Parkinson's disease can be challenging to identify in its early stages, but catching emerging signs allows earlier intervention with medication and other support.
There's no clinically validated biomarker, so a diagnosis relies upon physicians identifying symptoms that might be subtle and difficult, particularly initially, to sort out from other conditions. One meta-analysis published 2016 in Neurology, which incorporated 11 studies that used pathology for comparison, found that physicians' ability to diagnose idiopathic Parkinson's disease was 80.6% overall. That accuracy rate hasn't changed significantly over 25 years, the researchers wrote.
Nearly 1 million Americans live with Parkinson's, a number that's projected to reach 1.2 million by 2030, according to a prevalence analysis by the Parkinson's Foundation.
Men are 50% more likely to be diagnosed. Despite the lack of medication to slow disease progression, earlier diagnosis can improve patients' quality of life, said Houman Homayoun, MD, an assistant professor of neurology at the University of Pittsburgh Medical Center. Myriad related conditions, including constipation, depression, and sleep difficulties, can be monitored and treated, and patients can be educated about the importance of regular vigorous exercise, which in a recent study appeared to demonstrate some protective effects.
While primary care physicians can manage a lot of the ongoing care, including prescribing, they might periodically need to refer the patient back to a neurologist, for issues ranging from reassessing the diagnosis to adjusting medication, Dr. Homayoun said. “It's kind of a back-and-forth relationship over the course of a slow but progressive disease.”
Primary care physicians also can reassure patients that there's no reason to delay medication once tremors, rigidity, and other mobility symptoms interfere with their quality of life, said Jori Fleisher, MD, MSCE. The assistant professor of neurological sciences at Chicago's Rush University said that she's been referred patients who could have benefited from levodopa sooner.
“What we hear a lot from our patients,” Dr. Fleisher said, “is that they were told by their primary care doctor, ‘Hold off on medicine, the medicine will stop working.’” But research hasn't supported that stance, she said. “You want to treat the patient in front of you and optimize their functioning today, so that they can do as well as possible in the long run.”
Catching emerging signs
Physicians might be able to pick up early signs of the disease in the course of a routine clinical exam, Dr. Fleisher said. For instance, pay attention if patients always keep one hand tucked into a pocket, she said, as they might be trying to hide tremor. Another possible sign: Does the patient hold items, such as a magazine, with a nondominant hand?
If Parkinson's disease is suspected, there are a few informal tests to perform without unduly alarming the patient, Dr. Fleisher said. A subtle tremor might become more visible if the patient is distracted, so patients could be asked to rest their hands in their lap and, after closing their eyes, recite the names of the months in the year starting backwards. Along with serving as a good test of working memory, that quick screen might reveal a subtle tremor at rest, one that's more likely to emerge in the hands, legs, lips, and chin, she said.
It can be challenging to sort out a diagnosis in older patients, who might already be coping with other significant health conditions and mobility challenges, said Kyle Moylan, MD, FACP, an internist and geriatrician in St. Louis, Mo. Dr. Moylan, who has gotten some additional training in Parkinson's disease, notes if the tremor seems to be confined to or worse on one side. The tremor of Parkinson's disease tends to be more asymmetric than the tremor of another common condition, essential tremor. Not all people with Parkinson's develop a tremor, however, he noted.
When feasible, Dr. Moylan checks out how patients walk, such as when they are making their way to the exam room. “If you have a chance to see them in action, when they don't even know that they are being watched, that can be helpful,” he said.
Or during the exam, Dr. Moylan might ask the patient to walk down the hallway. He'll watch out for shorter shuffling steps or differences in arm movement. As the patient walks, does one arm swing freely while the other seems more constrained?
A patient with Parkinson's disease also might freeze momentarily during moments of transition, such as rising from a chair or crossing the exam threshold into the hallway, Dr. Fleisher said, “almost like someone stepped in glue on the floor and is stuck for a second and then goes.” One question she sometimes will ask patients: Are they wearing out their shoes unevenly with more wear near the toe? That's a possible sign that patients are shuffling their feet, she said.
Dr. Fleisher also cautioned physicians not to misattribute any emerging signs in their female patients. In some cases, a tremor might begin internally at first. A woman might express that she feels shaky, a potential sign that shouldn't be assumed to be anxiety, she said.
Women with Parkinson's disease have been shown to experience delays in diagnosis and appropriate referral to treatment, Dr. Fleisher noted. While constipation, depression, and anxiety are all common symptoms that primary care physicians encounter on a daily basis, some or all of these, especially if it's also in the setting of an internal sense of tremor, should raise concerns for Parkinson's disease. If in doubt, refer to neurology.
According to 2015 diagnostic criteria from the Movement Disorders Society, physicians should consider a diagnosis when someone experiences bradykinesia along with either a rest tremor or rigidity. Meanwhile, other causes must be ruled out, such as an essential tremor, which is common in older individuals, said Dr. Homayoun, who authored an “In the Clinic” overview of Parkinson's, published in 2018 in Annals of Internal Medicine. “Sometimes when people develop this tremor, they get worried about Parkinson's disease,” he said.
The diagnosis is more likely to be essential tremor if the tremor only becomes apparent when the patient is moving the extremity, such as while writing or eating, Dr. Homayoun said. Essential tremor usually affects both sides of the body, he said.
Drug-induced parkinsonism also must be ruled out as some medications, such as earlier-generation antipsychotics, can be the culprit, said Stephen Reich, MD, the Frederick Henry Prince Distinguished Professor in Neurology at the University of Maryland School of Medicine in Baltimore. Don't just ask patients about medications they are taking now, but about those taken in recent months as well, because the effects might linger for as long as a year, he said.
Dr. Reich, who co-edited “Therapy of Movement Disorders,” published by Springer in 2019, said that primary care physicians can often make an initial diagnosis based on a clinical exam, but it's best to have that diagnosis confirmed by a neurologist.
The patient also should be referred if the initial diagnosis is uncertain or if symptoms fail to unfold in an anticipated way, which might signal an atypical parkinsonian syndrome, Dr. Reich said. Some of those red flags include the symptoms progressing unusually rapidly or the patient's motor symptoms not responding to levodopa. For that reason, he noted, one of the American Academy of Neurology's (AAN) quality measures is to review a Parkinson's diagnosis annually.
Along with referring the patient to a neurologist for confirmation, there are some advantages to delaying medication until the patient has seen a specialist, said Melissa Heiry, MD, a clinical assistant professor of neurology at Thomas Jefferson University's Sidney Kimmel Medical College in Philadelphia. Patients in the early stages of the disease might be interested in joining one of the studies looking at potentially disease-modifying medications, and they would likely be excluded if they were already taking levodopa, she said.
While medication, once it's started, should be individualized to each patient, levodopa is typically the best option for most, and especially for older patients, Dr. Reich said. For patients with young-onset Parkinson's, a dopamine agonist could be prescribed first in the hope that it might delay the emergence of dyskinesia and other motor fluctuations, he said.
But the agonists are less effective than levodopa and have some worrisome side effects, including an increased risk of sleepiness and impulse control disorders, Dr. Reich said. They should therefore be avoided in those patients who already report sleep difficulties or have a current or prior pattern of problems with alcohol, gambling, or other impulse-linked behaviors, he said.
Levodopa, in combination with carbidopa to prevent nausea, is usually prescribed three times daily, and the doses should be spread across the patient's waking hours to maximize the mobility benefits, Dr. Fleisher said. A typical starting dose is carbidopa (25 mg) and levodopa (100 mg), she said, advising physicians to steer clear of a lower-dose 10-mg/100-mg combination. At least 25 mg of carbidopa three times daily is needed to enable the levodopa to cross the blood-brain barrier, she said. Plus, the lower carbidopa dose might not be sufficient to prevent nausea.
When newly referred patients report that levodopa didn't help when they tried it before and had made them nauseous, Dr. Fleisher said, “It is not uncommon that they were on 10/100.”
The dosage of levodopa, as well as how often it's prescribed, likely will be adjusted over the years as the patient's brain makes less dopamine, Dr. Homayoun said. Physicians have several newer formulations as options as well, such as extended-release levodopa, which can address problems with the medicine wearing off between doses, he said. A new formulation can be inhaled. “It can provide rapid relief for some patients if the medication suddenly stops working,” Dr. Homayoun said.
A physician might refer a patient to be evaluated for deep-brain stimulation—a surgical treatment that delivers electrical impulses to basal ganglia, the brain's motor function region—in several scenarios, Dr. Homayoun said. The patient might still be responding to the levodopa but it might not always be effective or the dose might wear off quickly, he said. A patient who experiences medication-related dyskinesia or hallucinations or medication-refractory tremor might be a candidate. But don't delay too long in making the referral, he said, as patients who have already developed cognitive changes will not benefit.
Regardless of the treatment prescribed, there's one nonclinical intervention that should be stressed: exercise. A randomized, phase 2 clinical trial enrolling patients with early-stage disease who were not on medication found that those who exercised vigorously on a treadmill three times a week had roughly the same level of functioning six months later. But those patients who did moderate or no exercise experienced a slight decline.
The study, published in 2018 in JAMA Neurology, was designed to assess safety primarily of high-intensity exercise. Additional research will be needed to quantify clinical benefits, the researchers wrote.
But the data provide yet another reason to strive to limit patients' symptoms so they are mobile enough to remain active, Dr. Fleisher said. “Even though the medicine is not neuroprotective, exercise seems like it is,” she said. “And often people can't exercise because they're so slow or they're so stiff.”
As Parkinson's disease progresses, one of the challenges is monitoring all of the potential nonmotor effects, some of which might not be visible, Dr. Moylan said. Patients should be asked about everything from sleeping difficulties to constipation to advance care planning, he said. They should be screened for cognitive changes as well as for osteoporosis, given that they're more vulnerable to falls.
Regularly screen for depression and other mood changes, as they can go undiagnosed and erode a patient's quality of life, Dr. Moylan said. The AAN's quality measures include screening patients for psychiatric symptoms annually. For the newly diagnosed, the Parkinson's Foundation has compiled an online package of resources that physicians can either print out or refer patients to for more education, Dr. Fleisher said.
When meeting with patients, be sure to check in with their caregivers, who might accompany them to the visit, Dr. Reich said. Remind those caregivers that they should not neglect their own health and that it's OK to seek out mental health or other support, he said. “Even just acknowledging that it's challenging to be a caregiver and they are doing a good job by itself can go a long way.”
As patients' motor and other symptoms worsen, they likely will require more visits with the neurologist to explore medication options beyond levodopa, Dr. Heiry said. But she and others said that it's important to paint a positive picture for patients in the early stages as they adjust to the diagnosis, alerting them that studies continue into potentially disease-modifying drugs.
“I know it's scary to be diagnosed with something that's neurodegenerative,” Dr. Heiry said. “But there's also I think a lot of hope out there in terms of the research that's going on. And we have a lot of good treatment options medication-wise and surgically.”