Eleftherios Stamboulis

Cognitive Impairment Is Related to Increased Arterial Stiffness and Microvascular Damage in Patients With Never-Treated Essential Hypertension

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Peripheral neuropathies in Sjögren syndrome: a new reappraisal

Background 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. Methods 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. Results 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. Conclusion 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.

Evidence of an association between the scavenger receptor class B member 2 gene and Parkinson's disease†‡§

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 Parkinsons 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 (ORG) 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.

Genetic assessment of familial and early-onset Parkinson's disease in a Greek population

Although the first mutation associated with Parkinsons disease (PD) was identified several years ago in the alpha‐synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population.

Association of Target Organ Damage With Three Arterial Stiffness Indexes According to Blood Pressure Dipping Status in Untreated Hypertensive Patients

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Human Herpesvirus 6 Infection as a Trigger of Multiple Sclerosis

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.

Clinical and subclinical autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy

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, 2005

Double seronegative myasthenia gravis with anti-LRP 4 antibodies

About 10% of patients with generalized myasthenia gravis do not have detectable antibodies to acetylcholine receptor or muscle specific kinase (double seronegative myasthenia). The presence of anti-low density lipoprotein receptor-related protein 4 antibodies (LRP4 Abs) has recently been reported in variable proportion of double seronegative cases. We report the presenting characteristics of two double seronegative myasthenic patients from Greece with anti-LRP4 antibodies shortly after disease onset. The first patient, a 52-year-old male, presented with a one month history of isolated neck extensor weakness; the second patient is a 52-year-old female with three months history of ocular-bulbar-cervical myasthenic weakness. Both patients presented with mild severity and responded promptly and adequately to pyridostigmine. In the female patient thymic residual tissue was detected on CT of the mediastinum. She underwent thymectomy, and histological examination revealed follicular hyperplasia. This is the first clinical report of the presenting features of newly diagnosed myasthenia with anti-LRP4 antibodies. The clinical and therapeutic implications of the anti-LRP4 antibody positivity remain to be clarified.

Increased dimerization of alpha-synuclein in erythrocytes in Gaucher disease and aging

Gaucher disease (GD) patients and carriers of glucocerebrosidase mutations are at an increased risk for Parkinsons 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.

Isolated delusional syndrome in Parkinson’s Disease

Psychotic features in patients with Parkinsons 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 Parkinsons 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.