9-Year-old With Altered Mental Status

CASE HISTORY A 9-year-old previously healthy female child from Kansas, USA presented to the emergency room (ER) with altered mental status. The symptoms started 24 hours earlier with severe headache followed by vomiting and decreased oral intake. Review of the family and social history revealed that the patient owned a cat and a dog as pets. She was engaged in competitive water sports and recently traveled to the Bahamas. Over the weekend before admission, she went camping at the family’s cabin where she was exposed to mosquitoes and ticks and swam in a nearby lake. At the ER, her laboratory reports revealed a white blood cell count of 24.14 × 103/mm3, absolute neutrophil count of 21.2 × 103/mm3 (87.8%), normal hemoglobin and platelet counts, and low serum Na of 135 mEq/L. Attempts at lumbar puncture were not successful. The patient was subsequently admitted from the ER with worsening mental status and high fever and was intubated for airway protection. Work up revealed normal chest radiograph and urinalysis with trace glucose and ketones. Computed tomography scan of the head was normal. A respiratory panel for influenza A (subtypes H1, 2009 H1, H3), influenza B, respiratory syncytial virus, adenovirus, human metapneumovirus, parainfluenza 1, 2, 3, 4, rhinovirus/enterovirus, Bordetella pertussis, Chlamydophila pneumoniae, Mycoplasma pneumoniae and coronavirus (HKU1, NL63, OC43 and 229E) was negative. Polymerase chain reaction tests for enterovirus and herpes viruses 1 and 2 were negative. Bacterial and viral cultures from urine, blood, and respiratory secretions did not yield any growth. The patient’s condition subsequently deteriorated, and a lumbar puncture was performed. A cloudy colorless cerebrospinal fluid (CSF) was obtained that had a white blood cell count of 3224/μL including 85% segmented neutrophils, 7% lymphocytes and 8% monocytes. CSF protein was 419 mg/dL (normal 12–54 mg/dL). A CSF smear stained with Wright-Giemsa revealed the diagnosis (Fig. 1). No wet mount examination or other serologic/polymerase chain reaction tests were performed. The patient was started on empiric antibiotic and antiviral therapy for suspected meningitis.FIGURE 1.: Different levels of magnification of the CSF smear stained by Giemsa showing prominent leukocytosis with numerous neutrophils that are surrounded by large organisms with irregular outlines, central nuclei and cytoplasmic vacuoles. A: Wright-Giemsa ×100. B: Wright-Giemsa ×400. C: Wright-Giemsa ×400.DENOUEMENT The Wright-Giemsa stain of the CSF revealed large organisms with ovoid or irregular outlines containing small central nuclei and ample cytoplasm, consistent with ameba (Fig. 1). However, the patient expired few minutes after the results were called. A Computed tomography scan of the head before death revealed cerebral edema. The diagnosis of amebic meningoencephalitis was later confirmed from the stained CSF slide by the Center for Disease Control and Prevention. Amebic meningoencephalitis is caused by free-living amebae of the genera Naegleria, acanthamoeba, Balamuthia, and Sappinia. It is a rapidly progressive rare disease that can cause acute or subacute illness in immunocompromised as well as immunocompetent patients. Since 1960, the number of published reports has been steadily increasing. Of more than 30 species of Naegleria, only 1 species, Naegleria fowleri, is responsible for most of the reported cases of acute and fulminant brain infection in children and young adults that is usually referred to as primary amebic meningoencephalitis.1,2Naegleria fowleri is a thermophilic bacteria-eating ameba that is found in freshwater habitats such as ponds, rivers and lakes and can also be found in unchlorinated swimming pools and water heaters. It exists in 3 morphologic forms: cyst, flagellate and the trophozoite form, which is the infectious form. Several countries have reported this disease with the USA having the highest incidence. Most USA cases have occurred in the southern regions such as Texas and Florida and is rare in Kansas.3 The infection is transmitted through swimming and diving and has been reported to occur with the use of nasal pots.3 The organism enters the body through the nose crossing the cribriform plate to reach the brain. After a short incubation period of 2–3 days, the rapidly progressive disease causes severe hemorrhagic necrosis of the olfactory bulb. The diagnosis of primary amebic meningoencephalitis is suspected from the characteristic history and from finding of high protein and neutrophils counts in the CSF with low or normal glucose levels. Various parasites can affect the brain and cause meningitis, including Toxoplasma, Angiostrongylus, Baylisascaris and Gnathostoma. These organisms can be visualized for their characteristic morphology with microscopic CSF examination using wet mounts or on fixed smears stained with Methylene blue or Giemsa stains. Ameba can clearly be differentiated by its large size, ovoid or geometric morphology and small round nucleus with a large nucleolus.4 A wet mount may reveal its characteristic movement using phase contrast microscopy. Lack of eosinophilia helps to exclude more common causes of parasitic meningoencephalitis. In this case, the organism’s morphology reflected some degree of degeneration with cytoplasmic vacuoles, pale staining and indistinct nucleolus; however, the organism’s overall size and irregular shape with small central nucleus was diagnostic (Fig. 1). The presence of ameba may be confirmed with immunofluorescence, enzyme-linked immunosorbent assay, or reverse transcription polymerase chain reaction.5 The disease is almost always fatal and only very few patients of >200 reported cases have survived.2,6 Surviving patients were treated early with amphotericin B in various combinations with azithromycin, rifampin, fluconazole or miconazole.4 These anti-infectives may have mild amebicidal activity but exhibit a considerable synergistic effect when given in combination.4,5 The rapid progression of symptoms and signs of meningoencephalitis in a patient with history of swimming in fresh water may lead to early suspicion and prompt attainment of a diagnostic CSF specimen. In this case, there was undue delay in the management, as the diagnosis was not suspected despite suggestive clinical presentation and social history, a lumbar puncture was not performed early at initial presentation in the ER, and the fact that it took the pathologist several hours to stain, review and relay the CSF cytology results. Thus, early suspicion, accurate and rapid diagnosis through CSF cytology and prompt treatment are essential for patient’s survival and prevention of mortality. Rapid diagnosis can easily be achieved by good communication between the treating physicians and pathologists.