Tuesday, August 2, 2022

Is Restless Leg Syndrome Related To Parkinson’s

What Are Common Signs And Symptoms Of Restless Legs

Neurology 20 Parkinson’s Restless Leg Syndrome

People with RLS feel the irresistible urge to move, which is accompanied by uncomfortable sensations in their lower limbs that are unlike normal sensations experienced by people without the disorder. The sensations in their legs are often difficult to define but may be described as aching throbbing, pulling, itching, crawling, or creeping. These sensations less commonly affect the arms, and rarely the chest or head. Although the sensations can occur on just one side of the body, they most often affect both sides. They can also alternate between sides. The sensations range in severity from uncomfortable to irritating to painful.

Because moving the legs relieves the discomfort, people with RLS often keep their legs in motion to minimize or prevent the sensations. They may pace the floor, constantly move their legs while sitting, and toss and turn in bed.

A classic feature of RLS is that the symptoms are worse at night with a distinct symptom-free period in the early morning, allowing for more refreshing sleep at that time. Some people with RLS have difficulty falling asleep and staying asleep. They may also note a worsening of symptoms if their sleep is further reduced by events or activity.

People with RLS can sometimes experience remissionsspontaneous improvement over a period of weeks or months before symptoms reappearusually during the early stages of the disorder. In general, however, symptoms become more severe over time.

Who Gets Restless Legs Syndrome

About 10% of people have restless legs syndrome, also called RLS. About 2% to 3% of them have moderate to severe symptoms that affect their quality of life. Also:

  • Slightly more women than men get it.
  • Most people with severe RLS are middle-aged or older.
  • Only 2% of children get RLS.
  • People with RLS in their family usually get it at a younger age.

Is There A Link Between Restless Leg Syndrome And Parkinson’s Disease

Previous studies have suggested that there is a link between RLS and PD due to both conditions sharing the common feature of dysfunction in the part of the brain that produces dopamine. Another commonality between these two conditions is that they have been shown to run in the family. About half of the cases are in patients that have relatives with the disorder. Another argument for the medical linkage of these neurological disorders is that they share the same treatments – no other common disorder is treated with the same dopamine agents.

Even though earlier studies have shown a significant prevalence of RLS in patients with Parkinsons, researchers have not been able to find a common patient demographic or Parkinsons treatment to reliably predict the development of restless leg syndrome. Also through studies, they have found that though both conditions present dysfunction in the dopamine-producing neurons in the brain, the actual mechanisms, or how the neurons are affected, are not identical.

Earlier studies involved patients with advanced cases of Parkinsons disease that have been taking dopamine drugs for years, which may account for the significance of RLS. The use of dopamine drugs makes it much harder to correctly diagnose restless leg syndrome. The dopamine can cause restlessness that may be confused with RLS.

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Iron And Its Relation To The Dopamine System

Iron is an important cofactor in several DA metabolisms and can also produce neurotoxic species.

Usually iron accumulates in the normal aging brain, in particular in the putamen, globus pallidus, red nucleus, and substantia nigra . Elemental iron plays a critical role in oxidative metabolism and it also serves as a cofactor in the synthesis of neurotransmitters .

In PD, neurodegeneration occurs mainly in SNc , while other iron-rich areas remain unaffected. In early stages of the disease the identification through the use of transcranial ultrasonography of a hyperechogenicity of the SNc correlates positively with the increase of iron and ferritin evaluated in post-mortem analysis , allowing an early identification of patients at risk for PD .

The increase in neuronal iron may be secondary to an increase in influx, facilitated by transferrin receptor-2/divalent metal transporter-1 endocytosis or the diffusion of ferric citrate , an increase in efflux, due to alteration of the activity of ceruloplasmin, or a dysregulation of iron homeostasis, mediated mainly by the iron storage protein ferritin .

Some studies have shown reduced ferritin concentrations in the SN from Parkinson’s disease brain, suggesting an alteration of this storage mechanism and a consequent increase in the level of free and potentially harmful iron .

In Vivo Corneal Confocal Microscopy

(PDF) Restless legs syndrome in Parkinson

All participants underwent IVCCM bilaterally, or unilaterally if one eye met exclusion criteria. The central corneal subbasal nerve plexus was imaged as previously described. Briefly, a topically anesthetized eye was examined with the Heidelberg Retinal Tomograph 3 laser-scanning confocal microscope with the Rostock Corneal Module . A single examiner performed all eye scanning, recording images of the subbasal nerve plexus across a wide area of the plexus using the built-in fixation light to access paracentral regions and continually adjusting the focus to the plexus depth. Mosaics were generated with an automated computer algorithm to select nerve plexus images from the recorded data using tissue classification and to stitch together adjacent images. Depth variations of subbasal nerve fiber paths were mapped onto a single two-dimensional mosaic image. A separate automated algorithm was used for detection and tracing of nerve paths and branching points, from which the mean values of CNFL and CNBD were calculated,. Averaged values between both eyes were used where applicable.

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Are There Treatments For Restless Legs Syndrome

There are four FDA-approved drugs for restless legs syndrome: Horizant, Mirapex, Neupro, and Requip.

Doctors also use other drugs not specifically made to treat RLS. These include:

Does Having Rls Increase The Risk Of Developing Pd

Since RLS affects as much as 4-10% of the US adult population, it is clear that the vast majority of those with RLS do not ever develop PD.

Despite this, it still might be the case that RLS increases the risk of subsequently developing PD. There have been many studies trying to figure this out with conflicting results. Some studies show that there is no increased risk and others show that having RLS confers about a two-fold increased risk of developing PD over the general population.

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Parkinson’s Disease And Restless Legs Syndrome

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What Is The Link Between Restless Legs Syndrome And Periodic Limb Movement Disorder

Can Parkinson’s Disease Cause Restless Legs Syndrome (RLS)?

More than 80% of people with restless legs syndrome also have periodic limb movement disorder, or PLMD. In PLMD, the arms or legs twitch or jerk during the night. The movements disturb sleep and can cause chronic sleepiness.

Many people have periodic limb movement disorder by itself and will never develop restless legs syndrome. If you think you have PLMD, see your doctor.

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What Impact Does Dbs Surgery For Pd Have On Rls

The emergence of RLS after subthalamic nucleus deep brain stimulation in patients with PD has been reported . Eleven of 195 patients with STN DBS reported new problematic symptoms of RLS after surgery. The mean reduction in antiparkinsonian medication was 74%. The authors suggested that reduction of anti-parkinsonian medication during STN DBS may unmask symptoms of RLS. However, a recent prospective study of 17 patients undergoing STN DBS identified 6 patients with RLS with a mean IRLSSG rating score of 23 preoperatively. Postoperative scores at 4 weeks and 6 months were significantly improved at 14.8 and 13.8 respectively. None of the patients developed RLS postoperatively .

Professor Of Nutritional Sciences Xiang Gao Director Of The Nutritional Epidemiology Lab Will Present The 2021 Pattishall Research Lecture On April 21

UNIVERSITY PARK, Pa. Xiang Gao, professor of nutritional sciences and director of the Nutritional Epidemiology Lab at Penn State, will present the 2021 Pattishall Research Lecture.

The lecture, “Parkinsons and Restless Legs Syndrome: Risk Factors and Consequences,” will be presented at 3:30 p.m. on Wednesday, April 21, via Zoom webinar. All are welcome to attend.

Parkinsons disease is one of the most common degenerative diseases of the brain, and it is often accompanied by shaking, stiffness, and difficulty with balance and coordination.

Restless legs syndrome causes the overwhelming urge to move ones legs and can be very uncomfortable. RLS typically occurs when people are resting and is considered a sleep disorder.

Xiang Gao Credit: Penn State. Creative Commons

People take Parkinsons disease very seriously, Gao said. RLS, however, is poorly understood. Some people doubt that it is a significant problem at all, but it is a very real condition.

Both Parkinsons disease and RLS relate to dopamine levels in the brain. This connection provided a pathway for Gao and his collaborators to examine different risk factors for these seemingly unrelated conditions.

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Problems With The Common Pathophysiology Theory

Symptoms of RLS in PD are milder than in patients with idiopathic disease and may be difficult to differentiate from other sensory and motor symptoms in PD, in particular akathisia affecting the lower extremities . RLS symptoms may also be a manifestation of wearing-“off” phenomenon, a levodopa related complication of PD .

Prolonged dopaminergic therapy in RLS patients, in particular with levodopa use, may result in a phenomenon known as augmentation in which the severity of symptoms increases, onset of symptoms begin earlier in the day and more rapidly, and spread of distribution to other body parts occurs. In contrast, PD patients develop dyskinesias and motor fluctuations after treatment with dopaminergic agents. These complications are not seen in RLS patients.

Hypofunction of the endogenous opioid system has been postulated to be a mechanism related to the pathogenesis of RLS. Exposure to the iron chelator desferoxamine in cell cultures of rat substantia nigra resulted in DNA fragmentation while pre- administration of enkephalin significantly protected the cells from damage by iron deficiency .

What Is Restless Legs Syndrome

(PDF) Restless Legs Syndrome and Parkinson Disease: A ...

Restless legs syndrome , also called Willis-Ekbom Disease, 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 . 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.

RLS is one of several disorders that can cause exhaustion and daytime sleepiness, which can strongly affect mood, concentration, job and school performance, and personal relationships. Many people with RLS report they are often unable to concentrate, have impaired memory, or fail to accomplish daily tasks. Untreated moderate to severe RLS can lead to about a 20 percent decrease in work productivity and can contribute to depression and anxiety. It also can make traveling difficult.

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What Research Is Being Done

The mission of the National Institute of Neurological Disorders and Stroke is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NINDS is a component of the National Institutes of Health , the leading supporter of biomedical research in the world.

While the direct cause of RLS is often unknown, changes in the brains signaling pathways are likely to contribute to the disease. In particular, researchers suspect that impaired transmission of dopamine signals in the brains basal ganglia may play a role. There is a relationship between genetics and RLS. However, currently there is no genetic testing. NINDS-supported research is ongoing to help discover genetic relationships and to better understand what causes the disease.

The NINDS also supports research on why the use of dopamine agents to treat RLS, Parkinsons disease, and other movement disorders can lead to impulse control disorders, with aims to develop new or improved treatments that avoid this adverse effect.

More information about research on RLS supported by NINDS or other components of the NIH is available through the NIH RePORTER , a searchable database of current and previously funded research, as well as research results such as publications.

Attention Deficit Hyperactivity Disorder

There is significant overlap between some of the symptoms and treatments for RLS and attention deficit hyperactive disorder . Up to a quarter of children diagnosed with attention-deficit hyperactivity disorder may also have RLS, sleep apnea, or PLMD. These conditions may actually contribute to inattentiveness and hyperactivity. The disorders have much in common, including poor sleep habits, twitching, and the need to get up suddenly and walk about frequently. Some evidence suggests that the link between the diseases may be a deficiency in the brain chemical dopamine.

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Detections Of The Levels Of Iron And Related Proteins In Csf And Serum

The levels of iron and related proteins, including ferritin, transferrin and lactoferrin in CSF and serum from PD patients were detected by Enzyme Linked Immunosorbent Assay. Ab83366 kit for iron, Ab108837 kit for ferritin and Ab108911 kit for transferrin were from Abcam Company . E01L0224 kit for lactoferrin was from Shanghai Lanji Biological Limited Company .

What Is The Connection Between Iron And Restless Legs Syndrome

Drug Patch for Parkinson’s & Restless Legs Syndrome ABC7

Not enough iron in the diet is one cause of restless legs syndrome. Taking iron pills may improve RLS in these people.

Even in people who are not anemic and have normal iron levels, iron levels may be involved. Studies show a “brain iron deficiency” in many people with restless legs syndrome. A doctor may prescribe iron supplements even if a person’s iron levels are within normal range. However, too much iron can lead to liver damage and other health problems.

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Home Care Tips For Restless Legs Syndrome

The following approaches can reduce symptoms in patients with mild or moderate RLS and may be used in combination with medication in RLS patients who have severe symptoms.

  • Sleep hygiene: Good sleep hygiene means maintaining a bedroom environment and a daily routine that supports high-quality sleep. Avoiding alcohol and caffeine is especially important for RLS patients because these substances can worsen symptoms.
  • Exercise: Because physical inactivity often triggers RLS symptoms, exercise may be helpful. A research study found that RLS patients showed af 39% reduction in symptom severity after six weeks of engaging in an exercise program compared to an 8% symptom reduction in patients who did not exercise.
  • Pneumatic pressure therapy: Pneumatic compression devices increase blood flow to the legs by filling with air to squeeze the legs. Researchers found that the device improved RLS symptoms, quality-of-life, and fatigue after one month of daily use compared to a control group.
  • Massage and hot baths: Using massage and hot baths to stimulate the legs is widely recommended in RLS literature however, there is limited scientific evidence supporting the effectiveness of these methods at this time.

Learn more about treating RLS here.

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Risk Factors For Periodic Limb Movement Disorder

About 6% of the general population has PLMD. However, the prevalence in older adults is much higher, reaching almost 60%. Studies suggest that PLMD may be especially common in older women. As with RLS, there are many conditions that are associated with PLMD. They include sleep apnea, spinal cord injuries, stroke, narcolepsy, and diseases that destroy nerves or the brain over time. Certain drugs, including some antidepressants and anti-seizure medications, may also contribute to PLMD. About a third of people with PLMD also have RLS.

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Interrupted Sleep: Exploring Links Between Parkinsons Disease And Restless Leg Syndrome

Restless Legs Syndrome and Parkinsons disease have interesting dopamine connections. Some Parkinsons pain may actually be restless legs or arms. Could changes in RLS treatment over the past few years be relevant to getting a good nights 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 Id rather be running around outside. That is far from being an accurate description of this medical condition.

The USA National Institutes of Health describes RLS as follows:

I know the feeling all too well. Sitting anywhere for more than an hour or so where I cant 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 arent 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 torturealthough an aisle seat usually provides me with enough wiggle room to endure until intermission.

What causes RLS?

According to the NIH:

Suggested further reading:

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