Clinical characteristics of multiple system atrophy in Serbian population

Background/Aim. Mulstiple system atrophy (MSA) is a neurodegenerative central nervous system disorder, characterized by any combination of extrapyramidal, cerebellar, pyramidal or autonomic disturbance. The aims of our study were to define clinical characteristics of MSA patients in our population, to account for neuroradiological and electrophysiological profile of the disease and to evaluate one-dose levodopa response. Methods. We have diagnosed 29 patients as MSA, with disease duration from the first symptom 5 years on average on examination. The examinating procedure included an anamnesis and complete neurological investigations, as well as neurootological and neuroradiological examinations. The study included the patients of the Institute of Neurology of the Clinical Center of Serbia in the period of 1996-2001, who completed both clinical and diagnostic criteria for a possible and probable MSA. Results. Autonomic disturbances were documented in 93.1%, whereas extrapyramidal symptoms were seen in additional 89.3% with symmetrical onset in 60%. Levodopa response was poor or moderate. Cerebellar signs were present in 63%, while pyramidal signs occured in 78.7%. There was no a cognitive deterioration (MMSE > 24). CT scan and MRI showed cerebellar and brainstem atrophy, as well as diffuse cortical atrophy. Conclusion. Failure of additional diagnostic procedures to distinguish MSA patients required a precise understanding of their clinical specificities. Our results support this statement

Craniocervical Dystonia Questionnaire (CDQ-24): Validation and Cross-Cultural Adaptation in Serbian Patients

The purpose of this study was to investigate the validation of the translated and culturally adapted CDQ-24 questionnaire on a group of Serbian patients. The study was comprised of 100 consecutive patients with idiopathic cervical dystonia (CD) and blepharospasm (BSP) who were evaluated at the Institute of Neurology, Clinical Centre of Serbia in Belgrade between March and June 2007. The linguistic validation of CDQ-24 involved 3 steps, according to an internationally accepted methodology. Most of the patients with CD and BSP accepted the CDQ-24 questionnaire. The internal consistency reliability ranged from 0.81 to 0.97. The mean total score of the CDQ-24 was 35.6±23.5. Patients with BSP had better HRQoL scores in the Pain subscale (p=0.025) compared with CD patients. However, patients with CD had better HRQoL sores in the Activities of Daily Living subscale (p=0.028) compared with BSP patients. Statistically significant positive correlations were registered between the Dystonia Movement Scale score and almost all CDQ-24 scales. The Serbian version of CDQ-24 should be recommended for HRQoL evaluation among patients with CD and BSP as an important outcome measure

When do the symptoms of autonomic nervous system malfunction appear in patients with Parkinson’s disease?

Background/Aim. Dysautonomia appears in almost all patients with Parkinson’s disease (PD) in a certain stage of their condition. The aim of our study was to detect the development and type of autonomic disorders, find out the factors affecting their manifestation by analyzing the potential association with demographic variables related to clinical presentation, as well as the symptoms of the disease in a PD patient cohort. Methods. The patients with PD treated at the Clinic of Neurology in Belgrade during a 2-year period, divided into 3 groups were studied: 25 de novo patients, 25 patients already treated and had no long-term levodopa therapy-related complications and 22 patients treated with levodopa who manifested levodopa-induced motor complications. Simultaneously, 35 healthy control subjects, matched by age and sex, were also analyzed. Results. Autonomic nervous system malfunction was defined by Ewing diagnostic criteria. The tests, indicators of sympathetic and parasympathetic nervous systems, were significantly different in the PD patients as compared with the controls, suggesting the failure of both systems. However, it was shown, in the selected groups of patients, that the malfunction of both systems was present in two treated groups of PD patients, while de novo group manifested only sympathetic dysfunction. For this reason, the complete autonomic neuropathy was diagnosed only in the treated PD patients, while de novo patients were defined as those with the isolated sympathetic dysfunction. The patients with the complete autonomic neuropathy differed from the subjects without such neuropathy in higher cumulative and motor unified Parkinson’s disease rating score (UPDRS) (p < 0.01), activities of daily living scores (p < 0.05), Schwab-England scale (p < 0.001) and Hoehn-Yahr scale. There was no difference between the patients in other clinical-demographic characteristics (sex, age at the time of diagnosis, actual age, duration of disease, involved side of the body, pain and freezing), but mini mental status (MMS) score and Hamilton depression and anxiety rating scale were significantly lower (p < 0.05). Conclusion. Our results confirm a high prevalence of autonomic nervous system disturbances among PD patients from the near onset of disease, with a predominant sympathetic nervous system involvement. The patients who developed complete autonomic neuropathy (both sympathetic and parasympathetic) were individuals with considerable level of functional failure, more severe clinical presentation and the existing anxiety and depression. [Projekat Ministarstva nauke Republike Srbije, br. 175090

Impact of depression on gait variability in Parkinson's disease

Objective The goal of this study was to analyze how depression associated with Parkinson’s disease (PD) affected gait variability in these patients using a dual-task paradigm. Additionally, the dependency of the executive functions and the impact of depression on gait variability were analyzed. Patients and Methods Three subject groups were included: patients with PD, but no depression (PD-NonDep; 14 patients), patients with both PD and depression (PD-Dep; 16 patients) and healthy controls (HC; 15 subjects). Gait was recorded using the wireless sensors. The participants walked under four conditions: single-task, motor dual- task, cognitive dual-task, and combined dual-task. Variability of stride length, stride duration, and swing time was calculated and analyzed using the statistical methods. Results Variability of stride duration and stride length were not significantly different between PD-Dep and PD-NonDep patients. The linear mixed model showed that swing time variability was statistically significantly higher in PD-Dep patients compared to controls (p = 0.001). Hamilton Disease Rating Scale scores were significantly correlated with the swing time variability (p = 0.01). Variability of all three parameters of gait was significantly higher while performing combined or cognitive task and this effect was more pronounced in PD-Dep group of patients. Conclusions Depression in PD was associated with swing time variability, and this effect was more prominent while performing a dual-task. Significance Diagnosing and treating depression might be important for gait improvement and fall reduction in PD patients

Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale

Objectives: Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods: A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results: The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion: Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence

CAVITATION RESISTANCE OF THE MATERIAL PA 3200 GF PRODUCED BY SELECTIVE LASER SINTERING

The present study focuses on the results of cavitation resistance research of samples obtained by the Selective Laser Sintering technology. The material used was Polyamide powder PA 3200 GF reinforced with glass fibers. The laser-sintered samples were produced from 100% new and recycled powder mixed with 70% of new powder. The samples were tested under cavitation conditions using an ultrasonic vibration method with a stationary sample according to the ASTM G-32 standard. Examination of the morphology of cavitation damage was investigated by scanning electron microscopy. The change in mass loss during different cavitation times was measured on the tested samples. The main objective of the research was to determine the validity application of the tested material in cavitation condition

Fluoksetin ne remeti motornu funkciju kod bolesnika sa Parkinsonovom bolešću - korelacija raspoloženja i motorne funkcije sa koncentracijom fluoksetina/norfluoksetina u plazmi

Background/Aim. Selective serotonin reuptake inhibitors are the most commonly chosen antidepressants in patients with Parkinson's disease (PD). The aim of our study was to assess the influence of fluoxetine (Flu) on motor functions in patients with PD. Methods. In this prospective, controlled, open-label study, 18 patients with PD and mild depression [(10 ≤ Hamilton Rating Scale for Depression (HDRS) ≤ 23)] without dementia [(25 ≤ Mini-Mental State Examination (MMSE)] were treated with Flu. Both single and repeated dose effects of Flu were assessed on days 1-80. Plasma concentrations of Flu and norfluoxetine (NORFlu) were correlated with the results of selected motor function performance scores: The Unified Parkinsons Disease Rating Score (UPDRS), Finger Tapping Test (FTT) and Purdue Pegboard Test (PPT). Severity of PD, depression and dementia were evaluated using standard tests [(Hoehn and Yahr stages (HY), activity of daily living (ADL), UPDRS, HDRS, MMSE)]. Results. Steady-state for Flu/NORFlu was reached after 18 days of treatment. Such a plateau correlated with significant improvements in both scores of depression and Parkinson's disability (HDRS, UPDRS and ADL, respectively). In addition, FTT and PPT scores also increased until day 18, with further slight fluctuations around the plateau. Optimal motor performances correlated with Flu concentrations of approximately 60-110 μg/L. Conclusion. Flu (20 mg/day) significantly reduced depression in PD patients while it did not impair their motor performances. Because substantial placebo effects may arise in studies of PD and depression, large, prospective, randomized, placebo-controlled clinical trials are warranted.Uvod/Cilj. Selektivni inhibitori ponovnog preuzimanja serotonina su antidepresivi koji se najčešće koriste u lečenju obolelih od Parkinsonove bolesti (PB). Cilj ovog istraživanja bio je da se proceni uticaj fluoksetina (Flu) na motorne funkcije bolesnika sa PB. Metode. U ovom prospektivnom, kontrolisanom, otvorenom kliničkom ispitivanju, 18 bolesnika sa PB i blagom depresijom [10 ≤ Hamiltonova skala za depresiju (10 ≤ HDRS) ≤ 23)], bez demencije [(25 ≤ Mini mental test (MMSE)] lečeni su primenom Flu. Procenjivana su dejstva kako pojedinačne, tako i ponovljene doze Flu od prvog do osamdesetog dana. Plazma koncentracije Flu i norfluoksetina (NORFlu) korelisane su sa rezultatima odeđenih testova za motorne funkcije: skala za procenu težine PB (UPDRS), test spretnosti kucanja (FTT) i Purdue pegboard Test PPT). Izraženost PD, depresije i demencije procenjivane su korišćenjem standardnih testova [(test dnevnih aktivnosti (ADL), Hoehn.-Yahr. stadijumi (HJ), HDRS, MMSE)]. Rezultati. Ravnotežno stanje za Flu/NORFlu postignuto je 18. dana lečenja. Takav plato u koncentraciji Flu/NORFlu bio je praćen značajnim poboljšanjem rezultata, kako testova za depresiju, tako i za izraženost PB (HDRS, UPDRS i ADL, sledstveno). Dodatno, rezultati FTT-a i PPT-a bili su u porastu do 18. dana, sa blagim fluktuacijama oko platoa. Optimalna motorna postignuća zabeležena su pri koncentraciji Flu od oko 60-110 μg/L. Zaključak. Flu (20 mg/dan) značajno redukuje depresiju kod bolesnika sa PB i ne remeti motorne funkcije. S obzirom na mogući placebo efekat u istraživanjima sa PB i depresijom, neophodna su obimnija, prospektivna, randomizovana, placebo- kontrolisana klinička ispitivanja

Genotype–phenotype correlation in PRKN- associated Parkinson’s disease

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson’s disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p < 0.05). Furthermore, variants located in the N-terminus of the protein, a region enriched with frameshift variants, were associated with an earlier age at onset. The phenotype of PRKN-PD was characterised by slow motor progression, preserved cognition, an excellent motor response to levodopa therapy and later development of motor complications compared to early-onset PD. Non-motor symptoms were however common in PRKN-PD. Our findings on the relationship between the type of variant in PRKN and the phenotype of the disease may have implications for both genetic counselling and the design of precision clinical trials