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Parkinsonism and Parkinson-Plus Syndromes

Parkinsonism and Parkinson-Plus Syndromes

Scope of this article:

This article covers parkinsonism as an umbrella clinical syndrome, including its main causes and the key Parkinson-plus / atypical parkinsonian syndromes.

For idiopathic Parkinson’s disease, see Parkinson’s Disease (PD)

Terms and Definitions

Four commonly confused terms that are related but not interchangeable:

Term Definition
Parkinsonism (Parkinsonian syndrome) An umbrella term, a clinical syndrome defined by the presence of bradykinesia plus at least one of the following: tremor, rigidity, postural instability
Parkinson’s disease Idiopathic (primary) form of parkinsonism. Parkinson’s disease is the most common form of parkinsonism

Caused by dopaminergic neuron degeneration in the substantia nigra due to Lewy body deposition

Parkinson-plus syndromes (atypical parkinsonism) A group of primary neurodegenerative disorders that mimic Parkinson’s disease with additional “plus” features and are often poorly responsive to levodopa

Key examples include Lewy body dementia, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration

Secondary parkinsonism Parkinsonism caused by an identifiable cause (i.e. non-idiopathic), such as drugs or toxins

Parkinsonism Causes

There are 3 categories of Parkinsonism causes: [Ref1][Ref2]

Category Description / causes
Parkinson’s disease Parkinson’s disease refers to the primary idiopathic form and the most common cause of Parkinsonism
Parkinson-plus syndromes (atypical parkinsonism) A group of primary neurodegenerative disorders, key ones include:

  • Dementia with Lewy bodies
  • Multiple system atrophy (MSA)
  • Progressive supranuclear palsy (PSP)
  • Corticobasal degeneration (CBD)
Secondary parkinsonism Drug-induced (non-exhaustive):

  • Antipsychotics
    • Higher risk with 1st generation / typical ones (e.g. haloperidol, chlorpromazine)
    • Lower risk with 2nd generation (atypical ones (e.g. aripiprazole, clozapine, olanzapine, quetiapine, risperidone)
  • Anti-emetics
    • Prochlorperazine
    • Metoclopramide
  • Less common drugs =

Toxin-induced:

  • MPTP
  • Manganese, lead, mercury
  • Acute carbon monoxide poisoning

Neurological conditions

  • Vascular Parkinsonism
  • Normal pressure hydrocephalus
  • Wilson’s disease
  • Huntington’s disease
  • Brain tumour
  • Chronic traumatic encephalopathy

Features of Parkinsonism

Parkinsonism is defined by the presence of bradykinesia plus at least one of the following: tremor, rigidity, postural instability

Category Description / symptoms
Bradykinesia Bradykinesia: slowness in initiating and performing voluntary movement + progressive reduction in speed and amplitude of sustained repetitive actions

May present as:

  • Impaired fine motor movement (e.g. doing buttons, opening jars, using utensils)
  • Micrographia (small and slow handwriting)
  • Hypomimia (facial masking) (reduced or flat facial expression)
  • Reduced blinking (→ Myerson’s sign)
  • Trouble / slowness getting out of a chair
  • Difficulty turning in bed
  • “Parkinsonian gait”
    • Difficulty initiating gait
    • Slow, shuffling gait
    • Reduced arm swing + short steps
    • Festination (the patient’s gait becomes progressively faster)
    • Difficulty turning
    • Stooped posture

Bradykinesia can be assessed clinically by asking the patient to perform repetitive movements like finger tappinghand opening and closing, and foot tapping

Look for slowness, reduced amplitude, and progressive decrement.

Rigidity Asymmetrical, predominantly affecting the side of onset

  • Lead-pipe rigidity – smooth, constant resistance to passive movement throughout the full range of motion (like bending a pipe)
  • Cogwheel rigidity – rigidity with a ratchet-like, stop-start quality during passive movement (like the limb is moving in small clicks or catches like a cogwheel)
Tremor
  • Asymmetrical
    • Often unilateral at onset, but may later become bilateral
    • Even when bilateral, it often remains more prominent on one side
  • Resting tremor
    • Low-frequency tremor, often described as “pill-rolling”
    • Typically affects the thumb and index finger
    • May also affect the wrist, leg, lips, chin or jaw
    • Usually improves with voluntary movement
    • The tremor rarely involves the head, neck, or voice (more likely in essential tremor)

A tremor can be absent in up to 20% of patients with PD

Postural instability Postural instability is suggested by the ‘pull test’ – a tendency to fall backwards after a sharp forward pull from the examiner

Drug-induced parkinsonism typically presents as: [Ref]

  • Symmetrical parkinsonism
  • Prominent bradykinesia and rigidity
  • Symptoms typically resolve within weeks to months after withdrawing the causative agent

Note that it can also closely mimic Parkinson’s disease.

Parkinson-Plus Syndromes (Atypical Parkinsonism)

Parkinson-plus syndromes are characterised by:

  • Parkinsonism, and
  • Additional ‘plus’ features (e.g. faster progression, symmetrical onset), and
  • Poor response to levodopa

The specific clinical features vary depending on the underlying syndrome.

Dementia with Lewy Bodies

Core tetrad features:

  • Parkinsonism
  • Fluctuating cognition
  • Visual hallucinations (tend to involve humans or animals)
  • REM sleep disorder

Autonomic failure (e.g. orthostatic hypotension) is also common. Memory impairment may not be apparent in early stages

For management, see the Dementias article

Dementia with Lewy bodies vs Parkinson’s disease dementia

They are closely related conditions within the spectrum of Lewy body disease, a textbook rule:

  • Dementia with Lewy bodies: dementia develops before or within 1 year of parkinsonism
  • Parkinson’s disease dementia: dementia develops after 1  year of parkinsonism

Multiple System Atrophy (MSA)

Typical presentation: [Ref]

  • Parkinsonism
    • Tends to be rapidly progressive
    • Bradykinesia and rigidity are usually predominant (a classic pill-rolling tremor is rarely seen)
  • Autonomic failure – a core feature
    • Orthostatic hypotension, syncope
    • Urinary incontinence
    • Erectile dysfunction
  • Cerebellar ataxia

MSA is classified into 2 subtypes based on the predominant presenting features: MSA-C (cerebellar features) or MSA-P (parkinsonian features) [Ref]

MRI brain can be used to differentiate MSA from Parkinson’s disease: [Ref]

  • Changes seen in the brainstem and basal ganglia
  • Classic “hot cross bun” sign – bright, cross-shaped pattern (cruciform hyperintensity) in the middle of the pons on transverse view

Exam tip:

Parkinsonism + autonomic failure = multiple system atrophy

Progressive Supranuclear Palsy (PSP)

Typical presentation: [Ref]

  • Parkinsonism
    • Symmetrical parkinsonism
    • Tends to cause axial rigidityupright +/- retrocollis posture (as opposed to the stooped posture in Parkinson’s disease)
  • Abnormal eye movement
    • Classically impaired vertical eye movement
  • Recurrent falls (classically backwards)
  • Behavioural and cognitive features
    • Executive function
    • Verbal fluency
    • Apathy (seen in 80% of patients)
    • Impulsivity

MRI brain can be used to differentiate PSP from Parkinson’s disease: [Ref]

  • Midbrain atrophy
  • Classic “hummingbird sign” – atrophied midbrain resembles the head and beak of a hummingbird on sagittal view

Exam tip:

Parkinsonism + falls + eye movement problems = progressive supranuclear palsy

Corticobasal Degeneration (CBD)

Typical presentation: [Ref]

  • Parkinsonism
    • Markedly asymmetrical limb rigidity or akinesia
    • +/- Dystonia and myoclonus
    • Typical resting tremor is often absent
  • Higher cortical features (key in distinguishing CBD from Parkinson’s disease)
    • Alien limb phenomenon – the patient feels that the limb does NOT belong to them / the limb has a will of its own / the limb independently performs complex unintentional tasks
    • Sensory loss
    • Apraxia
    • Progressive non-fluent aphasia
  • Cognitive impairment and behavioural changes

MRI brain is helpful, but NOT diagnostic; diagnosis of CBD is primarily clinical: [Ref]

  • Typical finding: asymmetric atrophy primarily involving the frontal and parietal cortices

Related Articles

Parkinson’s Disease (PD)

Essential Tremor

Hyperthyroidism and Thyrotoxicosis

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