An Unusual Case of Cryptococcal Meningitis in an Immunocompetent 5-Year-Old: A Case Report

Article information

Ann Child Neurol. 2026;34(1):103-107

Publication date (electronic) : 2025 December 31

doi : https://doi.org/10.26815/acn.2025.01179

Kritika Goel, MD¹, Subhalaxmi Behera, MBBS¹, Bijoy Patra, MD^,1, Hema Gupta Mittal, MD¹, Shardul Tyagi, MD², Supriya Sachan, MD³

¹Department of Pediatrics, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital, Delhi, India

²Department of Radiodiagnosis, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital, Delhi, India

³Department of Microbiology, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital, Delhi, India

Corresponding author: Bijoy Patra, MD Department of Pediatrics, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital, 501, Technology Apartment, I.P Extension, Patparganj, Delhi 92, India Tel: +98-18334525, E-mail: bijoypatra@gmail.com

Received 2025 October 15; Revised 2025 November 5; Accepted 2025 November 12.

Cryptococcal meningitis is a life-threatening fungal infection primarily caused by Cryptococcus neoformans [1], typically affecting immunocompromised individuals, particularly those with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), malignancies, or those receiving immunosuppressive therapy [2,3]. We present a rare case of cryptococcal meningitis in an apparently immunocompetent child, emphasizing its unusual neuro-ophthalmic manifestations and the diagnostic challenges encountered.

A 5-year-old male child with no prior medical or hospitalization history presented with fever, vomiting, and headache for the previous 4 months, progressive protrusion of both eyes for 2 months, and a noticeable decline in vision over the last 10 days. Fever was intermittent, reaching up to 38.89°C, and vomiting was non-bilious. The headache was continuous and localized to the bilateral frontal region. There was no history of abnormal behavior, memory disturbances, hearing loss, dysphagia, gait abnormalities, or urinary or bowel dysfunction. There was also no history of head trauma, seizures, or contact with tuberculosis or exposure to pigeon droppings or bird habitats. The child, second in birth order, was born full-term via normal vaginal delivery to a non-consanguineous couple and cried immediately after birth. He received age-appropriate immunizations, and developmental milestones were appropriate for his age.

The child was hemodynamically stable (heart rate, 86/minute; respiratory rate, 26 breaths/minute; blood pressure, 90/64 mm Hg). Growth parameters were appropriate for age (weight, 16 kg; height, 106 cm). There were no neurocutaneous markers or syndromic features. On neurological examination, higher mental functions and memory were intact. Right lateral rectus palsy was present (Fig. 1A), along with a right upper motor neuron-type seventh cranial nerve palsy. Tone and power were normal in all four limbs. Deep tendon and superficial reflexes were normal, with bilateral flexor plantar responses. Sensory examination revealed no deficits. Neck rigidity was noted. Fundus examination showed no signs of raised intracranial pressure or papilledema. Vision evaluation showed only perception of light.

Fig. 1.

(A) Right lateral rectus palsy, demonstrated by inward deviation of the right eye (esotropia) in the primary gaze position, indicating right sixth cranial nerve involvement. Mild bilateral proptosis is also evident. (B) India ink preparation of cerebrospinal fluid showing encapsulated round yeast cells of Cryptococcus neoformans, appearing as clear halos against a dark background on light microscopy (arrow). (C, D) Non-contrast computed tomography of the head demonstrating dilated lateral ventricles consistent with communicating hydrocephalus, along with periventricular hypodensities suggestive of trans-ependymal cerebrospinal fluid ooze. No focal lesions or mass effect are noted.

Based on the clinical history and examination findings, a provisional diagnosis of chronic meningitis with raised intracranial pressure was made. The child was started on intravenous antibiotics and supportive measures to reduce intracranial pressure. Further investigations were planned to identify the underlying etiology, including tuberculous meningitis, chronic bacterial meningitis, fungal meningitis, and neoplastic meningitis.

Routine laboratory investigations showed a total leukocyte count of 4,900/mm³ (54% polymorphs and 26% lymphocytes), mild anemia (hemoglobin, 9.6 g/dL; mean corpuscular volume, 76 fL), and a normal platelet count. C-reactive protein was 0.8 mg/dL. Blood cultures were sterile. Visual evoked potentials were non-recordable from both eyes. Opening pressure could not be documented during the initial lumbar puncture due to unavailability of a manometer. Cerebrospinal fluid (CSF) examination revealed 30 cells/mm³ (100% lymphocytes), protein of 30 mg/dL, and glucose of 58 mg/dL. Microscopy showed budding yeast cells, and India ink demonstrated a characteristic halo against a dark background (Fig. 1B). Non-contrast computed tomography (NCCT) revealed hydrocephalus with periventricular ooze (Fig. 1C and D). Given the suspicion of fungal meningitis, intravenous liposomal amphotericin B (5 mg/kg/day) and oral flucytosine (100 mg/kg/day in four divided doses) were started for 6 weeks (induction phase). Over the next 5 days, CSF cryptococcal antigen tested positive, and fungal culture-confirmed C. neoformans. CSF bacterial culture remained sterile. Contrast-enhanced magnetic resonance imaging (MRI) of the brain and orbits (Fig. 2) showed multiple T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities in the subcortical, periventricular, and deep white matter of the bilateral cerebral hemispheres and centrum semiovale. Dilatation of the bilateral lateral ventricles with a temporal horn width of 7 mm suggested communicating hydrocephalus. Bilateral optic nerve hyperintensities were noted in the posterior segments, consistent with bilateral optic neuritis, without contrast enhancement.

Fig. 2.

(A, B) T2-weighted axial images showing hyperintensities in the subcortical, deep white matter, and periventricular regions. (C, D) High-resolution T2-weighted axial orbital images demonstrating hyperintensities in the intra-orbital segments of both optic nerves. The dilated ventricular system, consistent with communicating hydrocephalus, is also noted (arrows).

The absence of tuberculosis contact history, normal CSF protein and glucose levels, sterile bacterial cultures, and the lack of basal exudates or mass lesions on neuroimaging made tuberculous, bacterial, and neoplastic meningitis less likely. In contrast, the presence of encapsulated budding yeast cells on India ink preparation, positive CSF cryptococcal antigen, culture-confirmed C. neoformans, and MRI findings of communicating hydrocephalus and optic nerve involvement established the diagnosis of cryptococcal meningitis.

Given the rarity of fungal meningitis in immunocompetent children, an extensive evaluation was performed to identify potential predisposing conditions. Ultrasound of the abdomen ruled out occult intra-abdominal abscesses, and otoscopic examination excluded underlying ear pathology. Thyroid function tests were performed due to the proptosis and were normal. Screening for diabetes mellitus (hemoglobin A1c, 4.7%) and viral infections (HIV, hepatitis B and C) was negative. Chest radiography was conducted to exclude pulmonary tuberculosis and disseminated cryptococcosis and was normal. Immunological evaluation revealed normal immunoglobulin (Ig) levels (IgA, 78 mg/dL; normal, 70–406 mg/dL; IgG, 748 mg/dL; normal, 748 mg/dL) and normal T-cell and natural killer cell subsets, with a marginally decreased B-cell percentage that was not suggestive of a primary immunodeficiency disorder. IgG subclass testing was unavailable.

The child showed symptomatic improvement during a 6-week hospital stay while receiving intravenous liposomal amphotericin B and oral flucytosine. He developed hypokalemia as an amphotericin B side effect, which was managed conservatively. NCCT of the head at discharge demonstrated ventricular prominence with an Evan’s index of 0.30 and no interval worsening of hydrocephalus, suggesting stable ventricular size and adequate intracranial pressure control. The child was discharged on oral high-dose fluconazole (400 mg per day) for 8 weeks (consolidation phase), followed by oral fluconazole (200 mg) for 6 months (maintenance phase), according to the Infectious Diseases Society of America 2010 guidelines (1) for cryptococcal disease (Table 1).

Table 1.

Summary of antifungal therapy phases according to the Infectious Diseases Society of America (IDSA) 2010 guidelines

A follow-up MRI after 3 months showed persistent but reduced T2/FLAIR hyperintensities in the subcortical, deep, and periventricular white matter, with mild prominence of the lateral ventricular horns and resolution of the previously observed optic nerve and chiasmal signal abnormalities. These findings indicated radiologic improvement with ongoing therapy. Clinically, the child demonstrated partial recovery of right lateral rectus function and improved visual perception, with no recurrence of symptoms or radiologic progression of hydrocephalus; therefore, surgical intervention was not required.

Cryptococcal meningitis is exceptionally rare in immunocompetent pediatric patients. Although most reported cases occur in HIV-positive or immunocompromised individuals, only sporadic cases have been documented in immunocompetent children worldwide. In a large pediatric series by Joshi et al. [4], cryptococcal infections accounted for only six cases per million pediatric hospital admissions. A Chinese study involving 34 HIV-negative children (median age 5.6 years) found that 76% had no identifiable immunodeficiency [5]. Gupta et al. [6] reported a 2-year-old boy with disseminated cryptococcosis without detectable immune defects, and a similar case was described in a 4-year-old child from Colombo [7]. In previously published cases, visual manifestations were typically restricted to papilledema or isolated cranial nerve palsies related to raised intracranial pressure [8], whereas the concurrent occurrence of bilateral optic neuritis and proptosis, as seen in our patient, has rarely been reported. Prior literature has documented visual loss due to optic nerve infiltration or edema [8,9], while proptosis is exceedingly uncommon and usually implies optic nerve sheath involvement or orbital extension resulting from severe meningeal inflammation [10].

This case therefore represents an unusual presentation of cryptococcal meningitis in an immunocompetent child, distinguished by the exceptionally rare combination of bilateral optic neuritis and proptosis. Recognition of such atypical neuro-ophthalmic signs is critical, as they may provide important diagnostic clues in children presenting with subacute meningitis and visual disturbances. Although no overt immunodeficiency was identified, emerging evidence suggests that subtle or transient immune abnormalities may predispose apparently healthy individuals to cryptococcal disease. Proposed mechanisms include defects in the interleukin-12/interferon γ (IFN- γ) signaling pathway, idiopathic CD4 lymphocytopenia, or anti–IFN-γ autoantibodies, all of which can impair macrophage-mediated fungal clearance [11]. Environmental exposure to a high fungal inoculum, such as contaminated soil or bird droppings, has also been implicated in pediatric cases without identifiable immune compromise, suggesting that overwhelming environmental exposure may exceed intact host defenses.

In our patient, early CSF analysis demonstrating encapsulated budding yeasts on India ink, together with positive cryptococcal antigen and culture results, enabled timely diagnosis. Management followed standard treatment protocols, including induction therapy with liposomal amphotericin B and oral flucytosine for 6 weeks, followed by high-dose fluconazole for consolidation and maintenance [1]. Aggressive control of raised intracranial pressure was essential to prevent further neurological deterioration.

Despite treatment, pediatric cryptococcal meningitis carries a guarded prognosis. Mortality remains high in untreated cases, and outcomes worsen with diagnostic delays or complications such as hydrocephalus or optic nerve injury. Although immunocompetent children may have more favorable outcomes than immunocompromised patients, published data remain limited.

No International Review Board approval was required to prepare this case report; ethical guidelines were strictly followed to ensure patient privacy. Written consent from the patient’s guardians was obtained before procuring photographs for educational use in a peer-reviewed medical journal.