A 3-year-old former 24-week gestation female was transferred to our institution’s emergency department (ED) from a referring hospital with headache and neck pain for 2 to 3 weeks and 1 day of fever. About 3 weeks prior to presentation, she began complaining of frontal headaches without photophobia or gait abnormalities. The headaches lasted approximately 1 hour, were associated with weakness, and possibly decreased movement.
Initially, the headaches were relieved with acetaminophen until they became persistent and were accompanied by neck pain and occasional emesis, including 2 episodes on the day of presentation. The patient denied any paresthesias or bowel/bladder incontinence. She had no prior medications except acetaminophen and no recent antibiotic courses. Two weeks prior to presentation, she was evaluated for headache at another institution and had a normal head computed tomography (CT) scan as per parental report. At the other hospital her physical examination was of concern for meningitis. Laboratory studies were unremarkable: white blood cell (WBC) count was 14,900/mcL; platelet count was 345,000/mcL; C-reactive protein (CRP) was 1.3 mg/L (normal range < 3 mg/L); erythrocyte sedimentation rate (ESR) was 24 mm/hr (normal < 35 mm/hr). She had a rapid Strep swab that was negative; urinalysis was unremarkable. A lumbar puncture was not performed.
She was given 15 mg/kg of vancomycin and 100 mg/kg of ceftriaxone intravenously prior to transfer to our institution.
On admission, the patient was alert but complaining of a headache in the frontal region. Her temperature was 38.6°C; her pulse was 86 beats per minute, her blood pressure (BP) was 94/47 mm Hg; and her respiratory rate was 28 breaths per minute. She was oriented to person, communicating easily but complaining of neck pain, sitting with her neck hyperextended. Her pupils were equally round and reactive with extra-ocular muscles intact. Her oropharynx was mildly erythematous, and her cardiac examination revealed a normal rate and rhythm with no murmur. Her lungs were clear to auscultation bilaterally with no wheezing or crackles present. A skin exam revealed no lesions or rashes. A neurologic exam revealed no focal deficits, 2+ patellar reflexes, no gait abnormalities, and normal rectal tone.
The patient underwent a lumbar puncture in the ED. The cerebrospinal fluid (CSF) WBC count was 5,890/mcL (79% neutrophils, 4% lymphocytes), the red blood cell count was 25/mcL, glucose was 28 mg/dL, and protein was 108 mg/dL. No organisms were seen on Gram stain. Additional blood work showed an ESR of 70 mm/hr and CRP was 175 mg/L. Basic metabolic panel was unremarkable.
Given the physical exam and CSF findings, with elevated white blood cells, low glucose, and elevated protein, the patient was admitted with suspected bacterial meningitis on intravenous (IV) antibiotics (vancomycin and ceftriaxone) at doses for meningitis treatment. Overnight, the patient developed a disconjugate gaze and changes in her vital signs (pulse of 68 beats per minute and BP of 135/65 mm Hg).
An emergent head CT with contrast was obtained given these new focal neurologic findings and the patient’s vital sign alterations that were consistent with Cushing’s triad. The CT revealed a homogenous, nonenhancing fluid collection in the left cerebellar-pontine angle and left prepontine cistern causing mass effect on the pons and medulla and extending inferiorly into foramen magnum (see Figure 1).
Figure 1. Computed tomography scan of the head. There is homogenous fluid density collection with no associated rim enhancement in the left cerebellopontine angle and left prepontine cistern, causing mass effect on the pons and medulla and extending inferiorly into the foramen magnum. All images courtesy of Rukmini Velamati, MD.
Further history revealed that the patient’s maternal grandmother, who lived with the family, was a health care worker in a nursing home. Given the patient’s rapidly deteriorating neurologic symptoms, the decision was made to expand antibiotic coverage to include tuberculous meningitis with a 4-drug regimen. Because tuberculous meningitis is typically associated with very low glucose levels, elevated protein, and pleocytosis in CSF, it would be more fitting with her indolent clinical course.
A magnetic resonance image (MRI) showed a 17.2-mm extra-axial paramedian mass over the pons and medulla extending through foramen magnum (see Figure 2 and Figure 3). Diffusion-weighted MRI was consistent with an epidermoid cyst (see Figure 4). In consultation with neurosurgery, the patient was started on IV dexamethasone and had rapid improvement in her neurologic symptoms. Although her emesis had subsided, she refused to take oral medications and the decision was made to discontinue the anti-tuberculous regimen given the low overall likelihood, her rapid improvement with IV steroids, and the contraindications to proceeding with monotherapy with rifampin, the only IV anti-tuberculous medication. The patient completed an empiric 7-day course of IV vancomycin and ceftriaxone, despite a negative CSF culture, as a precaution because she was treated with antibiotics before a lumbar puncture was obtained.
Figure 2. Axial fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scan of the brain. Extra-axial paramedian mass over pons and medulla extending through foramen magnum.
Figure 3. Sagittal T1 magnetic resonance imaging (MRI) scan of the brain demonstrating the paramedian mass.
Figure 4. Diffusion-weighted magnetic resonance imaging (MRI) scan of the brain demonstrating mild restricted diffusion.
On day 9 of admission, neurosurgery resected a large cystic mass abutting the C1 nerve root and cranial nerve V that was filled with creamy, white fluid. A histopathology confirmed it was an epidermoid cyst. The patient tolerated the procedure well; repeat imaging revealed postoperative changes but complete resection of the mass. Subsequent imaging at 3- and 6-month intervals did not reveal any recurrence of the mass and her neurologic symptoms had completely resolved.
Ruptured extra-axial epidermoid cyst with resulting chemical meningitis.
Need for Broad Differential Diagnosis
Given this patient’s unusual course, a broad differential diagnosis for possible intracranial sources was required. Her antibiotic exposure presented a confounding factor when interpreting her CSF findings.
The effect of prior antibiotic exposure is uncertain, although in 2002, researchers studied 128 patients, 30% of whom had received IV antibiotics prior to a lumbar puncture; 43% of these patients had serial lumbar punctures. Sterilization of CSF can be swift: IV antibiotics were able to sterilize CSF with meningococcus by 2 hours after antibiotic dose and pneumococcal meningitis by 4.3 hours. CSF cultures with group B Streptococcus were still positive 8 hours after IV antibiotics.1 Despite affecting culture data, antibiotic pretreatment does not affect CSF WBC count or absolute neutrophil count, according to a study published in 2008; however, the study also reports that pretreatment can lead to increased CSF glucose and decreased CSF protein.2
The challenge of distinguishing between aseptic, bacterial, fungal, and tuberculous meningitis is sometimes aided by preliminary findings in the CSF, such as protein, glucose, and the WBC differential. Bacterial meningitis is typically correlated with a much higher overall WBC count (100 to 20,000, mean 800), whereas aseptic, fungal, and tuberculous have mean WBC counts between 80 and 200.
A polymorphonuclear predominance (PMN) is often seen in bacterial and early viral meningitis whereas other etiologies have more evenly divided cell type differentials or, in the case of tuberculous meningitis, up to 70% lymphocyte predominance. Tuberculous meningitis also has the distinguishing characteristic of exceedingly low CSF glucose.1,3,4
Differentiating Clinical Presentations of Meningitis
Our patient’s findings of an elevated WBC with PMN predominance and low glucose thus prompted broad-spectrum coverage and continued concern for tuberculous meningitis. Tuberculous meningitis would also be more fitting with slowly progressive clinical symptoms over the course of days to weeks,5 as compared with bacterial meningitis, which is known to progress quickly, within hours to days. Both can result in significant morbidity and mortality if left untreated.
The clinical presentation of viral meningitis can often be indistinguishable from other sources with predominant symptoms of fever, headache, vomiting, and neck stiffness, although it is more common in the summer and autumn months; our patient presented in February. A study from Greece published in 2007 demonstrated that use of enterovirus CSF polymerase chain reaction decreased duration of hospitalization and exposure to antibiotics by rapid identification of the etiology of meningitis.6
Intracranial abscess and malignancy should also remain high on the differential diagnosis for any patient with new-onset neurologic symptoms. Intracranial extension of sinusitis has been described with primary clinical presentation of prolonged headache and vomiting.7 Brain abscesses are rare and correlated with underlying conditions, including cyanotic congenital heart disease, immunosuppressed state, hematogenous dissemination, contiguous infection, and penetrating traumatic injuries.8
Pediatric Epidermoid Cysts
Epidermoid cysts are rare causes of intracranial masses and are especially uncommon in the pediatric population. Epidermoid cysts represent 1% to 1.5% of all intracranial masses and usually present in the second to third decade of life. The most common symptoms are headache and seizure, although tinnitus, hearing loss, facial spasm, and trigeminal neuralgia have been described.9
Epidermoid cysts are distinguished histologically from other cysts, such as dermoid and arachnoid cysts, as they are comprised of stratified squamous epithelial tissue surrounding cystic fluid. This stratified squamous lining continuously creates and sheds a keratinized layer of debris consisting largely of cholesterol. Spontaneous rupture of epidermoid cysts is rare but often presents as a chemical meningitis and can be fatal.
Dermoid cysts, in contrast, typically contain retained hair, sweat, and sebaceous glands.9–13 Diffusion-weighted MRI is the imaging modality of choice to distinguish epidermoid cysts from dermoid and arachnoid cysts secondary to fluid content because epidermoid cysts restrict diffusion.14
Epidermoid cysts are primarily congenital and thought to be a defect in separation of the ectoderm from the neural tube that occurs between the third to fifth week of gestation. Occasionally they can develop after lumbar punctures or trauma in which ectodermal tissue is introduced into the spinal column.9–13 There have been isolated case reports of epidermoid cysts transforming into squamous cell carcinoma.15
Challenge of Epidermoid Cyst Management
Surgical management of epidermoid cysts presents challenges given their location in the cerebellar pontine angle or petrous ridge, and their predilection toward enveloping cranial nerves and blood vessels. The surgical approach is typically suboccipital or through the middle fossa, although there are several reports of coordinated surgeries with neurosurgeons and otolaryngologists utilizing a translabyrinthine approach.
Given the benign histopathologic characteristics, the optimum management is complete surgical resection with preservation of the surrounding structures. Aggressive resection can result in cranial nerve deficits from direct trauma; spillage of cyst contents into the subarachnoid space through tears in the capsule can result in communicating hydrocephalus or inflammation resulting in a chemical or reactive meningitis.16 A similar inflammatory response is, however, noted in up to 40% of patients with a subtotal cyst resection and subsequent cystic rupture.
This review of an interesting case of presumed pretreated bacterial meningitis in a patient with an indolent course of headache and progressive neurologic symptoms was revealed to be a ruptured epidermoid cyst. Epidermoid cysts, which are congenital in origin, are diagnosed in pediatric and adult populations but typical presentation occurs between the ages of 20 to 30 years because of the slow growth of these lesions.
Our patient presented with chemical (inflammatory) meningitis, but given her exposure to IV antibiotics prior to lumbar puncture, a negative CSF culture did not exclude bacterial meningitis. Given her history, acute onset of fever, and CSF pleocytosis, it was important to keep a broad differential diagnosis of the etiology of her meningitis, treat presumptively for bacterial meningitis and consider new options as her symptoms progressed.
- Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics. 2002;108(5):1169–1174.
- Nigrovic LE, Malley R, Macias CG, et al. American Academy of Pediatrics, Pediatric Emergency Medicine Collaborative Research Committee. Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis. Pediatrics. 2008;122(4):726–730 doi:10.1542/peds.2007-3275 [CrossRef] .
- Pickering LK, Baker CJ, Kimberlin DW, eds. American Academy of Pediatrics Red Book. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.
- Nigrovic LE, Malley R, Kuppermann N. Cerebrospinal fluid pleocytosis in children in the era of bacterial conjugate vaccines: distinguishing the child with bacterial and aseptic meningitis. Pediatr Emerg Care. 2009;25(2):112–117 doi:10.1097/PEC.0b013e318196faeb [CrossRef] .
- Rich AR, McCordick HA. The pathogenesis of tuberculous meningitis. Bull John Hopkins Hosp. 1933;52:5–37.
- Athanasios G. Aseptic meningitis in children: analysis of 506 cases. PLoS ONE. 2007;2(8):e674 doi:10.1371/journal.pone.0000674 [CrossRef] .
- Goytia VK, Giannoni CM, Edwards MS. Intraorbital and intracranial extension of sinusitis: comparative morbidity. J Pediatr. 2011;158(3):486–491 doi:10.1016/j.jpeds.2010.09.011 [CrossRef] .
- Frazier JL, Ahn ES, Jallo GI. Management of brain abscesses in children. Neurosurg Focus. 2008;24(6):E8 doi:10.3171/FOC/2008/24/6/E8 [CrossRef] .
- Iaconetta G, Carvalho GA, Vorkapic P, Samii M. Intracerebral epidermoid tumor: a case report and review of the literature. Surg Neurol. 2001;55(4):218–222 doi:10.1016/S0090-3019(01)00346-9 [CrossRef] .
- Gopalakrishnan CV, Dhakoji A, Nair S. Epidermoid cyst of the brainstem in children: case based update. J Child Neurol. 2012;27(1):105–112 doi:10.1177/0883073811414709 [CrossRef] .
- Caldarelli M, Massimi L, Kondageski C, Di Rocco C. Intracranial midline dermoid and epidermoid cysts in children. J Neurosurg. 2004;100(5 Suppl Pediatrics):473–480.
- Caldarelli M, Colosimo C, Di Rocco C. Intra-axial dermoid/epidermoid tumors of brainstem in children. Surg Neurol. 2001;56(2):97–105 doi:10.1016/S0090-3019(01)00542-0 [CrossRef] .
- Lunardi P, Missori P, Gagliardi FM, Fortuna A. Dermoid and epidermoid cysts of the midline in posterior cranial fossa. Neurosurg Rev. 1992;15(3):171–175 doi:10.1007/BF00345926 [CrossRef] .
- Mascalchi M, Filippi M, Floris R, Fonda C, Gasparotti R, Villari N. Diffusion-weighted MR of the brain: methodology and clinical application. Radiol Med. 2005;109(3):155–197.
- Acciarri N, Padovani R, Foschini MP, Giulioni M, Finizio FS. Intracranial squamous cell carcinoma arising in an epidermoid cyst. Br J Neurosurg. 1993;7(5):565–569 doi:10.3109/02688699308995081 [CrossRef] .
- Ahmed I, Auguste KI, Vachhrajani S, Dirks PB, Drake JM, Rutka JT. Neurosurgical management of intracranial epidermoid tumors in children. J Neurosurg Pediatr. 2009;4(2):91–96 doi:10.3171/2009.4.PEDS08489 [CrossRef] .