Clinical course. Two days after admission the patient deteriorated, with a Glasgow Coma Scale score of 14 and visual hallucinations. He was prepared for lumbar puncture and, pending results, was started on ceftriaxone, acyclovir and dexamethasone for suspected encephalitis. Tests for Salmonella, Brucella and malaria (rapid test) were negative.

The patient was continued to improve on fluconazole therapy, recovered fully, and was discharged from hospital on fluconazole therapy on day 10 of admission.

Discussion

Cryptococcus neoformans is a ubiquitous encapsulated yeast and the most common cause of CM worldwide. The first isolation of the organism was reported in 1894 by Otto Busse, who identified yeast-like cells in a sarcoma of the tibia, and independently by Abraham Buschke in the same year (6). Francesco Sanfelice isolated a morphologically similar yeast from peach juice and termed it Saccharomyces neoformans (7). In 1901, Jean Paul Vuillemin reclassified the organism into the genus Cryptococcus on the basis of its lack of ascospore formation, which distinguished it from the true Saccharomyces yeasts (8).

Cryptococcus neoformans is most classically associated with exposure to bird droppings, though the exact relationship between exposure and disease is not clear. Resultant meningitis or meningoencephalitis is thought to result from inhalation of the organism from the environment into the respiratory tract, with hematogenous dissemination to the central nervous system (CNS), possibly with tropism to the CNS by Cryptococcus (9). The proposed reasoning relates to the fact that Cryptococcus species possess multiple virulence factors that allow it to traverse the blood-brain barrier and survive in the relatively nutrient-deplete environment of the CNS (9). Entry into the body via respiratory inhalation and ability to grow preferentially in the CNS leads to simultaneous pulmonary and CNS involvement on presentation, noted among multiple case reports on our literature review.(10-11). Disseminated cryptococcus may involve multiple organ structures, with common sites including skin, lungs, eyes, and CNS, but has also been seen to affect bone and soft tissue. (10-12)^.

Clinical presentation of cryptococcal meningoencephalitis in HIV-negative individuals, according to a multicenter case study involving patients with predisposing risk factors, included headache (73%), constitutional symptoms (fever, weight loss, and night sweats; 68%), and altered mental status (42%) with predisposing factors including corticosteroid therapy (25%), solid organ transplant (15%), chronic organ failure (41%), chronic lung disease (4%), hematologic malignancies (11%), and other malignancies (5%). However, there was no significant predisposing factor reported in 30% of patients with CNS involvement. (13)^. Radiographic imaging is frequently unrevealing, though may demonstrate hydrocephalus. HIV-negative patients are, however, more likely to exhibit cryptococcoma and hydrocephalus.³ Given previously described tropism to the CNS, meningitis is the most common clinical presentation of cryptococcal disease; however, pulmonary disease may also be present.

To date, the diagnostic dilemma in cases of CM remains a significant challenge, especially in patients with no clinical features suggestive of immunosuppression. This aligns with emerging evidence showing that unexpected neurological collapse in seemingly immunocompetent individuals can resemble other acute intracranial pathologies. Previous research has demonstrated how nontraumatic brain injury in sudden and unexpected deaths may clinically mimic infectious or inflammatory neurological conditions, underscoring the diagnostic challenges in this population (14). Consequently, delays in diagnosis and treatment are usually associated with higher rates of morbidity and mortality even in immunocompetent patients. Many studies have emphasized the importance of maintaining a strong index of clinical suspicion for CM even in individuals who are immunocompetent, especially when high opening pressure is demonstrated in LP.

The antifungal strategy for CM mainly comprises three phases: induction, consolidation, and maintenance. Recent WHO guidelines in 2022 recommended a single high-dose liposomal amphotericin B in combination with other standard medications (flucytosine or fluconazole) as part of induction therapy for PLHIV, which aids in rapid sterilization of CSF due to potent fungicidal activity. In the absence of specific clinical guidelines for HIV-negative patients, we adhered to the induction regimen recommended by both the Infectious Diseases Society of America (IDSA) and the Malaysia National Antimicrobial Guideline (2024) for CM, which consists of amphotericin B and flucytosine (15).

Temporary percutaneous lumbar drain or ventriculostomy may be indicated in patients requiring recurrent daily drainage. Ventriculo-peritoneal shunt placement may also be considered for elevated intracranial pressures failing conservative management.¹⁵ Other adjunctive agents such as mannitol, acetazolamide, and glucocorticoids are not supported for lowering intracranial pressure in this setting (16) .

Conclusion

Cryptococcal meningitis without a known underlying immunocompromised state carries mortality of 12% and is often delayed in presentation due to the frequently subacute nature of symptom development. (12)

This case illustrates that cryptococcal meningitis can affect a previously healthy adult with no recognized immunocompromising condition. In a patient with persistent fever, severe headache and progressive neurological change, including altered consciousness and hallucinations, clinicians should consider cryptococcal infection early and perform lumbar puncture with CSF microscopy for the organism. In this patient, prompt CSF diagnosis and treatment with high-dose fluconazole were followed by full clinical recovery.

Acknowledgements

Not applicable.

Authors and Affiliations

Gastroenterology and Hepatology department, Damietta Fever and Gastroenterology hospital, Ministry of Health and Population, Egypt.

Abdelmoneim Elhadidy & & Emad Balah & Heba Ali Attia1& Hossam Abdelaziz Abdelshafi1& Kareem Samy Awad1,

Clinical pharmacy department, Damietta Fever and Gastroenterology hospital, Ministry of Health and Population, Egypt.

Nermeen El Ghandour

Clinical Pathology and Microbiology, Damietta Fever and Gastroenterology hospital, Ministry of Health and Population, Egypt.

Awatif Nawara , Amira Hodiehd

Authors’ contributions

All authors are responsible for the modification and giving final approval of the manuscript. Abdelmoneim Elhadidy was a contributor in writing the manuscript. All authors read and approved the final manuscript.

Funding

The authors received no funding for this study.

Availability of data and materials

Please contact the corresponding author for data requests.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.