Parkinson disease

Parkinson disease is a degenerative disorder involving a progressive loss of dopaminergic neurons in the substantia nigra. This deficit in dopaminergic function results in resting tremor and difficulty in the control of voluntary movement. Cardiovascular function, bowel motility, and cognitive function are often compromised. Although not directly associated with the motor system pathology, the functional deficits are emotionally devastating to the patient, resulting in depression and other mood disorders. The predominant pharmacological approach in the management of Parkinson disease is the enhancement of dopaminergic function in the affected brain regions. Among the earliest successful approaches was the use of levodopa (l-dopa), a precursor of dopamine in the central nervous system (CNS). The use of this agent (and all agents to date) only enhances the dopaminergic function in remaining neurons. This approach has no effect on the progressive loss of neurons. In addition to central conversion of l-dopa to dopamine in the substantia nigra, a similar conversion occurs in the limbic system, a brain center associated with the regulation of behavior. Excessive dopaminergic influence in the limbic system has been associated with aberrant behaviors, including paranoia, delusions, hallucinations, and related psychiatric disturbances that may influence sleep and mood. These behavioral changes are obviously antagonistic to any therapeutic plan. In addition to l-dopa, a dopamine precursor, agents that inhibit the breakdown of dopamine, enhance the release of dopamine, or have dopaminergic agonist activity will have similar behavioral effects (Box 36-1). Dopaminergic agents may produce postural hypotension and syncope by virtue of their ability to produce vasodilation on the basis of CNS and peripheral actions.^3,4 If clients are unable to take their medication, an increasing danger exists (with extended therapy) that movement may be impossible and the normal chest wall expansion and contraction may be compromised (see Chapter 30).

Because Parkinson disease is progressive in nature, clients may have different presentations depending on the stage of the disease and the presence of pharmacological interventions. In the early months of the disease, the motor signs may be particularly subtle, and patients may report only slowness, stiffness, and trouble with handwriting. Particular attention to the history of tremor, slowness of fine motor control, a hunched and slightly flexed posture, and micrographia may lead the physician to diagnose Parkinson disease in its early phases.⁵ As Parkinson disease advances, patients have increasing difficulty in activities of daily living and gait as well as bradykinesia and distal tremor.

Once a definitive diagnosis has been made, controlling symptoms of the disease and the side effects of medications is balanced with the level of functional involvement. The physician and client may discuss the option of a number of medications (see Box 36-1) but must determine the best approach on the basis of the clinical presentation. One limitation is the side effect of involuntary movements (dyskinesias). These dyskinesias can be difficult to control and are different from the involuntary movements caused by the disease itself. As mentioned earlier, dopamine agonist regimens that do not cause dyskinesias can also be prescribed, but their effect on symptoms is not as potent.⁶ Often physicians may begin treatment with a dopamine agonist and continue with the agonist as long as symptoms are satisfactorily controlled. Later the physician can initiate treatment with l-dopa when the disease is in the advanced stages. With the elderly client who has cognitive deficits, combination therapy may be the initial choice. Once a medication regimen has been initiated, the client and therapist may notice improvement in Parkinson disease symptoms and therefore functional abilities. After taking a medication over time, clients may find that the effect of the medication begins to wear off before the next dose is scheduled. At this point consultation with the rehabilitation team is recommended to potentially change the medication timing or release ability or combine the treatment with other antiparkinsonian medications.

Great emphasis is placed on treating the motor features of Parkinson disease, but clients may have nonmotor manifestations, including depression, anxiety, cognitive impairment, and dementia. Often the client does not mention these difficulties because he or she does not link them to Parkinson disease. Clients may demonstrate some of these difficulties, and the therapist should recognize the symptoms and refer the client for further follow-up.

The major problems that patients have after 5 years of treatment for Parkinson disease are fluctuations (both motor and nonmotor), dyskinesias, and behavioral or cognitive changes.⁷ The mechanisms behind these complications relate both to the underlying Parkinson disease and to the effects of medications. Motor fluctuations take several forms. Most commonly, a predictable decline in motor performance occurs near the end of each medication dose (“wearing off”). Patients change gradually from “on” with a good medication response into an “off” period 30 minutes to 1 hour before the next medication dose is due. Often patients have involuntary movements (dyskinesias) as a peak-dose complication, and sometimes similar movements occur at the end of the dose. Sudden and severe cataclysms of motor fluctuation occur rarely, with ambulatory patients becoming immobilized over a period of seconds (“sudden on-off”).⁸ Because these fluctuations occur throughout the day, accurate detection requires the cooperation of the patient, who must be trained to complete diaries of function.⁹ These journals generally divide the 24-hour day into 30-minute segments to detect good medication response (“on”), poor medication response (“off”), disabling dyskinesias, and sleep.

In general, therapists working with clients taking antiparkinsonian medication must be aware of both the positive and the negative side effects of medications to meet functional goals and outcomes effectively. Learning the difference between tremor and dyskinesia is crucial. The therapist must coordinate therapy sessions during good medication response times to assist optimal outcomes. In addition, clients should be monitored for postural hypotension, dizziness, and cognitive changes. Therapists have the unique opportunity to determine the best timing, frequency, and duration of the treatment, and understanding the impact of a client’s drug regimen will only enhance the outcome. Therapists must also be aware that exercise increases metabolism. Increased metabolism may use up the medication faster; thus an individual who generally remains symptom free (no off times between doses) will again exhibit signs of the disease (distal tremors and axial or proximal rigidity). These increases in symptoms may be a drug dosage problem, not signs of further degeneration of the basal ganglia. All changes in symptoms should be discussed with both the pharmacist and the physician.

Cancer

Cancer is a general term for classifying disorders associated with abnormal and uncontrolled cell growth. Virtually any organ system in the body can be affected, either as the primary site of the disorder or as a secondary site associated with metastasis. Cancer may interfere with neurological rehabilitation in various ways. Tumors within the brain may interfere with cognitive and motor function as well as autonomic and metabolic control (see Chapter 25). Peripherally, tumors may interfere with peripheral nerve function and associated motor control or may produce pain. In addition, drugs that reduce cancer pain may interfere with cognitive and motor function.¹⁰ Among these, morphine and related opiate derivatives are notable (Box 36-2). A significant degree of tolerance to the CNS depressant effects of these agents will develop with long-term administration. In cancer chemotherapeutic regimens, many antiemetic agents are used. These include dopaminergic antagonists (which may produce motor deficits similar to Parkinson disease), dronabinol (a chemical component of marijuana, which can affect cognitive function), as well as high-dose corticosteroids (which affect mood). Some antitumor agents may be neurotoxic; a reduction in deep tendon reflex, paresthesias, and demyelination is associated with vincristine (Oncovin).¹¹ Naturally, any change in drugs that involves a cancer treatment regimen (directly or indirectly) requires the approval of the client’s oncologist.

The main role of rehabilitation specialists is to help patients with cancer recover from the physical changes that accompany their illness, promote function in activities of daily living, and help provide adaptations to activities within the limits of each patient’s function and the illness. Clinicians should be aware of chemotherapy side effects and the side effects of medications given to treat the toxic effects of chemotherapy.

A number of chemotherapeutic and nonchemotherapeutic medications are used to fight cancer. Most therapies against cancer operate on the simple principle that because cells in tumors are actively dividing, agents that kill dividing cells will kill tumor cells.¹² Tissues that rapidly divide in the body are therefore at risk, including hair, mucosal lining, bone marrow, immune cells, and skin epithelial cells. Nonchemotherapy medications called biological response modifiers (BRMs) are naturally made by the body but delivered in large quantities and at higher doses than what the body is capable of producing.¹³ Interferon and interleukin are two of the most commonly used medications. Monoclonal antibodies are also used as chemotherapy to suppress the immune system.

Chemotherapy often has side effects that affect the integumentary, GI, hematological, and neurological systems. Each type of therapy has potential side effects as well as more general side effects of the treatment regimen. As a result of chemotherapeutic treatment of cancer, patients often have muscular weakness, fatigue, pain, immobility, and reduced flexibility. Often the therapist will have to be supportive and flexible with treatment plans to accommodate for changing physiological, psychological, and social factors during treatment.

GI symptoms such as nausea and vomiting may occur, and medications such as Compazine and Reglan may be given to help control these episodes. Symptoms of diarrhea may be addressed through prescriptions or the use of over-the-counter (OTC) medications including milk of magnesia and magnesium citrate. The development of mucositis or esophagitis is also possible. A prescription solution of three medications (Benadryl, nystatin, viscous lidocaine) can help relieve the pain, inflammation, and potential associated fungal infections. Bone marrow suppression from chemotherapeutic regimens may lead to increased risk of infections, increased risk of bleeding, and increased fatigue and lack of exercise capacity resulting in musculoskeletal weakness. Patients undergoing chemotherapy may receive one or more medications to signal the bone marrow to increase output of white blood cells (Neupogen), stimulate the production of red blood cells (Epogen), and stimulate increased production of platelets (Neumega). These therapies may be instituted to help the patient more quickly reverse suppression of bone marrow and allow the chemotherapy to continue without interruption.¹⁴ Generalized symptoms include fever, body aches and pains, and feelings of ill health and fatigue. No specific medications are used to improve these symptoms. In general, taking medications such as acetaminophen, ibuprofen, or narcotics for fever and pain may help. The use of exercise as an adjunct therapy for cancer treatment–related symptoms has gained favor in oncology rehabilitation as a promising intervention.^15,16 Exercise is thought to help improve endurance and functional abilities.¹⁵ The major side effects associated with BRMs and monoclonal antibodies are generalized as well and include fever and flulike symptoms with associated arthralgia and myalgia. Other side effects include lymphedema characterized by fluid retention caused by disruption of lymphatic drainage or removal of lymph nodes. As mentioned earlier, neurological changes may occur, with the development of neurological signs as well as forgetfulness, suicidal ideation, and depression. The rehabilitation professional is an important team member in oncology because he or she potentially affects quality of life.

Seizure disorders (epilepsy)

Epilepsy is associated with a diverse group of neurological disorders resulting in motor, psychic, and autonomic manifestations. Many antiseizure medications may produce drowsiness, ataxia, and vertigo (Box 36-3). Some may produce cognitive disorders in children and adults.^17,18 Although these adverse effects may be exhibited throughout therapy, they are most troublesome during initiation of drug therapy, addition of a drug, and dosage escalation. Sudden discontinuation of antiseizure medications may result in status epilepticus, which may be fatal. Many antiseizure medications are finding successful applications outside epilepsy, especially in the area of pain management.

The practicing clinician working with clients who have a history of seizure disorders must be prepared for the onset of a seizure and be aware of any adverse side effects of medications. Adverse side effects are typically determined on a clinical basis, signifying the importance of recognition by the health care provider. Many of the common side effects can also have negative implications for motor learning, especially while the client is getting used to the medication or the dosage is being elevated or tapered.

The treatment of seizure disorders with pharmacotherapy is typically intended to control the seizure activity completely without producing unwanted side effects. Pharmacological intervention usually begins with one medication (monotherapy); if this drug is unsuccessful a second is added while dosage of the first is tapered. Or a combination may be needed. The effects of the medications vary and may include enhancing the inhibitory effects of γ-aminobutyric acid (GABA) (benzodiazepines); reducing posttetanic potentiation, thereby reducing seizure spread (iminostilbenes); or modulating neuronal voltage-dependent sodium and calcium channels (hydantoin).¹⁹ The overall result is a reduction in abnormal electrical impulses in the brain. The choice of antiseizure drugs primarily depends on the seizure type and, if possible, the diagnosis of a specific syndrome. If seizures are recurrent and occur during critical periods of childhood, adolescence, and early adulthood, they may result in significant impairments in function and increased disability.

Some side effects may be slow to develop and difficult to diagnose because seizures can often be mistaken for sedation or cognitive dysfunction, especially in children, who may not report drug side effects. Practitioners can also mistakenly accept reversible drug toxicity as a necessary consequence of a seizure disorder. The number of seizures occurring during physical or occupational therapy should be tracked to assist in determining appropriate pharmacotherapy.

One common antiseizure medication, valproic acid (Depakene), may cause nausea, vomiting, hair loss, tremor, tiredness, dizziness, and headache. Valproic acid has also been reported to aggravate absence seizure in clients with absence epilepsy.²⁰ Metabolic side effects may include an increase in glucose-stimulated pancreatic insulin secretion, which may be followed by an increase in body weight.²¹ Long-term valproic acid use is known to increase bone resorption in adult epileptic patients and lead to a decreased bone mineral density.²²

Another seizure medication, carbamazepine (Tegretol), is considered a safe drug but has a long list of adverse events, most commonly ataxia and nystagmus.²³ Other systems frequently involved are the skin, the hematopoietic system, and the cardiovascular system. Gabapentin (Neurontin) is another well-tolerated antiseizure medication with proven clinical efficacy and a low incidence of adverse events in clinical trials. Common side effects include dizziness, fatigue, and headache. Phenytoin (Dilantin) has adverse reactions including ataxia, nystagmus, slurred speech, confusion, dizziness, and, at high doses, peripheral neuropathy.

Benzodiazepines (e.g., diazepam) are useful in managing status epilepticus, but their effects are not long lasting so they are often used along with a primary anticonvulsant. The most frequent side effects are dose-related sedation, difficulty with concentration, dizziness, and difficulty walking.

Pharmacological adverse events that occur under the influence of seizure medications must be recognized by the rehabilitation specialist to participate in a team approach to patient care. Therapists can assist in determination of effectiveness of a specific treatment regimen, appropriate timing of rehabilitation interventions, and the overall progress of the client during rehabilitation.

Stroke, hypertension, and related disorders

Stroke, by virtue of the interference with blood flow and oxygenation, produces both reversible and irreversible neurological deficits (see Chapter 23). The loss of function associated with stroke has at least two major causes. The first involves loss of oxygenation to a critical brain region, followed by glutaminergic rebound and excessive calcium influx with apoptosis (programmed cell death). Current drugs and those under development are aimed at restoring blood flow and inhibiting glutaminergic hyperexcitability and intracellular apoptotic mechanisms.²⁴ The second pathogenic issue is related to reperfusion injury associated with oxygen radicals and associated cellular damage. In this case, free radical scavengers have shown some promise in animal models of stroke.²⁵ To reduce the damage associated with thromboembolism in such cases, tissue plasminogen activator has been recommended. However, this agent is most effective when given within an hour after the vascular insult. Drugs with other mechanisms used to improve the prognosis of stroke are under development. However, drugs used for concurrent conditions (atherosclerosis and hypertension) before and after a stroke are complicating factors for optimal outcomes from rehabilitation. These drugs include β-adrenergic antagonists, which reduce heart rate and correspondingly reduce exercise tolerance. Occasionally, calcium channel blockers, α-adrenergic blockers, and related agents may cause similar effects, including weakness, dizziness, syncope, and cognitive disorders. Changes in serum electrolytes induced by diuretics and the angiotensin-converting enzyme inhibitors may affect the heart, the vasculature, and skeletal muscle and ultimately cause impairments in areas such as strength of contraction.²⁶ Box 36-4 lists many of these drugs. Many of the cholesterol synthesis inhibitors (agents used to reduce serum cholesterol) may induce muscle weakness (Box 36-5).^27,28 Abrupt discontinuation of antihypertensive medications may result in a hypertensive crisis, dramatically increasing the risk of stroke and related disorders.

Clinicians caring for patients with stroke, hypertension, and cardiac disorders will benefit from understanding the impact of any medication on the therapeutic plan. These clients may be taking any number of medications to manage the acute and subacute complications of cardiovascular impairments and their resulting sequelae. Other complications after stroke that may require pharmacological intervention include urinary tract infections, musculoskeletal pain, deep vein thrombosis, pressure sores, shoulder subluxation, and depression. All these medications have their own issues, and health care providers must be aware of adverse events and any alteration in function of the heart that may occur in relation to exercise.

Anticoagulants such as heparin, warfarin, and aspirin (so-called blood thinners) are used to prevent another stroke after the first one has occurred. Side effects may include bleeding, allergic reactions, thrombocytopenia, and, in the case of aspirin, stomach irritation.²⁹ Blood thinners make the client more susceptible to bruising; therefore care must be taken in client handling and choice of activity. Antiarrhythmics are used to restore normal conduction patterns of the heart. Antiarrhythmic drugs may make some clients experience lightheadedness, dizziness, or faintness when they get up after sitting or lying down (orthostatic hypotension).³⁰ Antiarrhythmic drugs may also cause low blood sugar or changes in thermoregulation.³¹ The most common side effects are dry mouth and throat, diarrhea, and loss of appetite.³² These problems usually go away as the body adjusts to the drug and do not require medical treatment. Therapists must be prepared for hypotensive events and the need to educate clients on positions that will reduce the effects of orthostatic hypotension.

Hypertension is a common disorder that is frequently encountered when treating patients in the rehabilitation environment. Antihypertensive medications are used to lower blood pressure (see Box 36-4) by limiting plasma volume expansion, decreasing peripheral resistance, and decreasing plasma volume. Often clients under medical management will undergo changes in dose and additions or deletions of medication, which may lead to problems during rehabilitation. Side effects of these medications may include increased frequency of urination, increased urinary excretion of potassium, orthostatic hypotension, hypotension, dehydration, tiredness, fatigue, cold hands and feet, and dizziness.³³ When working with a client taking antihypertensive medications, health care providers should monitor for side effects, clinical signs, and the client’s perceived exertion. Generally, people on antihypertensive medications require careful cardiovascular monitoring during any physical activity.

Many clients may become depressed after a neurological disorder such as stroke or a cardiac event.³⁴ It may be attributable to a natural loss of physical function or a neurochemical response to changes in brain chemistry. Clients with signs and symptoms of depression (sadness, anxiousness, hopelessness, suicidal ideation) should be referred for further follow-up by the physician. Many antidepressant medications take at least 2 weeks to achieve a therapeutic level. Antidepressants may cause temporary side effects (sometimes referred to as adverse effects) in some people. These side effects are generally mild. Any unusual reactions, side effects, or behaviors that interfere with functioning should be reported to the doctor immediately. The most common side effects of tricyclic antidepressants (TCAs) are dry mouth, constipation, bladder problems, sexual problems, blurred vision, dizziness, and drowsiness.³⁵ The newer antidepressants have different types of side effects, including headache, nausea, nervousness, insomnia, agitation, and sexual problems.³⁶ Therapists working with clients who are depressed may need to delay rehabilitation until the depression is well managed.

Hyperlipidemia is considered a modifiable risk factor for heart disease and stroke. Many clients may be receiving pharmacological treatment to reduce their cardiovascular risk. Several types of drugs are available for cholesterol lowering, including statins, bile acid sequestrants, nicotinic acid, and fibric acids.³⁷ The statins are considered first-line drugs and are generally well tolerated but can produce myopathy under some circumstances.³⁷ An elevation of creatine kinase level is the best indicator of statin-induced myopathy and should be checked for when clients report leg pain. Bile acid sequestrants also produce moderate reductions in cholesterol. Sequestrant therapy can produce a variety of GI symptoms, including constipation, abdominal pain, bloating, fullness, nausea, and flatulence. Nicotinic acid (niacin) therapy can be accompanied by a number of side effects. Flushing of the skin is common with the crystalline form and is intolerable for some persons. However, most persons have tolerance to the flushing after more prolonged use of the drug. The fibrates have the ability to lower serum triglycerides and are generally well tolerated in most persons. GI symptoms are the most common reports, and fibrates appear to increase the likelihood of cholesterol gallstones.³⁷

Overall, clients taking cardiovascular medications need careful monitoring for any drug impact on cardiorespiratory or metabolic responses in relation to rehabilitation activities. Thus the effects of drugs must be considered in developing the rehabilitation plan (see Chapter 30).