Parkinson disease

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Parkinson disease

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Questions

USMLE® Step 1 style questions USMLE

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A 70-year-old man with a history of Parkinson disease comes to the office for follow-up. He was diagnosed 6 years ago, and since then, the condition has been well-controlled with levodopa/carbidopa. However, for the past 2 months, the patient reports increased difficulty ambulating, loss of balance and increased rigidity. He is compliant with the treatment and describes fluctuations in the symptoms that improve after he takes the medication. Physical examination reveals diffuse cogwheel rigidity and difficulty walking. A decision is made to add a medication that will descrease the symptoms between levodopa/carbidopa doses. Which of the following best describes the mechanism of action of this medication?  

External References

First Aid

2024

2023

2022

2021

Akinesia in Parkinson disease p. 725

Antimuscarinic drugs

Parkinson disease p. 563

Antipsychotic drugs p. 591

Parkinson-like syndrome p. 250

Dopamine p. 241, 332

Parkinson disease p. 563

Gait disturbance

Parkinson disease p. 537

Gait disturbances

Parkinson disease p. 725

MAO inhibitors p. 593

Parkinson disease p. 563

Metoclopramide p. 407

Parkinson-like syndrome p. 250

Muscarinic antagonists p. 240, 706

Parkinson disease p. 563

Nausea

Parkinson disease drugs p. 564

Neurons p. 502

Parkinson disease p. 563

Parkinson disease p. 534

basal ganglia lesions p. 524

benztropine for p. 240

dopaminergic pathways p. 509

drug therapy for p. 563

Lewy bodies p. 534

neurotransmitters for p. 507

nigrostriatal pathway and p. 509

presentation p. 725

proteasome and p. 46

resting tremor in p. 533

seborrheic dermatitis association p. 484

trihexyphenidyl p. 240

Parkinson-like syndrome p. 250

Reserpine

Parkinson-like syndrome p. 250

Rigidity in Parkinson disease p. 725

Substantia nigra

Parkinson disease p. 725

Transcript

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Parkinson’s disease, which is sometimes called Parkinson disease, Parkinson’s, or PD, is a movement disorder where the dopamine-producing neurons in the substantia nigra of the brain undergo degeneration.

Parkinson’s is one of the most common neurological disorders. It’s a progressive, adult-onset disease, and it gets more common with age. Most of the time, there’s no known cause. But in a few cases, there might be a genetic cause, like mutations in the PINK1, parkin, or alpha synuclein genes, and in rare cases, Parkinsonian symptoms may be caused by MPTP, a toxic impurity that can be found in the recreational drug MPPP or desmethylprodine, which is a synthetic opioid.

In other people, one or more risk factors, rather than a single outright cause, might contribute to Parkinson’s, for example pesticide exposure or DNA variants in genes like LRRK2.

No matter what the cause is, Parkinson’s derives from the death of dopamine-producing, or dopaminergic, neurons in the substantia nigra. The name substantia nigra means “black substance,” since it is darker than other brain regions when you look at a slice of the brain on an autopsy.

We usually refer to the substantia nigra as if it’s in a single location, but there are actually two of these regions in the brain, one on each side of the midbrain. The substantia nigra is a part of the basal ganglia, a collection of brain regions that control movement through their connections with the motor cortex.

In Parkinson’s, these darkened areas of substantia nigra gradually disappear. Under a microscope, Lewy bodies, which are eosinophilic, round inclusions made of alpha-synuclein protein are present in the affected substantia nigra neurons before they die. The function of alpha-synuclein is unknown, as well as the significance of Lewy bodies, and they are both found in other diseases like Lewy body dementia and multiple system atrophy.

The substantia nigra actually can be split into two sub-regions.

First, there’s the pars reticulata, which receives signals from another part of the basal ganglia called the striatum, which is a term for the caudate and putamen put together, and relays messages to the thalamus via neurons rich in the neurotransmitter GABA, also known as gamma-aminobutyric acid.

Summary

Parkinson's is a progressive movement disorder caused by degeneration of dopamine-producing neurons in the substantia nigra, specifically in the pars compacta, which leads to resting tremor, rigidity, problems initiating movement, and postural instability, and for which therapy primarily focuses on increasing brain dopamine.

There is no cure for this condition, but medications can increase dopamine levels in the brain and control tremors. There is also deep-brain stimulation, which involves an implantable device that directly sends electrical signals to the basal ganglia that counteract the abnormal signaling in Parkinson's.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 7/E (ENHANCED EBOOK)" McGraw Hill Professional (2014)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw Hill Professional (2019)
  5. "Parkinson's disease" The Lancet (2015)
  6. "Parkinson's disease" The Lancet (2004)
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