A 46-year-old man presented to the Emergency Department complaining of acute onset diplopia for one day, as well as worsening intermittent occipital headaches over the past 3 months. His medical history was significant for HIV/AIDS with most recent CD4 count 100 cells/muL and viral load 38,541 copies/mL, with poor adherence to his antiretroviral therapy regimen for the past 6 months. He also described occasional subjective fevers and drenching night sweats but denied dyspnea, cough, chest pain, or other respiratory symptoms. He denied known drug allergies, and his current medications were abacavir, dolutegravir, and lamivudine. He denied tobacco smoking or drug use and reported drinking 1-2 beers during the weekends. He worked as a truck driver and had trips across the Midwest and Southern regions of the US. Six days prior to admission he was discharged from another hospital, where he was hospitalized for chronic headaches. During that hospitalization, a lumbar puncture revealed a CSF with mild pleocytosis of monocytic predominance, normal CSF protein and glucose and negative Gram stain. He was treated with ampicillin, ceftriaxone and acyclovir empirically. CSF Herpes Simplex PCR was negative. Neuroimaging, including magnetic resonance imaging (MRI) and MR angiography of the brain were reported as unremarkable. His symptoms were attributed to an aseptic meningitis of probable viral etiology and he was discharged home off antimicrobials.
On arrival to our hospital, the patient was afebrile and hemodynamically stable and in no acute distress, with oxygen saturation 100% on room air. Cardiopulmonary and abdominal exam were unremarkable. Neurological examination revealed binocular diplopia with left ptosis, exotropia and inability to adduct the left eye. Laboratory exams were remarkable for mild leukopenia with white blood cell (WBC) count of 2.6 x 103/muL, absolute neutrophil count of 1.4 x 103/muL, and normocytic anemia. Transaminases were mildly elevated at ALT 63, AST 45. Initial computed tomography (CT) scan of the head without contrast was unremarkable. Despite concern for ischemic stroke, the patient was not a candidate for thrombolysis due to onset of symptoms being 24 h prior. A transthoracic echocardiogram was negative for thrombi or vegetations.
Given the history of headaches, subjective fevers, and AIDS, a lumbar puncture was performed on day 1, to assess for chronic meningitis. CSF study showed WBC of 8/muL and 13/muL red blood cells, with 88% lymphocytes and 10% monocytes. CSF protein was 45 gm/dL and glucose was 52 mg/dL. Gram stain was negative for any organisms. Also on day 1, a brain MRI revealed an acute lacunar infarct with restricted diffusion in the left paramidline midbrain, in the expected position of the oculomotor nerve nucleus (Fig. 2). At this point, studies were sent on serum and CSF to evaluate the suspected conditions in the differential diagnosis, including tuberculosis, endemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis), and syphilis. On further testing, a chest CT scan with contrast revealed bilateral numerous tiny miliary nodules of apical predominance, concerning for miliary tuberculosis versus fungal or malignant etiologies (Fig. 3). A bronchoscopy showed normal airways and the bronchoalveolar lavage (BAL) Gram stain revealed rare budding yeasts. The oculomotor nerve palsy resolved spontaneously over the next 4 days only with supportive therapy. Consecutive acid-fast bacillary sputum and BAL smears were negative. Eventually the results of serum, urine and CSF Histoplasma antigens returned as positive. Intravenous liposomal amphotericin B was initiated for disseminated histoplasmosis with CNS involvement for 6 weeks and the patient was then transitioned to oral itraconazole. He continued to have regular follow-ups at the infectious disease clinic after a year of treatment and had no relapses to date.
Chest CT scan with contrast revealing bilateral micronodules predominantly in the upper lung fields in a "miliary pattern" (coronal view).