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Epilepsy

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A 26 year-old woman comes into the emergency room because of a seizure. She has a past medical history of epilepsy, diagnosed when she was a child. This episode was not like the previous seizures. On examination, the patient is weak in her right upper and lower extremities but has normal strength on her left side. The patient is alert and oriented and follows commands appropriately. Physical examination is otherwise normal. The seizure happened about 3 hours ago and involved clonic spasms of her entire right side which rapidly spread to encompass her entire body. Which of the following is the most likely diagnosis?

Transcript

Content Reviewers:

Rishi Desai, MD, MPH

Contributors:

Tanner Marshall, MS

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.

Some patients with epilepsy seem to have genetic mutations in which their GABA receptors are dysfunctional, and so they aren’t able to help inhibit signals.

In addition to potentially having a primary genetic cause, though, these receptors and ion channels might be affected by all sorts of things like brain tumors, brain injury or infection.

Whether it’s a decrease in inhibition or an increase in activation, when groups of neurons start firing simultaneously, over and over, it’s often noticed by others as obvious outward signs, like jerking, moving, and losing consciousness, but can also be subjective experiences that are only noticed by the person experiencing it, like fears or strange smells, it all depends on which neurons in the brain are affected.

People with epilepsy experience recurring episodes of some form of seizures, and we can start grouping the seizures by the region of the brain that’s affected.

When the affected area is limited to one hemisphere - or one half of the brain - or sometimes even a smaller area like a single lobe, we call it a partial or a focal seizure.

These seizures can be subcategorized by whether someone remains conscious during the seizure which is called the simple partial seizure or whether someone has impaired consciousness during the seizure which is called the complex partial seizure.

Simple partial seizures typically affect a small area of the brain, and can involve the person experiencing strange sensations, like hearing or tasting something, but can also involve jerking movements in specific muscle groups if the neurons controlling those muscles are affected

If the jerking activity starts in a specific muscle group, and spreads to surrounding muscle groups as more neurons are affected, it’s referred to as a Jacksonian march.

Typically, the person is conscious, meaning that they are awake and alert and will usually know that something is happening and will remember the seizure afterwards.

Complex partial seizures, on the other hand, involve losing consciousness completely or having impaired awareness and responsiveness, so they might not remember exactly what happened during a seizure.

Now, in contrast to the partial or focal seizure, a generalized seizure is where both hemispheres of the brain are affected. Sometimes, a seizure will start out as a partial seizure and then quickly develop into a generalized seizure.

And in those situations they’d called a “secondary generalized seizure” because a partial seizure came before it and was the primary event. Just like partial seizures, there are some subcategories of generalized seizures as well.

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)