There is a lot of misinformation about concussions, their recovery, and their long-term effects. As someone who has participated in thousands of patients' concussion recoveries over the last decade, I can tell you that people can recover from concussions. However, sometimes the road to recovery is quick and easy; other times it can be long and difficult. In this blog post, I will share my perspective, created from research and experience, on what the journey of recovering from a concussion may look like.
Disclaimer: This post is for educational purposes only. Nothing in this post is intended to be medical advice. As with every medical issue, you should always consult with a medical professional licensed in your area.
In an earlier post titled, "A Simple Guide to a Not-So-Simple Concussion," we covered a lot of ground, introducing and defining what a concussion is, what happens to the brain during a concussion, some of the symptoms associated, what to do after a concussion, the types of treatment offered for concussion-rehabilitation, and more.
We also emphasized the importance of seeking medical attention as soon as possible to get the correct treatment for concussions depending on their severity. An accurate diagnosis and treatment plan are essential for recovering after a concussion.
In this post, we will focus on the recovery process from a concussion. Concussion recovery can be a daunting process. Concussions are a complex, multi-system injury that requires a vast understanding of human physiology. It is important to work with a trained, experienced, and certified doctor in treating concussions. Immediately after sustaining a concussion, it's important to be evaluated to make sure no life-threatening injuries exist.
One of the most challenging parts of a concussion is the variability in its presentation. Sometimes a concussion will have immediate symptoms. Other times concussion symptoms may not present themselves for 3 days. The MOST important thing everyone should do is err on the side of caution if a concussion is suspected. That's where the saying, "when in doubt, sit it out," comes from. While the first concussion has not healed, a second concussion might be fatal.
After a doctor has ruled out all life-threatening injuries, the next most important step to recovery is to rest. The research poorly defines "rest, " and many doctors have differing opinions. We know that bed rest (especially too much of it) is not beneficial. We also know that resuming daily activities too soon can be disastrous. Essentially, what we are looking for is the perfect amount of rest. Unfortunately, that doesn't exist. My general advice for “rest” is to do more than laying in bed all day, but less than your normal activity, with a primary goal of avoiding flaring up concussion symptoms, reducing (physical, mental, and emotional) stress, and just giving your brain time to settle and restore normal physiology.
A recommended schedule for the 24 hours after the head injury for an average person with a concussion:
It is completely normal to have common symptoms such as headache, head pressure, neck pain, dizziness, nausea, fogginess, fatigue, blurred vision, and sound/light sensitivity. If you have these concussion symptoms, let your doctor know so they can prescribe something to help alleviate them. It is not normal to vomit multiple times, to have a worsening headache, black eyes, and bruising behind your ears. Those are indications that you should head to the Emergency Room.
During these 48 hours, you should avoid anything that might thin your blood/promote bleeding, such as ibuprofen, Aspirin, Pepto-Bismol, and some supplements, unless your doctor advises it is safe. Your doctor will often tell you to take Tylenol (Acetaminophen/Paracetamol) for pain. If your doctor is trained in nutrition and neurochemistry, they may prescribe dietary supplementation or hormones that can help restore cellular function, modulate inflammation, improve fuel delivery and blood flow, and also help hasten your recovery.
On your third day after sustaining a concussion, you should have an appointment to be evaluated by a concussion specialist. These specialists can be medical doctors, chiropractors, physical therapists, or athletic trainers that have completed extensive training and are board certified to manage concussions. However, most general practitioners (“GPs”), chiropractors, physical therapists, and other professionals without board certifications are not typically comfortable or adequately trained to manage concussions.
From this point, every concussion journey is different. No two concussions are ever the same, even in the same person. Nearly all recommendations should be based on their examination findings and the patient's presentation.
Research suggests that as early as 48 hours is the best time to begin "physical activity," defined as light walking without exertion and/or prescribed, supervised, graded, light aerobic exercise. This type of exercise can be implemented and aid in recovery by helping blood flow, decreasing inflammation, increasing chemicals that help your brain heal, and improving your emotional state. This exercise must be done under the supervision of a trained specialist to prevent further injury.
Depending on your situation, the specialist may also be able to prescribe a course of brain rehabilitation exercises to help your brain regain its healthy function. These exercises are critical to decreasing recovery time. After a concussion, your brain function begins to remodel. Certain areas/networks of your brain (that are injured) are not as efficient, so your brain uses other areas/networks to perform daily tasks. In the short term, this is beneficial, but if left uncorrected can lead to long-term inefficiencies and persisting concussion symptoms.
Taking your time in the recovery journey to talk to your concussion rehabilitation expert before starting any exercise program during this delicate period is important. Remember that taking it slowly and resting are key components of recovering from a concussion successfully.
Understanding how long a concussion takes to heal is an important part of managing this condition for children, adults, and athletes alike. Unfortunately, the answer is not straightforward, as different people can take varying lengths to recover from a concussion. Athletes recover from their injury most quickly, usually in 10-14 days. In non-sport-related concussions, adults are typically symptom-free in 3 weeks. Children and teenagers sustaining both sport and non-sport concussions often recover the slowest. Their concussion symptoms may last up to 30 days. Anyone with symptoms past 30 days is considered to have a protracted recovery and absolutely needs treatment. This occurs in approximately 30% of all concussions.
Researchers have been able to identify several concussion symptoms and factors that are correlated with a longer recovery time:
Healing is an interesting term. Cuts heal... as scars. Bones heal... but their break can still be seen on X-rays for life. Concussions may "heal" on their own, but the brain may be dysfunctional for life, if not treated.
Most research leading up to 2015 defined "recovery" as restoring symptoms to baseline (prior concussion). Using that definition anywhere from 33-70% of all individuals with concussions will have symptoms 3 months after injury (PMID: 27784191). Approximately 10% of all individuals with concussions will have permanent (defined as greater than 3 years duration) symptoms.
Other studies suggest that "while symptoms may abate, only 27% of the concussions fully spontaneously recover (based on fMRI); each additional symptom reduces the recovery rate by 20%" (PMID: 27784191)
If someone has a concussion and doesn't seek care, their odds are stacked against them. They may "heal" or "recover" and may not notice any differences in their life compared to before their concussions. But they may also develop migraines or ADHD 2 years later, seemingly disconnected. Or, they may be the 1 in 10 that will always have symptoms.
Fortunately, our understanding of the brain and how it works, and breaks have grown exponentially, especially in functional neurology. Functional neurologists specialize in using techniques to improve the function of the nervous system, especially the brain. They work to identify and treat the underlying causes of various neurological symptoms and conditions.
Some of the things a functional neurologist may do include:
The goal of a functional neurologist is to help improve the overall functioning of the nervous system, leading to improved quality of life for patients, including those suffering from concussion.
A concussion is a serious brain injury that requires the attention and supervision of a trained professional. Concussion recovery is not uniform and tends to be different for each concussion. Many people with concussions will fully recover, but every brain injury needs to be evaluated appropriately. A functional neurologist trained by the Carrick Institute and certified by the American Board of Brain Injury and Rehabilitation is a great choice to manage a concussion. They have extensive training and experience in diagnosing, managing, and rehabilitating concussions.
Have you, or has someone you care about, recently sustained a head injury or a concussion? Or maybe you suffered a concussion and are on the road to recovery but still don't feel like you are "yourself" again. Perhaps you found this article because you want to understand what is happening to you. Or maybe you're searching for answers to get past the brain injury and symptoms you're experiencing and return to life as it was before. You're not alone. Best estimates suggest that approximately 1 in 10 people will sustain a concussion in any particular year. Due to a lack of public education causing underreporting, a precise definition, standard of care, and inadequate data collection, the number of concussions that occur each year may never be discovered.
Concussions confuse everyone, including doctors and researchers, for many reasons. There is very little formal training/ medical education on concussions. In the research, over 30 "official" definitions of concussions are established, all with different diagnostic criteria. Alone, this makes establishing a concussion diagnosis difficult. Additionally, a head injury is not always a concussion. All concussions are considered mild traumatic brain injuries, but not all mild traumatic brain injuries are considered concussions. And research suggests that as few as 23% of concussions will make a full recovery, based on the resolution of symptoms. The rest of those concussed may persist to post-concussion syndrome, lasting from 3 months to years (sometimes considered permanent). Confused yet? Everyone else is.
Before 2023, a concussion was reserved for mild traumatic brain injuries sustained while participating in a sport. The American College of Rehabilitation Medicine (one of the original groups of lexicographers of the definition of concussion/mTBI back in 1993), now being led by Dr. Noah Silverberg of the University of British Columbia and Dr. Grant Iverson of Harvard University, has clarified the diagnosis of TBI, mTBI, concussion, and introduced the term "suspected mTBI". Dr. Antonucci recorded a 30-minute video to explain the definition and criteria fully.
It is important to note that all concussions are mTBIs, and all mTBIs are (clearly) TBIs, but the opposite is not true. Therefore, we need to know the criteria that will allow us to diagnose the form of brain injury someone has sustained accurately.
The "mild" TBI qualifier can be applied when none of the following have been met
A "concussion" is an mTBI (meeting the criteria above) in which imaging was either negative or was not warranted.
A "suspected mTBI" should only be diagnosed when an individual has a presentation after a biomechanically plausible mechanism of injury that does not fully meet the criteria of a concussion or mTBI.
In 2014, Dr. Chris Giza published a seminal paper describing, in detail, a concussion's complex and system effects. A concussion is caused by a rapid change in the velocity of the head (from still to moving or moving to still). That quick change in speed causes stretching of brain tissue, similar to when you sprain a ligament or strain a muscle. That stretching causes damage to nerve cells which disrupts signaling, causing them to "short circuit" and become active when they're not supposed to be. This is why some people "see stars" or get their "bell rung"; because the brain area responsible for seeing or hearing (respectively) is injured. At the same time, blood vessels that deliver energy-sustaining oxygen and sugar are also stretched and sometimes even torn. This causes decreased blood flow and fuel to the same over-excited areas. This decoupling of fuel and energy causes brain cells to die. The injured brain cells release chemicals that cause inflammation, which causes swelling (causing someone to experience nausea, vomiting, and headache- possibly necessitating medical attention and treatment). This process triggers a healing response that removes dead brain cells and causes injured cells to hibernate. This all occurs within the first 48 hours. The brain naturally begins to re-organize during that time based on the demand. This remodeling process (plasticity) is not good in this scenario. This is why it is imperative to rest until this process has ended (less than 72 hours). The injury of brain tissue, combined with the reorganization of brain function, causes short- and long-term concussion symptoms. It needs to be addressed in any concussion treatment for successful concussion recovery.
Always play it safe. If someone hits their head, immediately get that person to a safe and quiet place where they can be evaluated by someone trained in concussion management. The first priority is to prevent repeated concussions. If they are an athlete playing a contact sport and sustained a sports concussion, this might be a coach or an athletic trainer. If it is not a sports-related mTBI, it may be a sports medicine/family medicine doctor, a physical therapist, chiropractor, EMT, or other health care provider. If, for some reason, nobody around is trained in managing concussions, talk to the person and observe their behavior. Here is a sample conversation that you might have.
Your job is to listen and observe. Do they sound calm, collected, clear-headed, and oriented? Are they slurring their words? They should receive medical attention and a concussion evaluation immediately if anything seems abnormal. Failure to receive proper treatment, or a second concussion that occurs before an initial concussion has not healed, can cause permanent brain damage.
A concussion will always have two or more symptoms that begin within 72 hours of injury. Suppose you or someone you know sustained a head trauma or trauma that caused their head to shake violently. In that case, it should be assumed that they have a concussion unless proven otherwise by a healthcare provider trained in concussion. Symptoms may appear at the time of injury or sometimes as late as 3 days after. The most common symptom is a headache, but there are more than 50 symptoms that someone with a concussion might experience. These symptoms may include including feeling frustrated or impatient, anxious, sad, irritable, more emotional, restlessness, sweats/chills, hot/cold extremities, pressure in the head, worse symptoms after physical exertion, nausea, light headed/ uncomfortable standing, bladder discomfort/changes, irregular/rapid heart rate, trouble with memory, difficulty concentrating, slower speed of thinking, confusion, trouble word/name finding, feeling in a fog, not feeling right, fatigue/low energy, trouble falling or staying asleep, not feeling rested, sleeping too much, needing more sleep, muscle weakness, numbness or tingling, sensitivity to noise, back pain, headaches, muscle pain/aches, eye pain, skin/muscle twitching, balance problems, neck pain (stiffness), dizziness, sensitivity to light, blurry/double vision, difficulty with moving scenery, motion intolerance, visual disturbance (snow, spots), eye strain, and more. The reality is that your brain is the organ that dictates your perception and function. If the brain is injured, any element of our life could be affected.
Once a healthcare provider determines that you or someone has sustained a concussion, there are many fallacies about what to do next. Some of them are blatantly wrong, like "head injuries are part of life/part of the game," and they aren't anything to worry about. Others are more of a misunderstanding of the facts, like "do not let the person go to sleep at night." Or "lock them in a dark room and do not engage in any activities until they are better."
Here's the truth. Concussions, like any injury, need time to heal before returning to normal activity. The critical time for rest is the first 48-72 hours. During that period, get plenty of sleep (it's perfectly fine to check in on the person to make sure they're breathing properly and they are resting peacefully- but don't wake them up), physical rest (refrain from anything more than mild physical activity), cognitive rest (refrain from any intense mental activity), and avoid any situation where a second concussion might occur. Take time off from work/school. It's essential to be extra cautious because natural healing processes are happening during that time, and sustaining another injury could be catastrophic. Contact a primary care doctor and schedule a follow-up appointment. Consult with a doctor to see if over-the-counter medications could be taken to help with symptoms. Often taking Asprin or NSAIDs (ibuprofen, naproxen, etc.) will be discouraged because they mask symptoms and thin the blood, which may increase the risk of bleeding the injury. Tylenol is most recommended for pain, and other over-the-counter medications for symptoms.
It's always better to err on the side of safety. Unless someone trained in concussion evaluation has advised that a hospital visit is unnecessary, it is always safe. Not many people have regretted going to the emergency room and being told: "everything is alright." If you are not able to be evaluated, here are some things to consider
Imaging is only warranted under particular conditions (typically over the age of 60, severe headache, unmanageable neck pain or instability, suspected skull fracture, deteriorating neurological signs, or multiple episodes of vomiting), in which case a non-contrast CT scan of your brain will often be ordered. If at least one of the Canadian CT Head Rules conditions is not met, a brain scan is likely unnecessary. MRIs are rarely helpful in the diagnosis or management of concussions. You should not return to regular activity until a second concussion evaluation is performed, the testing has normalized (you may still have symptoms), and you have been "cleared" to return to your normal activities by a licensed and trained healthcare provider. Returning to sports or activities too soon and sustaining another concussion may result in a more severe concussion or second impact syndrome, which can have deadly consequences.
Your body is miraculous at healing itself. However, healing does not always equate to "getting back to normal." For example, your body will heal if you get cut, but a scar will remain. If you roll your ankle, it will heal. Still, that ankle will be more susceptible to future injuries if it is not rehabilitated. The same is true for brain injuries. Research suggests that for a first concussion, the symptoms will resolve in approximately ten days for adults and 14 days for children (typically 50% longer for multiple concussions). This is true in many circumstances, but in many cases (10-77%), symptoms will persist for months or years, which was called "post-concussion syndrome, but is not being referred to as "persisting post-concussion symptoms." Research has also found fewer cases resolve without treatment when looking at brain function instead of symptoms. This is even true for "mild" concussions. Additionally, there is some support that repetitive sub-concussive injuries may lead to chronic traumatic encephalopathy (or CTE).
Commonly, after 10-14 days have passed, and a patient is not feeling back to normal again, a primary care provider will refer the patient to a concussion specialist. These specialists are often neurologists, physical therapists, chiropractors, neuropsychologists, athletic trainers, occupational therapists, neuro-optometrists, or other disciplines trained in concussion management.
Additionally, the relationship between head injury and neck injury is often overlooked. The mechanism of injury that causes a concussion may also injure the neck, especially in women. Therefore, an evaluation by a chiropractor or a sports medicine physician is essential to resolving concussion symptoms (particularly neck pain).
When it comes to concussion treatment or concussion treatments, there is no "one size fits all" treatment. Brain injuries are as unique as one's brain; therefore, a concussion program for a brain injury must also be as unique as each brain.
Doctors use two main methods to determine what type of concussion therapy will be prescribed: symptom-based or function-based approaches.
The 50± concussion symptoms were once divided into three types: physical symptoms, cognitive symptoms, and emotional symptoms. More recently, these symptoms have been further categorized into categories. These categories are called concussion subtypes (or phenotypes). We will expand upon these phenotypes in other articles.
There are also 2 "associated categories" that often occur secondary to the subtypes above:
By assessing your symptoms and assigning them to their proper phenotype, a doctor can choose to manage your concussion symptoms with medications or refer you to a concussion clinic for a specific type of symptom-based concussion therapy.
Symptom-based management is a traditional method of treating concussions (and many other conditions). In this style, care is directed at eliminating symptoms with a "cookie cutter" approach, with little consideration for brain function. This type of treatment typically involves medications or therapies to reduce symptoms affecting the individual with the concussion. Drugs and some therapies are very effective at reducing symptoms but often come with undesirable side effects, do not address underlying brain dysfunction from the injury, and sometimes have rebound effects (symptoms worsen when therapy is discontinued).
The symptom-based approach is like a game of "whack-a-mole." It is reactive (chasing symptoms) instead of proactive (fixing function). Usually, both the doctor and the patient end up frustrated.
While people often feel better with the symptoms-based approach, the FDA has not approved any drugs to treat concussions. No evidence supports that medications or drugs effectively resolve or shorten a concussion's duration.
The second approach to concussion treatment is function-based management. This type of management uses a systematic approach to collect health information (history, etc.), concussion symptoms and measure brain health through particular types of testing. The provider will then examine the function of each subtype, compare your values to normative data, and identify what functions/areas have sustained an injury and need rehabilitation. This method allows the provider to uncover the root cause of your symptoms, often employed by functional neurologists trained explicitly in concussion care.
The function-based approach to concussion is central to functional neurology (See "What is Functional Neurology"). This approach looks at the brain's functional integrity through sophisticated testing, advanced imaging, and/or a thorough physical examination. The data collected from these evaluations are then interpreted, considered against your concerns and goals, and compared against solid scientific research to create unique treatment plans that help rehabilitate the brain through neural plasticity (See "What is plasticity?"). While there is not a lot of research supporting the efficacy of these programs, there is support for their safety. With everything in life, when making a decision, you should always consider potential risks to potential benefits.
A primary cause of concussion symptoms and post-concussive syndrome is remodeling brain function and inflammation. These changes occur due to genetics, plasticity, or the brain's remodeling to injury. Functional neurology attempts to identify decompensated functions (not functioning normally) and create a treatment program to restore their function, once again, through plasticity. By prescribing specific sensory, motor, and cognitive exercises, a functional neurologist or a provider trained at the Carrick Institute and certified by the American College of Functional Neurology can re-wire the brain after an injury. They employ therapies that include vision therapy, physical therapy, occupational therapy, speech therapy, sports medicine, physical rehabilitation, chiropractic, vestibular therapy, mental health coaching, balance training, cardiovascular conditioning, cognitive rehabilitation, coordination training, sensory-motor processing drills, QEEG-guided neurofeedback, hyperbaric oxygen therapy (HBOT), photobiomodulation, nerve stimulation, and other modalities. Remember, the most important treatments are the ones that are appropriate for the individual concussion, and that's impossible to determine without a formal consultation and a comprehensive evaluation.
Ensuring that a person follows a physician-guided returning to activities (RTA) or returning to play (RTP) protocol after a concussion is critical to prevent permanent damage. Ideally, every person in the world would have a Brain Health Assessment before sustaining a concussion. If so, the healthcare provider could measure precisely when the person's brain has healed and when they can resume normal activities/contact sports. However, many people are not proactive about their brain health, so that's not usually the case. A concussion doctor tries to aim without a target when they do not have data from a pre-injury baseline test. We look at symptoms, assessments, performance, and tolerance to increased demand to determine when a patient has returned to "normal." The challenge is that your normal may differ from someone else's. We allow patients to return to full activities and sports once we have established that you have achieved their normal pre-concussion status.
Please share this article on your social outlets. Understanding concussions and how they can be treated may change someone's life or give hope to someone who may feel like they've run out of options.
In 2003, Heiko Braak identified a pattern of Lewy body deposition, in the synucleinopathies (the term that is given to any disease that results in the accumulation of alpha-synuclein proteins), which include Parkinson's Disease (PD), Multiple Systems Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and Dementia (LBD). The pattern that he identified has been termed the Braak Staging of Lewy Body inclusions. More current research shows that Lewy Body pathology can spread from one area of the nervous system to another, and it's conceivable that this happens in a prion-like fashion. There are also some studies that show alpha-synuclein is not only just an intracellular protein but is extracellular as well, which could explain to some degree, the progression to other areas of the brain. The first three stages of Braak's staging, are largely "asymptomatic" to the uninformed individual.
In stage 1, inclusion bodies begin accumulating in the olfactory bulb (which is the first step of the smell pathway) and a part of our brainstem called the Vagus Nucleus. Symptoms at this point may include a change in the ability to smell and taste, as well as a constellation of symptoms we call autonomic symptoms, which are often casually related to "aging". The symptoms may, or may not include: constipation, sexual dysfunction, dry eyes, dry skin, light-headedness, high blood pressure, insulin resistance, swelling of the hands and feet, bladder dysfunction, an increase in heart rate or arrhythmia, dizziness when getting out of a chair or bed, etc. In stage 2, inclusion bodies begin to form in a part of our brain stem called the locus ceruleous, and vestibular gain setting nuclei. The result of inclusion body formation in these areas leads to difficulty with arousal, wakefulness, and excessive sleepiness. The vestibular gain setting nuclei participate in the maintenance of balance, posture, motion tolerance, as well as eye movement. The involvement of a large brainstem nucleus called the nucleus gigantocellularis can begin to cause tightening and decreased mobility of the neck. In stage 3, as alpha-synuclein ubiquitinates and deposits in the midbrain substantia nigra, some of the classical symptoms associated with Parkinson's disease begin to emerge. The compacted portion of the midbrain produces dopamine to facilitate motor function, while the net-like, or reticular portion of the midbrain produces an inhibitory neurotransmitter called GABA, which has a role in both body movement, and fast eye movements. Typical symptoms at this point time are slowness of movement, usually on one side of the body first, a decrease in motivation, changes in sleep patterns and dreams/hallucinations, smaller handwriting, slowing of walking speed, difficulty walking down stairs, blurred vision, joint stiffness, and more. It is around this time that a Parkinson's expert often first identifies a possibility of the PD diagnosis, which is usually about 7 years after stage 1. At the first appearance of motor signs, it is estimated that about 30%-50% of dopamine neurons have been lost. When the mesocortex, which is a part of the brain between the midbrain and the forebrain, is affected, an individual will begin having changes in emotion. Often this results in a lack of impulse control, anxiety, depression, slowing of speech, avolition (lack of motivation), and flat affect. These are all signs of stage 4. Often in stage four, a tremor may emerge in one hand. It is in stage 4, usually about 10 years after stage 1, that general practitioners start to recognize the signs of Parkinson's disease in their patients. In the final two stages of Parkinson's disease, proteins begin depositing in the sensory association areas of the brain (Stage 5), followed by the supplementary and primary motor areas (Stage 6), leading to slowness, of movement, rigidity, stooped posture (termed camptocormia) slowness of movement (bradykinesia), freezing (akinesia), tremor, slowness of thought (bradyphrenia), difficulty or slowness in swallowing (dysphagia), weakness of voice (hypophonia), and eventually dementia.
Although Parkinson's Disease is not a fatal disease, meaning that individuals do not die of Parkinson's Disease, the effects of the disease can lead to morbidity and mortality, with falls being the number one most common (68.3%) and preventable cause of death in Parkinson's afflicted individuals. There is no standard imaging for Parkinson's Disease, although DaTscan, a variation of SPECT scan that can observe dopamine transport, has shown to be promising. The diagnosis of Parkinson's Disease currently lies in the clinical examination. Authors have indicated that the sensitivity and specificity of accurate diagnosis by a trained and experienced clinician is (Jenkins 2012) 95% and 98% respectively. At this point in time, DaTscan can confirm or at least increase the confidence of an accurate diagnosis. Identifying a problem without suggesting a solution is almost as bad as not knowing about the problem at all.
Since 1978, the Carrick Institute for Graduate Studies has been training doctors around the world to be able to identify Parkinson's Disease quickly, effectively, and early, so that various non-pharmaceutical interventions can improve the quality of life, safety, and well-being of individuals developing, or with Parkinson's Disease. You can contact the Carrick Institute to locate a Functional Neurologist near you.
In the upcoming articles, we will discuss a clinical grading scale termed the UPDRS (or United Parkinson's Disease Rating Scale) that has been developed to measure the progression or regression of Parkinson's Disease. We will also discuss non-pharmaceutical individualized patient-centered applications for Parkinson's Disease, and other neurological conditions.
Further Reading and Reference:
In a past post on the history of Parkinson's disease, I discussed a little bit about how we have arrived at our current understanding of this very prevalent neurodegenerative condition. In this blog post, we will discuss how Parkinson's Disease develops on a cellular level.
As a quick recap from our previous post, scientists have determined that the main neurological structure involved and Parkinson's disease is a part of the midbrain called the substantia nigra pars compacta; The area involved with producing dopamine, which is a mood, emotion, arousal, and movement neurotransmitter. Scientists have also determined that one of the cellular mechanisms that are associated with Parkinson's disease, is an accumulation of a protein called alpha-synuclein. Alpha-synuclein is an intracellular protein that is found mainly in neurological tissues but is also found in small quantities in heart muscle as well as some skeletal muscle. Despite its diffuse presence in tissue, the function of alpha-synuclein it's still not completely understood. However, leading researchers believe that it is intimately involved with the transport of neurotransmitters, particularly dopamine. Some researchers believe that it functions as a structural protein, called a microtubule-associated protein, or MAP, very similar to the other protein (tau protein) found accumulated in neurodegenerative conditions, such as Alzheimer's disease. The function of these MAP proteins is thought to facilitate the transportation of neurotransmitters from the cell body to the part of the neuron that communicates with other neurons, called the synaptic cleft. These microtubule-associated proteins of tau and alpha-synuclein either maintain the integrity of the transport tubules or facilitate the release of the neurotransmitters, respectively. Some studies have shown that mice lacking alpha-synuclein show an increase in dopamine release in movement-sensitive areas of the brain. Other studies in mice show that decreasing alpha-synuclein is detrimental to neurological functions, particularly with spatial learning, and working memory. Alpha-synuclein has been shown to be involved in calcium regulation, mitochondrial function, and modulation of calcium-gated voltage channels on neurons. Other studies show that alpha-synuclein actually serves to regulate dopamine levels, to protect an individual from dopamine toxicity, by blocking dopamine transporters and re-uptake. So the question becomes, "if these proteins have a purpose for maintaining the proper neurological function, why would they accumulate in individuals with neurological diseases?" In the presence of a couple of different scenarios, these types of proteins begin to accumulate, or clump together and damage the neurons where they accumulate. This process is called ubiquitination.
Ubiquitination is the process by which a polypeptide called ubiquitin (which is found everywhere in our body, as the name would suggest), is attached to a substrate protein, such as alpha-synuclein. Think of this process as Velcro touching your favorite cashmere sweater. In this example, the Velcro would be ubiquitin, and your sweater is alpha-synuclein. When the ubiquitin sticks to alpha-synuclein it causes the protein to fold over and stick to itself, and clump together. Independently, they are not sticky, but when they touch, they join and are difficult to separate. When these proteins begin to accumulate and clump together, they form what are called Lewy Bodies.
Lewy Body disease is named after the neurologist, Dr. Frederick Lewy, who discovered them while working with Dr. Alois Alzheimer in the early 1900s. (Dr. Lewy is standing on the right, with Dr. Alzheimer standing third from the right). Photo courtesy of the Alzheimer's Association. You may be thinking that we need to determine a way to stop ubiquitination. However, this process is very important in certain functions like mitosis, antibody-antigen responses, apoptosis (or programmed cell death of unhealthy cells), the formation of intracellular organelles and ribosomes, synaptic vesicle transportation, etc. In light of its importance, the scientific community is focusing efforts on trying to determine is what causes ubiquitination to become deregulated and target these dopamine-producing neurons. Researchers have identified a number of different situations that seem to promote ubiquitination:
As alpha-synuclein goes through the ubiquitination process and Lewy bodies begin to form, they render the neurons in that area begin to lose their ability to transmit neurological impulses, decrease their ability to produce neurotransmitters, and dysfunctional. It is estimated that at the time of death, an individual with Parkinson's Disease will have lost approximately 60% of their functional brain tissue to Lewy Body disease. In my next post, we'll discuss the 6 stages of Lewy Body inclusions, termed Braak's Staging.
More reading: Alexander, G. E. (2004, September). Biology of Parkinson's disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Retrieved June 17, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181806/ Greffard S, Verny M, Bonnet AM, et al. Motor score of the Unified Parkinson Disease Rating Scale as a good predictor of Lewy body-associated neuronal loss in the substantia nigra. Arch Neurol. 2006;63:584–588. Retrieved June 17, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/16606773 Olanow CW, Kieburtz K, Schapira AH. Why have we failed to achieve neuroprotection in Parkinson's disease? Ann Neurol. 2008;64 2:S101–S110. Retrieved June 17, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/19127580
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