Parkinson Disease 帕金森病 (Reading & Sharing)

Parkinson’s Disease (PD) is a chronic degenerative disease of the nigrostriatal pathway that affects the dopamine producing neurons in the brain which cause an imbalance and impairment motor function that led to its name as a Shaking Palsy Disease when it was discovered in the 1800’s by Dr. Parkinson (Braun et al, 2017). The pathophysiology of PD shows a reduction of dopamine in the corpus striatum of the brain which upsets the normal balance between the inhibitory dopamine and excitatory acetylcholine neurotransmitters. This prevents the affected brain cells from performing their normal inhibitory function within the CNS and causes most of the parkinsonian symptoms which appears as characterized by tremor, bradykinesia, rigidity, and postural instability (Ekman et al ,2013):

• Resting tremor, may be worse on one side of the body affecting the limbs and sometimes involves the head, neck, face, and jaw
• Bradykinesia is slowness of movement, loss of spontaneous movement, and delay in initiating movement; and akinesia which is absence or poverty of normal movement
• Rigidity in performance of all movements, and increased during movement.
• Mask like facies secondary to rigidity and drooling.
• Postural abnormalities: head bent forward, stooped posture, loss of postural reflexes
• And other manifestations such as poor balance, autonomic disorders, depression, gait difficulties, verbal fluency impaired, and etc.

The above clinical manifestations could lead to complications such as injury from 1) Falls, 2) Food Aspiration due to impaired swallowing, 3) Urinary Tract Infections, and 4) Skin breakdown due to increased immobility. It is therefore of prime importance to measure the patient’s quality of life since PD is a debilitating disease and patient’s emotional and social well being are affected by its physical symptoms.

Parkinson disease has a prevalence rate of 1 million people in North America (Ferri, 2018, p. 957). It is the second most common neurodegenerative disease worldwide, the first is Alzheimer’s disease (MedlinePlus, 2017, p. 1). The age groups that are effective are <40 = <5/100,000 are affected and >70 = 700/100,000 are affected. It occurs more in White population and has the lowest incidence in Asian and African American (Ferri’S, 2018). Unfortunately, Parkinson illness is among the neurological disorders that becoming more frequent today.

The contributing factors of the disease remain elusive. Some studies suggest that there are environmental factors that lead to PD. They include some viral infections that influence nigral cell loss, and some toxins including wood dust and pesticides. Genetic causes or predispositions include population studies that have identified definitive genetic contributions to PD (Savitt, J.M., 2006). Although much of this research is in progress, new research shows that single gene mutations responsible for causing disease phenotypes, can be indistinguishable from those of PD mutations that are responsible for causing the disease. Though these studies look at gene mutation, more research is needed into familial genetic transference (Savitt, J.M,2006).

Common pharmacologic therapy with levodopa or other dopamine agonists are currently among the most common PD treatments available, although surgical interventions also exist. In the past, pallidotomy and thalamotomy were the only options but current trend in surgical procedure is Deep Brain Stimulation where the electrodes from an electrical generator are connected to the defective brain site to receive electrical impulses for stimulation. Other treatments include Physical Therapy that focuses on active and passive exercises, activities of daily living (ADL) like walking coupled with  baths and massage to help relax muscles (Palmer et al, 2000) (Elkman et al,2013).

Here are the medications for PD and their indications/actions as shown on the table below (Eckman et al, 2013)

Classification	Drugs	Indication/ Action
Dopamine Replacement	LEVODOPA	Control the signs & symptoms for the first 2-5 years
Dopamine Precursor	STALEVO	Given when Levodopa & Carbidopa are no longer effective throughout the dosing interval.
Dopamine Agonist	CARBIDOPA	Adjunct drug that could not pass through the brain barrier but could  increase the longevity of Levodopa in the periphery where it becomes weak.
Anticholinergic	Trihexyphenidyl or Benztropine (Cogentin)	Given in combination with Levodopa when it is non-effective or too toxic by controlling tremors and rigidity.
Antihistamines	Diphenhydramine	Control tremors with its sedative effect when combined with Levodopa.
Anti -Viral	Amantadine	Reduce tremors, rigidity & akinesia
Anti-Depressant	Tricyclic	Controls Depression
Dopamine Agonist	ENTACAPONE	Supports and prolongs the time that levodopa is active in the brain.

There are no tests that will determine the early onset of PD but the development of biomarkers before the onset of symptoms has been the focus in the diagnostic arena of PD as per Braun et al (2017). However, urinalysis may reveal decreased dopamine levels, and CT scan or MRI may rule out other disorders such as intracranial tumors as per Elkman et al (2013).

Evidence Based studies shows that the Health-Related Quality of Life (HRQoL) generic questionnaire and the 39 item Parkinson’s Disease Questionnaire (PDQ39) is reported to be the most frequently used generic short form and disease specific questionnaires that reflect the patient’s lifestyle changes and adaptation as the PD progresses. It has been recommended by the Movement Disorder Society as per Tu et al (2017). This is therefore, a valuable resource for Mrs. J’s nursing management of Glaucoma and PD. Both have sensory and related motor problems that must be assessed and monitored for positive patient outcomes.

Part II Cognitive Impairment 

PD is often hallmarked by its motor degenerative nature and concern for progressive motor disability. However, the cognitive impairment (CI) associated with PD more frequently places PD patients in nursing homes than decline in motor skills. Recent attention has been brought to the significant impact of cognitive impairment on PD patients because of the increasing awareness of the prevalence of this component. Clearly, 20-50% of PD patients present with CI at some point during their disease (Watson, G.S., and Leverenz, J.B., 2010). Symptoms of cognitive impairment can be classified dependent on the inclusion or exclusion of dementia. At the time of diagnosis, 20% of patients without dementia have other symptoms of CI. Patients with dementia have a cross-sectional prevalence of CI of 30% and an 80% chance of CI during their life time (Watson, G.S., and Leverenz, J.B., 2010). Despite the high life-long risk of dementia in PD patients overall, it has been found that there is a significant delay in PD patients until the of onset of dementia (10-20 years) (Diaz-Cirarda, M., et al, 2018).

None the less, cognitive impairment, with or without dementia poses a diminished quality of life and a struggle for caregivers. Patients present with a neuropsychological profile that may be very heterogenous. They also include a distinct fluctuation over time in symptoms which may include working memory problems, slowed learning processing, impoverished learning, decreased recall and subtle executive functioning (Macniven, J., 2009).

The Domains of Cognition that may be affected in Parkinson’s Disease include the following:

1. Executive functioning ~ An important universal life function, including the following abilities; planning, judgement, flexibility in thinking, self-regulation and monitoring, time-management and goal realization.
2. Information processing speed ~ thinking speed.  Impairment common in PD.
3. Attention ~ working memory. digit span, spatial span, ability to hold and process information over a short period of time. Very common in early PD.
4. Memory ~ new learning and free recall both impaired in PD. Note: in assessing memory loss one must place the patient’s sadness, depression in accepting their memory loss into perspective.
5. Language ~ Patients with dementia, have impaired naming and verbal fluency.
6. Language ~ Patients without dementia, rarely have primary language impairment, but may have comprehension and expression difficulties.
7. Visuospatial and visuoperceptual functioning ~ impairment of route-planning, facial recognition, inability to recognize depth, ie: stairs.  Often first clinical impairment in PD.
8. General intellectual functioning ~ general intelligence remains intact in PD unless dementia is present.

(Macniven, J., 2009)

In addition to the above domain of cognition components in PD there has, over a long period of time, been a recognition of Mood Disorders in these patients. They include:

• Depression ~ prevalence of depression in PD is between 30 and 40 %
• Anxiety ~ generalized anxiety, phobias, panic attacks, significant agitation are very common in PD.  Anxiety and depression can occur concurrently.
• Psychosis ~ The most distressing, most disabling and most difficult to treat.  Occurs in 15-25% of patients treated with dopaminergic drugs.  Hallucinations and delusions can occur. Up to 50% of PD patients may experience mild psychotic symptoms.

(Macgiven, L., 2009)

Treatment for all the above, is at best nominal.  First, there is a propensity to treat the motor deficits of PD first. Second, as the etiology of the majority of these psychological issues is multifactorial with phenotypic heterogenicity, diagnosis is difficult and often missed. It is therefore prudent to involve qualified clinical neuropsychologists in the diagnosis and treatment of Parkinson’s patients as an important component of a comprehensive, holistic package of care.

References:

Braun,C.,A.,&Anderson C.,M.(2017) Applied Pathophysiology: a Conceptual Approach      to the Mechanisms of Disease.(3^rd Edition) Baltimore: Wolters Kluwer.

Cynthia S. Palmer, a., Jordana K. Schmier, a., Edward Snyder, a., & Burton Scott, a.        (2000). Patient Preferences and Utilities for ‘Off-Time’ Outcomes in the Treatment of Parkinson’s Disease. Quality Of Life Research, (7), 819.

Diaz-Cirarda, M., Ibarretxe-Bilbao, N., Pena, J., Ojeda., N., (2018) Neurorehabilitation in Parkinson’s Disease: A Critical Review of Cognitive Rehabilitation Effects on Cognition and Brain. Neural Plasticity 2018: 1.

Eckman, M., & Share, D. (2013). Pathophysiology Made Incredibly Easy!. Philadelphia:    LWW.

Ferri, F. F. (2018). Ferri’s Clinical Advisor. The Warren Alpert Medical School. Brown University. Providence: Rhode Island.

Levy, O. A., Malagelada, C., & Greene, L. A. (2009). Cell death pathways in Parkinson’s disease: Proximal triggers, distal effectors, and final steps. Apoptosis: An International Journal on Programmed Cell Death, 14(4), 478-500. doi:http://dx.doi.org/10.1007/s10495-008-0309-3

Macgiven, J., (2009) Psychological Services for People with Parkinson’s Disease. British Psychological Society 2009

MedlinePlus. (2017). Alzheimer’s disease. Retrieved from https://medlineplus.gov/alzheimersdisease.html

Savitt, J.M., Dawson, V.L, Dawson, T.M., (2006) Diagnosis and Treatment of Parkinson’s Disease: molecules to medicine. J Clin Invest  2006: 116(7) 1744-1754.

Tu, X., Hwang, W., Hsu, S., & Ma, H. (2017). Responsiveness of the short-form health           survey and the Parkinson’s disease questionnaire in patients with Parkinson’s disease. Health And Quality Of Life Outcomes, 15(1), 75. doi:10.1186/s12955-017-0642-8

Watson, G.S., and Leverenz, J.B., (2010) Profile of Cognitive Impairment in Parkinson’s Disease. Brain Pathol 2010: 20(3) 640-645.