CNS Lesions and HIV

Recently in Morning Report at both TGH and TWH, we heard about cases in which patients with HIV presented with CNS symptoms consistent with meningitis. In each case, we had a discussion about the differential diagnosis for space occupying lesions in the brain in patients with HIV. 

To CT Head or not to CT Head?

First, let's start off with an overview: Which patients presenting with signs and symptoms of meningitis require a CT Head prior to LP? Keep in mind that the purpose for the CT Head is not to diagnose meningitis, but to make rule out contraindications for LP, namely increased ICP due to a mass/bleed in the brain. Performing a CT Head should not delay the initiation of treatment - antibiotics should be started prior to the completion of a CT Head in those where indicated:

                       

The following risk factors are listed in the IDSA recommendations because these patients are more likely to have space-occupying lesions:

                              

As you can see, one of the indications to performing a CT Head prior to LP is HIV, due to the higher than average probability that patients will have a space-occupying lesion. These lesions can all also present with fever, seizure, focal neurological deficits, and decreased LOC. If one is found, what is the differential for such a mass? There are 3 main differentials:

1) Toxoplasmosis - Usually multiple ring-enhancing lesions. Seen in patients with a CD4 count less than 100 and localized to frontal or parietal lobes (corticomedullary junction), and basal ganglia.

2) Primary CNS Lymphoma - Single or sometimes multiple homogeneously or ring-enhancing lesions near the subependymal surfaces. Lesions that cross the corpus callosum are suspicious for this diagnosis.

3) Abscess - Ring-enhancing capsule with central low attenuation (pus) in the late capsular stage of abscess formation. Most common pathogens include Staphylococcus, Streptococcus, Aspergillus, and Nocardia. Rarely, but more often than in non-HIV patients, the lesions can include cryptococcomas, tuberculomas, and syphillis (gummas).

 

       CNS Lymphoma in an HIV patient

                                                                                   Abscess in an HIV patient

What do I do next?

Investigate!

If a space-occupying lesion is found, the next step in management may include performing an MRI to better delineate the etiology of the lesion (e.g. abscess vs. lymphoma). A biopsy (the gold standard) may also be required, depending on the clinical status of the patient. Less invasive testing may also help differentiate the problem - such as serum and CSF analysis. Once an LP can safely be done, helpful CSF tests include bacterial cultures, fungal cultures, AFB staining, PCR for JC virus/Toxoplasmosis/EBV, cryptococcal antigen, VDRL, and opening pressure (may be high in cryptococcal meningitis). 

Treat!

Again, antibiotic therapy should not be delayed when a suspected CNS infection is found, and empiric therapy in an HIV patient may include ceftriaxone (to cover usual meningitis organisms), flagyl (protozoal infections), pyrimethamine and sulfadaizine (both to treat toxoplasmosis), and possible quadruple therapy for suspected CNS TB.

One last point...

Keep in mind that not all infections of the CNS in HIV patients will present with large masses and mass effect. Some will be seen as white matter changes on MRI with no mass effect:

1) PML- Demyelinating disease due to the JC virus. Can present with rapidly progressive focal deficits such as hemiparesis, field deficits, ataxia, and aphasia. Asymmetric multifocal demyelination.

2) CMV encephalitis - seen in patients with CD4 counts less than 50. Periventricular white matter changes with possible enhancement.

3) HSV encephalitis -  Affects the medial temporal lobes, insular cortex, and inferolateral frontal lobes along with the brain stem.

4) HIV encephalopathy -  Present with memory and psychomotor slowing, depression, movement disorders. Symmetric periventricular white matter changes, possibly with cerebral atrophy.

But wait, there's more....

There are also some entities which have no CNS lesions on imaging, such as any cause of meningitis (eg. bacterial, TB, cryptococcal) and neurosyphillis. 
Ok. All done!

Resources:

A recent NEJM article reviewed the management of brain abscess in HIV and non-HIV patients.
Click here for IDSA Guidelines for Meningitis from 2004.