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Article ; Online: The association between weight during early life and multiple sclerosis onset in a nationwide Dutch birth year cohort.

Loonstra, Floor C / de Ruiter, Lodewijk R J / Strijbis, Eva M M / de Jong, Brigit A / Uitdehaag, Bernard M J

2023 Volume 27, Issue 5, Page(s) 499–505

Abstract: Background: The relationship between being overweight during early life and disease course in multiple sclerosis (MS) is unresolved. We investigated the association between being overweight or obese during early life (childhood and adolescence) and MS ... ...

Abstract	Background: The relationship between being overweight during early life and disease course in multiple sclerosis (MS) is unresolved. We investigated the association between being overweight or obese during early life (childhood and adolescence) and MS case status, age of first symptom onset and onset type in people with MS (pwMS) of the same birth year. Methods: We enrolled 363 PwMS and 125 healthy controls (HC) from Project Y, a Dutch population-based cross-sectional cohort study including all PwMS born in 1966 and age and sex-matched HC. The associations between weight during childhood and adolescence (non-overweight vs. overweight or obese) and MS, age at symptom onset and onset type (relapsing vs. progressive) were assessed using logistic and linear regressions. In addition, sex-separated associations were explored. Results: Being overweight or obese during childhood (OR = 2.82, 95% CI 1.17-6.80) and adolescence (OR = 2.45, 95% CI 1.13-5.34) was associated with developing MS. Furthermore, being overweight or obese during adolescence was associated with a younger age of onset ( Conclusion: In a nationwide population-based birth year cohort, being overweight or obese during childhood or adolescence is associated with MS prevalence and an earlier age of onset, but does not seem to associate with the type of onset.
MeSH term(s)	Adolescent ; Humans ; Middle Aged ; Overweight/complications ; Overweight/epidemiology ; Multiple Sclerosis/complications ; Multiple Sclerosis/epidemiology ; Cross-Sectional Studies ; Body Mass Index ; Obesity/epidemiology ; Obesity/complications
Language	English
Publishing date	2023-07-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1447449-9
ISSN	1476-8305 ; 1028-415X
ISSN (online)	1476-8305
ISSN	1028-415X
DOI	10.1080/1028415X.2023.2225271
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Article ; Online: Association of volumetric MRI measures and disability in MS patients of the same age: Descriptions from a birth year cohort.

de Ruiter, Lodewijk R J / Loonstra, Floor C / Jelgerhuis, Julia R / Coerver, Eline M E / Toorop, Alyssa A / van Leeuwen, Ilona C E / Noteboom, Samantha / Moraal, Bastiaan / Strijbis, Eva M M / Schoonheim, Menno M / Uitdehaag, Bernard M J

Multiple sclerosis and related disorders

2023 Volume 71, Page(s) 104568

Abstract: Background and objectives: Although MRI-based markers of neuroinflammation have proven crucial for the diagnosis of multiple sclerosis (MS), predicting clinical progression with inflammation remains difficult. Neurodegenerative markers such as brain ... ...

Abstract	Background and objectives: Although MRI-based markers of neuroinflammation have proven crucial for the diagnosis of multiple sclerosis (MS), predicting clinical progression with inflammation remains difficult. Neurodegenerative markers such as brain volume loss show stronger clinical (predictive) correlations, but also harbor age-related variation that must be disentangled from disease duration. In this study we investigated how clinical disability is related to volumetric MRI measures in a cohort of MS patients and healthy controls (HC) of the same age: Project Y. Methods: This study included 234 MS patients born in 1966 and 112 HC born between 1965 and 1967 in the Netherlands. Disability was quantified using the expanded disability status scale (EDSS), nine hole peg test (9HPT), and timed 25 foot walking test (T25FWT). Volumes were quantified on 3T MRI as normalized whole brain (NBV) and regional gray matter (GM) volumes using the same scanner and MRI protocol: cortical (normalized cortical gray matter volume; NCGMV), deep (NDGMV), thalamic (NThalV), and cerebellar (NCbV) GM volumes. In addition, mean upper cervical cord area (MUCCA), white matter lesion volume (LV), and spinal cord lesions were assessed. These measures were compared between patients and HC, and related to disability measures using linear regression. Results: Mean age of people with MS (PwMS) was 52.8 years (SD 0.9) and median disease duration 15.8 years (IQR 8.7-24.8). All global and regional brain measures were lower in MS patients compared to HC. Univariate regression models showed that NDGMV (β = -0.20) and MUCCA (β = -0.38) were most strongly related to the EDSS in all PwMS. After subtype stratification, MUCCA was most strongly related to the EDSS (β = -0.60) and 9HPT (β = -0.55) in secondary progressive PwMS. Multivariate regression models demonstrated that in all PwMS, the EDSS was best explained by lower MUCCA, longer disease durations and a progressive disease course (adjusted-R (Sastre-Garriga et al., 2017) = 0.26, p < 0.001). MUCCA was a consistent correlate in separate models of the EDSS for all PwMS, relapsing and progressive onset PwMS. The 9HPT (adjusted-R (Sastre-Garriga et al., 2017) = 0.20, p < 0.001) was best explained by lower MUCCA, higher LV and pack years, while lower limb disability (adjusted-R (Sastre-Garriga et al., 2017) = 0.11, p < 0.001) was best explained by lower MUCCA, progressive onset MS and female sex. Discussion: Our results indicate that in a cohort unbiased by age differences, spinal cord and deep gray matter volumes best related to physical disability. Our results support the use of these measures in clinical practice and trials.
MeSH term(s)	Humans ; Female ; Middle Aged ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/pathology ; Magnetic Resonance Imaging/methods ; Gray Matter/pathology ; Multiple Sclerosis, Chronic Progressive/pathology ; Brain/diagnostic imaging ; Brain/pathology ; Disability Evaluation ; Atrophy/pathology
Language	English
Publishing date	2023-02-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2023.104568
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Article ; Online: The role of diet in multiple sclerosis onset and course: results from a nationwide retrospective birth-year cohort.

Loonstra, Floor C / de Ruiter, Lodewijk R J / Schoonheim, Menno M / Moraal, Bastiaan / Strijbis, Eva M M / de Jong, Brigit A / Uitdehaag, Bernard M J

Annals of clinical and translational neurology

2023 Volume 10, Issue 8, Page(s) 1268–1283

Abstract: Objective: To examine (1) the association between childhood diet and developing MS, age of onset and onset type and (2) the association between diet at age 50 and disability and MRI volumes in people with MS (PwMS).: Methods: The study enrolled 361 ... ...

Abstract	Objective: To examine (1) the association between childhood diet and developing MS, age of onset and onset type and (2) the association between diet at age 50 and disability and MRI volumes in people with MS (PwMS). Methods: The study enrolled 361 PwMS born in 1966 and 125 age- and sex-matched healthy controls (HCs). Information on individual dietary components (fruit, vegetables, red meat, oily fish, whole-grain bread and candy, snacks and fast food) and MS risk factors at the age of 10 and 50 years were collected using questionnaires. Overall diet quality score was calculated for each participant. Multivariable regression analyses were used to evaluate the association between diet at childhood and developing MS, age of onset and onset type and to evaluate diet at age 50, disability and MRI outcomes. Results: Poorer overall diet quality and individual dietary components during childhood (less whole-grain bread, more candy, snacks and fast food and oily fish) were associated with developing MS and onset type (all p < 0.05), but not with the age of onset. Fruit consumption at age 50 was associated with lower disability (Q3 vs. Q1: -0.51; 95% CI: -0.89 to -0.13). Furthermore, several individual dietary components at age 50 were associated with MRI volumetric measures. Higher-diet quality at age 50 was only associated with lower lesion volumes in PwMS (Q2 vs. Q1: -0.3 mL; 95% CI: -0.5 to -0.02). Interpretation: We demonstrate significant associations between dietary factors in childhood and developing MS, age of onset and onset type and between dietary factors at age 50 and disability and MRI-derived volumes.
MeSH term(s)	Animals ; Humans ; Middle Aged ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/etiology ; Retrospective Studies ; Diet/adverse effects ; Fruit ; Vegetables
Language	English
Publishing date	2023-07-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51788
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Article ; Online: COVID-19 in multiple sclerosis: The Dutch experience.

Loonstra, Floor C / Hoitsma, Elske / van Kempen, Zoé LE / Killestein, Joep / Mostert, Jop P

Multiple sclerosis (Houndmills, Basingstoke, England)

2020 Volume 26, Issue 10, Page(s) 1256–1260

Abstract: Here, we provide an extensive overview of all reported COVID-19 cases in multiple sclerosis (MS) patients in the Netherlands between 27 February and 9 June 2020, gathered by the Dutch MS Taskforce of the Netherlands Society of Neurology. A total of 86 MS ...

Abstract	Here, we provide an extensive overview of all reported COVID-19 cases in multiple sclerosis (MS) patients in the Netherlands between 27 February and 9 June 2020, gathered by the Dutch MS Taskforce of the Netherlands Society of Neurology. A total of 86 MS patients were reported, 43 of whom tested positive for COVID-19. Of 43 patients who tested positive, 22 patients were hospitalized. Three intensive care unit (ICU) admissions and four deaths were reported. Our findings show no apparent difference in disease-modifying treatment (DMT) use and COVID-19 disease course in Dutch MS patients. In addition, a clear link between low lymphocyte count and severe disease was not observed.
MeSH term(s)	Adult ; Aged ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/blood ; Coronavirus Infections/epidemiology ; Coronavirus Infections/mortality ; Coronavirus Infections/physiopathology ; Female ; Hospitalization/statistics & numerical data ; Humans ; Immunologic Factors/therapeutic use ; Intensive Care Units ; Lymphocyte Count ; Lymphopenia/blood ; Lymphopenia/epidemiology ; Male ; Middle Aged ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/epidemiology ; Netherlands/epidemiology ; Pandemics ; Pneumonia, Viral/blood ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/mortality ; Pneumonia, Viral/physiopathology ; SARS-CoV-2 ; Severity of Illness Index ; Young Adult
Chemical Substances	Immunologic Factors
Keywords	covid19
Language	English
Publishing date	2020-07-14
Publishing country	England
Document type	Journal Article
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458520942198
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Article ; Online: Response to letter 'Lymphocyte counts and the risk of COVID-19 in people with MS'.

Loonstra, Floor C / van Kempen, Zoé LE / Strijbis, Eva M / Killestein, Joep / Hoitsma, Elske / Mostert, Jop P

Multiple sclerosis (Houndmills, Basingstoke, England)

2020 Volume 27, Issue 10, Page(s) 1626–1627

MeSH term(s)	COVID-19 ; Humans ; Lymphocyte Count ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-10-16
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458520965468
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Article ; Online: Association of Arachidonic Acid-Derived Lipid Mediators With Disease Severity in Patients With Relapsing and Progressive Multiple Sclerosis.

Broos, Jelle Y / Loonstra, Floor C / de Ruiter, Lodewijk R J / Gouda, Mariam / Fung, Wing Hee / Schoonheim, Menno M / Heijink, Marieke / Strijbis, Eva M M / Teunissen, Charlotte / Killestein, Joep / de Vries, Helga E / Giera, Martin / Uitdehaag, Bernard M J / Kooij, Gijs

Neurology

2023 Volume 101, Issue 5, Page(s) e533–e545

Abstract: Background and objectives: Excessive activation of certain lipid mediator (LM) pathways plays a role in the complex pathogenesis of multiple sclerosis (MS). However, the relationship between bioactive LMs and different aspects of CNS-related ... ...

Abstract	Background and objectives: Excessive activation of certain lipid mediator (LM) pathways plays a role in the complex pathogenesis of multiple sclerosis (MS). However, the relationship between bioactive LMs and different aspects of CNS-related pathophysiologic processes remains largely unknown. Therefore, in this study, we assessed the association of bioactive LMs belonging to the ω-3/ω-6 lipid classes with clinical and biochemical (serum neurofilament light [sNfL] and serum glial fibrillary acidic protein [sGFAP]) parameters and MRI-based brain volumes in patients with MS (PwMS) and healthy controls (HCs). Methods: A targeted high-performance liquid chromatography-tandem mass spectrometry approach was used on plasma samples of PwMS and HCs of the Project Y cohort, a cross-sectional population-based cohort that contains PwMS all born in 1966 in the Netherlands and age-matched HCs. LMs were compared between PwMS and HCs and were correlated with levels of sNfL, sGFAP, disability (Expanded Disability Status Scale [EDSS]), and brain volumes. Finally, significant correlates were included in a backward multivariate regression model to identify which LMs best related to disability. Results: The study sample consisted of 170 patients with relapsing remitting MS (RRMS), 115 patients with progressive MS (PMS), and 125 HCs. LM profiles of patients with PMS significantly differed from those of patients with RRMS and HCs, particularly patients with PMS showed elevated levels of several arachidonic acid (AA) derivatives. In particular, 15-hydroxyeicosatetraenoic acid (HETE) ( Discussion: In PwMS of the same birth year, we show that ω-3 and ω-6 LMs are associated with disability, biochemical parameters (sNfL, GFAP), and MRI measures. Furthermore, our findings indicate that, particularly, in patients with PMS, elevated levels of specific products of the AA pathway, such as 15-HETE, associate with neurodegenerative processes. Our findings highlight the potential relevance of ω-6 LMs in the pathogenesis of MS.
MeSH term(s)	Humans ; Middle Aged ; Multiple Sclerosis/pathology ; Arachidonic Acid ; Cross-Sectional Studies ; Multiple Sclerosis, Chronic Progressive ; Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging ; Patient Acuity
Chemical Substances	Arachidonic Acid (27YG812J1I)
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000207459
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Article ; Online: Adipokines in multiple sclerosis patients are related to clinical and radiological measures.

Loonstra, Floor C / Falize, Kim F / de Ruiter, Lodewijk R J / Schoonheim, Menno M / Strijbis, Eva M M / Killestein, Joep / de Vries, Helga E / Uitdehaag, Bernard M J / Rijnsburger, Merel

Journal of neurology

2022 Volume 270, Issue 4, Page(s) 2018–2030

Abstract: Background: An imbalance of adipokines, hormones secreted by white adipose tissue, is suggested to play a role in the immunopathology of multiple sclerosis (MS). In people with MS (PwMS) of the same age, we aimed to determine whether the adipokines ... ...

Abstract	Background: An imbalance of adipokines, hormones secreted by white adipose tissue, is suggested to play a role in the immunopathology of multiple sclerosis (MS). In people with MS (PwMS) of the same age, we aimed to determine whether the adipokines adiponectin, leptin, and resistin are associated with MS disease severity. Furthermore, we aimed to investigate whether these adipokines mediate the association between body mass index (BMI) and MS disease severity. Methods: Adiponectin, resistin, and leptin were determined in serum using ELISA. 288 PwMS and 125 healthy controls (HC) were included from the Project Y cohort, a population-based cross-sectional study of people with MS born in the Netherlands in 1966, and age and sex-matched HC. Adipokine levels and BMI were related to demographic, clinical and disability measures, and MRI-based brain volumes. Results: Adiponectin levels were 1.2 fold higher in PwMS vs. HC, especially in secondary progressive MS. Furthermore, we found a sex-specific increase in adiponectin levels in primary progressive (PP) male patients compared to male controls. Leptin and resistin levels did not differ between PwMS and HC, however, leptin levels were associated with higher disability (EDSS) and resistin strongly related to brain volumes in progressive patients, especially in several grey matter regions in PPMS. Importantly, correction for BMI did not significantly change the results. Conclusion: In PwMS of the same age, we found associations between adipokines (adiponectin, leptin, and resistin) and a range of clinical and radiological metrics. These associations were independent of BMI, indicating distinct mechanisms.
MeSH term(s)	Female ; Humans ; Male ; Adipokines ; Leptin ; Resistin ; Adiponectin ; Multiple Sclerosis/diagnostic imaging ; Cross-Sectional Studies
Chemical Substances	Adipokines ; Leptin ; Resistin ; Adiponectin
Language	English
Publishing date	2022-12-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-022-11519-8
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Article: COVID-19 in multiple sclerosis: The Dutch experience

Loonstra, Floor C / Hoitsma, Elske / van Kempen, Zoé LE / Killestein, Joep / Mostert, Jop P

Mult Scler

Abstract	Here, we provide an extensive overview of all reported COVID-19 cases in multiple sclerosis (MS) patients in the Netherlands between 27 February and 9 June 2020, gathered by the Dutch MS Taskforce of the Netherlands Society of Neurology. A total of 86 MS patients were reported, 43 of whom tested positive for COVID-19. Of 43 patients who tested positive, 22 patients were hospitalized. Three intensive care unit (ICU) admissions and four deaths were reported. Our findings show no apparent difference in disease-modifying treatment (DMT) use and COVID-19 disease course in Dutch MS patients. In addition, a clear link between low lymphocyte count and severe disease was not observed.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #646629
Database	COVID19

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Article ; Online: COVID-19 in multiple sclerosis

Loonstra, Floor C / Hoitsma, Elske / van Kempen, Zoé LE / Killestein, Joep / Mostert, Jop P

Multiple Sclerosis Journal

The Dutch experience

2020 Volume 26, Issue 10, Page(s) 1256–1260

Abstract	Here, we provide an extensive overview of all reported COVID-19 cases in multiple sclerosis (MS) patients in the Netherlands between 27 February and 9 June 2020, gathered by the Dutch MS Taskforce of the Netherlands Society of Neurology. A total of 86 MS patients were reported, 43 of whom tested positive for COVID-19. Of 43 patients who tested positive, 22 patients were hospitalized. Three intensive care unit (ICU) admissions and four deaths were reported. Our findings show no apparent difference in disease-modifying treatment (DMT) use and COVID-19 disease course in Dutch MS patients. In addition, a clear link between low lymphocyte count and severe disease was not observed.
Keywords	Neurology ; Clinical Neurology ; covid19
Language	English
Publisher	SAGE Publications
Publishing country	us
Document type	Article ; Online
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458520942198
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Article ; Online: Project Y: The search for clues explaining phenotype variability in MS.

Loonstra, Floor C / De Ruiter, Lodewijk R J / Doesburg, Djoeke / Lam, Ka-Hoo / Van Lierop, Zoë Y G J / Moraal, Bastiaan / Strijbis, Eva M M / Killestein, Joep / Uitdehaag, Bernard M J

Multiple sclerosis and related disorders

2021 Volume 57, Page(s) 103337

Abstract: Background: To study phenotypic variability in MS patients, well-defined unbiased cohort studies are necessary. The most common and probably most important confounding factor when studying disease phenotype in MS is age.: Objective: To describe study ...

Abstract	Background: To study phenotypic variability in MS patients, well-defined unbiased cohort studies are necessary. The most common and probably most important confounding factor when studying disease phenotype in MS is age. Objective: To describe study design and subject characteristics of a unique birth cohort (Project Y). The overall aim of Project Y is to identify determinants associated with phenotypic variability in MS, eliminating the possibility of confounding by age. Methods: Project Y is a population-based cross-sectional study of all people with MS born in the Netherlands in 1966. Patients and healthy controls were subjected to comprehensive examinations: functional and static imaging, physical and cognitive measurements, and lifestyle factors early and later in life. In addition body fluids were collected and stored for future biomarker research. Results: 452 eligible MS patients were identified. Between December 2017 and January 2021, 367 MS patients and 125 healthy controls participated. The total number of identified cases results in a current prevalence of at least 189/100.000 for people born in the year 1966 in The Netherlands. Conclusion: Project Y is a unique cohort designed to identify factors associated with phenotypic variability in MS patients without the confounding effects of age. This first description of the Project Y cohort indicates that the prevalence of MS in the Netherlands might be higher than previously presumed. Various studies using Project Y data are ongoing and results will be published in upcoming years.
MeSH term(s)	Biological Variation, Population ; Cohort Studies ; Cross-Sectional Studies ; Humans ; Longitudinal Studies ; Multiple Sclerosis/epidemiology ; Phenotype
Language	English
Publishing date	2021-10-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2021.103337
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