Neurodevelopmental Outcomes of Neonatal Rotavirus-Associated Leukoencephalopathy

Abstract

Rotavirus infection has been reported to be associated with neonatal seizures with a diffuse and symmetrical diffusion restriction of periventricular white matter, namely, neonatal rotavirus-associated leukoencephalopathy. The extensive white matter injury seen in this cohort raises concerns about the long-term neurodevelopmental outcomes. In the present study, we prospectively assessed the neurodevelopmental outcomes of 13 patients with neonatal rotavirus-associated leukoencephalopathy at a median age of 26 months (range, 23–68 months). Neurodevelopmental outcomes were evaluated using a neurological examination, developmental evaluations, and magnetic resonance imaging (MRI) of the brain. Overall, 6 of the 13 patients (46%) had abnormal neurodevelopmental outcomes: 1 patient had mental retardation, visual–motor integration (VMI) dysfunction, cerebral palsy, and epilepsy; 1 patient had cerebral palsy and VMI dysfunction; remaining 4 patients had VMI dysfunction. Follow-up MRI in 12 of 13 patients showed an increased signal intensity on periventricular white matter in all patients. These findings suggested that neonatal rotavirus-associated leukoencephalopathy could not be assumed to be benign in long-term neurodevelopment, particularly in VMI function. Early intervention and long-term follow-up are necessary for these patients. Our findings raise caution for rotavirus infection in this vulnerable population for infants.

Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease

“…Our results support previous studies linking rotavirus-induced autoimmunity to arthritis, vasculitis, and neurologic diseases. 31 , 32 Previous studies indicated that rotavirus infection could potentially trigger autoimmunity in immune-privileged sites, 2 including the intestine, 3 , 6 pancreas, 12 , 33 brain, 12 , 13 , 14 , 26 , 32 kidney, 30 and lymph nodes. 29 , 34 Furthermore, animal studies demonstrated that rotavirus can penetrate host cells and replicate in nonenterocytes, possibly evading immune responses and systemic sequelae, 35 indicating potential associations with conditions like type 1 diabetes, 36 vasculitis, 37 and neurologic disorders.…”

“…Vaccinations have reduced the prevalence of rotavirus disease, but postinfection illnesses persist. There is also evidence linking rotavirus infection to autoimmune diseases, such as celiac disease, type 1 diabetes, pancreatitis, and neuropathy . However, previous studies had limitations in terms of controls, small sample sizes, and study design .…”

“…There is also evidence linking rotavirus infection to autoimmune diseases, such as celiac disease, 4 , 6 , 9 type 1 diabetes, 7 , 10 , 11 pancreatitis, 12 and neuropathy. 13 , 14 However, previous studies had limitations in terms of controls, 4 , 6 , 11 small sample sizes, 12 , 13 , 14 and study design. 7 , 10 , 13 While there is supporting evidence from humans and animals, clinical epidemiology studies have only provided limited support.…”

“… 13 , 14 However, previous studies had limitations in terms of controls, 4 , 6 , 11 small sample sizes, 12 , 13 , 14 and study design. 7 , 10 , 13 While there is supporting evidence from humans and animals, clinical epidemiology studies have only provided limited support. We performed a systematic literature search and analyzed a nationwide population-based database of nearly 2 million individuals to investigate the association between rotavirus-associated hospitalization and subsequent autoimmune disease, while accounting for confounding factors.…”