A Myel-In, a Long Way to Go (Slides)

A 9-year-old previously healthy female with two recent admissions for presumed diagnosis of ADEM re-presented with persistent headache and ataxic gait. During her initial admissions, she presented with fever, acute onset of ataxia, facial asymmetry and abnormal eye movements. Inpatient ocular exam showed normal vision and fundus in both eyes, but her motility exam revealed right 6th and 7th nerve palsy. MRI showed dorsal brainstem and right cerebellar lesions concerning for ADEM, and additional lesions extending to the 4th ventricle with associated mass effect. After extensive negative infectious disease/rheumatology work ups, she was treated with a course of IVIG and steroids during each admission, and both times demonstrated considerable clinical response with near total resolution of her ataxia and cranial nerve deficits. Four days after 2nd discharge, she presented with symptoms of slurred speech, diplopia, ataxia and severe occipital headache. On examination, she had 20/20 vision and full visual fields bilaterally. She was noted to have new horizontal nystagmus, and right 4th, 6th and 7th nerve palsy. MRI demonstrated worsening of brainstem/cerebellar lesions, new diffusion restriction in the pons concerning for ischemic infarction, and an acute communicating hydrocephalus requiring emergent EVD placement. These new findings shifted the diagnostic focus to potential etiologies of stroke including CLIPPERS, CNS vasculitis, infection, and rheumatologic disease, though extensive work up was unrevealing, including cerebral and conventional angiogram which were normal. Given the uncertainty of diagnosis, a novel plasma detection test for microbial cell-free DNA (cfDNA) identified free DNA from Cladophialophora bantiana fungi. A brain biopsy was performed with gross visualization of intraventricular pus and black, web-like material. Histopathology confirmed branching hyphae, and fungal PCR testing was positive for Cladophialophora bantiana, which validated the cfDNA test. Anti-fungal treatment was initiated aystemically, and locally with novel intraventricular approach to directly target the ventricular fungal burden.