Sleep quality, excessive daytime sleepiness, and depression in Parkinson's disease: implications for improved patient outcomes.

OBJECTIVES: Sleep disorders are frequently encountered non-motor symptoms that significantly impact the lifestyle quality of individuals with Parkinson's disease (PD). Our research endeavors to research the sleep quality of PD patients and define the occurrence of excessive daytime sleepiness (EDS) and nocturnal difficulties within this population. METHODS: We incorporated 140 patients diagnosed with PD and 75 healthy individuals as controls. The modified Hoehn & Yahr Staging Scale (HYS) was employed for the clinical classification of PD stages, while the evaluation of clinical intensity utilized the Unified Parkinson's Disease Rating Scale (UPDRS). The assessment of sleep quality utilized the Pittsburgh Sleep Quality Index (PSQI), along with the Parkinson's Disease Sleep Scale (PDSS), and the Epworth Sleepiness Scale (ESS). Additionally, the subjective depression levels of attendees were assessed by the Beck Depression Inventory. RESULTS: In contrast to the healthy controls, the patient cohort demonstrated notably higher scores across the PSQI scale, ESS, and Beck Depression Scale (p < 0.05). Within the PD patient group, 66.4% exhibited poor sleep quality, and 17.1% reported excessive daytime sleepiness. A significant positive correlation was between poor sleep quality and factors such as H&Y stage, duration of levodopa exposure, scores on the ESS, and the BDI (p < 0.05). Additionally, EDS was positively correlated with UPDRS-I scores, Levodopa equivalent daily dose, PSQI, and BDI scores (p < 0.05). DISCUSSION: Addressing the specific etiology of sleep disorders in Parkinson's patients has the potential to result in improved treatment outcomes and enhanced functionality in their daily lives.

Alexithymia, depression, and cognition in patients with Parkinson's disease.

BACKGROUND: Basal ganglia are connected to dorsal prefrontal and orbitofrontal structures, which have an important role in emotional experience. Alexithymia is defined as the inability to recognize and verbalize emotions. There is little known about alexithymia and cognitive dysfunction and its relationship with depression. In this study, we examined the relation of alexithymia with cognition and depression in non-demented patients with Parkinson's disease (PD). MATERIALS AND METHODS: Fort-two consecutive non-demented patients PD and 40 healthy controls were enrolled in the study. The Turkish version of the Montreal Cognitive Assessment scale (MOCA-TR), 20-item Toronto Alexithymia Scale (TAS-20) (F1, F2, F3 subgroups), and Beck Depression Inventory (BDI-I) were used to evaluate cognitive functions, alexithymia, and depression, respectively, in both groups. RESULTS: The total TAS-20 score was 55.71 ± 19 in the PD group and 46.33 ± 8.21 in the control group. There was a statistically significant difference in the total TAS-20 scores between the groups (p < 0.001). In subgroups of alexithymia, all mean scores of F1, F2, and F3 were higher in the PD group (p = 0.019, p < 0.001, and p = 0.005, respectively). In the MOCA-TR test, the mean scores in visuospatial and delayed recall of patients with PD were statistically lower than in the control group (p = 0.044 and p = 0.04, respectively). The MOCA-TR and BDI total scores were significantly correlated with TAS-20 total scores. In subgroup analysis, we only found an association between the visuospatial domain of MOCA-TR and the F3 subgroup of TAS-20 (r = - 0.22, p = 0.03). There was no relation between alexithymia and disease duration or total levodopa dose (p < 0.05). CONCLUSION: Alexithymia is not a rare symptom in PD. It should be accepted as an independent non-motor symptom, and patients should be interrogated accordingly.

The Influence of ADORA2A on Levodopa-Induced Dyskinesia.

Background: Dopamine deficiency causes Parkinson's disease (PD), and on treatment, levodopa is the gold standard. Various drug-metabolizing enzymes and drug receptors are believed to be involved in prompting dyskinesias due to the extended usage of levodopa. Shreds of evidence in genomic studies have presented that ADORA2A receptor antagonism has beneficial outcomes to avoid these drug-induced side effects. Objective: The aim of this study was to study the polymorphisms of rs2298383, rs35060421, and rs5751876 in the ADORA2A in patients diagnosed as PD and describe their possible relationships with levodopa-induced dyskinesias (LID). Methods: One-hundred and seventy-two patients were recruited and separated as the study and the control group. DNA was achieved from peripheral venous blood, high resolution melting analysis, and reverse-transcriptase PCR was performed. Results: The allele differences among the groups were not statistically significant. Although it was not statistically significant, the rs35060421 allele was observed to repeat more frequently. However, we did not find an association between such polymorphisms of ADORA2A and LID. Conclusions: Although this result showed that a higher sample number might produce different results as possible, current results in the Turkish sample indicated that these alleles of ADORA2A might not be related to LID in patients.

Uric acid: The role in the pathophysiology and the prediction in the diagnosis of Parkinson's disease: A Turkish-based study.

BACKGROUND AND PURPOSE: Oxidative stress has been associated as an essential contributor to the development of neurodegenerative diseases. Recent developments in the field of Parkinson's Disease (PD) pathophysiology have led to a renewed interest in this field. As an antioxidant, uric acid (UA) has arisen as a potential neuroprotectant. Higher concentrations of UA are linked to reducing the risk of the development of the disease and preventing its progression. However, the expositions are unsatisfactory because the outcomes of these reports have not been consistent. This study is set out to assess the association of whether lower UA concentrations increased the PD risk by investigating its relationship with patients' demographic and clinical data, and to determine whether previous studies are compatible with the Turkish-sampled population. Furthermore, we aimed to determine UA's probability of being an early-stage diagnostic marker. METHODS: A total of 305 patients and 100 healthy controls were included. Serum UA levels of patients and controls were compared with clinical features. We classified the patients into three motor subtypes and determined the disease severity by modified Hoehn&Yahr Staging Scale (mH&Y) and Unified Parkinson's Disease Rating Scale (UPDRS). Standardized Mini-Mental State Examination (MMSE-TR) was assessed for cognition. RESULTS: There were not any significant differences of age and sex between patients and controls (p=0.030, p=0.132). The mean UA was 5.06±1.33 mg/dL in patients and 5.46±1.44 in controls, and a statistical significance was detected (p=0.022). The mean MMSE-TR were 24.83±4.35 in patients and 27.09±2.13 in controls, and statictical significance was revealed (p=0.001). The mean duration of the disease was 6.31±4.16 years, mean UPDRS scores were 59.74±22.33, and mH&Y scores were 2.29±0.91. In binary comparisons, patients with tremor-dominant motor subtype had lower UA concentrations than controls (p=0.014). ROC curve analysis revealed UA's cut-off as ≤9.15, the specificity was 99.3, the sensitivity was 10.0, and the area under the curve was 0.576 (p<0.005). Regression analysis revealed age as an independent risk factor on UA values. Oxidative stress might be a factor in the development of PD, and UA may be a possible prospective protecting factor in the clinical course of the disease. However, it does not affect the severity. CONCLUSION: Our results support that lower uric acid concentrations are associated with PD; however, it is not a powerful indicator for predicting PD risk. As we reveal more about UA and its effect in further investigations, its significant role will become well-defined.

Adult-onset subacute sclerosing panencephalitis presenting with tonic motor seizures.

PURPOSE/AIM OF THE STUDY: Subacute sclerosing panencephalitis (SSPE) is a degenerative disease of the brain caused by a persistent measles virus infection occurring mostly in childhood or early adolescence. The spectrum of epileptic phenomena associated with SSPE is wide, varying from partial or generalized tonic-clonic seizures and atypical absences to myoclonic-atonic attacks. Tonic seizures are very rare in SSPE. MATERIALS AND METHODS: Herein, we discuss a case of 25 years old male that presented with adult-onset SSPE with tonic seizures accompanying myoclonic seizures. RESULTS: Patient was treated with clonazepam 5 mg/day and an isoprinosine regimen with a dose of 70 mg/kg/day. This is the fourth case of SSPE presenting with myoclonic and tonic seizures and the first case of SSPE with myoclonic and tonic seizures reported in an adult-onset case in the English literature. CONCLUSIONS: Adult-onset SSPE with tonic seizures is rare and may be confusing, thus, it is important to recognize the presence of this type of tonic motor seizures in SSPE patients.

A Case of Pregabalin-Induced Parkinsonism.

Drug-induced parkinsonism is the second common movement disorder after Parkinson's disease. It occurs due to the use of not only neuroleptics but also some other medications as pregabalin. Pregabalin is an antiepileptic drug and a structural analog of gamma-aminobutyric acid (GABA), and its use decreases the release of several neurotransmitters. In this case report, we present a 53-year-old female patient with the signs of parkinsonism following pregabalin treatment. Drug-induced parkinsonism was diagnosed based on the clinical features, investigations, and resolution of the complaints. The symptoms relieved after the treatment stopped at a follow-up of 10 days. Due to the rare report of pregabalin-induced parkinsonism, we aim to enhance clinicians' awareness of pregabalin's probable side effects.

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

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

Serum vitamin D status does not correlate with the severity of obstructive sleep apnea in male adults: A controlled study design with minimized factors influencing serum vitamin D levels.

Observational studies performed in homogeneous groups to objectively investigate the cause and effect relationship between vitamin D deficiency and sleep disorders are scarce. In this study, it was aimed to analyze the relationship between the severity of OSAS and vitamin-D levels among the participants whose features affecting serum vit-D levels were minimised. Serum 25-OH vitamin-D levels in 121 OSAS Male patients diagnosed by polysomnography without any systemic disease or vitamin-D supplement that may effect the vitamin-D metabolism were measured. The study was conducted in winter (latitude: 41°). Anthropometric measures and biochemical tests were also performed. The distribution of vitamin-D levels was determined as severe deficiency, deficiency, insufficiency and sufficiency. Apnea-hypopne index (AHI) < 5 was considered as a control group. Patients were categorized into four groups according to AHI as control, mild, moderate and severe. The groups were similar in terms of age, BMI, lipid profile, serum calcium, anthropometric measures and smoking. There was no significant difference in the distribution of vitamin-D levels between the patient and control groups and also within OSAS subgroups (p = 0.57, p = 0.86, respectively). Odds ratio to have OSAS in patients with vitamin-D deficiency was found as 0.745 (95 %CI: 0.33-1.7). Multinominal regression analysis showed no significant relationship between the OSAS severity and the extent of vitamin-D status. Correlation analysis showed no significant relationship between vitamin-D and AHI (r = 0.017, p = 0.877). Vitamin-D status does not alter the severity of OSAS. Vitamin-D deficiency might be the result of lifestyle changes due to OSAS rather than a cause.

Multicenter study of levodopa carbidopa intestinal gel in Parkinson's disease: the Turkish experience

Background/aim: Our purpose was to determine the efficacy of levodopa carbidopa intestinal gel (LCIG) in a series of Turkish patients with Parkinson's disease (PD). Materials and methods: We had telephone calls with 54 patients from 11 neurology centers who were on LCIG treatment, and 44 patients or their caregivers were included in an eight-item survey between September 2015 and June 2016. The reliability and validity of the survey were evaluated with intraclass correlation coefficients for every question separately. Results: Average age of the patients were 63.48 and the duration of PD was 12.79 years. Average LCIG treatment period was 15.63 months. Percentages of the patients who reported they were 'better' after LCIG treatment were as follows: 80% for time spent off, 55% for dyskinesia, 65% for tremor, 85% for gait disorder, 50% for pain, 50% for sleep disorders, 42.5% for depression, 32.5% for incontinence, and 70% for activities of daily living. Cronbach's alpha was 0.795 and the intraclass correlation coefficient was reliable for the items. Conclusion: As detected by a survey performed by telephone calls with good interrater reliability, patients with PD improve with LCIG treatment in many aspects of the disease.

Susac's syndrome as a rare arterial stroke mimic.

Susac's syndrome is an uncommon autoimmune microangiopathy characterised mainly by encephalopathy, hearing loss and branch retinal artery occlusions. We present here a case of Susac's syndrome with initial isolated arterial stroke symptoms which are not an uncommon feature of the disease.

The Relation of Circulating Levels of Leptin with Cognition in Patients with Alzheimer's Disease.

INTRODUCTION: To investigate the relation of circulating levels of leptin with cognition in Alzheimer's disease (AD) patients. METHODS: Thirty patients meeting the clinical diagnostic criteria for AD, and twenty-five healthy controls were enrolled into the study. At baseline, all patients underwent standing height, weight measurements, and waist circumference (in centimeters) using a standard scale. Body mass index (BMI) was then calculated as weight (in kilograms). A single 5-ml fasting blood sample was obtained from each patient. All subjects were evaluated by Turkish version of Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR) and Global Deterioration Scale (GDS). RESULTS: The mean age of patients and controls were 72.33±10.11 and 67.20±8.95, respectively. There was not any significant difference between age of the patients and the controls (p=0.054). Both patient and control groups consisted of mostly women (60% and 56% respectively). The mean waist circumferences (WC) of patients and controls were 95.46±10.87 and 97.76±10.07, respectively and was not statistically different (p=0.424). The mean serum leptin levels in patients and controls were 5.49±4.06 ng/dL 5.71±4.45 ng/dL, respectively. Leptin levels were not statistically different between patients and controls (p=0.84). The mean MMSE scores of AD patients and controls were 17±6.54 and 27.32±2.15 respectively, and AD patients had significantly lower MMSE scores than the controls (p=0.000). The mean BMI of patients and controls were 25.72±3.98 and 27.92±3.08 respectively. The BMI of controls were higher than patients and there was statistically significant difference between two groups (p=0.029). In the patient group, there were no correlations between leptin levels and age (p=0.067), BMI (p=0.098), WC (p=0.113), MMSE (p=0.203), CDR (p=0.519) and GDS (p=0.587). Similarly in control group leptin levels were not correlated with BMI (p=0.718), WC (p=0.755) and MMSE (p=0.859). CONCLUSION: In the present study, we could not find any relation between blood leptin levels and cognition in AD patients.

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

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

Mutation analysis of the PARKIN, PINK1, DJ1, and SNCA genes in Turkish early-onset Parkinson's patients and genotype-phenotype correlations.

OBJECTIVE: Variations in PARK genes (PRKN, PINK1, DJ-1, and SNCA) cause early-onset Parkinson's disease (EOPD) in different populations. In the current study, we aimed to evaluate the frequencies of variations in PARK genes and the effects of these variations on the phenotypes of Turkish EOPD patients. METHODS: All coding regions and exon-intron boundaries of the PRKN, PINK1, DJ-1, and SNCA genes were screened by heteroduplex analysis followed by direct sequencing of the detected variants in 50 Turkish EOPD patients. These variants were evaluated using SIFT, PolyPhen, HSF, and LOVD web-based programs. RESULTS: The frequency of EOPD-associated variations in the PRKN gene was 34%. Among these variations, p.A82E in exon 3 and p.Q409X in exon 11 was determined to be pathogenic. We also defined previously unknown cryptic variations, including c.872-35 G>A and c.872-28T>G in exon 8 of PRKN and c.252+30 T>G and c.322+4 A>G in exons 4 and 5 of DJ1, respectively, that were associated with EOPD. Although no significant association was observed between the PARK gene mutations and clinical features (P>0.05), the alterations were related to the clinical symptoms in each patient. CONCLUSION: An increasing number of studies report that PRKN, PINK1, DJ1 and SNCA mutations are associated with early-onset Parkinson's disease; however, a limited number of studies have been conducted in Turkey. Additionally, our study is the first to evaluate the frequency of SNCA mutations in a Turkish population. The aim of this study was determine the frequency distributions of the PRKN, PINK1, DJ1, and SNCA gene mutations and to analyze the relationships between these genetic variations and the clinical phenotype of EOPD in Turkish patients.

Serum Leptin Levels and Cognition in Parkinson's Disease Patients.

INTRODUCTION: To investigate the relationship between serum leptin levels and cognition in Parkinson's disease (PD) patients. METHODS: Thirty patients with idiopathic PD and 30 healthy controls were enrolled. At baseline, all patients had their standing height, weight, and waist circumference measurements taken using a standard scale. Their body mass index was then calculated. A fasting blood of 5 ml was obtained from each patient in the morning. ELISA was used to analyze leptin concentrations. The severity of PD was evaluated using the Hoehn and Yahr scale, and the clinical status of patients was evaluated using the Unified Parkinson's Disease Rating Scale. The cognitive status of whole patients was evaluated using a validated form of the Montreal Cognitive Assessment Scale in Turkey (MoCA-TR). RESULTS: The mean ages of the patients and controls were 59.37±9.22 and 58.50±9.85 years, while the mean leptin levels were 4.13±3.61 and 3.12±2.43 ng/mL, respectively. Leptin levels did not differ between PD patients and the controls. PD patients had significantly lower MoCA-TR scores than the controls (p=0.028). MoCA-TR scores were not correlated to leptin levels in PD patients. CONCLUSION: In this study, we could not find a relationship between blood leptin levels of PD patients and cognition as assessed by MoCA-TR. Larger longitudinal studies are needed.

Neurosyphilis: a case report.

Syphilis is a multisystem chronic infection caused by treponema pallidum. It can cause psychiatric disorders including depression, mania, psychosis, personality changes, delirium and dementia. With the introduction of penicillin into practice, the number of cases with syphilis decreased and its incidence increased with AIDS and HIV seropositivity. In this article, we present a case of neurosyphilis that manifested itself with neuropsychiatric symptoms.

Serum leptin concentrations in Turkish Parkinson's disease population.

Objectives. To investigate leptin levels and their relationship to body composition and demographic and clinical characteristics of Turkish patients with Parkinson's disease (PD). Patients and Methods. Forty eligible PD patients and 25 healthy controls were included in the study. Body composition measurements (height, weight, waist circumference (WC), and body mass index (BMI)) of the whole sample and clinical findings of PD patients were evaluated in the on-state. A single 5 mL fasting blood sample was obtained from each participant in the morning. Severity of PD was evaluated using the Hoehn and Yahr scale and the Unified Parkinson's Disease Rating Scale. Results. The mean age of the patients and controls was 60.8 ± 9.4 and 61.8 ± 5.8 years, while the mean BMI was 30.17 ± 5.10 and 28.03 ± 3.23 and the mean leptin levels were 6.8 ± 6.9 and 3.9 ± 3.8 ng/mL, respectively. Only age and gender were correlated with leptin levels. There was a significant difference (P < 0.001) in leptin levels between male (3.6 ± 3.1 ng/mL) and female (14.3 ± 7.7 ng/mL) PD patients. Among the male PD patients, older age and higher BMI and WC values were associated with higher mean leptin levels. There was not any significant relationship between leptin levels and clinical findings in PD patients. Conclusion. These results may suggest that leptin levels have no determinative role in the follow-up of PD patients with regard to the severity and clinical prognosis of PD.

Validation of the Turkish Version of the Montreal Cognitive Assessment Scale (MoCA-TR) in patients with Parkinson's disease.

The study aimed to examine the reliability and validity of the Turkish version of the Montreal Cognitive Assessment Scale (MoCA-TR) as a screening tool for cognitive dysfunction in Parkinson's disease (PD). A total of 50 patients with PD and 50 healthy controls were included. The screening instruments-MoCA-TR followed by the Mini-Mental Status Examination (MMSE-TR) and MoCA-TR retest within 1 month-and detailed neuropsychological testing were administered to the PD patients. MoCA-TR and MMSE-TR were also administered to controls. The discriminant validities of the MoCA-TR and MMSE-TR as screening and diagnostic instruments were ascertained. The concurrent and criterion validity, test-retest reliability, and internal consistency of the MoCA-TR and MMSE-TR were examined. The Cronbach's alpha of the MoCA-TR as an index of internal consistency was 0.664, and the test-retest reliability of MoCA-TR was 0.742. With a cut-off score of < 21 points, the MoCA-TR showed sensitivity of 59% and specificity of 89% in the detection of cognitive dysfunction in PD. The area under the receiver-operating characteristics curve (95% confidence interval) for MoCA-TR was 0.794 (0.670-0.918), p<.001. The present results indicated that the MoCA-TR has acceptable psychometric properties and it should be used to assess mild cognitive impairment and early dementia in PD patients, whereas the MMSE-TR should remain the instrument of choice to assess cognitive impairment in PD dementia.

Lack of association between cerebral microbleeds and low serum cholesterol in patients with acute intracerebral hemorrhage.

BACKGROUND: The association of cerebral microbleeds (CMBs) with intracerebral hemorrhage (ICH) is well known and its relationship with low serum cholesterol in ICH patients might be of interest. METHODS: A total of 105 patients with ICH were evaluated. In all subjects cholesterol levels were measured after 12h of fasting and gradient-echo magnetic resonance imaging (GE-MRI) was performed for detecting CMBs. RESULTS: CMBs were more common among patients with hypertension and leukoaraiosis (p=0.008 and p=0.001). Patients with and without CMBs did not differ according to total cholesterol, LDL cholesterol, triglycerides and HDL cholesterol levels. CONCLUSION: In this study, 61% of Turkish ICH patients had CMBs, which was not associated with lipid profiles. Leukoaraiosis was independently associated with CMBs.