β-Glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease

An increasing number of clinical, neuropathological and experimental evidence linking Gaucher disease and a spectrum of synucleinopathies, including Parkinson's disease (PD) has emerged over the last decade. In particular, several studies, despite individual differences, have shown that mutations in the β-glucocerebrosidase gene (GBA) are a risk factor for PD. Recently a study from Northern Greece has shown a significant overrepresentation of such mutations only in patients with early onset PD. In the present study 8 different GBA mutations covering 87% of the mutations identified in Gaucher disease patients diagnosed in Greece were investigated in two ethnic Greek cohorts of patients with sporadic Parkinson's disease. Cohort A included patients residing and originating from Thessaly, Central Greece (n=100) and cohort B included patients residing and/or originating from the greater area of Athens (n=105). Age-gender-ethnicity matched healthy individuals from the same areas were included as controls (n=206). In patients of cohort A 11 carriers of GBA mutations were identified (5/11:N370S, 2/11:L444P, 2/11: D409H;H255Q, 1/11:H255Q, 1/11D409H) as opposed to 3 in the controls (n=105) (1/3:N370S, 1/3:H255Q, 1/3:Y108C) (p=0.021, OR 4.2, 95% CI=1.14-15.54). In patients of cohort B 10 carriers of GBA mutations were identified (4/10:L444P, 4/10:D409H;H255Q, 1/10:N370S, 1/10:IVS10-1G→A) as opposed to 4 in controls (n=101) (3/4:N370S, 1/4:L444P). However the difference was not statistically significant (p=0.113, OR 2.5, 95% CI=0.77-8.42). In both cohorts, patients with PD harboring a GBA mutation had an earlier onset of symptoms than non-carriers (p=0.034, p=0.004). The overall difference in the number of carriers identified in PD patients and controls was statistically significant (p=0.006; OR 3.24; 95% CI=1.35-7.81). The association was reinforced in the early onset PD patients (EOPD; n=28, p=0.000, OR 11.37; 95% CI=3.73-34.6). In conclusion GBA mutations were identified with increased frequency in both geographical cohorts of patients with sporadic PD studied compared to control individuals, with the difference being statistically significant only in cohort A. An impressive association with EOPD was found and one third of the EOPD patients examined harbored a GBA mutation. Qualitative differences regarding the type of mutations and/or their relative frequencies were observed between cohorts A and B of PD patients. Genetic and/or environmental factors may account for the observed differences.     

Absence of aprataxin gene mutations in a Greek cohort with sporadic early onset ataxia and normal GAA triplets in frataxin gene

Phenotype of patients with the aprataxin gene mutation varies and according to previous studies, screening of aprataxin gene could be useful, once frataxin gene mutation is excluded in patients with normal GAA expansion in frataxin gene. In the present study, we sought to determine possible causative mutations in aprataxin gene (all exons and flanking intronic sequences) in 14 Greek patients with sporadic cerebellar ataxia all but one without GAA expansion in frataxin gene (1 patient was heterozygous). No detectable point mutation or deletion was found in the aprataxin gene of all the patients. Our results do not confirm the previous studies. This difference may be attributed to the different populations studied and possible different genetic background. It is still questionable whether the screening for aprataxin mutation in Greek patients’ Friedreich ataxia phenotype is of clinical importance; larger, multicenter studies are necessary to clarify this issue.     

The Rotaglide mobile-bearing total knee arthroplasty: no difference between cemented and hybrid implantation

Purpose

The optimal fixation of the Rotaglide total knee arthroplasty’s (TKA) components is controversial. It is hypothesized that the hybrid fixation (cementless femoral component) in a mobile-bearing TKA system might cause increased rate of loosening—especially in the femoral part—and finally failure of the arthroplasty. Consequently, the aim of this study was to compare the survival and revision rates and also the clinical and radiological outcomes of the cemented and hybrid fixation of the Rotaglide TKA.

Methods

One hundred patients, who underwent TKA with the Rotaglide prosthesis, were randomly placed in two groups. In the first group, the prosthesis was cemented, and in the second group, the hybrid technique was used. Revision and mortality rates were compared after 8–12 years of follow-up. Knee and Osteoarthritis Outcome Score (KOOS) questionnaire and the Knee Society Roentgenographic Evaluation and Scoring System were used to demonstrate clinical and radiographic differences.

Results

There were no statistically significant differences in revision (n.s.) or mortality (n.s.) rates between the two treatment arms. The clinical outcome at the time of last follow-up (mean 9.5 years, SD ±1.4) ranged from very good to excellent (77.8 ± 17.5 for the cemented group and 77.2 ± 20.4 for the hybrid group). No statistically significant differences in all KOOS subscales. Radiographs showed no significant difference in prosthesis alignment and no evidence of loosening between groups.

Conclusion

The hypothesis that the hybrid fixation in a mobile-bearing TKA system might cause increased rate of loosening and finally failure of the arthroplasty was not confirmed. The fixation technique (cemented or hybrid) had no influence on the prosthesis’s survivorship, and also on mortality rates, clinical and radiographic outcomes in a mean follow-up time of 9.5 ± 1.4 years. The Rotaglide TKA is a safe and reliable prosthesis regardless the fixation technique.

Level of evidence

Prospective comparative study, II.     

Endoscopic Fibrin Sealing of High-output Non- healing Gastrocutaneous Fistulas after Vertical Gastroplasty in Morbidly Obese Patients

Background: Fibrin glue was used in a various fields of surgery during the last 15 years, but its use has not been reported in bariatric surgery yet. Methods: In 2 out of 215 morbidly obese patients who underwent vertical banded gastroplasty, a nonhealing gastrocutaneus fistula (GCF) developed. In both patients sepsis occurred, caused by a leak of the posterior gastric wall, which was managed by means of an unsuccessful reoperation. After that, sepsis recurred, and a non-healing GCF developed. These GCF were managed endoscopically by the use of a fibrin sealant (Beriplast P 2 ml set, Behring?) as a tissue adhesive. Results: One injection was needed for the first case and six for the second in achieving full healing of the fistulas. No evidence of fistula was observed at gastroscopy 3 and 24 months after the end of therapy. Conclusions: Endoscopic use of human fibrin sealant is simple, safe, effective and in some cases life-saving. This is a therapeutic option in high output GCF in morbidly obese patients.     

The Longitudinal Association of Lifestyle with Cognitive Health and Dementia Risk: Findings from the HELIAD Study

The aim of the current study was to investigate whether a Total Lifestyle Index (TLI), including adherence to the Mediterranean diet, sleep duration, physical activity and engagement in activities of daily living, is associated with cognitive health over time and dementia risk, in a representative cohort of older people. A total of 1018 non-demented community-dwelling older adults ≥65 years old (60% women) from the HELIAD study were included. A comprehensive neurological and neuropsychological assessment was conducted at baseline and at the 3-year follow-up evaluating cognitive functioning, and a dementia diagnosis was set. Diet, physical activity, sleep duration and engagement in activities of daily living were assessed using standard, validated questionnaires at baseline. Sixty-one participants developed dementia at follow-up; participants who developed dementia were older and had fewer years of education compared with participants with normal cognition. With the exception of sleep duration, participants with normal cognition at follow-up scored higher in the individual lifestyle factors compared to those who developed dementia. Regarding TLI, values were lower for participants with dementia compared with those with normal cognition. Each additional unit of the TLI was associated with 0.5% of a standard deviation less decline per year of the Global Cognition score, whereas for each additional unit of the TLI, the risk for dementia was reduced by 0.2% per year (p < 0.05). Our results suggest that greater adherence to a healthy lifestyle pattern is associated with a slower decline of cognitive function and reduced dementia risk.     

Bsm1 Vitamin D Receptor Polymorphism and Calcium Homeostasis Following Bariatric Surgery

Purpose/Aim: To evaluate the association between the Bsm1 vitamin D receptor polymorphism and the calcium-vitamin D-parathormone axis following bariatric surgery. Materials and Methods: This cross-sectional study included 86 morbidly obese patients, who underwent either gastric bypass or sleeve gastrectomy, with a mean follow-up of four years. Calcium metabolism indices and bone turnover markers were assessed according to the presence of secondary hyperparathyroidism and the Bsm1 vitamin D receptor genotypes. Results: Secondary hyperparathyroidism (42.2% of sample) was associated with lower levels of 25hydroxyvitamin D and elevated markers of bone turnover. In subjects without secondary hyperparathyroidism, presence of the unfavorable B allele resulted in higher levels of parathormone (Bb and BB vs. bb genotype: 50.3 ± 8.2 pg/dl vs. 44.4 ± 10.7 pg/dl, p = .011, adjusted for weight loss, baseline body mass index, 25hydroxyvitamin D, surgical procedure, and duration after surgery). In the whole sample, patients bearing the unfavorable B allele exhibited lower weight loss, a parameter that was negatively associated with markers of bone resorption. Conclusions: Secondary hyperparathyroidism is highly prevalent after bariatric surgery. Bsm1 vitamin D receptor polymorphism may have an effect in early stages of calcium metabolism imbalance, while no association is detected in patients who have already developed secondary hyperparathyroidism. Moreover, vitamin D receptor polymorphism is associated with post-surgery weight loss, a process related to bone turnover.     

Peak alpha frequency: an electroencephalographic measure of cognitive preparedness.

OBJECTIVE: Electroencephalographic (EEG) peak alpha frequency (PAF) (measured in Hz) has been correlated to cognitive performance between healthy and clinical individuals, and among healthy individuals. PAF also varies within individuals across developmental stages, among different cognitive tasks, and among physiological states induced by administration of various substances. The present study suggests that, among other things, PAF reflects a trait or state of cognitive preparedness. METHODS: Experiment 1 involved 19-channel EEG recordings from 10 individuals with traumatic brain injury (TBI) and 12 healthy matched controls, before, during, and after tasks of visual and auditory attention. Experiment 2 involved EEG recordings from 19 healthy young adults before and after a working memory task (WAIS-R Digit Span), repeated on 2 different days to measure within-individual differences. RESULTS: Experiment 1 showed significantly lower PAF in individuals with TBI, mostly during post-task rest. Experiment 2 showed PAF during pre-task baseline to be significantly correlated with Digit Span performance of the same day but not with Digit Span performance of another day. Moreover, PAF was significantly increased after Digit Span for those participants whose PAF was lower than the sample median before the task, but not for those who had it higher. Finally, both PAF and Digit Span performance were increased during the second day. CONCLUSIONS: PAF was shown to detect both trait and state differences in cognitive preparedness, as well as to be affected by cognitive tasks. Traits are better reflected during post-task rest, whereas states are better reflected during initial resting baseline recordings.