(824) Acute Neurologic Changes in a 13-Month-Old With a History of Neonatal HSV and Variant in RNF213

Introduction: We report a patient with a pathogenic variant in RNF213 who presented with acute neurologic changes. She was found to have recurrent HSV encephalitis and likely secondary anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis. Although pathogenic variants of the RNF213 gene are associated with Moyamoya disease, murine models also suggest a role in the suppression of herpes viruses [Tian et al PIMD 36917666]. Emerging pathology associated with genetic variants can help critical care clinicians make comprehensive diagnostic and treatment decisions.

Description: A 13-month-old female with a history of neonatal HSV-1 encephalitis and a pathogenic variant in the RNF213 gene presented with left-upper extremity stiffening and left-sided facial droop. Her c.14429G>A (p.Arg4810Lys) heterozygous variant in RNF213 was previously identified via targeted single-gene sequencing after a sibling was diagnosed with Moyamoya disease. An MRI showed right MCA and PCA distribution infarcts, but her MRA and MRV showed no ICA stenosis or collateral vessels. She was admitted to the pediatric ICU for neurologic monitoring. Despite completing 12 months of acyclovir for neonatal HSV-1 three weeks prior to her presentation, a CSF PCR was positive for HSV-1. She completed a 21-day course of acyclovir for recurrent HSV meningoencephalitis. Repeat CSF PCR was negative for HSV-1 and she was discharged home on valacyclovir. She was readmitted four days later with left upper extremity movements and orofacial dyskinesias. A repeat CSF PCR was negative for HSV-1 but positive for anti-NMDA antibodies. After receiving IVIG, her neurologic exam improved, and she was discharged home.

Discussion: Emerging pathologic associations with known genetic variants may improve comprehensive diagnosis. Though classically associated with Moyamoya disease, murine models demonstrate that haploinsufficiency for RNF213 enhances reactivation of herpesviruses. In patients with a pathologic variant of RNF213 who present with acute neurologic changes, CNS viral reactivation should be considered in addition to Moyamoya disease. Although rare, recurrent neurologic symptoms despite treatment of HSV-1 should raise suspicion for secondary autoimmune encephalitis.