Publications

7 Nov 2023

Metabolic connectivity as a predictor of surgical outcome in mesial temporal lobe epilepsy

Objective: The study investigated metabolic connectivity (MC) differences between patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and healthy controls (HC), based on [18 F]-fluorodeoxyglucose (FDG)-PET data. We focused on the MC changes dependent on the lateralization of the epileptogenic lobe and on correlations with postoperative outcome.

Methods: FDG-PET scans of 47 patients with unilateral MTLE with histopathologically proven HS and 25 HC were included in the study. All the patients underwent a standard anterior temporal lobectomy and were more than two years after the surgery. MC changes were compared between the two HS groups (left HS, right HS) and HC. Differences between the metabolic network of seizure-free and non-seizure-free patients after surgery were depicted afterward. Network changes were correlated with clinical characteristics.

Results: The study showed widespread metabolic network changes in the HS patients as compared to HC. 

7 Nov 2023

Parkinson´s disease cardiovascular symptoms: A new complex functional and structural insight

Background: The known impairments of the cardiovascular system in Parkinson´s disease (PD) are caused by autonomic dysfunction and manifested mainly in postural hypotension, chronotropic insufficiency, and reduced heart rate variability. Other dysfunctions, mainly stress response, arrhythmia occurrence, and heart morphology changes, are still the subject of research.

Objectives: To assess the heart rate and blood pressure reaction during exercise, advanced measurements of heart volumes and mass using cardiac magnetic resonance (CMR), and occurrence of arrhythmias in PD patients.

Methods: Thirty PD patients (19 men, mean age 57.5 years) without known cardiac comorbidities underwent bicycle ergometry, electrocardiogram Holter monitoring and CMR. Exercise and CMR parameters were compared with controls (24 subjects for ergometry, 20 for CMR).

7 Nov 2023

Entropy in scalp EEG can be used as a preimplantation marker for VNS efficacy

Vagus nerve stimulation (VNS) is a therapeutic option in drug-resistant epilepsy. VNS leads to ≥ 50% seizure reduction in 50 to 60% of patients, termed "responders". The remaining 40 to 50% of patients, "non-responders", exhibit seizure reduction < 50%. Our work aims to differentiate between these two patient groups in preimplantation EEG analysis by employing several Entropy methods. We identified 59 drug-resistant epilepsy patients treated with VNS. We established their response to VNS in terms of responders and non-responders. A preimplantation EEG with eyes open/closed, photic stimulation, and hyperventilation was found for each patient. The EEG was segmented into eight time intervals within four standard frequency bands. In all, 32 EEG segments were obtained. Seven Entropy methods were calculated for all segments. Subsequently, VNS responders and non-responders were compared using individual Entropy methods. VNS responders and non-responders differed significantly in all Entropy methods except Approximate Entropy. Spectral Entropy revealed the highest number of EEG segments differentiating between responders and non-responders. 

7 Nov 2023

Selected neuroendocrine factors as potential molecular biomarkers of early non-affective psychosis course in relation to treatment outcome: A pilot study

The aim of this pilot study was to find whether the dysregulation of neuroendocrine biomarker signaling pathways in the first episode of non-affective psychosis is a predictive factor of treatment outcome. Patients with the first episode of non-affective psychosis (N = 29) were examined at admission, at discharge, and at follow-up (N = 23). The biomarkers included serum aldosterone, cortisol, free thyroxine, thyroid stimulating hormone, and prolactin. We revealed lower baseline aldosterone and higher baseline cortisol concentrations in patients with very good outcome compared to those with good outcome after one year. We failed to reveal any significant association between treatment outcome and neurohumoral biomarkers in the whole sample at 1-year follow-up. However, baseline aldosterone concentrations negatively correlated with total PANSS scores at the discharge. Lower baseline aldosterone and higher baseline cortisol concentrations have the potential to predict a more favorable outcome for patients with the first episode of psychosis.

19 Sep 2023

Delivery of acute ischaemic stroke treatments in the European region in 2019 and 2020

Introduction: We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020.

Patients and methods: We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively.

Results: The estimated mean number of acute SUs in 2019 was 3.68 (95% CI: 2.90-4.45) per one million inhabitants (MIH) with 7/44 countries having less than one SU per one MIH. The estimated mean annual number of IVTs was 21.03 (95% CI: 15.63-26.43) per 100,000 and 17.14% (95% CI: 12.98-21.30) of the AIIS in 2019, with highest country rates at 79.19 and 52.66%, respectively, and 15 countries delivering less than 10 IVT per 100,000. The estimated mean annual number of EVTs in 2019 was 7.87 (95% CI: 5.96-9.77) per 100,000 and 6.91% (95% CI: 5.15-8.67) of AIIS, with 11 countries delivering less than 1.5 EVT per 100,000. 

19 Sep 2023

Endemic parkinsonism: clusters, biology and clinical features

The term 'endemic parkinsonism' refers to diseases that manifest with a dominant parkinsonian syndrome, which can be typical or atypical, and are present only in a particular geographically defined location or population. Ten phenotypes of endemic parkinsonism are currently known: three in the Western Pacific region; two in the Asian-Oceanic region; one in the Caribbean islands of Guadeloupe and Martinique; and four in Europe. Some of these disease entities seem to be disappearing over time and therefore are probably triggered by unique environmental factors. By contrast, other types persist because they are exclusively genetically determined. Given the geographical clustering and potential overlap in biological and clinical features of these exceptionally interesting diseases, this Review provides a historical reference text and offers current perspectives on each of the 10 phenotypes of endemic parkinsonism. Knowledge obtained from the study of these disease entities supports the hypothesis that both genetic and environmental factors contribute to the development of neurodegenerative diseases, not only in endemic parkinsonism but also in general. 

29 Aug 2023

Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.

Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.

Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.

Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life.

29 Aug 2023

How registry data are used to inform activities for stroke care quality improvement across 55 countries: A cross-sectional survey of Registry of Stroke Care Quality (RES-Q) hospitals

Background and purpose: The Registry of Stroke Care Quality (RES-Q) is a worldwide quality improvement data platform that captures performance and quality measures, enabling standardized comparisons of hospital care. The aim of this study was to determine if, and how, RES-Q data are used to influence stroke quality improvement and identify the support and educational needs of clinicians using RES-Q data to improve stroke care.

Methods: A cross-sectional self-administered online survey was administered (October 2021-February 2022). Participants were RES-Q hospital local coordinators responsible for stroke data collection. Descriptive statistics are presented.

Results: Surveys were sent to 1463 hospitals in 74 countries; responses were received from 358 hospitals in 55 countries (response rate 25%).

29 Aug 2023

Interictal High-Frequency Oscillations, Spikes, and Connectivity Profiles: a Fingerprint of Epileptogenic Brain Pathologies

Introduction: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for pre-resective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies.

Methods: Interictal awake SEEG recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone (SOZ) and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs.

29 Aug 2023

Eslicarbazepine-induced hyponatremia: A retrospective single-center real clinical practice study

Hyponatremia is a typical side effect of antiseizure drugs from the dibenzazepine family. The study investigated the prevalence of hyponatremia in patients with epilepsy who were treated with eslicarbazepine. We aimed to determine the prevalence of hyponatremia, reveal the factors leading to the discontinuation of treatment, and identify possible risk factors for the development of hyponatremia including the dose dependency. The medical records of 164 patients with epilepsy taking eslicarbazepine in our center were analyzed. The overall prevalence of hyponatremia was 30.5%. The prevalence of mild hyponatremia, seen in 14% to 20% of patients, was not dose dependent. The prevalence of moderate and severe hyponatremia was significantly dose dependent. The severity of hyponatremia was significantly dose dependent. Severe hyponatremia was found in 6.1% of patients. Hyponatremia was asymptomatic in the majority of cases, and in 48% did not require any management. Hyponatremia was the reason for discontinuation in 6.2% of patients. The major risk factor for developing hyponatremia was older age.

29 Aug 2023

EEG Microstates in Mood and Anxiety Disorders: A Meta-analysis

To reduce the psycho-social burden increasing attention has focused on brain abnormalities in the most prevalent and highly co-occurring neuropsychiatric disorders, such as mood and anxiety. However, high inter-study variability in these patients results in inconsistent and contradictory alterations in the fast temporal dynamics of large-scale networks as measured by EEG microstates. Thus, in this meta-analysis, we aim to investigate the consistency of these changes to better understand possible common neuro-dynamical mechanisms of these disorders.In the systematic search, twelve studies investigating EEG microstate changes in participants with mood and anxiety disorders and individuals with subclinical depression were included in this meta-analysis, adding up to 787 participants.The results suggest that EEG microstates consistently discriminate mood and anxiety impairments from the general population in patients and subclinical states. Specifically, we found a small significant effect size for B microstates in patients compared to healthy controls, with larger effect sizes for increased B presence in unmedicated patients with comorbidity. In a subgroup meta-analysis of ten mood disorder studies, microstate D showed a significant effect size for decreased presence.

29 Aug 2023

Lifelong effects of prenatal and early postnatal stress on the hippocampus, amygdala, and psychological states of Holocaust survivors

This study focuses on hippocampal and amygdala volume, seed-based connectivity, and psychological traits of Holocaust survivors who experienced stress during prenatal and early postnatal development. We investigated people who lived in Central Europe during the Holocaust and who, as Jews, were in imminent danger. The group who experienced stress during their prenatal development and early postnatal (PreP) period (n = 11) were compared with a group who experienced Holocaust-related stress later in their lives: in late childhood, adolescence, and early adulthood (ChA) (n = 21). The results of volumetry analysis showed significantly lower volumes of both hippocampi and the right amygdala in the PreP group. Seed-based connectivity analysis revealed increased connectivity from the seed in the right amygdala to the middle and posterior cingulate cortex, caudate, and inferior left frontal operculum in the PreP group. Psychological testing found higher levels of traumatic stress symptoms (TCS-40) and lower levels of well-being (SOS-10) in the PreP group than in the ChA group.

21 Aug 2023

Longitudinal study of epigenetic aging and its relationship with brain aging and cognitive skills in young adulthood

Introduction: The proportion of older adults within society is sharply increasing and a better understanding of how we age starts to be critical. However, given the paucity of longitudinal studies with both neuroimaging and epigenetic data, it remains largely unknown whether the speed of the epigenetic clock changes over the life course and whether any such changes are proportional to changes in brain aging and cognitive skills. To fill these knowledge gaps, we conducted a longitudinal study of a prenatal birth cohort, studied epigenetic aging across adolescence and young adulthood, and evaluated its relationship with brain aging and cognitive outcomes.

Methods: DNA methylation was assessed using the Illumina EPIC Platform in adolescence, early and late 20 s, DNA methylation age was estimated using Horvath's epigenetic clock, and epigenetic age gap (EpiAGE) was calculated as DNA methylation age residualized for batch, chronological age and the proportion of epithelial cells. Structural magnetic resonance imaging (MRI) was acquired in both the early 20 s and late 20 s using the same 3T Prisma MRI scanner and brain age was calculated using the Neuroanatomical Age Prediction using R (NAPR) platform. 

4 Aug 2023

Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson's disease

The biological basis of the neurodegenerative movement disorder, Parkinson's disease (PD), is still unclear despite it being 'discovered' over 200 years ago in Western Medicine. Based on current PD knowledge, there are widely varying theories as to its pathobiology.

The aim of this article was to explore some of these different theories by summarizing the viewpoints of laboratory and clinician scientists in the PD field, on the biological basis of the disease. To achieve this aim, we posed this question to thirteen "PD experts" from six continents (for global representation) and collated their personal opinions into this article.

The views were varied, ranging from toxin exposure as a PD trigger, to LRRK2 as a potential root cause, to toxic alpha-synuclein being the most important etiological contributor. Notably, there was also growing recognition that the definition of PD as a single disease should be reconsidered, perhaps each with its own unique pathobiology and treatment regimen.

4 Aug 2023

Consensus Paper: Cerebellum and Ageing

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. 

26 Jun 2023

Genetic algorithm designed for optimization of neural network architectures for intracranial EEG recordings analysis

Objective.The current practices of designing neural networks rely heavily on subjective judgment and heuristic steps, often dictated by the level of expertise possessed by architecture designers. To alleviate these challenges and streamline the design process, we propose an automatic method, a novel approach to enhance the optimization of neural network architectures for processing intracranial electroencephalogram (iEEG) data.Approach. We present a genetic algorithm, which optimizes neural network architecture and signal pre-processing parameters for iEEG classification.Main results. Our method improved the macroF1 score of the state-of-the-art model in two independent datasets, from St. Anne's University Hospital (Brno, Czech Republic) and Mayo Clinic (Rochester, MN, USA), from 0.9076 to 0.9673 and from 0.9222 to 0.9400 respectively. Significance. By incorporating principles of evolutionary optimization, our approach reduces the reliance on human intuition and empirical guesswork in architecture design, thus promoting more efficient and effective neural network models. 

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.