Savvas Papacostas

Cyprus Institute of Neurology and Genetics · Neurology Clinic B

Gap junctions (GJs) are specialized transmembrane channels assembled by two hemi-channels of six connexin (Cx) proteins that facilitate neuroglial crosstalk in the central nervous system (CNS). Previous studies confirmed the crucial role of glial GJs in neurodegenerative disorders with dementia or motor dysfunction including Alzheimer’s disease (AD...

Purpose The mediator (MED) multisubunit-complex modulates the activity of the transcriptional machinery, and genetic defects in different MED subunits (17, 20, 27) have been implicated in neurologic diseases. In this study, we identified a recurrent homozygous variant in MED11 (c.325C>T; p.Arg109Ter) in 7 affected individuals from 5 unrelated famil...

Background: KCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyse the clinical phenotype, genetic background, and biophysical function of d...

The coronavirus disease (COVID-19) pandemic fundamentally disrupted humans’ social life and behavior. Public health measures may have inadvertently impacted how people care for each other. This study investigated prosocial behavior, its association well-being, and predictors of prosocial behavior during the first COVID-19 pandemic lockdown and soug...

We aim to understand the factors that drive citizens of different countries adhere to recommended self-protective behaviors during the COVID-19 pandemic. Survey data obtained through the COVID Impact project was used. We combined previous evidence and change-point detection analysis to establish variations in self-protective behaviors across partic...

A population-based cross-sectional study was conducted during the first COVID-19 wave, to examine the impact of COVID-19 on mental health using an anonymous online survey, enrolling 9565 individuals in 78 countries. The current sub-study examined the impact of the pandemic and the associated lockdown measures on the mental health, and protective be...

The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of autosomal recessive lysosomal storage disorders that are characterized by neurodegeneration, progressive cognitive decline, motor impairment, ataxia, loss of vision, seizures, and premature death. To date, pathogenic variants in more than 13 genes have been asso...

Introduction: Following the onset of the COVID-19 pandemic, most countries imposed strict governmental lockdowns. Research investigating the psychological impact of pandemic-induced lockdowns is accumulating, though to date no study has examined the psychological health and associated parameters of well-being in countries that underwent additional...

Background: The COVID-19 pandemic is a massive health crisis that has exerted enormous physical and psychological pressure. Mental healthcare for healthcare workers (HCWs) should receive serious consideration. This study served to determine the mental-health outcomes of 1,556 HCWs from 45 countries who participated in the COVID-19 IMPACT project, a...

Background Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3 , DLK1 , KISS1 , a...

Background Despite the demonstrated effectiveness of behavioural headache interventions, it is not yet known which intervention processes account for treatment responses. Acceptance and commitment therapy (ACT), an emerging behavioural intervention for headaches, proposes psychological flexibility (PF) processes as the mechanisms via which interven...

Objective: The effects of normal cognitive aging on executive functions (EF), Verbal Episodic Memory (VEM) and the contribution of age, sex, education, and APOΕ ε4 in a group of old Greek Cypriots across a five-year period were investigated. Design: NEUROAGE, the first project on cognitive aging in Cyprus, is a prospective longitudinal study with a...

Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on ge...

Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on ge...

Background KCNC2 encodes a member of the shaw-related voltage-gated potassium channel family (KV3.2), which are important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. Methods Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic and function...

This study aimed to compare the mediation of psychological flexibility, prosociality and coping in the impacts of illness perceptions toward COVID-19 on mental health among seven regions. Convenience sampled online survey was conducted between April and June 2020 from 9130 citizens in 21 countries. Illness perceptions toward COVID-19, psychological...

Objective: Illness perceptions (IP) are important predictors of emotional and behavioral responses in many diseases. The current study aims to investigate the COVID-19-related IP throughout Europe. The specific goals are to understand the temporal development, identify predictors (within demographics and contact with COVID-19) and examine the impac...

Background The COVID-19 pandemic triggered vast governmental lockdowns. The impact of these lockdowns on mental health is inadequately understood. On the one hand such drastic changes in daily routines could be detrimental to mental health. On the other hand, it might not be experienced negatively, especially because the entire population was affec...

Background In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs co...

Glial gap junction proteins, called connexins (Cxs), form gap junctions in the central nervous system (CNS) to allow the bidirectional cytosolic exchange of molecules between adjacent cells. Their involvement in inheritable diseases and the use of experimental animal models that closely mimic such diseases revealed the critical role of glial GJs in...

Objective Transcranial magnetic stimulation (TMS), a non-invasive procedure, stimulates the cortex evaluating the central motor pathways. The response is called motor evoked potential (MEP). Polyphasia results when the response crosses the baseline more than twice (zero crossing). Recent research shows MEP polyphasia in patients with generalized ge...

Prevention of headaches via avoidance of triggers remains the main behavioral treatment suggestion for headache management despite trigger avoidance resulting in increases in potency, lifestyle restrictions, internal locus of control decreases, pain exacerbation and maintenance. New approaches, such as Acceptance and Commitment Therapy (ACT), inste...

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychi-atric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked toPFBC.However, morethan50% ofindividualsaffectedby PFBChavenomoleculardiagnosis. We...

Epileptic seizure detection and prediction by using noninvasive measurements such as scalp EEG signals or invasive, intracranial recordings, has been at the heart of epilepsy studies for at least three decades. To this end, the most common approach has been to consider short‐length recordings (several seconds to a few minutes) around a seizure, aim...

According to the amyloid hypothesis of Alzheimer’s disease (AD) the deposition of prefibrillar and fibrillar Aβ peptide sets off the pathogenic cascades of neuroinflammation and neurodegeneration that lead to synaptic and neuronal loss resulting in cognitive decline. Various approaches to reduce amyloid load by reducing production of the Aβ peptide...

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder affecting a substantial proportion of the elderly Cypriot population. The objective of this study was to evaluate PD risk variants that have been identified previously in Genome Wide Association Studies (GWAS) and to find environmental factors that are predictors for PD onset in...

Background and purpose: Progressive multifocal leukoencephalopathy (PML) is a debilitating disease of the central nervous system caused by the ubiquitous polyomavirus JC (JCV) in immunocompromised hosts. In recent years, a new subpopulation of patients at risk for PML has emerged, due to the growing use of immunomodulatory or immunosuppressive the...

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilep...

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilep...

This research investigates the chronic effect of moderate to severe traumatic brain injury on brain white matter integrity, as reflected by diffusion tensor imaging metrics, and the assessment of their correlation to neuropsychological response. Thirteen male participants with traumatic brain injury (8.4 years average post-injury time) were compare...

Background: Imaging studies demonstrated localized anatomical and functional brain changes in headache sufferers. Use of magnetic resonance imaging (MRI) allows the exploration of brain activation in resting state connectivity alterations and how these relate to headaches. How behavioral variables and individual difference factors relate to anatomi...

Purpose The de novo development of PNEA has been described after brain surgery [1]. De novo psychogenic non-epileptic attacks (PNEA) after epilepsy surgery has an estimated incidence of 1.8% to 8.8% [2,3] and is not well studied. This is a European multicenter retrospective cohort study to record patients with de novo psychogenic non-epileptic atta...

Objective To identify disease‐causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods We performed genome‐wide sequencing, homozygosity mapping, and segregation analysis for novel disease‐causing gene discovery. We used circular dichroism to show secondary structure changes...

See Karakaya and Wirth (doi:10.1093/brain/awz273) for a scientific commentary on this article. Neurofascin (NFASC) isoforms are immunoglobulin cell adhesion molecules involved in node of Ranvier assembly. Efthymiou et al. identify biallelic NFASC variants in ten unrelated patients with a neurodevelopmental disorder characterized by variable degrees...

It is well-established that both volume conduction and the choice of recording reference (montage) affect the correlation measures obtained from scalp EEG, both in the time and frequency domains. As a result, a number of correlation measures have been proposed aiming to reduce these effects. In our previous work, we have showed that scalp-EEG based...

Average degree of the functional brain network of Patient 4 using cross-correlation and the bipolar montage, constructed using multivariate phase randomization surrogate data (blue line), and thresholding as in Figure 2 (red line; threshold value: 0.65). The surrogate method yielded more densely connected networks. While the temporal patterns are s...

Clustering coefficient of the functional brain networks of Patient 4 as a function of time, using corrected cross correlation for assessing pairwise correlations. The vertical dashed line indicates seizure onset and the gray bars indicate sleep intervals. In contrast to cross correlation (Figure S3), corrected cross correlation yields the same 24 h...

Lomb-Scargle periodogram of the average degree of the functional brain network of Patient 4 obtained using cross-correlation and bipolar montage, whereby binarization was performed using surrogate data. As suggested in Figure S2, the circadian periodicity is less pronounced compared to networks obtained using thresholding.

Lomb-Scargle periodogram of the average degree of the functional brain network of Patient 6 (psychogenic seizure patient) using cross-correlation, corrected cross-correlation, coherence, imaginary coherence, PLI, and WPLI for common reference (blue line) and bipolar montage (red line). The dotted horizontal lines denote the statistical significance...

Efficiency of the functional brain networks of Patient 4 as a function of time, using cross correlation for assessing pairwise correlations. The vertical dashed line indicates seizure onset and the gray bars indicate sleep intervals. Cross correlation yields an opposite 24 h periodic pattern when using the average reference. However, we can clearly...

Efficiency of the functional brain networks of Patient 4 as a function of time, using corrected cross correlation for assessing pairwise correlations. The vertical dashed line indicates seizure onset and the gray bars indicate sleep intervals. In contrast to cross correlation (Figure S2), corrected cross correlation yields the same 24 h periodic pa...

Clustering coefficient of the functional brain networks of Patient 4 as a function of time using cross correlation for assessing pairwise correlations. The vertical dashed line indicates seizure onset and the gray bars indicate sleep intervals. Cross correlation yields an opposite 24 h periodic pattern when using the average reference, similarly in...

Efficiency of the functional brain networks of Patient 4 as a function of time (broadband signal), using WPLI for assessing pairwise correlations. The vertical dashed line indicates seizure onset and the gray bars indicate sleep intervals. Similarly, to corrected cross correlation (Figures S2, S3), WPLI yields the same 24 h periodic pattern for all...

Clustering coefficient of the functional brain networks of Patient 4 as a function of time (broadband signal), using WPLI for assessing pairwise correlations. The vertical dashed line indicates seizure onset and the gray bars indicate sleep intervals. Similarly to corrected cross correlation (Figures S2, S3), WPLI yields the same 24 h periodic patt...

Lomb-Scargle periodogram of the average degree of the functional brain network of Patient 4 using cross-correlation, corrected cross-correlation, coherence, imaginary coherence, PLI, and WPLI for all montages. The dotted horizontal lines denote the statistical significance level (p = 0.05). The arrows in the inset figures denote the periods around...

Sequencing-based studies have identified novel risk genes for rare, severe epilepsies and revealed a role of rare deleterious variation in common epilepsies. To identify the shared and distinct ultra-rare genetic risk factors for rare and common epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals...

The task of automated epileptic seizure detection and prediction, by using non-invasive measurements such as scalp EEG signals or invasive, intracranial recordings, has been at the heart of epilepsy studies for at least three decades. By far, the most common approach for tackling this problem is to examine short-length recordings around the occurre...

Objective Motor evoked potentials (MEP) using magnetic stimulation are a non-invasive method that assesses the integrity of the central motor pathway. A phase is a part of the motor unit action potential that falls between two baseline crossings. Previous studies suggest that voluntary muscle contraction increases the appearance of MEP polyphasia....

Objective: The aim of this study was to examine the effects of experiential avoidance (EA) on the indirect relationship of chronic pain patients’ illness representations to pain interference, through pain catastrophising Design and main outcome measure: The sample consisted of 162 patients diagnosed with an arthritis-related or a musculoskeletal di...

Objective This paper proposes supervised and unsupervised algorithms for automatic muscle artifact detection and removal from long-term EEG recordings, which combine canonical correlation analysis (CCA) and wavelets with random forests (RF). Methods The proposed algorithms first perform CCA and continuous wavelet transform of the canonical compone...

Treating brain as a complex system is currently among the most popular approaches that are used to understand its function and explain encephalopathies. The networked epileptic brain has already been studied through various neuroimaging modalities based on estimates of functional connectivity. Here, we suggest that additional insights to epileptoge...

Introduction Mean Fractional Anisotropy (FA) along with Longitudinal and Transverse Apparent Diffusion Coefficients (ADC) are the established measures in assessing white matter (WM) integrity in TBI patients. A question is raised whether mean FA performs better than Shannon Entropy (SE) as a measure of discrimination between controls and patients w...

We investigated the correlation of epileptic seizure onset times with long term EEG functional brain network properties. To do so, we constructed binary functional brain networks from long-term, multichannel electroencephalographic data recorded from nine patients with epilepsy. The corresponding network properties were quantified using the average...

Objectives: Characterize the scale and pattern of long-term atrophy in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) in chronic moderate-severe traumatic brain injury (TBI) and its relationship to neurocognitive outcomes. Participants: The TBI group consisted of 17 males with primary diagnosis of moderate-severe closed head...

Objective To assess the effect of duty cycle (DC) increments on seizure frequency (SF) in patients undergoing adjunctive Vagus Nerve Stimulation (VNS) therapy and exhibiting suboptimal responses. To our knowledge, altering only the DC has not been reported. | Methods Thirteen patients with idiopathic or symptomatic epilepsy, with focal and generali...

Background/aims: This study investigated quality of life (QoL) in relation to cognitive-linguistic performance and demographic characteristics (age, education and gender) in a large cohort of cognitively healthy older adults. Method: A total of 578 Greek-Cypriots aged 60-91 years were recruited from the Neurocognitive Study on Aging. Of those, 3...

Background: Sudden unexpected death in epilepsy (SUDEP) affects 0.09-9.3 per 1,000 person-years depending on the population studied and constitutes the most common cause of death in people with epilepsy. The purpose of this study was to analyze epidemiological data of patients with SUDEP, identify possible risk factors in the population of a terti...

AimsThis study explores dementia caregiver burden and depression in the context of social capital and investigates the relationship of caregivers' burden with the perceptions of social capital of a non-caregivers' group.Background Social capital is the range of social contact that gives access to social, emotional and practical support, but little...

Automatic detection and removal of muscle artifacts plays an important role in long-term scalp electroencephalography (EEG) monitoring, and muscle artifact detection algorithms have been intensively investigated. This paper proposes an algorithm for automatic muscle artifacts detection and removal using canonical correlation analysis (CCA) and wave...

We report on a 29-year-old Greek-Cypriot female with a de novo 6.3 Mb distal 10q26.2q26.3 deletion. She had a very mild neurocognitive phenotype with near normal development and intellect. In addition, she had certain distinctive features and postural orthostatic tachycardia. We review the relevant literature and postulate that certain of her featu...

The Electroencephalogram (EEG) is often contaminated by muscle artifacts. EEG is a widely used recording technique for the study of many brain related diseases such as epilepsy. The detection and removal of muscle artifacts from the EEG signal poses a real challenge and is crucial for the reliable interpretation of EEG-based quantitative measures....

Two cases with partial onset epilepsy who developed status epilepticus (SE) on lacosamide (LCM) monotherapy are reported. LCM is an effective adjunctive antiepileptic drug (AED) for partial-onset epilepsy and as infusion in SE. It has also shown efficacy in monotherapy. The reported cases achieved control of seizures with adjunctive LCM treatment a...

It is well established that both volume conduction and the choice of recording reference (montage) affect the connectivity measures obtained from scalp EEG, in the time and frequency domains. A number of measures have been proposed aiming to reduce this influence. Our purpose in this work is to establish the extent to which volume conduction and mo...

Madness and Leadership studies leaders and followers from social, cultural, and biologic perspectives and explores aspects of their personalities that induce them to assume their respective roles. It proposes that leadership and followership are evolutionary adaptations, developed to enhance survival and group cohesion; that leaders possess certain...

Seizure detection and prediction studies using scalp- or intracranial-EEG measurements often focus on short-length recordings around the occurrence of the seizure, normally ranging between several seconds and up to a few minutes before and after the event. The underlying assumption in these studies is the presence of a relatively constant EEG activ...

The clinical differentiation between simple partial epileptic seizures of temporal lobe origin and panic attacks is often difficult on clinical grounds alone, because both conditions are characterized by common symptomatology which includes the feeling of fear, autonomic system dysfunction, disorientation and alternation of the level of consciousne...

Background: ALGEA, the Greek word for suffering, is a joint research effort developed by the Universities of Cyprus and Crete in order to examine the quality of life in patients with a chronic pain condition and develop an intervention program based on ACT. Here, we report some preliminary results that refer to differences in illness perception and...

Introduction: Reports about cervical vestibular evoked myogenic potentials (cVEMPs) in central nervous system lesions are scarce. Our experience with cerebellar lesions is still evolving, with only a few cases published. The purpose of this article is to present our cVEMP findings of 3 cases with cerebellar lesions. Materials and Methods: cVEMPs we...

Background: Numerous studies have reported that caring for a person with dementia is a stressful experience. Nevertheless, quality of life (QoL) measures have commonly focused on patients, while factors that influence caregivers' QoL have not been clearly identified. In order to contribute to the understanding of caregivers' QoL, we explored how Q...