Automated segmentation reveals silent radiographic progression in adult-onset vanishing white-matter disease

Adult-onset vanishing white-matter disease (VWM) is a rare autosomal recessive disease with neurological symptoms such as ataxia and paraparesis, showing extensive white-matter hyperintensities (WMH) on magnetic resonance (MR) imaging. Besides symptom-specific scores like the International Cooperative Ataxia Rating Scale (ICARS), there is no established tool to monitor disease progression. Because of extensive WMH, visual comparison of MR images is challenging. Here, we report the results of an automated method of segmentation to detect alterations in T2-weighted fluid-attenuated-inversion-recovery (FLAIR) sequences in a one-year follow-up study of a clinically stable patient with genetically diagnosed VWM. Signal alterations in MR imaging were quantified with a recently published WMH segmentation method by means of extreme value distribution (EVD). Our analysis revealed progressive FLAIR alterations of 5.84% in the course of one year, whereas no significant WMH change could be detected in a stable multiple sclerosis (MS) control group. This result demonstrates that automated EVD-based segmentation allows a precise and rapid quantification of extensive FLAIR alterations like in VWM and might be a powerful tool for the clinical and scientific monitoring of degenerative white-matter diseases and potential therapeutic interventions.

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Vanishing White-Matter Disease: A Case of Severe Adult Onset With Prolonged Course Under Anticonvulsive Therapy

Journal of Neuropsychiatry ◽

10.1176/appi.neuropsych.11100246 ◽

2012 ◽

Vol 24 (4) ◽

pp. E24-E25 ◽

Cited By ~ 2

Author(s):

Agorastos Agorastos ◽

Christian G. Huber

Keyword(s):

White Matter ◽

White Matter Disease ◽

Adult Onset ◽

Vanishing White Matter Disease ◽

Vanishing White Matter

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Intra-familial phenotypic heterogeneity in adult onset vanishing white matter disease

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2008.08.003 ◽

2008 ◽

Vol 110 (10) ◽

pp. 1068-1071 ◽

Cited By ~ 8

Author(s):

Nathalie Damon-Perriere ◽

Patrice Menegon ◽

Anne Olivier ◽

Odile Boespflug-Tanguy ◽

Florence Niel ◽

...

Keyword(s):

White Matter ◽

Phenotypic Heterogeneity ◽

White Matter Disease ◽

Adult Onset ◽

Vanishing White Matter Disease ◽

Vanishing White Matter

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Decreased Asialotransferrin in Cerebrospinal Fluid of Patients with Childhood-Onset Ataxia and Central Nervous System Hypomyelination/Vanishing White Matter Disease

Clinical Chemistry ◽

10.1373/clinchem.2005.055053 ◽

2005 ◽

Vol 51 (11) ◽

pp. 2031-2042 ◽

Cited By ~ 31

Author(s):

Adeline Vanderver ◽

Raphael Schiffmann ◽

Margaret Timmons ◽

Katherine A Kellersberger ◽

Dan Fabris ◽

...

Keyword(s):

Mass Spectrometry ◽

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

White Matter ◽

Control Group ◽

White Matter Disease ◽

Childhood Onset ◽

Vanishing White Matter Disease ◽

Vanishing White Matter

Abstract Background: A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would have clinical utility and pathophysiologic significance. Methods: We used 2-dimensional gel electrophoresis/mass spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/VWM with that of unaffected controls. We characterized selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry. Results: A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and extraction, was found to be consistent with earlier reports. Conclusions: The transferrin isoform abnormality in the cerebrospinal fluid of patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.

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A case of adult onset vanishing white matter disease developed after minor head trauma

Rinsho Shinkeigaku ◽

10.5692/clinicalneurol.52.561 ◽

2012 ◽

Vol 52 (8) ◽

pp. 561-566 ◽

Cited By ~ 2

Author(s):

Shunsuke Koga ◽

Yukari Sekiguchi ◽

Kazuaki Kanai ◽

Mayumi Mutoh ◽

Satoshi Kuwabara

Keyword(s):

White Matter ◽

Head Trauma ◽

White Matter Disease ◽

Minor Head Trauma ◽

Adult Onset ◽

Vanishing White Matter Disease ◽

Vanishing White Matter

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Adult-onset vanishing white matter disease presenting as dementia

Annals of Alzheimer's and Dementia Care ◽

10.17352/aadc.000017 ◽

2021 ◽

pp. 004-008

Author(s):

Belarbi Soreya ◽

Bensemmane Selma Dounia ◽

Bouguerra Imene ◽

Ouali Meriem ◽

Mokrane Samira Makri

Keyword(s):

White Matter ◽

White Matter Disease ◽

Adult Onset ◽

Vanishing White Matter Disease ◽

Vanishing White Matter

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Adult-onset vanishing white matter disease with psychiatric manifestation: A case report

Journal of the Neurological Sciences ◽

10.1016/j.jns.2021.118258 ◽

2021 ◽

Vol 429 ◽

pp. 118258

Author(s):

Rim Smaoui ◽

Khadija Sonda Moalla ◽

Nouha Farhat ◽

Salma Sakka ◽

Olfa Hdiji ◽

...

Keyword(s):

Case Report ◽

White Matter ◽

White Matter Disease ◽

Adult Onset ◽

Psychiatric Manifestation ◽

Vanishing White Matter Disease ◽

Vanishing White Matter

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096 A 47-year old female with slowly progressive cognitive impairment and motor decline

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.95 ◽

2018 ◽

Vol 89 (6) ◽

pp. A38.2-A38

Author(s):

Wilson Vallat ◽

Timothy Kleinig

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Cognitive Dysfunction ◽

Translation Initiation Factor ◽

Initiation Factor ◽

White Matter Disease ◽

Adult Onset ◽

Extrapyramidal Signs ◽

Vanishing White Matter Disease ◽

Vanishing White Matter

IntroductionWe present the case of a woman with an 8 year history of slowly progressive cognitive dysfunction and gait disturbance, and a diagnosis of vanishing white matter disease (VWMD).CaseThe patient struggled at work as an accountant, her hand writing became illegible, she had difficulty judging distances when driving and she had developed gait instability, slowing and falls. Her past medical history was unremarkable save for premature menopause at 35. Examination showed marked cognitive impairment ACE-R 59/100 (attention and orientation – 13/18, memory – 16/26, fluency – 1/14, language – 21/26, visuospatial – 8/16), reduced dexterity of hands, left upper limb ataxia and high- level gait dysfunction. MRI brain showed leukodystrophy with frontal predominance. Relevant investigations – white cell enzymes, very long chain fatty acids, phytanic acid, CSF were normal. In view of the clinical and radiological features genetic testing with leukodystrophy panel was performed which revealed homozygous eukaryotic translation initiation factor B3 (EIF2B3) mutation (p.Ala87Val variant). Adult onset leukodystrophies are rare genetic metabolic disorders of the glial cells. The white matter (WM) degeneration causes disruption of distributed neural networks resulting in variable constellation of cognitive dysfunction, ataxia, pyramidal and extrapyramidal signs. The clinical and radiological phenotypes overlap and there are up to 60 genes that account for adult onset leukodystrophy, which makes diagnosis challenging. Vanishing white matter disease due to EIF2B gene mutation are a group of disorders that result from mutation of any of the EIF2B subunits (1 to 5). Two thirds have associated premature ovarian failure. MRI shows confluent WM T2 high signal, subcortical U Fibre sparing, periventricular WM rarefaction and cerebral atrophy. Management is symptomatic.ConclusionAdult onset VWMD is a rare and devastating condition. When evaluating these patients targeted gene testing guided by clinical and radiological phenotype is likely to provide the highest diagnostic yield. Establishing the diagnosis is important as it has implications on future generations.

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