Dissecting genetic architecture of rare dystonia: genetic, molecular and clinical insights.

BACKGROUND: Dystonia is one of the most common movement disorders. To date, the genetic causes of dystonia in populations of European descent have been extensively studied. However, other populations, particularly those from the Middle East, have not been adequately studied. The purpose of this study is to discover the genetic basis of dystonia in a clinically and genetically well-characterised dystonia cohort from Turkey, which harbours poorly studied populations. METHODS: Exome sequencing analysis was performed in 42 Turkish dystonia families. Using co-expression network (CEN) analysis, identified candidate genes were interrogated for the networks including known dystonia-associated genes and genes further associated with the protein-protein interaction, animal model-based characteristics and clinical findings. RESULTS: We identified potentially disease-causing variants in the established dystonia genes (PRKRA, SGCE, KMT2B, SLC2A1, GCH1, THAP1, HPCA, TSPOAP1, AOPEP; n=11 families (26%)), in the uncommon forms of dystonia-associated genes (PCCB, CACNA1A, ALDH5A1, PRKN; n=4 families (10%)) and in the candidate genes prioritised based on the pathogenicity of the variants and CEN-based analyses (n=11 families (21%)). The diagnostic yield was found to be 36%. Several pathways and gene ontologies implicated in immune system, transcription, metabolic pathways, endosomal-lysosomal and neurodevelopmental mechanisms were over-represented in our CEN analysis. CONCLUSIONS: Here, using a structured approach, we have characterised a clinically and genetically well-defined dystonia cohort from Turkey, where dystonia has not been widely studied, and provided an uncovered genetic basis, which will facilitate diagnostic dystonia research.

Autoimmune Encephalitis with Antibodies Against A-Amino-3hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor and γ-Aminobutyric Acid-Beta Receptor: Case Report.

Introduction: Limbic encephalitis is a rapidly progressing disease that presents with seizures, psychiatric symptoms, and recent memory loss. Detection of more than one autoantibody is a rare condition in this disease where an underlying autoantibody is frequently detected. Although different autoantibodies have been reported in the literature, no case has been reported regarding the association of anti-γ-aminobutyric acid-beta-receptor (anti-GABABR) and anti-α-amino-3 hydroxy-5-methyl-4-isoxazolepropionic acid (anti-AMPAR). Case: In this presentation, a 46-year-old female patient with subacute development of short-term memory loss and behavioral symptoms will be described. Anti-GABABR and anti-AMPAR were positive in the anti-neuronal antibody panel sent from the cerebrospinal fluid and serum. Small cell lung cancer was detected as a result of malignancy screening tests. The patient's complaints and autoantibody positivity regressed after immunotherapy. Conclusion: In this case report, a case with coexistence of anti-GABABR and anti-AMPAR antibodies, which has not been previously reported in the literature, is described. As more cases with the coexistence of these two antibodies are detected, knowledge on clinical aspect, laboratory and treatment will increase.

Cultural adaptation and clinical validation of Rapid Cognitive Screening Test in Turkish.

BACKGROUND: The Rapid Cognitive Screen (RCS) is a brief, easy to administer score screening tool for cognitive dysfunction which can be very useful for cognitive screening in busy clinical settings. We aimed to cross-culturally adapt and validate RCS in Turkish. METHODS: A total of 172 community-dwelling older participants from geriatric and neurology clinics, aged 60 and older were included. The translation and cultural adaptation process was carried out in five stages: (i) two initial translations from English to Turkish; (ii) combination of these two translations; (iii) backward translations; (iv) an expert committee that consisted of three geriatricians and two neurologists, one Turkish lecturer reviewed to compare backward translations with the English test; and (v) pretest. The inter-rater reliability and test-retest reliability were performed. To diagnose each type of dementia, gold standard diagnostic criteria specifically defined for each dementia were used. Performances of RCS test for dementia and mild cognitive impairment (MCI) were analyzed by using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The receiver operating characteristic analysis was performed to determine the area under the curve (AUC) with 95% confidence intervals (CI). RESULTS: Among participants, 37.2% were considered as cognitively normal, 25.6% with MCI and 37.2% with dementia. The sensitivity, specificity, PPV, and NPV of RCS (cut-off point of 4) for dementia were 89.06%, 92.56%, 87.7%, and 93.5%, respectively whereas the values were 77.27%, 51.56%, 52.3%, and 76.7% for MCI with a cut-off point of 8. The RCS predicted dementia (AUC = 0.972, 95% CI: 0.935-0.991) and MCI (AUC = 0.720%, 95% CI: 0.626-0.802). CONCLUSION: The cross-cultural adaptation was successfully achieved. The Turkish-RCS was found to be a reliable and valid test for screening of cognitive dysfunction.

Evaluation of Post-Swallow Residue with Visual Analysis of Swallowing Efficiency and Safety in Patients with Idiopathic Parkinson's Disease.

Objectives: Dysphagia is common in idiopathic Parkinson's disease (IPD) and is associated with impairments in both swallowing safety and swallowing efficiency. The goals of this study were to define post-swallow residue patterns in people with IPD and describe pathophysiological endoscopic findings affecting residue accumulation. Methods: This was a prospective single-blinded cross-sectional cohort study of patients with the diagnosis of IPD recruited from a Movement Disorder Clinic. Clinical variables included patient age, cognitive function, and measures of disease severity, and laryngoscopic examinations with a flexible endoscopic evaluation of swallowing (FEES) were completed for each patient. Visual Analysis of Swallowing Efficiency and Safety (VASES) was used to analyze FEES. Post-swallow residue outcomes and non-residue endoscopic outcomes including the Bowing index, Penetration Aspiration Scale (PAS) score, premature leakage, and build-up phenomenon were evaluated. Multiple regression models were used to evaluate factors affecting the residue at different anatomic levels. Results: Overall 53 patients completed the study. The multiple regression analyses showed a relation between (1) the presence of residue at the level of oropharynx and epiglottis with premature leakage, (2) the presence of residue at the level of the laryngeal vestibule and vocal folds with build-up phenomenon, and (3) the presence of residue at the level of the hypopharynx, laryngeal vestibule, and subglottis with airway invasion. Conclusion: Residue pattern during FEES is associated with specific swallow dysfunctions in IPD. Using residue localization and quantification may be a helpful tool in assessing the impact of targeted swallowing interventions in patients with IPD and dysphagia.

An Investigation of Affective Personality Traits in Alzheimer's Disease: SEEKING as a Possible Predictor for Early-Stage Alzheimer's Dementia.

OBJECTIVE: The aim of the current study was to investigate affective personality traits in Alzheimer's disease, a neurodegenerative condition mainly characterized by episodic memory impairment. METHOD: The sample included 69 participants from 3 diagnostic categories. Twenty-five participants were diagnosed with subjective cognitive impairment (SCI), 26 participants were diagnosed with mild cognitive impairment of the amnestic type (aMCI), and the remaining 18 participants were diagnosed with early-stage Alzheimer's dementia (ADD). Diagnostic labels were given as a result of detailed neurological, neuropsychological, and neuroradiological assessment. Affective personality traits were assessed via Affective Neuroscience Personality Scales (ANPS). RESULTS: The only significant intergroup difference was obtained for the SEEKING subscale of ANPS. Here, ADD group scored significantly lower compared to the SCI group. The results of logistic regression analysis also indicated that SEEKING score successfully predicted early-stage ADD diagnosis. CONCLUSION: The results suggest that a specific personality constellation characterized by reduced investment in the outside world might be associated with Alzheimer's disease, either as a risk factor or a byproduct of the neurodegenerative process initiated by AD pathology.

Validity and Reliability of the Pictures of Facial Affect (POFA) in Healthy People and Patients with Essential Tremor in the Turkish Population.

Introduction: This study aimed to conduct the validity and reliability of the (Pictures of Facial Affect) POFA test for the Turkish population and contribute to increasing the number of tests that are still insufficient in our country. Methods: This descriptive, randomized controlled study was conducted in two steps, namely Step 1 (Pilot Study and Validity Studies) and Step 2 (Reliability Study Step). The number of participants was planned regarding the original study by which the POFA test was developed. The EYES test was also used for comparison. In the pilot study, the most widely identified emotions from 47 of 110 photos in the POFA test were chosen as the new POFA picture set to be used in the reliability and validity study under the name "POFA Test Short Form". A total of 100 participants, including 82 healthy volunteers and 18 essential tremor (ET) patients, were enrolled in the first step of the study. Another cohort of 22 healthy volunteers was enrolled in the second step of the study for test-retest reliability analysis. Results: A significant positive correlation was found between the total POFA Test Short Form and EYES Test scores in the healthy volunteer group in terms of criterion-related validity (r=0.44, p<0.01). There were statistically significant differences between healthy volunteers and ET groups regarding EYES Total, POFA Total, POFA Sadness, POFA Anger, and POFA Neutral scores. It was observed that the 47-item POFA Test Short Form total score showed skewness and kurtosis, which demonstrated suitability for clinical use. Conclusion: The POFA Test Short Form was found to be a valid and reliable assessment tool in the Turkish population to be used in studies on emotion recognition and was shown to be beneficial for the discrimination of healthy individuals and ET patients.

Caregiver support and burden drive intention to engage in a peer-to-peer exchange of services among caregivers of dementia patients.

Introduction: The number of people diagnosed with dementia is increasing, creating significant economic burden globally. With the progression of the disease, patients need a caregiver whose wellbeing is important for continuous care. Providing respite as a service, through sharing the responsibility of caregiving or support for the caregiver, is a costly initiative. A peer-to-peer online support platform for dementia caregivers, motivated by the sharing economy, putting exchange of knowhow, resources, and services at its center, has the potential to balance cost concerns with a search for respite. The aim of this research is to assess caregivers' intention to engage in peer-to-peer exchange. Methods: A survey including sociodemographic, technology use, and caregiving variables, structured questionnaires (Zarit caregiver burden, WHO brief quality of life scale, ADCS-ADL and chronic stress scale) were administered, January 2018-May 2019, in the dementia outpatient clinic of a university hospital, to a convenience sample of n = 203 individuals identifying themselves as primary caregivers. A path analysis exploring the drivers of an intention to engage in peer-to-peer service exchange was conducted. Results: In the path model, caregivers experiencing higher caregiver burden showed higher intention to engage (0.079, p < 0.001). Disease stage had no effect while patient activities of daily living, chronic social role related stressors of the caregiver and general quality of life were significant for the effect on the caregiver burden. Existing household support decreased the caregiver burden, affecting the intention to engage. Caregivers who can share more know-how demonstrate a higher intention to engage (0.579, p = 0.021). Caregiver technology affinity (0.458, p = 0.004) and ability and openness to seek professional help for psychological diagnoses (1.595, p = 0.012) also increased intention to engage. Conclusion: The model shows caregiver burden to be a major driver, along with caregiver characteristics that reflect their technology affinity and openness to the idea of general reciprocity. Existing support for obtaining knowhow and exchanging empathy have a direct effect on the intention to engage. Given the scarcity of caregiver support in the formal care channels, the identified potential of enlarging informal support via a peer-to-peer exchange mechanism holds promise.

Morphometric analysis of medial temporal lobe subregions in Alzheimer's disease using high-resolution MRI.

The spread pattern of progressive degeneration seen in Alzheimer's disease (AD) to small-scale medial temporal lobe subregions is critical for early diagnosis. In this context, it was aimed to examine the morphometric changes of the hippocampal subfields, amygdala nuclei, entorhinal cortex (ERC), and parahippocampal cortex (PHC) using MRI. MRI data of patients diagnosed with 20 Alzheimer's disease dementia (ADD), 30 amnestic mild cognitive impairment (aMCI), and 30 subjective cognitive impairment (SCI) without demographic differences were used. Segmentation and parcellation were performed using FreeSurfer. The segmentation process obtained volume values of 12 hippocampal subfields and 9 amygdala nuclei. Thickness values of ERC and PHC were calculated with the parcellation process. ANCOVA was performed using age, education and gender as covariates to evaluate the intergroup differences. Linear discriminant analysis was used to investigate whether atrophy predicted groups at an early stage. ERC and PHC thickness decreased significantly throughout the disease continuum, while only ERC was affected in the early stage. When the hippocampal and amygdala subfields were compared volumetrically, significant differences were found in the amygdala between the SCI and aMCI groups. In the early period, only volume reduction in the anterior amygdaloid area of the amygdala nuclei exceeded the significance threshold. Research on AD primarily focuses on original hippocampocentric structures and their main function which is episodic memory. Our results emphasized the significance of so far relatively neglected olfactocentric structures and their functions, such as smell and social cognition in the pre-dementia stages of the AD process.

Eating Difficulties and Relationship With Nutritional Status Among Patients With Dementia.

BACKGROUND: One of the most common behavioral problems in patients with dementia is eating problems, which are known to increase the risk of malnutrition. However, few studies have been conducted in this patient group regarding the relationship between eating difficulties and nutritional status. PURPOSE: This study was designed to determine the eating difficulties faced by patients with dementia and to evaluate the relationship in this population between eating difficulties and malnutrition. METHODS: This study was carried out in a dementia outpatient clinic of a university hospital in Istanbul, Turkey. This cross-sectional, case-control study included 50 patients and 50 healthy controls as participants. Participants were assessed for eating difficulties and for nutritional, cognitive, and functional statuses. RESULTS: The patients with dementia had more difficulties in terms of self-feeding skills. Although problems related to manipulating food on the plate and the use of utensils were not seen in the control group, these problems were found in 30% of the participants in the dementia group ( p < .001). Moreover, 30% of the patients in the dementia group were unable to eat without assistance ( p < .001). Associations were found between eating difficulties and age, duration of illness, and cognitive and functional (basic and instrumental activities of daily living) statuses. In addition, self-feeding skills were found to be associated with nutritional status. Rate of malnutrition or risk of malnutrition was higher in patients with dementia than in those in the control group. CONCLUSIONS: In this study, compared with the control group, patients with dementia had more problems in self-feeding skills such as manipulation of food on a plate, use of utensils, need for assistive tools, ability to eat without assistance, and negative eating behaviors (refusal to eat). An association was found between eating difficulties and nutritional status. Evaluating eating difficulties is recommended in patients with dementia to prevent nutritional deterioration.

Medication management and treatment adherence in Parkinson's disease patients with mild cognitive impairment.

INTRODUCTION: The key feature that distinguishes mild cognitive impairment (MCI) from dementia is the absence of significant functional decline because of cognitive impairment. In Parkinson's disease patients (PD) with MCI (PD-MCI), the effect of cognitive impairment on complex instrumental daily activities, such as medication management, is not well established. METHOD: 26 patients with PD-MCI (diagnosed to Level 2 Movement Disorders Society diagnostic criteria) and 32 idiopathic PD patients without cognitive impairment participated in the study. A detailed neuropsychological testing battery (including tests for attention and working memory, executive functions, language, visuospatial functions, episodic memory) and various prospective memory tasks were applied to the patients. Medication taking behaviors were evaluated using two different methods based on the performance (medication management ability assessment) and self-reporting (adherence scale). RESULTS: The PD-MCI group obtained significantly lower scores in medication management assessment and made more mistakes on following prescription instructions (e.g., they took more or less tablets and did not use medications as instructed with regard to meal times). Cognitive areas predicting success in medication management performance were language, event-based prospective memory and visuospatial functions. There was no significant difference between the two groups' self-reporting of adherence. CONCLUSION: Mild cognitive impairment in patients with PD adversely affects medication management. Diagnosing MCI in PD is important to ensure that the appropriate measures can be taken to provide support and improve the medication management process. Adherence assessments based on self-reporting may not provide reliable and sensitive information in patients with PD-MCI.

TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently sporadic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations.

Anticholinergic Burden, Polypharmacy, and Cognition in Parkinson's Disease Patients with Mild Cognitive Impairment: A Cross-Sectional Observational Study.

INTRODUCTION: Anticholinergic burden may be an important risk factor for the cognitive impairment. Especially in polypharmacy, even drugs with low anticholinergic effects may contribute to a significant anticholinergic burden. The drugs with anticholinergic effects are used in treatment of motor and nonmotor symptoms of Parkinson's disease (PD). Therefore, it is important to screen for polypharmacy and anticholinergic burden in PD patients with mild cognitive impairment (MCI). METHODS: This cross-sectional study was conducted with 58 patients with PD. PD-MCI was diagnosed according to MDS Level 2 Comprehensive Assessment. Cognitive performance (attention - working memory, executive functions, language, memory, and visuospatial functions) of patients was evaluated. The anticholinergic burden was scored by Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), and Anticholinergic Drug Scale (ADS). RESULTS: There was no significant difference in anticholinergic burden between PD-MCI and PD-normal cognition. A significant concordance was observed between ACB, ARS, and ADS scores (p < 0.001; Kendall's W = 0.653). While the variable predicting anticholinergic burden was the total number of drugs for ACB and ADS scales, it was the number of antiparkinson drugs for ARS scale. CONCLUSION: Patients with PD are at high risk for polypharmacy and anticholinergic burden. Anticholinergic burden should be considered in the selection of drugs, especially for comorbidities in patients with PD. No significant correlation was found between the cognition and anticholinergic burden in patients with PD-MCI. Although the risk scores of antiparkinson and other drugs were different among the 3 scales, significant concordance was observed between scales.

Identification of metabolic correlates of mild cognitive impairment in Parkinson's disease using magnetic resonance spectroscopic imaging and machine learning.

OBJECTIVE: To investigate metabolic changes of mild cognitive impairment in Parkinson's disease (PD-MCI) using proton magnetic resonance spectroscopic imaging (1H-MRSI). METHODS: Sixteen healthy controls (HC), 26 cognitively normal Parkinson's disease (PD-CN) patients, and 34 PD-MCI patients were scanned in this prospective study. Neuropsychological tests were performed, and three-dimensional 1H-MRSI was obtained at 3 T. Metabolic parameters and neuropsychological test scores were compared between PD-MCI, PD-CN, and HC. The correlations between neuropsychological test scores and metabolic intensities were also assessed. Supervised machine learning algorithms were applied to classify HC, PD-CN, and PD-MCI groups based on metabolite levels. RESULTS: PD-MCI had a lower corrected total N-acetylaspartate over total creatine ratio (tNAA/tCr) in the right precentral gyrus, corresponding to the sensorimotor network (p = 0.01), and a lower tNAA over myoinositol ratio (tNAA/mI) at a part of the default mode network, corresponding to the retrosplenial cortex (p = 0.04) than PD-CN. The HC and PD-MCI patients were classified with an accuracy of 86.4% (sensitivity = 72.7% and specificity = 81.8%) using bagged trees. CONCLUSION: 1H-MRSI revealed metabolic changes in the default mode, ventral attention/salience, and sensorimotor networks of PD-MCI patients, which could be summarized mainly as 'posterior cortical metabolic changes' related with cognitive dysfunction.

Does transcranial direct current stimulation enhance cognitive performance in Parkinson's disease mild cognitive impairment? An event-related potentials and neuropsychological assessment study.

BACKGROUND: Parkinson's disease-mild cognitive impairment (PD-MCI) is garnering attention as a key interventional period for cognitive impairment. Currently, there are no approved treatments for PD-MCI and encouraging results of transcranial direct current stimulation (tDCS) combined with other interventions have been proposed, though the efficacy and neural mechanisms of tDCS alone have not been studied in PD-MCI yet. OBJECTIVES: The present double-blind, randomized, sham-controlled study assessed the effects of tDCS over the dorsolateral prefrontal cortex on cognitive functions via neuropsychological and electrophysiological evaluations in individuals with PD-MCI for the first time. METHOD: Twenty-six individuals with PD-MCI were administered 10 sessions of active (n = 13) or sham (n = 13) prefrontal tDCS twice a day, for 5 days. Changes were tested through a comprehensive neuropsychological battery and event-related potential recordings, which were performed before, immediately, and 1 month after the administrations. RESULTS: Neuropsychological assessment showed an improvement in delayed recall and executive functions in the active group. N1 amplitudes in response to targets in the oddball test-likely indexing attention and discriminability and NoGo N2 amplitudes in the continuous performance test-likely indexing cognitive control and conflict monitoring increased in the active group. Active stimulation elicited higher benefits 1 month after the administrations. CONCLUSION: The present findings substantiate the efficacy of tDCS on cognitive control and episodic memory, along with the neural underpinnings of cognitive control, highlighting its potential for therapeutic utility in PD-MCI. TRIAL REGISTRATION: NCT 04,171,804. Date of registration: 21/11/2019.

Genotype-Phenotype correlations of SCARB2 associated clinical presentation: a case report and in-depth literature review.

BACKGROUND: Biallelic pathogenic variants in the SCARB2 gene have been associated with action myoclonus-renal failure (AMRF) syndrome. Even though SCARB2 associated phenotype has been reported to include typical neurological characteristics, depending on the localization and the feature of the pathogenic variants, clinical course and the presentations have been shown to differ. CASE PRESENTATION: Whole exome sequencing (WES) analysis revealed a homozygous truncating variant (p.N45MfsX88) in SCARB2 gene in the index case, and subsequent sanger sequencing analysis validated the variant in all affected family members from a Turkish family with the clinical characteristics associated with AMRF and related disorders. Intrafamilial clinical heterogeneity with common features including dysarthria, tremor and proteinuria, and distinct features such as peripheral neuropathy (PNP), myoclonus and seizures between the affected cases, was observed in the family. In-depth literature review enabled the detailed investigation of the reported variants associated with AMRF and suggested that while the type of the variant did not have a major impact on the course of the clinical characteristics, only the C terminal localization of the pathogenic variant significantly affected the clinical presentation, particularly the age at onset (AO) of the disease. CONCLUSIONS: In this study we showed that biallelic SCARB2 pathogenic variants might cause a spectrum of common and distinct features associated with AMRF. Of those features while the common features include myoclonus (100%), ataxia (96%), tonic clonic seizures (82%), dysarthria (68%), tremor (65%), and renal impairment (62%), the uncommon features involve PNP (17%), hearing loss (6.8%), and cognitive impairment (13.7%). AO has been found to be significantly higher in the carriers of the p.G462DfsX34 pathogenic variant. SCARB2 pathogenic variants have not been only implicated in AMRF but also in the pathogenesis of Parkinson's disease (PD) and Gaucher disease (GD), suggesting the importance of genetic and functional studies in the clinical and the diagnostic settings. Given the proven role of SCARB2 gene in the pathogenesis of AMRF, PD and GD with a wide spectrum of clinical symptoms, investigation of the possible modifiers, such as progranulin and HSP7, has a great importance.

Genetic variants of vitamin D metabolism-related DHCR7/NADSYN1 locus and CYP2R1 gene are associated with clinical features of Parkinson's disease.

PURPOSE/AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (canvas): an important cause of late-onset ataxia with unique clinical features.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slowly progressive disorder characterized by cerebellar ataxia, sensory neuropathy and bilateral vestibulopathy. Recently, a biallelic intronic AAGGG repeat expansion, (AAGGG)exp, in the Replication Factor C1 (RFC1) gene was identified as the cause of this disorder. In this study, we describe the phenotypic features of five patients from five different families diagnosed as CANVAS. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. The mean age at onset was 49.00 ± 9.05 years (between 34 and 56 years) and the most frequent presenting symptom in CANVAS was gait ataxia, followed by sensory disturbances. Persistent coughing was prominent in three patients, and it preceded the onset of ataxia and sensory symptoms in two patients. Parental consanguinity was present in three patients. Two patients showed symptoms or signs suggesting autonomic involvement. Sural nerve biopsy revealed axonal neuropathy in two patients. Our study describes clinical findings, histopathological features and diagnostic clues of CANVAS from Turkey, a country with a high consanguineous marriage rate. Repeat expansion in the RFC1 gene should be considered in all cases with late-onset ataxia, especially when sensory disturbances, vestibular involvement and persistent coughing coexist.

Intensive voice treatment (the Lee Silverman Voice Treatment [LSVT®LOUD]) for individuals with Wilson's disease and adult cerebral palsy: two case reports.

Objective: In this case report, we aimed to examine the effects of an intensive voice treatment (the Lee Silverman Voice Treatment [LSVT®LOUD]) for Wilson's disease (WD), and adult cerebral palsy (CP), and dysarthria.Method: The participants received LSVT®LOUD four times a week for 4 weeks. Acoustic, perceptual (GRBAS) analyses were performed and data from the Voice Handicap Index (VHI) were obtained before and after treatment.Results: Besides the Harmonics-to Noise Ratio (HNR) value (dB) of the participant with WD, for both participants' fundamental frequencies (Hz), jitter (%), and shimmer (%) values showed significant differences (p < .05) after therapy. Both participants showed significant improvements (p < .05) in the duration (s) and the sound pressure level (dB, SPL) of sustained vowel phonation (/a/), in SPL (dB) of pitch range (high and low /a/) and reading and conversation (p < .01). There was a positive improvement in the high-frequency values (Hz) of both participants but not in the low-frequency values (Hz) in the participant with WD. Perceptual analysis with GRBAS judgements of sustained vowel (/a/) and paragraph reading of two participants also showed improvement. After therapy, perceived loudness of the participants' voice increased.Conclusions: The findings provide some preliminary observations that the individuals with WD and the adult individuals with CP can respond positively to intensive speech treatment such as LSVT®LOUD. Further studies are needed to investigate speech treatments specific to WD and adult CP.