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BETA
Landtblom, Anne-MarieORCID iD iconorcid.org/0000-0001-9567-470x
Alternative names
Publications (10 of 83) Show all publications
Herman, S., Niemelä, V., Emami Khoonsari, P., Sundblom, J., Burman, J., Landtblom, A.-M., . . . Kultima, K. (2019). Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects. Scientific Reports, 9, Article ID 4129.
Open this publication in new window or tab >>Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington's disease subjects
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4129Article in journal (Refereed) Published
Abstract [en]

Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD. These metabolites demonstrated moderate to strong associations to measures of disease severity and symptoms. Thyroxine and dopamine also correlated with the five year risk of onset in premanifest HD subjects. The phenylalanine and the purine metabolisms were also significantly altered, but associated less to disease severity. Decreased levels of lumichrome were commonly found in mutated HTT carriers and the levels correlated with the five year risk of disease onset in premanifest carriers. These biochemical findings demonstrates that the CSF metabolome can be used to characterize molecular pathogenesis occurring in HD, which may be essential for future development of novel HD therapies.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-379886 (URN)10.1038/s41598-019-40186-5 (DOI)000460754600020 ()30858393 (PubMedID)
Funder
Åke Wiberg FoundationEU, Horizon 2020, 654241
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-10-23Bibliographically approved
Berntsson, S. G., Gauffin, H., Melberg, A., Holtz, A. & Landtblom, A.-M. (2019). Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms. Stereotactic and Functional Neurosurgery, 97(1), 18-23
Open this publication in new window or tab >>Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms
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2019 (English)In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 97, no 1, p. 18-23Article in journal (Refereed) Published
Abstract [en]

Background: Intrathecal baclofen (ITB) treatment is considered a powerful tool in the management of severe spasticity in neurological conditions such as multiple sclerosis, cerebral palsy, and traumatic spinal cord and brain injury.

Objectives: The objective of this study was to assess the effectiveness of the ITB in patients with inherited ataxia suffering from severe painful spasms and/or spasticity.

Method: A total of 5 patients with spinocerebellar ataxia 3 or 7 or Friedreich's ataxia were included in this observational multicenter study. The patients were interviewed and completed outcome measures assessing pain (The Brief Pain Inventory), fatigue (Fatigue Severity Scale), and life satisfaction (LiSAT-9) before and 1 year after the treatment. Spasticity (Modified Ashworth Scale) and spasm frequency (SPFS) were measured objectively for each patient.

Results: The mean treatment time was 1.9 years. Evaluation of established standard forms revealed symptomatic relief from spasticity, spasms, pain, and fatigue in addition to improved body posture, sleep, and life satisfaction after ITB treatment.

Conclusions: We report the potential beneficial effects of ITB treatment in patients with inherited ataxia who also suffer from spasticity/spasms. ITB treatment indication in neurological disorders allows for extension to the treatment of spasticity/spasms in patients with hereditary ataxia.

Keywords
Intrathecal baclofen treatment, Inherited ataxia, Spasms, Spasticity, Pain
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-384476 (URN)10.1159/000497165 (DOI)000467683300003 ()31050312 (PubMedID)
Available from: 2019-06-05 Created: 2019-06-05 Last updated: 2019-10-18Bibliographically approved
Hallberg, P., Smedje, H., Eriksson, N., Kohnke, H., Daniilidou, M., Öhman, I., . . . Wadelius, M. (2019). Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival. EBioMedicine, 40, 595-604
Open this publication in new window or tab >>Pandemrix-induced narcolepsy is associated with genes related to immunity and neuronal survival
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2019 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 40, p. 595-604Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The incidence of narcolepsy rose sharply after the swine influenza A (H1N1) vaccination campaign with Pandemrix. Narcolepsy is an immune-related disorder with excessive daytime sleepiness. The most frequent form is strongly associated with HLA-DQB1*06:02, but only a minority of carriers develop narcolepsy. We aimed to identify genetic markers that predispose to Pandemrix-induced narcolepsy.

METHODS: We tested for genome-wide and candidate gene associations in 42 narcolepsy cases and 4981 controls. Genotyping was performed on Illumina arrays, HLA alleles were imputed using SNP2HLA, and single nucleotide polymorphisms were imputed using the haplotype reference consortium panel. The genome-wide significance threshold was p < 5 × 10-8, and the nominal threshold was p < 0.05. Results were replicated in 32 cases and 7125 controls. Chromatin data was used for functional annotation.

FINDINGS: Carrying HLA-DQB1*06:02 was significantly associated with narcolepsy, odds ratio (OR) 39.4 [95% confidence interval (CI) 11.3, 137], p = 7.9 × 10-9. After adjustment for HLA, GDNF-AS1 (rs62360233) was significantly associated, OR = 8.7 [95% CI 4.2, 17.5], p = 2.6 × 10-9, and this was replicated, OR = 3.4 [95% CI 1.2-9.6], p = 0.022. Functional analysis revealed variants in high LD with rs62360233 that might explain the detected association. The candidate immune-gene locus TRAJ (rs1154155) was nominally associated in both the discovery and replication cohorts, meta-analysis OR = 2.0 [95% CI 1.4, 2.8], p = 0.0002.

INTERPRETATION: We found a novel association between Pandemrix-induced narcolepsy and the non-coding RNA gene GDNF-AS1, which has been shown to regulate expression of the essential neurotrophic factor GDNF. Changes in regulation of GDNF have been associated with neurodegenerative diseases. This finding may increase the understanding of disease mechanisms underlying narcolepsy. Associations between Pandemrix-induced narcolepsy and immune-related genes were replicated.

Keywords
(MeSH), Autoimmune diseases, Drug-related side effects and adverse reactions, Genetic variation, Genome-wide association study, Glial cell line-derived neurotrophic factor, H1N1 subtype, Influenza A virus, Influenza vaccines, Narcolepsy, Pharmacogenetics, RNA, long noncoding
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-377169 (URN)10.1016/j.ebiom.2019.01.041 (DOI)000460696900067 ()30711515 (PubMedID)
Funder
Swedish Research Council, 521-2011-2440Swedish Research Council, 521-2014-3370Swedish Research Council, 2018-03307Swedish Heart Lung Foundation, 20120557Swedish Heart Lung Foundation, 20140291Swedish Heart Lung Foundation, 20170711Erik, Karin och Gösta Selanders FoundationThuréus stiftelse för främjande av geriatrisk forskningSwedish Research Council, 2017-00641
Available from: 2019-02-15 Created: 2019-02-15 Last updated: 2019-05-13Bibliographically approved
Landtblom, A.-M., Guala, D., Martin, C., Olsson-Hau, S., Haghighi, S., Jansson, L. & Fredrikson, S. (2019). RebiQoL: A randomized trial of telemedicine patient support program for health-related quality of life and adherence in people with MS treated with Rebif. PLoS ONE, 14(7), Article ID e0218453.
Open this publication in new window or tab >>RebiQoL: A randomized trial of telemedicine patient support program for health-related quality of life and adherence in people with MS treated with Rebif
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 7, article id e0218453Article in journal (Refereed) Published
Abstract [en]

RebiQoL was a phase IV multicenter randomized study to assess the impact of a telemedicine patient support program (MSP) on health-related quality of life (HRQoL) in patients with relapsing-remitting MS (RRMS) being administered with Rebif with the RebiSmart device. The primary endpoint was to assess the impact of MSP compared to patients only receiving technical support for RebiSmart on HRQoL at 12 months, using the psychological part of Multiple Sclerosis Impact Scale (MSIS-29), in patients administered with Rebif. A total of 97 patients diagnosed with RRMS were screened for participation in the study of which 3 patients did not fulfill the eligibility criteria and 1 patient withdrew consent. Of the 93 randomized patients, 46 were randomized to MSP and 47 to Technical support only. The demographic characteristics of the patients were well-balanced in the two arms. There were no statistical differences (linear mixed model) in any of the primary (difference of 0.48, 95% CI: -8.30-9.25, p = 0.91) or secondary outcomes (p>0.05). Although the study was slightly underpowered, there was a trend towards better adherence in the MSP group (OR 3.5, 95% CI 0.85-14.40, p = 0.08) although not statistically significant. No unexpected adverse events occurred. This study did not show a statistically significant effect of the particular form of teleintervention used in this study on HRQoL as compared to pure technical support, for MS patients already receiving Rebif with the RebiSmart device.

Trial Registration: ClinicalTrials.gov: NCT01791244.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-389751 (URN)10.1371/journal.pone.0218453 (DOI)000484936300017 ()31276502 (PubMedID)
Available from: 2019-07-23 Created: 2019-07-23 Last updated: 2019-10-18Bibliographically approved
Drissi, N. M., Warntjes, M., Wessén, A., Szakacs, A., Darin, N., Hallböök, T., . . . Engström, M. (2019). Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin. NeuroImage: Clinical, 23, Article ID 101875.
Open this publication in new window or tab >>Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin
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2019 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id 101875Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate structural changes in the brain stem of adolescents with narcolepsy, a disorder characterized by excessive daytime sleepiness, fragmented night-time sleep, and cataplexy. For this purpose, we used quantitative magnetic resonance imaging to obtain R1 and R2 relaxation rates, proton density, and myelin maps in adolescents with narcolepsy (n = 14) and healthy controls (n = 14). We also acquired resting state functional magnetic resonance imaging (fMRI) for brainstem connectivity analysis. We found a significantly lower R2 in the rostral reticular formation near the superior cerebellar peduncle in narcolepsy patients, family wise error corrected p = .010. Narcolepsy patients had a mean R2 value of 1.17 s-1 whereas healthy controls had a mean R2 of 1.31 s-1, which was a large effect size with Cohen d = 4.14. We did not observe any significant differences in R1 relaxation, proton density, or myelin content. The sensitivity of R2 to metal ions in tissue and the transition metal ion chelating property of neuromelanin indicate that the R2 deviant area is one of the neuromelanin containing nuclei of the brain stem. The close proximity and its demonstrated involvement in sleep-maintenance, specifically through orexin projections from the hypothalamus regulating sleep stability, as well as the results from the connectivity analysis, suggest that the observed deviant area could be the locus coeruleus or other neuromelanin containing nuclei in the proximity of the superior cerebellar peduncle. Hypothetically, the R2 differences described in this paper could be due to lower levels of neuromelanin in this area of narcolepsy patients.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Locus coeruleus, Myelin, Neuromelanin, Orexin/hypocretin, Quantitative MRI (qMRI), Relaxation time
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-386196 (URN)10.1016/j.nicl.2019.101875 (DOI)000485804400070 ()31174102 (PubMedID)
Funder
Medical Research Council of Southeast Sweden (FORSS), FORSS-480551Knut and Alice Wallenberg Foundation, KAW 2013.0076
Available from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-10-28Bibliographically approved
Demirbuker, S. S., Kagström, S., Fält, A., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 701-702
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 701-702Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369957 (URN)000446861401580 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Kagström, S., Fält, A., Demirbuker, S. S., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 699-700
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 699-700Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369956 (URN)000446861401578 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Fält, A., Kågström, S., Demirbuker, S. S., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 706-707
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 706-707Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369958 (URN)000446861401586 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Fält, A., Kagstrom, S., Demirbuker, S. S., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 696-697
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 696-697Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369955 (URN)000446861401574 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Demirbuker, S. S., Kågström, S., Fält, A., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY. Multiple Sclerosis, 24, 922-923
Open this publication in new window or tab >>A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4)
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2018 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, p. 922-923Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-369960 (URN)000446861402334 ()
Conference
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), OCT 10-12, 2018, Berlin, GERMANY
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9567-470x

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