Seizures, Partial and Generalized

Basics
DESCRIPTION
Transient involuntary alteration of consciousness, behavior, motor activity, sensation, or autonomic function owing to
abnormal electrical neuronal discharges in the cerebral cortex:

Seizures are classified by location of their onset: Partial (begins in local area of cerebral cortex) and primary
generalized (begins simultaneously in both hemispheres).

Partial seizures types:

1. Simple partial (consciousness not impaired)
2. Complex partial (consciousness impaired)
3. Partial seizures evolving to generalized tonicclonic convulsions

Primary generalized seizure types:

1. Absence
2. Atypical absence
3. Myoclonic
4. Clonic
5. Tonic
6. Atonic
7. Tonicclonic
EPIDEMIOLOGY

Incidence
46% of children will have at least 1 seizure in the 1st 16 years of life; the highest incidence is in childhood, with 30% of
1st seizures occurring before age 4 years and nearly 80% occurring before age 20 years
RISK FACTORS

History of previous seizure (afebrile or febrile)

Recent withdrawal of anticonvulsant medication

Brain tumor

Neurodegenerative disorder

History of remote neurologic insult (stroke, intracranial hemorrhage, cerebral palsy, head trauma, meningitis)

Family history of seizures

Genetics

Idiopathic seizures may have a multifactorial genetic pattern. Several epilepsy syndromes have recently been
associated with defined genetic loci (e.g., generalized epilepsy with febrile seizures, autosomal dominant nocturnal
frontal lobe epilepsy, benign familial neonatal convulsions, severe myoclonic epilepsy of infancy).

Other common epilepsy syndromes (including benign rolandic, childhood and juvenile absence, and juvenile
myoclonic epilepsy) are genetically heterogeneous and have an autosomal dominant inheritance pattern with
variable penetrance.

Diagnosis
SIGNS AND SYMPTOMS
History

Inquire regarding gestation, birth, general health, growth and development, and current medications; recent onset of
headaches, weakness, sensory deficits, change in vision, behavior, balance, or gait

Neurodevelopmental abnormality (autism, cerebral palsy, retardation) puts child at risk of epilepsy.

Precipitating factors:
1. Fever
2. Preceding illness
3. Sleep deprivation
4. Recent head trauma
5. Ingestion, change in antiepileptic medication
6. See Risk Factors.
Physical Exam

Vital signs: Fever, respiratory failure (such as adequacy of air exchange, abnormal breathing pattern),
tachycardia/bradycardia, or hypertension (suggesting intracranial hypertension)

Signs of head trauma and child abuse: Retinal hemorrhages, evidence of intracranial hypertension (bulging
fontanelle)

Head circumference/abnormal head growth velocity: Microcephaly suggests underlying neurologic abnormality.

Signs of systemic infection: Meningismus (CNS infection)

Skin examination: Caf au lait or ash leaf spots; facial hemangioma, suggesting neurocutaneous disorder

Neurologic examination: Pupillary asymmetries, altered mental status, fixed eye deviations, and focal motor
weakness (Todd paralysis) suggest focal onset of seizures and possibility of an underlying structural lesion.

Convulsions: If actively convulsing, neurologic examination is often limited and should be directed toward
determining possibility of intracranial hypertension and any focal abnormalities (see Status Epilepticus chapter).
TESTS

LABORATORY
Initial:

Glucose

Electrolytes

Blood urea nitrogen

Antiepileptic drug (AED) levels

CBC

Liver function tests

Toxicology screen

Urinalysis

Oximetry or arterial blood gas indicated if child is actively seizing

IMAGING

Neuroimaging: CT (often logistically more feasible) or MRI (more sensitive than CT). Urgent imaging is indicated
in children with new-onset partial seizures, focal neurologic signs, history of head trauma, or difficult-to-control
seizures.

Repeat imaging may be indicated in known epileptics with a significant change in clinical status.

Focally abnormal EEG following a generalized seizure should prompt (nonurgent) MRI. For nonurgent imaging,
MRI is preferred as it provides more detailed images.
DIAGNOSTIC PROCEDURES

EEG:
1. Indicated immediately if convulsions continue or the patient fails to awaken within hours after convulsions
cease (children with neurologic deficits may have longer recovery)
2. Nonurgent EEGs are indicated in all children with 1st afebrile seizure, complicated febrile seizure, and
known epilepsy with recent change in baseline functioning.

Lumbar puncture: Indicated in nearly all children younger than 2 years of age and any older child in whom CNS
infection is suspected (unless contraindicated: Intracranial hypertension, cerebral mass lesion, or obstructive
hydrocephalus). If these conditions are suspected, lumbar puncture should be deferred until after head CT.
DIFFERENTIAL DIAGNOSIS

Suspected seizures:
1. Seizure (e.g., generalized tonicclonic, complex partial, absence, myoclonic, tonic, atonic)
2. Syncope, breath-holding syncope
3. Hyperventilation
4. Psychogenic seizures
5. Movements related to gastroesophageal reflux (Sandifer syndrome)
6. Narcolepsycataplexy
7. Night terrors
8. Startle disease
9. Migraine
10. Shuddering spells, paroxysmal dyskinesias, tics, drug-induced dystonia

11. Benign sleep myoclonus (in neonates/infants), segmental myoclonus

Definite seizure or epilepsy:

1. Idiopathic (presumed genetic)
2. Remote symptomatic (previous history of stroke, intracranial hemorrhage, birth asphyxia, head trauma,
meningitis)
3. Febrile
4. Acute symptomatic: CNS infection, anoxia, trauma, stroke/hemorrhage, intoxication, metabolic
encephalopathy, anticonvulsant withdrawal
5. Neurodegenerative disorder
6. Brain tumor
7. Malformations of cortical development (lissencephaly, agenesis of corpus callosum, holoprosencephaly)
8. Neurocutaneous syndromes (tuberous sclerosis, Sturge-Weber syndrome, neurofibromatosis)
9. Febrile seizure: Diagnosis of exclusion in a child with 1st seizure associated with fever. History may
suggest other possibilities; those younger than 18 months should undergo lumbar puncture (see SeizuresFebrile chapter).

Treatment
GENERAL MEASURES

Need for long-term antiepileptic drug (AED) therapy after a 1st seizure depends on the cause, patients age, and
circumstances in which seizure occurred.

Chronic AED therapy is not indicated after acute symptomatic seizures (transient metabolic disturbances
[e.g., hyponatremia, intoxication]) or after a single unprovoked seizure in a child with normal neurologic
examination and EEG.

Chronic AED therapy often administered after 1st seizure symptomatic of a structural brain lesion;
1. Indicated if child has had 2 or more unprovoked seizures, and in patients with a history of seizure free
intervals who have had recurrent seizures.
MEDICATIONS

The choice of AED for long-term management depends on the specific seizure type. Therapy should be started with
a single drug, because in ~75% of children with epilepsy it will be fully controlled with monotherapy, and
polytherapy increases the risk of toxicity and decreases compliance.

Partial-onset seizures (with or without secondary generalization): Carbamazepineis frequently the initial therapy
and is begun at 510 mg/kg/d and slowly advanced to 2030 mg/kg/d divided b.i.d. (sustained-release preparations
only) or t.i.d. Therapeutic blood concentrations range from 812 mg/mL. Liver function tests and CBC must be
monitored because of potential risk of thrombocytopenia, aplastic anemia, and hepatotoxicity. Newer agents (see
below) may have lower toxicity.

Alternatives for patients with partial-onset seizures include:

1. Oxcarbazepine: 2030 mg/kg/d
2. Lamotrigine: 515 mg/kg/d in patients not taking valproate, 15 mg/kg/d in patients on valproate

3. Topiramate: 410 mg/kg/d; build up dose slowly to minimize cognitive side effects.
4. Valproate: 1015 mg/kg/d, increased to 2060 mg/kg/d for blood levels of 50100 mg/dL
5. Gabapentin: 2030 mg/kg/d
6. Levetiracetam (initial dosing of 1040 mg/kg/d and increase to a maximum dose of 60 mg/kg/d in b.i.d.)
7. These medications all have pediatric labeling and formulations.

Another option: Zonisamide (initial dosing 12 mg/kg/d and increase to maximum dose of 10 mg/kg/d in daily or
b.i.d. dosing); has been demonstrated to be effective for partial seizures in children, but does not yet have FDA
indication for use in children younger than 16 years of age

Phenytoin (57 mg/kg/d) and phenobarbital(37 mg/kg/d) are older AEDs that are frequently used acutely to
rapidly control seizures but are used less for chronic maintenance therapy because of cognitive, behavioral, and
cosmetic side effects. In young infants, (<1 year), phenobarbitalcontinues to be used as a first-line agent.

Primary generalized epilepsies (including absence, myoclonic, tonic, or clonic seizures):

1. Ethosuximide (20 mg/kg/d in 23 divided doses, increased as needed for blood levels of 40100 mg/mL)
is initial AED of choice for childhood absence seizures.
2. Alternatives for generalized seizures: Valproate, lamotrigine, topiramate, and zonisamide. Adverse effects
of valproate include thrombocytopenia, pancreatitis, hyperammonemia, and fatal hepatotoxicity. CBC
and liver function tests should be routinely monitored. Children younger than 5 years have an increased
risk of hepatotoxicity from valproate, and children younger than 10 years have an increased risk of serious
rash from lamotrigine.

Prolonged seizures (>5 minutes) or acute repetitive seizures: Rectal diazepam (0.30.5 mg/kg per dose) can be
administered. Restrictions re-repetitive dosing or with phenobarbital co-administration. Very effective at stopping
the seizure with minimal risk of respiratory depression, but families should be trained in cardiopulmonary
resuscitation.

Patients refractive to medical therapy: Other therapeutic options include the ketogenic diet, vagal nerve stimulator,
and surgical resection.
CLINICAL:

Hyponatremic seizures: Serum sodium<120 mEq/dL in infants with gastroenteritis. Judicious sodium correction
may prevent neurologic effects of rapid shifts in osmolarity. Many clinicians administer normal saline to bring the
sodium up to 120 mEq/dL, with slower correction thereafter.

Apnea and hypoventilation may result from excessive administration of benzodiazepines or phenobarbital. In
general, patients treated with these drugs intravenously should have their ventilation and oxygenation closely
monitored. Excessively large or rapidly administered doses should be avoided when possible.

Follow-up Recommendations
EXPECTED COURSE/PROGNOSIS

The reported risk of recurrence after a single unprovoked seizure in children varies from 27>70%.

The risk is lowest (2740%) in children with normal neurologic examinations, daytime spells, and normal EEGs.
The risk is increased (up to 80%) in children with abnormal examinations, focally abnormal EEGs, onset of seizure
in sleep, positive familial history of seizures, partial seizure, or postictal (Todd) paralysis.

POSSIBLE COMPLICATIONS

Brain damage:
1. From brief seizures: No convincing evidence exists.
2. From prolonged seizures (>30 minutes): Brain injury may occur secondary to hypoxia (respiratory
compromise) and loss of cellular energy stores (see Status Epilepticus chapter).

Injuries: Rarely, serious injury occurs with brief seizures from loss of consciousness and resultant falls.

Daily precautions: Few restrictions are needed with the exceptions of driving (related state laws), operating heavy
machinery, or particularly dangerous sports, such as scuba diving, parachuting, and rock climbing. All children
with epilepsy should be closely supervised when in or around water (swimming or bathing).

Very frequent seizures, even if brief, may impair learning.

Frequently Asked Questions

Q: How do you know my child has epilepsy?

A: The term epilepsy is applied to children with recurrent seizures (>1) not owing to fever or other transient
toxic/metabolic disturbance.

Q: Will my child always have epilepsy?

A: Depending on the circumstances, children may grow out of their seizure disorder. In many cases,
anticonvulsants can be discontinued if the child has been seizurefree for 2 years.

Q: Why take an anticonvulsant(s)?

A: The purpose of anticonvulsant medication is to prevent interference with normal behavior associated with brief
seizures and/or accidents and to prevent status epilepticus.

Q: Why did my childs seizures change?

A: In some epilepsy syndromes (e.g., absence), there is the possibility of having different types of seizures (i.e.,
staring type and convulsive type). Partial seizures often change as the child grow older, or under the influence of
medication (i.e, often milder).