II. Epidemiology
- Onset after age 50 years
- New diagnoses: 60,000 per year in U.S.
-
Prevalence (U.S.)
- Overall: 0.3%
- Age over 60 years: 1%
- Age over 80 years: 4%
- Associated with positive Family History in >25% cases
- More common in men
III. Pathophysiology
- Slow degeneration of Substantia Nigra (within the Basal Ganglia) of the Midbrain
-
Dopaminergic Neurons degenerate in the nigrostriatal pathway
- Nigrostriatal pathway regulates movement initiation and control
- Dopaminergic Neurons from the Substantia Nigra are inhibitory at the caudate and Putamen
- Parkinsonism results in loss of these inhibitory Neurons
- Allows for uncountered excitatory Cholinergic Activity at the caudate and Putamen
- Antiparkinsonism medications act primarily in 2 ways
- Increase Dopamine neurotransmission (e.g. Carbidopa-Levodopa)
- Decrease Cholinergic neurotransmission (e.g. Benztropine)
- Degeneration progressively effects extrapyramidal systems
- Start in Substantia Nigra pars compacta
- Continue via Striatum to Globus Pallidus
- Basal Ganglia project to cortex
- Lewy bodies accumulate in residual DopamineNeurons
- Lewy bodies are not specific to Parkinsonism (associated with many neurodegenerative diseases)
- Ascending process (Lower Brainstem affected first)
IV. Symptoms: Prodromal
- Non-specific symptoms may precede motor symptoms and Tremor by 20 years
- Non-specific symptoms
- References
V. Signs
-
Bradykinesia (PPV >4 when combined with rigidity)
- Smaller handwriting (micrographia) (PPV 2.8)
- Masklike stare (flat or masked facial expressions)
- Infrequent blink
- Slowed walking and dressing
- Soft Voice trails off
- Difficult manual dexterity
- Difficulty opening jars (PPV 6.1)
- Difficulty rolling over in bed (PPV 13)
- Impaired gait and mobility
- Change in stride
- Poor Heel to toe gait (Tandem Walking) (PPV 2.9)
- Short, shuffling steps (PPV 3.3)
- Festinating gait (involuntary gait acceleration)
- Parkinsonism Gait Video
- Postural Instability
- Imbalance while walking or standing
- Frequent falls
- Stooping forward to maintain center of gravity
- Resting Tremor (primarily, although also displays Action Tremor as well)
- Hands and feet considerably affected
- Begins as low frequency, pill-rolling finger motion, typically unilateral
- Progresses to involve Forearm pronation and supination
- Then involves elbow flexion and extension
- Also affects head, face, lips, Tongue, jaw and neck
- Regular Rhythm (3-6 beats/sec)
- Tremor onset at rest and better with voluntary movement
- Presenting Symptom in 50-75% of Parkinson's patients
- Tremor absent in up to 20% of Parkinson's Disease
- Resting Tremor video
- Pill Rolling Tremor video
- Hands and feet considerably affected
- Rigidity (PPV >4 with Bradykinesia)
- Onset on same side of body with Tremor
- May alter gait and Posture, and result in myalgias
- May affect breathing, eating, Swallowing, and speech
- Cogwheel rigidity (ratchet-like limb movement)
- Lead-pipe rigidity (uncommon, rigid throughout passive motion)
- Freezing of movement (sudden, transient motor blocks)
- Secondary Effects
- Akathisia
- Cognitive Impairment
- Depressed Mood
- Fatigue
- Impotence
- Increased Salivation
- Orthostatic Hypotension,
- Paroxysmal drenching sweats
- Seborrheic Dermatitis
- Urinary Frequency
- Constipation
- Decreased olfaction
- REM Sleep Disorder
- References
VI. Diagnosis: Criteria
- Response to Levodopa or Dopamine Agonist challenge and
- Classic symptoms and signs
- Distal resting Tremor at 3-6 beats per second (Hz)
- Rigidity
- Bradykinesia
- Asymmetric and gradual onset
- Parkinsonism usually presents with one limb affected more than others
- Common pitfall in missed diagnosis is ruling-out Parkinsonism based on asymmetry
VII. Diagnosis: Findings that suggest alternative diagnosis
- Poor Levodopa response
- Falls in the early stages of disease
- Symmetric involvement at onset
- Rapid progression
- Absent Tremor
- Hallucinations
- Prominent and early Dementia
- Early postural instability
- Severe and early Autonomic Dysfunction
- Upward Gaze Paralysis
- Involuntary movements beyond Tremor
- Suchowersky (2006) Neurology 66(7): 968-75 [PubMed]
VIII. Differential Diagnosis: Secondary Parkinsonism and Other Alternative Diagnoses
-
Dementia with Lewy Bodies
- Resting Tremor often absent in Lewy Body Dementia
- Prominent Visual Hallucinations and signficant fluctuations in attention and cognition
- Poor response to Carbidopa/Levodopa
- Drug Induced Parkinsonism: Dopamine blocking drugs
- Toxin-Induced Parkinsonism
- Vascular Parkinsonism
- Occurs in Cerebrovascular Disease (TIA, CVA) in step-wise progression with each vascular event
- Refractory to Carbidopa/Levodopa
- Focal neurologic deficits may be present
- Basal Ganglia or thalamic infarctions on CT Head or MRI Brain
- Structural lesions
- Cortical degeneration
- Brainstem Infarction
- Multiple system atrophy (e.g. Shy-Drager syndrome)
- Progressive Supranuclear Palsy
- Hydrocephalus
- Atypical Pakinsonism
-
Essential Tremor
- Symmetric Postural Tremor of the distal extremities, head and voice
- Worse with movement and better with Alcohol, Beta Blockers
- Miscellaneous causes
IX. Differential Diagnosis: Based on specific findings
- Stiff and slow without Tremor (seen in >20% of Parkinsonism)
- Progressive supranuclear palsy
- Isolated Tremor
-
Tremor of entire hand
- Essential Tremor
- Cerebellar disorder
-
Bradykinesia and gait change
- Advanced age
- Vascular Parkinsonism
-
Dementia
- With mild Bradykinesia: Alzheimer's Disease
- With Hallucinations: Lewy Body Dementia
- With Incontinence: Normal Pressure Hydrocephalus
- Prominent autonomic symptoms
- Shy-Drager Syndrome
X. Imaging
- SPECT Imaging (1231-FP-CIT SPECT or DaTSCAN)
- Consider in unclear cases of Parkinsonism to differentiate from other causes
- Visualizes integrity of CNS Dopaminergic pathways
- Vlaar (2007) BMC Neurol 7:27 [PubMed]
-
MRI Head or CT Head
- Not routinely indicated
- Order if atypical presentation (see above)
- Evaluates for alternative diagnosis (e.g. progressive supranuclear palsy)
- Transcranial Ultrasonography
XI. Management
- See Parkinsonism Management
- See Carbidopa/Levodopa (Sinemet)
- See Dopamine Agonist
XII. Prognosis
- Disability and need for ADL assistance at 3 to 7 years after disease onset
- Poor outcome within 10 years of disease onset in 77% of patients
- Postural instability
- Death
- Dementia
- Predictors of rapid progression
- Advanced age at diagnosis
- Badykinesia or rigidity at time of diagnosis
- In contrast, prominent Tremor is associated with slower progression
- Complications
- Dementia (40%)
- Psychosis (20-40%, esp. Hallucinations, paranoid Delusions)
XIII. References
- Ahlskog (2011) Mayo Internal Medicine Review Lecture
- Schim (2001) CMEA Medicine Lecture, San Diego
- Clarke (2003) Clin Evid 10:1582-98 [PubMed]
- Clarke (2004) Lancet Neurol 3:466-74 [PubMed]
- Gazewood (2013) Am Fam Physician 87(4): 267-73 [PubMed]
- Halli-Tierney (2020) Amf fam Physician 102(11):679-91 [PubMed]
- Nutt (2005) N Engl J Med 353:1021-7 [PubMed]
- Olanow (2001) Neurology 56:S1-88 [PubMed]
- Rao (2006) Am Fam Physician 74:2046-56 [PubMed]
- Young (1999) Am Fam Physician 59(8):2155-67 [PubMed]