A 40-year old male with Human Immunodeficiency Virus (HIV) infection on anti-retroviral therapy presents with a two-week history of severe headache followed by fever, malaise, vomiting and confusion. A CT scan of his brain is reported as normal.
His blood CD4 count is reported as 77 cells/µL* (normal range: > 500). Cerebrospinal fluid examination shows the following:
|
Parameter |
Patient Value |
Adult Normal Range |
|
Opening Pressure |
35 cmH2O* |
12 – 25 |
|
Total protein |
0.90 g/L* |
0.15 – 0.45 |
|
Glucose |
2.1 mmol/L* |
3.3 – 4.4 |
|
White Cell Count |
48 cells/µL* |
< 5 |
|
Mononuclear cells |
42 cells/µL* |
< 3 |
|
Polymorphonuclear cells |
6 cells/µL* |
0 |
|
Gram-stain |
No organisms |
a) What is the most likely diagnosis? (15% marks)
b) What is the most appropriate anti-microbial therapy for this condition? (10%)
1. Cryptococcus Neoformans (cryptococcal) meningitis*
2. IV Amphotericin plus Flucytosine
* Although other causes infective meningitis with mononuclear preponderance (e.g. TB) are possible; headache on presentation, CD4 count < 100, CSF white cell count <50 makes cryptococcal meningitis the most likely diagnosis.
This subacute onset of meningoencephalitis-sounding symptoms could be a whole range of things in a HIV patient whose CD4 count is in the "advanced disease" range (<200). Of the possible culprits, there are several equally likely possibilities:
The normal CT makes toxoplasmosis unlikely. The non-Gram-staining CSF does not discriminate between the others two, but the lack of visible organisms (and the relatively low CSF WCC) does not favour the more routine range of community-acquired pathogens. In TB meningitis among HIV patients, the CSF sample would be expected to have a normal cell count (≤5 cells/µL), a polymorphonuclear cell predominance, and normal glucose levels (Marais et al, 2011). Moreover, cryptococcal meningitis classically presents with a very high opening pressure (Spec & Powderly, 2020). So, that's probably what this is.
Empirical management for cryptococcal meningitis is usually liposomal amphotericin and flucytosine. Super high dose fluconazole (1200mg daily) is a less effective alternative, if you prefer to sacrifice the liver instead of the kidneys.
Marais, Suzaan, et al. "Presentation and outcome of tuberculous meningitis in a high HIV prevalence setting." PloS one 6.5 (2011).
Spec, Andrej, and William G. Powderly. "Cryptococcal meningitis in AIDS." Handbook of clinical neurology. Vol. 152. Elsevier, 2018. 139-150.