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1.
Brain Behav ; 14(6): e3548, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38841819

RESUMO

BACKGROUND: The revised Lublin classification offers a framework for categorizing multiple sclerosis (MS) according to the clinical course and imaging results. Diagnosis of secondary progressive MS (SPMS) is often delayed by a period of uncertainty. Several quantitative magnetic resonance imaging (qMRI) markers are associated with progressive disease states, but they are not usually available in clinical practice. METHODS: The MAGNON project enrolled 629 patients (early relapsing-remitting MS (RRMS), n = 51; RRMS with suspected SPMS, n = 386; SPMS, n = 192) at 55 centers in Germany. Routine magnetic resonance imaging (MRI) scans at baseline and after 12 months were analyzed using a centralized automatic processing pipeline to quantify lesions and normalized brain and thalamic volume. Clinical measures included relapse activity, disability, and MS phenotyping. Neurologists completed questionnaires before and after receiving the qMRI reports. RESULTS: According to the physicians' reports, qMRI results changed their assessment of the patient in 31.8% (baseline scan) and 27.6% (follow-up scan). For ∼50% of patients with RRMS with suspected SPMS, reports provided additional information that the patient was transitioning to SPMS. In >25% of all patients, this information influenced the physicians' assessment of the patient's current phenotype. However, actual changes of treatment were reported only in a minority of these patients. CONCLUSIONS: The MAGNON results suggest that standardized qMRI reports may be integrated into the routine clinical care of MS patients and support the application of the Lublin classification as well as treatment decisions. The highest impact was reported in patients with suspected SPMS, indicating a potential to reduce diagnostic uncertainty.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Feminino , Adulto , Masculino , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Progressão da Doença , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/terapia , Alemanha
2.
Brain Commun ; 3(4): fcab229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34755108

RESUMO

The objective of this study was to investigate confirmed progression independent of relapse activity in relapsing-remitting multiple sclerosis patients under long-term natalizumab treatment. We performed a retrospective, cross-sectional study of clinical data captured between 1994 and 2019 at two German multiple sclerosis tertiary referral centres. Data files of all relapsing-remitting multiple sclerosis patients treated with natalizumab for ≥24 months were analysed. Confirmed progression independent of relapse activity was defined as ≥12 week confirmed disability progression on a roving Expanded Disability Status Scale reference score by 1 point in patients with an Expanded Disability Status Scale score ≤3 or 0.5 in patients with an Expanded Disability Status Scale score ≥3.5 in the absence of a relapse. Cox proportional hazard models were used to analyse the probability of developing confirmed progression independent of relapse activity depending on both disease and natalizumab treatment duration. Among the 184 patients identified, 44 (24%) developed confirmed progression independent of relapse activity under natalizumab irrespective of the Expanded Disability Status Scale score at natalizumab onset. Time to confirmed progression independent of relapse activity was not affected by Expanded Disability Status Scale at natalizumab onset (categorized by Expanded Disability Status Scale score ≤3.5 versus >3.5) nor by duration of disease nor by duration of therapy. Confirmed progression independent of relapse activity occurred earlier in the disease course in patients with an earlier natalizumab therapy onset with regard to disease duration. A stepwise forward regression analysis revealed disease duration as the main factor for confirmed progression independent of relapse activity development (P = 0.005). Taken together, confirmed progression independent of relapse activity occurs in a substantial proportion of patients on long-term natalizumab treatment and independent of Expanded Disability Status Scale score at natalizumab onset. Our findings suggest that patients who are initiated on natalizumab early during disease course, usually in order to treat an aggressive clinical phenotype, have a higher risk of early confirmed progression independent of relapse activity.

3.
Ther Adv Neurol Disord ; 14: 17562864211039648, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422112

RESUMO

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

4.
Nervenarzt ; 92(8): 773-801, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34297142

RESUMO

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).


Assuntos
Esclerose Múltipla , Sistema Nervoso Central , Consenso , Europa (Continente) , Alemanha , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológico
5.
Nervenarzt ; 90(8): 843-857, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31375848

RESUMO

Chronic neurodegenerative and neuroinflammatory diseases, such as idiopathic Parkinson's syndrome, amyotrophic lateral sclerosis and multiple sclerosis, represent a therapeutic challenge. Their pathophysiology is not well understood and a cure for any of these diseases is not possible. Over the past decades lifestyle and nutritional habits in modern industrial nations have changed and evidence is increasing that the prevalence of chronic diseases as well their clinical presentation are also changing. Epidemiological investigations indicate that nutritional components might have an impact on the pathogenesis of chronic neurological diseases. A profound understanding of these correlations could foster a better prevention as well as treatment of such chronic disabling diseases. This continuing medical education article summarizes the current understanding of selected nutritional components and their effect on the development and clinical course of chronic neurological disorders.


Assuntos
Doenças do Sistema Nervoso , Doença Crônica , Humanos , Doenças do Sistema Nervoso/dietoterapia , Doenças do Sistema Nervoso/prevenção & controle
6.
CNS Drugs ; 32(7): 637-651, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29992409

RESUMO

The oral potassium channel blocker 4-aminopyridine has been used in various neurological conditions for decades. Numerous case reports and studies have supported its clinical efficacy in ameliorating the clinical presentation of certain neurological disorders. However, its short half-life, erratic drug levels, and safety-related dose restrictions limited its use as a self-compounded drug in clinical practice. This changed with the introduction of a prolonged-release formulation, which was successfully tested in patients with multiple sclerosis. It was fully approved by the US FDA in January 2010 but initially received only conditional approval from the European Medicines Agency (EMA) in July 2011. After additional clinical studies, this conditional approval was changed to unrestricted approval in August 2017. This article reviews and discusses these recent studies and places aminopyridines and their clinical utility into the context of a broader spectrum of neurological disorders, where clinical efficacy has been suggested. In 2010, prolonged-release 4-aminopyridine became the first drug specifically licensed to improve walking in patients with multiple sclerosis. About one-third of patients across disease courses benefit from this treatment. In addition, various reports indicate clinical efficacy beyond multiple sclerosis, which may broaden its use in clinical practice.


Assuntos
4-Aminopiridina/uso terapêutico , Axônios/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Bloqueadores dos Canais de Potássio/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Resultado do Tratamento , Animais , Humanos , Esclerose Múltipla/patologia
7.
Ann Clin Transl Neurol ; 4(12): 909-914, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29296620

RESUMO

The increasing number of potent treatments for multiple sclerosis warrants screening for infections. To investigate the prevalence of infections in two independent German patient cohorts with multiple sclerosis/neuromyelitis optica spectrum disorders (NMOSD), we performed a retrospective chart review study of multiple sclerosis/NMOSD patients who underwent testing for infections between 2014 and 2016. We show that 6 out of 80 tested patients (Düsseldorf cohort) and 2 out of 97 tested patients (Münster cohort) had a latent tuberculosis infection; total 3.95%, 95% CI: 2-8%. Our findings suggest that latent tuberculosis infection is frequent (>1%). Screening should be performed before embarking on immunomodulatory therapies to allow treatment and mitigation of the risk of a reactivation.

8.
Ther Adv Neurol Disord ; 9(4): 336-43, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27366241

RESUMO

Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients.

10.
J Peripher Nerv Syst ; 21(2): 85-7, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26968589

RESUMO

Fampridine-PR is a voltage-gated potassium channel inhibitor potentially improving nerve conduction in demyelinated axons. Based on its established clinical efficacy in patients with demyelination in the central nervous system, we assessed if fampridine-PR is also effective in patients with inflammatory demyelination of the peripheral nerve. In this small open-label study, 10 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were treated with fampridine-PR 10 mg BID for 28 days and assessed clinically as well as by nerve conduction studies. In this study, Fampridine-PR failed to improve CIDP based on clinical measures and nerve conduction studies. Our findings suggest that Fampridine-PR appears to be ineffective in demyelinating polyneuropathies. These observations may indicate a more complex mode of action beyond improving action potential conduction in demyelinated axons.


Assuntos
4-Aminopiridina/administração & dosagem , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Bloqueadores dos Canais de Potássio/administração & dosagem , Resultado do Tratamento , Avaliação da Deficiência , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
11.
Neurology ; 83(23): 2153-7, 2014 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-25361781

RESUMO

OBJECTIVE: To assess whether pretreatment-lymphocyte counts, treatment before fingolimod, age, sex, or body mass index (BMI) affects the risk of fingolimod-induced lymphopenia in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Data were obtained from a German multicenter, single-arm, open-label study of patients with RRMS treated with fingolimod, and findings were validated in an independent Swedish national pharmacovigilance study. RESULTS: Four hundred eighteen patients with RRMS from Germany and 438 patients from Sweden were included. A nadir ≤0.2 × 10(9) lymphocytes/L was reached in 15% (95% confidence interval [CI] 12%-17%) of all 856 patients. Patients with lower starting lymphocyte counts (below 1.6 × 10(9)/L) and patients with BMI lower than 18.5 kg/m(2) (women only) were at higher risk of developing lymphopenia with values ≤0.2 × 10(9)/L in the combined analysis, increasing the risk in these subgroups to 26% (95% CI 20%-31%) or 46% (95% CI 23%-71%), respectively. In the German cohort, infection rates were similar in patients who developed severe lymphopenia and those who did not. CONCLUSIONS: Our findings suggest that patients with low baseline lymphocyte counts and underweight women in which fingolimod treatment will be initiated should possibly be monitored more closely.


Assuntos
Índice de Massa Corporal , Imunossupressores/efeitos adversos , Linfopenia/induzido quimicamente , Esclerose Múltipla/tratamento farmacológico , Propilenoglicóis/efeitos adversos , Esfingosina/análogos & derivados , Adulto , Idoso , Estudos de Coortes , Feminino , Cloridrato de Fingolimode , Humanos , Imunossupressores/uso terapêutico , Contagem de Linfócitos , Pessoa de Meia-Idade , Propilenoglicóis/uso terapêutico , Esfingosina/efeitos adversos , Esfingosina/uso terapêutico
12.
J Immunol ; 193(6): 2678-90, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25108020

RESUMO

The NOD mouse strain spontaneously develops autoimmune diabetes. A deficiency in costimulatory molecules, such as B7-2, on the NOD genetic background prevents diabetes but instead triggers an inflammatory peripheral neuropathy. This constitutes a shift in the target of autoimmunity, but the underlying mechanism remains unknown. In this study, we demonstrate that NOD mice deficient for isoforms of ICAM-1, which comediate costimulatory functions, spontaneously develop a chronic autoimmune peripheral neuritis instead of diabetes. The disease is transferred by CD4(+) T cells, which infiltrate peripheral nerves together with macrophages and B cells and are autoreactive against peripheral myelin protein zero. These Icam1(tm1Jcgr)NOD mice exhibit unaltered numbers of regulatory T cells, but increased IL-17-producing T cells, which determine the severity, but not the target specificity, of autoimmunity. Ab-mediated ICAM-1 blockade triggers neuritis only in young NOD mice. Thymic epithelium from Icam1(tm1Jcgr)NOD mice features an altered expression of costimulatory molecules and induces neuritis and myelin autoreactivity after transplantation into nude mice in vivo. Icam1(tm1Jcgr)NOD mice exhibit a specifically altered TCR repertoire. Our findings introduce a novel animal model of chronic inflammatory neuropathies and indicate that altered expression of ICAM-1 on thymic epithelium shifts autoimmunity specifically toward peripheral nerves. This improves our understanding of autoimmunity in the peripheral nervous system with potential relevance for human diseases.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Molécula 1 de Adesão Intercelular/genética , Neurite Autoimune Experimental/genética , Neurite Autoimune Experimental/imunologia , Transferência Adotiva , Animais , Autoimunidade/imunologia , Linfócitos B/imunologia , Epitélio , Interleucina-17 , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Proteína P0 da Mielina/imunologia , Bainha de Mielina/imunologia , Nervos Periféricos/imunologia , Nervos Periféricos/patologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Timo/citologia
13.
JAMA Neurol ; 70(3): 390-3, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23599943

RESUMO

BACKGROUND: Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system in which aberrant antibody responses to the astrocytic water channel aquaporin 4 have been described. Experimental evidence is emerging that NMO is partly driven by the proinflammatory cytokine interleukin 6 (IL-6), which propagates the survival of disease-specific B cell subclasses, and deviates CD4+ T helper cell differentiation toward IL-17-producing T helper 17 cells. Tocilizumab is a recombinant humanized monoclonal antibody against the IL-6 receptor approved for treatment of rheumatoid arthritis. OBJECTIVES: To study clinical and paraclinical effects of tocilizumab in a patient with NMO. DESIGN: Case report. SETTING: Academic neurology department. PATIENT: A patient with highly active aquaporin 4­seropositive NMO who failed numerous immunosuppressive interventions, including high-dose corticosteroids, mitoxantrone, plasma exchange (PE), rituximab (anti-CD20), and alemtuzumab (anti-CD52), before receiving tocilizumab. MAIN OUTCOME MEASURES: Clinical disability, magnetic resonance imaging, cytokines and transcription factors levels in the cerebrospinal fluid, and peripheral blood mononuclear cells. RESULTS: A patient who continued to accumulate neurological disability and magnetic resonance imaging activity while receiving numerous immunoactive therapies stabilized, and eventually improved clinically and on magnetic resonance metrics after treatment initiation with tocilizumab. Treatment and clinical response correlated with a significant reduction of IL-6 levels in the CSF as well as a diminished expression of signal transducer and activator of transcription 3. CONCLUSIONS: Tocilizumab might be effective in NMO, here in a patient not responding to leukocyte depletion. Our findings further support data that implicate IL-6 as a critical molecule in the immunopathogenesis of NMO, and a critical role for T cells in the pathogenesis of this disorder.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunidade Celular/imunologia , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Adulto , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Neuromielite Óptica/diagnóstico , Resultado do Tratamento
14.
Ther Adv Neurol Disord ; 5(5): 255-66, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22973422

RESUMO

A large proportion of patients with multiple sclerosis (MS) have spasticity, which has a marked impact on their quality of life. Anecdotal evidence suggests a beneficial effect of cannabis on spasticity as well as pain. Recently, randomized, double-blind, placebo-controlled studies have confirmed the clinical efficacy of cannabinoids for the treatment of spasticity in patients with MS. Based on these data, nabiximols (Sativex), a 1:1 mix of Δ-9-tetrahydrocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, received approval for treating MS-related spasticity in various countries around the globe. In this article we review the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option addressing spasticity in patients with MS.

15.
Clin Immunol ; 142(1): 68-75, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21733757

RESUMO

There is an unmet need for more potent and convenient drugs in the treatment of patients diagnosed with multiple sclerosis (MS). Among five currently investigated oral drugs with an ongoing or completed phase III program, promising efficacy data for oral cladribine have recently been published. However, benefits need to be weighed against potential risks to define the role of this compound within current treatment regimens. Here we review present data on efficacy of oral cladribine and discuss known and anticipated risks of this drug.


Assuntos
Cladribina/uso terapêutico , Ensaios Clínicos como Assunto , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Humanos
16.
Curr Opin Neurol ; 24(3): 238-43, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21483261

RESUMO

PURPOSE OF REVIEW: The aim is to describe and discuss the ongoing debate on how to balance an increase in clinical efficacy against a heightened risk of developing serious side-effects, as has surfaced recently with some novel therapies for relapsing forms of multiple sclerosis. RECENT FINDINGS: New therapies are emerging that differ with regard to their mechanism of action, their mode of administration, their side-effect profile and the clinical benefits that they offer to patients in comparison with established therapeutic modalities in multiple sclerosis. Treating physicians will need to make choices on the best treatments for their patients on the basis of limited experience. This process requires optimal assessment of risks and benefits. SUMMARY: Careful assessment of the risk-benefit profile of the various options may allow treatment choices and perhaps ensure that patients obtain the most benefit from treatment without being exposed to unnecessary risk.


Assuntos
Esclerose Múltipla/terapia , Medição de Risco , Ensaios Clínicos como Assunto , Humanos , Resultado do Tratamento
17.
Arch Neurol ; 66(2): 259-61, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19204165

RESUMO

OBJECTIVE: To describe 2 patients with relapsing-remitting multiple sclerosis (RRMS) receiving long-term treatment with the monoclonal antibody rituximab. The clinical and paraclinical efficacy of rituximab was demonstrated recently in a phase 2 clinical trial in patients with RRMS. DESIGN: Case series. SETTING: Tertiary care university medical center. PATIENTS: Two young patients with highly active RRMS in whom standard therapy had failed before receiving rituximab for up to 48 months. MAIN OUTCOME MEASURES: Relapse rate, clinical disability, and results of magnetic resonance imaging. RESULTS: Both patients tolerated rituximab treatment well and have been clinically stable throughout the study period. CONCLUSION: Long-term therapy with rituximab appears safe and effective in some patients with RRMS. Our observation should be confirmed in controlled long-term trials.


Assuntos
Anticorpos Monoclonais/farmacologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Terapia de Imunossupressão/métodos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/imunologia , Proliferação de Células/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/patologia , Avaliação da Deficiência , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Rituximab , Prevenção Secundária , Tempo , Resultado do Tratamento , Adulto Jovem
20.
J Neurol ; 255 Suppl 6: 15-21, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19300955

RESUMO

Multiple sclerosis (MS) represents the prototypic inflammatory autoimmune disorder of the central nervous system and the most common cause of neurological disability in young adults. The mainstays in the immunomodulatory therapy of MS are currently interferon beta and glatiramer acetate, both of which have proven to be clinically and paraclinically effective. Current clinical evidence indicates that treatment should be initiated as early as possible. In this review we summarize available data from clinical studies on clinical efficacy of immunomodulatory drugs for treating patients with multiple sclerosis.


Assuntos
Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Animais , Ensaios Clínicos como Assunto , Humanos
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