PATIENT 1
A 2-year-old female with standard risk B-cell acute lymphoblastic leukemia (B-ALL) and CNS leukemia at diagnosis developed myoclonic twitching during week 22 of continuation chemotherapy. She became increasingly somnolent, irritable, and developed bouts of agitation, difficulty in walking, inability to communicate, and dysphagia. A magnetic resonance imaging (MRI) of the brain demonstrated cerebral volume loss and a nonspecific ill-defined FLAIR hyperintensity in the cerebral white matter. Electroencephalogram (EEG) showed diffuse slowing. CSF bacterial and fungal cultures were negative (Supplemental Table 1). PCR panel did not detect micro-organisms, autoimmune panel resulted negative, and cytology showed no evidence of leukemia. For presumed autoimmune encephalitis, she was treated with intravenous immunoglobulin (IVIG) with no improvement. CSF m-NGS resulted positive for HAstV-VA1. Management was based on a previously published case11 and included ribavirin, methylprednisolone, IVIG and Peg-INF-alpha 2b. In addition, we added oral nitazoxanide due to its efficacy in vitro against HAstV-VA1.19,20 Due to side effects, Peg-INF-alpha 2b was discontinued after 3 doses. (Supplemental Fig 1)
To further optimize her treatment, we tested 9 lots of IVIG for HAstV antibodies and did not find any significant difference (Supplemental Fig.2A). None showed significant viral neutralization (Supplemental Fig.2B, 2C).
MRI demonstrated T2 prolongation in thalami and restricted water diffusion consistent with acute necrotizing encephalitis that improved over time. (Fig.1) She was discharged after 108 days of hospitalization on PO ribavirin, nitazoxanide and IVIG. Her chemotherapy was held and restarted 15 days after astrovirus treatment initiation. Dexamethasone and vincristine were omitted from therapy to prevent further CNS damage. She was treated for astrovirus infection for approximately 8 months (Supplemental Fig.1) and has shown gradual yet significant neurologic improvement. At her most recent follow up, 16 months after diagnosis, she could socially interact but was minimally verbal, remained without seizures with improving hypertonia, and demonstrated clinical improvement even after stopping astrovirus directed therapy.