A 72-year-old Caucasian male of Italian-American descent was admitted for unremitting, severe, right frontal headache, gait ataxia, and slurred speech for the preceding five days. His past medical history was notable for insulin-dependent diabetes, hypertension, and mitral valve replacement. Social history was unremarkable; he was a retired shipyard laborer. The patient's wife denied recent travel or pets.
The history goes back ten days prior to presentation when the patient was evaluated at an outside institution for persistent headaches and gait ataxia. At that time, computed tomography of the head was negative for an acute bleed or mass. The patient was presumed to have metabolic encephalopathy and was admitted to the rehabilitation ward for further evaluation of the gait disturbance. He was transferred back to the medical ward for change in mental status and worsening encephalopathy.
Initial vital signs were notable for a maximum temperature of 101.2°F, BP 120/70 mmHg, pulse 78 beats/min., respiratory rate 20 breaths/min. Physical examination revealed a lethargic man, but who was arousable to verbal and tactile stimuli; he moved all extremities. Reflexes were intact and he followed simple commands. The remainder of the physical exam was normal.
Admission labs were notable for glucose of 225 mg/dL, creatinine of 1.4 mg/dL, ammonia level of 58 umol/L, and WBC count 14.3 × 103cells/mm3 (81% neutrophils, 10% lymphocytes). Other routine labs were unremarkable. The urinalysis showed moderate bacteruria and blood with 12-20 WBCs/hpf.
Computed tomography of the head, chest radiograph, and EKG were unremarkable. Renal ultrasound revealed normal kidneys with no evidence for hydronephrosis. Blood and urine cultures were drawn; the patient was started on intravenous ciprofloxacin, and was admitted for change in mental status secondary to urosepsis.
Over the next 48 hours, the patient began spiking fever above 101°F and became non-verbal. A lumbar puncture was conducted and revealed clear, colorless CSF, with 150 WBC/mm3 (95% lymphocytes, 5% neutrophils), 0 RBC/mm3, protein 158 mg/dL, glucose 73 mg/dL (serum level, 380), chloride 121 mEq/L. Opening pressure of the CSF was not measured. The CSF gram stain showed the presence of budding yeast and India ink stain was positive (See figure ). The patient was started on intravenous amphotercin B and flucytosine.
Figure 1 India ink preparation of cerebrospinal fluid from a patient with cryptococcal meningitis showing the budding yeast cells of C. neoformans surrounded by a characteristic wide gelatinous capsule. The yeasts also show narrow-base budding and characteristic (more ...)
Over the next few days, the patient became more responsive and mild improvement in mental status was noted. However, there was no improvement in his speech. During this time, his serum glucose remained elevated, ranging between 274 mg/dL to 364 mg/dL. The amphotericin B was changed to a liposomal formulation because of renal insufficiency. Subsequent CSF cytology revealed organisms consistent with Cryptococcus neoformans. The CSF culture was also positive for C. neoformans. The CSF cryptococcal antigen titer using latex particle agglutination was over 1:1024. Further testing for Lyme antibodies and HIV antibodies was negative. An echocardiogram revealed normal left ventricular size and function with no vegetations. Blood and urine cultures were negative. The antifungals were continued.
By hospital day 10, the patient became more arousable to verbal and tactile stimuli and would answer simple questions. However, he remained lethargic and febrile. The WBC count remained elevated at 13.9 × 103/mm3, with 89% granulocytes. The serum glucose was 263 mg/dL and continued to be uncontrolled. A repeat CT head showed the new development of moderately enlarged third and lateral ventricles consistent with mild communicating hydrocephalus. A repeat lumbar puncture was recommended to assess the CSF opening pressure. While the LP was being attempted, the patient became cyanotic and unresponsive. The patient was emergently intubated and advanced cardiac life support was started. The initial cardiac rhythm was asystole, which with ACLS became a wide complex bradycardia, then subsequently ventricular fibrillation and finally refractory asystole. Despite aggressive attempts at resuscitation, the patient expired.
An autopsy was conducted. The CNS examination revealed findings consistent with cryptococcal meningitis affecting the basal leptomeninges, which were opaque and thickened. Furthermore, there was reactive connective tissue obstructing the outflow of CSF consistent with hydrocephalus. There was marked cerebral edema with uncal grooving and midbrain compression. Sections of the brain showed numerous areas of tissue destruction and gelatinous, mucoid material within the subarachnoid space. The meningeal exudate consisted of chronic inflammatory cells along with cryptococci. Some sections of the brain also disclosed macrophages and multinucleated giant cells indicating granulomatous inflammation. The cause of death was herniation of the cerebellar tonsils through the foramen magnum with subsequent impaction and acute compression of the medulla oblongata causing respiratory and circulatory arrest. There was no evidence of acute myocardial infarction or pulmonary embolism.