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Fagius, Jan
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Publications (10 of 34) Show all publications
Silfverberg, T., Zjukovskaja, C., Ljungman, P., Nahimi, A., Ahlstrand, E., Dreimane, A., . . . Burman, J. (2024). Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study. Journal of Neurology, Neurosurgery and Psychiatry, 95(2), 125-133
Open this publication in new window or tab >>Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study
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2024 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 95, no 2, p. 125-133Article in journal (Refereed) Published
Abstract [en]

Background A growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare.

Methods We assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT.

Results With a median follow-up time of 5.5 (IQR: 3.4–7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (±SD: 1.5) for grade 3 events and 0.06 (±SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality.

Conclusions Treatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2024
Keywords
multiple sclerosis, haematology, clinical neurology
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-528598 (URN)10.1136/jnnp-2023-331864 (DOI)001072638600001 ()37748927 (PubMedID)
Funder
Marianne and Marcus Wallenberg FoundationRegion StockholmSwedish Research CouncilSwedish Society for Medical Research (SSMF), 2020-02700Swedish Society of Medicine
Available from: 2024-05-24 Created: 2024-05-24 Last updated: 2024-05-24Bibliographically approved
Fagius, J., Klar, J. & Dahl, N. (2023). Early-onset hereditary isolated non-neurogenic orthostatic hypotension in a Swedish family. Clinical Autonomic Research, 33(4), 421-432
Open this publication in new window or tab >>Early-onset hereditary isolated non-neurogenic orthostatic hypotension in a Swedish family
2023 (English)In: Clinical Autonomic Research, ISSN 0959-9851, E-ISSN 1619-1560, Vol. 33, no 4, p. 421-432Article in journal (Refereed) Published
Abstract [en]

Methods One severely affected individual underwent thorough investigation with neurophysiological and blood pressure (BP) measurements, including direct recording of baroreflex-governed sympathetic nerve signalling and induction of BP rise with phenylephrine. Family members underwent parts of the examination. Genetic analysis using exome sequencing was performed.

Results Marked postural hypotension with greatly reduced cardiac preload was observed, but without signs of autonomic nervous system dysfunction: sympathetic nerve signalling was normal, as were catecholamine levels, and phenylephrine stimulation revealed a normal increase in BP. The results of the genetic analysis using exome sequencing comprising all known genes associated with the regulation of BP and catecholamine metabolism were normal.

Conclusion The combined findings suggest an autosomal dominant form of early-onset orthostatic hypotension with variable clinical expression and without any additional autonomic dysfunction. It is possible that further investigation will reveal an as yet undescribed entity of orthostatic hypotension transmitted as an autosomal dominant trait.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2023
Keywords
Orthostatic hypotension, Autonomic nervous system, Microneurography, Autosomal dominant hereditary disorder
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-509534 (URN)10.1007/s10286-023-00963-9 (DOI)001031361100001 ()37460866 (PubMedID)
Funder
Uppsala University
Available from: 2023-08-20 Created: 2023-08-20 Last updated: 2023-10-05Bibliographically approved
Fagius, J. & Fagius, G. (2022). Hemisfärernas musik – ur barnets perspektiv: Barn kan och vill sjunga. Socialmedicinsk Tidskrift, 99(5-6), 684-696
Open this publication in new window or tab >>Hemisfärernas musik – ur barnets perspektiv: Barn kan och vill sjunga
2022 (Swedish)In: Socialmedicinsk Tidskrift, ISSN 0037-833X, E-ISSN 2000-4192, Vol. 99, no 5-6, p. 684-696Article in journal (Refereed) Published
Abstract [sv]

Barn kan tillgodogöra sig musik. Nyfödda barn uppmärksammar musik; prematura barns näringsintag effektiviseras av vaggsång; föredrar konsonant harmoniserad musik framför dissonans; föredrar skalor med olikstora skalsteg framför ”falskklingande” skala med sju likstora tonsteg. Hos 4 dagar gamla spädbarn aktiveras hjärnan på likartat sätt som hos vuxna vid åhörandet av musik harmoniserad enligt musikalisk syntax, medan syntaxbrott ger ”kaotiskt” aktiveringsmönster. Spädbarn avstressas av tilltalet ”mödriska” och än mera av vaggsång. – Småbarn vill sjunga. Sånglusten bör välkomnas, på barnets fysiologiska villkor. Stämbanden är korta och vulnerabla. Barnets spontana tonläge ligger högre än den vuxnes; vid gemensam sång måste ett för barnet bekvämt tonläge väljas. Om barnet försöker imitera den vuxnes tonläge uppkommer pratsång, som försvårar barnets sångliga utveckling och kan skada rösten. Kungl. Musikaliska Akademien driver ett angeläget projekt om Sjungande barn (https://www.sjungandebarn.se).

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-491716 (URN)
Available from: 2022-12-22 Created: 2022-12-22 Last updated: 2024-09-04Bibliographically approved
Burman, J., Fagius, J. & Nyholm, D. (2020). Den neurologiska konsultationen. In: Nyholm, Burman (Ed.), Neurologi: . Liber
Open this publication in new window or tab >>Den neurologiska konsultationen
2020 (Swedish)In: Neurologi / [ed] Nyholm, Burman, Liber, 2020Chapter in book (Other academic)
Abstract [sv]

Neurologi är en pedagogisk lärobok med förankring i diagnostisk och terapeutisk tradition i Sverige. I denna sjätte upplaga har texten genomgått en omfattande revision. Boken har fått en helt ny disposition samt ett nytt kapitel om funktionella neurologiska sjukdomar. Även i denna upplaga betonas alltjämt neurologins fundament, dvs. noggrann anamnes, somatisk undersökning och klinisk analys. 

Place, publisher, year, edition, pages
Liber, 2020
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-430227 (URN)978-91-47-12858-7 (ISBN)
Available from: 2021-01-08 Created: 2021-01-08 Last updated: 2021-10-14Bibliographically approved
Burman, J., Fagius, J. & Nyholm, D. (2020). Neurologisk symtomlära. In: Neurologi: . Liber
Open this publication in new window or tab >>Neurologisk symtomlära
2020 (Swedish)In: Neurologi, Liber, 2020Chapter in book (Other academic)
Place, publisher, year, edition, pages
Liber, 2020
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-430226 (URN)978-91-47-12858-7 (ISBN)
Available from: 2021-01-08 Created: 2021-01-08 Last updated: 2021-09-24Bibliographically approved
Burt, R. K., Balabanov, R., Burman, J., Sharrack, B., Snowden, J. A., Oliveira, M. C., . . . Helenowski, I. B. (2019). Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial. Journal of the American Medical Association (JAMA), 321(2), 165-174
Open this publication in new window or tab >>Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial
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2019 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, no 2, p. 165-174Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS).

OBJECTIVE To compare the effect of nonmyeloablative HSCT vs disease-modifying therapy (DMT) on disease progression.

DESIGN, SETTING, AND PARTICIPANTS Between September 20, 2005, and July 7, 2016, a total of 110 patients with relapsing-remitting MS, at least 2 relapses while receiving DMT in the prior year, and an Expanded Disability Status Scale (EDSS; score range, 0-10 [10 = worst neurologic disability]) score of 2.0 to 6.0 were randomized at 4 US, European, and South American centers. Final follow-up occurred in January 2018 and database lock in February 2018.

INTERVENTIONS Patients were randomized to receive HSCT along with cyclophosphamide (200mg/kg) and antithymocyte globulin (6mg/kg) (n = 55) or DMT of higher efficacy or a different class than DMT taken during the previous year (n = 55).

MAIN OUTCOMES AND MEASURES The primary end point was disease progression, defined as an EDSS score increase after at least 1 year of 1.0 point or more (minimal clinically important difference, 0.5) on 2 evaluations 6 months apart, with differences in time to progression estimated as hazard ratios. RESULTS Among 110 randomized patients (73 [66%] women; mean age, 36 [SD, 8.6] years), 103 remained in the trial, with 98 evaluated at 1 year and 23 evaluated yearly for 5 years (median follow-up, 2 years; mean, 2.8 years). Disease progression occurred in 3 patients in the HSCT group and 34 patients in the DMT group. Median time to progression could not be calculated in the HSCT group because of too few events; it was 24 months (interquartile range, 18-48 months) in the DMT group (hazard ratio, 0.07; 95% CI, 0.02-0.24; P < .001). During the first year, mean EDSS scores decreased (improved) from 3.38 to 2.36 in the HSCT group and increased (worsened) from 3.31 to 3.98 in the DMT group (between-group mean difference,-1.7; 95% CI,-2.03 to -1.29; P < .001). There were no deaths and no patients who received HSCT developed nonhematopoietic grade 4 toxicities (such as myocardial infarction, sepsis, or other disabling or potential life-threatening events).

CONCLUSIONS AND RELEVANCE In this preliminary study of patients with relapsing-remitting MS, nonmyeloablative HSCT, compared with DMT, resulted in prolonged time to disease progression. Further research is needed to replicate these findings and to assess long-term outcomes and safety.

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC, 2019
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-375869 (URN)10.1001/jama.2018.18743 (DOI)000455606300015 ()30644983 (PubMedID)
Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved
Skoog, B., Link, J., Tedeholm, H., Longfils, M., Nerman, O., Fagius, J. & Andersen, O. (2019). Short-term prediction of secondary progression in a slinding window: A test of a prdicting alogrithm in a validation cohort. Multiple Sclerosis Journal, Experimental, Translational and Clinical, 5(3), 1-10
Open this publication in new window or tab >>Short-term prediction of secondary progression in a slinding window: A test of a prdicting alogrithm in a validation cohort
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2019 (English)In: Multiple Sclerosis Journal, Experimental, Translational and Clinical, E-ISSN 2055-2173, Vol. 5, no 3, p. 1-10Article in journal (Refereed) Published
Abstract [en]

Introduction The Multiple Sclerosis Prediction Score (MSPS, www.msprediction.com) estimates, for any month during the course of relapsing–remitting multiple sclerosis (MS), the individual risk of transition to secondary progression (SP) during the following year.

Objective Internal verification of the MSPS algorithm in a derivation cohort, the Gothenburg Incidence Cohort (GIC, n =  144) and external verification in the Uppsala MS cohort (UMS, n = 145).

Methods Starting from their second relapse, patients were included and followed for 25 years. A matrix of MSPS values was created. From this matrix, a goodness-of-fit test and suitable diagnostic plots were derived to compare MSPS-calculated and observed outcomes (i.e. transition to SP).

Results The median time to SP was slightly longer in the UMS than in the GIC, 15 vs. 11.5 years (p = 0.19). The MSPS was calibrated with multiplicative factors: 0.599 for the UMS and 0.829 for the GIC; the calibrated MSPS provided a good fit between expected and observed outcomes (chi-square p = 0.61 for the UMS), which indicated the model was not rejected.

Conclusion The results suggest that the MSPS has clinically relevant generalizability in new cohorts, provided that the MSPS was calibrated to the actual overall SP incidence in the cohort.

Place, publisher, year, edition, pages
SAGE Publications, 2019
Keywords
Epidemiology, multiple sclerosis, outcome measurement, progressive, relapsing/remitting
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-402262 (URN)10.1177/2055217319875466 (DOI)000679156300006 ()35145727 (PubMedID)
Available from: 2020-01-13 Created: 2020-01-13 Last updated: 2022-06-30Bibliographically approved
Tolf, A., Fagius, J., Carlson, K., Åkerfeldt, T., Granberg, T., Larsson, E.-M. & Burman, J. (2019). Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation. Acta Neurologica Scandinavica, 140(5), 320-327
Open this publication in new window or tab >>Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation
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2019 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 140, no 5, p. 320-327Article in journal (Refereed) Published
Abstract [en]

Objectives: To determine whether treatment with autologous hematopoietic stem cell transplantation (HSCT) can induce sustained complete remission in patients with multiple sclerosis (MS).

Material and methods: Case series of patients with relapsing‐remitting MS (n = 10) treated at a single center between 2004 and 2007 and followed up for 10 years. The patients were treated with a BEAM/ATG conditioning regimen (n = 9) or a cyclophosphamide/ATG conditioning regimen (n = 1) followed by infusion of unmanipulated autologous hematopoietic stem cells. The primary endpoint was sustained complete remission. Sustained complete remission was defined as “no evidence of disease activity‐4,” sustained for a period of at least 5 years without any ongoing disease‐modifying treatment. Furthermore, MS was considered as “resolved” if intrathecal IgG production and cerebrospinal fluid neurofilament light levels were normalized as well.

Results: Five out of 10 patients were in sustained complete remission at the end of the study. In three of them, MS was resolved.

Conclusions: Our data demonstrate that sustained complete remission after autologous HSCT for MS is possible.

 

Keywords
cerebrospinal fluid, hematopoietic stem cell transplantation, magnetic resonance imaging, multiple sclerosis
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-390961 (URN)10.1111/ane.13147 (DOI)000479109700001 ()31297793 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF)
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2023-10-26Bibliographically approved
Tolf, A., Granberg, T., Larsson, E.-M., Landtblom, A.-M., Fagius, J. & Burman, J. (2017). Corpus callosum atrophy in MS is halted by autologous haematopoietic stem cell transplantation. Paper presented at 7th Joint European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS)-Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS), OCT 25-28, 2017, Paris, FRANCE. Multiple Sclerosis Journal, 23, 1006-1007
Open this publication in new window or tab >>Corpus callosum atrophy in MS is halted by autologous haematopoietic stem cell transplantation
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2017 (English)In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, p. 1006-1007Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SAGE PUBLICATIONS LTD, 2017
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-345575 (URN)000413730206044 ()
Conference
7th Joint European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS)-Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS), OCT 25-28, 2017, Paris, FRANCE
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2022-09-15Bibliographically approved
Fagius, J., Feresiadou, A., Larsson, E.-M. & Burman, J. (2017). Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients: First line drugs vs natalizumab. Multiple Sclerosis and Related Disorders, 12, 82-87, Article ID S2211-0348(17)30010-X.
Open this publication in new window or tab >>Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients: First line drugs vs natalizumab
2017 (English)In: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 12, p. 82-87, article id S2211-0348(17)30010-XArticle in journal (Refereed) Published
Abstract [en]

BACKGROUND: Several disease-modifying drugs (DMD) are available for the treatment of MS, and most patients with relapsing-remitting disease are currently treated. Data on when and how DMD treatment can be safely discontinued are scarce.

METHODS: Fifteen MS patients, treated with natalizumab for >5 years without clinical and radiological signs of inflammatory disease activity, suspended treatment and were monitored with MRI examinations and clinical follow-up to determine recurrence of disease activity. This group was compared with a retrospectively analysed cohort comprising 55 MS patients treated with first-line DMDs discontinuing therapy in the time period of 1998-2015 after an analogous stable course.

RESULTS: Natalizumab discontinuers were followed for on average 19 months, and follow-up data for 56 months were available for first-line DMD quitters. Two-thirds of natalizumab treated patients experienced recurrent inflammatory disease activity, and one third had recurrence of rebound character. In contrast, 35% of first-line DMD quitters had mild recurrent disease activity, and no one exhibited rebound.

CONCLUSIONS: Withdrawal of a first-line DMD after prolonged treatment in middle-aged MS patients with stable disease appears to be relatively safe, while natalizumab withdrawal in a similar group of patients cannot be safely done without starting alternative therapy.

Keywords
Multiple sclerosis, Natalizumab discontinuation, Rebound, Treatment discontinuation
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-317425 (URN)10.1016/j.msard.2017.01.009 (DOI)000396908400017 ()28283113 (PubMedID)
Available from: 2017-03-14 Created: 2017-03-14 Last updated: 2018-09-04Bibliographically approved
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