Third International Scientific Symposium on Parkinson’s Disease and Restless Legs Syndrome

O ver 350 neurologists from all over the world converged on Cannes, France in October for the 3rd International Scientific Symposium on Parkinson’s Disease and Restless Legs Syndrome. The two-day symposium was supported by an unrestricted educational grant from Boehringer Ingelheim and accredited by the European Federation of Neurological Societies (EFNS). Welcoming delegates to the first day of the meeting, Oliver Rascol (Toulouse, France) pointed out that although effective treatments have deeply modified the clinical spectrum of Parkinson’s Disease (PD), the presence of multiple options make it a challenge in setting a consensus and a unified strategy for the optimal management of the individual patient. Marie Vidailhet (Paris, France) highlighted the non-motor symptoms of PD. She said that although PD is typically defined as a syndrome consisting of tremor, bradykinesia, rigidity and postural instability, the clinical spectrum was much more diverse. “Beyond these principally motor features”, she said, “there is increasing recognition of non-motor problems including cognitive impairment, mood disorders and autonomic failure”. And she stressed that it was these aspects of the illness rather than the motor symptoms that lead to the most profound disability, and impact on quality of life. Anthony Schapira (London, UK) then took to the floor to discuss the dopaminergic and nondopaminergic actions of dopamine agonists. He said that recently dopamine agonists have attracted attention as potential disease modifying agents, adding that they appear able to prevent cell death in a variety of cell culture and animal model systems. He also presented evidence showing that the D2/D3 agonist pramipexole has been shown to significantly reduce dopaminergic cell loss in the nigra of MPTP treated primates. He also presented data from the CALM-PD study that used imaging of the nigrostriatal system as a surrogate marker for disease progression in patients receiving pramipexole or levodopa. The results showed a significant reduction in the rate of loss of imaging marker over the four-year study period with pramipexole. The focus then turned back to the non-motor symptoms of PD. Paolo Barone (Naples, Italy) said that depression was a common complication of PD with a prevalence averaging 40% in patients attending outpatient clinics. He also highlighted that the quality of life of PD patients was significantly and inversely associated with depression. Yet he stressed: “There is little evidence for the efficacy and safety of antidepressant therapies in PD”. He went on to present findings from an open-label randomised study comparing the efficacy and tolerability of pramipexole versus the selective serotonin reuptake inhibitor sertraline in the treatment of depression in stable PD patients without fluctuations and under levodopa monotherapy. Pramipexole was found to have significant antidepressant effects in patients with PD. Less pramipexole patients discontinued as a result of side effects and in a secondary analysis of the intent-to-treat population, the percentage of patients recovering from depression was statistically significantly higher with pramipexole at 60.6% compared with sertraline (27.3%). Barone commented: “These findings suggest that there may be significant advantage for PD patients with depression to receive the dopamine agonist pramipexole in preference to a classic antidepressant.” Werner Poewe (Innsbruck, Austria) then reviewed disorders of sleep in PD patients. He stressed that the management of sleep disorders in PD was complex and has to target underlying mechanisms. He said that dopamine agonists might be helpful with sleep fragmentation due to nocturnal motor disability due to either restless legs syndrome or periodic limb movements in sleep. Andrew Lees (London, UK) highlighted that a small number of PD patients develop cognitive and neuropsychiatric disturbances that may be directly related to taking increasing doses of dopaminergic drugs well in excess of those needed to control motor symptoms. He said that such patients could be identified by a demand for escalating doses of dopamine replacement therapy often against medical advice. He said that treatment involved early identification for risk and stringent enforced restriction of medication with minimisation of short duration formulations. Ken Marek (New Haven, USA) provided an update on imaging. He said that imaging “continues to expand its role in translating clinical neuroscience into better understanding and more effective therapies for PD”. One of the most exciting potential uses he spent some time elaborating on was preliminary work demonstrating that combining imaging with other potential PD screening tools may enable presymptomatic screening for PD in at risk groups. Continuing on this theme, Christopher Goetz (Chicago, USA) highlighted the need for the development of new scales for the clinical assessment of PD. Goetz has been recruited by the MDS to organise a committee to provide a new UPDRS. The new scale retains the original structure of the UPDRS with four newly titled components: non-motor experience of daily living (part I and II), motor examination and motor complications. In addition, an official appendix recommends more in-depth assessment for several of the non-motor items including depression, cognitive deficits, insomnia and quality of life. Concluding the first day, Warren Olanow, (New York, USA) outlined new and future therapies for the treatment of PD. These included cell based therapies; trophic factors; gene therapies and neuroprotective approaches. The second day of the meeting was devoted to Restless Legs Syndrome (RLS). Karl Ekbom, son of Karl-Axel Ekbom who in 1945 published a doctoral thesis on restless legs, provided an introduction to the day highlighting the potential promise of dopamine agonists. Markku Partinen (Helsinki, Finland) reviewed the clinical presentation and diagnosis of RLS. He stressed that all symptoms of the RLS quartet must be present in order to make the diagnosis – an urge to move usually accompanied by unpleasant sensations in the legs; aggravation of symptoms at rest; relief of symptoms with activity and a circadian pattern with worse symptoms experienced in the evening or night. Wayne Hening (New Brunswick, USA) then elaborated on the clinical importance of RLS. He highlighted findings from the recent REST study showing that 3% of the primary care population reported that they had RLS symptoms at least twice a week and that when the symptoms occurred they caused moderate to severe distress. Among these patients, 82% reported that they were bothered by the leg discomfort and more reported difficulties with sleep. Over half of RLS sufferers reported significant problems with functions the day after nocturnal symptoms – including fatigue and cognitive difficulties. Overall he stressed that RLS had a significant impact on quality of life, adding that treatment of RLS can both alleviate symptoms and improve quality of life. Richard Allen (Baltimore, USA) then reviewed the pathophysiology of RLS highlighting the importance of dopamine abnormalities. He said that levodopa and all dopamine agonists provide dramatic and immediate relief of symptoms when used at doses much lower than those used for treatment of PD. Luigi Ferini-Strambi (Milan, Italy) proposed that RLS was a poorly recognised and undertreated condition. Reviewing latest epidemiological studies he said that around one in ten of the adult population have RLS – a truly common disease; and that women were twice as often affected as men. Turning to treatment options, Diego GarciaBorreguero (Madrid, Spain) reviewed the efficacy and safety of dopaminergic compounds. Although he said that several ergoline-derived dopamine receptor agonists have been investigated, due to the higher incidence of side effects research is now focused on the non-ergoline derivatives including pramipexole and ropinirole. He cited studies showing that pramipexole has been shown to be more effective than placebo at a dose of 0.125 mg per day and is currently being investigated in large, double blind randomised controlled trials. He also said that pramipexole had the advantage of having therapeutic efficacy at the initial dosage. This he said meant that if confirmed by future studies pramipexole could be used not only for as a continuous treatment but also for non-daily treatment of RLS. Conference Report