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 Prominent episodic or semantic memory loss (Alzheimer disease) Language impairment* (frontotemporal dementias). Visuospatial impairment (diffuse dementia with Lewy bodies)
Multiple system atrophy	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
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 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
Normal-pressure hydrocephalus	Usually characterized by normal CSF pressure and caused by various mechanisms (eg, increased CSF pulsatility, reduced CSF drainage [1])
Hypoparathyroidism	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
Antipsychotics	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) , long-term use	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.

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

Prominent episodic or semantic memory loss (Alzheimer disease)
Language impairment* (frontotemporal dementias).
Visuospatial impairment (diffuse dementia with Lewy bodies)

Multiple system atrophy

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

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 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

Normal-pressure hydrocephalus

Usually characterized by normal CSF pressure and caused by various mechanisms (eg, increased CSF pulsatility, reduced CSF drainage [1])

Hypoparathyroidism

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

Antipsychotics

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)

, long-term use

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.

In these topics

Secondary and Atypical Parkinsonism