Epilepsy overview

# Overview
Epilepsy is a common chronic neurological disorder that is characterized by recurrent unprovoked seizures. These seizures are transient signs and/or symptoms due to abnormal, excessive or synchronous neuronal activity in the brain. About 50 million people worldwide have epilepsy at any one time. Epilepsy is usually controlled, but not cured, with medication, although surgery may be considered in difficult cases. Not all epilepsy syndromes are lifelong  some forms are confined to particular stages of childhood. Epilepsy should not be understood as a single disorder, but rather as a group of syndromes with vastly divergent symptoms but all involving episodic abnormal electrical activity in the brain.

# Historical Perspective
The word epilepsy is derived from the Greek epilepsia, which in turn can be broken in to epi- (upon) and lepsis (to take hold of, or seizure). In the past, epilepsy was associated with religious experiences and even demonic possession. Claudius Galen was the first person who described epilepsy as a brain disease. Boerhaave was the first person who differentiate petit mal epilepsy, grand mal epilepsy and hysteria. Marshall Hall described reflex theory in which paroxysmal nervous discharges are responsible for epilepsy seizures. The very first evidence of epilepsy treatment goes back to 10,000 years ago when making holes in skull bones was done in order to treat epilepsy. In the past three decades anti-epileptic drugs are used widely for symptomatic control of epileptic patients.

# Classification
Epilepsy may be classified according to type of onset into focal, generalized and unknown. Each of these groups can be further divided into motor and non-motor subgroups.

# Pathophysiology
It is understood that epileptic seizure is the result of uncontrolled unusual synchronized, localized or widely distributed neuronal electrical discharges. The underlying event in all types of seizures is the paroxysmal depolarization shift (PDS) which also causes the EEG changes. In a normal circumstance we have a refractory period after every action potential, but in PDS, the absence of refractory period causes a prolonged membrane depolarization. In order to cause a seizure, so many PDSs most happen in the same time. Any alternation in a synaptic characteristics such as amount of neurotransmitters, function of inhibitory neurons, function of excitatory neurons, synaptic structure and ion channels involved in neurotransmitter release and conduction of action potential can prone a person to epilepsy. In focal epilepsy, epileptiform activity starts in a specific area of brain. It can further spread and cause secondary generalized seizure. In generalized epilepsy seizures occur in both cerebral hemispheres simultaneously or spread so fast from one to another that in EEG, we can see bilateral epileptiform activity from the start.

# Causes
Common causes of epilepsy include head trauma, brain tumor, brain hemorrhage, encephalitis, hypoglycemia, hypoxic encephalopathy, stroke, cerebral palsy, electrolyte disturbances, epileptic encephalopathy - Lennox-Gastaut type, febrile seizures, Huntington's disease, intoxication and uremia.

# Differentiating epilepsy from other diseases
Epilepsy must be differentiated from psychogenic nonepileptic attacks (PNEAs), syncope, hypoglycemia, panic attacks, acute dystonic reactions, hemifacial spasm, nonepileptic myoclonus, parasomnias, cataplexy, hypnic jerks, transient ischemic attacks, migraines and transient global amnesia.

# Epidemiology and Demographics
Epilepsy's approximate annual incidence rate is 4070 per 100,000 in industrialized countries and 100190 per 100,000 in resource-poor countries; socioeconomically deprived people are at higher risk. The prevalence of active epilepsy is roughly in the range 510 per 1000 people. Many studies have demonstrated that mortality rate is higher in people with epilepsy. The most common causes of death in these patients are trauma, pneumonia, suicide, status epilepticus and sudden unexpected death. Epilepsy is one of the most common of the serious neurological disorders. Genetic, congenital, and developmental conditions are mostly associated with it among younger patients; tumors are more likely over age 40; head trauma and central nervous system infections may occur at any age. There is no evidence of race differences in incidence and prevalence of epilepsy. It was demonstrated that nonsymptomatic epilepsy such as cryptogenic localization-related and idiopathic generalized epilepsy are more common in women while symptomatic localization-related epilepsy is more common in men.

# Risk Factors
Common triggers of seizure include sleep deprivation, fever, light flashing, hyperventilation, alcohol, physical stress such as physical exercise or illness, psychological stress, depression.

# Screening
There is insufficient evidence to recommend routine screening for epilepsy.

# Natural History, Complications and Prognosis
If left untreated, 23% to 71% of patients with a single unprovoked seizure may experience it again within 2 years. After the second unprovoked seizure, the chance of having another seizure increase to 73%. Recurrent seizures with no underlying illness emphasis on epilepsy diagnosis. Common complications of epilepsy include status epilepticus, sudden unexpected death, submersion Injury, dental injury, burns, fractures, head injury, soft tissue injury and motor vehicle accidents.

# Diagnosis

## Diagnostic Study of Choice
There is no single diagnostic study of choice for the diagnosis of epilepsy, but epilepsy can be diagnosed based on history, symptoms and physical examination of a patient with seizure complain. Among the patients who present with clinical signs of seizure, the EEG is the most efficient test for diagnosis. Video-EEG monitoring is a combination of recording EEG and clinical behavior of the patient. Although it's more expensive, it is more effective in differentiating different type if seizures. With the first seizure, we should perform laboratory study ( electrolytes, glucose, calcium, magnesium, complete blood count, renal function tests, liver function tests, urinalysis, toxicology screens), imaging study ( MRI, CT Scan), EEG, video-EEG monitoring and lumbar puncture.

## History and Symptoms
A positive history of family member with epilepsy, brain traumatic injuries, meningitis and encephalitis, febrile seizure in the childhood, enuresis, drug abuse and previous episod of seizure is suggestive of epilepsy. The most common symptoms of epileptic seizure include paroxysmal manner, similarity to each other in a patient in the aspect of duration and general characteristics, presenting with a motor phenomena which can be accompanied with sensory and autonomic manifestation, impaied consciousness, aura (sensory, autonomic, or psychic symptoms), starting with a triggers, post-ictal drowsiness, tongue biting and urine and fecal incontinence.

## Physical Examination
Common physical examination findings of epileptic seizure include Automatic behaviors, upward eye rolling, unconsciousness, drooling, cyanosis, post-ictal drowsiness, fever, tachycardia, hypertension, mydriasis, nystagmus, urine and fecal incontinence, disorientation to persons, place, and time, altered mental status, automatic behaviors (repetitive muscle movement), Muscle rigidity and hyper-reflexia.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of epilepsy include elevated creatine phosphokinase (CPK), elevated cortisol, elevated white blood cell count, elevated lactate dehydrogenase and elevated neuron-specific enolase.

## Electroencephalogram
An ECG may be helpful in the diagnosis of epilepsy. Findings on an EEG suggestive of epilepsy include synchronous generalized spikes and waves in all leads in tonic-clonic seizures, spike and wave activity at a frequency of approximately 3 HZ in absence seizures, localized epileptic activity over the seizure focus in focal seizures with intact consciousness and temporal slow waves or spikes in focal seizures with impaired consciousness.

## X-Ray
There are no x-ray findings associated with epilepsy.

## Echocardiography/Ultrasound
In one case report, a 65-year-old woman presented with seizure. Echocardiography was performed and revealed a left atrium tumor.

## CT Scan
CT Scan is mostly used in patients who are contraindicated for MRI or in the cases with skull fracture suspicious.

## MRI
MRI may be helpful in the diagnosis of epilepsy. Findings on MRI suggestive epileptic seizure include mesial temporal sclerosis, sequelae of head injury, congenital anomalies, brain tumors, cysticercosis, vascular lesions, strokes, cerebral degeneration and neoplasms.

## Other Imaging Findings
There are no other imaging findings associated with epilepsy.

## Other Diagnostic Studies
Lumbar puncture may be helpful in differentiating epilepsy from infectious etiology of seizures.

# Treatment

## Medical Therapy
Supportive therapy for Guillain-Barre syndrome include respiratory assistance, Heart rate and blood pressure monitoring, prevention of thromboembolic complications by heparin, minimal sedation in intensive care units, pain control and early passive movements. Immunomodulating therapy for Guillain-Barre syndrome include plasma exchange, high dose immunoglobulin and Corticosteroids.

## Surgery
Surgery is not the first-line treatment option for patients with epilepsy. Surgery is usually reserved for patients who their seizure continues to happen despite using maximum dosage of anti-seizure drugs.

## Primary Prevention
Effective measures for the primary prevention of epilepsy include reducing the chance of possible epilepsy causes to happen (Head trauma, Hypoglycemia, Cerebral palsy, Electrolyte disturbances, fever, drug abuse and Vitamin deficiency) and reduce the seizure triggers (sleep deprivation, fever, light flashing, hyperventilation, alcohol, physical stress such as physical exercise or illness, psychological stress and depression).

## Secondary Prevention
Effective measures for the secondary prevention of epilepsy include early diagnosis and effective treatment.