Eleftherios Kavroulakis

Bio: Eleftherios Kavroulakis is an academic researcher from University of Crete. The author has contributed to research in topics: White matter & Resting state fMRI. The author has an hindex of 5, co-authored 17 publications receiving 106 citations. Previous affiliations of Eleftherios Kavroulakis include University of Marburg & RMIT University.

Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus erythematosus.

Abstract: Objectives Cerebral perfusion abnormalities have been reported in systemic lupus erythematosus (SLE) but their value in distinguishing lupus from non-lupus-related neuropsychiatric events remains elusive. We examined whether dynamic susceptibility contrast-enhanced perfusion MRI (DSC-MRI), a minimally invasive and widely available method of cerebral perfusion assessment, may assist neuropsychiatric SLE (NPSLE) diagnosis. Methods In total, 76patients with SLE (37 primary NPSLE, 16 secondary NPSLE, 23 non-NPSLE) and 31 healthy controls underwent conventional MRI (cMRI) and DSC-MRI. Attribution of NPSLE to lupus or not was based on multidisciplinary assessment including cMRI results and response to treatment. Cerebral blood volume and flow were estimated in 18 normal-appearing white and deep grey matter areas. Results The most common manifestations were mood disorder, cognitive disorder and headache. Patients with primary NPSLE had lower cerebral blood flow and volume in several normal-appearing white matter areas compared with controls (P Conclusion Primary NPSLE is characterised by significant hypoperfusion in cerebral white matter that appears normal on cMRI. The combination of DSC-MRI-measured blood flow in the brain semioval centre with conventional MRI may improve NPSLE diagnosis.

Myelin content changes in probable Alzheimer's disease and mild cognitive impairment: Associations with age and severity of neuropsychiatric impairment.

Abstract: Background Existing indices of white matter integrity such as fractional anisotropy and magnetization transfer ratio may not provide optimal specificity to myelin content. In contrast, myelin water fraction (MWF) derived from the multiecho T2 relaxation time technique may serve as a more direct measure of myelin content. Purpose/Hypothesis The goal of the present study was to identify markers of regional demyelination in patients with probable Alzheimer's disease (AD) and mild cognitive impairment (MCI) in relation to age and severity of neuropsychiatric impairment. Population The sample included patients diagnosed with probable AD (n = 25) or MCI (n = 43), and cognitively intact elderly controls (n = 33). Field Strength/Sequence Assessment Long T2, short T2, and MWF values were measured with a 1.5T scanner in periventricular and deep normal-appearing white matter (NAWM), serving as indices of intra/extracellular water content and myelin content. A comprehensive neuropsychological and neuropsychiatric assessment was administered to all participants. Statistical Tests, Results AD patients displayed higher age-adjusted long and short T2 values and reduced MWF values in left temporal/parietal and bilateral periventricular NAWM than controls and MCI patients (P < 0.004; one-way analysis of covariance [ANCOVA] tests). Short T2/MWF values in temporal, frontal, and periventricular NAWM of controls and/or MCI patients were significantly associated with episodic and semantic memory performance and depressive symptomatology (P < 0.004; partial correlation indices). The impact of age on memory performance was significantly (P < 0.01; mediated linear regression analyses) mediated by age-related changes in short T2 and MWF values in these regions. Data Conclusion Age-related demyelination is associated with memory impairment (especially in prodromal dementia states) and symptoms of depression in an anatomically specific manner. Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

Age‐related deep white matter changes in myelin and water content: A T 2 relaxometry study

Abstract: BACKGROUND According to the retrogenesis hypothesis, the rate of age-related changes in white matter (WM) myelin content varies between early myelinating (parietal, occipital) and late myelinating (prefrontal, lateral-posterior temporal) areas. The multiecho spin echo (MESE), PD-to-T2 -weighted sequence provides an index of myelin content (myelin water fraction [MWF]) derived from measurements of myelin water (via the short T2 component [10-50 msec]) and intra- and extracellular water (via the long T2 component [>50-200 msec]). PURPOSE To assess the shape and regional variations in the rate of age-related myelin and water content changes in deep WM regions using the MESE sequence. STUDY TYPE Prospective, cross-sectional. POPULATION In all, 90 healthy adults aged 22-81 years. FIELD STRENGTH/SEQUENCE 1.5T/ T1 w, T2 w, fluid attenuated inversion recovery (FLAIR), MESE sequences. ASSESSMENT Short T2 , long T2 , and MWF values were measured in prefrontal, parietal, lateral-posterior temporal, and occipital normal-appearing WM (NAWM) areas. STATISTICAL TESTS Linear and quadratic effects of age on long T2 and MWF were assessed through regression analyses. Regional variations in the effect of age on long T2 and MWF values at both the individual and group level were examined, using regression and analysis of covariance (ANCOVA) analyses, respectively, controlling for total WM volume. RESULTS The rate of age-related changes in long T2 and MWF was higher for older persons and a significant increase or decline, respectively, was first noted at 60-69 years (P < 0.0033). MWF values peaked earlier (at 30 years of age) and displayed a steeper age-related reduction in prefrontal and lateral-posterior temporal NAWM as compared with the occipital lobes (P < 0.05). The opposite pattern of age-related effect was found for long T2 values. DATA CONCLUSION Significant age-related reductions in myelin content were closely followed by corresponding increases in intra- and extracellular water content. These changes were more pronounced among elderly people and followed an anterior-posterior pattern. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1393-1404.

Quantitative Identification of Functional Connectivity Disturbances in Neuropsychiatric Lupus Based on Resting-State fMRI: A Robust Machine Learning Approach.

Abstract: Neuropsychiatric systemic lupus erythematosus (NPSLE) is an autoimmune entity comprised of heterogenous syndromes affecting both the peripheral and central nervous system. Research on the pathophysiological substrate of NPSLE manifestations, including functional neuroimaging studies, is extremely limited. The present study examined person-specific patterns of whole-brain functional connectivity in NPSLE patients (n = 44) and age-matched healthy control participants (n = 39). Static functional connectivity graphs were calculated comprised of connection strengths between 90 brain regions. These connections were subsequently filtered through rigorous surrogate analysis, a technique borrowed from physics, novel to neuroimaging. Next, global as well as nodal network metrics were estimated for each individual functional brain network and were input to a robust machine learning algorithm consisting of a random forest feature selection and nested cross-validation strategy. The proposed pipeline is data-driven in its entirety, and several tests were performed in order to ensure model robustness. The best-fitting model utilizing nodal graph metrics for 11 brain regions was associated with 73.5% accuracy (74.5% sensitivity and 73% specificity) in discriminating NPSLE from healthy individuals with adequate statistical power. Closer inspection of graph metric values suggested an increased role within the functional brain network in NSPLE (indicated by higher nodal degree, local efficiency, betweenness centrality, or eigenvalue efficiency) as compared to healthy controls for seven brain regions and a reduced role for four areas. These findings corroborate earlier work regarding hemodynamic disturbances in these brain regions in NPSLE. The validity of the results is further supported by significant associations of certain selected graph metrics with accumulated organ damage incurred by lupus, with visuomotor performance and mental flexibility scores obtained independently from NPSLE patients.

Update οn the diagnosis and management of systemic lupus erythematosus

Abstract: Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.

In an early SLE cohort the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria classify non-overlapping groups of patients: use of all three criteria ensures optimal capture for clinical studies while their modification earlier classification and treatment

Abstract: Objectives Classification criteria are biased towards classifying long-standing disease. We compared the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)-2019, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and ACR-1997 criteria in an early (median 48 months) systemic lupus erythematosus (SLE) cohort. Methods Patients diagnosed with SLE (n=690) or control diseases (n=401). Sensitivity, specificity of the criteria and time-to-classification were calculated. Modified classification algorithms were derived from a random 80% and validated in the remaining 20% of the dataset running multiple iterations. Results At last assessment, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 85.7%, 91.3% and 88.6%, with specificities 93.0%, 93.8% and 97.3%, respectively. Both SLICC and EULAR/ACR enabled earlier classification. Only 76.7% of patients with SLE met all three criteria suggesting non-overlapping groups. Notably, unclassified patients had high prevalence of British Isles Lupus Assessment Group moderate/severe manifestations (43.3%–60%) and SLICC/ACR organ damage (30%–50%). At diagnosis, criteria missed 25.6%–30.5% of patients. Modification of EULAR/ACR and SLICC algorithms to include hypocomplementaemia and/or positive anti-phospholipid antibodies as alternative entry criterion, and/or allow classification with fewer clinical criteria from multiple organs, increased their sensitivity at diagnosis (median 82.0% and 86.2%) and overall (93.7% and 97.1%) with modest decreases in specificity. Importantly, patients who were still missed by the modified criteria had lower incidence of major organ involvement, use of immunosuppressive/biological therapies and organ damage. Conclusions The SLICC and EULAR/ACR are more sensitive than the ACR and the EULAR/ACR criteria have superior specificity in early SLE, although patients with significant disease can be missed. Combination and/or modification of the classification algorithms may enhance their sensitivity, allowing earlier classification and treatment of more patients with high disease burden.

Neuromuscular electrical stimulation-promoted plasticity of the human brain.

Abstract: The application of neuromuscular electrical stimulation (NMES) to paretic limbs has demonstrated utility for motor rehabilitation following brain injury. When NMES is delivered to a mixed peripheral nerve, typically both efferent and afferent fibres are recruited. Muscle contractions brought about by the excitation of motor neurons are often used to compensate for disability by assisting actions such as the formation of hand aperture, or by preventing others including foot drop. In this context, exogenous stimulation provides a direct substitute for endogenous neural drive. The goal of the present narrative review is to describe the means through which NMES may also promote sustained adaptations within central motor pathways, leading ultimately to increases in (intrinsic) functional capacity. There is an obvious practical motivation, in that detailed knowledge concerning the mechanisms of adaptation has the potential to inform neurorehabilitation practice. In addition, responses to NMES provide a means of studying CNS plasticity at a systems level in humans. We summarize the fundamental aspects of NMES, focusing on the forms that are employed most commonly in clinical and experimental practice. Specific attention is devoted to adjuvant techniques that further promote adaptive responses to NMES thereby offering the prospect of increased therapeutic potential. The emergent theme is that an association with centrally initiated neural activity, whether this is generated in the context of NMES triggered by efferent drive or via indirect methods such as mental imagery, may in some circumstances promote the physiological changes that can be induced through peripheral electrical stimulation.

Decreased cerebral blood flow in chronic pediatric mild TBI: an MRI perfusion study

Abstract: We evaluated cerebral blood flow (CBF) in chronic pediatric mild traumatic brain injury (mTBI) using arterial spin labeling (ASL) magnetic resonance imaging perfusion. mTBI patients showed lower CBF than controls in bilateral frontotemporal regions, with no between-group cognitive differences. Findings suggest ASL may be useful to assess functional abnormalities in pediatric mTBI.

Is the extrastriate body area part of the dorsal visuomotor stream

Abstract: The extrastriate body area (EBA) processes visual information about body parts, and it is considered one among a series of category-specific perceptual modules distributed across the occipito-temporal cortex. However, recent evidence raises the possibility that EBA might also provide an interface between perception and action, linking the ventral and dorsal streams of visual information processing. Here, we assess anatomical evidence supporting this possibility. We localise EBA in individual subjects using a perceptual task and compare the characteristics of its functional and structural connectivity to those of two perceptual areas, the lateral occipital complex (LOC) and the fusiform body area (FBA), separately for each hemisphere. We apply complementary analyses of resting-state fMRI and diffusion-weighted MRI data in a group of healthy right-handed human subjects (N = 31). Functional and structural connectivity profiles indicate that EBA interacts more strongly with dorsal-stream regions compared to other portions of the occipito-temporal cortex involved in processing body parts (FBA) and object identification (LOC). These findings provide anatomical ground for a revision of the functional role of EBA. Building on a number of recent observations, we suggest that EBA contributes to planning goal-directed actions, possibly by specifying a desired postural configuration to parieto-frontal areas involved in computing movement parameters.