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.

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.

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.

Frontal assessment battery in patients with Parkinson disease in a Turkish population.

OBJECTIVE: The aims of this study were to assess frontal dysfunction in Turkish patients with idiopathic Parkinson disease (PD) by using frontal assessment battery (FAB), and to determine the relationship among FAB scores and education, Mini-Mental State Examination (MMSE), and severity of the disease. BACKGROUND: Cognitive impairment in patients with PD mainly involves executive dysfunction. Executive dysfunction is mainly related to the frontal lobes and their connections with the thalamus and basal ganglia. FAB is an easily applicable and valid test to examine frontal functions. METHOD: Forty patients diagnosed with PD and 52 healthy controls were included in the study. Age, sex, disease duration, and Unified Parkinson's Disease Rating Scale scores were noted. FAB and MMSE were administered to all participants. Both groups were compared according to FAB scores, MMSE, age, and education. RESULTS: FAB scores were significantly lower in patients with PD (P=0.00) than in healthy controls. In patients with PD, FAB scores were solely correlated with MMSE. In the subgroup analysis, the performance of patients with PD was worse than the healthy participants on similarities and fluency tasks. CONCLUSIONS: FAB scores are lower in Turkish patients with PD than in the healthy participants, and could be used for the evaluation of subtle cognitive deficits in these patients.

Quantitative analysis of reduced arm swing frequency in essential tremor.

BACKGROUND: Essential tremor (ET) has recently been accepted as a heterogeneous disorder which may be associated with synuclein pathology or a variety of other genetic disorders. METHODS: We observed decreased arm swing frequency in 18 of 136 definite ET patients, and recorded the associated arm movements in 18 ET patients and 33 sex- and age-matched healthy controls. RESULTS: The mean frequency of the right arm (p = 0.047), left arm (p = 0.025) and leg (p = 0.030), and the mean arm/leg frequency on the right side (p = 0.048) were significantly lower in ET patients. The mean frequencies for both arms and legs were significantly lower for the more affected side of the body (p = 0.034 and p = 0.036, respectively). CONCLUSION: We conclude that ET may be associated with decreased arm and leg swing frequencies, especially on the more affected side of the body.

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.

Cerebral microbleeds in ischemic stroke patients on warfarin treatment.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are known to be indicative of bleeding prone microangiopathy. Little is known about its significance in anticoagulated patients. We aimed to determine the frequency of CMBs in ischemic stroke patients on warfarin treatment. METHODS: A total of 141 ischemic stroke patients on warfarin therapy were enrolled in this study. One hundred five patients with similar demographic features who do not use warfarin were chosen as controls. We compared vascular risk factors and radiological findings including CMBs and leukoaraiosis between the groups. RESULTS: CMBs on gradient-echo MRI (GE-MRI) were found in 31 patients (22%) and 17 controls (16%) and there was not a significant difference between 2 groups (P=0.25). Study patients with CMBs were older than patients without CMBs (P=0.04) and frequency of leukoaraiosis was significantly higher (P=0.008). Mean duration of warfarin treatment was not different between the patients with and without CMBs (P=0.83). CONCLUSIONS: Although patients with CMBs were older and had more leukoaraiosis the impact of warfarin treatment on CMBs is still controversial.

Intrathecal methotrexate-induced acute chorea.

Intrathecal methotrexate is the mainstay of central nervous system prophylaxis in acute lymphoblastic leukemia. We describe a patient who developed acute chorea after last dose of intrathecal methotrexate therapy and recovered completely.

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.

Assessment of valvulopathy in Parkinson's disease patients on pergolide and/or cabergoline.

OBJECTIVE: To assess the effect of ergot derivatives on cardiac valves in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Echocardiography was performed on 46 PD patients who used either pergolide or cabergoline (MonoPD) or both (MixPD) for a minimum of 1 year and 49 age-matched healthy controls. Valvular regurgitation was graded as mild, moderate and severe. MonoPD and MixPD groups were compared with regard to demographic features, drug profile and valvulopathy. RESULTS: The PD group had a mean age of 63 years, agonist duration of 3.8 years and agonist equivalent dose of 3.5mg/day. Moderate regurgitation in all three valves was significantly more common in the PD group than the controls. Severe valvular regurgitation was not observed in either group, with the exception of one PD patient. The frequency of valvulopathy and doses of agonists did not differ between MixPD and MonoPD groups. CONCLUSION: PD patients on dopamine ergot agonists are prone to moderate valvular regurgitation more than age-matched controls. However, the frequency of valvulopathy was similar in patients who used either one or more agonists.

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.

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.