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ABSTRACT: Gaucher disease (GD) patients and carriers of glucocerebrosidase mutations are at an increased risk for Parkinson's disease (PD). The presynaptic protein alpha-synuclein (AS) is linked to PD. In the current work we examined biochemical properties of AS in GD patients. We generated membrane-enriched lysates from erythrocytes of 27 patients with GD and 32 age- and sex-matched controls and performed Western immunoblotting with antibodies against AS. Levels of monomeric AS did not differ between GD patients and controls and did not change as a function of age. However, the ratio of dimeric to monomeric AS was significantly increased in GD patients, and showed a significant positive correlation with age. Therefore, two major risk factors for PD, aging and GD status, are associated with an increased AS dimer to monomer ratio in erythrocytes. This ratio needs to be validated in further studies as a potential biomarker for PD risk.
Neuroscience Letters 09/2012; 528(2):205-9. · 2.11 Impact Factor
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ABSTRACT: B lymphocytes seem to have a fundamental role in multiple sclerosis, acting as sensors, coordinators, and regulators of the immune response. Furthermore, they are important in activating T cells and they can mediate tissue injury through diverse mechanisms. Such findings have important therapeutic implications in autoimmune central nervous system diseases in a fashion similar to other autoimmune processes. The best known monoclonal antibody targeting B cells that has been used as a novel therapy for various autoimmune conditions, as well as multiple sclerosis, is rituximab. This review summarizes the available data on the role of B cell in multiple sclerosis and further reports on current knowledge on the B-cell-depleting monoclonal antibody rituximab, its mechanism of action, and its efficacy on multiple sclerosis. Data presented were categorized in 3 groups based on the nature of data presented (radiological, clinical, and immunological data). Both case-control studies and case reports were included, while table classification was in chronological order.
Clinical neuropharmacology 03/2012; 35(2):90-6. · 2.35 Impact Factor
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Helen Michelakakis,
Georgia Xiromerisiou,
Efthimios Dardiotis,
Maria Bozi,
Demetrios Vassilatis,
Persa-Maria Kountra,
Gianna Patramani,
Marina Moraitou,
Dimitra Papadimitriou, Eleftherios Stamboulis,
Leonidas Stefanis,
Elias Zintzaras,
Georgios M Hadjigeorgiou
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ABSTRACT: Lysosomal protein 2 (LIMP2), the product of the scavenger receptor class B member 2 (SCARB2) gene, is a ubiquitously expressed transmembrane protein that is the mannose-6-phosphate-independent receptor for glucocerebrosidase (β-GCase); a deficiency in this protein causes Gaucher disease. Several studies have shown a link between mutations in the β-GCase gene and diseases characterized clinically by Parkinsonism and by the presence of Lewy body-related pathology. We hypothesized that genetic variants in the SCARB2 gene could be risk factors for Parkinson's disease (PD). A candidate-gene study of 347 Greek patients with sporadic PD and 329 healthy controls was conducted to investigate the association between 5 polymorphisms in the SCARB2 gene (rs6824953, rs6825004, rs4241591, rs9991821, and rs17234715) and the development of PD. The single-locus analysis for the 5 polymorphisms revealed an association only for the rs6825004 polymorphism: the generalized odds ratio (OR(G) ) was 0.68 (95% confidence interval [CI], 0.51-0.90), and the OR for the allelic test was OR = 0.71 (95% CI, 0.56-0.90). Haplotype analysis showed an association for the GCGGT haplotype (P < .01). Our study supports a genetic contribution of the SCARB2 locus to PD; future studies in larger cohorts are necessary to verify this finding.
Movement Disorders 01/2012; 27(3):400-5. · 4.51 Impact Factor
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ABSTRACT: Transforming growth factor beta (TGF-β) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-β and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-β and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role in the pathophysiology of this disorder by using references from embryonic experimental research. Available literature in the TGF/BMP signalling cascade, mostly during embryonic development of the nervous system is being reviewed. An attempt is made to further elucidate a potential role of TGF/BMP signalling in the pathophysiology of MS. During demyelination, BMP signaling, through various molecular mechanisms, directs the development of the adult neural stem cell in the astrocyte rather than the oligodendrocyte direction, therefore inhibiting the repair process. Further understanding of the above relationships could lead to the development of potentially efficient therapies for MS in the future.
Neurochemistry International 06/2011; 59(5):542-50. · 2.86 Impact Factor
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Georgia Xiromerisiou,
Elli Kyratzi,
Efthimios Dardiotis,
Maria Bozi,
Vana Tsimourtou, Eleftherios Stamboulis,
Styliani Ralli,
Demetrios Vassilatis,
Vanessa Gourbali,
Persa-Maria Kountra,
Kostas Fountas,
Alexandros Papadimitriou,
Leonidas Stefanis,
Georgios M Hadjigeorgiou
Movement Disorders 05/2011; 26(10):1955-7. · 4.51 Impact Factor
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Helen Triantafyllidi,
Stavros Tzortzis,
John Lekakis,
Ignatios Ikonomidis,
Chrysa Arvaniti,
Paraskevi Trivilou,
Konstantinos Kontsas,
Nikolaos Siafakas,
Loukia Zerva, Eleftherios Stamboulis,
Dimitrios Kremastinos,
Maria Anastasiou-Nana
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ABSTRACT: Subclinical organ damage represents an intermediate stage in the continuum of vascular disease and a determinant of overall cardiovascular risk. We investigated the associations of pulse wave velocity (PWV), ambulatory arterial stiffness index (AASI), and office pulse pressure (PP) with several target organ damages (TODs) in newly diagnosed and never-treated patients with essential hypertension with respect to their dipping profile.
One hundred sixty-eight hypertensive patients with recently diagnosed and never-treated stage I-II essential hypertension were evaluated with respect to the relationship of PWV, AASI, and office PP with TOD including microalbumin (MAU) levels, cognitive function, intima-media thickness (IMT), coronary flow reserve (CFR), left ventricular mass (LVM), left ventricular filling pressures, diastolic dysfunction, and left atrium (LA) enlargement.
Simultaneous estimation of AASI, PWV, and office PP independently associated with the following: (i) CFR (P < 0.01), 24-h urine albumin excretion rates (P < 0.05), left ventricular diastolic dysfunction (P < 0.01), and LA enlargement (P < 0.01) in never-treated hypertensive patients; (ii) CFR (P < 0.05), IMT (P < 0.01), left ventricular diastolic dysfunction (P < 0.05), and LA enlargement (P < 0.05) in dippers; and (iii) CFR (P < 0.05) and LA enlargement (P < 0.01) in nondippers. Nonindependent relationships revealed between (i) AASI and left ventricular filling pressures and (ii) PWV and cognitive dysfunction in never-treated hypertensive patients.
The simultaneous estimation of three noninvasive indexes of arterial stiffness leads to valuable information regarding their association with TOD including CFR, MAU levels, IMT, left ventricular diastolic dysfunction, and LA enlargement in never-treated hypertensive patients regarding their dipping status.
American Journal of Hypertension 12/2010; 23(12):1265-72. · 3.18 Impact Factor
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ABSTRACT: The prevalence of peripheral neuropathy in patients with Sjögren syndrome remains unclear owing to conflicting results in the published series, with numbers ranging from 2% to over 60% of Sjögren syndrome patients. Whether peripheral neuropathy is a feature of the systemic or glandular disease or whether it is related to a circulating antineuronal antibody remains also uncertain.
The authors reviewed the records of patients with primary Sjögren syndrome (pSS), fulfilling the Revised European-American Classification Criteria, seen in their department from 1992 to 2009. The patients with previously recorded neuropathic features were re-examined clinically and electrophysiologically. Other causes of polyneuropathy were excluded. The authors also searched for circulating antineural antibodies using immunofluorescence and western blot and for antibodies against muscarinic and nicotinic acetylcholine receptors as potential biomarkers.
509 cases met the diagnostic criteria for pSS. Among these, 44 patients were recorded as having neuropathic symptoms. After completing the evaluation, however, only nine (1.8%) had polyneuropathy with objective clinical signs and abnormal electrophysiological findings. The neuropathy was axonal in all, in five pure sensory and in four sensorimotor. The patients with peripheral neuropathy had extraglandular manifestations such as palpable purpura and vasculitis. No evidence of antineural autoimmunity was found, and no candidate biomarkers were identified.
Polyneuropathy is a rare manifestation of pSS occurring in 1.8% of patients. In the majority of patients, it is a late event and frequently associated with systemic disease or risk factors for lymphoma development.
Journal of neurology, neurosurgery, and psychiatry 12/2010; 82(7):798-802. · 4.87 Impact Factor
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ABSTRACT: We systematically reviewed the existing evidence to determine whether a relationship exists between infection with human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) and, if so, to define the strength of that relationship. The following terms were used in searches of the Entrez-PubMed database (1966-2009): human herpes virus 6, HHV 6, demyelination, multiple sclerosis, pathogenesis, diagnosis, serology, cerebrospinal fluid, IgG antibodies, IgM antibodies, PCR, and lymphoproliferative techniques. Study quality was assessed using the criteria proposed by Moore and Wolfson and by the classification criteria used by the Canadian Task Force on the Periodic Health Examination. Studies were categorized both by experimental technique and by quality (high [A], intermediate [B], and low [C]) as determined by the Moore and Wolfson criteria. Overall, 25 (41%) of 61 studies, 15 (60%) of which were classified as A quality, reached a statistically significant result. According to the Canadian Task Force classification, all studies were categorized as evidence of quality II-1. Limitations of the available experimental techniques and perspectives for future research are discussed. The current review supports the need for further, objective, evidence-based examination of the relationship between HHV-6 infection and multiple sclerosis.
Mayo Clinic Proceedings 10/2010; 85(11):1023-30. · 5.70 Impact Factor
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ABSTRACT: Psychotic features in patients with Parkinson's Disease usually present as visual hallucinations against a background of cognitive deterioration and dopaminomimetic therapy. Isolated delusions are rare. We report here 4 patients with Parkinson's Disease who developed a delusional syndrome resembling schizophreniform psychosis in the absence of changes in alertness, visual hallucinations or dementia. We suggest that this syndrome may be more common than previously recognized, and that it may be related to the use of dopaminergic medications and environmental triggers on a background of a susceptible individual. This syndrome suggests interesting parallels with the pathophysiology of amphetamine-induced psychosis and schizophrenia.
Parkinsonism & Related Disorders 09/2010; 16(8):550-2. · 3.80 Impact Factor
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ABSTRACT: It is known that essential hypertension may be implicated in the development of cognitive impairment that is associated to microvascular disease of the brain. It has been hypothesized that increased arterial stiffness of the large arteries may lead to microvascular changes due to increased pulsatile flow. Our study tests the hypothesis that large artery stiffness and microvascular damage are related to brain microcirculation changes as reflected by impaired cognitive function.
We studied 110 nondiabetic patients aged 40-80 years (mean age 53.8 +/- 11.2 years, 57 men) with recently diagnosed stage I-II essential hypertension. Mini-Mental State Examination (MMSE) was used as a screening test for global cognitive impairment. We performed both 2-D echocardiography and carotid-femoral pulse wave velocity (PWV) in order to evaluate arterial stiffness. Twenty-four hour urine microalbumin excretion was measured as a marker of microvascular damage.
In the entire population, MMSE was negatively correlated with age (r = -0.42, P < 0.001), 24-h pulse pressure (PP) (r = -0.18, P < 0.05), and PWV (r = -0.3, P = 0.003). Additionally, MMSE was not independently correlated with microalbuminuria in patients aged over 65 years (r = -0.58, P = 0.003).
Impaired cognitive function is associated with increased large artery stiffness and microalbumin excretion in newly diagnosed, untreated hypertensive patients. These findings support the hypothesis that cognitive impairment induced by impaired microcirculation is linked to large artery stiffness and microvascular damage.
American Journal of Hypertension 03/2009; 22(5):525-30. · 3.18 Impact Factor
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ABSTRACT: Asymptomatic median mononeuropathy (AMM) and diabetic polyneuropathy (DPN) often coexist and can be difficult to distinguish electrophysiologically. Moreover, the potential association between AMM and DPN has not been extensively evaluated.
We investigated the relation between AMM and DPN severity in consecutive diabetic patients.
The non-dominant limb was studied electrophysiologically in 100 consecutive diabetic patients with no symptoms of carpal tunnel syndrome on the non-dominant side. AMM was diagnosed based on previously validated electrophysiological criteria. DPN severity was graded according to the Michigan diabetic neuropathy score.
AMM was discovered in 28% of the study population (Adjusted Wald 95% CI: 20%-37%). It was more common in women, displayed a tendency of being more common in patients over 50 years old and correlated with the severity of DPN and the number of abnormal nerves on nerve conduction studies. It was present in 18.1% of patients without evidence of DPN. No correlation was found with the duration and type of diabetes. In multivariate logistic regression models increasing severity of DPN was independently associated with the presence AMM (Wald test=10.557, df=3, p=0.014). Patients with DPN stage III and IV had a five-fold (OR=5.06, 95% CI=1.49-17.19) and a four-fold (OR=4.50, 95% CI=1.15-17.65) respectively increased likelihood to present with AMM in comparison to DPN stage I (reference group).
Our results confirmed the high incidence of AMM in diabetic patients. AMM was present in a significant number of patients in the absence of DPN and the likelihood of AMM detection increased with increasing severity of DPN.
Journal of the Neurological Sciences 01/2009; 278(1-2):41-3. · 2.35 Impact Factor
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ABSTRACT: Gender hormones are associated with the evolution of Multiple Sclerosis (MS) like changes in experimental models of MS. Several clinical studies have attempted to elucidate the role of gender hormones in the evolution of the clinical spectrum of the disease. We attempt to describe the currently known data regarding such associations emphasizing the potential clinical applications in different MS scenarios i.e. pregnancy, menstruation, use of oral contraceptives and hormonal replacement therapy. Moreover we discuss relevant effects of gender hormones on immunological parameters relating to MS pathogenesis. Beneficial neuroprotective effects were noted for elevated levels of estrogens, progesterone and elevated dosages of androgens. Some of these changes may be explained by a favorable immunological shift from a Th1 to Th2 response. Further elucidation of the clinical implications of such associations is necessary.
Current neurovascular research 12/2008; 5(4):224-35. · 3.23 Impact Factor
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ABSTRACT: Autonomic neuropathy, although common in Guillain-Barré syndrome, is considered rare in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and has not been systematically investigated in that disorder. The present study was aimed at determining the prevalence of autonomic dysfunction and investigating the integrity of autonomic nervous system (ANS) reflexes in CIDP. We studied 17 patients with idiopathic CIDP and 20 healthy controls. Six quantitative autonomic function tests (AFTs) were used: Valsalva ratio, 30/15 ratio, and inspiration-expiration difference for parasympathetic function; and tilt test, handgrip test, and sympathetic skin response for sympathetic function. Eleven patients had symptoms of autonomic dysfunction. AFTs were abnormal in 13 patients. Parasympathetic and sympathetic systems were affected with equal frequency. The tilt test was abnormal most frequently, followed by the 30/15 ratio. Three patients developed postural hypotension with loss of consciousness during the tilt test. Abnormality of AFTs did not correlate with the presence of dysautonomic symptoms; duration, severity, and clinical course of the disease; or with age or gender of patients. Our study suggests a higher frequency of clinical and subclinical involvement of the ANS in CIDP than previously estimated. Dysautonomic symptoms are frequent but are mild. However, upon prolonged passive standing, autonomic failure can lead to loss of consciousness. The subclinical involvement of the ANS affects mainly the sympathetic vasomotor and parasympathetic cardiovascular fibers.
Muscle & Nerve 02/2006; 33(1):78-84. · 2.37 Impact Factor
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European Neurology 02/2004; 51(1):51. · 1.81 Impact Factor
