Movement Disorder Society, 15th International Congress of Parkinson’s Disease and Movement Disorders, Toronto
Bicycling Ability Maintained in Parkinson’s Disease Patients With Freezing of Gait
Cycling—using either a real bicycle outdoors or, as a safer alternative, a stationary bicycle at home—may be an effective way of promoting physical activity in patients with Parkinson’s disease to prevent the many complications of immobility, according to a recent study.
Anke Snijders, MD, from the Donders Institute for Brain in Nijmegen, the Netherlands, showed cycling to be less affected than walking when used as a physical rehabilitation method for patients with freezing of gait in Parkinson’s disease.
Of the 53 patients with Parkinson’s disease interviewed for the study, 23 experienced freezing of gait. Only one patient experienced episodes of freezing of gait while cycling, though it was less severe than during walking. Eight patients with freezing of gait reported that the feet sometimes exerted an irregular pressure on the pedals, but without obvious obstruction.
Commenting on the study, Daniel Tarsy, MD, of Beth Israel Deaconess Medical Center in Boston, said, “Recent anecdotal reports indicate that patients with Parkinson’s disease who suffer from gait freezing can ride a bicycle much more easily than they can walk. The study by Snijders indicates this may be a relatively common phenomenon. Only one of 23 patients who reported gait freezing experienced similar difficulty while cycling. If this can be confirmed by direct observation, it indicates that individuals with gait freezing can enjoy useful physical exercise. Whether this occurs by utilizing an alternative motor system, taking advantage of sensory cues provided by rotating bike pedals, or by other mechanisms, is of great interest and will be worth investigating.”
Caffeine May Influence the Age at Onset of Huntington’s Disease
Recent research suggests that caffeine could be the first environmental modifier of age at onset in Huntington’s disease.
Because phenotypic expression is variable in Huntington’s disease, mutation in the IT15/HD1 gene statistically predicts the age at onset. However, on an individual basis, repeat length accounts for about 60% of its variance; 40% of the remaining variance is due to additional genetic and/or environmental factors. Association of age at onset with genetic factors has been previously reported. In contrast, whether environmental factors are also able to influence age at onset remains unknown.
Cecile Duru, MD, from the Department of Neurology at Amiens University Hospital in France, investigated caffeine because it affects the neurons that express receptors vulnerable to Huntington’s disease. As a type of adenosine receptor agonist, caffeine can affect the function of many tissues, including slowing metabolic activity in the brain.
Information on 80 patients with Huntington’s disease regarding caffeine consumption, alcohol consumption, and smoking habits during the last 10 years was collected using a validated self-questionnaire. All patients were evaluated using the Unified Huntington’s Disease Rating Scale. Relation between age at onset and potential predictors was tested by bivariate analysis adjusted on CAG repeat length with a linear regression or a covariance analysis.
Results showed that after adjustment of CAG repeat length and smoking habits, patients having a high caffeine consumption (>185 mg/day) had an earlier age at onset (45.4) compared with patients who had a caffeine consumption less than 185 mg/day (age at onset, 49.5).
Studying caffeine consumption as an environmental factor for the age at onset for Huntington’s disease in comparison to alcohol consumption and smoking shows that caffeine consumption may lower the age at onset for patients with Huntington’s disease. According to Dr. Duru, these findings could have an interesting therapeutic impact as modulation of A2A receptors may represent a new strategy for treating Huntington’s disease.
Kathleen Shannon, MD, of Rush University Medical Center in Chicago, commented on Dr. Duru’s findings. “Given the severe nature of Huntington’s disease, there is a critical need to identify environmental influences that may delay onset of clinically manifest disease. This abstract suggests that onset is earlier in subjects whose intake during the prior 10 years was greater than 185 mg/day (about two cups of coffee) compared with those whose intake was less than 185 mg/day. Although this study did not mention the outcome measure, did not allow that caffeine is a movement enhancer, or did not state if the patients were using caffeine to treat sleepiness, this is somewhat interesting and should be pursued in a larger population.”
Safety and Efficacy of Octanoic Acid for Treating Essential Tremor
Results of a low-dose, proof-of-concept study indicate that octanoic acid is safe and well tolerated. Study data also suggest the superiority of octanoic acid in reducing tremor in patients with essential tremor compared with placebo at 2.5 hours postdose and later.
The long chain alcohol 1-octanol has been demonstrated to effectively alleviate tremor symptoms in essential tremor. Deitrich Haubenberger, MD, from the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Maryland, explored the suggested effect through its metabolite, octanoic acid.
Through a double-blind, placebo-controlled, crossover phase 1–2 clinical trial assessing the effect of a single oral dose of octanoic acid (4 mg/kg) in 19 subjects with essential tremor, postural tremor power was recorded using accelerometry at baseline and multiple time points up to five hours after administration. No signs of intoxication were observed, and adverse events were mild and equally present in the octanoic acid and placebo groups. Although many people with essential tremor find relief from rest and alcohol consumption, patients with essential tremor received similar relief with no signs of intoxication from octanoic acid.
Roger Elble, MD, PhD, of Southern Illinois University School of Medicine, commented, “Many patients with essential tremor experience significant benefit from ethanol. The question is whether some other alcohol would be more beneficial and less intoxicating. Hallett and colleagues at the NINDS previously showed that octanol was superior to placebo in ethanol-responsive essential tremor patients. In this study, Dr. Haubenberger found that the metabolite of octanol, octanoic acid, is superior to placebo, suggesting that octanoic acid is the active agent. This was only a single dose study, and the efficacy of octanolol/octanoic acid needs to be confirmed in a longer randomized placebo-control trial. The effect of octanoic acid was no better than that previously reported for propranolol and primidone. It is unclear whether all essential tremor patients respond or only those who are ethanol-responsive.”
Polysomnographic Findings in Sleep-Disturbed Parkinson’s Disease Patients
Among patients with Parkinson’s disease in the advanced stage of the disease, sleep disturbances are common, according to recent findings. Further, REM sleep behavior disorder in neurodegeneration is not only a preclinical marker but also a relevant clinical finding in advanced stages of the disease.
Sleep disturbances frequently occur in patients with Parkinson’s disease, and they are not always attributable to a nocturnal lack of dopaminergic treatment. Often, patient and/or caregivers’ reports do not yield sufficient information for identifying the correct diagnosis as a prerequisite for efficient treatment. To better understand various sleep disturbances in Parkinson’s disease, Friederike Sixel-Döring, MD, from the Center of Parkinsonism and Movement Disorders, Paracelsus-Elena-Klinic in Kassel, Germany, investigated sleep efficiency.
The study evaluated 463 patients with reports of a relevant sleep disturbance by patient and/or caregiver, daytime vigilance problems, written informed consent to video-supported polysomnography, and scientific evaluation of data. Video-supported polysomnography was used, and analysis of demographic and clinical data was performed.
Cynthia Comella, MD, of Rush University Medical Center in Chicago commented, “This abstract is significant in that it confirms previous work demonstrating the high frequency of sleep disorders in Parkinson’s disease patients in a large group of patients using polysomnography.”
Results showed that patients with Parkinson’s disease in advanced stages of the disease experienced reduced sleep efficiency, sleep fragmentation, increased periodic leg movements indices, and reduced slow wave sleep. Almost half (46%) were found to have REM behavior disorder and more than one third (35%) were diagnosed with a sleep-related breathing disorder.
Genetic Mutation May Predispose Some Parkinson’s Disease Patients to Cancer
Preliminary research suggests that Ashkenazi Jewish Parkinson’s disease patients with the LRRK2 G2019S mutation seem to be at higher risk for nonskin cancers.
Cancer patterns in patients with Parkinson’s disease differ from those of the general population for unknown reasons. Rivka Inzelberg, MD, from the Sheba Medical Center in Tel Hashomer, Israel, examined germline mutations in the LRRK2 gene associated with the most common autosomal dominant form of Parkinson’s disease to find the differences.
The study examined 490 consenting Jewish patients with Parkinson’s disease who were genotyped for the predominant G2019S mutation in the LRRK2 gene. Oncologic data were obtained by personal systematic questioning before DNA sampling and confirmed by reviewing patient files. Logistic regression models were applied to predict the occurrence of cancer among LRRK2 carriers versus noncarriers using the following variables: age, gender, LRRK2 status, and ethnic group (Ashkenazi/non-Ashkenazi).
Results showed that 79 patients (39 females) carried the G2019S mutation. Seventy-seven (16%) patients had a cancer; of those, 2% had two primary cancers. Nonskin cancers were observed in 18 (23%) of LRRK2 carriers versus 49 (12%) of noncarriers.
David Grimes, MD, of the Ottawa Hospital Civic Campus stated, “Epidemiologic evidence has demonstrated that individuals with Parkinson’s disease have a higher risk of skin cancer (especially melanoma) and a lower incidence of many other cancers. The reason for this difference remains a mystery, but changes in the function of Parkinson’s disease–causing genes have been proposed. This study suggests that LRRK2 may be one of those factors and raises the question of whether this gene may have implications for cancer risks in general. However, the higher rate of only nonskin cancers in LRRK2 mutation–positive Parkinson’s disease individuals doesn’t explain the higher rate of melanoma seen in Parkinson’s disease individuals. Therefore, LRRK2’s potential role as a cancer predisposition gene needs to be explored in a much larger population prior to being implicated with certainty.”
Early Dietary Treatment of Galactosemia May Not Prevent Movement Disorders
Movement disorders, mainly in the form of dystonia and tremor, are a frequent complication of adult patients with galactosemia, despite early and adequate treatment, according to researchers who investigated the two conditions. The study authors reported no correlation with systemic complications.
Ignacio Rubio-Agusti, MD, from the Sobell Department for Movement Disorders at the Institute of Neurology in London, led the study, which found that patients with the rare metabolic disorder galactosemia can develop a movement disorder or other neurologic problems, despite early dietary treatment of the disease.
The study analyzed 18 patients, all of whom had been diagnosed early in life and placed on a restricted diet since diagnosis. Despite early treatment, many of the patients still experienced neurologic complications and, in some cases, developed a movement disorder. Therefore, according to the researchers, dietary treatment alone is not adequate to prevent neurologic problems when treating patients with galactosemia.
Jonathon Mink, MD, PhD, Professor of Neurology at the University of Rochester in New York, added to these findings by stating, “With the implementation of newborn screening for inborn errors of metabolism, individuals with certain previously devastating diseases are now living well into adulthood. In galactosemia, early treatment with a galactose-restricted diet reduces the toxic burden of accumulated galactose and its metabolites, but does not reverse the enzyme deficiency. Dr. Rubio-Augusti reported the important finding that a substantial number of adults with diet-treated galactosemia develop neurologic complications, with the majority manifesting a movement disorder. These findings indicate that early diagnosis and treatment with dietary restriction is not sufficient to prevent long-term neurologic complications in up to half of affected adults. It is unknown whether other types of intervention may reduce the risk of these complications.”
Inhaled Apomorphine Reduces ‘Off’ Periods in Parkinson’s Disease
Results of a phase II study indicate that inhaled apomorphine rapidly aborts “off” periods in patients with Parkinson’s disease. Although apomorphine is effective as a subcutaneously injection, Katherine A. Grosset, MD, of the Institute of Neurological Sciences in Glasgow, United Kingdom, investigated a noninvasive, oral inhalation for the potential additional advantages of improved safety, local tolerability, and rapid benefit.
Inhaled apomorphine was tested under double-blind, placebo-controlled, randomized conditions in patients with Parkinson’s disease who had motor fluctuations and recognizable “off” periods. Four ascending doses of the investigational product in a pre-metered inhaler were tested in the clinic to establish therapeutic benefit. The patient then administered this dose at home for four weeks to abort “off” episodes. Results demonstrated that patients with Parkinson’s disease experienced significant improvement in the UPDRS III with apomorphine but not placebo. They also experienced reduced “off” periods and more aborted “off” periods.
Andrew Lees, MD, of Reta Lila Weston Institute of Neurological Studies in London, commented, “Inhaled apomorphine is a quick-acting, reliable rescue device for patients with debilitating ‘off’ periods in Parkinson’s disease. If further trials confirm its long-term safety, then it is likely to replace subcutaneous apomorphine injections and also be suitable for patients who are unable or unwilling to inject themselves.”