THE PARKINSON’S CAREGIVER: 101
New medical advances—and a revolutionary surgical treatment—offer some relief
After being diagnosed with Parkinson’s disease, former U.S. Attorney General Janet Reno took up kayaking and ran for governor of Florida. Heavyweight champion Muhammad Ali traveled the world to promote racial peace and raise money for Parkinson’s research. And actor Michael J. Fox starred in Spin City and then took on an even bigger role: heading a foundation that funnels millions to scientists searching for a cure for Parkinson’s. They haven’t let their struggle with this degenerative neurological disorder stop them from living fulfilling and productive lives.
Though there is no cure yet, ever-improving treatments—including a daring new surgery—can help control symptoms such as shaking and shuffling so Parkinson’s sufferers can live near-normal lives for longer periods. “Clinical data show that most people with Parkinson’s disease will do extremely well for many years,” says neurologist Mark Stacy, MD, director of the Movement Disorders Center at Duke University Medical Center in Durham, North Carolina.
WHAT TRIGGERS PD?
Ali, Reno and Fox may be the public faces of Parkinson’s, but they are among an estimated one million Americans who have this serious movement disorder. Although Fox was just 30 when his rare young-onset Parkinson’s disease (PD) was diagnosed, most patients are over 60 years old.
PD is caused by the gradual destruction of brain cells (neurons) that produce dopamine, a chemical involved in starting a circuit of messages that tell the body when and how to move. When levels of dopamine drop by as much as 80 percent, brain signals directing movement misfire and symptoms appear: tremors, stiff muscles, slow movement and/or poor balance.
“Having Parkinson’s is like having your brain talk to your body on a cell phone in a tunnel,” is the way Fox characterizes this cellular miscommunication.
What causes these brain cells to die off isn’t completely clear. Under investigation are genetic predisposition, environmental toxins and other factors, and a combination of the two. Pesticides have been implicated in several studies and gene mutations have been linked to some inherited cases of PD. But only “about 20 percent of patients have a family history of Parkinson’s disease,” says Mary Mouradian, MD, the William Dow Lovett professor of neurology and director of the Center for Neurodegenerative and Neuroimmunologic Diseases at UMDNJ-Robert Wood Johnson Medical School in New Brunswick, New Jersey.
Whatever the causes, the result is a gradual loss of motor function that often starts on one side of the body. Yet, despite its signature symptoms, Parkinson’s disease can be difficult to diagnose. In fact, about 20 percent of patients are misdiagnosed.
“There is no screening test for Parkinson’s,” explains Dr. Mouradian. Tests may be done to rule out conditions with similar symptoms, such as a brain tumor or stroke, but “a diagnosis of Parkinson’s disease is based on a patient’s symptoms, medical history and a neurological exam,” she says. “Correct diagnosis really depends on the experience of the doctor.”
Although it was once called “shaking palsy,” as many as 30 percent of patients don’t have tremors, which typically occur when a hand or leg is at rest and diminish or disappear upon performing a purposeful action, such as reaching for a cup or starting to walk. Slow movement is the telltale symptom doctors must see for a PD diagnosis, says Dr. Mouradian. Signs include difficulty doing up buttons, arms that don’t swing quite naturally when walking, handwriting that becomes smaller, and/or soft or slurred speech. Since diagnosis is a judgment call, it is crucial to see a neurologist who specializes in movement disorders if Parkinson’s is suspected.
TAILORING TREATMENT TO THE PATIENT
Another reason to see a PD specialist: No two cases are the same so there is no “cookbook” approach to treatment. Whether to start medication immediately and what drug to use depends on potential side effects and a patient’s symptoms, age, and degree of disability.
Treatment involves replacing lost dopamine via various medications. The gold standard of PD therapy is levodopa, an amino acid that converts to dopamine in the brain. The most commonly prescribed levodopa drug, Sinemet, also includes carbidopa, which reduces side effects such as nausea.
Nearly every PD patient eventually winds up taking levodopa. But the longer the drug is used, the greater the chance of adverse effects, “so we want to use it judiciously,” says Dr. Mouradian. Involuntary writhing and wriggly movements known as dyskinesias are one of levodopa’s most bothersome long-term side effects.
Because they are less likely to trigger dyskinesias, dopamine agonists—weaker drugs that mimic dopamine’s effect in the brain—often are the first-choice treatment for patients under 70 with mild, early-stage PD. However, they may cause daytime sleepiness, “sleep attacks” in which patients nod off without warning, and in rare cases, even compulsive behavior such as gambling.
FINE-TUNING PD THERAPY
As PD progresses and levels of dopamine continue to fall, doctors must modify treatment to try to keep a fairly constant level of this movement-controlling chemical in the brain. This may mean changing the dose, timing or formulation of a drug; adding dopamine-boosting drugs to the regimen; and/or having patients eat most protein-rich foods at night to increase the odds that levodopa will be absorbed by the body and transported to the brain, where it is needed.
Common options include adding selegiline, which is also used as a one-drug treatment for early PD, or a COMT inhibitor. These drugs prolong levodopa’s effects by blocking enzymes that break down the amino acid. Switching from Sinemet to Stalevo, which contains a COMT inhibitor, also may give patients better and longer symptom control. Stalevo has been shown to improve motor function, increase “on time”—the period when PD sufferers move almost normally—and decrease “off time,” when medications stop working and symptoms reappear. When patients are “off,” tremors may return or they may be barely able to move.
“About half of people with Parkinson’s experience these on-off fluctuations within five years, and most have them by ten years,” says Dr. Mouradian. Caregivers need to be aware that motor fluctuations are sometimes unpredictable, so they don’t mistakenly think patients who moved easily earlier aren’t “trying hard enough” if they now ask for help.
If motor fluctuations are disabling, a fast-acting medication can come to the rescue. For example, a shot of apomorphine, a dopamine agonist, can reverse off time in as little as 10 minutes, but it also wears off rapidly.
“Part of the problem with Parkinson’s treatment is that we can’t give levodopa continuously in a convenient manner,” says Dr. Mouradian. But two new medications expected to receive FDA approval later this year may compensate for levodopa’s shortcomings. The first is a skin patch that delivers a steady dose of rotigotine, an absorbable dopamine agonist, round the clock.
The second, rasagiline, is a stronger cousin of selegiline. Rasagiline has been found to reduce the time later-stage PD patients on levodopa experience poor or no muscle function by more than an hour a day, according to a study in The Lancet. What’s more, another study suggests rasagiline may actually slow the progression of PD. Parkinson’s patients who began taking rasagiline six months earlier than counterparts in a control group fared better. It is currently used in Europe as both a one-drug therapy for newly diagnosed PD and as an add-on drug for more advanced cases.
As PD progresses, patients typically require a cocktail of drugs to control both motor symptoms and side effects such as depression, pain, sleep disturbances, constipation and confusion. In some cases, medications may be prescribed to treat problems; in others, adjusting or switching drugs may bring relief.
SHORT-CIRCUITING ABNORMAL BRAIN SIGNALS
If drugs fail, surgery may be an option. The newest surgical treatment that aims to get Parkinson's sufferers moving smoothly again is deep brain stimulation (DBS). With DBS, a pacemaker-like device implanted under the collarbone transmits continual electrical pulses to minute electrodes inserted in the brain.
Though experts aren't exactly sure how such “shock therapy” improves PD, the treatment makes sense. The brain doesn’t function properly when damaged cells interrupt the circuit connections, and DBS blocks the abnormal signals that cause disabling motor symptoms.
According to experts at Mayo Clinic, DBS seems most effective for Parkinson’s when electrodes are implanted in the subthalamic nucleus, an olive-size cluster of cells involved in regulating movement. “The vast majority of patients who undergo subthalamic deep brain stimulation get between a sixty and eighty percent reduction in the severity of various symptoms, including trembling, rigidity, slowness and balance problems,” says neurosurgeon Brian Harris Kopell, MD, formerly an assistant professor of neurosurgery at the Medical College of Wisconsin in Milwaukee.
What’s more, most patients are able to dramatically decrease their dosage of levodopa and thus are less likely to experience abnormal jerking or twisting movements. “Dyskinesias, which is sometimes more disabling than Parkinson’s disease itself, can be reduced by up to eighty percent by deep brain stimulation,” says Dr. Kopell.
Though DBS is far less risky than older surgeries that lessened symptoms by destroying malfunctioning brain cells, its success depends on the surgeon’s skill in targeting a tiny area of the brain. “Hitting the right part of the subthalamic nucleus is like being in Earth’s orbit and trying to hit home plate at Yankee Stadium with a baseball,” says Dr. Kopell. “If you put it in the wrong area, you’re going to get more side effects or you’re not going to get the beneficial effects you want.”
Parkinson’s sufferers considering DBS should look for an experienced neurosurgeon and also ask how the procedure is done. Some hospitals rely solely on brain scans to spot the target; at others, mapping electrodes are used as well. When inserted into the brain, these wires enable the surgeon to zero in on the subthalamic nucleus by listening for a particular firing pattern (each region has a characteristic “sound”) and by watching brainwave patterns on a digital display. “The mapping electrode allows better accuracy,” says Dr. Kopell.
With the right technique and the right candidate, results can seem miraculous. Dr. Kopell has had patients who, prior to surgery, shuffled and shook when they took a few steps. After DBS, they walked almost normally.
The best candidates for the procedure don’t have dementia and still respond to levodopa, which indicates their brain circuits are still working to some extent. Unlike in Europe, where DBS is used earlier in the disease, in the U.S. the treatment is approved only for advanced cases of PD in which symptoms are no longer controlled by drugs.
Dr. Kopell believes “this is a disservice to people with Parkinson’s. I tell my patients, ‘It's not about getting you out of the nursing home, it’s about getting you back on the golf course.’”
MANAGING PARKINSON’S DAY BY DAY
Though fatigue and loss of agility may cause Parkinson’s sufferers to avoid physical activity, more and more health professionals believe that exercise is vital to living well with this increasingly disabling disease. It is good for stiff muscles and aching joints, says Dr. Mouradian, and it may help improve flexibility, strength and endurance.
The latest research hints that exercise even may have protective powers. Evidence from animal studies and one clinical trial suggest exercise may help counter or compensate for PD damage, perhaps by producing protective brain chemicals called neurotrophic factors. In a small study at the University of Pittsburgh, researcher Anthony Delitto, PhD, PT, found that patients who exercised three times a week showed improvement in balance and the ability to perform daily tasks.
“Although further research is essential, I do believe that exercise will slow the progression of Parkinson’s disease,” says researcher Michael Zigmond, PhD, a neuroscientist at the University of Pittsburgh.
But there’s no need to wait to see if larger studies confirm these preliminary findings before people with Parkinson’s start a doctor-approved fitness program that includes stretching, strengthening and aerobic exercises. Even if the research doesn’t pan out, “exercise is not going to hurt you,” says Dr. Zigmond. “If we were talking about a drug, I’d say wait. But there are no side effects to working out.”
Besides an exercise regimen, physical and/or speech therapy can improve the quality of life of some Parkinson’s patients. So can relaxation techniques such as guided imagery, to relieve stress that may worsen PD symptoms. Moreover, little tricks can foil frustrating and embarrassing problems like trembling and freezing that make PD sufferers self-conscious. For instance, marching in place or stepping over an imaginary object may get patients going again, while twiddling a pencil or threading a coin through the fingers—which suppresses shaking—can be a good way to disguise tremors.
PUSHING THE ENVELOPE
As Parkinson’s progresses, treatments become less effective. That’s why scientists are looking for innovative new ways to fight this complex disease. Under investigation are drugs that may preserve brain cells destroyed by PD, gene therapy that might reverse the process and stem cells that may be able to replace lost dopamine-producing neurons.
Though a cure isn’t on the horizon—even the most promising therapies will require at least 10 years of testing to ensure safety and effectiveness—great progress is being made against Parkinson’s, says Dr. Zigmond. “I am hopeful that my grandchildren will not have to deal with the disease.”