Joint Program in Nuclear Medicine

Imaging of CNS Complications in AIDS

Alexander Matthies, MD 
David E. Drum, MD

January 7, 1997

Presentation

Four months prior to presentation, a 48 year old male with AIDS had right sided weakness. Magnetic resonance imaging (MRI) showed a ring enhancing lesion in the left basal ganglia. A stereotactic biopsy was consistent with toxoplasmosis and antitoxoplasmosis treatment resulted in clinical response.

At presentation, he had new onset visual blurring and diplopia as well as reoccurring right sided hemiparesis. Computed tomography CT (10/18/96) revealed a new contrast enhancing lesion in the right parietal-occipital region. The left basal ganglia lesion had shrunken. A repeat CT scan 12 days later showed progression of the lesions despite continuation of antitoxoplasmosis treatment.

Imaging Findings

A Tl-201 SPECT scan revealed several foci of moderately intense tracer uptake in the central basal ganglia, in the right frontoparietal region, in the right posterior portion of the corpus callosum and in the right occipital cortex. Most of these foci matched lesions on the CT. These findings are suggestive of CNS lymphoma.

Discussion

Features of CNS pathologies in AIDS

AIDS continues to be one of the most important causes of morbidity and mortality, especially in the age group between 20 and 45 years. While neurological symptoms account for only about 10% of initial presentations of AIDS (1), studies have shown, that neurological complications occur in 40-60% of patients (2). Autopsy results indicate an even higher rate of CNS involvement (73-87%) (1). The most frequent causes of CNS complications include: Less common are: Clinical presentations include focal neurological manifestations like hemiparesis, hemianopsia, aphasia and ataxia as well as nonfocal signs and symptoms, i. e. headache, lethargy, altered mental status, seizures, progressive dementia, fever and night sweats (2/3). However none of these findings favour lymphoma or any of the opportunistic infections. Serology is fairly sensitive, but nonspecific. While toxoplasma IgG antibodies are positive after recent or distant exposure, they do not indicate that single or multiple enhancing brain lesions are due to toxoplasma gondii(3). Furthermore about 20% of patients with CNS lesions due to Toxoplasma gondii have negative antibody titers.

Diagnostic imaging of CNS complications in AIDS:

The most frequent pathologies in this patient population - primary lymphoma and toxoplasmosis - have strong resemblance on CT and MR in 50 to 80% of cases (4).

Imaging characteristics are :
CT MR 
T1 T2 
Toxoplasmosis  hypodense mass(es), ring or nodular enhancement  low signal, enhancing with gadolinium  high signal foci, moderate edema 
Lymphoma  hypo or hyperdense, ring or nodular enhancement  low signal, enhancing with  intermediate to high signal, moderate edema gadolinium 
Lymphoma is more likely when the enhancing lesion is subependymal, periventricular or in the corpus callosum. Rapid progression in short intervals also favours lymphoma. Enhancing lesions in the basal ganglia or the corticomedullary junction are more likely due to Toxoplasma gondii.

Current standard practice for AIDS patients with enhancing CNS lesions by CT/MR and positive toxoplasma serology is an empirical cause of antitoxoplasmosis treatment for 10 to 21 days. If no clinical and/or radiographic response occurs, alternative diagnoses are considered more closely (6).

In AIDS patients with primary CNS lymphoma this approach has a significantly negative impact on morbidity and duration of survival, as these patients have only an average survival time of 4 months with radiation therapy. and 1.5 months without radiation therapy. A fast and accurate differentiation between lymphoma and infectious causes is of vital importance for this patient group.

In order to improve the diagnostic accuracy several new approaches to imaging have been developed in recent years, among these Tl-201 SPECT and FDG-PET.

Malley et al. (5) used Tl-201 Brain SPECT in 13 AIDS patients with enhancing CNS lesions on CT/MR. Six patients had negative images with uptake ratios (ROI lesion / ROI contralateral hemisphere) of 0.77-1.95 (mean 1.45). Four were diagnosed as having toxoplasmosis, while progressive multifocal leukoencephalopathy and venous angioma were the established cause in 1 patient each. Six of 7 patients with positive Tl-201 images had biopsy proven large cell lymphomas with uptake ratios of 2.95-4.3 (mean 3.65). One image set showed increased uptake in 1 of 3 lesions, while the retrospectively calculated uptake ratio was only 1.8. Autopsy in this patient revealed 3 concurrent infections (toxoplasmosis/CMV/tuberculosis).

Ruiz et al. (4) studied 37 patients by Tl-201 SPECT. Twelve patients, all with negative serology, exhibited increased thallium uptake, that matched the lesions on CT/MR. All of these patients had biopsy or autopsy proven primary CNS lymphoma. 25 of the 37 patients had no abnormal uptake on Tl-201 imaging. 24 of these had toxoplasma antibodies and improved clinically on antitoxoplasma antibiotics with resolution of lesions on serial follow-up CT scans within 2 to 6 weeks.

Hoffman et al. (2) performed FDG-PET studies on 11 patients with enhancing CNS lesions. They found significant differences between the uptake in lymphoma (5 patients, of these 4 biopsy proven) and the other diagnoses (toxoplasmosis 4, syphilis 1, PML 1 patient each). The uptake ratio in lymphoma was 1.8 vs. toxoplasmosis (0.65), syphilis (0.7), PML (1.3) ; (p <0.006).

Villringer et al. (1) also studied 11 patients with known enhancing brain lesions by FDG-PET. Image analysis was performed quantitatively by standard uptake value(SUV) of lesion and contralateral normal tissue as well as the ratio of both values. The SUV ratios in the 7 patients with cerebral infections (toxoplasmosis, tuberculoma) were between 0.3 and 0.7 and significantly lower than in 4 patients with lymphoma (1.7 to 3.1).

Pierce et al. (6) examined 18 patients with FDG-PET. All of seven examined patients with toxoplasmosis had hypometabolic lesions, while all 6 patients with lymphoma showed hypermetabolic lesions. Lesions in PML were hypermetabolic or hypometabolic (1 case each). One lesion due to cryptococcoma and a combination of tuberculoma and toxoplasma (1 patient each) showed also hypometabolic activity.

Conclusions

The above described studies with Tl-201 SPECT show good sensitivity and specificity in differentiating CNS lymphoma from other pathologies. Limitations of diagnostic accuracy occur in lesions that are smaller than SPECT resolution (6-8mm) allows to detect, lesions close to orbitae, skull base, scalp or in lymphoma with diffuse leptomeningeal spread.

Campbell et al. (7) reported recently a case of an AIDS patient with biopsy proven CNS lymphoma, that showed no uptake on Tl-201 SPECT despite a lesion size of 32 mm by MR. It is conceivable that necrosis in the center of the tumor has contributed to the false negative result. To avoid false positive results, it appears it be important to calculate the uptake ratio between ROI lesion and a mirrored ROI on the contralateral normal brain hemisphere (5).

As far as our patient is concerned, it remains unclear, whether the positive scan represents a true or false positive result. Only a biopsy could established this. As suggested by several authors a larger, multicenter trial for both modalities Tl-201 SPECT as well as FDG- PET is needed to establish sensitivity and specificity values for a larger number of patients.

References

1. Villringer et al. : Differential Diagnosis of CNS Lesions in AIDS Patients by FDG-PET. J Comp Ass Tomo 1995; 19(4): 532-536.

2. Hoffman et al. : FDG-PET in Differentiating Lymphoma from Nonmalignant Central Nervous System Lesions in Patients with AIDS. JNM 1993; 34: 567-575.

3. Chang et al. : Radiologic-Pathologic Correlation - Cerebral Toxoplasmosis and Lymphoma in AIDS. AJNR 1995; 16: 1653-1663. 4. Ruiz et al. : Use of Thallium 201 Brain SPECT to Differentiate Cerebral Lymphoma from Toxoplasma Encephalitis in AIDS Patients. Am J Neuroradiol 1994; 15: 1885-1894.

5. O’Malley et al. : Diagnosis of Intracranial Lymphoma in Patients with AIDS : Value of TL 201 SPECT. AJR 1994; 163: 417-421.

6. Pierce et al. : Evaluating Contrast-Enhancing Brain Lesions in Patients with AIDS by Using Positron Emission Tomography. Ann Int Med 1995; 123 : 594-598.

7. Campbell et al. : False -negative Single Photon Emission CT in AIDS Lymphoma: Lack of Effect of Steroids. AJNR 1996; 17: 1000-1001.

8. Lorberboym et al.: Rapid differential diagnosis of cerebral toxoplasmosis and primary CNS lymphoma by thallium -201 SPECT. J Nuc Med, July 1996.

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J. Anthony Parker, MD PhD, Tony_Parker@bidmc.harvard.edu