Roztroušená skleróza (RS) je chronické potenciálně invalidizující onemocnění CNS podmíněné fokální i difuzní patologií. Současné terapeutické možnosti se opírají zejména o podání metylprednisolonu při relapsu a chronické podávání léků ovlivňujících přirozený průběh nemoci (DMD léky). Tyto léky působí velmi dobře na fokální patologii reprezentovanou imunologickým zánětem, méně pak na difuzní patologii reprezentovanou neurodegenerací a axonální ztrátou, která je však právě tou částí patofyziologie RS, která má zásadní prognostický význam pro nemocného s RS. NEDA-4 koncept (no evidence of disease activity) přináší nový pohled na výsledek léčby pacienta s RS, a to jednak zavedením principu „freedom of the disease“, tedy nepřítomnosti aktivity a progrese nemoci v klinickém i radiologickém obraze a také zahrnutím hodnocení atrofie mozku, která koreluje s difuzními změnami CNS. Dosažení co nejdelšího trvání NEDA-4 je významným cílem terapie RS u individuálních nemocných.

Multiple sclerosis (MS) is a chronic potentially disabling disease of the central nervous system (CNS) with underlying focal and diffuse pathology. Current therapeutic options are based on administration of methylprednisolon during relapse and chronic treatment with disease modifying drugs (DMD). These drugs highly influence focal pathology represented by immune inflammation, but are less effective on diffuse pathology represented by neuro-degeneration and axonal loss which is however this part of MS pathophysiology that has major prognostic impact for MS patient. NEDA-4 concept (no evidence of disease activity) brings a new insight to MS treatment outcomes by introduction of the “freedom of the disease” principle (i.e. absence of disease activity and progression in both clinical and radiological point of view) and inclusion of assessment of brain atrophy which correlates with diffuse changes of the CNS. Achievement of long-term NEDA-4 is an important goal of MS treatment in individual patients.

• Keywords
• NEDA-4 koncept,
• MeSH
• Atrophy MeSH
• Precision Medicine MeSH
• Humans MeSH
• Brain pathology   MeSH
• Disease Progression MeSH
• Multiple Sclerosis, Relapsing-Remitting * diagnosis   physiopathology   therapy   MeSH
• Multiple Sclerosis * diagnosis   physiopathology   therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• Publication type
• Meeting Abstract MeSH

Roztroušená skleróza je chronické zánětlivé onemocnění, které je charakterizováno infiltrací leukocytů do centrálního nervového systému, lokální destrukcí myelinových obalů nervových vláken a postupnou ztrátou oligodendrocytů a axonů. Kognitivní deficit se vyskytuje ve všech stadiích tohoto onemocnění. Typickým nálezem je postižení zpracování informací, paměti a výkonných funkcí s relativním zachováním jazykových funkcí. Je diskutován koncept NEDA-4, testování kogitivní dysfunkce a léčba.

Multiple sclerosis is a chronic inflammatory disease which is characterized by infiltration of leukocytes into the central nervous system. This situation leads to the destruction of myelin and to the loss of axons and olidendrocytes. Cognitive dysfunction is present in all stages of multiple sclerosis. The impairment of information processing, memory and executive functions are typical findings. The NEDA-4 concept, testing of cognitive dysfunction and treatment are discussed.

• Keywords
• NEDA-4,
• MeSH
• Cognitive Dysfunction MeSH
• Cognition Disorders * diagnosis   etiology   drug therapy   MeSH
• Humans MeSH
• Neuropsychological Tests MeSH
• Disease Progression MeSH
• Recurrence MeSH
• Multiple Sclerosis * diagnosis   complications   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Kniha seznamuje čtenáře s konceptem dlouhodobé stabilizace onemocnění (disease free concept), NEDA 3 (no evidence of disease activity), NEDA 4, kde je hodnocení magnetické rezonance nálezu jejich součástí. Nakladatelská anotace. Kráceno; Monografie navazuje na předchozí publikaci Magnetická rezonance a roztroušená skleróza mozkomíšní z roku 2010. Podnětem k jejímu vzniku byla poptávka po zpracování nových poznatků v diagnostice a MR monitoraci pacientů vzhledem k velkému rozvoji výzkumu v těchto oblastech s cílem přispět i k rozšíření MR monitorace do širší klinické praxe. Nově byla zařazena kapitola týkající se signálových charakteristik v MR obraze u onemocnění bílé hmoty, rozšířena pasáž o monitoraci pacientů, která byla na pracovišti MR Radiodiagnostické kliniky 1. LF UK jako první na světě v roce 2009 implementována do klinické praxe. Kniha seznamuje čtenáře s konceptem dlouhodobé stabilizace onemocnění (disease free concept), NEDA 3 (no evidence of disease activity), NEDA 4, kde je hodnocení MR nálezu jejich součástí. Kapitola o diferenciální diagnostice je mj. nově rozdělena na fyziologické nálezy a onemocnění s podobným nálezem na MR jako u RS, velká pozornost je věnována vzácné oportunní infekci – progresivní multifokální leukoencefalopatii, která se u RS pacientů může vyskytovat v souvislosti s léčbou. Značný prostor je věnován i onemocnění neuromyelitis optica, kde došlo ke změnám v diagnostických kritériích. Samostatně je zařazena též skupina vrozených vad a metabolických poruch (poruchy myelinizace).

• MeSH
• White Matter diagnostic imaging   pathology   MeSH
• Demyelinating Diseases diagnostic imaging   MeSH
• Diagnosis, Differential MeSH
• Magnetic Resonance Imaging utilization   MeSH
• Multiple Sclerosis diagnostic imaging   MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• neurologie
• radiologie, nukleární medicína a zobrazovací metody

BACKGROUND: No evidence of disease activity (NEDA) has been proposed as a new treatment goal in multiple sclerosis (MS). NEDA-3 status is defined as the absence of magnetic resonance imaging (MRI; new/enlarging/enhancing lesions and increased whole brain volume loss in NEDA-4) and clinical disease activity. OBJECTIVES: To investigate the persistence of NEDA status over long-term follow-up in MS patients treated with weekly intramuscular interferon beta-1a. METHODS: We included 192 patients after the first demyelinating event suggestive of MS, that is, clinically isolated syndrome (CIS) and 162 relapsing-remitting MS (RRMS) patients. RESULTS: NEDA-3 status was observed in 40.1% of CIS and 20.4% of RRMS patients after 1 year. After 4 years, 10.1% of CIS patients had NEDA-3 status. After 10 years, none of the RRMS patients had NEDA-3 status. Only 4.6% of CIS and 1.0% of RRMS patients maintained NEDA-4 status after 4 years. Loss of NEDA-3 status after the first year was associated with a higher risk of disability progression (hazard ratio (HR) = 2.3-4.0; p = 0.005-0.03) over 6 years. CONCLUSIONS: Despite intramuscular interferon beta-1a treatment, loss of NEDA status occurred in the vast majority of individuals. Loss of NEDA status during the first year was associated with disability progression over long-term follow-up; however, specificity for individual patient was low.

• MeSH
• Time Factors MeSH
• Goals MeSH
• Adult MeSH
• Interferon beta-1a therapeutic use   MeSH
• Interferon-beta therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Disease Progression MeSH
• Multiple Sclerosis drug therapy   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348). METHODS: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs). RESULTS: Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined. CONCLUSIONS: Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses. CLINICALTRIALSGOV IDENTIFIER: NCT00530348; NCT00930553. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.

• MeSH
• Time Factors MeSH
• Antibodies, Monoclonal, Humanized adverse effects   therapeutic use   MeSH
• Immunologic Factors adverse effects   therapeutic use   MeSH
• Humans MeSH
• Brain diagnostic imaging   drug effects   MeSH
• Follow-Up Studies MeSH
• Disability Evaluation MeSH
• Multiple Sclerosis, Relapsing-Remitting diagnostic imaging   drug therapy   MeSH
• Organ Size MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

BACKGROUND AND OBJECTIVES: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS). METHODS: ENSEMBLE was a prospective, 4-year, international, multicenter, single-arm, open-label, phase IIIb study. Patients were treatment naive, aged 18-55 years, had early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) score ≤3.5, and ≥1 clinically reported relapse(s) or ≥1 signs of brain inflammatory activity on MRI in the prior 12 months. Patients received IV ocrelizumab 600 mg every 24 weeks. Effectiveness endpoints over 192 weeks were proportion of patients with no evidence of disease activity (NEDA-3; defined as absence of relapses, 24-week confirmed disability progression [CDP], and MRI measures, with prespecified MRI rebaselining at week 8), 24-week/48-week CDP and 24-week confirmed disability improvement, annualized relapse rate (ARR), mean change in EDSS score from baseline, and safety. Cognitive status, patient-reported outcomes, and serum neurofilament light chain (NfL) were assessed. Descriptive analysis was performed on the intention-to-treat population. RESULTS: Baseline characteristics (N = 678) were consistent with early-stage RRMS (n = 539 patients, 64.6% female, age 40 years and younger; median age: 31.0 years; duration since: MS symptom onset 0.78 years, RRMS diagnosis 0.24 years; mean baseline EDSS score [SD] 1.71 [0.95]). At week 192, most of the patients had NEDA-3 (n = 394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP over the study duration. Adjusted ARR at week 192 was low (0.020, 95% CI 0.015-0.027). NfL levels were reduced to and remained within the healthy donor range, by week 48 and week 192, respectively. No new or unexpected safety signals were observed. DISCUSSION: Disease activity based on clinical and MRI measures was absent in most of the patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab. Although this single-arm study was limited by lack of a parallel group for comparison of outcome measures, the positive benefit-risk profile observed may provide confidence to adopt ocrelizumab as a first-line treatment in newly diagnosed patients with early RMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that adult patients with early-stage MS who were treatment naive maintained low disease activity (NEDA-3) over 4 years with ocrelizumab treatment; no new safety signals were detected. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT03085810; first submitted March 16, 2017; first patient enrolled: March 27, 2017; available at clinicaltrials.gov/ct2/show/NCT03085810.

• MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   adverse effects   administration & dosage   MeSH
• Immunologic Factors * therapeutic use   adverse effects   administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Adolescent MeSH
• Young Adult MeSH
• Disability Evaluation MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Multiple Sclerosis, Relapsing-Remitting * drug therapy   diagnostic imaging   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy. METHODS: In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed. RESULTS: Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3-5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1-5: -0.48%, -0.22%, -0.10%, -0.19%, -0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter. CONCLUSIONS: Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.

• MeSH
• Atrophy diagnostic imaging   prevention & control   MeSH
• Time Factors MeSH
• Antibodies, Monoclonal, Humanized adverse effects   therapeutic use   MeSH
• Immunologic Factors adverse effects   therapeutic use   MeSH
• Kaplan-Meier Estimate MeSH
• Humans MeSH
• Brain diagnostic imaging   drug effects   MeSH
• Follow-Up Studies MeSH
• Disability Evaluation MeSH
• Multiple Sclerosis, Relapsing-Remitting diagnostic imaging   drug therapy   MeSH
• Organ Size MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Importance: To our knowledge, the Oral Ponesimod Versus Teriflunomide In Relapsing Multiple Sclerosis (OPTIMUM) trial is the first phase 3 study comparing 2 oral disease-modifying therapies for relapsing multiple sclerosis (RMS). Objective: To compare the efficacy of ponesimod, a selective sphingosine-1-phosphate receptor 1 (S1P1) modulator with teriflunomide, a pyrimidine synthesis inhibitor, approved for the treatment of patients with RMS. Design, Setting, and Participants: This multicenter, double-blind, active-comparator, superiority randomized clinical trial enrolled patients from April 27, 2015, to May 16, 2019, who were aged 18 to 55 years and had been diagnosed with multiple sclerosis per 2010 McDonald criteria, with a relapsing course from the onset, Expanded Disability Status Scale (EDSS) scores of 0 to 5.5, and recent clinical or magnetic resonance imaging disease activity. Interventions: Patients were randomized (1:1) to 20 mg of ponesimod or 14 mg of teriflunomide once daily and the placebo for 108 weeks, with a 14-day gradual up-titration of ponesimod starting at 2 mg to mitigate first-dose cardiac effects of S1P1 modulators and a follow-up period of 30 days. Main Outcomes and Measures: The primary end point was the annualized relapse rate. The secondary end points were the changes in symptom domain of Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) at week 108, the number of combined unique active lesions per year on magnetic resonance imaging, and time to 12-week and 24-week confirmed disability accumulation. Safety and tolerability were assessed. Exploratory end points included the percentage change in brain volume and no evidence of disease activity (NEDA-3 and NEDA-4) status. Results: For 1133 patients (567 receiving ponesimod and 566 receiving teriflunomide; median [range], 37.0 [18-55] years; 735 women [64.9%]), the relative rate reduction for ponesimod vs teriflunomide in the annualized relapse rate was 30.5% (0.202 vs 0.290; P < .001); the mean difference in FSIQ-RMS, -3.57 (-0.01 vs 3.56; P < .001); the relative risk reduction in combined unique active lesions per year, 56% (1.405 vs 3.164; P < .001); and the reduction in time to 12-week and 24-week confirmed disability accumulation risk estimates, 17% (10.1% vs 12.4%; P = .29) and 16% (8.1% vs 9.9; P = .37), respectively. Brain volume loss at week 108 was lower by 0.34% (-0.91% vs -1.25%; P < .001); the odds ratio for NEDA-3 achievement was 1.70 (25.0% vs 16.4%; P < .001). Incidence of treatment-emergent adverse events (502 of 565 [88.8%] vs 499 of 566 [88.2%]) and serious treatment-emergent adverse events (49 [8.7%] vs 46 [8.1%]) was similar for both groups. Treatment discontinuations because of adverse events was more common in the ponesimod group (49 of 565 [8.7%] vs 34 of 566 [6.0%]). Conclusions and Relevance: In this study, ponesimod was superior to teriflunomide on annualized relapse rate reduction, fatigue, magnetic resonance imaging activity, brain volume loss, and no evidence of disease activity status, but not confirmed disability accumulation. The safety profile was in line with the previous safety observations with ponesimod and the known profile of other S1P receptor modulators. Trial Registration: ClinicalTrials.gov Identifier: NCT02425644.

• MeSH
• Adult MeSH
• Hydroxybutyrates pharmacology   MeSH
• Immunologic Factors therapeutic use   MeSH
• Crotonates pharmacology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   MeSH
• Magnetic Resonance Imaging methods   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Nitriles pharmacology   MeSH
• Disease Progression MeSH
• Multiple Sclerosis, Relapsing-Remitting drug therapy   MeSH
• Thiazoles pharmacology   MeSH
• Toluidines pharmacology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

Publikace se zaměřuje na zdravý spánkový režim a na různé spánkové poruchy. Určeno široké veřejnosti.; Spánek je zásadní pro naše zdraví a pohodu. Tři pilíře úspěšného života V programu Sleep Sense mezinárodní odbornice na spánek dr. Katharina Lederle čerpá z nejnovějších poznatků o tom, jak je spánek spojen s každým ze tří pilířů úspěšného života: fyzické zdraví, kognitivní výkon a emoční pohoda. A protože jsou tři pilíře vzájemně propojeny, je-li člověk oslabený, může být naše celkové zdraví snadno narušeno. Nejdůležitější informace o spánku První část knihy přináší čtenáři nejdůležitější informace o spánku – jak a kde se vytváří a reguluje, proč je pro spánek tak důležité světlo a jaké jsou odlišnosti u obou pohlaví. Krátce se dotkne také snění zdůrazňujíc, že snít je normální a to, o čem sníme, je tak trochu užitečné. Zdravé spánkové návyky Druhá část knihy podrobně zkoumá, jak spánek postihuje každý ze tří pilířů, vysvětluje poruchy spánku a předkládá několik možností zdravého spánku, ze kterých si čtenáři mohou vybrat, aby si vytvořili zdravé spánkové návyky, které nejlépe vyhovují jejich životu. Dosáhněte lepšího zdraví díky spánku Výsledkem je kniha, která informuje, ale i vzdělává, protože stanoví jasné pokyny a praktické rady, jak můžete dosáhnout lepšího zdraví díky lepšímu spánku.

• MeSH
• Sleep Wake Disorders MeSH
• Sleep MeSH
• Health MeSH
• Life Style MeSH
• Publication type
• Monograph MeSH
• Popular Work MeSH

• Conspectus
• Zdraví a hygiena volného času, rekreace a spánku
• NML Fields
• psychologie, klinická psychologie