Parkinson's Disease

Parkinson's disease occurs when neurons in a brain area called the substantia nigra begin to die. These neurons produce dopamine, a chemical messenger crucial for smooth, coordinated muscle movements. When dopamine levels drop, it causes the characteristic movement problems of Parkinson's.

Key Facts

• Second most common neurodegenerative disorder after Alzheimer's
• Affects about 1 million Americans
• 10 million worldwide have Parkinson's
• Average age of onset: 60 years
• 10-20% diagnosed before age 50 (young-onset)
• 1.5 times more common in men

What Causes Parkinson's?

The exact cause remains unknown, but likely involves a combination of:

• Genetic factors:
  • 15-25% have a family history
  • Several genes identified (SNCA, LRRK2, PARK7)
  • Most cases are sporadic
• Environmental factors:
  • Pesticide and herbicide exposure
  • Heavy metals
  • Well water in rural areas
  • Head trauma
• Other factors:
  • Age (biggest risk factor)
  • Male gender
  • Reduced coffee/caffeine intake
  • Non-smoking (smoking oddly protective)

Pathophysiology

• Loss of dopamine-producing neurons in substantia nigra
• Presence of Lewy bodies (alpha-synuclein protein clumps)
• By symptom onset, 60-80% of dopamine neurons already lost
• Also affects other neurotransmitter systems
• Spreads to other brain areas over time

Parkinson's symptoms are divided into motor (movement) and non-motor symptoms. The disease typically starts subtly and progresses slowly over years.

Cardinal Motor Symptoms

At least two of these must be present for diagnosis:

1. Tremor (70% of patients):

• Resting tremor (4-6 Hz)
• Often starts in one hand
• "Pill-rolling" appearance
• Improves with movement
• Worsens with stress
• May involve jaw, chin, legs

2. Bradykinesia (slowness of movement):

• Most disabling symptom
• Difficulty initiating movement
• Reduced arm swing when walking
• Small, cramped handwriting (micrographia)
• Masked facial expression
• Quiet, monotone speech

3. Rigidity:

• Muscle stiffness
• "Cogwheel" resistance to passive movement
• Can cause pain
• Stooped posture

4. Postural instability:

• Usually later symptom
• Loss of balance reflexes
• Tendency to fall backward
• Difficulty turning

Other Motor Symptoms

• Gait changes:
  • Shuffling steps
  • Festination (acceleration)
  • Freezing of gait
  • Difficulty turning
• Speech/swallowing:
  • Soft, monotone voice
  • Slurred speech
  • Drooling
  • Difficulty swallowing
• Dystonia: Sustained muscle contractions

Non-Motor Symptoms

Often precede motor symptoms by years:

Autonomic dysfunction:

• Constipation (most common early symptom)
• Urinary urgency/frequency
• Orthostatic hypotension
• Excessive sweating
• Sexual dysfunction

Sleep disturbances:

• REM sleep behavior disorder
• Insomnia
• Excessive daytime sleepiness
• Restless legs syndrome
• Sleep apnea

Cognitive/psychiatric:

• Depression (40%)
• Anxiety
• Apathy
• Cognitive impairment
• Dementia (late stage)
• Hallucinations (usually visual)
• Impulse control disorders

Sensory symptoms:

• Loss of smell (often earliest symptom)
• Pain and sensory disturbances
• Fatigue

Disease Progression

• Usually starts on one side (unilateral)
• Gradually becomes bilateral
• Rate of progression varies greatly
• Symptoms fluctuate throughout the day

Parkinson's diagnosis is primarily clinical, based on medical history and neurological examination. No single test can definitively diagnose Parkinson's.

UK Brain Bank Criteria

Step 1: Bradykinesia PLUS one of:

• Resting tremor
• Rigidity
• Postural instability

Step 2: Exclude other causes

Step 3: Supportive features (3+ required):

• Unilateral onset
• Rest tremor present
• Progressive disorder
• Persistent asymmetry
• Excellent response to levodopa
• Levodopa-induced dyskinesias
• Levodopa response 5+ years
• Clinical course 10+ years

Diagnostic Tests

Imaging:

• DaTscan (SPECT):
  • Shows dopamine transporter density
  • Helps distinguish from essential tremor
  • Cannot differentiate types of parkinsonism
• MRI:
  • Usually normal in Parkinson's
  • Rules out other conditions
  • May show subtle changes

Other tests:

• Levodopa challenge test:
  • Improvement with levodopa supports diagnosis
  • 30%+ improvement significant
• Smell test:
  • 90% have reduced smell
  • May precede motor symptoms

Differential Diagnosis

Other parkinsonian syndromes:

• Multiple system atrophy (MSA)
• Progressive supranuclear palsy (PSP)
• Corticobasal degeneration (CBD)
• Lewy body dementia

Secondary parkinsonism:

• Drug-induced (antipsychotics, antiemetics)
• Vascular parkinsonism
• Normal pressure hydrocephalus
• Wilson's disease
• Post-encephalitic

Other conditions:

• Essential tremor
• Dystonic tremor
• Psychogenic movement disorder

Treatment is individualized based on symptoms, age, and lifestyle. The goal is to maintain quality of life and functional independence.

Medications

Levodopa/Carbidopa:

• Gold standard treatment
• Converts to dopamine in brain
• Most effective for motor symptoms
• Side effects:
  • Nausea (early)
  • Dyskinesias (involuntary movements)
  • Motor fluctuations
  • "Wearing off" phenomenon
• Forms: immediate-release, controlled-release, intestinal gel

Dopamine agonists:

• Pramipexole, ropinirole, rotigotine patch
• Directly stimulate dopamine receptors
• Less motor complications than levodopa
• Side effects:
  • Impulse control disorders
  • Hallucinations
  • Sleepiness
  • Leg swelling
• Often used in younger patients

MAO-B inhibitors:

• Selegiline, rasagiline, safinamide
• Block dopamine breakdown
• Mild benefit alone
• Can reduce "off" time
• Well tolerated

COMT inhibitors:

• Entacapone, tolcapone, opicapone
• Extend levodopa effect
• For motor fluctuations
• Always used with levodopa

Other medications:

• Amantadine:
  • For dyskinesias
  • Mild benefit for tremor
• Anticholinergics:
  • For tremor in younger patients
  • Avoid in elderly (confusion risk)

Surgical Treatment

Deep Brain Stimulation (DBS):

• Electrodes implanted in brain
• Targets: STN or GPi
• Candidates:
  • Good levodopa response
  • Motor fluctuations/dyskinesias
  • Medication-refractory tremor
  • No significant cognitive impairment
• Benefits:
  • Reduces "off" time
  • Improves dyskinesias
  • May reduce medications
• Risks: infection, bleeding, hardware issues

Other procedures:

• Focused ultrasound thalamotomy
• Pallidotomy (less common now)

Non-Motor Symptom Management

• Depression: SSRIs, SNRIs, counseling
• Psychosis: Quetiapine, pimavanserin
• Cognitive impairment: Rivastigmine
• Orthostatic hypotension: Fludrocortisone, midodrine
• Constipation: Fiber, polyethylene glycol
• Sleep disorders: Melatonin, clonazepam (RBD)
• Drooling: Botulinum toxin, glycopyrrolate

Exercise and Physical Therapy

• Benefits of exercise:
  • Improves mobility and balance
  • Reduces falls
  • May slow progression
  • Improves mood and cognition
• Recommended activities:
  • Walking/treadmill
  • Tai chi (excellent for balance)
  • Dance (especially tango)
  • Swimming
  • Cycling
  • Boxing programs
• Physical therapy focus:
  • Gait training
  • Balance exercises
  • Flexibility/stretching
  • Cueing strategies
  • Fall prevention

Occupational Therapy

• Fine motor skills training
• Adaptive equipment
• Home safety modifications
• Energy conservation techniques
• Handwriting exercises

Speech Therapy

• LSVT LOUD program
• Voice exercises
• Swallowing strategies
• Communication devices

Nutrition

• Protein timing (may interfere with levodopa)
• High-fiber diet for constipation
• Adequate hydration
• Small, frequent meals
• Calcium and vitamin D
• Mediterranean diet may be beneficial

Daily Living Tips

• Mobility:
  • Remove throw rugs
  • Install grab bars
  • Use walking aids as needed
  • Wear proper footwear
• Dressing:
  • Velcro instead of buttons
  • Slip-on shoes
  • Elastic waistbands
• Eating:
  • Weighted utensils
  • Non-slip mats
  • Cups with lids

Driving

• Regular assessments needed
• Consider occupational therapy evaluation
• Be aware of medication effects
• Plan for eventual driving cessation

Hoehn and Yahr Scale

• Stage 1:
  • Symptoms on one side only
  • Minimal functional impairment
  • Tremor in one limb
• Stage 2:
  • Symptoms on both sides
  • No balance impairment
  • Minimal disability
• Stage 3:
  • Balance impairment
  • Mild to moderate disability
  • Physically independent
• Stage 4:
  • Severe disability
  • Can walk or stand unassisted
  • Needs help with daily activities
• Stage 5:
  • Wheelchair bound or bedridden
  • Requires constant care

Disease Course

• Highly variable progression
• Average time to Hoehn & Yahr stage 4: 9-14 years
• Life expectancy slightly reduced
• Quality of life can remain good for many years
• Most people die with, not from, Parkinson's

Factors Affecting Prognosis

• Better prognosis:
  • Younger age at onset
  • Tremor-dominant type
  • Good response to levodopa
  • Slower initial progression
  • Regular exercise
• Poorer prognosis:
  • Older age at onset
  • Early cognitive impairment
  • Early postural instability
  • Poor levodopa response
  • Rigid-akinetic type

Complications

• Falls and fractures
• Aspiration pneumonia
• Dementia (40% after 10 years)
• Depression and anxiety
• Medication side effects

While Parkinson's disease is progressive, modern treatments can significantly improve symptoms and maintain quality of life. Early diagnosis, appropriate medical management, regular exercise, and a strong support system are key to living well with Parkinson's. Research continues to advance our understanding and treatment options, bringing hope for even better outcomes in the future.