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Secondary and Atypical Parkinsonism

By Hector A. Gonzalez-Usigli, MD

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Secondary parkinsonism refers to a group of disorders that have features similar to those of Parkinson disease but have a different etiology. Atypical parkinsonism refers to a group of neurodegenerative disorders other than Parkinson disease that have some features of Parkinson disease but have some different clinical features and a different pathology. Diagnosis is by clinical evaluation and response to levodopa. Treatment is directed at the cause when possible.

Parkinsonism results from drugs, disorders other than Parkinson disease, or exogenous toxins.

In secondary parkinsonism, the mechanism is blockade of or interference with dopamine’s action in the basal ganglia. The most common cause of secondary parkinsonism is

  • Use of drugs that decrease dopaminergic activity

These drugs include antipsychotics (eg, phenothiazine, thioxanthene, butyrophenone), antiemetics (eg, metoclopramide, prochlorperazine), and drugs that deplete dopamine (eg, tetrabenazine, reserpine).

Atypical parkinsonism encompasses neurodegenerative disorders such as progressive supranuclear palsy, diffuse Lewy body dementia, corticobasal degeneration, and multiple system atrophy.

Some Causes of Secondary and Atypical Parkinsonism

Cause

Comments

Neurodegenerative disorders

Amyotrophic lateral sclerosis–parkinsonism-dementia complex of Guam

Responds poorly to antiparkinsonian drugs

Corticobasal degeneration

Begins asymmetrically, usually after age 60

Causes cortical and basal ganglia signs, often with apraxia, dystonia, myoclonus, and alien limb syndrome (movement of a limb that seems independent of the patient’s conscious control)

Causes immobility after about 5 yr and death after about 10 yr

Responds poorly to antiparkinsonian drugs

Dementia (eg, Alzheimer disease, chromosome 17–linked frontotemporal dementias, diffuse Lewy body dementia)

Parkinsonism often preceded by dementia most typically with

  • Prominent memory loss (Alzheimer disease)

  • Language impairment (frontotemporal dementias)

  • Visuospatial impairment (diffuse Lewy body dementia)

Multiple system atrophy

May include prominent autonomic dysfunction

May include prominent cerebellar dysfunction

May include severe parkinsonian features, usually with poor response to levodopa

Often causes early falls and balance problems

Responds poorly to antiparkinsonian drugs

Progressive supranuclear palsy

First manifests with gait and balance problems

In its classic form, causes progressive ophthalmoparesis, starting with impairment of downward gaze

Responds poorly to antiparkinsonian drugs

Spinocerebellar ataxias (usually type 2 or 3)

Usually first manifests with imbalance and poor coordination

Responds poorly to antiparkinsonian drugs

Other disorders

Cerebrovascular disease

Manifests with rigidity and bradykinesia or akinesia (akinetic-rigid syndrome) that predominantly involves the lower extremities, with prominent gait disturbance and symmetric symptoms

Rarely responds to antiparkinsonian drugs

Brain tumors near the basal ganglia

Manifests with hemiparkinsonism (ie, restricted to one side of the body)

Repeated traumatic brain injury

Often causes dementia (as in dementia pugilistica)

Hydrocephalus

Usually characterized by normal CSF pressure (normal-pressure hydrocephalus) and caused by various mechanisms

Rarely caused by obstructed CSF flow with increased CSF pressure (obstructive hydrocephalus)

Hypoparathyroidism

Causes calcification of the basal ganglia

May cause chorea and athetosis

Viral (eg, West Nile) encephalitis, infectious or postinfectious autoimmune

Can cause parkinsonism transiently during the acute phase or, rarely, permanently (eg, postencephalitic parkinsonism after the epidemic of encephalitis lethargica in 1915–1926)

In postencephalitic parkinsonism, forced, sustained deviation of the head and eyes (oculogyric crises); other dystonias; autonomic instability; depression; and personality changes

Drugs

Antipsychotics

Can cause reversible* parkinsonism

Meperidine analog ( N -MPTP)

Can cause sudden, irreversible parkinsonism

Occurs in IV drug users

Metoclopramide

Reserpine

Lithium, long-term use

Can cause reversible* parkinsonism

May be dose-dependent or related to susceptibility (risk factors include older age and female sex)

With lithium, Sometimes results in cerebellar dysfunction

Toxins

Carbon monoxide

Can cause irreversible parkinsonism

Methanol

As contaminated moonshine, can cause hemorrhagic necrosis of the basal ganglia

Manganese

Can cause parkinsonism with dystonia and cognitive changes when toxicity is chronic

Usually related to occupation (eg, welding) but can result from abuse of methcathinone (in bath salts made from ephedrine)

*When drugs are withdrawn, symptoms usually resolve within a few weeks, although they may persist for months.

N -MPTP results from unsuccessful attempts to produce meperidine for illicit use.

N -MPTP = N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Symptoms and Signs

Parkinsonism causes the same symptoms as Parkinson disease (eg, resting tremor, rigidity, bradykinesia, postural instability).

Diagnosis

  • Clinical evaluation, response to levodopa therapy, and, for differential diagnosis, sometimes neuroimaging

To differentiate Parkinson disease from secondary or atypical parkinsonism, clinicians note whether levodopa results in dramatic improvement, suggesting Parkinson disease.

Causes of parkinsonism can be identified by the following:

  • A thorough history, including occupational, drug, and family history

  • Evaluation for neurologic deficits characteristic of neurodegenerative disorders other than Parkinson disease

  • Neuroimaging when indicated

Deficits that suggest neurodegenerative disorders other than Parkinson disease include gaze palsies, signs of corticospinal tract dysfunction (eg, hyperreflexia), myoclonus, autonomic dysfunction (if early or severe), cerebellar ataxia, prominent dystonia, ideomotor apraxia (inability to mimic hand motions), early dementia, early falls, and confinement to a wheelchair.

Treatment

  • Treatment of the cause

The cause of secondary parkinsonism is corrected or treated if possible, sometimes resulting in clinical improvement or disappearance of symptoms.

Drugs used to treat Parkinson disease are often ineffective or have only transient benefit. But amantadine or an anticholinergic drug (eg, benztropine) may ameliorate parkinsonism secondary to use of antipsychotic drugs.

Physical measures to maintain mobility and independence are useful (as for Parkinson disease). They include physical and occupational therapy, exercise, and use of adaptive devices. Good nutrition is essential.

Key Points

  • Parkinsonism can be caused by drugs, toxins, neurodegenerative disorders, and other disorders that affect the brain (eg, stroke, tumor, infection, trauma, hypoparathyroidism).

  • Suspect parkinsonism based on the clinical evaluation and differentiate it from Parkinson disease based on lack of response to levodopa; neuroimaging may be needed.

  • Check for deficits that suggest a neurodegenerative disorder other than Parkinson disease.

  • Correct or treat the cause if possible, and recommend physical measures to maintain mobility.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • LITHOBID
  • REGLAN
  • No US brand name
  • COMPRO
  • DEMEROL
  • COGENTIN

* This is the Professional Version. *