Causes and Diagnosis of Unprovoked Seizures in Children

Etiology of Unprovoked Seizures

• Unprovoked seizures in children arise from idiopathic epilepsy, structural brain abnormalities, genetic epilepsy syndromes, or remain truly idiopathic without identifiable cause, according to the American Academy of Pediatrics 1, 2
• Idiopathic epilepsy represents the most common cause of unprovoked seizures in children, occurring without identifiable structural or metabolic abnormalities, as stated by the American Academy of Neurology 2
• Genetic epilepsy syndromes are particularly prevalent in pediatric populations and may present as specific electroclinical syndromes with characteristic EEG patterns, as noted by the International League Against Epilepsy 2, 3, 4
• Malformations of cortical development are a significant cause of unprovoked seizures in children, according to the American Academy of Neurology 2
• Remote traumatic brain injury can cause unprovoked seizures, as stated by the Centers for Disease Control and Prevention 2
• Prior stroke represents a structural cause of unprovoked seizures, as noted by the American Heart Association 2
• Intracranial hemorrhage and perinatal ischemic stroke account for 10-12% of neonatal seizures, according to the Neonatal Seizure Registry 2
• CNS mass lesions including tumors can present with unprovoked seizures, as stated by the National Cancer Institute 2
• Hypoxic ischemic injury is the most common cause of seizures in both term and preterm infants, accounting for 46-65% of neonatal seizures, as noted by the American Academy of Pediatrics 2
• Approximately 90% of hypoxic ischemic encephalopathy seizures occur within 2 days of birth, according to the Neonatal Seizure Registry 2
• An underlying cause can be identified in approximately 95% of neonatal seizures, as stated by the American Academy of Pediatrics 2
• Unprovoked seizures and epilepsy occur in up to 15% of patients with 22q11.2 deletion syndrome, as noted by the National Institute of Mental Health 3, 4
• Structural brain abnormalities in patients with 22q11.2 deletion syndrome include polymicrogyria, gray matter heterotopia, and Chiari malformation, according to the National Institute of Neurological Disorders and Stroke 3, 4

Diagnostic Approach

• EEG is recommended as a standard part of the neurodiagnostic evaluation of the child with an apparent first unprovoked seizure, as stated by the American Academy of Neurology 1, 7
• MRI is the preferred neuroimaging modality when a neuroimaging study is obtained, according to the American College of Radiology 1, 7
• Laboratory tests should be ordered based on individual clinical circumstances, including suggestive historic or clinical findings, as noted by the American Academy of Pediatrics 1, 7
• Toxicologic screening should be considered across the entire pediatric age range if there is any question of drug exposure or substance abuse, as stated by the Substance Abuse and Mental Health Services Administration 1, 7
• 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, according to the American College of Emergency Physicians 1, 7
• 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, as noted by the American Academy of Neurology 1, 7
• 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, as stated by the Infectious Diseases Society of America 1, 7

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, as noted by the American Academy of Pediatrics 2
• Focal neurologic examination findings have 97% correlation with symptomatic seizures, making thorough neurologic examination essential, according to the American Academy of Neurology 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, as stated by the National Institute of Mental Health 3, 4