Parkinson’s Disease by Gage Anderson
On September 20th, 2019 an elderly female patient was admitted to the inpatient orthopedic center as she recovered from a UCL reconstruction surgery that resulted from a fall. UCL reconstruction surgery is generally an outpatient procedure, however, the patient suffered from Parkinson’s disease and had recently undergone surgery to implant a deep brain stimulator and required additional attention. This paper will discuss the epidemiology, symptoms, potential causes, mechanism, diagnosis, and treatment of Parkinson’s disease.
Parkinson’s disease is a neurodegenerative disease that primarily affects dopamine-producing neurons. Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s, affecting approximately 1% of the population over 60 and 5 % of the population over 85 (2). The disease has a gradual progression with symptoms generally beginning on one side of the body and eventually spreading to the entire body (1). Symptoms for the disease can vary depending on the patient but generally include dyskinesia (involuntary muscle movements), stiffness of limbs, slowness of movement, impaired balance, parkinsonian gait (small shuffling steps and a general slowness of movement), along with non- motor symptoms like depression, bladder issues, lightheadedness, and dementia (3). Parkinson’s disease is not considered a fatal condition as the disease itself does not affect life expectancy, but many conditions that occur along with the disease such as imbalances leading to falls can be fatal (3).
While many specifics regarding the initiation of Parkinson’s are still unknown, scientist have found the primary cause for the majority of the symptoms associated with the disease. The disease starts with the misfolding of the protein alpha-synuclein which is an abundant protein in the brain that may play a key role in the recycling of neurotransmitters and regulation of dopamine levels (4). The reasons for this misfolding is still unknown but the mechanism for it seems to similar to that of prions, which can be caused by either exposer to similar misfolded protein carried by bacteria or a shift in the brain’s homeostasis that can make a certain confirmation of that protein more favorable (3). One proposed mechanism for the disease shares commonality with Alzheimer’s disease and is caused by a dysregulation of the brain’s iron homeostasis leading to an accumulation of this iron that sets off this misfolding (7). Once these proteins have misfolded, they form clumps in nerve cells called Lewy Bodies that cause death of the dopamine-producing cells in the substantia nigra region of the brain through a process unknown (4). The substantia nigra is located in the midbrain which is part of the basal ganglia (5). The substantia nigra consists of two parts the substantia nigra pars compacta and the substantia nigra pars reticulata which contain dark-colored dopamine neurons (5). Parkinson’s disease is specifically associated with the death of dopamine neurons in the substantia nigra pars compacta (5). The loss of the dopamine produced by these cells can definitely explain the majority of the motor symptoms associated with the disease and potentially some of the non-motor symptoms although full mechanism are sparse with the current knowledge of Parkinson’s disease.
The motor symptoms are mostly due to the effect dopamine has on specific cells in the striatum (a portion of the basal ganglia) and how those cells excite or inhibit different movement pathways (6). This portion of the basal ganglia is responsible for making the decision as to whether or not to allow movements is based on the excitement or inhibition of the indirect and direct pathways (6). The direct pathway starts and helps voluntary movements, whereas the indirect pathway tries to prevent movements that may be unwanted (6). Dopamine excites cells in the stratum that are related to the direct pathway and inhibits striatal cells that are related to the indirect pathway (6). So, when there is a lack of dopamine present the indirect pathway-related cells in the striatum aren’t fully inhibited and the direct pathway-related cells in the striatum aren’t fully excited. This results in lower motor activity and very slow processing of movements causing dyskinesia and many other motor symptoms.
Beings Parkinson’s disease can have such a variety of symptoms and no real accepted cause, diagnosis can often be difficult and in the past relied heavily on the physician’s experience and knowledge of the disease creating misdiagnosis rates anywhere from 10-20% (8). While there are no widely accepted tests that exist to diagnose Parkinson’s disease many hospitals rely on a set of criteria created by international Parkinson’s and movement society (9). This set of criteria is labeled with the acronym MDS-UPDRS and sets out to standardize the diagnosis of Parkinson’s disease through a four-part examination focusing an all facets of the disease from motor to non-motor symptoms (9). While this set of criteria generally leads to fairly thorough examination there are scans that can’t necessarily diagnose the disease own there own but can help to confirm a diagnosis and rule out other disorders (10). While many of these scans cannot generally diagnose Parkinson’s disease one new method for MRI scanning has been shown to accurately diagnose early-stage Parkinson’s disease with 85% accuracy (11). This new method of conduction an MRI is called resting-state fMRI. resting-state fMRI operates at lower frequencies than an average MRI and does not require the patient to perform any tasks other than resting and in doing so this method can help determine the connectivity of brain networks in the basal ganglia (11).
Once diagnosed with Parkinson’s disease the plan of treatment can vary widely depending on the severity of the disease and the symptoms experienced. Parkinson’s disease cannot be cured so treatment is often only to reduce symptoms and is generally a combination of medication and physical therapy (10). Since most symptoms of Parkinson’s disease are caused by low dopamine levels most medications serve to either mimic dopamine’s effect in the brain or convert to dopamine once in the brain as dopamine itself cannot enter the brain (10). While there is an extensive list of these medications the most effective is a mixture of Carbidopa and Levodopa (10). Levodopa is a natural chemical that is able to enter the brain and once inside the brain it can be converted to dopamine by the enzyme DOPA decarboxylase, Carbidopa is added to prevent the conversion of levodopa before the chemical enters the brain (10). For mild cases of Parkinson’s disease MAO B inhibitors may be used in order to inhibit the enzyme monoamine oxidase B which metabolizes dopamine in the brain (10). Unfortunately, many of these medications will lose their effect or stop working after a period of time making long term treatment very difficult. In the case of Levodopa, long term use of this drug triggers increased DNA methylation specifically in nerve cells located in the striatum (12). This DNA methylation isn’t necessarily a good thing, but it does offer some insight into the future of Parkinson’s medication and potential to prolong the effect of drugs like Levodopa (12). Once patients do become non-responsive to drugs like Levodopa the only option left may be surgical intervention. The primary surgical option for the treatment of Parkinson’s disease is currently a Deep Brain Stimulation implant or DBS implant (10). A DBS implant requires surgeons to implant many electrodes in certain parts of the brain that affect movement, these electrodes are then connected to a generator that is generally implanted near the collar bone (10). This device sends electrical pulses to the brain and may diminish or halt Parkinson’s disease motor symptoms (10).
While there is still much to learn about Parkinson’s disease current research has led to some effective treatments that can greatly improve quality of life for patients suffering from this disease. That being said there is still substantial room for improvement in regards to treating Parkinson’s disease and it is imperative that this research continues to further improve the lives of those suffering from this disease.
- Frei K., Troung D., Wolters E. “Case Studies In The Advancement Of Parkinson’s Disease.” CNS Spectr. 2008. 13(12 Suppl 18):1-6 https://www.researchgate.net/publication/51435640_Case_Studies_in_the_Advancement_of_Parkinson’s_Disease
- Pool, Jessica, and Emily Downward. “How Common Is Parkinson’s Disease?: Parkinson’s Statistics.” ParkinsonsDisease.net, 2019, parkinsonsdisease.net/basics/statistics/.
- “Parkinson’s Disease.” National Institute on Aging, U.S. Department of Health and Human Services, 2017, www.nia.nih.gov/health/parkinsons-disease.
- Paddock, Catharine. “Parkinson’s Disease: Why Do Brain Cells Die?” Medical News Today, MediLexicon International, 2018, www.medicalnewstoday.com/articles/321073.php.
- Neurosci. “Know Your Brain: Substantia Nigra.” Neuroscientifically Challenged, Neuroscientifically Challenged, 16 Nov. 2014, www.neuroscientificallychallenged.com/blog/know-your-brain-substantia-nigra.
- “Motor Systems Basal Ganglai .” Neuroanatomy, www.neuroanatomy.wisc.edu/coursebook/motor2.pdf.
- Xie, Anmu, et al. “Shared Mechanisms of Neurodegeneration in Alzheimer’s Disease and Parkinson’s Disease.” BioMed Research International, Hindawi Publishing Corporation, 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4037122/.
- Hess, Christopher W, and Michael S Okun. “Diagnosing Parkinson Disease.” Continuum (Minneapolis, Minn.), U.S. National Library of Medicine, Aug. 2016, www.ncbi.nlm.nih.gov/pubmed/27495197.
- Goetz, Christopher, et al. MDS-UPDRS. 2008, www.movementdisorders.org/MDS-Files1/PDFs/Rating-Scales/MDS-UPDRS_English_FINAL_Updated_August2019.pdf.
- “Parkinson’s Disease.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 30 June 2018, www.mayoclinic.org/diseases-conditions/parkinsons-disease/diagnosis-treatment/drc-20376062.
- “MRI Brain Scans Detect People with Early Parkinson’s.” University of Oxford, www.ox.ac.uk/news/2014-06-12-mri-brain-scans-detect-people-early-parkinsons#.
- Kegel, Magdalena. “Researchers Discover Why L-DOPA Stops Working in Parkinson’s Patients.” Parkinson’s News Today, 4 Aug. 2016, parkinsonsnewstoday.com/2016/08/04/researchers-discover-why-l-dopa-stop-working-parkinsons-seeking-prolonged-treatment/.