SVIBOR - Project code: 3-01-104

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Project code: 3-01-104


EXTRAPIRAMIDAL DISORDERS BASIC AND CLINICAL ASPECTS


Main researcher: RELJA, MAJA (40774)


Assistants
Type of research: applied
Duration from: 01/01/91. to 12/15/95.
Papers on project (total): 25
Papers on project quoted in Current Contents: 3
Institution name: Medicinski fakultet, Zagreb (108)
Department/Institute: Laboratory for extrapyramidal disorders and clin.neuropharmacol. Department of Neurology, School of Medicine University of Zagreb
Address: Kišpatićeva 12,10000 Zagreb
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (1) 2335-595
Fax: 385 (1) 424-001
Summary: We developed a new computerized method for measuring rigidity with an albow device ("TONOMETER"). The data from 127 subjects (103 controls and 24 parkinsonian patients) were investigated to show the clinical utility of the method. The instrumental quantification of rigidity correlates highly with clinical ratings of parkinsonian rigidity. The test-retest repetability was excellent. In parkinsonian patients versus normal controls significantly higher values of measured rigidity were observed. Moreover, activation procedure significantly increases rigidity only in parkinsonian patients. Activated rigidity in control subjects is lower than basal rigidity. For the first time, during the levodopa test we applied a computerized elbow device (instrumental rigidity quantification) for assessing the responsiveness of parkinsonian patients to dopaminergic medication. Our investigation showed that instrumental rigidity quantification is more sensitive compared to clinical scoring in assessment of motor response to levodopa in parkinsonian patients. In addition, instrumental procedure is capable of detecting even the smallest change caused by therapy, and are useful for following up long-term treatment. Precise numerical values of measured rigdity have more statistical power then clinical scale when using in research. Thus, clinical pharmacological investigations of extrapyramidal disorders may benefit from quantitative measurement of rigidity.

Keywords: Parkinson's disease, rigidity quantification, levodopa-test; activated rigidity, positron emission tomography-PET; catechol-O-methyl transferase - COMT, selegiline, neuroprotection.

Research goals: Parkinson's disease (PD) is the most common of the neurodegenerative disorders that results in an akinetic-rigid syndrome. While levodopa is the most effective symptomatic therapy of PD, introduction of selegiline (selective MAO-B type inhibitor) indicates that new treatment might retard the death of s.nigra neurons and slow the progression of disease. Possibility of neuroprotection makes early diagnosis very important. PET for the time being is the only method that can detect "subclinical" striatal dopamine deficiency. But method is to expensive , it is labour intensive and it is not widely available. Many tests (biochemical, neurophysiological) vie for the title of "diagnostic test for the early or subclinical PD". None have yet won the prize. Our results showed that measurement of activated rigidity using our own-developed instrumental elbow device, demonstrates even greater differences between PD patients and controls then basal rigidity measurements. Rigidity quantification can be reliable and widely available method for assessimg early stage of PD. We are entering a new era in PD reserch and if preventive or neuroprotective therapy is to become a reality we will require development of reliable and widely a vailable methods for assessing early stage of PD. Thus, the aims of present projects proposal are: - application of rigidity quantification in detecting preclinical stage of PD - to investigate the effect of aging on rigidity in control subjects - investigation of new therapy approaches in PD by using rigidity quantification - to investigate how long the symptomatic, therapeutic effect of selegiline lasts after withdrawal of the drug As expected results our investigation can provide newer, more readiliy available and cheaper technology for detecting presymptomatic early stage of Parkinson's disease.

COOPERATION - INSTITUTIONS


  1. Name of institution: Department of Neurology, University of Turku
    Type of institution: University/Faculty
    Type of cooperation: Occasional exchange of experts
    City: Turku, Finska

OTHER ACHIEVEMENTS


  1. Name: Konstrukcija nove mašine za kvantifikaciju rigora - TONOMETAR
    Type of achievement: Prototypes
    Authors: Relja Maja, Kolar Miroslav
Other information about the project.
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