Alessandra Mertens Brainer-Lima

Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

Objective To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Design Retrospective study with a case series. Setting Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. Participants 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Results Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus—the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Conclusion Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem.

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.

Nonmicrocephalic Infants with Congenital Zika Syndrome Suspected Only after Neuroimaging Evaluation Compared with Those with Microcephaly at Birth and Postnatally: How Large Is the Zika Virus “Iceberg”?

BACKGROUND AND PURPOSE: Although microcephaly is the most prominent feature of congenital Zika syndrome, a spectrum with less severe cases is starting to be recognized. Our aim was to review neuroimaging of infants to detect cases without microcephaly and compare them with those with microcephaly. MATERIALS AND METHODS: We retrospectively evaluated all neuroimaging (MR imaging/CT) of infants 1 year of age or younger. Patients with congenital Zika syndrome were divided into those with microcephaly at birth, postnatal microcephaly, and without microcephaly. Neuroimaging was compared among groups. RESULTS: Among 77 infants, 24.6% had congenital Zika syndrome (11.7% microcephaly at birth, 9.1% postnatal microcephaly, 3.9% without microcephaly). The postnatal microcephaly and without microcephaly groups showed statistically similar imaging findings. The microcephaly at birth compared with the group without microcephaly showed statistically significant differences for the following: reduced brain volume, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, an enlarged extra-axial space, an enlarged cisterna magna (all absent in those without microcephaly), and polymicrogyria (the only malformation present without microcephaly). There was a trend toward pachygyria (absent in groups without microcephaly). The group with microcephaly at birth compared with the group with postnatal microcephaly showed significant differences for simplified gyral pattern, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, and an enlarged extra-axial space. CONCLUSIONS: In microcephaly at birth, except for polymicrogyria, all patients showed abnormalities described in the literature. In postnatal microcephaly, the only abnormalities not seen were a simplified gyral pattern and calcifications outside the cortico-subcortical junction. Infants with normocephaly presented with asymmetric frontal polymicrogyria, calcifications in the cortico-subcortical junction, mild ventriculomegaly, and delayed myelination.

Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis

BACKGROUND AND PURPOSE: Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. MATERIALS AND METHODS: Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. RESULTS: At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis (P = .018). CONCLUSIONS: Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent.

Follow-up brain imaging of 37 children with congenital Zika syndrome: case series study

Objective To compare initial brain computed tomography (CT) scans with follow-up CT scans at one year in children with congenital Zika syndrome, focusing on cerebral calcifications. Design Case series study. Setting Barão de Lucena Hospital, Pernambuco state, Brazil. Participants 37 children with probable or confirmed congenital Zika syndrome during the microcephaly outbreak in 2015 who underwent brain CT shortly after birth and at one year follow-up. Main outcome measure Differences in cerebral calcification patterns between initial and follow-up scans. Results 37 children were evaluated. All presented cerebral calcifications on the initial scan, predominantly at cortical-white matter junction. At follow-up the calcifications had diminished in number, size, or density, or a combination in 34 of the children (92%, 95% confidence interval 79% to 97%), were no longer visible in one child, and remained unchanged in two children. No child showed an increase in calcifications. The calcifications at the cortical-white matter junction which were no longer visible at follow-up occurred predominately in the parietal and occipital lobes. These imaging changes were not associated with any clear clinical improvements. Conclusion The detection of cerebral calcifications should not be considered a major criterion for late diagnosis of congenital Zika syndrome, nor should the absence of calcifications be used to exclude the diagnosis.

Perinatal Chikungunya Virus-Associated Encephalitis Leading to Postnatal-Onset Microcephaly and Optic Atrophy.

Chikungunya virus is capable of affecting the nervous system of children and adults. We describe a case of sepsis and encephalitis triggered by this agent in a newborn whose mother developed symptoms of acute infection 2 days before delivery. Consequently, the infant had severe encephalitis that evolved with postnatal-onset microcephaly, bilateral optic atrophy, epilepsy and cerebral palsy.

Neuroimaging Findings of Congenital Zika Syndrome

The imaging and pathological findings in congenital Zika syndrome include moderate and severe microcephaly, in as many as 75% of the cases [1], ophthalmological and auditory abnormalities [2, 3], and arthrogryposis [4]. However, these are not the only abnormalities that can be found, and the complete disease spectrum is still unknown. Some babies are born with head circumference at the lower limit of the normal range, but later progress to microcephaly. In the authors’ experience, they correspond to about 10% of microcephaly cases confirmed with positive IgM CSF (unpublished data). However, the clinical spectrum of the effects of Zika virus infection during pregnancy is not yet known.

Chiari 1 Malformation surgery: comparing non-violation of the arachnoid versus the arachnoid opening and thermocoagulation of the tonsils

OBJECTIVE Evidence is lacking concerning the myriad surgical techniques for type 1 Chiari malformation. This study evaluated the impact of arachnoid violation with tonsil thermocoagulation during surgical craniovertebral junction decompression. METHODS The evaluation included aspects of the neurologic examination and parameters of cerebrospinal fluid flow on magnetic resonance imaging during preoperative and postoperative periods. All patients underwent craniovertebral junction decompression and opening of the dura mater. Patients were divided into 2 study groups. Patients in group 1 did not undergo arachnoid violation. Patients in group 2 underwent tonsil manipulation and systematic opening of the fourth ventricle outlet. RESULTS There were 16 patients enrolled in each group (total of 32 patients). Regarding clinical improvement, there were no significant differences between groups in the postoperative period. Group 2 had more adverse events (relative risk 2.45, 95% confidence interval 1.55-3.86). In terms of cerebrospinal fluid flow parameter analyses, patients in group 1 achieved better results (P < 0.05). CONCLUSIONS For treatment of symptomatic type 1 Chiari malformation, craniovertebral junction decompression with arachnoid preservation (i.e., without tonsillar manipulation) seems more suitable than the addition of arachnoid opening and thermocoagulation of the tonsils.

Global hippocampal atrophy in major depressive disorder: a meta-analysis of magnetic resonance imaging studies

INTRODUCTION Major depressive disorder (MDD), an incapacitating mental disorder, is characterized by episodes of at least 2 weeks of apparent changes in mood, cognition, and neurovegetative functions. Many neuroimaging studies using magnetic resonance imaging (MRI) have examined morphometric changes in patients with MDD, but the results are not conclusive. This study aims to review the literature and perform a meta-analysis on hippocampal volume (HcV) in patients with MDD. METHODS Studies on HcV in patients with MDD diagnosis were identified from major databases (MEDLINE, EMBASE, The Cochrane Library, Scopus, PsycINFO, and SciELO) using the search terms depression, major depressive disorder, MDD, unipolar, magnetic resonance imaging, MRI, and hippocampus. RESULTS A meta-analysis of 29 studies fulfilling specific criteria was performed. The sample included 1327 patients and 1004 healthy participants. The studies were highly heterogeneous with respect to age, sex, age of onset, and average illness duration. However, the pooled effect size of depression was significant in both hippocampi. MDD was associated with right (-0.43; 95% confidence interval [95%CI] -0.66 to -0.21) and left (-0.40; 95%CI -0.66 to -0.15) hippocampal atrophy. CONCLUSIONS MDD seems to be associated with global HcV atrophy. Larger longitudinal follow-up studies designed to analyze the influence of sociodemographic variables on this relationship are required to yield better evidence about this topic.

Hippocampal Volume Changes in Patients with Mood Disorders: A Systematic Review of MRI Studies

Background and objectives: due to the neurotoxic effect caused by high levels of cortisol, 13 studies suggest that stress and certain psychiatric disorders, such as mood disorders, have 14 influences under the hippocampus, causing a decrease in volume and consequent memory changes. 15 This study aims to evaluate the relationship between hippocampal volume in patients with mood 16 disorders under therapy. Materials and Methods: the PRISMA protocol for systematic reviews was 17 followed. Pubmed, Cochraine and Scielo databases were searched by terms “Hippocampus”, 18 “Mood Disorders” and “MRI”, and variants in other languages, in human, from January 2011 to 19 September 2016. The individual quality of the articles was analyzed using the Cochraine modified 20 scale for clinical trials and the Agency for Healthcare Research and Quality scale for observational 21 studies. Results: all studies showed reduction of hippocampal volume in depressive patients. 22 Change in hippocampal volume is not related to the use of antidepressant. Particularly the sub23 region of the subculum is more reduced, without lateralizations. Significant relationship between 24 stress and right hippocampal reduction. The findings seem to point out: a common pathway of 25 hippocampus reduction, mediated by stress, explaining memory deficits due to depression, where 26 the cortisol pathway seems to act; alteration in the prefrontal cortex; reduction in the subiculum 27 related to inhibition of the hypothalamic-pituitary-adrenal axis, corroborating the hypothesis of 28 cortisol. Conclusions: the papers suggest: association between global hippocampal atrophy with 29 mood disorders; reduction of hippocampal subiculum; refractoriness to clinical treatment among 30 patients with lower hippocampal volume. 31