Tremor

Parkinson's Disease

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Parkinson's Disease, Parkinsonism, Parkinsons Disease, Parkinson Disease

  • Epidemiology
  1. Onset after age 50 years
  2. Prevalence (U.S.)
    1. Overall: 0.3%
    2. Age over 60 years: 1%
    3. Age over 80 years: 4%
  3. Associated with positive Family History in >25% cases
  4. More common in men
  • Pathophysiology
  1. Slow degeneration of Substantia Nigra in Midbrain
  2. Dopaminergic Neurons degenerate
    1. Effects Extrapyramidal systems
      1. Start in Substantia Nigra pars compacta
      2. Continue via Striatum to Globus Pallidus
      3. Basal Ganglia project to cortex
    2. System regulates movement initiation and control
  3. Lewy bodies accumulate in residual DopamineNeurons
  4. Ascending process (Lower Brainstem affected first)
    1. Step 1: Medulla and later, Pons affected
      1. REM Sleep disorder
      2. Depression
      3. Dysautonomia
      4. Olfactory deficits
    2. Step 2: Midbrain and later basal forebrain affected
      1. Parkinsonian motor symptoms
    3. Step 3: Prefrontal cortex and ultimately neocortex affected diffusely
      1. Dementia
  • Symptoms
  • Prodromal
  1. Non-specific symptoms may precede motor symptoms and Tremor by 20 years
  2. Non-specific symptoms
    1. Hyposmia
    2. Constipation
    3. Fatigue
  3. References
    1. Hawkes (2010) Parkinsonism Relat Disord 16(2): 79-84 [PubMed]
  • Signs
  1. Bradykinesia (PPV >4 when combined with rigidity)
    1. Smaller handwriting (micrographia) (PPV 2.8)
    2. Masklike stare
    3. Infrequent blink
    4. Slowed walking and dressing
    5. Soft Voice trails off
    6. Difficulty opening jars (PPV 6.1)
    7. Difficulty rolling over in bed (PPV 13)
  2. Impaired gait and mobility
    1. Change in stride
    2. Poor Heel to toe gait (tandem walking) (PPV 2.9)
    3. Short, shuffling steps (PPV 3.3)
  3. Postural Instability
    1. Imbalance while walking or standing
    2. Frequent falls
    3. Stooping forward to maintain center of gravity
  4. Resting Tremor (primarily, although also displays Action Tremor as well)
    1. Hands and feet considerably affected
      1. Begins as low frequency, pill-rolling finger motion, typically unilateral
      2. Progresses to involve Forearm pronation and supination
      3. Then involves elbow flexion and extension
    2. Also affects head, face, lips, Tongue, jaw and neck
    3. Regular Rhythm (3-6 beats/sec)
    4. Tremor onset at rest and better with voluntary movement
    5. Presenting Symptom in 50-75% of Parkinson's patients
    6. Tremor absent in up to 20% of Parkinson's Disease
    7. Resting Tremor video
      1. https://www.youtube.com/watch?v=7uhT2ipQpKs
    8. Pill Rolling Tremor video
      1. https://www.youtube.com/watch?v=e532YW-Zwf0
  5. Rigidity (PPV >4 with Bradykinesia)
    1. Affects breathing, eating, swallowing, and speech
    2. Cogwheel rigidity or lead-pipe rigidity
  6. Secondary Effects
    1. Akathisia
    2. Cognitive Impairment
    3. Depression
    4. Fatigue
    5. Freezing of movement (motor blocks)
    6. Impotence
    7. Increased Salivation
    8. Orthostatic Hypotension,
    9. Paroxysmal drenching sweats
    10. Seborrheic Dermatitis
    11. Urinary Frequency
    12. Decreased olfaction
    13. Micrographia
  7. References
    1. Rao (2003) JAMA 289:347-53 [PubMed]
  • Diagnosis
  • Criteria
  1. Response to Levodopa or Dopamine Agonist challenge and
  2. Classic symptoms and signs
    1. Distal resting Tremor at 3-6 beats per second (Hz)
    2. Rigidity
    3. Bradykinesia
    4. Asymmetric onset
      1. Parkinsonism usually presents with one limb affected more than others
      2. Common pitfall in missed diagnosis is ruling-out Parkinsonism based on asymmetry
  • Diagnosis
  • Findings that suggest alternative diagnosis
  1. Poor Levodopa response
  2. Falls in the early stages of disease
  3. Symmetric involvement at onset
  4. Rapid progression
  5. Absent Tremor
  6. Hallucinations
  7. Prominent and early Dementia
  8. Early postural instability
  9. Severe and early Autonomic Dysfunction
  10. Upward Gaze Paralysis
  11. Involuntary movements beyond Tremor
  12. Suchowersky (2006) Neurology 66(7): 968-75 [PubMed]
  • Differential Diagnosis
  • Secondary Parkinsonism
  1. Dementia with Lewy Bodies
    1. Resting Tremor often absent in Lewy Body Dementia
    2. Prominent Visual Hallucinations and signficant fluctuations in attention and cognition
    3. Poor response to Carbidopa/Levodopa
  2. Drug Induced Parkinsonism: Dopamine blocking drugs
    1. Metoclopramide (Reglan)
    2. Reserpine
    3. Antipsychotic (e.g. Haloperidol, Risperidone)
  3. Toxin-Induced Parkinsonism
    1. See Toxin-Induced Parkinsonism
    2. See Drug-Induced Tremor
  4. Vascular Parkinsonism
    1. Occurs in Cerebrovascular Disease (TIA, CVA) in step-wise progression with each vascular event
    2. Refractory to Carbidopa/Levodopa
    3. Focal neurologic deficits may be present
    4. Basal Ganglia or thalamic infarctions on CT Head or MRI Brain
  5. Structural lesions
    1. Cortical degeneration
    2. Brainstem infarction
    3. Multiple system atrophy (e.g. Shy-Drager syndrome)
  6. Hydrocephalus
    1. Normal Pressure Hydrocephalus
  7. Atypical Pakinsonism
    1. See Atypical Pakinsonism
  8. Essential Tremor
    1. Symmetric Postural Tremor of the distal extremities, head and voice
    2. Worse with movement and better with Alcohol, Beta Blockers
  9. Miscellaneous causes
    1. CNS Infection
    2. Other Tremor
      1. Rest Tremor
  • Differential Diagnosis
  • Based on specific findings
  1. Stiff and slow without Tremor (seen in >20% of Parkinsonism)
    1. Progressive supranuclear palsy
  2. Isolated Tremor
    1. Essential Tremor
    2. Drug-Induced Tremor (e.g. Wellbutrin, Valproic Acid)
  3. Bradykinesia and gait change
    1. Advanced age
    2. Vascular Parkinsonism
  4. Dementia
    1. With mild Bradykinesia: Alzheimer's Disease
    2. With Hallucinations: Lewy Body Dementia
    3. With Incontinence: Normal Pressure Hydrocephalus
  5. Prominent autonomic symptoms
    1. Shy-Drager Syndrome
  • Imaging
  1. SPECT Imaging (1231-FP-CIT SPECT or DaTSCAN)
    1. Consider in unclear cases of Parkinsonism to differentiate from other causes
    2. Visualizes integrity of CNS Dopaminergic pathways
    3. Vlaar (2007) BMC Neurol 7:27 [PubMed]
  2. MRI Head or CT Head
    1. Not routinely indicated
    2. Order if atypical presentation (see above)
    3. Evaluates for alternative diagnosis (e.g. progressive supranuclear palsy)
  3. Transcranial Ultrasonography
    1. Bartova (2014) Ultrasound Med Biol 40(10): 2365-71 [PubMed]