|Home | About | Journals | Submit | Contact Us | Français|
To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus.
We performed a cross-sectional study of children seen at a single ED between 1995–2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 minutes or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE.
We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29–43%) children with 15 (8.5%, 95% confidence interval 5.2–14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology.
A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe.
Status epilepticus is one of the most common neurologic emergencies in childhood.1–4 The primary goals of emergency care are to abate seizure activity and to identify potentially life-threatening or reversible etiologies of the seizure.5 However, the role for emergent neuroimaging in this evaluation remains controversial.
Evidence around whether to obtain emergent neuroimaging in children with a new-onset seizure presenting with status epilepticus is limited.6 Previous pediatric series have reported overall neuroimaging abnormalities in 34%–49%6–9 of children with status epilepticus, although many of these radiologic findings did not require urgent or emergent intervention. The American Academy of Neurology practice parameter states there is insufficient evidence to support or refute recommending routine neuroimaging.10 Conversely, the International League Against Epilepsy (ILAE) recommends new-onset seizures/epilepsy with a medical emergency such as status epilepticus always merit emergency imaging.10–12
To further explore the role for neuroimaging, we sought to determine the yield of emergent neuroimaging among children presenting to a pediatric emergency department (ED) with new-onset seizures presenting as status epilepticus.
We performed a retrospective cohort study of children age 3 month to 18 years who presented to the ED of a single large urban pediatric tertiary care center between October 1995 and September 2012. The study was approved by the Institutional Review Board with a waiver of informed consent.
We performed case identification in two phases. First, we created a computer-assisted key word screening tool using regular-expression matching to search the electronic medical record and identify potentially eligible ED encounters.13,14 This technique provides a more comprehensive and inclusive search than key word searching by including misspelled and mistyped variations. Second, we refined the output of the search tool by manual medical record review.
We included children with no prior history of seizure and those with only a history of febrile seizure presenting with status epilepticus. Status epilepticus was defined in one of the following three ways: 1) a single convulsive seizure lasting ≥ 30 minutes, 2) multiple seizures with a cumulative duration ≥ 30 minutes without a return to neurologic baseline, or 3) a physician diagnosis of status epilepticus (only if neither of the preceding criteria were met and the seizure duration was not specifically documented as < 30 minutes).15–18 We excluded children with: documented head trauma in the preceding seven days, neurosurgery within 30 days, known central nervous system tumor, presence of a ventricular shunt, or known toxic ingestion.
We reviewed the complete medical records of all study patients. A document hierarchy was created for the purpose of increasing consistency. We abstracted data in a hierarchal fashion as follows: 1) ED note, 2) neurology consultation note, 3) admission note, 4) discharge summary, and 5) daily progress notes. We utilized documents lower in the hierarchy only to identify data elements that were missing from records given higher priority in the hierarchy. When attending and trainee medical records differed, we abstracted data from the attending documentation.
We collected the following factors: patient demographics, date of visit, duration of symptoms and clinical features, patient management including neuroimaging obtained and disposition. For the purpose of this study, we defined focality to a seizure as unilateral eye deviation, head tilt, or focal motor activity.17 We defined febrile status epilepticus as status epilepticus with documented fever greater than or equal to 38.0° Celsius obtained at home or by a medical provider.10 We reviewed all available records to obtain available long term clinical follow-up. We included all cranial computed tomography (CT) and magnetic resonance imaging (MRI) imaging studies performed within 30 days of initial ED evaluation for status epilepticus. Because some children are too unstable to undergo imaging in the Emergency Department, we defined emergent neuroimaging as neuroimaging performed during the initial hospital visit. We included imaging 30 days after the index visit as well to identify any cases of urgent or emergent pathology that may have been missed had neuroimaging not been performed emergently.
Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging (CT or MRI), which we defined as findings requiring emergent or urgent changes in patient management. In 2009, the ILAE defined 5 categories for neuroimaging abnormalities in recent onset epilepsy (Table 1).11 We utilized this classification scheme to categorize neuroimaging results. We classified categories 4 and 5 as urgent or emergent intracranial pathology as they were conditions that would change management beyond seizure control. Importantly, sinusitis was not considered a clinically significant abnormality.
A single study neuroradiologist (SBP), blinded to the clinical history, reviewed the neuroimages, interpreted each study and classified the results according to the ILAE system. In ambiguous cases, an ED physician (AAK), a pediatric neurologist (TL) and a neuroradiologist (SBP) came to a consensus classification.
We utilized Bayesian credible intervals to calculate the percentage (and confidence intervals) for the rate of children with neuroimaging abnormalities, including those that were urgent or emergent. We compared patients with and without intracranial pathology requiring acute intervention with Mann-Whitney tests for continuous variables and χ2 tests for categorical variables. We utilized the Fisher Exact test when expected cell counts were fewer than 5.
For our primary analysis we assumed that all children who did not have neuroimaging performed did not have urgent or emergent intracranial pathology. We then performed a sensitivity analysis to determine the impact of varying the proportion of these children who had urgent or emergent intracranial pathology.
All analyses were conducted using the Statistical Package for the Social Sciences (IBM SPSS Statistic Version 21, IBM Inc., Chicago, IL).
During the study period there were 801 ED visits for status epilepticus accounting for less than 0.1% of all ED visits (Figure 1). Among the ED visits for status epilepticus, 586 (73% of visits) were for children with a previous history of at least one afebrile seizure. Thirty-eight children met additional exclusion criteria. We included the remaining 177 ED visits from children with status epilepticus of whom 145 (82%) had no history of previous seizure and 32 (18%) had a prior simple febrile seizure(s). We describe the clinical characteristics and management of the 177 study patients in Table 2.
Neuroimaging was performed in 170 (96%) children. Of these, 98 (58%) had a non-contrast CT alone, 11 (6.5%) had an MRI alone and 61 (36%) had both CT and MRI. Among children with neuroimaging performed, 164 (96.5%) had their imaging performed during their index hospital visit with 159 (97%) receiving imaging in the ED and 5 (3%) during their index hospitalization. Of the 159 children with neuroimaging performed in the ED, 157 (98.7%) had a non-contrast CT scan, and 2 (1.3%) had an MRI. Six (3.5%) children had imaging performed following discharge from their index hospitalization and were included to assess for urgent or emergent pathology that may have been missed during the index hospitalization. Of the seven study patients who did not have any neuroimaging performed, long-term clinical follow-up was available for six. None of these children died, underwent neurosurgery or were subsequently diagnosed with neuroimaging findings requiring emergent or urgent intervention.
Of the 177 study patients, 64 children [36%, 95% confidence interval (CI) 29–43%] had abnormalities on neuroimaging (Figure 2). Fifty-four (84%) of these findings were new findings, and 10 (16%) had been identified on previous neuroimaging. Urgent or emergent intracranial pathology was identified in 15 (8.5%, 95% CI 5.2–14%). All of these findings were new. We identified the following urgent or emergent intracranial pathology on neuroimaging studies: 5 cases of vascular pathology, 4 cases of generalized cerebral edema, 2 cases of acute demyelinating encephalomyelitis (ADEM), 3 cases of acute central nervous system infection and one case of an intracranial lesion with mass effect (Table 3). Among these children, 4 (27% of those requiring acute intervention) were discovered on follow-up MRI performed after a normal non-contrast CT scan. These findings included the two cases of ADEM, one case of meningoencephalitis and one case of multi-focal acute ischemic strokes. All of the urgent or emergent intracranial pathology seen on CT scan was also evident on the MRI images. Both cases of ADEM were subsequently treated based on the results of MRI. The child with meningoencephalitis subsequently underwent lumbar puncture as a result of MRI and was started on empiric treatment for HSV. The child with ischemic stroke underwent further evaluation for hypercoagulability and was put on prophylactic aspirin for life based on the results of MRI.
We compared clinical and demographic findings of patients with and without intracranial pathology (Table 2). Children with urgent or emergent intracranial pathology were older and had longer duration of their seizures. Rates of emergent neuroimaging findings did not differ between those children with febrile SE (8%) vs. afebrile SE (9.2%, p = 0.79). The management of children with urgent or emergent intracranial pathology also differed with higher rates of intubation and ICU admission. In addition, we also found a higher mortality rate among children with urgent or emergent intracranial pathology.
We then performed a sensitivity analysis to determine the impact of our primary assumption that the 7 children without initial neuroimaging did not have urgent or emergent intracranial pathology. If we assumed all of these children had urgent or emergent intracranial pathology, the overall rate would increase to 22/177 (12.5%, 95% CI 8.4–18%).
We identified a large cohort of children with new-onset seizures presenting with status epilepticus. Of these children, 8.5% had urgent or emergent intracranial pathology identified on neuroimaging. Among children with urgent or emergent findings on neuroimaging over a quarter were missed on non-contrast CT scan and not discovered until a subsequent MRI scan. We found that older children and children with longer duration of seizures may have higher rates of urgent or emergent pathology on neuroimaging.
Data on the yield of neuroimaging in children with status epilepticus is limited. In one review of neuroimaging data for children with status epilepticus, structural lesions that would likely be detected by neuroimaging were present in 7.8%, with 5.1% corresponding to lesions we would classify as urgent or emergent intracranial pathology. However, not all of these children underwent neuroimaging. Actual neuroimaging data was only available for 198 children (174 CT and 24 MRI) from six studies with a mean of 49% abnormal (range 29–70%).19–23 However, these data were not limited to children with new-onset seizures in status epilepticus. In a second study examining 144 children with status epilepticus as a presentation of new-onset seizure, the combination of CT and MRI identified an underlying reason for SE in 30% of which 10% were described as “acute” abnormalities.6 A recent analysis found that 11% of children with new unprovoked seizure had neuroimaging abnormalities but only 0.8% representing emergent findings. This study however only included 11% of patients with seizure > 15 minutes, and seizure duration > 15 minutes was associated with an increased incidence of abnormal neuroimaging findings.24 Our data add and expand to the previously reported yield of neuroimaging; in this cohort of children with new-onset seizure and status epilepticus we found of 36% of children with abnormal neuroimaging of which 8.5% had pathology requiring urgent or emergent interventions.
Practice guidelines regarding the need for emergent neuroimaging in status epilepticus are not conclusive. In 2006 the American Academy of Neurology published a practice parameter that was endorsed by the American Academy of Pediatrics recommending neuroimaging for the child with status epilepticus “if there are clinical indications or if the etiology is unknown.”10 Our study inclusion criteria meet this definition by including only children with no seizure history [or children with a history of simple febrile seizure(s)] with new-onset seizure presenting as status epilepticus. The 2009 ILAE guidelines call for neuroimaging for infants and children with recent onset epilepsy. While these guidelines are for children in whom acute asymptomatic etiologies for seizures have been excluded, they recommend “new-onset seizures/epilepsy presenting with evidence for a medical emergency such as increased intracranial pressure or status epilepticus always merit emergency imaging.”11
Emergent neuroimaging may require moving an ill patient, limit access to the patient if they were to deteriorate, possibly expose that patient to the risks of ionizing radiation25,26 and/or sedation,27 and delay other management. Conversely, the clinical assessment of these children is challenging as they are post-ictal, sedated from anti-epileptic medications and frequently intubated (45% in our study). Therefore, a significant enough proportion of children should have clinically urgent or emergent findings to justify performing emergent imaging on a routine basis. Our data support the recommendations of the ILAE for routine emergent neuroimaging in status epilepticus with 12 studies needing to be performed to diagnose one urgent or emergent case of intracranial pathology. While older age and longer seizure duration were associated with increased risk of urgent or emergent findings on neuroimaging in our study, 4/11 children with these findings were under age 2 years. Identifying a low-risk population who might not need to undergo emergent neuroimaging would be useful for providers. However, we were unable to identify such a population. Because a significant portion of patients with SE are intubated, utilizing historical factors and physical examination findings to identify a low-risk population is challenging. Further studies are needed with larger numbers to identify children at sufficiently low risk of urgent or emergent findings that neuroimaging could be deferred to a later time.
Both the American Academy of Neurology and ILAE guidelines call for MRI as the imaging modality of choice for first time seizure when safe and available.10,11,28 In our study, 27% of children with emergent neuroimaging findings were subsequently discovered on MRI scan after a normal non-contrast CT scan. In addition, all 15 emergent or urgent findings were identified by MRI. This finding is consistent with data previously reported by Singh, et al. where 14/44 (32%) children with new-onset seizure presenting as status epilepticus had a normal CT but abnormal MRI.6 Non-contrast head CT is the emergent neuroimaging modality of choice at many institutions. Despite this preference, MRI offers higher image quality and additional diagnostic information and should be strongly considered in stabilized children.6,29,30 However, while none of the emergent abnormalities discovered on CT were missed by MRI, we recognize children with SE are frequently unstable and MRI may need to be deferred until clinical status has improved. Because CT scans can detect abnormalities in which earlier treatment may improve outcomes, CT can be a useful in unstable children in whom MRI cannot safely be performed in a reasonable time interval.
Our study has several limitations. First, our study was retrospective and not all data elements could be completely abstracted from the medical record. However, our primary outcome was an objective diagnostic radiologic study which was available for all patients in which it was performed. Second, not all children included underwent neuroimaging, and when neuroimaging was performed it was at the discretion of the ordering provider. However, 96% of children did undergo neuroimaging. Moreover, follow-up was available for 6/7 of those who did not, with none having sequela of missed urgent or emergent intracranial pathology. We also performed a sensitivity analysis to determine the impact that children who did not undergo neuroimaging would have had on our results had they all had urgent or emergent pathology. Third, there is a potential for referral center and related selection bias, as 46% of patients were transferred from another institution. However, the rate of neuroimaging abnormalities between children transferred and those who presented primarily to Boston Children’s Hospital was equivalent. Finally, we chose a strict definition of status epilepticus as seizure ≥ 30 minutes.10 We chose this definition because it is the definition utilized in the American Academy of Neurology Practice Parameter, and endorsed by the Epilepsy Foundation of America.10,15 Newer definitions of status epilepticus have included shorter seizure duration,31,32 which may impact the yield of emergent neuroimaging.
A substantial minority of children with first time seizure presenting with status epilepticus have intracranial pathology requiring urgent or emergent intervention. Clinicians evaluating these children should strongly consider emergent neuroimaging, with MRI as the preferred imaging modality when available and safe.
Funding source: No funding was secured for this study.
Statistical Analyses Performed By: Todd W. Lyons, MD
Prior Presentations: The data presented in this paper was presented in the Pediatric Academic Societies Meeting in Washington, D.C. on May 05, 2013.
Todd W. Lyons: Dr. Lyons aided in the conceptualization and design of the study, performed data abstraction, carried out the initial analyses, drafted the initial manuscript and approved the final manuscript as submitted.
Kara B. Johnson: Dr. Johnson performed data abstraction, reviewed and revised the manuscript, and approved the final manuscript as submitted.
Kenneth A. Michelson: Dr. Michelson aided in the conceptualization and design of the study, performed data abstraction, reviewed and revised the manuscript, and approved the final manuscript as submitted.
Lise E. Nigrovic: Dr. Nigrovic assisted in the design of the study, aided in data analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted.
Tobias Loddenkemper: Dr. Loddenkemper assisted in the conceptualization and design of the study, provided expert neurologic opinion, reviewed and revised the manuscript, and approved the final manuscript as submitted.
Sanjay P. Prabhu: Dr. Prabhu reviewed all neuroimaging results, reviewed and revised the manuscript, and approved the final manuscript as submitted.
Amir A. Kimia: Dr. Kimia conceptualized and designed the study, performed study participant identification providing text processing expertise, supervised data collection and analysis, critically reviewed the manuscript, and approved the final manuscript as submitted.
Financial disclosures: All authors have no financial relationships relevant to this article to disclose.
Conflict of Interest: All authors have no conflicts of interest to disclose.