Episode 159. Parkinson's Disease with Associate Professor Ernie Butler (part 1)
In this episode, we delve deeply into Parkinson’s Disease (PD), a progressive neurodegenerative disorder primarily impacting dopamine-producing neurons in the substantia nigra. PD affects movement and leads to a range of motor and non-motor symptoms due to the loss of dopamine and other key neurotransmitters. Join us as we explore this complex disease with expert insights from Associate Professor Ernie Butler, consultant neurologist and founding member of the Frankston Neurology Group.
Parkinson’s Disease Pathophysiology
Parkinson's disease predominantly targets the dopaminergic neurons in the substantia nigra, leading to dopamine loss. Dopamine, a crucial neurotransmitter, enables smooth and purposeful movement through communication between the substantia nigra and the corpus striatum. When dopamine levels drop significantly—usually by 60-80%—patients experience impaired movement.
In addition to dopamine loss, many with PD also lose nerve endings that produce norepinephrine, impacting the autonomic nervous system responsible for pulse and blood pressure regulation. This may explain PD’s non-motor symptoms, such as fatigue and blood pressure irregularities. Another characteristic finding in PD is the presence of Lewy bodies, protein aggregates (mainly alpha-synuclein) that may contribute to neuronal death.
Global Impact
Parkinson's is now the second most common neurodegenerative disorder, with an alarming global rise in prevalence. In Australia alone, over 200,000 people are affected, with 38 new diagnoses every day. One in five diagnoses occurs before age 50, with 10% diagnosed under 40.
Core Symptoms of Parkinson’s Disease
PD manifests through four primary motor symptoms:
Tremor - Often beginning in the hand, this rhythmic “pill-rolling” tremor is most visible at rest.
Rigidity - Muscles remain tense, leading to stiffness or “cogwheel” rigidity, especially noticeable when an examiner moves the patient’s limb.
Bradykinesia - A slowness in spontaneous movement, bradykinesia complicates daily activities and reduces facial expression.
Postural Instability - PD often leads to impaired balance and a characteristic gait, with forward-leaning, small steps (festination), and episodes of “freezing.”
Parkinson’s Plus Syndromes
There are several conditions that resemble PD but present additional features, known as Parkinson’s Plus conditions:
Multiple System Atrophy (MSA): Progressive, with central and autonomic nervous system involvement; often features symptoms like poor coordination and slurred speech.
Lewy Body Dementia: Associated with widespread Lewy bodies, presenting both motor and Alzheimer’s-like symptoms, often with fluctuating cognition and visual hallucinations.
Progressive Supranuclear Palsy (PSP): Rare, affecting brainstem cells, leading to gait instability, eye movement issues, and mood changes.
Corticobasal Degeneration (CBD): Causes rigidity, balance problems, and distinctive motor and cognitive symptoms, with tau protein deposits.
Risk Factors
Though the precise cause of PD remains unclear, several risk factors have been identified:
Age: Average onset is around 70, though early-onset PD affects a small percentage of patients under 50.
Biological Sex: PD is more common in men.
Genetics: Up to 25% of people with PD have a relative with the disease; genetic mutations like GBA, LRRK2, and PINK1 have been implicated.
Environmental Exposure: Rural living and exposure to pesticides have been linked to a higher PD risk.
Diagnosis and Management
PD diagnosis relies on medical history, neurological examination, and diagnostic tests to rule out other conditions. CT and MRI scans often appear unremarkable in PD patients.
Treatment Options
While there is no cure for PD, treatments help manage symptoms:
Medications:
PD treatments focus on increasing dopamine levels or managing symptoms that result from dopamine loss. Since dopamine itself doesn't easily cross the blood-brain barrier, the main drugs are dopamine precursors and related agents:
Dopamine Precursors
Levodopa, a precursor to dopamine, can cross the blood-brain barrier and convert to dopamine in the brain, making it the most widely used PD drug. It’s often paired with carbidopa, which inhibits levodopa's conversion outside the brain, ensuring more reaches the central nervous system.COMT Inhibitors
These drugs, like entacapone, opicapone, and tolcapone, inhibit catechol-O-methyltransferase, an enzyme that breaks down dopamine. By slowing dopamine degradation, they extend levodopa's effects.Dopamine Agonists and Other Neurotransmitter Modulators
Drugs that mimic dopamine or affect other neurotransmitters also relieve PD symptoms. Anticholinergics (e.g., trihexyphenidyl, benztropine, ethopropazine) reduce tremors by blocking acetylcholine. Additionally, amantadine, an antiviral, can reduce both PD symptoms and levodopa-induced dyskinesia, though its exact mechanism remains unclear.Symptom-Specific Medications
Beyond motor control, PD can cause non-motor symptoms like depression, which may be treated with antidepressants.
Surgical Intervention:
Deep Brain Stimulation (DBS) is an option for patients unresponsive to medications. Electrodes implanted in the brain can significantly improve motor symptoms.
Associate Professor Ernie Butler, a consultant neurologist and senior neurology specialist at Frankston Neurology Group and Monash Health, brings extensive expertise in managing PD, multiple sclerosis, and myasthenia gravis. Previously featured in episodes on Multiple Sclerosis (Episode 88) and Myasthenia Gravis (Episode 89), Professor Butler’s insights continue to enlighten listeners on complex neurological conditions.
References
Frankston Neurologyhttps://www.frankstonneurology.com.au › ...Our Neurologists
Parkinson's Foundationhttps://www.parkinson.org › what-is...What is Parkinson's?