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.