Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease.

In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele "A" for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele "A" for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group "female"; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.

Evaluation of the effect of non-ergot dopamine agonists on left ventricular systolic function with speckle tracking echocardiography.

OBJECTIVE: Parkinson's disease (PD) is a neurological disorder, and ergot dopamine agonists (DAs) are no longer usually preferred in the treatment due to the increased risk of valvular heart disease. Some recent studies have shown that commonly used non-ergot DA also increases the risk of heart failure. On the other hand, there are studies showing conflicting data about this relationship. The aim of the present study was to investigate the cardiac effects of non-ergot DAs in patients with PD using echocardiography. METHODS: Conventional echocardiography and two-dimensional (2D) speckle tracking strain echocardiography were performed to determine the possible systolic dysfunction prior to the development of apparent systolic heart failure. Ninety-one (55 male, 64±10 years) patients with PD were included in the study. Furthermore, 25 subjects with newly diagnosed PD and using no drug were enrolled as the control group. All patients were divided into groups according to their medication. Patients using levodopa were classified as Group 1 (36), levodopa+pramipexole as Group 2 (27), and levodopa+ropinirole as Group 3 (28). RESULTS: Left ventricle dysfunction with non-ergot DA use in patients with PD was not established with conventional echocardiographic evaluation. For 2D strain analysis, global longitudinal strain values were obtained as -18.5%, -18.5%, and -18.9% in the groups, respectively. Strain and strain rate values of the left ventricle were not different between the groups (p=0.816 and p=0.881, respectively). CONCLUSION: There was no significant relationship between left ventricular dysfunction and use of non-ergot DA in patients with PD. Similar results were obtained in strain analysis showing left ventricular subclinical dysfunction. Our study appears to confirm the safety of non-ergot DA in the point of heart failure risk. To our knowledge, this is the first study to evaluate the effect of this group of drugs on subclinical left ventricular systolic function.

Epigenetic approach to early-onset Parkinson's disease: low methylation status of SNCA and PARK2 promoter regions.

Background and aim The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD). Materials and methods The promoter region methylation status of SNCA and PARK2 genes was evaluated by methylation specific-PCR (MSP) in 91 patients with EOPD and 52 healthy individuals. Results The methylation of SNCA and PARK2 promoter regions were significantly lower in EOPD patients compared to the control group (P = 0.013 and P = 0.03, respectively). We also found that the methylation status of the SNCA might be associated with positive family history of PD (P = 0.042). Conclusion Although it should be supported by further analysis, based on the results of the present study, the methylation status of SNCA and PARK2 genes might contribute to EOPD pathogenesis.

Assessment of voiding dysfunction in Parkinson's disease: Reliability and validity of the Turkish version of the Danish Prostate Symptom Score.

AIMS: To investigate the reliability and validity of the Turkish version of the Danish Prostate Symptom Score (Dan-PSS) questionnaire in patients with Parkinson's disease (PD) and to compare the burden of LUTS (Lower urinary tract symptoms) in men and women. METHODS: For analysis of test-retest reliability, the Turkish version of the Dan-PSS scale was developed using the back translation method, and it was administered on the day of admission and repeated 1 week after in 60 patients with PD. The OAB-q (Overactive Bladder Questionnaire) and PDQ-39 (Parkinson's Disease Questionnaire-39) were administered to 73 patients for validity analysis. RESULTS: Both the internal consistency (Cronbach's alpha coefficient: 0.99-1.00) and the test-retest reliability (intraclass correlation coefficient: 0.99-1.00) of the Dan-PSS were found to be high in patients with PD. Although weak to moderate correlations were found between the subscales of the Dan-PSS and PDQ-39 (r: 0.20-0.42; P < 0.05), a strong correlation was found with the OAB-q (r: 0.60-0.79; P < 0.05). Nocturnal urination was the most frequent (93.2%), and bothersome (54.8%) symptom. The majority of the symptom and bother responses were similar in men and women. CONCLUSIONS: Current study shows that the Turkish version of the Dan-PSS questionnaire is an internally consistent, reliable, and valid scale for patients with PD. Therefore, it can be used to evaluate frequency and severity of LUTS in PD. LUTS are commonly seen in patients with PD in both sexes. It is suggested that all patients with PD should be referred for urological assessment.

Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease.

Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.

A comparison between stereotactic targeting methods of the subthalamic nucleus in cases with Parkinson's disease.

BACKGROUND: Several methods are used for targeting of the subthalamic nucleus (STN) for the surgical treatment of Parkinson's disease (PD). The goal of this study is to determine the most suitable morphological method for localizing the STN in order to perform deep brain stimulation (DBS) in the treatment of PD. METHODS: Twelve cases with PD underwent bilateral STN-DBS and followed up for 5 years. Indirect calculation of the STN using AC-PC coordinates, and direct targeting of the STN using stereotactic CT/MRI fusion, were used for targeting. A microelectrode recording method was used to localize the STN. RESULTS: Direct targeting of the STN using CT/MRI fusion was very precise in every case, based upon evaluation of the intraoperative microelectrode recordings, postoperative MRI scans, and clinical follow-up of the cases. The coordinate differences obtained from these two methods were statistically significant. CONCLUSION: Direct targeting method of the STN using CT/MRI fusion provided higher precision than the indirect calculation method. This method may be used as a standard targeting technique, and may obviate the need for using complicated technologies such as microelectrode recording, which may sometimes be risky and counterproductive.

Does treadmill training improve lower-extremity tasks in Parkinson disease? A randomized controlled trial.

OBJECTIVE: To investigate whether gait training with treadmill improves functional tasks of lower extremities in patients with Parkinson disease (PD). DESIGN: Randomized controlled trial including two groups, the treadmill training group and the nonintervention group. SETTING: University hospital. PATIENTS: Thirty consecutive patients diagnosed with idiopathic PD, who were on stable regimens of antiparkinsonian medication, able to walk independently, and had not participated in a rehabilitation program in the previous 3 months. Patients with severe cognitive impairments or severe musculoskeletal, cardiopulmonary, neurologic, or other systemic disorders were excluded. Twenty-four patients completed the study. INTERVENTIONS: Group I attended a training program on a treadmill for 6 weeks, and group II served as the control group. Both groups were instructed in home mobility exercises. MAIN OUTCOME MEASUREMENTS: The primary study outcome measures were timed functional lower-extremity tasks (walking at a corridor, U-turn, turning around a chair, stairs, standing on one foot, standing from a chair), and secondary outcome measures were exercise test and patient's global assessment. Assessments were performed at baseline and at the end of the study. RESULTS: There were significant improvements in functional lower-extremity tests, exercise test parameters, and patients' global assessment in group I, whereas no significant improvements were observed in group II. CONCLUSIONS: Even though long-term effects remain unknown and the study sample was small, it was concluded that treadmill training in PD patients led to improvements in lower-extremity tasks, thus improving patients' physical well-being in daily life.