Levodopa is a double-edged sword

Horak labJuly 24, 2015

July’s featured paper is "Levodopa Is a Double-Edged Sword for Balance and Gait in People With Parkinson's Disease,” published in Movement Disorders. The paper is by a team from the Horak Lab: Carolin Curtze, Ph.D., John G. Nutt, M.D., Patricia Carlson-Kuhta, Ph.D., Martina Mancini, Ph.D. and Fay B. Horak, Ph.D.

Parkinson’s disease is a progressive, degenerative disorder of the nervous system that affects movement. Tremor is the most well-known sign of Parkinson’s disease (PD), but the disorder also commonly causes slowness of movement  muscle stiffness and  difficulty with balance and gait. PD cannot be cured, but medications can help with symptoms.  

Levodopa (L-dopa) is often used to treat PD symptoms. Despite frequent use, the effect of levodopa on balance and walking in people with PD is controversial. Although L-dopa improves many symptoms of PD, people with PD still fall five times more than other community-dwelling older adults. 

The existing body of research on L-dopa’s effect on balance and gait is fragmented and consists of small studies. These studies are further complicated by the tendency to treat balance and gait as one function: new research indicates that balance and gait are controlled by separate neural networks.  

In addition to underlying gait and balance issues, many people with PD also suffer from dyskinesia – involuntary movements. Previous research did not map the effects of L-dopa on balance and walking with change in disease progression or the presence of dyskinesia. To develop a comprehensive picture, this month’s featured paper from the Horak laboratory reports on a large study of subjects with a wide range of disease severities to understand the effects of L-dopa on balance and gait.  

“What intrigued me about this paper was the deep dive into different aspects of the motor disturbance in Parkinson’s disease,” said Mary Heinricher, Ph.D., associate dean for basic research in the OHSU School of Medicine. “We tend to think that PD is simply a loss of dopamine, and then we wonder why giving L-dopa doesn’t entirely restore function. By looking at different aspects of movement, Dr. Horak and colleagues were able to provide some unique insights into the complexities of movement and gait disturbances in PD patients,” said Dr. Heinricher.  

“Levodopa truly is a double-edged sword,” said Fay Horak, Ph.D., professor of neurology. “We conducted a large study of 104 subjects with idiopathic PD and 64 age-matched control subjects, and we examined a wide spectrum of balance and walking activities. Through this work, we gained a fine-graded delimitation of the effect of levodopa on mobility function." 

By examining subjects as they were standing quietly for 30 seconds, initiating gait, walking seven meters and turning 180 degrees, Horak’s team was able to capture 34 different measures of mobility using body-worn, inertial sensors.  

“We found that there was a wide spectrum of L-dopa-induced changes in mobility that could improve or worsen symptoms,” said Dr. Horak. “The results indicate that gait and balance are not a single function; rather, there are distinct as well as overlapping circuits involved.”  

The double-edged sword was that L-dopa treatment improved walking, but balance got worse – patients taking L-dopa walk and turn more quickly, but become unstable during standing.  “The worsening of balance was related to dyskinesia more than to disease severity,” added Dr. Horak.  

“This research not only tells us something about the organization of motor circuits and the pathology of PD, it also has practical implications for patient care,” said Dr. Heinricher. “Most important, knowledge of L-dopa-induced changes in balance and walking will help optimize management of the disease.”  

“For example,” added Dr. Horak, “patients with PD who are taking levodopa should consult with physical therapists to include balance training into their exercise programs so they can prevent falls.”

“We hope to extend our work to include continuous monitoring of mobility in the homes and community of people with PD,” said Dr. Horak. Subjects will wear sensors on their shoes that measure the quality of their walking and turning, and the Horak team will observe how their symptoms fluctuate throughout the day.  

“These motor fluctuations are a common side effect of long-term use of levodopa, and our lab is working to better understand long-term levodopa effects on balance and gait," she said. "We are also examining other medications, genetic predisposition and cognitive impairments on balance and gait in PD." 

With improved continuous monitoring technology and further research, the Horak lab will undoubtedly improve our understanding of the complexities of PD treatment. 


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Levodopa Is a Double-Edged Sword for Balance and Gait in People With Parkinson's Disease.Movement Disorders 2015 Jun 12. doi: 10.1002/mds.26269. [Epub ahead of print]Carolin Curtze PhD, John G. Nutt MD, Patricia Carlson-Kuhta PhD, Martina Mancini PhD and Fay B. Horak PhD, PT

Pictured above, from left to right: Drs. Carlson-Kuhta, Horak, Curtze

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About the School of Medicine Paper of the Month

The OHSU School of Medicine spotlights a recently published faculty research paper each month. The goals are to describe to the public the exceptional research happening at OHSU as well as inform our faculty of the innovative work underway across the school’s departments, institutes and disciplines. The monthly paper is selected by Associate Dean for Basic Research Mary Heinricher, Ph.D.