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Patient Care

Grand Rounds: The Pathophysiology of Seizures

Grand Rounds is a new monthly blog series developed by EMS World and FlightBridgeED that will feature top EMS medical directors exploring the intricacies of critical care in EMS practice. In this first installment, FlightBridgeED Associate Medical Director Jeffrey Jarvis, MD, PM, breaks down seizures. 

You respond to a 48-year-old male who’s conscious and verbally responsive. You notice abnormal twitching movements in his left arm, but he has an otherwise healthy appearance. He tells you he has a seizure disorder and that the arm twitching is how his seizures manifest.

He denies fever, headache, trauma, or other illness. He takes Keppra for seizures and has been taking it as prescribed. He usually gets between 3–5 of these seizures a month, and once or twice a year, it becomes a generalized seizure during which he loses consciousness. 

You wonder if this isolated arm twitching is really a seizure and if you should give him midazolam or not.

Keep this case in mind as we discuss the pathophysiology and types of seizures.

Uncontrolled Depolarization

First it’s important to understand a broader definition. A seizure is not defined by movement but by the abnormal electrical activity within a part of the brain. There are lots of causes for these, but at a fundamental level they are caused by uncontrolled neuronal depolarization. Depolarization is caused by the movement of ions across the cell membrane. It occurs when channels along the neuronal membrane open in response to something, allowing sodium to bring its positive charge from outside the membrane to inside. This causes the polarity, or “charge,” inside the membrane—which has a (-70)-mV charge at its resting potential—to become more positive. This typically happens gradually until the inside charge gets to around -55 mV, which is the threshold potential.

This is special because there are a lot more sodium channels on the membrane that have yet to open. They are “voltage-gated,” and they open when the inside charge gets above -55 mV. When they open, a lot more sodium enters, and the entire membrane rapidly becomes positive on the inside and negative on the outside. Because this polarity is the opposite of what it is at rest, this is called depolarization.

Depolarization continues until the charge inside the membrane reaches around 30 mV. At that point the sodium channels close, and depolarization ends. At 30 mV voltage-gated potassium channels open, allowing positively charged potassium ions (which are more prevalent inside the cell) to rush out of the cell, taking their positive charge with them. Eventually the membrane returns to its resting (-70)-mV potential. This process of resetting the polarity back to its negative resting charge is called repolarization.

When a segment of a neuron depolarizes, it acts on the voltage-gated sodium channels of the segments next to it, causing them to depolarize as well. In this fashion the action potential is propagated down the neuron. This is how normal neuronal action potentials occur. Seizures happen when an area of the brain starts to depolarize abnormally. This can happen because of damage to the cells, inherited defects of the channels (something called channel patties), or drugs that alter the resting potential and make it easier to depolarize. 

The physical movements we see in some types of seizures are motor manifestations of the electrical activity. The location and type of movement are determined by the section of the brain that’s misbehaving. For example, if the right motor cortex responsible for arm movement has a seizure, the left arm will convulse. If the section of the brain responsible for smell has a seizure, the manifestation will be the patient experiencing abnormal smells. Speech and eyesight are similar. It is not uncommon for patients with migraines to experience blindness because the area of the brain responsible for sight is adversely impacted by seizure-like activity. These are called complex migraines and can be difficult to tell from seizures or strokes.

It is also common for one area of the brain to be the nidus, or origin, for a seizure that manifests as a convulsion of the arm but then spreads across the brain until it includes the lower parts responsible for consciousness. We would see this as a conscious patient who begins to have arm twitching that then turns rapidly into unconsciousness and total body tonic-clonic activity.

By the way, the mainstay of seizure treatment is the administration of benzodiazepines like midazolam. These drugs work on GABA (gamma-Aminobutyric acid) receptors that, when stimulated, open chloride ion channels, allowing negative ions into the cell and making it more negatively charged. This makes it harder to depolarize and thus aborts the seizure.

Focal vs. Generalized

Enough pathophysiology; let’s talk about types of seizures. We can broadly break them down into focal or generalized. Another term for focal is partial. The difference is that generalized seizures involve loss of consciousness and both hemispheres of the brain, while focal/partial seizures are isolated to one. Partial seizures may or may not include altered cognition. In the presence of altered cognition, they are called complex partial, while simple partial seizures do not involve altered cognition.

What should be on our differential when caring for a patient we think is having a seizure? First make sure it’s not “VF seizure” that occurs because of a sudden drop in cerebral blood flow from a cardiac arrest. We obviously treat those differently. Sometimes sudden and profound drops in blood pressure can cause a brief seizure.

We should consider some common causes of seizures, such as eclampsia and toxic encephalopathy from alcohol (particularly alcohol withdrawal, tetanus, or strychnine). Complex migraines and hyponatremia should also be on the list. Finally think about psychogenic nonepileptiform seizures (PNES). We used to call these pseudoseizures. Treat them like seizures and understand that while they’re not actual seizures, the patient does not have control over them and is not malingering or “faking it.”

Hypoglycemia can cause and result from seizures. Absolutely check the blood glucose in patients who are still seizing (after the benzos, of course) or still altered following the seizure. If they’ve returned to being alert, the seizure wasn’t from hypoglycemia, and their finger can probably remain unmolested.

Most of the seizures we’re called for will have stopped by the time we get there. This can sometimes make it challenging to tell the difference between seizures and syncope. Here are some characteristics of seizures that can help differentiate them:

  • Sudden onset
  • Brief duration
  • Altered mental status
  • Purposeless activity
  • Unprovoked
  • Postictal state 

Obviously syncope patients may have some of these characteristics, but the more that are present, the more likely a seizure was the cause. We can also look for signs such as tongue-biting or urinary incontinence to support a seizure.

Make It Stop

Now for the treatment.

I think we all know benzodiazepines are the first-line therapy, but how much to give? The RAMPART trial compared intramuscular Versed to intravenous Ativan and found that, in patients without an existing IV, IM Versed achieved faster seizure cessation. This is due to the time it takes to start the line. We can extrapolate from this that, because of the rapid onset of IM Versed, it will also be faster than IV Versed.

If a patient is having a generalized tonic-clonic seizure, giving benzos is an easy decision. We often err, though, by thinking we can quickly drop a line in. Just administer a big-boy dose of IM Versed while you’re starting the line. I don’t care how good you are at IVs in seizing patients, the IM route is faster. Just do it.

How about the patient with a partial seizure isolated to, say, an arm only, who is still alert? Should we treat these? In general, yes. The good news is that these patients are in less danger because there is less brain involved. We can probably take our time and get an IV started and give a lower dose of Versed to these folks. 

At the Emergency Department

Let’s talk a bit about what I’m going to do for them in the ED.

If this is a new-onset, afebrile seizure, I’m going to investigate the cause. I’ll get a CT of their head to look for bleeding (like from a SAH) or tumor causing mass effect. I’ve treated a lot of first-time seizures and only found an abnormality on CT once or twice. I’ll also check some labs to look for hyponatremia or other electrolyte abnormalities. If they look good and the patient hasn’t seized again, I’ll discharge them without any antiseizure medications, have them follow up with neurology, and tell them the state of Texas prohibits them from driving after a seizure until cleared by a neurologist. 

If it’s not a first-time seizure, I’ll look for any provoking illness/injury. I’ll ensure the patient did not have status with multiple seizures uninterrupted by a return to baseline and look into whether they need a loading dose of their seizure medication if they haven’t been compliant. Most of these patients get cleared by history alone without any additional testing. I rarely image these patients.

If they have a fever and a seizure, it’s a whole different ballgame, unless they are between 3 months and 5 years. Simple pediatric febrile seizures are treated just like we would treat the fever. If they are less than 3 months or more than 5 years, I’ll work them up for meningitis. 

Jeffrey L. Jarvis, MD, MS, EMT-P, FACEP, FAEMS, is an associate medical director for FlightBridgeED,LLC, an EMS medical director for the Williamson County EMS system and Marble Falls Area EMS, and an emergency physician at Baylor Scott & White Hospital in Round Rock, Tex. He is board-certified in emergency medicine and EMS. He began his career as a paramedic with Williamson County EMS in 1988 and continues to maintain his paramedic license.

 

Comments

Submitted byjer365@hotmail.com on 02/11/2020

Is there a way to determine if a medication is the cuasation of the seizure?

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