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MR imaging characteristics and neuropathology of the spinal cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
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2009 (Engelska)Ingår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 30, nr 2, s. 328-335Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND AND PURPOSE:

MR imaging findings in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms have been described in the brain, but no descriptions of MR imaging findings in the spinal cord have been published. Here, we describe MR imaging findings in the spinal cord in adult-onset ADLD with autonomic symptoms and histopathologic investigations of the spinal cord.

MATERIALS AND METHODS:

Twelve subjects from 2 families with adult-onset ADLD with autonomic symptoms identified by clinical investigation underwent MR imaging examination of the spinal cord. Sagittal and transverse sections were obtained. MR imaging examination of the brain was performed in 11 patients. One of the patients underwent postmortem examination, and the spinal cord was subjected to histopathologic analysis.

RESULTS:

In all family members with adult-onset ADLD with autonomic symptoms, even in the asymptomatic person, the spinal cord was thin. All examined family members also had a slight general white matter signal intensity (SI) increase in the whole spinal cord, mainly visible in T2-weighted transverse images. The pathologic examination revealed a discrete demyelination in the spinal cord. Brain MR imaging also showed increased T2 SI in the white matter.

CONCLUSIONS:

The spinal cord is affected in adult-onset ADLD with autonomic symptoms. Findings consist of atrophy and a diffuse T2 SI increase in the white matter. Transverse images are needed to assess these findings. The typical SI changes of the spinal cord are also present in subjects without clinical symptoms of the disease and with very limited changes in the brain.

Ort, förlag, år, upplaga, sidor
2009. Vol. 30, nr 2, s. 328-335
Nationell ämneskategori
Neurologi
Forskningsämne
Neurologi
Identifikatorer
URN: urn:nbn:se:uu:diva-98169DOI: 10.3174/ajnr.A1354ISI: 000263491200020PubMedID: 18945794OAI: oai:DiVA.org:uu-98169DiVA, id: diva2:173529
Tillgänglig från: 2009-02-16 Skapad: 2009-02-16 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
Ingår i avhandling
1. Autosomal Dominant Leukodystrophy with Autonomic Symptoms and Rippling Muscle Disease: Translational Studies of Two Neurogenetic Diseases
Öppna denna publikation i ny flik eller fönster >>Autosomal Dominant Leukodystrophy with Autonomic Symptoms and Rippling Muscle Disease: Translational Studies of Two Neurogenetic Diseases
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

There is a large variety of diseases caused by single-gene mutations. Although most of these conditions are rare, together they impose a significant burden to the population. This thesis describes clinical and genetic studies of two single-gene diseases:

1) Adult-onset autosomal dominant leukodystrophy with autonomic symptoms (ADLD) caused by LMNB1 gene duplications, and characterized by autonomic, pyramidal and cerebellar symptoms. Spinal cords of patients with ADLD were studied by MRI and found to be thin, with high signal intensity in white matter. Histopathology showed loss of myelinated fibres with some reactive gliosis. DNA samples from four different families with ADLD were obtained, and the LMNB1 gene was screened for duplications. Single nucleotide polymorphism array revealed LMNB1 duplications in all ADLD families. LMNB1 mRNA and protein levels were assessed in white blood cells using quantitative polymerase chain reaction and Western blot, and increased levels of LMNB1 mRNA and lamin B1 protein could be demonstrated. We concluded that spinal cord atrophy in patients with ADLD is a valuable differential diagnostic sign, and that increased levels of LMNB1 can be detected in peripheral blood.

2) Rippling muscle disease (RMD) is caused by CAV3 gene mutations. Clinical features are percussion-induced muscle mounding, –rapid contractions and undulating muscle contractions (rippling). The CAV3 gene was sequenced in 38 members of a family with RMD. Twenty-two individuals had clinical features of RMD. No muscle weakness was seen. All patients with signs of RMD carried the p.A46T CAV3 mutation, showing that the p.A46T mutation was benign and that the diagnosis can be made clinically. In vitro contracture test results from 10 of the subjects were collected, but no association between pathological test results and RMD was found.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2011. s. 76
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 726
Nyckelord
Inborn genetic diseases, Leukoencephalopathies, Lamin type B, Muscular disease, Caveolin 3
Nationell ämneskategori
Neurologi
Forskningsämne
Neurologi
Identifikatorer
urn:nbn:se:uu:diva-162048 (URN)978-91-554-8230-5 (ISBN)
Disputation
2012-01-13, Grönwallsalen, Akademiska sjukhuset, Ing 70, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2011-12-20 Skapad: 2011-11-23 Senast uppdaterad: 2012-01-03Bibliografiskt granskad

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