Why we can't cure Parkinson's 


A question that lingers in the mind of every Parkinson’s patient and nearly every researcher that is searching for ‘the cure’ must certainly be ‘Why can’t we find one and why is it so elusive?’ To answer that question, we must first understand the etiology of the disease and how it manifests into the unique, almost individualized symptoms that it so often does.

Unfortunately, we have a very good understanding of Parkinson’s but at the same time we are completely lost. Either you will take that as a useless rhetorical comment or you will conclude that I’m just stating an obvious fact. Regardless, the only way to make sense of Parkinson’s and our apparent inability to find a cure is to break it down one step at a time and understand things for what they are. There are a lot of reasons that a single one size fits all cure can’t be found with the apparent exception of one. We’ll get to that after we talk about the details of the disease, how it’s diagnosed, evaluated and treated. It is undoubtedly complicated and requires consistent research and comparison. Parkinson’s may even be morphological in nature, we’ll talk about that also.
I probably spend more time researching and tracking Parkinson’s than most neurologists and likely some researchers do, it’s become a part of my daily life. I don’t zero in on one treatment, cause or symptom. I look very closely at every aspect and possibility I can find. I am I my sixth year of Parkinson’s and my condition has changed little over that time period aside from self-mandated medication adjustments. I keep the medications to an absolute minimum by the way because quite frankly the side effects are a bitch. The medication has become a majority of my problem and it’s really difficult to discontinue these types of medications once you have been on them for any length of time. Accept the fact that it may be a daily ritual for life, just a fact at this point in time.
Every day I make it a point read articles, research papers, peer reviewed journals, drug trial information, patient stories, environmental news, clinical studies, plant and food chemistry and biology, demographics, developments in treatment, comparisons to similar conditions and anything else that could even be remotely related. I always find something, it helps to maintain a positive attitude and more importantly hope. I also share anything relevant that I find in the event that someone will find it useful. This is how we all must research Parkinson’s disease, it’s not going to solve itself and no one knows it better than patients.
Sometimes I will read an article or review a study and think; Eureka they’ve got it! Only to find that it was such a poorly structured and isolated study that it will never have any meaning, nor will it benefit patients.
A majority of the information that comes out doesn’t merit reading past the first paragraph. Parkinson’s is not new by any means and little has been individually overlooked. I’m sorry to say it, but it’s the truth. Medical research is at wits end, and don’t think for a second that they aren’t trying because they are. The problem is compound. It is both isolationism and painting the disease with a broad brush.
We are just starting to individualize Parkinson’s, but doing so means weeding out all the bad information and dead end research that has been done and moving on. There is no need to wake a sleeping giant that has already been put to bed more than once.
I strongly support the study of orphan drugs and believe it should continue on the condition that it is applied to the treatment of specific symptoms and not the general condition, it will be much more successful and useful.
As far as the miracle cures go, we need to literally just delete most of them from the annals of history and never listen to it again. It’s harmful to the patients more than anything, most researchers are not fooled by your books, videos or websites. If you’re a miracle worker, try to stop being selfish and have a little compassion for those that suffer. It’s wrong to get someone’s hopes up and despicable to take their money in the process as well as shameful. Now that I’ve gotten that out of the way, let’s move forward. Sorry, it’s just my personal opinion.
Sometimes we need to take a step back and quite frankly, just start from scratch. Forget everything we know and take a new approach to see what we find. Ok, I don’t literally mean forget everything. I mean that nothing should be off the table when we approach it. I am reminded of a time when I was soliciting questions for a Parkinson’s survey a few years ago. One of the questions suggested was “Have you ever been struck by lightning?” I wasn’t expecting that one and obviously 10 million people worldwide haven’t developed Parkinson’s due to a lightning strike. Or have they? Well there’s only one way to find out, and that is to check it out, consider it and either include it or exclude it, don’t just blindly dismiss it. That’s what keeping it on the table means.
Too often I have heard people say that their symptoms are discounted, ignored and never investigated. I’ve had it happen several times myself. It’s insulting to your intelligence, demeaning to your person and dismissive of your physical problems. It happens all the time.
I once knew someone that told me about an employee he had who was diagnosed with Parkinson’s. We discussed it a bit and I asked him what ultimately happened to him because he was a fairly young man like myself. He died of stomach cancer before the age of 50. I hope a huge red flag just flashed just popped up for you because this is a serious problem.
The misdiagnosis rate for Parkinson’s could be as high as 50% or more. A physician will probably never tell you that but a researcher likely will. Nothing should ever be overlooked, and things always are. I have personally seen over 40 doctors for this condition and have literally had to demand specific tests, paying for them out of pocket because the insurance companies won’t. I asked one doctor if this could be cancer of some type and his response was “could be...”
I requested genetic testing and was told it was a waste of time because I responded to levodopa. I’m not saying that I don’t have Parkinson’s. I have somewhat of an unusual case and the symptoms are present but I still don’t believe every avenue has been exhausted. I do know that I went through quite a bit of very expensive, unnecessary and duplicate MRI’s that weren’t needed. That belief was solidified even more when I was in Bogota, Colombia and compared the cost of the same neck MRI that I had in the United States. The cost in Bogota was $308 while the cost in the states was over $4000. I’ll let you decide the motivation.
I recently read an article about a woman having been treated for Parkinson’s for 10 years and ended up having colon cancer, not Parkinson’s. The only reason that they even bothered to pursue other causes is because the medication was extremely problematic, although it did work to a degree. The official diagnosis was a condition called ‘Paraneoplastic Stiff Person Syndrome’. Unfortunately, this isn’t an isolated case.
There was another recent case documented with a 67-year-old male that also responded to Parkinson’s medications and even underwent DBS for the condition. The root cause has yet to be determined and it is being called “Comorbid Idiopathic Parkinson’s and Stiff Person Syndrome” The question here certainly leaves us to wonder if the Parkinson’s developed from the drug treatment or if they are truly comorbid. It may never be determined.
These two cases alone show the danger and uncertainty of diagnosing something with a pill, it’s not 100% effective or accurate. It’s diagnosis by committee and that leaves room for error. To make the situation worse, once you are on a long-term dosage of dopaminergic drugs, you will in fact develop symptoms of Parkinson’s from the therapy alone. Then you encounter an even bigger problem when you try to discontinue using them. These are serious and potent medications that effectively alter your brain and body chemistry making it nearly impossible to separate the diagnosis of Parkinsonism from idiopathic Parkinson’s over time. It’s not a wonder that people ‘surprisingly’ die from other causes when diagnosed with movement disorders.
Hepatic encephalopathy as a cause is also commonly overlooked, probably much more often than you would expect. There can be a wide range of neurological symptoms that present, one of them being Parkinsonism. Hepatic encephalopathy can present with mental disturbances, cognitive problems, the appearance of Wilson’s disease and other disorders. Ammonia levels generated in the liver and transferred to the brain can affect glutamate and GABA pathways and systems in dopaminergic pathways. This alone can lead to neurological problems. If properly diagnosed, this condition can often be reversed. If dopamine therapy is initiated there is certainly the possibility of causing other irreversible problems because it is treating the symptom and not the cause. It is known and documented that this condition can present as Parkinsonism but it is not often if ever in the standard workup for a diagnosis. Doctors should be educated and aware of this possibility.
Lewy body disease is frequently misdiagnosed as Parkinson’s dementia. It is just now being very specifically differentiated from Parkinson’s. It does have many of the same symptoms of both Parkinson’s and Alzheimer’s. Until recently it has been considered somewhat of a secondary condition to these diseases. This is due to the fact that lewy bodies can accumulate in both of these conditions. It is obviously not clearly understood, as some abstract research has actually shown the accumulation of lewy bodies to occur without the presence of dementia or in some cases any symptoms.
Dementia and psychosis is not always a product of Parkinson’s disease. It is however present in lewy body disease which may or may not be coupled with a movement disorder. That fact alone makes lewy body disease a different illness. Parkinson’s always has movement disorder and is never pure autonomic dysfunction or pure psychosis and dementia.
Lewy body disease commonly begins with movement problems but dementia and psychosis appear early in the disease making it distinguishable. Hallucinations can often be the first sign of lewy bodies along with autonomic dysfunction. This is not the case with Parkinson’s which almost always begins with slowed movements. Dementia can take years to set in and hallucinations in Parkinson’s are uncommon other than medication side effects.
Lewy body disease is an illness that should be considered a cognitive disorder and probably should be separated from Parkinson’s and Alzheimer’s even though it has the same hallmarks regarding protein accumulation. It can be difficult to diagnose but understanding and differentiation from other illnesses is developing rapidly. I fully expect that the illnesses will be separated within the next five to ten years once a positive clinical test has been developed. For now, it will continue to be misdiagnosed but probably less frequently due to expanding knowledge.
Sorry folks, one thing that isn’t it is Lyme disease, just so you know, that ship sailed a long time ago along with the celiac theory. If you’re diagnosed with Parkinson’s and they tell you it’s Lyme without a positive blood test, see another doctor. The symptoms are quite different. If you’re being treated for ‘drug resistant Lyme’, there’s a reason for it. It’s not Lyme disease, so you can’t cure something you don’t have. If you are unsure about Lyme symptoms and diagnosis, I recommend reviewing the section on Lyme in the Merck professional manual or the CDC website. It’s very specific about symptoms without the conspiracy theories.
This problem with misdiagnosis is disconcerting at the very least. Many patients reading this are probably shaking their heads after going through a long and arduous diagnosis wondering if it’s correct. You should be a little angry about it, but more importantly you should be diligent in finding out if you are properly diagnosed and receiving the correct treatment.
Movement disorders are in no way a one size fits all type of illness and you should never stop searching for the cause. Treatments vary with symptoms and it’s ok to try different forms of treatment and medications with your doctor’s guidance. Just remember to take as little medication as possible to be functional and happy. Overdosing is extremely easy on these medications and is clearly exhibited in side effects. If you’re having a lot of side effects, that translates into either too much or wrong drug, simple as that. You know what feels right better than anyone and don’t be afraid to speak up about it. Everyone has a different genome and will respond differently to treatments than others.
Lets’ look at Parkinson’s logically and see what we might be missing. Often times things are staring us in the face and we overlook them as if we’re wearing blinders. We get so overwhelmed by the details that we completely ignore the obvious. The first place to start when evaluating illness is always with the obvious and that is the symptoms.
We can learn a lot from symptoms, especially when it comes to Parkinson’s because rarely are the symptoms exactly the same but there is a definitive pattern. On the other hand, certain symptoms differ enough and are localized enough to immediately divide them into two categories if not more. I’m pretty sure the doctor didn’t tell you that when they diagnosed you now did they?
Symptoms: Tremor is most often the primary symptom that people correlate with Parkinson’s. Note that I don’t call it the primary symptom because it’s not. Tremor also is not the violent flailing that you see on YouTube videos put out by snake oil salesman. Tremor is a distinctive mild shaking at rest that resembles trembling or muscle fasciculation. In Parkinson’s there is what is called pill rolling associated with this tremor. Patients appear to roll an imaginary pill between their thumb and index finger. This actually differentiates Parkinson’s from another disorder called essential tremor.
Approximately 30% of Parkinson’s diagnosis’s lack tremor and actually never develop tremor. We now immediately have two different conditions right out of the gate. If pill rolling tremor is going to be a symptom of Parkinson’s, so be it. The other 30% don’t have ‘Idiopathic Parkinson’s’ if they lack tremor, they have a similar neurological condition with a secondary cause. Find out what it is and call it that, it may be another form of Parkinson’s but it needs to be separated and treated with a different approach.
A symptom frequently associated with tremor is cognitive impairment. In the non-tremor group, dementia and cognitive impairment are relatively uncommon or sometimes non-existent. If they do develop, it is often from the medications prescribed to treat the movement control issues or occurs very late in the course of the disease.
A feature of non-tremor dominant Parkinson’s is often a shorter course of disease and more rapid deterioration often due to secondary causes. You would probably suspect that we are looking at two distinct illnesses here if we were approaching them blindly.
The tremor dominant group is most likely afflicted by some type of metal or mineral intoxication or imbalance while the other group is not, as this is quite common with tremor.
Now that you are looking at two groups, you could easily be looking at three by adding the lewy body dementia group, another disease often misdiagnosed or simply mislabeled as Parkinson’s, which was already discussed. You can see the pattern begin to emerge. Let’s get back to symptoms though.
The primary symptom of Parkinson’s is actually slowness of movement or more specifically the inability to initiate slow movements coupled with the progressive slowing of repetitive movements. This is called bradykinesia. It is the key feature in Parkinson’s and is also present in other movement disorders.
Akinesia can also be present, it is rigidity coupled with the loss of voluntary muscle movement with the latter being the medical definition. It is typically coupled with bradykinesia in a Parkinson’s diagnosis although they are different.
Bradykinesia is the slowness of the actual movement itself whereas akinesia is the slowness in initiating the movement in the first place. It may not sound like a huge difference, but neurologically they can be worlds apart. Hypokinesia is another term associated with this. Again, we have some distinctions present that may be worth separating during diagnosis and observation. This is not as significant as the tremor issue but it may have some relevance.
One of the criteria for idiopathic Parkinson’s is that the onset is unilateral with the lower extremities becoming bilateral within three years. When the three-year bell tolls if it has not become bilateral, it becomes secondary, atypical or Parkinsonism. At any rate, what that means is that it is a Parkinson’s type syndrome and not actually Parkinson’s disease.
Once again, we are changing the parameters of the condition and still calling it Parkinson’s disease when in fact it may not be. By calling it Parkinson’s and treating it as such, we are evading making the correct diagnosis and rescinding our ability to make a determination of what the condition is and treat it. This helps no one and is of great disservice to patients and the scientific community alike.
These cases and subsequent treatments need to be well documented and available in the scientific record. Just one case of a person with a specific symptom that turns out not to be Parkinson’s but something treatable could potentially change the lives of tens of thousands. If Parkinson’s becomes excluded over time it is imperative to stop treatment for Parkinson’s and further investigate the cause. Is that such a difficult concept to grasp?
The number of symptoms required to attain an initial Parkinson’s diagnosis amount to two quantitatively. The way it’s worded is “Bradykinesia and one or more of the following....” Which are muscle rigidity, 4-6 hz resting tremor and postural instability.
This is step one and as you might guess, it makes it relatively easy for a doctor to pass sentence on to you almost without trial. Step two is exclusion criteria and step three is supportive criteria required for a definite diagnosis. We’ll go over all three sets of criteria individually.
Most of what occurs during a Parkinson’s diagnosis is nothing more than ringing up a massive bill because ultimately the diagnosis comes from a trial dose of levodopa to test for responsiveness. In reality, this trial could be initiated at first suspicion of Parkinson’s and much of the clinical testing for exclusion criteria would face elimination along with greatly reduced cost.
In my case, the diagnosis took nearly a year and cost close to $100,000 even though in retrospect the symptoms were quite obvious. In fact, indications of Parkinson’s are so obvious that I can now almost spot Parkinson’s at a glance. I can usually differentiate it from other movement disorders immediately just by simple observations and I’m not a physician by any means. You simply have to know what you’re looking for, and any neurologist should absolutely know what the signs are at a glance. If they don’t, I’m sure flipping burgers hasn’t changed much from when they were in college, maybe there’s an opening.
Unfortunately, Parkinson’s disease has been grossly mischaracterized both publicly and in the medical community. The tremor myth as I like to call it has been spread far and wide, not being clearly defined at all.
A majority of people believe tremor to be the rampant epileptic like fits as shown on YouTube or the pronounced chorea associated with levodopa induced dyskinesia. Neither of which are remotely accurate. It only compounds the problem when general physicians and even a high percentage of specialists believe the same thing. It puts the undiagnosed in a great deal of emotional distress and it shouldn’t. They never suspect Parkinson’s due to the lack of tremor and often fear for the worst.
A significant number of physicians, including orthopedists, neurosurgeons and brain surgeons don’t seem to be aware of the fact that bradykinesia is the primary indication of Parkinson’s. I find it almost unbelievable that this can happen into today’s medical community. I say this because I saw all of the above along with two other neurologists and many more specialists of other disciplines. To be quite honest with you, none of them had a clue. Even when I saw the neurologist that finally diagnosed me, he initially told me that I might have MSA before putting me on a levodopa trial. It seemed to be more important to perform another $15,000 duplicate MRI instead. Over the years, I’ve heard the same story repeatedly and it’s unacceptable.
With Parkinson’s becoming as common as it is, we need to focus on training medical professionals from nurses to orthopedists what the initial clinical signs and symptoms of this disease are.
We also need to accurately and definitively track this disease in order to realize the true scope of it. Currently we really have no idea how many people are afflicted with Parkinson’s. The numbers are all over the board. When you consider life expectancy, misdiagnosis and undiagnosed patients, the numbers could easily swell.
With a growing population, we cannot continue to estimate a mere 60,000 new cases per year in the U.S. with a total of one million afflicted, it just doesn’t make sense. That number and estimate has essentially remained unchanged in the six years I have been studying the disease, although it has slowly begun to creep higher due to pressure from a variety of sources. Realistic estimates are more in the neighborhood of 200,000 new cases per year with around ten million afflicted worldwide and five to seven million afflicted in the U.S. alone. The worldwide number could also be dramatically higher, but as long as countries have borders, so will doctors. Parkinson’s appears to be headed for epidemic levels within the next 25 years. We need to acknowledge that and act on it now, not later.
Getting back to symptoms and diagnosis; As stated previously, bradykinesia or slowness of movement is the cardinal symptom of Parkinson’s disease. It may actually be much more than that. It is not known what the initial symptoms of this are or how they manifest.
It is suggested that micrographia or a decrease in the size of handwriting may be one of the earliest symptoms. I personally am somewhat on the fence with this as my handwriting wasn’t affected until the symptoms fully set in. After taking a long retrospective look considering every possibility of what could have been a symptom, I have somewhat settled on what the initial onset felt like but still find it difficult to describe.
The first identifiable movement symptom for me began about two years before the ‘onset’. It was almost imperceptible, just one of those things that didn’t feel quite right. I started noticing that my left arm felt weak in an odd sort of way. This wasn’t something that you would even consider going to the doctor for. It was a feeling somewhat akin to that of when your arm falls asleep, only the feeling wasn’t that of the arm tingling or being numb. The feeling was more the sensation that you have right after the numbness wears off and you are just finally getting the movement back without the tingling but don’t quite have full control yet. It could also be described as a feeling that if you were using a punching bag, you could easily move your arm and punch the bag but not with any degree of force. The feeling would subside and come back off and on over the next couple of years. Activity made the sensation go away but it had to be constant, strenuous movements, and it was temporary. Then after a year or so of having that feeling I noticed that I would drop things like pens or most specifically my cigarette when holding it between my fingers. It would just drop from my fingers and I never felt it go, I just noticed it on the ground. It was odd and I thought it peculiar but couldn’t pin it to anything at all, I just wondered why all of the sudden I had this slight loss of dexterity.
The actual onset occurred overnight. When I say onset and overnight, that’s exactly what I mean. I was perfectly fine one day and woke up this next morning dragging my left leg looking like I was on the run from a chain gang with the ball still attached. From then on, it was a much slower progression. Again, we have a definitive, specific symptom at onset. We can let the funny feeling in the arm slide but the overnight onset cannot be ignored. This is known to occur in paraneoplastic syndromes as well as certain types of dystonia but there is no indication of either as of yet, although I did have one neurologist suspect dystonia.
The rapid onset and lack of tremor must be considered in the diagnosis. Simple things like this can define different types of specific illnesses and provide a course to better treatments. We have to start somewhere to break these symptoms down into sub-groups and define them. Believe me when I say that it gets a lot more complicated when you are trying to isolate the cause of a specific symptom, but it must be done or there will never be a cure. We can only individualize to a certain degree and maintain feasibility. Truth be told, any step forward would be a giant leap considering that treatment really hasn’t advanced in nearly fifty years.
I am using parts of my case for examples because it is the one I know the best. So far, we have no tremor at any time coupled with a sudden onset of illness and no cognitive or psychological issues (Yes, I have undergone thorough examination). After six years, we’re still at the point of ‘If I had to guess, I would say it was Parkinson’s.’ That incidentally was an exact quote from a University neurologist that just didn’t know what to call it. It hasn’t changed but it still fits the bill. I’ve also been told it was an unusual presentation of Parkinson’s. My diagnosis is based on slowness of movement and subtle rigidity in one or more limbs. Other than that, the clinical path of this illness does not match the criteria for Parkinson’s, nor is there specific evidence of Parkinsonism.
The initial diagnostic criteria of bradykinesia plus rigidity or tremor are easy to meet as you can see. Exclusion criteria are a bit more complex and this is where essentially all of the testing takes place. The idea is to rule out any underlying disease, illness or injury that may be contributing or causing the movement disorder. I very specifically say movement disorder because that is what the criteria outline in the first step of diagnosis. With just two symptoms, it’s not enough to assign a diagnosis, even with a levodopa trial.
The exclusion criteria are by far the most critical components of this diagnosis, it’s make or break. Unfortunately, this is where things are most easily overlooked and mistakes get made. It is ultimately what this whole discussion is about, and that is proper diagnosis and treatment. Testing should be performed sequentially and follow specific criteria. I can assure you that for the most part this does not happen, at least in any type of orderly fashion. This is something that needs to change and it needs to change now if we’re going to progress.
Secondary causes are highly likely in any case of Parkinson’s. In fact, they may be responsible for up to 95% of all cases, with the other 5% being hereditary. We’ll get to that later and you’ll understand why that is and what it means. Much of the research that has been conducted points in a general direction to the cause of Parkinson’s, and there are some very specific biological anomalies that are common in Parkinson’s.
Diagnosis is divided further by supportive criteria and followed by absolute exclusion criteria. There are problems with both. The 2015 MDS update on diagnostic criteria partially dealt with this issue, but it is still not completely definitive. Let’s briefly cover supportive criteria before we get to the more complex exclusion criteria.
Supportive Criteria:
The primary components of supportive criteria revolve mostly around levodopa therapy. Stick with what we know right? Marked response to levodopa, on/off fluctuations, dyskinesia or dose dependent response are supportive criteria for a positive diagnosis of Parkinson’s for part one and two. The third criteria is the appearance of tremor at rest. The fourth criteria is two part, the first being olfactory loss and the second being a radiographic procedure to exclude Multiple System Atrophy. That is the extent of it.
The main problem here is with the levodopa. Yes, it is known to work well for Parkinson’s disease. The criteria has been updated to include how effective it is which is a positive step. The issue is that we do not know for certain that levodopa is not effective in treating other movement disorders other than dystonia or if it is perhaps effective in musculoskeletal disorders or other issues due to the fact that levodopa can be absorbed and converted directly within muscle tissues. This is the primary reason that carbidopa is added to levodopa, it is to direct the levodopa to the brain by inhibiting vitamin B6 metabolism. Without carbidopa, levodopa is absorbed peripherally. Carbidopa is not added to prevent nausea from levodopa as some falsely state. The addition of carbidopa by the way is a bad thing. Inhibition of B6 can devastate an organism and may be responsible for more rapid deterioration in Parkinson’s.
Carbidopa strips the body of its ability to metabolize many nutrients. It essentially starves you to death internally. I documented my weight throughout the diagnosis from the medical records. I was consistently 190 lbs. Exactly 6 weeks after starting carbidopa, I was 175 lbs. I made no other changes of any kind. I mean none whatsoever. I have brought this to the attention of several neurologists and they quickly deny it blaming the disease or the levodopa. The evidence is pretty clear as far as I can see. I did have one University researcher agree marginally but it almost felt like coercion. The U.S. trained neurosurgeon I saw in Colombia agreed right away and called it quite common. Carbidopa is also being investigated as a diet drug. What are they thinking? Anyhow, that’s just a side note.
We rely on these supportive criteria because there is no definitive clinical test for Parkinson’s disease as of yet. The only available testing must be conducted post mortem and that often is deceptive because it is typically after years of dopaminergic therapy which likely damages the brain. So, for the time being this is what we have. This makes the absolute exclusion criteria far more critical in a diagnosis. It would probably be prudent to go far beyond the exclusion criteria and perform follow up testing for non-fatal causes biannually to ensure the diagnosis is correct.
Now it’s time to move on to the absolute exclusion criteria. Take a good breath, hold onto your hats and probably grab a dictionary, we might get a little deep on this one. The human body and genome is a fascinating and complicated thing. It is utterly amazing how systems affect each other and interact. The complexity in Parkinson’s is that it happens at the most basic and microscopic of cell levels affecting the entire organism. There is however one definitive feature in Parkinson’s that cannot be ignored and it is treatable but not feasible. Of all the research I have done, I have seen no other method of treatment that is as definitive. It is almost indisputable and clinically proven. We’ll conclude this chapter with it and fit the puzzle pieces in place. Ok, let’s see what else they like to look for in Parkinson’s
Absolute Exclusion Criteria:
This set of criteria focuses largely on brain abnormalities, drug induced causes and involvement along with related conditions. There are a total of 9 sets of criteria with the last one being the most vague and also the most critical. Let’s just touch the first 8 briefly and then get to the real alternate causes of the disease along with the manifestations.
Parts one through three relate to brain abnormalities, vision problems, walking problems due to physical abnormalities in the brain and early or rapid onset dementia. Most of these problems can be identified through a few tests and eliminated if it is Parkinson’s. The first tests to be performed in no particular order are Videonystagmography/Electronystagmography (VNG/ENG), Transcranial Doppler ultrasonography (TCD), Electromyogram (EMG), MRI , occasionally PET scans, and Electroencephalogram (EEG).
Briefly, the VNG/ENG are tests that evaluate ocular movements, gaze and coordination of the eyes and ears. The reason for this is to determine if there are any abnormalities that may affect balance, cause dizziness, indicate the presence of possible tumors or frontal cranial pressure affecting the eyes. TCD is a test that checks blood flow in the brain to determine if there are clots or indications of past or present stroke. EMG tests are nerve conduction studies that tests for continuity of the nerves in the body to the brain. An advanced form of an EMG that is called Somatosensory Evoked Potentials (SSEP) may be performed if there is suspicion of other nerve damage. EEG’s are used to examine brain wave patterns and view electrical activity in the brain. In Parkinson’s, these tests will almost always be normal, although neuropathy is commonly noted.
MRIs are almost routinely conducted for a Parkinson’s diagnosis. Typically, one high resolution weighted MRI of the brain is sufficient to diagnose any physical abnormalities. It is not uncommon to perform MRI’s of the cervical and thoracic spine to look for spinal cord abnormalities. They are looking for things like hydrocephalus, pineal or pituitary gland problems, brain deterioration and swelling, spinal cord impingement, nerve damage, fluid on the spine and the like. Once again, if it’s Parkinson’s, there will be few if any abnormalities detected.
Spinal fluid samples are also frequently taken. To rule out items like Multiple Sclerosis or bacterial infections. Blood tests are simply standard blood tests which will include VRDL and RBG for syphilis and other spirochetes if you request it. Abnormalities are rarely seen in these blood tests outside of slightly elevated white blood cells or low serum levels of vitamins which is perfectly normal. The indications that nothing is wrong begins to pave the way for a Parkinson’s diagnosis.
Part four of the MDS guidelines call for exclusion if only the lower limbs are affected after three years’ time. The U.K. Brain Bank calls for exclusion if the condition remains unilateral after three years. That’s actually quite a distinction, but both are quite possibly correct. It seems that both would give the indication that dopamine producing cells are not progressively dying off. This is interesting because what if in fact it was yet another variation of Parkinson’s in which only a finite number of cells are destroyed leaving the condition stagnant? This would certainly be worth investigating. The first obvious treatment option would be a stem cell transplant in the affected area of the brain. If there was an uncorrected underlying cause, the brain cells would once again die. This could be tested and studied in the lab environment to look at viability. Any possibility must be reviewed and studied. We not only need to find better treatments, we need to find an accurate method of diagnosis which is sorely lacking.
Parts 5 deals with drugs and medication. The use of drugs that block or deplete dopamine are cited as drug induced Parkinson’s. These would be uncommon but need to be investigated. A more likely scenario for drug induced Parkinson’s is one in which illegal or street drugs are a party.
Methamphetamine users for example are said to be about 150 times more likely to develop Parkinson’s than others, especially women that use. This is probably a realistic number but not for the reasons you would think. The first inclination is to say that it’s ‘Illegal meth’, which creates cause and effect based entirely on stigma. The reality about meth induced Parkinson’s is that it probably isn’t the drug itself but the solvents and chemicals used to manufacture it. Now we have cause and effect. Solvents are known to cause movement disorders and the symptoms are documented for a great deal of these solvents and other chemicals that have been used in the manufacture of methamphetamine.
Now here’s an interesting thing that may be contributing to the rise in Parkinson’s cases as be an unintended consequence of drug enforcement. In the late 1990’s and forward, the government began tightly regulating chemicals used in the manufacture of methamphetamine, making them unavailable to the public. This led illegal drug manufacturers to finding similar chemicals to manufacture. The problem is that the substitute chemicals are far more toxic than the banned chemicals previously used, especially when mixed into concoctions used to extract specific compounds for the drug. Many of the new chemicals more than likely leave a residue on the drug itself whereas the banned chemicals may not have. The other problem is that with mixed chemicals that are not well documented, we don’t know what the symptoms of ingestion are nor the consequences.
Another good example of street drug causation is the case of heroin users in the 1970’s who purchased heroin with a drug called MPPP in it. The only problem was that during the manufacture process it was converted accidentally into a potent neurotoxin called MPTP which almost immediately induces a type of Parkinsonism. It is still used widely today for testing but will likely never yield any usable results due to the fact that it doesn’t duplicate exact symptoms. It creates more of a Parkinson’s plus syndrome and is more resistant to treatment. It is more of an akinetic, rigid syndrome causing more of a paralysis than slowness of movement or tremor.
To summarize, drug induced Parkinson’s is a distinct possibility, but chemicals are far more likely a culprit. Being honest with the doctor about illicit drug use can save a lot of grief and money. At this point you have nothing to lose and are only hurting yourself if you don’t discuss it. You may even be denying yourself proper treatment.
Part 6 is short but sweet. If there is no response to levodopa, then it must be excluded or secondary. It specifically states that dosage of over 600mg of levodopa daily be used and considered in combination with UPDRS score to qualify this as an exclusion.
Part 7 lists several different exclusion criteria including loss of sensation to touch, loss of ability to coordinate hand eye movements such as mimicking a movement and the progressive loss of speech. These indicate degeneration in the brain or other neurological disease. Conditions causing these symptoms would likely be detected on an MRI.
Part 8 considers only functional neuroimaging of the dopaminergic system. Probably a DAT scan or PET scan. Neither of these yield any definitive results. DAT scans were thought to be able to definitively diagnose Parkinson’s initially but subsequently have only been used to differentiate it from essential tremor. We simply do not have the advanced type of imaging technology to identify Parkinson’s disease in the brain. Perhaps we are not looking in the right places.
Part 9 is deliberately vaguely worded. It basically states that anything else that has been ‘documented’ and is known to cause Parkinson’s symptoms making it more likely than Parkinson’s disease. It does not include lewy body dementia but does consider Parkinson’s plus syndromes. That pretty much forces the Parkinson’s diagnosis or leaves it wide open when you think about it.
The U.K. Brain Bank is a little more specific and includes strokes, head injury, encephalitis, remission, hereditary links and a few other brain disorders that would be found with other testing I have listed. There are a lot of things that can cause symptoms of Parkinson’s when you go by the listed criteria.
What you might have noticed about the diagnostic testing and procedures is that out of all of them, only the lumbar puncture is an invasive procedure. Everything else is external and all major organs are completely omitted aside from the brain and the most basic of blood tests. Why is that? Remember when I said we overlook the obvious? Well that’s exactly what’s happening. It’s staring us right in the face.
Let’s add some parameters here and then see if we can back them up with research and facts. If we change the statement “Parkinson’s is a brain disease” to “Parkinson’s is a disease that affects the brain” we open up more possibilities of diagnosis and treatment. Currently we work on treating the symptoms of brain disease and it’s not progressing. The treatments are mildly to moderately effective, drug side effects are often intolerable and the progression of the disease remains the same. All we’ve accomplished is getting people somewhat functional at best. What if we examine other organs in the body that have a role in creating chemicals that affect the brain? Some researchers have taken this approach and actually had some success with it. It’s the obvious, we overlook the entire organism and focus on the symptoms in one part of the body. Coincidentally, that part of the body is fed and relies almost entirely on the rest of the internal organs in order to function.
As scientists have worked backwards from the brain deficits, much has been discovered. It has been traced back to the mitochondrial level in the cell and the transcription of DNA to mrna to polypeptides. This gets insanely complicated but we’ll get through it in some sort of layman’s terms. This is just one part of the problem in Parkinson’s. If it was the only problem, we would literally be on the verge of a cure but it’s not and we aren’t. There is an entire chain of events that occur throughout multiple systems in the body from serotonin production to the creation of enzymes to detoxify cells throughout the body. Every system is affected in Parkinson’s and it seems impossible to isolate that ‘one thing’ that flips the switch causing the illness. Perhaps there is a one thing that correlates to each symptom or leads to a particular deficit. It could be that the one thing affects multiple processes at one time. It could be an autoimmune response, a genetic coding error, a virus, bacteria, a poison or a combination of any or all of them. This is why it’s so difficult to understand. We are just beginning to look at these things and evaluate them, and there’s a lot.
Starting with the brain is obviously logical or should we say was logical. We’ve learned a lot from the studies conducted. Now we’re just kicking a dead horse. Yes, a-synuclein accumulates in the brain in Parkinson’s, we get it. It has been studied, manipulated, removed, altered and anything else you can think of. No real progress has been made and we still don’t know what it does. It’s believed that it plays a role in autophagy which is the removal of junk material within the cells. So why the accumulation? Is there something wrong with the cells? Is there something wrong with the protein? Why won’t the a-synuclein enter the cell and do its job and is it supposed to? Those are serious questions we need the answers to.
There are two approaches to this dilemma. One is to look at the cell and its function, the other is to look at a-synuclein and its function. Maybe we should look at the cell first since the latter has yielded little so far.
The cells that are affected by a-synuclein aggregation in Parkinson’s are found mostly in the basal ganglia region of the brain, although other cells are also affected. Regardless, the affected cells die when this protein accumulates. When neuronal cells die, it affects movement. Other affected cells can affect autonomic dysfunction such as that seen in MSA. It is also present in lewy bodies. It can therefore be assumed that the protein aggregation affects more than just movement. In theory, a-synuclein as a protein could affect a whole host of different cells and their functionality. This just hasn’t been discovered in regard to Parkinson’s as of yet.
The reason for the aggregation of a-synuclein isn’t currently understood. It is thought that it could be an aid to neurotransmission or possibly a prion (infectious agent). That is neither here nor there. The one thing that is known is that it is misfolded in all of these diseases. So, where in the body does the misfolding (improper coding) occur? At the time the protein is produced or when it tries to enter or combine with the cell? This is a critical question. If this protein misfolding occurs where a-synuclein is produced, we need to look at the point of inception. If it occurs when it reaches the cell, we should be looking at the cell itself and probably which enzymes or proteins provide the cell with coding information. Either way, we have to find the point of inception.
A-synuclein may try to enter the cell in two different ways, the cell membrane or the nucleus. With either one, the coding of the protein must be correct. It more likely enter through the cell membrane and interacts with the mitochondria in the cell cytoplasm. (Just a guess based on basic biology). Knowing that the cell can effectively change the lock on its door, we must consider the reasons this might occur. There are two possibilities. One is that the cell has essentially malfunctioned internally and coded a protein incorrectly preventing a-synuclein from combining with it. The other stronger possibility is that the cell has been instructed by a messenger protein to block the a-synuclein from entering altogether. This will make a lot of sense later, remember it. So how does that cause misfolding? Picture trying to force something like soft butter into a container that is already full. The excess will be forced out, only in this case the a-synuclein is the butter and it just continues to become deformed, never entering the cell resulting in accumulation. If this is the case, it’s neither the cell or the protein. That means that it’s something else. I wonder where that messenger protein got its instructions.... that could be a clue.
If the case turns out to be the a-synuclein being misfolded at inception, a different approach is required. First, we have to find out where it comes from and what components are required for its production. A-synuclein is found in the brain, blood and tissues in the body. It is a protein made up of 140 amino acids. Scientists have been able to edit the amino acid chain to prevent aggregation. This has been unsuccessful in identifying what makes it toxic to the cells. It’s an all or nothing approach and has been ultimately unsuccessful. Even though specific mutations have been identified, altering them does not produce the expected effect. This leads us to the rationalization that it must have a functional purpose and it must interact with other enzymes, proteins or amino acids to perform its necessary function.
A-synuclein is produced or secreted by the SCNA gene. It has been recently found to interact with lipid membranes and is also considered to be a chaperone protein, meaning that it binds with other proteins to perform a function. Although its true function is still unknown, it is thought to play a role in several key areas including regulation of glucose, prevention of programmed cell death, the release of dopamine from neurons and other protective functions. What stimulates the production of a-synuclein remains somewhat of a mystery. This is the missing link in understanding this protein. It could well be a combination of different chemical reactions and synthesis of multiple or even hundreds of proteins and amino acids that stimulate production, it is literally unknown at this time. I’m being very general in discussing a-synuclein because it is infinitely complex and overwhelming to try to explain or understand in short context. What we are doing is discussing the theoretical function and propagation of this protein as it is a known player in the pathology of Parkinson’s. As I suggested before, we don’t even know if it is a causative factor or a byproduct of some other aberrant process that leads to Parkinson’s or other diseases.
If we consider it as an effect and not the cause, it opens doors to more research and brings us back to looking at the entire organism, not just the presence of a-synuclein in its aggregated form in the brain. In essence, that translates into forward engineering rather than reverse engineering which is what the current method has been. Rather than trying to unravel the changes in the protein, we should be trying to stimulate its production and in turn its misfolding. Remember, this is entirely conceptual but based on real scenarios. I know the a-synuclein discussion seems a bit out of place with part 9 of the MDS exclusion criteria, but we were using it to differentiate between brain disease and disease that affects the brain. We’ll get back to it in concept and theory of its dysfunction and aggregation.
For now, let’s put a-synuclein aside and look at some other potential causes of Parkinson’s symptoms and why. Some known causes of Parkinsonism are cancers, encephalitis, head injury, poisoning, chemical exposure, infection, viral or bacterial causes, autoimmune responses, liver dysfunction, vascular causes and psychological problems. It sounds a lot more treatable when you assign specific causes doesn’t it?
Rather than asking stupid questions like ‘Has there been any other documented cause?’ Perhaps a better diagnostic approach would be something like ‘Let’s rule out possible cancer, infections, and psychological causes before proceeding to diagnosis.’ The current method appears to suggest that only already known potential causes should be considered. One of the definitions of diagnose is: to analyze the cause or nature of. Thorough diagnosis and workup is imperative in neurological disorders. It should not be limited to imaging and patient history. The more we pursue causes and in effect find treatable conditions that cause Parkinsonism, the better we will become at diagnosing the disease and in turn treating it.
Cancers are known to cause Parkinsonism in certain instances, although they are rarely considered in a diagnosis unless there are obvious signs or a history of cancer. Remember that staring us in the face bit? Well here’s another one to look at.
In nearly any diagnostic workup, a blood test is usually performed. Within that test is typically a white blood cell count. There is a range that is considered normal for white blood cells that is somewhere between 4,000 and 11,000 per cubic millimeter of blood. Lymphocytes are another type of white blood cell that range between 1,500 and 4,500. These are simple tests to perform. Abnormalities are usually an indication that something is wrong, whether the counts are low or high. Low lymphocytes can indicate cancer, just as a high WBC can indicate the possibility of leukemia. High white blood cell counts are often dismissed or flat out ignored. I know this for a fact because I have had a persistent high count for more than a decade. It’s only between 13,000 and 16,000 so it’s not excessively high. It could also be due to the Parkinson’s and mediated immune response. The problem is that it’s never been investigated any further because there are no outward symptoms. I have asked multiple doctors to look into it and been flatly denied. It has ultimately transformed into ‘Well, that must be normal for you.’ I always ask them “What if it’s not?”, then I’m told that there’s nothing they can test for if there are no symptoms. Hello! I’ve been diagnosed with Parkinson’s disease; Wouldn’t you call that a symptom?
This points to the direct failure of our medical system when it comes to accurate diagnosis and treatment. This has to change but it will be like trying to turn a battleship around with only a set of oars. If we continue with this type of attitude towards patient concerns, failure becomes our only option.
The types of cancer that are known to cause Parkinsonian like symptoms are usually called paraneoplastic syndromes, but this is not exclusive by any means. One of the most common cancers worldwide that is known to present as Parkinson’s is colorectal cancer. Brain cancer or tumors are also known to present with movement and cognitive disorders, which is entirely logical.
Over the years, studies have indicated that cancer and Parkinson’s have in inverse relationship, meaning that a low risk of cancer is associated with it. Unfortunately these studies have become somewhat of a guideline for diagnosis which suggests that there is a low likelihood of cancer associated with Parkinson’s symptoms.
It has recently been determined that cancer may actually have a direct link to the onset of symptoms. This association has been verified right down to the gene mutations expressed in multiple forms of Parkinson’s along with other movement disorders. This would certainly explain the variations in symptoms and lack of effectiveness in universal treatments. The problem here is that we now have a convoluted medical record showing little to no association between Parkinson’s and cancer when it turns out exactly the opposite is true.
Researchers have been able to link specific genes implicated in Parkinson’s to specific forms of cancer. This of course makes genetic testing relevant because the presence of a particular gene mutation could lead to diagnostic procedures to check for that type of cancer. If found, the symptoms of that cancer would then be documented as a known cause of Parkinson’s. Hopefully these symptoms would be nearly identical in all patients thus identifying one particular type of Parkinson’s and narrowing the diagnostic criteria of idiopathic Parkinson’s. This is at least a novel idea in a perfect world, but I’m sure you get the gist.
In colorectal cancer, documented cases of misdiagnosis most frequently occur when there are metastases (secondary growths) present, often in the lungs and liver and less commonly in the brain. The symptoms will present well within the range of a Parkinson’s diagnosis, nearly identical to atypical variants. In some cases, these symptoms are the only ones present and cancer is not initially suspected. In some documented cases, the removal of tumors in the colon have exacerbated the neurological condition to a degree that renders the patient completely dependent due to rigidity and complete akinesia. It leaves us to wonder how many of these cases are never identified. Multiple types of tumors can cause these symptoms. They are being reported and identified much more frequently than in the past. This is simply because the cases are documented and there is now an association between colon cancer and neurological symptoms. This could certainly save many lives. The obvious drawback is that by the time symptoms present from this type of tumor, it may be too late for treatment. This is why early and correct diagnosis is imperative.
Brain tumors are known to cause Parkinson’s symptoms. They are often treatable and the symptoms completely subside when the tumor is removed. These would of course be expected to show up on MRI’s and often do. They are said to be uncommon in Parkinson’s cases, likely due to the fact that they are caught on imaging. On the other side of that, a case was documented of a man that had a renal cell carcinoma history then later presented with symptoms of secondary Parkinson’s. It was identified as a brain metastasis upon subsequent imaging. This demonstrates once again how other types of cancer can lead to not only brain lesions but undetected tumors tied to other types of cancer in the body. More documentation is certainly needed, ideally this would include signs of Parkinson’s prior to the discovery of cancer as with the woman I mentioned previously who lived with a 10-year diagnosis of Parkinson’s. I would suspect that this is far more common than suggested, with all types of cancer and lymphoma. Cancer screening should be inclusive to diagnostic procedures for Parkinson’s.
Encephalitis should always be a primary consideration along with meningitis and other forms of brain infection or inflammation. Encephalitis is acute inflammation of the brain. There are many different causes such as autoimmune reactions, viral or bacterial infection and also hepatic encephalopathy which is what we are particularly interested in for Parkinson’s.
Viral causes and immune reactions are entirely different because they affect the brain directly. There are multiple types of viral infections that can cause this. Herpes, Epstein Barr, measles, HIV and viruses transmitted by insects. There are likely more but the cause of encephalitis is usually unknown. In the case of autoimmune reactions, the immune system attacks and kills brain cells. It is not understood, but it may be relevant to Parkinson’s disease and hepatic dysfunction. Most forms of encephalitis are treatable but still a danger during the inflammation period. Different types of encephalitis appear with different symptoms.
Hepatic encephalopathy is most common when Parkinson’s symptoms are involved. It is also the most difficult to diagnose and treat. It is almost always coupled with non-alcoholic cirrhosis of the liver. This has been documented at least as far back as 1975. In other words, it shouldn’t be a shocking discovery if found and definitely should be included in a diagnosis. Essentially what happens is that the liver is unable to remove toxins from the blood stream and eventually they reach the brain causing damage to the same cells responsible for Parkinson’s symptoms. It may sound like chance, and it may in fact be chance, but that’s how it happens. Hepatocerebal degeneration is the form that causes progressive neurological problems and Parkinson’s symptoms. Cognitive impairment is also a dominant feature.
The rate of hepatic encephalopathy in Parkinson’s patients is relatively low. It is estimated at around 3%. The limitations to this are the study parameters which only used a 7-year time frame. The only factor limiting this study is the time frame. The liver can manage a toxic load until it reaches a certain tipping point and begins to fail. When this is coupled with the fact that the liver regenerates itself, the length of time for individual liver failure could be far more than 7-years or far less than 3. It’s impossible to say and based on the individual. A 20 or 25-year study would be far more revealing as would a review of autopsy reports of individuals with Parkinson’s. This is just one way that the liver can act in the manifestation of Parkinson’s. It may be a key player in many other ways.
Infection could also play a leading role in the development of Parkinson’s symptoms. This would correlate directly to autoimmune reactions also. We already briefly looked at viral infection which was sufficient. Bacterial infection is similar and more limited in possibility. Spirochetes can cause Parkinsonism, specifically Treponema pallidum, which causes Syphilis. It is not syphilis itself that will cause Parkinson’s, it is syphilis in the latent stages that can manifest as Parkinson’s. It is often called the great imitator and resembles Parkinson’s exactly. It is difficult to diagnose and requires an exceptionally keen neurologist to identify it. This presentation of Parkinson’s is commonly misdiagnosed and at the same time rare. It is the only spirochete that actually causes the exact symptoms of Parkinson’s, but there are more pronounced psychiatric disorders associated with it. If you’ve had syphilis and it went untreated, it didn’t clear up, just so you know.
There are two other spirochetes associated with Parkinson’s that we need to address. They’re the subject of internet lore and I’ll explain why they’re not the cause. First of all, they have both been thoroughly studied and the connection just isn’t there.
The first is Helicobacter pylori. It is a bacterium found in cat feces. It is often passed from cats to the humans through innocuous contact and causes gastric ulcers. Of course, it is found in Parkinson’s patients, we have cats too. In many different studies, there has not been any substantial implication suggesting that these bacteria have any correlation with Parkinson’s symptoms. The only tangible evidence found was that upon eradicating H. Pylori from the body, it improved the absorption of levodopa. That’s it, nothing else could be proven. It is not considered a cause of Parkinson’s and is essentially not considered.
The second is Lyme disease, this is a fun one and you guessed it: Not it! It’s a really popular conspiracy theory so we’ll look at the symptoms in detail and see if it meets a diagnosis of Parkinson’s. The symptoms of Lyme begin with a bullseye shaped rash at the site of a tick bite within 3 to 30 days in about 70 to 80% of the cases. Enough said about that, let’s scratch that one off. Later symptoms include headaches and neck stiffness, additional rashes on other areas of the body, arthritis, facial paralysis, intermittent tendon, muscle and joint pain, heart palpitations, dizziness or shortness of breath, inflammation of the brain and spinal cord, nerve pain, shooting pains, numbness or tingling in the hands and feet, short term memory problems, neurological problems (mostly related to radiculopathy, lymphocytic meningitis and Bell’s palsy), resolving within months and occurring prior to onset of arthritis, cysts in later stages, low grade fever, fatigue and mood or sleep disorders. Now that’s a lot of commas, but there are almost no symptoms of Lyme disease that correlate to Parkinson’s symptoms at all. This doesn’t even consider comparing the distribution of Lyme disease and Parkinson’s which makes it even less plausible. Symptoms are taken from the CDC website and cross referenced with the Merck professional manual.
There may be other bacterial causes of Parkinson’s but they have yet to be identified. Protozoan infection is also suggested to cause symptoms, specifically Toxoplasmosis gondii. It too comes from cat feces and is actually a common infection that humans have developed antibodies to. Those with weak immune systems such as people with HIV and other immune disorders are most susceptible to illness. Multiple studies have been conducted trying to find a link between toxoplasmosis and Parkinson’s yet no correlation has been found. As with Lyme, the symptoms don’t even match up and it’s the same kind of witch hunt. Protozoans and parasites should absolutely not be ruled out as there is distinct possibility that they can cause neurological problems.
There has been research documenting the absence of specific bacteria in the gut microbes of Parkinson’s patients but there is no conclusive evidence of cause or effect. Further investigation is merited. As a side note, a few free-spirited Parkinson’s patients have rather unscientifically exchanged their gut bacteria for normal cultures with no success.
There could possibly be a correlation between bacteria and serotonin production in the gut in Parkinson’s. Serotonin is a precursor to dopamine and along with many other chemicals, it is deficient in Parkinson’s. 80% of serotonin in the body is produced in the intestines. Low serotonin also correlates to other conditions such as depression. It may or may not have an effect on dopamine production in Parkinson’s. One would be led to believe that it is minimal because adding levodopa to the brain results in dopamine synthesis suggesting that serotonin requirements are not excessive in the production of dopamine as a neurotransmitter.
There are three different types of gut bacteria but there are also 100 trillion of them in the human gut. It’s worth investigating but probably insignificant in the grand scheme. A lack of bacteria could simply be caused by one of the many deficiencies associated with Parkinson’s. The key bacteria to study would be foreign invaders such as the spirochetes.
Infection could easily be a cause of neurological problems by either provoking an outright immune response or alternatively an autoimmune response. Outright immune responses are relatively easy to detect and observe because they most often involve white blood cells and lymphocytes. The standard course for this type of reaction is for the white blood cells to rush to the site of infection, surround the invaders and attempt to kill the affected cells. This type of response could not be responsible for Parkinson’s disease because it would not occur over a period of years in slow progression such as happens with the death of neurons in Parkinson’s.
Autoimmune responses operate under an entirely different set of rules. These types of responses often operate on the threat of infection or insult through messenger proteins. In Parkinson’s there are no apparent abnormalities or obvious signs of infection present making it a prime candidate for what is currently being coined as an innate autoimmune response. It is the body attacking its own brain cells on the false pretense that there is illness or threat to those cells? It may very well be the case and it could also explain the a-synuclein mystery.
Apoptosis is what is known as programmed cell death. This means that through some mechanism, cells are being programmed to die. This is effective in cancer treatment when it can be properly executed, but what about when it occurs with healthy cells? The results could be disastrous, causing disease rather than curing it. We have to look at the concept of the autoimmune system and its functions to understand this.
Autoimmune responses work something along the lines of being sentries in the body. It’s defined as a condition in which the immune system mistakenly attacks its own tissues. This might not be the most scientific explanation but it’s rational at the very least. More importantly, you will understand it and how it might be implicated in Parkinson’s.
The basic idea is that the body produces an immune response by generating either a protein or an enzyme that provides a set of instructions to other cells. Don’t worry about where the instructions come from, we’ll get to that. For now, let’s just focus on the process.
Instructions for an autoimmune response are encoded in proteins or enzymes that tell the other cells how to manufacture the necessary proteins of their own to both function correctly and protect the cell. This all occurs at the deepest of cellular levels. Mitochondrial RNA or mRNA is essentially what begins the coding process for DNA when combined with enzymes or polymerase. In certain cases, such as in epigenetic change which is what occurs in Parkinson’s it is believed that these enzymes provide the encoding information to form the DNA. The process by which these enzymes are coded remains partially in question. We know how the instructions are handed out but not who decides what the instructions are. That’s the missing link in this scenario.
Most proteins and enzymes are created in the liver, or at least pass through it at some point. Cytokines are proteins that are secreted by the immune system to essentially communicate between other cells. They can be produced by a variety of cell types. In the case of Parkinson’s disease, it is believed that cytochrome P450 is an enzyme family which helps to detoxify substances that pass through the liver. They receive their instructions from cytokines as well as other enzymes. We’re sticking to cytokines for simplicity.
If a cytokine is a messenger, imagine that it travels back and forth between specific cells and conveys messages. In our case, dopamine producing cells and the cells that express P450 enzymes. If the cytokines report back to the liver cells that there is a problem it activates the P450 enzyme to correct the problem by sending the correct polypeptide to combine with the mRNA in the cell and change the DNA. This is classic epigenetics, we now have a method of DNA alteration that is traceable. We still don’t know what the problem is or why. We’ve only established a method of possible gene expression in disease.
As it goes, everyone just continues along doing their job and all is seemingly well. The cells are encoding the new DNA as instructed but the messenger is still receiving the same message. The actual message sent to the cell was to produce one strand of DNA, lock the doors and commit suicide. The problem reported by the cell was unsolvable, so the liver sent a P450 enzyme coded for apoptosis. It was the only way to fix it.
Now the situation is getting worse because the problematic cells are nearly gone and physical symptoms are starting to present as a movement disorder. The immune system is doing its job but it’s still encoding the toxic strand of DNA and replicating it because there is no information being passed on saying that it is defective. It continues to kill cells by simply doing what it was instructed to do.
The original protein that should have been coded with the mRNA is now locked out of the cells that are still living and can’t get in to correct the DNA strand. This protein has nothing to combine with and begins to become misfolded or unravel in the surrounding cells as the neurons disappear one by one. This accumulation on the cytoplasm begins to poison the cells, spreading to other cells as it continues to be produced and not absorbed. This progressive damage continues and leads to more symptoms like dementia and psychosis. Could this be the role of a-synuclein? It’s just a concept and food for thought.
The other option with a-synuclein accumulation is that it is a defective protein structure within itself and it simply unravels as it tries to penetrate the cell membrane. Sounds too easy, doesn’t it? Maybe even obvious? Well, that was the first thing that was explored in research and it hasn’t borne fruit as of yet. It wouldn’t be any less complicated anyhow because the problem of where the coding or aggregation originated from is still unresolved and that is the key to resolving this entire mystery. You cannot have effect without cause and without understanding the cause, you will never grasp the effect.
All we can say for sure is that these protein conversions more than likely occur in the liver which strongly suggests a toxic load, a virus or some other threat to the immune system. Autoimmune response is most likely due to liver damage caused by toxic load, a specific toxin or simply the inability of the liver to detoxify properly leading to inevitable cellular damage. This is the most likely possibility because the liver is essentially responsible for what is called innate immune function.
One aspect of autoimmune function that should always be investigated is underlying infection. In fact, it should be investigated before anything else. We covered this a little bit in discussing white blood cells. Underlying infection can be widespread in causes. Common causes would be the digestive tract, sinuses and believe it or not the most obvious and by far the most common is oral infection and tooth decay. An infected tooth can kill you. It can also be the source of a long term underlying infection.
An interesting thing about teeth is that they will become extremely painful at first infection, provoking an autoimmune response that can present in many different ways from swelling to rashes or fever. Once thee infection is managed, the pain will often subside and the tooth doesn’t get fixed. The immune system is still active and fighting the infection and this may over time provoke epigenetic change to continually fight the infection. Eventually the tooth will become re-infected and require tending. This is not necessarily a good thing because even after the tooth has been fixed or removed, the immune system has adapted itself to constantly fight that infection and may attack other cells. It’s a possibility. Regardless, teeth should be the first thing checked with any sign of infection. We’re still not finished with the liver. We have a few other things to cover first.
Other abnormalities in the brain that can cause movement disorders are almost always the first area of concern, thus justifying imaging as a first course of diagnosis. We covered several of these procedures already so let’s just touch on the conditions to provide familiarity.
Structural brain abnormalities can come in several forms. We’re going to include a few things that don’t actually fit the criteria technically but qualify in a functional sense.
Obvious things like cerebellar, frontal lobe and basal ganglia deterioration will be apparent with imaging and Parkinson’s is not even a consideration. This is also true for tumors and other growths. Other exclusionary items that will appear on MRI’s are hydrocephalus (water on the brain), pineal cysts and fluid accumulation in the spine such as with a syrinx or communicating hydrocephalus. If any of this appears on your imaging and you still get a Parkinson’s diagnosis, find another doctor.
There are other obvious possibilities that may cause movement disorders which cannot be disqualified in Parkinson’s disease.
Poisoning is a known risk but unless there is clear evidence with supporting symptoms, it cannot be excluded. Manganese intoxication is one type of identifiable poisoning and is evident from basal ganglia deterioration. Rotenone on the other hand is highly suspected to cause Parkinson’s but definitive testing is far beyond most laboratories and isn’t likely to occur so it can not be ruled out. Mercury poisoning is of course a possibility when tremor is present and can be identified by both symptom and serum testing. It’s very relevant to the type of poison or chemical and available testing when it comes to exclusion.
Head injury or other injuries such as spinal cord damage can create symptoms but can usually be ruled out. Chronic Traumatic Encephalopathy was often mistaken for Parkinson’s but is now more easily diagnosed due to the fact that nothing was taken off the table, which is what we need to do in Parkinson’s.
As with anything it is possible and I do say ”possible” that Parkinson’s is a psychosomatic illness. It is however unlikely. If you have Parkinson’s, you have likely been accused of this. It’s been done to me both by physicians and at work. I was told “We talked about it and figured that after this amount of time you must not be faking it.” Really? Was the fact that I was coming to work, not asking for anything and not blaming the company any indication of that? It’s insulting, but it’s just because they don’t understand. Don’t take it personally. Nonetheless, it is as I said possible that it could be psychological. This is highly unlikely due to the fact that Parkinson’s would be very difficult to fake and people usually fake other more common issues like back problems and the like because pain is not as easily discounted and often a better source if ulterior motives are present. The potential of faking Parkinson’s also diminishes over time due to progression and medication response.
Genetics are frequently cited for the causing Parkinson’s but we must tread lightly here. It is genetic but not in the sense that most people associate genetics with. Hereditary forms of Parkinson’s are actually uncommon and account for somewhere between 2% and 15% of all cases. This was somewhat of a shocking discovery. We would have a more accurate number if we actually bothered to track the demographics. Parkinson’s is an epigenetic illness with unknown causes for the most part. Hopefully I have been able to impress that on you even if it’s been in an unorthodox manner. Let’s get to the final discussion and viewpoint.
In nearly six years of consistent study of Parkinson’s I have been trying to find an associative cause that is both plausible and fits in with the diagnostic criteria and symptoms. The complexity is absolutely mind blowing, definitely a needle in a haystack. There is one thing however that continued to appear over and over again.
Before I continue, remember that this is my opinion based on thousands upon thousands of hours of research and I am sharing it as my contribution to understanding this wacky illness. I don’t claim to have the solution to Parkinson’s, I just know what I have determined to be a common feature amongst all forms once all other causes have been ruled out. You may not agree with it and that’s perfectly fine, pursue Lyme disease, low testosterone levels, DHA, Glutathione or whatever you like. As far as I can surmise, Parkinson’s disease is almost entirely centered in liver dysfunction.
Why is Parkinson’s a liver disorder? First of all, this has been suspected for a very long time. I have found documents as far back as 1940 implicating the liver and the associations continue. There are many reasons to focus our research directly on the liver, there is too much evidence to ignore. It seems as though we dance around the subject looking for a cure because we do not know enough about this complex organ to isolate the problems at hand. It’s definitely going to take a researcher or group of researchers that are bold, diligent, open minded and above all intelligent. The overall detailed function of the liver is not for the faint of heart.
As a history and sociology study by nature I decided to do a little investigating into the history of Parkinson’s and compare it to our technical and industrial development. I found an interesting correlation that loosely supports the liver theory but it’s just for novelty and nothing else.
Parkinson’s type syndromes were first cited around 1200 to 1000 B.C. It then becomes notably absent from the historical record until 1817 when Parkinson published his paper on shaking palsy. This prompted me to ask myself what occurred during those two different time periods. There were two specific things that immediately appear. The first is the Iron age from 1200 to 1000 B.C. and the second being the end of the first industrial revolution around 1820. What they really have in common is the unwitting exposure to new toxins from smelting in the iron age and the production of textiles in the industrial revolution. Exposure to toxins is one of the most highly suspected causes of Parkinson’s and it would in turn wreak havoc on the detoxifying systems of the liver. Just a fun little side note from my studies.
There are a few things currently that are lending credence to the liver theory on Parkinson’s. One of them is the orphan drug program. In the last few years there have been multiple drugs found that appear to stop or reverse the symptoms of Parkinson’s disease.
These drugs are both alkaloid and acidic based compounds, some naturally occurring. Obviously, they are stimulating some type of enzyme within the liver which needs to be isolated with each one. Some of them have shown clinical improvements within weeks.
A drawback to the laboratory testing of these drugs is the use of MPTP to induce Parkinson’s. There are multiple factors relating to symptoms that do not coincide with Parkinson’s. Rotenone or paraquat administered systemically would be a better choice to determine actual efficacy although with orphan drugs it is possible to go directly to human trial. There would undoubtedly be plenty of volunteers.
There have been a substantial number of cases documenting non-alcoholic fatty liver cirrhosis presenting as Parkinson’s disease. Hepatitis has also recently been implicated in the pathogenesis of Parkinson’s. This is just another huge red flag to the research world to pursue liver dysfunction ahead of nearly everything else. The evidence for cirrhosis is demonstrated pretty clearly in a study of liver transplant patients with Parkinson’s disease.
Before we look at the results of that let’s do a quick review on probability numbers in scientific studies. You may be familiar with the statistical probability used and the level of shock therapy associated with it. Typically, a 1% higher probability is touted as highly likely, 3% is extremely likely, 5% is almost considered absolute proof and anything over 10% is lopping off limbs to prevent certain death from a hangnail. In my book, under 5% isn’t even significant enough for review regardless of the confidence interval.
Many Parkinson’s studies cite 1% higher risk or probability of developing the disease. That’s the estimated rate of the general population with Parkinson’s so technically you’re about as likely to fall out of an airplane than you are to develop Parkinson’s from some of the causes listed in studies.
In the liver transplant study (Chronic Parkinsonism Associated with Liver Cirrhosis Diana Apetauerova, MD, Peter Hildenbrand, MD, Janet Zani, NP and Stephanie Scala, MA, CCRPNeurology, Lahey Clinic, Burlington, MA, USA), 19 patients with chronic Parkinsonism underwent liver transplantation. Improvements were noted within 6 weeks in all patients but not clinically significant. Improvement was considered significant at 3 months but not statistically significant. These improvements were in bradykinesia, rigidity and tremor as documented on UPDRS scores. At 1 year, 16 of the patients continued to show clinical improvement and 14 distinct improvement on MRI’s with hyperintesity being completely resolved. T1 pituitary signals found in 59%of the patients were also completely resolved in MRI findings.
As far as I can tell, 73% of these patients had significant improvement possibly leading to full recovery from this procedure while all patients showed statistical improvement after one year. Granted it may be a shotgun approach to treating Parkinson’s and unfeasible to implement but it definitely implicates the liver in the disease. Any study that shows such significant improvement across the board is what I would consider definitive. Of course, there have been cases that have gone the other way where patients have developed Parkinson’s after a liver transplant. It’s unfortunate but also directly implicates the liver in the pathogenesis in Parkinson’s.
There is a preponderance of evidence that this is a liver disease and the evidence continues to mount. It should be the focal point of research not only for Parkinson’s but for many types of incurable diseases that have confounded science for decades, they may also be a product of liver dysfunction.
If there are any takeaways from this chapter of Hidden Truths, it should not be just understanding a little bit about why Parkinson’s is so difficult to treat and ultimately cure. It should be a signal to doctors and researchers to focus on eliminating all possible secondary causes of Parkinson’s before handing down a diagnosis. It should also encourage using a different approach to research methods because what we’ve been doing hasn’t been working, it’s one failure after another. We need to find the cause. I know I’ve been beating that dead horse for years now, but it’s the truth. Find the cause and it will lead you to the cure.
For patients like myself hopefully this gives you a little glimpse into why this is so frustrating for everyone. It’s frustrating and no one is at fault. It’s an incredibly complex and confusing subject. I try to impress that if you eat right, exercise and keep the medications to a minimum, you will be doing yourself a huge favor and likely have a much easier time managing the disease. It has made things much more manageable for me and I actually feel pretty well after six years of this. I firmly believe that this illness will be resolved in the near future and I have faith in science. Be positive, look forward, enjoy every day as if it were your first and as always,

Be Well,