Parasitic Diseases of the Central Nervous System: The Diagnostic Challenge

This article, based on a recent publication by Arturo Carpio, MD, Universidad de Cuenca, Ecuador, and colleagues, is the second in a 3-part series on parasitic diseases of the central nervous system (CNS). It will highlight some of the techniques that clinicians use for the diagnosis of parasitic diseases of the CNS.

Unfortunately, by the time symptoms of parasitic CNS infections appear, the parasite has usually already invaded the brain and in some cases caused irreversible damage.

Early definitive diagnosis of these infections is therefore critical in the control and treatment of these conditions.

According to the authors, “The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges.”

Diagnosis: Laboratory Techniques

Neurologists typically routinely collect samples of cerebrospinal fluid (CSF), as well as blood, from patients who present with neurological symptoms. In conditions such as malaria, toxoplasmosis, and human African trypanosomiasis, direct identification of the causative parasite in CSF samples by using microscopy enables definitive diagnosis. However, this is not feasible in many of the CNS parasitic infections.

And although eosinophilia can be identified in the CSF and/or blood in some CNS parasitoses—especially in helminthic infections such as toxocariasis, cysticercosis, schistosomiasis, and paragonimiasis—this finding is also relatively nonspecific.

Detection of anti-parasite antibodies remains the most frequently used diagnostic tool in these cases. The presence of these antibodies indicates that the patient has been exposed to the parasite. However, this approach still has limitations. In particular, detection of these antibodies does not necessarily indicate current infection with live parasites, because these antibodies can persist for months after the parasite is eliminated.

Both serum and CSF samples are commonly used for the detection of these antibodies. However, it is important to remember that although the presence of antibodies in CSF indicates cerebral involvement and damage, it does not provide any information about the presence of the parasite in other regions of the body. Similarly, the presence of antibodies in the serum does not necessarily indicate a CNS infection.

Detection in the CSF or serum of products that are secreted by viable parasites is also possible in some conditions.

Molecular detection of parasite DNA by using a polymerase chain reaction (PCR) test is another diagnostic approach that is becoming more popular. However, one drawback of the PCR test is its inability to differentiate between viable and dead parasites.

In addition to standard diagnostic techniques, some complementary methods in particular are used in the diagnosis of specific parasitic conditions in the CNS:

Cysticercosis: The HP10 antigen detection assay is used to detect the secreted metacestode glycoprotein. This assay is useful is the long-term follow up of patients, both during and after treatment. Decreasing antigen levels in CSF indicate effective treatment, whereas continued presence of the antigen indicates ineffective treatment.

Toxoplasmosis: In addition to assays to detect circulating Toxoplasma gondii antigens and anti-toxoplasma antibodies, PCR-based techniques are also used. And because different clonal types of T. gondii are associated with different clinical manifestations of toxoplasmosis, techniques such as serotyping and DNA sequencing may be used to determine which clonal type of the parasite is involved. Diagnosis of toxoplasmosis can also be challenging in immunocompromised individuals who often have low antibody titers. Differentiation of CNS infection with T. gondii from infection with Trypanosoma cruzi is also important in these patients, and requires a combination of serology, PCR and examination of CSF by microscopy.

Human African Trypanosomiasis: Similar to the situation with toxoplasmosis, diagnosis of trypanosomiasis can also be challenging in immunocompromised individuals because of low antibody titers. The Card Agglutination Test for Trypanosomes (antibody-mediated agglutination of fixed trypanosomes) is often used initially in the diagnosis of CNS trypanosomiasis, and is followed by direct visualization of the parasite in CSF.

Malaria: Various PCR-based methods and immunodiagnostic tests to detect antibodies to parasite proteins (such as the histidine-rich protein and lactate dehydrogenase) are available.

Diagnosis: Neuroimaging Studies

Although conventional computed tomography (CT) scan and magnetic resonance imagine (MRI) studies are important in the diagnosis of CNS parasitic infections, the results of these studies must be considered alongside those of laboratory tests to make a definitive diagnosis.

However, in some conditions, neuroimaging studies may highlight features that do allow a definitive diagnosis to be made. For example, the presence of a daughter cyst within a cystic lesion on MRI is considered a pathognomonic sign of an echinococcus cyst. CT and MRI findings can also be used to diagnose cysticercosis, and different stages of the disease present different characteristic findings. However, MRI is superior to CT in highlighting certain features of the parasite such as the scolex.

Advanced neuroimaging techniques are also used in the diagnosis of CNS parasitic infections. These techniques include fluid attenuation inversion recovery (FLAIR), diffusion MRI, perfusion MRI, 3-dimensional MRI sequences, and magnetic resonance spectroscopy.

“Neuroimaging studies (CT scan and MRI) play an important role in early diagnosis; however, there is a wide range of neuroimaging findings in CNS parasite infections, often with considerable overlap, which makes diagnosis difficult,” the authors emphasize. “The development of specific and sensitive serodiagnostic and molecular biological (PCR) assays for viable parasites is an urgent priority that will complement and confirm clinical examination,” they conclude.

Read the first article in the series here: Part I: Parasitic Diseases of the Central Nervous System: The Global Burden

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.