Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - The XIX World Congress on Parkinson’s Disease and Related Disorders

Shanghai, China / December 11-14, 2011

Shanghai - Here at the World Congress on Parkinson’s Disease and Related Disorders, experts in the field discussed the progress being made in identifying the earliest signs and symptoms of Parkinson’s disease before the onset of motor parkinsonism. In their presentations, researchers scoured trends and recent reports in cerebrospinal fluid biomarkers, neuronal vulnerability, molecular risk factors and neuroimaging in search of practical suggestions for physicians. They also presented promising leads for further research.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

Neuroimaging

Neuroimaging in Parkinson’s disease (PD) yields very intriguing findings but no clear guidelines yet for routine clinical use in early detection, noted Dr. A. Jonathan Stoessl, Director, Pacific Parkinson’s Research Centre and National Parkinson Foundation Centre of Excellence, Vancouver, British Columbia. He added, “Autonomic dysfunction has received a lot of attention as an indicator of PD,” as he commented on a report to illustrate the promise and also the challenges of neuroimaging for the disorder.

That report, co-authored by Dr. David S. Goldstein, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, describes a patient with primary chronic autonomic failure who underwent biennial brain and myocardial scanning over 4 years. In their report published earlier this year (Clin Auton Res 2011 Jul 28;Epub ahead of print), the authors noted that neuroimaging evidence in that patient of “cardiac noradrenergic denervation and subsequent progressive striatal dopaminergic denervation fit with Braak staging.” Commenting on this paper during the congress, Dr. Stoessl said of the patient, “He had no evidence of neurologic dysfunction at the time, but went on to manifest PD. It’s an extremely interesting example.”

But then he offered another report to demonstrate that the findings from neuroimaging studies are not yet very simple and predictable. “If you think of rapid eye movement (REM) sleep behaviour disorder as a pre-motor form of PD, you would expect that people with PD have further progression of autonomic dysfunction by the time they develop overt symptoms. In fact, we see the opposite.”

Dr. Stoessl explained that patients with isolated REM sleep behaviour disorder have quite severe cardiac denervation. Patients with advanced PD go on to develop the same degree of denervation, but he noted, “If you look at early PD, there may be relative preservation of cardiac sympathetic innervation.”

He told delegates that overall as a biomarker, there is a good relationship between the degree of abnormality on imaging and the clinical dysfunction. The problem is that that association does not apply very well to changes in clinical function.

In a review of a number of studies over the last 10 years, Dr. Stoessl reported, “If you try to look at the change in an imaging marker over a limited period of time—say, 2 years—and the degree of change in clinical function, these are often very poorly correlated.”

One reason he cited may be due to compensatory changes in the brain and these may change over time. One paper (De la Fuente-Fernandez et al. Ann Neurol 2011;69:803-10), for example, found that younger-onset patients may compensate better for their loss. Another article cited by Dr. Stoessl found that the degree of compensation for dopamine denervation declines over time (Nandhagopal et al. Brain 2011;134(Pt 11):3290-8).

He offered the prediction that in the next 5 to 10 years, there would be an enormous emphasis on multimodal imaging that would bring the best of the various technologies together. Included on that list would be anatomical resolution of MRI, neurochemical specificity of PET, temporal resolution of EEG and MEG.

From Non-Motor to Motor Symptoms

Researchers have begun preparing physicians for the possibility of treating even the earliest non-motor symptoms before overt PD. Prof. Erik Wolters, President, World Federation of Neurology-Association of Parkinsonism and Related Disorders, and Professor of Neurology, VU University Medical Center, Amsterdam, The Netherlands, noted that symptoms, such as REM sleep behaviour disorder and autonomic dysfunction, may precede the first signs and symptoms of motor parkinsonism by up to 20 years.

He suggested, “Maybe in the near future it will be possible because of the presence of those pre-motor symptoms to come to an earlier diagnosis. And in case there is a disease-modifying strategy, it is very important to start treatment as soon as possible.”

Olfactory dysfunction, restless legs syndrome, sleep disorders, depression and constipation are other common non-motor symptoms that frequently precede the onset of motor parkinsonism. Prof. Wolters added that non-motor symptoms have a bigger impact than the motor symptoms on patient quality of life.

He noted that exercise might be helpful for many patients, because indirect evidence suggests exercise increases neuroplasticity in both motor and non-motor disorders. He cited a study that showed 35% improvement in patient motor function resulting from a program of forced exercise on a tandem bike, requiring patients to pedal faster than they would on their own (Alberts et al. Exerc Sport Sci Rev 2011;39(4):177-86). In that study, a trainer regulated the pedalling speed on the tandem bike. “Of course, this was only an indication because it was an open study. But it alerted us because maybe forced exercise was indeed helpful for neurodegenerative disease,” Prof. Wolters told delegates.

A recent 12-month, randomized controlled trial found that patients treated with an exercise program reduced the daily medication doses in the treated PD patients whereas it was significantly increased in the control patients. “These findings suggest that natural worsening of symptoms associated with PD can be effectively counteracted by a properly designed forced exercise program.”

Sleep Dysfunction

Sleep dysfunction affects so many PD patients—60% to nearly 100%—that physicians have become concerned that the therapies they prescribe to treat PD may contribute to this problem. For example, some experts suggest that selegiline, because it is metabolized to amphetamine, may be one of the most likely to cause sleep-onset insomnia. But that remains controversial, since the L-amphetamine analogue may not have any receptors in the brain.

It was of interest to evaluate the impact of rasagiline treatment on sleep disturbance in subjects with PD. In a poster presentation here at the congress, researchers reported it improved sleep experience in this patient population.

In his poster presentation on the Rasagiline Effect on Sleep Trial (REST), co-principal investigator Dr. Sylvain Chouinard, Clinical Assistant Professor of Medicine, Université de Montréal, Quebec, reported that rasagiline improved mean Parkinson’s Disease Sleep Scale (PDSS) scores from 96.2 at baseline to 105.5 at 2 months (treatment effect 9.1 points, P=0.003 [n=97]).

In the study, the mean patient age was 67 years; most patients were stage II on the Hoehn and Yahr Scale, and 80% received rasagiline as adjunct therapy. All participants were diagnosed with idiopathic PD. All participants were eligible for the drug, based on the investigator’s clinical assessment and in accordance with the Canadian product monograph.

Dr. Chouinard reported significant differences from baseline (P<0.05) in overall quality of sleep, nocturnal restlessness, nocturnal motor symptoms and sleep refreshment. Scores on the Epworth Sleepiness Scale were slightly diminished but the change was not statistically significant. He concluded, “In this open-label study, 2 months’ treatment with rasagiline improved sleep experience in patients with PD.”