Managing Motor And Nonmotor Symptoms In Advanced Disease
Most patients respond well to levodopa however, in 40%50% of patients, motor fluctuations and dyskinesias will develop within five years of chronic levodopa treatment and in 70%80%, after 10 years of treatment.34,82,83 Motor fluctuations are unexpected variations in the motor response, which may be erratic, to dopaminergic therapy, whereas dyskinesias are unwanted and intrusive, predominantly choreiform, movements resulting from levodopa .84 Dyskinesias are less likely to develop in patients receiving less than 400500 mg per day of levodopa.85 A higher cumulative incidence of dyskinesias, wearing off and onoff fluctuations in symptoms occurs in patients with early-onset disease and perhaps in women .24,61,82,86,87 Dyskinesias may indicate better response to medication, and most patients prefer to be on with dyskinesia than off.87
In advanced Parkinson disease, many disabling nonmotor symptoms emerge that are not improved by levodopa.42 Nonmotor symptoms and their management are reviewed in Appendix 3.
What Is Integrative Medicine
Integrative medicine is a medical approach that integrates aspects from other healthcare systems Ayurveda, traditional Chinese medicine, etc. along with Western approaches . It is a system of care that attempts to activate the bodys innate healing process rather than relying on cure-oriented medicine.
There is an understanding that the mind and body can be incredibly resilient and that they are fundamentally connected. It speaks to the World Health Organizations definition that health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.
It includes a holistic, lifestyle-oriented approach, emphasizing health promotion and prevention. It places the patient and their loved ones in the center of the circle of care with the team of providers working together around them as partners in the healing process.
Latest News In Parkinson Disease: Treatment Progress Cognition Improvements And More
An overview of the latest news in Parkinson disease reported across MJH Life Sciences.
An overview of the latest news in Parkinson disease reported across MJH Life Sciences.
FDA Approves Investigational NDA for Ketamine in Levodopa-Induced Dykinesia
As the gold standard of treatment for PD, levodopa effectively reduces parkinsonian symptoms, although long-term use has been linked with several adverse events. Chief among these, frequency of OFF time and abnormal involuntary movements, known as levodopa-induced dyskinesia , have been shown to significantly impact quality of life and treatment efficacy.
There are no approved treatments to address LID however, an article by NeurologyLive® indicates there may be some progress in addressing this issue. Last week, the FDA approved PharmaTher Holdings investigational new drug application for ketamine, an N-methyl-D-aspartate receptor-modulating drug, in the treatment of LID in patients with PD.
A phase 2 clinical trial evaluating the safety, efficacy, and pharmacokinetics of ketamine compared with the active control treatment of midazolam is expected to begin patient enrollment in the third quarter of this year. Pending success, the manufacturer noted that it will seek an agreement with the FDA to proceed to a phase 3 clinical study next year.
Neurological Disease Link With COVID-19 Severity, Death
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Aptinyx Focuses On Parkinsons Disease Cognitive Impairment
Aptinyx is amid a Phase II trial targeting one of the biggest unmet needs in Parkinson’s disease treatment: cognitive impairment and dementia.
In patients with PD, Lewy bodies and alpha-synuclein, which are implicated in the pathology of PD, can spread into the cortex, causing forms of cognitive impairment and dementia in a large percentage of patients, Kordower explains. Theres no current treatment, so any clinical trial that has some benefit is incredibly valuable, he says.
Aptinyxs NYX-458, which targets the N-methyl-D-aspartate receptor, has placebo-controlled Phase II results expected at the end of 2022 or early 2023. The trial lists eight primary endpoints, ranging from the incidence adverse events to reductions in scales of psychosis and suicidal ideation.
“There’s no current treatment, so any clinical trial that has some benefit is incredibly valuable.”
Jeffrey Kordower
Targeting NMDA is a good start, says Dr David Eidelberg, neurologist at the Feinstein Institutes for Medical Research. However, showing reduction in cognitive impairment may be more difficult in PD than in Alzheimers disease, where changes are typically more pronounced, he notes.
Nevertheless, experts are encouraged that a trial is taking aim at this substantial unmet need. According to GlobalData consensus forecasts, NYX-458 has expected peak sales of $323 million in 2028.
Mickan Against Parkinsons Gala Dinner 2019
At The Mickan against Parkinsons Adelaide, SA. Congratulations to Ms.Nassaris and the team at Adelaide Oval for putting this together .Thanks for inviting Mr Girish Nair as a speaker for the event to speak about his involvement in Mr. Mickans care as a treating Neurosurgeon
Thanks for having Neuroaxis at this event celebrating a true Champion in footy and in the fight against Parkinsons. We are proud to be part of Marks Parkinson journey.
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What Has Changed In The Treatment Of Advanced Parkinson Disease
In advanced Parkinson disease, the efficacy of levodopa can decline and fluctuate throughout the day switching between on and off medication periods.92 The motor and nonmotor fluctuations mirror those seen in levodopa plasma concentrations resulting from levodopas short half-life.93 Providing continuous dopaminergic stimulation is the goal of treating fluctuations in patients with advanced Parkinson disease.9496 We now have surgical options, including deep brain stimulation and levodopacarbidopa intestinal gel, to provide treatment to such patients. Currently, deep brain stimulation has the highest level of evidence with the largest number of randomized controlled trials.97 Emerging therapies currently being studied in Parkinson disease are listed in Appendix 7, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.151179/-/DC1.
Editorial Note On The Review Process
F1000 Faculty Reviews are commissioned from members of the prestigiousF1000 Faculty and are edited as a service to readers. In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions .
The referees who approved this article are:
- Fredric P. Manfredsson, Parkinson’s Disease Research Unit, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USANo competing interests were disclosed.
- Tipu Z. Aziz, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKNo competing interests were disclosed.
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Forced Cycling: Beneficial For People With Severe Motor Symptoms
Findings from researchers in the US have revealed that high-cadence dynamic cycling in which people cycle on stationary bikes programmed to intermittently quicken pedal speed may help to ease motor symptoms in people with Parkinsons.
Scientists at Kent State University in Ohio analysed data from 31 patients who had undergone this intervention, and identified that those with the most severe motor symptoms determined by a higher score on the Unified Parkinsons Disease Rating Scale were more likely to experience improvements.
What Is The Pathophysiology Of The Disease
Parkinson disease is a neurodegenerative syndrome involving multiple motor and nonmotor neural circuits.8,9 It is characterized by two major pathologic processes: premature selective loss of dopamine neurons the accumulation of Lewy bodies, composed of -synuclein, which become misfolded and accumulate in multiple systems of patients with Parkinson disease. It is unclear which process occurs first. Based on pathologic studies,10 there is a stepwise degeneration of neurons over many years, with each affected site corresponding to specific symptomatology in Parkinson disease . When motor symptoms become evident, there is 3070% cell loss evident in the substantia nigra on pathologic examination.11 The mainstay of therapy aims to replace dopamine with dopaminergic medications and modulate the dysfunctional circuit. Cognitive dysfunction, mood disorders and impulse control disorders are related to deficits of dopamine outside the basal ganglia or in serotonergic and noradrenergic systems.12,13 Autonomic dysfunction has been related to pathologies outside the brain, including the spinal cord and peripheral autonomic nervous system.14
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Patients Depression Often Carries Over To Care Partners
More disability and higher levels of depression in Parkinsons disease patients predicted an increase in burden and depression of their care partners, such as family and friends, over two years, a study concluded. The findings underscore the need to monitor the burden of care partners over time. Treatment targeting disease severity,
Fight Against Migraine Symposium 2018
In August 2018, Girish Nair was invited to speak at the Fight Against Migraines conference held in Melbourne. He is pictured here with Dr David Dodick, a world leader in the field of headache and migraine.
Former AFL player, Mark Mikan was diagnosed with Parkinsons disease in 2016. Until recently, he experienced debilitating tremors in his hands and feet. His symptoms have been greatly reduced since undergoing brain surgery. Find out about the operation using the latest in deep brain stimulation technology.
A new surgical technique lead by neurosurgeon Girish Nair is having a remarkable impact on the symptoms of Parkinsons disease. The new and improved deep brain stimulation therapy uses 3D printed equipment that is fitted to the patients head. This results in a faster, more accurate and ultimately less intimidating operation for the patient. Previously any patient undergoing deep brain stimulation would be secured to an operating table with a cumbersome head frame. They were often kept awake for the operation which lasted many hours making the treatment almost intolerable.
In a world first, stem cells have been injected into the brain of a Parkinsons disease sufferer as part of an experimental treatment in Melbourne.
Interviewees: Mr Girish Nair, Neurosurgeon & Dr Andrew Evans, Neurologist
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Irlab Celon Target Parkinsons Disease Motor Symptoms
While levodopa can reduce PD symptoms by increasing dopamine levels in the brain, prolonged use can cause increased bouts of dyskinesia during OFF time when the drug has reduced effects. IRLAB Therapeutics and Celon Pharma have Phase II trials aiming to reduce levodopa-induced dyskinesia using two different approaches.
IRLABs mesdopetam, which targets the dopamine D3 receptor, has placebo-controlled Phase II trial results expected the second half of this year. Mesdopetam has estimated peak sales of $226 million in 2026, according to GlobalDatas consensus forecast. GlobalData is the parent company of Clinical Trials Arena.
As a primary endpoint, the Phase II mesdopetam trial assesses change in ON time, defined as hours in the day where patients experience the positive effects of levodopa without the negative effects of dyskinesia. Before and after 12 weeks of treatment, patients record their hours of ON time over the course of 24 hours.
Meanwhile, Celon s CPL500036, which targets phosphodiesterase 10A , also has placebo-controlled Phase II results expected this year. The four-week study uses a primary endpoint of the Unified Dyskinesia Rating Scale , which measures the severity of dyskinesia side effects.
Of the two primary endpoints, change in ON time is a better measure than the UDyRS, Kordower says. My understanding is that patients would much rather have less time spent in dyskinesias than decreased magnitude of dyskinesia, he explains.
What Misunderstandings About Integrative Medicine Would You Like To Dispel In Regard To Parkinsons
Integrative medicine used to be known as complementary and alternative medicine, and a lot of people think that means that we do not value standard Western approaches. The point is to marry the best of both worlds.
I am a strong believer in optimizing medications such as levodopa and then adding on lifestyle approaches such as a solid exercise plan or a mind-body approach such as yoga to get the best of both worlds. I do not try to keep people off of levodopa replacement if it is indicated due to motor issues that would get in the way of exercise or social connection.
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Exploring Seven Recently Approved Parkinsons Treatments
Remarkably, in the last five years, seven new medications have been approved for the treatment of the motor symptoms of Parkinsons disease , with two approved in 2020. Thats exciting progress! And while it is great to have so many choices, the various options can be confusing so today I will describe these new medications and their uses.
Advances In Deep Brain Stimulation
Deep brain stimulation is another established treatment for PD that is useful in treating dopamine-dependent motor symptoms when levodopa-induced side effects become particularly problematic. DBS involves the surgical implantation of electrodes that stimulate subcortical structures including the subthalamic nucleus and globus pallidus internus9194. DBS offers significant improvements in motor symptoms and fluctuations in comparison to best medical therapy in some advanced PD patients, but dopamine-resistant symptoms other than tremor respond poorly95. It has also been suggested in an open-label trial that DBS is beneficial in early PD patients, with improved tremor scores and reduced development ofde novo tremor96. In addition to surgical complications, DBS strategies may cause cognitive and neuropsychiatric adverse effects as well as speech dysfunction. Novel DBS approaches, including adaptive DBS, targeting different regions, and refined intra-operative imaging techniques promise to offer improved clinical applicability and reduce the impact of adverse effects97.
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Older Age Low Physical Activity Linked With Faster Motor Decline
An older age at diagnosis, but also reduced physical activity due to medical or social conditions, were significantly linked with faster motor decline in people with Parkinsons disease, a Japanese study has found. According to its authors, maintaining daily physical activity and allowing patients to move freely is paramount
Neuroaxis In The Media
The highly skilled neurosurgeons at Neuroaxis are known around the world for being highly skilled in their field. Here you will find media coverage recognising the contribution of our neurosurgeons to find new innovative ways of treating patients.
While we are dedicated to furthering medical research and being part of breakthrough, pioneering treatments, we also care deeply about our community of patients. Youll find details of our charity commitments to help support the conditions many of our patients suffer from.
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Are There Generally Helpful And Safe Forms Of Integrative Medicine You Tend To Recommend To Parkinsons Patients
In Parkinsons disease, lifestyle approaches make a lot of sense to incorporate early on from diagnosis. Sleep, exercise, a Mediterranean diet, social connection, and mind-body approaches are all things that most clinicians would agree make sense in Parkinsons, but there is not a lot of formal data on these approaches and most clinicians still focus on pharmacological and surgical treatments of Parkinsons.
My main focus has been on the mind-body approaches in Parkinsons, including meditation, breath work, yoga, and tai chi. I feel these hold a lot of promise for our patients, especially in treating nonmotor issues and mental health issues in Parkinsons.
What Is The Prognosis
Life expectancy is decreased in Parkinson disease , and medical treatments do not appear to alter mortality or delay the onset of nonmotor symptoms.114 Although progression is slower in patients with early-onset disease and there is longer absolute survival, this comes at the expense of increased years of life lost .24,115 Late-onset Parkinson disease is associated with more rapid disease progression and cognitive decline,116 which may be related to a lack of compensatory strategies against cell death.24 Data on the long-term outcomes and in the older population are lacking.117
Prognostic factors are summarized in Table 4. Patients with early-onset disease were slower to reach stage IIIV on the Hoehn and Yahr scale119 . The distribution of Hoehn and Yahr staging according to disease duration is listed in Appendix 8b. In the Rotterdam Study, Parkinson disease was associated with an increased risk of dementia and increased risk of death . When dementia prevalence was controlled for, risk of mortality was only slightly higher than among the general population.120
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Impact On Families And Carers
Informal carers spendmany hours dailyproviding care for people living with PD.This can be overwhelming. Physical, emotional and financial pressures can cause great stress to families and carers, and support is required from the health, social, financial and legal systems. Useful support resources from other conditions can be drawn upon, such as WHOs iSupport programme for dementia.
Brain Ultrasound Signals Linked To Motor Disability Gait
Enhanced ultrasound signals in the substantia nigra, the area of the brain impacted by Parkinsons disease, are associated with increased motor disability and gait disturbances, a study concluded. The researchers noted that these ultrasound signals, called hyperechogenicity, may be useful a biomarker that reflects disease severity. Our results may
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What In Integrative Medicine Research Makes You Most Hopeful For The Parkinsons Population
I am very excited to see more and more evidence for things like exercise and mind-body approaches. Increased study in the area of social connection is also huge, given the pandemic. Hopefully we can use telehealth technologies to connect patients to these modalities and include social connection to make these more accessible to all people with Parkinsons worldwide.
Expert Voices is a monthly series involving a Q& A with an expert in the Parkinsons space about a specific topic. These topics and questions are curated from a survey in which we ask readers what they want to learn more about from experts. If youd like to submit topics or questions for consideration in a future installment of the series, click here to take the survey.
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