Konstantinos Spengos

Eginition Hospital Athens, Athínai, Attica, Greece

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Publications (103)331.46 Total impact

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    ABSTRACT: Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by mutations of the NOTCH3 gene, which result in degeneration of vascular smooth muscle cells, arteriolar stenosis, and impaired cerebral blood flow. For clinicians this is the commonest hereditary adult-onset condition causing stroke and vascular dementia at middle age. Atypical phenotypes have been recognized, and the disease is probably underdiagnosed in the wider stroke population. Coexistence of autoimmunity is atypical and has been described only in occasional patients. Methods: Three members of a Greek family from the island of Lesvos of North East Greece were evaluated. The patients come from a four-generation family in which there were at least seven members with clinical data suggestive of CADASIL. We describe here the clinical, imaging and biochemical findings in this family with R169C mutation at exon 4 and presenting additional clinical and biochemical findings suggestive of autoimmune disorder. DNA was extracted from whole blood using standard procedures for sequencing. Results: Three affected members of this family carried the R169C. In a phenotypic analysis of affected individuals from four generations with CADASIL, the disease was characterized by migraine attacks, recurrent subcortical infarcts, and cognitive decline with typical anterior temporal lobe white matter lesions. At least 3 mutation carriers from two generations had increased antinuclear antibody (ANA) titers and various combinations of rash, joint pains, photosensitivity, and renal involvement. Conclusion: This is a rare description of the coexistence of autoimmunity in CADASIL patients with possible worsening clinical effects. The study extends the spectrum of atypical presentation of CADASIL. The coexistence of autoimmunity does not necessarily exclude CADASIL, but may cause an additional diagnostic and therapeutic challenge. This autoimmune disorder may have increased the severity of the disease and, additionally, may be related to the pathogenetic mechanisms of CADASIL. It is possible that the NOTCH3 mutation alone is not enough to trigger autoimmunity since, in the case of our family, the R169C mutation has already been described in other families with no evidence of coexistent autoimmunity. Other genetic or environmental factors or interactions and/or common pathways between the vascular and immune systems are probably co-operating. Further, prospective studies are needed to clarify the prevalence and types of autoimmune disorders present in CADASIL families. © 2014 S. Karger AG, Basel.
    Cerebrovascular diseases (Basel, Switzerland). 11/2014; 38(4):302-307.
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    ABSTRACT: A new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced, but no such population has been described yet. Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospective ischemic stroke registry using the proposed diagnostic criteria.
    11/2014;
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    ABSTRACT: Muscle Lim Protein (MLP) has emerged as a critical regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, while aberrant expression patterns are reported in human cardiac and skeletal muscle diseases. Increasing evidence suggests that MLP has an important role in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles has not been delineated. We report the discovery of an alternative splice variant of MLP, designated as MLP-b, showing distinct expression in neuromuscular disease and direct roles in actin dynamics and muscle differentiation. This novel isoform originates by alternative splicing of exons 3 and 4. At the protein level, it contains the N-terminus first half LIM domain of MLP and a unique sequence of 22 amino acids. Physiologically it is expressed during early differentiation, whereas its overexpression reduces C2C12 differentiation and myotube formation. This may be mediated through its inhibition of MLP/CFL2-mediated F-actin dynamics. In differentiated striated muscles, MLP-b localizes to the sarcomeres and binds directly to Z-disc components including α-actinin, T-cap and MLP. Our findings unveil a novel player in muscle physiology and pathophysiology that is implicated in myogenesis as a negative regulator of myotube formation, and in differentiated striated muscles as a contributor to sarcomeric integrity. This article is protected by copyright. All rights reserved.
    FEBS Journal 05/2014; · 4.25 Impact Factor
  • Georgios Koutsis, Gerasimos Siasos, Konstantinos Spengos
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    ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs approximately 22 nucleotides in length that play a pivotal role in post-transcriptional gene regulation by binding to complementary sites in the 3'-untranslated region of messenger RNAs. In the past decade, their role in several human diseases, from cancer to cardiovascular disease, has been established by a wealth of evidence. Stroke is responsible for 10% of deaths worldwide and is one of the leading causes of disability. MiRNAs are involved in stroke risk factors including hypertension, atherosclerosis, atrial fibrillation, diabetes and dyslipidemia. The role of miRNAs in the pathophysiology of stroke has been the subject of more recent investigations. Animal studies, which dominate the field, have demonstrated the differential expression of miRNAs in brain and blood following ischemic or hemorrhagic insult and the potential use of miRNA antagonists to reduce focal cerebral damage. In particular, antagomirs to miR-145, -497, -181a, -1 and let-7f have been found to be neuroprotective in vivo. The discovery of circulating miRNAs in peripheral blood, which are unexpectedly stable, has allowed the recent completion of several studies in human stroke patients that have confirmed the differential expression of specific miRNAs following stroke and have addressed their potential use as diagnostic and prognostic markers. With miRNA research in stroke still in its infancy, it is anticipated that in the next few years significant discoveries that may have important therapeutic implications will emerge.
    Current topics in medicinal chemistry 05/2013; · 4.47 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate the effect of a combination of eccentric and ballistic strength training program on muscle fiber composition and fiber cross-sectional area. METHODS: Eight male university students (age: 21±2 yrs, height: 177±5 cm, body mass: 78±8 kg, body fat: 8.9±2.5 %) trained three times per week for 6 weeks. During session 1 and 3 of each week, participants performed six sets of two repetitions of eccentric half squats against a load of 65% of one repetition maximum (1RM), separated by 4 min of recovery. Participants were instructed to lower the weight fast and then decelerate rapidly until knee angle reached 90o. The weight was then lifted by two assistants and the next repetition was performed. During session 2 of each week, participants performed six sets of four maximal effort jump squats against a load corresponding to 30% of 1RM, separated by 4 min of recovery. In the first, second and third minute of each recovery interval of all sets in every training session, participants performed a maximal countermovement jump. Before and after 6 weeks of training, vertical jump height was assessed and muscle biopsies were obtained from the vastus lateralis of seven participants. Muscle biopsy data were analyzed using two-way ANOVA with repeated measures and performance data were compared using paired t-test (p<0.05). RESULTS: Vertical jump height increased from 37.3±4.1 to 43.7± 5.4 cm (p=0.002). The percentage of type I, IIA and IIX fibres remained unchanged after training (type I: 46.8±3.0 vs. 46.2±3.4%, type IIA: 40.2±3.4 vs. 41.0±4.4%, type IIX: 13.0±1.5 vs. 12.8±1.6%, pre vs. post training). However, fiber cross-sectional area increased equally (by 9.4±2.0%, p<0.01) in all fiber types after training (type I: from 4705±243 to 5132±225 μm2, type IIA: from 5939±263 to 6421±271 μm2, type IIX: from 5004±253 to 5568±325 μm2, p=0.003). CONCLUSION: These data show that this combination of eccentric and ballistic strength training increases leg muscle power and muscle fibre cross sectional area in all fibre types, without causing a decrease in the percentage of type IIX fibres. The relatively large increase in vertical jump performance (17.0±3.3%) over a relatively short training period (6 weeks or 18 training sessions) suggests that this program may be effective for fast gains in leg muscle power
    ACSM 60th Annual Meeting 2013, Indianapolis, Indiana, USA; 05/2013
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    ABSTRACT: OBJECTIVES: Time rate of blood pressure (BP) variation is a measure of the speed of BP fluctuations derived from a computerized analysis of ambulatory BP monitoring. The aim of this study was to identify pathophysiological differences in the time rate of BP variation between stroke subtypes, on the basis of the Trial of Org 10172 in Acute Stroke Treatment criteria, in the acute phase and to examine the impact of time rate of BP variation on outcome at 1 year after stroke. PATIENTS AND METHODS: A consecutive series of 109 first-ever stroke patients, who fulfilled our inclusion criteria, underwent 24 h ambulatory BP monitoring within 24 h after the onset of stroke. On the basis of the patients' Modified Rankin Scale score at 1 year after stroke, the study population was divided into two groups: patients with a positive (n=73) and those with a negative outcome (n=36). RESULTS: The 24-h rate of systolic BP variation is higher in patients with large artery atherosclerosis [0.692 mmHg/min; 95% confidence interval (CI) 0.627-0.757] compared with those with lacunar strokes (0.609 mmHg/min; 95% CI 0.579-0.640) or strokes of unknown etiology (0.586 mmHg/min; 95% CI 0.522-0.649). Moreover, patients with higher 24-h rates of systolic BP variation were more likely to have a negative outcome at 1 year (odds ratio 1.96; 95% CI 1.16-3.32). Moreover, each 0.1 mmHg/min increase in the 24-h rate of SBP variation was associated with a 1.96-fold increase in the odds of a negative outcome (95% CI 1.16-3.32). CONCLUSION: Time rate of BP variation shows significant differences between stroke subtypes in the acute phase of the event, and it is associated with outcome at 1 year. Lowering the time rate of BP variation, in the acute phase, might lead to better outcomes in patients who have had a cerebrovascular incident.
    Blood pressure monitoring 02/2013; · 1.62 Impact Factor
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    ABSTRACT: The Color Trails Test (CTT) is a neuropsychological test that measures perceptual tracking and sustained and divided attention. Recently, its use has been increased in neurological diseases such as Alzheimer's disease, brain injury, and subclinical infarction. The aim of the present study was to provide normative data for the CTT in the Greek population. A total of 321 native Greek speakers with various professional backgrounds took part in the study. Exclusion criteria involved the existence of neurological and psychiatric diseases, history of alcohol and/or drug dependence, traumatic brain injury, and a Mini-Mental State Examination score below 27. Our results showed that age and education are important factors to consider for the interpretation of scores in all CTT variables. Older participants took more time and exhibited more errors, more near-misses, and more prompts compared with younger participants. Also, more-educated participants took less time, made fewer errors, had fewer near-misses, and rewired fewer prompts compared with less educated participants. CTT is a promising tool for the measurement of attention in the Greek population. Further research is needed to use this test in Greek patients with various neurological diseases.
    Applied Neuropsychology 01/2013; 20(1):47-52. · 1.32 Impact Factor
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    ABSTRACT: The purpose of the present study was to investigate the effects of 6 weeks strength vs. ballistic-power (Power) training on shot put throwing performance in novice throwers. Seventeen novice male shot-put throwers were divided into Strength (N = 9) and Power (n = 8) groups. The following measurements were performed before and after the training period: shot put throws, jumping performance (CMJ), Wingate anaerobic performance, 1RM strength, ballistic throws and evaluation of architectural and morphological characteristics of vastus lateralis. Throwing performance increased significantly but similarly after Strength and Power training (7.0-13.5% vs. 6.0-11.5%, respectively). Muscular strength in leg press increased more after Strength than after Power training (43% vs. 21%, respectively), while Power training induced an 8.5% increase in CMJ performance and 9.0 - 25.8% in ballistic throws. Peak power during the Wingate test increased similarly after Strength and Power training. Muscle thickness increased only after Strength training (10%, p < 0.05). Muscle fibre Cross Sectional Area (fCSA) increased in all fibre types after Strength training by 19-26% (p < 0.05), while only type IIx fibres hypertrophied significantly after Power training. Type IIx fibres (%) decreased after Strength but not after Power training. These results suggest that shot put throwing performance can be increased similarly after six weeks of either strength or ballistic power training in novice throwers, but with dissimilar muscular adaptations. Key pointsBallistic-power training with 30% of 1RM is equally effective in increasing shot put performance as strength training, in novice throwers, during a short training cycle of six weeks.In novice shot putters with relatively low initial muscle strength/mass, short-term strength training might be more important since it can increase both muscle strength and shot put performance.The ballistic type of power training resulted in a significant increase of the mass of type IIx muscle fibres and no change in their proportion. Thus, this type of training might be used effectively during the last weeks before competition, when the strength training load is usually reduced, in order to increase muscle power and shot put performance in novice shot putters.
    Journal of sports science & medicine 01/2013; 12(1):130-7. · 0.89 Impact Factor
  • Blood pressure monitoring 10/2012; 17(5):220-1. · 1.62 Impact Factor
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    ABSTRACT: We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe. We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital- or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons. In the study cohort (n=3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (n=1868; median age, 43 years) and northern (n=1330; median age, 44 years) European patients, southern Europeans (n=746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged <34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions. Primary preventive strategies for ischemic stroke in young adults-having high rate of modifiable risk factors-should be targeted according to sex and age at continental level.
    Stroke 07/2012; 43(10):2624-30. · 6.16 Impact Factor
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    ABSTRACT: Current evidence suggests cardiac involvement and electrocardiographic changes of increasing frequency with age in patients with myotonic dystrophy type 2 (DM2). Myocyte hypertrophy with concurrent fibrosis seems to be the anatomical correlate. Moreover, morphological and functional changes indicative of subclinical cardiomyopathy have been demonstrated by means of cardiac magnetic resonance imaging (CMRI) and spectroscopy in patients with no overt cardiac disease. We present a 68-year-old woman with genetically established DM2 and no clinical, electrocardiographic or echocardiographic signs indicative of cardiac involvement. CMRI revealed delayed contrast enhancement of the anterior portion of the interventricular septum, indicating myocardial involvement. Contrast-enhanced CMRI might be a useful diagnostic tool in assessing cardiac involvement in cases of DM2. The role of delayed contrast enhancement should be further investigated in order to elucidate the cardiac features of this fascinating multisystem disease.
    Hellenic journal of cardiology: HJC = Hellēnikē kardiologikē epitheōrēsē 07/2012; 53(4):324-6. · 1.23 Impact Factor
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    ABSTRACT: The authors sought to determine the relative efficacy and tolerability of duloxetine versus citalopram and sertraline in the treatment of poststroke depression (PSD), anxiety, and fatigue. A group of 60 patients with PSD were assigned to receive duloxetine, citalopram, or sertraline and were assessed over a 3-month period for depression, anxiety, and fatigue. Improvement of depression and anxiety, but not fatigue, was observed in all study groups. Duloxetine was well tolerated and significantly more effective than citalopram and sertraline for the treatment of anxiety symptoms in PSD patients. None of the antidepressants used was effective for reducing symptoms of fatigue.
    The Journal of neuropsychiatry and clinical neurosciences 06/2012; 24(3):349-53. · 2.34 Impact Factor
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    ABSTRACT: Non-ketotic hyperglycemia may be a cause of hemiballism-hemichorea. We present an elderly female type II diabetic patient with right-sided hemiballism-hemichorea of acute onset during hypoglycemia following insulin overtreatment of non-ketotic hyperglycemia. Brain computerized tomography and magnetic resonance imaging scans revealed characteristic hyperdensity and T1 hyperintensity, respectively, in the left basal ganglia, in addition to pallido-dentate calcifications, suggestive of Fahr's syndrome. Although extremely rare, hypoglycemia may be a cause of hemiballism-hemichorea especially in the presence of predisposing factors such as previous hyperglycemic episodes and Fahr's syndrome.
    Neurological Sciences 04/2012; · 1.41 Impact Factor
  • Muscle & Nerve 03/2012; 45(3):452. · 2.31 Impact Factor
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    ABSTRACT: Raising interest towards genes implicates the effect of estrogen receptor-alpha (ESR1) gene on cerebrovascular disease, but data are lacking regarding the effect of estrogen receptor-beta (ESR2) gene. We assessed the hypothesis that AluI (G/A) polymorphism of the ESR2 gene (rs 4986938) is associated with ischemic stroke in a Caucasian population. Four hundred twenty four consecutive stroke patients and 430 age and gender-matched controls were enrolled in three stroke centers in Greece over one-year period. Patients and controls were compared in regard to the prevalence of the aforementioned polymorphism. No association was found between variations in the ESR2 gene and risk of stroke or stroke subtype in men and women. Of note, a gender-specific association of G allele with the onset of stroke at a younger age in male patients was found (63.68 ± 12.687 years in G allele (GG+AG) carriers vs. 68.95 ± 10.757 years in non-carriers (AA), p=0.008). Further population independent studies are needed to establish the role of ESR2 gene polymorphisms in relation to ischemic stroke in both genders. Such studies could lead to ERβ agonists being validated in individuals with certain genotypes and/or alleles towards the development of efficient strategies to preventing ischemic stroke in both men and women.
    Journal of the neurological sciences 02/2012; 316(1-2):126-30. · 2.32 Impact Factor
  • Konstantinos Spengos, Evangelos Anagnostou, Sofia Vassilopoulou
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    ABSTRACT: One day after a minor accident, an 85-year-old man developed headache and proximal left leg weakness. He was on warfarin due to atrial fibrillation. On hospital admission, a right posterior parasagittal subdural haematoma that was visualised on CT was considered as cause of all symptoms. Although no surgical intervention was performed he stayed for 2 weeks in a neurosurgical ward. Clinical deterioration occurred within the first days as he was not able to stand on his left leg or rise up from the sitting position. Headache had ceased, but the patient reported low abdominal pain. This condition remained stable for over 2 months although haematoma size decreased significantly. He was then examined for the first time by a neurologist who documented typical clinical features of femoral nerve palsy. Pelvic CT established the diagnosis of traumatic iliacus- and iliopsoas-muscle haematoma under anticoagulants as cause of subacute femoral mononeuropathy.
    Case Reports 01/2012; 2012.
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    ABSTRACT: Viral infection is a rare cause of painful ophthalmoplegia. We report on a 67-year-old patient who developed painful double vision after a vesicular skin rash on the left forehead. MRI disclosed simultaneous inflammatory lesions in all extraocular muscles, the second and third cranial nerve, as well as pathological signal intensity along the spinal trigeminal tract and nucleus within the medulla oblongata and the pons. Cerebrospinal fluid and serum tests for varicella zoster were positive. The patient was treated effectively with intravenous acyclovir and methylprednisolone. Simultaneous lesions in various neighbouring neural structures may be characteristic for the highly neurotropic behaviour of the herpesviridae and should be considered as a cause of painful ophthalmoplegia that can be depicted by appropriate imaging.
    Case Reports 01/2012; 2012.
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    ABSTRACT: Pompe disease is an inherited metabolic disorder characterized by α-glycosidase deficiency, which leads to lysosomal glycogen accumulation in many different tissues. The infantile form is the most severe with a rapidly fatal outcome, while the late onset form has a greater phenotypic variability, characterized by skeletal muscle dysfunction and early respiratory involvement. Bone mineral density (BMD) has been recently reported to be reduced in many patients with both forms of the disease. Enzyme replacement therapy (ERT) is now available with an undefined, impact on BMD in patients with late onset disease. The present study aimed to investigate BMD in patients with late onset form of Pompe disease before and after ERT initiation. Dual x-ray absorptiometry (DEXA) was examined in four newly diagnosed patients with late onset Pompe disease and in four adults under ERT before and after ERT initiation with a treatment duration of 18 to 36 months. The initial DEXA showed normal total body BMD z-score in all the patients, while L2-L4 and femoral neck BMD was reduced in three and two patients, respectively. After ERT administration, two patients had an improvement in L2-L4 lumbar spine and one patient in femoral neck BMD z-score with values within normal range. The results suggested that regional BMD may moderately reduce in some patients with the late onset form of Pompe disease, although profound osteopenia was not observed. The improvement of measurements in L2-L4 and femoral neck BMD z-score in some patients with low pre-treatment values after ERT administration needs to be confirmed in larger scale studies.
    International journal of endocrinology and metabolism. 01/2012; 10(4):599-603.
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    ABSTRACT: The involvement of different brain areas in spontaneous eyeblink rate control is largely unknown. Spontaneous eyeblink rate was assessed in 211 consecutive acute stroke patients within two days after symptom onset and was correlated with infarction location as well as with other parameters such as the presence of hemineglect or significant small vessel disease in MRI or CT scans. Blink rates were measured in two conditions: (1) during a trivial conversation requiring no cognitive effort and (2) during mental arithmetic. Patients and healthy controls displayed similar average blink rates at rest (19.1 and 17.3 blinks/min, respectively) and during mental arithmetic (22.6 and 20.2 blinks/min, respectively). The latter condition reliably increased blinking frequency in both patients and control subjects. The subgroups of patients with frontal, frontoparietal and frontotemporal infarctions exhibited a significantly higher blink rate modulation, expressed as an increased relative difference of blinking at rest compared with blinking during mental arithmetic. As a whole, patients with acute cerebrovascular disease do not show changes in blink rate. Subjects with frontal infarcts, however, systematically increase their blink rates during cognitive effort, most probably due to a lack of frontal inhibitory control on blinking modulation.
    European Neurology 12/2011; 67(1):39-44. · 1.50 Impact Factor
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    ABSTRACT: The precise innervation of the sternocleidomastoids is uncertain. Of clinical interest is whether a unilateral hemispheric lesion leads to an ispilateral or contralateral sternocleidomastoid weakness. Sternocleidomastoid strength was assessed in 124 consecutive acute stroke patients during yaw, pitch, and roll head movements. This was correlated with limb paresis and neuroimaging findings. The incidence and the degree of sternocleidomastoid paresis were low (16.9%). In all cases, head rotation weakness away from the affected hemisphere was observed. Lateral tilt and vertical head rotations were unaffected. No weakness was detected in lesions that did not cause manifest limb paresis. Our data point to an ipsihemispheric sternocleidomastoid control. Sternocleidomastoid paresis in stroke is expected only with concomitant limb paresis and is always less severe. Head tilt is not affected probably due to sparing of ancillary neck-muscle function.
    The Neurologist 11/2011; 17(6):309-11. · 1.48 Impact Factor

Publication Stats

712 Citations
331.46 Total Impact Points

Institutions

  • 2003–2014
    • Eginition Hospital Athens
      Athínai, Attica, Greece
  • 2013
    • Idaho State University
      • Department of Communication Sciences and Disorders and Education of the Deaf
      Pocatello, ID, United States
  • 2007–2013
    • Athens State University
      Athens, Alabama, United States
    • University of Alabama at Birmingham
      • Department of Neurology
      Birmingham, AL, United States
  • 2005–2013
    • National and Kapodistrian University of Athens
      • Division of Neurology II
      Athínai, Attica, Greece
  • 2011
    • University of Ioannina
      • Division of Internal Medicine II
      Ioánnina, Ipeiros, Greece
  • 2003–2010
    • Alexandra Regional General Hospital
      Athínai, Attica, Greece