Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 56, Num. 1, 2010, pp. 31-34

Journal of Postgraduate Medicine, Vol. 56, No. 1, January-March, 2010, pp. 31-34

Case Report

Neurotoxoplasmosis mimicking intracranial tuberculoma

Doraiswamy V, Vaswani RK, Lahiri KR, Kondekar SS

Department of Pediatrics, Seth G.S. Medical College and KEM Hospital, Mumbai, India

Correspondence Address: Dr. Rajwanti K Vaswani, Department of Pediatrics, Seth G.S. Medical College and KEM Hospital, Mumbai, India, anukvaswani@hotmail.com

Date of Submission: 07-Mar-2009
Date of Decision: 24-Jul-2009
Date of Acceptance: 17-Sep-2009

Code Number: jp10010

PMID: 20393248

DOI: 10.4103/0022-3859.62432

Abstract

Keywords: Immunocompromised, toxoplasmosis, tuberculoma

Cerebral toxoplasmosis is one of the most common causes of cerebral mass lesions in immunocompromised patients. This is true even in the developing world where tuberculosis is endemic and a frequent cause of such lesions. ^[1] Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. Toxoplasmic encephalitis usually occurs in human immunodeficiency virus (HIV)-infected patients with an absolute CD4 T-cell counts < 100 cells/ml ^[2] and if diagnosed late and left untreated could lead to considerable morbidity and mortality. The incidence of central nervous system (CNS) toxoplasmosis among HIV-infected patients in India and the world has been reported to be about 1.33-3.33% in various studies. ^[3] Till date, only a few cases have been reported in children in our country. Herein, we report a case of an intracranial granuloma detected using computerized tomography (CT), initially diagnosed and treated as tuberculoma, which later turned out to be toxoplasmosis. The patient was subsequently diagnosed to be HIV-infected.

Case Report

A 11-year-old Indian boy presented with lethargy, headache, fever and recurrent generalized seizures since one month. His father have died seven years prior due to some unknown neurological disease. CT brain done two weeks prior to presentation revealed a ring enhancing lesion in the left basal ganglia and edema in the gangliothalamic region bilaterally causing a mass effect [Figure - 1] and [Figure - 2] which was reported as tuberculoma. Cerebrospinal fluid (CSF) studies, chest X-ray and Mantoux test were normal. The patient was put on antituberculous therapy. Two weeks later, the patient continued to deteriorate neurologically in the form of persistent seizures and altered sensorium. On physical examination, the Glascow coma scale was 5/15 and there was hypertension. On neurological examination, the patient had generalized hypertonia, brisk reflexes, extensor plantars and signs of meningeal irritation. In view of non-responsiveness to treatment and clinical deterioration, the CT scan was reviewed wherein the unusual site of the lesion prompted us to consider a differential diagnosis of toxoplasmosis. Antitoxoplasma IgM antibody titers were not detectable and IgG was> 200 IU/ml (Normal IgG < 10 IU/ml) ^[4] by enzyme linked immunosorbent assay (ELISA) (Euroimmun, Equipar). The patient and his mother were subsequently diagnosed to be HIV-infected. Absolute CD4 count of the patient was 24 cells/ml.

The patient was put on sulphadiazine and pyrimethamine combination along with folinic acid and antiretroviral therapy- with stavudine, lamivudine and efavirenz which was changed to nevirapine after the completion of antituberculous therapy. The patient made a steady recovery, became ambulatory and was discharged on Day 15 of treatment. Magnetic resonance imaging (MRI) done three weeks after treatment showed substantial decrease in edema and resolution of the lesion [Figure - 3] and [Figure - 4]. The patient has completed antitoxoplasmosis therapy, recovered fully and is only on HAART.

Discussion

Neurotoxoplasmosis is a disease of the immunocompromised presenting in 25-50% of acquired immunodeficiency syndrome (AIDS) patients who have toxoplasma antibodies. These patients present with fever, headache, altered mental status, cognitive impairment, seizures and focal neurological deficits. ^[5] The diagnosis of a recent infection of acquired toxoplasmosis in immunocompetent individuals is made by documenting seroconversion from -ve to +ve IgG antibody (in the absence of blood transfusion); a two-tube increase in toxoplasma-specific IgG antibody when paired sera are obtained three weeks apart and tested in parallel, or the detection of toxoplasma-specific IgM antibody in conjunction with other serological tests but never alone. ^[5] However, the diagnosis of toxoplasmosis presents a difficult problem in the immunocompromised patients because IgG antibody titers may be low and toxoplasma-specific IgM is often absent. ^[5] In our patient, IgM was negative and IgG was> 200 IU/ml. This was estimated in the late stage of the disease, which was high abnormal, and so a rising titer of IgG could not be demonstrated as seen in the Melbourne study where IgM was negative in all 39 of their patients and in 15 of their patients, a rising titer of IgG could not be demonstrated of which it had already reached the maximum value in seven patients. ^[6] IgG titers peak within one to two months after infection but remain elevated for life. Toxoplasma gondii serology is useful to identify HIV-infected patients at risk for developing toxoplasmosis. Between 97% and 100% of HIV-infected patients with toxoplasmic encephalitis have anti-IgG antibodies. Thus, the absence of antibodies against Toxoplasma gondii makes the diagnosis of toxoplasmosis unlikely in these patients. Most patients with AIDS-associated toxoplasmosis in the United States lack detectable anti-IgM antibodies because the illness represents reactivation of a chronic infection. ^[7],[8]

The CT scan of our patient showed a basal ganglia ring enhancing lesion. Such an unusual location should alert the clinician to consider alternate diagnoses of toxoplasmosis and lymphoma besides tuberculoma. Primary CNS lymphomas in immunocompetent individuals are primarily solitary but in immunocompromised patients they are just as likely to be multiple as solitary. Majority of lesions are supratentorial (85%) and located in the periventricular area (60%) (basal ganglia, thalamus and corpus callosum). For AIDS patients, the differential diagnosis of multiple ring enhancing lesions includes both CNS lymphoma and toxoplasmosis. ^[9] Primary CNS lymphoma cannot be distinguished from toxoplasmosis solely on the basis of neuroradiological criteria (both present as contrast-enhancing lesions with mass effect). ^[7] Although CNS lymphoma may have more of a propensity for periventricular and corpus callosal location, this is not definitive. The prevalence of these two lesions is similar. ^[9] Because they respond to different treatments, differentiation is essential. In neurotoxoplasmosis, CT scans of the brain may show single (30%) or multiple nodular lesions. More commonly, following the IV administration of contrast medium, CT scan studies demonstrate thin-walled cavitating lesions with ring enhancement. Edema of the surrounding white matter is often depicted as well. Approximately 75% of the nodules are located in the basal ganglia, but others are scattered throughout the brain at the gray matter-white matter junction. ^[7],[10] In MRI, on T1-weighted precontrast MRIs, the lesions are hypointense relative to brain tissue. On T2-weighted MRIs, the foci of infection are usually hyperintense, but they can occasionally be isointense to hypointense. Active lesions are often surrounded by edema. ^[10] MRI is more sensitive than CT scan and thus is the preferred imaging technique, especially in patients without focal neurologic abnormalities. Patients with only one lesion or no lesions on CT scan should undergo MRI to determine whether more than one lesion is present. The presence of solitary lesion should lead us towards CNS lymphoma rather than toxoplasmosis. ^[7] The advent of MR spectroscopy has increased the ability to differentiate between various CNS lesions. MR spectroscopy of lymphoma in patients with AIDS has been shown to demonstrate increased lactate and lipid peaks, as well as a prominent choline peak, decreased N-acetyl aspartate, creatine, and myoinositol signals. This pattern differs from that of toxoplasmosis, which typically has elevated lactate and lipid peaks but an absence of the other metabolites. Lymphoma tends to have low apparent diffusion coefficient values; this differs from toxoplasmosis, which typically has significantly greater values than lymphoma lesions. ^[10] Positron emission tomography (PET) scan using the glucose analog [18F] has been used to differentiate toxoplasmosis from cerebral lymphoma. ^[11] 201Tl brain single photon emission computed tomography (SPECT) does not accumulate in non-neoplastic lesions like hematomas, radiation necrosis and infectious processes like toxoplasmosis. ^[12] These modalities if available should be used before histopathological diagnosis, which is definitive for lymphoma, thereby reducing the waiting time required for a treatment response in toxoplasmosis. The other differential considered was tuberculosis. In children, tuberculomas are predominantly located in the infratentorial compartment. ^[13] Tuberculomas are rare in the basal ganglia. In fact, they were not demonstrated in a study conducted in South Africa involving 35 children with tuberculomas (cerebellum being the commonest site). ^[14] The most frequent outcome is the resolution of tuberculoma and complete resolution has also been seen as early as 12 weeks but more than two-thirds of tuberculomas show incomplete resolution by 18 months. ^[15],[16] Our patient was on antituberculous therapy for two weeks before starting treatment for toxoplasmosis and there was no improvement. Clinical and radiological improvement within two and three weeks respectively of initiating antitoxoplasmosis therapy makes the presumptive diagnosis almost certain as seen in our patient. ^[5]

Imaging studies of the brain are indispensable for diagnosis and management of patients with toxoplasma encephalitis, ^[17] as definite diagnosis namely biopsy is invasive and difficult. When investigations like CSF polymerase chain reaction (PCR), PET or SPECT and brain biopsy of lesion are not available, CT findings of granulomatous lesion as suggested above with positive serology warrant a suspicion of toxoplasmosis and HIV and a trial therapy thereby reducing mortality and morbidity. Such a case report would serve to sensitize the clinicians on making a proper differential diagnosis and start appropriate treatment without wasting time and increasing morbidity and mortality.

References

Copyright 2010 - Journal of Postgraduate Medicine

The following images related to this document are available:

Photo images