WASHINGTON, DC—Although a variety of medications are effective in controlling the primary motor symptoms of Parkinson’s disease, an increasing number of symptoms either fail to respond to medication or respond poorly to traditional therapy as the disease progresses. Such symptoms can worsen quality of life, even while symptoms such as tremor, slowness, clumsiness, and muscle stiffness are well managed with medication or surgery.

At the 2006 World Parkinson Congress, investigators gathered to discuss the hidden challenges faced by many patients with Parkinson’s disease, as well as methods for coping with these challenges.

UNRESPONSIVE MOTOR ASPECTS

According to Anthony E. Lang, MD, the Jack Clark Chair for Parkinson’s Disease Research and a Professor of Neurology in the Department of Medicine at the University of Toronto, examples of unresponsive motor symptoms of Parkinson’s disease include speech abnormalities; swallowing difficulties; problems with walking, such as freezing; and postural instability. "Interestingly, these symptoms are especially concentrated in what we call the axial structures of the body—the midline structures," said Dr. Lang, who is also the Director of the Morton and Gloria Shulman Movement Disorders Clinic in Toronto.

"There’s a myriad of disturbances of speech—not just the softening of speech and difficulties being understood—but there may be tremendous hesitancy of speech, there may be a stuttering kind of speech abnormality, and there may be a repetitive kind of nature of their speech," said Dr. Lang. He noted that a number of studies have demonstrated that certain types of speech therapy can be helpful for some of these disturbances.

Another axial, or midline, disturbance, he said, is abnormalities related to swallowing—slowness of chewing; difficulty moving food from one part of the mouth to another; difficulty moving food to the back of the throat; and difficulty initiating the swallowing process and ensuring that food does not enter the lungs. Dr. Lang said that swallowing disruptions leading to aspiration pneumonia can be a serious complication of neurologic diseases such as Parkinson’s disease.

In addition to speech and swallowing abnormalities, freezing can be extremely common as the disease progresses and becomes increasingly resistant to drug therapy. Even more debilitating is freezing accompanied by postural instability. "Usually, when normal individuals without Parkinson’s disease are thrown off balance, we right ourselves, make corrective movements, and throw our arms out in time to catch ourselves if we’re going to fall," said Dr. Lang. However, "patients with Parkinson’s disease lack those corrective mechanisms; they have difficulty making the activations of various muscles in their legs and in their trunk to stop themselves from falling, and so falls are not an uncommon problem in the later stages of the disease."

Dr. Lang noted that all of these midline disturbances become more burdensome as the disease progresses. "They increasingly become resistant to the medication that we have, and so this is a major challenge in the later stages [of Parkinson’s disease]."

Growing evidence suggests that Parkinson’s disease is, in fact, a multisystem disease, involving underlying mechanisms in addition to just dopamine deficiency, according to Dr. Lang. The challenge now, he said, is to understand these disease processes and to develop therapies that interact with and improve the problems that have been observed in the later stages of the disease.

PSYCHIATRIC ASPECTS

In addition to unresponsive motor symptoms, a significant percentage of patients with Parkinson’s disease also contend with one or more psychiatric disorders. "Depressive disorders are the most common psychiatric disorders in Parkinson’s disease, and they affect about 50% of patients. Anxiety disorders have received much less attention than depression, but they affect about 25% to 40% of patients," remarked Laura Marsh, MD, an Associate Professor in the Departments of Psychiatry and Neurology at Johns Hopkins University School of Medicine in Baltimore. The rates of these disorders "are greater than what you would expect in a population of similar age, and they’re also greater than what you would expect in people who have comparable disability," she said.

"What’s striking is what patients tell us—that depression has a greater influence on quality of life than their actual motor symptoms. They can cope with Parkinson’s disease, but not when they’re depressed," said Dr. Marsh.

Patients with mood disorders tend to have worse motor deficits and greater physical disability compared with those without mood disorders. Also, patients with depression are more likely to have additional psychiatric disorders such as anxiety disorders, dementia, and/or psychosis.

Though it may seem inherent that someone with Parkinson’s disease would become depressed or anxious simply due to the debilitating nature of the disease, "multiple lines of evidence have shown that depression and anxiety are related to the underlying disease processes," said Dr. Marsh. Recent studies have found that brain levels of neurotransmitters (eg, noradrenaline, serotonin, acetylcholine) change during the course of Parkinson’s disease.

Dr. Marsh pointed out that the presence of comorbid mood disorders in patients with Parkinson’s disease "can be extremely distressing to families, particularly because they often haven’t associated this psychiatric problem with their Parkinson’s disease itself. This lack of awareness means they don’t tell their doctors about it." She added, however, that "it’s not just the patients who aren’t recognizing it necessarily—it’s also the clinicians." Even at specialized movement disorder centers, comorbid mood disorders are undiagnosed in up to 75% of patients, Dr. Marsh noted. "Among the minority who actually are diagnosed, at least half tend to be untreated or undertreated."

While many patients contend with comorbid mood disorders, a significant portion of patients—possibly up to 10%—are burdened by impulse control disorders. These range from pathological gambling and compulsive shopping to hypersexuality and excessive eating. Impulse control disorders, like mood disorders, often go unrecognized in the majority of patients. "These are reward-driven behaviors that are often done covertly, and we aren’t told by our patients when they’re actually acting on these drives."

According to Dr. Marsh, psychiatric disorders in patients with Parkinson’s disease are treatable, "and because they’re treatable, it’s very important that they’re recognized and diagnosed so that we can reduce the excess disability and burdens of the disease. The first part of treatment that I always use is education, so that I can help patients understand what their symptoms are and they can tell me about them. It’s very important for families and patients to be able to talk to you about their symptoms so they know what you’re treating." The second part of treatment involves psychotherapy and/ or pharmacotherapy.

THE PARKINSON’S PYRAMID

"There are more than 8,736 hours in a year, and a Parkinson’s disease patient sees his or her neurologist approximately two hours during that year—maybe four visits at a half hour each. That leaves about 8,734 hours for that patient to be his or her own health advocate, in a manner of speaking," said David Heydrick, MD, a Scientific Adviser at the Parkinson’s Action Network in Washington, DC, and a neurologist in Frederick, Maryland. He emphasized that patients "can and should be proactive in their own health."

In addition to practicing neurology, Dr. Heydrick himself is a Parkinson’s disease patient. He began formulating a proactive strategy for managing the physical and mental health of patients with Parkinson’s disease after a patient asked him what his own strategy for the long term was—and he realized he didn’t have one. "As a patient, and as a doctor for that matter, you’re kind of taught that that’s the way it’s going to be. But it got me thinking that maybe, just maybe, Parkinson’s disease doesn’t have to be so progressive," said Dr. Heydrick. "So I started developing a strategy for use in my own life, involving wise use of symptomatic therapies, putative nutritional elements, and a variety of exercise that trains the body and brain sensory motor pathways." He calls this strategy the Parkinson’s Pyramid.

According to Dr. Heydrick, patients can take charge of their own health by learning about Parkinson’s disease research and noting where the findings are leaning strongly. Patients should also rearrange their priorities, he believes, making their health their ultimate concern. The first step, he said, is managing stress, which is important for patients with Parkinson’s disease because environmental stress can cause oxidative stress, thus injuring cells, and because patients’ symptoms can worsen due to stress.

"I want to emphasize that this paradigm does not exclude working closely with one’s doctor," said Dr. Heydrick. Patients should work closely with a doctor who has " a positive attitude" and who also acknowledges and treats nonmotor symptoms of the disease, said Dr. Heydrick. At the base of his pyramid, along with stress management, are symptomatic therapies, which emphasize the wise use of medications—particularly, using the lowest effective dose for any given medication, and even employing surgical treatments such as deep brain stimulation (DBS). Dr. Heydrick commented that patients should "consider DBS earlier rather than later ... to preserve function and quality of life, rather than trying to restore it when it is more difficult."

But as important as medical therapies and stress reduction are for controlling certain symptoms, following a diet focused on combating cell demise, such as one rich in antioxidants, is a key component to maintaining physical and mental health, he asserted. Consuming antioxidants can help patients combat oxidative stress. Sources of antioxidants include supplements such as curcumin and N-acetyl-cysteine and foods such as blueberries, broccoli, spinach, green tea, dark chocolate, dried fruits and beans, avocado, asparagus, walnuts and almonds, and grape juice or red wine. Dr. Heydrick noted that his goal "is not to tell people exactly what to eat; it’s just to encourage them to develop a strategy for wise eating to hopefully reduce cell loss."

Exercise, as well, is beneficial in reducing stress and maintaining one’s physical health, he said. Dr. Heydrick noted that accumulating evidence suggests that exercise can be neuroprotective and may even help "rewire" the brain to some extent. Examples of physical exercises that patients with Parkinson’s disease might want to consider include stretching such as yoga or Pilates, strength training such as weight lifting, and repetitive movement therapy—for example, walking on a treadmill, bicycling, and/ or swimming, or participating in exercise programs such as Think BIG (and LOUD), The Art of Moving, and Motivating Moves. Speech therapy is another example of repetitive movement therapy (of the vocal chords). Eastern therapies such as tai chi and qi gong may also be beneficial, he said.

"I’ve talked to many patients who have altered their environment ... through behavioral modification and decreased their stress, and the symptom relief—or at least improvement—was significant, and was in my life, too," concluded Dr. Heydrick.

NR

—Karen L. Spittler

Suggested Reading
1. Global Parkinson’s Disease Survey Steering Committee. Factors impacting on quality of life in Parkinson’s disease: results from an international survey. Mov Disord. 2002;17:60-67.
2. Marsh L, McDonald WM, Cummings J, et al. Provisional diagnostic criteria for depression in Parkinson’s disease; report of an NINDS/NIMH Work Group. Mov Disord. 2006;21:148-158.
3. Menza M, Marsh L, eds. Psychiatric Issues in Parkinson’s Disease: A Practical Guide. New York, NY: Taylor & Francis; 2005.
Shulman LM, Taback RL, Rabinstein AA, Weiner WJ. Non-recognition of depression and other non-motor symptoms in Parkinson’s disease. Parkinsonism Relat Disord. 2002;8:193-197.

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