Radiology in AIDS

Nervous system manifestations

 

Cerebral pathology

The occurrence of AIDS has made cerebral infection a routine problem. Diagnostic difficulties are related to the multiplicity of pathology that occurs in association with cerebral HIV infection, often treatable opportunistic infections arise as a consequence of the immunodeficiency and simultaneously, tumours, especially primary CNS lymphomas, develop with increased frequency. Neuroimaging techniques (CT and/or MR scans) have a triple role: detection, diagnosis and monitoring under treatment. MRI is the most sensitive procedure, providing more precise evaluation of not only infra- but also supratentorial lesions, detection of the white matter and meningeal lesions, which are invisible or highly underestimated with CT, and better detection of hemorrhagic lesions. Furthermore, because of the underlying immunodeficiency, with poor

	Figure 1. Toxoplasmosis. Post-contrast CT scan. Ring-enhanced lesions in the right basal ganglia and the left frontal lobe with a large mass effect and peripheral oedema.
	Figure 2. Toxoplasmosis. Post-contrast CT scan. A very large, single, ring-enhanced parieto-occipital lesion with a large mass effect and peripheral oedema.

host-defence mechanisms, contrast-medium enhancement is often poor. Enhancement is better detected with MRI because of its high contrast sensitivity; with CT, a delayed scan may detect enhancement related to dye diffusion which is more intense about an hour after contrast injection. Doubling the dose of injected contrast medium has also been proposed to improve scan sensitivity, but the poor renal function frequently

Figure 3. Toxoplasmosis. Axial gadolinium-enhanced TI MR-image. Punctiform nodular enhanced lesion is clearly seen at the left frontal corticomedullary junction. Note the ventricular enlargement.

associated with HIV infection limits this possibility.

Parenchymatous lesions
These lesions can be subdivided schematically into cerebral masses and white matter lesions.

Cerebral masses
Cerebral masses, which have as a common denominator contrast enhancement, are represented predominantly by opportunistic infections and primary CNS lymphoma. The radiological findings are often quite suggestive of the diagnosis, but the lesions may resemble one another quite closely. Therefore, disease monitoring of the lesion during an antitoxoplasma treatment test may confirm the diagnosis and should be undertaken before stereotaxic biopsy is considered.

In France, haematogeneously spread toxoplasmosis is the most common opportunistic infection. Its characteristic appearance (Fig. l) consists of multiple, bilateral, infra- and supratentorial lesions, which are most frequently found at the corticomedullary junction and in the basal ganglia. Single lesions (Fig. 2) are less common but can be observed even with MR. The diagnosis of toxoplasmosis is based on the appearance of the lesions, but their site and response to anti-toxoplasma treatment is also very important. The lesions may appear as nodular (Fig. 3) (toxoplasmic granulomas) or ring-like (Figures 1, 2) (toxoplasmic abscesses) areas, surrounded by extensive oedema with a mass effect seen even in small-sized lesions. On CT scans, the lesions are iso- or hypodense. On MR-images, the sharply-defined lesions appear as TI hypo and T2 hyperintense areas with the more hypointense centre of the ring-like lesions corresponding to the central necrosis. Most lesions are focally enhanced (Figs. 1-3). Contrast uptake, which can be absent or doubtful on CT scans, is more frequently observed on MR images, but non-enhanced lesions can be seen on MR, which probably reflects the extent of immunodeficiency. Haemorrhagic areas, usually of small-size are not rare; they are best detected on MR; they occur frequently after effective anti-toxoplasmia treatment, and thus are strongly suggestive of toxoplasmosis (in the absence of steroid treatment which can induce hemorrhagic necrosis within lymphomatous lesions).

Under anti-toxoplasma treatment, the other criteria of therapeutic efficacy include; the diminution of the volume and/or the number of lesions; the lesions can remain unchanged, but oedema and the mass effect can be reduced (without associated steroid treatment). In the absence of these findings, in the case of an initial atypical clinical presentation, if the lesions do not increase in size within 8-10 days a priori, this represents a criterion in favour of the diagnosis of toxoplasmosis and the efficacy of the treatment.

Primary cerebral non-Hodgkin's lymphoma (Fig. 4) is common, usually immunoblastic or lymphoblastic B type. It occurs in 2-5 % of cases. Early diagnosis enables the rapid initiation of radiotherapy with significant improvement in survival despite the poor overall prognosis. Lymphoma can be unifocal but, in more than 50% of the cases, lesions are multiple and their sizes vary. The masses have been described as being predominantly located supratentorially within the basal ganglia or cortex; in contrast to toxoplasmosis, the deep white matter may also be affected. Locations within the corpus callosum and caudate nucleus are also characteristic. These tumours are highly infiltrative with only moderate edema and mass effect. On non-contrast-enhanced CT they are usually heterogeneous, iso- or hypodense; on MR, their appearance is hypointense as compared to the normal brain on TI, iso- or hyperintense on T2 sequences. In the absence of steroid treatment haemorrhagic stigmata are not demonstrated. Following intravenous contrast medium administration, moderate or marked enhancement is evident; it can be homogeneous, but ring-enhancing patterns (well-delineated, quite similar

Figure 4. Primary lymphoma. Post-contrast CT scan. Large homogeneously enhanced periventricular mass with mild peripheral oedema and mass effect.

to toxoplasmosis) have been observed, sometimes with a more typical irregular serpiginous enhancement. Lymphomas characteristically exhibit a thick irregular periventricular enhancement; the alternative diagnosis is CMV encephalitis.

Cryptococcal disease (Cryptococcus neoformans) is very frequently associated with AIDS, most often presenting as cryptococcal meningitis. Cryptococcomas can also develop, but CT is often non-contributory to the diagnosis because of the weakness of the inflammatory reaction. These lesions are most likely to be seen on MR, they are often small, located in the basal ganglia or cortex, exhibit minimal oedema and mass effect and are uniquely homogeneously, but minimally, enhanced.
Other aetiologies of cerebral masses are more rarely diagnosed.

Cerebral candidiasis (Candida albicans) occurs much more frequently in the United States. CT and MR findings are similar to those described above for toxoplasmosis. Nocardial brain infection (Nocardia asteroides) is reported to show multiloculated, cystic lesions that exhibit ring enhancement with contrast. Tuberculosis is not rare, and may characteristically manifest itself as meningitis. As in non-immuno compromised patients, tuberculomas can develop, detected as nodular or ring-enhanced masses with an appearance similar to that of toxoplasmic abscesses. Tuberculous "cerebritis" displays an ill-defined TI hypointense and T2

Figure 5. HIV encephalitis. Plain CT scan. Bilateral and symmetric diffuse hypodensity in the periventricular white matter without any mass effect.

hyperintense pattern in both cortex and white matter; post-contrast studies show a diffuse, irregular gyral-like enhancement.

White matter lesions
HIV encephalitis and viral infections are the most common white matter abnormalities. Their prognosis is very poor, but their neuroimaging patterns must be recognised to enable differentiation from the other more treatable lesions.

MR is the best neuroimaging technique for evaluation of gliosis and demyelination foci due to HIV infection; the most frequently reported abnormality on CT is cerebral atrophy, rarely white matter hypodense abnormalities are observed (Fig. 5); early cerebral atrophy is considered to be a poor prognostic element. Progressive subacute HIV encephalitis, early in its evolution, appears on MR as small-sized T2 hyperintense areas that, as time passes, progressively coalesce becoming larger with ill-defined margins within the periventricular white matter. The diffuse T2 hyperintense white matter zones seen in the HIV leukoencephalopathy are bilateral and symmetric and spare the arcuate fibres. In both cases, no hyposignal is detected on T1 sequences, and the absence of a mass effect and lack of contrast enhancement are constant.

Progressive multifocal leukoencephalopathy (PML) (Papova JC virus) remains fatal. On MR, the areas of demyelination, with oedema, appear as asymmetrical, uni- or bilateral, T1 hypointense and T2 hyperintense areas. They are predominantly in the parieto-occipital regions, usually extending, with sharp margins, to the inferface between grey and white matter. They reach the paracentral regions without any mass effect or gadolinium enhancement. CT reveals hypodense lesions, but their extent is underestimated and subtle enhancement cannot be eliminated; in such cases, MR remains essential.

Cytomegalovirus infection (CMV), initially thought to be the causal agent of AIDS induces encephalitis, demyelination and neuronal lesions that are rarely detected by CT; when they are, scans show hypodense ill-defined non-enhanced areas. On MR, nodular hyperintense areas located in the basal ganglia and cortex with white matter lesions are highly suggestive of CMV when they are associated with the characteristic subependymal lesions.

Vascular lesions
Vascular lesions can be of embolic origin (endocarditis), vasculitis (tuberculosis, aspergillosis, CMV, candidiasis) can have ischaemic (vascular narrowing or occlusion) or hemorrhagic (infectious aneurysms or haemorrhagic infarcts) presentations.

Subependymal and leptomeningeal lesions
Subependymal lesions are rare and are essentially due to CMV necrotizing ventriculoencephalitis. On CT, as on MR, the ventricular interfaces are finely underlined with a characteristically enhanced border. When the lesions extend into the parenchyma, differentiation from lymphoma can become difficult and a stereotaxic biopsy may be necessary.

Although meningitis is frequently diagnosed based on clinical examination (HIV, CMV, toxoplasmosis, Candidiasis, Coccidioidomycosis, Histoplastomosis, Listeriosis ...), diffuse meningeal enhancement is rarely detected even on MR scans. In addition, tuberculous meningitis can display a more characteristic pattern as an intensely thickened basal cisternal meningeal enhancement. Cryptococcal meningitis is characterized by the presence of small cystic collections of cryptococcal organisms in the perivascular (Virchow-Robin) spaces which display focal non-enhanced areas of increased T2 and decreased TI signals in the basal

Figure 6. Lymphoma. Axial T1 MR image at the T4 level. Extensive spinal cord compression (arrows) with adjacent corporeal erosion (arrowheads).

ganglia regions. Lastly, meningeal lesions can be observed with primary lymphoma or more often with distant localizations of systemic malignant lymphoma.

Spinal pathology

Neuroimaging (particularly MRI) is essentially devoted to the detection of extradural compression of the spinal cord or its nerve roots by, for example, lymphoma (Fig. 6), immunoblastic sarcoma, plasmocytoma, metastases and more rarely, spondylodiscitis (candidiasis, tuberculosis). The clinically, frequently observed HIV myelopathy and polyneuropathies do not lend themselves to radiological diagnosis (non-specific hyperintense medullary signal, rarely thickened nerve roots).

 

Marie-France Bellin, Philippe Grenier and Nadine Martin- Duverneuil