Early Diagnostic Value of Contrast-Enhanced MRI in Distinguishing Toxoplasmic Encephalitis from CNS Lymphoma: A Case Report of AIDS with Seronegative Toxoplasmosis

Abstract

Toxoplasmic encephalitis (TE) and primary central nervous system (CNS) lymphoma are the major differential diagnoses of ring-enhanced brain lesions in acquired immunodeficiency syndrome (AIDS). Biopsy may be difficult; thus, empirical anti-toxoplasma therapy is often initiated. We report an AIDS patient receiving chemotherapy for Kaposi's sarcoma who developed TE. Weekly gadolinium-enhanced magnetic resonance imaging (MRI) demonstrated diminishment of ring enhancement 7 days after treatment, preceding neurological improvement and lesion size reduction. This early radiological change, captured by rare weekly gadolinium-enhanced MRI, was useful for differentiating TE from lymphoma before neurological improvement.

Plain Language Summary

Using MRI to Quickly Tell Apart a Brain Infection and a Brain Tumor in a Person with HIV

People living with HIV can sometimes develop serious brain problems. Two of the most common are toxoplasmic encephalitis, a brain infection caused by a parasite, and primary central nervous system lymphoma, a type of malignant brain disease. These conditions can look very similar on brain scans, and blood tests do not always give clear answers. Doctors often begin treatment for toxoplasmic encephalitis based on suspicion. If the patient improves, the diagnosis is confirmed; if not, it is important to move quickly to testing for lymphoma. This makes early diagnosis critical, because it helps doctors decide whether to continue treatment for toxoplasmosis or to promptly investigate lymphoma. We describe the case of a patient with HIV who developed toxoplasmic encephalitis, even though the usual blood test was negative. Weekly MRI scans were performed after treatment started. The MRI showed improvement very quickly—earlier than the patient's neurological symptoms improved. This finding shows that repeated MRI scans can reveal treatment effects sooner than symptoms, helping doctors make a faster and more confident diagnosis. Such quick diagnosis directly supports timely and appropriate treatment, which is essential for better patient care.

Keywords

HIV/AIDS immunology opportunistic infections co-infections malignancy

Introduction

In acquired immunodeficiency syndrome (AIDS), focal brain lesions most frequently represent toxoplasmic encephalitis (TE), followed by primary central nervous system (CNS) lymphoma.^1,2 Initial magnetic resonance imaging (MRI) findings often overlap, making early differentiation challenging. Because treatment can be effective, early diagnosis is very valuable. It is common practice to presumptively diagnose and treat TE in patients with AIDS. If the reaction to treatment is poor, it is important to perform brain biopsy immediately. It is based on clinical and radiological response.^3,4 We present a case in which early diminishment of ring enhancement on weekly gadolinium (Gd)–enhanced MRI preceded neurological recovery, aiding rapid differentiation from lymphoma. Such serial imaging data during TE treatment are rarely reported and provide valuable insights for early diagnosis.

Case Report

A 28-year-old Japanese man was diagnosed with AIDS based on an HIV-1 RNA level of 6.2 × 10⁵ copies/mL and a CD4+ T-cell count of 52 cells/μL. He had pneumocystis pneumonia, cytomegalovirus retinitis, and Kaposi's sarcoma. Antiretroviral therapy with tenofovir/emtricitabine and raltegravir was initiated after treatment of opportunistic diseases. His past medical history included herpes zoster at the age of 20 years and chlamydial pneumonia at the age of 22 years. His family history and genetic background were unremarkable. He had been employed as a nurse prior to his first admission, with no notable psychosocial risk factors. Nine months later, while still receiving chemotherapy for Kaposi's sarcoma (i.e., pegylated liposomal doxorubicin), he developed right-sided weakness and tremor. At that time, his HIV-1 viral load was 40 copies/mL, and CD4+ T-cell count was 107 cells/μL.

Head Gd-enhanced MRI revealed multiple ring-enhanced lesions with edema (Figure 1). His serum showed negative results for antitoxoplasma antibody (PHA method), cryptococcal antigen, and anticryptococcal antibody, and a normal level of soluble interleukin-2 receptor. Pathogen-specific tests of his cerebrospinal fluid were negative for antitoxoplasma antibody, cryptococcus antigen, HHV-8 DNA, and Mycobacterium tuberculosis PCR. Chemistry results showed normal levels of protein and glucose. Bacterial culture was negative. 201TlCl single-photon emission computed tomography (SPECT) revealed no clear intracerebral uptake. Differential diagnoses included TE and primary CNS lymphoma.

Figure 1.

Head Gd-enhanced MRI (A) T1WI and (B) T2WI on admission showing multiple, ring-enhanced lesions with edema. Time course of brain lesions in empirical TE treatment (C) on admission, (D) therapy day 7 showing diminishing ring enhancement, (E) therapy day 14, (F) therapy day 21, (G) therapy day 35 showing size reduction of lesions.

Empirical treatment for TE, consisting of 50 mg of pyrimethamine, 4 g of sulfadiazine, and 10 mg of leucovorin, was initiated. Weekly head Gd-enhanced MRI was performed using a standardized MRI protocol. Ring enhancement of the lesions on Gd-enhanced T1-weighted MRI began to diminish after 7 days of treatment. The tremor of the extremities disappeared on day 10. The right upper and lower extremity muscle strength was improved on day 17, and the size of the brain lesions was reduced on Gd-enhanced MRI on day 36 (Figure 1). Ring enhancement of the lesions on Gd-enhanced MRI disappeared about 2 months later, and antitoxoplasma drugs were tapered to a prophylactic dose. The surrounding edema remarkably diminished within 3.5 months and almost disappeared within 1 year. The patient expressed that he felt the medication was effective, noticed improvement in his strength, and smiled as he stated his hope to resume his nursing work.

Discussion

According to reports provided to the Centers for Disease Control and Prevention in the United States, the most frequent disease involving focal brain lesions in patients with AIDS is TE (50%-70% of patients with neurological symptoms), followed by primary CNS lymphoma (20%-30%) and progressive multiple leukoencephalopathy (10%-20%). Herpes, tuberculosis, fungal infection, cryptococcus mycetoma, and bacterial abscess are less frequent.¹ In AIDS, severe immunosuppression can impair antibody production; therefore, negative toxoplasma serology does not exclude TE. In the previous report,³ 22% (4 of 18 cases) of histologically proven TE were seronegative.

In addition, SPECT may yield false-negative results in small lesions, making it insufficient to rule out lymphoma.

Our patient developed TE 9 months after ART initiation, beyond the typical 3-month window for TE-related immune reconstitution inflammatory syndrome. Persistently low CD4 counts and chemotherapy for Kaposi's sarcoma likely contributed to sustained immunosuppression.⁵

When biopsy is not feasible, empirical therapy is recommended, but early and reliable markers of treatment response are crucial. Suzuki et al. reported that Gd-enhanced MRI demonstrated reduction of focal ring enhancement and lesion size with neurological improvement after 7 days of TE therapy.^6,7 However, they did not specify whether regression of ring enhancement preceded neurological recovery. In contrast, our case clearly demonstrated that the reduction of ring enhancement occurred earlier than neurological improvement, supporting the role of Gd-enhanced MRI as a highly useful tool for rapid therapeutic diagnosis of TE.

Conclusion

This case highlights that early radiological improvement on Gd‑enhanced MRI can precede clinical recovery in seronegative TE. Prompt recognition of these changes may facilitate differentiation from CNS lymphoma and timely initiation of appropriate therapy.

This case report was prepared in accordance with the CARE reporting guideline,⁸ and the CARE checklist⁹ was used during manuscript revision (Supplementary File).

Supplemental Material

sj-docx-1-jia-10.1177_23259582251407370 - Supplemental material for Early Diagnostic Value of Contrast-Enhanced MRI in Distinguishing Toxoplasmic Encephalitis from CNS Lymphoma: A Case Report of AIDS with Seronegative Toxoplasmosis

Supplemental material, sj-docx-1-jia-10.1177_23259582251407370 for Early Diagnostic Value of Contrast-Enhanced MRI in Distinguishing Toxoplasmic Encephalitis from CNS Lymphoma: A Case Report of AIDS with Seronegative Toxoplasmosis by Rinko Katsuda, Dai Watanabe, Yasuharu Nakahara, Yasuyuki Mizumori and Tetsuji Kawamura in Journal of the International Association of Providers of AIDS Care (JIAPAC)

Footnotes

Acknowledgments

None.

ORCID iDs

Rinko Katsuda

Dai Watanabe

Yasuharu Nakahara

Yasuyuki Mizumori

Tetsuji Kawamura

Consent for Publication

Written informed consent was obtained from the patient for publication of this case report and images.

Informed Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. The patient consented to publication in a medical journal, with the understanding that the report would be publicly accessible. All efforts have been made to ensure anonymity.

Author Contributions

All authors meet the ICMJE authorship criteria, approved the final manuscript, and agree to be accountable for all aspects of the work.

Rinko Katsuda (RK): Principal physician in charge of this case; performed the diagnosis, treatment, and management of toxoplasmic encephalitis; led discussions with the co-authors and drafted the manuscript through its final version; takes full responsibility for the integrity of the entire work.

Dai Watanabe (DW): Provided expert consultation in infectious diseases; advised on diagnostic strategy and treatment direction for toxoplasmic encephalitis; made substantial contributions to manuscript drafting and critical revision; approved the final manuscript and is accountable for the accuracy and integrity of the work.

Yasuharu Nakahara (YN): Contributed to clinical management and interpretation of radiological findings; provided substantial input to manuscript revision and intellectual content; approved the final manuscript and agrees to be accountable for all aspects of the work.

Yasuyuki Mizumori (YM): Evaluated the therapeutic response and clinical course of toxoplasmic encephalitis; contributed to discussion of clinical findings and supported manuscript preparation and review; approved the final manuscript and is accountable for accuracy and integrity.

Tetsuji Kawamura (TK): Supervised clinical management and the overall case reporting process; contributed to manuscript composition and revision; approved the final version for publication and is accountable for all aspects of the work.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplemental Material

Supplemental material for this article is available online.

Ethical Approval

Ethical approval to report this case was obtained from the National Hospital Organization Himeji Medical Center, Clinical Research Review Board (Approval No. HMC2025-17). The report was conducted in accordance with the principles of the Declaration of Helsinki.

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Supplementary Material

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