Vanishing white matter disease: imaging, clinical and molecular correlation in Brazilian families.

PURPOSE: To characterize Vanishing White Matter Disease (VWM) cases from a Brazilian University Tertiary hospital, focusing on brain magnetic resonance image (MRI) aspects, clinical and molecular data. METHODS: Medical records and brain MRI of 13 genetically confirmed VWM patients were reviewed. Epidemiological data such as age at symptom onset, gender and main symptoms were analyzed, along with genetic mutations and MRI characteristics, such as the distribution of white matter lesions and atrophy. RESULTS: The majority of patients were female, with the age of symptom onset ranging from 1 year and 6 months to 40 years. All mutations were identified in the EIF2B5 gene, the most prevalent being c.338G > A (p.Arg113His), and a novel mutation related to the disease was discovered, c.1051G > A (p.Gly351Ser). Trauma or infection were significant triggers. The most frequent symptoms were ataxia and limb spasticity. All MRI scans displayed deep white matter involvement, cystic degeneration, with U-fibers relatively spared and a predilection for the frontoparietal region. Lesions in the corpus callosum and posterior fossa were present in all patients. Follow-up exams revealed the evolution of white matter lesions and cerebral atrophy, which correlated with clinical deterioration. CONCLUSIONS: VWM affects various age groups, with a significant clinical and genetic variability. A novel mutation associated with the disease is highlighted. MRI reveals a typical pattern of white matter involvement, characterized by diffuse lesions in the periventricular and deep regions, with subsequent extension to the subcortical areas, accompanied by cystic degeneration, and plays a crucial role in diagnosis and follow-up.

"A case of vanishing bone disease complicated by chylothorax- diagnosis and treatment".

A 16-year old girl with Gorham-Stout disease is presented. She had progressive replacement of the bones of her left arm and shoulder girdle by fibroadipose tissue and numerous proliferated, non-neoplastic, lymphatic channels. The clinico-pathologic features of this condition are discussed, as are its possible complications and available therapeutic modalities.

Relación médico legal de la enfermedad de sustancia blanca evanescente como un estado anterior y su implicación ante el trauma craneoencefálico: reporte de caso / Medical-legal relationship of evanescent white matter disease as a previous state and its implication in the cranioencephalic trauma: case report

Resumen La enfermedad de sustancia blanca representa una enfermedad poco común en usuarios que se apersonan al Organismo de Investigación Judicial, por este motivo al valorar un caso es necesario investigar los antecedentes de la medicina legal para establecer mecanismos causales con hechos representados en la sociedad. Además, es necesario abordar la enfermedad de sustancia blanca desde su aparición, incidencia, aspectos clínicos, hallazgos ante una posible autopsia, explorar el desarrollo de fisiopatología como indagar acerca de las formas de diagnosticar la enfermedad y valorar las opciones terapéuticas. Estos conocimientos son base para establecer una relación médico legal y analizar si el caso de una niña de 9 años tiene correlación con una historia de trauma en cabeza que no evidencia cambios inflamatorios, aumento de volumen de tejidos blandos o duros, excoriaciones, equimosis, hematomas, cicatrices, gradas o callos óseos y con valoraciones médicas que indican tetraparesia flácida en ausencia de hallazgos patológicos al reporte de tomografía axial computarizada y resonancia magnética de columna cervicodorsal.

Abstract White matter disease represents a rare disease in users who go to the Organismo de Investigación Judicial (Judicial Investigation Agency) for this reason, when evaluating a case, it is necessary to investigate the antecedents of legal medicine to establish causal mechanisms with facts represented in society. In addition, it is necessary to address white matter disease from its appearance, incidence, clinical aspects, findings in a possible autopsy, explore the development of pathophysiology such as inquire about ways to diagnose the disease, and assess therapeutic options. This knowledge is the basis for establishing a legal medical relationship and analyzing whether the case of a 9-year-old girl has a correlation with a history of head trauma that does not show inflammatory changes, increased soft or hard tissue volume, excoriations, bruising, bruising. , scars, bleachers or calluses and with medical evaluations that indicate flaccid tetraparesis in the absence of pathological findings on the report of computed tomography and magnetic resonance imaging of the cervicodorsal spine.

Uniportal video-assisted thoracic surgery bullectomy in vanishing lung syndrome - What about giant bullae?

A 36-year-old-woman, smoker, without other relevant medical history, presented with symptoms of dyspnea, right localized chest pain, and non-productive cough. On the emergency department, the chest X-ray was interpreted as a giant right pneumothorax and a chest drain was inserted. Thoracic computed tomography demonstrated a giant emphysematous bulla with 23 cm on her right upper lobe. We report the first uniportal video-assisted thoracic surgery bullectomy for a bulla greater than 20 cm, in a patient with vanishing lung syndrome.

Una mujer de 36 años de edad, fumadora, se presentó en la sala de emergencias por disnea, tos y dolor torácico derecho. La radiografía fue interpretada como neumotórax y se colocó un tubo de drenaje. La tomografía computarizada del tórax mostró una bulla enfisematosa gigante, de aproximadamente 23 cm. Reportamos el primer caso de bullectomía por uniportal VATS en una paciente con síndrome del pulmón evanescente que presentaba una bulla mayor de 20 cm.

¿Qué hacer ante un pT0 en cáncer de próstata? Revisión a propósito de un caso / What to do with a pT0 in Prostate Cancer? Review of the Literature and Case Report

Introducción y Objetivos El cáncer de próstata es la segunda causa de mortalidad por cáncer en hombres en Colombia y en el mundo. El efecto "vanishing" en cáncer de próstata, es un fenómeno poco frecuente que se define como la ausencia de tumor en el estudio histológico postquirúrgico de pacientes llevados a prostatectomía radical como manejo curativo diagnóstico previo confirmado por biopsia o RTUP. Su incidencia en diferentes series llega hasta el 0,86%, por lo cual existen pocos estudios aleatorizados al respecto y aún no es clara la conducta con ese tipo de tumores. Reportamos un caso de un paciente con cáncer de próstata pT0 y realizamos una revisión de la literatura respecto del seguimiento y manejo que se deberían seguir al enfrentarnos a ese tipo de tumor. Métodos y Materiales Revisión de la literatura y reporte de caso clínico. Reporte de Caso Hombre de 58 años sintomático urinario, con PSA elevado por lo que se realizó biopsia transrectal de próstata, con resultado de adenocarcinoma de próstata confirmado por inmunohistoquímica. Al realizarse la prostatectomía radical no se encuentra tumor en la patología. En la literatura se encuentran factores asociados con la presencia del tumor cuando hay RTUP previa y uso de hormonoterapia neoadyuvante en el contexto de tumores de bajo volumen. A pesar de no encontrarse tumor en la patología, está descrita la recaída bioquímica y progresión clínica de esos tumores, por lo que debe realizarse el seguimiento usual para esa patología. Conclusiones El hallazgo de pT0 en cáncer de próstata, aunque poco frecuente, demanda una guía de manejo Proponemos la revisión de la patología con el protocolo descrito para reducir los falsos positivos y el seguimiento usual con los pasos estandarizados en las guías internacionales.

Introduction and Objectives Prostate cancer is the second leading cause of death related with cancer in men in Colombia and the world. "Vanishing" phenomenon in prostate cáncer is a rare event, where the post-surgical histologic review in patiets that underwent radical prostatectomy is negative, all of them with previous diagnosis of CaP by biopsy or TUR. The incidence of CaP in different series reaches 0.86%, whereby there are few randomized studies and the management and follow up of this type of tumors is not clear. In this article we report a case of a pT0 prostate cancer patient. We perform a systematic review of the literature to determine the medical behavior and medical follow up in cases presenting with pT0 prostate cancer. Materials and Methods Review of the literature & case report. Results Patient of 58 years old with medical history of recent progressive LUTS and high PSA levels that underwent a trans-rectal prostate biopsy with report of adenocarcinoma, that were confirmed by immunohistochemistry. In the pathology report after the radical prostatectomy no tumor cells were found. In the literature, there is reference about factors associated with pT0 prostate cancer in patients with previous RTUP and that were taken to hormonal coadjutant therapy in lesser degree tumors. Despite the absent of cancer findings in the pathology, it is well described biochemistry relapses and clinical progression of this tumors; usual protocol follow up must be made. Conclusion In patients with pT0 prostate cancer, even though to be a rare finding, must be studied and follow up with the steps mentioned above with the aim to reduce the false positive cases. Also the follow-ups steps must fully meet the requirements of standardized protocols guidelines.

Leucoencefalopatia com substância branca evanescente: um relato de caso / Leukoencephalopathy with evanescent white matter: a case report

RESUMO Objetivo: Descrever uma criança diagnosticada com leucoencefalopatia com substância branca evanescente (LSBE), uma doença genética rara que possui padrão de herança autossômico recessivo. Descrição do caso: Criança do sexo masculino, com 5 meses de idade, que mostrava recusa da amamentação e sonolência, começou a apresentar quadro de desidratação, com boca seca, aumento da temperatura corporal e adipsia. Com o passar dos dias, os sintomas agravaram-se. O lactente apresentou-se muito sonolento e foi transferido para a unidade de tratamento intensivo (UTI), onde permaneceu por uma semana. Nesse período, foi identificada, na ressonância magnética de crânio, uma alteração de sinal com predomínio hiperatenuado T2, comprometendo particularmente a substância branca, de aspecto difuso e simétrico. O lactente apresentou crises convulsivas desde então. Aos 11 meses foi diagnosticado com tonsilite, demonstrando quadros recorrentes de picos febris e sonolência excessiva. Na evolução do quadro, o lactente entrou em estado comatoso progredindo a óbito. O diagnóstico de LSBE foi confirmado em exames realizados após o óbito, e tardiamente foi identificada uma doença genética decorrente de mutações em um dos cinco genes que são responsáveis pela codificação do complexo fator de iniciação da tradução de eucariontes 2B (eIF2B), envolvido com o controle da tradução de proteínas, sendo descrita como patogênica em indivíduos com LSBE. Comentários: A LSBE é uma doença cerebral hereditária com início na infância. A doença apresenta-se de maneira crônica e progressiva, com episódios adicionais de rápida deterioração, como evidenciado no presente relato de caso.

ABSTRACT Objective: To describe the case of a child diagnosed with leukoencephalopathy with vanishing white matter (LVWM), a rare genetic disease with autosomal recessive inheritance pattern. Case description: A 5-month-old male child started to refuse breast-feeding, showing somnolence and signs of dehydration,with dry mouth, increasing body temperature and adipsy. As days went by, the symptoms got worse. The infant was very sleepy and was transferred to the intensive care unit, where he stayed for one week. At this time, a signal alteration with hyper attenuated T2 predominance was identified in the magnetic resonance imaging, compromising the white matter, which had diffuse and symmetrical aspect. At this time, the infant started to present seizures. When the infant was 11 months old, he was diagnosed with tonsillitis and presented recurrent fever peaks and extreme sleepiness. After hospital admission, the infant progressed to a comatose state and died. The diagnosis of LVWM was confirmed in examinations performed after death. As a late diagnosis, a genetic disease was identified with a mutation in one of the five genes responsible for the codification of complex eukaryotic translation initiation factor 2B (eIF2B), involved with the control of the protein translation and which is described as pathogenic in individuals with LVWM. Comments: LVWM is a hereditary brain disease that occurs primarily in children. The disease is chronic and progressive, with additional episodes of rapid deterioration, as shown in the present case report.

Asociación entre la mutación homocigota c.318A>T en el exón 2 del gen EIF2B5 y la forma infantil de la leucoencefalopatía con sustancia blanca evanescente / Association between homozygous c.318A>GT mutation in exon 2 of the EIF2B5 gene and the infantile form of vanishing white matter leukoencephalopathy

Resumen: Introducción: La leucoencefalopatía con sustancia blanca evanescente es una de las leucodistrofias más frecuentes. Generalmente inicia en la infancia y presenta un patrón de herencia autosómica recesiva. El 90% de los casos manifiesta mutaciones en uno de los genes que codifican para las cinco subunidades del factor de iniciación eucariótica 2 (EIF2B5). El diagnóstico se realiza por las manifestaciones clínicas, hallazgos en la resonancia magnética cerebral y estudios moleculares confirmatorios. Caso clínico: Paciente masculino de 13 meses con neurodesarrollo previo normal. Antecedente de internamiento por vómito, hipertermia, irritabilidad y rechazo a la vía oral de 15 días de evolución. Ante la exploración presentó perímetro cefálico y pares craneales normales. Se encontró hipotónico, con reflejos incrementados, sin datos meníngeos ni de cráneo hipertensivo. La tomografía de cráneo mostró hipodensidad generalizada de la sustancia blanca. Egresó sin recuperar deambulación. A los 15 días presentó somnolencia y crisis convulsivas focales después de traumatismo craneoencefálico. En la resonancia magnética se observó hipointensidad generalizada de sustancia blanca. Ante la sospecha de leucoencefalopatía con sustancia blanca evanescente, se solicitó la secuenciación del gen EIF2B5, que reportó mutación homocigota c.318A>T en el exón 2. El paciente requirió múltiples hospitalizaciones por hipertermia y descontrol de crisis convulsivas. Posteriormente mostró deterioro cognitivo, motor y pérdida de la agudeza visual. Falleció a los 6 años por neumonía severa. Conclusiones: Este caso contribuye a conocer el espectro de mutaciones que se presenta en pacientes mexicanos y permite ampliar el fenotipo asociado con esta mutación.

Abstract: Background: Vanishing white matter disease is one of the most frequent leukodystrophies in childhood with an autosomal recessive inheritance. A mutation in one of the genes encoding the five subunits of the eukaryotic initiation factor 2 (EIF2B5) is present in 90% of the cases. The diagnosis can be accomplished by the clinical and neuroradiological findings and molecular tests. Case report: We describe a thirteen-month-old male with previous normal neurodevelopment, who was hospitalized for vomiting, hyperthermia and irritability. On examination, cephalic perimeter and cranial pairs were normal. Hypotonia, increased muscle stretching reflexes, generalized white matter hypodensity on cranial tomography were found. Fifteen days after discharge, he suffered minor head trauma presenting drowsiness and focal seizures. Magnetic resonance showed generalized hypointensity of white matter. Vanishing white matter disease was suspected, and confirmed by sequencing of the EIF2B5 gene, revealing a homozygous c.318A> T mutation in exon 2. Subsequently, visual acuity was lost and cognitive and motor deterioration was evident. The patient died at six years of age due to severe pneumonia. Conclusions: This case contributes to the knowledge of the mutational spectrum present in Mexican patients and allows to extend the phenotype associated to this mutation.

Gorham-Stout Disease: a Clinical Case Report and Immunological Mechanisms in Bone Erosion.

Gorham-Stout disease (GSD) is a rare condition of osteolysis with excessive lymphangiogenesis within bone tissue. The etiology of this condition remains unknown but seems to affect mainly children and young adults of both genders all over the world. Unfortunately, there is no standardized method for diagnosis; however, histopathology remains as the gold standard. This condition is often misdiagnosed due to its varying clinical presentations from case-to-case. Here, we report the case of an 8-year-old girl who presented with chronic mandibular pain during mastication and received multiple antibiotic treatment due to infectious origin suspicion. After integrating information from clinical manifestations, radiographic, laboratory, and histopathology information, she was diagnosed with GSD. Additionally, due to the lack of literature with respect to insights into biological mechanisms and standardized treatment for this condition, we underwent a literature revision to provide information related to activation of cells from the immune system, such as macrophages, T-cells, and dendritic cells, and their contribution to the lymphangiogenesis, angiogenesis, and osteoclastogenic process in GSD. It is important to consider these mechanisms in patients with GSD, especially since new studies performed in earlier stages are required to confirm their use as novel diagnostic tools and find new possibilities for treatment.

[Association between homozygous c.318A>GT mutation in exon 2 of the EIF2B5 gene and the infantile form of vanishing white matter leukoencephalopathy]. / Asociación entre la mutación homocigota c.318A>T en el exón 2 del gen EIF2B5 y la forma infantil de la leucoencefalopatía con sustancia blanca evanescente.

BACKGROUND: Vanishing white matter disease is one of the most frequent leukodystrophies in childhood with an autosomal recessive inheritance. A mutation in one of the genes encoding the five subunits of the eukaryotic initiation factor 2 (EIF2B5) is present in 90% of the cases. The diagnosis can be accomplished by the clinical and neuroradiological findings and molecular tests. CASE REPORT: We describe a thirteen-month-old male with previous normal neurodevelopment, who was hospitalized for vomiting, hyperthermia and irritability. On examination, cephalic perimeter and cranial pairs were normal. Hypotonia, increased muscle stretching reflexes, generalized white matter hypodensity on cranial tomography were found. Fifteen days after discharge, he suffered minor head trauma presenting drowsiness and focal seizures. Magnetic resonance showed generalized hypointensity of white matter. Vanishing white matter disease was suspected, and confirmed by sequencing of the EIF2B5 gene, revealing a homozygous c.318A> T mutation in exon 2. Subsequently, visual acuity was lost and cognitive and motor deterioration was evident. The patient died at six years of age due to severe pneumonia. CONCLUSIONS: This case contributes to the knowledge of the mutational spectrum present in Mexican patients and allows to extend the phenotype associated to this mutation.

Muerte fetal única en la gestación múltiple

La muerte fetal única en el contexto de una gestación múltiple es un evento poco frecuente pero con severas consecuencias para el cogemelo. Es más frecuente en el primer trimestre, denominándose el cuadro clínico como feto evanescente, pudiendo afectar el normal desarrollo del otro feto. El entendimiento de la complejidad de las anastomosis vasculares en la gestación monocorial ha ayudado a dilucidar la fisiopatología de la muerte fetal y del daño cerebral, siendo la explicación la exsanguíneo transfusión de un gemelo a otro. Ello determina la probabilidad de muerte del feto sobreviviente y/o daño neurológico, que están estrechamente relacionados a la edad gestacional de ocurrencia del evento, prematuridad al nacimiento y monocorionicidad. Estos casos exigen un seguimiento individualizado del feto sobreviviente, con neurosonografía y resonancia magnética.

Single twin demise in the context of multiple pregnancy is rare but with severe consequences for the other twin. This event is more common in the first trimester and is clinically called vanishing twin; it may affect the normal development of the other twin. Understanding the complexity of vascular anastomosis in monochorionic gestation has helped to elucidate the pathophysiology of fetal death and brain damage, explained by exchange transfusion from one twin to the other, and determining the probability of death of the surviving fetus and neurological damage related to gestational age of occurrence, premature birth and monochorionicity. These cases require individual monitoring of the su rviving fetus, neurosonography and magnetic resonance imaging.

Revisiting the vanishing refuge model of diversification.

Much of the debate around speciation and historical biogeography has focused on the role of stabilizing selection on the physiological (abiotic) niche, emphasizing how isolation and vicariance, when associated with niche conservatism, may drive tropical speciation. Yet, recent re-emphasis on the ecological dimensions of speciation points to a more prominent role of divergent selection in driving genetic, phenotypic, and niche divergence. The vanishing refuge model (VRM), first described by Vanzolini and Williams (1981), describes a process of diversification through climate-driven habitat fragmentation and exposure to new environments, integrating both vicariance and divergent selection. This model suggests that dynamic climates and peripheral isolates can lead to genetic and functional (i.e., ecological and phenotypic) diversity, resulting in sister taxa that occupy contrasting habitats with abutting distributions. Here, we provide predictions for populations undergoing divergence according to the VRM that encompass habitat dynamics, phylogeography, and phenotypic differentiation across populations. Such integrative analyses can, in principle, differentiate the operation of the VRM from other speciation models. We applied these principles to a lizard species, Coleodactylus meridionalis, which was used to illustrate the model in the original paper. We incorporate data on inferred historic habitat dynamics, phylogeography and thermal physiology to test for divergence between coastal and inland populations in the Atlantic Forest of Brazil. Environmental and genetic analyses are concordant with divergence through the VRM, yet physiological data are not. We emphasize the importance of multidisciplinary approaches to test this and alternative speciation models while seeking to explain the extraordinarily high genetic and phenotypic diversity of tropical biomes.