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Key Points

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  • Disease summary:

    • Parkinson disease (PD) is marked by tremor, muscle rigidity, and slowed movement and known to have multiple etiologies both genetic and idiopathic. Many genetic risk factors are known but environmental factors are not established.

    • A cardinal pathologic feature is the presence of Lewy bodies in the substantia nigra, although a minority of cases may not exhibit this finding.

    • The disease presents with bradykinesia and often with a resting tremor. At first the disease responds well to l-dopa and related therapies, but as the disease progresses, therapy becomes more problematic with shorter periods of drug efficacy and dyskinesias as an effect of treatment. Cognitive and other complications increase during the disease progression.

    • Anatomic involvement: While the major motor symptoms of the disease result from the damage to the substantia nigra, recent studies from Braak have suggested that the disease may start in the lower brain stem and spread progressively.

  • Differential diagnosis:

    • It includes progressive supranuclear palsy, multiple system atrophy, and essential tremor.

  • Monogenic forms:

    • Many monogenic forms exist, both recessive and dominant; see Table 126-1.

  • Family history:

    • An affected first-degree relative confers an increase in risk of disease, but this varies both with age, and naturally is dependent on the precise etiology in any family.

  • Twin studies:

    • Monozygotic twins have a 20% to 50% concordance rate in PD, lower in dizygotic twins. Since this is a late-onset disease and a disease in which the onset in twin can vary enormously, precise figures are not available and are, in any event, difficult to interpret.

  • Environmental factors:

    • None are known, although smoking and caffeine intake are negatively associated with disease occurrence. Whether this relates to the role of dopamine in the reward system and therefore is related to premorbid addictive behavior is not clear. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin which causes permanent symptoms of PD and has been used to study disease models in various animal studies; MPTP has caused human cases when injected but has no association with typical disease presentations.

  • Genome-wide associations:

    • Many associations exist. Disease-associated genetic variants (single-nucleotide polymorphisms [SNPs]) provide insight into disease pathogenesis; testing for SNPs is not yet clinically validated to diagnose or guide management of PD (Table 126-2).

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Table Graphic Jump Location
Table 126-1Mendelian Genes for Parkinson Disease
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Table Graphic Jump Location
Table 126-2Risk Loci for Parkinson Disease With Approximate Odds Ratios and Likely Type of Variability Which Is Important at the Locus

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