Audiologic and Otologic Complications of Cryptococcal Meningoencephalitis in Non-HIV Previously Healthy Patients

Abstract

Objective: To identify audiologic and otologic outcomes in previously healthy non-HIV patients with cryptococcal meningoencephalitis (CM).

Study design: Retrospective case review of a subset of patients recruited in a prospective observational study following previously healthy individuals who developed CM.

Setting: Tertiary referral center, National Institutes of Health Clinical Center.

Patients: Previously healthy adult patients with CM without immune suppressive therapy before disease onset.

Interventions: Diagnostic evaluations included audiometry, acoustic immittance, otoacoustic emissions, and auditory brainstem response studies, in addition to neurotologic assessment.

Results: Twenty-nine patients (58 years) underwent audiologic evaluation between 6 months and 3.5 years after CM diagnosis; 21 patients were seen for longitudinal assessment with an average duration of follow up of 20.3 months. Nearly three-quarters (73%) of the cohort presented with hearing loss, most commonly (90%) sensorineural in origin. The most frequent degree of loss was mild and then moderate, although some patients had severe or profound impairment. Hearing loss improved (43%) or remained stable (38%) in most cases. Ears with internal auditory canal enhancement on magnetic resonance imaging (MRI) had significantly more hearing loss than those without enhancement, although a similar finding was not observed with gyral enhancement or the presence of ependymitis or ventricular volume expansion. Hearing loss was not associated with reduced cerebrospinal fluid (CSF) glucose, CSF total protein, cryptococcal antigen, or total cell count.

Conclusions: Hearing loss is a common manifestation of cryptococcal meningitis in previously healthy patients and may involve a cochlear or neural site of lesion, or both. Routine surveillance of hearing in patients is recommended, regardless of symptomatology, to ensure early and appropriate intervention and care.

Figure 1:

A) Audiograms representing the worse hearing threshold in 29 patients with CM, assessed at the initial complete evaluation following hospital admission. Shaded gray denotes range of normal hearing sensitivity. B) Thresholds for males at 4 kHz plotted against age- and sex-matched norms. Top black line = 95^th percentile; dashed line = 50^th percentile; bottom light grey line = 5^th percentile of ISO norms. Gray filled circles, right ear; black filled circles, left ear.

Figure 2:

Distribution of types and degree of hearing loss and ABR interpretation as indicated.

Figure 3:

Change in pure-tone hearing sensitivity by frequency from the initial to the most recent assessment in 21 patients with longitudinal hearing data. Median with interquartile range reported.

Figure 4:

Internal auditory canal (IAC) enhancement in relation to hearing (.5/1/2/4 kHz) is shown in panel A, where R positive vs. R negative U=39.5, L positive vs. L negative U=40, and Ears positive vs. Ears negative U=162. IAC enhancement with initial CSF glucose levels is shown in panel B, where IAC positive vs. IAC negative U=36.5. IAC enhancement and CSF cryptococcal antigen levels are shown in panel C, where IAC positive vs. IAC negative U=60.5 Bar indicates median with interquartile range. R, right; L, left; pos, positive; neg, negative.

Figure 5:. Clinical vignette of acute hearing loss in CM

A 49-year-old male referred with clinical deterioration despite multiple courses of Amphotericin B + 5-Fluorocystine and negative cerebrospinal fluid (CSF) cultures. He presented for initial audiometric exam on Day 1 of his admission at the NIH with c/o decreased hearing since his diagnosis of CM at an outside hospital 5 months prior (A). The following day he reported acute onset of tinnitus and vertigo. He returned to clinic on Day 3 for ABR study and reported a sudden decline in hearing, roaring tinnitus, and aural fullness, in the left ear (B). ABR study was WNL to right ear stimulation, and abnormal (retrocochlear) to left ear stimulation. He was started on oral prednisone 1 mg/kg daily and returned 1 month post-steroids with improved symptoms and hearing (C). Contrast enhanced FLAIR (left panel) and T1 (right panel) MRIs on D) day 1 and E) 30 days after oral corticosteroids. White arrow points to the 8^th cranial nerve on day 1; Blue arrow indicates the 8^th cranial nerve 30 days after pulse corticosteroids.