Diagnostic tool

I thought this was so cool, I wanted to share it when I saw it this morning. I just cut and pasted the entire article from Parkinson’s News Today, an online forum. And it reminded me of the first time I met a movement disorder specailist, she took one look at me and said: “YES, you have Parkinson’s” I asked her how she could be so sure, we just barely met. She said:” Your facial mask, your arms don’t swing when you walk, and now that I’ve heard you speak, your soft voice.” I asked her what she meant by mask. She explained that PwP loose the ability to show much emotion.

I’d like to see them do a second study with people with ‘early onset Parkinson’s I’d like to see the medical profession be aware of a diagnostic tool to assist, when they are stumped to determine a cause for unexplainable symptoms. There may soon be a tool to assist in diagnosing or ruling out.


From Parkinson’s News Today Marta Figueiredo PhD | September 13, 2021

An artificial intelligence (AI) tool was able to distinguish, with great accuracy, Parkinson’s patients from healthy peers by analyzing short videos of facial expressions, particularly smiles, a small study shows.

The predictive accuracy of the new tool was comparable to that of video analysis that uses motor tasks to detect Parkinson’s, pinpointing facial expressions as a potential digital, diagnostic biomarker of the disease.

This type of biomarker could allow remote diagnosis without the need for personal interaction and extensive testing. This would be particularly relevant in situations such as a pandemic, in cases of reduced mobility, or in underdeveloped countries where few neurologists exist but most people have access to a phone with a camera, researchers noted.

The study, “Facial expressions can detect Parkinson’s disease: preliminary evidence from videos collected online,” was published as a brief communication in the journal npj Digital Medicine.

Parkinson’s-associated motor symptoms, such as tremors and muscular rigidity, affect facial muscle movements, leading to overall reduced facial expression, also known as facial masking or hypomimia

An increasing number of studies suggest that reduced facial expressions may be an “extremely sensitive biomarker for [Parkinson’s disease], making it a promising tool for early diagnosis,” the researchers wrote.

In addition, facial expression analysis is a non-invasive tool that only requires a webcam or a phone with a camera, in contrast to the expensive, non-scalable, wearable sensors currently used to analyze movements during motor tasks as digital biomarkers of Parkinson’s.

Now, a team of researchers at the University of Rochester, New York, showed that analyses of facial micro-expressions using an AI tool can accurately detect Parkinson’s.

The study involved the analysis of 1,812 videos, collected online through a web-based tool (Park test), of 604 people (61 with Parkinson’s and 543 without the disease). In these videos, participants were asked to make three facial expressions — a smiling, disgusted, and surprised face — each followed by a neutral face.

Participants’ mean age was 63.9 years, and most of them were white and living in the U.S. Patients with Parkinson’s had been living with a diagnosis of the disease for a mean of 8.4 years.

Changes in muscle movements in each of the three facial expressions were objectively measured and computed in terms of nine action units, or micro-expressions.

In agreement with previous research, the analysis showed that Parkinson’s patients had fewer facial muscle movements than people without the disease. This was particularly significant for three micro-expressions: raising cheeks and pulling the lip corner — typically observed when people smile — and lowering the brows, usually seen when people express a disgusted face.

According to the team, “the smiling facial expression has the greatest potential in differentiating individuals with and without” Parkinson’s, the researchers wrote.

The team then used these differences in micro-expressions to train a machine learning tool to distinguish between individuals with and without Parkinson’s. Machine learning is a form of AI that uses algorithms to analyze data, learn from its analyses, and then make a prediction about something.

In agreement with previous research, the analysis showed that Parkinson’s patients had fewer facial muscle movements than people without the disease. This was particularly significant for three micro-expressions: raising cheeks and pulling the lip corner — typically observed when people smile — and lowering the brows, usually seen when people express a disgusted face.

According to the team, “the smiling facial expression has the greatest potential in differentiating individuals with and without” Parkinson’s, the researchers wrote.

The team then used these differences in micro-expressions to train a machine learning tool to distinguish between individuals with and without Parkinson’s. Machine learning is a form of AI that uses algorithms to analyze data, learn from its analyses, and then make a prediction about something.

They found that their AI tool could correctly identify Parkinson’s patients based on their facial expressions with an accuracy of 95.6%, which is comparable to the 92% prediction accuracy reported for existing state-of-the-art video analysis that relies on limb movements.

“We show that an algorithm’s ability to analyze the subtle characteristics of facial expressions, often invisible to a naked eye, adds significant new information to a neurologist,” the team wrote.

As such, facial expressions, especially smiling, “may become a reliable biomarker for [Parkinson’s disease] detection,” they added.

Dat Scan and Dopamine

Last time I went to the neurologist, I told him, “I do not see any difference between when I take the carb/Levo or don’t take it” He told me to discontinue taking it and “You will see”. Well, I do not see any difference, and I think this article explains why. I intend to take a copy of the article, highlighting the part I have in Bold Blue and underlined. So I am not taking any more dopamine for the immediate future.


“Using advanced computer models, neuroscience researchers at the University of Copenhagen have gained new knowledge about the complex processes that cause Parkinson’s disease. The findings have recently been published in the Journal of Neuroscience.

“The defining symptoms of Parkinson’s disease are slow movements, muscular stiffness and shaking. There is currently no cure for the condition, so it is essential to conduct innovative research with the potential to shed some light on this terrible disruption to the central nervous system that affects one person in a thousand in Denmark.”

“Dopamine is an important neurotransmitter which affects physical and psychological functions such as motor control, learning and memory. Levels of this substance are regulated by special dopamine cells. When the level of dopamine drops, nerve cells that constitute part of the brain’s ‘stop signal’ are activated.”

“This stop signal is rather like the safety lever on a motorised lawn mower: if you take your hand off the lever, the mower’s motor stops. Similarly, dopamine must always be present in the system to block the stop signal. Parkinson’s disease arises because for some reason the dopamine cells in the brain are lost, and it is known that the stop signal is being over-activated somehow or other. Many researchers have therefore considered it obvious that long-term lack of dopamine must be the cause of the distinctive symptoms that accompanies the disease. However, we can now use advanced computer simulations to challenge the existing paradigm and put forward a different theory about what actually takes place in the brain when the dopamine cells gradually die,” explains Jakob Kisbye Dreyer, Postdoc at the Department of Neuroscience and Pharmacology, University of Copenhagen.”

A thorn in the side

“Scanning the brain of a patient suffering from Parkinson’s disease reveals that in spite of dopamine cell death, there are no signs of a lack of dopamine — even at a comparatively late stage in the process.”

“The inability to establish a lack of dopamine until advanced cases of Parkinson’s disease has been a thorn in the side of researchers for many years. On the one hand, the symptoms indicate that the stop signal is over-activated, and patients are treated accordingly with a fair degree of success. On the other hand, data prove that they are not lacking dopamine,” says Postdoc Jakob Kisbye Dreyer.”

Computer models predict the progress of the disease

“Our calculations indicate that cell death only affects the level of dopamine very late in the process, but that symptoms can arise long before the level of the neurotransmitter starts to decline. The reason for this is that the fluctuations that normally make up a signal become weaker. In the computer model, the brain compensates for the shortage of signals by creating additional dopamine receptors. This has a positive effect initially, but as cell death progresses further, the correct signal may almost disappear. At this stage, the compensation becomes so overwhelming that even small variations in the level of dopamine trigger the stop signal — which can therefore cause the patient to develop the disease.”

The new research findings may pave the way for earlier diagnosis of Parkinson’s disease.

Story Source:

Materials provided by University of Copenhagen – The Faculty of Health and Medical Sciences

Swallowing in PD

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson’s Disease Patients    https://pubmed.ncbi.nlm.nih.gov/26041249/


Dysphagia is common in Parkinson’s disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

…………………………………………………………… ncbi.nlm.nih.gov/pmc/articl…

Dysphagia is very common in patients with Parkinson’s disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Unfortunately, current therapies are largely ineffective for dysphagia. As pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD for Lewy pathology. Sensory nerves supplying the pharynx were excised from autopsied pharynges obtained from patients with clinically diagnosed and neuropathologically confirmed PD (n = 10) and healthy age-matched controls (n = 4). We examined: the glossopharyngeal nerve (IX); the pharyngeal sensory branch of the vagus nerve (PSB-X); and the internal superior laryngeal nerve (ISLN) innervating the laryngopharynx. Immunohistochemistry for phosphorylated α-synuclein was used to detect potential Lewy pathology. Axonal α-synuclein aggregates in the pharyngeal sensory nerves were identified in all of the PD subjects but not in the controls. The density of α-synuclein-positive lesions was significantly greater in PD subjects with documented dysphagia compared to those without dysphagia. In addition, α-synuclein-immunoreactive nerve fibers in the ISLN were much more abundant than those in the IX and PSBX. These findings suggest that pharyngeal sensory nerves are directly affected by the pathologic process of PD. This anatomic pathology may decrease pharyngeal sensation impairing swallowing and airway protective reflexes, thereby contributing to dysphagia and aspiration.

Keywords: Alpha-synuclein aggregates, Dysphagia, Glossopharyngeal nerve, Immunohistochemistry, Internal superior laryngeal nerve, Lewy neurites, Nerve degeneration, Parkinson disease, Peripheral nervous system, Pharyngeal sensory nerves, Pharynx, Swallowing, Vagus nerve


Parkinson disease (PD) is a multiple system neurodegenerative disorder characterized by a large number of motor and non-motor features. In addition to the hallmark symptoms (resting tremor, bradykinesia, rigidity, and postural instability), PD patients frequently exhibit a number of secondary motor symptoms such as dysphagia, dysarthria, sialorrhoea, and non-motor symptoms including autonomic dysfunction and sensory abnormalities (). Among these, impaired swallowing and voice/speech represent a large clinical problem in PD as approximately 90% of patients with PD develop these disorders (). It is estimated that there are about 8 million or more people in the world each year that have or will have swallowing and speech disorders (). Unfortunately, treatment outcomes for these disorders have been disappointing. Although anti-PD drugs and deep brain stimulation have significant therapeutic effects on limb motor functions, their effects on swallowing in PD are less impressive, and in some cases, adverse (). Importantly, 25% to 50% of PD patients experience tracheal penetration/aspiration (). Aspiration pneumonia is the leading cause of death among PD patients with dysphagia (). As dysphagia is a challenging clinical issue, an urgent need exists to understand its pathophysiological mechanism for the development of effective therapies.

Despite the extremely high incidence of dysphagia in PD, the exact mechanism of this deficit remains unknown. Oropharyngeal swallowing involves a complex integration of motor and sensory modalities, many of which may be compromised in PD. Therefore, oropharyngeal dysphagia and associated aspiration can be caused by dysfunction of the motor and/or sensory nervous system controlling the upper aerodigestive tract. It is well known that the sensory branches of the glossopharyngeal nerve (cranial nerve IX) and vagus nerve (cranial nerve X) are major contributors to sensory innervation of the pharynx () and play important roles in reflex initiation and modulation of patterned motor behavior (). We hypothesized that oropharyngeal dysphagia may be associated, at least in part, with sensory dysfunction as a result of PD-induced nerve damage. An important aspect of understanding oropharyngeal dysphagia and aspiration is to determine whether the sensory nervous system of upper aerodigestive tract is affected in PD as peripheral sensory mediation of the pharynx and larynx is crucial for triggering swallowing and upper airway protective reflexes.

What I’ve been up to

I just wanted to give y’all an update, related to Covid-19 vs Parkinson’s. I have officially joined in the Pfizer clinical research study.

So please don’t worry about me… “These vaccines do not contain the whole virus, or the parts of the virus that can make you ill., instead the vaccines are made up of part of the virus’s genetic code, surrounded by fatty particles called lipids. They use your own cells’ protein making machinery to produce some, or all, of the spike protein seen on the outside of the virus. This spike protein, made by your own body, may help your own body to produce antibodies to fight against COVID-19. We (they) will check how many antibodies you make by taking blood samples and testing them.”

I will receive two injections 3 weeks apart. There are 6 scheduled times for testing my blood: 1st time was yesterday, prior to when I received the first injection. (I also was given a nasal swab test), when I receive the 2nd injection, then at 1 month, 6 month, 12 month and 24 month. To determine how long the antibodies remain in the body.

They had us download an app on my phone, where we are to maintain our e-Diaries. “Complete the vaccination part of the e-Diary for seven days after each vaccination, once a day in the evening with the first day being the vaccination.” … “The vaccination part of the e-Diary (once per week) will also ask other questions about potential side effects you may have after the injection.”

I am pleased to report I have no redness or swelling at the point of the injection. John had some minor swelling, more like a welt at his injection last night. I had some minor arm pain as I retired last night, which still lingers, but John says he doesn’t feel any discomfort.

Our children have purchased round trip flights, for John and me to have a trip to Utah in October. Being able to receive the vaccine gives me a bit of peace of mind. But we will continue to maintain our distance, wash our hands and wear our masks.

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Of Mice and Men

It remains to be seen if the success with mice can also be incorporated in humans. But the implications from this recent Press Release from the University of California in San Diego are incouraging.

June 24, 2020 | By Heather Buschman, PhD

One-Time Treatment Generates New Neurons, Eliminates Parkinson’s Disease in Mice

Inhibiting a single gene converts many cell types directly into dopamine-producing neurons

Left: mouse astrocytes (green) before reprogramming; Right: neurons (red) induced from mouse astrocytes after reprogramming with PTB antisense oligonucleotide treatment.

Xiang-Dong Fu, PhD, has never been more excited about something in his entire career. He has long studied the basic biology of RNA, a genetic cousin of DNA, and the proteins that bind it. But a single discovery has launched Fu into a completely new field: neuroscience. 

For decades, Fu and his team at University of California San Diego School of Medicine studied a protein called PTB, which is well known for binding RNA and influencing which genes are turned “on” or “off” in a cell. To study the role of a protein like PTB, scientists often manipulate cells to reduce the amount of that protein, and then watch to see what happens. 

Several years ago, a postdoctoral researcher working in Fu’s lab was taking that approach, using a technique called siRNA to silence the PTB gene in connective tissue cells known as fibroblasts. But it’s a tedious process that needs to be performed over and over. He got tired of it and convinced Fu they should use a different technique to create a stable cell line that’s permanently lacking PTB. At first, the postdoc complained about that too, because it made the cells grow so slowly.

But then he noticed something odd after a couple of weeks — there were very few fibroblasts left. Almost the whole dish was instead filled with neurons.  

In this serendipitous way, the team discovered that inhibiting or deleting just a single gene, the gene that encodes PTB, transforms several types of mouse cells directly into neurons. 

More recently, Fu and Hao Qian, PhD, another postdoctoral researcher in his lab, took the finding a big step forward, applying it in what could one day be a new therapeutic approach for Parkinson’s disease and other neurodegenerative diseases. Just a single treatment to inhibit PTB in mice converted native astrocytes, star-shaped support cells of the brain, into neurons that produce the neurotransmitter dopamine. As a result, the mice’s Parkinson’s disease symptoms disappeared.

The study is published June 24, 2020 in Nature.


2020 Clinical trial … phase two testing of MCC950

PERHAPS I can have an opportunity to participate in this one, too???

“The progress of MCC950 to market appears to be happening rather quickly. Both the Michael J Fox Foundation for Parkinson’s Research and the Ireland-based drug company Inflazome are keen for human trials to start as soon as possible.

Dr Woodruff said much of the preclinical work was already completed.

The biggest hurdle, apart from funding, is that MCC950 came off a patent. This means the researchers have had to develop variations of the original drug for intellectual property reasons. Those new drugs are currently being tested and, according to Dr Woodruff, proving to be even more effective.

There are 10 million people with Parkinson’s disease worldwide. They still have a few years to wait and see if the magic in the lab can be replicated in people.

The phase-one tests next year will determine whether or not the drug is safe in healthy people. All going well, volunteers with Parkinson’s will be recruited for phase-two testing in 2020.

Whether Michael J Fox himself will be one of those volunteers is not yet known.”


Alpha-Synuclein updates

I am posting this just prior to the four strategies for gut health… You should see why. 🙂

You may recall from an earlier post: STUDY PURPOSE: The most urgent unmet medical need in Parkinson’s disease is a treatment targeting the underlying disease mechanism and thus prevent the disease from progressing rather than only controlling symptoms. The study drug tested in this study is a new chemical compound called UCB0599, which could have such effects by preventing the aggregation of alpha-synuclein in the brain, which is thought to be the main driver of the disease progression.

Since the alpha-synuclein is the focus of our current clinical trial… I found the following to be of great interest.

Notes from the convention as passed on by Laura Kennedy Gould’s Blog : THE MAGIC TRICK-Life With Parkinson’s

Alpha-Synuclein in your gut

I attended a technical lecture about alpha synuclein (A-syn).  Since the last congress three years ago, A-syn has been found in the appendix.  Apparently, a-syn spreads from the appendix to the gut and by the vagus nerve to the brain.   Different shapes of a-syn aggregation have been identified with each representing a different disease – i.e. PD (spaghetti), ALS (ribbon fibril) or MSA (linguine).  These aggregates form Lewy bodies.  The scientists have discovered that a-syn connects with 178 proteins; however it is not yet known if any of these cause PD or are a result of it.  What I gather from this is that the researchers have learnt a lot but are no closer to finding a cure.  Additional testing and research is needed to further define the role of a-syn and Lewy bodies in relation to PD.

Nearing its conclusion

I was scheduled to have my end of clinical trial Spinal Tap tomorrow, but since the doctor they take us to had them reschedule… I had mine a day early! The return ride ‘home’ i.e. back to Deland could have been responsible for giving me a headache, if one had developed. Gratefully, I was spared. But I have been hypersensitive to odors the last few days, and I held my sweater over my nose, the entire ride, because the perfume or car freshener seemed so offensive … assaulting my nostrils.

But YEA ! The Doctor learned from the last time and today, the Spinal Tap procedure was smoother and speedier…(I only jumped three times.) And it is done! Tomorrow, I’ll have a full day of blood tests, EKG and vital signs and the last dosing of the trial medication. Thursday is called my free day. They just hold us for observation. Friday, after vital signs and breakfast… we should be heading home. 🙂

One of the medics brought in a Wii for us to use for exercising. I am currently the champ. Last game I bowled 199. Far cry from real life. When I tried with the grandchildren a year ago… I think my final score was something like 38! I definitely needed the bumper rails up, to keep out of the gutter.

In anticipation of having other things needing my attention when we return home, I have been typing some posts, scheduling them to come out later in the month. When you go to the index, you see some topics that as yet have not been linked to a post. I am going to focus on addressing those topics. If you have a question or suggestion about something you’d like to see research on, please let me know.

Placebo or the Real deal

I have been baffled, because not every one in the study has the same restrictions on eating.

Where as I am not to eat for three hours prior to a dosing or half an hour after I take the pill, another test subject is required to go eleven hours without food and only eats twice a day.

Although we arrived for the study on the same day, they told him he had to wait an extra day to begin his dosing, because his medication hadn’t arrived from Belgium until then. (Weird)

{ I just noticed the rule: i before e, except after c doesn’t apply to the word weird…} (Weird)

Anyway, the study partner with the med from Europe (I’ll call him ‘E’) has been experiencing phenomenal improvements i.e. reductions in his symptoms.

  • When ‘E’ arrived, he used a cane, due to instability. soon he no longer felt a need for a cane, but he was still shuffling his feet. This morning, as I watched ‘E’walk down the hallway back to his room, ‘E’ was picking up his feet… an obvious confident walk with no shoe sliding!
  • It was ‘E’ who pointed out to me, that he could now snap his fingers. (When I tried snapping my fingers today, I could with one hand, barely.. but not the other… typical ups & downs of PD)
  • ‘E’ reports he his speech & articulation are much improved.
  • ‘E’ reports only a slight tremor in one hand remains.
  • ‘E’ was excited this morning, to report he hadn’t drooled for the last two nights, as noted by the fact the sleeve of his sleeping attire had remained dry

As I visited with ‘E’ this morning, as we discussed the differences in our protocol, he suggested how I might determine if I was receiving the placebo. He said he didn’t swallow the capsule (cheeked it) then he allowed the capsule to dissolve in his mouth. Once was enough. His expectation was that if it was a sugar pill, it would be sweet. ‘E’ said what hit his taste buds was not sweet. Cautioning me to have water close, to wash the pill on down after it dissolved because what he had tasted horrible!

Naturally, I had to try it for myself. First off, it was not sweet… but it was nearly flavorless, but it did have a slight aftertaste. So… am I getting the placebo? or does ‘E’ have more keen taste? Do I have the test med, at a much lower dose? I’ll probably never know.

But what I do know, is there is something coming down the research pipeline that I hope will be available to turn back the symptoms… hopefully in the not too distant future.

Strange Happenings

I want to tell you about our sleeping quarters at the clinic where the Parkinson’s clinical trial is being conducted. There are 9 beds in the ward that John & I were assigned to. We could have our choice of beds. Wouldn’t you know… I picked a bed with a mind of its own?

We have individual curtains which could be pulled around for privacy, but no need. There are currently only 6 people here and with three wards, we have ours to ourselves. We are free to stay in our room, or sit in the dining room, or one of the two other rooms designated for TV watching, game playing, etc,

There is no specific time for waking up or retiring for the night. On the free days when there are only vital signs and pills to be taken, each participant has a few guidelines. For me, I am not to eat anything for three hours before they give me my dose (capsule) and I am not to eat anything for at least half-an-hour after dosing. I get my meds at 8:25 a.m [so breakfast is served at 8:55] Then the evening meal is served at 5:00 pm {I need to be through eating by 5:25} And my evening dose is 8:25.

I have read 3 novels & John is working on his third jigsaw puzzle. This is day 12 of the 30 day study.

On our first night here, I was pretty soundly asleep, when I heard the motor on the bed and it elevated my head slightly, and stopped. Due to my sleepiness, I didn’t rouse much. After the bed’s bizarre behavior had happened twice more, I had awakened sufficiently to recognize the need to trot to the little girl ‘s room. “What the?” When I returned and started to get into bed, the top half of the bed was all the way up! Perpendicular! As if sitting up straight!

The bed’s shenanigans had aroused John enough, that he thought I was having a hard time sleeping, not realizing I wasn’t in the bed, till I returned from the bathroom. We unplugged the bed, after coaxing it to lay back down.

When we reported the malfunction to the medic, Doug, in the morning, he related what had transpired, the last time the dorm had been used. The clinic had had a larger study going on and the room had been full of ladies. They had come running out of the room declaring one of the beds was possessed. He thought they were just messing with him, talking about poltergeist. The bed never acted out when he was in the room.

Doug had a good laugh, when John told him, ‘When he’d plugged the bed in, he’d noticed that the grounding prong was missing. So we’d figured that must account for the strange happenings.’