Neuroimaging of CNS involvement in HIV.

AuthorDescamps, M.J.L.
PositionLEADING ARTICLE - Central nervous system - Report

Introduction

Central nervous system (CNS) involvement in HIV infection has a significant associated morbidity and mortality if not recognised early. One-third of AIDS-defining illnesses involve the CNS and 40% of patients with HIV suffer from neurological symptoms [1]. Neuroimaging is crucial in these patients, where characteristic imaging features not only enable detection, diagnosis and initiation of treatment but are also used to verify treatment response and to guide brain biopsy.

Since the introduction of highly active antiretroviral therapy (HAART), HIV/AIDS has become a chronic disorder with marked reductions in mortality and morbidity, not only from the virus itself but also from opportunistic infections and tumours. However, HAART has led to a number of complications not previously seen in HIV medicine, and including immune reconstitution syndrome (IRIS) [2].

In this review we describe the major imaging findings of CNS involvement in HIV-infected patients. For the purposes of the review, conditions of the CNS in HIV-positive patients are subdivided into the following categories:

* Direct effects of HIV;

* Opportunistic infections in the immunocompromised host;

* CNS tumours;

* Cerebrovascular complications;

* Effects of treatment with HAART.

There are often multiple coexisting pathologies (or layers) in the CNS [3] where treatment may not produce the expected clinical benefit. In addition, unmasking of a subclinical condition by a new insult is often seen. For example, subclinical HIV encephalopathy may be unmasked by cryptococcal infection such that the patient develops symptoms of HIV encephalopathy rather than cryptococcal symptoms [3].

Direct effects of HIV

At seroconversion, up to 70% of HIV-infected individuals can have a symptomatic glandular fever-like syndrome, which in 10% of these cases is associated with neurological symptoms and signs such as aseptic meningitis, encephalitis, acute disseminated encephalomyelitis, transverse myelitis, polymyositis, brachial neuritis or a cauda equine syndrome [4].

HIV encephalopathy is part of the acute HIV syndrome during seroconversion whereas AIDS dementia complex, also known as HIV-associated dementia complex, is characterised by cognitive, motor and behavioural features in advanced AIDS when the CD4 lymphocyte count falls below 200 cells/[mm.sup.3]. In the post-HAART era, the incidence of HIV dementia has fallen from 21 cases per 1000 person-years to 10.5 cases per 1000 person-years in the USA and a less severe dysfunction, minor cognitive motor disorder, has become more common [5].

The virus can affect all cell types in the brain, causing glial and neuronal degeneration, and is found most commonly in the white matter, especially the deep white matter of the centrum semiovale [6], followed by the subcortical grey matter and much less commonly in the cortical grey matter.

Imaging studies can support the diagnosis of AIDS dementia complex and can exclude other neurological opportunistic infections or neoplasms. The most common finding is diffuse cortical atrophy, often occurring before there are clinical symptoms [7]. However, even in severe HIV infection, atrophy is often not seen [8,9]. T2-weighted magnetic resonance sequences demonstrate hyperintense white matter lesions in a periventricular distribution with particular involvement of the centrum semiovale (Figure 1) [8]. In the early stages, the lesions tend to be patchy and can be very subtle with ill-defined borders. As the disease progresses they become more diffuse and can involve large areas of the cerebral white matter, thereby mimicking advanced stages of multiple sclerosis or small vessel ischaemic disease [10]. Infection of the brain with cytomegalovirus (CMV) can produce a pattern indistinguishable from the above.

Recent advances in neuroimaging techniques have enabled detection of selective patterns of brain deficits in HIV-infected patients with cognitive impairment. Diffusion abnormalities in the splenium of the corpus callosum in patients infected with HIV correlate with dementia severity and deficits in motor speed [11]. High-resolution imaging has revealed decreased cortical grey matter thickness of 15% in primary sensory,motor and premotor cortices in patients with AIDS [12], which in another study correlated with cognitive impairment and the CD4 T-lymphocyte depletion [13]. Recently, decreases in caudate blood flow and volume have been shown to be significantly associated with increasing HIV-associated neurocognitive impairment [14].

Opportunistic infections in the immunocompromised host

ToxoplasmosiS

Toxoplasmosis is the most common opportunistic central nervous system (CNS) infection and the most common cause of a space-occupying lesion in AIDS patients [15]. Approximately 30% of HIV-positive people will develop toxoplasmosis encephalitis at some point in the illness [16], usually from reactivation of latent infection.

Toxoplasmosis produces necrotising encephalitis. Lesions are usually multiple and bilateral but may be solitary. They are found within the brain parenchyma, spreading to the meninges, but widespread meningitis is rare. Lesions are typically supratentorial, mainly at the corticomedullary junction (as a result of haematogenous spread), the basal ganglia or the thalamus. Infratentorial (especially cerebellar) lesions are also seen [17].

Non-enhanced CT demonstrates rounded masses that are isodense to grey matter with oedema and mass effect. Occasionally these masses are hyperdense due to haemorrhagic necrosis [1]. The lesions may show nodular homogeneous enhancement or ring enhancement, unless the patient has a very low cellular immunity in which case there may be no enhancement (CD4 cell count

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

MRI is more sensitive than CT in detecting toxoplasmosis lesions. On T1-weighted sequences the lesions are hypo- or isointense to grey matter and on T2-weighted sequences they are hyper- or isointense to grey matter (Figure 2a). Early in therapy the lesions tend to be hyperintense in T2-weighted sequences due to necrosis, becoming isointense after many weeks of treatment. Contrast enhancement is seen in the majority (Figure 2b) although ring enhancement may be minimal and ill defined if the CD4 cell count is low. It is very rare to detect no abnormality on MRI. There is usually surrounding vasogenic oedema and satellite lesions may also be present [1].

Ventricular enlargement is often associated with CNS toxoplasmosis and this may be due either to atrophy or hydrocephalus (communicating or non-communicating) [6]. Rare manifestations include toxoplasmosis myelitis but there are usually coexistent brain lesions. The spinal cord demonstrates homogeneous contrast enhancement [19,20].

The main differential of toxoplasmosis is primary CNS lymphoma (PCNSL), which is more likely if the lesions are located in the basal ganglia or if there is subependymal spread of periventricular lesions. PCNSL may show variable enhancement (especially ring enhancement) and microhaemorrhage [6].

Magnetic resonance spectroscopy can aid in the diagnosis, with toxoplasmosis demonstrating an increase in the lipid and lactate peaks and a decrease in other metabolites. PCNSL demonstrates a marked increase in the choline peak as it is the more cellular of the two [21]. Diffusion-weighted imaging (DWI) may also help in the differential diagnosis of cerebral toxoplasmosis: there is more restriction of water diffusion in the core of a pyogenic abscess than in a toxoplasmosis lesion [22] and there are significantly higher apparent diffusion coefficient values in toxoplasmosis lesions than in PCNSL [23]. In spite of all these imaging differences, assessment of response to empiric therapy may be the only way to diagnose a toxoplasmosis lesion definitively.

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