What are the causes and management of unprovoked seizures in pediatric patients?

Causes of Unprovoked Seizures in Children

Unprovoked seizures in children arise from idiopathic epilepsy, structural brain abnormalities (malformations of cortical development, prior stroke, remote traumatic brain injury), genetic epilepsy syndromes, or remain truly idiopathic without identifiable cause. 1, 2

Primary Etiologic Categories

Idiopathic/Genetic Epilepsy

• Idiopathic epilepsy represents the most common cause of unprovoked seizures in children, occurring without identifiable structural or metabolic abnormalities. 2
• Genetic epilepsy syndromes are particularly prevalent in pediatric populations and may present as specific electroclinical syndromes with characteristic EEG patterns. 2, 3
• Some epilepsy syndromes are self-limited and resolve spontaneously, while others (developmental and epileptic encephalopathies) are pharmacoresistant and associated with intellectual disability and poor long-term outcomes. 3

Structural Brain Abnormalities

• Malformations of cortical development are a significant cause of unprovoked seizures in children. 2
• Remote traumatic brain injury (occurring >7 days before seizure onset) can cause unprovoked seizures. 2
• Prior stroke (>7 days before seizure) represents a structural cause of unprovoked seizures. 2
• Intracranial hemorrhage and perinatal ischemic stroke account for 10-12% of neonatal seizures. 2
• CNS mass lesions including tumors can present with unprovoked seizures. 2

Hypoxic-Ischemic Injury (Neonatal Context)

• Hypoxic ischemic injury is the most common cause of seizures in both term and preterm infants, accounting for 46-65% of neonatal seizures. 2
• Approximately 90% of hypoxic ischemic encephalopathy seizures occur within 2 days of birth. 2
• An underlying cause can be identified in approximately 95% of neonatal seizures. 2

Special Population: 22q11.2 Deletion Syndrome

• Unprovoked seizures and epilepsy occur in up to 15% of patients with 22q11.2 deletion syndrome. 1
• Structural brain abnormalities in this population include polymicrogyria, gray matter heterotopia, and Chiari malformation. 1

Critical Distinction: Provoked vs. Unprovoked

Unprovoked seizures occur without acute precipitating factors, distinguishing them from provoked (acute symptomatic) seizures that occur within 7 days of an acute insult. 2

Common Provoked Causes to Exclude:

• Hypocalcemia and hypomagnesemia (particularly in 22q11.2DS, renal failure, chronic alcoholism) 1, 2
• Hypoglycemia 2
• Hyponatremia and other electrolyte abnormalities 2
• Fever/infection 1
• Toxic ingestions (cocaine, tricyclic antidepressants, antihistamines, theophylline) 2
• CNS infections (meningitis, encephalitis) 1, 2
• Acute traumatic brain injury 2

Diagnostic Approach for Unprovoked Seizures

Mandatory Investigations

• EEG is recommended as a standard part of the neurodiagnostic evaluation of the child with an apparent first unprovoked seizure. 1
• MRI is the preferred neuroimaging modality when a neuroimaging study is obtained. 1

Laboratory Testing

• Laboratory tests should be ordered based on individual clinical circumstances including suggestive historic or clinical findings such as vomiting, diarrhea, dehydration, or failure to return to baseline alertness. 1
• Toxicologic screening should be considered across the entire pediatric age range if there is any question of drug exposure or substance abuse. 1

Neuroimaging Indications

• Emergent neuroimaging should be performed in any child who exhibits a postictal focal deficit that does not quickly resolve or who has not returned to baseline within several hours after the seizure. 1
• Nonurgent MRI should be seriously considered in children with significant cognitive or motor impairment of unknown etiology, unexplained abnormalities on neurologic examination, seizure of partial onset with or without secondary generalization, an EEG that does not represent benign partial epilepsy or primary generalized epilepsy, or in children aged <1 year. 1

Lumbar Puncture

• LP is of limited value in the child with a first non-febrile seizure and should be used primarily when there is concern about possible meningitis or encephalitis. 1

Common Pitfalls

• Do not assume all seizures in children with fever are simple febrile seizures—consider CNS infection if the child has not returned to baseline or has focal findings. 2
• History and physical examination predict most metabolic abnormalities, but occasional cases of hypoglycemia and structural lesions may not be predicted clinically. 2
• Focal neurologic examination findings have 97% correlation with symptomatic seizures, making thorough neurologic examination essential. 2
• In patients with 22q11.2DS, always investigate for hypocalcemia and hypomagnesemia even in unprovoked seizures, as these metabolic abnormalities are common in this population. 1