Persistent Cryptococcal Brain Infection despite Prolonged Immunorecovery in an HIV-Positive Patient
Table 1
The patient’s relapsing clinical course with setting, symptoms, signs, investigations, imaging, and treatment choices.
Months after 1st presentation
Presenting complaint and potential precipitant
LP results
HIV parameters
MRI results
Brain biopsy
Treatment and length of stay
3 Inpatient
Fever and meningism No obvious precipitant
↑OP/lymphocytes/protein CRAG 1 : 100 and yeast cells seen Culture negative
CD4 76 cells/L (6%) HIV VL 601 copies/mL
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Fluconazole changed to itraconazole due to MIC Steroids started and patient discharged after two week stay on slowly tapering prednisolone dose
4 Inpatient
Two focal seizures with secondary generalization. New neurological signs: RUL spastic catch, BL lower limb spasticity and ↑right plantar Patient ran out of prednisolone
↑OP/lymphocytes/protein CRAG 1 : 32 Yeast cells not seen Culture negative
CD4 67 cells/L (5%) HIV VL 95 copies/mL
Worsening right occipito-parietal focal meningeal inflammation (Figure 1(b))
Reactive gliosis and focally distended perivascular spaces containing cryptococcus (Figure 2(a)) No other organisms were identified or cultured
Itraconazole dose increased and prednisolone reinstated Lamotrigine commenced Discharged after two week in-patient stay on itraconazole, prednisolone, and lamotrigine
8 Outpatient
Asymptomatic
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CD4 190 cells/L (9%) HIV VL 40 copies/mL
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Itraconazole changed to fluconazole Prednisolone tapered by 1 mg per week
15 Outpatient
Non-attendance at clinic Self-cessation of fluconazole despite good compliance otherwise
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CD4 473 cells/L (18%) HIV VL < 40 copies/mL
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Fluconazole not restarted at this point
16 Inpatient
Left-sided focal motor seizures with secondary generalization Neurological examination normal, no headache 10/40 pregnant but miscarried
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Lamotrigine increased and clobazam added to anti-epileptic regimen Efavirenz substituted with lopinavir plus ritonavir for ↑CNS penetration Total inpatient stay of five days
17 Inpatient
Headache, nausea and increasing unsteadiness Clinical left sided dysdiadochokinesis with unsteady gait and inability to walk heel-to-toe.
First: ↑lymphocyte count (88/cu mm)/↑protein CRAG/viral screen/AAFB No observable yeast Culture negative Second: Improving lymphocyte count (14/cu mm), all else as per first LP
CD4 560 cells/L (24%) HIV VL < 40 copies/mL
Large clusters of ring-enhancing lesions and leptomeningeal inflammation in R occipito-parietal area with oedema and midline shift. Smaller clustered ring-enhancing lesions in R thalamus and L frontal and temporal lobes (Figure 1(c))
Brain biopsy showed cryptococcal, encapsulated, budding yeast forms, scattered singly with some surrounding necrosis and moderate chronic inflammation No granulomata were seen (Figure 2(b)) No other organisms were identified or cultured
Ambisome 3 mg/kg once daily, flucytosine and high dose dexamethasone commenced Ambisome/flucytosine stopped when CSF CRAG result negative Ambisome restarted without flucytosine when brain biopsy results became available One month stay, discharged on 600 mg fluconazole orally (changed to 400 mg in OPD clinic 6 weeks later) and a reducing steroid dose
40 Outpatient
Full resolution of neurological symptoms No further seizures
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Resolution of MRI features
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Self-discontinued fluconazole. Since discharge developed steroid-induced DM and avascular necrosis
