Individuals with PD can present with cognitive impairment, memory loss, apathy, and confusion, as well as psychiatric manifestations such as major depression, anxiety disorders, and hallucinations. The person with PD can present with reduced self-esteem and lack of confidence. Approximately 24% to 31% of patients develop dementia (7). Interestingly, early PD can be mistaken for depression (8). The cognitive and psychiatric manifestations of PD can place additional stress on the patients and their families. The behavioral impairments in PD can lead to negative thoughts and adverse psychological effects in the patient’s life.

Other features of PD include micrographia; anosmia; sensory disturbances (e.g., pain); sleep disturbances; autonomic disturbances; orthostatic hypotension; gastrointestinal disturbances such as constipation, incontinence, and altered visceral sensitivity (9); genitourinary disturbances (10); and sexual dysfunction (11,12).

Myerson sign or glabellar sign is often present and can be tested by tapping the glabella and observing blinking of the eyes. The blinking should normally stop after tapping a few times in the non-PD individual; however, it does not in those with PD.

There are several scales available to assist the clinician in the staging of PD. The modified Hoehn and Yahr and the Unified Parkinson’s Disease Rating Scale (UPDRS) are the two commonly used (13,14). The impact of PD on ADLs can be evaluated using the Schwab and England Activities of Daily Living rating scale. In this scale the individual’s ability to perform daily activities and the extent of dependency for completion of these tasks on others is rated on a scale of 0% to 100%. The lower the percentage, the higher the level of dependency on others (15).

As mentioned earlier, there is an increased risk of falls in the person with PD. This is often due to characteristics intrinsically associated with the disease such as rigidity, bradykinesia, postural instability, orthostatic hypotension, festinating gait, shuffling gait, stooped forward posture, and freezing of gait (FOG)—a late feature of the disease. FOG may present as an inability to initiate walking, or a failure to continue to move forward. When FOG is present, a patient should not be pulled or pushed to continue to walk, but should be allowed to wait until he or she is able to ambulate to minimize the risk of falling. FOG is generally short in duration, usually lasts less than 10 seconds, and is seen mainly in the form of start or turning hesitation. FOG may be minimized by asking the person to focus on each step, and using external cues. By providing visual cues for each step, patients can achieve a better cadence. One such example is spaced lines on the floor, adjusted for their stride length based on their age, height, and sex (16). Another external cue like auditory stimulation, such as rhythmic music or a metronome, would also be effective (17).

The medications commonly used to treat PD can pose their own problems due to side effects; in addition, their efficacy often decreases as the disease progresses. Side effects of anti-PD medications include increased confusion, clumsiness, dizziness, and agitation, all of which can predispose to a fall. Levodopa (L-dopa) is the most effective medical treatment for PD. However, motor complications uniquely related to L-dopa treatment may emerge that may be difficult to manage. These include fluctuating L-dopa responses and involuntary movements and postures known as dyskinesia and dystonia (18).

Additional safety risks of concern for the person with PD include aspiration-related complications and decubitus ulcers. A person with PD has a 3.7 times higher risk of developing aspiration-related complications compared to non-PD patients (19). The incidence of pressure sores is markedly increased when PD and dementia coexist (20). In severe cases, persons with PD can also develop contractures (21).

A key characteristic in persons with PD is their gradual reduction in ability to move. There are limited and controversial studies with respect to the role of physical therapy in improvement of gait in PD. One single-blind study documented improvement in UPDRS, ADLs, and motor function, but not their mentation. However, 6 months following physical therapy patients did not exercise regularly and their UPDRS regressed to the baseline (22). Another study studied flexibility/balance/functional (FBF) exercise versus aerobic exercise (AE) and home-based exercise (control) and documented outcome measures at 4, 10, and 16 months. This trial showed overall functional improvement at 4 weeks in the FBF group and increased walking economy in the AE group. There was no significant difference in overall functional improvement in either group at 10 months and 16 months compared to the control group (23). There was no true control in this study. Another trial showed that home-based therapy was beneficial for PD patients (24). Results were similar in other studies. A large meta-analysis showed only short-term benefit of physical therapy in patients with PD (25).

Strength training (26) alone does not appear to be enough to improve gait. Tactile, auditory, or visual external sensory cues that are timed with step initiation or step maintenance may be of benefit as is training in how to successfully navigate around obstacles. Other areas of focus in the rehabilitation program include strength, flexibility, balance, and endurance training. Training is also provided for ADLs such as transfers, bed mobility, dressing, grooming, and hygiene, and appropriate assistive devices are provided as needed. Since orthostatic hypotension can be common in patients with PD, pressure garment, stockings, and abdominal binders can be of help. Speech/swallow evaluation and treatment and a rehabilitation nursing program in neurogenic bowel and bladder management are also very useful. Social work and psychological interventions are also an important part of the treatment plan.

MEDICAL KNOWLEDGE

GOALS

Demonstrate knowledge of established and evolving biomedical, clinical epidemiological, and sociobehavioral sciences pertaining to PD, as well as the application of this knowledge to guide holistic patient-centered care.

OBJECTIVES

About one-fifth of the patients with a diagnosis of PD live in the United States, surpassing over a million cases. From the 1994 U.S. government census 1% of Americans over 50 and 2.5% of Americans over 70 had PD, leading to an additional $20 billion increase in societal cost. The earlier the onset of disease, the greater the vocational impact for this group of patients.

Although onset of the disease may be in early adulthood, typical age of onset is in the 60s. About 10% of the PD population is below the age of 40. Juvenile PD has been found in patients as young as 10 years of age, and has been linked with LRRK-2 gene (Parkin 9 gene) in 50% of these cases (27).

PD is more common in elderly men than women and more in African Americans than Caucasian, Asian, or Hispanic populations. Loss of dopaminergic receptors in substantia nigra seems cause loss of motor function (28). In the vast majority of cases, the etiology of parkinsonism is unknown. Genetic influence in PD has not been conclusively proven by twin studies. Environmental factors play an important role in the older population, while genetic factors do so in the younger population. An NIH-funded twin study published in 2011 finds occupational solvent exposure, trichloroethylene (TCE), perchloroethylene (PERC), and carbon tetrachloride (CCl4) can increase risk of PD (29). Some chemical and infectious exposure has been associated with PD. These include toxic exposures (pesticides/herbicides, solvents, wood preservatives, mercury, industrial residue), infectious exposures (influenza, whooping cough), and other miscellaneous exposures (head trauma, dietary vitamin C, introvert personality, dietary vitamin E, rural living, well water) (30).

The basal ganglia are part of a neuronal network organized in parallel circuits. The “motor circuit” is most relevant to the pathophysiology of movement. Abnormal increment or reduction in the inhibitory output activity of basal ganglia gives rise, respectively, to poverty and slowness of movement (i.e., PD) or to dyskinesias (31). Inputs from the cerebral cortex, especially the primary motor strip and primary somatosensory cortex, are received in the basal ganglia and the substantia nigra. The outputs of these two areas are the primary motor cortex, supplementary motor area, the motor nuclei of the brainstem, and (via the thalamus) the premotor cortex. The location of these nuclei and pathway for movement is a circular loop that enables the basal ganglia to receive information about planned movements and motion that is performed by the primary motor cortex. With this knowledge, the basal ganglia control the motor cortex (32). The inputs from the primary motor cortex and the primary somatosensory cortex are projected to the putamen. Next, the signal is sent to the caudate and then to globus pallidus, which has two different outputs: the motor nuclei of the brainstem and the subthalamic nucleus. From the globus pallidus, the signal is then projected to the motor cortex via the ventrolateral thalamus. The feedback loop is complete when information from the primary motor and primary somatosensory cortex is sent to the putamen (33).

Specifically, the loop is maintained by two neurotransmitters: glutamate and gamma-aminobutyric acid (GABA). The substantia nigra via dopamine sends both excitatory and inhibitory signals to the caudate, which innervates different areas of the putamen. The inhibitory signal is received in the putamen and relayed to the external globus pallidus. As a result, an inhibitory postsynaptic potential (IPSP) is produced at the subthalamic nucleus. This inhibition results in an excitatory postsynaptic potential (EPSP) at the internal globus pallidus. Consequently, an inhibitory signal is sent to the thalamus, which produces an EPSP. This excitatory message is then projected to the motor cortex, which results in motor movement. The excitatory input from the substantia nigra has a somewhat similar pathway. Like the inhibitory pathway, an IPSP is produced at the globus pallidus, but at a different location, in the internal globus pallidus (33).

Pathophysiology of gait: The underlying pathophysiology leading to fall in a person with PD is complex. The basal ganglia play an important role in regulating muscle contraction, muscle force, and multijoint movement. The ability to maintain a steady gait rhythm and a stable, steady walking pattern with minimal stride to stride changes is impaired in persons with PD.

Indeed, a clinical diagnosis of resting tremor, rigidity, movement, and postural deficiencies usually reflect greater than 50% loss of the nigrostriatal system in disease. Imaging of the brain dopamine system in PD with positron emission tomography (PET) or single-photon emission computed tomography (SPECT) shows reduced uptake of striatal dopaminergic markers, particularly in the posterior putamen. Imaging can be useful in difficult cases or research studies but is rarely necessary in routine practice, as the diagnosis can usually be established on clinical criteria alone.

Medical management of PD intervenes with three components: (a) slowing of disease progression, (b) symptomatic relief of motor symptoms, and (c) amelioration of nonmotor manifestations. Additional medications may be needed to address the adverse effects of anti-PD medications. Several agents have been identified as neuroprotective agents in PD. The American Academy of Neurology recommends the following initial therapies for the initial treatment of PD:

Some monoamine oxidase B (MAO-B) inhibitors are also shown to have some mild benefit in the treatment of PD including selegiline (Eldepryl) and rasagiline (Azilect). Unlike L-dopa, these medications do not slow the progression of PD. At a certain point during the day, the effect of L-dopa wears off and symptoms can return. Azilect will slow the breakdown of dopamine, and is recommended for use for off-time treatment for PD. Similarly, a catechol-O-methyltransferase (COMT) inhibitor entacapone (Comtan) helps prolong the effects of L-dopa by blocking an enzyme that breaks down dopamine. Entacapone is also recommended for off-time treatment.

Large, well-designed, randomized controlled trials are needed to judge the effect of physiotherapy in PD. A meta-analysis that included 39 trials of 1,827 participants reported physiotherapy has short-term benefits in PD. Clinically significant outcomes were seen in 9 of 18 areas including speed, balance, PD rating, ADLs, and motor subscore (34).

The treatment of advanced PD is difficult, but can be systematically approached to provide the best course of action for the patient. Treatment can incorporate both medical and surgical treatments to work in concert together to provide the optimal alleviation of symptoms. Deep brain stimulation (DBS) is a surgical treatment in which a mechanical neurostimulator is planted in the thalamus, subthalamic nucleus, and globus pallidus that delivers electrical stimulation; this blocks the abnormal nerve signals that cause PD symptoms (35). DBS may help improve the motor fluctuations in some patients with PD. Other surgical procedures such as pallidotomies, thalamotomies, and subthalamotomies are also done in treating PD after other treatments fail. Although symptoms of PD are somewhat improved after the surgery, they are very expensive and may have a multitude of complications. These include bleeding in the brain, infection, behavioral and personality changes, trouble speaking and swallowing, facial paralysis, and visual abnormalities. Weight gain and depression after surgery are also common.

A clinical research study evaluated the impact of DBS in patients with PD on their quality of life using the Parkinson Disease Questionnaire (PDQ-39). This questionnaire evaluates eight domains: mobility, ADLs, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Responses are interpreted numerically from 0 (best) to 100 (worst). Overall QOL index was worse in patients who had DBS. Difficulties were reported with mobility and communication; however, cognition was slightly improved (36).

A few studies used 36-item Short-Form Health Survey (SF-36) to monitor quality of life in patients with PD. SF-36 evaluates the physical and mental health of the patient and found depression was most significantly associated with the patient’s quality of life. They have recommended taking every effort to recognize and treat depression early on in the disease process (37, 38).

Some treatments currently being studied involve fetal cell transplantation, the use of stem cells, and gene therapy. There are various ethical issues to consider in this kind of research. There is still ongoing research about various PD treatments. Medical scientists are now investigating the effect of scope of stem cell implantation and genetic engineering with the use of a virus. These novel ideas are still preliminary.

The role of physical therapy in the treatment of PD patients is widespread. Patients benefit from therapeutic exercises, range of motion (ROM), biofeedback, functional electrical stimulation, balance training, transfer training, progressive ambulation with assistive devices, and stair climbing. PT will also emphasize on proper gait sequence and posture stability.

Gait retraining is one of the most important concerns in the rehabilitation of patients with PD. In advance cases with gait disturbance, patients also have FOG. Physical activity and exercise can result in some measurable improvement in postural instability and balance task performance measures (39). Sufficient evidence is yet not available in regard to therapy schedules and components at different stages of the disease. Also, longer-term tier one studies need to be performed. A patient with PD usually gets 10 days to 2 weeks of patient rehabilitation from his or her insurance.

Exercise is an important component of rehabilitation. Physical therapy may help with physical function and quality of life. It usually includes active and passive exercises, gait training, and practice of normal activities. To date, no specific approach has been proven better than others. Speed-dependent treadmill training has shown to improve mobility and reduce postural instability and fear of falling in PD patients (40).

Occupational therapy helps patients with PD who can benefit from ROM of upper extremities, therapeutic exercises, fine and gross motor coordination, weights to their wrist to reduce tremor, ADLs and self-care, transfers, bed and wheelchair mobility, and posture/balance training. Patients may also benefit from adaptive devices like weighted feeding utensils, drinking cups, plate guards, and so on.

To improve the quality of speech and swallow, speech therapy is also a part of the medical treatment. Other areas that they assist in are content by specific therapies such as oropharyngeal exercises. Dysphagia treatment consisting of smaller bolus size, mechanically altered food consistency, thickened liquids, chin tuck, and head tilt techniques may be of help. Such treatment can help reduce potential aspiration; in addition, improved speech will help prevent social isolation and make their needs known, which will help direct the health care provider. They may need to coordinate with nutritionists to determine food consistency and caloric intake. Dysphagia may require use of modified barium swallow (MBS) and/or fiberoptic endoscopic evaluation of swallow studies (FEES).

Neuropsychology evaluation and treatment may be helpful and needed in patients with cognitive decline, depression, and agitation management. Patients and relatives should receive psychological counseling and learn new coping strategies for their ADLs and instrumental ADLs (IADLs). Patients and caregivers need to learn the basics of the disease and need training to cope adequately with difficult caring situations (41).

Specific rehabilitation nursing can continue to provide help in ADLs, self-care, and transfer activities that have been introduced in OT. Bedside ROM during a.m./p.m. care is important to prevent any contractures. In addition to monitoring for any skin breakdown, frequent changes in position while in bed with relief of pressure areas are important to prevent the development of decubitus ulcers. Monitoring bowel and bladder function is required to prevent urinary retention, incontinence, or constipation.

Patients with PD face a multitude of challenges as their disease progresses. Taking a simple step becomes a big hurdle. The physical activity limitation early in the disease process will prevent patients from being gainfully employed, causing financial difficulty. This may lead to difficulty obtaining medications, outpatient therapy, transportation, home care services, and medical supervision. As the patient has further functional decline, the patient becomes homebound, leading to increased assistance from family and caregivers. Patients will require constant supervision to prevent falls, aspirations, and contractures.

Patients and their families/caregivers have to be educated about the disease process, health care proxy, living will, and do not resuscitate/do not intubate (DNR/DNI), especially when patients are still cognitively intact. Emphasis is to be made on tube feeding and other end-of-life care methods.

Exceptions to the standard of care have been made in special situations where a patient has been allowed to dictate his medical care for quality of life reasons. For example, continuing oral feeds despite the risk for aspiration, allowing patients to ambulate ad lib, even though they are at a risk for falls.

Timing of the medications seems to be very important in the treatment of patients with PD. Following consideration should be prioritized (42):

A French study done in 2005 looked at cost effectiveness of bilateral subthalamic nucleus stimulation in PD. It documented relatively low risk and little cost burden on the patient population with a total cost of $50,215 per patient for the surgery and 12-month follow-up. In this study, the UPDRS motor score improved by 51% at 3-month follow-up and 57% at 12-month follow-up (43).