Morning Bradykinesia Common, Device-based Study Confirms

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by Steve Bryson, PhD |

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Using a wrist-worn device that continuously monitors body movements, a U.S. study has found 85% of people with Parkinson’s disease experience  bradykinesia — abnormally slow movements — in the morning.

Even after the first daily dose of levodopa, a standard Parkinson’s therapy, 64% had continued morning bradykinesia. Moreover, morning bradykinesia was more severe in those who responded to levodopa.

These data suggest that some people with Parkinson’s disease may be under-treated or need additional treatments, the researchers noted.

The study, “Evaluation of morning bradykinesia in Parkinson’s disease in a United States cohort using continuous objective monitoring,” was published in the journal Clinical Parkinsonism & Related Disorders.

Parkinson’s disease is marked by a deficiency in dopamine, a molecule that sends messages between nerve cells to control various body processes, including movements. A lack of dopamine leads to characteristic motor symptoms, such as tremors, muscle rigidity, and bradykinesia.

Standard treatment for Parkinson’s is L-dopa, or levodopa, a precursor molecule that is converted to dopamine in the brain. Over time, however, patients taking levodopa may develop motor complications, including motor fluctuations and involuntary movements called dyskinesia.

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Motor fluctuations involve periods when motor symptoms improve after a dose of levodopa, referred to as “on” episodes, followed by periods when the medications are no longer effective, and symptoms reoccur, known as “off” episodes.

Morning “off” episodes consist of motor fluctuations or bradykinesia in the morning, which may be caused by reduced benefit from the last levodopa dose the night before, or a delay after the first daily dose. These morning episodes may cause significant disability, which affects patients’ quality of life.

However, “off” episodes can be difficult to define clinically because reporting methods often rely on patient-derived diaries, which can be problematic due to inaccurate recall, reduced compliance and diary fatigue, and a lack of awareness of motor symptoms caused by the side effects of medications.

Wearable devices that can monitor Parkinson’s symptoms may provide continuous objective measurements (COM) and help define morning “off” periods. One such device — the Personal KinetiGraph (PKG) — is a wrist-worn watch that continuously monitors bradykinesia over a six-day period.

Researchers based at the Parkinson’s Disease and Movement Disorders Center of Boca Raton, in Florida, now have applied the PKG to examine the prevalence and severity of morning bradykinesia, as a surrogate measure for morning “off” episodes, in a large group of Parkinson’s patients in the U.S.

Scores for bradykinesia as well as dyskinesia were generated based on two-minute interval PKG recordings between 9 a.m. and 6 p.m. during the six days the watch was worn. A median bradykinesia score of 26 or higher, and a median dyskinesia score of seven or more, were considered abnormal.

Bradykinesia and dyskinesia data were available for 3,288 individuals with Parkinson’s, with a median age of 71.9 years, of whom 67% were male. Overall, the median bradykinesia score was 28.6, and 65% of participants had abnormal scores, while the median dyskinesia score was 1.1, with 3% above the abnormal score level.

The time in bradykinesia rose with with increasing median bradykinesia scores. Time in bradykinesia of 30% or more was estimated to have occurred in 79% of individuals, including all of those with abnormal bradykinesia scores. Most had scores from 24 to less than 26, and a smaller proportion of individuals had scores from 22 to less than 24.

Levodopa responsiveness was estimated by calculating an improvement in bradykinesia score at effect time versus time of the first levodopa dose of the day. A significant levodopa response corresponded to a 14-point decrease (improvement) in scores from the UPDRS Part III, a standardized motor function assessment tool.

Among the 677 with data that could be evaluated, a significant levodopa response was observed in about one-third of participants.

A significant levodopa response became less common with an increased median bradykinesia score. A 39%–50% response rate was found in those with median bradykinesia scores from 23 to less than 28, 30%–46% in patients with scores from 28 to less than 34, and 8%–29% responses among those with the highest bradykinesia score of 34 to 38 or above.

Of 1,933 individuals with levodopa responsiveness data, 1,524 had data for morning bradykinesia. Morning bradykinesia was identified in 1,298 (85%) individuals. Continued morning bradykinesia after the first daily levodopa dose was observed in 954 of the 1,501 participants (64%) with available data. Lastly, 48% spend more than 75% of their time in bradykinesia from 9 a.m. to 6 p.m.

Among those who had a significant levodopa response, the severity level of morning bradykinesia was high regardless of the time in bradykinesia. In contrast, morning bradykinesia severity was low in individuals with an insignificant levodopa response.

“Data obtained from COM technology using the PKG system suggest that a substantial number of individuals with [Parkinson’s disease] in the US treated with levodopa have morning bradykinesia, which persists in most individuals after the first daily dose,” the authors concluded.

“Among individuals with morning bradykinesia, approximately half spent most of their time in bradykinesia during the day, and the severity level of morning bradykinesia was high,” they added. “Many patients in the US may experience a limited beneficial response to their first daily levodopa dose.”