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.

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.

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.

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.

Socioeconomic Status May Impact Functional Outcome of Deep Brain Stimulation Surgery in Parkinson's Disease.

OBJECTIVES: To investigate the association between socioeconomic status and deep brain stimulation (DBS) outcomes in Parkinson's disease (PD). MATERIALS AND METHODS: We analyzed a cohort of PD patients who underwent DBS from 2007 to 2011, who had Clinical Global Impression Scale-Improvement subscale (CGI-I) scores at approximately one year postsurgery. We also analyzed a subgroup of patients who had pre and postoperative Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II (functional subscale) and European Quality of Life Scale (EQ5D) scores. We performed regression analyses to determine the association between their median household income and their improvement in the MDS-UPDRS Part II, EQ-5D, and CGI-I post-DBS surgery. RESULTS: We analyzed 125 PD patients with CGI-I at one year post-DBS, including a subset of 43 patients who had pre- and post-DBS MDS-UPDRS Part II and EQ5D scores at 6 and 12 months. Median income was not significantly associated with the one-year CGI-I, the six-month MDS-UPDRS II, and the six-month and one-year EQ5D score. However, after adjusting for preoperative MDS-UPDRS II score, for every $10,000 increase in household median income, there was a 2.15-point improvement on the MDS-UPDRS II score after one year (95% confidence interval = -3.63 to -0.66, p = 0.0060). CONCLUSIONS: PD patients with higher household incomes had better functional improvement at one year. However, this did not necessarily translate to better quality of life or overall clinical improvement when compared with PD patients with lower household incomes. The influence of household income on DBS and other advanced therapies for PD will need further investigation.

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.

Clinical properties of regional thalamic hemorrhages.

BACKGROUND: Thalamic hemorrhage constitutes 6% to 25% of intracerebral hemorrhages. Vascular lesions affecting the thalamus may cause a variety of clinical symptoms. This retrospective study aims to evaluate localization of hemorrhage and clinical symptoms in patients with thalamic hemorrhage. METHODS: One hundred and one patients with thalamic hemorrhage were examined retrospectively in our department. Hemorrhages were classified into 5 groups according to computed tomography: medial (thalamoperforate), anterolateral (tuberothalamic), posterolateral (thalamogeniculate), dorsal (posterior choroidal), and global. The relation between volume, localization, and penetration to adjacent structures/ventricles of hemorrhage and risk factors, clinical features, and prognosis were evaluated. RESULTS: The study group included 101 patients. Eighty-two percent of the patients had hypertension, 19.8% had diabetes mellitus, 14.9% had cardiac disease, and 5.9% had chronic renal failure. Mean blood pressure was 173/101 mm Hg. Decreased Glasgow coma scale was significantly higher in the global hemorrhage group than in all regional groups (Chi-square, 10.54; P = .002). Medial group hemorrhages had a significantly higher rate than anterolateral, posterolateral, and dorsal intraventricular expansion. Out of speech disorders, 49% of patients had a right thalamic lesion (especially dysarthria) and 51% of patients had a left thalamic lesion (mostly aphasia). CONCLUSIONS: In the study, we detected that the most important risk factor in thalamic hemorrhage is hypertension. The prognosis is worse in global and medial group hemorrhages, especially those which rupture to the ventricle, than the other groups. Thalamic lesions cause a variety of symptoms, including forms of aphasia, such as crossed dextral aphasia.

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.

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.

Two-stage surgical approach with dermofat graft and lipofilling for the treatment of established Frey syndrome and facial depression deformity.

Frey syndrome and facial contour deformity commonly occur after parotid surgery. Although the treatment of established Frey syndrome has focused on medical solutions, surgical solutions to established Frey syndrome have been less reported. Moreover, these methods may not resolve the facial depression. In the presented case here, we used 2-stage surgical approach with dermofat graft and lipofilling for the treatment of established Frey syndrome and facial depression deformity. We considered that this technique provides the easiest, most practical, satisfying, and effective solution for Frey syndrome that develops in the late follow-up period after superficial parotidectomy.

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.

Serum adiponectin, TNF-α, IL-12p70, and IL-13 levels in multiple sclerosis and the effects of different therapy regimens.

OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory disease of the human central nervous system. In the present study, we aimed to determine adiponectin, tumor necrosis factor-α, interleukin (IL)-12p70, and IL-13 levels in the sera of patients with MS and to investigate the effects of interferon (IFN), glatiramer acetate (GA), and immunosuppressive treatment regimens on these parameters. METHODS: Fifty-seven patients with MS and 34 healthy controls were enrolled into the study. Serum cytokine levels were measured using enzyme immunoassay. RESULTS: Significantly elevated levels of IL-12p70 and IL-13 were found in the sera of patients with MS, but decreased adiponectin levels were found in patients' sera compared to healthy controls. The levels of IL-12p70 and IL-13 in the IFN therapy group were higher than those of the healthy controls. However, the IL-12p70 and IL-13 levels in the GA therapy group were not different from those of the healthy controls. There were no differences with regard to adiponectin levels among the subgroups of patients with MS according to therapy regimen and the healthy controls. At the end of a 2-year follow-up period, Expanded Disability Status Scale (EDSS) values were found to be increased in the IFN therapy group but unchanged in the GA therapy group. CONCLUSIONS: These findings suggest that adiponectin, IL-12p70, and IL-13 may play a role in the pathogenesis of MS. Additionally, GA therapy regimens in MS are more effective than IFN therapy with respect to decreasing the levels of IL-12p70 and IL-13 and stabilizing the EDSS value.

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.

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.

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.