Association of Severe Hydrocephalus With Congenital Zika Syndrome

Abstract

IMPORTANCE Hydrocephalus is a treatable but potentially fatal complication that has not been previously described in congenital Zika syndrome (CZS).OBJECTIVE To describe the clinical features and imaging findings in 24 patients with congenital Zika syndrome (CZS) who developed hydrocephalus. DESIGN, SETTING, AND PARTICIPANTSThis case series included patients with hydrocephalus who were born in October and November 2015 and followed up until mid-2017 in the 2 largest national referral centers for CZS in Brazil. The participants included consecutively enrolled children with a clinical and laboratorial diagnosis of CZS who developed clinical and/or image findings suggestive of hydrocephalus and who were confirmed to experience increased intracranial hypertension during ventriculoperitoneal shunt procedures. MAIN OUTCOMES AND MEASURESTo retrospectively describe clinical and image findings in these 24 patients. RESULTS This multicenter cohort included 308 patients with CZS; 24 consecutive children were enrolled in this study. These children were aged between 3 to 18 months, and 13 of 24 (54%) were female. All patients presented with at least 1 positive test result for anti-Zika antibodies in cerebrospinal fluid or serum and had classic signs of CZS. At the time of hydrocephalus diagnosis, only 14 of 24 patients (58%) had symptoms and signs suggestive of hydrocephalus (mainly worsening seizures, vomiting, irritability, and/or sudden increase of head circumference percentile). Two of 24 patients (8%) had no symptoms suggestive of hydrocephalus but were found to have reduced brain volume on repeated imaging. Cerebellar or brainstem hypoplasia on baseline imaging were found in 18 of 23 patients (78%). At the second computed tomographic scan, all patients showed a marked increase of ventricular volume, compatible with communicating hydrocephalus, and reduction of brain tissue that was visibly worse than on baseline imaging for the 23 patients with repeated scans. CONCLUSIONS AND RELEVANCEWe present evidence that hydrocephalus is a complication of CZS in at least a proportion of patients. The clinical spectrum of this condition continues to evolve, but given that presenting signs and symptoms of hydrocephalus can be challenging to recognize in CZS, we provisionally recommend that high suspicion and appropriate monitoring for hydrocephalus should be part of the standard care of patients with CZS.

Continuous epileptiform discharges during sleep as an evolutionary pattern in patients with congenital Zika virus syndrome

“…The clinical and neuroimaging protocol is part of a more comprehensive study, and the findings are described elsewhere. 9,11,13 The inclusion criteria were:…”

What We Can Find Beyond the Classic Neuroimaging Findings of Congenital Zika Virus Syndrome?

“…4) and are difficult to differentiate from periventricular cysts [21,[24][25][26][27][28][29][30][31][32][33][34][35]. Hydrocephalus van der Linden et al [38] described that hydrocephalus is a complication of SCZ in at least a proportion of patients. In this study, 14 of 24 children with CZVS (58%) evolutionarily followed showed signs and symptoms suggestive of hypertensive hydrocephalus, characterized by vomiting, irritability, and/or sudden increases in head circumference percentile, with 2 of these patients (8%) evolving with age-appropriate head circumference.…”

“…van der Linden et al [38] also suggested that the progressive increase in CSF pressure may contribute additional harm to the CNS and cause stretching and loss of brain mass directly as a result of both its physical compressive effect and by opposing or overcoming blood perfusion pressures. In this context, the main mechanisms that physiologically regulate the turnover of CSF (including its production at choroid plexuses, venous absorption by dural Pachionian granulations, the inflow of CSF through the periarterial pathway toward the neuropil, and the outflow of CSF and interstitial fluid throughout the paravenous vessels pathways of the lymphatic system would hardly be impaired because of the progressive regression of brain mass structures as a whole.…”

“…In this context, the main mechanisms that physiologically regulate the turnover of CSF (including its production at choroid plexuses, venous absorption by dural Pachionian granulations, the inflow of CSF through the periarterial pathway toward the neuropil, and the outflow of CSF and interstitial fluid throughout the paravenous vessels pathways of the lymphatic system would hardly be impaired because of the progressive regression of brain mass structures as a whole. Additionally, the outflow that connects the paravenous system, with the dural lymphatic system draining into deep cervical lymph nodes, would likely also be impaired by the increased hydrostatic pressure determined by the CSF constraint [38].…”

Indicators of the physical status of the patients with congenital hydrocephalus

“…У них отмечена грубая задержка психического развития, у больных с выраженной активной водянкой головного мозга диагностировалась в 2 раза меньше, чем у детей с пассивной резидуальной формой ВГ с полидисгинезиями головного мозга (P<0,01). Все данные подтверждаются и исследованиями ряда зарубежных авторов [9][10][11][12][13][14].…”