Bradykinesia in patients with Parkinson's disease having levodopa-induced dyskinesias

We investigated the likelihood that bradykinesia coexisted with levodopa-induced dyskinesias (LID) in 10 dyskinetic Parkinson's disease patients (DPD). Their motor performance was compared to that of 10 age/gender-matched non-dyskinetic patients (NDPD) and 10 healthy controls. Whole-body movement (WBM) and rapid alternating movements (RAM) at the wrist were recorded simultaneously using 6-degree of freedom magnetic motion tracker and forearm rotational sensors, respectively. WBM was recorded prior to, and while subjects performed pronation-supination movements of their dominant hand with maximal rotational excursion, and as fast as possible for 10s. RANGE, VELOCITY and IRREGULARITY of pronation-supination cycles were quantified to assess motor performance. Results show that DPD patients had greater WBM than NDPD and controls during rest and RAM performance, as expected. There were no differences in motor performance between DPD and NDPD groups for RANGE and VELOCITY, despite significantly longer disease duration for the DPD group (15.5+/-6.2 years versus 6.6+/-2.6 years). However, both the NDPD and DPD groups showed significantly lower RANGE and reduced VELOCITY compared to controls, suggesting the presence of bradykinesia. For IRREGULARITY, DPD patients showed increased fluctuations in pronation-supination cycle amplitude compared to NDPD and controls. However, the lack of correlation between WBM magnitude and IRREGULARITY within the DPD group (Spearman's rank order, rho = 0.31, p > 0.05), suggests that LID were not the primary cause of increased IRREGULARITY. In conclusion, our results demonstrated that bradykinesia can coexist with dyskinesias, suggestive of distinct neural circuits. Our results also demonstrated that the occurrence of LID is not inevitably accompanied with worsening of motor performance.

[1]  A. Beuter,et al.  Analysis of rapid alternating movements in Cree subjects exposed to methylmercury and in subjects with neurological deficits. , 1999, Environmental research.

[2]  A Schrag,et al.  The EQ-5D—a generic quality of life measure—is a useful instrument to measure quality of life in patients with Parkinson's disease , 2000, Journal of neurology, neurosurgery, and psychiatry.

[3]  C. F. Snyder,et al.  Evaluation of a measurement strategy for Parkinson's disease: Assessing patient health-related quality of life , 2000, Quality of Life Research.

[4]  T. Paolo,et al.  Chronic treatment withl-DOPA, but not bromocriptine induces dyskinesia in MPTP-parkinsonian monkeys. Correlation with [3H]spiperone binding , 1986, Brain Research.

[5]  Andreas Daffertshofer,et al.  A dynamical model for mirror movements , 1999 .

[6]  M. Hallett,et al.  Pathophysiology of bradykinesia in Parkinson's disease. , 2001, Brain : a journal of neurology.

[7]  J. Nutt,et al.  Motor fluctuations and dyskinesia in Parkinson's disease. , 2001, Parkinsonism & related disorders.

[8]  J. Larsen,et al.  Health related quality of life in Parkinson's disease: a prospective longitudinal study , 2000, Journal of neurology, neurosurgery, and psychiatry.

[9]  H. Glick,et al.  Preference-based quality-of-life in patients with Parkinson’s disease , 2002, Neurology.

[10]  J. Nutt Fluctuations in response to treatment for Parkinson's disease. , 2001, Advances in neurology.

[11]  E. Melamed Early-morning dystonia. A late side effect of long-term levodopa therapy in Parkinson's disease. , 1979, Archives of neurology.

[12]  J L Vitek,et al.  Physiology of hypokinetic and hyperkinetic movement disorders: model for dyskinesia. , 2000, Annals of neurology.

[13]  M. Merello,et al.  Sleep benefit in parkinson's disease , 1997, Movement disorders : official journal of the Movement Disorder Society.

[14]  M. Piercey,et al.  Continuous administration decreases and pulsatile administration increases behavioral sensitivity to a novel dopamine D2 agonist (U-91356A) in MPTP-exposed monkeys. , 1995, The Journal of pharmacology and experimental therapeutics.

[15]  Neither simple nor sequential arm movements are bradykinetic in parkinsonian patients with peak-dose dyskinesias , 2005, Clinical Neurophysiology.

[16]  M. Muenter,et al.  Patterns of dystonia ("I-D-I" and "D-I-D-") in response to l-dopa therapy for Parkinson's disease. , 1977, Mayo Clinic proceedings.

[17]  D J Brooks,et al.  Neuroimaging of dyskinesia. , 2000, Annals of neurology.

[18]  G. Naglie,et al.  Quality of life in early Parkinson's disease: Impact of dyskinesias and motor fluctuations , 2004, Movement disorders : official journal of the Movement Disorder Society.

[19]  J L Bradshaw,et al.  Mirror movements in normal adult subjects. , 1994, Journal of clinical and experimental neuropsychology.

[20]  W R Woodward,et al.  The "on-off" phenomenon in Parkinson's disease. Relation to levodopa absorption and transport. , 1984, The New England journal of medicine.

[21]  A. E. Lang,et al.  Identification and characterization of neurons with tremor-frequency activity in human globus pallidus , 1997, Experimental Brain Research.

[22]  Joseph Jankovic,et al.  Motor fluctuations and dyskinesias in Parkinson's disease: Clinical manifestations , 2005, Movement disorders : official journal of the Movement Disorder Society.

[23]  Abbas F. Sadikot,et al.  The impact of ventrolateral thalamotomy on tremor and voluntary motor behavior in patients with Parkinson’s disease , 2006, Experimental Brain Research.

[24]  M. Delong,et al.  Functional and pathophysiological models of the basal ganglia , 1996, Current Opinion in Neurobiology.

[25]  M. Vidailhet,et al.  Worsening of levodopa‐induced dyskinesias by motor and mental tasks , 1999, Movement disorders : official journal of the Movement Disorder Society.

[26]  C. Goetz,et al.  Levodopa-induced myoclonus. , 1975, Archives of neurology.

[27]  P. Beek,et al.  Coordination disorders in patients with Parkinson's disease: a study of paced rhythmic forearm movements , 2000, Experimental Brain Research.

[28]  R. Wenzelburger Peak-dose dyskinesia; an acceptable price for mobility in late-stage Parkinson's disease? , 2005, Clinical Neurophysiology.

[29]  M Okada A method for quantification of alternate pronation and supination of forearms. , 1983, Computers and biomedical research, an international journal.

[30]  Laurent Gerbaud,et al.  Impact of the motor complications of Parkinson's disease on the quality of life , 2005, Movement disorders : official journal of the Movement Disorder Society.

[31]  J G Nutt,et al.  Levodopa‐induced dyskinesia , 1990, Neurology.

[32]  Y. Agid,et al.  Pathophysiology of L-dopa-induced abnormal involuntary movements. , 1985, Psychopharmacology. Supplementum.

[33]  R. Camicioli,et al.  Adverse Reactions to Controlled Release Levodopa/Carbidopa in Older Persons: Case Reports , 1995, Journal of the American Geriatrics Society.

[34]  Christine A. Armatas,et al.  Handedness and performance variability as factors influencing mirror movement occurrence. , 1996, Journal of clinical and experimental neuropsychology.

[35]  U Sabatini,et al.  Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia. , 1998, Brain : a journal of neurology.

[36]  A. Sadikot,et al.  The relationship between physiological tremor and the performance of rapid alternating movements in healthy elderly subjects , 2001, Experimental Brain Research.

[37]  Bernard R. Rosner,et al.  Fundamentals of Biostatistics. , 1992 .

[38]  M. Caligiuri,et al.  A quantitative study of levodopa-induced dyskinesia in Parkinson's disease , 1993, Journal of neural transmission. Parkinson's disease and dementia section.