A Cryptic Case: Isolated Cerebral Mucormycosis
Presentation
A rare infection raging within the brain of a 50-year-old African-American man was impossible to diagnose until after his death. He presented to the emergency department after the acute onset of garbled speech, confusion, right-arm weakness, and right facial droop. His medical history was significant for poorly controlled diabetes mellitus and poly-substance abuse, including intravenous drug abuse. He had never had a stroke, had no sick contacts, and had not traveled recently.
Assessment
On examination, the patient was cachectic and febrile with a temperature of 102.2°F (39°C). General examination showed no lesions of the nose, paranasal sinuses, orbits, or skin. He was drowsy but arousable to verbal stimuli, produced incomprehensible words, and did not follow any commands. Laboratory investigations disclosed hyperglycemia (blood sugar, >600 mg/dL), and a urine drug screen was positive for cocaine, opiates, and methadone. The patient was admitted to the neurointensive care unit and empirically treated with vancomycin and ceftriaxone because of concern for bacterial meningitis.
Initial noncontrast computed tomography (CT) of the head showed left basal ganglia hypodensity suggestive of subacute infarction. Brain magnetic resonance imaging (MRI) demonstrated diffusion-restricting lesions within the head of the left caudate nucleus, lentiform nucleus, and internal capsule without surrounding edema. Areas of gradient susceptibility indicated a hemorrhagic component (Figure 1). Curvilinear enhancement along the ependymal margin of the left frontal ventricle on postcontrast images indicated some degree of damage to the blood-brain barrier. Magnetic resonance angiography of the head and neck did not disclose evidence of stenosis or thrombosis of any major intracranial blood vessel.
Cerebrospinal fluid analysis indicated the presence of meningitis with an elevated white blood cell count of 513 × 103 cells/mm3 (59% neutrophils, 34% lymphocytes, 7% monocytes), a red blood cell count of 1.88 million cells/mm3, increased protein of 153 mg/dL, and low cerebrospinal fluid glucose of 54 mg/dL (serum glucose was 176 mg/dL). The following investigations were done and were negative: serial blood cultures for bacteria and fungi and serology for human immunodeficiency virus 1, syphilis, Toxoplasma species, and Aspergillusspecies. Cultures of cerebrospinal fluid were negative for bacteria, viruses, fungi. Cerebrospinal fluid, also analyzed via polymerase chain reaction, proved negative for herpes simplex viruses 1 and 2, varicella zoster virus, and Aspergillus species. Results of a transthoracic echocardiogram were normal, revealing no valvular vegetations or intracardiac masses.
Diagnosis
Despite antibiotic treatment, the patient continued to spike fevers for 2 days. Repeat MRI of the brain, obtained 48 hours after the first images, revealed a new diffusion-restricting lesion of the right basal ganglia and right parietal white matter (Figure 2). More evidence of hemorrhage was seen within the previous infarction of the left basal ganglia, and signs of hemorrhage were also seen in the right basal ganglia infarction.
Because the patient remained feverish and his condition was worsening, the neurosurgery department was consulted, and a brain biopsy was performed. Histopathology of the left frontal biopsy specimen disclosed small fragments of white matter with scattered noncaseating granulomas. It was negative for any fungal stain. Over the next 3 days, the patient rapidly deteriorated, becoming deeply comatose. He died from brain herniation 9 days after the onset of symptoms.
At autopsy, his brain was swollen without any exudate on the surface. Sections from the deep basal ganglia and thalamus were marked by extensive hemorrhagic necrosis with numerous microabscesses and small granulomas with giant cells. The tissue and giant cells were permeated with fungal hyphae, which were broad but irregular in thickness and frequently branched at right angles (Figure 3). This finding confirmed a diagnosis of mucormycosis. Sections from blood vessels at the base of the brain showed thrombosed vessels with numerous fungal hyphae. General autopsy did not show any evidence of involvement at the paranasal sinuses, orbits, pharynx, or chest, all sites that are more commonly infected.
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– Monica B. Dhakar, MD, MS, Mahmoud Rayes, MD, William Kupsky, MD, Alexandros Tselis, MD, Gregory Norris, MD
This article originally appeared in the December 2015 issue of The American Journal of Medicine.
