Restless Legs Syndrome and Parkinson’s disease have interesting dopamine connections. Some Parkinson’s pain may actually be restless legs or arms. Could changes in RLS treatment over the past few years be relevant to getting a good night’s sleep with PD?
To those unfamiliar with the condition, the terminology “Restless Legs” makes it difficult to accept as the serious condition that it is. Whenever I hear the term Restless Legs Syndrome, my brain thinks “ants in my pants”. I picture myself back in elementary school, being forced to sit at a desk, when I’d rather be running around outside. That is far from being an accurate description of this medical condition.
The USA National Institutes of Health (NIH) describes RLS as follows:
Restless legs syndrome (RLS) causes unpleasant or uncomfortable sensations in the legs and an irresistible urge to move them. Symptoms commonly occur in the late afternoon or evening hours, and are often most severe at night when a person is resting, such as sitting or lying in bed. They also may occur when someone is inactive and sitting for extended periods (for example, when taking a trip by plane or watching a movie). Since symptoms can increase in severity during the night, it could become difficult to fall asleep or return to sleep after waking up. Moving the legs or walking typically relieves the discomfort but the sensations often recur once the movement stops. RLS is classified as a sleep disorder since the symptoms are triggered by resting and attempting to sleep, and as a movement disorder, since people are forced to move their legs in order to relieve symptoms. It is, however, best characterized as a neurological sensory disorder with symptoms that are produced from within the brain itself.
I know the feeling all too well. Sitting anywhere for more than an hour or so where I can’t stretch/straighten out my legs leads to extreme pain that can usually be walked off with just a few minutes of movement. Gymnasium bleachers are the worst for me. I used to prefer bulkhead rows on airplanes, but now they can be painful because I cannot stretch my legs into the space under the seat in front of me. Movie theaters generally aren’t a problem, as the old theaters have been replaced by megaplexes that are focused more on comfy recliner seats. By contrast, traditional theatre can be torture…although an aisle seat usually provides me with enough wiggle room to endure until intermission.
Did I mention that I’ve never actually been diagnosed with Restless Leg Syndrome? Even though I have complained of the above symptoms consistently over the past 5 years at almost every appointment with a neurologist or movement disorder specialist (MDS), and even though the NIH clearly considers it to be a movement disorder.
I think I understand why they’ve never discussed RLS with me. It’s because when I describe my symptoms, I throw them a curveball.
I have trouble sleeping, but it’s not because of my legs, it’s my arms that have trouble staying comfortable. I am a stomach sleeper, and I frequently wake up in the middle of the night with pain or discomfort in my elbow or wrist, which is alleviated by moving my arm, often very subtly, but sometimes it is then difficult to fall back to sleep.
My first MDS diagnosed this (with a quick cursory examination) as carpal tunnel syndrome in both wrists and prescribed wearing wrist splints to bed…a diagnosis that I never took seriously.
A quick review of available literature does confirm that while considerably less common, sensations associated with RLS can present in the arms. In fact, the NIH document that I referenced earlier mentions this, and drops a bit of a PD related bombshell in the process. But, I’m getting ahead of myself, as we need to explore the complicated relationship between PD and RLS first.
What causes RLS?
According to the NIH:
In most cases, the cause of RLS is unknown (called primary RLS). However, RLS has a genetic component and can be found in families where the onset of symptoms is before age 40. Specific gene variants have been associated with RLS. Evidence indicates that low levels of iron in the brain also may be responsible for RLS.
Considerable evidence also suggests that RLS is related to a dysfunction in one of the sections of the brain that control movement (called the basal ganglia) that use the brain chemical dopamine. Dopamine is needed to produce smooth, purposeful muscle activity and movement. Disruption of these pathways frequently results in involuntary movements. Individuals with Parkinson’s disease, another disorder of the basal ganglia’s dopamine pathways, have increased chance of developing RLS.
If that second paragraph sounds familiar, that is because dopamine dysfunction in the basal ganglia is what causes the primary motor symptoms of Parkinson’s disease.
It doesn’t take a rocket scientist to realize that many people with PD are likely to experience symptoms similar to RLS. But because every disease or syndrome has its own box to fit into, when it happens to someone who has been diagnosed with PD, we can’t call it RLS or restless legs, because another disease association already owns the trademark (just kidding, but it feels that way). So when it occurs with PD, we call it Parkinson’s pain, and researchers produce ridiculous research, such as this:
People with Parkinson’s disease may be more likely to have a movement disorder called leg motor restlessness, but not true restless legs syndrome as previous studies have suggested...
Restless legs syndrome is a sleep and movement disorder. People with the disorder have the urge to move their legs to stop uncomfortable sensations. The urge occurs when the person is at rest, in the evening, and is temporarily relieved by movement. In leg motor restlessness, people also have the urge to move their legs, but it is either not worse when they are at rest or during the evening or it does not go away when they move their legs.
The study found that restless legs syndrome was not significantly more common in people with Parkinson’s disease than it was in those without the disease. But people with Parkinson’s were nearly three times more likely to have leg motor restlessness than those without Parkinson’s.
In case you’re still confused, according to these researchers, it is only Restless Leg Syndrome (RLS) if it happens at night and is temporarily relieved by movement. If it happens during other times of the day, or is not consistently relieved by movement, then it is leg motor restlessness, and you cannot use the catchy acronym. Most sane people would instead question that as we do not fully understood the disorder(s), isn’t it more likely that the latter is a more severe case of the former?
As mentioned earlier, RLS is believed to be related to a dopamine dysfunction in the basal ganglia, which is the same area blamed for triggering the primary motor symptoms of PD. Although restless legs symptoms are sometimes an early symptom of PD, usually RLS does not get progressively worse like PD. However, due to similarities in the area of the brain affected, RLS is often treated with dopaminergic therapies, drugs that are primarily used to treat Parkinson’s disease.
They have been shown to reduce symptoms of RLS when they are taken at nighttime. The FDA has approved ropinirole, pramipexole, and rotigotine to treat moderate to severe RLS. These drugs are generally well tolerated but can cause nausea, dizziness, or other short-term side effects. Levodopa plus carbidopa may be effective when used intermittently, but not daily.
Of course, levodopa plus carbidopa also is only effective for 4-5 hours, so it would wear off during the night.
But here is the part that is really interesting:
Although dopamine-related medications are effective in managing RLS symptoms, long-term use can lead to worsening of the symptoms in many individuals. With chronic use, a person may begin to experience symptoms earlier in the evening or even earlier until the symptoms are present around the clock. Over time, the initial evening or bedtime dose can become less effective, the symptoms at night become more intense, and symptoms could begin to affect the arms or trunk. Fortunately, this apparent progression can be reversed by removing the person from all dopamine-related medications.
That’s depressing. If you have PD with restless legs (or arms), removing yourself from all dopamine related medications is not an option.
Nonetheless, this is extremely interesting to know. If long term use of dopamine related meds in people with RLS eventually causes a worsening of RLS symptoms, why does this happen? It’s great that they can simply stop the drug and reset…then try a different drug. But understanding why this happens might provide new insight into managing Parkinson’s pain.
Interestingly, the NIH fact sheet on RLS mentions this:
Anti-seizure drugs are becoming the first-line prescription drugs for those with RLS. The FDA has approved gabapentin enacarbil for the treatment of moderate to severe RLS, This drug appears to be as effective as dopaminergic treatment (discussed below) and, at least to date, there have been no reports of problems with a progressive worsening of symptoms due to medication (called augmentation).
That’s interesting because when I was first diagnosed with PD, I remember also reading about RLS, and the dopamine related meds seemed to be the more common treatment. What changed?
Apparently, a relatively small Johns Hopkins research study, with results released in May 2013, led to a major change in how RLS is treated.
Neurologists have long believed RLS is related to a dysfunction in the way the brain uses the neurotransmitter dopamine, a chemical used by brain cells to communicate and produce smooth, purposeful muscle activity and movement. Disruption of these neurochemical signals, characteristic of Parkinson’s disease, frequently results in involuntary movements. Drugs that increase dopamine levels are mainstay treatments for RLS, but studies have shown they don’t significantly improve sleep. An estimated 5 percent of the U.S. population has RLS.
The small new study, headed by Richard P. Allen, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine, used MRI to image the brain and found glutamate — a neurotransmitter involved in arousal — in abnormally high levels in people with RLS. The more glutamate the researchers found in the brains of those with RLS, the worse their sleep.
The findings are published in the May issue of the journal Neurology.
“We may have solved the mystery of why getting rid of patients’ urge to move their legs doesn’t improve their sleep,” Allen says. “We may have been looking at the wrong thing all along, or we may find that both dopamine and glutamate pathways play a role in RLS.”
If confirmed, the study’s results may change the way RLS is treated, Allen says, potentially erasing the sleepless nights that are the worst side effect of the condition. Dopamine-related drugs currently used in RLS do work, but many patients eventually lose the drug benefit and require ever higher doses. When the doses get too high, the medication actually can make the symptoms much worse than before treatment. Scientists don’t fully understand why drugs that increase the amount of dopamine in the brain would work to calm the uncontrollable leg movement of RLS.
Allen says there are already drugs on the market, such as the anticonvulsive gabapentin enacarbil, that can reduce glutamate levels in the brain, but they have not been given as a first-line treatment for RLS patients.
6 years later, the drug mentioned in that study is now the first-line treatment.
We need research like this looking into sleep disruption in PD!
The sleep disruption that I experience sounds like restless leg syndrome that has progressed to my arms. Has several years of dopamine therapies made it worse? Now that I understand it better, I will definitely discuss this with my latest movement disorder specialist during my next appointment.
From my limited understanding of brain chemistry, I would not be surprised to find that I have higher levels of glutamate, especially at night. And perhaps fluctuations in the ratio between dopamine and glutamate are to blame. Those are questions for a neuroscientist.
But the questions to be raised with a movement disorder specialist are much more practical, as both PD and RLS are movement disorders. Do I have aspects of both PD and RLS, and if so, is it worth trying a RLS medication to reduce glutamate levels in my brain to see if this helps improve my sleep?
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