Amebic Meningoencephalitis Workup

Updated: Sep 07, 2016
  • Author: Linda Nguyen, MD; Chief Editor: Russell W Steele, MD  more...
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Approach Considerations

Lumbar puncture for cerebral spinal fluid (CSF) analysis is the primary diagnostic tool for PAM, whereas tissue diagnosis is essential for GAE. Nonetheless, amebic meningoencephalitis is seldom diagnosed prior to autopsy. Difficulties in diagnosis and rapid progression make this condition extremely difficult to treat effectively. For this reason, aggressively pursue the diagnosis in patients with CSF findings consistent with bacterial meningitis, a negative CSF gram stain, and a history of water exposure.

CSF findings differ somewhat between patients with PAM and those with GAE. CSF analysis in GAE typically demonstrates less inflammation than in PAM. In addition, trophozoites may be present in the CSF of patients with PAM but are not observed in the CSF of patients with GAE. Histopathologic examination of tissue biopsies has a higher yield for detecting GAE pathogens.


CSF Analysis

Primary amebic meningoencephalitis

As previously mentioned, lumbar puncture for CSF analysis is the primary diagnostic tool for PAM. CSF analysis is indistinguishable from that of acute bacterial meningitis, except that Gram stain findings are always negative. Opening pressure is high (median of 385 mmH2O), red blood cells are elevated (median of 265 cells/uL), white blood cell count is high (median of 2,400 cells/uL; predominantly neutrophils), protein is high (median of 365 mg/dL), and glucose is low (median of 23 mg/dL). [22]

If PAM is suspected, light microscopy with phase contrast on fresh, still-warm CSF may reveal motile trophozoites. Clinicians should also consider a cell culture assay, which will demonstrate cytotoxicity within 48 hours of inoculation in the presence of N fowleri.

A triplex real-time polymerase chain reaction (PCR) assay for N. fowleri, Acanthamoeba spp, and B. mandrillaris has been developed by the Centers for Disease Control and Prevention (CDC). [24] Multiplex PCR for the above and for Sappinia species is likely to become available in the near future. [25]

Granulomatous amebic encephalitis

As with PAM, lumbar puncture for CSF analysis is the first step in diagnosing GAE. CSF analysis typically demonstrates less inflammation than that observed in PAM, and trophozoites are typically not seen in the CSF. Opening pressure is elevated. Similar to aseptic meningitis, a lymphocytic pleocytosis (typically fewer than 500 cells/mm3) is seen. There may be elevated protein levels (up to 1000 mg/dL) early in the clinical course. Often, near-normal or slightly decreased glucose levels are seen.


Imaging Studies

Head computed tomography (CT) scanning or magnetic resonance imaging (MRI) should precede lumbar puncture if clinical signs of focal CNS involvement or elevated intracranial pressure (ICP) is present. In PAM, CT scan or MRI shows obliteration of the cisterns surrounding the midbrain and subarachnoid space, which are nonspecific findings. [26]

In individuals with GAE, focal lesions are very common and may be found scattered throughout the CNS. [27] CT and MRI of the brain typically show multifocal low-density lesions in both cortical and subcortical regions. Enhanced CT may show progressive hydrocephalus, meningeal thickening, pseudotumoral lesions, large isolated lesions, or multifocal ring-enhancing lesions. MRI may demonstrate multifocal lesions, edema, and multiple ring-enhancing lesions. [26] However, given these nonspecific findings, neuroimaging only has the potential for suggesting the diagnosis of PAM or GAE amidst a range of other possible etiologies and is never diagnostic.


Other Tests

For GAE, the conventional method used is histologic detection of the trophozoite and cyst forms of the parasite in biopsied tissue. Biopsy sites may include skin, sinus, lung, and brain tissue.

In PAM, N. fowleri serology is not clinically useful given the rapid progression of disease. However, in GAE, the subacute or chronic progression allows for the potential of serologic testing to be of diagnostic value. Various methods, such as indirect immunofluorescence, ELISA, and flow cytometry may be used to detect antibodies. [15]


Histologic Findings

Biopsies and postmortem specimens from persons with PAM reveal severe, suppurative meningoencephalitic changes and necrotic brain tissue within which amebic trophozoites and macrophages are visualized. [28, 29]

A biopsy of focal granulomatous lesions in GAE is essential for diagnosis. Moderate granulomatous inflammation with prominent vascular involvement is typically present on brain biopsy. Multiple hemorrhagic and necrotic lesions can be found in the cerebrum, thalamus, midbrain, pons, medulla, and cerebellum.  Liquefactive necrosis, marked edema, hemorrhage, and necrotizing vasculitis are associated with the accumulation of amoebic trophozoites, amoebic cysts, and inflammatory cells. [30, 31]

Immunohistochemistry has been widely used to detect the amoebae in histologic specimens. Immunofluorescent antibodies targeting amebic antigens are added to biopsied tissue to differentiate tissue macrophages and necrosed keratinocytes from amoebae. [2]

Tissue-based polymerase chain reaction (PCR) assay has been proposed as a diagnostic aid in patients infected with free-living amoebae, but is not commercially available. [24]