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Spinal Cord Stimulation Fails to Improve Mobility in Advanced Parkinson’s Patients

spinal cord stimulation trial

Despite being safe, spinal cord stimulation does not lead to significant improvements in mobility in patients with advanced Parkinson’s disease, including those taking levodopa, a prospective trial has found.

The trial findings were reported in the study, “Spinal Cord Stimulation for Very Advanced Parkinson’s Disease: A 1-Year Prospective Trial,” published in the journal Movement Disorders.

Like deep brain stimulation (DBS), spinal cord stimulation (SCS) is a form of treatment that involves implanting a small device that sends electrical signals. In the case of SCS, these electrical signals go through nerves in a patient’s spinal cord, masking pain signals before they reach the brain. This form of therapy is approved in the U.S. for treating chronic pain.

Lately there has been increasing interest in SCS as a form of treatment for Parkinson’s, based on data from studies reporting that patients who underwent SCS experienced improvements in their gait and motor function.

To explore the therapeutic potential of SCS at alleviating Parkinson’s motor symptoms, researchers at the University of Toronto in Canada conducted a prospective, open-label trial in which they assessed the safety and effectiveness of the therapy in six pain-free patients with advanced disease.

Trial participants — three men and three women, ages 31–76, who had Parkinson’s for 12–18 years — underwent surgery to have two cylindrical electrodes implanted. After surgery, all patients were followed for a period of one year.

The Unified Parkinson’s Disease Rating Scale (UPDRS) and the freezing of gait (FOG) questionnaire were used to evaluate patients’ motor function and gait impairments, respectively. Assessment evaluations were performed in all patients before, one, three, six, and 12 months after surgery.

Apart from one patient who had a temporary delirium episode after surgery, none of the study participants experienced any adverse side effects.

However, SCS had no significant effects on patient’s motor function, balance, or gait, at any time-point. Additionally, investigators found no evidence suggesting that SCS could work together with levodopa at alleviating motor symptoms of the disease.

“Despite the (…) promising outcomes reported in short, small, and open-label PD [Parkinson’s disease] studies, our study confirms safety but shows no clinically meaningful effect on patientsmobility, particularly while on L-dopa, thus failing to improve the motor signs resistant to dopaminergic treatment,” the researchers wrote.

“[W]e need further studies, enrolling larger samples and using a double-blind design, which will be possible thanks to more recent SCS modalities (e.g., burst stimulation), [to assess the therapeutic potential of SCS for Parkinson’s disease],” they added.

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Parkinson’s Symptoms May Help to Judge Ability to Do Daily Tasks

motor skills

The clinical symptoms experienced by people with Parkinson’s disease, like dyskinesia or postural instability, may help to distinguish and group patients whose ability to perform daily activities are more or less affected, a new study suggests.

These findings were detailed in, “Can We Predict the Motor Performance of Patients With Parkinson’s Disease Based on Their Symptomatology?,” a study published in Frontiers in Bioengineering and Biotechnology.

Parkinson’s is characterized by motor symptoms like tremor, slowness of movement (bradykinesia), uncontrolled involuntary movement (dyskinesia), and postural instability, as well as by non-motor symptoms like sleep problems and cognitive decline.

These symptoms affect to differing degrees a person’s ability to go about activities of daily life. But currently there is no way of knowing how a person’s symptoms, taken together, correlate with an ability to perform daily tasks requiring motor skills.

To investigate this, researchers at the Université de Sherbrooke, in Canada, assessed symptoms and motor performance in a group of 115 Parkinson’s patients, mean age of 67, without psychosis and who could walk without assistance. A group of 69 elderly individuals without this disease, matched by age and sex, served as controls.

At examination, patients were asked to take their regular medication and were equipped with a suit containing 17 sensors to objectively measure their motor symptoms.

All were then asked to perform three motor tasks: rising from a chair, walking, turning, sitting down (the Timed-Up and Go, or TUG, test), eating soup, and inserting pins into a board using both hands, alternately, for 30 seconds (the Purdue Pegboard test). They also answered a questionnaires providing socio-demographic data, as well as information about their cognitive health and quality of life.

Based on patients’ performance on the three motor tasks, researchers broke them into four groups: those within normal range for all tasks (group 1), those whose fine motor skills (or dexterity) were slightly affected (group 2), those mainly affected on the TUG test (suggesting limited mobility; group 3), and patients affected in all these activities (group 4).

Notably, some symptoms and medications were significantly different among groups, including postural instability, dyskinesia, bradykinesia, rigidity, freezing of gait, and the use of amantadine (marketed as Gocovri, among other brand names).

An increase in postural instability was found to be linked to a four to nine times greater likelihood of poor performance in the TUG test or in all activities (assignment to groups 3 or 4), the researchers reported. Low-to-moderate dyskinesia increased the chances of being in the normal group (relative to the groups 2 or 3, those slightly affected in fine motor tasks or mainly affected during TUG).

Higher levels of rigidity increased the likelihood of being affected in all activities (group 4).

Amantadine as part of a treatment regimen was seen to lower the risk of being in the group 3 (limited mobility).

The model showed a good accuracy overall, being able to place 76% of patients in their correct motor group based solely on their symptoms and medication. But researchers suggest that the grouping of patients according to their motor performance on tests could be further refined; the soup eating test, for instance, was not seen to be relevant in this classification.

Still, “this study demonstrated that it is possible to predict the mobility performance of any patient, based on personal clinical features,” the researchers wrote.

“[T]hese results appear promising, and may lead to more personalized treatment by identifying and targeting symptoms that specifically impede a particular patient’s motor performance,” they concluded.

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Fatigued Patients Walk Slower, Endure Shorter Distances, Study Finds

fatigue, walking problems

Fatigue may compromise and predict Parkinson’s patients’ mobility and their ability to walk over long distances, according to a recent study.

The results of the study, “Can fatigue predict walking capacity of patients with Parkinson’s disease?” were published in Arquivos de Neuro-Psiquiatria.

Lack of energy, or fatigue is one of the most common — and most disabling — symptoms in Parkinson’s disease (PD), and has a significant impact on patients’ quality of life.

“Although fatigue is an important symptom in PD, only few studies have assessed its association with mobility, walking capacity, and physical activity in patients,” the researchers noted.

Fatigue has been shown — following freezing of gait and general self-walking difficulties — as the third strongest factor that independently contributes to walking problems among people with Parkinson’s. Freezing of gait is a Parkinson’s motor symptom in which a person’s feet feel like they’ve become briefly “glued to the floor,” preventing forward movement despite an intention to walk.

A team of Brazilian researchers now investigated whether fatigue can predict mobility and walking capacity among people with Parkinson’s.

A total of 48 patients — 27 men and 21 women, mean age 67.2 years — were involved in the study, with 22 diagnosed with fatigue as measured by the Parkinson’s Fatigue Scale. All had their mobility and walking capacity tested using clinically validated tools, namely the Timed Up and Go or TUG test, the 10-Meter Walk Test (at usual and fastest speed), and the 6-Minute Walk Test, or 6WMT. The 6WMT assesses the distance a person walks over six minutes as a measure of aerobic capacity and endurance. The 10-Meter test, which measures walking speed over a short distance, is used to determine functional mobility, gait, and vestibular function, located in the inner ear.

Compared with the non-fatigued patients, individuals with fatigue were older, had worse cognitive functions, more severe and advanced disease, higher motor impairment (as assessed by higher scores on the UPDRS scale), and higher levels of functional dependence according to the Schwab and England Activities of Daily Living Scale.

Fatigued patients also walked slower. The results showed they had smaller comfortable and maximum gait speeds and distance covered during the 6MWT than participants without fatigue.

Among all participants, 31.2% spent more than 16 seconds performing the Timed Up and Go test, which indicates an increased risk of falling.

Fatigue, age, and motor symptoms were found to predict the participants’ endurance and their ability to walk over longer distances, as measured by the 6-Minute Walk Test, with fatigue being the most significant predictor.

According to the researchers, a study limitation was that any links between antidepressants intake — known to influence Parkinson’s patients — and non-motor symptoms were not assessed.

“From a clinical perspective, our results suggest that fatigue may reduce functionality in everyday activities of PD patients and prolong periods of sedentary behaviors. This is particularly important seen that PD-related fatigue is one of the most common and disabling symptoms in these patients,” the researchers said.

“Our results highlight the importance of recognition and management of this symptom,” the team concluded.

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Deleting Specific Region of Alpha-Synuclein Protein May Prevent Parkinson’s Symptoms, Fly Study Suggests

alpha-synuclein study

By deleting a section of alpha-synuclein, a protein that forms damaging clumps in the brains of Parkinson’s disease patients, researchers were able to prevent Parkinson’s-like symptoms in fruit flies, a study reports.

The study, “The Non-amyloidal Component Region of α-Synuclein Is Important for α-Synuclein Transport Within Axons,” was published in the journal Frontiers in Cellular Neuroscience.

Parkinson’s disease is characterized by the buildup of toxic forms of the alpha-synuclein protein within nerve cells, or neurons, causing clumps and blockages that stop these cells from functioning correctly.

Proper transport of alpha-synuclein is thought to be crucial for its localization and function at the synapse — the junction between two nerve cells that allows them to communicate.

A particular section of the alpha-synuclein protein called the non-amyloidal component (NAC) has been linked to the formation of these clumps.

“Previous work has shown that defects in long distance transport within [neurons] occur early in PD [Parkinson’s disease], but how such defects contribute to PD is unknown,” the researchers wrote.

To understand whether the NAC region is involved in alpha-synuclein’s motility, researchers used fruit fly larvae genetically engineered to express higher levels of the human form of alpha-synuclein protein. They then deleted the NAC region in these flies’ alpha-synuclein and studied the resulting animals for signs of Parkinson’s disease.

They observed that excess alpha-synuclein accumulated in clumps and disrupted the normal transport of other proteins along neuronal axons — long projections that conduct electrical impulses away from the neuron’s cell body toward another nerve cell.

To understand how deleting the NAC region affected motor symptoms, the scientists measured how fast the flies were able to crawl. Flies with too much alpha-synuclein crawled at a significantly slower speed than normal flies. This was likely due to the blockages that occur in the neurons. The higher the levels of alpha-synuclein aggregation within neurons, the more aggravated these symptoms became.

Flies that produced too much alpha-synuclein typically showed Parkinson’s-like symptoms, but if the NAC section of alpha-synuclein was deleted, the protein no longer formed clumps within neurons and crawling speeds returned to normal.

“Our work highlights a potential early treatment strategy for Parkinson’s disease that would leverage the use of deletion of the NAC region,” lead investigator Shermali Gunawardena, PhD, associate professor of biological sciences from the University at Buffalo, said in a press release.

Gunawardena and her team were also interested in how alpha-synuclein gets transported along neuron cells. The researchers thought the movement of alpha-synuclein could be linked to how it interacts with neuronal cell membranes.

They found that when they deleted the NAC region, less alpha-synuclein was able to bind to neuronal membranes, preventing it from being transported along axons. Instead, the alpha-synuclein stayed in the wider sections of neurons and did not cause aggregates.

“While further study is needed to isolate the structural details of how the NAC region facilitates [alpha]-syn protein–protein interactions on membranes, taken together our observations indicate that the NAC region plays an essential role in [alpha]-syn associations on axonal membranes and its transport within axons under physiological conditions,” the researchers wrote.

Overall, the work identifies a pathway that can be targeted in early-stage Parkinson’s disease before symptoms such as neuron loss and behavior changes occur.

“One reason this study is important is because it shows rescue of [alpha]-synuclein aggregates, synaptic morphological defects and locomotion defects seen in Parkinson’s disease in the context of a whole organism,” Gunawardena said.

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After a Nasty Fall, I Think of Those Who Came to My Aid

kindness of strangers

We must accept finite disappointment but never lose infinite hope.” –Martin Luther King Jr.

Fallen, again

Not even two weeks after I put the finishing touches on my walking with mindfulness column, I had a very nasty fall. My first fall occurred in July 2017. Since my left foot tends to drag, I find I must focus on how I am walking so that I don’t trip. As I was heading to my car, my mind was going a mile a minute thinking about what I needed to do that day. I was not remaining in the present moment.

Lost in thought, I was not mindful of my walking, tripped, and did a face-plant on the sidewalk. As I lay on the ground wondering what just happened, I remember hearing voices asking if I was OK. As I sat up, blood poured from my face and I found myself surrounded by concern and compassion.

What do I remember?

Most of what happened in the moments surrounding the time I fell is still a blur. What I do remember is a few people crowding around me. There was a police officer, a local postal employee who also is an EMT, a man who gave me his handkerchief to stem the blood flow, and someone who ran to the drugstore to get bandages and peroxide. I am still overwhelmed with gratitude for the support of these strangers. I will say it once again, kindness matters. It was such a time of great vulnerability for me, and through the caring and concern of these strangers, I did not feel so alone.

“Remember there’s no such thing as a small act of kindness. Every act creates a ripple with no logical end.” –Scott Adams

Emotional and physical pain

As I drove myself to the emergency room, I broke down in tears. This was partly because of the pain, but more due to the fact that I believe my Parkinson’s disease may be progressing. Luckily, I only had some minor swelling, a few cuts and bruises, and a chipped tooth. However, my emotional healing is taking longer than my physical recovery from this fall.

Lessons learned

  1. Practice what I preached in my previous column.
  2. Remember the kindness of strangers that day, which has helped me to physically heal.
  3. I am not alone.
  4. I need to accept the fact that my mind moves a lot faster than my body and I no longer can multitask. I must pay attention to the task at hand.

If you can’t fly, run; if you can’t run, walk; if you can’t walk, crawl; but by all means keep moving.” –Martin Luther King Jr.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Hydrotherapy Improves Balance, Mobility in Parkinson’s Patients, Study Reports

hydrotherapy

Hydrotherapy may provide significant balance and mobility benefits in patients with Parkinson’s disease compared to medication and land-based exercises, according to a review study.

The research, “The Effects of Hydrotherapy on Balance, Functional Mobility, Motor Status, and Quality of Life in Patients with Parkinson Disease: A Systematic Review and Meta-analysis,” was published in the journal PM&R.

Impairments such as muscle rigidity and tremor affect the balance and mobility of people with Parkinson’s. Combined with fear of falling, it promotes a sedentary lifestyle and reduces quality of life.

Water-based exercise is often prescribed to these patients, providing a safe environment that reduces the risk of falling. Prior studies have reported that hydrotherapy improves motor symptoms. However, the evidence about  hydrotherapy as a treatment strategy in Parkinson’s is scarce.

To address this gap, researchers conducted a systematic review of the available scientific literature and a meta-analysis — a type of statistical analysis that combines the results of various studies.

The scientists focused on hydrotherapy’s effectiveness on patients’ balance, mobility, quality of life and motor function.

For this purpose, the investigators searched seven online databases as well as unpublished or ongoing clinical trials from inception through December 2017. Nineteen studies were identified, of which eight were randomized controlled trials (RCTs). Overall, the studies had 484 participants, with a mean age ranging from 54 to 78 years and an average disease duration ranging from three to 10 years.

The studies had different designs, which included comparisons of hydrotherapy with land-based exercises or medications, combinations of hydrotherapy with land-based therapy, and assessments of low-intensity and muscular resistance water-based exercises.

Hydrotherapy could include balance training, stretching, strengthening, trunk mobility, and gait exercises. The sessions ranged from 40 to 60 minutes, one to five days per week, for three to 20 weeks, for a total of eight to 60 sessions. Water temperature was set between 28ºC (82ºF) and 34ºC (93ºF) in the 12 studies that reported this parameter.

All but two studies with available information on levodopa usage evaluated patients’ in the “on” phase, which refers to the period when this medication is effective and has not yet worn off.

The meta-analysis on balance and mobility included five RCTs, which had a total of 133 patients. The results showed that hydrotherapy with or without land-based exercises significantly improved both balance and mobility compared to land-based therapy or usual care with medication alone.

Three other studies not included in the meta-analysis due to lacking a control group also found significant benefits with hydrotherapy in balance. One RCT not included in the statistical comparison did not report differences with hydrotherapy and land-based therapy, while another showed that aquatic obstacles training is more beneficial for balance than traditional water-based exercises.

In turn, two RCTs not included in the respective analysis failed to show mobility improvements with hydrotherapy.

As for quality of life, an analysis of three RCTs with 76 patients showed no benefits with hydrotherapy compared to land-based treatment, which the researchers attributed to the small number of studies included. This also was observed in one RCT not included in the meta-analysis. In contrast, five other studies, including two non-randomized trials, found significant improvements with water-based treatment.

Results of a meta-analysis of five RCTs with 140 patients also did not reveal improvements in motor function in comparison to land-based exercise. This can be explained by patients having types of motor complications not expected to improve with hydrotherapy, the team said.

Of note, two other RCTs and a non-randomized trial also did not find different results with hydrotherapy compared to other approaches in motor function.

Overall, the scientists wrote, “hydrotherapy, combined or not with other therapies, may improve balance and functional mobility of patients with [Parkinson’s] when compared to land-based therapy alone or usual care.”

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