A 27-year-old female with a history of intravenous heroin use and chronic hepatitis C presented to the emergency department with a 10-month history of headaches and progressive bilateral vision loss. She last injected heroin 10 months prior, just before her symptoms began. She described her headaches as constant, bi-frontal, and throbbing in nature without any exacerbating or alleviating factors. She reported associated nausea with occasional vomiting, a 40-lb weight loss, and associated cervical and thoracic back pain. Additionally, she denied fevers, tinnitus, loss of consciousness, weakness, or seizures. Within the past 2 months, she developed progressive bilateral vision loss (left greater than right) and presented to an ophthalmology clinic on the day of admission, where she was diagnosed with papilledema and referred to the emergency department.
On physical examination, the patient appeared well. Her temperature was 98.3 F (36.8 C), pulse was 90 beats per min, blood pressure was 113/65 mmHg, respirations were 16 breaths per min, and her oxygen saturation was 97% on room air. Her pupils were dilated at 4 mm bilaterally. Visual acuity was 20/20 in her right eye and grade II papilledema was noted. Examination of her left eye revealed complete loss of vision and grade IV papilledema. The rest of her physical examination was unremarkable, including no evidence of neck rigidity and negative Kerning's and Brudzinski's signs. She refused a jolt accentuation test.
To further evaluate for infectious meningitis, a lumbar puncture was performed, which showed an opening pressure of 35 cm H2O. Cerebrospinal fluid (CSF) analysis revealed clear, colorless fluid, glucose of 14 mg/dL (reference range 40-70 mg/dL), a total white blood cell count of 730/mm3 (reference range 0-10/mm3) with a differential of 58% neutrophils, 30% lymphocytes and 12% monocytes, a red blood cell count of 8.0/mm3 (reference range 0.0-5.0/mm3), and protein level of 251 mg/dL (reference range 15.0-46.0 mg/dL). Additional CSF testing from the initial lumbar puncture was negative for the following tests: VDRL, flow cytometry for lymphoma, cryptococcal antigen, acid-fast bacteria (AFB) smear, GeneXpert  MTB/RIF PCR, Biofire  Filmarray  meningitis/encephalitis multiplex PCR and Gram stain without organisms present. A comprehensive metabolic panel and complete blood count with differential were normal, with the exception of an elevated aspartate transaminase of 106 IU/L (reference range 15-37 IU/L) and alanine transaminase of 152 IU/L (reference range 12-78 IU/L). Initial imaging with an MRI venogram of the head was negative for dural venous thrombosis. An MRI brain with and without contrast revealed increased leptomeningeal enhancement involving the posterior fossa and visualized proximal spinal cord (Figure 1A), concerning for tuberculosis, neurosarcoidosis, or CNS carcinomatosis. Given these findings, the patient was admitted to the hospital for treatment of suspected bacterial meningitis and infectious diseases was consulted.
The patient was empirically started on vancomycin and ceftriaxone, but antibiotics were stopped when CSF cultures remained negative at 48 hours. The patient admitted to prior incarceration and living in homeless shelters but denied Mycobacterium tuberculosis (TB) exposures. Given known TB risk factors, hypoglycorrhachia with a partial lymphocytic pleocytosis, and confirmed leptomeningeal enhancement evidenced on MRI, she was empirically started on rifampin, isoniazid, pyrazinamide, and ethambutol for potential tuberculous meningitis while additional TB tests were pending. Given her reported thoracic back pain, a subsequent MRI of her total spine with and without contrast was performed which showed diffuse leptomeningeal enhancement of the cervical (Figure 1B), thoracic (Figure 1C) and lumbar spinal cord (Figure 1D), including the cauda equina, distal pons, medulla and basal cisterns. Further, enhancing intradural extramedullary nodules at the level of T3, T7 and T10 were seen within the cord.
To further narrow the differential diagnosis, additional serum testing was performed which showed normal ACE levels, negative HIV-1/2 serologies, a negative RPR, and a negative T-spot. A repeat lumbar puncture was performed on day 5 to obtain additional CSF for repeat GeneXpert  MTB/RIF testing and CSF cultures. On hospitalization day 11, a CSF fungal culture from the second lumbar puncture grew Candida dubliniensis. A 3rd lumbar puncture was performed to repeat the CSF fungal culture, which again grew C. dubliniensis, and to obtain a CSF Beta-(1,3)-D-glucan level, which was above the limit of detection >500 pg/mL, (reference range <60 pg/mL). A diagnosis was made of C. dubliniensis meningitis.
Upon confirmation of the diagnosis of C. dubliniensis meningitis, tuberculosis treatment was stopped and intravenous amphotericin B lipid complex (5 mg/kg/day) was initiated. After 14 days of amphotericin, a repeat lumbar puncture was performed and a CSF fungal culture was negative; the CSF beta-D-glucan level had decreased to 36 pg/mL (reference range <60 pg/mL). The patient was then discharged with 4 weeks of oral fluconazole 800 mg daily to complete 6 weeks of treatment. The patient was seen 2 weeks post-discharge in the infectious diseases clinic and reported adherence to treatment and complete resolution of her headache, neck and back pain; her vision remained unchanged.