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Melberg, Atle
Alternative names
Publications (10 of 35) Show all publications
Finnsson, J., Sundblom, J., Dahl, N., Melberg, A. & Raininko, R. (2015). LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course. Annals of Neurology, 78(3), 412-25
Open this publication in new window or tab >>LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course
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2015 (English)In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 78, no 3, p. 412-25Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Duplication of the LMNB1 gene encoding lamin B1 causes adult-onset autosomal-dominant leukodystrophy (ADLD) starting with autonomic symptoms, which are followed by pyramidal signs and ataxia. Magnetic resonance imaging (MRI) of the brain reveals characteristic findings. This is the first longitudinal study on this disease. Our objective is to describe the natural clinical and radiological course of LMNB1-related ADLD.

METHODS: Twenty-three subjects in two families with LMNB1 duplications were studied over two decades with clinical assessment and MRI of the brain and spinal cord. They were 29 to 70 years old at their first MRI. Repeated MRIs were performed in 14 subjects over a time period of up to 17 years.

RESULTS: Pathological MRI findings were found in the brain and spinal cord in all examinations (i.e., even preceding clinical symptoms). MRI changes and clinical symptoms progressed in a definite order. Autonomic dysfunction appeared in the fifth to sixth decade, preceding or together with gait and coordination difficulties. Motor signs developed ascending from spastic paraplegia to tetraplegia and pseudobulbar palsy in the seventh decade. There were clinical, radiological, and neurophysiological signs of myelopathy. Survival lasted more than two decades after clinical onset.

INTERPRETATION: LMNB1-related ADLD is a slowly progressive neurological disease. MRI abnormalities of the brain and spinal cord can precede clinical symptoms by more than a decade and are extensive in all symptomatic patients. Spinal cord involvement is a likely contributing factor to early autonomic symptoms and spastic paraplegia. Ann Neurol 2015;78:412-425.

National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-261207 (URN)10.1002/ana.24452 (DOI)000360218800008 ()26053668 (PubMedID)
Note

Atle Melberg och Raili Raininko delar sistaförfattarskapet.

Available from: 2015-08-31 Created: 2015-08-31 Last updated: 2018-01-11Bibliographically approved
Hedberg, C., Melberg, A., Dahlbom, K. & Oldfors, A. (2014). Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain [Letter to the editor]. Brain, 137(4), e270
Open this publication in new window or tab >>Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain
2014 (English)In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 137, no 4, p. e270-Article in journal, Letter (Refereed) Published
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-223630 (URN)10.1093/brain/awt305 (DOI)000333260900006 ()24231549 (PubMedID)
Available from: 2014-04-23 Created: 2014-04-23 Last updated: 2017-12-05Bibliographically approved
Finnsson, J., Sundblom, J., Melberg, A. & Raininko, R. (2014). O151-Longitudinal MRI Study of the Spinal Cord in Lamin B1 Autosomal Dominant Leukodystrophy: Do the first symptoms come from the spinal cord?. Paper presented at XXth Symposium Neuroradiologicum, 7-12 September, 2014, Istanbul, Turkey.. Neuroradiology, 56(Suppl 1), S246
Open this publication in new window or tab >>O151-Longitudinal MRI Study of the Spinal Cord in Lamin B1 Autosomal Dominant Leukodystrophy: Do the first symptoms come from the spinal cord?
2014 (English)In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 56, no Suppl 1, p. S246-Article in journal, Meeting abstract (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-246089 (URN)10.1007/s00234-014-1405-4 (DOI)
Conference
XXth Symposium Neuroradiologicum, 7-12 September, 2014, Istanbul, Turkey.
Available from: 2015-03-02 Created: 2015-03-02 Last updated: 2017-12-04Bibliographically approved
Feresiadou, A., Eriksson, U., Larsen, H.-C., Raininko, R., Nygren, I. & Melberg, A. (2014). Recurrence of Susac Syndrome following 23 Years of Remission. Case Reports in Neurology, 6(2), 171-175
Open this publication in new window or tab >>Recurrence of Susac Syndrome following 23 Years of Remission
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2014 (English)In: Case Reports in Neurology, ISSN 1662-680X, E-ISSN 1662-680X, Vol. 6, no 2, p. 171-175Article in journal (Refereed) Published
Abstract [en]

Susac syndrome is an autoimmune microangiopathy affecting the brain, retina and inner ear (cochlea and semicircular canals), leading to encephalopathy, branch retinal artery occlusions (BRAOs) and asymmetric neurosensory hearing loss, respectively. The natural history and long-term prognosis are variable as the disease has been shown to be monophasic and self-limiting, polycyclic or chronic continuous. We describe a 35-year-old woman who presented with a sudden hearing loss in the left ear in the 37th week of her second pregnancy. She subsequently developed BRAO in the right eye 2.5 months after having given birth. MRI findings included round lesions in the corpus callosum which are pathognomonic for Susac syndrome. Previous patient records documented encephalopathy, sudden deafness of the right ear and visual field defects in the left eye at the age of 12, followed by permanent hearing and visual defects. We expand on the variability in the course of Susac syndrome as recurrence may occur after as long as 23 years. Cases of monophasic self-limiting Susac syndrome may in fact turn polycyclic with an interval of more than 2 decades between the bouts of the disease. In these cases, suspecting the development of exacerbation early is important in order to start the treatment promptly.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-231588 (URN)10.1159/000362868 (DOI)24987361 (PubMedID)
Available from: 2014-09-09 Created: 2014-09-09 Last updated: 2017-12-05Bibliographically approved
Finnsson, J., Melberg, A. & Raininko, R. (2013). 1H-MR spectroscopy of adult-onset autosomal dominant leukodystrophy with autonomic symptoms. Neuroradiology, 55(8), 933-939
Open this publication in new window or tab >>1H-MR spectroscopy of adult-onset autosomal dominant leukodystrophy with autonomic symptoms
2013 (English)In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 55, no 8, p. 933-939Article in journal (Refereed) Published
Abstract [en]

Adult-onset ADLD with autonomic symptoms is a rare disease with a clinical course somewhat similar to chronic progressive MS but with different imaging findings consisting of extensive white matter changes in the cerebrum and cerebellar peduncles. Patients usually present in the fourth to sixth decade with autonomic symptoms, manifesting later symptoms from the pyramidal tracts and ataxia. Here, we present magnetic resonance spectroscopy (MRS) findings in this disease. Fourteen subjects, from two non-related families, with genetic linkage to the disease were studied with magnetic resonance imaging and single-voxel MRS. Clinically, they ranged from asymptomatic to wheelchair-using. Their results were compared to those of age- and sex-matched healthy controls. One MRS was excluded due to suboptimal quality. The remaining 13 subjects manifested characteristic evidence of pathology on MRI, 11 of them exhibited extensive changes. The metabolite concentrations of total Cr, total Cho, and total NAA measured in millimolars, using internal water as a reference, were significantly lower in these 11 subjects compared to controls, and we found linear correlations between all these metabolite levels. When total Cr was used as a reference, we found no difference between subjects and controls. No lactate was detected. The decreased metabolite concentrations measured using internal water as a reference are most likely due to increased water content in the tissues, diluting all metabolites to a similar degree. This is also in agreement with the high signal intensity exhibited in the white matter on T2-weighted MR images and with the reported histopathological findings of vacuolated myelin.

National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-204429 (URN)10.1007/s00234-013-1174-5 (DOI)000322020900002 ()23636437 (PubMedID)
Available from: 2013-08-05 Created: 2013-08-05 Last updated: 2017-12-06Bibliographically approved
Sundblom, J., Melberg, A., Rücker, F., Smits, A. & Islander, G. (2013). A family with discordance between Malignant hyperthermia susceptibility and Rippling muscle disease. Journal of Anesthesia, 27(1), 128-131
Open this publication in new window or tab >>A family with discordance between Malignant hyperthermia susceptibility and Rippling muscle disease
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2013 (English)In: Journal of Anesthesia, ISSN 0913-8668, E-ISSN 1438-8359, Vol. 27, no 1, p. 128-131Article in journal (Refereed) Published
Abstract [en]

Rippling muscle disease (RMD) is a benign disorder affecting striated muscle.Malignant hyperthermia (MH) susceptibility is a potentially lethal disorder in which otherwise healthy individuals can develop an extreme hypermetabolism and muscle rigidity/rhabdomyolysis during anesthesia with potent inhalational agents and/or succinylcholine. Disturbed calcium homeostasis has been suggested as the cause of RMD symptoms. Uncontrolled increase in intracellular calcium concentration starts a MH reaction.

Purpose

To investigate if there is a relation between RMD and MH susceptibility in a family with both RMD and MH susceptibility.

Materials and methods

Ten members of a family segregating RMD had, prior to RMD diagnosis, been investigated for MH susceptibility. Results from MH and RMD investigations and anesthesia outcomes were cross-referenced and evaluated to find connections or phenotype variations predicted by in vitro contracture test results.

Results

There was no relation between RMD and MH susceptibility. There were no adverse anesthesia reactions recorded in this family.

Conclusions

RMD and MH susceptibility did not co-segregate. RMD patients should probably not be considered at risk for MH reactions.

Keywords
Caveolin 3, Malignant Hyperthermia, Rippling muscle disease, Calcium, Anesthesia
National Category
Anesthesiology and Intensive Care Neurology
Research subject
Anaesthesiology and Intensive Care; Neurology
Identifiers
urn:nbn:se:uu:diva-162047 (URN)10.1007/s00540-012-1482-7 (DOI)000315042200021 ()22976939 (PubMedID)
Available from: 2011-11-23 Created: 2011-11-23 Last updated: 2017-12-08Bibliographically approved
Pedroso, J. L., Povoas Barsottini, O. G., Lin, L., Melberg, A., Oliveira, A. S. & Mignot, E. (2013). A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient. Sleep, 36(8), 1257-1259
Open this publication in new window or tab >>A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient
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2013 (English)In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 36, no 8, p. 1257-1259Article in journal (Refereed) Published
Abstract [en]

STUDY OBJECTIVES: Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is caused by DNMT1 mutations. Diagnosing the syndrome can be difficult, as all clinical features may not be present at onset, HLA-DQB1*06:02 is often negative, and sporadic cases occur. We report on clinical and genetic findings in a 31-year-old woman with cerebellar ataxia, deafness, and narcolepsy, and discuss diagnostic challenges.

DESIGN: Clinical and genetic investigation in a patient and family members.

SETTING: Ataxia clinic, São Paulo, Brazil.

PATIENTS OR PARTICIPANTS: One patient and her family members.

INTERVENTIONS: N/A.

MEASUREMENTS AND RESULTS: Narcolepsy was supported by polysomnographic and multiple sleep latency testing. HLA-DQB1*06:02 was positive. CSF hypocretin-1 was 191 pg/mL (normal values > 200 pg/mL). Mild brain atrophy was observed on MRI, with cerebellar involvement. The patient, her asymptomatic mother, and 3 siblings gave blood samples for genetic analysis. DNMT1 exons 20 and 21 were sequenced. Haplotyping of polymorphic markers surrounding the mutation was performed. The proband had a novel DNMT1 mutation in exon 21, p.Cys596Arg, c.1786T > C. All 4 parental haplotypes could be characterized in asymptomatic siblings without the mutation, indicating that the mutation is de novo in the patient.

CONCLUSIONS: The Brazilian patient reported here further adds to the worldwide distribution of ADCA-DN. The mutation is novel, and illustrates a sporadic case with de novo mutation. We believe that many more cases with this syndrome are likely to be diagnosed in the near future, mandating knowledge of this condition and consideration of the diagnosis.

National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-204874 (URN)10.5665/sleep.2898 (DOI)000322578500020 ()23904686 (PubMedID)
Available from: 2013-08-12 Created: 2013-08-12 Last updated: 2017-12-06Bibliographically approved
Giorgio, E., Rolyan, H., Kropp, L., Chakka, A. B., Yatsenko, S., Gregorio, E. D., . . . Padiath, Q. S. (2013). Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele-Specific Expression. Human Mutation, 34(8), 1160-1171
Open this publication in new window or tab >>Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele-Specific Expression
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2013 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 34, no 8, p. 1160-1171Article in journal (Refereed) Published
Abstract [en]

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication-based mechanisms such fork stalling and template switching or microhomology-mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients' fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele-specific LMNB1 expression levels.

National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-204408 (URN)10.1002/humu.22348 (DOI)000321759900015 ()23649844 (PubMedID)
Available from: 2013-08-02 Created: 2013-08-02 Last updated: 2017-12-06Bibliographically approved
Berntsson, S. G., Holtz, A. & Melberg, A. (2013). Does intrathecal baclofen have a place in the treatment of painful spasms in friedreich ataxia. Case Reports in Neurology, 5(3), 201-203
Open this publication in new window or tab >>Does intrathecal baclofen have a place in the treatment of painful spasms in friedreich ataxia
2013 (English)In: Case Reports in Neurology, ISSN 1662-680X, E-ISSN 1662-680X, Vol. 5, no 3, p. 201-203Article in journal (Refereed) Published
Abstract [en]

We present the case of a 50-year-old female patient with Friedreich ataxia (FA) who was treated successfully with an intrathecal baclofen (ITB)-delivering pump for painful spasms. To our knowledge, this is the second reported case of FA where ITB relieved painful and disabling spasms. We suggest that ITB should be considered in the treatment of disabling spasms in patients with FA.

National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-223629 (URN)10.1159/000356823 (DOI)24348400 (PubMedID)
Available from: 2014-04-23 Created: 2014-04-23 Last updated: 2017-12-05Bibliographically approved
Hedberg, C., Melberg, A., Kuhl, A., Jenne, D. & Oldfors, A. (2013). Functional characterization of desmin mutant p.P419S Reply [Letter to the editor]. European Journal of Human Genetics, 21(6), 590-590
Open this publication in new window or tab >>Functional characterization of desmin mutant p.P419S Reply
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2013 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 21, no 6, p. 590-590Article in journal, Letter (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-203414 (URN)10.1038/ejhg.2012.214 (DOI)000319497700008 ()
Available from: 2013-07-10 Created: 2013-07-10 Last updated: 2017-12-06Bibliographically approved
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