NOTICE: Posting schedule is irregular. I hope to get back to a regular schedule as the day-job allows.

Friday, July 22, 2011

Seizures and Epilepsy[Full link to blog for email clients.][FT:C44]

So, what constitutes or causes a seizure? 

To explain, let me back up and describe normal activity in the brain:  Individual neurons respond to a stimulus by creating an electrical current called an "action potential."  This current is caused by a rapid movement of positively charged sodium ions into the neuron from the fluid surrounding it.  This electrical activity - called a "spike" or "unit discharge" when speaking of assemblies of neurons - is the essential information carrying actviity of a neuron. 

Normally when a neuron generates a spike, neighboring neurons are quiet.  This is because a combination of neural connections and neurotransmitter chemmicals at those connections act to block the spikes generated by the nearest neurons.  This ensures that the neuron is responding to its own inputs, and not that of its neighbors.  It also keeps the representation of information "sparse" to allow a lot of *diifferent* information to be represented.

If the inhibitory connections (using the neurotransmitter GABA - gamma aminobutyric acid) are too weak, the activity of a given neuron can influence or even spread to its neighbors.  If the inhibition is too strong, the activity tends to "bounce" or oscillate between active (not inhibited) and inactive (inhibited) states.  Either instance can cause neurons within a region to begin firing spikes that are synchronized - all firing at the same time.

This is the essence of a seizure.  If the synchronous activity is limited to just a small area, it is termed a "focal seizure" and the patient may experience nothing more than a slight muscle twitch, speech disturbance, visual disturbance, etc.  If the synchronous activity spreads, the patient experiences a "generalized seizure" with convulsions and even loss of consciousness.  The initial synchronous activity can mimic sensory inputs and cause the patient to "see", "hear" or "smell" something unusual.  This "aura" commonly signals to the patient that a seizure is imminent, since it precedes the generalization of seizure activity that leads to convulsions.

If the seizure originates in prefrontal or limbic (hippocampal) regions and does not spread to motor cortex, the patient experiences an altered state of consciousness where they are unaware of and unresponsive to their surroundings - but without convulsions.  This is called an "absence" seizure, and can be rather difficult to treat because the symptoms can be easy to miss.  Absence seizures are more common in children and youth than in adults; they usually last for less than a minute, and are typically not preceeded by an aura.

Following a seizure, neurons act like any other cells of the body that have had an extreme workout - i.e. they are fatigued.  Doctors call the period of a seizure the "ictal phase" and the lethargy, dullness and depression that follows a seizure the "post-ictal phase."  In many patients the siezure itself may be undetected (lasting <2 min), and only the post-ictal phase (lasting tens of minutes) is observed. 

In many ways, brief focal seizures and TIAs can have similar effects - a transient disruption of brain function that passes in minutes.  A key difference is that seizures will tend to always occur in the same part of brain, and the "aura" with seizure onset allows the patient to always predict when an event will occur.  Critical to diagnosing the difference between a vascular event and a seizure is the EEG.   TIAs and strokes are characterized by a reduction in neural activity while seizures demonstrate an increase and a synchronization simuilar to the EEG shown in the previous blog.

What then, constitutes epilepsy?  Is an convulsion or seizure reason to worry about a diagnosis of epilepsy with all of the attendant social issues (fear of seizure in public, loss of driving privileges, etc.)?

No.  As mentioned last blog, convulsions can be caused by fever or head trauma and never recur once the fever is lowered or the trauma is treated.  Focal seizures without loss of consciousness - especially if preceded by an aura - need not occur with sufficient regularity to warrant medication or treatment.  However, recurrent seizure, with altered consciousness, and impairment of thinking, vision, hearing or movement following a seizure *is* epilepsy.  Like so many other brain disorders, it represents a continuum from mild seizure to severe, full-body conculsion that can lead to serious injury. 

Epilepsy is diagnosed primarily by recorded the EEG from multiple sites on the skull during a seizure.  Synchronous firing of neurons in wide areas of the brain signifies an epileptic seizure, and is considered "proof" of diagnosis.  Causes of the disease vary, but the consensus is that the "focus" of a seizure (its point of origin) is a region of brain that is predisposed to fire synchronously.  Neurologists call this an "irritable" focus, and may indicate that the normal recurrent inhibitory connections which prevent synchronous firing are damaged.  As stated before, an irritable focus may result from injury, stroke or disease, and can sometimes be detected on MRI or CT scan.

Treatment of epilpesy and mild seizure disorders is usally via medications that can prevent synchronous firing from developing.  Since the medication targets unusual activity, it typically doesn't alter the patients sense of their own brain activity, but if high dosages are required, the patient can feel dull, listless, lethargic or have "fuzzy thinking."  Neurologists and pharmacologist have attempted to develop drugs to treat seizures via manipulations of GAB neurotransmitter, but have not been as successful as with other systems.  The GABA drugs *do* make good medications for intractable nerve pain, however.  If the seizures cannot be controlled with medication, but the "irritable focus" can be accurately identified, it is possible to perform neurosurgery to remove that brain area and stop the initiation of seizures.

The results of such surgeries have been... interesting... to say the least.

Since this blog is now running quite long - I'll stop here and resume next time with "curious things we learned from epilepsy surgery" which should provide plenty of inspiration for the imaginations authors and readers alike!

Stay tuned for LabRat Adventures this weekend and Monday Funnies next week.

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