Parkinson's Disease

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Vol. 1 No. 1 (2024)

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Submitted
May 23, 2024
Published
July 28, 2024

Parkinson’s disease: Causes, Symptoms, Diagnosis, and Treatment

https://doi.org/10.69512/ajphi.v1i01.44
Gauri Adhikari, MD
Nepalese Army Institute of Health Sciences-College of Medicine, Kathmandu, Nepal
Ritu Pokhrel, MD
Saint Joseph Medical Center, NJ, United States

Corresponding Author(s) : Gauri Adhikari, MD

gauryadhikary@gmail.com

The American Journal of Patient Health Info, Vol. 1 No. 1 (2024)

Abstract


  1. Parkinson's disease is caused by degeneration of dopamine-producing neurons.

  2. Common muscular symptoms include resting tremors, bradykinesia (slowness of movement), muscle rigidity, and postural instability, which can impact a person's ability to move and perform daily activities.

  3. Parkinson’s disease is typically diagnosed in mid to late adulthood, with an average age of onset around sixty years, although early-onset cases can occur before the age of fifty.

  4. While there is no cure for Parkinson’s disease, medications such as levodopa and dopamine agonists are prescribed to manage symptoms.

  5. Deep brain stimulation surgery may be considered in advanced cases of Parkinson's disease.

Keywords

Deep Brain Stimulation Levodopa Parkinsonism Parkinson’s Disease Tremor
Adhikari, MD, G., & Pokhrel, MD, R. (2024). Parkinson’s disease: Causes, Symptoms, Diagnosis, and Treatment. The American Journal of Patient Health Info, 1(1). https://doi.org/10.69512/ajphi.v1i01.44
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References
  1. Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. Journal of Neural Transmission. 2017 Feb 1;124(8):901–5. Available from: https://pubmed.ncbi.nlm.nih.gov/28150045/
  2. Brigo F, Erro R, Marangi A, Bhatia K, Tinazzi M. Differentiating drug-induced parkinsonism from Parkinson’s disease: An update on non-motor symptoms and investigations. Parkinsonism Relat Disord 2014;20(8):808–14.
  3. Abusrair AH, Elsekaily W, Bohlega S. Tremor in Parkinson’s Disease: From Pathophysiology to Advanced Therapies. Tremor and Other Hyperkinetic Movements 2022;12(1).
  4. Bohnen NI, Costa RM, Dauer WT, Factor SA, Giladi N, Hallett M, et al. Discussion of Research Priorities for Gait Disorders in Parkinson’s Disease. Movement Disorders 2022;37(2):253–63.
  5. Eklund M, Nuuttila S, Joutsa J, Jaakkola E, Mäkinen E, Honkanen EA, et al. Diagnostic value of micrographia in Parkinson’s disease: a study with [123I]FP-CIT SPECT. J Neural Transm (Vienna) 2022;129(7):895–904.
  6. Pu T, Huang M, Kong X, Wang M, Chen X, Feng X, et al. Lee Silverman Voice Treatment to Improve Speech in Parkinson’s Disease: A Systemic Review and Meta-Analysis. Parkinsons Dis 2021;2021:3366870.
  7. Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, et al. Cognitive decline in Parkinson disease. Nat Rev Neurol 2017;13(4):217–31.
  8. Marsh L. Depression and Parkinson’s disease: current knowledge. Curr Neurol Neurosci Rep 2013;13(12):409.
  9. Stefani A, Högl B. Sleep in Parkinson’s disease. Neuropsychopharmacology 2020;45(1):121–8.
  10. Chen Z, Li G, Liu J. Autonomic dysfunction in Parkinson’s disease: Implications for pathophysiology, diagnosis, and treatment. Neurobiol Dis 2020;134:104700.
  11. Weber etal. Parkinson’s Disease Risk Factors and Causes www.hopkinsmedicine.org. 2022 [cited 2022 Dec 19]
  12. Fayyad M, Salim S, Majbour N, Erskine D, Stoops E, Mollenhauer B, et al. Parkinson’s disease biomarkers based on α-synuclein. J Neurochem 2019;150(5):626–36.
  13. Parkinson's Foundation. Genetics and Parkinson’s [Internet]. Parkinson’s Foundation. 2017. Available from: https://www.parkinson.org/understanding-parkinsons/causes/genetics
  14. Simon DK, Tanner CM, Brundin P. Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology. Clin Geriatr Med 2020;36(1):1–12.
  15. De Miranda BR, Goldman SM, Miller GW, Greenamyre JT, Dorsey ER. Preventing Parkinson’s Disease: An Environmental Agenda. J Parkinsons Dis 2022;12(1):45–68.
  16. Brett BL, Gardner RC, Godbout J, Dams-O’Connor K, Keene CD. Traumatic Brain Injury and Risk of Neurodegenerative Disorder. Biol Psychiatry 2022;91(5):498–507.
  17. O’Bryant SE, Petersen M, Zhang F, Johnson L, German D, Hall J. Parkinson’s Disease Blood Test for Primary Care. J Alzheimers Dis Parkinsonism 2022;12(4).
  18. Pyatigorskaya N, Gallea C, Garcia-Lorenzo D, Vidailhet M, Lehericy S. A review of the use of magnetic resonance imaging in Parkinson’s disease. Therapeutic Advances in Neurological Disorders. 2014 Jul 1;7(4):206–20. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082302/
  19. Stefanis L. α-Synuclein in Parkinson’s Disease. Cold Spring Harbor Perspectives in Medicine. 2011 Dec 13;2(2):a009399–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281589/
  20. Gandhi KR, Saadabadi A. Levodopa (L-Dopa). PubMed. Treasure Island (FL): StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov
  21. Pirker W, Katzenschlager R, Hallett M, Poewe W. Pharmacological Treatment of Tremor in Parkinson’s Disease Revisited. J Parkinsons Dis 2023;13(2):127–44.
  22. Regensburger M, Ip CW, Kohl Z, Schrader C, Urban PP, Kassubek J, et al. Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations. J Neural Transm (Vienna) 2023;130(6):847–61.
  23. de Oliveira LM, Barbosa ER, Aquino CC, Munhoz RP, Fasano A, Cury RG. Deep Brain Stimulation in Patients With Mutations in Parkinson’s Disease-Related Genes: A Systematic Review. Mov Disord Clin Pract 2019;6(5):359–68.
  24. Church FC. Treatment Options for Motor and Non-Motor Symptoms of Parkinson’s Disease. Biomolecules 2021;11(4):612.
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Gauri Adhikaria, Ritu Pokhrelb

a Nepalese Army Institute of Health Sciences-College of Medicine, Kathmandu, Nepal

b Saint Joseph Medical Center, NJ, United States

Background

Parkinson's Disease (PD) is a progressive neurodegenerative disorder that involves gradual loss of nerve cells and their function. This disorder primarily affects movement. This motor system problem results from the loss of dopamine-producing brain cells. Dopamine is an important neurotransmitter that plays a vital role in the regulation of movement and coordination. One to two people out of every thousand people suffer from Parkinson's Disease at any given moment. 1% of people over 60 have Parkinson's disease, with a prevalence that rises with age. 1

Parkinson’s Disease and Parkinsonism

Parkinsonism is a comprehensive term encompassing a spectrum of neurological disorders that share common motor symptoms resembling those seen in Parkinson's disease. Parkinson's disease represents a specific and prevalent form of Parkinsonism. The progressive loss of dopamine-producing neurons in the brain marks Parkinson's disease. In contrast, parkinsonism can arise secondary to various factors, such as certain medications, toxins, vascular changes, or other neurological disorders. These secondary forms, collectively known as atypical parkinsonian syndromes, include conditions like multiple system atrophy and progressive supranuclear palsy. 2

Symptoms of Parkinson’s Disease

Parkinson’s disease primarily affects movement. Its symptoms often develop gradually over time, varying from person to person. The symptoms of Parkinson's disease include:

Figure 1.

  • Tremors: People with Parkinson’s disease often show involuntary shaking or trembling, usually starting in one hand or fingers. The tremors are most noticeable when the affected limb is at rest. 3
  • Bradykinesia: Slowness of movement is a common feature of Parkinson's disease. Patients may experience a gradual reduction in their ability to initiate and complete movements, leading to a general slowing down of everyday activities. 3
  • Muscle Rigidity: Stiffness or tightness of muscles can occur, making it difficult for individuals to move smoothly. This rigidity can be uncomfortable and may affect various parts of the body.3
  • Postural Instability: People with Parkinson's disease may have difficulty maintaining balance and upright posture, which can increase the risk of falls. 3
  • Shuffling Gait: Parkinson's disease can cause changes in walking patterns, leading to a shuffling gait with shorter steps. This can contribute to difficulties in walking and maintaining balance. 4
  • Micrographia: A characteristic of Parkinson's disease is the development of small, cramped handwriting. Over time, writing may become more difficult and less legible. 5
  • Speech Changes: Individuals with Parkinson's disease may experience changes in their voice, such as softness, monotone, or slurring. Communication difficulties may arise as a result.6
  • Facial Expression Changes: Reduced facial expressions, often called a "masked face," can occur, giving the impression of decreased emotional expressiveness.
  • Other Symptoms: Non-motor symptoms of Parkinson's disease are diverse and can significantly impact a patient's quality of life, often more so than the motor symptoms. These include cognitive impairments such as memory issues and slowed thinking and mood disorders like depression and anxiety. 7,8 Sleep disorders are common, with patients experiencing insomnia, excessive daytime sleepiness, and REM sleep behavior disorder.9 Autonomic dysfunction can lead to problems like orthostatic hypotension, constipation, urinary incontinence, and erectile dysfunction. Sensory symptoms, such as pain and a diminished sense of smell, are also prevalent.10

Risk Factors and Causes of Parkinson’s Disease

Figure 2.

  • Age: The incidence increases significantly with advanced age, with an average age of onset of about sixty years. A small number of patients experience "early-onset" disease, meaning their symptoms start before the age of Fifty. 11
  • Idiopathic: This is the most common type of Parkinson’s disease. Scientists believe that idiopathic Parkinson’s disease is due to the misfolding of alpha-synuclein protein, which gets deposited in various parts of the brain as clumps called Lewy bodies. However, the exact cause of this is unknown. 12
  • Genetics: Individuals who have one or more close relatives with Parkinson's disease are at a higher risk of getting the illness themselves. An estimated 10 percent of patients have a familial cause of Parkinson’s disease. 13. Certain genetic mutations have been linked to this disease.14
  • Drugs: Drug-induced Parkinson’s disease is the second most common cause after idiopathic. Certain drugs like phenothiazine, risperidone, and metoclopramide are found to cause symptoms similar to parkinsonism and are called drug-induced parkinsonism. This type can get better after reducing the dose or stopping the drug. However, in some cases, the effects can stay for longer, even after stopping the drug. 2
  • Environmental Causes: Occasionally, exposure to toxins like manganese dust, fumes, or certain pesticides has been recognized as the cause of Parkinsonian disease. However, they are yet to be confirmed.15
  • Head Injury: People who have repeated head injuries in sports like boxing, hockey, football, etc, are also found to have post-traumatic parkinsonism.16

Diagnosis of Parkinson’s Disease

Diagnosing Parkinson's disease involves a comprehensive evaluation by a healthcare professional, usually a neurologist. There are no definitive tests for Parkinson's disease, so the diagnosis is based on clinical assessments, medical history, and the presence of characteristic symptoms. The tests that are performed are as follows:

Figure 3.

  • Blood Test: Blood tests are usually performed to rule out other conditions like toxins or drug exposure. Tests like thyroid function tests or quantitative measurement of copper may be done to rule out thyroid disorders or Wilson’s disease that mimic Parkinson’s disease. 17
  • Computed tomography (CT) Scan/ Magnetic Resonance Imaging (MRI): CT scan is an imaging test that uses a series of X-rays and a computer to create a detailed brain image. In contrast, MRI uses magnetic fields to create similar images. These tests help to rule out other structural brain abnormalities that may mimic Parkinson’s disease. MRI methods may also be used to track the development of the disease and identify brain abnormalities in preclinical patients or those who are at risk of developing Parkinson's disease. 18
  • Genetic Testing: In cases with a family history of Parkinson's disease or early-onset cases, genetic testing may be considered to identify specific genetic mutations associated with familial forms of the disease. 13,14
  • Detection of Alpha-Synuclein: This is a new approach to diagnosing the condition. Researchers have suggested two tests to detect the protein involved in Parkinson’s disease that can be a possible marker. The tests are a spinal tap and study of cerebrospinal fluid (CSF) to look for misfolded protein, and the other one is a biopsy of nerves on the skin surface.19

Treatment of Parkinson’s Disease

While there is no cure for Parkinson’s disease, various treatment strategies focus on improving quality of life, managing symptoms, and providing support. Here are key aspects of the management of Parkinsonism.

Figure 4.

1. Medical Management of Parkinson’s Disease

  • Levodopa: In Parkinson’s disease, there is not enough dopamine. Providing your body with dopamine is central to the treatment of the condition. Levodopa is a precursor to dopamine, and it helps replenish dopamine levels in the brain and alleviate motor symptoms. It is usually used in combination with a drug named carbidopa, which helps to stop the premature conversion of levodopa to dopamine outside of the brain. The drug levodopa, however, causes side effects like dizziness, orthostatic hypotension, anxiety, dyskinesia, confusion, and even hallucinations in some cases. Over time, the effectiveness of levodopa can change due to the changes your body goes through, so dose adjustments might be needed later in the process.20
  • Dopamine Agonists: Drugs like pramipexol and ropinirole are dopamine agonists. These medications mimic the effects of dopamine and can be used alone or in combination with levodopa. The side effects of this drug are similar to those of levodopa but are milder than those of levodopa itself. 21
  • MAO-B Inhibitors and COMT Inhibitors: These are drugs like entacapone, tolcapone and amantadine. These medications help increase the duration of the effects of levodopa by stopping its breakdown in the body. The side effects of these drugs include dyskinesia, diarrhea, nausea, ankle swelling, skin color changes, and even hallucination.22
  • Additional Treatment: Patients with parkinsonism also need treatment for conditions like erectile dysfunction, constipation, sleep-related issues, or depression.

2. Surgical Management of Parkinson’s Disease

  • Deep Brain Stimulation (DBS): DBS is one of the most commonly discussed surgical procedures used as a treatment for Parkinson's disease and other movement disorders. For the procedure, a particular type of electrode is implanted into specific brain regions, which are then connected to a neurostimulator, a device similar to a pacemaker placed under the skin near the collarbone. This neurostimulator sends electrical impulses to the brain, modulating abnormal neural activity and alleviating motor symptoms associated with Parkinson's disease. DBS is typically considered for individuals with advanced Parkinson's disease who have motor complications, such as fluctuations in medication effectiveness (wearing-off) and medication-induced dyskinesias (involuntary movements). Candidates for DBS undergo a thorough evaluation, including neurological assessments, imaging studies, and psychological evaluations, to ensure they are suitable candidates. 23

Occupational and Speech Therapy in Parkinson’s Disease

Occupational therapy aims to help individuals with Parkinson’s disease perform daily activities more independently. Your therapy team may suggest adaptive strategies and techniques to address difficulties in tasks such as dressing, writing, and cooking. Speech therapy can help manage speech and swallowing problems that may arise in Parkinsonism. Exercises and techniques are employed to improve communication and reduce the risk of aspiration.6,24

Role of a Neurologist in Parkinson’s Disease

Figure 5.

Referral to a neurologist is crucial in the comprehensive management of Parkinson's disease. Typically initiated by primary care physicians, these referrals are critical for a specialized evaluation that includes a thorough neurological examination, detailed medical history assessment, and diagnostic testing to differentiate Parkinson's disease from other movement disorders. In cases of advanced Parkinson's disease, neurologists may consider referrals for DBS surgery to alleviate motor complications. Care from a neurologist ensures that individuals with Parkinson's disease receive specialized care tailored to their unique needs, fostering optimal management and support.

Questions To Ask Your Doctor

  1. What is the typical progression of Parkinson's disease?
  2. How will Parkinson’s affect my daily life and my family?
  3. How frequently will follow-up appointments be needed to monitor the progression of the disease?
  4. What support services are available for individuals with Parkinson's disease and their caregivers?
  5. Can specific lifestyle changes, such as exercise or dietary modifications, benefit someone with Parkinson's disease?

References

  1. Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. Journal of Neural Transmission. 2017 Feb 1;124(8):901–5. Available from: https://pubmed.ncbi.nlm.nih.gov/28150045/
  2. Brigo F, Erro R, Marangi A, Bhatia K, Tinazzi M. Differentiating drug-induced parkinsonism from Parkinson’s disease: An update on non-motor symptoms and investigations. Parkinsonism Relat Disord 2014;20(8):808–14. Available from: https://pubmed.ncbi.nlm.nih.gov/24935237/
  3. Abusrair AH, Elsekaily W, Bohlega S. Tremor in Parkinson’s Disease: From Pathophysiology to Advanced Therapies. Tremor and Other Hyperkinetic Movements 2022;12(1). Available from: https://pubmed.ncbi.nlm.nih.gov/36211804/
  4. Bohnen NI, Costa RM, Dauer WT, Factor SA, Giladi N, Hallett M, et al. Discussion of Research Priorities for Gait Disorders in Parkinson’s Disease. Movement Disorders 2022;37(2):253–63. Available from: https://pubmed.ncbi.nlm.nih.gov/34939221/
  5. Eklund M, Nuuttila S, Joutsa J, Jaakkola E, Mäkinen E, Honkanen EA, et al. Diagnostic value of micrographia in Parkinson’s disease: a study with [123I]FP-CIT SPECT. J Neural Transm (Vienna) 2022;129(7):895–904. Available from: https://pubmed.ncbi.nlm.nih.gov/35624405/
  6. Pu T, Huang M, Kong X, Wang M, Chen X, Feng X, et al. Lee Silverman Voice Treatment to Improve Speech in Parkinson’s Disease: A Systemic Review and Meta-Analysis. Parkinsons Dis 2021;2021:3366870. Available from: https://pubmed.ncbi.nlm.nih.gov/35070257/
  7. Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, et al. Cognitive decline in Parkinson disease. Nat Rev Neurol 2017;13(4):217–31. https://pubmed.ncbi.nlm.nih.gov/28257128/
  8. Marsh L. Depression and Parkinson’s disease: current knowledge. Curr Neurol Neurosci Rep 2013;13(12):409. Available from: https://pubmed.ncbi.nlm.nih.gov/24190780/
  9. Stefani A, Högl B. Sleep in Parkinson’s disease. Neuropsychopharmacology 2020;45(1):121–8. Available from: https://pubmed.ncbi.nlm.nih.gov/31234200/
  10. Chen Z, Li G, Liu J. Autonomic dysfunction in Parkinson’s disease: Implications for pathophysiology, diagnosis, and treatment. Neurobiol Dis 2020;134:104700. Available from: https://pubmed.ncbi.nlm.nih.gov/31809788/
  11. Weber etal. Parkinson’s Disease Risk Factors and Causes www.hopkinsmedicine.org. 2022 [cited 2022 Dec 19]. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/parkinsons-disease/parkinsons-disease-risk-factors-and-causes
  12. Fayyad M, Salim S, Majbour N, Erskine D, Stoops E, Mollenhauer B, et al. Parkinson’s disease biomarkers based on α-synuclein. J Neurochem 2019;150(5):626–36. Available from: https://pubmed.ncbi.nlm.nih.gov/31265130/
  13. Parkinson's Foundation. Genetics and Parkinson’s [Internet]. Parkinson’s Foundation. 2017. Available from: https://www.parkinson.org/understanding-parkinsons/causes/genetics
  14. Simon DK, Tanner CM, Brundin P. Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology. Clin Geriatr Med 2020;36(1):1–12. Available from: https://pubmed.ncbi.nlm.nih.gov/31733690/
  15. De Miranda BR, Goldman SM, Miller GW, Greenamyre JT, Dorsey ER. Preventing Parkinson’s Disease: An Environmental Agenda. J Parkinsons Dis 2022;12(1):45–68. Available from: http://pubmed.ncbi.nlm.nih.gov/34719434/
  16. Brett BL, Gardner RC, Godbout J, Dams-O’Connor K, Keene CD. Traumatic Brain Injury and Risk of Neurodegenerative Disorder. Biol Psychiatry 2022;91(5):498–507. Available from: https://pubmed.ncbi.nlm.nih.gov/34364650/
  17. O’Bryant SE, Petersen M, Zhang F, Johnson L, German D, Hall J. Parkinson’s Disease Blood Test for Primary Care. J Alzheimers Dis Parkinsonism 2022;12(4). Available from: https://pubmed.ncbi.nlm.nih.gov/37006377/
  18. Pyatigorskaya N, Gallea C, Garcia-Lorenzo D, Vidailhet M, Lehericy S. A review of the use of magnetic resonance imaging in Parkinson’s disease. Therapeutic Advances in Neurological Disorders. 2014 Jul 1;7(4):206–20. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082302/
  19. Stefanis L. α-Synuclein in Parkinson’s Disease. Cold Spring Harbor Perspectives in Medicine. 2011 Dec 13;2(2):a009399–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281589/
  20. Gandhi KR, Saadabadi A. Levodopa (L-Dopa). PubMed. Treasure Island (FL): StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov
  21. Pirker W, Katzenschlager R, Hallett M, Poewe W. Pharmacological Treatment of Tremor in Parkinson’s Disease Revisited. J Parkinsons Dis 2023;13(2):127–44. Available from: https://pubmed.ncbi.nlm.nih.gov/36847017/
  22. Regensburger M, Ip CW, Kohl Z, Schrader C, Urban PP, Kassubek J, et al. Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: practical considerations. J Neural Transm (Vienna) 2023;130(6):847–61. Available from: https://pubmed.ncbi.nlm.nih.gov/36964457/
  23. de Oliveira LM, Barbosa ER, Aquino CC, Munhoz RP, Fasano A, Cury RG. Deep Brain Stimulation in Patients With Mutations in Parkinson’s Disease-Related Genes: A Systematic Review. Mov Disord Clin Pract 2019;6(5):359–68. Available from: https://pubmed.ncbi.nlm.nih.gov/31286005/
  24. Church FC. Treatment Options for Motor and Non-Motor Symptoms of Parkinson’s Disease. Biomolecules 2021;11(4):612. Available from: https://pubmed.ncbi.nlm.nih.gov/33924103/

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