Clinical Characteristics of Patients With Neuromyelitis Optica Spectrum Disorders With Early Onset.

Neuromyelitis optica spectrum disorder is a severe and disabling disease that manifests with severe relapses of optic neuritis, longitudinally extensive myelitis, and/or brainstem syndromes. The disease is complex and, although onset typically occurs in middle age, children and adolescents may be affected. The present study adds to the literature through detailed clinical data from 36 Brazilian patients with neuromyelitis optica spectrum disorder starting before age 21. This was a retrospective assessment of medical records from 14 specialized units in Brazil. The results showed that the course of neuromyelitis optica spectrum disorder was worse in patients with disease onset before the age of 12 years. Gender and ethnic background did not influence disability accumulation. Over a median period of 8 years, 14% of the patients who presented the initial symptoms of neuromyelitis optica spectrum disorder before the age of 21 years died. In conclusion, the present study adds to the reports from other authors examining the severity of early-onset neuromyelitis optica spectrum disorder.

Auditory brainstem function in microcephaly related to Zika virus infection.

OBJECTIVE: To study the effect of prenatal Zika virus (ZV) infection on brainstem function reflected in brainstem auditory evoked potentials (BAEPs). METHODS: In a cross-sectional study in 19 children (12 girls) with microcephaly related to ZV infection, aged between 12 and 62 weeks, the brainstem function was examined through BAEPs. The latencies of wave peaks I, III, and V of the left and right ears (n = 37) were standardized according to normative data, and compared between them by 2-tailed t test. The confounding variables (cephalic perimeter at the born and chronological age) were correlated with the normalized latencies using Pearson test. RESULTS: All patients showed, in general, clear waveforms, with latencies within 3 SDs of the normative values. However, statistically increased latencies of waves I and III (I > III, p = 0.031) were observed, relative to wave V (p < 0.001), the latter being closer to respective normative value. The latency of wave I was observed to increase with age (r = 0.45, p = 0.005). The waves, in turn, did not depend on cephalic perimeter. CONCLUSIONS: These results are consistent with the functional normality of the brainstem structure and its lack of correlation with microcephaly, suggesting that the disruption produced by the ZV infection does not act in the cell proliferation phase, but mostly in the processes of neuronal migration and differentiation in the telencephalon.

Neurological manifestations of congenital Zika virus infection.

INTRODUCTION: In 2015, it was observed a rise in the number of microcephalic newborns associated with a history of non-specific febrile sickness and rash during pregnancy in Brazil. Since then, microcephaly has emerged as a public health concern. A few months after, the causal relation between congenital microcephaly and the Zika virus was discovered. Zika virus, an arbovirus, is a new TORCH member that leads to congenital infection through vertical transmission and harms the developing brain, disrupting synaptogenesis, and causing other central nervous system lesions. OBJECTIVE: The purpose of this article is to report the congenital Zika syndrome (CZS) and to emphasize the need for follow-up of the affected children to better know the evolutionary history of this new agent and to optimize the provision of healthcare and improve the quality of life of these patients. METHODS: We review the most relevant literature about clinical manifestations and neuroimaging findings related to neurotropism of Zika virus to characterize the congenital Zika syndrome and suggest the systematization of some exams and procedures to evaluate children exposed to ZIKV with or without microcephaly, according to the author's own experience. CONCLUSIONS: Vertical ZIKV infection can cause a wide spectrum of neurological manifestations that go beyond microcephaly, and even the non-microcephalic child should be followed during the first years of life, because infection may be asymptomatic or lead to neuropsicomotor delay, epilepsy, and visual abnormalities. The appropriate prospective multidisciplinary follow-up of these patients aims to understand the natural history of this new agent and to provide a better development and quality of life for them and their families.

Segmental uniparental isodisomy of chromosome 6 causing transient diabetes mellitus and merosin-deficient congenital muscular dystrophy.

Segmental uniparental isodisomy (iUPD) is a rare genetic event that may cause aberrant expression of imprinted genes, and reduction to homozygosity of a recessive mutation. Transient neonatal diabetes mellitus (TNDM) is typically caused by imprinting aberrations in chromosome 6q24 TNDM differentially-methylated region (DMR). Approximately, 15.12 Mb upstream in 6q22-q23 is located LAMA2, the gene responsible of merosin-deficient congenital muscular dystrophy type 1A (MDC1A). We investigated a patient diagnosed both with TNDM and MDC1A, born from a twin dichorionic discordant pregnancy. Parents are first-degree cousins. Methylation sensitive-PCR of the imprinted 6q24 TNDM CpG island showed only the non-methylated (paternal) allele. Microsatellite markers and SNP array profiling disclosed normal biparental inheritance at 6p and a segmental paternal iUPD, between 6q22.33 and 6q27. Sequencing of LAMA2 exons showed a homozygous frameshift mutation, c.7490_7493dupAAGA, which predicts p.Asp2498GlufsX4, in exon 54. Her father, but not her mother, was a carrier of the mutation. While segmental paternal iUPD6 causing TNDM was reported twice, there are no previous reports of MDC1A caused by this event. This is a child with two genetic disorders, yet neither is caused by the parental consanguinity, which reinforces the importance of considering different etiological mechanisms in the genetic clinic.

Ossificação pulmonar dendriforme / Dendriform pulmonary ossification

A ossificação pulmonar difusa é uma condição rara, de etiologia desconhecida, na qual osso maduro é encontrado no parênquima pulmonar. É quase sempre descoberta como um achado incidental de autópsias. Freqüentemente afeta homens de meia-idade e é assintomática. Relata-se o caso de um paciente de 75 anos, que apresentou uma radiografia torácica com comprometimento pulmonar difuso e cujo diagnóstico foi baseado no exame histopatológico de fragmento pulmonar obtido através da biópsia a céu aberto, o qual demonstrou fibrose intersticial acentuada com ossificação do parênquima pulmonar.

Diffuse pulmonary ossification is a rare condition of unknown pathogenesis in which mature bone is found in the pulmonary parenchyma. It is almost invariably discovered as an incidental finding at autopsy. Most commonly, it affects middle-aged men and is asymptomatic. We present the case of a 75-year-old man in which the chest X-ray showed diffuse interstitial infiltrate. Diagnosis was based on histopathological examination by open-lung biopsy, which revealed interstitial fibrosis with pulmonary ossification.

Dendriform pulmonary ossification.

Diffuse pulmonary ossification is a rare condition of unknown pathogenesis in which mature bone is found in the pulmonary parenchyma. It is almost invariably discovered as an incidental finding at autopsy. Most commonly, it affects middle-aged men and is asymptomatic. We present the case of a 75-year-old man in which the chest X-ray showed diffuse interstitial infiltrate. Diagnosis was based on histopathological examination by open-lung biopsy, which revealed interstitial fibrosis with pulmonary ossification.