Dataset Information

Quantitative Measurement of Akinesia in Parkinson's Disease.

ABSTRACT: Background:There is great interest in developing simple, user-friendly, and inexpensive tools for the quantification and elucidation of motor deficits in patients with Parkinson's disease (PD). These systems could help to monitor the clinical status of patients with PD, to develop better treatments, and to identify individuals who have subtle motor signs that might pass unnoticed in the conventional neurological examination. Methods:Mememtum, a smartphone application that allows for the quantification of several parameters of movement, such as regularity, rhythm, and changes in the number of taps while taping with a single finger and with alternating fingers, was developed and then tested in a pilot study in Madrid and in an extensive study in Quito, Ecuador. Results:Almost all patients could successfully perform single-finger tapping, but approximately 10% of patients with severe parkinsonism had problems taping with alternating fingers. The results revealed changes in the regularity of the pressure applied while tapping and a reduction in the number of taps on the device screen when alternating tapping among patients who had idiopathic PD and vascular parkinsonism compared with controls and individuals who had prediagnostic motor abnormalities of PD. Conclusion:Applications available in smartphones could be used for investigation and treatment of patients with PD, but much research is needed to optimize the ideal parameters to be investigated and the potential usefulness of this technique for patients with PD in different stages of the disease.

SUBMITTER: Lalvay L

PROVIDER: S-EPMC6174408 | biostudies-literature | 2017 May-Jun

REPOSITORIES: biostudies-literature

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Quantitative Measurement of Akinesia in Parkinson's Disease.

Lalvay Lissette L Lara Miguel M Mora Andrea A Alarcón Fernando F Fraga Manuel M Pancorbo Jesús J Marina José Luis JL Mena María Ángeles MÁ Lopez Sendón Jose Luis JL García de Yébenes Justo J

Movement disorders clinical practice 20160803 3

<h4>Background</h4>There is great interest in developing simple, user-friendly, and inexpensive tools for the quantification and elucidation of motor deficits in patients with Parkinson's disease (PD). These systems could help to monitor the clinical status of patients with PD, to develop better treatments, and to identify individuals who have subtle motor signs that might pass unnoticed in the conventional neurological examination.<h4>Methods</h4>Mememtum, a smartphone application that allows f ...[more]

PMID: 30363442

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Project description:Akinesia is a major manifestation of Parkinson's disease (PD) related to difficulties or failures of willed movement to occur. Akinesia is still poorly understood and is not fully alleviated by standard therapeutic strategies. One reason is that the area of the clinical concept has blurred boundaries referring to confounded motor symptoms. Here, we review neuroimaging studies which, by providing access to finer-grained mechanisms, have the potential to reveal the dysfunctional brain processes that account for akinesia. It comes out that no clear common denominator could be identified across studies that are too heterogeneous with respect to the clinical/theoretical concepts and methods used. Results reveal, however, that various abnormalities within but also outside the motor and dopaminergic pathways might be associated with akinesia in PD patients. Notably, numerous yet poorly reproducible neural correlates were found in different brain regions supporting executive control by means of resting-state or task-based studies. This includes for instance the dorsolateral prefrontal cortex, the inferior frontal cortex, the supplementary motor area, the medial prefrontal cortex, the anterior cingulate cortex or the precuneus. This observation raises the issue of the multidimensional nature of akinesia. Yet, other open issues should be considered conjointly to drive future investigations. Above all, a unified terminology is needed to allow appropriate association of behavioral symptoms with brain mechanisms across studies. We adhere to a use of the term akinesia restricted to dysfunctions of movement initiation, ranging from delayed response to freezing or even total abolition of movement. We also call for targeting more specific neural mechanisms of movement preparation and action triggering with more sophisticated behavioral designs/event-related neurofunctional analyses. More work is needed to provide reliable evidence, but answering these still open issues might open up new prospects, beyond dopaminergic therapy, for managing this disabling symptom.

Project description:Pramipexole and ropinirole are dopamine agonists that are efficacious in treating motor disturbances of neuropathologies, e.g., Parkinson's disease and restless legs syndrome. A significant portion of treated patients develop impulsive/compulsive behaviors. Current treatment is dose reduction or switching to an alternative dopamine replacement, both of which can undermine the motor benefits. Needed is a preclinical model that can assist in identifying adjunct treatments to dopamine agonist therapy that reduce impulsive/compulsive behaviors without interfering with motor benefits of the dopamine agonist. Toward that objective, the current study implemented a rat model of Parkinson's disease to behaviorally profile chronically administered pramipexole. This was accomplished with male Sprague-Dawley rats wherein (i) 6-hydroxydopamine-induced lesions of the dorsolateral striatum produced Parkinson's disease-like akinesia, measured in the forelimbs, (ii) intracranial self-stimulation-mediated probability discounting indicated impulsivity/risk-taking, and (iii) two doses of pramipexole were continuously administered for 14-28days via osmotic minipumps to mirror the chronic, stable exposure achieved with extended release formulations. The atypical antidepressant, mirtazapine, is known to reduce behaviors associated with drug addiction in rats; thus, we demonstrated model utility here by determining the effects of mirtazapine on pramipexole-induced motor improvements versus probability discounting. We observed that forelimb akinesia subsequent to striatal lesions was attenuated by both pramipexole doses tested (0.3 and 1.2mg/kg/day) within 4h of pump implant dispensing 0.3mg/kg/day and 1h by 1.2mg/kg/day. By contrast, 12-14days of infusion with 0.3mg/kg/day did not alter discounting, but increases were obtained with 1.2mg/kg/day pramipexole, with 67% of 1.2mg/kg/day-treated rats meeting categorical criteria for 'high risk-taking'. Insertion of a second minipump delivering mirtazapine did not alter motor function during 14days of co-administration with pramipexole, but was sufficient to attenuate risk-taking. These outcomes revealed distinct probability discounting and anti-akinesia profiles for pramipexole, indicating that pharmacotherapy, (e.g., mirtazapine treatments), can be developed that reduce risk-taking while leaving motor benefits intact.

Dataset Information

Quantitative Measurement of Akinesia in Parkinson's Disease.

Publications

Quantitative Measurement of Akinesia in Parkinson's Disease.

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