Cerebellofaciodental syndrome in an adult patient: Expanding the phenotypic and natural history characteristics.

Cerebellofaciodental syndrome is characterized by facial dysmorphisms, intellectual disability, cerebellar hypoplasia, and dental anomalies. It is an autosomal-recessive condition described in 2015 caused by pathogenic variants in BRF1. Here, we report a Brazilian patient who faced a diagnostic challenge beginning at 11 months of age. Fortunately, whole-exome sequencing (WES) was performed, detecting the BRF1 variants NM_001519.3:c.1649delG:p.(Gly550Alafs*36) and c.421C>T:p.(Arg141Cys) in compound heterozygosity, thus finally achieving a diagnosis of cerebellofaciodental syndrome. The patient is currently 25 years old and is the oldest patient yet reported. The clinical report and a review of published cases are presented. Atlanto-occipital fusion, a reduced foramen magnum and basilar invagination leading to compression of the medulla-spinal cord transition are skeletal findings not reported in previous cases. The description of syndromes with dental findings shows that such anomalies can be an important clue to relevant differential diagnoses. The cooperation of groups from different international centers made possible the resolution of this and other cases and is one of the strategies to bring medical advances to developing countries, where many patients with rare diseases are difficult to diagnose definitively.

Brain abnormalities in myelomeningocele patients.

BACKGROUND: Myelomeningocele (MMC) is often related to hydrocephalus and Chiari malformation (CM) type 2; however, other brain abnormalities have been reported in this population. In order to better understand and quantify other forebrain abnormalities, we analyzed magnetic resonance imaging (MRI) of MMC patients treated in utero or postnatal. METHODS: Between January 2014 and March 2017, 59 MMC were treated in our hospital. Thirty-seven patients (32 postnatal and 5 intrautero repair) had brain MRI and were enrolled at the study. MRI was analyzed by two experienced neuroradiologists to identify the supra and infratentorial brain abnormalities. RESULTS: A wide range of brain abnormalities was consistently identified in MMC patients. As expected, the most common were hydrocephalus (94.5%) and CM type II (89.1%). Of note, we found high incidence of corpus callosum abnormalities (86.4%), mostly represented by dysplasia (46%). CONCLUSIONS: The data are consistent with the concept that brain abnormalities related to MMC can be both infratentorial and supratentorial, cortical, and subcortical. More studies are needed to correlate these forebrain abnormalities to long-term functional outcome and their prognostic value for these patients.

Cerebrovascular Anomalies in the Fetus.

Four distinct vascular anomalies can be seen to affect the brain on fetal imaging: vein of Galen malformations, nongalenic arteriovenous pial fistulas, dural sinus malformations, and intracranial venous malformations. These congenital disorders affect the arteries and veins of the developing brain and are rarely seen beyond the neonatal stage. The 4 fetal cerebrovascular anomalies are associated with quite disparate natural histories and prognoses. MRI plays a pivotal role in the evaluation of fetuses with these conditions because of its ability to definitively establish the diagnosis, to detect subtle parenchymal injuries, to delineate the course of abnormal vessels in detail and to some extent the nature of vascular flow, and to identify ischemic, thrombotic, and hemorrhagic complications. Recently, an investigational transuterine embolization procedure targeted at treating fetuses with vein of Galen malformations who are at high risk for neonatal decompensation has emerged as a promising alternative to expectant management and postnatal embolization, with imaging being used to identify suitable patients for the intervention and in preprocedural planning. This manuscript reviews the essential imaging and clinical features of these 4 fetal neurovascular anomalies and underscores the practical aspects related to counseling, prognosis, and the multidisciplinary management of these entities.

Methylene Blue and Blood Transfusion in Hemorrhagic Shock Resuscitation: An Experimental Porcine Study.

INTRODUCTION: Hemorrhagic shock requires immediate treatment to prevent mortality and organ dysfunction. This study evaluates the efficacy of methylene blue (MB) with blood transfusion (BT) as a potential rescue therapy in acute severe bleeding in pigs. METHODS: Thirty animals were randomly assigned to one of six groups following the induction of fixed-pressure hemorrhagic shock, after reaching a mean arterial pressure (MAP) of 55 mmHg - Group 1 (60 BT: BT after 60 minutes), Group 2 (60 MB: MB infusion after 60 minutes), Group 3 (60 MB + BT: MB and BT after 60 minutes), Group 4 (15 MB + BT: MB and BT after 15 minutes), Group 5 (15 BT + 60 MB: BT after 15 minutes and MB infusion after 60 minutes), and Group 6 (15 MB + 60 BT: MB infusion after 15 minutes and BT after 60 minutes). Hemodynamic and blood gas parameters were meticulously recorded, reversal of the shock was considered when MAP reached 90% of the baseline MAP. RESULTS: Except for Group 2, all groups reverted from the shock. However, groups that received MB in combination with BT, specifically Groups 3 and 4, exhibited statistically significant higher ratios of maximum MAP to baseline MAP. CONCLUSION: Using MB concomitant with BT allowed the reversal of hemorrhagic shock with higher median arterial pressure levels compared to BT alone or applying MB separately from BT. This suggests that simultaneous application of MB and BT could be a more effective strategy for reversing the effects of severe acute bleeding.

Brain Spectroscopy Analysis in Retired Soccer Players With Chronic Exposure to Mild Traumatic Brain Injuries.

Soccer players are at risk of suffering cranial injuries in the short and long term. There is growing concern that this may lead to traumatic brain injury in soccer players. Magnetic resonance spectroscopy (MRS) is an analytical method that enables the measurement of changes in brain metabolites that usually occur before significant structural changes. This study aimed to use MRS to compare variations in brain metabolite levels between retired soccer players and a control group. Twenty retired professional soccer players and 22 controls underwent magnetic resonance imaging, including MRS sequences and Mini-Mental State Examination (MMSE). Metabolite analysis was conducted based on absolute concentration and relative ratios. N-acetyl-aspartate, choline, glutamate, glutamine, and myoinositol were the metabolites of interest for the statistical analysis. Retired soccer players had an average age of 57.8 years, whereas the control group had an average age of 63.2 years. Median cognitive evaluation score, assessed using the MMSE, was 28 [26-29] for athletes and 29 [28-30] for controls (p = 0.01). Uni- and multi-variate analyses of the absolute concentration of metabolites (mM) between former athletes and controls did not yield any statistically significant results. Comparison of metabolites to creatine ratio concentrations did not yield any statistically significant results. There were no changes in concentrations of brain metabolites that indicated brain metabolic changes in retired soccer players compared with controls.

Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy - a Genotype/Phenotype Correlation.

BACKGROUND: LAMA2-related muscular dystrophy is a disorder that causes muscle weakness and varies in severity, from a severe, congenital type to a milder, late-onset form. However, the disease does not only affect the muscles, but has systemic involvement and can lead to alterations such as brain malformation, epilepsy and intellectual disability. OBJECTIVE: Describe the frequency of cortical malformations, epilepsy and intellectual disability in LAMA2-RD in a Brazilian cohort and correlate the neurological findings to genetic and motor function. METHODS: This is an observational study of 52 LAMA2-RD patients, who were divided into motor function subgroups and compared based on brain MRI findings, epilepsy, intellectual disability, and type of variants and variant domains. RESULTS: 44 patients (84.6%) were only able to sit, and 8 patients (15.4%) were able to walk. 10 patients (19.2%) presented with cortical malformations (polymicrogyria, lissencephaly-pachygyria, and cobblestone),10 patients (19.2%) presented with epilepsy, and 8 (15.4%) had intellectual disability. CNS manifestations correlated with a more severe motor phenotype and none of the patients able to walk presented with cortical malformation or epilepsy. There was a relation between gene variants affecting the laminin-α2 LG-domain and the presence of brain malformation (P = 0.016). There was also a relation between the presence of null variants and central nervous system involvement. A new brazilian possible founder variant was found in 11 patients (21,15%) (c.1255del; p. Ile419Leufs*4). CONCLUSION: Cortical malformations, epilepsy and intellectual disability are more frequent among LAMA2-RD patients than previously reported and correlate with motor function severity and the presence of variants affecting the laminin-α2 LG domain. This brings more insight fore phenotype-genotype correlations, shows the importance of reviewing the brain MRI of patients with LAMA2-RD and allows greater attention to the risk of brain malformation, epilepsy, and intellectual disability in those patients with variants that affect the LG domain.

Clinical Artificial Intelligence Applications in Radiology: Neuro.

Radiologists have been at the forefront of the digitization process in medicine. Artificial intelligence (AI) is a promising area of innovation, particularly in medical imaging. The number of applications of AI in neuroradiology has also grown. This article illustrates some of these applications. This article reviews machine learning challenges related to neuroradiology. The first approval of reimbursement for an AI algorithm by the Centers for Medicare and Medicaid Services, covering a stroke software for early detection of large vessel occlusion, is also discussed.