Parkinson's Disease - Detailed Answer for 15 Marks

1. Definition

• Harrison's Principles of Internal Medicine 22E, p. 3537

2. Epidemiology

• Mean age of onset: ~60 years
• Lifetime risk: ~3% in men, ~2% in women
• Prevalence increases with age; cases can occur in the 20s (especially genetic forms)
• About 15% of cases are familial; the remainder are sporadic

3. Etiology and Pathogenesis

Pathological Hallmarks

• Loss of dopaminergic neurons in the substantia nigra pars compacta
• Lewy bodies - intracytoplasmic eosinophilic inclusions containing misfolded alpha-synuclein protein
• Neuronal loss also affects: norepinephrine neurons (locus coeruleus), cholinergic neurons (nucleus basalis of Meynert), serotonin neurons (raphe nuclei), olfactory system, and peripheral autonomic nervous system
• Braak staging suggests Lewy pathology begins in the peripheral autonomic / olfactory system and spreads caudorostrally to the SNpc and finally cerebral cortex

Basal Ganglia Circuit Disruption

• Overactivity of the indirect pathway (STN and GPi become overactive)
• Underactivity of the direct pathway
• Net result: increased inhibitory GABAergic output from basal ganglia → thalamus suppressed → reduced cortical motor activation → hypokinesia

Genetic Factors

• Harrison's, Table 446-4

Environmental Factors

• MPTP (mitochondrial toxin) - established experimental model
• Pesticides, solvents, rural living, well water - epidemiological associations
• Possible protective factors: caffeine, cigarette smoking, NSAIDs, calcium channel blockers

4. Clinical Features

Cardinal Motor Features (TRAP)

1. T - Tremor (Resting tremor): "Pill-rolling" tremor at rest (4-6 Hz), most prominent in the hand, disappears with intentional movement and during sleep. Presenting symptom in up to 70% of patients.
2. R - Rigidity: Increased muscle tone throughout the range of passive movement. Can be:
   • Lead-pipe rigidity - uniform throughout movement
   • Cogwheel rigidity - ratchet-like, especially when superimposed on tremor
3. A - Akinesia/Bradykinesia: Slowness of movement initiation and execution. Key finding on examination. Manifests as micrographia, reduced arm swing, hypomimia (masked face), hypophonia.
4. P - Postural instability: Late feature; loss of postural reflexes leads to tendency to fall. Assessed by the "pull test" (retropulsion).

Other Motor Features

• Festinating gait: Short, shuffling steps, forward-flexed posture, reduced arm swing, difficulty initiating gait (start hesitation)
• Freezing of gait (FOG): Sudden transient inability to continue walking, especially at doorways or turns
• Micrographia: Small, cramped handwriting
• Hypomimia: Reduced facial expression ("masked face")
• Hypophonia: Soft, monotone voice
• Dysphagia: Present in up to 82% on objective testing; risk of aspiration
• Dystonia: Commonly presents as foot dystonia in early-onset PD

Non-Motor Features

• Harrison's Table 446-1

5. Diagnosis

• Bradykinesia PLUS at least one of: rest tremor, rigidity, or postural instability
• No atypical features (supranuclear gaze palsy, early falls, cerebellar signs)
• Positive supportive features: unilateral onset, rest tremor, levodopa response, asymmetric progression

• No definitive blood/CSF test
• MRI brain: Normal in early PD; used to exclude secondary parkinsonism
• DaTscan (SPECT): Shows reduced dopamine transporter uptake in striatum - confirms dopaminergic deficit
• Levodopa challenge: Significant improvement supports diagnosis

6. Hoehn and Yahr Scale (Staging)

7. Differential Diagnosis (Secondary Parkinsonism)

• Drug-induced parkinsonism: Antipsychotics (dopamine blockers)
• Progressive Supranuclear Palsy (PSP): Early falls, supranuclear gaze palsy, symmetric onset
• Multiple System Atrophy (MSA): Autonomic failure, cerebellar signs
• Dementia with Lewy Bodies (DLB): Cognitive symptoms precede motor features; visual hallucinations
• Vascular parkinsonism: Lower-body predominant, step-wise progression

8. Medical Management

Levodopa (Gold Standard)

• Levodopa + Carbidopa (peripheral decarboxylase inhibitor to prevent peripheral conversion)
• Most effective drug; improves bradykinesia and rigidity more than tremor
• Complications with long-term use:
  • Motor fluctuations: Wearing-off, on-off phenomena
  • Dyskinesias: Involuntary choreiform movements at peak dose
  • Hallucinations, cognitive impairment

Dopamine Agonists

• Pramipexole, ropinirole, rotigotine (patch)
• Used as first-line in younger patients to delay levodopa-related complications
• Side effects: Impulse control disorders, somnolence, orthostatic hypotension, hallucinations

MAO-B Inhibitors

• Selegiline, rasagiline, safinamide
• Block MAO-B oxidative metabolism of dopamine → increased synaptic dopamine
• Used as monotherapy in early stages or as adjunct in fluctuating patients

COMT Inhibitors

• Entacapone, tolcapone, opicapone
• Block peripheral COMT metabolism of levodopa → prolong levodopa half-life and brain availability
• Reduce "off" time in fluctuating patients

Deep Brain Stimulation (DBS)

• Targets: Subthalamic nucleus (STN) or Globus pallidus internus (GPi)
• STN DBS: Larger benefit in "off" state; allows greater medication reduction
• GPi DBS: Better dyskinesia suppression; safer neuropsychiatric profile
• Indicated in advanced PD with motor fluctuations not controlled by medication
• Bradley and Daroff's Neurology in Clinical Practice; Harrison's 22E

9. Physiotherapy Management

Assessment Tools Used in Physiotherapy

• Unified Parkinson's Disease Rating Scale (UPDRS) - motor and ADL subscores
• Hoehn and Yahr Scale - disease staging
• Timed Up and Go (TUG) test - mobility/fall risk
• Berg Balance Scale (BBS) - balance assessment
• 6-Minute Walk Test (6MWT) - endurance
• Mini-BESTest - dynamic balance
• FOG Questionnaire - freezing of gait

A. LSVT BIG (Lee Silverman Voice Treatment - BIG)

• Protocol: 16 sessions, 4 sessions/week, 1 hour/session, for 4 weeks
• Principle: Recalibrate the patient's internal sense of movement amplitude. PD patients perceive normal-sized movements as "too big," so they default to small movements.
• Exercises: Maximal whole-body movements - large stepping, big arm swings, forward/sideways reaching, transitions (sit-to-stand, kneeling to standing)
• Focus: Cognitive engagement + high-amplitude + task-specific practice
• Outcome: Improves motor performance, gait speed, balance, ADL, and quality of life
• Validated by RCT evidence; recommended by European Physiotherapy PD Guidelines

B. Gait Training

1. Auditory rhythmic cueing (metronome): Walking to a metronome beat improves cadence and stride length. Auditory cues bypass the defective internal rhythm generation in PD.
2. Visual cueing: Transverse lines on the floor (e.g., tape), laser lines projected from a walking frame - prompt the patient to take bigger steps ("step over the line").
3. Treadmill training: Improves walking speed, stride length, and cadence; provides sensory feedback and forced movement pattern. Can be used with or without body-weight support.
4. Attentional strategies: Teaching the patient to consciously focus on step size and weight transfer (compensates for defective automatic motor control).
5. Obstacle navigation training: Practicing stepping over obstacles, negotiating doorways (common freezing triggers).
6. Dual-task training: Combining walking with cognitive tasks to improve automatic gait under real-world conditions.

C. Balance and Fall Prevention Training

• Static balance exercises: Single-leg stance, tandem stance, standing on foam
• Dynamic balance exercises: Weight shifting, reaching activities, lateral stepping, reactive balance training
• Tai Chi: Evidence supports improved balance and reduced fall risk in PD
• Perturbation-based balance training: Unexpected platform perturbations to train reactive postural responses
• Hip and trunk stabilization exercises: Strengthen core musculature to improve postural alignment
• A randomized crossover study showed significant improvement in UPDRS ADL and motor subscores (bradykinesia and rigidity) with structured exercise including stretching, endurance, balance, gait, and fine motor exercises (3x/week, 4 weeks). Gains were lost 6 months after stopping - reinforcing the need for ongoing programs.
• Bradley and Daroff's Neurology in Clinical Practice, p. 3305

D. Strength and Resistance Training

• Progressive resistance exercises for proximal muscles (hip extensors, knee extensors, plantar flexors)
• Addresses the secondary deconditioning that occurs in PD
• Improves muscle power, transfers, and walking ability
• Resistance training reduces fall risk by improving muscular strength and reaction time

E. Flexibility and Stretching

• Passive and active stretching for the axial muscles (neck, trunk extensors, hip flexors)
• Addresses the characteristic forward-flexed posture of PD (camptocormia)
• Range-of-motion exercises for upper and lower limbs
• Rotation exercises for the trunk - important for walking and turning

F. Postural Re-education

• Backward lean training to counteract typical flexed posture
• Mirror feedback training to correct posture
• Proprioceptive training
• Alexander Technique: A structured technique focusing on posture and movement re-education, showing benefit in PD

G. Aerobic Exercise

• Cycling (stationary bike), swimming, walking programs
• Aerobic exercise is safe and well-tolerated in PD
• May have neuroprotective effects (BDNF upregulation, neuroplasticity)
• Improves cardiovascular fitness, reduces fatigue, improves mood and sleep

H. Functional Task Training

• Sit-to-stand transfers: Practice with cues ("lean forward, feet back, push up on 3")
• Bed mobility training
• Turning in bed - significant problem in PD due to axial rigidity
• Upper limb functional training: buttoning, writing, feeding
• Studies show that twice-a-week practice for 3 months in whole-body movements (sitting, kneeling, standing up, throwing) significantly improved mobility speed in moderately disabled PD patients. - Bradley and Daroff's

I. Cueing Strategies for Freezing of Gait

• Auditory cues: Metronome app, music with a clear beat
• Visual cues: Floor markings, laser cane (projects a red line)
• Mental imagery: Imagining stepping over an object
• Attentional cues: "Big step, look up"
• Weight-shifting cues: Marching on spot before initiating walking
• Cuing will increase stride length and reduce freezing episodes - Bradley and Daroff's

J. Group-Based Rehabilitation and Multidisciplinary Approach

• Physiotherapy works best as part of a multidisciplinary team:
  • Occupational Therapist: ADL modifications, assistive devices, home modifications
  • Speech and Language Therapist: LSVT LOUD for voice, swallowing therapy
  • Neurologist: Medical management, DBS timing
  • Psychologist: Depression, anxiety, cognitive support
  • Dietitian: Nutritional support, constipation management
• Group classes improve social engagement and motivation
• Inpatient rehabilitation (4-week) improves QoL for at least 3 months post-intervention

K. Technology-Assisted Physiotherapy (Emerging)

• Virtual reality (VR) based balance training
• Wearable sensor feedback for gait retraining
• Telerehabilitation: LSVT BIG via synchronous video - shown to be feasible and effective in RCTs (2024 data)
• Exergaming (Nintendo Wii, Xbox Kinect): Interactive balance and coordination training

L. Physiotherapy Goals by Disease Stage

10. Prognosis

• PD is progressive but the rate of progression varies widely
• Most patients can remain functional for 10-15+ years with appropriate management
• Falls, aspiration pneumonia (from dysphagia), and dementia are major causes of morbidity and mortality
• Without an ongoing formal exercise program, exercise gains are lost within 6 months - underscoring the need for lifelong active rehabilitation

Quick Summary for Exam