Publications

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). 

18 May 2023

A Pilot Study on the Functional Stability of Phonation in EEG Bands After Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative condition with constantly increasing prevalence rates, affecting strongly life quality in terms of neuromotor and cognitive performance. PD symptoms include voice and speech alterations, known as hypokinetic dysarthria (HD). Unstable phonation is one of the manifestations of HD. Repetitive transcranial magnetic stimulation (rTMS) is a rehabilitative treatment thathas been shown to improve some motor and non-motor symptoms of persons with PD (PwP). This study analyzed the phonation functional behavior of 18 participants (13 males, 5 females) with PD diagnosis before (one pre-stimulus) and after (four post-stimulus) evaluation sessions of rTMS treatment, to assess the extent of changes in their phonation stability. Participants were randomized 1:1 to receive either rTMS or sham stimulation. 

18 May 2023

Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study

Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20-30% or a tumor was rediscovered after radiological disappearance; (2) The patient's clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%.

18 May 2023

Safety and Efficacy of Baseline Antiplatelet Treatment in Patients Undergoing Mechanical Thrombectomy for Ischemic Stroke

Purpose: Baseline use of antiplatelet medication before mechanical thrombectomy (MT) for acute ischemic stroke (AIS) can provide benefit on reperfusion and clinical outcome, but could also carry an increased risk of intracranial hemorrhage (ICH). This nationwide study investigates the safety and efficacy of baseline antiplatelet treatment in AIS patients undergoing MT.

Materials and methods: All consecutive AIS patients treated with MT with and without intravenous thrombolysis (IVT) between January 2012 and December 2019 in all centers performing MT nationwide were reviewed. Data were prospectively collected in national registries (SITS-TBY, RES-Q). Primary outcome was functional independence (modified Rankin Scale 0-2) at three months, secondary outcome was ICH.

26 Apr 2023

Physics-informed deep learning approach to quantification of human brain metabolites from magnetic resonance spectroscopy data

Purpose: While the recommended analysis method for magnetic resonance spectroscopy data is linear combination model (LCM) fitting, the supervised deep learning (DL) approach for quantification of MR spectroscopy (MRS) and MR spectroscopic imaging (MRSI) data recently showed encouraging results; however, supervised learning requires ground truth fitted spectra, which is not practical. Moreover, this work investigates the feasibility and efficiency of the LCM-based self-supervised DL method for the analysis of MRS data.

Method: We present a novel DL-based method for the quantification of relative metabolite concentrations, using quantum-mechanics simulated metabolite responses and neural networks. We trained, validated, and evaluated the proposed networks with simulated and publicly accessible in-vivo human brain MRS data and compared the performance with traditional methods. 

26 Apr 2023

Assessment of Functional Capacity of Immune System in Patients with Multiple Sclerosis using QuantiFERON Monitor

Background: The QuantiFERON®-Monitor (QFM) is an assay that measures interferon-γ production and was developed to provide an objective marker of complex immune response. In this study, we evaluated the use of the QFM test in patients with two forms of multiple sclerosis (MS), relapsing-remitting form treated with fingolimod (fMS) and secondarily progressive form not treated pharmacologically (pMS), and in healthy controls (HC). We hypothesized that IFN-γ levels would be lower in those subjects who are relatively more immunosuppressed and higher in those with normal or activated immune function.

Methods: This single-center observational study was conducted from November 2020 to October 2021 and compared results in three groups of patients: 86 healthy controls, 96 patients with pMS, and 78 fMS. Combination of lyophilized stimulants was added to 1 ml heparinized whole blood within 8 hr of collection. Plasmatic IFN-γ was measured using the ELISA kit for the QFM and data were obtained in IU/ml.

26 Apr 2023

The effect of deep brain stimulation in Parkinson's disease reflected in EEG microstates

Mechanisms of deep brain stimulation (DBS) on cortical networks were explored mainly by fMRI. Advanced analysis of high-density EEG is a source of additional information and may provide clinically useful biomarkers. The presented study evaluates EEG microstates in Parkinson's disease and the effect of DBS of the subthalamic nucleus (STN). The association between revealed spatiotemporal dynamics of brain networks and changes in oscillatory activity and clinical examination were assessed. Thirty-seven patients with Parkinson's disease treated by STN-DBS underwent two sessions (OFF and ON stimulation conditions) of resting-state EEG. EEG microstates were analyzed in patient recordings and in a matched healthy control dataset. Microstate parameters were then compared across groups and were correlated with clinical and neuropsychological scores. Of the five revealed microstates, two differed between Parkinson's disease patients and healthy controls. 

17 Apr 2023

Specialist Perspectives on the Imaging Selection of Large Vessel Occlusion in the Late Window

Background: The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window.

Methods: We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists.

17 Apr 2023

The interacting brain: Dynamic functional connectivity among canonical brain networks dissociates cooperative from competitive social interactions

We spend much our lives interacting with others in various social contexts. Although we deal with this myriad of interpersonal exchanges with apparent ease, each one relies upon a broad array of sophisticated cognitive processes. Recent research suggests that the cognitive operations supporting interactive behaviour are themselves underpinned by several canonical functional brain networks (CFNs) that integrate dynamically with one another in response to changing situational demands. Dynamic integrations among these CFNs should therefore play a pivotal role in coordinating interpersonal behaviour. Further, different types of interaction should present different demands on cognitive systems, thereby eliciting distinct patterns of dynamism among these CFNs. To investigate this, the present study performed functional magnetic resonance imaging (fMRI) on 30 individuals while they interacted with one another cooperatively or competitively. 

17 Apr 2023

Predictive factors of multiple sclerosis relapse after the first demyelinating event: A 5-year follow-up

Keywords: Clinically isolated syndrome; Demyelinating diseases; Magnetic resonance imaging; Multiple sclerosis; Oligoclonal bands.

17 Apr 2023

Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro

Cyanobacterial blooms are known sources of environmentally-occurring retinoid compounds, including all-trans and 9-cis retinoic acids (RAs). The developmental hazard for aquatic organisms has been described, while the implications for human health hazard assessment are not yet sufficiently characterized. Here, we employ a human neural stem cell model that can differentiate in vitro into a mixed culture of neurons and glia. Cells were exposed to non-cytotoxic 8-1000 nM all-trans or 9-cis RA for 9-18 days (DIV13 and DIV22, respectively). Impact on biomarkers was analyzed on gene expression (RT-qPCR) and protein level (western blot and proteomics) at both time points; network patterning (immunofluorescence) on DIV22. RA exposure significantly concentration-dependently increased gene expression of retinoic acid receptors and the metabolizing enzyme CYP26A1, confirming the chemical-specific response of the model. Expression of thyroid hormone signaling-related genes remained mostly unchanged. 

17 Apr 2023

Peripheral Inflammatory Markers in Subtypes and Core Features of Depression: A Systematized Review

Introduction: The aim of this work was to summarize relationships between two subtypes of major depressive disorder (melancholic and atypical) and four core features of depression that reflect the domains identified consistently in previous studies of major depressive disorder endophenotypes (exaggerated reactivity to negative information, altered reward processing, cognitive control deficits, and somatic symptoms) on the one hand and selected peripheral inflammatory markers (C-reactive protein [CRP], cytokines, and adipokines) on the other.

Methods: A systematized review was conducted. The database used for searching articles was PubMed (MEDLINE).

Results: According to our search, most peripheral immunological markers associated with major depressive disorder are not specific to a single depressive symptom group. 

17 Apr 2023

Decompression alone versus decompression with instrumented fusion in the treatment of lumbar degenerative spondylolisthesis: a systematic review and meta-analysis of randomised trials

Objective: To determine the efficacy of adding instrumented spinal fusion to decompression to treat degenerative spondylolisthesis (DS).

Design: Systematic review with meta-analysis.

Data sources: MEDLINE, Embase, Emcare, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to May 2022.

Eligibility criteria for study selection: Randomised controlled trials (RCTs) comparing decompression with instrumented fusion to decompression alone in patients with DS.