26 Jun 2023

Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries

Background: In relapsing-remitting multiple sclerosis (RRMS) the most common treatment strategy has been to start with low-moderate efficacy disease modifying therapy (LE-DMT) and to escalate to more efficacious treatments in cases of breakthrough disease activity. However, recent evidence suggests a better outcome in patients commencing with moderate-high efficacy DMT (HE-DMT) immediately after clinical onset.

Objective: The aim of this study is to compare disease activity and disability outcomes in patients treated with the two alternative strategies using the Swedish and Czech national multiple sclerosis registries, taking advantage of the fact that the relative frequency of each strategy differs markedly between these two countries.

26 Jun 2023

Is breastfeeding in MS harmful or not? An answer from real-world Czech data

Introduction: The influence of breastfeeding and it´s duration on the course of multiple sclerosis (MS) is unclear. Here we analyzed a real-world data for breastfeeding women with MS and their disease course collected from a Czech national registry ReMuS.

Objectives: To identify risk factors associated with not initiating breastfeeding after delivery, to analyze the impact of breastfeeding on the MS disease course, evaluate the assumption, that breastfeeding is not harmful in MS patients, and compare the disease course by breastfeeding status.

Materials and methods: Using propensity score matching we compared Expanded Disability Status Scale (EDSS), confirmed disease worsening (CDW) and annual relapse rate (ARR) in breastfeeding and non-breastfeeding MS patients according to disease duration, disease modifying treatment (DMT) before pregnancy, last EDSS score before conception, age, and ARR during pregnancy.

16 Jun 2023

Response: Can biomarkers of the epileptogenic zone be characterized in patients rendered seizure free alone?

The role ofpresurgical evaluation with intracranial elec-troencephalography (iEEG) is to localize the minimal amount ofbrain tissue which, ifresected, will achieve sei-zure freedom in the treated patient. From the definition ofthe epileptogenic zone (EZ)1being “the area ofcortex that is indispensable for the generation ofepileptic seizures,” it is the EZ that we want to localize. At the same time we will only know retrospectively in patients with seizure-free outcome that we were indeed able to identify the EZ. 

This brings us to the localization dilemma. We either attempt to stick to the primary goal oflocalization ofthe EZ and use only good outcome patients or use something else as a localization target that is well defined in both good and poor outcomes. For poor outcome patients the latter remains less clear apart from the fact that at least part ofthe predicted target, localized by an algorithm, should be outside of the resection cavity.

16 Jun 2023

Six years of the Angels Initiative: Aims, achievements and future directions to improve stroke care worldwide

The rate of stroke-related death and disability is four times higher in low- and middle-income countries (LMICs) than in high-income countries (HICs), yet stroke units exist in only 18% of LMICs, compared with 91% of HICs. In order to ensure universal and equitable access to timely, guideline-recommended stroke care, multidisciplinary stroke-ready hospitals with coordinated teams of healthcare professionals and appropriate facilities are essential.Established in 2016, the Angels Initiative is an international, not-for-profit, public-private partnership. It is run in collaboration with the World Stroke Organization, European Stroke Organisation, and regional and national stroke societies in over 50 countries.

The Angels Initiative aims to increase the global number of stroke-ready hospitals and to optimise the quality of existing stroke units. It does this through the work of dedicated consultants, who help to standardise care procedures and build coordinated, informed communities of stroke professionals.

15 Jun 2023

Twenty-five years of epilepsy surgery at a Central European comprehensive epilepsy center-Trends in intervention delay and outcomes

Objective: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy.

Methods: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center.

Results: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001). 

15 Jun 2023

Editorial: The brain barriers in diseases of the nervous system

The central nervous system is protected against harmful substances from the blood by three major barriers: the blood–brain barrier, the choroid plexus blood–cerebrospinal fluid barrier, and the arachnoid blood–cerebrospinal fluid barrier. Under disease conditions (neurodegenerative, traumatic, oncologic, autoimmune), inflammatory responses within the brain barriers change their permeability. Therefore, the aim of this Research Topic was to provide new insights into (1) inflammatory responses within the brain barriers, (2) barrier changes associated with brain disorders, and (3) barrier modulation for drug delivery and treatment. This Research Topic consists of six articles, two reviews, and four original articles, written by authors with different expertise. All articles were focused on changes in the blood–brain barrier.

Keywords: blood-brain barrier; blood-cerebrospinal fluid barrier; choroid plexus; drug delivery; meningeal blood-cerebrospinal fluid barrier; stroke.

15 Jun 2023

Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate

Background: Apolipoprotein E (ApoE) ε4 genotype is the most prevalent risk factor for late-onset Alzheimer's Disease (AD). Although ApoE4 differs from its non-pathological ApoE3 isoform only by the C112R mutation, the molecular mechanism of its proteinopathy is unknown.

Methods: Here, we reveal the molecular mechanism of ApoE4 aggregation using a combination of experimental and computational techniques, including X-ray crystallography, site-directed mutagenesis, hydrogen-deuterium mass spectrometry (HDX-MS), static light scattering and molecular dynamics simulations. Treatment of ApoE ε3/ε3 and ε4/ε4 cerebral organoids with tramiprosate was used to compare the effect of tramiprosate on ApoE4 aggregation at the cellular level.

Results: We found that C112R substitution in ApoE4 induces long-distance (> 15 Å) conformational changes leading to the formation of a V-shaped dimeric unit that is geometrically different and more aggregation-prone than the ApoE3 structure.

1 Jun 2023

Single-center long-term results of vagus nerve stimulation for pediatric epilepsy: a 10-17-year follow-up study

Purpose: A retrospective study, based on a prospectively built database, presents the results of long-term follow-up care of pediatric vagus nerve stimulation (VNS) patients in terms of seizure outcome, surgical aspects, the potential impact of maturation, and medication changes.

Methods: From a prospectively built database, 16 VNS patients (median age 12.0 years, range 6.0 to 16.0 years; median seizure duration 6.5 years, range 2.0 to 15.5 years) followed for at least 10 years were graded as non-responder - NR (seizure frequency reduction < 50%), responder - R (reduction ≥ 50% and < 80%), and 80% responder - 80R (reduction ≥ 80%). Data about surgical aspects (battery replacement, system complications), seizure dynamics, and medication changes were taken from the database.

Results: The early percentages of good results (80R + R) were 43.8% (year 1), 50.0% (year 2), and 43.8% (year 3).