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Epilepsy

Description

An in-depth report on the types, causes, diagnosis, and treatment of epilepsy.

Causes

The cause of a seizure is determined in about 28% of partial epilepsy patients. In the rest, however, epilepsy is deemed idiopathic , which means that the cause is unknown. The age of seizure onset can sometimes offer a clue. Idiopathic epilepsy is rare in children and young adults.

General Biologic Mechanisms Involved with Seizures

Epileptic seizures are triggered by abnormalities in the brain that cause a group of nerve cells in the cerebral cortex to become activated simultaneously, emitting sudden and excessive bursts of electrical energy. A seizure's effect depends on the location in the brain where this electrical hyperactivity occurs. Effects range from brief moments of confusion to minor spasms to loss of consciousness.

Ion Channels. Sodium, potassium, and calcium act as ions in the brain. They produce electric charges that must fire regularly in order for a steady current to pass from one nerve cell in the brain to another. If the ion channels that carry them are genetically damaged, a chemical imbalance occurs. This can cause nerve signals to misfire, leading to seizures. Abnormalities in the ion channels are believed to be responsible for absence and many other generalized seizures.

Neurotransmitters. Abnormalities may occur in neurotransmitters , the chemicals that act as messengers between nerve cells. Three neurotransmitters are of particular interest:

• Gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. GABA deficiencies are of particular interest to researchers in epilepsy. Researchers have recently discovered epilepsy-related genetic factors that regulate the GABA signaling system. The discovery is emphasizing the GABA's importance in the disease process.
• Serotonin's role in epilepsy is also being studied. Serotonin is a brain chemical that is important for well-being and associated behaviors (eating, relaxation, sleep). Imbalances in serotonin are also associated with depression. A 2005 study indicated that depression may be risk factor for epilepsy and that the two conditions may share common chemical pathways in the brain.
• Acetylcholine is a neurotransmitter that is important for learning and memory.

Hippocampal Sclerosis. Hardened tissue (sclerosis) in the brain's hippocampus is the most commonly identified abnormality in patients with partial epilepsy. Such abnormal brain tissue leads to structural reorganization, and both the loss and regeneration of nerve cells.

Genetic Factors

Dozens of genetic syndromes representing a variety of seizure patterns may account for the different forms epilepsy. The following epilepsy syndromes are known to be caused by single genetic defects:

• Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). ADNFLE appears to be caused by an alteration in the brain receptor neuronal nicotinic acetylcholine.
• Benign familial neonatal convulsions (BFNC). BFNC appears to be caused by genetic defects that affect ion channels in nerve cells that carry potassium.
• Contactin-associated protein-like 2 (CASPR2) . CASPR2 is associated with a childhood epilepsy and autism disorder found in closely related relatives in Amish communities.

A genetic cause has been identified for at least some cases of juvenile myoclonic epilepsy, which represents 10% of all epilepsy cases. (Such research and other studies have pointed to the GABA signaling system as an important player in many cases of epilepsy.)

Causes of Childhood Seizures

Febrile Seizures. Febrile seizures are caused by high fever. They usually occur in children ages 3 months - 5 years. Between 10 - 15% of children with epilepsy have a history of febrile seizures before they develop epilepsy. However, febrile seizures are quite common and occur in about 3% of all children under 5 years old. Nearly all are brief and have no long-lasting effect.

Vaccinations. In young children, high fever from a vaccination can, in rare instances, trigger seizures. These seizures are almost always temporary and have no serious consequences. Some controversy arose a few years ago over the possibility that the DTP (diphtheria-tetanus-pertussis) vaccine might trigger epilepsy or other neurologic diseases. Some experts suggest that children who have neurologic events following their DTP shot already have a preexisting impairment such as epilepsy, which is revealed, but not caused by, the vaccine. Children with existing epilepsy may be at risk for seizures 2 or 3 days after the vaccination. Infants with suspected neurologic problems may have their vaccinations delayed until their neurologic situation is clarified, but not beyond their first birthday.

Head Injuries in Infants and Children. Infants are at high risk for head trauma. In fact, one study suggested that any infant who had a scalp fracture with a hematoma may be at risk for brain injury. A hematoma is a swelling caused by a broken blood vessel, which creates a large purplish hue like a bruise. Hematoma is quite common after childbirth, but typically causes no problems.

Childhood Viral Infections. A small 2001 study of children with status epilepticus (sustained periods of convulsions) indicated the presence of several pediatric viruses. Human herpesvirus 6 was particularly associated with severe seizures. Herpesvirus 6 is common in children and causes roseola infantum, an acute, but usually benign, illness that can lead to high fever and skin rash.

Hydrocephalus and Shunts. Hydrocephalus occurs when cerebrospinal fluid (CSF) accumulates in the brain, leading to excessive swelling of the brain ventricles. The resulting pressure can damage the brain's tissue. Hydrocephalus itself is not commonly known to cause seizures, but its treatment, which involves insertion of a shunt, may. The shunt is a device that drains the excess fluid from the brain. A 2001 study noted that up to half of children who receive shunts may experience epileptic seizures, particularly if the shunt is placed before 2 years of age. More research on its relationship to epileptic seizures is needed.

Focal Cortical Dysplasia. This is an abnormality in fetal development in which the normal migration of nerve cells is altered. It can cause very severe epilepsy that is difficult to treat.

Other Causes of Seizures in Children. Seizures in infants and children may be due to birth defects, difficulties during delivery, or poisoning.

Causes of Adult-Onset Seizures

Alcohol Abuse. Alcohol abuse is one of the most common causes of adolescent- and adult-onset seizures. Seizures, nearly always generalized tonic-clonic, occur in about 10% of adults during withdrawal. Multiple seizures happen in about 60% of these patients. The first seizure occurs 7 hours to 2 days after the last drink, and the time between the first and last seizure is usually 6 hours or less. [For more information, see In-Depth Report #56: Alcoholism.]

Head Injuries in Adults. Head injuries to adults can cause seizures, with the risk highest in severe head trauma. A first seizure related to the injury can occur years later. People with mild head injuries, which involve loss of consciousness for less than 30 minutes, have only a slight risk that lasts up to 5 years after the injury.

Sleep Disorders. Some sleep disorders, such as obstructive sleep apnea or narcolepsy, have been associated with seizures, although a causal relationship is unclear. Sleep apnea and hereditary nocturnal frontal lobe epilepsy have very similar symptoms (feeling of choking, abnormal motor activity during sleep, and excessive sleepiness during the day). A 2000 study reported that a third of patients with epilepsy who did not respond to medications were later diagnosed with obstructive sleep apnea. Other studies have found that when sleep apnea is treated in patients with both epilepsy and the sleep disorder, seizure activity decreases. More research is needed.

Stroke. Seizure is a symptom of a major stroke. In some cases, injury to the brain from small strokes may cause seizures. Studies report that between 15 - 23% of stroke patients consequently have seizures. A 2005 study found that 3% of patients who have had a stroke go on to develop epilepsy. Patients who had a severe stroke were 5 times more likely to develop epilepsy than patients who had a mild stroke.

Other Causes in Adults. Other known or possible causes of epilepsy in teenage or adult years include:

• Drug abuse or withdrawal from drugs.
• Sudden withdrawal from certain antianxiety or antidepressant drugs.
• Occupational exposure to environmental triggers. High exposure to certain chemicals has been linked with seizures. A 2000 study of utility company employees revealed an association between high exposure to electromagnetic fields (EMF) and an increased risk of epilepsy and neurologic diseases that affected motor control.
• Alzheimer's or other degenerative brain diseases in the elderly.
• Nervous system infection by tapeworm larvae is an important cause of epilepsy in developing nations.

Causes of Seizures That Can Occur at Any Age

Infections of the Brain and Central Nervous System (CNS). Acute infections of the brain and the CNS can cause seizures. Some cases are complicated by brain damage that can lead to recurrent seizures afterward. The most common central nervous system infections are encephalitis and meningitis. Researchers have also found an association between epileptic seizures and CNS-occurring herpes simplex virus infections. More research is needed before any causative role can be proved.

Hypoglycemia. Seizures can be caused by low blood sugar (hypoglycemia), a complication of diabetes in both children and adults.

Brain Tumors. Both cancerous and noncancerous brain tumors can cause seizures in all patients.

Cavernous Angiomas. Cavernous angiomas are blood vessels that grow abnormally and, like a tumor, can put pressure on nerve tissue.

Pseudoepilepsy. Between 20 - 45% of cases of untreatable seizures have a psychologic rather than physical origin. In this form of epilepsy, known as pseudoepilepsy or psychogenic epilepsy, the patient has no conscious intent of forcing a seizure and does not show unusual emotional behavior or signs of hysteria. It is very difficult to treat and can be very disabling. Pseudoepilepsy can usually be distinguished from true epilepsy using an electroencephalogram (EEG), which measures brain waves. The cause of pseudoepilepsy is unknown.

• Review Date: 11/15/2006
• Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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