In December 2016, a 59-year-old man who had suffered from headaches, slowdown in speech, inability to walk, and weakness was admitted to the hospital. On examination, his body temperature was 37.2  C, with blood pressure 140/80 mmHg, a heart rate 84 beats/min, and respiratory rate 24 breaths/min. His neurological and fundoscopic examination were normal. Cranial MRI revealed bilateral cerebral-cerebellar multiple millimetric gliotic lesions and leptomeningeal enhancement. Based on the radiological appearance, infectious pathologies, lymphoma, or vasculitis were considered presumptively in the differential diagnosis (Fig. 1A). Lumbar puncture (LP) was performed, and the appearance of cerebrospinal fluid (CSF) was clear. The other CSF findings were as follows; the opening pressure (OP) of 19 cmH2O, total leucocyte count (TLC) of 302/muL (polymorphonuclear 5%, lymphomononuclear 95 %), protein 113 mg/dL, glucose 30 mg/dL, and simultaneous blood glucose level 147 mg/dL. CSF lymphoma, paraneoplastic panel, Mycobacterium tuberculosis PCR and Cryptococcus neoformans with India ink were all negative. The acute ischemic cerebrovascular event was determined by cranial MR imaging and acetylsalicylic acid was ordered (Fig. 1B). The patient's clinical condition slightly improved day by day, but his headache did not remit.
Eight months later, the patient presented with a slowdown in speech, sleepiness, and weakness. His neurological examination was unremarkable except for dysarthria and inability to walk. For the stroke etiology, we re-evaluated the cardiac source and large vessel occlusion, but we found all these sources in the normal range. Cerebral digital subtraction angiography was performed and left anterior cerebral artery segment A1, and right posterior cerebral artery segment P1 was reported as hypoplastic. Based on the acute multiple ischemic lesions in diffusion-weighted imaging and the clinical status of the patient, the vasculitis was presumptively diagnosed. Therefore, seven days of pulse steroid and one-day of cyclophosphamide treatments were given. The next day, fever was detected as 38.1  C without headache and neck stiffness. We performed lumbar puncture (LP) which revealed an increased OP of 23 cmH2O, with leucocyte count of 193 u L (polymorphonuclear 67 %, lymphomononuclear 32 %), protein 313 mg/dL, glucose 11 mg/dL, simultaneous blood glucose 101 mg/dL and therapeutic CSF drainage was performed due to high OP. Biofire Film Array Meningitis/Encephalitis panel was positive for Cryptococcus neoformans/gattii. On microscopic examination of CSF, cryptococcus-like encapsulated yeasts were demonstrated with India ink (Fig. 2).
Liposomal amphotericin B (AmB) 5 mg/kg and fluconazole 800 mg/day were started immediately (flucytosine was not available in Turkey). Seven days later Cryptococcus neoformans was grown in CSF culture. A thorax tomography revealed no evidence of lung disease suggesting pulmonary cryptococcosis. The lesions in the previously performed cranial imaging were interpreted as cryptococcoma (Fig. 1C). The patient had not any known immune-suppressive disease or well-known risk factors for cryptococcosis. At the beginning of his hospitalization, a pulse steroid and cyclophosphamide were given with the suspicion of CNS vasculitis. HIV testing was negative and CD4 count was found in normal range for twice (1004-33% and 630-31%, respectively). On day 17 of treatment, LP was repeated and C.neoformans/gattii was positive in the Biofire FilmArray meningitis panel but yeast culture was negative. His clinical condition of the patient was improved partially after twenty days with consciousness, ability of walking, and speaking improving. At the end of six weeks of AmB treatment, it was withdrawn, and the patient was discharged with fluconazole for maintenance treatment.
Two weeks later, while the patient was taking 800 mg/day fluconazole, he presented with a deterioration of the general condition, confusion, aphasia. Cranial MRI was performed and the triventricular hydrocephaly was detected (Fig. 1E). Antiedema treatment was started and flucytosine was supplied. The antifungal treatment was started over again with flucytosine and AmB. Eight weeks later, induction treatment was stopped and switched to fluconazole. Fluconazole was given fifteen months totally for maintenance and consolidation therapy. His clinical condition was improved completely, and cranial imaging showed regression of previous lesions (Fig. 1F). After 8 months of finishing antifungal drugs, his condition was good and stable without any neurological findings or symptoms.