Seizures and Epilepsy

CHAPTER 3 

DEFINITIONS AND EPIDEMIOLOGY 

A general simplified definition 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 find 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 deficits, 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. 2–4 

A number of congenital malformations increase 

the risk for epilepsy. Disorders associated with migrational 

Seizures and Epilepsy 

Paul R. Carney and James D. Geyer 

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. 5–7 

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 

Phakomatoses—tuberous sclerosis, von Hippel–Lindau 

disease, neurofibromatosis 

Phenylketonuria (PKU) 

Sturge–Weber syndrome

Table 3-2. 

Toxic/Metabolic Causes of Seizures 

Drug Intoxication 

Amphetamines 

Cocaine 

Lidocaine 

Theophylline 

Tricyclic antidepressants 

Drug withdrawal 

Antiepileptic drugs (AEDs) 

Barbiturates 

Benzodiazepines 

Ethanol 

Electrolyte—hypo/hypernatremia, hypo/hyperglycemia, 

hypocalcemia, hypomagnesemia 

Heavy metals—lead, mercury 

Hyperosmolarity 

Hypoxia 

Liver failure 

Porphyria 

Pyridoxine deficiency 

Thyroid storm 

Uremia (usually following 3 days of anuria) 

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. 

CLINICAL PRESENTATION 

Epilepsy is divided into several categories with significant 

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 Classification 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 

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 identified, 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 follows 10 : 

Primary generalized epilepsy 

Symptomatic generalized epilepsy 

Cryptogenic epilepsy 

A number of seizures and epilepsies may be very 

difficult to categorize. The Revised International Classification 

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. 

DIAGNOSIS 

Seizure Types 

CHAPTER 3 Seizures and Epilepsy ■ 31 

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.

32 ■ 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 

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 

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 findings. 

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 

Infantile spasms 

West syndrome typically begins between 3 months and 

3 years of age. 14–16 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 

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 fibers (MERRF) 

Neuronal ceroid lipofuscinosis (NCL) (also known as Batten 

disease) 

Noninfantile Gaucher disease 

Sialidosis 

Unverricht–Lundborg disease (Baltic myoclonus) 

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 

Lennox–Gastaut syndrome 

Lennox–Gastaut 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 

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, fingers, 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. 

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

Table 3-4. 

Distinguishing Characteristics of the Progressive 

Myoclonic Epilepsies 

Clinical Features 

Chorea 

Dentorubral-pallidoluysian atrophy 

Juvenile neuroaxonal dystrophy 

Juvenile Gaucher disease 

Deafness 

Biotin-responsive encephalopathy 

MERRF 

Sialidosis type II 

Focal Occipital Spikes 

MERRF 

Unverricht–Lundborg disease 

Little or No Dementia 

Biotin-responsive encephalopathy 

Noninfantile Gaucher disease 

Myoclonus—nal failure 

Sialidosis type I 


Severe Dementia 

GM2 gangliosidosis 

Juvenile neuroaxonal dystrophy 

Lafora disease 

Late infantile NCL 

Severe Myoclonus 

Lafora’s disease 

MERRF 

Sialidosis 

Genetics 

Autosomal Dominant 

Dentatorubral-pallidoluysian atrophy 

Kuf disease 

Geography 

Canada 

Myoclonus—renal failure 

Finland 

Santavori disease 


Japan 

Dentatorubral pallidoluysian atrophy 

Sialidosis type II 

Sweden 

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 

21, 22 

are rare. The seizures resolve by age 16 years. 


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 findings such as déjà vu. The 

ictal findings or semiology include oral or motor 

automatisms, alteration of consciousness, head and 

eye deviation, contralateral twitching or tonic–clonic 

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. 24–30 

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. 31–36


Table 3-6. 

Frequency of Aura Types by Location 

Temporal Frontal Occipital 

Aura Type (%) (%) (%) 

Auditory 10 0 0 

Cephalic 5 15 5 

Epigastric 50 15 5 

General 10 15 5 

Gustatory 10 0 10 

None 15 40 5 

Olfactory 10 0 10 

Psychical 15 5 15 

Somatosensory 5 15 0 

Visual 10 5 50 

Vertiginous 10 2 0 

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 

Landau–Kleffner syndrome. Landau–Kleffner 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 transection 46 are used in refractory 

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 significant language or behavioral deficits. 47 

Rasmussen encephalitis. Rasmussen encephalitis is a 

syndrome of diffuse lymphocytic infiltration 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 cuffing on pathologic sections, and 

antibodies to the glutamate subunit GluR3 are commonly 

identified. The disorder is usually unilateral. Rasmussen 

encephalitis is very difficult 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 fluid balance profile (FBP), Ca++, 

Aura Types 

Table 3-7. 

Psychical Auras Illusion Hallucination 

Memory Déjà vu, jamais Flashbacks 

vu, strangeness 

Sound Advancing, receding, Voices, music 

louder, softer, clearer 

Self-image Depersonalization, Autoscopy 

remoteness 

Time Stand-still, rushing, 

slowing 

Vision Macropsia, micropsia, Objects, faces, 

near, far, blurred scenes

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. 

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. 

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 

Table 3-9. 49 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 

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 

Cingular 

Amnesia 

Facial expressions of fear and anger 

“Psychotic” appearance 

Dorsolateral frontal 

Simple partial 

Tonic eye and head contraversion 

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 

Supplementary Motor Area 

Contralateral tonic posture 

Simple motor seizure 

Somatosensory aura 

Tonic eye and head contraversion 

Vocalizes 

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. 

Table 3-10. 

Patient Selection Criteria for Treatment After a Single 

Seizure 

Probably 

AVM 

Brain tumor 

CNS infection 

Immediate family history of epilepsy 

Probably Not 

Acute febrile illness 

Drug withdrawal or intoxication 

Electrolye imbalance 

EtOH withdrawal 

Hyper/hypoglycemia 

Immediate posttraumatic seizure 

Severe sleep deprivation–related seizure


Table 3-11. 

Prognostic Factors for Stopping AEDs 

Favorable Unfavorable 

Primary generalized epilepsy Partial epilepsy 

Idiopathic epilepsy Identifiable lesions 

Childhood onset Adult onset 

Easy to control Difficult to control 

Normal neurological examination Abnormal neurologic 

examination 

Normal intelligence Mental retardation 

More than 2–3 years seizure-free Less than 3 years seizurefree 

Normal EEG 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 

Neonatal seizures are poorly classified, under-recognized, 

especially in sick neonates, and often difficult to treat. 

Table 3-12. 

Antiepileptic Drug Selection a 

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 

difficult 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 

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. 

Seizure Type VPA LTG TPM LVT ETX ACTH GBP CBZ PHT PHB 

Infantile spasms 1 2 

Absence 2 2 1 

Tonic-clonic 1 2 2 2 3 2 4, 1 bb 

Myoclonic 1 2 

Atypical absence 1 2 

Simple partial 3 2 2 2 1 2 1 bb 

Complex partial 2 2 2 2 2 1 2 1 bb 

aNumbers refer to order of preference for use in specific seizure types. 

bb 

Infants. 

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

Table 3-13. 


Drug–Drug Interactions: Effects on Serum Concentration of Adding a Second Antiepileptic Drug to First 

Antiepileptic Drug 

Original Drug Added Drug 

Effects of Added Drug on Serum 

Concentration of Original Drug 

Carbamazepine Clonazepam No change 

Phenobarbital Decrease 

Phenytoin Decrease 

Primidone Decrease 

Clonazepam Phenobarbital Decrease 


Valproate No change 

Ethosuximide Carbamazepine Decrease 

Methylphenobarbital Increase 

Phenobarbital No change 

Phenytoin No change 

Primidone No change 

Valproate Increase or no change 

Phenobarbital Carbamazepine No change 

Clonazepam Data conflicting 

Methsuximide Increase 

Phenytoin Increase 

Valproate Increase 

Phenytoin Carbamazepine Increase or decrease 

Clonazepam Data conflicting 

Ethosuximide No change 

Methsuximide Increase 

Phenobarbital Decrease, increase, or no change 

Primidone No change 

Valproate Decrease 

Primidone Carbamazepine Increased concentration of derived phenobarbital 

Clonazepam No change 


Phenytoin Increased concentration of derived phenobarbital 

Valproate Increase 

Valproate Carbamazepine Decrease, increase, or no change 

Clonazepam No change 


Phenobarbital Decrease 


Primidone Decrease 

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. 58–61 

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 flexion of 

upper limbs and tonic extension of lower limbs (mimicking 

decerebrate posturing). There are no EEG 

changes in 85% of cases. 58–61 

Myoclonic. Focal myoclonic seizures usually involve 

flexor 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. 58–61


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. 58–61 

Fifth-day fits 

Fifth-day fits 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 fits progress to status 

epilepticus in 80% of cases. 58–61 

Benign neonatal sleep myoclonus 

Benign neonatal sleep myoclonus begins during the first 

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. 58–61 

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. 58–61 

Treatment 

The clinician should first search for underlying etiologies 

producing the seizures and treat (hypoglycemia, 

hypocalcemia, sepsis). If the clinician cannot find a 

readily identifiable 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 efficacy 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 

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 ideal—a long half-life and a small volume of distribution, 

which prolongs its retention at high levels in the 

brain. 

REFERENCES 

Table 3-14. 

Neonatal AED Dosing Suggestions 

Phenobarbital—20 mg/kg load over 10 to 15 min. 

If necessary add more phenobarbital in 5-mg/kg boluses 

Fosphenytoin—20 mg/kg at 1 mg/kg/min 

Ativan—0.1 mg/kg 

From Rennie J, Boylan G. Treatment of neonatal seizures. Arch Dis Child Fetal 

Neonatal 2007;92:F148–F150. 

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