Reflections on Medical Education: 🔬 Pathophysiology of Seizures: What’s Going Wrong?

Tuesday, 22 July 2025

🔬 Pathophysiology of Seizures: What’s Going Wrong?

Seizures are caused by abnormal, excessive, synchronous electrical activity in groups of neurons. Seizures are like a power surge in the brain. Instead of orderly, purposeful neural signals, you get a storm of chaotic, excessive firing across neuron groups.

This hyperactivity disrupts normal function — from movement and sensation to awareness and behaviour.

⚡ The Balance Between Calm and Chaos

Our brains rely on two kinds of chemical messengers to keep activity in check:

Excitatory neurotransmitters (like glutamate) push neurons to fire.
Inhibitory neurotransmitters (like GABA) tell them to slow down or stop.

Think of these as the “accelerator” and “brake” systems of the brain. A healthy brain keeps a careful balance between the two.

🧩 How This Balance Tips in Seizures

In seizure conditions, this balance breaks down:

There may be too much excitatory signalling — glutamate floods the scene, pushing neurons to fire.
At the same time, there's often a loss of inhibitory control — GABA isn’t doing its job to apply the brakes.

Together, this leads to hypersynchronous firing, where large groups of neurons fire together abnormally — like a crowd shouting over each other.

🔄 What Causes the Breakdown?

Healthy neuron networks balance excitatory and inhibitory signals.
In seizures, there's a shift toward excitation (often via glutamate) and a loss of inhibition (often via GABA).

Several factors can disrupt this balance:

Structural brain changes, like scar tissue or tumours
Genetic mutations affecting ion channels or neurotransmitter receptors (e.g. sodium/potassium channel dysfunction)
Metabolic disturbances, such as low blood sugar or electrolyte imbalances
Infections or inflammation that alter neural function (encephalitis, autoimmune causes)

These triggers can either lower the seizure threshold or create a local area of hyperexcitable tissue that acts as a seizure focus.

🧪 A Systems View for Clinical Reasoning

We can approach this like a systems malfunction:

Input dysfunction: Excitatory pathways are overstimulated.
Processing failure: Inhibitory networks can't dampen the signal.
Output disruption: The brain sends uncontrolled messages to the body — manifesting as muscle jerks, altered awareness, or sensory changes.

🧬 Case Vignette: A Flicker in the Wires

Patient: Emily, a 20-year-old university student
Presentation: Emily was attending a tutorial when she suddenly stopped responding, stared blankly ahead, and began lip-smacking. The episode lasted around 30 seconds and she was confused afterward. Her friend noted similar events have happened before, often when Emily is sleep-deprived.

🧠 What’s Going On Behind the Scenes?

This episode suggests a focal seizure with impaired awareness — likely originating in the temporal lobe, given the automatisms (lip-smacking) and altered consciousness.

Here’s how the pathophysiology might play out:

A group of neurons in Emily’s temporal lobe has become hyperexcitable — primed to fire due to changes in neurotransmitter balance or ion channel dysfunction.
Excitatory glutamate signalling surges past normal levels.
Inhibitory GABAergic control can’t contain the spread.
Neurons in this area begin firing in a synchronous and abnormal rhythm — like a sudden electrical storm.
The seizure remains localized, but alters behaviour and awareness by disrupting temporal lobe function — key in memory and emotional processing.

🧪 Tying Mechanism to Manifestation

Mechanism	Clinical Correlation
Increased excitatory transmission	Sudden neuronal firing → seizure onset
Failed inhibition	No brakes → uncontrolled spread
Focal neural hyperexcitability	Automatisms, impaired awareness
Temporal lobe involvement	Staring, confusion, lip-smacking

📦 Want to learn more?

Reflections on Medical Education