Leukoencephalopathy with vanishing white matter: report of four cases from three unrelated Brazilian families

Rosemberg, Sérgio; Leite, Cláudia da Costa; Arita, F.; Kliemann, Suzana; Lacerda, M. T. C.

doi:10.1016/s0387-7604(02)00034-7

Cited by 17 publications

(17 citation statements)

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“…Several phenotypic variations have been described encompassing i) rapidly fatal variants with antenatal onset and involvement of multiple organs, ii) onset in early infancy before 2 years of age (6 -10), iii) a classical form with onset in late infancy/early childhood followed by a relapsingremitting/chronic progression over half a decade (1,2,(11)(12)(13)(14)(15), iv) juvenile onset cases with a protracted progression over 1-2 decades (3), and v) mild adolescence/adult forms, in females often associated with ovarian failure (16 -22).…”

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confidence: 99%

Early Reduction of Total N-Acetyl-Aspartate-Compounds in Patients With Classical Vanishing White Matter Disease. A Long-Term Follow-Up MRS Study

et al. 2008

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ABSTRACT:The neuropathology of vanishing white matter (VWM) disease is characterized by a loss of white matter (WM). Although recent histopathological studies suggest a primary glial dysfunction, the purpose of this work was to assess the extent of axonal involvement in VWM using long-term follow-up proton MR spectroscopy. White and gray matter of nine children with genetically proven VWM and late infancy/early childhood onset were investigated with short-echo time, single-voxel proton MR spectroscopy over up to 8 years starting as early as less than 2 years after the onset of symptoms (5 patients). Total N-acetyl-aspartate (Ϫ51% from normal control), creatine and phosphocreatine (Ϫ47%), and myo-inositol (Ϫ49%) were reduced in WM at early disease stages. Cholinecontaining compounds were less severely decreased (Ϫ31%). Follow-up investigations revealed progressive reduction of all metabolites in WM. In gray matter, no distinct changes were detected at early stages. Later total N-acetyl-aspartate decreased slightly (Ϫ22%). Assuming the metabolite alterations to primarily reflect changes in cellular composition, the observed pattern indicates early axonal involvement or loss as well as relatively enhanced turnover of myelin. These early stages are followed by a complete cellular loss in cerebral WM. V anishing white matter (VWM) disease (MIM 603836)-also known as myelinopathia centralis diffusa and childhood ataxia with diffuse central nervous system hypomyelination-was first separated from the vast group of unknown leukoencephalopathies in the early 90s (1,2). The MR imaging (MRI) and MR spectroscopy (MRS) features of VWM are unique and therefore considered diagnostic. MRI characteristically reveals bilaterally symmetric, diffuse involvement of cerebral white matter (WM) at the onset of symptoms and progressive cystic degeneration into an appearance like cerebrospinal fluid (CSF) over the course of the disease (3). Proton MRS shows a reduction of all WM metabolites except for the presence of lactate (Lac) and glucose (Glc) in concentrations typical for CSF (1,4,5).Several phenotypic variations have been described encompassing i) rapidly fatal variants with antenatal onset and involvement of multiple organs, ii) onset in early infancy before 2 years of age (6 -10), iii) a classical form with onset in late infancy/early childhood followed by a relapsingremitting/chronic progression over half a decade (1,2,11-15), iv) juvenile onset cases with a protracted progression over 1-2 decades (3), and v) mild adolescence/adult forms, in females often associated with ovarian failure (16 -22).The mode of inheritance is autosomal recessive. Mutations in each of the five subunits ␣-⑀ of the eucaryotic translation initiation factor 2B (eIF2B) have been found to cause the disease in most patients (23). eIF2B plays an essential role for initiation and regulation of cell protein synthesis. There is growing evidence that the mutations cause a decrease in eIF2B activity by different mechanisms and to a different extent. They may impai...

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confidence: 99%

Early Reduction of Total N-Acetyl-Aspartate-Compounds in Patients With Classical Vanishing White Matter Disease. A Long-Term Follow-Up MRS Study

et al. 2008

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“…Thus, these DWI findings may reflect a histological state in better preserved white matter, where the myelin degeneration is still going on. It is quite surprising that until now reduced proton diffusion in VWM was rarely reported, despite of extensive studies in the past few years (1)(2)(3)(4)(5)(6)11). In addition to the fact that very little reports dealt with diffusion weighted images, the possible reasons could be that the active degenerative process in VWM occurs only in a short time period during which the accompanied restriction of proton diffusion is observable, and more distinctively in younger patients.…”

Section: Discussionmentioning

confidence: 99%

“…VANISHING WHITE MATTER disease (VWM) is an inherited leukoencephalopathy with wide phenotypic variation, from cases with antenatal onset and early demise to such of adult-onset and slow progression (1)(2)(3)(4)(5)(6). The genetic causes of the disease are mutations in one of the five subunits of the eucaryotic translation initiation factor eIF2B (7).…”

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Imaging evidence of early brain tissue degeneration in patients with vanishing white matter disease: A multimodal MR study

Ding

Bley

Ohlenbusch

et al. 2011

Magnetic Resonance Imaging

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To find imaging signs of active degenerative processes in vanishing white matter disease (VWM), six VWM patients and six matched controls underwent MR examinations. The data were analyzed with modified Scheltens scales for morphological findings and determined quantitatively for apparent diffusion coefficient (ADC). Single‐voxel MR spectra were acquired at the parietal white matter and analyzed with LCModel. Typical VWM brain lesions were found in all patients accompanied by proton diffusion abnormalities: Increased ADC appeared in brain regions with severe myelin destruction in all patients, and reduced ADC in two of six younger patients in remaining white matter adjacent to the lesions or at the borders around the lesions, who had a short history of the disease (≤ 1 year). The MR spectroscopy revealed reductions of NAA, Cho, and Cr, which correlate to the grade of white matter abnormalities. An increase of myo‐inositol as marker of reactive gliosis was missing. Thus, restricted proton diffusion was evident in younger VWM patients with short history of disease, which in combination with lack of reactive gliosis may reflect early white matter degeneration in VWM. The multimodal MR methods are useful for characterizing such tissue degeneration in brain in vivo. J. Magn. Reson. Imaging 2012;35:926–932. © 2011 Wiley Periodicals, Inc.

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“…A idade não foi usada como critério diagnóstico porque estudos realizados com relação à variação fenotípica da doença demonstraram não haver relação entre a idade de inicio do aparecimento dos sintomas e a evolução 3 . Depois dos trabalhos iniciais, vários autores têm relatado a ocorrência desta nova enfermidade na literatura pertinente [4][5][6][7][8][9][10][11][12] . Por se tratar de enfermidade que apresenta diferentes alterações reveladas pela RNM, é que trabalhos recentes têm procurado abolir a denominação de síndrome de van der Knaap, para referir uma nomenclatura baseada nos achados neurorradiológicos: leucoencefalopatia megalencefálica com cistos subcorticais ou leucoencefalopatia megalencefálica com substância branca evanescente (alternativamente chamada de ataxia da infância com hipomielinização central) 13 .…”

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Leucoencefalopatia megalencefálica com substância branca evanescente e cistos subcorticais

Oliveira

Machado

Jesus

et al. 2004

Arq. Neuro-Psiquiatr.

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RESUMO -Apresentamos três casos de leucoencefalopatia megalencefálica com substancia branca evanescente e cistos subcorticais, diagnosticados através da ressonância nuclear magnética.Os casos estudados apresentam quadro clinico e radiológico de acordo com os critérios diagnósticos estabelecidos na descrição inicial desta enfermidade. São discutidos os aspectos clínicos e neuroradiológicos. PALAVRAS-CHAVE: leucoencefalopatia, megalencefalia, substância branca evanescente, síndrome de van der Knaap. Megalencephalic leukoencephalopathy with vanishing white matter and cystic formationABSTRACT -We present three cases of megalencephalic leukoencephalopathy with vanishing white matter and cystic formation in both temporal lobes, diagnosed through magnetic resonance imaging. All the cases presented clinical and radiological aspects according to the diagnostic criteria that were established in the initial description of the syndrome. Clinical and radiological aspects are discussed.KEY WORDS: leukoencephalopathy, megalencephaly, vanishing white matter, van der Knaap syndrome.Em 1995, van der Knaap et al.1 descreveram pela primeira vez uma síndrome caracterizada pela presença de leucoencefalopatia e megalencefalia de início na infância com imagens características através da ressonância nuclear magnética (RNM). Dois anos após os primeiros relatos e já com estudos mais aprofundados da nova enfermidade, foram propostos pelos autores os critérios para diagnósti-co: 1-Desenvolvimento psicomotor inicial normal ou moderadamente afetado; 2 -Aparecimento na infância de episódios de deterioração neurológica ou curso crônico progressivo; esta deterioração pode ser precedida por quadro infeccioso ou por traumatismo cranioencefálico moderado; 3 -Presença de quadro neurológico caracterizado por sinais piramidais, ataxia cerebelar, atrofia óptica, epilepsia e preservação das funções mentais; 4 -Envolvimento simétrico da substância branca dos hemisférios cerebrais os quais apresentam à RNM sinal semelhante ao líquido céfalorraquidiano (LCR), bem como atrofia cerebelar com envolvimento primário do vermis 2 . A idade não foi usada como critério diagnóstico porque estudos realizados com relação à variação fenotípica da doença demonstraram não haver relação entre a idade de inicio do aparecimento dos sintomas e a evolução 3 . Depois dos trabalhos iniciais, vários autores têm relatado a ocorrência desta nova enfermidade na literatura pertinente [4][5][6][7][8][9][10][11][12]

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Leukoencephalopathy with vanishing white matter: report of four cases from three unrelated Brazilian families

Cited by 17 publications

References 8 publications

Early Reduction of Total N-Acetyl-Aspartate-Compounds in Patients With Classical Vanishing White Matter Disease. A Long-Term Follow-Up MRS Study

Early Reduction of Total N-Acetyl-Aspartate-Compounds in Patients With Classical Vanishing White Matter Disease. A Long-Term Follow-Up MRS Study

Imaging evidence of early brain tissue degeneration in patients with vanishing white matter disease: A multimodal MR study

Leucoencefalopatia megalencefálica com substância branca evanescente e cistos subcorticais

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