11.1 Introduction to Parkinson’s Disease

Etiology

The exact cause of PD is still unknown. Theories exist related to the causes of the degeneration of the basal ganglia including viral infections, blunt head trauma, encephalitis, atherosclerosis, and exposure to certain drugs and environmental factors, such as pesticides. There is also most likely an interaction between genetic predisposition and environmental factors. Parkinson-like symptoms may arise because of antipsychotic drugs. Antipsychotics block dopamine receptors, interfering with the same neural pathway and functions affected by the insufficient amount of dopamine. They also produce movement disorders, which involve extrapyramidal reactions, such as dystonia (involuntary muscle contractions causing repetitive or twisting movements), akathisia (restless, constant moving), tardive dyskinesia (sudden involuntary and uncontrollable movements), and parkinsonism (stooped posture, shuffling gait, and muscle rigidity). Antipsychotics are discussed in more detail in Psychopharmacologic Drugs.

Pathophysiology

A part of the basal ganglia called the substantia nigra (see Figure 11.2) contains nerves that secrete dopamine; this secretion of dopamine progressively degenerates with PD. Because the basal ganglia works with the cerebral cortex and thalamus, it helps with both coordination of complex patterns of motor activity and cognitive control of motor activity. In PD, neurons in the substantia nigra begin to atrophy, become impaired, or die; some contain Lewy bodies, which are alpha-synuclein protein aggregates that impair transport of dopamine and contribute to neuronal death. Mutations in the mitochondria, resulting in free radicals, can also damage membranes, proteins, DNA, and other components of the cells in PD. Furthermore, depigmentation of the dopamine-producing neurons contributes to an inflammatory response from the extracellular melanin (pigments produced by melanocytes that gives color to the skin and eyes) in surrounding brain tissue (Capriotti, 2020). Another midbrain structure, called the ventral tegmental area (VTA), also contains cell bodies that produce dopamine essential for movement. The VTA is also involved in PD and gradually degenerates as the disease progresses.

Figure 11.2 The substantia nigra is part of the basal ganglia. It contains nerves that secrete dopamine; the amount of dopamine secreted decreases with PD. (credit: modification of work from Psychology 2e. attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

The two major neurotransmitters implicated in the disease process are dopamine and acetylcholine (ACh). The correct ratio of these neurotransmitters is essential in regulating balance, posture, standing, walking, and writing. People with PD have an imbalance that results in a decrease in dopamine and an excess of ACh. With the lack of dopamine, the excitatory ACh is the dominant neurotransmitter. There are also multiple glutamate pathways that are excitatory in this area of the brain. The result of this imbalance between excitation and inhibition of the motor system is apparent as the manifestations of PD arise (Capriotti, 2020).

Diagnostics

Currently, no single definitive test exists to diagnose PD. The diagnosis is based on these factors:

• Medical history and clinical manifestations
• Blood and laboratory tests to rule out other disorders that may be causing the symptoms
• Brain scans to rule out other disorders (Note that computed tomography [CT] and magnetic resonance imaging [MRI] scans of people with PD usually appear unremarkable.)
• Positron emission tomography (PET) or single photon emission CT (SPECT) that show reduced uptake of dopaminergic markers
• Substantial and sustained responses to medications for PD

In rare cases, where people have a clearly inherited form of PD, researchers can test for known gene mutations as a way of determining an individual’s risk of developing the disease (Capriotti, 2020; Mayo Clinic, 2023).

Clinical Manifestations

Motor symptoms of PD occur late in the disease process. Usually 60%–80% of the dopamine-releasing neurons of the substantia nigra are already destroyed before the onset of motor symptoms (Parkinson’s Foundation, 2023e).

The four primary motor manifestations of overt PD (shown in Figure 11.3) are (Capriotti, 2020; National Institute of Neurological Disorders and Stroke, 2023b):

• Tremors: This involuntary quivering is progressive and often begins in one isolated area, such as the head or hands, and then often spreads to the legs. Tremors are seen when the body is at rest and disappear upon purposeful movement or during sleep. “Pill rolling” is a classic behavior. Clients rub the thumb and forefinger together as if an actual pill were between them. The tremors usually begin unilaterally but become bilateral as time progresses.
• Rigidity: Rigidity involves stiffness—the resistance to movement by both flexors and extensors. During passive range of motion, there is resistance and the client exhibits jerky movements, also known as cogwheel rigidity. The tongue and throat may become involved, leading to difficulty swallowing and talking. The client’s speech becomes soft and monotone with difficulty articulating words.
• Bradykinesia: This slowed movement is the most noticeable of all the symptoms. Clients with PD have difficulties initiating movement, such as walking or getting up out of a chair. Additionally, they have difficulty controlling fine muscle movements due to the loss of dexterity. Their writing becomes small and cramped, which is referred to as micrographia. During ambulation, clients can be seen shuffling their feet and not taking normal strides. Bradykinesia may progress to akinesia, which is the inability to move. Also, clients usually present with an expressionless face or flat affect due to facial rigidity. Blinking of the eyes is minimal. This is referred to as “masked face.”
• Postural instability: Clients with PD often demonstrate a stooped posture. They have a reduced arm swing and take small, quick steps while walking. They also may stop suddenly while walking. They do not have postural reflexes, so making corrective adjustments is challenging. The result is impaired balance and increased risk of falls. This symptom usually occurs later in the disease progression.

Figure 11.3 The lack of dopamine results in abnormal motor movements called dyskinesias. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Clients with PD also lose nerve endings that usually produce norepinephrine (NE). The neurotransmitter, NE, is the main chemical messenger that controls many automatic bodily functions. The loss of NE may explain several nonmotor manifestations seen in PD, including:

• Mood changes, such as depression and anxiety
• Cognitive changes, such as memory loss, impaired judgment, poor decision-making, and dementia
• Perceptual disturbances, such as hallucinations, delusions, and psychosis
• Sexual dysfunction due to the effects on nerve signals from the brain
• Sleep dysfunction (difficulty staying asleep, nightmares, acting out dreams that can be harmful)
• Difficulty with chewing and swallowing
  • Food and saliva may collect in the mouth and back of the throat, which can result in choking or drooling. It may be difficult for the client to obtain adequate nutrition.
• Autonomic symptoms, such as orthostatic hypotension, inability to release body heat, constipation, blurred vision, oily skin on the face, daytime sleepiness, and nighttime insomnia

Pharmacologic Management

Pharmacotherapy is essentially given to reduce distressing symptoms experienced in clients who have PD. The overall goal of medication is to maximize independence and mobility. With PD, there is too little dopamine and too much ACh, so the approach to treatment is to restore the balance between the two neurotransmitters. Drugs are classified into two broad categories: (1) dopamine agonists that directly or indirectly activate dopamine receptors through multiple mechanisms and (2) anticholinergic agents that block ACh receptors (National Institute of Neurological Disorders and Stroke, 2023b).

Nonpharmacologic Management

Nonpharmacologic strategies to slow the decline of motor function and/or manage the clinical manifestations of PD include physical therapy to encourage clients to be as active as possible and prevent skeletal deformities, occupational therapy to teach clients how to use adapted tools and methods to make activities of daily living easier, and speech therapy to help clients swallow safely and possibly assist with speech dysfunctions. Exercise is essential to increase strength, flexibility, and balance along with reducing depression and/or anxiety. Some alternative therapies that also may improve muscle strength and flexibility and reduce risk of falls are yoga and tai chi. To enhance mental well-being and reduce pain, meditation or relaxation techniques are useful (Mayo Clinic, 2023). Deep brain stimulation has been found to be effective in reducing tremors, bradykinesia, and rigidity. A pulse generator sends controlled electrical signals to electrodes surgically implanted in the brain. The electrodes painlessly stimulate the brain to block signals that cause many of the motor symptoms (Mayo Clinic, 2023).