Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.




Seizures, a common neurologic disorder that occurs in childhood, affect 4%-6% of all children. A seizure is defined as a transient, involuntary alteration of consciousness, behavior, motor activity, sensation, and/or autonomic function caused by an excessive rate and hypersynchrony of discharges from a group of cerebral neurons. Epilepsy is diagnosed after two or more unprovoked seizures. In other words, recurrent seizures only occurring with precipitating events such as illness, fever, or acute head trauma are typically not considered epilepsy, even though antiepileptic drugs may be used to treat the seizures acutely. The first step in formulating a differential diagnosis in a child who presents with “seizures” is to characterize the type of event. Seizures are classified into generalized seizures (such as a tonic-clonic seizure affecting the entire body simultaneously) or focal seizures (arising from a specific area or areas of the cortex, with or without spread to the entire brain). The underlying cause is divided into three categories: genetic, structural/metabolic, and unknown cause. Genetic epilepsy is defined by seizures caused by a known or presumed genetic defect (e.g., SCN1A mutation). Structural/metabolic seizures are due to a lesion, such as stroke or tumor, but may also include infection. Tuberous sclerosis complex, while caused by a genetic mutation, is classified in this category because it is the structural changes in the brain, rather than being directly caused by the mutation itself, that result in epilepsy. The etiology of epilepsy that does not have a recognized genetic or structural/metabolic cause is classified as unknown.

This chapter will discuss possible causes of seizures. However, seizures should be differentiated from other childhood paroxysmal events that can mimic seizure activity. For example, prolonged syncope and clonic jerks occurring in the setting of a syncopal event may resemble a generalized tonic-clonic seizure. Syncope is the most common alternative diagnosis assigned to otherwise healthy patients who fall to the ground without warning. Atonic seizures or “drop attacks” in which a child loses muscle tone are rare and typically occur in children with other seizure types as well (e.g., myoclonic and tonic seizures). Gastroesophageal reflux with opisthotonic posturing (Sandifer syndrome) frequently mimics seizures in infancy. Breath-holding spells, which occur in approximately 4% of infants, can resemble seizures and are also associated with cyanosis. A variety of movement disorders, such as benign myoclonus of infancy and Tourette syndrome, may also be mistaken for seizures. Additionally, seizure activity is often subtle, making seizures difficult to diagnose. For example, in the neonatal period seizures may present with horizontal eye movements, repetitive sucking, or pedaling and stepping motions that are difficult to distinguish from normal newborn infant activity. In older children, childhood absence epilepsy is characterized by a brief impairment of consciousness manifesting as a stare or behavioral arrest and is often mistaken for attention deficit disorder.


It is important to remember that a seizure does not constitute a diagnosis but is a symptom of an underlying pathologic process that requires a thorough evaluation. The causes of seizures and development of epileptic syndromes in childhood vary by age (Table 19-1). Many of the diagnoses in this table, such as infections and drug toxicities, are not specific to one age group. However, they were included with certain age categories due to increased susceptibility within that age group. While the etiology of seizures should be classified as genetic, structural/metabolic, or unknown, it is often helpful to develop a differential diagnosis by classifying the cause of seizures by category (Table 19-2).

TABLE 19-1. Selected causes of seizures or epilepsy in childhood by age.


TABLE 19-2. Causes of seizures in childhood by etiology.




Thorough history taking is essential to arrive at an accurate diagnosis in a child who presents with seizures. Consideration of seizure type, precipitating factors, and associated clinical features provides a useful framework for creating a differential diagnosis. The following questions may help to provide clues to the diagnosis:

• Did the seizure involve the entire body or only a portion?

—Focal (or partial) seizures reflect initial involvement from a localized lesion or lesions in the cerebral hemisphere(s). Focal seizures were previously classified on the basis of whether consciousness was impaired (complex partial seizure) or unaffected (simple partial seizure); however, these terms have been removed from the most recent classification recommendations for epilepsy. Although focal seizures are likely due to localized lesions, such structural causes are only found on magnetic resonance imaging (MRI) in 30%-50% of cases.

• Was there a preceding illness or fever?

—Febrile seizures occur most commonly in children 6 months to 5 years old. Febrile seizures occur in the setting of a systemic illness, such as a respiratory infection. Central nervous system infections, such as meningitis or encephalitis, are not considered febrile seizures but rather a separate category of primary central nervous system infection.

• Is there an ingestion or toxin exposure?

—Many medications and environmental toxins can lead to seizures including anticonvulsant medications, hypoglycemic agents, isoniazid, lithium, methylxanthines, heavy metals (e.g., lead), and tricyclic antidepressants.

• Is there recent headache, vomiting, lethargy, weakness, or alteration in gait?

—These symptoms suggest underlying central nervous system pathology and the need for neuroimaging. In neonates, the early onset of lethargy, vomiting, and seizures should prompt an evaluation for an underlying metabolic disorder, such as an aminoacidopathy, organic aciduria, and urea cycle defect; examples include phenylketonuria and maple syrup urine disease.

• Is there a history of previous seizures, febrile or afebrile, or neurologic abnormality?

—One-third of children with a simple febrile seizure will have a second episode. A previous afebrile seizure or existing neurologic abnormality increases the likelihood of a seizure disorder or epileptic syndrome.

• Is there a history of head trauma?

—Head trauma can result in epilepsy at any age. Seizures can occur within 1-2 weeks after the injury (early posttraumatic seizures), as an acute reaction to head trauma, or after intervals of several months or even years (late posttraumatic seizures). The risk of developing seizuresis related to the severity of the head injury. The child with a mild head injury (transient loss of consciousness without evidence of skull fracture or neurologic abnormality) is not at a significantly higher risk than the general population. Moderate head injuries are associated with an increased risk of epilepsy ranging from 2% to 10%. Children with severe head injuries, such as intracerebral hematoma or a history of unconsciousness more than 24 hours, have a 30% risk of developing epilepsy.

• Is there a history of a remote neurologic insult?

—A history of anoxic birth injury, cerebral palsy, stroke, intracranial hemorrhage, or meningitis places the child at increased risk for a seizure disorder. Intrauterine infection with cytomegalovirus, toxoplasma, or rubella is known to cause abnormal brain development and predispose the child to seizures.

• Are there skin abnormalities on physical examination, such as café-au-lait or ash leaf spots, or cutaneous vascular malformations?

—These findings suggest an underlying neurocutaneous disorder including neurofibromatosis, tuberous sclerosis complex, and Sturge-Weber syndrome.

• What is the child’s head morphology?

—Microcephaly suggests an underlying neurologic abnormality. A full or bulging fontanelle can signify elevated intracranial pressure due to meningitis, trauma, malignancy, or hydrocephalus.

• Is there a family history of seizures?

—Both febrile and afebrile seizures can be hereditary.

The following cases represent less common causes of seizures in childhood.