Stages of Parkinson’s Disease and Treatments

Parkinson’s Disease, a progressively worsening neurological disorder, primarily impacts the control of bodily movements. This condition is most commonly diagnosed in individuals who are between the ages of 55 and 65 years old. It has been observed that Parkinson’s Disease affects approximately 1% to 2% of individuals who are over the age of 60 years. This percentage increases to 3.5% for those aged between 85 and 89 years. When considering the general population, it is estimated that roughly 0.3% of people are affected by Parkinson’s Disease.

The disease is marked by a specific set of characteristics. One of the most notable is the selective loss of neurons that produce dopamine, a neurotransmitter that plays a crucial role in coordinating the body’s movements. Additionally, there is an accumulation of what are known as Lewy bodies. These are composed of a protein called α-synuclein. In patients with Parkinson’s Disease, this protein becomes misfolded and starts to accumulate in multiple systems within the body, contributing to the symptoms and progression of the disease.

What is Parkinson’s Disease?

Parkinson’s Disease, first described by Dr. James Parkinson in 1817 as a “shaking palsy”, is a neurodegenerative disorder primarily defined by two significant pathological processes. The first of these processes is the premature and selective loss of neurons that produce dopamine, a neurotransmitter that plays a crucial role in coordinating smooth and balanced muscle movement. The second defining pathological process is the accumulation of protein deposits known as Lewy bodies within the neurons. 

These two processes are not instantaneous but occur progressively over a span of many years, as evidenced by numerous pathological studies. This gradual, stepwise degeneration of neurons is directly linked to the manifestation of specific symptoms associated with Parkinson’s Disease, with each affected site within the brain corresponding to a particular symptom or set of symptoms. Thus, the disease’s progression and symptomatology are closely tied to these two major pathological processes.

stages of parkinson's disease
Stages and Symptoms of Parkinson’s Disease
Stage Sites affected by Lewy bodies Major symptoms
1
Dorsal motor nucleus of the vagus nerve and olfactory tract
Constipation, anosmia
2
Locus coeruleus and subcoeruleus complex
Sleep and mood dysfunction
3
Substantia nigra
Motor symptoms of Parkinson's Disease
4 - 5
Cortical involvement
Dementia, psychosis

A Deep Dive in Understanding the Cause of Parkinson's Disease

causes of parkinson's disease
Common causes of Parkinson’s Disease

Parkinson’s Disease (PD) stands as a complex neurological disorder that has perplexed the medical community for years. What causes Parkinson’s Disease? The aetiology (cause/s) of Parkinson’s Disease is not singular but believed to be multifaceted, involving an intricate interplay between genetic factors and environmental influences. This complexity makes PD a challenging condition to predict and prevent, necessitating a closer examination of its underlying causes.

Genetic Predisposition

One of the critical components in the aetiology of Parkinson’s Disease is genetic predisposition. Research has identified several genetic mutations that can increase an individual’s susceptibility to developing PD. These mutations are not universally present in all cases, but they do provide a significant clue towards understanding why some individuals are more prone to the disease. Genetic predisposition does not guarantee the onset of Parkinson’s but indicates a higher risk level, especially when combined with environmental factors.

Environmental Influences

Environmental factors play a substantial role in the aetiology of Parkinson’s Disease, acting upon the genetic susceptibility of an individual. These influences include exposure to certain toxins, pesticides, and heavy metals, which have been associated with an increased risk of developing PD. Additionally, head injuries and rural living environments have also been identified as potential risk factors. The exact mechanisms by which these factors contribute to Parkinson’s Disease are still under investigation, but they are believed to cause cellular damage or disrupt normal cellular processes, leading to the characteristic symptoms of PD.

The Interplay Between Genetics and Environment

The interplay between genetic predisposition and environmental influences is central to the aetiology of Parkinson’s Disease. It is this combination that likely sets the stage for the development of PD, with environmental factors triggering the disease in individuals who are genetically susceptible. This hypothesis is supported by the fact that not everyone exposed to the identified environmental risks develops Parkinson’s, and not all individuals with genetic mutations associated with PD will get the disease. It suggests a complex relationship where both elements are necessary but not sufficient on their own to cause Parkinson’s Disease.

Nonmodifiable risk factors Modifiable risk factors
Age (average age 65 yr), Sex (M:F = 1.5:1.0), Genetics (10% of cases)
Industrial exposure, Heavy metals, Pesticides, Obstructive sleep apnoea (maybe in women)

The table presents a classification of risk factors associated with a specific condition into two categories: non modifiable and modifiable. Nonmodifiable risk factors, which cannot be changed, include age with a mean (most common or average) age of 65 years, sex with a male to female ratio of 1.5:1, and genetics, accounting for 10% of cases. Modifiable risk factors, which can be influenced or controlled, include industrial exposure, exposure to heavy metals, pesticides, and possibly obstructive sleep apnoea in women. Understanding these risk factors can help in the prevention and management of the condition, with a focus on altering modifiable risks where possible.

Diagnosis of Parkinson's Disease

Understanding the Basics

Parkinson’s Disease is a complex neurological disorder that primarily affects the control of bodily movements. It is characterised by the selective loss of dopamine-producing neurons and the accumulation of Lewy bodies in the brain. The disease progresses gradually over time, with symptoms corresponding to the affected sites within the brain. The aetiology of Parkinson’s Disease is believed to involve a combination of genetic predisposition and environmental influences. Diagnosing Parkinson’s Disease relies on a careful evaluation of clinical symptoms and response to dopamine agents. 

Treatment options for Parkinson’s Disease include pharmacological treatments such as levodopa and dopamine agonists, as well as alternative therapies like physical therapy and deep brain stimulation. A holistic approach that combines both pharmacological and alternative treatments is crucial for effectively managing Parkinson’s Disease and improving the quality of life for patients.It’s crucial to acknowledge the distinct journey each individual faces with Parkinson’s Disease. 

As such, crafting a tailored treatment regimen that’s subject to ongoing evaluation is paramount in achieving optimal health outcomes. It’s imperative for anyone suspecting they or someone close might be navigating the challenges of Parkinson’s Disease to seek professional medical consultation without delay.

Role of Dopamine Agents in Diagnosis

A significant aspect of diagnosing Parkinson’s Disease involves the patient’s response to dopamine agents. Dopamine is a neurotransmitter that plays a critical role in controlling the movements of the body. In Parkinson’s Disease, the cells that produce dopamine in the brain die off, leading to the symptoms associated with the condition. 

Administering dopamine agents or medications that mimic dopamine’s effects can provide remarkable insights into the diagnosis of Parkinson’s Disease. Improvement in symptoms upon taking these medications is often considered a strong indicator of Parkinson’s Disease. This therapeutic response not only helps in confirming the diagnosis but also in assessing the severity of the condition.

Monitoring Motor Fluctuations

Over time, as the disease progresses, patients might develop motor fluctuations, which are variations in the control over movements throughout the day. These fluctuations can manifest as periods of good control (on periods) and poor control (off periods) of symptoms. The development and pattern of these fluctuations are critical in the ongoing assessment and management of Parkinson’s Disease. They provide invaluable information on the progression of the disease and the effectiveness of the current treatment regimen. Adjusting the treatment based on these observations is a key aspect of managing PD, aiming to maximise the quality of life for the patient.

Diagnosing Parkinson’s Disease is a complex process that requires a careful and detailed evaluation of clinical symptoms, patient history, and response to dopamine agents. The absence of a definitive test for PD makes the role of experienced neurologists central to the accurate diagnosis and management of the disease. Over time, monitoring the patient’s response to treatment and the evolution of motor fluctuations becomes crucial in tailoring the treatment to the patient’s specific needs, highlighting the personalised nature of managing Parkinson’s Disease.

Criteria for diagnosing Parkinson's Disease

  • Bradykinesia and at least one of the following:
    • Rigidity
    • Resting tremor (4–6 Hz)
    • Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction
  • Exclusion of other causes of parkinsonism
  • At least three of the following supportive (prospective) features:
    • Unilateral onset
    • Persistent asymmetry primarily affecting the side of onset
    • Resting tremor (hand, leg or jaw; low frequency [4–5 Hz], asymmetric, disappears with action)
    • Excellent response to levodopa (70%–100%)
    • Progressive disorder
    • Severe levodopa-induced chorea (dyskinesias)
    • Levodopa response for five years or more
    • Clinical course of 10 years or more

Treatment of Parkinson's Disease: Exploring All Therapeutic Options

alternative treatments for parkinson's disease
Treatment options for Parkinson’s Disease

While there is no cure for PD, a comprehensive treatment plan can significantly improve symptoms. This plan often includes both pharmacological treatments and alternative therapies. Here, we delve deeper into the pharmacological options, their modes of action, and dosages, followed by a detailed exploration of alternative treatments, including medical cannabis, ensuring balanced coverage.

Pharmacological Treatments for Parkinson's Disease

1. Levodopa

  • Mode of Action: Levodopa is converted to dopamine in the brain, compensating for the decreased dopamine production in PD.
  • Dosages: Typically starts at a low dose and is gradually increased. The dosage varies significantly among individuals, often combined with Carbidopa to reduce side effects.
  • Potential Side Effects:
    • Nausea and vomiting
    • Low blood pressure, especially upon standing (orthostatic hypotension)
    • Dyskinesias (involuntary movements) after long-term use
    • Motor fluctuations like ‘wearing-off’ effect or ‘on-off’ phenomena

2. Dopamine Agonists

  • Mode of Action: Mimic dopamine’s effects in the brain without having to be converted to dopamine, used to stimulate dopamine receptors directly.
  • Dosages: Varies based on the specific agent (e.g., Pramipexole, Ropinirole). These are initiated at low doses and adjusted based on response and tolerability.
  • Potential Side Effects:
    • Sleepiness and sudden onset of sleep
    • Hallucinations and confusion
    • Impulse control disorders such as compulsive gambling or eating
    • Leg swelling

3. MAO-B Inhibitors

  • Mode of Action: Prevent the breakdown of brain dopamine by inhibiting the monoamine oxidase B (MAO-B) enzyme, thus increasing dopamine availability.
  • Dosages: Selegiline and Rasagiline are common options, with dosages tailored to the patient’s condition and response.
  • Potential Side Effects:
    • Headache
    • Insomnia
    • Nausea
    • Potential interactions with other medications, leading to serotonin syndrome when combined with certain antidepressants

4. COMT Inhibitors

  • Mode of Action: Block the catechol-O-methyltransferase (COMT) enzyme that breaks down dopamine, enhancing and prolonging the effects of Levodopa.
  • Dosages: Entacapone and Tolcapone are examples, usually taken with each dose of Levodopa/Carbidopa.
  • Potential Side Effects:
    • Diarrhoea
    • Orange discoloration of urine
    • Dyskinesias
    • Possible liver function abnormalities (particularly with Tolcapone)

Alternative Treatments for Parkinson's Disease

1. Physical Therapy

  • Mode of Action: Custom exercises to improve gait, balance, and flexibility.
  • Key Benefits: Enhances mobility and reduces the risk of falls.
  • Dosages/Intensity: Tailored to individual capabilities; frequency and intensity are adjusted as needed.
  • Potential Side Effects:
    • Musculoskeletal pain from overexertion
    • Fatigue
    • Risk of injury if not properly supervised

2. Deep Brain Stimulation (DBS)

  • Mode of Action: Electrical impulses are sent to targeted brain areas to regulate abnormal impulses.
  • Key Benefits: Can significantly reduce symptoms in advanced PD.
  • Dosages/Intensity: Settings are adjustable based on symptom control and side effects.
  • Potential Side Effects:
    • Seizures or seizure-like activity
    • Infection at the implantation site
    • Hardware complications, such as lead displacement
    • Speech or balance problems
    • Mood changes or depression

3. Speech and Language Therapy

  • Mode of Action: Exercises and techniques to improve speech clarity and swallowing safety.
  • Key Benefits: Enhances communication and reduces the risk of aspiration.
  • Dosages/Intensity: Frequency of sessions varies based on individual needs and progress.
  • Potential Side Effects:
    • Frustration or emotional distress
    • Fatigue from intensive exercises

4. Dietary Adjustments

  • Mode of Action: Nutritional strategies to manage symptoms and overall health.
  • Key Benefits: Can alleviate constipation and improve energy levels.
  • Dosages/Intensity: Personalised according to dietary preferences and health requirements.
  • Potential Side Effects:
    • Nutrient deficiencies if not well-planned
    • Gastrointestinal discomfort with dietary changes

5. Medical Cannabis

  • Mode of Action: Cannabinoids like CBD and THC may have neuroprotective effects and improve symptoms like tremors, pain and rigidity.
  • Key Benefits: Potential relief from motor and non-motor symptoms.
  • Dosages/Intensity: Carefully titrated, considering legal status and individual response.
  • Potential Side Effects:
    • Dizziness and balance problems
    • Dry mouth and eyes
    • Altered mental status, including disorientation or confusion
    • Dependence or withdrawal symptoms

The treatment of Parkinson’s Disease requires a comprehensive and personalised approach, integrating both pharmacological and alternative therapies. Understanding the modes of action and appropriate dosages of pharmacological treatments is crucial for effective management. 

Similarly, exploring the benefits and considerations of alternative treatments, including physical therapy, DBS, speech and language therapy, dietary adjustments, and medical cannabis, allows for a holistic care plan. Collaboration with healthcare professionals is essential to tailor treatments to individual needs and to navigate the complexities of managing Parkinson’s Disease.

Closing Thoughts

Parkinson’s Disease is a complex neurodegenerative disorder that requires a sophisticated approach for both its diagnosis and management. The journey into the realm of Parkinson’s Disease encompasses an understanding of its physiological underpinnings as well as a thorough investigation into various treatment options.

Recognising the unique experience of each person with Parkinson’s Disease is essential. Tailoring a treatment plan that is regularly reviewed and adjusted is critical to ensure the best possible health outcomes.

For anyone who suspects they or a loved one might be experiencing the symptoms of Parkinson’s Disease, it is vital to seek immediate medical advice. Early consultation with healthcare professionals is a key step in addressing the challenges associated with this condition.

Written by

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

Written by

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

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