Publications by authors named "Efrosini Papadaki"

33 Publications

T2 Relaxometry Evidence of Microstructural Changes in Diffusely Abnormal White Matter in Relapsing-Remitting Multiple Sclerosis and Clinically Isolated Syndrome: Impact on Visuomotor Performance.

J Magn Reson Imaging 2021 May 6. Epub 2021 May 6.

Institute of Computer Science, Foundation of Research and Technology-Hellas, Heraklion, Greece.

Background: Although diffusely abnormal white matter (DAWM) is commonly seen in multiple sclerosis (MS), it is rarely considered in clinical/imaging studies.

Purpose: To evaluate quantitative markers of microstructural changes in DAWM of patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RR-MS) in relation to MS lesions and degree of neurocognitive impairment, by using a multi-echo spin echo (MESE) Proton Density PD-to-T2 sequence.

Study Type: Prospective, cross-sectional.

Population: Thirty-seven RR-MS patients, 33 CIS patients, and 52 healthy controls.

Field Strength/sequence: 1.5 T/T1-, T2-weighted, fluid-attenuated inversion recovery, and MESE sequences.

Assessment: Long T2, short T2, and myelin water fraction (MWF) values were estimated as indices of intra/extracellular water content and myelin content, respectively, in DAWM, posterior periventricular normal appearing white matter (NAWM), and focal MS lesions, classified according to their signal intensity on T1 sequences. Patients were, also, administered a battery of neuropsychological tests.

Statistical Tests: Comparisons of T2 and MWF values in DAWM, NAWM, and MS lesions were examined, using two-way mixed analyses of variance. Associations of Grooved Pegboard performance with T2 and MWF values in DAWM and NAWM were assessed using Pearson correlation coefficients.

Results: T2 and MWF values of DAWM were intermediate between the respective values of NAWM and T1 hypointense focal lesions, while there was no difference between the respective values of DAWM and T1-isointense lesions. T2 values in DAWM were strongly associated with visuomotor performance in CIS patients.

Data Conclusion: Intra/extracellular water and myelin water content of DAWM are similar to those of T1-isointense lesions and predict visuomotor performance in CIS patients.

Level Of Evidence: 2 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27661DOI Listing
May 2021

Anxiety and depression severity in neuropsychiatric SLE are associated with perfusion and functional connectivity changes of the frontolimbic neural circuit: a resting-state f(unctional) MRI study.

Lupus Sci Med 2021 04;8(1)

Computational Bio-Medicine Laboratory, Institute of Computer Science, Foundation for Research and Technology - Hellas, Heraklion, Crete, Greece

Objective: To examine the hypothesis that perfusion and functional connectivity disturbances in brain areas implicated in emotional processing are linked to emotion-related symptoms in neuropsychiatric SLE (NPSLE).

Methods: Resting-state fMRI (rs-fMRI) was performed and anxiety and/or depression symptoms were assessed in 32 patients with NPSLE and 18 healthy controls (HC). Whole-brain time-shift analysis (TSA) maps, voxel-wise global connectivity (assessed through intrinsic connectivity contrast (ICC)) and within-network connectivity were estimated and submitted to one-sample t-tests. Subgroup differences (high vs low anxiety and high vs low depression symptoms) were assessed using independent-samples t-tests. In the total group, associations between anxiety (controlling for depression) or depression symptoms (controlling for anxiety) and regional TSA or ICC metrics were also assessed.

Results: Elevated anxiety symptoms in patients with NPSLE were distinctly associated with relatively faster haemodynamic response (haemodynamic lead) in the right amygdala, relatively lower intrinsic connectivity of orbital dlPFC, and relatively lower bidirectional connectivity between dlPFC and vmPFC combined with relatively higher bidirectional connectivity between ACC and amygdala. Elevated depression symptoms in patients with NPSLE were distinctly associated with haemodynamic lead in vmPFC regions in both hemispheres (lateral and medial orbitofrontal cortex) combined with relatively lower intrinsic connectivity in the right medial orbitofrontal cortex. These measures failed to account for self-rated, milder depression symptoms in the HC group.

Conclusion: By using rs-fMRI, altered perfusion dynamics and functional connectivity was found in limbic and prefrontal brain regions in patients with NPSLE with severe anxiety and depression symptoms. Although these changes could not be directly attributed to NPSLE pathology, results offer new insights on the pathophysiological substrate of psychoemotional symptomatology in patients with lupus, which may assist its clinical diagnosis and treatment.
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http://dx.doi.org/10.1136/lupus-2020-000473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094334PMC
April 2021

Evidence of Age-Related Hemodynamic and Functional Connectivity Impairment: A Resting State fMRI Study.

Front Neurol 2021 23;12:633500. Epub 2021 Mar 23.

Department of Radiology, School of Medicine, University of Crete, University Hospital of Heraklion, Heraklion, Greece.

To assess age-related changes in intrinsic functional brain connectivity and hemodynamics during adulthood in the context of the retrogenesis hypothesis, which states that the rate of age-related changes is higher in late-myelinating (prefrontal, lateral-posterior temporal) cerebrocortical areas as compared to early myelinating (parietal, occipital) regions. In addition, to examine the dependence of age-related changes upon concurrent subclinical depression symptoms which are common even in healthy aging. Sixty-four healthy adults (28 men) aged 23-79 years (mean 45.0, = 18.8 years) were examined. Resting-state functional MRI (rs-fMRI) time series were used to compute voxel-wise intrinsic connectivity contrast (ICC) maps reflecting the strength of functional connectivity between each voxel and the rest of the brain. We further used Time Shift Analysis (TSA) to estimate voxel-wise hemodynamic lead or lag for each of 22 ROIs from the automated anatomical atlas (AAL). Adjusted for depression symptoms, gender and education level, reduced ICC with age was found primarily in frontal, temporal regions, and putamen, whereas the opposite trend was noted in inferior occipital cortices ( < 0.002). With the same covariates, increased hemodynamic lead with advancing age was found in superior frontal cortex and thalamus, with the opposite trend in inferior occipital cortex ( < 0.002). There was also evidence of reduced coupling between voxel-wise intrinsic connectivity and hemodynamics in the inferior parietal cortex. Age-related intrinsic connectivity reductions and hemodynamic changes were demonstrated in several regions-most of them part of DMN and salience networks-while impaired neurovascular coupling was, also, found in parietal regions. Age-related reductions in intrinsic connectivity were greater in anterior as compared to posterior cortices, in line with implications derived from the retrogenesis hypothesis. These effects were affected by self-reported depression symptoms, which also increased with age.
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http://dx.doi.org/10.3389/fneur.2021.633500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021915PMC
March 2021

MRI and dual-energy CT fusion anatomic imaging in Ru-106 ophthalmic brachytherapy.

Brachytherapy 2021 Mar 27. Epub 2021 Mar 27.

Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

Purpose: Brachytherapy with Ru-106 is widely used for the treatment of intraocular tumors, and its efficacy depends on the accuracy of radioactive plaque placement. Ru-106 plaques are MRI incompatible and create severe metal artifacts on conventional CT scans. Dual-energy CT scans (DECT) may be used to suppress such artifacts. This study examines the possibility of creating fusion images from MRI scans (preoperatively) and DECT scans (with the plaque in place) as a tool for confirming the anatomic accuracy of plaque placement.

Methods And Materials: Six patients with intraocular lesions (5 with choroidal melanoma and 1 with a retinal vasoproliferative lesion) were included. Fusion images of preoperative MRI scans and DECT scans with the plaque in place were created with the Demo version of the ImFusion suite (ImFusion GmbH, Munchen Germany). Clearance margins between the tumor and plaque edge in axial, transverse, and coronal planes as well as the elevation of the posterior plaque edge from the sclera were recorded and associated with the location of the lesion.

Results: Plaque-tumor clearance margins for transverse, sagittal, and coronal planes were higher for anteriorly located lesions (5.13 mm ± 0.11 [5.0-5.2], 5.10 mm ± 0.26 [4.9-5.4], and 5.33 mm ± 0.45 [4.9-5.8] respectively) than for posteriorly located lesions (4.16 mm ± 1.44 [2.5-5.1], 4.13 mm ± 1.42 [2.5-5.1], and 4.2 mm ± 1.21 [2.8-5.0], respectively). The elevation of the posterior plaque edge from the sclera was 0.33 mm ± 0.28 [0-0.5] and 0.63 mm ± 0.60 [0.7-1.2] for posterior and anterior lesions, respectively.

Conclusions: Fusion images between DECT and MRI scans may be used as a tool to confirm the accuracy of Ru-106 plaque placement in relation with the intraocular tumors in ophthalmic brachytherapy.
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http://dx.doi.org/10.1016/j.brachy.2021.01.003DOI Listing
March 2021

Extended perfusion protocol for MS lesion quantification.

Open Med (Wars) 2020 8;15(1):520-530. Epub 2020 Jun 8.

Foundation for Research and Technology - Hellas, Institute of Computer Science, Computational Bio-Medicine Laboratory, N. Plastira 100, Vassilika Vouton, GR-700 13 Heraklion, Crete, Greece.

This study aims to examine a time-extended dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocol and report a comparative study with three different pharmacokinetic (PK) models, for accurate determination of subtle blood-brain barrier (BBB) disruption in patients with multiple sclerosis (MS). This time-extended DCE-MRI perfusion protocol, called Snaps, was applied on 24 active demyelinating lesions of 12 MS patients. Statistical analysis was performed for both protocols through three different PK models. The Snaps protocol achieved triple the window time of perfusion observation by extending the magnetic resonance acquisition time by less than 2 min on average for all patients. In addition, the statistical analysis in terms of adj- goodness of fit demonstrated that the Snaps protocol outperformed the conventional DCE-MRI protocol by detecting 49% more pixels on average. The exclusive pixels identified from the Snaps protocol lie in the low range, potentially reflecting areas with subtle BBB disruption. Finally, the extended Tofts model was found to have the highest fitting accuracy for both analyzed protocols. The previously proposed time-extended DCE protocol, called Snaps, provides additional temporal perfusion information at the expense of a minimal extension of the conventional DCE acquisition time.
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http://dx.doi.org/10.1515/med-2020-0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711864PMC
June 2020

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

Brain Sci 2020 Oct 25;10(11). Epub 2020 Oct 25.

Computational Bio-Medicine Laboratory, Institute of Computer Science, Foundation for Research and Technology-Hellas, 70013 Heraklion, Greece.

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 ( = 44) and age-matched healthy control participants ( = 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.
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http://dx.doi.org/10.3390/brainsci10110777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692139PMC
October 2020

Orbital volume measurements from magnetic resonance images using the techniques of manual planimetry and stereology.

Natl J Maxillofac Surg 2020 Jan-Jun;11(1):20-27. Epub 2020 Jun 18.

Department of Ophthalmology, University Hospital of Heraklion, Heraklion, Crete, Greece.

Introduction: Current volume measurement techniques, for the orbit, are time-consuming and involve complex assessments, which prevents their routine clinical use. In this study, we evaluate the applicability and efficacy of stereology and planimetry in orbital volume measurements using magnetic resonance imaging (MRI).

Materials And Methods: Prospective imaging study using MRI. Sheep craniums and human subjects were evaluated. Water-filling measurements were performed in animal skulls, as the standard validation technique. Planimetry and stereology techniques were used in each dataset. Intraobserver and interobserver reliability testing were applied.

Results: In stereology customization, 1/6 systematic sampling scheme was determined as optimal with acceptable coefficient of error (3.09%) and low measurement time (1.2 min). In sheep craniums, the mean volume measured by water displacement, planimetry, and stereology was 17.81 ± 0.59 cm, 18.53 ± 0.24 cm, and 19.19 ± 0.17 cm, respectively. Planimetric and stereological methods were highly correlated ( = 0.94; ≈ 0.001). The mean difference of the orbital volume using planimetry and stereology was 0.316 ± 0.168 cm. In human subjects, using stereology, the mean orbital volume was found to be 19.62 ± 0.2 cm with a CE of 3.91 ± 0.15%.

Conclusions: The optimized stereological method was found superior to manual planimetry in terms of user effort and time spent. Stereology sampling of 1/6 was successfully applied in human subjects and showed strong correlation with manual planimetry. However, optimized stereological method tended to overestimate the orbital volume by about 1 cc, a considerable limitation to be taken in clinical practice.
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http://dx.doi.org/10.4103/njms.NJMS_9_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518488PMC
June 2020

Cerebral perfusion disturbances in chronic mild traumatic brain injury correlate with psychoemotional outcomes.

Brain Imaging Behav 2020 Jul 30. Epub 2020 Jul 30.

Institute of Computer Science, Foundation of Research and Technology-Hellas, Voutes, Heraklion, Greece.

The study explored associations between hemodynamic changes and psychoemotional status in 32 patients with chronic mild traumatic brain injury (mTBI) and 31 age-matched healthy volunteers. Cerebral blood flow (CBF) and cerebral blood volume (CBV) values were obtained using Dynamic Susceptibility Contrast Magnetic Resonance Imaging in brain regions suspected to play a role in anxiety and depression. Patients were administered self-report measures of anxiety and depression symptoms and underwent neuropsychological assessment. As a group mTBI patients scored significantly below age- and education-adjusted population norms on multiple cognitive domains and reported high rates of anxiety and depression symptomatology. Significantly reduced CBF values were detected in the mTBI group compared to controls in dorsolateral prefrontal areas, putamen, and hippocampus, bilaterally. Within the mTBI group, depressive symptomatology was significantly associated with lower perfusion in the left anterior cingulate gyrus and higher perfusion in the putamen, bilaterally. The latter association was independent from verbal working memory capacity. Moreover, anxiety symptomatology was associated with lower perfusion in the hippocampus (after controlling for verbal episodic memory difficulties). Associations between regional perfusion and psychoemotional scores were specific to depression or anxiety, respectively, and independent of the presence of visible lesions on conventional MRI. Results are discussed in relation to the role of specific limbic and paralimbic regions in the pathogenesis of symptoms of depression and anxiety.
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http://dx.doi.org/10.1007/s11682-020-00343-1DOI Listing
July 2020

Posterior Reversible Encephalopathy Syndrome, Multiple Sclerosis and interferon therapy: Association, co-incidence or convoluted interplay?

Mult Scler Relat Disord 2020 Oct 3;45:102356. Epub 2020 Jul 3.

Department of Neurology, University Hospital of Heraklion, Crete, Greece; Department of Neurology, School of Medicine, University of Crete, Crete, Greece; Department of Neurology & Comprehensive Stroke Center, Henry Ford Hospital, Detroit, MI, United States.

Background: Posterior reversible encephalopathy syndrome (PRES) has only rarely been reported in patients with multiple sclerosis (MS).

Methods: Case report of a patient with relapsing remitting (RR) MS patient on interferon (INF) treatment, who developed posterior fossa PRES.

Results: A 46-year-old male diagnosed with RR MS in 2010 was placed on INF beta-1a therapy. He remained in clinical remission for seven years. He then presented with headache of one month duration and worsening upper extremity ataxia. Cranial MRI revealed two new enhancing cerebellar lesions (one with tumefactive features). Within the next 10 days the patient developed severe holocephalic headache, vomiting, altered consciousness and gait instability. Urgent brain MRI revealed diffuse hyperintense lesions in T2WI and FLAIR sequences in bilateral cerebellar hemispheres and the right thalamus, with marked swelling, increased diffusivity indicative of vasogenic edema and patchy-nodular enhancement, while smaller lesions were also found in posterior temporal, parietal and occipital lobes. Severely elevated blood pressure was noted. Treatment with hypertonic agents, esmolol drip and IV steroids was instituted, resulting in remarkable improvement within the next several days. Repeat MRI showed almost complete resolution of the cerebellar lesions. Interferon beta was discontinued and blood pressure remained well controlled.

Conclusions: Patients with RR MS on IFN beta therapy can develop PRES via the combination of hypertension and endothelial dysfunction by IFN, even when stable on this treatment. Neurologists should be keen to differentiate the appearance of PRES lesions from those of fulminant MS relapse, opportunistic infections or malignancy.
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http://dx.doi.org/10.1016/j.msard.2020.102356DOI Listing
October 2020

Dual-energy CT imaging of orbits during episcleral brachytherapy with Ru-106 plaques: A phantom study on its potential for plaque position verification.

Phys Med 2020 May 8;73:1-7. Epub 2020 Apr 8.

University of Crete, Medical School, Department of Medical Physics, 71003 Heraklion, Crete, Greece.

Purpose: To investigate the potential of dual energy CT (DECT) to suppress metal artifacts and accurately depict episcleral brachytherapy Ru-106 plaques after surgical placement.

Methods: An anthropomorphic phantom simulating the adult head after surgical placement of a Ru-106 plaque was employed. Nine DECT acquisition protocols for orbital imaging were applied. Monochromatic 140 keV images were generated using iterative reconstruction and an available metal artifact reduction algorithm. Generated image datasets were graded by four observers regarding the ability to accurate demarcate the Ru-106 plaque. Objective image quality and visual grading analysis (VGA) was performed to compare different acquisition protocols. The DECT imaging protocol which allowed accurate plaque demarcation at minimum exposure was identified. The eye-lens dose from orbital DECT, with and without the use of radioprotective bismuth eye-shields, was determined using Monte Carlo methods.

Results: All DECT acquisition protocols were judged to allow clear demarcation of the plaque borders despite some moderate streaking/shading artifacts. The differences between mean observers' VGA scores for the 9 DECT imaging protocols were not statistically significant (p > 0.05). The eye-lens dose from the proposed low-exposure DECT protocol was found to be 20.1 and 22.8 mGy for the treated and the healthy eye, respectively. Bismuth shielding was found to accomplish >40% reduction in eye-lens dose without inducing shielding-related artifacts that obscure plaque delineation.

Conclusions: DECT imaging of orbits after Ru-106 plaque positioning for ocular brachytherapy was found to allow artifact-free delineation of plaque margins at relatively low patient exposure, providing the potential for post-surgery plaque position verification.
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http://dx.doi.org/10.1016/j.ejmp.2020.03.020DOI Listing
May 2020

Quantification of effective orbital volume and its association with axial length of the eye. A 3D-MRI study.

Rom J Ophthalmol 2019 Oct-Dec;63(4):360-366

Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

To measure the effective orbital volume (EOV) from magnetic resonance images, and investigate its relationship with axial length (AL) in those parameters. Cross-sectional, 3D-MRI study. 54 eyes of 54 patients (25 males) were included in this work. Patient weight, height and head circumference were also measured. Orbital and eyeball volumes were calculated after image segmentation. The difference between those values volume was assessed, estimating the EOV for each eye. Mean eyeball volume was 7.83 ± 2.27 mm3, mean orbital volume 26.81 ± 0.59 mm3 and EOV 21.64 ± 0.19 mm3. The orbital volume was significantly higher in the male group (Wilcoxon signed-rank tests Z=-1.51, p<0.001; Z=-3.57, p<0.001 respectively). EOV was significantly correlated with AL in both males (r=-0.71, p<0.001) and females (r=-0.73, p<0.001), whereas it was also significantly associated with patient height (r=0.261, p=0.03). Associations between EOV and other age, axial and anthropometric characteristics were not statistically significant. Findings of this study could be of valuable importance in various clinical situations in which quantification of orbital volume is needed, such as orbital decompression in Graves' orbitopathy, volume restoration in orbital fractures or other orbital reconstructive surgery. In surgical interventions, clinical relationships should be carefully taken under consideration to avoid iatrogenic injury. EOV = Effective orbital volume, AL = Axial length, ROI = Region of interest.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943286PMC
March 2020

Switching from fingolimod to alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis: Α case series.

Mult Scler Relat Disord 2020 Feb 11;38:101517. Epub 2019 Nov 11.

Laboratory of Clinical Neurophysiology, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi 1, Thessaloniki, 54636, Greece. Electronic address:

Background: The management of "aggressive" and "highly-active" relapsing-remitting multiple sclerosis remains problematic. Although a number of highly efficacious agents are currently available, the optimal timing of their use and the balancing between efficacy and immediate and long-term consequences are still a matter of conjecture.

Methods: We describe the clinical, radiological and immunological profile of three multiple sclerosis patients with persistent clinical and radiological disease activity under fingolimod treatment. After fingolimod cessation patients demonstrated severe disease exacerbation and were successfully treated with alemtuzumab.

Results: All patients experienced significant improvement after the administration of alemtuzumab and achieved no evidence of disease activity status that persisted after a median of 19 months of follow-up (range: 17-25 months). Confirmed disability improvement was achieved in all cases. Quantitative MRI data demonstrated a reduction of the T2 lesion load in 2 out of 3 patients and complete abrogation of inflammatory activity in all patients after the administration of alemtuzumab. Α patient presented a previously unreported, persistent lymphocytosis after alemtuzumab administration, that was not associated with infectious, lymphoproliferative or autoimmune diseases and had no apparent clinical implications.

Conclusions: Alemtuzumab appears to be an effective and safe short-term therapeutic option both as a rescue therapy for the disease flare-up associated with fingolimod withdrawal, as well as for the reversal of the deteriorating course observed in patients who fail treatment with fingolimod.
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http://dx.doi.org/10.1016/j.msard.2019.101517DOI Listing
February 2020

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

J Magn Reson Imaging 2019 11 12;50(5):1393-1404. Epub 2019 Mar 12.

Institute of Computer Science, Foundation of Research and Technology, Heraklion, Greece.

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-T -weighted sequence provides an index of myelin content (myelin water fraction [MWF]) derived from measurements of myelin water (via the short T component [10-50 msec]) and intra- and extracellular water (via the long T 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/ T w, T w, fluid attenuated inversion recovery (FLAIR), MESE sequences.

Assessment: Short T , long T , 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 T and MWF were assessed through regression analyses. Regional variations in the effect of age on long T 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 T 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 T 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.
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http://dx.doi.org/10.1002/jmri.26707DOI Listing
November 2019

Estimation of Morphological Characteristics in Asymmetrical Myopic Posterior Staphyloma using Optical Coherence Tomography.

Middle East Afr J Ophthalmol 2018 Jul-Dec;25(3-4):131-136

Department of Ophthalmology, University Hospital of Heraklion, Heraklion, Crete, Greece.

Purpose: Posterior staphyloma is an ocular complication associated with high myopia and reflects degenerative changes on the sclera. Its morphology is associated with chorioretinal atrophy and myopic maculopathy. The purpose of this study was to validate the efficacy of optical coherence tomography (OCT) in providing a simple estimation of the staphyloma pattern.

Materials And Methods: Observational case-series study of high myopic patients with posterior staphylomas. Patients were examined using the star scan pattern OCT in different radial planes. Three-dimensional (3D) magnetic resonance tomography was also performed to visualize the anatomical characteristics of the posterior pole. 3D-segmentation and curvature analysis were also performed.

Results: Eight patients were totally enrolled in this pilot study. Our study pool consisted of 2 wide macular staphylomas, 2 narrow macular staphylomas, and 4 barrel-shaped staphylomas. Our preliminary results revealed that patients displayed mirror-image distortion in the steeper staphyloma axis. In the barrel-shaped subtype, no image distortion was displayed in any plane.

Conclusion: We estimated the axis of the smaller base curvature by noting the distortion pattern in the different radial axis. The recognition of pathologic axial myopia is important since there is a risk of permanent vision loss from vision to threatening sequelae.
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http://dx.doi.org/10.4103/meajo.MEAJO_45_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348944PMC
April 2019

Investigating the Role of Model-Based and Model-Free Imaging Biomarkers as Early Predictors of Neoadjuvant Breast Cancer Therapy Outcome.

IEEE J Biomed Health Inform 2019 09 31;23(5):1834-1843. Epub 2019 Jan 31.

Imaging biomarkers (IBs) play a critical role in the clinical management of breast cancer (BRCA) patients throughout the cancer continuum for screening, diagnosis, and therapy assessment, especially in the neoadjuvant setting. However, certain model-based IBs suffer from significant variability due to the complex workflows involved in their computation, whereas model-free IBs have not been properly studied regarding clinical outcome. In this study, IBs from 35 BRCA patients who received neoadjuvant chemotherapy (NAC) were extracted from dynamic contrast-enhanced MR imaging (DCE-MRI) data with two different approaches, a model-free approach based on pattern recognition (PR), and a model-based one using pharmacokinetic compartmental modeling. Our analysis found that both model-free and model-based biomarkers can predict pathological complete response (pCR) after the first cycle of NAC. Overall, eight biomarkers predicted the treatment response after the first cycle of NAC, with statistical significance (p-value < 0.05), and three at the baseline. The best pCR predictors at first follow-up, achieving high AUC and sensitivity and specificity more than 50%, were the hypoxic component with threshold 2 (AUC 90.4%) from the PR method, and the median value of k (AUC 73.4%) from the model-based approach. Moreover, the 80 percentile of v achieved the highest pCR prediction at baseline with AUC 78.5%. The results suggest that the model-free DCE-MRI IBs could be a more robust alternative to complex, model-based ones such as k and favor the hypothesis that the PR image-derived hypoxic image component captures actual tumor hypoxia information able to predict BRCA NAC outcome.
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http://dx.doi.org/10.1109/JBHI.2019.2895459DOI Listing
September 2019

Ex vivo orbital volumetry using stereology and CT imaging: A comparison with manual planimetry.

Eur Radiol 2019 Mar 22;29(3):1365-1374. Epub 2018 Aug 22.

Department of Ophthalmology, University Hospital of Heraklion, 71110, Stavrakia, Heraklion, Crete, Greece.

Objectives: To evaluate the applicability of stereology and planimetry in orbital volume measurements using computed tomography (CT) and to compare the results between the two measurements.

Methods: Experimental study using sheep craniums for CT imaging. Water filling measurements were performed, as the validation technique. Quantification techniques were also evaluated in five human subjects. To examine the proportion of agreement among measurements, we tested intra- and inter-observer agreement.

Results: For stereology customization, a 1/8 systematic sampling scheme was considered as optimal; this resulted in a low coefficient of error (2.59 %) and low measurement time (1.9 mins). In sheep craniums, mean volume measured by water displacement, planimetry and stereology was 17.81 ± 0.59 cm, 17.87 ± 0.68 cm and 17.54 ± 0.49 cm, respectively. Total volumes, obtained by stereology, were highly correlated with the water-filling method (r=0.893; p = 0.001) and a paired t-test showed significant difference between methods (t=3.047; p = 0.014). Planimetry results displayed a high correlation with the water-filling method (r=0.957; p ≈ 0.001) but no statistically significant difference was found (p = 0.154). Mean difference using planimetry and stereology was 0.332 ± 0.322 cm. In human subjects, using stereology, the estimated volume ranged between 18.57 cm and 19.27 cm, and the mean orbital volume was 19.05 ± 0.50 cm with CE=3.75 ± 0.16 %. Mean measure time was 2.1 ± 0.1 mins.

Conclusions: Stereological measurements were superior to manual planimetry in terms of user effort and time spent. Stereology sampling of 1/8 was successfully applied in human subjects and yielded a strong correlation with manual planimetry.

Key Points: • Stereology can be applied to measure the orbital volume using computed tomography. • Stereological measurements display high correlation with gold standard planimetry and combine low coefficient of error (2.59%) with low measurement time (1.9 min). • Stereology is superior in terms of user effort and time spent.
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http://dx.doi.org/10.1007/s00330-018-5691-9DOI Listing
March 2019

Multinodular and vacuolating neuronal tumor incidentally discovered in a young man: Conventional and advanced MRI features.

Radiol Case Rep 2018 Oct 6;13(5):960-964. Epub 2018 Aug 6.

Department of Radiology, School of Medicine, University of Crete, Heraklion, Crete, Greece.

Multinodular and Vacuolating Neuronal Tumor (MVNT) has been included in the most recent (2016) as unique cytoarchitectural pattern of gangliocytoma. We present a case of a MVNT incidentally discovered in a 22-year old male, who presented with seizures after a head injury. Conventional MRI revealed a left parietal lesion with characteristic tiny, coalescent, well-defined, non-enhancing nodules, located in the juxtacortical white matter with partial involvement of an otherwise normal adjacent cortex and characterized by slight relative increase of the cerebral blood volume (CBV), compared to the contralateral white matter (lesional CBV/contralateral CBV = 1.112) and mild increase of choline and reduction of NAA (lesional choline/creatine ratio =1.36 and choline/NAA ratio=0.77, compared to 0.87 and 0.51, respectively). The patient fully responded to treatment with phenytoin and a follow-up MRI, six months later, showed the lesion without any substantial difference.
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http://dx.doi.org/10.1016/j.radcr.2018.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083006PMC
October 2018

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

Ann Rheum Dis 2018 03 19;77(3):441-448. Epub 2017 Dec 19.

Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodestrian University of Athens, Athens, Greece.

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<0.0001) and lower cerebral blood flow in the semioval centre bilaterally, compared with non-NPSLE and patients with secondary NPSLE (P<0.001). A cut-off for cerebral blood flow of 0.77 in the left semioval centre discriminated primary NPSLE from non-NPSLE/secondary NPSLE with 80% sensitivity and 67%-69% specificity. Blood flow values in the left semioval centre showed substantially higher sensitivity than cMRI (81% vs 19%-24%) for diagnosing primary NPSLE with the combination of the two modalities yielding 94%-100% specificity in discriminating primary from secondary NPSLE.

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.
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http://dx.doi.org/10.1136/annrheumdis-2017-212285DOI Listing
March 2018

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

J Magn Reson Imaging 2018 05 31;47(5):1359-1372. Epub 2017 Aug 31.

Department of Radiology, School of Medicine, University of Crete, Heraklion, Crete, Greece.

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 T 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 T , short T , 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 T 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 T /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 T 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 2018;47:1359-1372.
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http://dx.doi.org/10.1002/jmri.25849DOI Listing
May 2018

Mechanical optic neuropathy in high myopia.

Clin Exp Optom 2018 07 14;101(4):613-615. Epub 2017 May 14.

Department of Ophthalmology, University Hospital of Heraklion, Heraklion, Greece.

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http://dx.doi.org/10.1111/cxo.12548DOI Listing
July 2018

Neural foundations of overt and covert actions.

Neuroimage 2017 05 18;152:482-496. Epub 2017 Mar 18.

Institute of Applied and Computational Mathematics, Foundation for Research and Technology Hellas, Iraklion, Crete, Greece; Faculty of Medicine, School of Health Sciences, University of Crete, Iraklion, Crete, Greece. Electronic address:

We used fMRI to assess the human brain areas activated for execution, observation and 1st person motor imagery of a visually guided tracing task with the index finger. Voxel-level conjunction analysis revealed several cortical areas activated in common across all three motor conditions, namely, the upper limb representation of the primary motor and somatosensory cortices, the dorsal and ventral premotor, the superior and inferior parietal cortices as well as the posterior part of the superior and middle temporal gyrus including the temporo-parietal junction (TPj) and the extrastriate body area (EBA). Functional connectivity analyses corroborated the notion that a common sensory-motor fronto-parieto-temporal cortical network is engaged for execution, observation, and imagination of the very same action. Taken together these findings are consistent with the more parsimonious account of motor cognition provided by the mental simulation theory rather than the recently revised mirror neuron view Action imagination and observation were each associated with several additional functional connections, which may serve the distinction between overt action and its covert counterparts, and the attribution of action to the correct agent. For example, the central position of the right middle and inferior frontal gyrus in functional connectivity during motor imagery may reflect the suppression of movements during mere imagination of action, and may contribute to the distinction between 'imagined' and 'real' action. Also, the central role of the right EBA in observation, assessed by functional connectivity analysis, may be related to the attribution of action to the 'external agent' as opposed to the 'self'.
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http://dx.doi.org/10.1016/j.neuroimage.2017.03.036DOI Listing
May 2017

Cognitive event-related potentials in multiple sclerosis: Correlation with MRI and neuropsychological findings.

Mult Scler Relat Disord 2016 Nov 27;10:192-197. Epub 2016 Oct 27.

3rd Department of Neurology, Aristotle University of Thessaloniki, "G Papanikolaou" General Hospital, Exohi, Greece.

Background: Cognitive event-related potentials (ERPs) have been previously correlated with T2 lesion load (Τ2LL) in patients with multiple sclerosis (MS). It is currently unknown, however, whether ERPs also correlate with brain atrophy or the presence of T1 hypointense lesions ("black holes") which reflect tissue destruction and axonal loss. The primary aim of the current study is to explore the effect of neuroradiological parameters such as brain atrophy, T1 and T2 lesion load on auditory ERPs in MS patients. In addition, we correlated cognitive impairment with neurophysiological (ERP) and neuroradiological (MRI) variables and investigated whether a combination of ERP and MRI parameters is capable of distinguishing patients suffering from secondary progressive (SP), primary progressive (PP) and relapsing-remitting (RR) MS.

Materials And Methods: The study sample consisted of fifty nine MS patients (mean age±SD: 37.82±1.38 years; average disease duration: 6.76±5.3 years) and twenty six age-matched controls (mean age±SD: 41.42±15.39 years). The patients' EDSS and NRS scores were 3.77±2.14 (range: 1-7.5) and 75.88±11.99 (range: 42-94) respectively. ERPs were recorded using the auditory "odd-ball" paradigm. T1 and T2 lesions were automatically segmented using an edge-finding tool and total lesion volumes were calculated. MRI measures of brain atrophy included third ventricle width (THIRDVW) and the ratio of mid-sagittal corpus callosum area to the mid-sagittal intracranial skull surface area (CC/MISS). Statistical analysis was performed using multiple regression, principal component (PCA) and discriminant analysis.

Results: T1 lesion load emerged as the most significant predictor of P300 and N200 latency. The rest of the endogenous ERPs parameters (P300 amplitude, N200 amplitude) were not significantly correlated with the MRI variables. PCA of pooled neuroradiological and neurophysiological markers suggested that four components accounted for 64.6% of the total variability. Discriminant analysis based on ERP & MRI markers classified correctly 79.63% of patients in RR, PP and SP subgroups.

Conclusion: T1 lesion load is the most significant MRI correlate of auditory ERPs in MS patients. Importantly, ERPs in combination with MRI variables can be usefully employed for distinguishing patients with different subtypes of MS.
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http://dx.doi.org/10.1016/j.msard.2016.10.006DOI Listing
November 2016

High resolution MR eye protocol optimization: Comparison between 3D-CISS, 3D-PSIF and 3D-VIBE sequences.

Phys Med 2015 Nov 11;31(7):774-80. Epub 2015 Apr 11.

Department of Medical Physics, University of Crete, Heraklion, Crete, Greece.

Purpose: The purpose of this study was to compare selected MRI pulse sequences and to evaluate their utility for depicting specific anatomic regions in the eye.

Methods: A High-Resolution (HR) 0.08 × 0.08 × 0.60 mm(3) MRI protocol was developed on a 1.5-T clinical system and applied in the left eye of an albino rabbit, utilizing a small field of view surface coil. The comprehensive MRI protocol consisted of two 3D (T2/T1)w sequences (3D-PSIF and 3D-CISS), and one 3D T1w sequence (3D-VIBE). The T1w 3D-VIBE sequence was acquired, before and after intravenous injection of 0.2 mmol/kgr gadolinium-DTPA. Signal-to-Noise Ratios (SNR) and Contrast-to-Noise Ratios (CNR) amongst specific eye anatomical areas were calculated for each sequence. The presence of artifacts was rated subjectively utilizing a 5 point scale.

Results: 3D-PSIF and 3D-CISS provide better delineation and visualization of the eye as compared with 3D-VIBE sequences. 3D-CISS images present the highest SNR and revealed better discrimination of the ocular surrounding tissues; its basic drawback though is related to ghost artifacts appearing in the anterior chamber and resulting in the lowest image quality. In post-contrast imaging, the T1w 3D-VIBE sequence provided the best overall image quality. Moreover, 3D (T2/T1)w sequences can provide good anatomic depiction of the eye segments. Agreement between the two independent readers was good.

Conclusions: Optimization of a comprehensive MR eye imaging protocol is achieved. A higher SNR, a better spatial resolution and a reduction of the total scan time were obtained, thus making clinical MRI systems more reliable in eye imaging.
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http://dx.doi.org/10.1016/j.ejmp.2015.03.009DOI Listing
November 2015

A case of herpes simplex-associated encephalitis after brain irradiation for lung cancer metastases.

Anticancer Res 2014 Aug;34(8):4411-4

Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece

Background: Encephalitis caused by Herpes Simplex Virus-1 is a devastating disease with high mortality and disability rates despite adequate treatment. No clear risk factors have been identified although iatrogenic immunosuppression has been suggested, among others.

Case Report: A 59-year-old male smoker was diagnosed with metastatic lung adenocarcinoma and was treated with brain and spinal irradiation. Ten days after the completion of radiotherapy and before initiating platinum-based front-line chemotherapy, he developed low grade fever and personality change. Over the next few days, high fever and refractory seizures developed and the patient was diagnosed with Herpes simplex-associated encephalitis after detection of viral DNA in the cerebrospinal fluid via polymerase chain reaction. Despite treatment with acyclovir, the patient remained comatose and died three months after the initial presentation.

Conclusion: This case illustrates a possible association between brain irradiation and increased risk for Herpes simplex-associated encephalitis. However, the underlying mechanisms have not been elucidated.
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August 2014

Regional MRI perfusion measures predict motor/executive function in patients with clinically isolated syndrome.

Behav Neurol 2014 23;2014:252419. Epub 2014 Jan 23.

Department of Neurology, Faculty of Medicine, University of Crete, University Hospital, Heraklion, 71110 Stavrakia, Greece.

Background: Patients with clinically isolated syndrome (CIS) demonstrate brain hemodynamic changes and also suffer from difficulties in processing speed, memory, and executive functions.

Objective: To explore whether brain hemodynamic disturbances in CIS patients correlate with executive functions.

Methods: Thirty CIS patients and forty-three healthy subjects, matched for age, gender, education level, and FSIQ, were administered tests of visuomotor learning and set shifting ability. Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) values were estimated in normal-appearing white matter (NAWM) and normal-appearing deep gray Matter (NADGM) structures, using a perfusion MRI technique.

Results: CIS patients showed significantly elevated reaction time (RT) on both tasks, while their CBV and MTT values were globally increased, probably due to inflammatory vasodilation. Significantly, positive correlation coefficients were found between error rates on the inhibition condition of the visuomotor learning task and CBV values in occipital, periventricular NAWM and both thalami. On the set shifting condition of the respective task significant, positive associations were found between error rates and CBV values in the semioval center and periventricular NAWM bilaterally.

Conclusion: Impaired executive function in CIS patients correlated positively with elevated regional CBV values thought to reflect inflammatory processes.
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http://dx.doi.org/10.1155/2014/252419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006593PMC
December 2014

Coexistence of systemic lupus erythematosus and multiple sclerosis: prevalence, clinical characteristics, and natural history.

Semin Arthritis Rheum 2014 Jun 13;43(6):751-8. Epub 2013 Nov 13.

Department of Rheumatology, Clinical Immunology and Allergy, University Hospital of Heraklion, Heraklion, Greece; Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology-Hellas, Voutes, Heraklion, Greece; Biomedical Research Foundation of the Academy of Athens, Athens, Greece. Electronic address:

Objectives: The coexistence of systemic lupus erythematosus (SLE) and multiple sclerosis (MS) in the same individual has rarely been described. Our objective was to report on the prevalence, clinical characteristics, and prognosis of cases fulfilling the criteria for both SLE and MS.

Methods: We utilized existing patient cohorts from the Departments of Rheumatology and Neurology, University of Crete, and screened patients diagnosed with either SLE (n = 728) or MS (n = 819) for features of both diseases. The clinical, laboratory, and neuroimaging findings were assessed.

Results: We identified nine patients who fulfilled the diagnostic criteria for both SLE and MS, corresponding to a prevalence rate of 1.0-1.2% in each cohort. All patients were women, with an average age at SLE diagnosis of 42.1 years (range: 34-56 years). The diagnosis of SLE preceded the development of MS in five patients, with a time lag ≤ 5 years in four of them. Initial presentation of MS included spinal symptoms in seven patients. All patients had features of mild SLE with predominantly cutaneous, mucosal, and musculoskeletal manifestations. Accordingly, therapeutic decisions were mainly guided by the severity of the neurological syndrome. During the median follow-up of 4 years (range: 1-10 years), three patients remained stable and the remaining experienced gradual deterioration in their neurological status. SLE remained quiescent in all patients while on standard immunomodulatory MS therapy.

Conclusions: Occurrence of both diseases in the same individual is rare, corroborating data that suggest distinct molecular signatures. SLE and MS coexistence was not associated with a severe phenotype for either entity.
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http://dx.doi.org/10.1016/j.semarthrit.2013.11.007DOI Listing
June 2014

White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome.

Magn Reson Med 2012 Dec 24;68(6):1932-42. Epub 2012 Feb 24.

Medical Imaging, University Hospital of Heraklion, Crete, Greece.

The dynamic susceptibility contrast magnetic resonance imaging perfusion technique was used to investigate possible hemodynamic changes in normal appearing white matter and deep gray matter (DGM) of 30 patients with clinically isolated syndrome (CIS) and 30 patients with relapsing-remitting multiple sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood volume, cerebral blood flow (CBF), and mean transit time values were estimated. Normalization was achieved for each subject with respect to average values of CBF and mean transit time of the hippocampi's dentate gyrus. Measurements concerned three regions of normal white matter of normal volunteers, normal appearing white matter of CIS and patients with relapsing-remitting multiple sclerosis, and DGM regions, bilaterally. All measured normal appearing white matter and DGM regions of the patients with CIS had significantly higher cerebral blood volume and mean transit time values, while averaged DGM regions had significantly lower CBF values, compared to those of normal volunteers (P < 0.001). Regarding patients with relapsing-remitting multiple sclerosis, all measured normal appearing white matter and DGM regions showed lower CBF values than those of normal volunteers and lower cerebral blood volume and CBF values compared to patients with CIS (P < 0.001). These data provide strong evidence that hemodynamic changes--affecting both white and DGM--may occur even at the earliest stage of multiple sclerosis, with CIS patients being significantly different than relapsing-remitting multiple sclerosis patients.
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http://dx.doi.org/10.1002/mrm.24194DOI Listing
December 2012

A comparison of acute hemorrhagic stroke outcomes in 2 populations: the Crete-Boston study.

Stroke 2011 Dec 20;42(12):3640-2. Epub 2011 Oct 20.

Neurology Department, University Hospital of Heraklion, Voutes, 71021, Heraklion, Crete, Greece.

Background And Purpose: Although corticosteroid use in acute hemorrhagic stroke is not widely adopted, management with intravenous dexamethasone has been standard of care at the University Hospital of Heraklion, Crete with observed outcomes superior to those reported in the literature. To explore this further, we conducted a retrospective, multivariable-adjusted 2-center study.

Methods: We studied 391 acute hemorrhagic stroke cases admitted to the University Hospital of Heraklion, Crete between January 1997 and July 2010 and compared them with 510 acute hemorrhagic stroke cases admitted to Massachusetts General Hospital, Boston, from January 2003 to September 2009. Of the Cretan cases, 340 received a tapering scheme of intravenous dexamethasone, starting with 16 to 32 mg/day, whereas the Boston patients were managed without steroids.

Results: The 2 cohorts had comparable demographics and stroke severity on admission, although anticoagulation was more frequent in Boston. The in-hospital mortality was significantly lower on Crete (23.8%, n=340) than in Boston (38.0%, n=510; P<0.001) as was the 30-day mortality (Crete: 25.4%, n=307; Boston: 39.4%, n=510; P<0.001). Exclusion of patients on anticoagulants showed even greater differences (30-day mortality: Crete 20.8%; n=259; Boston 37.0%; n=359; P<0.001). The improved survival on Crete was observed 3 days after initiation of intravenous dexamethasone and was pronounced for deep-seated hemorrhages. After adjusting for acute hemorrhagic stroke volume/location, Glasgow Coma Scale, hypertension, diabetes mellitus, smoking, coronary artery disease and statin, antiplatelet, and anticoagulant use, intravenous dexamethasone treatment was associated with better functional outcomes and significantly lower risk of death at 30 days (OR, 0.357; 95% CI, 0.174-0.732).

Conclusions: This study suggests that intravenous dexamethasone improves outcome in acute hemorrhagic stroke and supports a randomized clinical trial using this approach.
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http://dx.doi.org/10.1161/STROKEAHA.111.632174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226858PMC
December 2011

Effective orbital volume and eyeball position: an MRI study.

Orbit 2010 Oct 2;29(5):244-9. Epub 2010 Sep 2.

Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

Purpose: Previous studies have examined factors affecting the position of the eyeball to the orbit. This study examined the role of effective orbital volume (EOV), defined as the difference between orbital and eyeball volume, as a determinant of eyeball position, using MRI scans.

Methods: Forty-six patients were recruited from the Department of Ophthalmology of the University Hospital of Heraklion, Crete Greece. Patients with a history of orbital disease were excluded. Distances between eyeball poles and orbital landmarks were measured in T1 weighted transverse, sagittal and coronal orbital images. The protrusion of the eyeball in the sagittal and transverse planes was recorded. The volume of the eyeball and bony orbit, the EOV, the volume of the extraocular muscles as well as clinical information (age, gender, Hertel exophthalmometry) were also recorded.

Results: EOV was significantly associated with orbital volume but not with eyeball volume. EOV was also significantly associated with transverse and sagittal globe protrusions. Females displayed significantly lower orbital and eyeball volumes as well as EOV than males but higher transverse globe protrusion than males.

Conclusions: Variations in EOV are associated with orbital volume rather than with eyeball volume. EOV is associated with globe protrusion and may be taken into account in the planning of various procedures, including orbital decompression, treatment of enophthalmos or the size of orbital implants following enucleation.
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http://dx.doi.org/10.3109/01676831003664319DOI Listing
October 2010