Can Voice Parameters Provide Cutoff Values to Predict Dysphagia in Individuals with Multiple Sclerosis?

In dysphagia assessment, along with well-defined measurements and signs, voice parameters can potentially support clinical decision as a marker, but more evidence is needed. This study aims to determine the voice parameters that can predict the risk of dysphagia and to determine optimal cutoff values in individuals with multiple sclerosis (IwMS). Seventy-six adults participated in the study, including 39 IwMS and 37 healthy individuals (HI). The study used the Dysphagia in Multiple Sclerosis Questionnaire (DYMUS), Gugging Swallowing Screen (GUSS), and Voice Handicap Index (VHI-10) and recorded voice samples using Praat programme. Voice recordings were taken pre- and post-swallowing. The voice parameters analysed are fundamental frequency (F0), standard deviation F0 (SD F0), jitter (local), shimmer (local), and harmonic-to-noise ratio (HNR). Roc analysis was performed to examine the diagnostic accuracy performance of the risk for dysphagia/penetration. The parameters of IwMS pre-swallowing differed significantly from those of HI on the VHI-10, DYMUS, GUSS scores, and jitter (local), shimmer (local), and HNR. IwMS but not HI exhibited significant differences in shimmer (local) and HNR between the pre- and post-swallowing measurements. In IwMS, GUSS revealed significant differences in shimmer (local) pre- and post-swallowing between the groups with and without dysphagia/penetration. In the ROC analysis results, the area under the curve (AUC) for shimmer (local) pre-swallowing was 73.1% (cutoff = 1.69); post-swallowing, it was 78.6% (cutoff = 1.57). In conclusion, IwMS can be associated with differences in shimmer (local) and HNR parameters, low quality of life-related to voice, and dysphagia/penetration risk. The AUC values for shimmer (local) in IwMS pre- and post-swallowing may help to strengthen diagnostic decisions of dysphagia risk.

Abducens Nerve Palsy in a Patient with COVID-19: A Case Report.

Numerous neurological manifestations associated with COVID-19 have been reported. However, abducens nerve palsy (ANP) associated with COVID-19 is very rare and mostly related to accompanying respiratory symptoms. Here we present a 29-year-old woman with unilateral ANP manifesting with diplopia and positive SARS-CoV-2 S antibodies, which were checked later. On admission, she had signs of viral pneumonia in thorax CT without any respiratory symptoms. Her cranial neuroimaging revealed no abnormality. Following treatment with favipiravir 2x1600 mg loading dose and then 2x600mg daily maintenance, dexamethasone 8 mg/day and enoxaparin 6000 IU/day, her CT findings recovered completely whereas her ANP only partially resolved. One week after the end of COVID-19 treatment, she also developed Herpes simplex keratitis which was successfully treated with valacyclovir. It should be kept in mind that isolated abducens nerve palsy may be the only finding of COVID-19 cases without any respiratory symptoms.

Drooling may be Associated with Dysphagia Symptoms in Multiple Sclerosis.

During the process of the multiple sclerosis (MS), persons with multiple sclerosis (PwMS) may experience drooling (sialorrhea) issues that are frequently disregarded. The exact cause of drooling in PwMS is poorly understood. This study aims to assess potential risk factors for drooling seen in PwMS. The study included 20 PwMS with drooling and 19 PwMS without drooling. The participants' sociodemographic data and clinical parameters were noted. To evaluate dysphagia, fatigue, and hypersalivation, the Dysphagia in Multiple Sclerosis Questionnaire (DYMUS), the Fatigue Severity Scale (FSS), and objective saliva flow rate measurement with cottons placed in Stensen ducts and under the tongue (swab test) were used, respectively. The study employed univariate and multivariate logistic regression models to identify the risk factors linked to drooling. Gender, age, disease duration, MS type, and Expanded Disability Status Scale scores did not differ between the two groups. There was a significant increase in the DYMUS and submandibular/sublingual (SM/SL) saliva flow rate values in PwMS with drooling (p = 0.009 and p = 0.019, respectively). However, in our study, hypersalivation was not observed in PwMS with or without drooling. In the univariate model, DYMUS, SM/SL saliva flow rate, and FSS were found to be risk factors for drooling in PwMS. But only DYMUS was shown to be a significant risk factor in the multivariate model obtained by the backward (Wald) elimination method (p = 0.023). Finally, our research is the first to demonstrate the relationship between drooling and the presence of dysphagia symptoms in PwMS. This is a very important study to determine the nature of drooling in PwMS. This finding shows that our study will serve as a reference for choosing the best method for drooling treatment.

Reliability and validity study of a Turkish version of the Communicative Effectiveness Survey-Revised (CES-R).

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.

Hypokinetic Dysarthria in Parkinson's Disease: A Narrative Review.

Numerous disabling motor and non-motor symptoms occur during Parkinson's disease (PD), including speech disorders, often referred to as hypokinetic dysarthria. PD is the most common cause of this type of dysarthria. About 90% of PD patients experience hypokinetic dysarthria, which is exacerbated as the disease progresses and makes it very difficult for other people to understand the person with PD. This disorder is characterized by a monotonous speech pattern, reduced and monotonous loudness, decreased stress, a breathy or hoarse voice quality, an increase in speech rate, rapid repetition of phonemes, and impreciseness in consonant production. However, patients may also have sensory symptoms including inaccurate perceptions of their own loudness and decreased awareness of speech problems. Hypokinetic dysarthria in PD may not only result from dopamine degeneration in the nigrostriatal pathway but also from disturbances in the motor and somatosensory systems. All speech components, such as phonation, articulation, respiration, resonance, and prosody should be assessed carefully in PD patients with hypokinetic dysarthria. Taking medical history, an oral motor assessment, a perceptual evaluation of speech characteristics, intelligibility, efficiency, and participation in communication all need to be a part of the assessment. The tasks of maximum phonation time, diadochokinetic rate, reading sentences, words, and passages, describing pictures, and spontaneous speech are used to assess the features of speech components and intelligibility. The evaluation should include physiological, acoustic, or imaging modalities as well. Speech therapy is typically the main treatment of speech problems in PD. The management of PD-related hypokinetic dysarthria basically focuses on speaker-oriented and communication-oriented strategies. In addition to these strategies, Augmentative Alternative Communication (AAC) should be considered in patients with severe dysarthria. Loudness, intelligibility, and sound perception may all significantly improve with the Lee Silverman Voice Therapy LOUD (LSVT LOUD) program which is an evidence-based program. The beneficial effect of pharmacological and surgical treatment approaches has not been proven in improving speech. Deep brain stimulation may carry the risk of the deterioration of speech as the illness progresses.

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson's Disease Project.

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.

Reliability and Validity Study of a Turkish Version of the Sialorrhea Clinical Scale for Parkinson's Disease (SCS-TR).

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. Forty-one 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.

Comparison of Clinical Characteristics of COVID-19-Related and Unrelated Acute Stroke Patients During the COVID-19 Pandemic in Turkey.

Objectives: Data on the co-occurrence of stroke and coronavirus disease 2019 (COVID-19) infection are limited and need to be improved. In our study, we aimed to evaluate the clinical and laboratory characteristics of COVID-19-related patients admitted to our center with acute stroke and compare them with acute stroke patients without COVID-19 infection during the same period. Methods: One hundred and eighty-four patients admitted with acute stroke from March 11, 2020, to May 11, 2020, were included in the study. Demographic and clinical characteristics, work-up studies, and clinical scales including National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (mRS) scores were examined retrospectively. All patients diagnosed with acute stroke who were also evaluated for COVID-19 before hospitalization were divided into two groups: COVID-19-related and unrelated cases. Results: COVID-19-related and unrelated acute stroke patients had similar characteristics in terms of age, gender, and stroke risk factors. The admission NIHSS (mean NIHSS: 9.8 vs. 5.9) scores and the discharge mRS values (mean mRS: 3.9 vs. 2.4) were significantly higher in the COVID-19-related stroke group (p=0.002 and p=0.001, respectively). The prognosis of the COVID-19-related stroke group was significantly worse (69.6% vs. 39.8%) and the mortality rate (39.1% vs. 6.2%) was significantly higher than the COVID-19-unrelated stroke group (p=0.007 vs. p=0.000, respectively). The proportion of patients with large infarcts in the COVID-19-related acute ischemic stroke group was significantly higher than the one in the COVID-19-unrelated acute ischemic stroke group (57.9% vs. 21.9%, p=0.003). Conclusion: This is the first comparative study to evaluate the clinical presentation and outcome of COVID-19-related acute ischemic and hemorrhagic stroke patients in Turkey. Our results suggest that COVID-19-related acute stroke is associated with more severe clinical presentation and worse outcome. This seems to be linked to the coagulation abnormalities induced by COVID-19 infection.

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.

LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol: Deep Phenotyping of an International Genetic Cohort.

Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions. Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data. Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA, RNA, serum/plasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2-linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants. Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn &Yahr, and Schwab & England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021). Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity Clinical Trial Registration:ClinicalTrials.gov, NCT04214509.

Low Levels of LRRK2 Gene Expression are Associated with LRRK2 SNPs and Contribute to Parkinson's Disease Progression.

Parkinson's disease (PD) is a chronic neurodegenerative disease that has relatively slow progression with motor symptoms. Leucine-rich repeat kinase 2 (LRRK2) gene mutations and polymorphisms are suggested to be associated with PD. In this study, we aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the LRRK2 gene, namely, rs11176013, rs10878371, rs11835105, and PD. Genotypes of 132 PD cases and 133 healthy individuals were determined by qRT-PCR. Haplotype analysis was performed. Additionally, LRRK2 mRNA expression levels were determined in 83 PD cases and 55 healthy subjects. The relationship between LRRK2 mRNA levels, the target SNPs, and clinical data was also investigated. Our results indicated that the "GG" genotype and "G" allele of rs11176013 and the "CC" genotype and "C" allele of rs10878371 were more frequent in cases. The "GCG" haplotype was significantly more frequent in cases. LRRK2 mRNA expression levels in patients were significantly lower than those in healthy individuals. The patients with the "CC" genotype for rs10878371 and the "GG" genotype for rs11176013 had decreased LRRK2 mRNA levels. We found that the rs11176013 "GG" genotype and the rs10878371 "CC" genotype were less frequently seen in cases with akinetic rigid or combined akinetic rigid and tremor-dominant initial symptoms. Consequently, our results demonstrate that the rs11176013 and rs10878371 polymorphisms are associated with PD in a Turkish cohort, and moreover, these results suggest that these polymorphisms may affect the expression of the LRRK2 gene and disease progression and thus play a role in the pathogenesis of PD.

Altered Transcriptional Profile of Mitochondrial DNA-Encoded OXPHOS Subunits, Mitochondria Quality Control Genes, and Intracellular ATP Levels in Blood Samples of Patients with Parkinson's Disease.

Mitochondrial dysfunctions are significant contributors to neurodegeneration. One result or a cause of mitochondrial dysfunction might be the disruption of mtDNA transcription. Limited data indicated an altered expression of mtDNA encoded transcripts in Alzheimer's disease (AD) or Parkinson's disease (PD). The number of mitochondria is high in cells with a high energy demand, such as muscle or nerve cells. AD or PD involves increased risk of cardiomyopathy, suggesting that mitochondrial dysfunction might be systemic. If it is systemic, we should observe it in different cell types. Given that, we wanted to investigate any disruption in the regulation of mtDNA encoded gene expression in addition to PINK1, PARKIN, and ATP levels in peripheral blood samples of PD cases who are affected by a neurodegenerative disorder that is very well known by its mitochondrial aspects. Our results showed for the first time that: 1) age of onset > 50 PD sporadic (PDS) cases: mtDNA transcription and quality control genes were affected; 2) age of onset <50 PDS cases: only mtDNA transcription was affected; and 3) PD cases with familial background: only quality control genes were affected. mtDNA copy number was not a confounder. Intracellular ATP levels of PD case subgroups were significantly higher than those of healthy subjects. We suggest that a systemic dysregulation of transcription of mtDNA or mitochondrial quality control genes might result in the development of a sporadic form of the disease. Additionally, ATP elevation might be an independent compensatory and response mechanism. Hyperactive cells in AD and PD require further investigation.

Factors Associated With Postoperative Confusion and Prolonged Hospital Stay Following Deep Brain Stimulation Surgery for Parkinson Disease.

BACKGROUND: Several patient and disease characteristics are thought to influence DBS outcomes; however, most previous studies have focused on long-term outcomes with only a few addressing immediate postoperative course. OBJECTIVE: To evaluate predictors of immediate outcomes (postoperative confusion and length of postoperative hospitalization) following deep brain stimulation surgery (DBS) in Parkinson disease (PD) patients. METHODS: We conducted a retrospective study of PD patients who underwent DBS at our institution from 2006 to 2011. We computed the proportion of patients with postoperative confusion and those with postoperative hospitalization longer than 2 d. To look for associations, Fisher's exact tests were used for categorical predictors and logistic regression for continuous predictors. RESULTS: We identified 130 patients [71% male, mean age: 63 ± 9.1, mean PD duration: 10.7 ± 5.1]. There were 7 cases of postoperative confusion and 19 of prolonged postoperative hospitalization. Of the 48 patients with tremors, none had postoperative confusion, whereas 10.1% of patients without tremors had confusion (P = .0425). Also, 10.2% of patients with preoperative falls/balance-dysfunction had postoperative confusion, whereas only 1.6% of patients without falls/balance-dysfunction had postoperative confusion (P = .0575). For every one-unit increase in score on the preoperative on-UPDRS III/MDS-UPDRS III score, the odds of having postoperative confusion increased by 10% (P = .0420). The following factors were noninfluential: age, disease duration, dyskinesia, gait freezing, preoperative levodopa-equivalent dose, number of intraoperative microelectrode passes, and laterality/side of surgery. CONCLUSION: Absence of tremors and higher preoperative UPDRS III predicted postoperative confusion after DBS in PD patients. Clinicians' awareness of these predictors can guide their decision making regarding patient selection and surgical planning.

Height and weight changes after deep brain stimulation in patients with Parkinson disease: role of clinical subtypes.

Increased body mass index (BMI) after deep brain stimulation (DBS) in Parkinson's disease (PD) has been repeatedly reported in literature. However, little is known about the effect of PD clinical subtypes on weight and height changes after DBS. We aimed to study the differential effect of tremor-predominant versus hypokinetic-rigid disease on weight and height changes after DBS. METHODOLOGY: we chart-reviewed PD patients who underwent DBS at our center from 2006 to 2011. Weight and height data were obtained at the pre-surgical period, at 1-year post-surgery, and at the latest available follow-up (LAF). RESULTS: There were 130 patients in the dataset (70% male, mean age 63+/-9.1). Eighty-eight patients had available data at 1-year post-DBS or longer. Mean LAF was 4.36+/-1.64 years. A BMI increment by 1 Kg/m2 or more was noticed in 35% after 1-year. Increased height (1cm-or-more) was seen in 24% of patients at 1-year. At 1-year post-DBS, 41.8% of patients with hypokinetic-rigid subtype increased in height compared to only 14.2% in the tremor-predominant group (OR 4.3, 95 % CI 1.3167-14.1246, P=0.015). There was no correlation between PD subtype and weight change after DBS. CONCLUSION: This study confirms BMI increase after DBS in PD patients and reports a novel finding of increased height after DBS in patients with hypokinetic-rigid PD. This might be secondary to improved axial rigidity following DBS. Resolution of tremor is probably unrelated to the increase in body weight after surgery since weight gain did not differ between patients with tremor-predominant and those with hypokinetic-rigid subtype.

A Computerized Cognitive behavioral therapy Randomized, Controlled, pilot trial for insomnia in Parkinson Disease (ACCORD-PD).

BACKGROUND: Parkinson disease (PD) is associated with a high prevalence of insomnia, affecting up to 88% of patients. Pharmacotherapy studies in the literature addressing insomnia in PD reveal disappointing and inconsistent results. Cognitive behavioral therapy (CBT) is a novel treatment option with durable effects shown in primary insomnia. However, the lack of accessibility and expense can be limiting. For these reasons, computerized CBT for insomnia (CCBT-I) has been developed. The CCBT-I program is a 6-week web-based course consisting of daily "lessons" providing learnable skills and appropriate recommendations to help patients improve their sleep habits and patterns. METHODS: We conducted a single-center, pilot, randomized controlled trial comparing CCBT-I versus standardized sleep hygiene instructions to treat insomnia in PD. Twenty-eight subjects with PD experiencing insomnia, with a score > 11 on the Insomnia Severity Index (ISI) were recruited. Based on a 6-point improvement in ISI in treatment group when compared to controls and an alpha = 0.05 and beta of 0.1 (power = 90%) a sample size of 11 patients (on active treatment) were required to detect this treatment effect using a dependent sample t-test. RESULTS: In total, 8/14 (57%) subjects randomized to CCBT-I versus 13/14 (93%) subjects randomized to standard education completed the study. Among completers, the improvement in ISI scores was greater with CCBT-I as compared to standard education (-7.9 vs -3.5; p = 0.03). However, in an intention-to-treat analysis, where all enrolled subjects were included, the change in ISI between groups was not significant (-.4.5 vs -3.3; p = 0.48), likely due to the high dropout rate in the CCBT-I group (43%). CONCLUSION: This pilot study suggests that CCBT-I can be an effective treatment option for PD patients with insomnia when the course is thoroughly completed. High drop-out rate in our study shows that although effective, it may not be a generalizable option; however, larger studies are needed for further evaluation.

Predictors of Functional and Quality of Life Outcomes following Deep Brain Stimulation Surgery in Parkinson's Disease Patients: Disease, Patient, and Surgical Factors.

OBJECTIVE: The primary objective was to evaluate predictors of quality of life (QOL) and functional outcomes following deep brain stimulation (DBS) in Parkinson's disease (PD) patients. The secondary objective was to identify predictors of global improvement. METHODS: PD patients who underwent DBS at our Center from 2006 to 2011 were evaluated by chart review and email/phone survey. Postoperative UPDRS II and EQ-5D were analyzed using simple linear regression adjusting for preoperative score. For global outcomes, we utilized the Patient Global Impression of Change Scale (PGIS) and the Clinician Global Impression of Change Scale (CGIS). RESULTS: There were 130 patients in the dataset. Preoperative and postoperative UPDRS II and EQ-5D were available for 45 patients, PGIS for 67 patients, and CGIS for 116 patients. Patients with falls/postural instability had 6-month functional scores and 1-year QOL scores that were significantly worse than patients without falls/postural instability. For every 1-point increase in preoperative UPDRS III and for every 1-unit increase in body mass index (BMI), the 6-month functional scores significantly worsened. Patients with tremors, without dyskinesia, and without gait-freezing were more likely to have "much" or "very much" improved CGIS. CONCLUSIONS: Presence of postural instability, high BMI, and worse baseline motor scores were the greatest predictors of poorer functional and QOL outcomes after DBS.

Clinical, Radiological and Electrophysiological Comparison of Immunomodulatory Therapies in Multiple Sclerosis.

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 IFN-B-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.

GC and VDR SNPs and Vitamin D Levels in Parkinson's Disease: The Relevance to Clinical Features.

Vitamin D deficiency is suggested to be associated with Parkinson's disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hundred eighty-two PD patients and 242 healthy subjects were included in this study. The serum 25OHD levels were investigated by CLIA, and GC and VDR SNPs were evaluated with LightSnip. Our results indicated a strong relationship between low serum 25OHD levels and PD (p < 0.001). rs7041 of GC and ApaI of VDR were associated with the PD risk (p < 0.05). Minor allele carriers for BsmI of VDR gene in both PD patients and healthy subjects had significantly higher levels of serum 25OHD (p < 0.05). The homozygous major allele carriers for rs2282679, rs3755967 and rs2298850 of GC gene in PD patients with slower progression had significantly higher levels of serum 25OHD (p  < 0.05). Minor allele carriers for FokI of VDR gene were more frequent in patients with advanced-stage PD (p < 0.05). Consequently, this is the first study demonstrating GC gene as a risk factor for PD. The relationship between PD's clinical features and low 25OHD or risk genotypes might have effects on PD independently.