Search

Estimates of the spectrum and frequency of pathogenic variants in Parkinsons disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinsons disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.

Background: Communication of people with Parkinson's disease (PwPD) is negatively affected. For PwPD with communication difficulties, it is important to use self‐assessment tools as a primary assessment approach to evaluate their perspectives on communication. It is also important to evaluate PwPDs with self‐assessment scales in order to determine in which situations their communicative effectiveness is affected and to include them in the intervention plan. Aims: To create a Turkish version of the Communicative Effectiveness Survey‐Revised (CES‐R), to examine its validity and reliability, and to investigate its applicability in PwPD. Method: The study included 106 PwPD and 106 healthy participants. The original form of the CES‐R was adapted into Turkish according to international guidelines. Every participant completed the Turkish version of CES‐R and the Voice Handicap Index‐10 form. The adapted scale was retested 2 weeks later. Outcomes and Results: Because the Kaiser‐Meyer‐Olkin coefficient was 0.956 in the exploratory factor analysis of the CES‐R and p < 0.01 for Bartlett's Test, the data set is 'perfectly' suitable for factor analysis. In the explanatory factor analysis applied in the CES‐R scale, the total explanatory ratio of the two dimensions was determined as 63.5%, and the validity condition was met. Cronbach's alpha coefficient was 0.958 in the PwPD group and 0.955 in the control group and the scale was found to be at the 'high reliability' level. Conclusion: The CES‐R is a valid, reliable, and useable self‐assessment scale for Turkish PwPD. Furthermore, this adaptation research was developed to assess possible communication difficulties for PwPD. With this tool, difficulties in communication skills that can be identified by a comprehensive evaluation should also be studied in the intervention processes. What this paper adds: What is already known on the subject: Self‐assessment tools are suggested as a primary use when evaluating people with Parkinson's disease (PwPD) with communication difficulties. The CES‐R is one of these self‐assessment scales. However, the validity and reliability study of the Communicative Effectiveness Survey‐Revised (CES‐R) in Turkish has not been conducted. What this paper adds to existing knowledge: This study demonstrates the validity and reliability of the Turkish CES‐R scale and its applicability to PwPD. Furthermore, this scale can be used in assessment procedures for possible communication difficulties for PwPD. What are the potential or actual clinical implications of this work?: The scale, which is unidimensional in the literature, was found to have two dimensions with eigenvalues > 1 in the Discovery Factor analysis in this study. The first dimension was named communication in general situations (CGS) and the second dimension was named communication in difficult situations (CDS). It is thought that this scale will be useful in research and clinics for the comprehensive assessment of PwPD with communication difficulties before and after treatment. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the validity and reliability of the Turkish version of the Sialorrhea Clinical Scale for Parkinson's disease (SCS-PD) for use in clinical settings. Methods: The original English version of SCS-PD has been adapted to Turkish (SCS-TR) in accordance with international guidelines. Fortyone patients with Parkinson's Disease (PD) and 31 healthy people were included in our study. SCS-TR, Movement Disorders Society United Parkinson's Disease Rating Scale (MDS-UPDRS) Part II (functional subscale 2.2 Saliva and drooling), Drooling Frequency and Severity Scale (DFSS) and The Non-Motor Symptoms Questionnaire (NMSQ) (1st question evaluating saliva) were applied to both groups. The adapted scale was re-tested in PD patients 2 weeks later. Results: A statistically significant relationship was determined between the SCS-TR scale score and all similar scale scores (NMSQ, MDS-UPDRS, DFSS) (p<0.001). The correlation between SCS-TR and similar scales scores was high, linear and positive (84.8% for MDS-UPDRS, 72.3% for DFSS and 70.1% for NMSQ). The Cronbach's alpha coefficient for the evaluation of the reliability of the sialorrhea clinical scale questionnaire was found to be 0.881 which indicates a very good internal consistency. Spearman's correlation test evaluating the relationship between the scores of the preliminary test and re-test of SCS-TR showed a high level, linear and positive relationship. Conclusion: SCS-TR is consistent with the original version of SCS-PD. As its validity and reliability in Turkey have been shown by our study, it can be used for the evaluation of sialorrhea in Turkish PD patients. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP/GC) genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) locus and vitamin D 25-hydroxylase (CYP2R1) gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features. Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene. There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease. In conclusion, genetic variants of the DHCR7/NADSYN1 locus and the CYP2R1 gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients. [ABSTRACT FROM AUTHOR]

Introduction: Although it has been shown that immunomodulatory therapies (IMTs) in multiple sclerosis (MS) can modify the course of the disease by reducing the relapse rate and delaying the progression of disability, no study comparing IMTs head-to-head in terms of clinical, radiological, and electrophysiological changes is available. We aimed to investigate the effects of interferon-beta (IFN-B) 1b, IFN-B-1a subcutaneous (sc), IFN-B-1a intramuscular (im), and glatiramer acetate (GA) therapies on clinical, electrophysiological, and radiological findings. Methods: We studied a cohort of 85 MS patients who were followed up for at least 2 years and had complete charting, including pre-treatment and post-treatment clinical, radiological, and electrophysiological findings. We compared the IMTs' effects on these findings retrospectively. Results: Annual relapse rates were 0.1 for IFN-B-1a sc, 0.2 for IFN-B- 1b, 0.3 for GA, and 0.5 for IFN-B-1 a im (p=0.01). The percentages of relapse-free patients after one year were 54.5% for IFN-B-1a im and GA, 82.9% for IFN-B-1a sc, and 86.4% for IFN-B-1b, and after two years the percentages were 27.3% for IFN-B-1a im, 54.5% for GA, 72.7% for IFNB- 1b, and 78% for IFN-B-1a sc (p<0.05). Disability scores after 2 years increased for IFN-B-1a im, decreased for IFN-B-1a sc (with a 0.1-point increase compared to the first year), and did not change for IFN-B-1b or GA compared to before treatment. Within the 2-year treatment period, no significant increase in the number of magnetic resonance T2 lesions was observed. No significant differences were found for any of the therapies in terms of evoked potentials. Conclusion: Our results revealed that high dose and more frequent regimens were more effective in terms of reducing the relapse rate, whereas there were no differences in terms of efficacy on radiological and electrophysiological findings between groups. Additional prospective studies comparing the efficacy of IMTs on MS are needed. [ABSTRACT FROM AUTHOR]

Sudden Unexpected Death in Epilepsy (SUDEP) is generally defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in patients with epilepsy, excluding documented status epilepticus. Reported SUDEP cases in Turkey are limited. Two cases of patients who died with diagnosis of probable SUDEP are described in the present report. Case 1: A 33-year-old female patient with generalized tonic-clonic seizures for nearly 20 years was referred to the clinic because of lack of complete seizure control despite years of different antiepileptic drug combinations. While in treatment, patient had a healthy pregnancy and seizure control was achieved with lamotrigine. Upon recurrence of seizures after pregnancy, valproate 300 mg/day was added to lamotrigine 150 mg/day. Patient died with diagnosis of probable SUDEP 2 years after the birth of the child. Case 2: A 42-year-old female patient with intractable complex partial and secondary generalized tonic-clonic seizures for about 30 years was admitted to the clinic. She had a history of epilepsy surgery. Topiramate therapy was added to carbamazepine 1200 mg/day and levetiracetam 2000 mg/day treatment. Subsequently, posterior temporal resection was performed, vagal nerve stimulation (VNS) was applied and barbexaclone 25 mg/day was added. Five months after the application of VNS, the patient died with diagnosis of probable SUDEP. These 2 cases of probable SUDEP may contribute to increased awareness of SUDEP and its features among neurologists. [ABSTRACT FROM AUTHOR]

Objectives: An analysis of clinical practice trends in use of conventional drugs to treat epilepsy versus newer antiepileptic drugs (AEDs) was conducted. Methods: Medical records of patients who presented at the clinic with diagnosis of epilepsy 2007-2012 were investigated retrospectively. Results: Data of 1126 patients were evaluated. Among them, 624 (55%) patients were treated using monotherapy, 449 (40%) patients received polytherapy, and 53 (5%) patients had no therapy. While 916 (81%) of the patients were using conventional AEDs, 447 (40%) of the patients were using newer AEDs. A total of 887 (79%) of the patients were using either valproate or carbamazepine. Of the 624 patients using monotherapy, 523 (84%) were on conventional AEDs and 101 (16%) patients were taking newer AEDs. Conclusion: In a previous study, the authors found the percentage choosing newer AEDs to be 1% before 1994, 10% in the period 1995-2000, and 14% in the period 2000-2007. Although the present study indicates that there was an increase (40%) in the use of newer AEDs in 2007-2012, it seems that conventional AEDs are still a first-line treatment choice, at least in Turkish clinical practice. Yet as both epileptologists and patients gain experience with newer AEDs, the trend is likely to change. [ABSTRACT FROM AUTHOR]