A 61-year-old female presented to the sleep clinic with discomfort in her legs and lower abdomen for 11 years. She felt an urge to move her legs, a creeping and restless sensation on her legs, and sometimes also felt a squeezing and rising sensation in her lower abdomen. The symptoms started when she would go to sleep and were temporarily relieved when she moved her legs. She had endoscopy for abdominal discomfort, and no abnormalities were identified. She underwent knee replacement surgery to improve the paresthesia of her legs, but the symptoms remained. She was then diagnosed with RLS at the local clinic and took ropinirole 1 mg before sleep. However, the discomfort in her legs became worse after the initial improvement and lasted for several months. She had a past medical history of hyperlipidemia and was taking no other medication except ropinirole and lipid-lowering drugs. She had no history of peripheral neuropathy or varicose veins, which can mimic RLS. She had no family history of RLS. Her body mass index (BMI) was 24.24 kg/m² (156 cm, 59 kg). Her baseline International Restless Legs Scale (IRLS) score was 19, and RLS-Quality of Life (RLS-QOL) Scale score was 85. Her Pittsburgh Sleep Quality Index (PSQI) was 7, Insomnia Severity Index (ISI) was 3, and Beck’s Depression Inventory (BDI) was 14. Her hemoglobin and serum iron levels were in the normal ranges (13.0 g/dL and 77 μg/dL), and her ferritin and transferrin saturation were lowered to 60.7 μg/L and 20.8%, respectively. Her brain MRI was within the normal range.

We reduced the dose of ropinirole to 0.5 mg and added pramipexole 0.25 mg at 9 p.m. (two hours before her bedtime). After one month, she felt improvement in her sensory symptoms by 50%. We then discontinued the ropinirole and administered intravenous (IV) iron therapy (ferric carboxymaltose 1000 mg). The symptoms were much improved for 6 months after IV iron injection. However, after 6 months, her RLS symptoms became worse. She complained of a squeezing sensation in her lower abdomen. Sometimes, she also felt like she had a lump in her stomach, with uprising sensations in her abdomen. She described her feelings as restlessness and weird feelings in the perineal area, with irritating sensations at the knee. Inappropriate sexual impulses had occurred prior to discomfort in the perineal area, but she could not talk frankly. The IRLS had progressed to 30, and the ISI and PSQI had also aggravated to 19 and 10, respectively. The patient received additional IV iron injection, but the symptoms remained, though follow-up ferritin and transferrin saturation were in the normal ranges (250.8 μg/L and 47.9%, respectively). We added pregabalin 50 mg at 9 p.m. and then increased the dosage to 75 mg after 5 months. After adding the pregabalin, the symptoms in the legs and genital area were well controlled. However, the symptoms recently became worse again after reducing the dose of pregabalin to 50 mg.

A 65-year-old female visited the sleep clinic complaining of aggravated insomnia after having endoscopic surgery one month ago. She had felt tingling sensations in her genital area and lower abdomen that spread up her trunk for 35 years. Sometimes she felt tingling sensations and restlessness on her thigh, but the symptoms were improved after taking a walk. The symptoms were aggravated at resting and at night and sometimes also occurred after overeating dinner. She reported that she had problems falling asleep because of the uncomfortable feelings in her groin and thigh.

She had a past medical history of gallbladder cancer, for which she had surgery one month ago. She was taking aspirin and statin for carotid atherosclerosis and painkillers for arthritis. She had no other medical history of RLS mimics and did not take antidepressants or dopamine antagonists that could cause RLS. She had no family history of RLS. Her BMI was 16.44 kg/m² (148 cm, 36 kg). Her baseline IRLS was 33, and her RLS-QOL Scale score was 37.5. Her PSQI was 13, ISI was 21, and BDI was 27. Her hemoglobin was in the normal range (14.0 g/dL), and serum iron was slightly reduced to 49 μg/dL. Her ferritin and transferrin saturation were significantly reduced to 27.2 μg/L and 16.4%, respectively.

Ropinirole 0.25 mg before sleep was ineffective. IV iron (ferric carboxymaltose 1000 mg) was injected, and her ferritin level increased to 717.5 μg/L. Her symptoms began to improve 4 weeks after IV iron therapy. Her IRLS was lowered to 20, and ISI and PSQI improved to 17 and 7, respectively.

After 9 months, the tingling sensation had expanded to her trunk and shoulder, and the abnormal sensation also occurred in the afternoon and evening. The dysesthesia of her thigh and perineal area was aggravated when she stayed still, such as when watching movies for several hours. We suspected augmentation of RLS and recommended that she take pregabalin at 5 p.m. However, the tingling sensation of the thigh and perineal area in the afternoon remained. Therefore, we changed the schedule of pregabalin from 5 p.m. to 3:30 p.m. and added additional pregabalin 75 mg before sleep. Her ferritin and transferrin saturation were reduced to 49.0 μg/L and 27.2%, respectively. The patient received additional IV iron, after which her symptoms markedly improved, and her ferritin level increased to 235.2 μg/L. Her IRLS was improved to 14, and ISI and PSQI also improved to 11. The medications have been maintained, and the tingling sensation on her perineal area has been well-controlled thus far.

A 51-year-old female visited the sleep clinic complaining of a tingling sense and restlessness on her thigh and leg that was aggravated at resting for 2.5 years. She also complained of a bloating sensation in her lower abdomen and sexual arousal without voluntary sexual desire. The sexual arousal and impulse increased especially when she had restlessness and discomfort in her lower extremities. She had no past medical history and was taking duloxetine and alprazolam from a local clinic to control the discomfort in her abdomen and lower extremities. She had no family history of RLS. Her hemoglobin, serum iron, and ferritin were in the normal ranges (13.1 g/dL, 49 μg/dL, and 85.6 μg/L, respectively).

We prescribed pregabalin 50 mg before sleep and recommended that she discontinue duloxetine, which may aggravate the RLS symptoms. The sensory symptoms nearly disappeared after she began taking pregabalin, but she complained of dizziness. We reduced the dosage of pregabalin to 25 mg, and the symptoms were well-controlled even after reducing the dosage.

A 50-year-old female visited the sleep clinic complaining of stuffy feeling on her external genitals and right toe with increased sexual impulse. She also had urge to move her right toe, which was aggravated at night or at resting. The unwanted sexual desire did not resolve after having intercourse, but transiently improved during she walks around. The symptoms first started when she was a teenager. Previously she had stuffy feelings on her knee, but the symptoms migrated to clitoris and right toe for one year. She had no past medical history and was not taking any medications. She had family history of RLS, including grandmother, father, and aunt. Her hemoglobin, serum iron, and ferritin were in the normal ranges (13.2 g/dL, 70.1 μg/dL, and 70.1 μg/L, respectively).

Ropinirole 0.5 mg and gabapentin 300 mg before sleep were given with considerable efficacy.

This study followed the principles of the Declaration of Helsinki, and was approved by the Seoul National University Hospital (2006-208-1137) and Wonkwang University Hospital (WMCSB202007-57) Institutional Review Board. All information of patients was sufficiently anonymized.