G. M. Hadjigeorgiou

Depressive Symptoms in Alzheimer's Disease: Natural Course and Temporal Relation to Function and Cognitive Status

Objectives: To examine the natural course of depressive symptoms in patients with probable Alzheimers disease (AD), specifically, the temporal relationship between depressive symptoms, function, and cognitive status.

A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family.

Autosomal dominant progressive external ophthalmoplegia (adPEO) is caused by mutations in at least three different genes: ANT1 (chromosome 4q34–35), TWINKLE, and POLG. The ANT1 gene encodes the adenine nucleotide translocator-1 (ANT1). We identified a heterozygous T293C mutation of the ANT1 gene in a Greek family with adPEO. The resulting leucine to proline substitution likely modifies the secondary structure of the ANT1 protein. ANT1 gene mutations may account for adPEO in families with different ethnic backgrounds.

Intradialytic aerobic exercise training ameliorates symptoms of restless legs syndrome and improves functional capacity in patients on hemodialysis: a pilot study.

We present the first study on the influence of exercise training on restless legs syndrome (RLS) in patients on hemodialysis (HD). Restless legs syndrome has been treated pharmacologically with satisfactory results; however, side effects and rebound phenomena have been reported. Intradialytic exercise training effectively counteracts uremia-induced catabolism; nevertheless, it remains unknown whether patients with RLS undergoing HD benefit from such programs. The aims of the current study were to evaluate the effect of 16-weeks aerobic exercise training in the severity of RLS and in the functional capacity and the quality of life of patients with RLS on HD. Fourteen patients on HD (four female, mean age 59 ± 16 years) with untreated RLS were assigned, according to their will, to either the exercise group (Ex-group, n = 7), and participated in a 16-week supervised intradialytic aerobic exercise training, or to the control group (Con-group, n = 7), and continued usual activities. Primary aim was to compare the International RLS (IRLS) study group rating scale, functional ability, and quality of life in baseline and the end of the 16 weeks. Exercise training reduced IRLS score by 42% (p = 0.02). Furthermore, it significantly improved indices of functional ability (p = 0.02), exercise capacity (p = 0.01), quality of life (p = 0.03), and sleep quality (p = 0.01). In the Con-group no changes were observed. In conclusion, aerobic exercise training is safe and efficacious in reducing RLS symptoms and improving quality of life in patients with RLS on HD.

Low RLS prevalence and awareness in central Greece: an epidemiological survey

Restless legs syndrome (RLS) is a sensorimotor disorder with a general population prevalence of 3–10%. A single, previous epidemiological study performed in south‐east Europe reported the lowest prevalence rate amongst European countries. We conducted a population‐based survey of RLS in central Greece. A total of 4200 subjects were randomly recruited. We used the international RLS study group criteria for diagnosis and the severity scale for severity assessment in subjects with RLS. We also included questions to assess the level of awareness of RLS in our region. A total of 3033 subjects were screened. The overall lifetime prevalence was 3.9% with a female‐to‐male ratio of 2.6:1. Nearly half of RLS patients reported moderate to severe intensity of symptoms. After adjustment for multiple comparisons we found no association of RLS with education level, smoking, alcohol intake, caffeine consumption, shift work, professional pesticide use or comorbid illness. Our study revealed a low level of awareness amongst the population and physicians in our region and sub‐optimal management. We provide further evidence for low prevalence of RLS in south‐east Europe and a low level of awareness of RLS in our region.

A New Mitochondrial DNA Mutation in ND3 Gene Causing Severe Leigh Syndrome with Early Lethality

We describe a new mitochondrial DNA mutation in a male infant who presented clinical and magnetic resonance imaging features of Leigh syndrome and died at the age of 9 mo. The patients development was reportedly normal in the first months of life. At the age of 5 mo, he presented severe generalized hypotonia, nystagmus, and absent eye contact. Laboratory examination showed increased lactate and pyruvate in both serum and cerebrospinal fluid. Brain magnetic resonance imaging revealed multiple necrotic lesions in the basal ganglia, brain stem, and thalamus. Muscle histopathology was unremarkable, whereas respiratory chain enzyme analysis revealed a severe complex I deficiency. The patient died after an acidotic coma at age 9 mo. Sequence analysis of the entire mtDNA disclosed a new T10158C mutation with variable tissue heteroplasm (muscle: 83%; blood: 48%). The mutation was undetectable in the blood of his unaffected mother. The transition changes a serine residue into a proline, in a highly conserved region of the NADH dehydrogenase subunit 3 (ND3). This is the first description of a mitochondrial ND3 gene in Leigh syndrome with early lethality.

IL-1RN and IL-1B gene polymorphisms and cerebral hemorrhagic events after traumatic brain injury.

Objective: To investigate the association of (variable number tandem repeat) interleukin (IL) 1RN and (-511) IL-1B gene polymorphisms with brain hemorrhagic events after traumatic brain injury (TBI). Methods: Data from brain CT, Glasgow Coma Scale (GCS) at admission, and 6-month Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) were collected for 151 prospectively recruited patients with TBI. IL-1RN and IL-1B genotypes were determined using standard methods. Presence vs absence of any type of brain hemorrhage was the main outcome. Type of brain hemorrhage, GCS at admission, and 6-month GOS and mRS were secondary outcomes. Odd ratios (ORs) and corresponding 95% CI were calculated using logistic regression analyses. In adjusted models, the associations were controlled for age, gender, diffuse brain edema, volume of intracranial hematoma, neurosurgical intervention, and GCS at admission. p values less than 0.01 were considered significant. Results: Compared with noncarriers, IL-1RN allele 2 carriers had higher odds of having cerebral hemorrhages after TBI (adjusted OR = 4.57; 95% CI = 1.67 to 12.96; p = 0.004). The associations for (-511) IL-1B polymorphism were not significant. Conclusion: There is an association between the presence of interleukin-1RN allele 2 and posttraumatic brain hemorrhage.

Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variants

Mutations in SNCA and LRRK2 genes, encoding alpha‐synuclein and leucine‐rich repeat kinase 2, respectively, cause autosomal dominant Parkinsons disease (AdPD). The LRRK2 G2019S (c.6055G > A) and R1441G (c.4321C > G) mutations have also been identified in sporadic PD (sPD). We studied 55 unrelated patients with AdPD, 235 patients with sPD, and 235 healthy age‐ and gender‐matched controls all of Greek origin. Patients with AdPD were screened for SNCA and LRRK2 mutations by direct sequencing. SNCA gene dosage analysis was also performed for AdPD using quantitative duplex polymerase chain reaction of genomic DNA. In addition, we investigated the frequency of the LRRK2 G2019S mutation in sPD. We found no missense mutations or multiplications in the SNCA gene. Here we report two novel variants, A211V (c.632C > T) and K544E (c.1630A > G) in LRRK2 gene in two patients with AdPD that was not present in controls. We identified only one patient with sPD (1/235; 0.4%) carrying the G2019S mutation. LRRK2 mutations are present in AdPD and sPD patients of Greek origin.

Lack of evidence for a genetic association between FGF20 and Parkinson's disease in Finnish and Greek patients

BackgroundFibroblast growth factor 20 (FGF20) is a neurotrophic factor preferentially expressed in the substantia nigra of rat brain and could be involved in dopaminergic neurons survival. Recently, a strong genetic association has been found between FGF20 gene and the risk of suffering from Parkinsons disease (PD). Our aim was to replicate this association in two independent populations.MethodsAllelic, genotypic, and haplotype frequencies of four biallelic polymorphisms were assessed in 151 sporadic PD cases and 186 controls from Greece, and 144 sporadic PD patients and 135 controls from Finland.ResultsNo association was found in any of the populations studied.ConclusionTaken together, these findings suggest that common genetic variants in FGF20 are not a risk factor for PD in, at least, some European populations.

Randomized trials of dopamine agonists in restless legs syndrome: A systematic review, quality assessment, and meta-analysis

BACKGROUND The use of dopamine agonists (DAs) for the treatment of restless legs syndrome (RLS) has been assessed in numerous randomized clinical trials (RCTs). OBJECTIVES The aims of this study were to assess the reporting quality of published RCTs according to the Consolidated Standards of Reporting Trials (CONSORT) statement and to synthesize the study results in terms of efficacy and tolerability to inform the clinical management of RLS. METHODS PubMed and Cochrane Controlled Trials Register were searched for English-language RCTs that assessed the effects of DAs in RLS. Quality of reporting was measured using the proportion of 17 CONSORT checklist items included in each study. The 2 primary outcomes were pooled mean change from baseline in International RLS (IRLS) Study Group rating scale score (Deltamu) (95% CI) and relative risk (RR) (95% CI) of response based on the Clinical Global Impression-Improvement (CGI-I) scale score. The pooled proportions of adverse events (PAEs) (95% CI) were also estimated. RESULTS Eighteen RCTs (N = 2848 patients) were included. Two of the 17 CONSORT checklist items were reported in 7 studies (39%) and 9 of the 17 items were reported in all 18 studies (100%). The differences in the IRLS scores and RR for CGI-I were significantly greater with pramipexole, ropinirole, rotigotine, and cabergoline compared with placebo. Results for heterogeneity were nonsignificant. The difference in Deltamu (95% CI) was significant with pramipexole (-6.63 [-9.15 to -4.10]) versus ropinirole (-3.64 [-4.76 to 2.51]) (P = 0.04). The difference between pramipexole and rotigotine was nonsignificant. The pooled PAEs (95% CI) for pramipexole, ropinirole, and rotigotine were 4.8% (2.0% to 8.7%), 10.2% (2.6% to 22.1%), and 7.6% (1.3% to 18.5%), respectively. In the trial of sumanirole, the PAE value was 2% (0% to 5.4%). CONCLUSION Based on the findings from the meta-analysis, DAs were significantly more efficacious in the treatment of RLS compared with placebo.

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.