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Parkinson-plus syndromes

Last updated: June 17, 2025

Summarytoggle arrow icon

Parkinson-plus syndromes, also known as atypical parkinsonian syndromes, are a group of rare, adult-onset neurodegenerative disorders manifesting with parkinsonism and additional differentiating clinical features. Unlike in Parkinson disease, varying combinations of basal ganglia, cerebral cortical, cerebellar, midbrain, and/or brainstem structures are affected. Differentiating features from Parkinson disease (e.g., poor levodopa response, rapid progression, prominent early cognitive decline, and/or significant autonomic dysfunction) prompt consideration of a Parkinson-plus syndrome. Management is primarily symptomatic and supportive. The prognosis is less favorable than in Parkinson disease, with a more accelerated progression.

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Overviewtoggle arrow icon

Overview of Parkinson-plus syndromes

Clinical features MRI findings Pathology
Macroscopic Microscopic
Dementia with Lewy bodies
Multiple system atrophy
  • Olivopontocerebellar and striatonigral atrophy
Progressive supranuclear palsy
Corticobasal degeneration

Differentiating features from Parkinson disease

Features that distinguish Parkinson-plus syndromes from Parkinson disease include: [1]

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Dementia with Lewy bodiestoggle arrow icon

Definition [2]

Dementia with Lewy bodies (DLB) is an α-synucleinopathy characterized by the abnormal deposition of Lewy bodies (made of α-synuclein) in neurons primarily in cortical and subcortical brain regions.

Epidemiology [3][4]

  • Second most common form of neurodegenerative dementia
  • Incidence: 3–7% of all dementia diagnoses; increases with age [3][4]
  • Mean age of onset: 75 years [5]
  • > (up to 4:1) [3]

Clinical features [6][7]

Individuals with dementia with Lewy bodies have visual hallewynations.

Dementia typically occurs within 1 year of motor symptom onset in DLB and is essential for diagnosis, whereas dementia typically develops later in Parkinson disease dementia. [8]

Diagnosis [6][9]

General principles

Neuroimaging

Pathology [11]

Treatment [2]

General principles

Pharmacological treatment

Antipsychotic treatment, especially with typical antipsychotics, is associated with severe sensitivity reactions, may worsen parkinsonism, and may precipitate a life-threatening akinetic crisis. [2]

Prognosis [13]

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Multiple system atrophytoggle arrow icon

Definition [15]

Multiple system atrophy (MSA) is an α-synucleinopathy characterized by the abnormal deposition of α-synuclein aggregates, primarily in glial cells, leading to neurodegeneration, including in the substantia nigra, cerebellum, brainstem, and autonomic nervous system structures.

Epidemiology [15]

  • Incidence: 1–3/100,000 individuals/year
  • Mean age of onset: ∼ 56 years

Clinical features [15][16]

MSA is classified into two subtypes based on the predominant features at initial presentation: MSA-C (cerebellar features) or MSA-P (parkinsonian features).

Diagnosis [15]

General principles

Neuroimaging

Pathology [18]

Treatment [15]

General principles

Pharmacological treatment

Prognosis

Mean survival: 7–9 years [19]

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Progressive supranuclear palsytoggle arrow icon

Definition [20]

Progressive supranuclear palsy (PSP) is a tauopathy characterized by the abnormal deposition of tau protein in the form of neurofibrillary tangles, causing brain atrophy and degeneration (e.g., in the brainstem, basal ganglia, and frontal lobe).

Epidemiology [21]

  • Incidence: ∼ 1/100,000 individuals/year
  • Mean age of onset: 60–70 years

Clinical features [7][22]

Diagnosis [23]

General principles

Neuroimaging

MRI brain findings include the hummingbird sign, which represents atrophy of midbrain structures with a relatively intact pons region. [24]

Pathology [20]

Treatment

General principles

  • Symptom management is the primary goal.
  • Management is led by neurology and supported by a multidisciplinary team (e.g., ophthalmology, physical therapy, occupational therapy).
  • Supportive care and other nonpharmacological interventions (e.g., ophthalmological interventions for gaze palsy) are indicated in all patients.
  • Reserve pharmacological treatment for bothersome symptoms and limit polypharmacy.

Pharmacological treatment [23]

Prognosis

Median survival: ∼ 5 years [25]

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Corticobasal degenerationtoggle arrow icon

Definition [26]

Corticobasal degeneration is a tauopathy characterized by the abnormal deposition of tau protein, leading to degeneration primarily in the cerebral cortex and basal ganglia.

Epidemiology [26]

  • Incidence: ∼ 1/100,000 individuals/year
  • Mean age of onset: ∼ 64 years

Clinical features [26][27]

  • Motor features: asymmetric, progressive motor abnormalities (e.g., parkinsonism, dystonia, and/or myoclonus) initially affecting only one limb
  • Cortical features, e.g.:
    • Ideomotor apraxia
    • Agnosia
    • Cortical sensory deficits
    • Alien limb phenomenon; : involuntary yet purposeful movement of a limb, accompanied by the perception that it does not belong to the affected individual
  • Cognitive impairment
    • Memory deficit
    • Language disturbances
  • Neuropsychiatric features (e.g., depression)

Diagnosis [26]

General principles

Neuroimaging

MRI brain findings include asymmetric focal cortical atrophy and atrophy of the basal ganglia.

Pathology [26]

Treatment [26]

General principles

Pharmacological treatment

Prognosis

Mean survival: ∼ 6.5 years [26]

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