Publications

23 Apr 2021

RAFF-4, Magnetization Transfer and Diffusion Tensor MRI of Lysophosphatidylcholine Induced Demyelination and Remyelination in Rats

Remyelination is a naturally occurring response to demyelination and has a central role in the pathophysiology of multiple sclerosis and traumatic brain injury. Recently we demonstrated that a novel MRI technique entitled Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) achieved exceptional sensitivity in detecting the demyelination processes induced by lysophosphatidylcholine (LPC) in rat brain. In the present work, our aim was to test whether RAFF4, along with magnetization transfer (MT) and diffusion tensor imaging (DTI), would be capable of detecting the changes in the myelin content and microstructure caused by modifications of myelin sheets around axons or by gliosis during the remyelination phase after LPC-induced demyelination in the corpus callosum of rats. We collected MRI data with RAFF4, MT and DTI at 3 days after injection (demyelination stage) and at 38 days after injection (remyelination stage) of LPC (n = 12) or vehicle (n = 9). Cell density and myelin content were assessed by histology.

23 Apr 2021

Editorial: Neuropsychology Through the MRI Looking Glass

Since its inception as a science, psychology has been explicitly preoccupied with the mind-body relationship, specifically with the role that the nervous system plays in shaping how we perceive the world around us and how we react in our interaction with it. The evidence in this regard are the second and third chapters of William James's 1890 “The Principle of Psychology” (Volume 1) (1), which explain the functions of the brain and the general conditions underlying its activity, as well as the entire work of Wilhelm Wundt's 1904 “Principles of Physiological Psychology” (2), which explicitly linked the evolution of various mental functions to the organization and physiology of the nervous system. Yet, it was not until 1980s when the neuropsychology has established itself as a branch of psychology in its own right, aiming to explain how the brain and the other parts of the nervous system influence one's cognition, emotions and behaviors using a variety of methods from observation and questionnaires to computerized tasks gathering reaction time and electrophysiology. The knowledge thus obtained in healthy individuals was then employed by neuropsychologists in assessing the impact of various diseases on brain structure and function.

23 Apr 2021

Memory outcomes of temporal lobe surgery in adults aged over 45 years

Objective: It is assumed that temporal lobe resection in older people is associated with worse seizure outcomes and potential postsurgical memory decline. We studied postsurgical memory development and surgical efficacy in patients over 45 years of age compared with younger patients.

Methods: We studied 88 patients (51 male and 37 female) after temporal lobe surgery, which involved hippocampal resection. The patients were evaluated before surgery and in the first (72 patients) and/or third (57 patients) postsurgical year. The Wechsler Memory Scale III test was performed to evaluate the MQ postsurgical development. Engel's classification was used to evaluate the postsurgical seizure outcome.

Results: The presurgical MQ (median 88) in ≥45 years age group was significantly lower than in both younger groups (median MQ = 100 for ≤30 years age group, p = 0.002; median MQ = 107 for 31-44 years age group, p = 0.002). Three years after the surgery, the MQ decreased significantly in ≤30 years age group (p = 0.012), while only non-significant MQ decline was observed in both older groups. We found no significant impact of age on the surgical outcome.

16 Apr 2021

Anomaly Detection Algorithm for Real-World Data and Evidence in Clinical Research

Background: Statistical analysis, which has become an integral part of evidence-based medicine, relies heavily on data quality that is of critical importance in modern clinical research. Input data are not only at risk of being falsified or fabricated, but also of being mishandled by investigators.

Objective: The urgent need to assure the highest data quality possible has led to the implementation of various auditing strategies designed to monitor clinical trials and detect errors of different origin that frequently occur in the field.

Methods: A particular electronic data capture (EDC) system, which is used for data management in clinical registries, is presented including its architecture and data structure. This EDC system features an algorithm based on machine learning designed to detect anomalous patterns in quantitative data. The detection algorithm combines clustering with a series of seven distance metrics that serve to determine the strength of an anomaly. For the detection process, the thresholds and combinations of the metrics were used and the detection performance was evaluated and validated in the experiments involving simulated anomalous data and real-world data.

12 Apr 2021

The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia: a preliminary MRI study

Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients.

12 Apr 2021

Non-steroidal anti-inflammatory drugs in the pathophysiology of vasospasms and delayed cerebral ischemia following subarachnoid hemorrhage: a critical review

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition associated with the development of early brain injury (EBI) and delayed cerebral ischemia (DCI). Pharmacological treatment of vasospasm following aSAH currently mainly comprises nimodipine administration. In the past few years, many drugs that can potentially benefit cases of subarachnoid hemorrhage have become available. The objective of this review is to critically assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) following aSAH. A systematic literature review was conducted following PRISMA guidelines. The search was aimed at studies addressing aSAH and NSAIDs during the 2010 to 2019 period, and it yielded 13 articles. Following the application of search criteria, they were divided into two groups, one containing 6 clinical articles and the other containing 7 experimental articles on animal models of aSAH. Inflammatory cerebral changes after aneurysm rupture contribute to the development of EBI, DCI and cerebral vasospasm.

6 Apr 2021

Concentrating stroke care provision in the Czech Republic: The establishment of Stroke Centres in 2011 has led to improved outcomes

This article describes policy processes that have led to the re-organisation of stroke care in the Czech Republic since 2011, which has been part of a broader process of care concentration in several medical fields. Currently, stroke care is provided by 13 Comprehensive and 32 Primary Stroke Centres. The paper explains factors that supported the reform implementation, reviews implications, and discusses future challenges. Mandatory reporting of quality indicators, the introduction of a benchmarking system, integration with pre-hospital emergency care, and the introduction of countrywide patient triage have supported more timely treatment for stroke patients and better quality of care. Data from the Stroke Care Quality Indicators of the Czech Stroke Society show positive trends in many areas: the number of patients treated with intravenous thrombolysis quadrupled in eight years, with 26.4 % of all acute stroke patients receiving thrombolysis in 2018. Czech Republic now ranks third in Europe in the number of thrombolysis per population and second in the number of mechanical thrombectomies per population.

31 Mar 2021

Arterial Spin Labeling is a Useful MRI Method for Presurgical Evaluation in MRI-Negative Focal Epilepsy

Arterial spin labeling (ASL) is an MRI technique measuring brain perfusion using magnetically labeled blood as a tracer. The clinical utility of ASL for presurgical evaluation in non-lesional epilepsy as compared with the quantitative analysis of interictal [¹⁸F] fluorodeoxyglucose PET (FDG-PET) was studied. In 10 patients (4 female; median age 29 years) who underwent a complete presurgical evaluation followed by surgical resection, the presurgical FDG-PET and ASL scans were compared with the resection masks using asymmetry index (AI) maps. The positive predictive value (PPV) and sensitivity (SEN), were calculated from the number of voxels inside the mask (true positive), and outside the mask (false positive). The comparison of the PPVs showed better PPV in 6 patients using ASL and in 2 patients with PET. SEN was better in 4 patients using ASL and in 5 patients with PET. According to the Wilcoxon signed rank test for PPV (p = 0.74) and for SEN (p = 0.43), these methods have similar predictive power. ASL is a useful method for presurgical evaluation in non-lesional epilepsy.

31 Mar 2021

Automated fusion of multimodal imaging data for identifying epileptogenic lesions in patients with inconclusive magnetic resonance imaging

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand-alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR-negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel-wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue.

31 Mar 2021

Are Functional (Psychogenic Nonepileptic) Seizures the Sole Expression of Psychological Processes?

Functional [psychogenic nonepileptic/dissociative] seizures (FND-seiz) and related functional neurological disorder subtypes were of immense interest to early founders of modern-day neurology and psychiatry. Unfortunately, the divide that occurred between the both specialties throughout the mid-twentieth century placed FND-seiz at the borderland between the two disciplines. In the process, a false Cartesian dualism emerged that labeled psychiatric conditions as impairments of the mind and neurological conditions as disturbances in structural neuroanatomy. Excitingly, modern-day neuropsychiatric perspectives now consider neurologic and psychiatric conditions as disorders of both brain and mind. In this article, we aim to integrate neurologic and psychiatric perspectives in the conceptual framing of FND-seiz. In doing so, we explore emerging relationships between symptoms, neuropsychological constructs, brain networks, and neuroendocrine/autonomic biomarkers of disease. Evidence suggests that the neuropsychological constructs of emotion processing, attention, interoception, and self-agency are important in the pathophysiology of FND-seiz.

31 Mar 2021

Global Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001).

31 Mar 2021

Thalamic oscillatory activity may predict response to deep brain stimulation of the anterior nuclei of the thalamus

We hypothesized that local/regional properties of stimulated structure/circuitry contribute to the effect of deep brain stimulation (DBS). We analyzed intracerebral electroencephalographic (EEG) recordings from externalized DBS electrodes targeted bilaterally in the anterior nuclei of the thalamus (ANT) in 12 patients (six responders, six nonresponders) with more than 1 year of follow-up care. In the bipolar local field potentials of the EEG, spectral power (PW) and power spectral entropy (PSE) were calculated in the passbands 1-4, 4-8, 8-12, 12-20, 20-45, 65-80, 80-200 and 200-500 Hz. The most significant differences between responders and nonresponders were observed in the BRIDGE area (bipolar recordings with one contact within the ANT and the second contact in adjacent tissue). In responders, PW was significantly decreased in the frequency bands of 65-80, 80-200, and 200-500 Hz (p < .05); PSE was significantly increased in all frequency bands (p < .05) except for 200-500 Hz (p = .06).

22 Mar 2021

Trends and outcomes for non-elective neurosurgical procedures in Central Europe during the COVID-19 pandemic

The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th-April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas.

9 Mar 2021

Automated seizure detection using wearable devices: A clinical practice guideline of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology

The objective of this clinical practice guideline (CPG) is to provide recommendations for healthcare personnel working with patients with epilepsy, on the use of wearable devices for automated seizure detection in patients with epilepsy, in outpatient, ambulatory settings. The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology developed the CPG according to the methodology proposed by the ILAE Epilepsy Guidelines Working Group. We reviewed the published evidence using The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and evaluated the evidence and formulated the recommendations following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

2 Mar 2021

A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence‐based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies.

Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web‐based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht‐like diseases. A consensus‐based questionnaire was generated for each disease.

2 Mar 2021

Sensory and pain modulation profiles of ongoing central neuropathic extremity pain in multiple sclerosis

Background: Central neuropathic extremity pain (CNEP) is the most frequent type of pain in multiple sclerosis (MS). The aim of the present study was to evaluate sensory and pain modulation profiles in MS patients with CNEP.

Methods: In a single-centre observational study, a group of 56 CNEP MS patients was compared with 63 pain-free MS patients and with a sex- and age-adjusted control group. Standardized quantitative sensory testing (QST) and dynamic QST (dQST) protocols comprising temporal summation and conditioned pain modulation tests were used to compare sensory profiles.

Results: Loss-type QST abnormalities in both thermal and mechanical QST modalities prevailed in both MS subgroups and correlated significantly with higher degree of disability expressed as Expanded Disability Status Scale (EDSS). Comparison of sensory phenotypes disclosed a higher frequency of the 'sensory loss' prototypic sensory phenotype in the CNEP subgroup (30%) compared with pain-free MS patients (6%; p = .003).

19 Feb 2021

Contemporary clinical neurophysiology applications in dystonia

The complex phenomenological understanding of dystonia has transcended from the clinics to genetics, imaging and neurophysiology. One way in which electrophysiology will impact into the clinics are cases wherein a dystonic clinical presentation may not be typical or a "forme fruste" of the disorder. Indeed, the physiological imprints of dystonia are present regardless of its clinical manifestation. Underpinnings in the understanding of dystonia span from the peripheral, segmental and suprasegmental levels to the cortex, and various electrophysiological tests have been applied in the course of time to elucidate the origin of dystonia pathophysiology. While loss of inhibition remains to be the key finding in this regard, intricacies and variabilities exist, thus leading to a notion that perhaps dystonia should best be gleaned as network disorder. Interestingly, the complex process has now spanned towards the understanding in terms of networks related to the cerebellar circuitry and the neuroplasticity.

18 Feb 2021

Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: A DTI study

In motor functional neurological disorders (mFND), relationships between interoception (a construct of high theoretical relevance to its pathophysiology) and neuroanatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bundle integrity and cardiac interoception. Voxel‐based analysis and tractography quantified fractional anisotropy (FA) in 38 mFND patients compared to 38 HCs. Secondary analyses compared functional seizures (FND‐seiz; n = 21) or functional movement disorders (n = 17) to HCs. Network lesion mapping identified gray matter origins of implicated fiber bundles. Within‐group mFND analyses investigated relationships between FA, heartbeat tracking accuracy and interoceptive trait prediction error (discrepancies between interoceptive accuracy and self‐reported bodily awareness). Results were corrected for multiple comparisons, and all findings were adjusted for depression and trait anxiety. mFND and HCs did not show any between‐group interoceptive accuracy or FA differences.