What are the treatment options for atypical parkinsonism, including Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), and Corticobasal Degeneration (CBD)?

Treatment Options for Atypical Parkinsonism Syndromes

Currently, there are no disease-modifying treatments for atypical parkinsonism syndromes including Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), and Corticobasal Degeneration (CBD), and management focuses primarily on symptomatic relief and supportive care. 1, 2, 3

Pharmacological Management

Dopaminergic Therapy

• Levodopa may provide limited symptomatic relief for parkinsonian features (bradykinesia and rigidity) in some patients, though benefits are typically minimal, short-lived, and often disappointing compared to Parkinson's disease 3
• Poor response to levodopa is actually part of the diagnostic criteria for PSP and CBD 3
• The response to levodopa therapy should be assessed with adequate dosing (at least 1000mg daily) before determining ineffectiveness 3

Management of Specific Symptoms

Movement Disorders

• Dystonia may be managed with:
  • Intramuscular botulinum toxin injections (particularly useful for focal dystonia) 3
  • Baclofen for more generalized dystonia 3
  • Benzodiazepines may help reduce dystonia but should be used cautiously due to risk of sedation and falls 3
• Myoclonus (particularly in CBD) may respond to:
  • Levetiracetam 3
  • Benzodiazepines such as clonazepam 3, 4

Autonomic Dysfunction (especially in MSA)

• Orthostatic hypotension management:
  • Midodrine (alpha-adrenergic agonist) 5
  • Fludrocortisone (mineralocorticoid) 5
  • Non-pharmacological measures: compression stockings, increased salt intake, elevation of head of bed 5
• Urinary dysfunction:
  • Anticholinergics for urgency (use with caution due to cognitive side effects) 5
  • Intermittent catheterization for retention 5

Secretion Management

• Sialorrhea (excessive drooling):
  • Intrasalivary gland botulinum toxin injections 3
  • Anticholinergic medications (with caution due to cognitive side effects) 3

Cognitive and Behavioral Symptoms

• Cognitive impairment:
  • Acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine) have limited evidence and may worsen parkinsonian symptoms 3, 5
  • Memantine has been tried with minimal evidence of benefit 5
• Behavioral symptoms:
  • Selective serotonin reuptake inhibitors (SSRIs) may help with depression and some behavioral symptoms 5
  • Atypical antipsychotics should be used with extreme caution as they can worsen parkinsonism 3

Non-Pharmacological Management

Multidisciplinary Care

• Patients should be managed by a coordinated team including neurologists, physical therapists, occupational therapists, speech therapists, and palliative care specialists 3
• Early referral to these services is recommended to maximize function and quality of life 3

Specific Therapies

• Physical therapy:
  • Gait training and fall prevention strategies 3
  • Balance exercises and mobility aids (e.g., rolling walkers) 3, 4
• Occupational therapy:
  • Adaptive equipment for activities of daily living 3
  • Home safety evaluation and modifications 3
• Speech therapy:
  • Swallowing assessment and strategies to prevent aspiration 3, 4
  • Communication aids for dysarthria and aphasia 3
• Nutritional support:
  • Dietary modifications for dysphagia 3
  • Consideration of feeding tube placement in advanced disease 3

Emerging Therapies

• Several disease-modifying approaches are being investigated in clinical trials, including:
  • Anti-tau therapies for PSP and CBD (tauopathies) 2, 5
  • Anti-alpha-synuclein approaches for MSA (synucleinopathy) 2, 5
  • Neuroprotective agents targeting oxidative stress and mitochondrial dysfunction 2
  • Stem cell therapies 2, 5
• Recent clinical trials of rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), and davunetide (PSP) have unfortunately shown negative results 6

Prognosis and Disease Course

• These disorders typically progress more rapidly than Parkinson's disease 1
• MSA has a mean survival of approximately 6 years from diagnosis 1
• As the disease advances, palliative care becomes increasingly important to manage symptoms and maintain quality of life 3

Diagnostic Considerations

• Accurate diagnosis is essential for appropriate management and prognostication 7
• MRI brain imaging is the preferred modality to support clinical diagnosis and exclude other causes 7
• FDG-PET can help differentiate PSP from Parkinson's disease by showing characteristic patterns of hypometabolism 7