Dana Horakova

Dana Horakova
Charles University in Prague | CUNI · Department of Neurology (1. LF)

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187
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Publications

Publications (187)
Preprint
Full-text available
Background: Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking. Methods: Data...
Article
Background New/enlarging T2 lesion count and T2-lesion volume (LV) are used as conventional secondary endpoints in clinical trials of patients with multiple sclerosis (PwMS). However, those outcomes may have several limitations, such as inability to account for heterogeneity of lesion formation/enlargement frequency and their dynamic volumetric beh...
Article
Objectives To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. Methods This was a retrospective cohort study from two large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the...
Article
Full-text available
Background and Purpose White matter (WM) tract disruption impacts volume loss in connected deep gray matter (DGM) over 5 years in people with multiple sclerosis (PwMS). However, the timeline of this phenomenon remains poorly characterized. Materials and Methods Annual serial MRI for 181 PwMS was retrospectively analyzed from a 10-year clinical tri...
Article
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Background: Early infratentorial and focal spinal cord lesions on magnetic resonance imaging (MRI) are associated with a higher risk of long-term disability in patients with multiple sclerosis (MS). The role of diffuse spinal cord lesions remains less understood. The purpose of this study was to evaluate focal and especially diffuse spinal cord le...
Article
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Background: COVID-19 vaccination and infection are speculated to increase the activity of immune-mediated diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to evaluate a short-term risk of relapse after COVID-19 vaccination and COVID-19 infection in patients with these demyelin...
Article
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Oxidative stress has been implied in cellular injury even in the early phases of multiple sclerosis (MS). In this study, we quantified levels of biomarkers of oxidative stress and antioxidant capacity in cerebrospinal fluid (CSF) in newly diagnosed MS patients and their associations with brain atrophy and iron deposits in the brain tissue. Consecut...
Article
Introduction Objective algorithms (OA; Ramanujam, 2020) identify SPMS in those with clinically assigned (CA) RRMS, suggesting SPMS is under-diagnosed in practice. It’s unclear if clinicians are aware of this evolution and escalate therapy in response to clinical worsening with highly active (HA) disease modifying treatments (DMT). Objective Assess...
Article
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Background: Prevention of disability over the long-term is the main treatment goal in multiple sclerosis (MS), however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained...
Article
Background and Objectives The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, ultraviolet B radiation exposure (UVB) and the severity of...
Article
Background The MSBase prediction model of treatment response leverages multiple demographic and clinical characteristics to estimate hazards of relapses, confirmed disability accumulation (CDA), and confirmed disability improvement (CDI). The model did not include Multiple Sclerosis Severity Score (MSSS), a disease duration-adjusted ranked score of...
Article
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Objective Pathology in multiple sclerosis is not homogenously distributed. Recently, it has been shown that structures adjacent to CSF are more severely affected. A gradient of brain tissue involvement was shown with more severe pathology in periventricular areas and in proximity to brain surfaces such as the subarachnoid spaces and ependyma, and h...
Article
Background: There is growing interest in the issue of disease reactivation in multiple sclerosis following fingolimod cessation. Relatively little is known about modifiers of the risk of post-cessation relapse, including the delay to commencement of new therapy and prior disease activity. Objective: We aimed to determine the rate of relapse foll...
Article
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Introduction Alemtuzumab is highly effective in the treatment of patients with relapsing multiple sclerosis (PwRMS) and selectively targets the CD52 antigen, with a consequent profound lymphopenia, particularly of CD4+ T lymphocytes. However, the immunological basis of its long-term efficacy has not been clearly elucidated. Methods We followed up...
Preprint
Multiple sclerosis (MS) is a leading cause of neurological disability in adults. Heterogeneity in MS clinical presentation has posed a major challenge for identifying genetic variants associated with disease outcomes. To overcome this challenge, we used prospectively ascertained clinical outcomes data from the largest international MS Registry, MSB...
Article
Background The effect of pregnancy on brain changes and radiological disease activity in women with multiple sclerosis (MS) is not well understood. Aims To describe the dynamic of lesion activity and brain volume changes during the pregnancy and postpartum periods. Methods This observational study of 62 women with relapsing-remitting MS included...
Article
Aim: Insufficient correlation between the findings on conventional MRI and physical disability, the so-called clinical-radiological paradox, complicates the estimation of individual prognosis and therapeutic decisions in patients with MS. The primary goal of our work was to elucidate the role of spinal cord atrophy in the situation of the clinical-...
Article
Full-text available
Background Patients with highly active relapsing-remitting multiple sclerosis inadequately responding to first-line therapies (interferon-based therapies, glatiramer acetate, dimethyl fumarate, and teriflunomide, known collectively as “BRACETD”) often switch to natalizumab or fingolimod.Objective The aim was to estimate the comparative effectivenes...
Article
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Background: There is a lack of knowledge about the evolution of cerebrospinal fluid (CSF) markers in multiple sclerosis (MS) patients undergoing natalizumab treatment. Aim: We aimed to evaluate the effect of natalizumab on basic inflammatory CSF and MRI measures. Methods: Together, 411 patients were screened for eligibility and 93 subjects wit...
Article
Background: A special care of MS women planning a pregnancy is highly demanding especially in the terms of disease modifying treatment (DMD) decisions and counselling regarding periods of conception, pregnancy and postpartum period. Objective: To provide data about impact of pregnancy, delivery or miscarriage/artificial abortion on MS disease cours...
Article
Background The added value of neurofilament light chain levels in serum (sNfL) to the concept of no evidence of disease activity-3 (NEDA-3) has not yet been investigated in detail. Objective To assess whether combination of sNfL with NEDA-3 status improves identification of patients at higher risk of disease activity during the following year. Me...
Preprint
Full-text available
Background: An early diagnosis together with an accurate disease progression monitoring of multiple sclerosis is an important component of successful disease management. Prior studies have established that multiple sclerosis is correlated with speech discrepancies. Early research using objective acoustic measurements has discovered measurable dysar...
Article
IntroductionNatalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined.Objective The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS s...
Article
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Background: Iron accumulates in brain tissue in healthy subjects during aging. Our goal was to conduct a detailed analysis of iron deposition patterns in the cerebral deep grey matter and cortex using region-based and whole-brain analyses of brain magnetic susceptibility. Methods: Brain MRI was performed in 95 healthy individuals aged between 21...
Article
Background Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON. Methods Via the MSBase Registry, data on patients from 41 centers was collected during r...
Article
Full-text available
The translational potential of MR-based connectivity modelling is limited by the need for advanced diffusion imaging, which is not part of clinical protocols for many diseases. In addition, where diffusion data is available, brain connectivity analyses rely on tractography algorithms which imply two major limitations. First, tracking algorithms are...
Article
When COVID-19 started to spread in 2019, concerns about its course among patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) arose. It seems that the course of this infection in MS patients is similar to the general population as well as the basic risk factors. However, anti-CD20 therapy and recent glucocorticoi...
Article
PurposeTo identify the clinical and paraclinical markers of employment status in multiple sclerosis (MS).Methods This was a cross-sectional sub-study investigating 1226 MS patients. To minimalized confounding effect, two groups of patients, matched by sex, age, and education, were selected: 307 patients with full time employment and 153 unemployed...
Conference Paper
Objective To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. Methods Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 were included (modern cohort). Annualised relapse rates (ARR) were calculated before, during and after pregnancy. Predictors of intrapar...
Article
Objective To compare the clinical effectiveness of high- and low-efficacy treatments in patients with recently active and inactive secondary progressive multiple sclerosis (SPMS) after accounting for therapeutic lag. Methods Patients treated with high- (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-...
Article
Background: When the novel coronavirus disease 2019 (COVID-19) appeared, concerns about its course in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) arose. This study aimed to evaluate the incidence, severity and risk factors of the more severe COVID-19 course among MS and NMOSD patients. Methods: From M...
Preprint
Full-text available
The translational potential of MR-based connectivity modelling is limited by the need for advanced diffusion imaging, which is not part of clinical protocols for many diseases. In addition, where diffusion data is available, brain connectivity analyses rely on tractography algorithms which imply two major limitations. First, tracking algorithms are...
Article
Full-text available
Objective To describe the dynamics of brain volume loss (BVL) at different stages of relapsing-remitting multiple sclerosis (RRMS), to describe the association between BVL and clinical measures, and to investigate an effect of treatment escalation on the rate of BVL. Methods Together, 1903 patients predominantly with RRMS from the Avonex-Steroids-...
Article
Background Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods By re-analyzing original published results from M...
Article
Objective To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. Methods Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disabili...
Article
Multiple sclerosis (MS) is a chronic disease of the central nervous system. It is characterized by autoimmune inflammation, progressive demyelination and neurodegeneration. The characteristics of inflammation and the representation of these processes are variable over time and interindividual. Nevertheless, certain specific common features allow th...
Article
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(1) Background: Cognitive deterioration is an important marker of disease activity in multiple sclerosis (MS). It is vital to detect cognitive decline as soon as possible. Cognitive deterioration can take the form of isolated cognitive decline (ICD) with no other clinical signs of disease progression present. (2) Methods: We investigated 1091 MS pa...
Article
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Background Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we : (1) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double‐blind and extended controlled periods (DBP+ECP); (2) quantify likely long‐term benefits by extrapolating results; (3) assess the plau...
Article
Secondary progressive multiple sclerosis (SPMS) is a debilitating condition characterized by gradual worsening after an initial relapsing disease course. Despite the recent advances in our understanding of the disease, the diagnosis and treatment of SPMS continue to be challenging in routine clinical practice. The aim of this review article is to p...
Article
Background A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods Data from MSBase, a...
Article
Objective To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis, we modelled disability outcomes in 14,717 patients. Methods We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year and exposed to a multiple sclerosis therapy, and a subset of patients with ≥...
Article
Full-text available
Background Few data exist concerning conversion to secondary progressive MS in patients treated with disease-modifying therapies. Objective Determine the proportion of alemtuzumab-treated patients converting from relapsing-remitting to secondary progressive MS during the CARE-MS core and extension studies. Methods Patients ( N = 811) were analyze...
Article
BACKGROUND AND PURPOSE A high variability of brain MRI volume change measurement renders challenging its interpretation in multiple sclerosis (MS). Occurrence and clinical relevance of observed apparent brain volume increase (BVI) in MS patients have not been investigated yet. The objective was to quantify the prevalence and factors associated with...
Article
Full-text available
At two meetings of a Central European board of multiple sclerosis (MS) experts in 2018 and 2019 factors influencing daily treatment choices in MS, especially practice guidelines, biomarkers and burden of disease, were discussed. The heterogeneity of MS and the complexity of the available treatment options call for informed treatment choices. Howeve...
Article
Full-text available
Background Magnetic resonance imaging (MRI) data from multiple sclerosis (MS) patients treated in real-world settings are important for understanding disease-modifying therapy effects, including no evidence of disease activity (NEDA) assessment. This longitudinal, retrospective, single-cohort analysis assessed MRI and clinical disease outcomes in p...
Article
Objective: To compare the effectiveness of glatiramer acetate (GA) vs intra-muscular Interferon beta-1a (IFNbeta-1a)), we applied a previously published statistical method, aimed at identifying patients' profiles associated with efficacy of treatments. Methods: Data from 2 independent multiple sclerosis datasets, a randomized study (the CombiRx...
Article
Background: Neurofilament light chain level in serum (sNfL) and cerebrospinal fluid (CSF-NfL) is a promising biomarker of disease activity in multiple sclerosis (MS). However, predictive value of neurofilaments for development of cognitive decline over long-term follow-up has not been extensively studied. Objective: To investigate the relationsh...
Article
Importance: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS). Objective: To investigate the association of pregnancy with time to CIS onset. Design, setting, and participant...
Article
In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple scle...
Article
Full-text available
Importance It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS). Objective To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or...
Article
Full-text available
Objective To determine whether serum neurofilament light chain (sNfL) levels are associated with recent MRI activity in patients with relapsing-remitting MS (RRMS). Methods This observational study included 163 patients (405 samples) with early RRMS from the Study of Early interferon-beta1a (IFN-β1a) Treatment (SET) cohort and 179 patients (664 sa...
Article
Background The role of cholesterol homeostasis in neuroaxonal injury in multiple sclerosis (MS) is not known. Objective To investigate the associations of CSF and serum neurofilament light chain levels (CSF-NfL and sNfL, respectively), which are biomarkers of neuroaxonal injury, with cholesterol biomarkers at the clinical onset of MS. Methods: sNf...
Article
Background Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear. Objective The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms. Methods This study used data from MSBase registry. Patients with e...
Article
Full-text available
Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are often presenting with overlapping symptoms. The aim of this study was to determine whether and how NMO and MS differ regarding cerebral iron deposits in deep gray matter (DGM) and the correlation between iron deposition and clinical severity as well as to regional atrophy of th...
Article
Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are pr...
Article
Background Increased blood brain barrier (BBB) permeability, CNS inflammation and neuroaxonal damage are pathological hallmarks in early multiple sclerosis (MS). Objective To investigate the associations of neurofilament light chain (NfL) levels with measures of BBB integrity and central nervous system (CNS) inflammation in MS during the first dem...
Article
Background High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients...
Article
Objective: Voice tremor represents a common but frequently overlooked clinical feature of neurological disease. Therefore, we aimed to quantitatively and objectively assess the characteristics of voice tremor in a large sample of patients with various progressive neurological diseases. Methods: Voice samples were acquired from 240 patients with...
Article
Background Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury. There is a lack of studies investigating the dynamics of relationships between sNfL levels and radiological disease activity over long-term follow-up in multiple sclerosis (MS). Objectives To investigate the relationship among repeated measures of sNfL, lesion bur...
Article
Full-text available
Slow and irregular oral diadochokinesis represents an important manifestation of spastic and ataxic dysarthria in multiple sclerosis (MS). We aimed to develop a robust algorithm based on convolutional neural networks for the accurate detection of syllables from different types of alternating motion rate (AMR) and sequential motion rate (SMR) paradi...
Preprint
Full-text available
Objective Whether immunotherapy improves long-term disability in multiple sclerosis has not been satisfactorily demonstrated. This study examined the effect of immunotherapy on long-term disability outcomes in relapsing-remitting multiple sclerosis. Methods We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year and...