These ion channel mutations tend to confer a depolarized resting state to neurons resulting in pathological hyper-excitability. This long-lasting depolarization in individual neurons is due to an influx of Ca2+ from outside of the cell and leads to extended opening of Na+ channels and repetitive action potentials. The following hyperpolarization is facilitated by γ-aminobutyric acid (GABA) receptors or potassium (K+) channels, depending on the type of cell. Equally important in epileptic neuronal hyper-excitability, is the reduction in the activity of inhibitory GABAergic neurons, an effect known as disinhibition. Disinhibition may result from inhibitory neuron loss, dysregulation of axonal sprouting from the inhibitory neurons in regions of neuronal damage, or abnormal GABAergic signaling within the inhibitory neuron. Neuronal hyper-excitability results in a specific area from which seizures may develop, known as a "seizure focus". Following an injury to the brain, another mechanism of epilepsy may be the up regulation of excitatory circuits or down regulation of inhibitory circuits. These secondary epilepsies occur through processes known as epileptogenesis. Failure of the blood–brain barrier may also be a causal mechanism. While blood-brain barrier disruption alone does appear to cause epileptogenesis, it has been correlated to increased seizure activity. Furthermore, it has been implicated in chronic epileptic conditions through experiments inducing barrier permeability with chemical compounds. Disruption may lead to fluid leaking out of the blood vessels into the area between cells and driving epileptic seizures.
Erythema marginatum is a type of erythema (redness of the skin or mucous membranes) involving pink rings on the torso and inner surfaces of the limbs which come and go for as long as several months. It is found primarily on extensor surfaces.An association with bradykinin has been proposed in the case of hereditary angioedema. Presentation
The rings are barely raised and are non-itchy. The face is generally spared. Associated conditions
It occurs in less than 5% of patients with rheumatic fever, but is considered a major Jones criterion when it does occur. The four other major criteria include carditis, polyarthritis, Sydenhams chorea, and subcutaneous nodules. In this case, it is often associated with Group A streptococcal infection, otherwise known as Streptococcus pyogenes infection, which can be detected with an ASO titer.It is an early feature of rheumatic fever and not pathognomonic of it. It may be associated with mild myocarditis (inflammation of heart muscle). It is also seen in conditions like allergic drug reactions, sepsis and glomerulonephritis.It often occurs as a harbinger of attacks in hereditary angioedema. In this case it may occur several hours or up to a day before an attack. Diagnosis
Types
Some sources distinguish between the following:
"Erythema marginatum rheumaticum"
"Erythema marginatum perstans"

Treatment
Erythema marginatum can be treated with hydrocortisone and adrenocorticotropc hormone (ACTH). References


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