Epilepsy

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Epilepsy

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Questions

USMLE® Step 1 style questions USMLE

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A 23-year-old woman is brought to the emergency department by ambulance because her body started shaking violently 10 minutes ago at a nearby bus stop. She was waiting for a bus with her partner when she suddenly fell down and started having stiffening and jerking movements involving all four extremities. Past medical history is significant for epilepsy, for which the patient takes lamotrigine. The partner notes the patient recently started taking a combined oral contraceptive pill. Her temperature is 37.5°C (99.5°F), pulse is 112/min and regular, respirations are 22/min and blood pressure is 108/68 mmHg. The patient is unable to respond to vocal commands. Physical examination shows ongoing symmetric rhythmic jerking of the limbs. After appropriate supportive treatment, the patient is given a drug intramuscularly, after which the jerking subsides. Which of the following best describes the mechanism of action of the drug administered?  

External References

First Aid

2024

2023

2022

2021

Absence seizures p. 531

drug therapy for p. 560

treatment p. 724

Ethosuximide p. 560

absence seizures p. 724

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Epilepsy means “seizure disorder”, so people with epilepsy have recurring and unpredictable seizures. A seizure is a period where cells in the brain, or neurons, are synchronously active, or active at the same time, when they’re not supposed to be.

Now when I say that neurons are “active”, I mean that they’re firing or sending a message using electrical signals relayed from neuron to neuron.

And if you look at a neuron under a microscope, each electrical signal that passes through it is really just ions flowing in and out of it through protein channels.

The way this ion flow is controlled is through neurotransmitters, a type of signaling molecule, and receptors. Neurotransmitters bind to the receptors and basically tell the cell to either open up the ion channels and relay the electrical message, called excitatory neurotransmitters, or close the ion channels and stop the electrical message, called inhibitory neurotransmitters.

During a seizure, clusters of neurons in the brain become temporarily impaired and start sending out a ton of excitatory signals, over and over again, and these are sometimes said to be paroxysmal.

These paroxysmal electrical discharges are thought to happen due to either too much excitation, or too little inhibition (which are kinda two sides of the same coin, right?).

The main excitatory neurotransmitter in the brain is glutamate, and NMDA is the primary receptor that responds to glutamate by opening ion channels that let calcium in, a positive ion that tells the cell to send signals.

Some patients with epilepsy seem to have fast or long-lasting activation of these receptors. On the flip side, the main inhibitory neurotransmitter in the brain is GABA, which binds to GABA receptors that tell the cell to inhibit the signal by opening channels that let in chloride ions, which are negative ions that tell the cell to inhibit signals.

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 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction" Nature Reviews Neuroscience (2013)
  6. "Epilepsies as Dynamical Diseases of Brain Systems: Basic Models of the Transition Between Normal and Epileptic Activity" Epilepsia (2003)
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