Udruženost polimorfizama gena za katehol-O- metiltransferazu sa terapijskim odgovorom i komplikacijama izazvanim levodopom kod Parkinsonove bolesti: Rezime sadašnjih saznanja

Catechol-O-methyltransferase (COMT) is one of the cardinal enzymes in the degradation of catecholamines and levodopa. Genetic variants of the COMT gene may affect COMT enzyme activity. The most examined COMT gene polymorphism is the nonsynonymous single nucleotide polymorphism (SNP) in exon 4 (Val108/158Met; rs4680). This highly functional polymorphism is responsible for fourfold variations in enzyme activity and dopamine catabolism. Recent data suggested that even synonymous SNPs of the COMT gene can lead to changes in enzyme activity. Genetically determined COMT activity can affect an individual's response to levodopa therapy and carries the risk of complications from prolonged levodopa use in Parkinson's disease (PD) patients. Identifying at-risk individuals through genetic susceptibility markers could help to prevent the development of levodopa-induced complications in PD.Katehol-O-metiltransferaza (engl. catechol-O-methyltransferase, COMT) je jedan od glavnih enzima u razgradnji kateholamina i levodope. Genetske varijante COMT gena mogu uticati na aktivnost COMT enzima. Polimorfizam COMT gena koji je najviše proučavan je nesinonimni jednonukleotidni polimorfizam (engl. single nucleotide polymorphism, SNP) u egzonu 4 (Val108/158Met; rs4680). Ovaj visoko funkcionalni polimorfizam odgovoran je za četvorostruke varijacije u aktivnosti enzima i katabolizmu dopamina. Nedavni podaci sugerišu da čak i sinonimni SNP COMT gena mogu da dovedu do promena u aktivnosti enzima. Genetski određene razlike u COMT aktivnosti mogu uticati na odgovor pojedinca na terapiju levodopom i nose rizik od komplikacija dugotrajne primene levodope kod pacijenata sa Parkinsonovom bolešću (PB). Identifikacija osoba u riziku putem markera genetske osetljivosti može pomoći u prevenciji komplikacija izazvanih levodopom kod PB

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

Social Cognition in Patients With Cerebellar Neurodegenerative Disorders

ObjectiveCerebellar neurodegenerative disorders (CDs) are a heterogeneous group of disorders. It is known that the cerebellum plays a role not only in motor, but also in cognitive and social cognitive functions. The aim of this study was to investigate social cognition in patients with different CDs.Materials and MethodsSocial cognition was examined in 34 patients, 12 with spinocerebellar ataxia type 1 (SCA1), 6 with spinocerebellar ataxia type 2 (SCA2), and 16 with idiopathic late onset cerebellar ataxia (ILOCA). All patients were clinically evaluated using the Scale for the Rating and Assessment of Ataxia. In addition, 34 age, sex, and education-matched healthy control (HC) subjects were similarly analyzed. Social cognition was studied using two tests: the Faux Pas Recognition Test and the Reading the Mind in the Eyes Test (RMET). An appropriate array of neuropsychological tests was used to assess the global cognitive status as well as the frontal functions and mood.ResultsCD patients achieved significantly worse results on both tests of social cognition compared to the HCs. The SCA1 + 2 group achieved the poorest results on the Faux Pas Recognition Test and exhibited poor performance on all cognitive tests, but was only significantly worse compared to the ILOCA group on the Free and Cued Selective Reminding Test (FCSRT) – recognition. The patients in the SCA1 + 2 and ILOCA groups obtained similar scores on RMET. In the SCA1 + 2 group the findings significantly correlated with clinical parameters of disease severity and duration and executive functions (EFs), and with mood and executive functions in the ILOCA group. In the SCA group EFs appeared as the only significant predictor of RMET achievement. The Boston Naming Test (BTN) was a significant predictor of the CD patients’ achievement on RMET, while the BTN, the Trail Making Test Part A and FCSRT – Delayed free recall predicted their performance on the Faux Pas Recognition Test.ConclusionPatients with CD have social cognitive impairments as demonstrated by the Faux Pas Test and the RMET test results. The SCA1 and 2 patients exhibited a more pronounced impairment compared with the ILOCA patients. The independent cognitive predictors of social cognition impairment were EFs and language

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

Spatiotemporal gait characteristics of Huntington's disease during dual-task walking

Purpose: Huntington's disease (HD) is an neurodegenerative genetic disorder with characteristic gait changes. HD also results in a range of cognitive impairments, such as difficulties to divide attention, or simultaneously monitoring two tasks. Aim: The impact of cognitive and/or motor tasks on HD gait has not been fully elucidated. The aim was to examine gait in HD patients while performing motor and/or cognitive dual-task walking. Methods: Gait was measured with and without performing concurrent cognitive and/or motor tasks. Sixteen HD patients and 24 healthy control (HC) subjects performed a self-paced basic walking task, a dual motor, a dual mental and a combined motor and mental task while walking. Results: Base walk gait parameters are significantly different between HD and HC groups. Same is true for motor, mental and combined tasks comparisons of HD and HC subjects. Gait velocity is also significantly reduced in HD compared to HC for all experimental conditions. Comparison of base walk and mental task performance showing differences in cycle time, stride length, double support time and CV of stride length, while base walk to motor task comparison is different only in stride length. No differences were found when motor and combined tasks were compared to mental task in HD patients. Conclusion: Gait pattern in HD patients while performing motor and/or cognitive dual tasks walking is remarkably preserved. Gait parameters are changed in order to reduce possible falls, and lack of differences of dual tasks gait parameters variability is attributed that patients minimizing risk of falling and preserving stability

Efficacy of Botulinum toxin type A in treatment of different forms of focal dystonias in the Serbian population: Experience of the Botulinum Toxin Outpatients Department

Background/Aim. Botulinum toxin (BTX) irreversibly inhibits presynaptic acetylcholine release with subsequent relaxation of abnormally contracting muscles. It is an effective and well tolerated treatment with long-term benefit in a variety of movement disorders and other neurological and non-neurological disturbances. The aim of our study was to present our experience with BTX type A in treatment of different forms of focal dystonias. Мethods. А hundred of patients with different focal dystonias (spastic torticollis, blepharospasm and graphospasm) from the Botulinum Toxin Outpatients Department, Clinic for Neurology, Clinical Center of Serbia, were included in the study. All the patients were examined and rated at baseline visit prior to BTX application and on the following visit, after 3-4 months, using self-assessment improvement questionnaire and standardized rating scales. Results. The improvement of ≥ 50% was presented in 68.2% of all (199) the analyzed applications. Independent predictors of good response to the therapy (improvement ≥ 50%) were male sex (p = 0.011), the presence of sensory trick (p = 0.013) and the total number of BTX applications (p = 0.002). The patients with spastic torticollis and blepharospasm showed a statistically significantly better BTX effect (improvement 57.3 ± 27.5% and 54.1 ± 28.3%), respectively than the graphospasm group (26.7 ± 25.6%). Most of the patients did not have therapy complications (81.4% and 72% in two applications). Side effects in the remaining patients (muscle weakness, dysphagia, ptosis, double vision, neck weakness and lacrimal dysfunction) lasted for 28.3 ± 18.6 days after the first treatment and 32.5 ± 36.2 days after the second one. Conclusion. BTX is safe and highly effective in long-term treatment of patients with different forms of focal dystonia, with only mild and well-tolerated side-effects. [Projekat Ministarstva nauke Republike Srbije, br. 175090

Gait alterations in Parkinson's disease at the stage of hemiparkinsonism-A longitudinal study.

BackgroundProgressive gait impairment in Parkinson's disease (PD) leads to significant disability. Quantitative gait parameters analysis provides valuable information about fine gait alterations.ObjectivesTo analyse change of gait parameters in patients with early PD at the stage of hemiparkinsonism and after 1 year of follow up, taking into account clinical asymmetry.MethodsConsecutive early PD outpatients with strictly unilateral motor features underwent clinical and neuropsychological assessment at the study entry and after 1 year of follow up. Gait was assessed with GAITRite walkway using dual-task methodology. Spatiotemporal gait parameters (step time and length, swing time and double support time) and their coefficients of variation (CV), gait velocity and heel-to-heel base support were evaluated.ResultsWe included 42 PD patients with disease duration of 1.3 years (±1.13). Progression of motor and non-motor symptoms, without significant cognitive worsening, was observed after 1 year of follow up. Significant shortening of the swing time, prolongation of the double support and increase of their CVs were observed during all task conditions similarly for most parameters on symptomatic and asymptomatic bodysides, except for CV for the swing time under the combined task.ConclusionAlterations of the swing time and double support time are already present even at the asymptomatic body side, and progress similarly, or even at faster pace, at this side, despite dopaminergic treatment These parameters deserve further investigation in larger, prospective studies to address their potential to serve as markers of progression in interventional disease modifying trials with early PD patients

Dynamics of impulsive-compulsive behaviors in early Parkinson's disease: a prospective study

Introduction Impulsive compulsive behaviors (ICBs) in Parkinson's disease (PD) are debilitating disorders of repetitive, excessive, and compulsive nature affecting up to one third of PD patients. Objectives are to address clinical, psychiatric, and cognitive characteristics of ICBs and to define risk factors in PD patients in the initial motor stage, followed up for 5 years. Methods We analyzed 106 consecutive PD outpatients at Hoehn and Yahr disease stage 1 and 125 healthy controls. The participants were assessed for the presence of any ICB using the current clinical criteria and underwent comprehensive clinical, psychiatric, and neuropsychological evaluations. The patients completed the same protocol at Years 1, 2, 3, and 5. Results ICBs were present in 21 (19.8%) PD patients and 13 (10.4%) healthy controls at baseline. Prevalence of ICBs increased to 29.2% at Year 5, significantly after Year 2. Multiple ICBs were present in 4,7% and 61.9% of PD-ICBs at the baseline and Year 5, respectively. ICBs resolved in 30% of cases (most often compulsive eating). Dopamine agonist treatment at the baseline carried five times higher risk of having or developing ICB(s) anytime during follow-up. We identified risk factors for compulsive eating (dopamine agonist treatment at baseline), hypersexuality (males), compulsive buying (depression and younger age), and punding (younger age and higher levodopa dose at baseline). Significant interaction of rate of motor progression and ICB diagnosis was shown. Conclusions PD patients showed increasing frequency of most ICBs during the 5-year follow-up. Specific risk factors were identified for different types of ICBs