• Clinical science

Parkinson-plus syndromes


Parkinson-plus syndromes (or atypical parkinsonism) are a group of neurodegenerative diseases that present with parkinsonism and a variety of additional features. Depending on the particular syndrome, a combination of basal ganglia, cerebral cortical, cerebellar, midbrain, and/or brainstem structures are affected. The prognosis is less favorable than in Parkinson disease. Parkinson-plus syndromes should be considered if parkinsonism does not respond to levodopa treatment, if dementia progresses rapidly, or if gait instability occurs early in the course of the disease. In most cases, only symptomatic treatment is possible.

Common characteristics of Parkinson-plus syndromes

Parkinson-plus syndromes have a number of features that differentiate them from Parkinson disease (PD):


Dementia with Lewy bodies

Patients with Lewy-body dementia have an increased risk of life-threatening akinetic crises under antipsychotic treatment!


Multiple system atrophy (MSA)

  • Differential diagnosis
    • Parkinson disease: IBZM-SPECT imaging
      • MSA: presynaptic and postsynaptic degeneration (decreased binding)
      • Parkinson disease: presynaptic degeneration and postsynaptic up-regulation (ligand accumulates here)
    • Pure autonomic failure (PAF)
      • Disorder of the autonomous functions that is not associated with symptoms of the central nervous system
      • In contrast to MSA, postganglionic lesions predominate in PAF.
      • Mainly affects male patients between the ages of 40 and 70
      • Clinical features: orthostatic dysregulation with life-threatening drops in blood pressure (esp. in situations involving blood redistribution, e.g., high temperatures, while standing up, or after a meal), fecal and urinary incontinence, disorder of thermoregulation due to anhidrosis, and/or erectile dysfunction. Neck pain is a common prodrome.
  • Therapy: no causal therapy


Progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome)

  • Clinical features
    • Postural instability (leading to frequent falls)
    • Frontal lobe abnormalities (e.g.,apathy, disinhibition, impaired reasoning)
    • Vertical gaze palsy, especially downward gaze, to complete external ophthalmoparesis
    • Rigor
    • Bradykinesia
    • Dysarthria, dysphagia
    • Dementia
  • Diagnosis
    • MRI: hummingbird sign showing atrophy of midbrain structures with a relatively intact pons region


Corticobasal degeneration

  • Clinical features
    • Dementia (at any stage)
    • Asymmetric motor abnormalities, often initially affecting only one limb
    • Alien limb phenomenon: The patient perceives the affected limb as not belonging to him or her.
  • Diagnosis: : asymmetric focal cortical atrophy and bilateral atrophy of the basal ganglia on MRI


Important differentiating signs of Parkinson-plus syndromes

Differential diagnoses of Parkinson-plus syndromes
Multiple system atrophy (MSA) Progressive supranuclear palsy (PSP) Corticobasal degeneration (CBD) Dementia with Lewy bodies (DLB)
  • Lewy bodies
  • Autonomic dysfunction with urogenital problems
  • Asymmetric motor symptoms
  • Alien limb phenomenon