Radiography
Findings
Plain radiographs play a limited role in the diagnosis of toxoplasmosis. An exception is congenital toxoplasmosis, in which calcification within the skull can occasionally be depicted. The skull vault may be thickened with opposed or overlapping sutures. In patients with AIDS, occasional pulmonary involvement may be shown as a lung infiltrate that is associated with hilar/mediastinal lymphadenopathy. Cardiac involvement, which is rare, may be demonstrated on chest radiographs as cardiomegaly in association with features of pulmonary venous hypertension.
Computed Tomography
Findings
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.
Toxoplasmosis has a propensity to involve the basal ganglia. 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. In addition, lesions may occur within the cerebellum, brainstem, and spinal cord. When the dose of contrast agent is doubled and CT scanning is delayed, the detection rate significantly improves.
Hemorrhage and calcification may occur following medical treatment, although ring calcification has been described on CT scans at the time of first diagnosis. However, ring calcification is rare in acquired disease compared with congenital disease. Concomitant cerebral atrophy is seen in approximately one third of patients; this is presumably the result of the direct cellular damage caused by the human immunodeficiency virus (HIV).
In 1994, Fellner et al described a case of unilocular toxoplasmosis that simulated intracerebral tumor in a patient without evidence of AIDS.1 The patient had a single, tumorlike lesion in the right parietal lobe, as shown on CT scan and MRI. During neurosurgical intervention, no tumor was found; however, the final diagnosis was based on histopathology.
In the congenital form of toxoplasmosis, CT scans may reveal diffuse hydrocephalus that is associated with multiple, irregular, nodular, cystlike or curvilinear calcifications in the periventricular areas and the choroid plexus. The lesions are bilateral and vary from a few millimeters to 2 cm, and there may be associated hydrocephalus. The skull vault may be thickened with opposed or overlapping sutures.
The characteristic sign of CNS toxoplasmosis is the asymmetric target sign, which is detectable on both CT scans and MRIs, although MRI is more sensitive. This asymmetric target sign represents a ring-enhancing abscess, which contains other similar ring-enhancing abscesses as well as similarly enhancing, eccentric nodules in the abscess cavity.
Degree of Confidence
See MRI Degree of Confidence.
False Positives/Negatives
See MRI False Positives/Negatives.
Magnetic Resonance Imaging
Findings
Toxoplasmosis is the most common cerebral mass lesion encountered in HIV-infected patients, and its incidence has increased markedly since the beginning of the AIDS epidemic. There are occasionally unusual appearances of CNS toxoplasmosis that make diagnosis by standard imaging techniques difficult or impossible. The advent of MR spectroscopy has increased the ability to differentiate between various CNS lesions.
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. Focal nodular or ring enhancement occurs in approximately 70% of patients after gadolinium enhancement. The lesions are rarely hemorrhagic; thus, MRI findings depend on the hemorrhagic stage of evolution.
As noted in the CT Scan Findings section, Fellner et al reported the case of patient without evidence of AIDS, who presented with unilocular toxoplasmosis that simulated an intracerebral tumor.1 Although the patient’s CT scans and MRI showed a single, tumorlike lesion in the right parietal lobe, no tumor was found at surgery. On histologic examination, the asymmetric target sign, which is detectable on both CT scans and MRIs, was observed, confirming the diagnosis.
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.2,3 This pattern differs from that of toxoplasmosis, which typically has elevated lactate and lipid peaks but an absence of the other metabolites.4 Lymphoma tends to have low apparent diffusion coefficient values; this differs form toxoplasmosis, which typically has significantly greater values than lymphoma lesions.5
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes;joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.
Periventricular ependymal enhancement
A study by Guerini et al described the importance of periventricular ependymal enhancement in adults,6 a finding that can signify an underlying pathology that requires prompt medical attention. The authors reported the pattern of periventricular contrast enhancement, basing the features they noted on the underlying infectious or tumor etiology. In addition, the differential diagnosis for each patient was derived from the patient's immune status and response to a trial of therapy, as well as the type of enhancement that was seen on MRI. The differential diagnosis included tumors (eg, lymphoma, ependymoma, germ cell tumor, or metastases), viral ependymitis (eg, cytomegalovirus, varicella-zoster virus), toxoplasmosis, and bacterial or tuberculous ventriculitis.
T2-weighted images to gauge therapeutic response
Brightbill et al sought to determine whether T2-weighted MRI signal characteristics of Toxoplasma encephalitis could be used to make a definitive diagnosis and/or to evaluate the efficacy of medical therapy.7 The authors concluded that the appearance of Toxoplasma encephalitis in lesions on T2-weighted images was so varied that a definitive diagnosis could not be reached based on signal-intensity characteristics alone. In fact, it appeared that T2-weighted hyperintensity was pathologically correlated with necrotizing encephalitis, whereas T2-weighted isointensity correlated with organizing abscesses. Brightbill et al further surmised that in patients receiving medical therapy, it was possible that the T2-weighted MRI appearance of hyperintensity to isointensity could be a transitional change as a function of a positive response to antibiotic treatment. Thus, the signal-intensity change might be a means to determine the effectiveness of medical therapy. By extrapolation, fluid-attenuated inversion recovery (FLAIR) signal alterations that are easer to evaluate can be used in a similar fashion.
Prenatal imagingIn 1993, D'Ercole et al compared the effectiveness of ultrasonography with that of MRI for the prenatal diagnosis of fetal cerebral abnormalities.8 The authors determined that MRI of the fetal brain could be used to confirm or exclude fetal cerebral defects in cases in which the ultrasonographic results were inconclusive or incomplete. D’Ercole et al reviewed 31 cases in which MRI verified ultrasonographic evidence of fetal brain defects. Histologic study of the fetus or postnatal radiologic examination confirmed the ultrasonographic evidence in 21 cases; MRI ruled out the ultrasonographic diagnosis in 10 cases (the infants were born healthy); and the MRIs were normal in 1 case of cerebral toxoplasmosis, in which ultrasonography showed periventricular calcifications. Overall, MRI confirmed or further documented the ultrasonographic findings for 20 cases; however, 4 of the 20 cases required fetal autopsy to determine the exact nature of the lesion.
Degree of Confidence
The asymmetric target sign is highly suggestive of CNS toxoplasmosis, but it is detected in only 30% of patients. Other MRI patterns that are presumably related to the patient's altered immune status are not as specific and may be mimicked by various CNS infections and lymphoma.
CNS lymphoma lesions are often solitary, whereas the nodules of CNS toxoplasmosis more often are multiple. A diagnosis of toxoplasmosis is favored over a diagnosis of lymphoma when more than 3 lesions or slender, ring-enhancing foci are seen or when marked edema is present. In addition, toxoplasmosis is more common subcortically than lymphoma and seldom affects the corpus callosum.
Meningeal or ependymal involvement should provoke a search for other entities, such as lymphoma or other infections. Although toxoplasmosis meningitis has been described, it is extremely rare. The degree of perilesional edema is correlated directly with the patient's ability to mount an inflammatory response. The greater the edema, the greater the inflammatory response, and the better the prognosis. Edema also correlates with CD4 counts.
Differential diagnostic problems with CT scanning and MRI
Miguel et al reviewed the imaging studies of 14 patients with CNS toxoplasmosis in the context of differential diagnostic problems with CT scanning and MRI.9 Although the findings of these modalities demonstrated low specificity for the CNS mass lesions of patients with AIDS, the authors noted certain features that were more typical for CNS toxoplasmosis than for other diseases: nearly 95% of the lesions were round and had ring or nodular enhancement; 81.3% involved multiple lesions; 60.2% of lesions were localized to the cerebral cortical or corticomedullary junction, in which 100% of cases had at least 1 lesion; and approximately 35% of the lesions were <1 cm in diameter.
On nonenhanced CT scans, 91.3% of the lesions were hypoattenuating; on T2-weighted MRIs, 53.4% of the lesions had at least 1 hypointense zone. Twenty-nine percent of the observed lesions on the T2-weighted MRIs included the presence of target-shaped lesions with hypointense centers, suggesting the diagnosis of CNS toxoplasmosis. The authors believed this finding had not been previously reported. Miguel et al also noted that the presence of isoattenuating or hyperattenuating lesions on nonenhanced CT scans or irregularly shaped lesions was uncommon in CNS toxoplasmosis and that the appearance of a solitary lesion per se on CT scanning or MRI was not a good criterion for the differential diagnosis of CNS toxoplasmosis.
Positive predictive value of MRI findings
In a hospital-based study of 188 consecutive patients who were seropositive for HIV type 1 (HIV-1) and who presented with possible signs or symptoms of first-ever CNS disease,10 the confirmed diagnoses included cerebral toxoplasmosis (47 patients, 25.0%), HIV-1 encephalopathy (19 patients, 10.1%), progressive multifocal leukoencephalopathy (PML) (9 patients, 4.8%), and cerebral lymphoma (1 patient, 0.5%). Nine patients (4.8%) had other conditions. In 73 (38.8%), the initial CT scans or MRIs showed focal brain lesions, which were assessed prospectively.
The positive predictive value for toxoplasmosis was 100% with the combined occurrence of multiple lesions and mass effect or contrast enhancement (23 patients) or in cases in which at least 1 space-occupying or enhancing lesion was located in the basal ganglia or the thalamus (26 patients). Solitary lesions with mass effect or contrast enhancement were also seen (26 patients), and cerebral toxoplasmosis was the cause in 22 patients (84.6%). Furthermore, 1 or more nonenhancing, nonmass lesions were present in 8 of the 9 patients with PML; however, this pattern had a predictive value of 47.1% for PML. The authors concluded that in the epidemiologic context of the study, specific imaging findings in HIV-1-seropositive patients are highly predictive for cerebral toxoplasmosis. However, findings may differ in other parts of the world where cerebral toxoplasmosis may be less prevalent among HIV-1-infected individuals.
Recurrences of brain toxoplasmosis have been reported to correlate with persistent contrast enhancement both on CT scanning and on MRI.11 The demonstration of such areas of persistent contrast enhancement in patients who have received treatment for initial toxoplasmosis may be a valuable sign that they are at risk for recurrence.
Correlation of MRI findings
The pathologic findings of T2- and T1-weighted MRI sequences in cases of HIV infection were assessed in a study of 11 formalin-fixed brains at 0.5 T.12 The extent of white matter abnormality that was seen on MRI broadly corresponded with the pathologic findings in 2 cases of PML and 1 case each of toxoplasmosis and lymphoma. Overall, however, histologic changes were more frequent than lesions on MRI, including cases in which conventional MRI did not reveal multiple tuberculous granulomas, multinucleate giant cells, microglial nodules, perivascular cuffing, and cytomegaloviral inclusions. On the other hand, 1 common finding on T2-weighted MRIs in 6 cases was punctate or patchy hyperintensity in the basal ganglia. The corresponding histologic changes included calcification of vessels with widened perivascular spaces and mineralized neurons.
Revel and associates reported the imaging findings of 5 patients with AIDS who had received a previous diagnosis of, and subsequent treatment for, toxoplasmosis.13 Nonenhanced CT scans obtained approximately 6 months after the CNS infection showed hyperattenuating lesions. MRI was performed in all cases: in 4 of the 5 patients, the hyperattenuating areas on the CT scans were characterized by high signal intensity on the T1-weighted MRIs. In 2 of the 4 cases, pathologic correlation confirmed hemorrhage. In the fifth case, pathologic correlation verified the MRI findings that had suggested calcification.
In another study of 12 cases of AIDS, the radiologic (MRI and CT scan) and pathologic findings in the brain were correlated.14 Balakrishnan et al noted 3 cases each of HIV encephalopathy, primary lymphoma, and toxoplasmosis and 1 case each of cryptococcosis, cytomegalovirus infection, and PML. MRI was better than CT scanning at clearly depicting the various cranial lesions; on the basis of MRI characteristics, HIV encephalopathy was distinguishable from other lesions, particularly PML. Although the basal ganglia were found to be the most common sites of involvement in opportunistic infections and primary lymphoma, reliable distinguishing features among lesions in the basal ganglia were not found, with the exception of a unique appearance for cryptococcal lesions.
False Positives/Negatives
False-positive findings may result from lymphoma, other CNS infections (particularly fungal infections), and CNS metastases.Ultrasonography
Findings
Antenatal ultrasonography is used to detect congenital toxoplasmosis. Ultrasonographic findings reveal toxoplasmosis in 36% of fetuses with the disease, including evolving symmetric ventriculomegaly, intracranial periventricular and hepatic/splenic densities, focal destruction of cerebral tissue that is associated with enlargement of the neighboring cistern or ventricle, ocular calcification, microphthalmia, metaphyseal bands, irregularity of the metaphyseal border of the growth plate, fetal ascites, and increased placental thickness. In fetal blood, Toxoplasma -specific immunoglobulin M levels are elevated.
Postnatal ultrasonography can be used to monitor ventricular size in infants up to 18 months of age or following closure of the fontanelles. In adult patients, abdominal ultrasonography may show hepatosplenomegaly and abdominal lymphadenopathy.
Degree of Confidence
Ultrasonographic findings combined with maternal serologic results are significantly related to clinical outcome.
Abdominal ultrasonography in adult patients with a history of abdominal pain and abnormal results on liver function tests may show hepatosplenomegaly and abdominal lymphadenopathy.
Nuclear Imaging
Findings
Preliminary research suggests that positron emission tomography (PET) scanning with fluorine-18-fluorodeoxyglucose (FDG) can reliably distinguish CNS infections from CNS malignancies, such as lymphoma, in patients with HIV infection.
Thallous chloride (201 Tl) and technetium-99m (99m Tc) sestamibi (MIBI) brain imaging has also been used to distinguish CNS infections from CNS lymphoma. MIBI imaging appears to be more helpful than201 Tl imaging because of its higher specificity and equal sensitivity.
Degree of Confidence
Larger prospective studies are required to confirm the impression that FDG-PET can reliably differentiate CNS infection from CNS lymphoma. MIBI imaging appears to have a higher specificity than201 Tl imaging.
False Positives/Negatives
False-negative scans may occur with both MIBI scanning and201 Tl scanning, as well as in patients following medical treatment for toxoplasmosis.
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References
Fellner F, Schmitt R, Helmberger T, Büsing CM, Obletter N. Unilocular toxoplasmosis simulating intracerebral tumor. Bildgebung. Mar 1994;61(1):44-6. [Medline].
Chang L, Miller BL, McBride D, et al. Brain lesions in patients with AIDS: H-1 MR spectroscopy. Radiology. Nov 1995;197(2):525-31. [Medline].
Simone IL, Federico F, Tortorella C, et al. Localised 1H-MR spectroscopy for metabolic characterisation of diffuse and focal brain lesions in patients infected with HIV. J Neurol Neurosurg Psychiatry. Apr 1998;64(4):516-23. [Medline].
Chinn RJ, Wilkinson ID, Hall-Craggs MA, et al. Toxoplasmosis and primary central nervous system lymphoma in HIV infection: diagnosis with MR spectroscopy. Radiology. Dec 1995;197(3):649-54. [Medline].
Camacho DL, Smith JK, Castillo M. Differentiation of toxoplasmosis and lymphoma in AIDS patients by using apparent diffusion coefficients. AJNR Am J Neuroradiol. Apr 2003;24(4):633-7. [Medline]. [Full Text].
Guerini H, Helie O, Leveque C, et al. [Diagnosis of periventricular ependymal enhancement in MRI in adults]. [French]. J Neuroradiol. Jan 2003;30(1):46-56. [Medline]. [Full Text].
Brightbill TC, Post MJ, Hensley GT, Ruiz A. MR of Toxoplasma encephalitis: signal characteristics on T2-weighted images and pathologic correlation. J Comput Assist Tomogr. May-Jun 1996;20(3):417-22. [Medline].
D'Ercole C, Girard N, Boubli L, et al. Prenatal diagnosis of fetal cerebral abnormalities by ultrasonography and magnetic resonance imaging. Eur J Obstet Gynecol Reprod Biol. Aug 1993;50(3):177-84. [Medline].
Miguel J, Champalimaud JL, Borges A, et al. [Cerebral toxoplasmosis in AIDS patients, CT and MRI images and differential diagnostic problems]. [Portugese]. Acta Med Port. Jan 1996;9(1):29-36. [Medline].
Steinmetz H, Arendt G, Hefter H, et al. Focal brain lesions in patients with AIDS: aetiologies and corresponding radiological patterns in a prospective study. J Neurol. Jan 1995;242(2):69-74. [Medline].
Laissy JP, Soyer P, Parlier C, et al. Persistent enhancement after treatment for cerebral toxoplasmosis in patients with AIDS: predictive value for subsequent recurrence. AJNR Am J Neuroradiol. Oct 1994;15(9):1773-8. [Medline].
Hawkins CP, McLaughlin JE, Kendall BE, McDonald WI. Pathological findings correlated with MRI in HIV infection. Neuroradiology. 1993;35(4):264-8. [Medline].
Revel MP, Gray F, Brugieres P, et al. Hyperdense CT foci in treated AIDS toxoplasmosis encephalitis: MR and pathologic correlation. J Comput Assist Tomogr. May-Jun 1992;16(3):372-5. [Medline].
Balakrishnan J, Becker PS, Kumar AJ, et al. Acquired immunodeficiency syndrome: correlation of radiologic and pathologic findings in the brain. Radiographics. Mar 1990;10(2):201-15. [Medline].
Berlit P, Popescu O, Weng Y, Malessa R. Disseminated cerebral hemorrhages as unusual manifestation of toxoplasmic encephalitis in AIDS. J Neurol Sci. Nov 1996;143(1-2):187-9. [Medline].
Chang KH, Han MH. MRI of CNS parasitic diseases. J Magn Reson Imaging. Mar-Apr 1998;8(2):297-307. [Medline].
Chang L, Ernst T. MR spectroscopy and diffusion-weighted MR imaging in focal brain lesions in AIDS. Neuroimaging Clin N Am. Aug 1997;7(3):409-26. [Medline].
Dietrich U, Maschke M, Dörfler A, Prumbaum M, Forsting M. MRI of intracranial toxoplasmosis after bone marrow transplantation. Neuroradiology. Jan 2000;42(1):14-8. [Medline].
Fahnehjelm KT, Malm G, Ygge J, et al. Ophthalmological findings in children with congenital toxoplasmosis. Report from a Swedish prospective screening study of congenital toxoplasmosis with two years of follow-up. Acta Ophthalmol Scand. Oct 2000;78(5):569-75. [Medline]. [Full Text].
Heald AE, Hoffman JM, Bartlett JA, Waskin HA. Differentiation of central nervous system lesions in AIDS patients using positron emission tomography (PET). Int J STD AIDS. Aug-Sep 1996;7(5):337-46. [Medline].
Hedlund GL, Boyer RS. Neuroimaging of postnatal pediatric central nervous system infections. Semin Pediatr Neurol. Dec 1999;6(4):299-317. [Medline].
Miller RF, Hall-Craggs MA, Costa DC, et al. Magnetic resonance imaging, thallium-201 SPET scanning, and laboratory analyses for discrimination of cerebral lymphoma and toxoplasmosis in AIDS. Sex Transm Infect. Aug 1998;74(4):258-64. [Medline].
Motomatsu T, Lis M, Seidah N, Chrétien M. Inhibition by beta-endorphin of dopamine-sensitive adenylate cyclase in rat striatum. Biochem Biophys Res Commun. Jul 11 1977;77(1):442-7. [Medline].
Murakami T, Nakajima M, Nakamura T, et al. Parkinsonian symptoms as an initial manifestation in a Japanese patient with acquired immunodeficiency syndrome and Toxoplasma infection. Intern Med. Dec 2000;39(12):1111-4. [Medline]. [Full Text].
Naddaf SY, Akisik MF, Aziz M, et al. Comparison between 201Tl-chloride and 99Tc(m)-sestamibi SPET brain imaging for differentiating intracranial lymphoma from non-malignant lesions in AIDS patients. Nucl Med Commun. Jan 1998;19(1):47-53. [Medline].
Ramsey RG, Gean AD. Neuroimaging of AIDS. I. Central nervous system toxoplasmosis. Neuroimaging Clin N Am. May 1997;7(2):171-86. [Medline].
Reardon W, Hockey A, Silberstein P, et al. Autosomal recessive congenital intrauterine infection-like syndrome of microcephaly, intracranial calcification, and CNS disease. Am J Med Genet. Aug 1 1994;52(1):58-65. [Medline].
Roelcke U, Leenders KL. Positron emission tomography in patients with primary CNS lymphomas. J Neurooncol. Jul 1999;43(3):231-6. [Medline].
Senat MV, Bernard JP, Schwärzler P, Britten J, Ville Y. Prenatal diagnosis and follow-up of 14 cases of unilateral ventriculomegaly. Ultrasound Obstet Gynecol. Nov 1999;14(5):327-32. [Medline].
Shefer-Kaufman N, Mimouni FB, Stavorovsky Z, Meyer JJ, Dollberg S. Incidence and clinical significance of echogenic vasculature in the basal ganglia of newborns. Am J Perinatol. 1999;16(6):315-9. [Medline].
Simpson D. HIV rounds at Cornell: selected neurologic complications of HIV disease. AIDS Patient Care STDS. Mar 1998;12(3):209-15. [Medline].
Tuchman RF. [Treatment of learning disorders]. [Spanish]. Rev Neurol. Aug 1998;27(156):285-9. [Medline].
Vyas R, Ebright JR. Toxoplasmosis of the spinal cord in a patient with AIDS: case report and review. Clin Infect Dis. Nov 1996;23(5):1061-5. [Medline].
Wastling J, Heap S, Ferguson D. Toxoplasma gondii--keeping our guests under control. Biologist (London). Nov 2000;47(5):234-8. [Medline].
Further Reading
Keywords
Toxoplasma gondii, T gondii, protozoal infection, parasitic infection, congenital toxoplasmosis, undercooked pork, undercooked lamb, raw meat, disseminated toxoplasmosis, acute toxoplasmosis, central nervous system toxoplasmosis, CNS toxoplasmosis, CNST
