Pharmacogenetics of drug response in Parkinson's disease.

Parkinson's disease (PD) is a debilitating, demoralizing and financially devastating condition affecting 1% of population at the age of 60 years. Thus, very important issue to address is individual therapy optimization. Recent results have shown evidence that variable efficacy of treatment and risk of motor and mental complications could have genetic origin. Significant roles in that process play (pharmaco)genomic/genetic studies of PD. Variability in genes coding for drug-metabolizing enzymes, drug receptors and proteins involved in drug pathway signaling is an important factor determining inter-individual variability in drug responses. Interpersonal differences in drug responses are clearly documented although individualized treatment of PD is not widely known. Treatment with antiparkinsonian drugs is associated with the development of complications, such as L-DOPA-induced dyskinesia (LID), hallucinations and excessive daytime sleepiness. Carriers of specific genetic polymorphisms are particularly susceptible to development of some of these drug adverse effects. Pharmacogenomics aims to understand the relationship between genetic factors and inter-individual variations in drug responses, and to translate this information in therapy tailored to individual patient genetics. Relatively few efforts have been made to investigate the role of pharmacogenetics in the individual response to anti-PD drugs. Thus, many genetic variations and polymorphisms in myriad of different proteins can influence individual response to anti-PD drugs.

A survey of female students with migraine: what is the influence of family history and lifestyle?

OBJECTIVES: To compare characteristics of migraine and some lifestyle habits in migraineurs with and without a positive family history for migraine. METHOD: The prevalence study was combined with a case-control study and comprised 245 female students with migraine. RESULTS: Out of 245 female students with migraine, 132 (53.9%) had a positive family history for migraine. In comparison with migraineurs who had not, those with a positive family history were younger at the onset of migraine and significantly more frequently reported menstrual migraine (p < 0.001), unilateral pain (p < 0.05) and pulsate pain (p < 0.05) as well as severe headache (p < 0.01). In comparison to migraineurs with a positive family history for migraine, those who did not report a significantly higher frequency of average number of meals per day of <3 (p < 0.001), missed meals (p < 0.05) and an average sleep duration of ≤ 6 h (p < 0.05). CONCLUSIONS: The results of the present study are in line with literature showing a high frequency of positive family history for migraine among migraineurs. They also suggest that subjects with a positive family history have a lower "migrainous threshold" for the development of migraine and that environmental factors are more important for the occurrence of migraine in subjects without a positive family history. Accordingly, the conclusions of this study are limited to reproductive aged women.

Infections as a risk factor for Parkinson's disease: a case-control study.

OBJECTIVES: The etiology of Parkinson's disease (PD) is unknown. The aim of the study was to test the hypothesis that some infectious diseases are related to the occurrence of PD. METHODS: The case-control study, conducted in Belgrade during the period 2001-2005, comprised 110 subjects diagnosed for the first time as PD cases, and 220 controls chosen among patients with degenerative joint disease and some diseases of the digestive tract. RESULTS: According to logistic regression analysis, PD was significantly related to mumps [odds ratio adjusted on occupation and family history of PD (aOR) = 7.86, 95% confidence interval (CI) = 3.77-16.36], scarlet fever (aOR = 12.18, 95% CI = 1.97-75.19), influenza (aOR = 8.01, 95% CI = 4.61-13.92), whooping cough (aOR = 19.90, 95% CI = 2.07-190.66) and herpes simplex infections (aOR = 11.52, 95% CI = 2.25-58.89). Tuberculosis, measles and chicken pox were not associated with PD. Other infectious diseases we asked for were not reported (12 diseases), or were too rare (four diseases) to be analysed. CONCLUSION: The results obtained are in line with the suggestion that some infectious diseases may play a role in the development of PD.

Vitamin D Serum Levels and Vitamin D Receptor Genotype in Patients with Parkinson's Disease.

BACKGROUND: Vitamin D is a steroid hormone, known to be involved in the pathogenesis of various neurodegenerative disorders, including Parkinson's disease (PD). We aimed to clarify the relationship between hypovitaminosis D and the predisposition for PD and its clinical presentation. An additional aim was to examine the specific gene polymorphisms associated with vitamin D level. MATERIAL AND METHODS: Total level of 25(OH)-vitamin D (25(OH)D) was measured in the serum of parkinsonian patients (n = 113) and controls (n = 82) using a commercial immunoassay. Genetic analyses were performed using Taqman assays on Real Time PCR amplification system. RESULTS: Higher frequency of vitamin D deficiency (<50 nmol/L) was observed in PD patients, compared to controls (40.7% and 23.2%, respectively, P = 0.010). It was also a positive predictive marker of PD (OR, 2.27; 95% CI, 1.206-4.298; P < 0.011). Significantly higher UPDRS (35.85 ± 1.35 and 32.09 ± 0.99, respectively, P = 0.023) and HY scores (2(1.5-2.5) and 1.5(1.0-2.0), respectively, P = 0.005) were present in patients with 25(OH)D level < 50 nmol/L compared to patients with 25(OH)D level ≥ 50 nmol/L. Despite some trends observed, differences in allelic and genotypic distribution between controls and patients, as well as between subgroups, did not reach the level of significance (P > 0.05). CONCLUSIONS: Findings of this study confirm the hypothesis of a significant relationship between hypovitaminosis D and PD. We demonstrated higher prevalence of vitamin D deficiency in PD patients, as well as its predictive potential for the onset and progression of PD.

Environmental factors and Parkinson's disease: a case-control study in Belgrade, Serbia.

A case-control study was performed in Belgrade in order to investigate the association between Parkinson's disease (PD) and some environmental factors. During the period 2001-2005, 110 new PD cases and 220 hospital controls were interviewed. Cases and controls were matched by sex, age (+/-2 years), and place of residence (urban/rural). According to multivariate conditional logistic regression analysis, PD was positively asssociated with exposure to insecticides (odds ratio (OR) 3.22, 95% confidence interval (95% CI) 1.32-7.87), dyes (OR 25.33; 95% CI, 2.89-222.0), and naphtha and its derivates (OR 9.53; 95% CI, 1.04-86.96), and with gardening (OR 5.51; 95% CI, 3.04-10.01), well water drinking (OR 2.62; 95% CI, 1.40-4.90), and spring water drinking (OR 2.19; 95% CI, 1.15-4.16). Negative association was found for service-sector working (OR 0.15; 95% CI, 0.04-0.59). The results obtained did not changed after adjustment for smoking. The findings of the present study support the role of environmental factors in the occurence of PD.

A method to assess hand motor blocks in Parkinson's disease with digitizing tablet.

The non-volitional sudden discontinuation of motor activity, called motor block (MB) or freezing is most commonly associated with Parkinson's disease (PD). MB extends beyond the classical manifestations of PD: akinezia, bradykinezia, rigidity, tremor, and postural instability. MB has been observed and quantified in internally cued repetitive movements such as gait, speech, handwriting, and manual tapping tasks as a distinct feature of PD. We present a simple measurement system for objective evaluation of MB during point-to-point hand movements in patients with PD. Hand trajectories were evaluated in eight PD patients based on values obtained from a digitizing tablet (DT) score. 50 trials per day were recorded in seven consecutive working days. Subjects were instructed to consciously prepare and self-initiate movements between arbitrarily fixed starting and target points without lifting a wireless magnetic mouse. MB was identified as the time interval during movement with no change in coordinates. We analyzed three kinematic parameters: duration, start and number of MBs. If MBs were documented, the DT score was 1, if not, 0. Results were then compared with the ratings of the question in motor section related to freezing of hands from the Unified Parkinson's Disease Rating Scale (UPDRS). For all patients, DT score was in agreement with the UPDRS. Present results indicate that DT is useful for assessing MBs during volitional planar hand movement. This low-cost instrument may be included in a clinical test battery because of short testing time and trouble-free preparation of patient.

Homocysteine serum levels and MTHFR C677T genotype in patients with Parkinson's disease, with and without levodopa therapy.

Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to elevated serum homocysteine levels in parkinsonian patients. We aimed to clarify the interplay of these factors in pathogenesis of Parkinson's disease (PD)-related hyperhomocysteinemia. Total serum levels of homocysteine (tHcy) and MTHFR C677T genotype were investigated in levodopa-treated and -untreated parkinsonian ("de novo") patients, as well as in control healthy subjects matched by age and gender (N=83, 30 and 53, respectively). MTHFR C677T genotypes were equally distributed in PD patients and control subjects, the T allele homozygosity being observed in app. 12-17% cases. tHcy concentrations were significantly higher in both levodopa-treated and -untreated PD patients than in control subjects, and in TT homozygotes than in CT or CC genotype carriers. tHcy levels significantly correlated with the duration of the disease in PD treated patients only, reaching the maximum after 3-6 years. However, there was no correlation between tHcy levels and total daily intake of levodopa in the same group of PD patients. In conclusion, MTHFR C677T genotype is a significant factor for hyperhomocysteinemia in patients with PD, levodopa-untreated and probably even more in levodopa-treated PD patients.

Why is nitric oxide important for our brain?

The freely diffusible gaseous compound nitric oxide (NO) has been shown to be an important messenger in many organ systems throughout the body, and particularly in the central nervous system (CNS). The importance of NO as an intermediary in cell communication in the brain is highlighted by the fact that the excitatory amino acid glutamate, the most abundant CNS neurotransmitter, is an initiator of the reaction that forms NO. Because of its numerous physiological and pathophysiological roles, the impact of NO on clinical medicine is developing. NO can act as a "double-edged sword" and it has been demonstrated that clarification of the dual effect of NO might have implications for clinical medicine, and could lead to the emergence of therapeutic opportunities. Accordingly, NO was proclaimed "Mole cule of the Year" in 1992 by the journal Science, while discovery of the pathways and roles of NO was acknowledged with the Nobel Prize in 1998. Additionally, the ubiquity of NO in the CNS implies that drugs designed to modify the biological activity of NO may have distinct effects. Thus, further clinical applications of NO, of its analogs or of newly developed NOS inhibitors are forthcoming. The therapeutic challenge would be to succeed in manipulating the NO pathways selectively.

Primary lymphoma of the brain in a young man whose brother died of hemophagocytic lymphohistiocytosis: case report.

INTRODUCTION: We represent the unique occurrence of primary central nervous system lymphoma (PCNSL) in a patient whose brother died of genetically confirmed hemophagocytic lymphohistiocytosis (HLH). CASE OUTLINE: We report a case of a 25-year-old male patient with primary aggressive diffuse large B-cell lymphoma affecting the brain and PCNSL. Despite one year of medical treatment outcome was lethal. However, our patient had a relatively longer survival compared to median survival time for PCNSL. Additionally, he had two older brothers who died at the age of about 11 years. One died of fulminate malignancy, shortly after pediatric admission, before the diagnosis could be established. The other one died from genetically confirmed (perforin mutation/PRF1) HLH. Our patient was heterozygous carrier of perforin mutation representing the genetic marker for HLH. Our patient's father was the carrier of the same mutation but had no symptoms of any disease. CONCLUSION: This case points at the presence of HLH and diffuse large B-cell PCNSL in brothers. Extensive assessment of patients with probable PCNSL and familial HLH is necessary, including genetic analysis for HLH.

Hereditary patterns of Belgrade university female students with migraine and nonmigraine primary headache.

Various studies have provided evidence that migraine is a multifactorial genetic disorder. The aim of the present study was to compare hereditary patterns of female students with migraine (245 subjects) and non-migraine primary headaches (1053 subjects). The prevalence study was performed combined with a case-control study. Migraineurs had significantly more frequently one or more first-degree and/or second-degree relatives with migraine. Students with menstrual migraine, in comparison with other subtypes of migraine (with the exception of premenstrual migraine), had significantly more frequently > or = 2 relatives with migraine. Among students with non-migraine primary headaches, those with menstrually related headache had more frequently relatives with migraine in comparison with students suffering from menstrually unrelated nonmigraine headache. The results obtained are in line with the results of genetic epidemiologic studies suggesting that genetic factors play a role in the occurrence of migraine.

The stressful life events and Parkinson's disease: a case-control study.

A case-control study was conducted in order to investigate the possible link between stressful life events and Parkinson's disease (PD). A group of 110 consecutive newly diagnosed PD cases treated at the Institute of Neurology, Faculty of Medicine, Belgrade University, was compared with a control group comprising 220 subjects with degenerative joint disease and some diseases of the digestive tract. The case and control subjects were matched by sex, age (±2 years) and place of residence (urban/rural). According to conditional multivariate logistic regression analysis, PD was found to be significantly related to retirement (odds ratio--OR 18.73, 95% confidence interval--95%CI 1.9-175.4), birth of own child (OR 66.22, 95%CI 8.3-526.3) and air raids (OR 5.66, 95%CI 2.4-13.5). The risk of PD significantly increased with the number of stressful events. The results of the present study support the hypothesis that stress may play a role in the development of PD.

A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats.

In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of µ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (±)-cis-3-methyl fentanyl (CM), (±)-cis-3-carbomethoxy fentanyl (C), (±)trans-3-carbomethoxy fentanyl (T) and (±)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27)>F(1)>C(0.35)≥T(0.11)≥B(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46)≥T(0.11)≥B(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-α,α,17-trimethyl-, (5α,7α) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)>O(5)≥T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3)≥T(2.3)>M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6-11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.

Cigarette smoking, coffee intake and alcohol consumption preceding Parkinson's disease: a case-control study.

OBJECTIVE: A case-control study was performed in Belgrade in order to investigate the association between Parkinson's disease (PD) and smoking, coffee and alcohol consumption. METHODS: During the period 2001-2005, 110 new PD cases and 220 hospital controls were interviewed. Cases and controls were matched by sex, age and place of residence (urban/rural). For the analysis of data conditional univariate and multivariate logistic regression methods were used. RESULTS: With PD were associated, independently from each other, current smoking [odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.23-0.82], alcohol consumption (OR = 4.78; 95% CI = 2.67-8.55) and coffee consumption (OR = 2.54; 95% CI = 1.36-4.75). In ever smokers the risk for PD significantly decreased with the increasing number of cigarettes smoked and with increasing duration of smoking. The risk for PD significantly increased with the increasing quantity of alcohol consumption. PD risk was significantly higher in subjects whose average daily consumption of coffee was 1 and 2-3 cups, and it was lower (but not significantly) in those whose daily coffee consumption was 4+ cups. Cases and controls did not differ in duration of alcohol and coffee consumption. The results of multivariate analyses did not substantially change after adjustment on family history positive on PD. CONCLUSION: The findings of this study support the hypotheses of inverse association of smoking with PD, but an inverse association with coffee was not confirmed. PD was found to be positively associated with coffee and alcohol consumption.

Fluoxetine does not impair motor function in patients with Parkinson's disease: correlation between mood and motor functions with plasma concentrations of fluoxetine/norfluoxetine.

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 < or = Hamilton Rating Scale for Depression (HDRS) < or = 23)] without dementia [(25 < or = 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 microg/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.

Suicide and suicidal ideation in Parkinson's disease.

Little is known about the prevalence and correlates of suicidal behavior in Parkinson's disease (PD). In the first part of the study, we followed a cohort of 102 consecutive PD patients for 8 years and found that the suicide-specific mortality was 5.3 (95% CI 2.1-12.7) times higher than expected. In the second part, we tested 128 PD patients for death and suicidal ideation and administered an extensive neurological, neuropsychological and psychiatric battery. Current death and/or suicidal ideation was registered in 22.7%. On univariate logistic regression analysis, psychiatric symptoms (depression, but also anxiety and hopelessness), but not the PD-related variables, were associated with such ideation. On multivariate logistic regression analysis this association held for major depression (odds ratio=4.6; 95% CI 2.2-9.4; p<0.001), psychosis (odds ratio=19.2; 95% CI 1.4-27.3; p=0.026), and increasing score of the Beck Hopelessness Scale (odds ratio=1.2; 95% CI 1.0-1.4; p=0.008). In conclusion, the suicide risk in PD may not be as high as it is expected, but it is certainly not trivial. According to our data almost a quarter of PD patients had death and/or suicidal ideation, that may significantly influence their quality of life.

[Dopa-responsive dystonia].

BACKGROUND/AIM: Dystonia is considered to be a prolonged involuntary contractions of the muscles leading to twisting, repetitive movements or irregular postures. Etiologically, it could be classified as primary and secondary dystonia. Dopa-responsive dystonia (DRD) belongs to a group of primary dystonia. The aim of this study was to detect the presence of gene GCH-I mutation in our population in patients with dopa-responsive dystonic dyskinesia and to analyse clinical specificity of the affected. METHODS: Out of the group of patients with dystonia of different distribution four patients were separated whose clinical picture indicated the diagnosis of DRD. Two patients had a positive family anamnesis while the other two were sporadic. Genetic analysis was performed by the use of a standard protocol, which included PCR amplification and DNK sequencing according to the method of Senger and autoradiografy. RESULTS: In the patients from the family DRD-1 new hetaerazygote point mutation 520G-->A in 4-m exson gene GCH-I was revealed. First symptoms of the disease showed in the age of seven by the torsion of the left foot, progressively advanced and got into the evolution of numbness in the legs, aggravated gait, tending to worsen in the evening, and the therapy with levodopa (500 mg) produced a dramatic effect. The second mutation in the female patient from the family DRD-2 was homozygote deletion in 1-m intron gene GCH-I (IVS1-85delA). Unwilling torsion of the foot, feeling of weakness in the lower extremities (that caused falling without loss of the consciousness) were clinical demonstrations of the disease. The application of levodopa (300 mg) caused regression of the symptoms of the disease. Hetaerazygote deletion of adenine in the position 209 in the first exon (209del A) was identificated in the patient DRD-3 with negative family anamnesis, in who in the age of ten the torsion of the foot inside occured for the first time following by trembling of both the left and right legs at rest; after a few years, tremor of hands also appeared, which became worse in stressful situations. The father of the patient was an asymptomatic bearer of mutation. The fourth mutation in gene GCH-I was found in I exon gene GCH-I, 208delA. The disease was started by torsion of the left foot, progressing easily, and worsening in the evenings, but at the age of 30, moving became harder, fatigue and pain in muscles, increased and at the age of 40 the patient recognised the change of speech. The application of levodopa (300 mg/daily) made the patient feel better and walk independently. CONCLUSION: The study presented four patients with genetic confirmation of the diagnosis of dopa-responsive dystonia. This entity is very significant in differential diagnostics of both early dystonia (< 26 years) and early parkinsonism (< 40 years) since it can be successfully managed by applyng relatively low doses of levodopa over a long period of time.

[Effects of new nitric oxide synthase inhibitors on spontaneous locomotor activity].

INTRODUCTION: New nitric oxide synthase (NOS) inhibitors: 3-bromo-7-nitroindazole (3-Br-7-NI), 1-(2-trifluoromethylphenyl) imidazole (TRIM), S-methyl-L-thiocitrulline (S-Me-TC) and 7-nitroindazole (7-NI) reduce spontaneous locomotor activity in mice. MATERIAL AND METHODS: In order to elucidate central effects of NOS inhibitors on locomotor activity, the influence of 7-NI on electroencephalographic (EEG) power spectrum in rats was investigated. RESULTS: 7-NI reduced the EEG power density in all frequency bands in rats, suggesting a depression of the central neuronal activity. The electrophysiologic power was most reduced in the range of 7-9 Hz of the rhythmic slow activity (theta rhythm), which is in accordance with decreased locomotor activity observed following administration of NOS inhibitors. CONCLUSION: The present results indicate that nitric oxide exerts an excitatory effect on central neuronal structures involved in regulation of locomotion.

[A rapid detection of motor block in patients with Parkinson disease during volitional movements of the hand]. / Brz metod za otkrivanje motornih blokova u toku voljnih pokreta rukom kod osoba s Parkinsonovom bolescu.

INTRODUCTION: An algorithm to study hand movements in patients with Parkinson's disease (PD) who experience temporary, involuntary inability to move a hand have been developed. In literature, this rather engimatic phenomenon has been described in gait, speech, handwriting and tapping, and noted as motor blocks (MB) or freezing episodes. Freezing refers to transient periods in which the voluntary motor activity being attempted by an individual is paused. It is a sudden, unplanned state of immobility that appears to arise from deficits in initiating or simultaneously and sequentially executing movements, in correcting inappropriate movements or in planning movements. The clinical evaluation of motor blocks is difficult because of a variability both within and between individuals and relationship of blocks to time of drug ingestion. In literature the terms freezing, motor block or motor freezing are used in parallel. AIM: In clinical settings classical manifestations of Parkinson's Disease (akinesia, bradykinesia, rigidity, tremor, axial motor performance and postural instability) are typically evaluated. Recently, in literature, new computerized methods are suggested for their objective assessment. We propose monitoring of motor blocks during hand movements to be integrated. For this purpose we have developed a simple method that comprises PC computer, digitizing board and custom made software. Movement analysis is "off line", and the result is the data that describe the number, duration and onset of motor blocks. METHOD: Hand trajectories are assessed during simple volitional self paced point-to-point planar hand movement by cordless magnetic mouse on a digitizing board (Drawing board III, 305 x 457 mm, GTCO Cal Comp Inc), Fig. 1. Testing included 8 Parkinsonian patients and 8 normal healthy controls, age matched, with unknown neurologic motor or sensory disorders, Table 1. Three kinematic indicators of motor blocks: 1) duration (MBT%); 2) onset (t%); and 3) number (N) of MB episodes, allow identification and quantification of motor blocks. Duration of motor blocks (MBT) is defined as the time sequence when (x,y) coordinates do not change their values and is expressed in percentage from the whole movement duration MBT% = MBT/T (%). If during some movements more than one motor block occurs (N > 1) then this movement is decomposed. The whole movement motor block (mbt) is the sum of all motor blocks MBT; during the same movement and expressed in percentage from the whole movement duration mbt% = mbt/T (%). The onset of motor block (t) is determined with the beginning of motor block and expressed in percentage from the whole movement duration: t% = t/T (%). After the determination of kinematic indicators of motor blocks (MBT, N, t) for healthy controls, their mean values are calculated. Statistical package ANOVA is applied to determine statistical significance of the difference between PD patients and mean values from age matched control healthy group. PD patients are then classified into two groups: one group consisting of PD patients with motor blocks and the other without motor blocks, similar to healthy controls. RESULTS: Acquired movements are processed and analyzed. Fig. 2 is an example of hand trajectories. Time course of (x, y) coordinates indicates motor block appearance, Fig. 3. Detailed presentation of kinematic indicators of motor block (MBT, N, t) is in Fig. 4. Intra-subject variability of these parameters is presented in Figs 5, 6 and 7 for patient #3. The results for N show that 45% of all patients #3 movements had none motor blocks (N = 0); 20% had N = 1; 15% had N = 2; 11.5% had N = 3; 5.7% had N = 4; 0.3% had N = 5; 0.7% had N = 6; 0.3% had N = 7 and 1% had N = 8 motor blocks. The results for t% show that 3% of all patients' #3 blocks started at first quarter, 17% started in the second, 36% in the third, and 44% in the last quarter of movement. The results for MBT% show that 14.5% of all movements had MBT% in the range 0-5%; 56% had MBT% 5-10%; 22% had MBT% 10-15%; 5.5% had MBT% 15-20% and 2% had MBT% 20-25%. No block lasted more than 25% from the whole movement duration. Table 2 is the summary of mean variability for kinematic indicators of motor block (N, mbt%, t%) and for the movement duration T during a 7 day-testing of patients #3. The analysis of calculated data for eight tested PD patients revealed a significant difference (p < 0.01) between healthy controls and three PD patients; data on five PD patients were not significantly different (ns). This method clustered 3 PD patients in the group that experience motor blocks, while the rest were in the group without their significant occurrence. DISCUSSION: This algorithm is an additional instrument in classical evaluation of PD patients during their clinical evaluation and treatment. It provides to clinician a rapid feedback on the changes of voluntary hand movements in everyday progress of illness. Furthermore, this method could be of assistance for developing strategies to overcome motor blocks in arm movements at their beginning, as well as for the feedback of the success of drug therapy.