The cause of idiopathic epilepsy (IE) has been debated for centuries starting when people first became aware of the disorder.
Modern molecular techniques are beginning to clarify the role of genetics in epilepsy as in many other diseases (O'Brien 2003).
Neurons are excitable cells with the driving force being the electrical potentials. Sodium is constantly pumped out of the
cell in an energy dependant process. This causes a -60 mVolt charge inside the cell (hyperpolarization). The balance of excitatory
and inhibitory signals a neuron receives controls whether an axon potential is generated. The major excitatory neurotransmitters
in the brain are acetylcholine and glutamate. These neurotransmitters receptors are linked to ion channels that are selectively
permeable to positively charged sodium or calcium. When these channels open, cations flow into the cell causing depolarization
of the cell. An accumulation of small depolarizations (excitatory post synaptic potentials) can cause the cell to reach threshold
and thereby produce an action potential. Gamma amino butyric acid (GABA) is the major inhibitory neurotransmitter. GABA receptors
are linked to an ion channel that is selectively permeable to chloride ions. Additionally, potassium currents are important
in repolarizing the cell after an action potential and controlling the excitability of the cell.
In its simplest form, epilepsy refers to repeated seizures over time. Studies of the role of genetics in epilepsy are confounded
by the occurrence of acquired disease, which can look identical clinically (phenocopy). The response of a normal brain to
some outside influence, such as an electrolyte disturbance or hypoglycemia is referred to as reactive epilepsy. Seizures caused
by a structural lesion of the brain, such as a brain tumor or vascular accident, are referred to as symptomatic epilepsy.
In this case, the seizure originates at a focal site of damage but sometimes spread causing a secondary generalized seizure.
Depending upon what area of the brain is affected, a focal onset might not be apparent. Appropriate imaging or tests identify
reactive or symptomatic seizures. Idiopathic epilepsy can be defined as repeated epileptic seizures where no underlying cause
is identified, and in dogs, it is likely to have an inherited basis in most instances.
By strict standards, an abnormal EEG is necessary to make a diagnosis of epilepsy. Obtaining a meaningful EEG in animals can
be difficult. Movement often obscures recordings in awake animals, whereas sedative drugs can suppress epileptic discharges.
In veterinary medicine we are, thus, dependant upon observation of the clinical signs to make a diagnosis of epilepsy. This
is not a big issue when classic seizures are observed but can be important when atypical episodes are reported. Videotapes
of the episodes sometimes can clarify what is actually occurring.
Epilepsy is a common condition affecting approximately 1 percent of the human population (McNamara 1998). While many epilepsies
have an identifiable cause (secondary epilepsy), about 40 percent of all human epilepsies are idiopathic and presumed to have
a hereditary basis (Steinlein 1998). Many of the idiopathic epilepsy syndromes in humans appear to have a complex mode of
inheritance that has yet to be elucidated. Recent advances in gene mapping have resulted in the identification of the causative
gene mutations in 13 uncommon human IE's (Scheffer 2003). In these isolated human populations, a strong founder effect and
minimal mixing of populations allowed the mutation to be widely spread in a local area. One interesting aspect of these families
is that in some cases the seizures have a focal onset. Since seizures secondary to localized damage typically have a focal
onset, it has long been assumed in people and dogs that focal epilepsies were acquired.
Ion channel mutations compromise most of these idiopathic epilepsy genes (Mulley 2003). This is not surprising given the important
role of ion channels in controlling neuronal excitability. Ion channel mutations have been found in other neurologic diseases
such as hereditary ataxias and hyperkalemic periodic paralysis, and the term "channelopathies" is sometimes used to describe
mutations in ion channels, which lead to disease (Terwindt 1998). Channels that have been found that cause idiopathic epilepsy
in people include voltage gated potassium channels, voltage-gated sodium channels, voltage gated calcium channels, GABA receptors,
and Acetylcholine receptors.