Clinical and genetic analysis of levodopa induced dyskinesia in patients with Parkinson's disease

Uvod. Dugotrajna pulsatilna stimulacija usled primene dopaminergičkih lekova i aberantna plastičnost sa denervacijom strijatuma su najvažniji faktori u nastanku diskinezija. Jedan od predpostavljenih faktora koji bi mogao da kontroliše plastičnost je i brain-derived neurotrophic factor (BDNF), čiji funkcionalni polimorfizam val66met je udružen sa smanjenjem njegove sekrecije. Ciljevi istraživanja. Ispitati učestalost val66met polimorfizma BDNF gena kod pacijenata sa PB, utvrditi tip, vreme javljanja i učestalost diskinezija kod obolelih sa PB, izdvojiti parametare koji najznačajnije doprinose pojavi diskinezija i ispitati uticaj val66met polimorfizma BDNF gena na učestalost, vreme pojave i težinu diskinezija. Materijal i metode. Istraživanje je obuhvatilo 177 bolesnika sa PB, koji su regrutovani na Neurološkoj klinici KCS (Beograd) tokom 2009-2011. godine. Dijagnoza PB postavljena je prema predhodno publikovanim kriterijumima Warda i Gibba. Demografski i klinički podaci su dobijeni korišćenjem detaljnog, za ovu studiju posebno konstruisanog, upitnika. Težina PB procenjivana je pomoću Unifikovane skale za procenu težine PB (UPDRS) a za određivanje stadijuma bolesti korišćen je sistem Hoenhove i Yahra (HY). Funkcionalnost u obavljanju dnevnih aktivnosti procenjivana je modifikovanom Skalom dnevnih aktivnosti. Diskinezije su kvantifikovane po modifikovanoj Skali za abnormalne nevoljne pokrete (Abnormal Involuntary Movement Scale; AIMS). Za procenu depresivnosti korišćena je Hamiltonova skala depresivnosti, anksioznosti Hamiltonova skala anksioznosti. a kognitivno funkcionisanje bolesnika procenjivano je pomoću Mini Mental State Examination testa (MMSE). Odredjivanje polimorfizma val66met BNDF gena vršilo se pomoću kita TaqMan SNP Genotyping Assay (PE Applied Biosystems, Foster City, CA, USA). Statistička analiza dobijenih podataka uključila je metode deskriptivne statistike, parametrijske i neparametrijske testove. Za poredjenje kontinuiranih varijabli korišćena je analiza varijanse, za kategorisana obeležja Hi kvadrat test. Kriterijumi za multivarinatni model bili su statistička značajnost na nivo 0,05 dobijena univarijantnom analizom. Kao mera efekta korišćen je relativni rizik (RR) sa 95% intervalima poverenja (95% IP)...Introduction. Long-term pulsatile dopaminergic stimulation from the use of drugs and aberrant plasticity of striatal denervation are the most important factors in the development of dyskinesia. One of the supervisory factors that could control the plasticity of the brain-derived neurotrophic factor (BDNF), which is a functional polymorphism val66met associated with decrease in it's secretion.. Objectives of research. To investigate the prevalence of the val66met BDNF gene polymorphism in patients with PD, to determine the type, time of occurrence and frequency of dyskinesia in patients with PD, to extract the most significant parameters that contribute to the appearance of dyskinesia in patients with PD and to examine the impact of BDNF gene polymorphism val66met, the frequency, time of occurrence and severity of dyskinesia. Materials and Methods. Our research included 177 patients with PD, who were recruited at the Neurological Clinic of the Clinical Center of Serbia (KCS Beograd) during the years 2009 to 2011. The PD diagnosis was made according to the aforepublished criteria of Ward and Gibb. Demographic and clinical data were obtained through the use of a detailed, specially designed questionnaire for this study. The PD weight (score) was assessed with reference to the Unified Scale for the Assessment of PD weight (UPDRS) and in order to determine the stage of disease, the Hoenhove and Yahra (HY) system was applied. The functionality and performance of daily activities was assessed using the modified Scale of Daily Activities. Dyskinesia was quantified per the modified Scale for Abnormal Involuntary Movements (“Abnormal Involuntary Movement Scale;” AIMS). In the assessment of depression, the Hamilton Scale of Depression was applied for anxiety, the Hamilton Scale was used (HAMA), and for patient cognitive function, the Mini Mental State Examination (MMSE) was applied. To determine the BDNF genotype, a single-nucleotide polymorphism was analyzed using a TaqMan assay (Applied Biosystems, Foster City, CA, USA). BDNF genotype single nucleotide polymorphisms (SNP) (rs6265) was analyzed using TaqMan assays (Applied Biosystems [ABI], Foster City, CA). Statistical analysis on the data received involved the following methods descriptive statistics, parametric and non-parametric tests, univariate and multivariate logistic regression analysis.