Parkinson's Disease PDF

Parkinson’s Disease Kelsy Bentz, Jake VanDyck, Marah Kittelson, Katie Lin  Where does the name Parkinson’s Come From? James Parkinson discovered the idea of Parkinson’s Disease but he called it The Shaking Palsy. It wasn’t until 50ish years after his death, a French Neurolog...

Parkinson’s Disease Kelsy Bentz, Jake VanDyck, Marah Kittelson, Katie Lin  Where does the name Parkinson’s Come From? James Parkinson discovered the idea of Parkinson’s Disease but he called it The Shaking Palsy. It wasn’t until 50ish years after his death, a French Neurologist, Jean-Martin Charcot, started referring to it as PD. Peter G. Beidler, 2020, “Who was James Parkinson?” James Parkinson  Lewy Bodies Introduction - Parkinson’s is a disease of the Central Nervous System that worsens movement overtime. - Early Stage symptoms may be unnoticable, such as small tremors in the hand - It may cause slowed movements and stiffness, increasing fall risk - It causes diminished/lack of facial expressions - Unsure of specific cause, but believed to be linked to Genetics and environmental toxins - Clumps of Proteins (called Lewy Bodies) in the brain are believed to be a clue into what triggers Parkinson’s Disease, but we are not sure why yet. (They are also associated with Dementia) Braak, H., Ghebremedhin, E., Rüb, U. et al. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318, 121–134 (2004). Stages of PD 5 stages: (not everybody has identical symptoms but these are a baseline reference) Stage 1 - Mild tremors and changes in posture, balance and facial expressions Stage 2 - Daily tasks get harder, Tremors worsen, may spread across the entire body Stage 3 - Loss of balance, consistently falling, Motor skills continually worse (may be able to still live independently) Stage 4 - Unable to live alone, if able to still walk they will need assistance, Severely disabling Stage 5 - Usually bedridden and requiring 24/7 care (Parkinsons.org) Dopamine - Dopamine is a neurotransmitter in the brain, meaning it carries messages from one part to another part of the body. - Dopamine is associated with many things including: Memory, Motivation, Pleasure rewards, Arousal, Mood, Attention and Sleep. - It may also act as a hormone by relaxing or constricting blood vessels, or lowering insulin production. Why a lack of it causes/correlates with Parkinson’s? Too much or too little dopamine may overly stimulate or reduce the messages your brain is trying to send to the body. This is why people with Parkinson’s may notice hand tremors, loss of balance and decreased motor function. Cleveland Clinic Parkinson’s  Dopamine Dopamine gets sent to the receptors to convey a message to/from the body/brain. Etiology (Cause of PD) Genetic and Environmental Factors Association In relation to prevalence of PD through the world, it is suggested that environmental and genetic factors along with ethnic differences may all play a role in the cause of PD (National institute of aging) Lack of Dopamine Striatal dopamine depletion, or lack of dopamine, is the major cause of the motor symptoms of PD May originate in the dorsal motor nucleus (a nerve in the brainstem that provides motor movements to the thorax and abdomen) (Radiopaedia). Lack of neurons and dopamine, begins in the brain stem and ascends to higher cortical levels. It affects the motor skills, which is why people with PD will shake. Etiology (cause of PD) Lack of Proteins and Lipids Potentially, also a lack of proteins and lipids (brain fat) known as Lewy Bodies, or LB Lewy bodies: “abnormal deposits of proteins called alpha- synculeus that can be found in brain cells (neurons). ○ Alpha synucleus: is an amino acid protein, member of the synuclein family which consists of alpha, beta, gamma synucleus- (proteins) that exist in ‘vertebrates’ (Benjamin et al, 2020). Taxonomy (Types of PD) Two Types 1. Primary Parkinsonism a. Parkinson’s disease b. Atypical parkinsonian disorders 2. Secondary Parkinsonism Primary Parkinsonism Primary parkinsonian disorders include Parkinson’s disease and atypical parkinsonian disorders. Both can be misdiagnosed, however a neurologist with training in movement disorders can help make an accurate diagnosis and coordinate care. Parkinson’s Disease A slow progressive neurological disease (Parkinsons.org) Atypical parkinsonian disorders Sporadic or not sporadic Progressive neurological disorders, also called Parkinsons plus syndromes (progressive supranuclear palsy, corticobasal degeneration, MSA (multiple systematrophy). (Parkinsons.org) These disorders typically progress faster than Parkinson’s disease  Secondary Parkinsonism This type of parkinsonism includes neurological disorders commonly caused by brain tumors, toxins or medications. Symptoms are similar to those seen in Parkinson’s disease and may sometimes go away with treatment, depending on the disorder. Drug Induced Parkinsonism Any drug that blocks the action of dopamine. (wyant et al, 2024). ○ Eg. Chlorpromazine (Thorazine) Vascular Parkinsonism Vascular parkinsonism is usually caused by clotting in the brain from multiple small strokes. While PD already experience gait, vascular parkinsonism people have more problems than gait over tremor. (Parkinsons.org) Prevalence & Incidence Prevalence -PD is one of the most common neurodegenerative disorders in the states, second most common in Canadians.(Parkinsons.org) -90,000 people are diagnosed every year compared to 60,000 a year before 2022. Incidence -it’s possible that individuals have developed PD in their 30’s or 40’s. -PD incidence estimates increase with age in the 65+ age range -PD incidence estimates are higher in males as compared to females at all ages https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1310084901 (2019/2020 results) https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1310078801 (2020 results only) Stats from 2011/2012 Disease exhibition and impact - Physical - Musculoskeletal Muscle rigidity(Parkinson's Foundation, 2024) Frozen shoulder - stiffness, pain and loss of range of movement in the shoulder Flexed fingers, toes or feet - one finger may extend, the thumb may fold inwards, fingers may clamp down onto the palm. In the leg, the foot may flex down or turn in, the big toe may flex upward while the other toes curl under. Stooped posture - the spine bends forward when walking, in the most severe cases by as much as 90 degrees. This posture arises because the hips and knees are flexed and will go away when lying down. Leaning sideways - involuntarily tilting of the trunk to one side when sitting, standing or walking; always to the same side. Scoliosis - sideways twisting, or curvature, of the spine. Dropped head - the head and neck flex forward; the chin may drop all the way down to the sternum Dystonia Dystonia is curled, clenched toes or a painful cramped foot  Disease exhibition and impact - Physical - Gastrointestinal Growing evidence suggests an increasing significance for the extent of gastrointestinal tract (GIT) dysfunction in Parkinson’s disease (PD) (Warnecke, T., Schäfer, KH., Claus, I. et al., 2022) Most patients suffer from GIT symptoms, including bloating, nausea, vomiting, pain and constipation during the disease course. ○ This problems can be caused from an array of different factors such as: Medication, water intake, exercise, diet and more. (Warnecke, T., Schäfer, KH., Claus, I. et al., 2022) Research is Ongoing- Today, GIT research is a promising and still growing field of inquiry and continues to provide neurologists and movement disorders specialists with novel and valuable data that can help to better understand the complexity of PD. At this point, we still have a multitude of jigsaw puzzle pieces that must be carefully pieced together. (Warnecke, T., Schäfer, KH., Claus, I. et al., 2022) Mental and emotional impact Treatment of Parkinson's disease (PD) is complex and often involves addressing behavioral changes in addition to the movement disorder. Patients with PD are susceptible to any psychiatric condition seen in the general population; some disorders, such as depression and anxiety, may result from PD-related neuropathological changes (Anderson, 2004) Depression Anxiety Disorders Hallucinations and psychosis Cognitive impairment and dementia Patients with PD frequently report or exhibit signs of anxiety, apathy, and depressed mood. These emotions may affect up to 70% of PD patients, in some cases taking the form of psychopathological syndromes and require treatment (Aarsland et al., 2007; Kulisevsky et al., 2008; Nègre-Pagès et al., 2010; Siri et al., 2010).  Social Implications Since dopamine lowers the ability for the brain to send messages to the body, people with Parkinson’s will experience: - a lack of facial expressions - Inability to comprehend verbal and non-verbal cues - Trouble using expressive/emotional language Facial Masking: Term used for the inability to instantly show facial expressions They still experience all the emotion but they are unable to express how they feel. This has been proven to have major negative social implications. - Even if they can still smile, often times it will not be a “Duchenne” smile (a real smile observed by wrinkling at the eyes) It may also work the other way, with PD patients unable to fake a smile in order to maintain business relationships. They will have trouble holding in the bit of frustration that shines through the Facial Masking. (Prenger et, al. 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790585/) Social Functioning Social withdrawal: Scoping review of over 80 full text articles, refined in two phases to 58 articles found: - 54% experienced social discomfort - 43% clinically diagnosed with a social phobia - Physical symptoms are the strongest predictor for social functioning - Randomized placebo controlled studies found social life improvement with intervention (Ahn, 2022) Sleep Disordered sleep or sleep disturbances - Reduced sleep capacity - Primary and secondary insomnia - REM sleep behaviour disorder - Restless legs - As a result, cellular functions (e.g. protein folding/degradation) are impaired - creating a positive feedback loop - Some studies suggest a link between sleep disturbance and increased PD development/ exacerbated symptoms (Bohnen, (Jewett & Thapa, 2022), (López & Chien, 2022), (Gandhi & Saadabadi, 2023), (Gandhi, 2023), (Levodopa, Carbidopa, and Entacapone, 2024), (Marsden, 1982), (Carbidopa and levodopa, 2024), (COMT inhibitors, n.d.), (Levodopa, Carbidopa, and Entacapone, 2024), (D, 2022), (Anticholinergics and antispasmodics, 2024), (Ghossein et al., 2023), (Mol, 2021), (Chang & Ramphul, 2023), (Standaert & Goldstein, 2018), (M, 2024). Drug Name Carbidopa-Levodopa Dopamine receptor Anticholinergics MAO-B COMT (Catechol-o- Amantadine agonists (monoamine methyltransferase) oxidase-B) inhibitors Inhibitors Mechanism Carbidopa - Preferred for - Block acetylcholine - Inhibits - Inhibits dopamine -Weak excitatory - Prevents Levodopa younger patients. activity dopamine and levodopa neurotransmitter breakdown degradation degradation antagonist - Bind to dopamine - Meets the lack of Levodopa receptor and dopamine by reducing - Sustains - Sustains levodopa - Helps balance - Precursor to initiate cellular acetylcholine dopamine levels and dopamine levels dopamine and dopamine response. (imitates longer longer excitatory - Can go straight into dopamine) neurotransmitters brain Dosage - 10-400 mg 2-4 times - 2-6 mg/24 hours - 0.5-5 mg 2-3 times - 0.5-5 mg 1-2 - 100-200 mg 3-8 - 50-200 mg taken daily daily times daily times daily 1-2 times daily - 4-8 hours between - 4-6 hours between - Once daily is - A few exceptions most common; with lower dosage in other brands the evening have variability (Jewett & Thapa, 2022), (López & Chien, 2022), (Gandhi & Saadabadi, 2023), (Gandhi, 2023), (Levodopa, Carbidopa, and Entacapone, 2024), (Marsden, 1982), (Carbidopa and levodopa, 2024), (COMT inhibitors, n.d.), (Levodopa, Carbidopa, and Entacapone, 2024), (D, 2022), (Anticholinergics and antispasmodics, 2024), (Ghossein et al., 2023), (Mol, 2021), (Chang & Ramphul, 2023), (Standaert & Goldstein, 2018), (M, 2024). Drug Name Carbidopa-Levodopa Dopamine Anticholinergics MAO-B COMT Amantadine receptor (monoamine (Catechol-o- agonists oxidase-B) methyltransfe Inhibitors rase) inhibitors Adverse/side - Confusion, - Nausea, - Dry mouth, fluid - Dry mouth, - Initial Levo - Low side effect profile effects hallucinations, orthostatic LBP, distribution nausea, induced delusion, psychosis, headache, issues, bowel diarrhea, dyskinesia - LBP, dry mouth, and dry mouth, appetite dizziness, and obstruction, constipation, worsening consciousness/alertness loss cardiac increased HR, drowsiness, when paired issues arrhythmia dilated pupils insomnia - Long term use can and blurry vision - Nausea, lead to movement - Long term use hypotension, disorders (e.g. may lead to hallucinations fidgeting, abnormal psychiatric and , sleep involuntary movement disorder, movements) disturbances urination changes and diarrhea Considerations Meet John Doe! John Doe has secondary parkinsonism He currently takes (carbidopa-levodopa) to help with his motor control, motivation, mood and cognition due to it helping to increase dopamine. Currently has a great fear of falling due to muscle rigidity and pain, socially he feels isolated due to his PD diagnosis and perceived stigma, has trouble with daily tasks due to diagnosis Age: 65 years old  Before exercise intervention Health condition - secondary parkinsonism Participation -Current medications can result in dehydration with exercise so Body Function Activity John doesn’t participate in exercise. -weak muscles - Relatively Sedentary -muscles shaking, muscle - No activity present, -He is not very social as he fears rigidity does not get out the judgement and looks of -sleep problems much others -dizziness and fainting Environmental factors Personal factors -medication decreasing -higher chance of mental/emotional hydration illness increases shaking, and the risk of falling -medication may help, but not much, eg. carbidopa-levodopa side effects induces shaking, and may not reduce it.  Impact on Exercise Exercise has a beneficial impact on PD patients BUT PD has a negative impact on the ability to exercise. As PD progresses, patients will lose joint flexibility, muscle strength and decreased cardiovascular capabilities. - This means that it will be harder to balance as well as harder to use the body as a whole for basic tasks. - This can cause a heightened fear of falling in PD patients, which leads to a sedentary lifestyle. Knowing the benefits of exercise in PD, the patient will have to find some form of exercise that suits their ability and personality. Some patients can run marathons while others have improved by doing Yoga classes. (Parkinson’s Foundation.) Impact on Exercise Chronotropic Incompetence is a condition commonly associated with Parkinson’s which makes one’s heart rate stay static (doesn’t rise) with Cardio. If the heart rate does not rise with exercise, this may cause feelings of lightheadedness and exhaustion to come up rather quickly. (Panassollo et, al. 2024) Hydrotherapy and PD Hydrotherapy includes swimming but it means any exercise done in the water. When patients are scared of falling, they can transfer into a shallow pool and do the exercises with more buoyancy. (UCLA Health, 2023) Swimming and PD Impact Swimming (or Hydrotherapy) is beneficial for multiple reasons: - Buoyancy of the water makes “impossible” movements, possible - Decreased Pain - Increased Mobility - Decreases Fear of Falling - Increases Balance - Increases Social Interaction (improving quality of life) (Naumann, K., 2021) “Hydrotherapy, combined or not with other therapies, may improve balance and functional mobility of patients with PD when compared to land-based therapy alone or usual care.” (Pinto. C, 2019) Case Study Case Study - https://www.sciencedirect.com/science/article/pii/S0765159711002401 Sixteen patients underwent an aquatic training program based on two weekly sessions during 12 weeks. Both the illness’ impact on their living and their fitness level were measured at the beginning and at the end of the intervention. The obtained results showed an improvement in the sample's fitness level and in their ability to perform daily activities. Water exercise is a safe physical therapy modality for Parkinson's disease patients, which can improve their fitness level and alleviate the illness’ impact on their lives (Ayán and Cancela) Dancing and PD Impact Rhythmic Auditory Stimulation (RAS) uses metronomes or rhythmically specific music to enhance neurological rehabilitation. It is well-known as a safe, easy and effective method for Parkinson’s Patients (classes are supervised and/or can do at home) “Rhythmically cued exercise interventions are effective in improving motor function in the early to middle stages of Parkinson disease. More than 10 weeks of intervention yielded better results. However, these interventions do not have a significant impact on cognition and mental states. Importantly, rhythmically cued exercise interventions are safe and well tolerated.” (Huang. X, 2024)  After the Hydrotherapy and/or dancing intervention Health condition Participation Secondary Parkinsonism -loves his dancing class and swimming class - Is interested to participate Body Function in more classes - Currently goes 3 times a -if shaking, the body can still week, for 1 hour but wants perform the necessary Activity to increase to every weekday movements in the water - Current medications can -sleep is better -after swimming result in dehydration but we and/or dancing much have created a hydration plan and pool temp helps manage Increased exercise has helped more effective dehydration manage the shaking and helped John’s confidence in his body Personal factors Environmental factors - Regulated water -Mental health has temperature helps improved greatly regulate his body -Made 5 new friends in the temperature swimming class - Sense of community as an exercise group References Aarsland D., Brønnick K., Ehrt U., De Deyn P. P., Tekin S., Emre M., et al. (2007). 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