Neurotransmitter 2.0 Technically Speaking May 2014

seizure headerSeizures.

A big subject that involves a great deal of information on what they are, how they are diagnosed and treated.  What is epilepsy?  What is a seizure emergency?  How do I know my patient/pet is having a seizure? In part I of the Seizure Series, we will take a bite out of the hair-raising basic facts about seizures by discussing the Who, What, Where, When, Why and How of seizures.

What is Epilepsy? What is a Seizure?

What is epilepsy?  Epilepsy is a disorder of the brain that is characterized by recurring, unpredictable seizures.  So what is a seizure? According to the International League Against Epilepsy, the definition of a seizure is the “transient occurrence of signs and symptoms due to abnormal excessive or synchronous neuronal activity in the brain.” In other words, the clinical signs (i.e. loss of consciousness, paddling, salivating) are symptoms of an underlying problem causing excessive electrical activity in the brain.

When Does a Seizure Happen?

In all patients, there are excitatory and inhibitory neurotransmitters that act as “traffic regulators” in the brain.  Both excitatory and inhibitory neurotransmission is essential for normal brain function.  As the brain develops, the balance between excitation and inhibition becomes finely tuned.  Excitatory neurotransmitters, primarily glutamate in the brain, will “speed up traffic,” but too much can lead to excitotoxicity and destroy neurons.  Inhibitory neurotransmitters, primarily Gamma-aminobutyric Acid (GABA) in the brain, will slow traffic and calm the brain down.

The seizure occurs when there is a shift toward excessive excitation in the brain. This shift then leads to the depolarization of neurons. The brain will establish local inhibitory zones surrounding the area of excited neurons and try to stop the spread of the epileptogenic (seizure producing) activity. If this inhibitory zone fails, more neurons will be recruited and excitation spreads. When the excitation spreads, the seizure occurs.

How do Seizures Present?

There are four parts to the seizure. First, is the prodrome. This part of the seizure is the least consistent and can occur within hours of the seizure. The patient may exhibit altered behavior such as hiding or clinginess. This part of the seizure is the least consistent, because sometimes there are no noticeable changes in the patient hours before a seizure. The second part of the seizure is the aura. The aura occurs seconds to minutes prior to onset of seizure. This can include motor or behavioral changes and it signifies the onset of ictus, which is the seizure itself.

Ictus is usually self-limiting lasting seconds to a couple of minutes.  The seizure can present in a large variety of ways.  It can be generalized, meaning it involves the patient’s entire body, or focal, meaning the seizure is limited to a particular part of the body or head.  Some seizures can even start off as a focal seizure, then progress to generalized seizure.      A common presentation is a generalized tonic-clonic seizure (GTCS). These patients are often non-responsive, have an increased muscle tone (tonic), and jerking movements (clonic), and exhibit autonomic signs (hypersalivation, urination, defecation, dilated pupils). Generalized seizures can also be tonic, clonic, atonic (loss of muscle tone), myoclonic or absence (altered or loss of consciousness only). Focal seizures can be simple (no loss of consciousness) or complex (loss or altered consciousness). They are further characterized by motor or autonomic disturbance or automatisms/paroxysms of behavior. With a variety of presentations, seizure diagnosis can be difficult and requires careful observation and examination of the patient, and collection of history from the owner.

The post-ictal period occurs after the seizure is over.  It can last seconds, minutes or hours after the patient’s seizure is over.  Patients can exhibit behavior changes, confusion, blindness, lethargy, thirst, hunger and have the need to urinate or defecate.  These symptoms can be mild or severe (extreme aggression towards owners or temporary paralysis).  Duration and severity of the post-ictal period has not been shown to be correlated with underlying disease causing the seizure.

Lastly, seizures can be isolated or present in clusters. An isolated seizure will be a single event within a 24 hour period, that resolves on its own and the patient returns to normal. Cluster seizures are those seizures where there are more than two seizures within a 24 hour period, they resolve on their own and the patient is normal between seizures. This is a more emergent situation, and may require medical intervention.  Status epilepticus is a seizure that persists for more than five minutes or when a patient that has two or more seizures in which the patient does not return to normal. This type of seizure activity is an emergency and will require immediate medical intervention.

Why do Seizures Occur?

The underlying causes for seizures are too numerous to list in this paper. Most commonly in neurology, causes for almost any disease can be found in the DAMNITV scheme. Please see chart for a list of common diseases under that scheme. Most common causes for seizures are primary genetic (a diagnosis of exclusion), inflammatory disease, or neoplastic. Once an underlying cause for the seizure has been found, or not found, a patient’s epilepsy can be classified:

-Primary/Genetic Epilepsy: Ultimate underlying cause(s) unknown, but is considered to be a disease unto itself.  This type of epilepsy is a diagnosis of exclusion.

-Unknown/Idiopathic Epilepsy: Cause of the seizure is unknown.  Is often grouped with primary/genetic epilepsy, but often patients with this epilepsy are thought to have an underlying cause.

– Symptomatic/ Structural Epilepsy: Patients that have seizures that occur secondary to an identifiable intracranial lesion or disease process.

-Reactive Epilepsy: Seizures that occur secondary to an extracranial cause.  Given the fact that epilepsy is by definition, a disorder of the brain, this type of seizure activity is not truly epilepsy, but is often referred to as such.

chart

Where do Seizures Come From?

Seizures occur in the cerebrum  or thalamus of the brain.  They can originate from a delineated part of the brain, called a seizure focus, or can occur from both hemispheres of the brain  at the same time.

Who Is Affected?

Seizures can occur in any patient, however statistically, they are more common in dogs than cats.  Dog breeds that have a higher incidence of seizure disorder include the Boxer, Cocker Spaniel, Saint Bernard and Siberian Husky. Furthermore, there are dog breeds that have a proven, or highly suspected genetic cause causing “idiopathic epilepsy” and they include the Beagle, Border Collie, Dachshund, Golden Retriever and Labrador Retriever.