Restless Legs Syndrome Treatment With Botulinum Toxin

The restless legs syndrome (RLS) is a chronic sensori-motor disorder affecting an estimated 7.2% to 11.5% of the adult population. It is characterised by a complaint of an irresistible urge to move the legs. This urge can often be accompanied by pain or other uncomfortable and unpleasant sensations, it either occurs or worsens with rest particularly at night, and improves with activity. RLS is diagnosed clinically by means of the four essential criteria established by the International Restless Legs Syndrome Study Group.

There is still no comprehensive understanding of the underlying pathophysiological processes of RLS, but the evidence for a primary dopaminergic role in RLS is to be found in the excellent pharmacological response to low-dose dopaminergic medications. Another recent evidence suggests an enhanced sensitization of central pain processing in patients with RLS. This had led to consider the botulinum toxin type A (BNT) as an alternative treatment in patients refractory to current RLS medications or in those suffering from adverse events. The therapeutic benefit of BNT injection in patients with recalcitrant RLS has been anecdotally reported lately but not confirmed by other reports.

The aim of our study is to evaluate the efficacy and tolerance of intradermal BNT injection in severely affected patients with idiopathic RLS.

For this we designed a phase II non comparative, open study. Patients with severe RLS will receive a one-time intradermal administration of BNT into the most symptomatic areas of both legs. Injections will be distributed in a grid distribution pattern covering a total of 20 equidistant sites per symptomatic area. Each symptomatic area will receive a maximum 250 units of BNT (12.5 units per injection). The total BNT injected units should not exceed 1000 units per patient.

Outcome measures will be evaluated at baseline, then at 2, 6, 12, 18 and 24 weeks following BNT administration and assessed by mean of the International RLS Rating Scale and Clinical Global Impression Scale.

Inclusion criteria

• Male or female > 18 years old
• Normal neurological clinical examination
• A minimum score of 21 on the RLS severity rating scale
• Primary RLS diagnosis based on (i) the presence of a characteristic clinical history and on (ii) the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria.
• Medications regimen for RLS must be stabilized for more than 6 weeks prior to entering the study
• informed consent

Exclusion criteria

• Medical history of diabetes, depression, kidney failure, myasthenia
• Iron deficiency
• Pregnancy, lactation, woman of childbearing age without efficient contraceptive method
• Patient undergoing aminosid antibiotherapy or BNT injection for other indication
• Any contra-indication to BNT injection
• Participation to other clinical study within 30 days
• Patient under any administrative or legal supervision