Introduction 

Restless leg syndrome (RLS) and fibromyalgia (FM) are different disease conditions that share similar clinical symptoms and have a significant negative impact on the quality of life of the affected individual.

What is restless leg syndrome?

Restless leg syndrome (RLS) can also be termed as Willis-Ekbom Disease. RLS is characterized by an uncontrollable need to move the legs, often accompanied by unusual or discomforting sensations, which can be characterized as tugging, pulling, or creeping ( Restless Leg Syndrome foundation). It is a common neurological condition. People with a family history of RLS are genetically predisposed.¹ The underlying cause of RLS is still not well understood. 

RLS can start at any age, showing a higher prevalence among adults and occurring more frequently in females.² In pediatric patients, early-onset restless legs syndrome is relatively common.³ The severity of RLS in pregnant women is notably more prominent during the third trimester.⁴

Research indicates that specific lifestyle factors, such as obesity, lack of physical activity, and smoking, are linked to the likelihood of developing RLS.⁵ 

Symptoms of restless leg syndrome 

The primary symptom of restless leg syndrome (RLS) is an overwhelming urge to move the legs, accompanied by a sensation of restlessness, which typically occurs at rest during the night and improves with movement.⁶ The sensations in the legs may feel like aching, throbbing, pulling, itching, crawling, or creeping.⁷ Symptoms are induced and worsen in a period of inactivity or when at rest and alleviated, either partially or completely, by movement such as walking or stretching, as long as the activity continues. 

The symptoms can also affect other parts of the body the legs, for example, limbs, abdomen (epigastrium, lower abdomen, and the inguinal region), pelvic area, facial area and skeletal structure.⁸

Symptoms start in the evening or at night, worsen as the night progresses, but usually subside by early morning. Chronic and persistent RLS symptoms typically occur at least twice a week on average and cause moderate to severe distress.

Causes of the disease

Genetic factors 

Genetic risk factors play a significant role in both the onset and exacerbation of RLS. Mutations in specific genes like BTBD9 and MEIS1 can increase the likelihood of developing the condition.⁹

Neurological factors and associated conditions.

RLS can manifest as either idiopathic or symptomatic. Symptomatic RLS is often linked to various underlying conditions including pregnancy, uraemia, iron deficiency, polyneuropathy (damage to multiple nerves), spinal disorders, and rheumatoid arthritis.¹⁰

RLS is intricately linked to brain iron deficiency, particularly in regions like the substantia nigra, putamen, caudate, and thalamus. Despite normal serum ferritin levels in most RLS patients, low cerebrospinal fluid ferritin suggests a localized brain iron deficit. This deficiency leads to hypoxia and demyelination due to impaired oxygen transport and myelin synthesis, respectively. Hypoxia activates pathways increasing dopaminergic activity, a hallmark of RLS symptoms. Additionally, high dopamine turnover and altered dopamine receptor expression further characterize RLS pathophysiology, underscoring the role of brain iron deficiency in its development.⁶

Diagnosis of RLS

To aid in diagnosis, a standard single question with high sensitivity and good specificity in large patient groups has been validated to screen for RLS.¹¹ According to standardized diagnostic criteria, the questions developed are ‘When you try to relax in the evening or sleep at night, do you ever have unpleasant, restless feelings in your legs that can be relieved by walking or movement?’¹¹ The severity of Restless Legs Syndrome (RLS) symptoms is evaluated by assigning scores based on the questions asked in the rating scale developed by the IRLSSG.¹²

The patient's medical history and a neurological examination to exclude peripheral neuropathy form the basis of RLS diagnosis.¹³

Several other blood tests are recommended to rule out secondary RLS.

Treatment of RLS

The treatment approach for RLS symptoms varies based on how severe and frequent they occur.¹⁴ Pharmacological and/or non-pharmacological approaches can be employed in managing the symptoms of RLS.

Non-pharmacological measures 

These measures such as warm water baths, and massages help control the symptoms. Several lifestyles factors can precipitate symptoms, therefore modifying these changes can help prevent triggers. They include:

• Reducing caffeine intake before bedtime
• Intense physical activity before bedtime
• Limiting alcohol intake 

Practicing good sleeping hygiene involves sleeping in a conducive environment, wearing clean and comfortable nightwear, and eliminating all forms of distractions at bedtime.

Pharmacological measures 

Dopaminergic agents are frequently employed as first-line therapies for treating RLS. Over time, long-term use of this agent may result in drug-induced augmentations.¹⁵ An example is levodopa (L-dopa). 

Alpha-2-delta ligands (gabapentin, pregabalin) is an off-label option for managing symptoms of RLS.

Opioids are useful to relieve any form of pain-associated symptoms. Examples of opioids are oxycodone and propoxyphene.

Iron-replacement therapy, whether administered through intravenous iron infusion or orally, is used for individuals showing evidence of low body iron levels. This treatment approach aims to alleviate or enhance the relief of intense and severe RLS symptoms.^15,16

Fibromyalgia 

Fibromyalgia (FM) is characterized by persistent, widespread musculoskeletal pain.¹⁷ Fibromyalgia can affect anyone and it is significantly more common in females. While most patients are diagnosed in middle age, 1–6% of cases occur in juveniles.¹⁸ Relatives of fibromyalgia patients have a high prevalence of the disorder, which may be influenced by both environmental and genetic factors.¹⁹

Individuals between the ages of 30 and 50, especially women, and those with related conditions such as lupus, rheumatoid arthritis, or osteoarthritis, are at increased risk of developing fibromyalgia (CDC).

Symptoms of fibromyalgia

The primary symptom of fibromyalgia (FMS) is widespread pain, which is often accompanied by stiffness, fatigue, sleep disturbances, cognitive impairments, and psychiatric symptoms.²⁰

Causes of the disease

The pathogenesis of the disease remains unknown. Fibromyalgia is a condition primarily caused by central sensitization, where dysfunctional neural circuits lead to abnormal pain perception, transmission, and processing, resulting in widespread musculoskeletal pain. Several factors including dysfunction of the central and autonomic nervous systems, neurotransmitters, hormones, immune system responses, external stressors, psychiatric factors, genetic predisposition and others, have been linked to the disease pathogenesis.^21,22

Several abnormalities in fibromyalgia include increased levels of excitatory neurotransmitters like glutamate and substance P, reduced serotonin and norepinephrine in spinal anti-pain pathways, prolonged pain sensation, dopamine dysregulation, and altered brain endogenous opioid activity, all of which contribute to the condition.¹⁷

Diagnosis 

Diagnosing fibromyalgia is challenging and relies heavily on patient history and physical examination.²³ A reliable self-assessment tool based on diagnostic criteria has been developed for diagnosing fibromyalgia. It quantifies the syndrome's symptoms effectively, with scores above certain thresholds showing good accuracy compared to the original criteria. This helps clinicians assess and differentiate fibromyalgia from other potential disorders that might explain similar symptoms.²⁴

Treatment 

When choosing drug therapy for patients with fibromyalgia (FMS), it is important to take into account the specific clinical features of the patient, the possible side effects of the medications, the patient's ability to tolerate the drugs, and how well the patient responds to the treatment.²⁰

Pharmacological therapy

Antidepressants and neuromodulating antiepileptics play a major role in treating fibromyalgia, as NSAIDs and opioids have limited effectiveness for this condition.²¹

Amitriptyline, Pregabalin, and Duloxetine are commonly used to treat FMS and, while they provide limited relief, they are helpful as adjuncts treatments alongside non-pharmacological therapies.²⁵

Non-pharmacological therapies

It encompasses exercise training (such as aerobic exercise), acupuncture, massage therapy, osteopathic joint mobilization, relaxation techniques, thermotherapy (application of warm or cold packs), transcutaneous electrical nerve stimulation (TENS), magnetic field therapy, brain stimulation, and psychological or behavioural therapies.²⁶

Summary

Resting Leg Syndrome (RLS) is characterized by an uncontrollable need to move the legs which is often accompanied by unusual or discomforting sensations on the other hand FM is characterized by persistent, widespread musculoskeletal pain.Fibromyalgia(FM) and RLS can affect individuals of any age but are more commonly found in women.

The symptoms associated with both conditions cause pain and discomfort, which can affect sleep. The pathogenesis of these conditions is unknown and can result from various factors. 

The primary goal for treatment in both conditions is to alleviate symptoms such as the uncomfortable sensation and urge to move the leg in RLS and to eliminate pain in the case of fibromyalgia, while also improving sleep and physical function. They are generally managed by pharmacological and non-pharmacological methods.