History and exam

Key diagnostic factors

common

bradykinesia

Slowness of movements, progressive reduction in amplitude of repeated movements, delay in initiating movements, and freezing of gait are eventually seen in all patients. Required sign for many diagnostic criteria.[1][87]

resting tremor

A 4-6 Hz tremor is noted at rest and dissipates with use of the limbs. Generally the onset is asymmetric. A chin tremor may occur as well. This tremor may re-emerge when the arms are outstretched.[88]

rigidity

Hypertonicity is defined as unvarying increased resistance within the range of passive movement about a joint.[89] Often cogwheeling will be noted, especially (although not only) if tremor is also present.

postural instability

Imbalance or falling observed with pull test or spontaneously; retropulsion; common in mid- to late-stage disease.

Other diagnostic factors

common

masked facies

Loss of spontaneous facial movement and expressivity, often noted only by the patient’s partner.

hypophonia

Reduced volume of voice.

hypokinetic dysarthria

Related to bradykinesia and rigidity of orobuccolingual and laryngeal musculature.

micrographia

Decrease in amplitude of handwriting/printing.

stooped posture

Related to rigidity.

shuffling gait

Related to rigidity and bradykinesia.

conjugate gaze disorders

Saccadic (jerky) pursuit and hypometric saccades (falling short of intended target).

fatigue

Disabling symptom reported commonly.

constipation

Reflection of autonomic dysfunction. May precede the development of motor symptoms.[17][71]

depression

Common neuropsychiatric complaint. Should be sought in patients. May precede the development of motor symptoms.[17]

anxiety

Often unrecognized, but common. Should be sought in patients. May precede the development of motor symptoms.[17]

dementia

Nonmotor symptom that should be screened for at consultations; common in mid- to late-stage disease.

uncommon

exposure to antipsychotics or antiemetics

Dopamine blocking agents may induce a secondary parkinsonism. Additionally, they may unmask incipient PD.

features of atypical parkinsonism

These include acute onset, rapidly progressive disease, cognitive impairment, prominent postural instability, severe autonomic dysfunction (e.g., orthostatic hypotension), and significant neuropsychiatric features (e.g., hallucinations, fluctuating levels of arousal).

hyposmia/anosmia

Often associated with PD, and may precede the development of motor symptoms.[17][68]

sleep disorders

Often associated with PD, and may precede the development of motor symptoms.[17][68]

Risk factors

strong

increasing age

Single most important risk factor.

Among residents of Olmsted County, Minnesota, the average annual incidence rate of parkinsonism was 0.8/100,000 person-years in people ages 0-29 years, increasing incrementally to 304.8/100,000 person-years in those ages 80-99 years.[3] A more recent review of prevalence of PD in Italy reported figures of 37.8 per 100,000 inhabitants in people ages 0-64 years, 578.7 in people ages 65-75 years, and 1235.7 in people ages 75 years and older.[4]

history of familial PD in younger-onset disease

In younger-onset disease, autosomal dominant and autosomal recessive mutations have been identified in familial PD cohorts.[16][18][22][45]

mutation in gene encoding glucocerebrosidase

Mutations in the gene encoding glucocerebrosidase (GBA), the enzyme that is deficient in Gaucher disease, have been shown to confer an increased risk of PD.[23][24][25]

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure

In the early 1980s this neurotoxin produced acute-onset parkinsonism in a group of people exposed inadvertently.[46] It is rarely found outside of laboratory models, and therefore poses minimal risk to populations at large. However, exposure would have a high association with parkinsonism.

weak

chronic exposure to metals

Chronic heavy metal exposure has been implicated as a risk factor.[31] Chronic manganese exposure (i.e., mining or welding) and elevated circulating manganese have been associated with parkinsonism, but findings are inconsistent.[47][48]

Hemochromatosis may cause a parkinsonism syndrome.[49]

male sex

Incidence and prevalence of PD appears to be greater in men than in women.[4][5][12][13] Age-standardized prevalence rates from 2016 indicate that PD is 1.4 times more common in men.[5]

additional genetic risk factors

Several other genetic variants have been mapped, and several of the genes involved have been identified, including SNCA, LRRK2, PRKN, PINK-1, GBA, DJ-1, TREM2, VPS35, and MHFTR.[18] One study identified identified 90 independent genome-wide significant risk signals for PD across 78 genomic regions.[16]

One study reported a cumulative incidence of 2% up to age 75 years in first-degree relatives of people with PD, versus 1% incidence among first-degree relatives of controls.[50]

head trauma

History of significant traumatic brain injury may increase risk.[51][52][53]

geographic influence

May be a contributing risk factor among numerous other multifactorial influences.

Regional variations in PD prevalence have been reported in North America.[10][12] 

Studies variously report an increased risk for PD in rural settings or clustering in industrial areas.[10][54][55]

Variations in the prevalence of the disease in individual racial groups in different geographic areas have suggested an increased risk associated with rural living.[56]

toxin exposure

Exposure to toxins such as solvents (e.g., carbon disulfide, trichloroethylene, perchloroethylene, and carbon tetrachloride) may contribute to PD, along with many other factors.[57]

Occupational exposures to insecticides and herbicides have been identified as risk factors.[57][58] Some cases of parkinsonism occurred after acute exposure to paraquat or glyphosate.[59][60] There is some evidence of an association between exposure to Agent Orange (a 1:1 mixture of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid) and PD.[61]

occupation

May be a contributing risk factor among numerous other multifactorial influences.

Increased risk for PD has been reported in healthcare providers.[62][63] High-level education and occupational complexity have been associated with increased risk.[63][64][65]

Risk of PD is increased in farmers exposed to pesticides.[66]

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