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

Interaction of different third intracellular loop fragments of human dopamine d2l receptor with a-subunit of gi1 protein - prospective therapeutic application

In order to find the essential structural motif of the D2L dopamine receptor necessary for the interaction with a-subunit of Gi1 protein, four fragments of the third cytoplasmic loop (CPL3) of this receptor were cloned, expressed in E. coli and purified. After that, fusion proteins with glutathione-S-transferase (GST) were prepared and the interactions quantified by a colorimetric assay for GST activity determination. The presence of D2L-CPL3 fragment-Gia1 complexes was detected by SDS-polyacrylamide gel electrophoresis (PAGE). Kd values for the interaction of the three fragments with Gia1 were similar and in nmol/L range of concentrations, while the peptide representing the insert in the long form of the dopamine D2 receptor expressed about 10-fold lower binding affinity. These results could serve to design new therapeutic agents that might act at the level of receptor/G protein interaction rather than at the level of ligand-receptor binding.U cilju pronalaženja bitnih strukturnih motiva potrebnih za interakciju sa a podjedinicom Gi1 proteina klonirana su, eksprimirana i prečišćena 4 fragmenta treće citoplazmatične petlje (CPL3) dopaminskog D2L receptora koji su dalje pripremljeni kao fuzioni proteini sa glutation-S-transferazom (GST). Interakcije su kvantifikovane bojenom reakcijom za određivanje aktivnosti GST. Postojanje kompleksa D2L-CPL3 fragment- Gia1 je dokazano elektroforetskom analizom na SDS-poliakrilamidnom gelu (PAGE). Kd vrednosti za tri fragmenta su bile vrlo slične i u nmol/L opsegu koncentracija, dok je peptid koji predstavlja insert u dugom obliku dopaminskog D2 receptora posedovao oko 10 puta manji afinitet vezivanja za Gia1. Ovi rezultati mogu biti osnova za sintezu novih terapeutskih agenasa koji bi delovali na nivou interakcije receptora i G proteina umesto na nivou vezivanja liganda za receptor

Kvantitativna i kvalitativna procena obrasca hoda kod bolesnika sa Parkinsonovom bolešću

Background/Aim. Postural impairments and gait disorders in Parkinson's disease (PD) affect limits of stability, impaire postural adjustment, and evoke poor responses to perturbation. In the later stage of the disease, some patients can suffer from episodic features such as freezing of gait (FOG). Objective gait assessment and monitoring progress of the disease can give clinicians and therapist important information about changes in gait pattern and potential gait deviations, in order to prevent concomitant falls. The aim of this study was to propose a method for identification of freezing episodes and gait disturbances in patients with PD. A wireless inertial sensor system can be used to provide follow-up of the treatment effects or progress of the disease. Methods. The system is simple for mounting a subject, comfortable, simple for installing and recording, reliable and provides high-quality sensor data. A total of 12 patients were recorded and tested. Software calculates various gait parameters that could be estimated. User friendly visual tool provides information about changes in gait characteristics, either in a form of spectrogram or by observing spatiotemporal parameters. Based on these parameters, the algorithm performs classification of strides and identification of FOG types. Results. The described stride classification was merged with an algorithm for stride reconstruction resulting in a useful graphical tool that allows clinicians to inspect and analyze subject's movements. Conclusion. The described gait assessment system can be used for detection and categorization of gait disturbances by applying rule-based classification based on stride length, stride time, and frequency of the shank segment movements. The method provides an valuable graphical interface which is easy to interpret and provides clinicians and therapists with valuable information regarding the temporal changes in gait.Uvod/Cilj. Poremećaji hoda i ravnoteže kod bolesnika sa Parkinsonovom bolešću (PD) uključuju i poremećaje stabilnosti, održavanja ravnoteže prilikom hoda i nemogućnost adekvatne reakcije na iznenadne perturbacije. U kasnijim fazama bolesti neki bolesnici razvijaju i epizode motornog bloka, odnosno 'frizing' tokom hoda. Objektivno praćenje i merenje karakteristika hoda i promena obrasca hoda tokom progresije bolesti mogu pomoći kliničarima jer ukazuju na promene koje bi dovele do padova i ugrozile bolesnika. Cilj rada bio je razvoj metode koja bi identifikovala ovakve epizode kod bolesnika sa Parkinsonovom bolesti. Razvijeni bežični sistem sa senzorima mogao bi se koristiti za posmatranje efekata terapije ili progresije bolesti. Metode. U radu je prikazan sistem za objektivnu procenu obrasca hoda. Korišćenjem bežičnog senzorskog sistema koji koristi akcelerometre, žiroskope i senzore sile, moguće je dobiti procenu parametara hoda, ali i identifikovati 'frizing' epizode karakteristične za PD. Uz pomoć ovog sistema snimljeno je 12 bolesnika, te je na osnovu snimljenih signala razvijen novi softverski alat koji omogućava praćenje parametara hoda. Rezultati. Na osnovu dužine koraka, trajanja koraka i frekvencije pokreta, razvijen je algoritam za klasifikaciju tipova koraka i uočavanje promena frekvencija pokreta tokom hoda. Prikaz rezultata ovog sistema je dat kroz primer jednog bolesnika. Zaključak. Opisani sistem za procenu hoda može biti korišćen za kategorizaciju poremećaja hoda kroz posmatranje promena u dužini i trajanju koraka, kao i frekvencija segmenata noge. Razvijeni metod omogućava iliustrativni prikaz i grafički interfejs koji je jednostavan za interpretaciju i omogućava dobijanje informacija koje kliničarima mogu ukazati na trenutne promene u obrascu hoda

Senzorski sistem za objektivnu motornu procenu na osnovu tapping-a prstima i stopalom

Background/Aim. Finger tapping test is commonly used in neurological examinations as a test of motor performance. The new system comprising inertial and force sensors and custom proprietary software was developed for quantitative estimation and assessment of finger and foot tapping tests. The aim of this system was to provide diagnosis support and objective assessment of motor function. Methods. Miniature inertial sensors were placed on fingertips and used for measuring finger movements. A force sensor was placed on the fingertip of one finger, in order to measure the force during tapping. For foot tapping assessment, an inertial sensor was mounted on the subject's foot, which was placed above a force platform. By using this system, various parameters such as a number of taps, tapping duration, rhythm, open and close speed, the applied force and tapping angle, can be extracted for detailed analysis of a patient's motor performance. The system was tested on 13 patients with Parkinson's disease and 14 healthy controls. Results. The system allowed easy measurement of listed parameters, and additional graphical representation showed quantitative differences in these parameters between neurological patient and healthy subjects. Conclusion. The novel system for finger and foot tapping test is compact, simple to use and efficiently collects patient data. Parameters measured in patients can be compared to those measured in healthy subjects, or among groups of patients, or used to monitor progress of the disease, or therapy effects. Created data and scores could be used together with the scores from clinical tests, providing the possibility for better insight into the diagnosis.Uvod/Cilj. Tapping tj. tapkanje prstiju šake i stopala se uobičajeno koristi u neurološkim ispitivanjima kao test motorike. Prikazan je novi sistem koji sadrži inercijalne senzore i senzore sile, kao i odgovarajući softver za kvantitativnu procenu dijagnostičkog motornog testa na osnovu tapping-a prstima i stopalima. Uz pomoć ovog sistema moguća je objektivna evaluacija motornog obrasca bolesnika, a samim tim i lakše postavljanje određenih dijagnoza i praćenje progresa bolesti ili terapije. Metode. Minijaturni inercijalni senzori su bili postavljeni na vrhove prstiju u cilju kvantifikovanja pokreta prstiju. Senzor sile postavljen je na jagodicu jednog prsta i merio je silu primenjenu u toku tapping-a - tapkanja kažiprsta o palac. Za ocenu tapping-a stopalom, inercijalni senzor je postavljen na gornji deo stopala ispitanika koje je bilo postavljeno na platformu za merenje sile. Pomoću ovog sistema mogu se posmatrati brojni parametri poput broja i trajanja svakog pokreta, ritma i promena ritma, brzine otvaranja i brzine zatvaranja prstiju, primenjene sile, promene ugla između prstiju, i na osnovu ovih parametara može se vršiti detaljna analiza motornog stanja bolesnika. Sistem je testiran na 13 bolesnika sa Parkinsonovom bolešću i 14 zdravih ispitanika. Rezultati. Sistem je omogućio jednostavno merenje navedenih parametara i grafički prikaz kvantitativnih razlika u ovim parametrima između zdravih ispitanika i bolesnika sa neurološkim oboljenjem. Zaključak. Novi sistem za tapping prstima i stopalima je kompaktan, jednostavan za upotrebu i efikasan za prikupljanje podataka o bolesniku. Izmereni parametri mogu se koristi za poređenje bolesnika sa zdravim ispitanicima, ili sa drugim grupama bolesnika, ali i za praćenje progresa bolesti ili efekata terapije. Dobijeni podaci mogu se koristiti zajedno sa rezultatima drugih kliničkih testova, dajući tako mogućnost za bolji uvid u dijagnozu

Promene ekscitabilnosti motorne kore udružene sa zamorom mišića kod obolelih od Parkinsonove bolesti

Background/Aim. Transcranial magnetic stimulation (TMS) is a standard technique for noninvasive assessment of changes in central nervous system excitability. The aim of this study was to examine changes in responses to TMS in patients suffering from Parkinson's disease (PD) during sustained submaximal isometric voluntary contraction [60% of maximal voluntary contraction (MVC)] of the adductor pollicis muscle, as well as during a subsequent recovery period. Methods. Cortical excitability was tested by single TMS pulses of twice of the motor threshold intensity applied over the vertex. Testing was carried out during the sustained contraction phase every 10 s before and every 5 s after the endurance point, as well as at rest and during brief 60% MVC contractions before (control), immediately after the sustained contraction, and at 5 min intervals during the recovery period. Results. Although the PD patients could sustain the contraction at the required level for as long period of time as the healthy subjects (though contraction level subsided more rapidly after the endurance point), effects of muscle fatigue on the responses to TMS were different. In contrast to the findings observed in the healthy people where motor evoked potentials (MEP) and EMG silent period (SP) in fatigued muscle gradually diminished during contraction up to the endurance point, and increased thereafter, in the majority of patients no changes occurred in MEP size (peak and area) of the adductor pollicis muscle, either before or after the endurance point. On the other hand, changes in the SP of this muscle differed among the subjects, showing a gradual increase, a decrease or no changes in duration. The trends of changes in both MEP size and SP duration in the musculus brachioradialis varied among the tested PD patients, without any consistent pattern, which was in contrast with the findings in the healthy people where both measures showed a gradual increase from the beginning of the sustained contraction. A complete dissociation between changes in MEP and SP during fatigue was also of note, which differed sharply from the findings in the healthy people in who fatigue induced changes in these measures followed identical patterns. Conclusion. These results in the PD patients suggest the presence of impairment and/or compensatory changes in mechanisms responsible for adaptation of voluntary drive as well as for matching between cortical excitation and inhibition which become manifest in demanding motor tasks such as those imposed by muscle fatigue.Uvod/Cilj. Transkranijalna magnetna stimulacija (TMS) je standardna tehnika za neinvazivnu procenu promena ekscitabilnosti centralnog nervnog sistema. Cilj rada je bio da se prikažu promene odgovora na TMS kod obolelih od Parkinsonove bolesti (PB) za vreme trajanja submaksimalne voljne izometrijske kontrakcije [60% maksimalne voljne kontrakcije (MVK)] mišića adductor pollicis, kao i tokom perioda oporavka. Metode. Kortikalna ekscitabilnost testirana je TMS pulsevima dvostruko većeg intenziteta od motornog praga. Testiranje je vršeno za vreme održavanja kontrakcije na svakih 10 s do tačke izdržljivosti i na svakih 5 s posle toga, a, takođe, u miru kao i za vreme kratkotrajnih 60% MVK u periodu pre (kontrola), neposredno posle održavanja kontrakcije, i u intervalima od pet minuta za vreme perioda oporavka. Rezultati. Iako su bolesnici sa PB mogli da održavaju zahtevani nivo kontrakcije jednako dugo kao i zdravi ispitanici (mada je nivo opadao brže nakon tačke izdržljivosti), efekti mišićnog zamora na odgovor izazvan TMS-om bili su različiti. Za razliku od zdravih ispitanika kod kojih se motorni evocirani potencijali (MEP) i trajanje perioda EMG tišine (PT) u zamaranom mišiću postepeno smanjuju tokom kontrakcije do tačke izdržljivosti, a zatim rastu, kod većine bolesnika nije došlo do promena veličine (maksimalna amplituda i površina) MEP mišića adductor pollicis, bilo pre ili posle tačke izdržljivosti. S druge strane, promene PT ovog mišića su se razlikovale među ispitanicima, pokazujući bilo postepeno povećanje, smanjenje ili odsustvo promena. Promene kako amplitude MEP tako i trajanje PT u EMG mišića brahioradialisa varirale su među bolesnicima sa PB, bez nekog dominantnog obrasca, po čemu su se, takođe, razlikovale od promena nađenih kod zdravih ispitanika, kod kojih su se oba parametra postepeno povećavala od početka održavanja tonične kontrakcije. Upadljiva je, takođe, i potpuna disocijacija između promena MEP i PT tokom zamora, što je u oštroj suprotnosti sa nalazom kod zdravih ispitanika gde su promene ovih parametara pratile identičan obrazac. Zaključak. Rezultati kod bolesnika sa PB ukazuju na postojanje oštećenja i/ili kompenzatornih promena mehanizmima odgovornih za adaptaciju voljne pobude i usklađivanja kortikalne eksitacije i inhibicije, koji se manifestuju tokom mišićnog zamora i u drugim zahtevnim motornim zadacima

Repetitivna transkranijalna magnetna stimulacija kao adjuvantna metoda u lečenju depresije - početna iskustva

Introduction Repetitive transcranial magnetic stimulation (rTMS) is a method of brain stimulation which is increasingly used in both clinical practice and research. Up-to-date studies have pointed out a potential antidepressive effect of rTMS, but definitive superiority over placebo has not yet been confirmed. Objective The aim of the study was to examine the effect of rTMS as an adjuvant treatment with antidepressants during 18 weeks of evaluation starting from the initial application of the protocol. Methods Four patients with the diagnosis of moderate/severe major depression were included in the study. The protocol involved 2000 stimuli per day (rTMS frequency of 10 Hz, intensity of 120% motor threshold) administered over the left dorsolateral prefrontal cortex (DLPFC) for 15 days. Subjective and objective depressive symptoms were measured before the initiation of rTMS and repeatedly evaluated at week 3, 6, 12 and 18 from the beginning of the stimulation. Results After completion of rTMS protocol two patients demonstrated a reduction of depressive symptoms that was sustained throughout the 15-week follow-up period. One patient showed a tendency of remission during the first 12 weeks of the study, but relapsed in week 18. One patient showed no significant symptom reduction at any point of follow-up. Conclusion Preliminary findings suggest that rTMS has a good tolerability and can be efficient in accelerating the effect of antidepressants, particularly in individuals with shorter duration of depressive episodes and moderate symptom severity.Repetitivna transkranijalna magnetna stimulacija (rTMS) je metoda moždane stimulacije koja se sve češće primenjuje u kliničkom i istraživačkom radu. Dosadašnja istraživanja su ukazala na moguće antidepresivno dejstvo rTMS, ali jasna nadmoćnost ove metode u odnosu na placebo još nije potvrđena. Cilj rada Cilj rada je bilo praćenje efekta rTMS kao adjuvantnog tretmana antidepresivima na jačinu depresivnosti tokom 18 nedelja primene protokola stimulacije. Metode rada Četiri bolesnika sa dijagnozom umerenog, odnosno teškog depresivnog poremećaja bila su uključena u studiju. Protokol je podrazumevao primenu 2.000 stimulacija na dan tokom 15 dana sa frekvencijom rTMS od 10 Hz, intenziteta 120% motornog praga, nad levim dorzolateralnim prefrontalnim korteksom. Subjektivni i objektivni simptomi depresije ocenjeni su pre početka primene rTMS i ponovo procenjeni u 3, 6, 12. i 18. nedelji od početka stimulacije. Rezultati Kod dva ispitanika je po završetku protokola rTMS uočeno povlačenje simptoma depresije koje se održalo tokom čitavog perioda nadgledanja. Kod jedne ispitanice zapažena je tendencija uspostavljanja remisije u prvih 12. nedelja kliničkog praćenja, ali je u 18. nedelji došlo do pojačanja simptoma depresije. Kod druge ispitanice nije zapaženo značajnije smanjenje simptoma depresije ni u jednom trenutku kliničkog praćenja. Zaključak Preliminarni rezultati ukazuju na dobru podnošljivost rTMS i efikasnost u pojačavanju delovanja antidepresiva, i to najpre kod epizoda depresije koje kraće traju i čiji su simptomi umerenog intenziteta

Interakcija različitih fragmenata treće citoplazmatične petlje dopaminskog d2l receptora čoveka sa a-podjedinicom gi1 proteina - moguća terapeutska primena

In order to find the essential structural motif of the D2L dopamine receptor necessary for the interaction with a-subunit of Gi1 protein, four fragments of the third cytoplasmic loop (CPL3) of this receptor were cloned, expressed in E. coli and purified. After that, fusion proteins with glutathione-S-transferase (GST) were prepared and the interactions quantified by a colorimetric assay for GST activity determination. The presence of D2L-CPL3 fragment-Gia1 complexes was detected by SDS-polyacrylamide gel electrophoresis (PAGE). Kd values for the interaction of the three fragments with Gia1 were similar and in nmol/L range of concentrations, while the peptide representing the insert in the long form of the dopamine D2 receptor expressed about 10-fold lower binding affinity. These results could serve to design new therapeutic agents that might act at the level of receptor/G protein interaction rather than at the level of ligand-receptor binding.U cilju pronalaženja bitnih strukturnih motiva potrebnih za interakciju sa a podjedinicom Gi1 proteina klonirana su, eksprimirana i prečišćena 4 fragmenta treće citoplazmatične petlje (CPL3) dopaminskog D2L receptora koji su dalje pripremljeni kao fuzioni proteini sa glutation-S-transferazom (GST). Interakcije su kvantifikovane bojenom reakcijom za određivanje aktivnosti GST. Postojanje kompleksa D2L-CPL3 fragment- Gia1 je dokazano elektroforetskom analizom na SDS-poliakrilamidnom gelu (PAGE). Kd vrednosti za tri fragmenta su bile vrlo slične i u nmol/L opsegu koncentracija, dok je peptid koji predstavlja insert u dugom obliku dopaminskog D2 receptora posedovao oko 10 puta manji afinitet vezivanja za Gia1. Ovi rezultati mogu biti osnova za sintezu novih terapeutskih agenasa koji bi delovali na nivou interakcije receptora i G proteina umesto na nivou vezivanja liganda za receptor