Acetyl-dl-leucine improves restless legs syndrome: a case report

Abstract

A 27-year-old male suffered from severe familial restless legs syndrome (RLS) since the age of 18 years (his mother and grandmother also have RLS). Symptoms included uncontrollable knee-jerks and an overwhelming urge to move his legs during the night. These symptoms were only occasionally and temporarily relieved if he moved his legs, causing a significant disruption of sleep and subsequent daily drowsiness, significantly impacting his everyday life. The symptoms were described as mild (a few times a month) until his early to mid-twenties, when a notable increase in severity (weekly episodes) was observed. The patient was reluctant to try treatment with l-Dopa or other drugs, because his relatives did not respond well to pharmacotherapy. The patient’s neurological examination was normal. In the 2 months prior to initiating treatment with acetyl-dl-leucine (ADLL), the patient reported severe RLS symptoms, at a higher frequency (3–5 nights a week) and intensity than previously observed. Based on a previous report of symptomatic cases of RLS [1], he was treated with the modified amino acid ADLL at a dose of 5 g/day (2 g in the morning, 2 g at noon and 1 g at night). Prior to beginning treatment, he was evaluated using the International Restless Leg Syndrome Rating Scale (IRLS) [2] with a score of 23 (“severe”). After initiating treatment, his symptoms were immediately less intense and ceased after 4 days. After 4-weeks of treatment, his IRLS score was 7 (“mild”). Given the frequency of RLS attacks in the months prior to treatment, and his RLS history, the patient commented on this highly unusual and outstanding improvement. The patient’s partner also confirmed the abrupt and sustained improvement, especially in involuntary leg jerks, sleep patterns, and daily fatigue levels. To evaluate the durability of ADLL’s treatment effect, the patient performed a washout after the initial 4-week treatment period. The patient remained off medication for 5 months, during which his condition remained very much improved, with a maximum of 1–2 nights a month with RLS episodes. After the 5-month washout, the patient reported a sudden onset of a “bad” week of RLS, with nightly episodes, with an IRLS of 27. He immediately re-started treatment due to the impact on his sleep and quality of life. Again, within 1 week, the episodes had subsided (IRLS score 13 “moderate”) with further improvements and no RLS symptoms from week two onward (IRLS score 6 “mild”). Following this 1-month treatment period, another washout was performed with a long-lasting improvement of symptoms for 3 months. The patient has since adhered to a regular treatment regime over the past 3 years: 1 month of treatment (5 g/ day), followed by a 3-month washout. The patient’s RLS remains effectively managed (average monthly IRLS score of 7). Throughout treatment, the patient has reported that the medication is well-tolerated, with no observed side-effects. ADLL was approved in France in 1957 for the treatment of acute vertigo. It has several primary and secondary mechanisms of action [3, 4]. In particular, electrophysiological studies showed that it stabilizes membrane potential of hyperand hypopolarized neurons [5] and an FDG-μPET study in a rat model of acute unilateral labyrinthectomy showed it activates the vestibulo-cerebellum and deactivates the posterolateral thalamus [6]. One assumed component of the pathophysiology of RLS is impaired functional connectivity, including decreased functional connectivity within the dopaminergic network (including nigrostriatal, mesolimbic, and mesocortical * Taylor Fields [email protected]