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, different pathology, and a different response to treatment, and the prognosis is worse. Diagnosis is by clinical evaluation and response to levodopa. Treatment is directed at the cause when possible.
(See also Overview of Movement and Cerebellar Disorders.)
In secondary parkinsonism, the mechanism is blockade of or interference with dopamine’s action in the basal ganglia.
Atypical parkinsonism encompasses neurodegenerative disorders such as
Corticobasal ganglionic degeneration
Certain spinocerebellar ataxias
Etiology of Secondary and Atypical Parkinsonism
Parkinsonism results from medications, disorders other than Parkinson disease, or exogenous toxins.
The most common cause of secondary parkinsonism is
Use of medications that decrease dopaminergic activity
These medications include
Antipsychotics (eg, phenothiazine, thioxanthene, butyrophenone)
Medications that deplete dopamine
Outside the United States, cinnarizine and flunarizine
Some Causes of Secondary and Atypical Parkinsonism
Cause | Comments |
|---|---|
Neurodegenerative disorders | |
Amyotrophic lateral sclerosis–parkinsonism-dementia complex of Guam | Responds poorly to antiparkinsonian medications |
Corticobasal ganglionic 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 years and death after about 7–10 years depending on the cause Responds poorly to antiparkinsonian medications |
Dementia (eg, Alzheimer disease, chromosome 17–linked frontotemporal dementias, diffuse dementia with Lewy bodies) | Parkinsonism often preceded by dementia most typically with
|
May include prominent autonomic dysfunction (orthostatic light-headedness, urinary or fecal incontinence) May include prominent cerebellar dysfunction May include severe parkinsonian features, usually with poor response to levodopa May include pyramidal signs Often causes early falls and balance problems Responds poorly to antiparkinsonian medications | |
First manifests with gait and balance problems In its classic form, causes progressive ophthalmoparesis, starting with impairment of downward gaze Responds poorly to antiparkinsonian medications | |
Spinocerebellar ataxias (usually type 1, 2, or 3) | Usually first manifests with imbalance and poor coordination but may have additional classical symptoms (eg, pyramidal tract signs in type 1, slow saccades and polyneuropathy in type 2, parkinsonism and dystonia in type 3) Responds poorly to antiparkinsonian medications |
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 |
Brain tumors near the basal ganglia | Manifests with hemiparkinsonism (ie, restricted to the side of the body opposite the lesion) |
Chronic traumatic encephalopathy (due to repeated traumatic brain injury) | Characterized by progressive parkinsonism, dementia, and mood disorders, including suicidal ideation Formerly known as dementia identified in boxers but now recognized in participants in various contact sports and in soldiers with blast injuries |
Usually characterized by normal CSF pressure and caused by various mechanisms (eg, increased CSF pulsatility, reduced CSF drainage [1]) | |
Causes calcification of the basal ganglia May cause parkinsonism, chorea, and athetosis | |
Viral encephalitis (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 |
Medications | |
Can cause reversible† parkinsonism (drug-induced or pharmacologic parkinsonism) | |
N-MPTP)‡ | Occurs in people who use IV drugs |
Reserpine (not available in the United States) | Can cause reversible† parkinsonism May be dose-dependent or related to susceptibility (risk factors include older age and female sex) |
Toxins | |
Carbon monoxide | Can cause irreversible parkinsonism due to bilateral internal globus pallidus necrosis |
Methanol | As contaminated moonshine, can cause hemorrhagic necrosis of the basal ganglia |
Can cause parkinsonism with dystonia and cognitive changes when toxicity is chronic; cock walk gait§ is characteristic, as well as T1-weighted hyperintensity in the lenticular nucleus | |
* Language impairment may involve expressive (nonfluent primary progressive) aphasia or receptive (primary progressive semantic) aphasia. | |
† When medications are withdrawn, symptoms usually resolve within a few weeks, although they may persist for months. | |
§ Features of dystonic gait include toe-walking, flexed elbows, and an erect spine. | |
CSF = cerebrospinal fluid; N-MPTP = N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. | |
Etiology reference
1. Wang Z, Zhang Y, Hu F, et al: Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus. CNS Neurosci Ther 26 (12):1230-1240, 2020. Epub 2020 Nov 26. doi: 10.1111/cns.13526
Symptoms and Signs of Secondary and Atypical Parkinsonism
Clinical features of secondary and atypical parkinsonism are similar to those of Parkinson disease (eg, resting tremor, rigidity, bradykinesia, postural instability).
Diagnosis of Secondary and Atypical Parkinsonism
Clinical evaluation
Poor response to levodopa therapy
For differential diagnosis, sometimes neuroimaging
Causes of parkinsonism can be identified by the following:
A thorough history, including occupational, medications and other substances, 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 of Secondary and Atypical Parkinsonism
Treatment of the cause
Physical measures
The cause of secondary parkinsonism is corrected or treated if possible, sometimes resulting in clinical improvement or disappearance of symptoms.
Physical measures to maintain mobility and independence are useful (as for Parkinson disease). Maximizing activity is a goal. Patients should increase daily activities to the greatest extent possible. If they cannot, physical or occupational therapy, which may involve a regular exercise program, may help condition them physically. Therapists may teach patients adaptive strategies, help them make appropriate adaptations in the home (eg, installing grab bars to reduce the risk of falls), and recommend adaptive devices that may be useful.
Good nutrition is essential.
Treatment references
1. Yoshiyama Y, Kojima A, Itoh K, Uchiyama T, Arai K: Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model. Neurobiol Dis 2012 45 (1):329-336, 2012. doi: 10.1016/j.nbd.2011.08.017
2. Yoshiyama Y, Kojima A, Itoh K, et al: Does anticholinergic activity affect neuropathology? Implication of neuroinflammation in Alzheimer's disease. Neurodegener Dis 15 (3):140-148, 2015. doi: 10.1159/000381484
Key Points
Parkinsonism can be caused by medications, 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 by the 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.
