A man in his 50s with a history of degenerative lumbar-disk and joint disease presented with headache and neck pain that had become progressively worse over the course of 8 days. The associated symptoms included nausea, malaise, fatigue, chills, and decreased appetite. The patient reported no fevers, rash, photophobia, or vision changes. Four weeks before presentation, he had received the latest in a series of epidural injections of methylprednisolone for low back pain. The patient had no history of immunosuppressing conditions and was not taking any additional immunomodulatory medications.

Table 1. Table 1. Results of Laboratory Testing.

Assessment of vital signs on presentation revealed a temperature of 36.7°C, pulse of 101 beats per minute, and blood pressure of 144/88 mm Hg. The physical examination was notable only for meningismus. Laboratory testing revealed a peripheral-blood leukocyte count of 7800 cells per cubic millimeter, with 88% polymorphonuclear cells. The remainder of the complete blood count and the comprehensive metabolic panel, including liver-function tests, were within normal limits. Computed tomography (CT) of the head without the administration of contrast material was unremarkable. A lumbar puncture was performed, and 8 ml of clear cerebrospinal fluid was removed. Analysis of the cerebrospinal fluid revealed an elevated protein level (147 mg per deciliter [reference range, 25 to 55]), low glucose concentration (31 mg per deciliter [1.7 mmol per liter], with a reference range of 45 to 75 mg per deciliter [2.5 to 4.2 mmol per liter]), and neutrophilic pleocytosis (2304 white cells per cubic millimeter; 72% polymorphonuclear cells) (Table 1). Gram's staining was negative for organisms. The patient was started on therapy with vancomycin, ceftriaxone, ampicillin, and glucocorticoids and was admitted to the hospital. Routine bacterial cultures of the blood and cerebrospinal fluid were negative, and the glucocorticoids were stopped. The patient's symptoms improved with antimicrobial therapy, as well as analgesia with opiate and nonsteroidal antiinflammatory drugs. He was discharged home to complete a course of vancomycin and ceftriaxone for presumed community-acquired meningitis.

The patient presented 1 week after discharge with symptoms of headache and low back pain that had been present and progressively worsening over the previous 2 days. On presentation, his temperature was 36.9°C and he appeared ill, uncomfortable, and agitated, with incomprehensible speech. No erythema or drainage was noted in the lower lumbar area. Neurologic examination was limited by the patient's inability to participate, but there were no gross deficits. Magnetic resonance imaging (MRI) of the brain with gadolinium contrast material revealed pial enhancement and ventriculitis; spinal imaging revealed thoracic and lumbar pial enhancement and an epidural collection at the L4 to L5 level that was less than 1 cm. A lumbar puncture was performed (Table 1). Findings included a protein level of 319 mg per deciliter, glucose concentration of 2 mg per deciliter (0.1 mmol per liter), and white-cell count of 4422 per cubic millimeter (89% polymorphonuclear cells). Treatment with intravenous vancomycin, meropenem, and levofloxacin was initiated. By hospital day 2, his mental status was markedly improved.

On hospital day 6, increased somnolence, intermittent staring spells, and a transient right facial droop developed. A head CT scan without the administration of contrast material showed mild hydrocephalus. An electroencephalogram (EEG) did not reveal seizure activity. Lumbar puncture was repeated (Table 1), and empirical treatment with liposomal amphotericin B was initiated. The following day, the microbiology laboratory reported that the cerebrospinal fluid sample from hospital day 1 of the current admission was growing Aspergillus fumigatus. Intravenous voriconazole was administered, and liposomal amphotericin B was continued. A CT scan of the chest did not show findings consistent with pulmonary fungal infection. Aspergillus antigen (galactomannan) testing from the three available cerebrospinal fluid samples was performed (Table 1). Tests for aspergillus antigen (galactomannan) in the serum were negative. A repeat MRI of the brain revealed new infarcts in the midbrain and cerebellum; examination of the paranasal sinuses was unremarkable.

Figure 1. Figure 1. Imaging Studies. Computed tomographic (CT) images of the head without the administration of contrast material, obtained on hospital day 11, show extensive hemorrhage into the fourth ventricle (Panel A, arrow) and subarachnoid hemorrhage in the perimesencephalic cistern (Panel B, dashed arrow). An angiographic image of the right vertebral artery (Panel C) shows focal segmental narrowing of the basilar artery that is consistent with vasospasm and a focal area of dilatation in the right superior cerebellar artery that is consistent with a mycotic aneurysm (arrow); a close-up view shows the mycotic aneurysm more clearly (Panel D). Diffusion-weighted images (Panels E and F) from magnetic resonance imaging of the brain performed on hospital day 16 show numerous areas of restricted diffusion (white) within cortical and deep structures, which are consistent with cerebral infarcts.

On hospital day 11, the patient abruptly became unresponsive, with rhythmic shaking of the head that was consistent with seizure activity. He was intubated and mechanical ventilation was initiated. A head CT scan showed intraventricular hemorrhage involving the lateral ventricles, subarachnoid hemorrhage in the perimesencephalic cistern, and worsening hydrocephalus (Figure 1A and 1B). An external ventriculostomy drain was placed. The results of tests performed on samples of cerebrospinal fluid are shown in Table 1. Cerebral angiographic imaging showed extensive vasospasm and focal dilatation of the right superior cerebellar artery that was suggestive of a mycotic aneurysm (Figure 1C and 1D) and was not amenable to intervention. The results of EEG monitoring were suggestive of seizure activity, and antiepileptic therapy was initiated. Findings from the repeat analysis of the cerebrospinal fluid are shown in Table 1.

Despite improving findings on cerebrospinal fluid testing and control of seizure activity, there was no meaningful neurologic recovery. On hospital day 15, a repeat brain MRI showed that additional cerebral and cerebellar infarcts had developed (Figure 1E and 1F). Given the severity of the neurologic injury, the family elected not to pursue aggressive medical intervention, and life support was discontinued. The patient died on hospital day 22, and an autopsy was performed.