Publications by authors named "Paulus Stefan Rommer"

11 Publications

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Predisposing Factors for Sexual Dysfunction in Multiple Sclerosis.

Front Neurol 2021 9;12:618370. Epub 2021 Feb 9.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Sexual dysfunction (SD) in people with multiple sclerosis (pwMS) has a detrimental impact on individual health-related quality of life (HRQoL). It is not clear whether SD in multiple sclerosis (MS) is an independent symptom or merely a byproduct of other symptoms such as depression or anxiety. This cross-sectional study of 93 pwMS determines risk factors for SD in MS based on prevalence, HRQoL, and associated disease outcomes. Diagnosis of SD was determined based on the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and correlated with physical disability (measured by Expanded Disability Status scale, EDSS), depression and anxiety [Hospital Anxiety and Depression Scale (HADS)], and HRQoL [Multiple Sclerosis Quality of Life-54 (MSQoL-54)]. Multivariate regression models were performed to determine independent risk factors for SD in pwMS. Almost half of the participants in this study (46%) reported SD. HRQoL was significantly poorer in patients with MS suffering from SD (median [IQR] MSQoL-54 scores: physical subscale 52 [41-68] vs. 81 [69-89], < 0.001; mental subscale 50 [38-82] vs. 86 [70-89], < 0.001). In the multivariate model, EDSS was the only independent risk factor for SD (OR 18.1 for EDSS ≥4 [95% CI 3.3-31.4, < 0.001]), while depression and anxiety were not. We conclude that the risk for SD is growing with increasing EDSS and is independent of depression or anxiety. Screening for SD becomes particularly relevant in patients with growing disability.
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http://dx.doi.org/10.3389/fneur.2021.618370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900565PMC
February 2021

Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI.

Brain 2021 Jan 23. Epub 2021 Jan 23.

Department of Neurology, Medical University of Vienna, Austria.

Recent data suggest that multiple sclerosis white matter lesions surrounded by a rim of iron containing microglia, termed iron rim lesions, signify patients with more severe disease course and a propensity to develop progressive multiple sclerosis. So far, however, little is known regarding the dynamics of iron rim lesions over long-time follow-up. In a prospective longitudinal cohort study in 33 patients (17 females; 30 relapsing-remitting, three secondary progressive multiple sclerosis; median age 36.6 years (18.6-62.6), we characterized the evolution of iron rim lesions by MRI at 7 T with annual scanning. The longest follow-up was 7 years in a subgroup of eight patients. Median and mean observation period were 1 (0-7) and 2.9 (±2.6) years, respectively. Images were acquired using a fluid-attenuated inversion recovery sequence fused with iron-sensitive MRI phase data, termed FLAIR-SWI, as well as a magnetization prepared two rapid acquisition gradient echoes, termed MP2RAGE. Volumes and T1 relaxation times of lesions with and without iron rims were assessed by manual segmentation. The pathological substrates of periplaque signal changes outside the iron rims were corroborated by targeted histological analysis on 17 post-mortem cases (10 females; two relapsing-remitting, 13 secondary progressive and two primary progressive multiple sclerosis; median age 66 years (34-88), four of them with available post-mortem 7 T MRI data. We observed 16 nascent iron rim lesions, which mainly formed in relapsing-remitting multiple sclerosis. Iron rim lesion fraction was significantly higher in relapsing-remitting than progressive disease (17.8 versus 7.2%; P < 0.001). In secondary progressive multiple sclerosis only, iron rim lesions showed significantly different volume dynamics (P < 0.034) compared with non-rim lesions, which significantly shrank with time in both relapsing-remitting (P < 0.001) and secondary progressive multiple sclerosis (P < 0.004). The iron rims themselves gradually diminished with time (P < 0.008). Compared with relapsing-remitting multiple sclerosis, iron rim lesions in secondary progressive multiple sclerosis were significantly more destructive than non-iron rim lesions (P < 0.001), reflected by prolonged lesional T1 relaxation times and by progressively increasing changes ascribed to secondary axonal degeneration in the periplaque white matter. Our study for the first time shows that chronic active lesions in multiple sclerosis patients evolve over many years after their initial formation. The dynamics of iron rim lesions thus provide one explanation for progressive brain damage and disability accrual in patients. Their systematic recording might become useful as a tool for predicting disease progression and monitoring treatment in progressive multiple sclerosis.
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http://dx.doi.org/10.1093/brain/awaa436DOI Listing
January 2021

Relapsing and progressive MS: the sex-specific perspective.

Ther Adv Neurol Disord 2020 23;13:1756286420956495. Epub 2020 Sep 23.

Department of Neurology, Neuroimmunological Section, University of Rostock, Rostock, Germany.

Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease whose aetiology is not fully understood. The female sex is clearly predominant, with a sex ratio between 2 and 3. In primary progressive MS the sex ratio almost balances out. Since the age at onset is higher for patients with progressive onset (POMS) than for relapsing onset (ROMS), it can be hypothesized that the age at onset is a decisive factor for the sex ratio.

Methods: To address this aspect, we compare clinical and demographic data between females and males for the different disease courses within the population of the German MS Register by the German MS Society. Only patients with complete details in mandatory data items and a follow-up visit since 01. Jan 2018 were included.

Results: A total of 18,728 patients were included in our analyses, revealing a female-to-male ratio of 2.6 (2.7 for patients with ROMS and 1.3 for POMS). The age at diagnosis is higher in patients with POMS (43.3 and 42.3 years for females and males 32.1 and 33.2 years, respectively). Females irrespective of disease course are statistically significantly more often affected by cognitive impairment (POMS:  = 0.013, ROMS:  = 0.001) and depression (POMS:  = 0.002, ROMS: 0.001) and suffer more often from pain (POMS and ROMS:  < 0.001). Fatigue is significantly more often seen in females with ROMS ( < 0.001) but not in POMS. Females with ROMS retire significantly ( < 0.001) earlier (42.8 44.2 years) and to a greater extent than males (28 24%). Disease progression was similar for women and men.

Conclusion: Our analysis shows that clinical and demographic data differ more between disease courses than between men and women. For pain, depression and cognitive impairment the female sex is the decisive factor. Whether these factors are responsible for the earlier retirement of females with ROMS is not clear. Appropriate measures for optimization of symptomatic treatment as well as to promote employment should be taken.
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http://dx.doi.org/10.1177/1756286420956495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521047PMC
September 2020

Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome.

J Neuroinflammation 2020 Mar 17;17(1):86. Epub 2020 Mar 17.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Background: Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome.

Methods: Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary.

Results: The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (r = 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability.

Conclusions: sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.
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http://dx.doi.org/10.1186/s12974-020-01737-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079539PMC
March 2020

Repurposing multiple sclerosis drugs: a review of studies in neurological and psychiatric conditions.

Drug Discov Today 2019 07 14;24(7):1398-1404. Epub 2019 May 14.

Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria.

Treatment options for multiple sclerosis (MS) have improved in the past 20 years, with new oral disease-modifying drugs and monoclonal antibodies becoming available. The success seen with these drugs in MS, and their various mechanisms of action, has led to them being investigated in other neurological and psychiatric disorders. This review article summarises the ongoing and completed studies of MS drugs in neurological and psychiatric conditions other than MS. The most promising results are for interferon beta in human T cell leukaemia virus 1 associated myelopathy/tropical spastic paraparesis and glioma, and for fingolimod in acute ischaemic stroke and intracerebral haemorrhage. The coming years could see the arrival of exciting new therapies for disorders that neurologists have historically found difficult to treat and that represent a significant unmet clinical need.
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http://dx.doi.org/10.1016/j.drudis.2019.05.009DOI Listing
July 2019

Aberrant expression of alternative splicing variants in multiple sclerosis - A systematic review.

Autoimmun Rev 2019 Jul 4;18(7):721-732. Epub 2019 May 4.

University of Rostock, Department of Neurology, Division of Neuroimmunology, Gehlsheimer Str. 20, 18147 Rostock, Germany.

Objective: Alternative splicing is an important form of RNA processing that affects nearly all human genes. The differential expression of specific transcript and protein isoforms holds the potential of novel biomarkers for complex diseases. In this systematic review, we compiled the existing literature on aberrant alternative splicing events in multiple sclerosis (MS).

Methods: A systematic literature search in the PubMed database was carried out and supplemented by screening the reference lists of the identified articles. We selected only MS-related original research studies which compared the levels of different isoforms of human protein-coding genes. A narrative synthesis of the research findings was conducted. Additionally, we performed a case-control analysis using high-density transcriptome microarray data to reevaluate the genes that were examined in the reviewed studies.

Results: A total of 160 records were screened. Of those, 36 studies from the last two decades were included. Most commonly, peripheral blood samples were analyzed (32 studies), and PCR-based techniques were usually employed (27 studies) for measuring the expression of selected genes. Two studies used an exploratory genome-wide approach. Overall, 27 alternatively spliced genes were investigated. Nine of these genes appeared in at least two studies (CD40, CFLAR, FOXP3, IFNAR2, IL7R, MOG, PTPRC, SP140 and TNFRSF1A). The microarray data analysis confirmed differential alternative pre-mRNA splicing for 19 genes.

Conclusions: An altered RNA processing of genes mediating immune signaling pathways has been repeatedly implicated in MS. The analysis of individual exon-level expression patterns is stimulated by the advancement of transcriptome profiling technologies. In particular, the examination of genes encoded in MS-associated genetic regions may provide important insights into the pathogenesis of the disease and help to identify new biomarkers.
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http://dx.doi.org/10.1016/j.autrev.2019.05.010DOI Listing
July 2019

A review of the evidence for a natalizumab exit strategy for patients with multiple sclerosis.

Autoimmun Rev 2019 Mar 11;18(3):255-261. Epub 2019 Jan 11.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS), but treatment for >2 years is associated with an increased risk of opportunistic infection and progressive multifocal leukoencephalopathy (PML). For this reason, patients and physicians may consider discontinuing natalizumab therapy. This article reviews the evidence for the various therapeutic approaches that may be taken in such patients. Stopping therapy altogether is unlikely to be appropriate for most patients, as it is associated with a high rate of relapse or rebound. Continuing natalizumab therapy with increased monitoring and vigilance for PML may be an acceptable option for some patients, while the data on extending the dosing interval of natalizumab look promising. In some patients whose pre-natalizumab disease activity was not very high and who did not relapse while on natalizumab, switching to a first-line treatment may be an option. In this case, dimethyl fumarate may carry a lower risk of relapse than interferon beta or glatiramer acetate. Fingolimod is the most studied post-natalizumab therapy, and the relapse rate appears to be higher than on natalizumab but lower than was seen before initiation of natalizumab. The evidence suggests that the washout period between natalizumab and fingolimod should not exceed 12 weeks. Finally, the limited evidence available for rituximab and alemtuzumab is promising, and further data on these and other newer therapies for RRMS are awaited.
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http://dx.doi.org/10.1016/j.autrev.2018.09.012DOI Listing
March 2019

Do elevated autoantibodies in patients with multiple sclerosis matter?

Acta Neurol Scand 2019 Mar 3;139(3):238-246. Epub 2018 Dec 3.

Department of Neurology, Medical University of Vienna, Vienna, Austria.

Objectives: The incidence and clinical impact of serum autoantibodies in patients with multiple sclerosis (MS) are controversially discussed. The aim of the study was to reassess the value of elevated serum autoantibodies in our MS study cohort.

Material & Methods: In total, 176 MS patients were retrospectively analyzed for coexistence and clinical impact of increased serum autoantibody levels.

Results: The 18.8% of the MS cohort showed elevated serum autoantibody levels, but only 10.2% of all MS patients were diagnosed with a further autoimmune disease (AI). Patients with elevated serum autoantibodies (AABS) were not significantly more often diagnosed with a clinical manifest AI as compared to patients with negative autoantibodies (P = 0.338). MS patients with disease duration of more than 10 years showed no significant increase of positive autoantibodies as compared to patients with a more recent disease onset (P = 1). MS patients with elevated serum autoantibodies did not exhibit a significantly worse disease course (P = 0.428).

Conclusions: According to our data, elevated serum autoantibodies do not have the potential to serve as a prognostic tool for disease severity in patients with MS Since MS patients with positive serum AABS did not significantly more often suffer from clinical manifest AIs than MS patients with negative serum AABS, the role of routine testing of serum AABS in MS patients should be critically called into question.
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http://dx.doi.org/10.1111/ane.13054DOI Listing
March 2019

Symptomatology and symptomatic treatment in multiple sclerosis: Results from a nationwide MS registry.

Mult Scler 2019 10 19;25(12):1641-1652. Epub 2018 Sep 19.

Department of Neurology, Neuroimmunological Section, University of Rostock, Rostock, Germany.

Background: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease. Over time, symptoms accumulate leading to increased disability of patients.

Objective: The objective of this article is to analyze the prevalence of symptoms and symptomatic treatment patterns in a nationwide MS registry.

Methods: Data sets from 35,755 patients were analyzed.

Results: More than two-thirds of patients were women with a mean age of 46.1 (±12.8) years. Median Expanded Disability Status Score (EDSS) was 3.0. The most frequently reported symptoms were fatigue, spasticity, and voiding disorders. In patients with short disease duration, fatigue was reported most frequently. Symptomatic treatment was most common for spasticity and depression, whereas fatigue was treated only in a third of affected patients. Almost a fifth of patients with EDSS ⩽ 3.5 and neuropsychological symptoms had retired from work.

Conclusion: Whereas treatment for spasticity and depression is common in our cohort, sexual dysfunction, dysphagia, cognitive dysfunction, and fatigue are treated to a far lesser extent. The need for psychological support, physical, and occupational therapy has to be recognized as neuropsychological symptoms have a great impact on retirement at an early stage. Overall symptomatic treatment rates for the most common symptoms have increased over the last years ( < 0.001).
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http://dx.doi.org/10.1177/1352458518799580DOI Listing
October 2019

Intravenous immunoglobulin treatment in multiple sclerosis: A prospective, rater-blinded analysis of relapse rates during pregnancy and the postnatal period.

CNS Neurosci Ther 2019 01 1;25(1):78-85. Epub 2018 Jun 1.

Department of Neurology, University Rostock, Rostock, Germany.

Background: Multiple sclerosis (MS) affects predominantly young women. Currently available disease-modifying drugs have neither been approved during pregnancy nor nursing.

Aims: Evaluating the effect of treatment with intravenous immunoglobulin (IVIg) in MS patients with desire to have a baby.

Methods: In all, 70 MS patients were either treated with IVIg before conception, during first trimester of pregnancy and 12 months postnatal (group I, n = 38) or started IVIg after delivery for 12 months (group II, n = 23) or were untreated (group III, n = 9). Relapse rates and disease progression were analyzed.

Results: Pre-gestational relapse rates differed between groups. Lowest relapse rates were observed during late pregnancy, followed by an elevated relapse rate after delivery compared to the pre-pregnancy year and the first trimester. Only in group I, the postnatal relapse rate did not exceed the relapse rate before conception. IVIg treatment did not influence disease progression after delivery.

Conclusions: In MS patients, IVIg treatment during and/or after delivery is an option to reduce the incidence of relapses during pregnancy and the postnatal period. Surprisingly, untreated patients becoming pregnant showed an increase in the relapse rate in the first trimester compared with the pre-gestational period. How alterations of hormone status during pregnancy affect disease activity in MS has to be further investigated.
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http://dx.doi.org/10.1111/cns.12985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436593PMC
January 2019

Long-Term Effects of Repeated Cycles of Intrathecal Triamcinolone Acetonide on Spasticity in MS Patients.

CNS Neurosci Ther 2016 Jan 20;22(1):74-9. Epub 2015 Nov 20.

Department of Neurology, University of Rostock, Rostock, Germany.

Main Problem: Spasticity is a common feature in patients with multiple sclerosis (MS). Although options have broadened over the last years, there are still patients with no response to common therapeutic agents. Intrathecal administered triamcinolone acetonide (TCA) has been tested for spasticity in patients with MS. However, the long run effects are not known so far. The aim of this study was to evaluate the effects of repeated cycles of intrathecal TCA instillations on clinical parameters.

Methods: A total of 54 patients with clinically definite MS and no response to commonly utilized antispastic drugs were enrolled. TCA was administered every 3 months for a period of 9 months. Clinical assessments including spasticity, disability (EDSS), mobility (walking distance, and timed 25-foot walk), bladder function, and quality of life were carried out prior to and at the end of each treatment cycle.

Results: Repeated TCA treatment led to repeated effects on spasticity (P < 0.01). Bladder function improved in every 10th patient. Quality of life improved during each cycle but did not reach significance at the end of study (P = 0.09). However, long-lasting improvement on spasticity or EDSS was not shown at end of the study. Effects diminished over 3 months.

Conclusion: Repeated TCA instillations led to replicable effects on spasticity; subgroup analyses suggest that higher spasticity, more frequent treatments, and higher EDSS may lead to pronounced effects on spasticity and EDSS. Intrathecal TCA treatment was safe and no severe side effects occurred. We hypothesize a significant time dependence of re-administration of TCA and that an interval of 3 months between the treatments might be too long.
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http://dx.doi.org/10.1111/cns.12474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492833PMC
January 2016