Restless Legs Syndrome (RLS) and ADHD

Having chronic or periodic involuntary limb movements, also called Periodic Limb Movement Disorder (PLMD) or Restless Legs Syndrome (RLS) are commonly seen in association with Attention Deficit/Hyperactivity Disorder (ADHD).





Comorbidity with Tourette’s Disorder (TD), TICS Disorder (TICS) and Autism Spectrum Disorder (ASD) are also seen in persons with ADHD.

Summary

In this article we research what is known about the correlation and take a look at the possible causuality and treatment options. We also present our own hypothesis for the interaction/correlation between RLS and ADHD, based on neuroscientific reasoning.

RLS can be characterised as involuntary movements (or more precisely an overwhelming discomfort in the legs, fueling an urge to move to remove the sensation. Others describe it as having “creepy/crawlies” within the leg muscles making them feel itchy.

Hypothesis of ADHD with Comorbid RLS

Restless Legs Syndrome (RLS) is one of the lesser known comorbidities with ADHD, but is nonetheless estimated to affect upwards of 25% of children with ADHD and 35% of adults with ADHD.

ADDspeaker

ADHD is a specific neurodevelopmental disorder related to neuronal dysfunction due to a delay in the physical growth in the brain structures, which causes the brain (anatomically and physiologically) to mature at a 30% slower pace, than normally seen according to age.

This causes a disruption in a wide variety of brain functions, some mature faster than others, primarily in the Inhibitory and Motor Systems, thereby causing verbal and non-verbal symptoms of immature and age-inappropriate behavior with impatient, inattentive and emotional unstable traits.

A child at age the physcial age of 10, with medicinally untreated ADHD will exhibit a behavior which can be expected of a child without ADHD at age 7. This is called Executive Age in reference to the Executive Functions in the Pre Frontal Cortex (PFC) and refers to maturity alone, not intellect.

The reason for this is that Motor Control System develops before the Inhibitory System, which causes the age-inappropriate behavior since the motor function responds to stimuli without the inhibitory intervention of the PFC (Executive Functions).

So this is why ADHD is a neurobiological mental disorder, not a psychosocial or personality disorder, in the same way that Diabetes is a biological disorder, not a eating disorder!

ADDspeaker

Understanding RLS

RLS, TICS or STIMS are not the same, TICS and STIMS are mostly motor related, where RLS is mainly sensory related. But they both seem to originate from some form af malfunction in the Inhibitory System, one of the sensory system and the other on the motor system, within the synapses that relays sensory information through the Central Nervous System (CNS) to the brain and receives instructions back from the brain with motor commands on which muscles to move (verbal and non-verbal, since speech is also considered a motor function). Refer to the “What The Science Says …” for more in-depth knowledge on RLS.


Neuroscience 101

Neuroscience is the science of studying the way our bodily functions work, as seen from a neuronal perspective. It is complex stuff, I admit, and I have tried to give your a picture of how it all connects, so that you can get an overview of the argument that I am proposing in this aticle.

The human body is ‘wired’ from top to bottom.
Anatomical and Functional map of the human nervous systems
A higher level map of the human nervous system
Illustration of the sense of touch
Map of nervous system connections from the organs to the brain
Map of the brain with connections to the senses
Illustration of the Sensory vs. Motor pathways

The Inhibitory System controls both verbal and non-verbal behavior, as is the root cause of the hyperactive/impulsive and inattentive symptoms of ADHD. But the Inhibitory System also impacts the sensory and motor functions in the body through regulating the excitability of neurons, excitatory and inhibitory, so as to control bodily functions, again verbally and non-verbally, by regulating the level of dopamine in the brain.

As previously explained, ADHD and RLS is related to a disturbance in the sensory system and the motor control system, which causes a breakdown in the communication between what we feel and how we respond. It seems that the internal signaling within the neuron pathways are somehow confused about what is going on around our body.

The internal communication in the brain is done via neuronal networks that interconnects the various regions and systems of the brain by a vast network of neuronal networks of synapses that uses electrical and chemical signals to relay information from synapse to synapse via small messenger packets called neurotransmitters.

The inside of a nerve cell called a Neuron
Illustration of the Synapse’ electrical and chemical functioning

One such neurotransmitter is Dopamine, also known as the key component in the brain’s reward system that activates when the brain wishes to reward behavior that is beneficial to the long-term survival of the species.

Table showing Neurotransmitters that control our body, brain and mind

The problem must be found within the neuronal networks and their synapses, either in the electrical signaling or in the chemical signaling. Studies have shown that dopamine deficiency can be related to RLS, and likewise science is now studying to see if Iron levels can be part of the problem.

Illustration of Action Potential in a Synapse

 

Hypothesis: Either the brain is asking the sensory system to check if our toes are still there, or our sensory system is flooding the brain with signals, telling the brain that our toes are still there. The result is an “urge to move your legs” … hence Restless Legs Syndrome

ADDspeaker

As far as I have found, nobody is studying the signaling pathways between the sensory and the motor systems and my intuition is telling me that it is a malfunction in the ‘request and response’ function, that causes the symptoms.

In a computer network, all data is transmitted in small information packets of bits (1’s and 0’s) and these are sent through the air from your iPhone to the WiFi Access Point, which is the connected to the Ethernet (fixed network) and onwards through the network out via our Gateway Router and onto the Internet. Try to imagine that our nervous system is similar to this, then it might be easier to understand, how this works.

If we look at a computer network, we know that there are fixed and wireless networks. Neurons are primarily fixed (The Nervous System), but at the end of the dendrites where the synaptic cleft is found, the presynaptic and the postsynaptic ends of the opposing synapses are communicating ‘wireless’ using neurotransmitters as messengers of information packets from one neuron to the next.

As a 25 year veteran in IT, I’ve experienced many weird things going on, on a network, and I believe that RLS is one such anomaly. So if we hypothesized that RLS is actually a signaling problem, not a functional problem per se, it would make sense to look at possible treatments that focuses on medicinal relief. Science points to medication that works on the Dopamine and GABA neurotransmitters, causing them to become less excitable and thereby reducing (or eliminating) the ‘urge to move your limbs”.

Personally I have had severe RLS before I was diagnosed with ADHD at age 40, and after I’ve begun treatment for my ADHD with dopamine, my RLS have reduced in strength and occurrence. I have also tried Gabapentin which is a medicine against neuronal pain and this works very well. I believe that by combining a low dose of Dexamphetamine and Gabapentin, many people would experience a reduction in their RLS symptoms.

ADDspeaker’s Conclusion

By doing some good old “logical deduction” I prepose that RLS is caused by a miscommunication within the sensory system, due to low levels of dopamine, which then confuses the brain to ask the motor system to move muscles, but since the low level of dopamine restricts the synapses to fire properly, there is created a “infinite loop” of stimulus/response between the limbs and the brain, resulting in a sensory irritability in the legs which then creates an irritability in the person, which then in turn may result in frustrated and aggressive behavior, due to overstimulation of the sensory system leading to an overstimulation of the emotional (self) regulation.


What The Science Says …

I’ve researched and reviewed some related articles on PubMed on the topic of RLS in relation to ADHD, and I have put them on as references at the end of this article.

Recommended ‘Best Practice’ is focused on combined medicinal treatment with Dopamine, Gabapentin and possibly with Iron supplements (pills/injections) as a yet scientifically unproven, third choice.

Is it just Bad behavior?

Symptoms are often misintrepreted as either hysteria or ODD, since the condition creates an enormous internal sensory imbalance which affect ones mood, frustration and anger levels. Persons with ADHD often suffer from comorbid sleeping disorders and RLS only worsens these.

No. It’s neurobiological!

Science have yet to agree on the root cause of RLS, but it is widely accepted to be related to dopamine levels in the brain, causing neurons to (mis)fire randomly, especially when the body is at a resting state.

What’s the reason for TICS, STIMS and RLS?

Dopamine is also used in a multitude of systems throughout the body, among them within the excitatory and inhibitory synpases which control muscle movements. By some, yet unknown, deficit(s) in the communication within the motor control system, involuntary verbal and non-verbal behavior can manifest, beyond the persons own control.

Low levels of dopamine causes less inhibitory control as well as low levels of energy, motivation and emotional self-regulation, focus, concentration, all classic symptoms of ADHD. But dopamine is also related to RLS as the neurons that regulates muscle control also runs on this system. When the system gets off track, symptoms of “sensory confusion” can cause involuntary muscle movements and sensory irritation, especially in the limbs and primarily when the body is at rest.

What’s the link between RLS and ADHD?

Neuronal dysfunction is an imbalance in the excitatory and inhibitory synapses due to lack of neurotransmitters like dopamine causing neurons to fire randomly, which again is caused by the neurodevelopmental delayed development of the physical brains structures and networks.

ADDspeaker

Core ADHD symptoms of hyperactive/impulsive behavior is attributed to lack of inhibitory control over verbal and non-verbal motor functions.

Restless Legs Syndrome (RLS)

[…] Restless legs syndrome (RLS) is a chronic neurological disorder that interferes with rest and sleep. It has a wide spectrum of symptom severity, and treatment is started when symptoms become bothersome. Dopamine agonists and calcium channel apha-2-delta antagonists (gabapentin, gabapentin enacarbil and pregabalin) are first-line treatments; calcium channel alpha-2-deltas are preferred over dopamine agonists because they give less augmentation, a condition with symptom onset earlier in the day and intensification of RLS symptoms. Dopamine agonists can still be used as first-line therapy, but the dose should be kept as low as possible. Iron supplements are started when the serum ferritin concentration is ≤75 µg/L, or if the transferrin saturation is less than 20%. For severe or resistant RLS, a combined treatment approach can be effective. Augmentation can be very challenging to treat and lacks evidenced-based guidelines.

Source:
Restless Legs Syndrome: Clinical features, diagnosis and a practical approach to management.
Wijemanne S, Ondo W.
Pract Neurol. 2017 Dec;17(6):444-452.
doi: 10.1136/practneurol-2017-001762. Epub 2017 Nov 2. Review.
PMID: 29097554

[…] Some authors have hypothesized that the typical daytime hyperactivity observed in ADHD may be mirrored by an increased motor activity during the night, which in turn may cause sleep disruption and therefore explain the reduced sleep quality mostly experienced by these patients. Furthermore, ADHD is often associated with sleep-related movement disorders, such as restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). It has been suggested that sleep disruption associated with these disorders and the motor restlessness of RLS while awake could contribute to the typical symptoms of inattention and hyperactivity seen in ADHD children. Also, some authors pointed out that all these conditions may share a similar pattern of periodic leg movements during sleep (PLMS), and even a possible common pathophysiology related to a central dopaminergic dysfunction or brain iron deficiency. […]

Source:
Leg Movement Activity During Sleep in Adults With Attention-Deficit/Hyperactivity Disorder. 
Garbazza C, Sauter C, Paul J, et al.
Front Psychiatry. 2018;9:179. Published 2018 May 4. doi:10.3389/fpsyt.2018.00179

Comorbidity

[…] Restless legs syndrome (RLS) is a relatively common neurological disorder in childhood, although it is usually overlooked due to the atypical presentation in children and associated comorbid conditions that may affect its clinical presentation. Here, we aimed to perform, for the first time, a systematic review of studies reporting the association between RLS in children and adolescents (<18 y) and somatic or neuropsychiatric conditions. We searched for peer-reviewed studies in PubMed, Ovid (including PsycINFO, Ovid MEDLINE®, and Embase), Web of Knowledge (Web of Science, Biological abstracts, BIOSIS, FSTA) through November 2015, with no language restrictions. We found 42 pertinent studies. Based on the retrieved studies, we discuss the association between RLS and a number of conditions, including growing pains, kidney disease, migraine, diabetes, epilepsy, rheumatologic disorders, cardiovascular disease, liver and gastrointestinal disorders, and neuropsychiatric disorders (e.g., attention deficit hyperactivity disorder (ADHD), depression, and conduct disorder). Our systematic review provides empirical evidence supporting the notion that RLS in children is comorbid with a number of somatic and neuropsychiatric conditions. We posit that the awareness on comorbid diseases/disorders is pivotal to improve the diagnosis and management of RLS and might suggest fruitful avenues to elucidate the pathophysiology of RLS in children. […]

Source:
Somatic and neuropsychiatric comorbidities in pediatric restless legs syndrome: A systematic review of the literature.
Angriman M, Cortese S, Bruni O.
Sleep Med Rev. 2017 Aug;34:34-45.
doi: 10.1016/j.smrv.2016.06.008.
Epub 2016 Jul 1. Review.
PMID: 27519964

Treatments

Gabapentin

Gabapentin is an antiepileptic drug (AED) by design expected to mimic the action of the neurotransmitter gamma-aminobutyric acid (GABA). However, its principal proposed mechanism of action is the interaction with the alpha 2-delta subunit of L-type voltage-regulated calcium channels. However, its principal proposed mechanism of action is the interaction with the alpha 2-delta subunit of L-type voltage-regulated calcium channels. Gabapentin possesses several desirable pharmacokinetic properties, along with few drug interactions, particularly with other AEDs. These properties make it a well-tolerated drug, with the most commonly reported adverse events being somnolence and dizziness. Gabapentin is one of the new first-generation AEDs that expanded its use into a broad range of neurologic and psychiatric disorders shortly after it was licensed in 1993 for use in drug-resistant partial epilepsy with or without secondary generalization. Nowadays, most worldwide prescriptions for gabapentin are for conditions other than epilepsy, especially the treatment of chronic pain of different etiologies.

Source:
Gabapentin: a Ca2+ channel alpha 2-delta ligand far beyond epilepsy therapy.
Striano P, Striano S.
Drugs Today (Barc). 2008 May;44(5):353-68.
doi: 10.1358/dot.2008.44.5.1186403. Review.
PMID: 18548137

Iron

[…] Low blood levels of iron are often seen in people who have restless legs syndrome. Low blood iron levels may be part of the cause of restless legs syndrome. Iron can be taken as a pill or given as an injection into the bloodstream. We performed this review to see if iron treatment reduces the symptoms of restless legs syndrome. Key results and quality of evidence; Overall, the studies showed that iron is better than a placebo for reducing the severity of restless legs syndrome symptoms, although the benefit was low to moderate. This is mostly based on studies using injections of iron, rather than iron pills. Iron was helpful even if blood iron levels were normal at the start of the study. The quality of the evidence was moderate, because not all completed studies have been published, not all important outcomes have been measured, and not enough people have been studied. Side effects were not more common with iron than with placebo. Based on one study, side effects were less common with iron than with another commonly used restless legs syndrome treatment, although the certainty in this result is very low.  More studies are needed to allow people with RLS and doctors to make decisions about who should take iron for restless legs syndrome treatment, using what type of iron, and for how long. The evidence is current to September 2017. Authors’ conclusions; Implications for practice: Iron probably improves restlessness in people with restless legs syndrome (RLS), compared to placebo, based largely on trials of intravenous iron of moderate quality. However, insufficient data are available to directly determine whether iron or dopamine agonists are more effective or better tolerated, and no data address the question of whether iron or alpha‐2‐delta ligands are more effective or better tolerated. Thus, the decision of whether to use iron as first‐line treatment, as combination therapy with a dopamine agonist or alpha‐2‐delta ligand, or only as a second‐line medication after first‐line agents fail, cannot be fully guided by currently available evidence. […]

Source:
Iron for the treatment of restless legs
Trotti LM, Becker LA.
Cochrane Database Syst Rev. 2019 Jan 4;1:CD007834.
doi: 10.1002/14651858.CD007834.pub3. [Epub ahead of print] Review.
PMID: 30609006

 

 

 

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.