Let's Talk About Parkinson's Disease

Many people struggle with tax completion in April, but for many families, this month bring another day-to-day struggle in managing and coping with Parkinson's disease (PD). We all know of someone who has been affected by this challenging central nervous system disorder. April is PD awareness month.

Pathology

Risk factors for PD are listed in Table 1. The origin of PD begins with a depletion of dopamine from the basal ganglia resulting in major disruptions in connections to the motor cortex and thalamus and leads to signs, such as bradykinesia.¹ In the beginning, compensatory mechanisms can work to mask or reduce the effects of dopamine depletion in the early phases of PD, but they are eventually overwhelmed by the disease as it progresses.¹ In general, the cardinal features of PD are bradykinesia, rigidity, and tremors, with a fourth feature, postural instability, that is commonly mentioned. However, postural instability does not generally occur until much later in the course of the disease and thus is not included in any published diagnostic criteria for PD.² Mutations occur in the gene that codes for alpha-synuclein, which is one of the most important elements of cell death in various neurodegenerative disorders.¹ These mutations are seen in other disease states, such as dementia with Lewy bodies, multiple system atrophy, and neurodegeneration with brain iron accumulation.¹ There are also non-motor symptoms (Table 2).

Table 1. Risk Factors for the Development of PD

Family history

History of traumatic brain injury

Reduced levels of dietary and sunlight-derived vitamin D

History of migraines that present with an aura

Living in industrial or urban areas and exposure to copper, lead, or manganese

Exposure to hydrocarbon solvents, particularly trichloroethylene

Living in rural areas

Agricultural or farm work

Using well water

High dietary intake of iron, especially in combination with high manganese intake

Excess body weight

Lower muscle strength in late adolescence

Disease Progression

Bradykinesia is the most difficult symptom for patients to describe. Fatigue, a lack of coordination, and weakness are often used to describe the decreased ability to initiate movement.² Bradykinesia generally starts distally, with decreasing dexterity of the fingers, dragging in the legs, a feeling of unsteadiness, and short shuffling steps being noted.² Bradykinesia is a slowness of movement, presents at the onset of PD in a large percentage of patients, and is arguably the major cause of disability in PD and is eventually seen in almost all patients.² Rigidity usually begins unilaterally and typically on the same side as a tremor, which eventually progresses to the opposite side and remains asymmetric throughout progression.² Rigidity can affect any part of the body and may contribute to complaints of pain and stiffness, such as a decreased arm swing when walking and a typical stooped posture.² Postural instability is an impairment of postural reflexes that cause a feeling of imbalance and a tendency to fall with a significant risk of injury.² A tremor usually starts unilaterally in the hand and spreads over several years, following the onset of symptoms. Traditionally, the side that is initially affected tends to be the more affected side throughout the course of the disease.²

Table 1. Non-motor Symptoms ²

Cognitive dysfunction and dementia

Psychosis and hallucinations

Depression & anxiety

Apathy

Sleep disturbances

Fatigue

Autonomic dysfunction

Olfactory dysfunction

Gastrointestinal dysfunction

Pain & sensory disturbances

Dermatologic disturbances

Rhinorrhea

Table 3. Common Drug Classes That Are Used in PD³

Levodopa

Dopamine agonists (DA)

Monoamine oxidase (MAO) B inhibitors

Anticholinergic agents

Catechol-O-methyltransferase (COMT) inhibitors

Amantadine

Treatments

The combination drug carbidopa-levodopa, branded as Sinemet, is available in capsules and tablets.³ An immediate-release formulation of carbidopa-levodopa (Parcopa) is available that dissolves on the tongue and can be taken without water. Its time of onset of action is quicker than that of the oral tablets.³ The DAs are synthetic agents that directly stimulate dopamine receptors. They include bromocriptine, pramipexole, ropinirole, rotigotine, and the injectable apomorphine (Table 3).³ Monoamine oxidase MAO type B (MAO B) inhibitors include rasagiline, safinamide, and selegiline. They selectively inhibit MAO B and are modestly effective as symptomatic treatment for PD and may have neuroprotective properties.³ Centrally acting anticholinergic drugs, such as benztropine and trihexyphenidyl have been used for many years in PD and continue to have a useful role.³ Amantadine is an antiviral agent that has mild antiparkinsonian activity, and its mechanism of action is uncertain, but it is known to increase dopamine release, inhibit dopamine reuptake, stimulate dopamine receptors, and it may possibly exert central anticholinergic effects.³ The COMT inhibitors entacapoine and tolcapone are only effective when given in combination with levodopa.³ They may potentiate and prolong the levodopa effect when given with a dose of levodopa and thus are known as levodopa extenders.³ Among the primary motor features of PD, gait difficulty and postural instability are the least responsive to dopaminergic therapies and are major contributors to disability in patients with PD.²

Resources

The Parkinson’s Disease Foundation website is a good resource for patients and their families. Caregivers and patients can find multiple resources, ranging from disease and mechanism coping questions, to books for patients and their families. The foundation also has a helpline for further information at 1-800-4PD-INFO (473-4636). One of the free books available on the website is Caring and Coping, A Caregiver’s Guide to Parkinson’s Disease. This book provides family members with numerous additional resources and answers many other questions.

Additional resources include the American Parkinson Disease Association, the National Parkinson Foundation, the

Parkinson's Disease Research, Education, and Clinical Center and Parkinson's Patients Support Groups, Inc. of Northern and Central California.

Conclusion

PD is a challenging disease. With many high-profile celebrities diagnosed with PD, the disease has been in the spotlight and attracted charitable giving. However, this will not change the immediate struggles of the families and patients who deal with this disease every day, though it may aid research in the long term. As clinicians, effective drug therapy management and management of the adverse drug effects can improve the quality of life for patients and caregivers.

This article was co-authored by Justin Powell, a PharmD candidate at Marshall University in Huntington, West Virginia.

References

1. Gerfen CR. Molecular effects of dopamine on striatal-projection pathways. Trends Neurosci. 2000;23(10 Suppl):S64-70.

2. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999;56(1):33-9.

3. Rogers G, Davies D, Pink J, Cooper P. Parkinson's disease: summary of updated NICE guidance. BMJ. 2017;358:j1951. doi: 10.1136/bmj.j1951.