Although cases of epilepsy in which cause remains unknown can often be managed effectively, determining a cause can sometimes point to a particular course of treatment. To determine the cause, or causes, of a child's epilepsy, physicians rely, in part, on information from parents and other family members. Some of the content in this section may help with those conversations.
Cause Identification May Lead to Improved Care
Epilepsy is a neurological disorder in which events called seizures disrupt normal brain function. These sudden surges of abnormal electrical activity can have a wide range of effects. Depending upon which brain regions are involved, seizures may influence behavior, sensory perception, motor function, or all of the above. In fact, physicians can often determine the location and extent of abnormal brain activity based solely upon the seizure type and its observed clinical effects.
Accurate diagnosis of seizure type often provides clues about the underlying cause of an individual's seizures. This information may be helpful in determining the risk of seizures recurring and worsening over time, and may also reveal an appropriate course of treatment.
One of the most difficult aspects of epilepsy diagnosis is that seizures are symptoms that can result from many different causes. Abnormal brain development and/or brain injuries, infection, inflammation, or specific gene mutations can all lead to seizures. Collectively, all cases of epilepsy that have a known cause are called symptomatic.
However, cause is not always easy to identify and remains unknown in 65 to 70 percent of epilepsy cases. These cases are called idiopathic.
Physicians use the term idiopathic to describe medical conditions for which there is no known cause. Despite marked advances in epilepsy research and clinical care in recent decades, idiopathic cases of epilepsy still make up the largest percentage (65 to 70 percent) of epilepsy diagnoses. This does not mean that such cases have no underlying cause, but rather that a cause cannot be determined. Often this is because a diagnostic test sensitive or specific enough to determine the cause does not yet exist.
Although determining the cause of seizures can serve an important role in diagnosis, prognosis, and treatment, it is not essential to finding effective treatments. In fact, idiopathic epilepsies can be successfully treated, and it is common for children with this diagnosis to grow out of their seizures entirely.
Even so, determining the cause of an individual's seizures can be helpful in identifying an appropriate course of treatment. As described in the Diagnosis section, neurologists rely on eyewitness accounts of the seizures and electroencephalogram (EEG) analysis to determine seizure type, and neuroimaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) to identify structural abnormalities in the brain. Also, physicians increasingly rely on genetic tests to determine the role that gene mutations might play in an individual's seizures.How epilepsy is diagnosed
Of the many known causes of epilepsy all fit into two broad categories: inherited and acquired.
Current research is revealing that many types of epilepsy have a genetic component. It has been recognized for some time that epilepsy tends to run in families, and it is now thought that up to 20 percent of childhood cases are inherited. Studies have found that the risk of epilepsy in siblings and children of individuals with the disorder ranges from 4 to 8 percent, compared to 1 to 2 percent in the general population. This increased risk does not imply that genes alone predetermine epilepsy but suggests that genes play an important role in some cases.
To date, researchers have linked more than 70 genes to disorders that can lead to epilepsy. Although the exact role many of these genes play is unknown, scientists believe that the alteration of any one of them increases an individual's risk of developing epilepsy. Some researchers estimate that more than 500 genes may ultimately be linked to epilepsy.
Scientists have identified some epilepsy types that are caused by the mutation of a single gene. These relatively rare epilepsy syndromes are caused by mutations that result in abnormal protein function, leading to seizures. A few examples include:
- benign familial neonatal convulsions—a type of epilepsy that usually begins prior to the third day of life and typically goes into remission after two or three weeks
- generalized epilepsy with febrile seizures plus (GEFS+)—an epilepsy type that arises in childhood, with seizures occurring during episodes of fever, and then progresses to generalized seizures
- autosomal dominant nocturnal frontal lobe epilepsy—a seizure type that is caused by a mutation in one of three genes and produces shaking movements mostly during sleep
In addition to these epilepsy syndromes, a number of other genetic disorders with wide-ranging manifestations can also give rise to epilepsy. Some of these disorders are:
- tuberous sclerosis complex—a disorder that can affect most major organs, including the brain, and causes seizures in approximately 80 percent of patients
- Sturge-Weber syndrome—a disorder characterized by a port wine birthmark on one side of the face, glaucoma, and seizures
- Aicardi syndrome—a rare disorder characterized by eye abnormalities, infantile spasms, and the partial or complete absence of the corpus callosum, the structure that links the two hemispheres of the brain
- Angelman syndrome—a disorder characterized by seizures, ataxia, language problems, and cognitive impairment
Although some of the disorders described above are uncommon, the identification of gene or chromosome abnormalities associated with many of them has enabled physicians to use relatively simple genetic tests and diagnostic criteria to diagnose patients and family members suspected of having a given disorder. Having identified some of the genes associated with these epilepsy syndromes, scientists can apply this knowledge in their search for similar genes involved in other types of epilepsy.
The search for genetic causes of epilepsy has not been straightforward. Even in cases where genes have been linked to specific types of epilepsy, they may only be part of the explanation. Researchers believe that the most common types of epilepsy are almost certainly caused or influenced by more than one gene, as well as by a number of environmental factors. Researchers hope that identifying the genetic causes of epilepsy may one day lead to better treatments and potentially a cure for some types of the disorder.
In addition to the role gene mutations play in causing epilepsy, it is also thought that genes may influence the effectiveness of treatment options for some people. A recent study demonstrated that many people with epilepsy have an abnormally active version of a gene that increases their resistance to drugs. This may explain why some individuals develop intractable or refractory epilepsy.
Some of the most common non-idiopathic causes of seizures in children are acquired, as opposed to being present at birth or developing as the result of genetic abnormalities. Acquired causes include, for example, lack of oxygen (hypoxia), head injuries, and infections of the central nervous system. Brain tumors and degenerative disorders are not as common in children as they are in older adults, but in rare cases they can also cause childhood epilepsy. Whatever the cause, it is important, especially with regard to treatment and follow-up, to distinguish between factors and conditions that cause isolated seizures and those that cause the recurrent seizures characteristic of epilepsy.
Lack of Oxygen (Hypoxia)
An insufficient supply of oxygen to the brain can cause seizures. Brain cells are extremely sensitive to oxygen deprivation and begin to function abnormally or die just minutes after oxygen supply has been cut off. Drowning, choking, suffocation, cardiac arrest, head trauma, and complications during birth can all lead to hypoxia and seizures. Treatment depends on the underlying cause of the hypoxia but typically involves basic life-support procedures, including ventilation, medications to support blood pressure and heart rate, and medications to suppress seizures.
Seizures resulting from head injuries are uncommon among infants and children. Because the skull offers a great deal of protection, these incidents seldom result in brain injury and subsequent epilepsy. Studies suggest that head injuries resulting in hematomas, wherein blood collects in a mass on the surface of the brain, are more likely to result in seizures and epilepsy.
Infections of the Central Nervous System
Brain infections can cause seizures during acute stages of the infection. In some cases, infections cause injury to the brain significant enough to cause recurrent seizures. The most common central nervous system infections are encephalitis and meningitis. Encephalitis is a brain inflammation often caused by a viral infection. Meningitis is an inflammation or infection of membranes covering the brain or spinal cord.
Both cancerous and benign brain tumors and other lesions can cause seizures. Researchers are unsure exactly why such growths cause seizures. It may be that they are made up of abnormal cells that affect the neuronal network and cause abnormal neuronal firing.
Seizure Threshold, Neurons, and Cell Membranes
A seizure can potentially occur in any individual. However, the conditions that lead to seizures vary from one individual to another. For example, a fever of 104 degrees Fahrenheit that leads to seizures in one child may not have that effect on another child. This is because of variability from one person to another in what doctors call seizure threshold, defined as the minimal conditions required to produce a seizure.
Key elements in understanding seizure threshold, and therefore finding good treatments, are the neurons themselves—in particular, the membranes of these neurons. Research has shown that neuronal cell membranes play a critical role in epilepsy, as they regulate the flow of electrical impulses between neurons. For this reason, researchers are investigating details of the membrane structure, focusing on how molecules cross these membranes and how the cell nourishes and repairs this semi-permeable boundary. A disruption in either of these processes may lead to epilepsy.
Normal brain activity relies on communication between networks of neurons and other types of cells in the body. This communication takes place via electrochemical signals. In essence, chemical messages passed from one neuron to another either turn on or turn off electrical activity in the target neuron. More specifically, these chemicals, including neurotransmitters and ions, either stimulate or inhibit the target neuron to fire its own electrochemical signals. Thus, neurons do their work by exciting or inhibiting the activity of other neurons.
Normal brain function generally requires a balance between excitation and inhibition. A balance of these influences enables the brain to send coordinated messages along networks of neurons that control behavior, learning, primary senses, motor function, and other vital functions.
One of the most studied epilepsy-related neurotransmitters is an inhibitory neurotransmitter called GABA, or gamma-aminobutyric acid. Research has led to drugs that alter the amount of GABA in the brain or change how the brain responds to it. Researchers also are studying excitatory neurotransmitters, such as glutamate.
Some environmental and metabolic conditions can trigger seizures by effectively lowering seizure threshold. These conditions include fever, stress, sleep deprivation, and others. The lower an individual's seizure threshold, the fewer the stimuli required to cause neurons in the brain to misfire.
Scientists think that many of the genes linked to epilepsy are involved in mechanisms that regulate the flow of electrical charges into and out of nerve cells, thereby affecting their electrical excitability and overall seizure threshold. A likely place for a gene mutation to affect neuron function in such a way as to cause epilepsy is at the level of the neurotransmitters, chemicals that act as messengers between nerve cells, as well as the ion channels that maintain the neuron's firing threshold.
An understanding of these regulatory mechanisms in the brain and how they malfunction in people with epilepsy has led to the development of medications that can help restore electrochemical balance and greatly reduce or eliminate seizures.About treatments for epilepsy
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