Parkinson’s Disease
Jill C. Cash
Definition
A.Parkinson’s disease (PD) is an idiopathic, progressive, chronic neurologic syndrome characterized by a combination of akinesia or bradykinesia, or reduction of spontaneous activity and movement; rigidity, or increase in spontaneous muscle tone and involuntary movements; tremor; and postural instability.
Incidence
A.There are more than 200,000 new cases of PD diagnosed per year. One percent of the population older than age 50 has PD. The mean age of onset is 55 to 60 years. Only 5% is seen between the ages of 21 to 40. There is no gender difference in prevalence. PD is seen most frequently in people of European ancestry.
Pathophysiology
A.For reasons that are unclear, degenerative changes occur in the basal ganglia and deplete the dopaminergic neurons in the substantia nigra, resulting in dopamine reduction in the striatum. This interrupts neuronal circuits and produces akinesia and rigidity. The pathophysiology of tremor is less clear, but thalamic involvement is implicated. Symptoms are caused by loss of neurons that produce dopamine. Certain nerve cells (neurons) in the brain break down or die.
Predisposing Factors
A.Antecedent encephalitis.
B.Arteriosclerosis.
C.Trauma.
D.Toxins.
E.Drugs, particularly phenothiazines.
F.Familial neurodegenerative diseases in which parkinsonism is a prominent feature.
G.Presence of Lewy bodies.
Common Complaints
Cardinal symptoms:
A.Tremor at rest: May be intermittent but progresses over time.
B.Rigidity: Joints are more rigid. Increased resistance to passive movement. Appears unilaterally and then progresses to the opposite side. Usually asymmetrical. Appears as decreased movement in arm swing when ambulating, stooped posture, cogwheel rigidity—resistance with tremor.
C.Bradykinesia, or slow voluntary movement, especially with daily activities such as cutting food, dressing self, and so forth. When walking, shorter steps are taken, shuffle-step, feeling of unsteadiness with walking. Postural instability.
Other Signs and Symptoms
A.Micrographia (handwriting that decreases in size when writing out name).
B.Voice changes: Fading, softness, hoarseness, and mumbling.
C.Saliva escaping mouth, especially at night.
D.Dysphagia.
E.Neuropsychiatric changes: Cognitive impairment/dementia/memory loss, sleep disturbance, fatigue, anxiety, depression, pain, and sensory changes.
F.Oily, greasy skin.
G.Excessive perspiration.
H.Constipation.
I.Urinary hesitancy or frequency.
J.Visual loss: Impaired vision, reflex, upward gaze, and convergence.
K.Impaired posture and balance.
Subjective Data
A.Elicit information regarding onset of symptoms. Note changes in progression of symptoms.
B.Talk with the patient and family to establish if there have been behavioral changes, problems with activities such as eating or getting out of chairs, or personality changes.
C.Determine if other family members have had similar symptoms.
D.Ascertain the patient’s medical history, including current medications, both prescription and over-the-counter (OTC).
E.Particularly in patients younger than 55 years, investigate substance abuse and exposure to herbicides or pesticides.
Physical Examination
A.Check pulse, respirations, blood pressure (BP), and weight: Note orthostatic hypotension.
B.Inspect:
1.Observe overall appearance.
2.Note asymmetric tremor at rest.
3.Note subtle facial masking, decreased frequency, and amplitude of eye blinks.
4.Note posture and gait disturbances: Festination, or shuffling, increasingly tiny steps; usually walking with arms down to side; difficulty turning; freezing, or inability to continue to move.
C.Palpate:
1.Palpate extremities, noting increased tone in resting muscles.
D.Neurologic exam:
1.Perform complete neurologic exam. Assess all cranial nerves (CNs). Assess deep tendon reflexes (DTRs).
2.Assess rapid alternating movements. Note difficulty with rapid alternating movements such as tapping fingers or turning palm alternately up and down.
3.Check cogwheel phenomenon, which is stepwise rigidity of movement with passive range of motion (ROM) rather than anticipated smooth movement through ROM. Best tested in wrists.
4.Perform mental status exam.
5.Assess the progression of the disease state with the scale of choice. Scales commonly used include:
a.Unified PD Rating Scale. Available at https://img.medscape.com/fullsize/701/816/58977_UPDRS.pdf.
b.International Parkinson and Movement Disorder Society. This site hosts a list of rating scales and questionnaires: www.movementdisorders.org.
c.Hoehn and Yahr Scale. Available at https://emedicine.medscape.com/article/2172546-overview.
d.Scales for Outcomes in PD—Psychiatric Complications (nonmotor evaluation) and Nonmotor Symptom Screening Questionnaire. Available at https://eprovide.mapi-trust.org/instruments/non-motor-symptoms-questionnaire.
Diagnostic Tests
A.There is no definitive diagnostic test for PD.
B.Urinalysis to rule out urinary tract infection (UTI) with any urinary symptoms.
C.Speech therapy evaluation of dysarthria and dysphagia to assess aspiration risk.
D.Brain CT scan or MRI to exclude mass lesion, multiple infarcts, or normal pressure hydrocephalus (NPH).
E.MRI of cervical spine if there is increased gait disturbance after a fall.
Differential Diagnoses
A.PD.
B.Essential tremor.
C.Multiinfarct dementia.
D.Alzheimer’s disease (AD).
E.Brain tumor.
F.Progressive supranuclear palsy.
G.NPH.
H.Shy–Drager syndrome.
I.Hypothyroidism.
J.Hereditary disease such as Huntington’s chorea or Wilson’s disease.
K.Chorea: Not generally seen in PD; its development in a patient with PD is generally a medication side effect and should be discussed with the patient’s neurologist.
Plan
A.General interventions:
1.Encourage regular exercise to maintain or improve flexibility.
2.The patient should follow a diet that is high in fiber and calcium, with adequate fluid intake, to limit complications due to constipation and osteoporosis. In some patients, protein intake may need to be timed to limit interactions with levodopa.
3.Emphasize the importance of the nonmotor symptoms being addressed and adequately treated. Encourage the family to notify the provider if these symptoms are not being controlled. Anxiety, depression, fatigue, mood, and behavioral issues need to be addressed and controlled for quality of life (QOL) for the patient and family.
4.Home safety evaluations are recommended because the symptoms of PD place patients at high risk for falls and accidental injury.
5.Surgery, such as pallidotomy or thalamotomy, is an option for severe PD in which tremor is poorly controlled with medications.
B. 
See Section III: Patient Teaching Guide Managing Your Parkinson’s Disease.
C.Pharmaceutical therapy:
1.Polypharmacy is the hallmark rather than the exception with PD. Always comanage with a neurologist.
2.Lower doses of several medications, rather than high doses of a single agent, aid in maximizing function while minimizing side effects.
3.Drug dosages are always tapered, not stopped abruptly.
4.First-line drug:
a.Levodopa, combined with a decarboxylase inhibitor, is the mainstay of treatment. Sinemet is the levodopa and carbidopa combination drug most often used:
i.The dose and dosing frequency are very individualized.
ii.Patients are often on a combination of sustained release and short-acting preparations.
iii.See literature for individual dosing. Titrate dose up every 3 days for adjustments.
iv.Long-term use is often associated with adverse effects requiring careful medication dosage.
5.Second-line therapy: Dopamine agonists. Generally given in conjunction with levodopa, these allow use of lower doses of levodopa that can delay or reduce levodopa-associated problems. Examples include pramipexole (Mirapex) and ropinirole (Requip).
6.Ergot derivatives include the following:
a.Bromocriptine and pergolide are the two dopamine agonists most often used:
i.Bromocriptine mesylate (Parlodel) is initiated at 1.25 mg daily or twice a day and slowly increased to 10 to 25 mg daily.
ii.Pergolide mesylate (Permax) is initiated at 0.05 mg daily and increased slowly to 2 to 3 mg in divided doses three times a day.
b.Nonergot drugs are preferred because of fewer side effects:
i.Pramipexole (Mirapex) 0.125 mg three times daily up to 4.5 mg/d maximum is useful for tremors or Ropinirole (Requip) 0.25 mg three times daily, maximum 24-hour period.
7.Neuroprotective agents:
a.Selegiline (Eldepryl), monoamine oxidase (MAO)-B inhibitor 5 mg at breakfast and at lunch, may have neuroprotective effects and slow progression of symptoms. Selegiline is often an initial treatment and is usually continued throughout the course of the disease. Maximum dose is 10 mg/d.
b.Amantadine (Symmetrel) is used as short-term monotherapy in patients younger than 60 years with mild to moderate PD in which akinesia and rigidity are more prominent than tremor:
i.Its effects tend to wane, and it should be tapered once other antiparkinsonian drugs are started.
ii.The usual dose is 100 to 300 mg twice daily. Adjust the dose gradually.
iii.Caution should be used with these medications due to the interactions with other medications and foods that can precipitate high BP to dangerous levels. Advise to avoid foods high in tyramine, such as some cheeses, tofu, and yeast extracts.
8.Anticholinergics: These are useful for treating resting tremor but not akinesia or impaired postural reflexes:
a.The centrally acting drug trihexyphenidyl HCl (Artane) is the most common anticholinergic used:
i.Drug is usually started at 0.5 to 1.0 mg twice daily with food and slowly increased to 2 to 3 mg three times daily.
ii.Dosage should always be tapered, never stopped abruptly.
iii.Use is not recommended in patients older than 60 or with dementia.
b.Benztropine mesylate (Cogentin) 0.5 to 1 mg at bedtime may also be used in PD. Maximum is 6 mg/d. Increase every 6 to 7 days.
9.Sleep disorders are common in PD and respond well to tricyclic antidepressants (TCAs), benzodiazepines, diphenhydramine, or low-dose chloral hydrate.
10.Excessive daytime sleepiness should first be evaluated as a symptom of depression before it is attributed to medications or effects of PD.
As PD progresses, patients often develop clear on
and off
times of medication effectiveness and functional ability, so medication schedules are very carefully customized to maximize on
times.
Follow-Up
A.PD requires lifelong management by a neurologist.
B.Frequency of appointments depends on severity of disease and response to medication. Depression and neuropsychiatric side effects of medications are often seen in patients with PD, so any office visit should involve screening for these. Inquire particularly about memory loss, vivid dreams or nightmares, hallucinations, symptoms of depression or anxiety, and occurrence of panic attacks. Discuss findings with the patient’s neurologist, as medication adjustments could be required.
Consultation/Referral
A.Managing PD requires referral to a neurologist to initiate and adjust medications.
B.If a PD patient requires the addition of medication for other conditions, consult the patient’s neurologist to evaluate for possible serious adverse effects.
C.Involvement with a support group can be helpful for the patient and family. Information about PD and local support groups can be obtained from:
1.The American Parkinson’s Disease Association, Inc.
135 Parkinson Avenue
Staten Island, NY 10305
800-223-2732 Fax 718-981-4399