SAN DIEGO—A new set of guidelines takes a comprehensive look at the diagnosis and treatment of Parkinson’s disease. Issued as four Practice Parameters by the American Academy of Neurology (AAN), the guidelines provide evidence-based reviews of aids to diagnosis, medical and surgical therapies, alternative therapies, and assessment and treatment of nonmotor complications, including dementia, depression, and psychosis.

The new guidelines were introduced at the 58th Annual Meeting of the AAN and published in the April 11 Neurology. They are meant to give general neurologists an authoritative overview of the evidence supporting their practice in Parkinson’s disease. "Over the decades, a huge number of articles have been published," said William Weiner, MD. "Some are good, and some are not so good. The guidelines are a very important way to look at the literature and to bring order out of the chaos." Dr. Weiner, who helped in the development of all four guidelines, is Director of the Maryland Parkinson’s Disease and Movement Disorders Center in Baltimore.

DIAGNOSIS AND PROGNOSIS

Stiffness, slowness, and tremor are the most common first signs of Parkinson’s disease. When the neurologist suspects Parkinson’s disease, there are several clinical factors confirmed in the literature to help in the decision, including asymmetric symptoms and signs, tremor at rest, and later onset of gait disturbance and falls. If the patient has these last two early on, said Dr. Suchowersky, "it’s a sign that it is probably not Parkinson’s disease." Similarly, if autonomic signs such as orthostatic hypotension occur early, "chances are they don’t have Parkinson’s disease but another condition."

A levodopa or apomorphine challenge test early on can help: If the patient shows improvement, "it’s a good hint it’s Parkinson’s disease," she said. Early loss of smell can also be used to strengthen diagnostic certainty. Imaging is not helpful in the differentiation of Parkinson’s disease from other causes of parkinsonism, except perhaps to rule out stroke.

Long-term follow-up is important to confirm the diagnosis. "You may not be able to be sure initially," she said. About 5% to 10% of those with Parkinson’s disease never receive that diagnosis, and about 20% of those with a Parkinson’s disease diagnosis actually have some other condition.

NEUROPROTECTION AND ALTERNATIVE THERAPIES

"Between 60% and 70% of all patients use minerals, vitamins, supplements, and other alternative therapies. One of the main things we found is that very little good research has been published," she said. Based on one of the few valid studies, it can be said unequivocally that vitamin E is not helpful. "Some patients are taking high doses, and these patients should be advised it is not helpful, and there is some recent evidence it is harmful."

In addition, few studies have been conducted on manual therapies, such as massage and chiropraxis. "What is quite helpful is exercise," Dr. Suchowersky said. It does not appear to matter what type of exercise is done, as long as it is performed regularly. "Exercising two to three times per week can help with motor function." Speech therapy was also found useful to maintain the ability to speak clearly and loudly.

TREATING MOTOR COMPLICATIONS

"We have therapies available for patients with these complications," said Rajesh Pahwa, MD, Professor of Neurology at the University of Kansas Medical Center in Kansas City. Dr. Pahwa and colleagues examined the evidence for 11 medical therapies that either are currently available in the United States or have received an "approvable" letter from the FDA. Deep brain stimulation was also examined.

There is "strong evidence" that both entacapone and rasagiline extend the duration of levodopa’s effect and reduce "off" time, and there is "good evidence" for dopamine agonists and tolcapone. The evidence is "weak" for apomorphine, selegiline, cabergoline, bromocriptine, and sustained-release levodopa/carbidopa. "There is not enough evidence that they help off time," Dr. Pahwa said. Only amantadine has been studied carefully enough to conclude that it can help reduce dyskinesias.

The efficacy of deep brain stimulation of the subthalamic nucleus was well supported by valid studies. "We feel neurologists need to discuss with their patients that deep brain stimulation of the subthalamic nucleus can reduce off time and dyskinesias and can improve motor function," Dr. Pahwa said. The response to levodopa was the only reliable predictor of the outcome after surgery. There was not enough evidence to support deep brain stimulation in the globus pallidus internus of the thalamus.

DIAGNOSIS AND TREATMENT OF NONMOTOR SYMPTOMS

Depression affects up to 70% of patients. "Patients may develop depression even before the motor signs of Parkinson’s disease," according to Janis Miyasaki, MD. The guidelines indicate that the Beck Depression Inventory is a readily available, practical tool for depression screening in Parkinson’s disease. There is "weak evidence" for the benefit of amitriptyline, but side effects of constipation, confusion, and drowsiness may limit its use in some patients. There is not enough evidence to recommend other agents, she said, "but in clinical practice some of these can be very effective." Dr. Miyasaki is Associate Clinical Director of the Movement Disorders Centre at Toronto Western Hospital.

The risk for dementia in persons with Parkinson’s disease is four times that of a healthy person of the same age, and the impairment brought on by motor symptoms is worsened when there are cognitive difficulties as well. As a result, she said, "dementia has a huge impact on the caring burden." The Mini-Mental State Examination can be used as a quick screen for dementia. Evidence has shown some benefit for two drugs commonly used for Alzheimer’s disease, donepezil and rivastigmine. "The benefit to thinking is modest, and there is some risk for worsening motor symptoms," she said.

Psychosis is the strongest indication for placement in a nursing home, Dr. Miyasaki said, "and when untreated, results in 100% mortality in one year." When psychosis is appropriately treated, that figure can be reduced to 28%. However, there is no reliable screening tool for psychosis, Dr. Miyasaki said. "We have to push the research for good practical tools. We need to give doctors the tools to diagnose these problems." Treatment of psychosis in Parkinson’s disease is especially challenging, because typical antipsychotics block dopamine. There is "good evidence" that clozapine is very effective for psychosis, without worsening motor symptoms. Based on the evidence, she said, olanzapine should not be used.

PATIENTS AS PARTNERS

He also commended the AAN for not "dumbing down" the accompanying summaries for patients and families. In a chronic disease such as Parkinson’s disease, he said, "the patient is signing on to a lifelong relationship with the physician." The summaries have the potential to improve that relationship, he noted, "because they treat patients as if they can read and think" and provide information that helps make the patient a partner in care.

Dr. Weiner concluded, "People often say evidence-based medicine promotes cookbook medicine, and they don’t want to be told how to take care of patients. But the guidelines don’t do that. They present information to the neurologist, who then uses his or her own experience and knowledge to take care of patients. In the end, the guidelines are about taking care of patients."

NR