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An Unusual Case of Meningitis in an Adolescent

Stanton, James E. ScM*; Wilkes, Jeremy S. MD; Syed, Salma S. DO*

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The Pediatric Infectious Disease Journal: September 2021 - Volume 40 - Issue 9 - p 864-865
doi: 10.1097/INF.0000000000003090
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CASE

A 17-year-old girl presented to an urgent care facility in January with several days of headaches, anorexia and vomiting. She was diagnosed with migraines and sent home on analgesics. Due to persistent symptoms for 1 week in addition to malaise and tactile fevers, she presented to the local emergency department. On physical examination, she had a temperature of 38.1 °C, heart rate of 80 beats/min, blood pressure of 100/58 mm Hg and oxygen saturation of 99% in ambient air. She was ill appearing with marked photophobia, nuchal rigidity and malaise. The remainder of the physical examination was normal.

Laboratory analysis demonstrated normal complete blood count and complete metabolic panel. Analysis of her cerebrospinal fluid (CSF) via lumbar puncture showed a markedly elevated white blood cell (WBC) count of 1398/mm3 (with differential of 6% neutrophils, 44% lymphocytes and 50% monocytes), elevated protein of 203 mg/dL and low glucose of 31 mg/dL. Given concern for bacterial meningitis, she was started on empiric intravenous vancomycin and ceftriaxone. A rapid molecular meningitis panel was negative for Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pneumoniae, cytomegalovirus, enterovirus, human parechovirus, herpes simplex virus type 1, herpes simplex virus type 2, human herpesvirus 6, varicella-zoster virus and Cryptococcus neoformans, and CSF culture was negative. Computed tomography of her brain was normal. Given the severity of her illness, she was transferred to an academic children’s hospital for a higher level of care.

The pediatric infectious disease service was consulted due to concern for bacterial meningitis. The patient denied sick contacts, recent travel or sexual partners. Her medical history and surgical history were significant for asthma, surgical repairs of a cleft lip and palate and myringoplasty. Her immunizations were up to date, except she had not yet received her meningococcal vaccine booster dose. She lived in a rural area with her parents and 2 sisters. Household animal exposures included a cat, dogs, chickens and ducks. The patient’s mother also described a pond near the house that spawned large numbers of mosquitoes.

Due to lack of clinical improvement after 48 hours and the need for further diagnostic testing, a repeat lumbar puncture was performed. CSF analysis showed improvement of pleocytosis (WBC 714/mm3 with 100% lymphocytes) but persistently elevated protein of 164 mg/dL) and low glucose of 29 mg/dL. Rapid molecular meningitis panel was again negative, and pathology was negative for malignancy. Magnetic resonance imaging of the brain was normal. Serologic testing for Epstein-Barr virus, human immunodeficiency virus, cytomegalovirus, Ehrlichia chaffeensis, Rocky Mountain spotted fever, Lyme disease, syphilis, Bartonella henselae and Mycoplasma pneumoniae were all negative, as was a tuberculin skin test. The patient was treated with a 7-day course of doxycycline for possible rickettsial infection, but vancomycin and ceftriaxone were discontinued after CSF cultures were negative.

Due to persistent bilateral photophobia and eye pain, ophthalmology consultation was ordered, which revealed bilateral iridocyclitis or anterior uveitis without any angle closure. The patient was treated with cyclopentolate 1% ophthalmic drops daily for 1 week and prednisolone acetate 1% ophthalmic drops twice a day for 1 week, followed by a weaning dose for an additional week.

Additional history prompted further testing, which led to the diagnosis.

For Denouement see P. 865.

DENOUEMENT

(Pediatr Infect Dis J 2021;40:865)

Continued from P. 864.

Further history revealed that field mice occasionally entered the patient’s house and room. After learning this information, CSF was sent for antibody titers to lymphocytic choriomeningitis virus (LCMV), but there was insufficient sample for LCMV polymerase chain reaction. The patient’s condition gradually stabilized after a week in the hospital. A few days following discharge to home, the CSF LCMV IgG and IgM titers via indirect fluorescent antibody returned positive with titers of 1:128 and 1:16, respectively.

On hospital follow-up approximately 2 weeks following discharge, the patient reported complete resolution of symptoms, including photophobia. Repeat serum LCMV IgG and IgM antibody titers were drawn in clinic and were again positive at >1:256 and 1:80, respectively, consistent with recent infection. Ophthalmology determined that the anterior uveitis had gradually resolved with her ophthalmic drops regimen. Further conversation revealed that the home was still infested with mice, and the patient admitted to playing with mice in her room on several occasions.

LCMV is a zoonotic virus of the family Arenaviridae that is transmitted by rodents.1 The house mouse is the most common vector; however, hamsters and other pet rodents have been known to carry the virus. Once infected, rodents chronically shed the virus in their urine and can pass it vertically to offspring. It is estimated that ~10% of wild mice are infected with LCMV.2 Humans can be incidentally infected when exposed to aerosolized particles of rodent nasal secretions, saliva, urine or feces. Viral replication initially occurs in the lungs before entering the bloodstream and central nervous system.3 Although transplacental transmission can occur in utero, human-to-human horizontal transmission has not been observed. Cases are most often sporadic, but outbreaks have occurred and are usually associated with rodent breeding facilities or laboratories conducting research using rodents.4 Some studies of urban areas of the country show seroprevalence of LCMV infection to be near 5%.2,5 Factors that increase risk of infection include crowded and substandard living conditions.6 Most infections tend to occur in the winter months, presumably as mice venture into homes for shelter and warmth. Our patient was predisposed to infection due to a constellation of risk factors including age, poor living conditions, infection occurring in January and mice entering the home.

There is a wide range of clinical disease associated with primary LCMV infection. Nearly one-third of patients are asymptomatic, and those that develop symptoms do so along a spectrum of 3 major clinical forms: influenza-like syndrome/constitutional symptoms, aseptic meningitis and meningoencephalitis.7 Atypical presentations including arthritis, pericarditis, diarrhea, orchitis and alopecia have also been reported.8 Symptom onset is typically 10–14 days following primary infection and occurs in a biphasic fashion. Initial symptoms include fever, headache, nausea, vomiting and anorexia before progressing to central nervous system disease.9 Although it is rarely fatal, the symptoms originating from meningitis are often described as severe, and sequelae, including deafness and hydrocephalus, can occur.10

There are no pathognomonic laboratory findings for LCMV, but leukopenia, thrombocytopenia and slight elevations of liver enzymes have been reported. CSF findings of LCMV meningitis are oftentimes difficult to distinguish from other viral causes of meningitis: pleocytosis with lymphocytic predominance, low/normal glucose and elevated protein.7 However, a significant pleocytosis of >3000 may occur, which would be unusual with other viral pathogens.11

LCMV has a strong tropism for neural tissue and will occasionally infect cells of the uvea and retina as they derive from the same embryonic tissue as the brain and spinal cord. Congenital exposure to the virus is known to be a cause of severe chorioretinitis in neonates.12 While LCMV infection has been described as an agent in chorioretinitis or posterior uveitis, there is limited information about cases of concurrent meningitis and anterior uveitis. However, given the low prevalence of infection in the general population, LCMV is not routinely evaluated in patients with meningitis or anterior uveitis. Therefore, data are scarce regarding the pathophysiology of LCMV-induced uveitis and its true prevalence. Our patient presented with severe bilateral eye pain that was initially attributed to meningitis, but subsequently, ophthalmologic examination revealed acute anterior uveitis.

LCMV is an underreported cause of aseptic meningitis due to lack of awareness and testing. The Centers for Disease Control and Prevention currently recommends only testing those with high suspicion of primary infection. The immunofluorescent antibody test, which detects both IgM and IgG, is more sensitive than complement fixation and is the preferred diagnostic tool.1 LCMV polymerase chain reaction from the CSF may confirm cases of LCMV meningitis during the acute stage of illness. Most cases in immunocompetent individuals fully resolve within a few weeks, and treatment is supportive. Prevention involves minimizing exposure to rodent vectors.

To our knowledge, this is the first documented case of pediatric LCMV meningitis with associated anterior uveitis. Although LCMV is a rare cause of meningitis, it may cause clinically significant symptoms for weeks to months. Recognition of key risk factors in a patient’s history in the context of highly suggestive CSF findings can play a role in diagnosis. Given that LCMV has a strong tropism for neural tissue, including cells of the retina and uvea, it is important to consider obtaining an ophthalmology consultation in patients with LCMV meningitis and photophobia to evaluate for concurrent anterior uveitis. Although the treatment of LCMV meningitis is supportive, prompt diagnosis of anterior uveitis will enable treatment with ophthalmologic drops to mitigate symptoms in affected patients.

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