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Parkinson's Disease

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Parkinson’s Disease
Part 1
Melissa Whisman
King University
NURS 3005
Pathophysiology
Jessica Belnap

Parkinson’s Disease
Part 1
Parkinson’s disease (PD) is a common and complex neurodegenerative disorder. It is second only to Alzheimer’s disease in commonality (Lees, A. J.,2011). Parkinson’s disease is a slowly progressive degenerative disorder and is usually idiopathic. The first extensive description of Parkinson’s Disease was written over 2 hundred years ago. In 1817, English physician James Parkinson write an essay describing six causes of a condition called paralysis agitans (Lees, A.J., 2011). The essay, titled “Essay on the Shaking Palsy” described characteristic traits such as resting tremor, abnormal posture and gait, paralysis, and decreased muscle strength, and the way the condition progressed over a period of time (Lees, A.J., 2011). Early neurologists such as Trousseau, Gowers, Kinnier Wilson, and Erb made contributions to the knowledge of Parkinson’s disease. But the most noteworthy was Jean-Martin Charcot. His specific studies between 1868 and 1881 proved to be the turning point in gaining knowledge about the disease (Lees, A.J., 2011). During this particular period of time, Charcot was able to distinguish between muscle rigidity, muscle weakness, and the slowness of movement, also known as bradykinesia. Charcot was instrumental in renaming the disease in honor of James Parkinson.
In 1912, Frederic Lewy observed microscopic particles in the brains of individuals affected by Parkinson’s disease. He later named these particles, Lewy bodies (Lees, A.J., 2011). In 1919, Konstantin Tretia Koff reported that the main cerebral structure affected by Parkinson’s disease was the substantia nigra. Unfortunately, his findings weren’t confirmed until further testing was conducted by Rolf Hassler in 1938. In the 1950’s, Arvid Carlsson detected underlying biochemical changes in the brain through his work on the neurotransmitter dopamine. It wasn’t until 40 years later that Spillantini, Trojanowski, and Goedert discovered that alpha-synuclein was found to be the main component in Lewy bodies (Schulz-Schaeffer, W.J., 2012). Early in the disease, anticholinergics and surgery that consisted of lesioning the corticospinal pathway were the only treatments for Parkinson’s disease. It wasn’t until the introduction of Levodopa in the mid-1960’s that the treatment and management of Parkinson’s disease improved dramatically. Deep brain stimulation (DBS) as a possible form of treatment was introduced in the late 1980’s by Alum-Louis Benabid (Lees, A.J., 2011).
The reason why Parkinson’s disease is important to me is two-fold. First, this author’s father was diagnosed with Parkinson’s disease 5 years ago. When the symptoms first appeared, he was a very active 75-year-old farmer who worked on the farm from dawn until dusk. Something he did for over 60 years. He also served as Chairman of the county Board of Supervisors for 16 years. Today, he is pretty much confined to his home and relies on moderate assistance with all activities of daily living. He no longer drives, or farms. Second, as long as this disease has been around, there is still much to be learned about the disease and its treatment. By choosing this topic, this author is hoping to further educate herself and others and improve the quality of life for this author’s father and family.
Epidemiology
Although state and local statistics were not available, Parkinson’s disease affects approximately 1 million people in the United States and 7-10 million people worldwide (Parkinson’s Disease Foundation, 2011). This author was unsuccessful in finding specific statistics on a state and local level. This is more than people with multiple sclerosis, muscular dystrophy, and amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) combined (Parkinson’s Disease Foundation, 2011). The ratio of men to women affected by the disease is 3:2 with men at a higher risk than women (Parkinson’s Disease Foundation, 2011). With regards to ethnicity in the United States, Parkinson’s disease is more prevalent in Hispanics followed by non-Hispanic Whites, Asains, and African Americans. Parkinson’s disease affects about 0.4% of people > 40 yrs., 1% of people ≥ 65 yrs., and 10% of people ≥ 80 yrs. with the peak age group for disease onset being 60-70 yrs (Parkinson’s Disease Foundation, 2011). This is important information because with the increase in life expectancy, studies have shown that the number of people with Parkinson’s disease is expected to increase by more than 50% by 2030 (Parkinson’s Disease Foundation 2011).
Other related factors in Parkinson’s disease is exposure to environmental agents such as herbicide and pesticide exposure, previous head injury, rural living to include farming as a primary occupation, B-blocker use, and drinking well water (Nuytemans, K., Theuns, J., & Cruts, M., 2012). It was determined that individuals that were exposed to herbicides or pesticides showed defects in the substantia nigra (Nuytemans, K., Theuns, J., & Cruts, M., 2012). Welding with exposure to certain metals such as iron, copper, lead, manganese, and aluminum have shown to increase the risk of Parkinson’s disease because of the accumulation of metals in the substantia nigra and the increase in oxidative stress (Nuytemans, K., Theuns, J., & Cruts, M., 2012). Surprisingly, exposure to cigarette smoke, caffeine, or alcohol consumption did not increase the risk to Parkinson’s disease (Nuytemans, K., Theuns, J., & Cruts, M., 2012).
Although the majority of Parkinson’s cases are not directly inherited, it has been discovered that several genes can cause the disease in a small number of families. Parkinson’s disease has traditionally been considered a non-genetic disease. Approximately 15% of people with Parkinson’s disease have first degree relative who has the disease (Nuytemans, K., Theuns, J., & Cruts, M. July 2012). Researchers have found that people who have a parent or sibling with Parkinson’s disease have a 4-9% greater chance of developing the disease (Nuytemans, K., Theuns, J., & Cruts, M., 2012). The mutation of specific genes has been shown to cause Parkinson’s disease. The specific gene codes are alpha-synuclein(SNCa), parkin (PRKN), leucine-rich repeat kinase 2 (RRK2), and PTEN-induced puntative kinase1 (PINK1) (Nuytemans, K., Theuns, J., & Cruts, M. July 2012).
Changes in behavior and mood are greater in Parkinson’s disease. These are usually seen in Parkinson’s disease with dementia. The most common changes are depression, apathy, and anxiety (Schulz-Schaeffer, W.J., 2011). Researchers have found that accurately diagnosing depression in a person with Parkinson’s is difficult due to decreased facial expression and decreased movement all of which can be found in a person who doesn’t have Parkinson’s disease but suffers from depression. There has also been documented cases of psychosis and impulse control behaviors in individuals with Parkinson’s disease all of which were discovered to be related to medications used to treat Parkinson’s disease.
Part 2
Patient Presentation
In Parkinson’s Disease, the loss of dopaminergic cells in the substantia nigra affects the basil ganglia’s ability to combine neural motor signals (Kwan and Whiteall, 2011). In Parkinson’s Disease, there are 4 motor symptoms that are observed as primary signs and symptoms that are associated with this particular disease. A mneumonic for these 4 core features is TRAP: (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012)
Tremor at rest
Rigidity
Akinesia (bradykinesia and hypokinesia)
Postural instability
Bradykinesia
Bradykinesia is the defining feature of Parkinson’s Disease. It is a clinical sign because the slowed motor movements are a direct correlation with the functional abnormality in the basal ganglia (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012).The slowed movements in bradykinesia interfere with limb control, dexterity associated with things such as tying shoes and buttoning shirts, and swallowing which is termed dysphagia. Bradykinesia may also be seen in decreased facial expression and eye blinking (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012).
Bradykinesia in a combination of bradykinesia (slowness) and hypokinesia (decreased movement). Bradykinesia is the reduction in the speed in initiating and executing any movement, and an alteration in fine motor control and dexterity (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012). It’s not just the slow movements alone, but it is also the slowness in the voluntary movement and the associated fatigue during the repetitive movements like finger and toe tapping. This slowness of movements, decrease in the speed of repeated movements, delay in initiating movements, and freezing gait is seen in 80% to 90% of patients with Parkinson’s Disease (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012).
Rigidity
Rigidity is the increase in muscle tone in the flexor and extensor muscle groups when muscles are at rest and resistance to stretch movements in the flexor and extensor muscle when the limb is relaxed (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012). Rigidity is present in 80% to 90% of patients with Parkinson’s Disease and is usually seen one side of the body with the onset of motor symptoms (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012). Rigidity is the result of altered firing rates of the basal ganglia which is a fundamental feature that is seen in patients with Parkinson’s Disease. There are two types of rigidity: lead pipe and cogwheel. Lead pipe rigidity is a constant resistance to motions throughout the entire range of motion. Cogwheel rigidity is resistance that stops and starts as the limb is moved through it range of motion.
Rest Tremor
One of the first visible motor symptoms to emerge in Parkinson’s Disease is the resting tremor of a limb that is supported and at rest. This symptom is seen in 70%-90% of patients with Parkinson’s Disease (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012). This tremor typically begins on one side of the body, usually in one hand. The most distinguishing rest tremor is referred to as the “pill-rolling” type, which is observed as a rubbing movement of the thumb and index finger against each other.
Postural Instability
Postural instability is defined as difficulty adjusting to postural change that includes gait impairment and postural abnormalities that makeup the motor signs of Parkinson’s Disease. Postural control problems tend to occur later with the progression of the disease.
Pathophysiology
The pathophysiology of Parkinson’s disease is still considered largely idiopathic. It likely involves the interaction of host susceptibility and environmental factors. But a small percentage are genetically linked and genetic factors are being closely studied. The progressive deterioration in motor abilities results in the neural degeneration in the substantia nigra pars compacta and the loss of dopaminergic regulation of the straitum (Perez, 2015). In Parkinson’s disease, the depletion of striatal dopamine stops the excitatory pathway and overexerts the inhibitory indirect pathway. The alterations in these two pathways inhibit voluntary movement (Perez, 2015).
In addition to the substantia nigra dopamine neuron loss, the presence of Lewy bodies is also seen in individuals with Parkinson’s disease. Lewy bodies are abnormal collections of proteins that develop inside the nerve cells of people with Parkinson’s disease (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012). Another pathologic feature of Parkinson’s disease is increased gliosis. Gliosis is an increase in the number and activity of astrocytes and microglia which are glial cell types that respond to injury or damage with the production of inflammatory molecules (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012). These findings help to support the role that the innate immune system has in the neurodegenerative process associated with Parkinson’s disease (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012).

Disease Progression
The progression of Parkinson’s disease varies from person to person. Once thing that is common in the disease progression is that all those effected by Parkinson’s disease experience a deterioration in motor function associated with increased impairment and disability and declining quality of life (Parkinson’s Disease, 2011). The later stages of the disease are characterized by reduced oral medication efficacy, increased medication-related side effects, dysphagia, cognitive delays with conversation, reduced mobility that leads to increased falls, and in many, the dependence on others for activities of daily living (Parkinson’s Disease, 2011). Motor symptoms can appear 10 years before a formal Parkinson’s disease diagnosis. It should be noted that not all patients exhibit full-blown motor and non-motor syndromes. Some patients exhibit motor features that are less severe for many years, or their cognitive and behavioral functions appear normal or minimally affected (Mhyre, T.R., Boyd, J.T., Hamill, R.W., &Maguire-Zeiss, K.A. 2012). Usually the mode of death is often pneumonia that is related to aspiration.

References
Lee, A.J., (September, 2011). Understanding issues relating to the shaking palsy on the celebration of James Parkinson’s 250th birthday. Movement Disorders 22(17), pp 327-334. doi: 10.1002/md.21684.
Schulz-Schaeffer, W.J. (August 2011). The synoptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies. Neuropathology 120(20) pp 131-143. doi: 10.1007/500401- 010-0711-0.
Parkinson’s Disease Foundation (2011). www.pdf.org
Nuytemans, K., Theuns, J., & Cruts, M. (July 2012). Genetic etiology of Parkinson’s disease. Human Mutation 31(7), pp 763-780. doi: 10.1002/humu.21277.
Kwan, L.A., and Whitehill, T., L., (April 2011). Perception of speech by individuals with Parkinson’s Disease: A review. Parkinson’s Disease 2011, Article ID 389767 11pp. Retrieved from http://www.hindawi.com/journals/pd/2011/389767/.
Perez, X.A. (2015). Preclinical evidence in Parkinson’s disease. Neuropsychological Review 25(4) pp 371-383.

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