Reducing unnecessary investigations in pediatric simple febrile and first-episode generalized unprovoked seizures

Clinical question

Do children older than 6 months with a simple febrile seizure or first-episode unprovoked generalized seizure require urgent investigations (blood work or neuroimaging)?

Bottom line

New-onset unprovoked seizures may be the first presentation of an epilepsy syndrome or may represent an isolated event in otherwise healthy children. Multiple Choosing Wisely Canada (CWC) recommendations and seizure guidelines advise against use of urgent investigations for both simple febrile and first unprovoked generalized seizures. When not indicated, investigations have the potential to cause unintended harm. To reduce low-value care, providers must address barriers such as discomfort with uncertainty, training gaps, learned practices, therapeutic illusion (tendency to overestimate the usefulness of investigations), and caregiver desire for investigation. This may be achieved through family education and engagement, clinician engagement, guideline implementation, clinical decision rules, and audit and feedback.

Evidence

Seizures in children are often categorized as febrile or afebrile, and focal or generalized.¹ Generalized seizures start on both sides of the brain simultaneously, cause loss of consciousness, and may cause abnormal movements on both sides of the body. Focal seizures begin on 1 side of the brain and can cause changes in awareness, behaviour, and sensation, or abnormal movements typically affecting 1 side of the body. Febrile seizures occur between the age of 6 months and 5 years in children without underlying brain abnormalities. Simple febrile seizures are generalized in nature, last less than 15 minutes, and do not recur in a 24-hour period.² Febrile seizures not meeting those criteria are defined as complex. Febrile seizures are the most common neurologic disorder in young children, with approximately 3% to 5% of children having a febrile seizure in the first 5 years of life.² Afebrile seizures may be provoked (ie, precipitated by central nervous system infection, trauma, or acute neurologic insult) or unprovoked. New-onset unprovoked seizures may be the first presentation of an epilepsy syndrome or may represent an isolated event in otherwise healthy children. Between 0.5% and 1% of children experience a nonrecurrent, single, unprovoked convulsive episode.³

Multiple CWC recommendations and seizure guidelines advise against use of urgent investigations for both simple febrile and first unprovoked generalized seizures (Table 1).^2,4-10 While guidelines have helped reduce unnecessary investigations in children with febrile seizures, ongoing efforts along with increased focus on first unprovoked seizures are warranted. Following an unprovoked seizure, 43% to 87% of children undergo blood testing^11-13 and 46% to 55% undergo urgent neuroimaging,^14,15 but these do not result in changes in urgent management in most cases.^16,17 Providers must address barriers such as discomfort with uncertainty, training gaps, learned practices, therapeutic illusion, and caregiver desire for investigation. Patients younger than 6 months, those with complex febrile seizures, and those presenting in status epilepticus (continuous seizure lasting more than 30 minutes or repeated seizures without returning to baseline in between) are excluded from these recommendations.

Laboratory investigations. Routine blood work is not recommended in the workup of either simple febrile seizures or first unprovoked generalized seizures and can be potentially harmful.^2,4,18-20 For febrile seizures, abnormal electrolyte levels are the cause in less than 1% of cases.^18,19,21 Additionally, the risk of serious bacterial infection, such as bacteremia, urinary tract infections, or meningitis, is the same in children with simple febrile seizures as those with fever alone.²² Reduction in the rate of laboratory testing since the 2011 American Academy of Pediatrics febrile seizure guidelines has not been associated with any increase in delayed diagnosis of bacterial meningitis.²³

For afebrile seizures, less than 10% of blood tests reveal an abnormality. Importantly, those with abnormalities were predictable based on history and physical examination alone.^11-13 Notably, infants younger than 6 months represent a higher-risk population for alternative diagnoses, and warrant screening of electrolyte and glucose levels even in the absence of suggestive features.⁶

Neuroimaging. The role of urgent neuroimaging is to identify a process that requires urgent interventions (eg, hydrocephalus, hemorrhage). While the rate of clinically relevant neuroimaging findings in children with afebrile seizure is 8% to 21%,^16,24,25 less than 1% of abnormalities require urgent intervention.^16,17 Several clinical predictors are associated with an increased risk of intracranial abnormalities in children with afebrile seizures. These predictors include a high-risk past medical history, focal seizure, focal neurologic deficits, age younger than 2 years, or prolonged seizure (Box 1).^{6,11-13,15,17,24-27} Limiting neuroimaging to this higher-risk population could reduce the number of computed tomography (CT) scans performed by 26% to 50%^11,15 without missing any urgent abnormalities. The potential harms and resource allocation associated with emergency neuroimaging must be weighed against the likelihood of obtaining crucial information.^28,29

Approach

When a child presents with a suspected seizure it is important to complete a thorough history and physical examination to determine indicated next steps. Children who have not returned to baseline neurologic status; who demonstrate focal neurologic deficits, signs of sepsis, meningitis, dehydration, or intoxication; or who have a history of trauma, nonaccidental trauma, or focal seizure should be immediately referred to the emergency department for urgent investigations.

Simple febrile seizures are frequently caused by viral illnesses and investigation for a bacterial source should follow the usual approach for children presenting with a fever. Patients with fever should be treated for comfort, as antipyretics have not been shown to prevent febrile seizures. About one-third of children experiencing a febrile seizure will go on to have at least 1 additional seizure in the future. The risk of developing an epilepsy syndrome is about 1% to 2% (only 1% higher than the general population).³⁰ Side effects of antiseizure medications outweigh the minor risks associated with future simple febrile seizure.⁵ Children with simple febrile seizures do not require assessment by a neurologist and generally outgrow them by 6 years.

Idiopathic seizures account for 70% of afebrile seizures and do not recur in 50% of cases.³¹ Laboratory tests for an afebrile seizure should be ordered based on individual risk that includes history or physical findings suggestive of metabolic disturbances (eg, substantial vomiting, diarrhea, signs of dehydration), prolonged seizures, or altered mental status (Box 1).^{6,11-13,15,17,24-27} Children with a first unprovoked seizure should be referred to a pediatrician or neurologist to ensure accurate diagnosis and appropriate management. Most children should undergo an outpatient electroencephalogram, which may help determine the type of seizure and guide further diagnostic and therapeutic choices. Many children will be candidates for nonurgent magnetic resonance imaging, which is the imaging modality of choice because of its superior anatomic resolution and lack of radiation.^6,7

Providers should be prepared to counsel families on seizure first aid, when to seek emergency care, and plans for follow-up.

Implementation

Family education and engagement. Seizures are distressing for caregivers. Exploring caregiver understanding of seizures and indications for investigations is key to avoiding unnecessary testing. Shared decision making to forgo emergency investigations requires understanding of the harms and benefits associated with these tests. Caregivers should be informed of red-flag symptoms that warrant emergency workup.³²

Patients need to have an appropriate follow-up plan. The time interval between initial assessment and follow-up can be a considerable source of stress for families. Written information and seizure action plans, like the Royal College of Paediatrics and Child Health leaflet for first afebrile seizure³³ can reinforce key messages and increase caregiver knowledge and comfort.³⁴

Guideline implementation and clinician engagement. The development and implementation of evidence-based guidelines or pathways for first unprovoked generalized seizures, along with the adaptation of existing simple febrile seizure guidelines, are key to supporting providers in delivering appropriate, high-value care. In a European study, systematic implementation of a practical evidence-based guideline for febrile seizures led to a 26% to 52% reduction in laboratory evaluation in multiple centres.³⁵ Interventions included adapting existing guidelines to the local context through stakeholder engagement, dissemination of posters and pocket guides for use at the point of care, education sessions, and availability of study champions at each site.

Clinical decision rules, audit, and feedback. There is an opportunity to apply lessons from minor head trauma management in children, where successful implementation of head CT decision rules has led to a reduction in neuroimaging use.^36,37 Successful interventions include creation of standardized assessment tools and algorithms outlining low-risk features versus red flags, educational sessions, visual aids, and documentation templates. Evidence also suggests that electronic health record–integrated decision rules can decrease head CT use.^38,39 This approach provides real-time decision support and leads to increased uptake of evidence-based practice over time. Finally, involving individual clinicians through performance audit, feedback, and peer comparison⁴⁰ can encourage engagement and motivate providers to reduce low-value testing.