Restless Legs, Restless Nights

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We've all experienced that unpleasant tingling in our legs after sitting too long on a long flight or felt a restless urge to move our limbs after hours stuck at the office. But for some people, these strange sensations and irresistible urges happen throughout the evening and night, robbing them of restorative sleep. These experiences could be symptoms of restless leg syndrome or periodic limb movement disorder - two closely related yet underdiagnosed conditions that can severely impact sleep quality and quality of life.

Restless leg syndrome (RLS) is a neurological disorder characterized by an overwhelming, irresistible urge to move the legs, usually accompanied by unpleasant sensations like tingling, aching, burning, or cramping in the legs. These urges to move the legs and uncomfortable limb sensations start or become more intense during periods of rest and inactivity. RLS symptoms typically emerge or worsen in the evening hours, especially around midnight, often leading to severely disrupted sleep. According to a recent review, it's estimated that RLS affects up to 10% of the US population, with symptoms beginning at any age usually getting worse with age. Consuming caffeine or alcohol, especially in the evening hours, can trigger or worsen the unpleasant sensations and restless urges associated with RLS. Certain conditions like diabetes and pregnancy may also increase the risk of developing RLS symptoms, potentially due to hormonal changes that disrupt dopamine regulation in the brain's motor control pathways.

Periodic limb movement disorder (PLMD) refers to involuntary, repetitive limb movements (arm and/or legs) that occur every 20-40 seconds during sleep, with the legs being most commonly affected. Each movement involves bending at the knee, hip or ankle in a jerking motion. These periodic limb movements can significantly fragment sleep quality and impair daily cognitive functioning. The individual is not aware of their movements since they happen during sleep, but the bed partner is usually the one noticing this. While PLMD may occur independently, around 80-90% of those with RLS also experience PLMD, suggesting the two disorders are closely linked.

So what is the cause of these movement disorders? Both RLS and PLMD appear connected to disruptions in dopamine signaling in the brain's movement control pathways. Dopamine is a key neurotransmitter that helps regulate muscle activity and control the brain's instructions for desired movements. With RLS and PLMD, it's thought there may be dysfunction in the dopamine pathways running through the brain's basal ganglia and substantia nigra regions. Dopamine levels naturally fall towards the end of the day, which may explain why the?symptoms of RLS are often worse in the evening and during the night. Interestingly, iron deficiency is a risk factor that can contribute to dopamine dysregulation and worsen RLS and PLMD symptoms. Iron is a critical for the proper synthesis and metabolism of dopamine in the brain. When iron stores are depleted, it can impair dopamine production and neurotransmitter signaling, potentially triggering or exacerbating the restless sensations of RLS or jerking movements of PLMD.

How can we help individuals with RLS/PLMD? While there are no cures, a variety of treatments can help manage symptoms of RLS and PLMD. Non-pharmacological treatments include lifestyle adjustments like getting regular exercise, treating nutrient deficiencies, putting heating pads or cold packs on the limbs in the evening, taking relaxing baths, massaging the limbs, improving sleep habits, and avoiding caffeine or alcohol. These can provide some relief.

If none of the non-pharmacological treatments provide relief, medications commonly prescribed include those potentiating the effect of dopamine (dopamine agonists) like pramipexole, anticonvulsants affecting calcium channels such as gabapentin enacarbil or pregabalin, benzodiazepines like clonazepam or diazepam, or in severe cases, opioids. Emerging therapies being studied involve pneumatic compression devices that massage the legs, brain stimulation techniques like transcranial magnetic stimulation, and mind-body practices such as meditation.

While restless leg syndrome and periodic limb movement disorder can significantly disrupt sleep and impair quality of life, understanding their neurological roots paves the way for better management strategies. By recognizing these conditions arise from dopamine dysregulation and motor control pathway disturbances in the brain, researchers can continue exploring more targeted therapies. With deeper scientific insights into their biological underpinnings, the outlook continues improving for the millions who suffer from these underdiagnosed yet highly disruptive movement disorders. Increasing awareness and access to effective treatments could help unlock restful nights for those kept in perpetual motion.

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About the author

Alen Juginovi? is a medical doctor and postdoctoral researcher in the Department of Neurobiology at Harvard Medical School studying the effect of poor sleep quality on health. He is public and keynote speaker and teacher at Harvard College. He and his team also organize international award-winning projects such as conferences which attracted 2400+ participants from 30+ countries, 10 Nobel laureates and major leaders in medicine (Plexus Conference), collaborative research projects, charity concerts and other events. He co-founded Med&X Association, a non-profit organization that organizes conferences with Nobel laureates and partners with leading universities and hospitals around the world to help accelerate the development of talented medical students and professionals. Feel free to contact Alen via LinkedIn for any inquiries.

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