A Practical Approach to Diagnosis of Spinal Dysraphism.

Spinal dysraphisms (SDs) are congenital malformations of the spinal cord, determined by derangement in the complex cascade of embryologic events involved in spinal development. They represent a heterogeneous group ranging from mild clinical manifestations-going unnoticed or being discovered at clinical examination-to a causal factor of life quality impairment, especially when associated with musculoskeletal, gastrointestinal, genitourinary, or respiratory system malformations. Knowledge of the normal embryologic development of the spinal cord-which encompasses three main steps (gastrulation, primary neurulation, and secondary neurulation)-is crucial for understanding the pathogenesis, neuroradiologic scenarios, and clinical-radiologic classification of congenital malformations of the spinal cord. SDs can be divided with clinical examination or neuroradiologic study into two major groups: open SDs and closed SDs. Congenital malformations of the spinal cord include a wide range of abnormalities that vary considerably in imaging and clinical characteristics and complexity and therefore may represent a diagnostic challenge, even for the experienced radiologist. Online supplemental material is available for this article. ©RSNA, 2021.

Clinical and molecular evaluation of 13 Brazilian patients with Gomez-López-Hernández syndrome.

We aim to characterize patients with Gomez-López-Hernández syndrome (GLHS) clinically and to investigate them molecularly. A clinical protocol, including a morphological and neuropsychological assessment, was applied to 13 patients with GLHS. Single-nucleotide polymorphism (SNP) array and whole-exome sequencing were undertaken; magnetic resonance imaging was performed in 12 patients, including high-resolution, heavily T2-weighted sequences (HRT2) in 6 patients to analyze the trigeminal nerves. All patients presented alopecia; two did not present rhombencephalosynapsis (RES); trigeminal anesthesia was present in 5 of the 11 patients (45.4%); brachycephaly/brachyturricephaly and mid-face retrusion were found in 84.6 and 92.3% of the patients, respectively. One patient had intellectual disability. HRT2 sequences showed trigeminal nerve hypoplasia in four of the six patients; all four had clinical signs of trigeminal anesthesia. No common candidate gene was found to explain GLHS phenotype. RES does not seem to be an obligatory finding in respect of GLHS diagnosis. We propose that a diagnosis of GLHS should be considered in patients with at least two of the following criteria: focal non-scarring alopecia, rhombencephalosynapsis, craniofacial anomalies (brachyturrycephaly, brachycephaly or mid-face retrusion), trigeminal anesthesia or anatomic abnormalities of the trigeminal nerve. Studies focusing on germline whole genome sequencing or DNA and/or RNA sequencing of the alopecia tissue may be the next step for the better understanding of GLHS etiology.

Gomez-López-Hernández syndrome: A case report with clinical and molecular evaluation and literature review.

Gomez-López-Hernández syndrome (GLHS) is characterized by rhombencephalosynapsis (RES), alopecia, trigeminal anesthesia and a distinctive phenotype, including brachyturricephaly. It has been suggested that GLHS should be considered as part of the spectrum of RES-associated conditions that include alopecia, trigeminal anesthesia, and craniofacial anomalies, rather than a distinct entity. To the best of our knowledge, 57 patients with GLHS have been described. Despite its first description in 1979, the etiology of this syndrome remains unknown. Here, we describe, to our knowledge, the first case of a patient with GLHS who was molecularly evaluated and had been prenatally exposed to misoprostol. We also reviewed the clinical and morphological features of the patients described to date to better delineate the phenotype and focus on any evidence for adverse pregnancy outcomes or exposure, including teratogens.

NFU1 -Related Disorders as Key Differential Diagnosis of Cavitating Leukoencephalopathy.

Genetic leukoencephalopathies represent an expanding group of inherited disorders associated with involvement of brain white matter. Cystic degeneration has been previously described with some acquired or inherited leukoencephalopathies. We describe a 6-month-old Brazilian boy with a 2-month history of severe and rapidly progressive developmental and psychomotor regression and seizures. Neurological examination showed spastic tetraparesis and lethargy. Neuroimaging showed diffuse and symmetric cavitating cystic leukoencephalopathy. Whole-exome sequencing revealed compound heterozygous mutations in the NFU1 gene, providing definite genetic diagnosis of multiple mitochondrial dysfunction syndrome type 1. We report a rare presentation of early-onset cystic leukoencephalopathy in the context of multiple mitochondrial dysfunction syndrome type 1.

New genetic causes for complex hereditary spastic paraplegia.

INTRODUCTION: Hereditary Spastic Paraplegia (HSP) represents a complex and heterogeneous group of rare neurodegenerative disorders that share a common clinical feature of weakness and lower limb spasticity that can occur alone or in combination with a constellation of other neurological or systemic signs and symptoms. Although the core clinical feature of weakness and lower limb spasticity is virtually universal, the genetic heterogeneity is almost uncountable with more than 70 genetic forms described so far. We performed review of medical records from twenty-one patients from seventeen Brazilian families with complex phenotype of HSP. All cases have previously negative mutations in SPG11/KIAA1840 and SPG7 gene and were evaluated by whole-exome sequencing. An extensive description of systemic and neurological signs has been described. RESULTS: Whole-exome sequencing was unremarkable in eight patients and established a definite genetic diagnosis in thirteen patients of twelve non-related families. Mutations were found in genes previously implicated in other neurodegenerative disorders such as Amyotrophic Lateral Sclerosis, Hereditary Neuropathy, Spastic Ataxias, Neurodegeneration with Brain Iron Accumulation, Glycogen Metabolism, Congenital Lipodystrophy and aminoacyl-tRNA synthetases disorders. CONCLUSIONS: We report thirteen new genetically-proven cases of complex HSP, expanding the clinical spectrum of presentations of HSP, providing new pathophysiological mechanisms and disclosing new potential therapeutic targets.

Using computed tomography enterography to evaluate patients with Crohn's disease: what impact does examiner experience have on the reproducibility of the method?

OBJECTIVE: To assess the impact that examiner experience has on the reproducibility and accuracy of computed tomography (CT) enterography in the detection of radiological signs in patients with Crohn's disease. MATERIALS AND METHODS: This was a retrospective, cross-sectional observational study involving the analysis of CT enterography scans of 20 patients with Crohn's disease. The exams were analyzed independently by two radiologists in their last year of residence (duo I) and by two abdominal imaging specialists (duo II). The interobserver agreement of each pair of examiners in identifying the main radiological signs was calculated with the kappa test. The accuracy of the examiners with less experience was quantified by using the consensus among three experienced examiners as a reference. RESULTS: Duo I and duo II obtained a similar interobserver agreement, with a moderate to good correlation, for mural hyperenhancement, parietal thickening, mural stratification, fat densification, and comb sign (kappa: 0.45-0.64). The less experienced examiners showed an accuracy > 80% for all signs, except for lymph nodes and fistula, for which it ranged from 60% to 75%. CONCLUSION: Less experienced examiners have a tendency to present a level of interobserver agreement similar to that of experienced examiners in evaluating Crohn's disease through CT enterography, as well as showing satisfactory accuracy in identifying most radiological signs of the disease.

OBJETIVO: Avaliar o impacto da experiência do examinador na reprodutibilidade e na acurácia de detecção de sinais radiológicos em exames de enterografia por tomografia computadorizada (entero-TC) de pacientes portadores da doença de Crohn. MATERIAIS E MÉTODOS: Análise retrospectiva de exames de entero-TC de 20 pacientes com doença de Crohn. Os exames foram analisados, independentemente, por dois radiologistas do último ano de residência (dupla I) e dois especialistas em imagem abdominal (dupla II). A concordância interobservador de cada dupla de examinadores para a identificação dos principais sinais tomográficos foi calculada pelo teste kappa. A acurácia da dupla I foi medida usando-se como referência um consenso entre três examinadores experientes. RESULTADOS: Ambas as duplas obtiveram concordância interobservador semelhante e com correlação moderada a boa para os sinais de estratificação mural, espessamento da parede, realce mucoso, densificação da gordura e sinal do pente (kappa: 0,45-0,64). Os examinadores menos experientes apresentaram acurácia superior a 80% para os sinais, exceto para linfonodos e fístula (entre 60% e 75%). CONCLUSÃO: Examinadores menos experientes têm tendência a apresentar grau de concordância entre si semelhante à de examinadores experientes na avaliação dos principais sinais tomográficos da doença de Crohn, com acurácia considerada satisfatória, para a maioria dos sinais.

Using computed tomography enterography to evaluate patients with Crohn's disease: what impact does examiner experience have on the reproducibility of the method? / Avaliação da doença de Crohn por meio da enterografia por tomografia computadorizada: qual o impacto da experiência dos examinadores na reprodutibilidade do método?

Abstract Objective: To assess the impact that examiner experience has on the reproducibility and accuracy of computed tomography (CT) enterography in the detection of radiological signs in patients with Crohn's disease. Materials and Methods: This was a retrospective, cross-sectional observational study involving the analysis of CT enterography scans of 20 patients with Crohn's disease. The exams were analyzed independently by two radiologists in their last year of residence (duo I) and by two abdominal imaging specialists (duo II). The interobserver agreement of each pair of examiners in identifying the main radiological signs was calculated with the kappa test. The accuracy of the examiners with less experience was quantified by using the consensus among three experienced examiners as a reference. Results: Duo I and duo II obtained a similar interobserver agreement, with a moderate to good correlation, for mural hyperenhancement, parietal thickening, mural stratification, fat densification, and comb sign (kappa: 0.45-0.64). The less experienced examiners showed an accuracy > 80% for all signs, except for lymph nodes and fistula, for which it ranged from 60% to 75%. Conclusion: Less experienced examiners have a tendency to present a level of interobserver agreement similar to that of experienced examiners in evaluating Crohn's disease through CT enterography, as well as showing satisfactory accuracy in identifying most radiological signs of the disease.

Resumo Objetivo: Avaliar o impacto da experiência do examinador na reprodutibilidade e na acurácia de detecção de sinais radiológicos em exames de enterografia por tomografia computadorizada (entero-TC) de pacientes portadores da doença de Crohn. Materiais e Métodos: Análise retrospectiva de exames de entero-TC de 20 pacientes com doença de Crohn. Os exames foram analisados, independentemente, por dois radiologistas do último ano de residência (dupla I) e dois especialistas em imagem abdominal (dupla II). A concordância interobservador de cada dupla de examinadores para a identificação dos principais sinais tomográficos foi calculada pelo teste kappa. A acurácia da dupla I foi medida usando-se como referência um consenso entre três examinadores experientes. Resultados: Ambas as duplas obtiveram concordância interobservador semelhante e com correlação moderada a boa para os sinais de estratificação mural, espessamento da parede, realce mucoso, densificação da gordura e sinal do pente (kappa: 0,45-0,64). Os examinadores menos experientes apresentaram acurácia superior a 80% para os sinais, exceto para linfonodos e fístula (entre 60% e 75%). Conclusão: Examinadores menos experientes têm tendência a apresentar grau de concordância entre si semelhante à de examinadores experientes na avaliação dos principais sinais tomográficos da doença de Crohn, com acurácia considerada satisfatória, para a maioria dos sinais.