Congenital Zika Virus Infection: a Review with Emphasis on the Spectrum of Brain Abnormalities.

PURPOSE OF REVIEW: In 2016, the World Health Organization declared the Zika virus (ZIKV) outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. Our aim is to review the clinical and neuroimaging findings seen in congenital Zika syndrome. RECENT FINDINGS: ZIKV injures neural progenitor cells in the hippocampus, a brain region important for learning, memory, cognition, and emotion/stress response. Positron emission tomography has revealed global neuroinflammation in ZIKV infection in animal models. Congenital Zika syndrome is associated with a spectrum of brain abnormalities, including microcephaly, parenchymal calcifications, malformations of cortical development and defective neuronal migration, corpus callosum abnormalities, ventriculomegaly, and brainstem and cerebellar abnormalities.

Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms.

OBJECTIVE: To provide clinical data on a cohort of 6 patients with massive expansion (>200 CAG repeats) of spinocerebellar ataxia type 2 (SCA2) and investigate possible pathways of pathogenesis using bioinformatics analysis of ATXN2 networks. METHODS: We present data on 6 patients with massive expansion of SCA2 who presented in infancy with variable combinations of hypotonia, global developmental delay, infantile spasms, and retinitis pigmentosa. ATXN2 is known to interact with a network of synaptic proteins. To investigate pathways of pathogenesis, we performed bioinformatics analysis on ATXN2 combined with known genes associated with infantile spasms, retinitis pigmentosa, and synaptic function. RESULTS: All patients had a progressive encephalopathy with autonomic dysfunction, 4 had retinitis pigmentosa, and 3 had infantile spasms. The bioinformatics analysis led to several interesting findings. First, an interaction between ATXN2 and SYNJ1 may account for the development of retinitis pigmentosa. Second, dysfunction of postsynaptic vesicle endocytosis may be important in children with this progressive encephalopathy. Infantile spasms may be associated with interactions between ATXN2 and the postsynaptic structural proteins MAGI2 and SPTAN1. CONCLUSIONS: Severe phenotype in children with massive expansion of SCA2 may be due to a functional deficit in protein networks in the postsynapse, specifically involving vesicle endocytosis.