Parkinson's Disease Treatment Guidelines Quiz

Parkinson's Disease

• A chronic, progressive neurological disorder characterized by tremor, bradykinesia, rigidity, and postural instability
• Current hypothesis links Parkinson's to genetic factors, toxin exposure, exogenous and endogenous factors like well water, farming, free radicals, infection and iron and emerging research into the gut microbiome and inflammation.
• 1817 - Essay on the Shaking Palsy
• 1884 - apomorphine
• 1961 - L-Dopa
• 1969 - dopa decarboxylase inhibitors
• 1973 - CR formulation
• 1977 - MPTP
• 1982 - pergolide
• 1994 - COMT inhibitors
• 2002 - DBS.
• In Parkinson's disease, degeneration of presynaptic nigrostriatal neurons inhibits thalamocortical circuit signaling to the motor cortex.
• Different dopamine tracts throughout the brain affect movement, arousal, motivation, reward, emotion, cognition, memory, and regulate prolactin release.
• D1 and D5 receptors result in depolarization, while D2, D3, and D4 receptors result in hyperpolarization of postsynaptic neurons.

Pathophysiology

• Dopaminergic pathways in the basal ganglia-thalamocortical circuit activate D1 and D2 receptors, leading to depolarization and hyperpolarization respectively, of postsynaptic neurons.
• Degeneration of presynaptic nigrostriatal neurons in Parkinson's disease inhibits thalamocortical circuit signaling to the motor cortex.
• Reduction in neurotransmitter activity occurs, impacting the signalling pathways in the globus pallidus externa (GPe), globus pallidus interna (GPi), substantia nigra pars compacta (SNc), substantia nigra pars reticulata (SNr), and the subthalamic nucleus (STN).

Risk Factors

• Increased risk factors: Age, rural residence, farming, pesticide exposure, and frequent dairy consumption
• Protective factors: Cigarette smoking, coffee, tea, caffeine (3-5 mg/kg dose), and dietary factors like Vitamin D, sex hormones, homocysteine, and hypertension. Medications like NSAIDs and statins may be protective.
• Environmental factors: Exposure to volatile organic compounds (VOCs, such as trichloroethylene) has been linked to an increased risk of Parkinson's in certain communities.
• Genetic factors: The Parkin gene and alpha-synuclein are implicated.
• Emerging research: Gut microbiome and inflammation are areas of ongoing study.

Secondary Parkinsonism

• Drug-induced causes: Dopamine blockers (antipsychotics, metoclopramide), dopamine depletors (methyldopa, reserpine), calcium channel blockers, antiepileptics, antidepressants, chemotherapy, and immunosuppressants.
• Medical causes: Normal pressure hydrocephalus (NPH), infarction, infections (e.g., neurosyphilis), trauma, and lesions/neoplasms affecting the substantia nigra.

Classification

• Idiopathic (unknown cause) vs. secondary Parkinson's
• Age of onset (young vs. old)
• Rate or progression (rapid vs. slow)
• Proposed subtypes (mild motor predominant, intermediate, diffuse malignant).

Epidemiology

• Incidence is 14-20 cases per 100,000 people (160 per 100,000 if aged 65 and above) in high-income countries.
• Prevalence is 300 cases per 100,000 population (may be as high as 572 per 100,000 for people aged 45 years and older).
• Race-related incidence is similar when comparing community populations, but significant early-onset rates exist when comparing early-onset residents to other residents.
• Lifetime risk at age 40 is about 2% for men and 1.3% for women, and these rates take competing risks like death from cardiovascular disease or cancer into account.

Hallmark Features

• Resting tremor
• Bradykinesia
• Rigidity
• Postural instability
• Festination Gait
• Shuffling Gait

Associated Characteristic Problems

• Motor symptoms (micrographia, masked face, decreased blink rate, shuffling gait, festination gait)
• Autonomic impairment (constipation, sweating, postural hypotension, dysphagia)
• Mental status (depression, cognitive impairment, dementia)

Canadian CPG for PD

• The guidelines for Parkinson's Disease begin with communication.
• Importance is placed on considering a holistic and palliative approach throughout the disease and diagnosis process.
• Guidelines address diagnosis, progression, treatment for motor symptoms in early and late PD, and surgical interventions.

Staging

• Hoehn and Yahr Scale is commonly used to stage Parkinson's disease based on symptom severity.

Goals of Therapy

• Relieve symptoms, maximize independence and function
• Prevent injury, prevent long-term drug complications
• Focus on quality of life

Questions - Answers

• Canadian CPG: The Canadian CPGs for Parkinson's disease begin with communication.
• Prognosis: The typical prognosis for midlife-onset Parkinson's disease is 1-2 years.
• Cause of death for most Parkinson's patients: None of those listed - Parkinson's does not directly kill.

Approach to Treatment

• Focuses on tremor and chronological age.
• Prioritizes patient function.
• Early-stage treatment options include levodopa and dopamine agonists.

Unified Parkinson's Disease Rating Scale (UPDRS)

• Rating scale used to track and monitor Parkinson's disease progression, including non-motor and motor aspects of daily living experiences, and motor complications.

Quality of Life (QOL) Measures - Parkinson's Impact Scale

• Measures self-perception, family relations, community relations, work, leisure, travel, safety, financial security, and sexuality.

AAN Guidelines

• Recommend starting treatment in early disease.

Dopamine Agonists

• Drugs used frequently to treat Parkinson's.
• Direct dopamine receptor stimulation. Minimizes the use of levodopa in early disease. Add-on option for levodopa in late stages.

DA (Older vs. Newer Agents)

• Older agents tend to be less receptor-specific, and lower cost.
• Newer agents are usually more receptor-specific, higher cost, lower adverse effects compared to older agents.

Levodopa

• Gold standard for PD treatment.
• Given in a combination with carbidopa or other entacapone to improve absorption and prevent early metabolism.

COMT Inhibitors (Entacapone, Tolcapone)

• Increase the duration of action of levodopa.
• Often used as an add-on to levodopa.

Adverse Effects of Medications in PD (ex: excessive daytime sleepiness)

• Excessive daytime sleepiness, confusion, nausea, orthostatic hypotension, hallucinations and dyskinesias.

Debates with Dopamine Agonists vs. Levodopa

• DA agonists tend to have a higher risk of side effects, requiring more frequent patient monitoring and sometimes result in a higher rate of treatment discontinuation.
• Levodopa is more effective for controlling many hallmarks of Parkinson's, but motor complications like dyskinesia tend to emerge in patients taking levodopa more frequently, and over a longer period compared to dopamine agonists.

Levodopa Pharmacodynamics

• The effects of levodopa tend to show a difference in intensity and duration over the course of the disease (during early, moderate, and advanced stages).

COMT Adverse Effects

• Confusion, nausea, and hallucinations, hepatotoxicity (tolcapone), Orthostasis.

Dietary Information and Interactions

• Protein with levodopa should be taken at a specific time of day or outside of medication administration.
• Certain medications in Parkinson's disease may interact with food items.

Surgical Interventions (DBS, etc.)

• Deep brain stimulation, thalamotomy, pallidotomy, fetal transplantation
• Overall, goal of these procedures is to improve the "on" time and quality of life for patients.
• Results tend to vary depending on patient case factors.

Monitoring for PD Treatments

• Tracking symptoms, improved or decreased function, LD dose, neurologic and cardiac toxicity.

Case Updates (Patient examples throughout the presentation)

• Case examples presented in the lecture/presentation allow for application of information to clinical cases.

Additional Considerations

• Understand the importance of considering the patient's values, preferences, and lifestyle regarding their treatment plan.

Test your knowledge on the AAN guidelines for treating Parkinson's disease. This quiz covers medication choices, symptoms, and rehabilitation strategies highlighted in the guidelines. See how well you understand critical concepts such as clinical equipoise and the Unified Parkinson Disease Rating Scale.