Case Presentation: A 65-year-old man presents with five days of altered mental status, ataxia, and headaches. Four months prior, he traveled to Arizona. Soon after, he sought care for sinus pain, cough, weight loss, and diplopia. Lumbar puncture (LP) at the time showed 492 white blood cells (WBCs)/μl (80% lymphocytes), protein 509 mg/dL, and glucose <20 mg/dL. Cerebrospinal fluid (CSF) bacterial and fungal cultures, and viral and Lyme PCRs were negative. He was treated with IV ceftriaxone for presumed Lyme meningitis with no improvement. Brain MRI showed non-specific perimesencephalic enhancement. PET scan showed uptake in mediastinal, hilar, and axillary lymph nodes. Lymph node biopsy showed non-necrotizing granulomas. He was diagnosed with multisystem sarcoidosis and started on prednisone although ANA was negative. Upon arrival, vital signs are notable for fever, tachycardia, and hypotension. LP shows 272 WBCs/μl (55% lymphocytes), total protein 1260 mg/dL, and glucose 4 mg/dL. CT head shows midline shift and ventriculomegaly. CT chest shows diffuse reticulonodular opacities. Workup returns positive for blood and CSF coccidiodies antibodies. Bronchial washings, mycolytic blood cultures, and CSF cultures grow coccidiodies immitis/posadasii. He is treated with fluconazole and amphotericin. Pathology from time of diagnosis with sarcoidosis is reviewed, showing rare fungal forms, consistent with coccidioidomycosis. Unfortunately, the patient develops multiple strokes and care is transitioned to comfort measures only.
Discussion: Altered mental status is a common diagnosis encountered in hospital medicine, with over 50% of emergency room visits for this being admitted for further workup. If routine chemistries and toxicology screen are unrevealing for the cause, imaging and LP should be pursued. In our patient, CSF studies were concerning for fungal meningitis given pleocytosis with a lymphocytic predominance, low glucose, high protein, and a negative gram stain. In addition, hydrocephalus was seen on imaging, which can occur in 50% of coccidioidal meningitis cases. In these patients, a thorough travel history should be obtained and CSF fungal cultures, antibodies, and antigen testing for cryptococcus, coccidioides, and histoplasma should be evaluated. Cytology should also be performed, as these findings can be seen in metastatic malignancy. In our patient, only a fungal culture was sent, which returns positive in only 15% of coccidioidal meningitis cases and can take weeks to grow. If coccidioidal meningitis goes untreated, it is lethal within two years in 95% of patients.
Conclusions: 1) Pursue lumbar puncture early in a patient presenting with altered mental status without a clear cause.2) Consider fungal meningitis or metastatic malignancy in patients whose CSF profile consists of low glucose, pleocytosis, and high protein.
3) Travel history can affect pre-test probability for fungal meningitis. For example, coccidiodies is endemic in Arizona, where our patient traveled before becoming ill.
4) Fungal meningitis carries a high mortality rate. Clinicians should be diligent in ruling out fungal meningitis with fungal antigens and antibodies, in addition to fungal cultures, given the low sensitivity of cultures alone.