- Understanding Parkinson's Disease (PD) And Its Care
- Treatment and Functional Issues - Medications for PD
- Functional Issues in PD
- Surgery for PD
PD is a disorder of some parts of the brain that control movement. One major area of involvement is the substantia nigra, in the rear part of the brain (midbrain). It is there that, for reasons we are still trying to discover, nerve cells in PD stop functioning normally and some cells die prematurely. Because of the usual slow worsening of PD, there are still enough working nerve cells to be able to respond to medications and surgical treatment for a long while.
We'd all like to prevent continued loss of nigral and other nerve cells in PD with "neuroprotective" medication treatment, and several groups in Michigan are involved in a long-term NIH study of such potentially useful drugs. However, results of such studies will take several years to be known, and our concern here is to address the practical, symptomatic treatment of PD for patients whose illness has interfered with work- and/or home-related activities most of the time. This covers the spectrum of disability we'd call moderate-advanced.
This is a general review of current concepts and practices regarding PD evaluation and treatment. Inevitably, statements made will reflect personal opinions and approaches, not buttressed here by citations from the medical literature. The statements must not be taken as reflecting what is happening to any particular person medically, or what's best for a particular person's treatment, now or in the future. The offering of this guide is not "practicing medicine" via informational exchange by website. The practice of medicine occurs when an individual consults a physician to obtain a diagnosis and treatment plan specifically for him or her. That's not what this guide can or should do, and it is no substitute for an individual consultation or an ongoing medical relationship between a doctor and a patient.
Medication doses or dose ranges are best dealt with at the individual doctor-patient level, addressing the need presented by particular clinical situations. The effects of treatment can vary enormously, and much telephone and clinic time is spent sorting out risks, benefits, side effect possibilities, alternate treatments, etc. This is the art of medicine. The desire to help people drives the passion.
The best model for care of any chronic medical disorder is to have a trusting, working relationship between patients, caregivers, doctors, nurses and other health professionals. Practically, this means having patients benefit from the expertise of the medical team and having the medical team benefit from the experience of patients as they try to create an effective treatment plan together. It means having as frequent contact between these individuals as is really needed to optimize care. This may be by phone calls, clinic visits and, in some instances, by e-mail or letters. It will vary, depending on the needs of patients and the needed availability of the medical team. The following points, through many years of experience, are most important:
- Get the right diagnosis and treatment. There are various forms of parkinsonism, aside from PD itself, which may evident early on, or only with the passage of time (e.g., multiple system atrophy [MSA], progressive supranuclear palsy [PSP], vascular parkinsonism [due to strokes]), and others. Such other illnesses may require various studies to diagnose or different treatments to be most helpful. A neurologist with expertise in movement disorders is best poised to make a definitive diagnosis and recommend treatment in this field, especially when the answers are not straightforward. Seek out such an opinion if your general doctor or neurologist cannot either make a diagnosis or, after a reasonable period of time and trials of treatment, can't help enough. However, don't assume that having a medication side effect means either that the doctor doesn't know what you have, or doesn't know how to treat it.
- Get enough time with the doctor or nurse to review details of how you're coping with daily activities in light of the anti-PD medication and other drug(s), doses and their timing, that you're taking. For those who are getting deep brain stimulation (DBS) as well, careful review of the electrical settings is also critical.
- Patients and caregivers often misunderstand verbal treatment directions, especially those that are complex. Be sure that you have understandable, written instructions.
- Important reasons for drug treatment "failure" may be that too little was either prescribed or taken. The latter may be because the timing of doses was impractical or ineffective, or that side effects may have developed and not brought to the attention of the medical team.
- You need to learn about PD to be a full partner in your care. Good doctors welcome that. There are several well-written books and pamphlets on the subject; ask the Michigan Parkinson Foundation staff about them. The internet can be helpful, but remember that it's a worldwide, uncensored bulletin board, not a "truth machine", so that what you get can span the gap between potentially misleading or unsubstantiated claims to truly high quality reviews of our current understanding of PD and its treatment. Among the latter are offerings on the websites of the Parkinson's Disease Foundation, National Parkinson Foundation and the American Parkinson's Disease Association.
- Remember, it's your life and you should live it to the fullest possible extent. PD is not your life, but some hurdle to cope with courageously, getting the help you need from loving family, friends, your religious community, health professionals and others. People want to see you do well. Speaking personally, nothing is more gratifying than to see patients make small gains or great strides as they live a meaningful life.
What is the goal of treatment in PD? It is the individualized crafting of a plan of care that allows each patient to get and maintain the best function that he/she can with few or no side effects of therapy. Because each plan is individualized, the ultimate functional outcome will vary, depending on the severity of the illness, as well as patients' ability to benefit from, and to tolerate, adequate doses of medications, DBS (if appropriate), as well as physical, occupational and speech therapy. We need to be realistic about what is achievable, and this may have to be revised as time goes on. Generally, we offer as few drugs, and as little of them, as patients need to be as functional as possible. Whenever possible, new drugs are introduced at low doses, and at a suitable, individualized pace, in order not to give more than is needed, as well as to limit potential side effects.
Not every symptom can, or needs to be, treated. Some symptoms are relatively minor, particularly when considering whether an otherwise effective treatment plan would have to be overhauled, complicating daily life unduly for unclear potential benefits. This is an important part of the cooperative realism that patient and doctor must discuss.
These drugs include Artane® (trihexyphenidyl) and Cogentin® (benztropine). They are useful for treatment of tremor of a hand or foot at rest, i.e., when supported, not when raised up or during action. They give little or no benefit for bradykinesia (slow movement), muscular rigidity (stiffness), or gait imbalance.
Neither drug should be used in those with dementia (loss of memory, other cognitive function), or in those with glaucoma, prostate enlargement, visual blurring, rapid heartbeat, or excessive constipation.
If a patient develops mental confusion, with or without visual hallucinations (seeing visions), while on them, they may need to be discontinued.
The drug is used either as a mild agent to help tremor, bradykinesia and rigidity, or to decrease choreic (jerky) limb dyskinesias (involuntary movements) due to excessive dopaminergic (dopamine-promoting) medications. Amantadine is usually well-tolerated, though it can cause foot or leg edema (swelling) and a leg rash that looks like a red roadmap, called livedo reticularis. Among demented individuals, it alone can be responsible for mental confusion, and/or hallucinations.
Recent data suggest that dopamine agonists (dopamine-mimicking drugs), may be used before Sinemet® (levodopa-carbidopa) to get adequate motor benefit, and that such benefit can persist in many patients for years. Moreover, unlike with Sinemet®, drug-induced motor fluctuations ("wearing-off" or "on-off" impairment of mobility between doses) are less likely with the agonists. For this reason, if a patient's condition permits it, an agonist may be a better initial choice than Sinemet®. However, more severely disabled patients may need Sinemet® from the start. Most patients with advanced PD will need both an agonist and Sinemet® (see below).
There are data that suggest that there may be a neuroprotective action of Requip® and Mirapex®, but this is an area of controversy. Further research is needed.
These drugs act on nerve cells in the brain that respond to dopamine, the major signaling chemical (neurotransmitter) that is low in PD. By stimulating the dopamine receptor (signal receiver), dopamine agonists act as though they were dopamine, and they activate the nerve cells they stimulate. In so doing, they improve motor function. However, they are not as powerful as Sinemet®.
The agonists were developed over many years, with Parlodel® and Permax® introduced earlier, and Requip® and Mirapex® becoming available more recently. All are potentially effective drugs, depending on whether a particular patient can tolerate enough medication to improve mobility adequately. The agonists have not often been tested directly against one another in clinical trials, but have either been tested against placebo (no effective drug) alone, or as additions to a Sinemet® regimen. One has a general impression of rough equality of efficacy among the agonists, if adequate doses of drug can be given, but it is possible that some patients may benefit from one or another to a greater extent. Only individual trials of medications with patients can establish that, however, and if a particular agonist is effective enough, it is unwise to try another. If sufficient side effects appear, though, a trial of a different agonist may be warranted. Any of the agonists may produce side effects, often having a similar dopamine-mediated motor and mental character (see 6, below).
This drug is accepted as the gold standard for symptomatic PD treatment, i.e., the most powerful one against which clinical effectiveness can be measured. Its introduction by the late Dr. George Cotzias and colleagues in 1967 was a watershed event in neurology, and one which brought great hope and functional benefit to patients with PD everywhere.
It used to be that nearly every patient with PD was begun on Sinemet® as soon as the diagnosis was made. However, many movement disorders neurologists today reserve that treatment for patients whose mobility, dexterity and tremor we judge will not be sufficiently responsive to either an anticholinergic, amantadine or an agonist, either by mental comparison of our experience with that of other patients, or after a trial of these other drugs sequentially. This is because many patients may benefit adequately from either an anticholinergic, amantadine or an agonist for several years, without the risk of motor fluctuations ("wearing off" or "on-off" effects, between Sinemet® doses) that levodopa treatment typically produces after several years of treatment.
In practice, as PD advances, most patients will need Sinemet® at some dose to function well. It will often be gratifying to them and to caregivers to see significant improvement, allowing more activities and independence to occur.
Following patients on Sinemet® or agonists involves balancing the doses needed for adequate mobility against the possibility of inducing dopamine-mediated side effects. Such effects may include:
- Drowsiness. This can be a dose-limiting side effect, i.e., one which prevents giving as much medication as would be needed to fully treat motor issues in PD. For that reason, it's best to review whether drowsiness is related to giving higher doses of Sinemet® or an agonist, or whether drowsiness is related to too little social interaction. If it is the latter, efforts to get the patient to be more active are very worthwhile.
- Nausea and vomiting. Taking the drug in mid-meals or with small snacks is the simplest solution. If this isn't successful, a trial of domperidone (available in Canada), about an hour before taking the drug, may eliminate the problem.
- Lightheadedness (near-fainting) on standing. Decreasing the drug dose and taking one's time when standing, and holding onto solid support, are often helpful. If not, try another drug that is tolerated.
- Rapid heartbeat. This uncommon side effect should be evaluated by an internist or cardiologist, and may require either reducing or discontinuing an anti-PD drug.
- Dyskinesias (involuntary bodily movements). These come in two basic varieties: 1) those jerky (choreic) excessive movements that occur after dopaminergic drug(s) (most often Sinemet®), and which almost always mean that too much medication has been taken; and 2) those dystonic (twisting, tightening) movements that occur before the next (most often Sinemet®) dose is due.
- Jerky, choreic dyskinesias can be controlled either by reducing Sinemet® prior to such episodes, watching for the re-emergence of PD slowing and related disability, and considering adding an agonist to maintain mobility, or by adding amantadine to the existing Sinemet® regimen. It is a fine clinical judgment about which of the anti-PD medications a patient is taking is/are responsible for the side effects seen, requiring frequent phone and/or clinic contact to regulate.
- Dystonic dyskinesias can often be controlled by increasing the dopaminergic medication a patient is taking before the dystonic episode occurs.
- Confusional (disorientation), hallucinatory (unreal visions) or delusional (unreal beliefs). Control of these symptoms will, most often, require reducing the number, types and doses of anti-PD medications (e.g., anticholinergics, Eldepryl® (selegilene), others). During this time, adequate medication needs to be taken to maintain mobility, while considering the use of anti-psychotic agents [e.g., first, Seroquel® (quetiapine), then Clozaril® (clozapine)], depending on the severity and frequency of hallucinations and delusions. In some cases, working on these issues closely with a knowledgeable psychiatrist can be of great value.
During the early stages of PD, patients don't notice a difference in motor function between medication (usually Sinemet®) doses. However, in moderate-advanced PD, an increasing number of patients will. They may become slower, stiffer and less coordinated, more tremulous, and have more gait imbalance before the next dose is due. If such disabilities are marked, they may not be able to get out of a chair, get dressed, bathe, or do other activities of daily living without help. Falling may be more likely at such times. This is distressing and potentially dangerous and needs to be dealt with.
Several choices are available. Though it is possible to increase each Sinemet® immediate release dose (i.e., 10/100, 25/100, 25/250) and/or to decrease the interval between doses, that is not what is preferred. This is because we wish to decrease the likelihood of Sinemet®-related side effects (see above), and to reduce later motor fluctuations. It is possible to add controlled-release Sinemet® (i.e., 25/100CR, 50/200) to the existing immediate-release Sinemet® regimen, but, again, it is desirable to limit total daily levodopa, if possible. This may not be possible in individual cases, however, and the giving of both immediate- and controlled-release Sinemet® is certainly a viable and valuable option for many patients.
With these issues in mind, it's often best to consider the use of a COMT inhibitor (Comtan® [entacapone], Tasmar® [tolcapone]), or an agonist. COMT inhibitors extend the duration of levodopa (but not agonist) action by preventing breakdown of brain dopamine. Comtan® is easy to use as individual 200 mg tablets, given at the same time as Sinemet® doses, matching the times of the day when wearing-off occurs. The recent incorporation of Comtan® into one pill with Sinemet® (Stalevo®) is suitable for those patients with wearing-off of all Sinemet® doses, but doesn't allow dose-by-dose individuation that using Comtan® alone permits.
Tasmar® is a highly effective COMT inhibitor, but came under special FDA guidelines when several patients died as a result of unmonitored liver injury. For this reason, Tasmar® may be used only when other medications have been found to be ineffective or not tolerated. If used, blood studies of liver enzymes (SGPT) must be done every two weeks, and even values just above normal must be taken as grounds for discontinuing the drug. There is no such issue with Comtan®.
The agonists are often helpful in treating wearing-off effects because their duration of action is relatively long (4-6 hours, depending on the drug).
Freezing is the sudden loss of the ability to walk forward. It may occur during a wearing-off episode (more commonly) or not, and may or may not be associated with a greater likelihood of falling. At such times, patients may recover if they either focus mental attention on walking, try marching in place or to either side, or get verbal or physical support to walk from someone else.
Falling is to be feared and avoided, if possible. Hips, arms, pelvises, necks, etc. can be broken and may not be repairable to restore adequate function. Heads can be injured, producing blood clots in or over the brain, requiring surgery.
Staying mobile, however, is essential. Whenever possible, patients should walk, within their own limitations. Others who can do more, physically, should.
Certainly, safe mobility must be maintained, whether that is achievable with some combination of medical, physical, occupational or surgical treatment. If these treatment modes alone cannot fully succeed, some form of physical support [i.e., cane, walker, scooter, or holding onto someone or some immovable object(s)] has to be used.
Speech and Swallowing
These issues are dealt with in detail elsewhere, but several general points are worth making. Communication with others is so important that it may be best to consult with a speech pathologist working with your doctor to optimize your individual function if you cannot be understood. Similarly, swallowing function needs to be evaluated in those patients who are choking on liquids or solids.
This important area of expertise is offered to patients who need special help to do activities of daily living, including standing, balancing, gait training, bathing and other bathroom activities, feeding, and others. Occupational therapists work well with others in the medical team to optimize function, offering individualized treatment programs.
This is very common, especially among those with moderate-advanced PD. It is because of an illness-related abnormality in the nerves supplying the bowel. It can be made worse by the use of anticholinergic drugs, and these may need to be discontinued if constipation poses a serious problem.
Patients often benefit from a high fiber diet, increased liquid intake, exercise, and the use of over-the-counter stool softeners. Frequent laxatives or enemas should be avoided, if possible, but these measures need to be discussed with a treating physician.
Patients will often notice an increased urgency to urinate, as well as an increased urinary frequency. In men, this may exaggerate ongoing symptoms of prostate enlargement, and such issues need to be clarified with urological consultation. Generally, it is useful to limit fluid intake after supper, and the use of either Ditropan® (oxybutynin) or Detrol® (tolterodine) may be considered.
Impotence (impaired erection) in men may occur in PD, as it does in nearly all cases of multiple system atrophy (MSA). One needs to consider the potential role of medications (e.g., beta-blockers, anti-anxiety drugs, anti-depressants, others), and of depression itself, when impotence occurs. Both men and women may experience a decrease in libido, independent of depression.
Depression is common among those with advancing PD, affecting as many as 30-50% over the course of the illness. There is often a loss of pleasure in usual activities, decreased desire to socialize, a loss of interest in sexual activity, insomnia, weight loss or gain, increased irritability, and, sometimes, a lesser ability to concentrate and perform other usual mental functions. Think about the possible presence of depression when these symptoms appear and go on for weeks or months. They rob people of the joy in life they otherwise might have and appear to make the motor portion of PD worse.
It is a common clinical experience that, unless depression is adequately treated with medication at least, and often also with some form of counseling, full responses of PD patients to their medications will not occur. So, not only should depression be treated on humanitarian grounds, but also to help the PD itself. Many experienced non-psychiatrists manage depression well, but some instances are best co-managed with a psychiatrist.
Some PD patients will have vivid dreams and/or insomnia because of one or more of their anti-PD medications. Such sleep disruptions may not only awaken the patient and his/her partner, but can also make it impossible to get all the rest that's needed to recuperate enough to do the next day's activities well or at all. In such circumstances, consider with your doctor reducing or eliminating late evening anti-PD medication dose(s).
We need to realize that some patients will require nighttime doses of anti-PD medication(s) to get out of bed to go to the bathroom, or simply to turn comfortably in bed to rest well. Obviously, this is another individual clinical decision to make, and one that may need revision over time.
Several years ago, it was reported that some patients may have "sleep attacks" (unheralded, sudden, irresistible sleep episodes) when taking agonist drugs. This remains an area of controversy since it isn't clear that such "attacks" haven't occurred because of another ongoing sleep disorder (e.g., due to excessive daytime sleepiness, depression, other medication effects, etc.). However, although there may be variable explanations for "attacks", the potential occurrence of dangerous sleep episodes (e.g., when driving a vehicle) makes it important to be aware of such a possibility. In my view, a physician should not hesitate to prescribe an otherwise potentially beneficial agonist or other anti-PD drug, and both doctor and patient should be vigilant about this uncommon, possible issue. As with many other therapeutic issues in PD, this needs thorough, individualized attention in a medical setting.
Dementia (loss of acquired cognitive function, including memory) can occur in about 30% of PD patients over the course of the illness. It is not inevitable.
When dementia occurs, it is important to try to identify the cause, as some 5-10% are potentially reversible, partly or fully. The list of potentially reversible causes includes hypothyroidism (low thyroid), vitamin B12 or folate deficiency, syphilis, subdural hematoma (blood clot over the brain), communicating hydrocephalus (impaired circulation of spinal fluid), and others. Studies to identify these disorders include blood tests (for thyroid [TSH and perhaps others], B12, folate, RPR or VDRL [syphilis], MRI or CT scan of the brain) and, perhaps, a spinal fluid examination for those whose dementia is rapidly advancing or otherwise atypical. Correcting the abnormalities, medically or surgically, will follow.
The same diagnostic studies, and perhaps others, may be needed to establish the cause of other forms of dementia. Some causes cannot be reversed, including:
- stroke(s) affecting areas of brain that cause, not PD itself, but both vascular parkinsonism (i.e., signs that mimic the motor effects of PD), often other neurological signs of disability, as well as dementia. Strokes are often seen in brain MRI or CT scans. The consultant neurologist will often want studies done to try to learn why the stroke(s) occurred, in an effort to prevent further damage. Such studies often include MRI of the brain, carotid Doppler ultrasound, echocardiographic ultrasound and EKG. Patients are often placed on aspirin or other medications.
- Alzheimer's disease is seen more commonly among PD patients with dementia than among non-PD dements. We believe that the two illnesses have shared genetic and/or environmental risk factors, though these have yet to be discovered. There is no specific test (e.g., MRI, PET or SPECT scan, blood or spinal fluid test) that can make the diagnosis during life, and a determination is made by excluding other possibilities. Though AD is irreversible, some mildly-moderately affected patients may benefit cognitively and socially by anticholinesterase medications, such as Aricept® (donepezil), Exelon® (rivastigmine), Reminyl® (galantamine), or other agents.
- Dementia with Lewy Bodies is a disorder of some PD dements that causes hallucinations when patients are not taking anti-PD drugs, causes variability in cognitive function even within parts of a day, and is progressive. It may appear relatively early in the course of PD, when motor disability is minor. Some patients may temporarily worsen if placed on anti-psychotic medications. Some may benefit from Reminyl® or other anticholinesterase medications.
Whatever the cause of dementia, its management should include having the patient live in a caring, safe, clean and comfortable environment. If possible, living at home is most desirable and least disruptive. Ideally, family, friends or paid help may share the burden of care. If this is not possible, moving a patient, with or without his/her spouse, to an assisted care facility should be considered. If this is unrealistic, a patient may be placed in a nursing home that family members determine provides good care. Often, an experienced social worker will be immensely helpful in reviewing realistic care options and in helping to implement them; most often, these professionals are associated with larger healthcare organizations. Moreover, the Michigan Parkinson Foundation (1.800.852.9781) and the Alzheimer's Diesease and Related Disorders Association (1.800.337.3827) are invaluable resources for caregivers of PD patients who face these difficult challenges.
The advent of functional surgery for PD, especially deep brain stimulation (DBS) of the subthalamic nucleus, has been a major advance in treatment for the right patients in the right medical setting. The subject is covered at length elsewhere, but several points are worth emphasizing:
- Appropriate patients should be selected. 1) Current evidence suggests that only those who have typical PD will have successful results, not those with atypical forms of parkinsonism. 2) Functional motor improvement is likely only among those who have clear responses to dopaminergic medication. 3) Patients without dementia must be selected because dementia may worsen if present pre-operatively. 4) Patients selected must be willing and able to work with members of the medical team to help regulate both electrical and medication doses in order to optimize their function. They must be full partners in their care. 5) Patients who are selected for surgery need to be in adequate general health. That is, they should not have significant cardiac disease, crippling arthritis, cancer, or other severe conditions pre-operatively.
- The timing of surgery is important. DBS is something that is offered to patients who have not been able to either fully benefit from, or to tolerate, anti-PD medications, after adequate trials of drugs, including combinations of medications at various doses.
- The surgical team must have sufficient skill and experience to be able to offer patients and caregivers adequate likelihood of success without undue risk.
Jay M. Gorell, MD, FAAN
President and Former Chairman, MPF
Professor in Neurology, Wayne State University School of Medicine
William T. Gossett Chair in Neurology
Head, Division of Movement Disorders
Department of Neurology
Henry Ford Health System
Former Chairman, Board of Directors
Michigan Parkinson Foundation