual hallucinations.37-39 Parietal lobe epilepsy. Parietal lobe seizures are also relatively uncommon. The may be seen as simple partial seizures but they will often propagate. The initial features can include contralateral paresthesias, contralateral pain, idiomotor apraxia, and limb movement sensations. As the seizure progresses and propagates, asymmetric tonic posturing and automatisms may develop.40-42 LandauKleffner syndrome. LandauKleffner syndrome is a rare, invariably progressive, idiopathic acquired aphasia related to a focal epileptic disturbance in the area of the brain responsible for verbal processing.43 The syndrome begins between ages 3 and 10 in a child with normally acquired language abilities. The child then develops a verbal auditory agnosia and infrequent nocturnal partial or secondarily generalized seizures. The syndrome has a pathognomonic EEG pattern consisting of high-voltage multifocal spikes, predominating in the temporal lobes.44 Treatment is usually with valproic acid and benzodiazepines.45 Sometimes corticosteroids and IV Ig or even surgery with subpial transection46 are used in refractory

Table 3-7. Aura Types Psychical Auras

Memory Sound Self-image Time Vision

Illusion
Dj vu, jamais vu, strangeness Advancing, receding, louder, softer, clearer Depersonalization, remoteness Stand-still, rushing, slowing Macropsia, micropsia, near, far, blurred

Hallucination
Flashbacks Voices, music Autoscopy

Objects, faces, scenes

CHAPTER 3 Seizures and Epilepsy

35

Mg++, and liver function tests (LFTs) is important for both the search for a potential cause of the seizures and for medication selection. Urine drug screening should be obtained for patients with new-onset seizures.

Table 3-9. Components of a Seizure History

Aura Birth and developmental history CNS infections Exacerbating factors (sleep, emotion, stress, menstrual cycle, substance abuse) Family history of epilepsy Head trauma Postictal state Seizure description by an eyewitness

TREATMENT
Physicians and families often agonize over the decision about whether to initiate therapy after a single seizure. In the absence of a structural cause for the seizures or a typical syndrome of epilepsy, most patients do not require long-term treatment with an antiepileptic medication. The patient selection criteria for treatment after a single seizure are listed in Table 3-8.48,49 Stopping the antiepileptic medication can also be a challenge. The prognostic factors used for making the decision regarding discontinuation are listed in Table 3-9.49

Table 3-8. Characteristics of Frontal Lobe Seizures by Region of Onset Anteromedial Frontal
Contralateral eye and head version Frequent generalization Somatosensory aura Tonic posture

The selection of a particular antiepileptic medication for a given subtype of epilepsy has long been the subject of controversy. When selecting a given drug, the concomitant medical disorders such as headache, bone marrow dysfunction, and liver insufficiency should be considered. Guidelines for the selection of antiepileptic drugs, the pharmacology of the common antiepileptic drugs, and potential interactions are reviewed in Tables 3-10 to 3-13.50-53 Surgery for epilepsy is an important but often underutilized treatment option. The surgical option provides an opportunity for some patients to become seizure free. However, this is a complex discussion and beyond the scope of this book.

Cingular
Amnesia Facial expressions of fear and anger Psychotic appearance

Dorsolateral frontal
Simple partial Tonic eye and head contraversion

Table 3-10. Patient Selection Criteria for Treatment After a Single Seizure Probably
AVM Brain tumor CNS infection Immediate family history of epilepsy

Frontopolar
Loss of tone Rapid generalization

Opercular/Insular
Complex seizures include gagging, swallowing, chewing, amnesia, genital manipulation Seizures include gustatory sensation, salivation, gagging

Orbitofrontal
Blinking or staring Complex automatisms

Probably Not
Acute febrile illness Drug withdrawal or intoxication Electrolye imbalance EtOH withdrawal Hyper/hypoglycemia Immediate posttraumatic seizure Severe sleep deprivationrelated seizure

Supplementary Motor Area

Contralateral tonic posture Simple motor seizure Somatosensory aura Tonic eye and head contraversion Vocalizes

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Section 2: Common Pediatric Neurologic Problems

Table 3-11. Prognostic Factors for Stopping AEDs Favorable

Primary generalized epilepsy Idiopathic epilepsy Childhood onset Easy to control Normal neurological examination Normal intelligence More than 23 years seizure-free Normal EEG

Unfavorable
Partial epilepsy Identiable lesions Adult onset Difcult to control Abnormal neurologic examination Mental retardation Less than 3 years seizurefree Epileptiform EEG

From Geyer J, Keating J, Potts D, Carney P, eds. Neurology for the Boards. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2006.

Non-epileptic Events
Non-epileptic events are unusual in the pediatric population, especially in the younger child. Several categories of non-epileptic events (thrashing, staring, etc.) have different natural histories and variable prognosis. Etiologies include conversion disorder, malingering, and medical conditions, especially cardiac disorders. Symptoms suggesting non-epileptic events include closed eyes, resisted eyelid opening, non-physiologic progression, pelvic thrusting, lack of cyanosis, lack of tongue biting, variable semiology, crying, and rapid reorientation following the event.54-56

Neonatal seizures are often the presenting clinical manifestation of underlying neurological conditions such as hypoxic-ischemic encephalopathy, stroke, intraventricular or intraparenchymal hemorrhages, meningitis, sepsis, or metabolic disorders. Of these, hypoxic ischemic encephalopathy is the most common etiology, accounting for 50% to 60% of patients with neonatal seizures.57 The neonatal brain is particularly vulnerable to seizure activity as a result of an imbalance of excitatory to inhibitory circuitry. The imbalance favors excitation, and does so to facilitate important developmental processes that occur during the neonatal period (synaptogenesis, apoptosis, progressive integration of circuitry, synaptic pruning). The imbalance occurs anatomically and physiologically by an overexpression of NMDA receptor in the hippocampus and neocortical regions of the neonatal brain, a delay in the maturation of the inhibitory system, and neurons in such regions as the hippocampus are excited rather than inhibited by the neurotransmitter GABA (normally the primary inhibitory neurotransmitter in the brain).

Clinical presentation Subtle. Subtle seizures are more common in premature infants. As the name suggests, the seizures may be difcult to identify with only tonic horizontal eye movements, sustained eye opening, chewing, or apnea. In some cases there may be boxing movements. These seizures may have limited EEG changes correlating with the seizure activity. 58-61

Neonatal Seizures
Neonatal seizures are poorly classied, under-recognized, especially in sick neonates, and often difcult to treat.

Clonic. Clonic seizures typically present as rhythmic,

slow movements. The movements have a frequency of 1 to 3 Hz. Focal clonic seizures involve one side of the body, and the infant is not clearly unconscious.

Table 3-12. Antiepileptic Drug Selectiona Seizure Type

Infantile spasms Absence Tonic-clonic Myoclonic Atypical absence Simple partial Complex partial
a

VPA
2 1 1 1 3 2

LTG
2 2 2 2 2

TPM

LVT

ETX
1

ACTH
1

GBP

CBZ

PHT
2

PHB

4, 1b

2 2

2 2

2 2

1 1

2 2

1b 1b

Numbers refer to order of preference for use in specic seizure types. Infants. From Geyer J, Keating J, Potts D, Carney P, eds. Neurology for the Boards. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2006.
b

CHAPTER 3 Seizures and Epilepsy

37

Table 3-13. DrugDrug Interactions: Effects on Serum Concentration of Adding a Second Antiepileptic Drug to First Antiepileptic Drug Effects of Added Drug on Serum Concentration of Original Drug
No change Decrease Decrease Decrease Decrease Decrease No change Decrease Increase No change No change No change Increase or no change No change Data conicting Increase Increase Increase Increase or decrease Data conicting No change Increase Decrease, increase, or no change No change Decrease Increased concentration of derived phenobarbital No change No change Increased concentration of derived phenobarbital Increase Decrease, increase, or no change No change No change Decrease Decrease Decrease

Original Drug
Carbamazepine

Added Drug
Clonazepam Phenobarbital Phenytoin Primidone Phenobarbital Phenytoin Valproate Carbamazepine Methylphenobarbital Phenobarbital Phenytoin Primidone Valproate Carbamazepine Clonazepam Methsuximide Phenytoin Valproate Carbamazepine Clonazepam Ethosuximide Methsuximide Phenobarbital Primidone Valproate Carbamazepine Clonazepam Ethosuximide Phenytoin Valproate Carbamazepine Clonazepam Ethosuximide Phenobarbital Phenytoin Primidone

Clonazepam

Ethosuximide

Phenobarbital

Phenytoin

Primidone

Valproate

From Geyer J, Keating J, Potts D, Carney P, eds. Neurology for the Boards. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2006.

Multifocal clonic seizures involve several body parts, often in a migrating pattern. Generalized clonic seizures are rarely observed in newborn because of the incomplete myelination of the brain.5861

upper limbs and tonic extension of lower limbs (mimicking decerebrate posturing). There are no EEG changes in 85% of cases.5861

Tonic. Focal tonic seizures result in sustained posturing of a limb, the trunk, or the neck. These seizures are usually accompanied by EEG changes. Generalized tonic seizures exhibit tonic extension of all limbs (mimicking decorticate posturing) or tonic exion of

Myoclonic. Focal myoclonic seizures usually involve exor muscles of an upper extremity. Often, there are no EEG changes. Conversely, generalized myoclonic seizures exhibit bilateral jerks of both upper and lower limbs, and may resemble infantile spasms. These generalized seizures are more likely to have EEG changes.5861

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Section 2: Common Pediatric Neurologic Problems

Syndromes
Benign familial neonatal seizures
Benign familial neonatal seizures occur as a genetic disorder with an autosomal dominant inheritance pattern associated with chromosome 20q. The seizures typically start on day of life 2 or 3. The neonate may have as many as 10 to 20 seizures per day. The syndrome is usually self-limited and benign, but approximately 10% of cases progress to an antiepileptic drug-requiring seizure disorder. Neurological development is normal.5861
Table 3-14. Neonatal AED Dosing Suggestions
Phenobarbital20 mg/kg load over 10 to 15 min. If necessary add more phenobarbital in 5-mg/kg boluses Fosphenytoin20 mg/kg at 1 mg/kg/min Ativan0.1 mg/kg
From Rennie J, Boylan G. Treatment of neonatal seizures. Arch Dis Child Fetal Neonatal 2007;92:F148F150.

Fifth-day ts
Fifth-day ts usually begin on day of life 4 to 6. The seizures are typically multifocal clonic seizures and are frequently associated with apnea. The seizures usually last for less than 24 hours. Fifth-day ts progress to status epilepticus in 80% of cases.5861

occur with intravenous infusion of the highly alkaline phenytoin. The drug of choice for neonates in status is lorazepam. This agent has several properties that make it ideala long half-life and a small volume of distribution, which prolongs its retention at high levels in the brain.

Benign neonatal sleep myoclonus

Benign neonatal sleep myoclonus begins during the rst week of life. The seizures are usually bilateral myoclonic jerks that last for several minutes and occur only during NREM sleep. The EEG is normal or slow. The seizures worsen with the administration of benzodiazepines. The seizures usually resolve within 2 months and neurological outcome is normal.5861

REFERENCES
1. Hauser WA, Beghi E. First seizure denitions and worldwide incidence and mortality. Epilepsia. 2008; 49(suppl 1): 8-12. 2. Teasell R, Bayona N, Lippert C, Villamere J, Hellings C. Post-traumatic seizure disorder following acquired brain injury. Brain Inj. 2007;21:201-214. 3. Statler KD. Pediatric posttraumatic seizures: epidemiology, putative mechanisms of epileptogenesis and promising investigational progress. Dev Neurosci. 2006;28: 354-363. 4. Agrawal A, Timothy J, Pandit L, Manju M. Post-traumatic epilepsy: an overview. Clin Neurol Neurosurg. 2006; 108:433-439. 5. Weber YG, Lerche H. Genetic mechanisms in idiopathic epilepsies. Dev Med Child Neurol. 2008;50:648-654. 6. Leventer RJ, Guerrini R, Dobyns WB. Malformations of cortical development and epilepsy. Dialogues Clin Neurosci. 2008;10:47-62. 7. Steinlein OK. Genetics and epilepsy. Dialogues Clin Neurosci. 2008;10:29-38. 8. Grifth JF, Chien LT. Herpes simplex virus encephalitis. Diagnostic and treatment considerations. Med Clin North Am. 1983;67:991-1008. 9. Geyer J, Keating J, Potts D, Carney P, eds. Neurology for the Boards. 3rd ed. Philadelphia: Lippincott Williams & Wilkins;2006. 10. Riviello JJ. Classication of seizures and epilepsy. Curr Neurol Neurosci Rep. 2003;3:325-331. 11. Durn RM, Medina MT, Martnez-Jurez IE, et al. Seizures of idiopathic generalized epilepsies. Epilepsia. 2005;46:34-47. 12. Gardiner M. Genetics of idiopathic generalized epilepsies. Epilepsia. 2005;46(suppl 9):15-20. 13. Jallon P, Latour P. Epidemiology of idiopathic generalized epilepsies. Epilepsia. 2005;46(suppl 9):10-14.

Benign myoclonus of early infancy

Benign myoclonus of early infancy has an onset at age 3 to 9 months but it can be much earlier. The seizures resemble infantile spasms but the EEG is normal. The seizures usually occur while the patient is awake. The seizures disorder may continue for 1 to 2 years but neurological outcome is normal.5861

Treatment
The clinician should rst search for underlying etiologies producing the seizures and treat (hypoglycemia, hypocalcemia, sepsis). If the clinician cannot find a readily identiable and treatable etiology, the frontline agent of choice for treating seizures is phenobarbital (see Table 3-14 for dosing suggestions).62 Phenobarbital as a single agent will stop seizure activity in 42% of patients. When the seizure does not respond to a single agent, phenytoin is added with an increase in efcacy to 65%. Currently, fosphenytoin, the salt ester of phenytoin, is preferred in the neonate because it is an aqueous solution that is soluble in glucose-containing solutions, can be administered more quickly than phenytoin, and will not cause purple glove syndrome.62 Purple glove syndrome is necrosis or injury of the soft tissue that can

CHAPTER 3 Seizures and Epilepsy 14. West WJ. On a peculiar form of infantile convulsions. Lancet. 1841;1:724-725. 15. Wong M, Trevanthan E. Infantile spasms Pediatr Neurol. 2001;24:89-98. 16. Riikonen R. The latest on infantile spasms. Curr Opin Neurol. 2005;18:91-95. 17. Hrachovy RA, Frost JD Jr. Infantile epileptic encephalopathy with hypsarrhythmia (infantile spasms/West syndrome). J Clin Neurophysiol. 2003;20:408-425. 18. Aicardi J. Aicardi syndrome. Brain Dev. 2005;27:164-171. 19. Markand ON. LennoxGastaut syndrome (childhood epileptic encephalopathy). J Clin Neurophysiol. 2003;20: 426-441. 20. Neubauer BA, Hahn A, Stephani U, Doose H. Clinical spectrum and genetics of Rolandic epilepsy. Adv Neurol. 2002;89:475-479. 21. Cameld P, Cameld C. Epileptic syndromes in childhood: clinical features, outcomes, and treatment. Epilepsia. 2002;43(suppl 3):27-32. 22. Saint-Martin AD, Carcangiu R, Arzimanoglou A, et al. Semiology of typical and atypical Rolandic epilepsy: a video-EEG analysis. Epileptic Disord. 2001;3:173-182. 23. Kellaway P. The electroencephalographic features of benign centrotemporal (rolandic) epilepsy of childhood. Epilepsia. 2000;41:1053-1056. 24. Rodriguez AJ, Buechler RD, Lahr BD, So EL. Temporal lobe seizure semiology during wakefulness and sleep. Epilepsy Res. 2007;74:211-214. 25. Maillard L, Vignal JP, Gavaret M, et al. Semiologic and electrophysiologic correlations in temporal lobe seizure subtypes. Epilepsia. 2004;45:1590-1599. 26. Hoffmann JM, Elger CE, Kleefuss-Lie AA. Lateralizing value of behavioral arrest in patients with temporal lobe epilepsy. Epilepsy Behav. 2008;13(4):634-636. 27. Marks WJ Jr, Laxer KD. Semiology of temporal lobe seizures: value in lateralizing the seizure focus. Epilepsia. 1998;39:721-726. 28. Geyer JD, Payne TA, Faught E, Drury I. Postictal noserubbing in the diagnosis, lateralization, and localization of seizures. Neurology. 1999;52:743-745. 29. French JA, Williamson PD, Thadani VM, et al. Characteristics of mesial temporal lobe epilepsy. I. Results of history and physical examination. Ann Neurol. 1983;34: 374-380. 30. Geyer JD, Bilir E, Faught RE, et al. Significance of interictal temporal lobe delta activity for localization of the primary epileptogenic region. Neurology.1999; 52:202-205. 31. OBrien TJ, Mosewich RK, Britton JW, Cascino GD, So EL. History and seizure semiology in distinguishing frontal lobe seizures and temporal lobe seizures. Epilepsy Res. 2008;82(2-3):177-182. 32. Battaglia D, Lettori D, Contaldo I, et al. Seizure semiology of lesional frontal lobe epilepsies in children. Neuropediatrics. 2007;38:287-291. 33. Lee JJ, Lee SK, Lee SY, et al. Frontal lobe epilepsy: clinical characteristics, surgical outcomes and diagnostic modalities. Seizure. 2008;17:514-523. 34. Bonelli SB, Lurger S, Zimprich F, Stogmann E, AssemHilger E, Baumgartner C. Clinical seizure lateralization in frontal lobe epilepsy. Epilepsia. 2007;48:517-523.

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35. Bleasel A, Kotagal P, Kankirawatana P, Rybicki L. Lateralizing value and semiology of ictal limb posturing and version in temporal lobe and extratemporal epilepsy. Epilepsia. 1997;38:168-174. 36. Gardella E, Rubboli G, Tassinari CA. Ictal grasping: prevalence and characteristics in seizures with different semiology. Epilepsia. 2006;47(suppl 5):59-63. 37. Taylor I, Berkovic SF, Kivity S, Scheffer IE. Benign occipital epilepsies of childhood: clinical features and genetics. Brain. 2008;131:2287-2294. 38. Ludwig, BI, Ajmone-Marsan C. Clincial ictal patterns in epileptic patients with occipital electroencephalographic foci. Neurology. 1975;25:463-471. 39. Blume WT, Wiebe S, Tapsell LM. Occipital epilepsy: lateral versus mesial. Brain. 2005;128:1209-1225. 40. Kim DW, Lee SK, Yun CH, et al. Parietal lobe epilepsy: the semiology, yield of diagnostic workup, and surgical outcome. Epilepsia. 2004;45:641-649. 41. Cascino GD, Hulihan JF, Sharborough FW, Kelly PJ. Parietal lobe lesional epilepsy: electroclinical correlation and operative outcome. Epilepsia. 1993;34:522-527. 42. Williamson PD, Boon PA, Thadani VM, et al. Parietal lobe epilepsy: diagnostic considerations and results of surgery. Ann Neurol. 1992;31:193-201. 43. Hirsh E, Valenti MP, Rudolf G, et al. LandauKleffner syndrome is not an eponymic badge of ignorance. Epilepsy Res. 2006;70:S239-S247. 44. Landau WM, Kleffner FR. Syndrome of acquired aphasia with convulsive disorder in children. Neurology. 1957; 7:523-530. 45. Mikati MA, Shamseddine AN. Management of Landau Kleffner syndrome. Pediatric Drugs. 2005;7:377-389. 46. Morrell F, Whisler WW, Smith MC, et al. LandauKleffner syndrome: treatment with subpial intracortical transaction. Brain. 1995;118:1529-1546. 47. Beaumanoir A. The LandauKleffner syndrome. In : Roger J, Bureau M, Dravet C, et al., eds. Epileptic Syndromes in Infancy, Childhood and Adolescence. London; John Libbey;1992:231-243. 48. Berg AT, Shinnar S. The risk of seizure recurrence following a rst unprovoked seizure: a quantitative review. Neurology. 1991;41:965-972. 49. Hughes JR, Fino JJ. Focal seizures and EEG: prognostic considerations. Clin Electroencephalogr. 2003;34:174-181. 50. Riikonen R. Infantile spasms: therapy and outcome. J Child Neurol. 2004;19:401-404. 51. Mackay MT, Weiss SK, Adams-Webber T, et al., for the American Academy of Neurology; Child Neurology Society. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004; 62:1668-1681. 52. Sato S, White BG, Penry JK, et al. Valproic acid vs ethosuximide in the treatment of absence seizures. Neurology. 1982;32(2):157-163. 54. Selwa LM, Geyer J, Nikakhtar N, Brown MB, Schuh LA, Drury I. Nonepileptic seizure outcome varies by type of spell and duration of illness. Epilepsia. 2000;41:1330-1334. 55. Geyer JD, Payne TA, Drury I. The value of pelvic thrusting in the diagnosis of seizures and pseudoseizures. Neurology. 2000;54:227-229.

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Section 2: Common Pediatric Neurologic Problems 60. Silverstein FS, Jensen FE. Neonatal seizures. Ann Neurol. 2007;62:112-120. 61. Specchio N, Vigevano F. The spectrum of benign infantile seizures. Epilepsy Res. 2006;70(suppl 1):S156-S167. 62. Rennie J, Boylan G. Treatment of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 2007;92:F148-F150.

56. Duncan R, Oto M, Russell AJ, Conway P. Pseudosleep events in patients with psychogenic non-epileptic seizures: prevalence and associations. J Neurol Neurosurg Psychiatry. 2004;75:1009-1012. 57. Tuxhorn I, Kotagal P. Classification. Semin Neurol. 2008;28:277-288. 58. Nabbout R, Dulac O. Epileptic syndromes in infancy and childhood. Curr Opin Neurol. 2008;21:161-166. 59. Tich SN, dAllest AM, Villepin AT, et al. Pathological features of neonatal EEG in preterm babies born before 30 weeks of gestational age. Neurophysiol Clin. 2007;37: 325-370.