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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).
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Esclerosis Múltiple , Sistema Nervioso Central , Consenso , Europa (Continente) , Alemania , Humanos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/tratamiento farmacológicoRESUMEN
Background: Teriflunomide is a once-daily oral disease-modifying therapy (DMT) for the treatment of relapsing-remitting multiple sclerosis (RRMS). Only limited information is available about its real-world use and changes over time. Objectives: To collect real-world data on teriflunomide use in clinical routine (and comparison to the previously conducted study TAURUS-MS). Design: National, open, non-interventional, prospective, multicenter study. Methods: TAURUS-MS II was conducted at 220 German sites between July 2017 and March 2022, including RRMS patients treated with teriflunomide. Data on patient demographics, MS history, previous treatment, therapy satisfaction, and safety were collected. Results: In total, 752 patients were included (65% female) with a mean age (±standard deviation) of 43 ± 11 years. Sixty-six percent had DMT before, and 46% had discontinued their last pretreatment ≤6 months prior to study entry. Among the latter, previous DMTs were interferon (21%), glatiramer acetate (11%), and dimethyl fumarate (9%), and reasons for discontinuation were adverse events (AEs; 55%) and insufficient efficacy (16%). Over 24 months, the mean treatment Satisfaction Questionnaire for Medication scores improved by 6 ± 29 points on effectiveness, 8 ± 20 on convenience, and 12 ± 25 on global satisfaction. The mean number of MS relapses decreased from 0.81 ± 0.81 in the 24 months prior to 0.27 ± 0.57 within 24 months after study entry. Non-serious AEs occurred in 423 patients (56%) and serious AEs in 49 patients (7%). Most reported AEs were alanine aminotransferase increase (11%), hypertension (8%), and alopecia (7%). Compared to TAURUS-MS, patients in TAURUS-MS II were younger, had a higher employment rate, and a higher share of treatment-naïve patients. Conclusion: Mean number of relapses was significantly reduced. Patient satisfaction was significantly improved compared to previous DMT. Tolerability was comparable to previous trials. Trial registration: Bundesinstitut für Arzneimittel und Medizinprodukte public database for non-interventional studies, number 7138.
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INTRODUCTION: Treatment adherence is a critical success factor in the disease-modifying therapy (DMT) of multiple sclerosis (MS). The REBISTART study prospectively evaluated adherence in patients using components of a patient support program (PSP). METHODS: The 12-month non-interventional multicenter study examined the real-world adherence to subcutaneously (sc) injected interferon beta-1a (Rebif®). Patient-assessed adherence was measured by a visual analog scale (VAS) and the Morisky Medication Adherence Scale (MMAS). Objective adherence data were obtained by readouts from the RebiSmart® injection device. RESULTS: Of 333 patients, 70.9% used the nursing service as the core component of the PSP. Self-assessed VAS-based adherence was stable over time at 94.0-96.3%. Similarly, MMAS score (maximum 4) was 3.8-3.9 at all visits, also reflecting high self-assessed adherence. In 269 patients using the RebiSmart® injection device, mean readout-based objective adherence was similarly high (93.0-98.4% throughout visits). At last available visit, VAS-based adherence was independent of participation in the PSP nursing service (93.1% with participation versus 91.7% without it). Adherence was also independent of injection method or disease-related measures, including fatigue, depression, cognition, and quality of life. The most frequent reason for the premature discontinuations (38.7% of patients) was "change of treatment" (10.0%). DISCUSSION: We suggest that subgroups that may specifically benefit from PSP include patients who live alone, use multiple comedications, and are affected by cognitive impairment, depression, and/or fatigue. Further studies should investigate the potential usefulness of PSPs in these populations. CONCLUSIONS: Very high adherence rates independent of the PSP nursing service over 1 year of treatment indicate that IFN beta-1a sc is an easy-to-use and well-tolerated disease-modifying drug. TRIAL REGISTRATION NUMBER: Vfa.de: No. 892. https://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_892 .
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INTRODUCTION: Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis (RMS) since 2017. A full treatment course comprises two treatment cycles given 1 year apart, followed by two treatment-free years. The management of cladribine-treated patients beyond year 4 needs to be addressed as patients have now passed the initial 4 years since European Medical Agency approval. AREAS COVERED: A panel of neurologists and a neuroradiologist experienced in MS treatment/monitoring evaluated clinical trial data and real-world evidence and proposed recommendations for the management of cladribine-treated patients beyond year 4. EXPERT OPINION: Continuous monitoring of disease activity during the treatment-free period is important. Subsequent management depends on the presence or absence of inflammatory disease activity, determined in the absence of consistent guidelines via practice-driven neurological decision criteria. Persisting or newly occurring inflammatory disease activity is an indication for further treatment, i.e. either re-initiation of cladribine or switching to another highly effective disease-modifying therapy. The decision to retreat or switch should be based on clinical and radiological evaluation considering disease course, treatment history, and safety aspects. In the absence of disease activity, either retreatment can be offered, or the treatment-free period can be extended under structured monitoring.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Cladribina/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , ComprimidosRESUMEN
BACKGROUND AND AIMS: To investigate effectiveness and safety of teriflunomide (14 mg once daily) in association with age and pre-treatment in unselected MS patients. METHODS: Prespecified analysis of a non-interventional, prospective, real-world study in Germany. RESULTS: A total of 558 (49.5%) patients were above 45 years old, and 593 patients (52.6%) had been pre-treated within 6 months prior to teriflunomide. Baseline Expanded Disability Status Scale (EDSS) was higher with older age, with lower number of relapses. Relapse rate decreased in all age groups, and in both treatment-naïve (0.82 ± 0.73 at baseline; 0.25 ± 0.55 under teriflunomide) and pre-treated (from 0.48 ± 0.76; 0.22 ± 0.50) patients after 12 months compared with the year before teriflunomide initiation. EDSS remained stable in patients of all age groups as well as in therapy-naïve and pre-treated patients over 24 months. The percentage of patients with adverse events (AEs) ranged between 29.2% (age group >25-35) and 38.9% (age group >55-65), with an increased discontinuation rate (most commonly due to diarrhoea, alopecia and nausea) in the higher age groups. AE rates were lower in pre-treated compared with treatment-naïve patients. CONCLUSION: Overall, patients of all age groups including older patients, and irrespective of pre-treatment, benefit from teriflunomide treatment in routine clinical practice. REGISTRATION: BfArM public study database number 2075.
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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).
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INTRODUCTION: Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis. A full treatment course comprises two treatment cycles given with 1 year of intermission. Further dosing is not routinely recommended in years 3 and 4. AREAS COVERED: The long-term management of patients treated with oral cladribine has not been fully defined on the basis of clinical studies as of yet. The authors provide their expert opinion on this. EXPERT OPINION: Based on available evidence and experience from routine clinical use, the authors suggest a structured approach to the long-term management of patients treated with cladribine tablets according to their responder type, i. e. the degree and timing of disease activity, if any, after treatment initiation. Informed treatment decisions require structured patient monitoring by established clinical and imaging parameters. In patients with relevant disease activity in year 3 or 4 and beyond, the use of additional cycle(s) of oral cladribine might become an option. For patients requiring a treatment switch, the choice of therapies primarily includes moderately to highly effective MS drugs.
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Cladribina/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Administración Oral , Cladribina/administración & dosificación , Cladribina/efectos adversos , Ensayos Clínicos como Asunto , Esquema de Medicación , Monitoreo de Drogas , Testimonio de Experto , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Esclerosis Múltiple/inmunología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/inmunología , Guías de Práctica Clínica como Asunto , Recurrencia , Comprimidos , Resultado del TratamientoRESUMEN
BACKGROUND: Teriflunomide is a once-daily oral immunomodulatory agent approved for the treatment of relapsing-remitting multiple sclerosis (MS). We aimed to obtain data on the effectiveness, tolerability, and subject satisfaction with teriflunomide (Aubagio®) under clinical practice conditions in unselected MS patients. METHODS: This work was a non-interventional, prospective, longitudinal, observational study in 307 sites in Germany. RESULTS: A total of 1128 patients were eligible for the efficacy analysis [67.5% female; mean age (± standard deviation) 44.9 ± 9.7 years, range 20-73 years]. Time since first MS symptoms was 10.6 ± 8.2 years, and time since MS diagnosis was 8.9 ± 7.6 years. Expanded Disability Status Scale (EDSS) score at inclusion was 2.3 ± 1.5 (70.4% with score < 3.5). The mean observation period was 16.3 ± 9.1 months. A total of 75.2% had received previous disease-modifying therapies (DMTs) at any time. Of these patients, 504 (44.7%) received no DMT within 6 months of study entry, 593 patients (52.6%) had DMT discontinued prior to study entry [glatiramer acetate in 10.6%, subcutaneous interferon-beta 1a (IFNß-1a) in 9.3%, intramuscular IFNß-1a or IFNß-1b in 6.6% each, azathioprine oral in 0.4%, other in 7.3%, last medication not known in 12.0%]. The mean annualized relapse rate decreased from 0.87 in the 24 months prior to study entry to 0.35 in the 24 months after study entry (n = 468; p ⩽ 0.001). EDSS and Fatigue Severity Scale remained stable. In patients who received previous MS treatments, Treatment Satisfaction Questionnaire (TSQM-9) values (maximum = 100), for the observation at 24 months improved by 8.1 points for effectiveness, 17.0 points for convenience, and 15.3 points for global satisfaction (p ⩽ 0.001 each, compared with study entry). In the safety cohort (n = 1139), the proportion of patients with adverse events (AEs) of any severity was 35.8%, and with serious events 13.0%. The most frequently reported AEs were diarrhea (n = 55), followed by MS relapse (n = 48), hair thinning (n = 38), and viral upper respiratory tract infection (n = 31). CONCLUSIONS: Relapse rate was halved during the observation period in comparison with the same time period before study entry. Patient satisfaction with teriflunomide was high in this real-world observation of patients, the majority of whom switched from other DMTs. The safety and tolerability profile of teriflunomide was similar to that reported in previous clinical trials.
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BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), 'no evidence of disease activity' (NEDA) is regarded as a key treatment goal. The increasing number of treatments allows for individualized treatment optimization in patients with suboptimal response to first-line disease-modifying therapies (DMTs). Therefore, monitoring of clinical and subclinical disease activity on DMTs has been recognized as an important component of long-term patient management. METHODS: EPIDEM was a multicenter non-interventional retrospective study in a large cohort of RRMS patients receiving injectable DMTs for at least 2 years in outpatient centers throughout Germany. It documented measures and ratings of disease activity on DMTs to characterize the factors that made the treating neurologists consider to switch therapy towards potentially more effective or better-tolerated drugs. RESULTS: The cohort included predominantly female patients with a mean age of 45 years and a mean disease duration of 9.6 years, who had been continuously treated with an injectable DMT for a median duration of 54 months. Overall, 34.0% of the patients had experienced ⩾1 relapse on any DMT in the previous 2 years; 21.0% exhibited magnetic resonance imaging (MRI) activity, and the Kurtzke Expanded Disability Status Scale (EDSS) score increased by at least 0.5 points in 20.1%. Overall, 50.3% of the patients with EDSS progression and 70.6% of the patients with relapses were assessed as clinically stable by the neurologists. A change of treatment was considered in a fraction of patients with disease activity: in 22.8% of those with relapse activity, in 37.8% of those with MRI activity and in 20.1% of those with EDSS progression. CONCLUSION: The results of EPIDEM underline the importance of standardized evaluation and documentation of ongoing disease activity and disability deterioration. Judged from the present data, the current paradigm of low tolerance for disease activity and recommendations for early treatment optimization have not been turned fully into action as yet. More widespread implementation of current guideline recommendations may allow patients to more benefit from the growing panel of effective treatment options.
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BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication. Data on efficacy and safety of alemtuzumab following fingolimod treatment are limited, but useful for clinical practice. METHODS: Clinical and MRI data of 50 RRMS patients with a history of therapy switch from fingolimod to alemtuzumab were retrospectively analyzed. Data were acquired from nine large German MS Centers from 2013 to 2016 and analyzed using descriptive statistics. RESULTS: On average, patients with disease duration of 12.9 years and median EDSS of 3.0 at baseline switched to alemtuzumab after 68 weeks of fingolimod treatment. Thereafter, patients on alemtuzumab were followed for a mean of 64 weeks. The annualized relapse rate decreased from 2.2 in the year prior to 0.34 in the following year after switching to alemtuzumab and EDSS stabilized. In a subgroup of patients (n = 23), MRI data point to a reduction in enhancing (4.47 vs. 0.26) and new/enlarging T2 lesions (5.8 vs. 0.27) after treatment adjustment. Side effects were generally as expected from published data for alemtuzumab (autoimmunity 2/50, severe infections 1/50). One patient suffered combined lethal necrotizing leukoencephalopathy and hemolytic anemia. DISCUSSION: Therapy switch was highly effective in reducing clinical and MRI surrogates of disease activity and was mainly well tolerated within one year of follow-up. Hence, alemtuzumab constitutes a promising therapy in RRMS with refractory disease activity despite fingolimod treatment. Further studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.
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Alemtuzumab/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Clorhidrato de Fingolimod/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Estudios de Cohortes , Evaluación de la Discapacidad , Femenino , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Adulto JovenRESUMEN
Endothelial cells of blood vessels forming the interphase between systemic circulation and tissues are crucial for maintenance of homeostasis and organ-related functions. Recent experiments support organ-specific endothelial differentiation and suggest differential gene expression patterns in endothelial cells. Here, we compared gene expression in primary human cerebral endothelial cells (HCEC), which are major constituents of the blood brain barrier (BBB), with human umbilical vein endothelial cells (HUVEC) by using cDNA array analysis of 375 genes. Under basal culture conditions, 35 genes were expressed only in HCEC, whereas 20 gene transcripts were detected only in HUVEC. A total of 78 genes were expressed in both endothelial cell types partly with distinct expression levels. Genes expressed by cerebral endothelial cells are important in vasculo- and angiogenesis (VEGF, erbB1) and immunoregulation (OSM-Rbeta, decorin, IL-6) or have growth-supporting properties (brain-derived neurotrophic factor, stem cell factor, transforming growth factor-beta). The differential gene expression profiles were confirmed at the protein level of cell cultures (ELISA, immunoblotting) and human tissues (immunohistochemistry). Identification and further functional characterization of genes specifically expressed by cerebral endothelial cells will have important impact on our understanding of endothelial function at the BBB.
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Encéfalo/metabolismo , Inductores de la Angiogénesis/biosíntesis , Encéfalo/citología , Células Cultivadas , Factores de Crecimiento Endotelial/biosíntesis , Endotelio/metabolismo , Endotelio Vascular/metabolismo , Receptores ErbB/biosíntesis , Perfilación de la Expresión Génica , Sustancias de Crecimiento/biosíntesis , Humanos , Factores Inmunológicos/biosíntesis , Microscopía Fluorescente , Modelos Biológicos , Factores de Crecimiento Nervioso/biosíntesis , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/análisisRESUMEN
OBJECTIVE: The introduction of new and potent therapies for the treatment of relapsing remitting multiple sclerosis (MS) has increased the desire for therapeutic success. There is growing doubt that the mere reduction of relapse rate, Expanded Disability Status Scale (EDSS) progression and magnetic resonance imaging (MRI) markers are exclusive and appropriate factors to monitor the new aim of 'no evidence of disease activity' (NEDA). However, there is no generally accepted definition so far. METHODS: To achieve the therapeutic aim of NEDA, a panel of MS experts searched the available literature on clinical and paraclinical outcomes to propose a test battery that is sensitive to detect disease activity in an everyday clinical setting. RESULTS: The panel proposed to include, besides relapse rate, disability progression and MRI, neuropsychological outcome measures such as cognitive status, fatigue, depression and quality of life. To standardize the examinations in an economic and schematic way, a multifactorial model [multiple sclerosis decision model (MSDM)] that includes the domains 'relapse', 'disability progression', 'MRI', and 'neuropsychology' is proposed. The scheme reflects the complexity of the disease even in the early stages when scales such as the EDSS are not able to distinguish low levels of progression. CONCLUSION: The MSDM aims to support early treatment decisions and uncover timely treatment failure. Prospective investigations are required to prove that such a disease-monitoring concept leads to an early and effective silencing of disease activity.
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BACKGROUND: Patients with multiple sclerosis who have poor adherence to treatment have a higher risk of relapse than adherent patients. This study assessed adherence to, and effectiveness and convenience of, treatment with subcutaneous (sc) interferon (IFN) ß-1a (Rebif®, Merck Serono SA) 44 or 22 µg three times weekly in patients with relapsing multiple sclerosis (RMS) using the RebiSmart® electronic, multidose, autoinjector for 1 year. STUDY DESIGN: European, multicentre, observational study among neurologists: inclusion criteria included RMS, Expanded Disability Status Scale score ≤ 6, sc IFN ß-1a administered by RebiSmart for ≤ 6 weeks. The primary endpoint was cumulative adherence recorded by RebiSmart. RESULTS: The safety population included 912 patients, 77.4% (n = 823) of whom completed the Month-12 visit. Mean (± standard deviation) cumulative adherence was 97.1 ± 7.3% (n = 791). The most common reason for missed injection was 'forgot to inject' (37.0%). At Month 12/ED, 79.5% of patients were relapse-free. Of 353 patients who rated the convenience of the device, 68.3% found injecting 'very easy'. No unknown safety issues were detected. CONCLUSIONS: Patients with RMS self-injecting sc IFN ß-1a with RebiSmart had excellent adherence at Month 12/ED, which was associated with good clinical outcomes and no unexpected safety issues. Patients rated RebiSmart as convenient and easy to use.
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Adyuvantes Inmunológicos/administración & dosificación , Interferón beta-1a/administración & dosificación , Cumplimiento de la Medicación , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Inflammation has always been thought of as detrimental in the pathophysiology of multiple sclerosis (MS). However, emerging genetic data, magnetic-resonance-imaging studies, and immunopathological evidence challenge this simplistic view. The evidence leads to the conclusion that inflammation is tightly regulated, and that its net effect may be beneficial in MS, thus explaining some of the results from recent trials of anti-inflammatory agents. We argue that the use of anti-inflammatory drugs to treat MS may not be appropriate in all cases. Precise identification of the inflammatory pathways to be targeted in the different phases of the disease and the timing of such interventions are therefore crucial.
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Inflamación , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Humanos , Inmunoterapia , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética/métodos , Esclerosis Múltiple/genética , Esclerosis Múltiple/terapia , Intensificación de Imagen RadiográficaRESUMEN
CONTEXT: Brain atrophy is an indicator of diffuse brain pathology that appears even in the early stages of multiple sclerosis (MS). Magnetic resonance imaging (MRI) techniques used in clinical trials suggest a correlation between ventricular enlargement and axonal pathology and clinical disability in MS. OBJECTIVE: To evaluate by transcranial sonography (TCS) and MRI ventricular diameters in order to assess prospectively the development of brain atrophy in MS. SETTING: MS outpatient clinic of a university hospital. PATIENTS AND METHODS: 38 MS patients (27 females, 11 males) were followed up for 2 years. Ventricular diameters (third ventricle, right and left lateral ventricle) were determined by TCS at baseline, 12 and 24 months and correlated with clinical disability (Expanded Disability Status Scale, EDSS), and the Multiple Sclerosis Functional Composite Score (MSFC). MRI was performed at study entry and after two years. MAIN OUTCOME MEASURE: Correlation of ventricular diameters measured by TCS and MRI with assessment of clinical disability in MS patients at baseline and after two years. RESULTS: TCS and MRI measurements especially of third ventricle diameter matched closely at study entry and after two years (r = 0.9; p < 0.0001). At all time points the width of the third ventricle was significantly correlated with clinical disability (EDSS: r = 0.6, p < 0.01; MSFC: r = -0.6, p < 0.02). In the follow-up over 2 years there was an increase of the width of the third ventricle in comparison with study entry (p < 0.002). Increase of third ventricular width at study entry was associated with higher EDSS levels after 2 years (p = 0.01). CONCLUSION: Assessment of ventricular diameters by TCS is a reliable tool with which to monitor brain atrophy in the longitudinal follow-up of MS patients. Because TCS is a simple, inexpensive, non-invasive and generally available bedside-test it may be used in clinical practice as well as in therapeutic trials to assess brain atrophy.
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Esclerosis Múltiple/diagnóstico por imagen , Tercer Ventrículo/diagnóstico por imagen , Adolescente , Adulto , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Tercer Ventrículo/patología , Factores de Tiempo , Ultrasonografía Doppler Transcraneal/métodosAsunto(s)
Alemtuzumab/efectos adversos , Factores Inmunológicos/efectos adversos , Leucoencefalopatías/complicaciones , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Alemtuzumab/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/patología , Resultado Fatal , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Leucoencefalopatías/patología , Esclerosis Múltiple Recurrente-Remitente/patologíaRESUMEN
We compared the gene expression patterns of fetal and adult porcine brains and identified a sequence tag that was more abundant in adult than in fetal brain. The RNA corresponding to the sequence tag has the highest expression level in adult cerebellum. Lower expression levels of the transcript were found in adult cerebrum, pituitary, and uterus, as well as in fetal brain, heart, intestine, kidney, and liver. The sequence tag was used to screen a cDNA library from adult porcine brain. Two independent clones of 2,273 nt and 1,701 nt were isolated. The shorter cDNA is a 5'-truncated form of the longer clone, and both clones have almost identical sequences with multiple start and stop codons in all three reading frames. Screening of two different human brain cDNA libraries with porcine cDNA probes resulted in four overlapping cDNA fragments, which were assembled to one contig of 2,336 nt in length. Like noncoding RNAs, the porcine and human sequences have no common conserved open reading frame and share stretches of high homology interrupted by stretches with almost no homology. The human and porcine RNAs were named UM 9(5)h and UM 9(5)p, respectively. They are part of larger transcripts, which are transcribed from single-copy genes, they have very similar tissue distributions, and their sequences are colinear with the respective genomic fragment.