Publications by authors named "Henrik Kahr Mathiesen"

13 Publications

  • Page 1 of 1

Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts.

CNS Drugs 2021 11 18;35(11):1217-1232. Epub 2021 Sep 18.

Neurology Unit, Garibaldi Hospital, Catania, Italy.

Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined.

Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest.

Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients' sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed with weighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score.

Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15-41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65-0.88); in those aged ≤ 38 years (0.64; 0.54-0.76); in those with disease duration ≤ 7 years (0.63; 0.53-0.76); in those with EDSS score < 4 (0.75; 0.64-0.88), < 6 (0.80; 0.70-0.91), and ≥ 6 (0.52; 0.31-0.86); and in patients with pre-baseline relapses (0.74; 0.64-0.86). A higher probability of confirmed disability improvement on natalizumab versus fingolimod (hazard ratio [HR]; 95% CI) was observed among women (1.36; 1.10-1.66); those aged > 38 years (1.34; 1.04-1.73); those with disease duration > 7 years (1.33; 1.01-1.74); those with EDSS score < 6 (1.21; 1.01-1.46) and ≥ 6 (1.93; 1.11-3.34); and patients with no new MRI lesion (1.73; 1.19-2.51).

Conclusions: Overall, in women, younger patients, those with shorter disease durations, and patients with pre-treatment relapses, natalizumab was associated with a lower frequency of multiple sclerosis relapses than fingolimod. It was also associated with an increased chance of recovery from disability among most patients, particularly women and those with no recent MRI activity.
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http://dx.doi.org/10.1007/s40263-021-00860-7DOI Listing
November 2021

[Fampridine and multiple sclerosis].

Ugeskr Laeger 2014 Jan;176(3A):V06130416

Neurologisk Klinik, Dansk Multipel Sklerose Center, Rigshospitalet, Blegdamsvej 9, 2100 København Ø.

The background for the use of fampridine, the indications, contraindications, side effects, and recommendations for Danish patients with multiple sclerosis are reviewed.
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January 2014

Cortical N-acetyl aspartate is a predictor of long-term clinical disability in multiple sclerosis.

Neurol Res 2014 Aug 21;36(8):701-8. Epub 2014 Jan 21.

Objective: To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS).

Methods: Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months for 24 months. Clinical examinations, including the expanded disability status scale (EDSS), were performed at baseline, month 24, and at year 7.

Results: Baseline cortical NAA/Cr correlated inversely with EDSS at month 24 (r  =  -0·61, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05). Baseline cortical NAA/Cr also correlated inversely with EDSS at the 7-year follow-up (r  =  -0·56, P < 0·05), and patients with EDSS ≧ 4 had a lower baseline cortical NAA/Cr compared to those with EDSS less than 4 (P < 0·05). Baseline brain parenchymal fraction (BPF) correlated inversely with EDSS at month 24 (r  =  -0·61, P < 0·05), but not with EDSS at year 7.

Discussion: Cortical NAA/Cr in early RRMS correlated with clinical disability after 2 and 7 years and may be used as a predictor of long-term disease outcome.
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http://dx.doi.org/10.1179/1743132813Y.0000000312DOI Listing
August 2014

[Diagnosis of multiple sclerosis--the 2010 revision of the McDonald criteria].

Ugeskr Laeger 2012 Mar;174(13):862-5

Dansk Multipel Sclerose Center, Neurologisk Klinik, Rigshospitalet, København Ø, Denmark.

The 2010 revision of the McDonald diagnostic criteria for multiple sclerosis is reviewed. The diagnostic criteria have been simplified, which allows earlier diagnosis and treatment of multiple sclerosis.
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March 2012

[Magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis].

Ugeskr Laeger 2008 Aug;170(34):2579-81

Rigshospitalet, Dansk Multipel Sclerose Center, København Ø.

The use of MRI in MS diagnosis and follow-up is reviewed. The acquirements to the MRI protocol given by the revised McDonald diagnostic criteria are discussed.
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August 2008

[Diagnosis of multiple sclerosis: revision of the McDonald criteria].

Ugeskr Laeger 2007 Nov;169(45):3853-6

Rigshospitalet, Dansk Multipel Sclerose Center.

The 2005 revision of the McDonald diagnostic criteria for multiple sclerosis is reviewed. A standard clinical approach to the diagnosis of multiple sclerosis, including the use of a standard MRI protocol, VEP, CSF evaluation and other paraclinical tests is suggested.
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November 2007

[Functional magnetic resonance imaging in multiple sclerosis].

Ugeskr Laeger 2007 Jun;169(26):2518-20

Hvidovre Hospital, MR-afdelingen, Hvidovre.

The use of functional magnetic resonance imaging (fMRI) in multiple sclerosis (MS) is reviewed. fMRI is an efficient method to map brain activity non-invasively and has shown that adaptive cortical changes take place as a consequence of demyelination and tissue loss in MS. These changes may help to maintain normal function in the course of MS, and to some extent they might explain the moderate correlation between conventional MRI findings and disability. fMRI can provide information about brain plasticity and thus improve our understanding of the disease.
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June 2007

The relationship between MRI and PET changes and cognitive disturbances in MS.

J Neurol Sci 2006 Jun 2;245(1-2):99-102. Epub 2006 May 2.

Department of Neurology 2082, Danish MS Research Center, Copenhagen University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.

Cognitive dysfunction in multiple sclerosis (MS) is present in approximately 50% of the patients. Only moderate correlations have been found between cognitive dysfunction and T(2) lesion load, black holes or atrophy. Cognitive dysfunction in MS is probably related to the overall disease burden of the brain including abnormalities in normal appearing white matter (NAWM) and cortical grey matter, which is undetected with conventional magnetic resonance imaging (MRI). Hence, imaging techniques that embrace such abnormalities are needed to achieve better correlation with cognitive dysfunction. MR spectroscopy (MRS) performed with multi-slice echo planar spectroscopic imaging (EPSI) and PET measurements of brain metabolism as the cortical cerebral metabolic rate of glucose are imaging methods that are able to provide information on axonal loss or dysfunction in both MS lesions and in NAWM and cortical grey matter. Measurements of global NAA using multi-slice EPSI is a new promising method for measurement of the global neuron capacity and can be repeated with only little discomfort and without any risk for the patient.
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http://dx.doi.org/10.1016/j.jns.2005.09.020DOI Listing
June 2006

Correlation of global N-acetyl aspartate with cognitive impairment in multiple sclerosis.

Arch Neurol 2006 Apr;63(4):533-6

Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.

Background: Whole-brain N-acetyl aspartate (NAA), a measure of neuronal function, can be assessed by multislice echo-planar spectroscopic imaging.

Objective: To test the hypothesis that the global brain NAA/creatine (Cr) ratio is a better predictor of cognitive dysfunction in multiple sclerosis than conventional magnetic resonance imaging measures.

Design: Survey.

Setting: Research-oriented hospitals.

Patients: Twenty patients, 16 women and 4 men (mean age, 36 years), with early relapsing-remitting multiple sclerosis (mean Expanded Disability Status Scale score, 2.5).

Main Outcome Measures: Correlation between the global NAA/Cr ratio and a cognitive dysfunction factor comprising 16 measures from an extensive neuropsychological test battery that best distinguished patients with multiple sclerosis from healthy control subjects.

Results: A significant partial correlation between the global NAA/Cr ratio and the cognitive dysfunction factor was found (partial r = 0.62, P = .01), and 9 cognitively impaired patients had significantly lower global NAA/Cr ratios than 11 unimpaired patients (P = .04). No significant correlations were found between the cognitive dysfunction factor and conventional magnetic resonance imaging measures (ie, brain parenchymal fraction and lesion volume).

Conclusions: Multislice echo-planar spectroscopic imaging provides global metabolic measures that distinguish between cognitively impaired and unimpaired patients with multiple sclerosis and correlate with a global cognitive measure. Standardization of the technique is needed, and larger-scale studies that include healthy controls are suggested.
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http://dx.doi.org/10.1001/archneur.63.4.533DOI Listing
April 2006

[Proton magnetic resonance spectroscopy in the evaluation of cognitive disturbances].

Ugeskr Laeger 2006 Jan;168(4):357-9

H:S Hvidovre Hospital, MR-afdelingen, Hvidovre.

Magnetic resonance spectroscopy can detect metabolic changes in the brain, including changes in N-acetyl aspartate, a metabolite generally believed to be a marker of neuronal integrity. The correlations between metabolic changes and cognitive status in normal subjects and in a range of neurological and psychiatric disorders are reviewed. Magnetic resonance spectroscopy seems to be a way to monitor the efficacy of existing and new treatments to prevent the development of cognitive deficits in a number of diseases.
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January 2006

Multi-slice echo-planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis.

Magn Reson Med 2005 Apr;53(4):750-9

Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark.

MR spectroscopy (MRS) provides information about neuronal loss or dysfunction by measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to be a marker of neuronal viability. In multiple sclerosis (MS), whole-brain NAA (WBNAA) has been suggested as a marker of disease progression and treatment efficacy in treatment trials, and the ability to measure NAA loss in specific brain regions early in the evolution of this disease may have prognostic value. Most spectroscopic studies to date have been limited to single voxels or nonlocalized measurements of WBNAA only, and longitudinal studies have often been hampered by standardization and reproducibility problems. Multi-slice echo-planar spectroscopic imaging (EPSI) is presented as a promising alternative to single-voxel or nonlocalized spectroscopy for obtaining global metabolite estimates in MS. In the same session, measurements of metabolites in specific brain areas chosen after image acquisition (e.g., normal-appearing white matter (NAWM), gray matter (GM), and lesions) can be obtained. The identification and exclusion of regions that are inadequate for spectroscopic evaluation in global assessments can significantly improve quality and reproducibility, as demonstrated by a low within-subject variance in healthy controls. The reproducibility of the technique makes it a promising tool for future longitudinal spectroscopic studies of MS.
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http://dx.doi.org/10.1002/mrm.20407DOI Listing
April 2005

[Magnetic resonance and multiple sclerosis II. New diagnostic techniques].

Ugeskr Laeger 2002 Feb;164(8):1031-6

MR-afdelingen, H:S Hvidovre Hospital, DK-2650 Hvidovre.

Conventional magnetic resonance imaging (MRI) techniques have proved important in the diagnosis and in the follow-up in clinical trials of patients with multiple sclerosis (MS). However, these techniques have low specificity for the pathological changes in the MS lesions, and the correlation between conventional MRI and the disability is poor. The last ten years have seen the development of new techniques with improved sensitivity and increased pathological specificity, such as magnetisation transfer imaging (MTI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging, and functional magnetic resonance imaging (fMRI). These techniques and their contribution to the knowledge about the pathophysiology of MS are described in this review.
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February 2002

[Magnetic resonance and multiple sclerosis I. Conventional diagnostic techniques].

Ugeskr Laeger 2002 Feb;164(8):1026-31

MR-afdelingen, H:S Hvidovre Hospital, DK-2650 Hvidovre.

Conventional magnetic resonance imaging (MRI) is still the standard technique in the diagnosis and follow-up of patients with multiple sclerosis (MS), despite low pathological specificity and poor correlation to the disability. The results of T2- and T1-weighted imaging with and without contrast and the lesion characteristics are presented in this review. The numerous differential diagnoses and the diagnostic MRI criteria are also reviewed.
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February 2002
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