Just the Flu?
Patient is a 13 month old M presenting to the ED via EMS following a tonic clonic seizure that per EMS, began around 9:30 AM and lasted at least 15 minutes. The patient’s family is primarily Spanish-speaking and was unable to give adequate history secondary to the language barrier. They were able to convey that the patient was sick since yesterday (no specific symptoms mentioned) was given Tylenol at 1:30 AM secondary to a fever. On arrival to the ED, the patient was responsive to suctioning and was tracking with his eyes but is shaking again upon arrival to the ED. En route, his heart rate was 208, BGL 212 and 30-60 RR.
Per mother’s report to EMS, the patient was alert and behaving normally at 9:30 AM (30 mins ago). She states that the patient was dancing and laughing with no noted complaints at that time. The patient was born full term with no complications and is fully vaccinated.
Pertinent Exam Findings:
Vitals: Rectal temperature of 102.9 F.
General Appearance: Rhythmic shaking upper and lower extremities, extremities full extension with toes and ankles flexed bilaterally, eyes deviated up and to the right, not responsive.
Head: No signs of trauma including hematoma, battle sign or raccoon eyes.
Eyes: Pupils equal and reactive but deviated up and to the right, no pallor or injection.
HENT: dry mucous membranes, normal tympanic membranes, no pharyngeal erythema, no tonsillar hypertrophy or exudates.
Respiratory: Clear to auscultation, no retractions.
Cardiovascular: Tachycardic, regular rhythm, normal capillary refill.
Gastrointestinal: Abdomen soft, no abdominal tenderness.
Genitourinary: Not circumcised.
Skin: Warm and dry, no rash. No ecchymosis, petechiae or purpura.
Musculoskeletal: Extremities are symmetrical, no deformity.
Neurological: Lower and upper extremities are rhythmically shaking, not following commands, appears to be active seizure.
Patient given 4 doses of ativan IV for active seizure (while waiting for fosphenytonin). Fosphenytonin loading dose given. Propofol and succinylcholine given for intubation. Propofol terminated the seizure.
The patient’s family arrived in the ED. They consented to LP. They deny any recent travel, or sick contacts and have verified the patient is up to date on his vaccinations. Only symptoms besides fever were rhinorrhea and cough today.
He again had another 3 episodes of seizure activity post intubation. He was loaded with 20mg/kg of keppra and started on propofol and versed drips for better seizure control. Total time of seizure in the ER was approximately 30 minutes. Full septic work-up was performed (LP, blood culture, urine culture, viral resp PCR) and started on vancomycin, rocephin, and acyclovir. Head CT showed no anatomical abnormality. He was then transferred to PICU for further management.
Neurology was consulted and recommended completing a total of 60mg/kg keppra load due to the prolonged seizure. Two days later, the patient was extubated. Normal MRI Brain. EEG showed slow wave form but likely due to postictal state and sedation, without seizures or epileptiform activity. He continued to improve and was discharged after 5 days. Per neurology, EEG and MRI reassuring at this point full recovery is likely. He does remain at risk for epilepsy, but still will likely not develop epilepsy given his normal development, EEG and MRI findings.
CSF culture: negative. HSV PCR: negative. Enterovirus PCR: negative. Blood cultures with no growth. RVP: Influenza A H1. Urine culture: negative. ETT aspirate culture: negative. Completed 10 doses of tamiflu.
Seizures affect up to 10% of Americans and 5% of kids before they reach age 16. The most common neurologic disturbance in children is the febrile seizure, most often occurring between the ages of 12 and 18 months. Febrile seizures can be classified by the presence of a fever above 38℃, lack of CNS inflammation, lack of acute metabolic disturbances, and no previous nonfebrile seizures. Further classification into simple versus complex seizures depends on clinical presentation. Delineating between the two types is relevant in terms of need for pharmacologic intervention, prognosis, and the need for further testing.
Simple seizures will typically lack focal features, last under ten minutes, occur in ages 6 months to 5 years of age, resolve on their own, have a normal neurologic exam and do not reoccur within 24 hours. In comparison, complex seizures may have unilateral focal features, last longer than 10 minutes, occur more than once within 24 hours, and require anticonvulsants. While febrile seizures are most often benign and can be diagnosed by history and physical, imaging and even lumbar puncture may be indicated to distinguish febrile seizures from more serious conditions. Based on current epidemiological studies, simple febrile seizures are not associated with an increased risk of sudden death. While complex febrile seizures are associated with a small increase in risk of sudden death, most of these cases involved patients with pre-existing neurological abnormalities. No associations have been found between febrile seizures and behavioral and cognitive functioning. While small, there is an association between febrile seizures and the development of epilepsy.
When initially presenting to the ED, a detailed history and clinical evaluation is essential to rule out more dangerous causes of seizure. Most febrile seizure patients are too young to communicate, and parents should be asked about the quality and duration of the seizure, details about the postictal phase, any recent infections or illnesses, immunization/vaccination history, previous seizures, family history, and trauma history. Often, seizures have stopped by the time a patient is brought to the ED, and parental reports of head, neck, extremity, and eye movement during episodes is helpful in diagnosing true seizure activity.
Management in ED:
Febrile seizure treatment in the ED begins with determining complex versus simple etiology. Management begins with establishing airway patency, cardiopulmonary monitoring, and circulation distally. Depending on the history we should consider giving glucose, naloxone, or pyrodixine. If return to baseline is delayed or additional complex factors are present, the standard seizure work-up includes non-contrast head CT, lumbar puncture, CBC, CMP, UA. First-line medications should begin with a benzodiazepine such as 0.05-0.1 mg/kg IV lorazepam. If the seizure continues beyond 15 minutes, second-line medications should be considered. While benzodiazepines are largely accepted as first-line, there is a lack of consensus on which medication is the “best” for second-line. The ESETT trial confirmed no significant difference in seizure resolution when treated with levetiracetam, fosphenytoin, and valproate. With no real difference in efficacy, the most tolerable drug with least risk should be used which is levetiracetam, then valproate, and fosphenytoin last. Regular reassessment of ABC’s is necessary – consider intubation if not already established as we progress to general anesthesia. In addition to propofol, recent systematic reviews have shown ketamine’s efficacy in seizure resolution especially in refractory seizure. A 2015 review by Zeiler reported no major complications with use of ketamine in addition to 63.5% resolution rate in pediatric seizure.
Risk of recurrent febrile seizures is around 35% overall with little risk for sequelae barring other pre-existing comorbidities. This risk is increased in patients younger than 18 months and those with a lower fever, short duration of fever before seizure onset, or a family history of febrile seizures. Even in complex febrile seizures, there is just a slightly increased risk for subsequent epilepsy or neurologic defect compared to simple etiology. Regardless of simple or complex etiology, children have low rates of sequelae following febrile seizure activity with 2% of those with simple and 10% of those with complex cases progressing to subsequent epilepsy diagnosis.
Mortality and Morbidity of Seasonal Influenza:
Despite recent hyper-focus on coronavirus during 2020, a much more common virus will continue to cause far more deaths with far less attention. According to the CDC, influenza kills between 10,000 and 61,000 people annually since 2010. This season’s preliminary estimates tell us that greater than 29 million people have contracted the flu and between 16,000-41,000 people have died from the virus. The vaccination is recommended as early as 6 months in otherwise healthy children in order to prevent deadly complications of viral infection. A conglomeration of 3 CDC studies covering seasonal influenza burden from 1976-2007 estimates that approximately 23,607 deaths a year were the result of the flu and its complications. Complications commonly include bacterial co-infection leading to pneumonia or benign post-viral myositis, but can also lead to severe inflammation and tissue death in the heart, brain, muscles, and other visceral organs. Viral myocarditis can lead to chronic heart disease and encephalitis or other visceral organ failure can be life-threatening. In children 5 years old and younger, the CDC estimates that 600 patients die annually from influenza and its complications.
Simple seizures will typically lack focal features, last <10 minutes followed by return of normal neuro exam findings, occur in 6mo to 5yo, resolve without anticonvulsant therapy, and fail to recur within 24 hours.
Simple seizures carry no increased risk of sudden death and less than 2% will progress to subsequent epilepsy while complex seizures carry a slight risk of sudden death with less than 10% progressing to epilepsy.
Complex seizures may require first-line benzodiazepine, followed by repeat doses, valproate, or fosphenytoin if symptoms continue. For refractory or continued seizure activity, propofol—and more recently—ketamine, has been proven safe and effective for seizure resolution.
This season’s preliminary estimates tell us that greater than 29 million people have contracted the flu and between 16,000-41,000 people have died from the virus.
In children 5 years old and younger, the CDC estimates that 600 patients die annually from influenza and its complications including, but not limited to, myocarditis and encephalitis.
Centers for Disease Control and Prevention. (2020). Burden of Influenza. [online] Available at: https://www.cdc.gov/flu/about/burden/index.html [Accessed 27 Feb. 2020].
Hernandez, R. and Silverberg, M. (2017). Treatment of Seizures in the Emergency Department: Pearls and Pitfalls – emDOCs.net – Emergency Medicine Education. [online] emDOCs.net – Emergency Medicine Education. Available at: http://www.emdocs.net/treatment-of-seizures-in-the-emergency-department-pearls-and-pitfalls/ [Accessed 27 Feb. 2020].
James, Millar, M.D., University of Oklahoma–Tulsa College of Medicine, Tulsa, Oklahoma Am Fam Physician. 2006 May 15;73(10):1761-1764
Kapur J, Elm J, Chamberlain J et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. New England Journal of Medicine. 2019;381(22):2103-2113. doi:10.1056/nejmoa1905795
Schachter SC. Evaluation and management of the first seizure in adults. UptoDate. https://www-uptodate-com.proxy.rvu.edu/contents/evaluation-and-management-of-the-first-seizure-in-adults?sectionName=DIFFERENTIAL DIAGNOSIS&search=complex simple seizure&topicRef=14094&anchor=H5&source=see_link#H5. Published August 11, 2019. Accessed February 15, 2020.
Zeiler, F. (2015). Early Use of the NMDA Receptor Antagonist Ketamine in Refractory and Superrefractory Status Epilepticus. Critical Care Research and Practice, 2015, pp.1-5.
Aaron Wolfe, DO, FACEP
Joshua Bridge, MSII