Medical disorders that can cause the restless legs syndrome
Is restless legs a sign of nerve damage?
Peripheral neuropathy is a condition whereby there is damage to the nerves in the hands and / or feet felt as numbness or tingling in the extremeties. There is a connection between peripheral neuropathy and RLS. Studies show that anywhere from 5% to over 30% of people with peripheral neuropathy also suffer from RLS, a rate much higher than reported in the general population. The RLS from peripheral neuropathy results from damaged nerves in the extremities sending signals to the brain telling it to move the limbs to alleviate the uncomfortable sensation. RLS on the other hand originates in the brain sending signals down to the legs. It can be difficult to deduce the source of the RLS uncomfortable sensations.
Medications like gabapentin or pregabalin (see the "Gabapentinoids" page) are commonly prescribed for nerve pain. Because these medications calm down the overactive "misfiring" peripheral nerves, they frequently pull double-duty and significantly reduce RLS symptoms as well.
Figure 2: Man with Parkinson's disease showing classical symptoms
Parkinson's disease and the restless legs syndrome
Parkinson’s disease and restless legs syndrome (RLS) can occur together, but they are two distinct neurological disorders. Their relationship appears to involve dopamine, iron regulation, sleep disruption and Parkinson’s medication. Parkinson’s disease is a result of a drop in dopamine in the brain region called the substantia nigra effecting movement, balance and coordination. Both Parkinson's and RLS are dopaminergic disorders. People with Parkinson's are more likely to develop RLS and in some cases the RLS occurs prior to the Parkinson's disorder. It is reported that about 20% of Parkinson's patients have RLS. Although results from clinical prevalence studies show a wide variation from 0% to 52%.
RLS in people with Parkinson’s has been associated with:
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More severe motor and non-motor symptoms
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Worsening depression and anxiety
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Poorer sleep
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Motor fluctuations and “off” periods
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Lower quality of life
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Lower iron stores in some patients
Some studies have found that people who have both conditions have lower ferritin than people with Parkinson’s alone. However, this finding has not been consistent across all studies.
Do varicose veins cause the restless legs syndrome?
Venous insufficiency has reportedly been found to occur in 22% of RLS patients. This has led some researchers to surmise that varicose veins play a role in causing RLS. Varicose veins / blood pooling is caused by damage to tiny valves in the veins that help stop blood pooling and direct the blood back to the heart. Action of the leg muscles, in particular the calf muscle, help the circulation of the blood out of the legs. Once a person with varicose veins becomes seated or supine there is no calf leg muscle activity to assist blood back to the heart and the blood pools in the calf causing build up of metabolic waste products and tissue inflammation.
RLS does not cause peripheral nerve damage (peripheral neuropathy). But peripheral neuropathy can lead to RLS symptoms.
Figure 1: Nerve fibre illustrating peripheral neuropathy
Figure 3: Calfs with varicose veins
Treatment for varicose veins may alleviate RLS symptoms. Treatment modalities include compression stockings, laser treatments and sclerotherapy.
Does thyroid function affect restless legs syndrome?
Research indicates a notable epidemiological and biological link between thyroid dysfunction and restless legs syndrome (RLS).
This build up in turn causes localized nerve irritation which manifests as an uncomfortable, creeping, or tingling sensation. Activating the calf muscles through movement results in the emptying of the stagnant blood out of your legs temporarily clearing the irritation. This leg discomfort-movement cycle is precisely the diagnostic criteria applied to RLS. However, in varicose veins the direction of restlessness is from the leg nerves to the central nervous system (CNS). Whereas in Primary RLS the direction of the restlessness is from the CNS to the legs (the opposite of varicose veins).
What is dopamine and how does it effect Restless Legs Syndrome (RLS)? Dopamine is a neurotransmitter that neurons (nerve cells) use to communicate with one another in the brain and the rest of the body. Dopamine's Core Function is with motivation and reward. It creates the anticipation and motivation to seek out rewarding experiences. It is involved in reinforcement: When you engage in a behavior that your brain deems beneficial (like eating, socializing, or achieving a goal), a surge of dopamine reinforces that pathway, making you more likely to repeat the action. Dopamine helps your brain decide what is "important" or worth paying attention to in your environment. While popularly referred to as the "pleasure chemical," its role is much more nuanced and fundamental to biology. Dopamine is essential for motor control. It is produced in several areas of the brain, including the substantia nigra. Within the basal ganglia (the brain's movement control center) dopamine acts as a regulator that helps ensure movements are smooth, coordinated, and properly initiated. In RLS there is a dysregulation of dopamine with low evening dopamine levels contributing to the "creepy crawly" leg sensations and the involuntary urges to move. The lack of dopamine inhibits the motor signals leading to RLS.
Studies consistently show that individuals with thyroid disorders, particularly hypothyroidism and Hashimoto’s thyroiditis, experience RLS at a higher rate (14.3%) than in the control group (8.1%). Subclinical hypothyroidism (where TSH levels are mildly elevated but standard thyroid hormone levels appear normal) has also been correlated with an increased risk of developing RLS symptoms.
Dopamine-thyroid feedback loop
Dopamine plays a major role in regulating the pituitary gland's secretion of Thyroid-Stimulating Hormone (TSH). Conversely, an imbalance in thyroid hormones can disrupt normal dopaminergic pathways. As RLS is linked to reduced effective dopamine signalling in the brain, disruptions in the dopamine-thyroid feedback may initiate or exacerbate RLS symptoms.
Thyroid hormones influence peripheral and central nerve excitability. Imbalances in these hormones may lower the sensory threshold of nerves in the lower limbs, intensifying the “crawling”, “tingling”, or “aching” sensations that are characteristic of RLS.
If managing a thyroid condition and RLS symptoms are present, it is worth discussing treatment options with a healthcare provider. By examining both thyroid panels (including TSH) and ferritin levels secondary treatable factors contributing to RLS symptoms may be identified. Optimizing thyroid hormone replacement or addressing underlying iron deficiencies may alleviate RLS severity for patients caught in the dopamine-thyroid feedback.
Did you know that the Restless Legs Syndrome (RLS) has a significant and well-documented impact on mental health. While RLS is primarily a neurological condition, its effects often extend far beyond physical discomfort to emotional distress and mental health issues. Approximately 2 out of every 5 people with RLS also experience a psychiatric condition. The severity of RLS is directly correlated with the severity of mental health symptoms. There is a well documented correlation between RLS symptoms and mental health symptoms. As RLS symptoms worsen, scores for mental health, vitality, and social functioning often decrease. There's a bit of the chicken and the egg happening with mental health and RLS. RLS related sleep deprivation can trigger or worsen depression and anxiety, while people with existing mental health conditions are also more likely to experience RLS symptoms. RLS can lead to anxiety and stress about, when will you get to sleep and when will the uncomfortable feeling in the legs stop. Chronic sleep loss leads to daytime sleepiness in turn causing chronic fatigue and lethargy. Other daytime symptoms of RLS include irritability, feelings of hopelessness, and difficulty finding joy in daily activities. All of these feelings can over time contribute to the development of clinical depression. There are a wide range of medications available to treat depression. However, many of these antidepressants can actually worsen the RLS symptoms. Work with your healthcare provider to take "RLS safe" medications.
Does sleep deprivation worsen the restless legs syndrome?
RLS and sleep deprivation are a classic medical viscous cycle. RLS can cause chronic sleep loss leading to sleep deprivation from an inability to fall asleep and disruption of sleep architecture once asleep. Sleep deprivation elicits a downregulation of dopamine receptors in the brain causing the central nervous system to become more sensitive lowering your pain and discomfort thresholds, causing RLS symptoms to strike earlier in the evening and feel significantly more intense.
Sleep deprivation caused by other mechanisms / disorders (e.g. sleep apnoea hypopnoea syndrome [SAHS], poor sleep hygiene or insomnia) can lead to worsening of RLS.
Figure 4: A sleep deprived male with excessive daytime sleepiness
Does kidney failure cause the restless legs syndrome?
The link between kidney failure (particularly End-Stage Renal Disease [ESRD]) and RLS is incredibly strong. While RLS affects roughly 5% to 12% of the general population, it skyrockets to affect 20% to 40% of patients on long-term dialysis.
One mechanism whereby kidney failure may cause RLS is Uremic Toxin Build up. This is elevated levels of toxins like urea, creatinine, and other metabolic by products. These circulating toxins are inherently neurotoxic. They irritate and damage peripheral nerves (causing peripheral neuropathy; see above) and alter brain chemistry, lowering the threshold for RLS symptoms to fire.
ESRD is related to severe iron deficiency and anemia. Kidneys produce a hormone called erythropoietin (EPO), which tells the body to make red blood cells. In kidney failure, EPO production plummets, leading to severe anemia. Dialysis itself also causes chronic iron loss, starving the central nervous system of the iron it needs to keep dopamine pathways functioning smoothly. (See "Iron" and "Dopamine"). The low iron and dopamine increase the propensity of RLS. In adults with RLS and ESRD, the American Academy of Sleep Medicine (AASM) suggests the use of gabapentin and Vitamin C (conditional recommendation, very low certainty of evidence). In adults with ESRD and RLS intravenous (IV) iron infusions are often given during dialysis to bypass absorption issues and directly boost iron stores. The AASM suggests the use of IV iron sucrose in patients with ferritin < 200 ng/mL and transferrin saturation < 20%.
Dogs may get restless legs syndrome (RLS), yes really. Signs that your pooch is having an episode of RLS are: 1. Dog frequently changing positions or appearing unable to settle while lying down. 2. Nighttime pacing such as getting up, moving around, lying down, and repeating this cycle frequently. 3. Kicking or twitching hind legs while resting. 4. Whining or barking, which may indicate physical discomfort during these periods of restlessness.
Figure 5: Woman having dialysis
When kidneys fail, calcium levels often drop while phosphate levels spike. This imbalance, alongside fluctuations in potassium and magnesium, makes peripheral nerves hyper-excitable, leading directly to the classic twitching, crawling, and cramping sensations of RLS. With kidney transplant RLS resolves in days to weeks. In adults with RLS and ESRD, the American Academy of Sleep Medicine (AASM) suggests the use of gabapentin a a treatment option.
Did you know that newborns need to sleep between 14-hours and 17-hours per day. A newborn's brain is working overtime to process a brand-new world. A significant portion of infant sleep is spent in REM (Rapid Eye Movement) sleep, which is vital for brain maturation, learning, and nervous system development. The pituitary gland releases a surge of growth hormones almost exclusively during deep sleep. This fuels rapid physical growth, muscle development, and tissue repair.
Who would have thought, jellyfish, even having no brain, still seem to manage sleep. Scientists have observed that jellyfish meet the three critical criteria for sleep: 1. Reduced Activity (Quiescence): They experience periods of inactivity, such as a decrease in the frequency of their rhythmic pulsing. 2. While in this quiescent state, jellyfish are less responsive to external stimuli (like water pulses) and slower to react to their environment. 3. If disturbed or "kept awake" during their rest, jellyfish exhibit a "rebound" effect, showing an increased tendency to fall into that sleep-like state during periods when they would normally be active. Because jellyfish have no actual brain, but rather decentralized neural networks (nerve nets), implies that sleep is a fundamental process for cellular maintenance that likely predates the evolution of complex brains. It appears that sleep is hardwired into the DNA of the most simple of living organisms. Evolution has maintained sleep as an important factor in humans and other living organisms. This suggests that even very simple nervous systems to complex animals (e.g. humans) require downtime for repair and stability.
Figure 6: Herniated disc compressing spinal nerve roots
Spinal cord conditions and the restless legs syndrome
The prevalence of RLS is significantly higher in individuals with spinal disorders than in the general population. The spinal cord acts as the main superhighway for communication between the brain and the limbs. When the spinal cord is damaged it can trigger the classic RLS symptoms: The brain normally sends calming, "inhibitory" signals down the spinal cord to keep the limbs quiet during rest. Spinal cord damage can block these signals. Without that natural braking system, the spinal cord's reflex pathways become hyperexcitable, creating the typical RLS uncomfortable restless sensations that forces movement.
There is a specific pathway of dopamine-producing cells (the A11 group) that runs from the brain down the entire span of the spinal cord. Because RLS is closely tied to dopamine dysfunction, any physical lesion or compression along the cord can disrupt this pathway triggering RLS symptoms. There are five spinal cord disorders that can result in RLS.
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Spinal Cord Injury (SCI): Research indicates that roughly 18% to 19% of people with SCI experience RLS. RLS is more frequently associated with incomplete spinal cord injuries and lower (lumbosacral) lesions.
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Myelopathy & Spinal Stenosis: Cervical or thoracic spondylotic myelopathy (severe spinal cord compression due to wear-and-tear or narrowing of the spinal canal) can cause treatment-resistant RLS.
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Herniated Discs and Nerve Impingement: A severe slipped or herniated disc that pinches nerve roots or presses directly against the cord can alter sensory feedback generating lower-limb RLS. See figure 6.
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Multiple Sclerosis (MS): MS causes the immune system to attack the protective coating of nerves in the central nervous system. Lesions specifically located in the spinal cord are highly correlated with RLS.
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Spinal Vascular Issues: Though rare, sudden, acute flare-ups of RLS have occasionally been traced back to spinal cord ischemia (a temporary lack of blood flow to the cord).
What role does diabetes play in the restless legs syndrome?
There is a strong and well-documented link between diabetes and RLS. While about 5% to 12% of the general population experiences RLS, that number jumps significantly for people living with diabetes to approximately 20%. There are 3 potential mechanisms whereby diabetes may worsen RLS.
1. Diabetic Neuropathy (Nerve Damage): Chronic high blood sugar can damage the tiny blood vessels that supply your nerves, especially in the legs and feet. This nerve damage can cause tingling, burning, or creepy-crawly sensations that mimic or directly trigger RLS symptoms.
Figure 7: Diabetic patient administering insulin
2. Iron Deficiency & Kidney Function: People with diabetes are at a higher risk for chronic kidney disease and anemia. Low iron levels and compromised kidney function are both major secondary causes of RLS.
3. The Sleep-Sugar Vicious Cycle: RLS causes sleep deprivation. Poor sleep throws off the body's insulin sensitivity and glucose metabolism, making blood sugar even harder to control the next day worsening the diabetes leading to increased RLS symptoms.
Multiple sclerosis (MS) is associated with the restless legs syndrome
There is a strong, established connection between Multiple Sclerosis (MS) and RLS. Research shows that people with MS are up to 4 times more likely to develop RLS than the general public. There are several mechanisms whereby MS leads to RLS.
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Central Nervous System Lesions: MS causes the immune system to attack the protective coating (myelin) of nerves in the brain and spinal cord. When these lesions form in the spinal cord or specific brain regions (like the basal ganglia, which controls movement), it disrupts the normal signaling pathways to the legs resulting in RLS symptoms.
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Dopamine Disruption: The basal ganglia relies heavily on dopamine (see the "Dopamine" section above). MS lesions can disrupt how the brain processes dopamine, which is the exact underlying mechanism that triggers RLS.
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Increased Nerve Irritation: MS already causes sensory symptoms like numbness, tingling, and "pins and needles" (dysesthesia). At night, these sensations can blend with or intensify the classic urge to move your legs.
Figure 8: A myelinated nerve fibre showing MS demyelinating lesions and exposed axon
Did you know that there are 2 types of sleep apnoea. Apnoea means stopping breathing. There is obstructive sleep apnoea (OSA) where the upper airway collapses stopping the flow of air while your brain and body attempt to continue to breathe against the blockage. The second type of sleep apnoea is central sleep apnoea. This is where the brain stops sending the signal to breathe. No effort is made to breathe during a central sleep apnoea.
Fatigue is already one of the most debilitating symptoms of MS. When RLS prevents falling or staying asleep, it creates a brutal fatigue cycle. Chronic sleep deprivation directly worsens MS-related fatigue, makes brain fog more severe, and can even increase your sensitivity to daily MS pain.
For more information on risk factors for RLS see the pages below:
Last reviewed: 07/09/2026