Clinical and Radiological Profiles of COVID-19 Patients with Neurological Symptomatology: A Comparative Study.

Patients with COVID-19 can require radiological examination, with chest CT being more frequent than neuro-imaging. The objective is to identify epidemiological, clinical and radiological factors considered as predictors of neurological involvement in patients with COVID-19 assessed by neuroimaging and to describe the neuroimaging findings. This retrospective study was performed with 232 consecutive confirmed COVID-19 patients, from two radiological units, which were divided into two groups: (1) those who underwent a brain CT/MRI scan (n = 35) versus (2) those who did not undergo the brain CT/MRI scan, but underwent only chest CT (n = 197). There was a statistically significant difference with associations regarding the COVID-19 brain scan group for: admission to ICU, greater severity of lung injuries, the use of a mechanical ventilator and sepsis. Statistical tendency was found for chronic renal failure and systemic arterial hypertension. Forty-percent of COVID-19 patients from the brain scan group were abnormal on brain CT and/or brain MRI (22.9% of the cases with bleeding or microbleeding, 8.6% with restricted diffusion lesions). One ischemic stroke case was associated with irregularity at the M1 segment of the right middle cerebral artery. There was a case of left facial nerve palsy with enhancement of the left geniculate ganglia. An analysis of the olfactory bulbs was possible in 12 brain MRIs and 100% had enhancement and/or microbleeding. In conclusion, a more severe COVID-19 disease from ICU, a more severe form of lung disease, the use of mechanical ventilator and sepsis were associated to the COVID-19 patients with neurological involvement who had undergone brain scans. Microvascular phenomenon was a frequent finding in the brain and olfactory bulbs evaluated by neuroimaging.

Association of Severe Hydrocephalus With Congenital Zika Syndrome.

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 Participants: This 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 Measures: To 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 Relevance: We 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.

Discordant clinical outcomes of congenital Zika virus infection in twin pregnancies.

Congenital Zika syndrome is an emergent cause of a congenital infectious disorder, resulting in severe damage to the central nervous system and microcephaly. Despite advances in understanding the pathophysiology of the disease, we still do not know all the mechanisms enrolled in the vertical transmission of the virus. As has already been reported in other types of congenital infectious disorders in dizygotic twin pregnancies, it is possible that the virus affects only one of the fetuses. In this article, we report on two cases of twin pregnancies exposed to the Zika virus, but with only one of the fetuses affected with microcephaly and brain damage. This indicates the urgent need for more studies regarding the pathophysiology of viral infection and the mechanisms involved in the natural protection against the virus.

Discordant clinical outcomes of congenital Zika virus infection in twin pregnancies / Evolução clínica discordante da infecção congénita do vírus Zika em gestação gemelar

ABSTRACT Congenital Zika syndrome is an emergent cause of a congenital infectious disorder, resulting in severe damage to the central nervous system and microcephaly. Despite advances in understanding the pathophysiology of the disease, we still do not know all the mechanisms enrolled in the vertical transmission of the virus. As has already been reported in other types of congenital infectious disorders in dizygotic twin pregnancies, it is possible that the virus affects only one of the fetuses. In this article, we report on two cases of twin pregnancies exposed to the Zika virus, but with only one of the fetuses affected with microcephaly and brain damage. This indicates the urgent need for more studies regarding the pathophysiology of viral infection and the mechanisms involved in the natural protection against the virus.

RESUMO A síndrome congênita do Zika vírus é uma causa de infecção congênita emergente, resultando em graves danos ao sistema nervoso central e microcefalia. Apesar dos avanços na compreensão da fisiopatologia da doença, ainda não conhecemos todo o mecanismo envolvido na transmissão vertical do vírus. Como já foi relatado em outros tipos de infecções congênitas em gestações gemelares dizigóticas, é possível que apenas um dos fetos seja afetado pelo vírus. Este artigo descreve 2 casos de gestações gemelares expostas ao vírus Zika, onde apenas um dos fetos foi afetado, com microcefalia associado a graves danos no sistema nervoso central. Isso indica a necessidade urgente de mais estudos sobre a fisiopatologia da infecção viral e os mecanismo envolvidos na proteção natural contra o vírus.

Description of 13 Infants Born During October 2015-January 2016 With Congenital Zika Virus Infection Without Microcephaly at Birth - Brazil.

Congenital Zika virus infection can cause microcephaly and severe brain abnormalities (1). Congenital Zika syndrome comprises a spectrum of clinical features (2); however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly (3). To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceará with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference (4).

Congenital Zika syndrome with arthrogryposis: retrospective case series study.

OBJECTIVE: To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. DESIGN: Retrospective case series study. SETTING: Association for Assistance of Disabled Children, Pernambuco state, Brazil. PARTICIPANTS: Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. MAIN OUTCOME MEASURES: Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. RESULTS: The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. CONCLUSIONS: Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis. The arthrogryposis was unrelated to the abnormalities of the joints themselves, but was possibly of neurogenic origin, with chronic involvement of central and peripheral motor neurones leading to deformities as a result of fixed postures in utero. Based on the neurophysiological observations, we suggest two possible mechanisms: tropism of neurones, with involvement of peripheral and central motor neurones, or a relation with vascular disorders.