From the Guidelines
Diagnosing advanced Parkinsonism requires a comprehensive clinical assessment focusing on both motor and non-motor symptoms, with imaging remaining an essential diagnostic tool in the evaluation of a patient presenting with Parkinsonian symptoms. The diagnosis is primarily clinical, based on the presence of cardinal motor features including bradykinesia, rigidity, resting tremor, and postural instability, as outlined in the acr appropriateness criteria® movement disorders and neurodegenerative diseases 1. In advanced stages, patients typically exhibit marked difficulty with activities of daily living, frequent freezing of gait, severe motor fluctuations, dyskinesias, and increased "off" periods despite optimal medication. Non-motor symptoms become more prominent and include cognitive impairment, psychosis, autonomic dysfunction, sleep disorders, and mood disturbances.
Key Diagnostic Considerations
- The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) can be used to quantify symptom severity
- DaTscan (dopamine transporter imaging) can help visualize dopaminergic neuron loss
- MRI can be used to rule out other conditions, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD) 1
- Levodopa challenge tests can help confirm dopamine responsiveness, with a significant improvement (typically >30%) in motor symptoms supporting the diagnosis
- Blood tests should be performed to exclude secondary causes of parkinsonism, including thyroid function, liver function, ceruloplasmin (for Wilson's disease), and complete blood count
Differential Diagnosis
- Parkinson disease (PD) is the most common cause of Parkinsonism, with other common causes including PSP, MSA, CBD, and vascular Parkinsonism 1
- Correctly diagnosing a Parkinsonian syndrome on clinical features alone can be quite challenging, and imaging remains an essential diagnostic tool in the evaluation of a patient presenting with Parkinsonian symptoms 1
- Advanced Parkinsonism is distinguished from early disease by treatment resistance, more severe disability, and the emergence of complications like medication-induced dyskinesias and autonomic failure, reflecting the progressive degeneration of both dopaminergic and non-dopaminergic neuronal systems.
From the FDA Drug Label
Advanced Parkinson’s Disease (with L-dopa): In the double-blind, placebo-controlled trials in patients with advanced-stage Parkinson’s disease, the most commonly observed adverse reactions in patients treated with ropinirole (incidence at least 5% greater than placebo) were dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, increased sweating, and headache Table 4 lists treatment-emergent adverse reactions that occurred in at least 2% of patients with advanced Parkinson’s disease (with L-dopa) treated with ropinirole who participated in the double-blind, placebo-controlled trials and were numerically more common than the incidence for placebo-treated patients.
The FDA drug label does not answer the question.
From the Research
Diagnosing Advanced Parkinsonism
- Advanced Parkinsonism is a neurodegenerative disorder characterized by motor symptoms such as resting tremor, rigidity, and bradykinesia 2
- The diagnosis of advanced Parkinsonism involves the assessment of motor complications, such as "wearing off" fluctuations and dyskinesias 3
- The Unified Parkinson's Disease Rating Scale (UPDRS) is a commonly used tool to evaluate the severity of Parkinson's disease symptoms, including motor and non-motor symptoms 4, 5
Treatment Options
- Levodopa remains the mainstay treatment for Parkinson's disease, but its long-term use is associated with motor complications 2, 3
- The combination of levodopa, carbidopa, and entacapone (Stalevo) has been shown to provide clinical improvements similar to those obtained by separate tablets of levodopa and entacapone, with a more positive effect on quality of life 2
- Dopamine agonists, such as pramipexole and ropinirole, have been found to be effective in treating Parkinson's disease, both as monotherapy and in combination with levodopa 4
- Levodopa-carbidopa intestinal gel has been shown to provide sustained and clinically meaningful benefits in advanced Parkinson's disease patients, with significant reductions in "off" time and increases in "on" time without dyskinesia 6
Non-Motor Symptoms
- Non-motor symptoms, such as cognitive impairment and dementia, are common in Parkinson's disease and can have a significant impact on quality of life 5
- Apomorphine has been found to be the most efficacious drug for treating non-motor symptoms of Parkinson's disease, according to a network meta-analysis 5
- Other drugs, such as ropinirole, rasagiline, and rotigotine, have also been found to be effective in treating non-motor symptoms, but with varying degrees of efficacy 5