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  • 1
    In: Der Nervenarzt, Springer Science and Business Media LLC
    Abstract: Ofatumumab (Kesimpta™) is a s.c. applicable anti-CD20 antibody, which has been used in Germany since 2021 for the treatment of relapsing multiple sclerosis (RMS). The self-application offers a high degree of independence from intravenous forms of application with highly effective immunotherapy. In this study we recorded the patient-centered experience in 99 out of 127 patients who were adjusted to the drug by us. The aim was to investigate the tolerability and acceptance from the patient’s perspective. Methods Data collection was carried out using doctor documentation, questionnaires and telephone interviews. Results The cohort consists of 127 patients. The patients received 2.8 (± SD 1.7) pre-therapies. The mean duration of therapy with Ofatumumab was 9.8 months (± SD 3.5). Structured data were collected from 99 patients. 23% of patients had no side effects during initial application. 19% rated the side effects as “very mild” and 18% as “mild”. In addition to chills/fever (48%), headache (46%), limb pain (45%) and “other symptoms” (19%) also occurred. For subsequent injections, 72% of patients reported no side effects. 87% of patients found handling the medication “very easy”. There was one relapse event during therapy. Conclusion Our study shows that Ofatumumab is well accepted and tolerated by patients. There was one relapse event during the observation period. The side effects are mild and occur during initial application. No increased tendency to infection could be observed. The data suggest that Ofatumumab is also an effective and safe treatment option for patients with relapsing remitting multiple sclerosis in real-world use.
    Type of Medium: Online Resource
    ISSN: 0028-2804 , 1433-0407
    RVK:
    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1462945-8
    detail.hit.zdb_id: 123291-5
    SSG: 2,1
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Neurology Vol. 269, No. 4 ( 2022-04), p. 1774-1775
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 269, No. 4 ( 2022-04), p. 1774-1775
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1421299-7
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Neurology Vol. 269, No. 9 ( 2022-09), p. 5144-5150
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 269, No. 9 ( 2022-09), p. 5144-5150
    Abstract: The phosphodiesterase-5 inhibitor sildenafil was postulated to reduce the risk for Alzheimer’s Disease. Since preclinical data revealed beneficial effects in Huntington’s Disease (HD), we now for the first time investigated effects of sildenafil in HD patients using the database ENROLL-HD. We demonstrate beneficial effects on motoric, functional and cognitive capacities in cross-sectional data. Those effects were not explained by underlying fundamental molecular genetic or demographic data. It remains unsolved, if effects are due to behavioral differences or due to direct dose-dependent neurobiological modulations.
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1421299-7
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  • 4
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 7 ( 2017-07), p. 1415-1422
    Abstract: Although statin pretreatment (SP) is associated with better outcomes in patients with acute cerebral ischemia after an ischemic stroke/transient ischemic attack, data on the underlying mechanism of this beneficial effect are limited. Approach and Results— We sought to evaluate the potential association between SP and microembolic signal (MES) burden in acute cerebral ischemia because of large artery atherosclerosis (LAA). We prospectively evaluated consecutive patients with first-ever acute cerebral ischemia because of LAA in 3 tertiary stroke centers over a 2-year period. All patients underwent continuous 1-hour transcranial Doppler monitoring of the relevant vessel at baseline (≤24 hours). SP was recorded and dichotomized as high dose or low-to-moderate dose. SP was documented in 43 (41%) of 106 LAA patients (mean age, 65.4±10.3 years; 72% men; low-to-moderate dose, 32%; high dose, 8%). There was a significant ( P =0.022) dose-dependent effect between SP and MES prevalence: no SP (37%), SP with low-to-moderate dose (18%), and SP with high dose (0%). Similarly, a significant ( P =0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with low-to-moderate dose (0.7±1.6), and SP with high dose (0±0). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, location of LAA, stroke severity, and other prevention therapies, SP was associated with lower likelihood of MES presence (odds ratio, 0.29; 95% confidence interval, 0.09–0.92; P =0.036). In addition, SP was found also to be independently related to higher odds of functional improvement (common odds ratio, 3.33; 95% confidence interval, 1.07–10.0; P =0.037). Conclusions— We found that SP in patients with acute LAA is related with reduced MES presence and lower MES burden with an apparently dose-dependent association.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1494427-3
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  • 5
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Neurology Vol. 94, No. 15_supplement ( 2020-04-14)
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 15_supplement ( 2020-04-14)
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 6
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 2019
    In:  Fortschritte der Neurologie · Psychiatrie Vol. 87, No. 11 ( 2019-11), p. 653-671
    In: Fortschritte der Neurologie · Psychiatrie, Georg Thieme Verlag KG, Vol. 87, No. 11 ( 2019-11), p. 653-671
    Abstract: Die Therapie der Multiplen Sklerose hat sich in den letzten Jahren durch die Entwicklung neuer Medikamente für die schubförmige Phase der Erkrankung umfangreich gewandelt. Die Entwicklung von Medikamenten für Progression war bisher hingegen weniger erfolgreich. Neue Substanzen umfassen den in Europa und den USA zugelassenen B-Zell depletierenden Antikörper Ocrelizumab, der bei primär progredienter MS mit Krankheitsaktivität zugelassen ist, sowie den Sphingosin-1-Phosphat Modulator Siponimod, der aktuell in der Zulassungsphase für sekundär-chronisch progrediente MS ist. Progression ist durch chronische Inflammation mit Aktivierung von T- und B-Zellen sowie Mikroglia mit Freisetzung reaktiver Sauerstoffmetabolite, altersabhängige Akkumulation von Eisen und damit einhergehend neuronaler Degeneration gekennzeichnet. In dieser Arbeit soll eine Übersicht über das Verständnis der Pathogenese und vielversprechende Therapieansätze für Progression in unterschiedlichen Stadien der Entwicklung gegeben werden.
    Type of Medium: Online Resource
    ISSN: 0720-4299 , 1439-3522
    RVK:
    Language: German
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2019
    detail.hit.zdb_id: 2037701-0
    SSG: 2,1
    SSG: 5,2
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  • 7
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 2017
    In:  Aktuelle Neurologie Vol. 44, No. 05 ( 2017-06), p. 348-349
    In: Aktuelle Neurologie, Georg Thieme Verlag KG, Vol. 44, No. 05 ( 2017-06), p. 348-349
    Type of Medium: Online Resource
    ISSN: 0302-4350 , 1438-9428
    Language: German
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2017
    detail.hit.zdb_id: 2056721-2
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  • 8
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 2017
    In:  Aktuelle Neurologie Vol. 44, No. 07 ( 2017-09), p. 510-512
    In: Aktuelle Neurologie, Georg Thieme Verlag KG, Vol. 44, No. 07 ( 2017-09), p. 510-512
    Type of Medium: Online Resource
    ISSN: 0302-4350 , 1438-9428
    Language: German
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2017
    detail.hit.zdb_id: 2056721-2
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  • 9
    In: Cells, MDPI AG, Vol. 12, No. 4 ( 2023-02-08), p. 542-
    Abstract: Background: Glatiramer acetate (GA) is a well-established treatment option for patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis (MS) with few side effects. The double transgenic mouse model spontaneous opticospinal encephalomyelitis (OSE), based on recombinant myelin oligodendrocyte glycoprotein35-55 reactive T and B cells, mimicks features of chronic inflammation and degeneration in MS and related disorders. Here, we investigated the effects of prophylactic GA treatment on the clinical course, histological alterations and peripheral immune cells in OSE. Objective: To investigate the effects of prophylactic glatiramer acetate (GA) treatment in a mouse model of spontaneous opticospinal encephalomyelitis (OSE). Methods: OSE mice with a postnatal age of 21 to 28 days without signs of encephalomyelitis were treated once daily either with 150 µg GA or vehicle intraperitoneally (i. p.). The animals were scored daily regarding clinical signs and weight. The animals were sacrificed after 30 days of treatment or after having reached a score of 7.0 due to animal care guidelines. We performed immunohistochemistry of spinal cord sections and flow cytometry analysis of immune cells. Results: Preventive treatment with 150 µg GA i. p. once daily significantly reduced clinical disease progression with a mean score of 3.9 ± 1.0 compared to 6.2 ± 0.7 in control animals (p 〈 0.01) after 30 d in accordance with positive effects on weight (p 〈 0.001). The immunohistochemistry showed that general inflammation, demyelination or CD11c+ dendritic cell infiltration did not differ. There was, however, a modest reduction of the Iba1+ area (p 〈 0.05) and F4/80+ area upon GA treatment (p 〈 0.05). The immune cell composition of secondary lymphoid organs showed a trend towards an upregulation of regulatory T cells, which lacked significance. Conclusions: Preventive treatment with GA reduces disease progression in OSE in line with modest effects on microglia/macrophages. Due to the lack of established prophylactic treatment options for chronic autoimmune diseases with a high risk of disability, our study could provide valuable indications for translational medicine.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-5-3)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-5-3)
    Abstract: Progressive multiple sclerosis is characterized by chronic inflammation with microglial activation, oxidative stress, accumulation of iron and continuous neurodegeneration with inadequate effectiveness of medications used so far. We now investigated effects of iron on microglia and used the previously identified neuroprotective antipsychotic clozapine in vitro and in chronic experimental autoimmune encephalomyelitis (EAE). Methods Microglia were treated with iron and clozapine followed by analysis of cell death and response to oxidative stress, cytokine release and neuronal phagocytosis. Clozapine was investigated in chronic EAE regarding optimal dosing and therapeutic effectiveness in different treatment paradigms. Animals were scored clinically by blinded raters. Spinal cords were analyzed histologically for inflammation, demyelination, microglial activation and iron accumulation and for transcription changes of regulators of iron metabolism and inflammation. Effects on immune cells were analyzed using flow cytometry. Results Iron impaired microglial function in vitro regarding phagocytosis and markers of inflammation; this was regulated by clozapine, reflected in reduced release of IL-6 and normalization of neuronal phagocytosis. In chronic EAE, clozapine dose-dependently attenuated clinical signs and still had an effect if applied in a therapeutic setting. Early mild sedative effects habituated over time. Histologically, demyelination was reduced by clozapine and positive effects on inflammation strongly correlated with reduced iron deposition. This was accompanied by reduced expression of DMT-1, an iron transport protein. Conclusions Clozapine regulates microglial function and attenuates chronic EAE, even in a therapeutic treatment paradigm. This well-defined generic medication might therefore be considered as promising add-on therapeutic for further development in progressive MS.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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