Achieving Effective Motor Control for Patients With Parkinson Disease

Parkinson disease (PD) is among the top motor control neurodegenerative disorders that affects nearly one million people in the United States in 2020—which is more than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy, and amyotrophic lateral scleroris.¹ 

PD attacks dopamine-producing neurons in the substantia nigra which produces a diverse set of symptoms including tremors, bradykinesia, limb rigidity, and gait/balance problems.¹ Other symptoms include loss of automatic movements, speech changes, and writing changes.²

While the intitial cause is unknown, primary risk factors for PD include age, heredity, sex, and exposure to toxins.² Adults aged 60 years or older are the most commonly affected. It has been observed that people with PD often have relatives who also had PD—genetic causes account for 10% to 15% of all PD cases.¹

PD manifests differently person to person but the Parkinson’s Foundation estimates that 4% of people are diagnosed before age 50 years and men are 1.5 times more likely than women to develop the disorder. Approximately 60,000 Americans are diagnosed with the disease each year and more than 10 million people worldwide.

The cost burden of PD is substantial, amounting to nearly $52 billion per year in the United States. For patients, medications alone cost an average of $2500 a year and therapeutic surgery could cost up to $100,000.³

Making a Diagnosis

Symptoms of PD typically present asymmetrically in the upper extremities, however, nonmotor symptoms often precede that development.^1,3 Most patients with PD have a substantial reduction in olfactory function (smell) by the time motor signs emerge.³

There are no laboratory biomarkers for PD so the use of routine magnetic resonance imaging and computed tomography (CT) scan are not typically helpful but can be used to rule out other diseases or disorders.

“Positron emission tomography (PET) and single-photon emission CT (SPECT) may show findings consistent with Parkinson disease, and olfactory testing may provide evidence pointing toward Parkinson disease, but these studies are not routinely needed,” stated Robert A Hauser, MD, MBA; in an article.³ 

However, to reach a clinical diagnosis, two of four main symptoms must be present for a period: shaking or tremor; slowness of movement (bradykinesia); stiffness or rigidity of the arms, legs or trunk; and/or trouble with balance and possible falls, also called postural instability.¹ Neurologists will also consult a detailed patient history, conduct speech and motor function tests, and use a DAT imaging scan to determine a patients dopamine levels.¹

Course of Treatment

There is no definitive cure for PD but the main objective is reducing symptoms and achieving effective motor control through medication and surgical therapy. The cornerstone of symptomatic treatment for PD is dopamine replacement therapy.³ Other contributors to management include lifestyle changes, like increased rest and exercise. Studies demonstrate that a patient's quality of life deteriorates quickly if treatment is not instituted at or shortly after diagnosis.³ 

Many patients with PD start multiple medications to manage motor control symptoms. The most commonly prescribed medication is carbidopa-levodopa, a natural chemical that when passed into a brain is converted into dopamine. This treatment may become less effective over time.² Inhaled carbidopa-levodopa, carbidopa-levodopa infusions, and dopamine agonists are also among top treatment choices. Inhaled carbidopa-levodopa has proven helpful in managing symptoms when oral medications cease effectiveness. 

“Since most symptoms of Parkinson’s disease (PD) are caused by a lack of dopamine in the brain, many PD drugs are aimed at either temporarily replenishing dopamine or mimicking the action of dopamine,” stated the Parkinson’s Foundation. “These types of drugs are called dopaminergic medications. They generally help reduce muscle rigidity, improve speed and coordination of movement, and lessen tremor.”¹

Other initial prescription medication includes agonists, MAO B inhibitors, catechol O-methyltransferase (COMT) inhibitors, anticholinergics, and amantadine.² 

Surgical intervention is reserved for patients who have exhausted medication options or who suffer from profound motor fluctuations. Surgical options include deep brain stimulation in which a gel formulation of carbidopa/levodopa is inserted into the small intestine.¹ 

Treating Off-Episodes

Recently, developments have been made in treating OFF-episodes—periods when medications are less effective or wear off causing motor fluctuation, a common issue in aging patients with PD. OFF episodes consist of the re-emergence and worsening of symptoms.⁴

Within the first 4 to 6 years after diagnosis, regardless of disease severity, up to 60% of people with PD experience OFF episodes.⁵ 

In May 2020, the US Food and Drug Administration approved apomorphine HCI (Kynmobi, Sunovion) a siblingual film for the acute treatment of OFF episiodes.⁴ Kynmobi dissolves under the tongue.

“Several years after a person is diagnosed with Parkinson’s disease they may notice problems such as having trouble getting out of bed in the morning or having difficulty getting out of a chair, or that they feel frozen while trying to walk as the effect of their maintenance medication diminishes,” said Stewart Factor, DO, professor of neurology, director of the movement disorders program and Vance Lanier Chair of Neurology at Emory University School of Medicine. “The approval of Kynmobi affords health care providers with a needed option that can be added to their patients’ medication regimen to adequately address OFF episodes as their Parkinson’s disease progresses.”⁴ 

References 

1. Understanding Parkinson's. Parkinson's Foundation [Accessed September 6, 2020]. https://www.parkinson.org/understanding-parkinsons. 
2. Parkinson’s disease. Mayo Clinic. Accessed September 6, 2020. https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055. 
3. Hauser RA. Parkinson disease clinical presentation: history, physical examination, staging [Published June 4, 2020. Accessed September 6, 2020]. https://emedicine.medscape.com/article/1831191-clinical.
4. Sunovion announces US FDA approval of KYNMOBI™ (apomorphine hydrochloride) sublingual film for the treatment of parkinson's disease OFF episodes. Business Wire. https://www.businesswire.com/news/home/20200521005786/en/Sunovion-Announces-U.S.-FDA-Approval-KYNMOBI™-apomorphine. Published May 21, 2020. Accessed September 6, 2020.
5. Schrag, A. Dyskinesias and motor fluctuations in Parkinson's disease: A community-based study. Brain. 2000 Nov;123 ( Pt 11):2297-305. doi:10.1093/brain/123.11.2297