ILLUSTRATIVE CASE
Cerebral Abscess Presenting as a Complex Febrile Seizure Anjoli Anand, MD,* Alicia Salas, DO,† Evan Mahl, MD,* and Marla C. Levine, MD, RDMS*
Abstract: Currently, there is no standardized approach to the management of complex febrile seizures in children and there are no published practice guidelines for the procurement of neuroimaging. Presented is a 2-year-old female patient who experienced a 3- to 5-minute episode of staring and unilateral mouth twitching associated with high fever. On initial presentation, the patient appeared well and had a normal neurological examination. No focus of infection was identified, and she was diagnosed with complex febrile seizure. The patient was discharged home with close neurology and primary care follow-up but returned the following day with altered mental status, toxic appearance, and right lower extremity weakness. Magnetic resonance imaging of the brain revealed left-sided cranial empyema and the patient was managed with antibiotics and surgical drainage. A literature review to answer the question “Do children with complex febrile seizures require emergent neuroimaging?” yielded a small number of retrospective reviews describing the utility of computed tomography, magnetic resonance imaging and lumbar puncture in the work-up of febrile seizures. Current evidence indicates that neuroimaging is not indicated in an otherwise healthy child who presents with complex febrile seizure if the patient is well appearing and has no evidence of focal neurological deficit on examination. As this case demonstrates, however, serious conditions such as meningitis and brain abscess (though rare) should be considered in the differential diagnosis of complex febrile seizure and physicians should remain aware that the need for neuroimaging and/or lumbar puncture may arise in the appropriate clinical setting. Key Words: cerebral abscess, complex febrile seizure (Pediatr Emer Care 2015;31: 499–502)
CASE A two-year-old female with no past medical history presented to the pediatric emergency department (PED) by ambulance after having had a seizure. As described by the mother, the episode was marked by unilateral mouth twitching and staring into space lasting approximately 3–5 minutes with no generalized body twitching or stiffening. Following the episode, the child appeared tired and, by report, was “not acting like herself.” The child was noted to have been febrile at home prior to presentation to the PED and had been experiencing high fevers for two days prior to presentation with a maximum temperature of 106°F. Further history revealed vomiting and intermittent abdominal pain one day prior to presentation. Also reported was a dry cough at night with decreased oral intake and decreased urine output. All immunizations were up to date. Review of systems was negative for ear pain, sore throat, and diarrhea. The patient’s vaccinations were up to date. At the time of presentation, vital signs were temperature 103°F, heart rate
From the Departments of *Emergency Medicine and † Pediatrics, Maimonides Medical Center, Brooklyn, NY. Disclosure: The authors declare no conflict of interest. Reprints: Anjoli Anand, MD, Department of Emergency Medicine, Maimonides Medical Center, 965 48th Street, Brooklyn, NY 11219 (e‐mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0749-5161
Pediatric Emergency Care • Volume 31, Number 7, July 2015
173 beats per minute, respirations 26 per minute, and oxygen saturation 100% on room air. On physical examination, she was a tired, nontoxic appearing child, well hydrated, and appropriately interactive with mother. She was normocephalic, atraumatic, visual acuity was grossly intact, pupils were equal and reactive to light, and extraocular movements were intact. Her tympanic membranes were normal bilaterally, and her posterior oropharynx was nonerythematous with moist mucus membranes. The neck was supple with full range of motion. Cardiovascular examination revealed a normal S1 and S2 with no murmurs, rubs, or gallops appreciated. On respiratory examination, she was breathing comfortably on room air without tachypnea or retractions, and auscultation revealed transmission of upper airway sounds. The abdomen was soft, non-tender, and without guarding. She was moving her extremities well and symmetrically. Her skin was well perfused, had normal turgor and revealed no rashes. On neurological assessment, she had normal tone, cranial nerves II through XII were intact bilaterally, and she ambulated without difficulty or ataxia. She remained seizure free and became more playful over the course of her PED visit. Given the elevated temperature reported at home and documented in the PED, a complete blood count (CBC), blood culture, urinalysis, urine culture, and a chest radiograph were obtained. The CBC showed a normal white blood cell count (WBC) of 11.3 x 103/μL with a left shift of 80% neutrophils. Bands were pending at the time of discharge and later resulted as 16%. The chest radiograph demonstrated questionable development of right lower lobe airspace disease with increased perihilar interstitial markings suggestive of bronchiolitis or viral syndrome. Based on the history of a focal neurological symptom, the unilateral mouth twitching, a diagnosis of complex febrile seizure was made, and pediatric neurology was consulted via telephone. As there were no residual focal findings at the time of the neurological examination, and the patient had reliable follow-up, she was discharged home with instructions to see her primary care physician the next day and to follow up promptly with magnetic resonance imaging (MRI) and pediatric neurology consultation on an outpatient basis. Given that the child was well appearing and at her baseline throughout her emergency department visit, the mother requested to be discharged and proceed with the aforementioned outpatient work up. The following day, the child returned to the PED with a chief complaint of “not acting right.” The mother reported that, since being discharged from the PED, the patient continued to have fevers and had became more lethargic and agitated. Additional history revealed that the child’s gait had become increasingly unsteady and that she could no longer stand upright. On examination, the patient’s vital signs were temperature 101.3°F, heart rate 189 beats per minute, respirations 32 per minute, blood pressure 118/73 mmHg, and oxygen saturation 100% on room air. The physical examination on this visit was remarkable for her toxic appearance and the development of a rash and focal neurological findings. A blanching, erythematous, urticarial rash was present with areas of confluence on the child’s trunk. On neurological examination, there was marked weakness of the right upper and lower extremities and the patient was observed to drag the right foot while attempting to walk. The child was unable to stand or www.pec-online.com
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dexamethasone, fosphenytoin and the following antibiotics: vancomycin, ceftriaxone, and metronidazole. Given the discreet fluid collection noted on imaging and the positive blood culture from the previous visit, antiviral medications were not administered. The patient was admitted to the Pediatric Intensive Care Unit where she remained febrile despite antipyretic and intravenous antibiotic therapy. On hospital day 7, the patient was taken to the operating room, where she underwent left craniectomy with evacuation of the subdural and epidural empyema. During the admission, the patient also developed a large left gluteal abscess which was drained by interventional radiology on hospital day 11. After drainage of the gluteal abscess, the patient remained afebrile and eventually exhibited improved neurological status. Seizure activity beyond the one that brought her to the PED initially was not observed. She continued to have difficulty standing and walking unassisted, but her speech returned to baseline, and extremity use became symmetric. She was discharged home on hospital day 19 on intravenous antibiotics via a peripherally inserted central catheter with instructions to follow-up with infectious diseases and neurology. FIGURE 1. Noncontrast CT scan of the head showing left-sided cerebral edema and a thin subdural collection overlying the left convexity. There is also effacement of the cortical sulci and partial effacement of the left lateral ventricle.
walk without assistance. No signs of trauma were present. Differential diagnosis at this time included acute disseminated encephalomyelitis, meningitis, transverse myelitis, encephalitis, brain abscess, malignancy, and stroke. Given the toxic appearance of the child at this time, a CBC, basic metabolic panel, erythrocyte sedimentation rate (ESR), Creactive protein (CRP), creatinine phosphokinase (CPK), and blood culture were obtained. CBC was notable for WBC 4.6 x 103/μL with 34% neutrophils and 49% bands. Other notable laboratory findings included ESR 60 mm/hr, CRP 37.5 mg/dL and CPK 354 IU/L. The blood culture obtained the previous day was positive for Staphylococcus aureus and was later identified as methicillinresistant (MRSA). Computed tomography (CT) of the head was remarkable for cerebral edema in the left hemisphere with a thin subdural collection overlying the left convexity with midline shift concerning for an infectious process (Fig. 1). Lumbar puncture was deferred due to risk of herniation, and the patient was then sent for MRI of the brain which demonstrated a left sided empyema in the frontoparietal area with a 2 mm midline shift to the right (Fig. 2). The child received intravenous crystalloid,
DISCUSSION Febrile seizures are defined as seizures that occur in the setting of a fever but in the absence of a central nervous system (CNS) infection or electrolyte imbalance.1 By definition, febrile seizures occur between 6 months and 6 years of age with median age of onset 18 months. They have a prevalence of 3% to 8% in children up to 7 years.1 Simple febrile seizures are brief in duration with spontaneous cessation within 15 minutes of onset, are generalized tonic-clonic with a return to baseline mental status, occur in the absence of preexisting neurological abnormality, and occur in the setting of documented fever. However, seizures can occur before documentation of fever. Seizures last longer than 15 minutes in about 9% of cases, and 4% to 16% of febrile seizures have focal features.1,2 Complex febrile seizures, on the other hand, are more loosely defined by the presence of at least one of the following features: duration longer than 15 minutes, multiple seizures within a 24-hour period, or focal features.1,2 There are instances of transient hemiparesis after what otherwise appears to be a simple febrile seizure, but this suggests a focal origin and should be explored further.2 There is no evidence to support the measurement of serum electrolytes or procurement of a head CT in the management of simple febrile seizures.2 Based on epidemiological data, approximately 0.23% of children presenting with febrile seizures have
FIGURE 2. MRI of the brain with and without intravenous contrast showing a small subdual empyema in the left frontoparietal area extending into the interhemispheric fissure with restricted diffusion and effacement of sulci, partial effacement of left lateral ventricle, and 2 mm midline shift to the right.
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Pediatric Emergency Care • Volume 31, Number 7, July 2015
meningitis, 24% of cases of children with meningitis present with seizure, although these cases also included other clinical signs of meningitis or toxic presentation.1,2 When children present with febrile status epilepticus, the presence of meningitis increases to 18%.1 It should be noted that in children younger than 2 years of age, meningismus may not be clinically evident, and other signs, such as drowsiness, petechiae, vomiting, and complex febrile seizures, could be observed.1 Regarding evaluation with lumbar puncture, the American Academy of Pediatrics revised their guidelines in 2011 to recommend that lumbar puncture is not indicated in children between 6 and 12 months of age who have been vaccinated for Haemophilus influenza and Streptococcus pneumoniae and who present with simple febrile seizures without exhibiting any other concerning clinical signs.2 A retrospective review from the Netherlands by Offringa and Moyer3 attempted to identify criteria to assess if meningitis could be ruled out clinically and without lumbar puncture. Their study looked at 309 children between the ages of 3 months and 6 years who presented with a first febrile seizure, 23 (7%) of whom were ultimately diagnosed with meningitis. The major signs of meningitis assessed were presence of petechiae, nuchal rigidity, and coma, at least one of which was present in 70% of patients diagnosed with meningitis. These major signs were absent in all patients without disease. Kimia et al4 conducted a retrospective review to evaluate the incidence of bacterial meningitis in 526 patients who presented to the emergency department with complex febrile seizure. Lumbar puncture was obtained in 340 of the patients, only 3 of whom ultimately had positive cerebral spinal fluid cultures, all growing Streptococcus pneumoniae. Two of the patients with confirmed meningitis presented before routine vaccination against Streptococcus pneumoniae. Of the remaining 186 patients who did not undergo lumbar puncture, 161 were monitored clinically, and none of them were subsequently diagnosed with meningitis, although 25 patients were lost to followup.4 In another series by Green et al5 which included 503 patients, there were no cases of bacterial meningitis with seizure as the sole manifestation. The initial level of consciousness in the majority of the 115 patients who had meningitis with seizure was described by practitioners as obtunded, lethargic, or comatose. In the 10 patients who were described as having a normal level of consciousness after a reported seizure, 2 were ultimately diagnosed with viral meningitis, and the other 8 were described as having other clinical signs of meningitis, such as nuchal rigidity, petechial rash, or prolonged seizures. A more recent review was published regarding patients who presented with symptoms consistent with complex febrile seizure who presented after the widespread vaccination against Streptococcus pneumoniae. In this study, factors associated with obtaining a lumbar puncture were no history of simple febrile seizure, seizure focality, status epilepticus, and requiring intubation. Of the 136 patients who underwent lumbar puncture, one was diagnosed with bacterial meningitis.6 There is no standardized approach to the management of complex febrile seizures, and it often falls to the clinician to determine the extent of diagnostic evaluation.2 At this time, the American Academy of Pediatrics does not publish practice guidelines for the use of emergent neuroimaging in cases of complex febrile seizure. A small number of retrospective reviews have suggested that the well-appearing child who presents to the emergency department with a first complex febrile seizure does not require emergent imaging.2 Such decisions are made based on clinical presentation and on a case-by-case basis. As mentioned above, instances of febrile status epilepticus or of a child who remains obtunded for a prolonged period of time should alert the clinician to the possibility of meningitis or encephalitis. A focal feature to the seizure should widen the © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Complex Febrile Seizure
differential diagnosis to include brain abscess, mass lesion, or herpes encephalitis. Teng et al7 attempted to assess the likelihood of significant intracranial pathology, such as abscess, mass lesion, or cerebral edema, requiring emergent intervention in patients presenting with their first complex febrile seizure. Of the 71 patients enrolled, 65% received some form of neuroimaging, whereas the remainder received follow-up phone calls. None of the study patients, with a 1-sided 95% confidence interval: 4% were found to have an emergent intracranial process, including abscess. Likewise, Kimia et al8 performed a retrospective review of 526 children who presented with complex febrile seizure of whom 268 patients underwent head CT, 6 had an MRI, and 8 had both. Of this subset, 4 patients had positive findings, including 2 intracranial bleeds, acute disseminated encephalomyelitis, and cerebellar findings. The authors concluded that in patients who are otherwise well appearing, presentation after a first complex febrile seizure likely does not require emergent neuroimaging. Given the dearth of clinical guidelines for imaging in the setting of pediatric seizures, Warden et al9 attempted to identify predictors of an abnormal head CT. Their results indicated that the variables most likely to be associated with abnormal findings are underlying high-risk conditions, such as malignancy, neurocutaneous disorder, or previous shunt placement, sustained seizure longer than 15 minutes, and development of a focal neurological deficit. In the absence of the above findings, head CT is unlikely to show a clinically significant abnormality. In a study by Yucel et al,10 head CTwas also only positive in patients with a post-ictal focal neurological deficit, but not in all of those who had focal characteristics of their febrile seizures. Brain abscesses in children remain a rare entity and, as a result, their management is guided largely by clinical experience and the results of case series. Twenty-five percent of brain abscesses occur in children younger than 15 years with a peak incidence at 4 to 7 years.11,12 Predisposing factors include hematological spread in children with congenital heart disease and direct spread from infections in contiguous sites such as otitis media and sinusitis. The location of the abscess influences the clinical presentation. Headache, fever, and vomiting occur in 60% to 70% of patients, and seizures, altered mental status, and focal neurological deficits in 25% to 50% of patients.11,12 It is important to note that, in children, many of the conventional signs of intracranial infectious processes may not be evident. By and large, laboratory testing is not routinely helpful, with 10% of blood cultures resulting as positive. Magnetic resonance imaging is the diagnostic modality of choice, and initial CT does not necessarily exclude the presence of an abscess. If imaging does show an abscess, lumbar puncture is not recommended.11,12 Treatment of choice is antimicrobial therapy and surgical drainage of the abscess. Previously, common organisms included streptococci species in up to 50% to 70% of abscesses, staphylococci in up 10% to 30%, and enteric bacteria in 10% to 25%. In a review from 2003 that included CNS abscesses in both adults and pediatrics, MRSA was isolated in 3% of patient. These cases, however, occurred in the setting of multitrauma or other known risk factors for MRSA.13 Of greater concern is the emergence of community acquired MRSA (CA-MRSA) over the last decade.14 The number of published case reports following this profile is still limited to a small handful, but what is remarkable is that the affected children did not typically have the usual risk factors for contracting MRSA. In a case report presenting a previously healthy infant who developed a CA-MRSA brain abscess, it was postulated that either a preceding course of antibiotics of an acute otitis media or contact with family members who previously had a CA-MRSA skin abscess could have placed the patient at risk.14 Our patient did not have a history of recent antibiotics use, but a www.pec-online.com
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large gluteal abscess that also grew MRSA was discovered during her hospital course. Though the literature on MRSA in CNS infections is sparse, similar literature regarding pathogens isolated from orbital cellulitis might be an indication of the trend. A recent review of orbital complications from acute sinusitis examined the most common pathogens both before and after the routine use of a heptavalent pneumococcal conjugate vaccine (PCV7).15 PrePCV7, Streptococcus pneumoniae was the most common isolate, but was not found in any of the cases after widespread use of the vaccine. Conversely, though Staphylococcus aureus species were found at a rate of 20% pre-PCV7, the prevalence doubled after the vaccine. Methicillin-resistant, which was not isolated in any cases before PCV7, was also isolated in statistically significant numbers.15 It is not clear how much of the increase is caused by immunity against Streptococcus pneumoniae versus the increased presence of CA-MRSA and its virulence.
CONCLUSIONS Febrile seizure is a common chief complaint in children presenting to pediatric emergency departments, and complex febrile seizures with a life-threatening etiology will continue to represent a fraction of these cases. Work-up of such patients requires attention to the clinical status of the child while considering a broad differential diagnosis. Although brain abscess is a rare clinical entity, the emerging role of CA-MRSA is of great concern and requires further investigation and surveillance. Based on the data presented above, routine imaging and lumbar puncture are not indicated in a well-appearing child with no subsequent focal neurological deficits who has reliable follow-up. However, as the presentation of our patient reveals, the decision to discharge without further work-up would benefit from consultation with pediatric neurology and should only be undertaken after establishing close follow-up should the patient subsequently exhibit a progression or change in symptoms. A high index of suspicion should always be maintained, and a consideration for the possible need for further work-up should be part of any diagnostic evaluation of a child presenting with complex febrile seizure. REFERENCES 1. Sadleir LG, Scheffer IE. Clinical review: febrile seizures. BMJ. 2007;334:307–311.
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2. Hampers LC, Spina LA. Evaluation and management of pediatric febrile seizures in the emergency department. Emerg Med Clin North Am. 2011;29:83–93. 3. Offringa M, Moyer VA. Evidence based management of seizures associated with fever. BMJ. 2001;323:1111–1114. 4. Kimia A, Ben-Joseph EP, Rudloe T, et al. Yield of lumbar puncture among children who present with their first complex febrile seizure. Pediatrics. 2010;126:62–68. 5. Green SM, Rothrock SG, Clem KJ, et al. Can seizures be the sole manifestation of meningitis in febrile children? Pediatrics. 1993;92:527–534. 6. Fletcher EM, Sharieff G. Necessity of lumbar puncture in patients presenting with new onset complex febrile seizures. West J Emerg Med. 2013;14:206–211. 7. Teng D, Dayan P, Tyler S, et al. Risk of intracranial pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children. Pediatrics. 2006;117: 304–307. 8. Kimia A, Ben-Joseph EP, Prabhu S, et al. Yield of emergent neuroimaging among children presenting with first complex seizure. Pediatr Emerg Care. 2012;28:316–321. 9. Warden CR, Brownstein DR, Del Beccaro MA. Predictors of abnormal findings of computed tomography of the head in pediatric patients presenting with seizures. Ann Emerg Med. 1997;29:518–525. 10. Yucel O, Aka S, Yaziciogly L, et al. Role of early EEG and neuroimaging in determination of prognosis in children with complex febrile seizure. Pediatr Int. 2004;46:463–467. 11. Yogev R, Bar-Meir M. Management of brain abscesses in children. Concise Rev Pediatr Infect Dis. 2004;157–159. 12. Sheehan JP, Jane JA, Ray DK, et al. Brain abscess in children. Neurosurg Focus. 2008;24:1–5. 13. Roche M, Humphreys H, Smyth E, et al. A twelve-year review of central nervous system bacterial abscesses; presentation and aetiology. Clin Microbiol Infect. 2003;9:803–809. 14. Stack A, Peterson-Carmichael SL, Yin DE, et al. CA-MRSA brain abscess in a healthy infant. J Pediatr Infect Dis. 2011;6:71–75. 15. Pena MT, Preciado D, Orestes M, et al. Orbital complications of acute sinusitis. JAMA Otolaryngol Head Neck Surg. 2013;139: 223–227.
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Cerebral Abscess Presenting as a Complex Febrile Seizure Anjoli Anand, MD,* Alicia Salas, DO,† Evan Mahl, MD,* and Marla C. Levine, MD, RDMS*
Abstract: Currently, there is no standardized approach to the management of complex febrile seizures in children and there are no published practice guidelines for the procurement of neuroimaging. Presented is a 2-year-old female patient who experienced a 3- to 5-minute episode of staring and unilateral mouth twitching associated with high fever. On initial presentation, the patient appeared well and had a normal neurological examination. No focus of infection was identified, and she was diagnosed with complex febrile seizure. The patient was discharged home with close neurology and primary care follow-up but returned the following day with altered mental status, toxic appearance, and right lower extremity weakness. Magnetic resonance imaging of the brain revealed left-sided cranial empyema and the patient was managed with antibiotics and surgical drainage. A literature review to answer the question “Do children with complex febrile seizures require emergent neuroimaging?” yielded a small number of retrospective reviews describing the utility of computed tomography, magnetic resonance imaging and lumbar puncture in the work-up of febrile seizures. Current evidence indicates that neuroimaging is not indicated in an otherwise healthy child who presents with complex febrile seizure if the patient is well appearing and has no evidence of focal neurological deficit on examination. As this case demonstrates, however, serious conditions such as meningitis and brain abscess (though rare) should be considered in the differential diagnosis of complex febrile seizure and physicians should remain aware that the need for neuroimaging and/or lumbar puncture may arise in the appropriate clinical setting. Key Words: cerebral abscess, complex febrile seizure (Pediatr Emer Care 2015;31: 499–502)
CASE A two-year-old female with no past medical history presented to the pediatric emergency department (PED) by ambulance after having had a seizure. As described by the mother, the episode was marked by unilateral mouth twitching and staring into space lasting approximately 3–5 minutes with no generalized body twitching or stiffening. Following the episode, the child appeared tired and, by report, was “not acting like herself.” The child was noted to have been febrile at home prior to presentation to the PED and had been experiencing high fevers for two days prior to presentation with a maximum temperature of 106°F. Further history revealed vomiting and intermittent abdominal pain one day prior to presentation. Also reported was a dry cough at night with decreased oral intake and decreased urine output. All immunizations were up to date. Review of systems was negative for ear pain, sore throat, and diarrhea. The patient’s vaccinations were up to date. At the time of presentation, vital signs were temperature 103°F, heart rate
From the Departments of *Emergency Medicine and † Pediatrics, Maimonides Medical Center, Brooklyn, NY. Disclosure: The authors declare no conflict of interest. Reprints: Anjoli Anand, MD, Department of Emergency Medicine, Maimonides Medical Center, 965 48th Street, Brooklyn, NY 11219 (e‐mail: [email protected]). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0749-5161
Pediatric Emergency Care • Volume 31, Number 7, July 2015
173 beats per minute, respirations 26 per minute, and oxygen saturation 100% on room air. On physical examination, she was a tired, nontoxic appearing child, well hydrated, and appropriately interactive with mother. She was normocephalic, atraumatic, visual acuity was grossly intact, pupils were equal and reactive to light, and extraocular movements were intact. Her tympanic membranes were normal bilaterally, and her posterior oropharynx was nonerythematous with moist mucus membranes. The neck was supple with full range of motion. Cardiovascular examination revealed a normal S1 and S2 with no murmurs, rubs, or gallops appreciated. On respiratory examination, she was breathing comfortably on room air without tachypnea or retractions, and auscultation revealed transmission of upper airway sounds. The abdomen was soft, non-tender, and without guarding. She was moving her extremities well and symmetrically. Her skin was well perfused, had normal turgor and revealed no rashes. On neurological assessment, she had normal tone, cranial nerves II through XII were intact bilaterally, and she ambulated without difficulty or ataxia. She remained seizure free and became more playful over the course of her PED visit. Given the elevated temperature reported at home and documented in the PED, a complete blood count (CBC), blood culture, urinalysis, urine culture, and a chest radiograph were obtained. The CBC showed a normal white blood cell count (WBC) of 11.3 x 103/μL with a left shift of 80% neutrophils. Bands were pending at the time of discharge and later resulted as 16%. The chest radiograph demonstrated questionable development of right lower lobe airspace disease with increased perihilar interstitial markings suggestive of bronchiolitis or viral syndrome. Based on the history of a focal neurological symptom, the unilateral mouth twitching, a diagnosis of complex febrile seizure was made, and pediatric neurology was consulted via telephone. As there were no residual focal findings at the time of the neurological examination, and the patient had reliable follow-up, she was discharged home with instructions to see her primary care physician the next day and to follow up promptly with magnetic resonance imaging (MRI) and pediatric neurology consultation on an outpatient basis. Given that the child was well appearing and at her baseline throughout her emergency department visit, the mother requested to be discharged and proceed with the aforementioned outpatient work up. The following day, the child returned to the PED with a chief complaint of “not acting right.” The mother reported that, since being discharged from the PED, the patient continued to have fevers and had became more lethargic and agitated. Additional history revealed that the child’s gait had become increasingly unsteady and that she could no longer stand upright. On examination, the patient’s vital signs were temperature 101.3°F, heart rate 189 beats per minute, respirations 32 per minute, blood pressure 118/73 mmHg, and oxygen saturation 100% on room air. The physical examination on this visit was remarkable for her toxic appearance and the development of a rash and focal neurological findings. A blanching, erythematous, urticarial rash was present with areas of confluence on the child’s trunk. On neurological examination, there was marked weakness of the right upper and lower extremities and the patient was observed to drag the right foot while attempting to walk. The child was unable to stand or www.pec-online.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
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dexamethasone, fosphenytoin and the following antibiotics: vancomycin, ceftriaxone, and metronidazole. Given the discreet fluid collection noted on imaging and the positive blood culture from the previous visit, antiviral medications were not administered. The patient was admitted to the Pediatric Intensive Care Unit where she remained febrile despite antipyretic and intravenous antibiotic therapy. On hospital day 7, the patient was taken to the operating room, where she underwent left craniectomy with evacuation of the subdural and epidural empyema. During the admission, the patient also developed a large left gluteal abscess which was drained by interventional radiology on hospital day 11. After drainage of the gluteal abscess, the patient remained afebrile and eventually exhibited improved neurological status. Seizure activity beyond the one that brought her to the PED initially was not observed. She continued to have difficulty standing and walking unassisted, but her speech returned to baseline, and extremity use became symmetric. She was discharged home on hospital day 19 on intravenous antibiotics via a peripherally inserted central catheter with instructions to follow-up with infectious diseases and neurology. FIGURE 1. Noncontrast CT scan of the head showing left-sided cerebral edema and a thin subdural collection overlying the left convexity. There is also effacement of the cortical sulci and partial effacement of the left lateral ventricle.
walk without assistance. No signs of trauma were present. Differential diagnosis at this time included acute disseminated encephalomyelitis, meningitis, transverse myelitis, encephalitis, brain abscess, malignancy, and stroke. Given the toxic appearance of the child at this time, a CBC, basic metabolic panel, erythrocyte sedimentation rate (ESR), Creactive protein (CRP), creatinine phosphokinase (CPK), and blood culture were obtained. CBC was notable for WBC 4.6 x 103/μL with 34% neutrophils and 49% bands. Other notable laboratory findings included ESR 60 mm/hr, CRP 37.5 mg/dL and CPK 354 IU/L. The blood culture obtained the previous day was positive for Staphylococcus aureus and was later identified as methicillinresistant (MRSA). Computed tomography (CT) of the head was remarkable for cerebral edema in the left hemisphere with a thin subdural collection overlying the left convexity with midline shift concerning for an infectious process (Fig. 1). Lumbar puncture was deferred due to risk of herniation, and the patient was then sent for MRI of the brain which demonstrated a left sided empyema in the frontoparietal area with a 2 mm midline shift to the right (Fig. 2). The child received intravenous crystalloid,
DISCUSSION Febrile seizures are defined as seizures that occur in the setting of a fever but in the absence of a central nervous system (CNS) infection or electrolyte imbalance.1 By definition, febrile seizures occur between 6 months and 6 years of age with median age of onset 18 months. They have a prevalence of 3% to 8% in children up to 7 years.1 Simple febrile seizures are brief in duration with spontaneous cessation within 15 minutes of onset, are generalized tonic-clonic with a return to baseline mental status, occur in the absence of preexisting neurological abnormality, and occur in the setting of documented fever. However, seizures can occur before documentation of fever. Seizures last longer than 15 minutes in about 9% of cases, and 4% to 16% of febrile seizures have focal features.1,2 Complex febrile seizures, on the other hand, are more loosely defined by the presence of at least one of the following features: duration longer than 15 minutes, multiple seizures within a 24-hour period, or focal features.1,2 There are instances of transient hemiparesis after what otherwise appears to be a simple febrile seizure, but this suggests a focal origin and should be explored further.2 There is no evidence to support the measurement of serum electrolytes or procurement of a head CT in the management of simple febrile seizures.2 Based on epidemiological data, approximately 0.23% of children presenting with febrile seizures have
FIGURE 2. MRI of the brain with and without intravenous contrast showing a small subdual empyema in the left frontoparietal area extending into the interhemispheric fissure with restricted diffusion and effacement of sulci, partial effacement of left lateral ventricle, and 2 mm midline shift to the right.
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Pediatric Emergency Care • Volume 31, Number 7, July 2015
meningitis, 24% of cases of children with meningitis present with seizure, although these cases also included other clinical signs of meningitis or toxic presentation.1,2 When children present with febrile status epilepticus, the presence of meningitis increases to 18%.1 It should be noted that in children younger than 2 years of age, meningismus may not be clinically evident, and other signs, such as drowsiness, petechiae, vomiting, and complex febrile seizures, could be observed.1 Regarding evaluation with lumbar puncture, the American Academy of Pediatrics revised their guidelines in 2011 to recommend that lumbar puncture is not indicated in children between 6 and 12 months of age who have been vaccinated for Haemophilus influenza and Streptococcus pneumoniae and who present with simple febrile seizures without exhibiting any other concerning clinical signs.2 A retrospective review from the Netherlands by Offringa and Moyer3 attempted to identify criteria to assess if meningitis could be ruled out clinically and without lumbar puncture. Their study looked at 309 children between the ages of 3 months and 6 years who presented with a first febrile seizure, 23 (7%) of whom were ultimately diagnosed with meningitis. The major signs of meningitis assessed were presence of petechiae, nuchal rigidity, and coma, at least one of which was present in 70% of patients diagnosed with meningitis. These major signs were absent in all patients without disease. Kimia et al4 conducted a retrospective review to evaluate the incidence of bacterial meningitis in 526 patients who presented to the emergency department with complex febrile seizure. Lumbar puncture was obtained in 340 of the patients, only 3 of whom ultimately had positive cerebral spinal fluid cultures, all growing Streptococcus pneumoniae. Two of the patients with confirmed meningitis presented before routine vaccination against Streptococcus pneumoniae. Of the remaining 186 patients who did not undergo lumbar puncture, 161 were monitored clinically, and none of them were subsequently diagnosed with meningitis, although 25 patients were lost to followup.4 In another series by Green et al5 which included 503 patients, there were no cases of bacterial meningitis with seizure as the sole manifestation. The initial level of consciousness in the majority of the 115 patients who had meningitis with seizure was described by practitioners as obtunded, lethargic, or comatose. In the 10 patients who were described as having a normal level of consciousness after a reported seizure, 2 were ultimately diagnosed with viral meningitis, and the other 8 were described as having other clinical signs of meningitis, such as nuchal rigidity, petechial rash, or prolonged seizures. A more recent review was published regarding patients who presented with symptoms consistent with complex febrile seizure who presented after the widespread vaccination against Streptococcus pneumoniae. In this study, factors associated with obtaining a lumbar puncture were no history of simple febrile seizure, seizure focality, status epilepticus, and requiring intubation. Of the 136 patients who underwent lumbar puncture, one was diagnosed with bacterial meningitis.6 There is no standardized approach to the management of complex febrile seizures, and it often falls to the clinician to determine the extent of diagnostic evaluation.2 At this time, the American Academy of Pediatrics does not publish practice guidelines for the use of emergent neuroimaging in cases of complex febrile seizure. A small number of retrospective reviews have suggested that the well-appearing child who presents to the emergency department with a first complex febrile seizure does not require emergent imaging.2 Such decisions are made based on clinical presentation and on a case-by-case basis. As mentioned above, instances of febrile status epilepticus or of a child who remains obtunded for a prolonged period of time should alert the clinician to the possibility of meningitis or encephalitis. A focal feature to the seizure should widen the © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Complex Febrile Seizure
differential diagnosis to include brain abscess, mass lesion, or herpes encephalitis. Teng et al7 attempted to assess the likelihood of significant intracranial pathology, such as abscess, mass lesion, or cerebral edema, requiring emergent intervention in patients presenting with their first complex febrile seizure. Of the 71 patients enrolled, 65% received some form of neuroimaging, whereas the remainder received follow-up phone calls. None of the study patients, with a 1-sided 95% confidence interval: 4% were found to have an emergent intracranial process, including abscess. Likewise, Kimia et al8 performed a retrospective review of 526 children who presented with complex febrile seizure of whom 268 patients underwent head CT, 6 had an MRI, and 8 had both. Of this subset, 4 patients had positive findings, including 2 intracranial bleeds, acute disseminated encephalomyelitis, and cerebellar findings. The authors concluded that in patients who are otherwise well appearing, presentation after a first complex febrile seizure likely does not require emergent neuroimaging. Given the dearth of clinical guidelines for imaging in the setting of pediatric seizures, Warden et al9 attempted to identify predictors of an abnormal head CT. Their results indicated that the variables most likely to be associated with abnormal findings are underlying high-risk conditions, such as malignancy, neurocutaneous disorder, or previous shunt placement, sustained seizure longer than 15 minutes, and development of a focal neurological deficit. In the absence of the above findings, head CT is unlikely to show a clinically significant abnormality. In a study by Yucel et al,10 head CTwas also only positive in patients with a post-ictal focal neurological deficit, but not in all of those who had focal characteristics of their febrile seizures. Brain abscesses in children remain a rare entity and, as a result, their management is guided largely by clinical experience and the results of case series. Twenty-five percent of brain abscesses occur in children younger than 15 years with a peak incidence at 4 to 7 years.11,12 Predisposing factors include hematological spread in children with congenital heart disease and direct spread from infections in contiguous sites such as otitis media and sinusitis. The location of the abscess influences the clinical presentation. Headache, fever, and vomiting occur in 60% to 70% of patients, and seizures, altered mental status, and focal neurological deficits in 25% to 50% of patients.11,12 It is important to note that, in children, many of the conventional signs of intracranial infectious processes may not be evident. By and large, laboratory testing is not routinely helpful, with 10% of blood cultures resulting as positive. Magnetic resonance imaging is the diagnostic modality of choice, and initial CT does not necessarily exclude the presence of an abscess. If imaging does show an abscess, lumbar puncture is not recommended.11,12 Treatment of choice is antimicrobial therapy and surgical drainage of the abscess. Previously, common organisms included streptococci species in up to 50% to 70% of abscesses, staphylococci in up 10% to 30%, and enteric bacteria in 10% to 25%. In a review from 2003 that included CNS abscesses in both adults and pediatrics, MRSA was isolated in 3% of patient. These cases, however, occurred in the setting of multitrauma or other known risk factors for MRSA.13 Of greater concern is the emergence of community acquired MRSA (CA-MRSA) over the last decade.14 The number of published case reports following this profile is still limited to a small handful, but what is remarkable is that the affected children did not typically have the usual risk factors for contracting MRSA. In a case report presenting a previously healthy infant who developed a CA-MRSA brain abscess, it was postulated that either a preceding course of antibiotics of an acute otitis media or contact with family members who previously had a CA-MRSA skin abscess could have placed the patient at risk.14 Our patient did not have a history of recent antibiotics use, but a www.pec-online.com
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Anand et al
large gluteal abscess that also grew MRSA was discovered during her hospital course. Though the literature on MRSA in CNS infections is sparse, similar literature regarding pathogens isolated from orbital cellulitis might be an indication of the trend. A recent review of orbital complications from acute sinusitis examined the most common pathogens both before and after the routine use of a heptavalent pneumococcal conjugate vaccine (PCV7).15 PrePCV7, Streptococcus pneumoniae was the most common isolate, but was not found in any of the cases after widespread use of the vaccine. Conversely, though Staphylococcus aureus species were found at a rate of 20% pre-PCV7, the prevalence doubled after the vaccine. Methicillin-resistant, which was not isolated in any cases before PCV7, was also isolated in statistically significant numbers.15 It is not clear how much of the increase is caused by immunity against Streptococcus pneumoniae versus the increased presence of CA-MRSA and its virulence.
CONCLUSIONS Febrile seizure is a common chief complaint in children presenting to pediatric emergency departments, and complex febrile seizures with a life-threatening etiology will continue to represent a fraction of these cases. Work-up of such patients requires attention to the clinical status of the child while considering a broad differential diagnosis. Although brain abscess is a rare clinical entity, the emerging role of CA-MRSA is of great concern and requires further investigation and surveillance. Based on the data presented above, routine imaging and lumbar puncture are not indicated in a well-appearing child with no subsequent focal neurological deficits who has reliable follow-up. However, as the presentation of our patient reveals, the decision to discharge without further work-up would benefit from consultation with pediatric neurology and should only be undertaken after establishing close follow-up should the patient subsequently exhibit a progression or change in symptoms. A high index of suspicion should always be maintained, and a consideration for the possible need for further work-up should be part of any diagnostic evaluation of a child presenting with complex febrile seizure. REFERENCES 1. Sadleir LG, Scheffer IE. Clinical review: febrile seizures. BMJ. 2007;334:307–311.
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2. Hampers LC, Spina LA. Evaluation and management of pediatric febrile seizures in the emergency department. Emerg Med Clin North Am. 2011;29:83–93. 3. Offringa M, Moyer VA. Evidence based management of seizures associated with fever. BMJ. 2001;323:1111–1114. 4. Kimia A, Ben-Joseph EP, Rudloe T, et al. Yield of lumbar puncture among children who present with their first complex febrile seizure. Pediatrics. 2010;126:62–68. 5. Green SM, Rothrock SG, Clem KJ, et al. Can seizures be the sole manifestation of meningitis in febrile children? Pediatrics. 1993;92:527–534. 6. Fletcher EM, Sharieff G. Necessity of lumbar puncture in patients presenting with new onset complex febrile seizures. West J Emerg Med. 2013;14:206–211. 7. Teng D, Dayan P, Tyler S, et al. Risk of intracranial pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children. Pediatrics. 2006;117: 304–307. 8. Kimia A, Ben-Joseph EP, Prabhu S, et al. Yield of emergent neuroimaging among children presenting with first complex seizure. Pediatr Emerg Care. 2012;28:316–321. 9. Warden CR, Brownstein DR, Del Beccaro MA. Predictors of abnormal findings of computed tomography of the head in pediatric patients presenting with seizures. Ann Emerg Med. 1997;29:518–525. 10. Yucel O, Aka S, Yaziciogly L, et al. Role of early EEG and neuroimaging in determination of prognosis in children with complex febrile seizure. Pediatr Int. 2004;46:463–467. 11. Yogev R, Bar-Meir M. Management of brain abscesses in children. Concise Rev Pediatr Infect Dis. 2004;157–159. 12. Sheehan JP, Jane JA, Ray DK, et al. Brain abscess in children. Neurosurg Focus. 2008;24:1–5. 13. Roche M, Humphreys H, Smyth E, et al. A twelve-year review of central nervous system bacterial abscesses; presentation and aetiology. Clin Microbiol Infect. 2003;9:803–809. 14. Stack A, Peterson-Carmichael SL, Yin DE, et al. CA-MRSA brain abscess in a healthy infant. J Pediatr Infect Dis. 2011;6:71–75. 15. Pena MT, Preciado D, Orestes M, et al. Orbital complications of acute sinusitis. JAMA Otolaryngol Head Neck Surg. 2013;139: 223–227.
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Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
