One-year treatment with standard and sustained-release levodopa: appropriate long-term treatment of restless legs syndrome?

To investigate the long-term efficacy and safety of sustained-release (SR) in combination with regular-release (RR) levodopa/benserazide in the treatment of restless legs syndrome (RLS), an open-label, prospective, extension study of a preceding double-blind crossover trial was performed for 12 months. Twenty-three severely disturbed RLS patients (7 men, 16 women) received a combination of RR and SR levodopa. Patients were treated on average for 10 months with a mean daily dose of 203 +/- 101 mg of RR and of 185 +/- 93 mg of SR levodopa. The mean daily total dose was 388 +/- 162 mg levodopa. Efficacy was documented using patient's rating scales, sleep diaries, and investigator's global ratings with the Clinical Global Impressions (CGI). Ten of 23 patients completed the 1-year extension. Between baseline of the crossover trial and endpoint of the extension study (last-observation-carried-forward method, intention-to-treat population), quality of sleep improved (+3.5 +/- 1.9, 7-point scale), sleep latency was shortened (-131 +/- 152 minutes), and total sleep time lengthened (+ 190 +/- 136 minutes). Severity of RLS at time of falling asleep (-6.5 +/- 3.4, 11-point scale) and during the night (-6.0 +/- 3.5) was markedly lower at the end of the extension but severity of RLS during the day (+1.9 +/- 5.0) slightly increased. Of 13 dropouts, 8 patients discontinued therapy because of worsening RLS during the day. This trial shows that long-term treatment with the combination of RR and SR levodopa/benserazide in RLS patients with late-night problems was efficacious and not limited by tolerability problems in 40% of patients, whereas in the majority of patients, aggravating daytime problems required termination of the levodopa therapy within the 1-year treatment period.

Endocrine rhythms in patients with restless legs syndrome.

There is increased evidence that the dopaminergic system plays a major role in the pathophysiology of the restless legs syndrome (RLS). Dopamine is the major inhibitory factor of prolactin release and also influences growth hormone (hGH) secretion. The aim of this study was to measure the endocrine activity of RLS patients, to compare it with that of normal subjects and to detect possibly altered patterns of hormonal secretion in RLS patients. Prolactin, hGH and cortisol plasma levels were measured every 20 min for 24 hours in 10 male never-medicated RLS patients (aged 56 +/- 6 years) who have had mild to moderate symptoms for 15 +/- 10 years and in 8 age-matched male controls (aged 57 +/- 5 years). The blood samples taken during the night were paralleled by polysomnographic recordings including the assessment of periodic leg movements (PLM). Plasma levels as well as frequency and amplitude of the pulses of prolactin, hGH and cortisol were not different between RLS patients and controls. Both groups showed the same rhythms during the night- and daytime for all hormones. Cross correlations resulted in high correlation coefficients for each hormone at lag 0 (0.964,0.943 and 0.971 for mean locations of cortisol, hGH and prolactin, respectively). Concerning sleep parameters, there were no significant differences between the two groups apart from a higher PLMS arousal index in RLS patients (25.9 +/- 17.1) compared with the controls (12.0 +/- 9.2; p < 0.05). It is suggested that a possible dysfunction of the dopaminergic system in RLS does not affect the release of prolactin and hGH from the pituitary gland.

Sleep and periodic limb movements in corticobasal degeneration.

Corticobasal degeneration (CBD) exhibits distinct features of akinesia, the 'alien limb' sign and cortical myoclonus. We report a 63-year old woman with a history of CBD for 18 months who was studied twice using all-night polysomnography with an interval of 13 months. Both recordings revealed frequent periodic arm and leg movements predominantly during non-REM sleep. To our knowledge this has not been described in a patient with CBD so far. Similar to a previous report we found REM sleep without atonia (RWA) in all REM episodes. However, the patient showed RWA and some non violent movements that fulfilled the diagnosis of subclinical REM sleep behavior disorder only in the second investigation. These observations may be due to the underlying degenerative process that involves not only cortical but also thalamic and brainstem structures.