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.

Leucoencefalopatía tóxica fatal: tres casos asociados al consumo de pasta base de cocaína / Fatal toxic leukoencephalopathy associated with consumption of pasta base of cocaine: Report of three cases

The prevalence of drug-associated toxic encephalopathy is unknown, but it is an uncommon condition. Toxic leukoencephalopathy was described associated with heroin consumption, it has been less commonly described with the use of cocaine and there are no reports of its association with consumption pasta base of cocaine (PBC). We report two females aged 31 years and a male aged 19 years, consumers of PBC who developed a fatal toxic leukoencephalopathy. They initiated their disease with severe and persistent headache, sequential focal neurologic deficits and a progressive impairment of consciousness that culminated with their death. Laboratory parameters such as blood count, cerebrospinal fluid analyses or infectious biological indices were normal. MRI showed multifocal lesions in brain white matter of both hemispheres confirming the leukoencephalopathy. There was no response to the use of methylprednisolone.

Multiorgan disorder syndrome (MODS) in an octagenarian suggests mitochondrial disorder / Síndrome mitocondrial no sindrómico con fallas de múltiples sistemas. Presentación de un caso

Non-syndromic, multi-organ mitochondrial disorders (MIDs) are frequently missed if treating physicians are not aware of them. We report a 85 years old Caucasian male, referred for tonic-clonic seizures, presenting with a plethora of abnormalities, including neurodermitis, atopic dermatitis, diabetes, hypertension, renal insufficiency, non-specific colitis, urine bladder lithiasis, bilateral cataracts, atrial fibrillation, diverticulosis, polyneuropathy, vitamin-D-deficiency, renal cysts, left anterior hemi-block, right bundle branch block, pulmonary artery hypertension, and heart failure. Neurological investigations revealed ptosis, quadriparesis, fasciculations, dysarthria, dysdiadochokinesia, tremor, hyperkinesia, ataxia, leukoencephalopathy, and basal ganglia calcification. Based upon this combination of abnormalities a non-syndromic mitochondrial multi-organ disorder syndrome (MIMODS, encephalo-myo-cardiomyopathy) was diagnosed.

Las alteraciones mitocondriales no sindrómicas y mutisistémicas pueden ser pasadas por alto si no se está consciente de su existencia. Presentamos un hombre de 85 años, referido por convulsiones tónico clónicas, que presentaba una plétora de anomalías tales como neurodermatitis, dermatitis atópica, diabetes, hipertensión, insuficiencia renal, colitis no específica, litiasis vesical, cataratas bilaterales, fibrilación auricular, diverticulosis, polineuropatía, deficiencia de vitamina D, quistes renales, hemibloqueo izquierdo anterior y bloqueo de rama derecha, hipertensión pulmonar e insuficiencia cardíaca. El estudio neurológico reveló la presencia de ptosis, cuadriparesia, fasciculaciones, disartria, disdiadocoquinesia, temblor, hiperquinesia, ataxia, leucoencefalopatía y calcificación de ganglios basales. Basados en estos hallazgos, se diagnosticó un síndrome mitocondrial no sindrómico con fallas de múltiples sistemas.

Hallazgo por neuroimaginología de microangiopatía cerebral retiniana con calcificaciones y quistes / Neuroimaging findings in cerebroretinal microangiopathy with calcifications and cysts

La microangiopatía cerebral retiniana con calcificaciones y quistes es una enfermedad poco frecuente, caracterizada por alteraciones cerebrales, retinianas y óseas, así como por predisposición al sangrado gastrointestinal. Existen pocos reportes de casos de esta condición, especialmente en adultos, en quienes la incidencia es baja. Los hallazgos por medio de neuroimágenes son característicos, con calcificaciones bilaterales y múltiples formaciones quísticas. El propósito de este artículo fue hacer una revisión bibliográfica e ilustrar dos casos cuyo diagnóstico fue posible con la ayuda de neuroimágenes.

Cerebroretinal microangiopathy with calcifications and cysts is a rare condition characterized by brain, retinal and bone anomalies, as well as a predisposition to gastrointestinal bleeding. There are few reported cases of this condition in adults, among whom the incidence is low. Neuroimaging findings are characteristic, with bilateral calcifications, leukoencephalopathy and intracranial cysts. The purpose of this article was to do a literature survey and illustrate two cases diagnosed with the aid of neuroimaging.

White matter hyperintensities, executive function and global cognitive performance in vascular mild cognitive impairment / Hiper-intensidades de substancia branca, funcao executiva e desempenho cognitivo global no comprometimento cognitivo leve vascular

Vascular mild cognitive impairment (VaMCI) represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction. Methods Twenty-six individuals (age: 73.11±7.90 years; 65.4% female; schooling: 9.84±3.61 years) were selected through neuropsychological assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals (n=15) were compared to normal controls (NC, n=11) and correlated with Fazekas scale. Results VaMCI performed significantly worse than NC in Trail-Making Test (TMT) B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination (CAMCOG) final scores. Correlations were found among scores in modified Fazekas scale and performances in TMT B (time to complete and errors), difference TMT B-A and CAMCOG total score. Conclusion Extension of white matter hyperintensities might be correlated to poorer global cognition and impairments in a set of fronto-executive functions, such as cognitive speed, set shifting and inhibitory control in VaMCI. .

Comprometimento cognitivo leve vascular (CCLV) representa um estágio sintomático precoce do comprometimento cognitivo vascular e associa-se à disfunção fronto-executiva. Métodos Vinte e seis indivíduos (idade: 73,11±7,90 anos; 65,4% mulheres; escolaridade: 9,84±3,61 anos) foram selecionados por meio de avaliação cognitiva e neuroimagem. Os dados clínicos e de neuroimagem do grupo CCLV (n=15) foram comparados com controles normais (CN; n=11) e correlacionados com a escala de Fazekas. Resultados CCLV apresentaram piores desempenhos que CN no Trail-Making Test (TMT) B, erros no TMT B, diferença TMT B-A e pontuação final do Cambridge Cognitive Examination (CAMCOG). Verificaram-se correlações entre escala de Fazekas e desempenhos no TMT B (tempo total e erros), diferença TMT B-A e a pontuação final do CAMCOG. Conclusão A extensão das hiper-intensidades de substância branca, no grupo CCLV, correlacionou-se com pior desempenho cognitivo global e com comprometimento em um grupo de funções fronto-executivas, como velocidade e alternância cognitiva e controle inibitório. .