Neurocryptococcosis may present atypically, entering the differential diagnosis of rapidly progressive dementias. We report the case of a 74-year-old female patient with a prior diagnosis of rheumatoid arthritis on chronic methotrexate, with past use of sulfasalazine, hydroxychloroquine, and, four months earlier, leflunomide—suspended one month prior due to hepatotoxicity. Treatment adjustments were underway with recent initiation of golimumab. Approximately four months before hospitalization, she developed apathy, asthenia, and psychomotor slowing. In the weeks preceding admission, she showed marked cognitive decline, becoming minimally interactive, disoriented in time and space, with significant forgetfulness (e.g., names of family members), postural imbalance and requiring assistance to walk, unable to stand unsupported. She also experienced a 7-kg weight loss and sphincter incontinence. Brain MRI revealed disproportionate hippocampal atrophy and microangiopathy. Given the subacute cognitive decline, differential diagnoses included neuroinfections, autoimmune encephalitis, metabolic disorders, and nutritional deficiencies. Lumbar puncture showed inflammatory cerebrospinal fluid with 25 leukocytes/mm³ (lymphomononuclear predominance), protein 72.8 mg/dL and glucose 36 mg/dL (capillary glucose 111 mg/dL), with initially negative cultures. A repeat lumbar puncture showed worsening inflammatory parameters, and immunochromatography was positive for cryptococcal antigen, confirming neurocryptococcosis. Opening pressure was measured at all punctures without evidence of intracranial hypertension. Treatment with liposomal amphotericin B and intravenous fluconazole was initiated. The patient showed progressive clinical improvement, with partial recovery of cognition and function, remaining lucid and oriented after three weeks of treatment. Follow-up CSF still showed an inflammatory pattern with hypoglycorrhachia, requiring continued parenteral antifungal therapy. This case underscores the importance of considering fungal central nervous system infection in subacute cognitive decline, especially in patients recently started on biologic immunomodulators.
Grubert et al. (Sun,) studied this question.