Seizure and Brain Damage

I'm doing research now to see if multiple seizures can ever cause brain damage and the answer is yes. If the seizures last very long or are close together, it can cause permanent damage or stroke. I definitely think it will be a good idea to have scans of my brain by a seizure specialist because they'll know what to look for. The guy I'm referred to, will, I hope, take me though I don't have money, but I'm also looking into possible support from a certain church to see if they'd donate to this to help me get evidence for getting my son back. See a few articles (i'll add them as I find them, below):

This important conference examined the scientific evidence about whether isolated, brief seizures have a negative effect on brain function. The evidence suggests that these seizures do have a negative effect and possibly result in loss of specific brain cells. However, the evidence also indicates that this is not true for all forms of epilepsy. We also do not yet know the consequences of these effects for thinking, memory, mood, and other aspects of daily life.

As was true before this conference, people with epilepsy are well advised to work with their doctors to achieve the best possible seizure control.

Steven C. Schachter, MD

Harvard Medical School

(Rovaniemi, Finland, June 2001)

Epilepsy researchers from around the world gathered in Rovaniemi, Finland, at the edge of the Arctic Circle, in June 2001 for a workshop aimed at addressing the question: "Do seizures damage the brain?" The workshop was organized by Dr. Tom Sutula, Chairman of Neurology at the University of Wisconsin, and Professor Asla Pitkänen, Director of Epilepsy Research at the A.I. Virtanen institute of Kuopio, Finland. The meeting was supported by the American Epilepsy Society and Elan Pharmaceuticals. Over 35 scientists from eight countries attended. Among them were specialists in both clinical and laboratory epilepsy research, as well as basic neuroscience. Presentations from the meeting were published in book form in 2002. (See details at end of this report.)

This workshop was aimed at discussing the question of whether isolated, brief seizures damage the brain. Although scientists and clinicians have long known that prolonged seizures, a condition referred to as "status epilepticus," kill brain cells, surprisingly little scientific evidence exists to support the notion that individual seizures do damage. This is not to say that individual seizures cause no harm to the brain, but proof of such damage is difficult to obtain for a number of reasons:

* It is often hard to separate the underlying brain injury that produces seizures from the effects of the seizures themselves.
* Most of the animal models used to study epilepsy involve prolonged seizures.
* Patients with epilepsy often are studied only after they have had seizures for many years, and clinicians do not have information, such as MRI scans, of the same individuals before their epilepsy developed.

However, scientific data are slowly accumulating to suggest that recurring seizures may contribute to nerve cell injury in the brain, and this may be associated with declines in cognitive function and quality of life.

Animal models of epilepsy

On the first day, investigators discussed experimental studies using animal models of epilepsy, typically laboratory rodents (rats and mice) in which seizures are induced and subsequent changes in the brain are measured. One way to assess whether seizures cause damage is to see if epileptic animals have fewer nerve cells in specific brain areas. Researchers count the cells using sophisticated computerized statistical analyses, a technique known as unbiased stereology. This technique presents significant technical challenges, however, because the brain (unlike other organs) contains irregularly shaped structures that have many different cell types.

In some experiments, electrical stimulation is used to induce seizures in rats (referred to as "electrical kindling"). These studies have shown that certain populations of brain cells may die after single or repeated brief seizures. Molecular signals inside nerve cells lead to their death. Researchers have identified many of the chemical pathways where this occurs. As a result, it may be possible to develop "neuroprotective" medical treatments specifically to prevent this kind of injury.

These studies have also shown that certain genes may protect the brain or make it more susceptible to injury after seizures. By comparing strains of mice in which many brain cells die after seizures with other strains of mice in which the same nerve cells survive, scientists are now on the trail of a number of these important genes.

Epileptic seizures adversely alter brain function in other ways besides killing cells. Rewiring of brain circuitry and the birth of new brain cells (neurons and glia) both may lead to seizures. The discussion at the end of the first day concentrated on definitions of damage and potential improvements in animal models used to study epileptic brain injury.

Studies in humans

The second day was focused on studies of epilepsy in individuals or populations. Many of the presentations concentrated on the use of brain MRI to measure injury after recurrent seizures. By using new MRI techniques, such as MRI volumetry or magnetic resonance spectroscopy (MRS), researchers can measure changes in the brain over time during the course of epilepsy.

Others discussed the role of prolonged seizures in early life as a risk factor for the later development of epilepsy. An important study being carried out at Duke University Medical Center is identifying infants and young children with prolonged seizures induced by fever (febrile status epilepticus). The researchers are performing a series of MRI scans on each of these children over a number of years, trying to find out whether brain damage is already present and whether those who go on to develop recurrent seizures will have further nerve cell injury.

Some presentations described studies of epileptic human brain tissue removed during surgery to treat focal epilepsy (mainly temporal lobe epilepsy). For many years we have known that in epilepsy certain nerve cells are lost in specific areas of the brain, such as the hippocampus, but these studies are showing that the amount of damage may depend upon the age at which the epilepsy began. The researchers discussed the importance of correlating findings in animal studies with research on human epilepsies.

Exciting new research is aimed at simultaneously measuring changes in the expression (the amount of protein a gene produces) of hundreds of genes after seizures. This new technology, referred to as genetic microarrays, or "gene chips," offers great potential for providing insight into the effects of epilepsy on the brain at the level of individual molecules.

The effects of seizures during early life

The third day of the workshop was devoted to animal models of childhood epilepsy and changes in the brain caused by seizures during early development. Research performed over several decades suggests that seizure-induced brain injury is highly dependent upon developmental age, with the juvenile and adult brain being more susceptible to damage and rewiring after seizures than the brain of the newborn.

Recent animal studies indicate that seizures early in life adversely affect learning and memory performance during adulthood. Experiments using animal models of prolonged febrile seizures in infancy (seizures induced by high fevers) have found that this type of seizure may lead to changes in brain structure and function that persist for many months.

Group discussions focused on the importance of studying the effects of seizures during early life, and determining why epilepsy affects the brain differently at different ages.

Cognitive effects

Presentations during the final day covered neuropsychological research into cognitive changes caused by epilepsy in children and adults. The talks focused on the effects of epilepsy on learning, memory, speech, and other higher brain functions. It was emphasized that researchers need to begin studying patients soon after diagnosis, monitoring their course with carefully chosen neuropsychological tests and brain imaging studies. Ongoing research is aimed at determining whether alterations in cognitive function after recurrent seizures correlate with changes in brain structure or function found on neuroimaging (for example, brain MRI or PET scans). Functional MRI (fMRI) is a new technique that measures changes in blood oxygen to indicate when a specific brain area is being activated (in use). This method is an extremely promising tool that eventually may allow doctors to determine the specific locations of brain functions and seizure development non-invasively, without injecting drugs into brain arteries or putting EEG electrodes directly over the brain, for instance, as we do now.

The discussion was directed at the difficulties of distinguishing the direct effects of seizures on neuropsychological measures from the effects of the underlying brain abnormalities. Attention was also focused on the idea that various types of epilepsy affect cognitive function differently, so further research concentrating on specific forms of epilepsy is needed.

Conclusions and future directions

The workshop provided an important forum for discussion among epilepsy researchers from a variety of disciplines, each with a different approach to understanding how seizures affect the brain. Many research controversies remain, but the meeting did lead to a number of important preliminary conclusions and directions for future study:

* Prolonged seizures are clearly capable of injuring the brain.
* Isolated, brief seizures are likely to cause negative changes in brain function and possibly loss of specific brain cells. This is not true for all forms of epilepsy, however, and is likely to be highly dependent upon the type of seizure and the specific cause of the epilepsy.
* Increased collaboration between clinicians and laboratory researchers is essential.
* Better experimental epilepsy models of relevance to many different, specific forms of human epilepsy are badly needed.
* New and better ways to image brain function in patients with epilepsy would be valuable.
* More long-term studies of the course of epilepsy are required. Such research should begin as soon as the person starts having seizures, and should include repeated neuroimaging and neuropsychological tests to look for evidence of ongoing brain injury due to epileptic seizures.

Details of this meeting have been published as Sutula T and Pitkänen A. Do seizures injure the brain. Progress in Brain Research 135. New York: Elsevier Science; 2002.

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Epilepsy is a brain disorder involving repeated seizures of any type.

Causes Return to top

Seizures ("fits") are episodes of disturbed brain function that cause changes in attention or behavior. They are caused by abnormal excited electrical signals in the brain.

Sometimes seizures are related to a temporary condition, such as exposure to drugs, withdrawal from certain drugs, or abnormal levels of sodium or glucose in the blood. In such cases, repeated seizures may not recur once the underlying problem is corrected.

In other cases, injury to the brain (for example, stroke or head injury) causes brain tissue to be abnormally excitable. In some people, an inherited abnormality affects nerve cells in the brain, which leads to seizures.

Some seizures are idiopathic, which means the cause can not be identified. Such seizures usually begin between ages 5 and 20, but they can occur at any age. People with this condition have no other neurological problems, but often have a family history of seizures or epilepsy.

Disorders affecting the blood vessels, such as stroke and TIA, are the most common cause of seizures after age 60. Degenerative disorders such as senile dementia Alzheimer type can also lead to seizures.

Some of the more common causes of seizures include:

* Developmental problems, genetic conditions present at birth, or injuries near birth (seizures usually begin in infancy or early childhood)
* Metabolic abnormalities may affect people of any age and may be a result of
o Diabetes complications
o Electrolyte imbalances
o Kidney failure, uremia (toxic accumulation of wastes)
o Nutritional deficiencies
o Phenylketonuria (PKU) -- can cause seizures in infants
o Other metabolic diseases, such as inborn error of metabolism
o Use of cocaine, amphetamines, alcohol, or certain other recreational drugs
o Withdrawal from alcohol
o Withdrawal from drugs, particularly barbiturates and benzodiazepines
* Brain injury
o Most common in young adults
o Seizures usually begin within 2 years after the injury
o Early seizures (within 2 weeks of injury) do not necessarily mean that chronic (ongoing) seizures (epilepsy) will develop
* Tumors and brain lesions (such as hematomas)
o May affect any age but are more common after age 30
o Partial (focal) seizures most common to start with
o May lead to generalized tonic-clonic seizures
* Infections
o May affect people of all ages
o May be a reversible cause of seizures
o Brain infections like meningitis and encephalitis can produce seizures
o Brain abscess
o Acute severe infections of any part of the body
o Chronic infections (such as neurosyphilis)
o Complications of AIDS or other immune disorders

Seizure disorders affect about 0.5% of the population. Approximately 1.5-5.0% of the population may have a seizure in their lifetime. Epilepsy can affect people of any age.

Risk factors include a family history of epilepsy, head injury, or other condition that causes damage to the brain.

The following factors may present a risk for worsening of seizures in a person with a previously well-controlled seizure disorder:

* Pregnancy
* Lack of sleep
* Skipping doses of epilepsy medications
* Use of alcohol or other recreational drugs
* Certain prescribed medications
* Illness

Symptoms Return to top

The severity of symptoms can vary greatly, from simple staring spells to loss of consciousness and violent convulsions. For many patients, the event is the same thing over and over, while some people have many different types of seizures that cause different symptoms each time. The type of seizure a person has depends on a variety of many things, such as the part of the brain affected and the underlying cause of the seizure.

An aura consisting of a strange sensation (such as tingling, smell, or emotional changes) occurs in some people prior to each seizure. Seizures may occur repeatedly without explanation.

Note: Disorders that may cause symptoms resembling seizures include transient ischemic attacks (TIAs), rage or panic attacks, and other disorders that cause loss of consciousness.

SYMPTOMS OF GENERALIZED SEIZURES

Generalized seizures affect all or most of the brain. They include petit mal and grand mal seizures.

Petit mal seizures:

* Minimal or no movements (usually, except for "eye blinking") -- may appear like a blank stare
* Brief sudden loss of awareness or conscious activity -- may only last seconds
* Recurs many times
* Occurs most often during childhood
* Decreased learning (child often thought to be day-dreaming)

Tonic-clonic (grand mal) seizures:

* Whole body, violent muscle contractions
* Rigid and stiff
* Affects a major part of the body
* Loss of consciousness
* Breathing stops temporarily, followed by sighing
* Incontinence of urine
* Tongue or cheek biting
* Confusion following the seizure
* Weakness following the seizure (Todd's paralysis)

SYMPTOMS OF PARTIAL SEIZURES (SIMPLE AND COMPLEX)

Partial seizures may be complex or simple. Partial seizures affect only a portion of the brain.

Symptoms of simple partial (focal) seizures may include:

* Muscle contractions of a specific body part
* Abnormal sensations
* Nausea
* Sweating
* Skin flushing
* Dilated pupils

Symptoms of partial complex seizures may include:

* Automatism (automatic performance of complex behaviors without conscious awareness)
* Abnormal sensations
* Nausea
* Sweating
* Skin flushing
* Dilated pupils
* Recalled or inappropriate emotions
* Changes in personality or alertness
* May or may not lose consciousness
* Problems with smell or taste -- if the epilepsy is focused in the temporal lobe of the brain

Exams and Tests Return to top

The diagnosis of epilepsy and seizure disorders requires a history of recurrent seizures of any type. A physical examination (including a detailed neuromuscular examination) may be normal, or it may show abnormal brain function related to specific areas of the brain.

An electroencephalograph (EEG), a reading of the electrical activity in the brain, may confirm the presence of various types of seizures. It may, in some cases, indicate the location of the lesion causing the seizure. EEGs can often be normal in between seizures, so it may be necessary to do prolonged EEG monitoring.

Tests may include various blood tests to rule out other temporary and reversible causes of seizures, including:

* CBC
* Blood chemistry
* Blood glucose
* Liver function tests
* Kidney function tests
* Tests for infectious diseases
* CSF (cerebrospinal fluid) analysis

Tests for the cause and location of the problem may include:

* Head CT or MRI scan
* Lumbar puncture (spinal tap)

Treatment Return to top

For treatment of seizures, please see Seizures - first aid.

If an underlying cause for recurrent seizures (such as infection) has been identified and treated, seizures may stop. Treatment may include surgery to repair a tumors or brain lesions.

Anti-convulsants taken by mouth may reduce the number of future seizures. How well medicine works depends on each individual's response to the drug. The type of medicine used depends on seizure type, and dosage may need to be adjusted from time to time. Some seizure types respond well to one medication and may respond poorly (or even be made worse) by others. Some medications need to be monitored for side effects and blood levels.

Epilepsy that does not respond to the use of several medications is called refractory epilepsy. Certain people with this type of epilepsy may benefit from brain surgery to remove the abnormal brain cells that are causing the seizures. Others may be helped with a vagal nerve stimulator, which is implanted in the chest. This stimulator can help reduce the number of seizures.

Sometimes, children are placed on a special diet to help prevent seizures. The most popular one is the ketogenic diet.

Patients should wear medical alert jewelry so that prompt medical treatment can be obtained if a seizure occurs.

Support Groups Return to top

The stress caused by having seizures (or being a caretaker of someone with seizures) can often be helped by joining a support group. In these groups, members share common experiences and problems. See epilepsy - support group.

Outlook (Prognosis) Return to top

Epilepsy may be a chronic, lifelong condition. In some cases, the need for medications may be reduced or eliminated over time. Certain types of childhood epilepsy resolve or improve with age. A seizure-free period of 4 years may indicate that reduction or elimination of medications is possible.

Death or permanent brain damage from seizures is rare, but can occur if the seizure is prolonged or 2 or more seizures occur close together (status epilepticus). Death or brain damage are most often caused by prolonged lack of breathing and resultant death of brain tissue from lack of oxygen. There are some cases of sudden, unexplained death in patients with epilepsy.

Serious injury can occur if a seizure occurs during driving or when operating dangerous equipment, so these activities may be restricted for people with poorly controlled seizure disorders.

Infrequent seizures may not severely restrict the person's lifestyle. Work, school, and recreation do not necessarily need to be restricted.

Possible Complications Return to top

* Prolonged seizures or numerous seizures without complete recovery between them (status epilepticus)
* Injury from falls, bumps, or self-inflicted bites
* Injury from having a seizure while driving or operating machinery
* Inhaling fluid into the lungs and subsequent aspiration pneumonia
* Permanent brain damage (stroke or other damage)
* Difficulty with learning
* Side effects of medications
* Many anti-epileptic medications cause birth defects -- women wishing to become pregnant should alert their doctor in advance in order to adjust medications

When to Contact a Medical Professional Return to top

Call your local emergency number (911) if this the first time a person has had a seizure or a seizure is occurring in someone without a medical ID bracelet (instructions explaining what to do). In the case of someone who has had seizures before, call the ambulance for any of these emergency situations:

* This is a longer seizure than the person normally has, or an unusual number of seizures for the person
* Repeated seizures over a few minutes
* Repeated seizures where consciousness or normal behavior is not regained between them (status epilepticus)

Call your health care provider if any new symptoms occur, including possible side effects of medications (drowsiness, restlessness, confusion, sedation, or others), nausea/vomiting, rash, loss of hair, tremors or abnormal movements, or problems with coordination.

Prevention Return to top

Generally, there is no known way to prevent epilepsy. However, adequate diet and sleep, and abstinence from drugs and alcohol, may decrease the likelihood of precipitating a seizure in people with epilepsy.

Reduce the risk of head injury by wearing helmets during risky activities; this can help lessen the chance of developing epilepsy.

Update Date: 8/7/2006

Updated by: Daniel Kantor, MD, Director of the Comprehensive MS Center, Neuroscience Institute, University of Florida Health Science Center, Jacksonville, FL. Review provided by VeriMed Healthcare Network.

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Letters to Nature
Nature 301, 520 - 522 (10 February 1983); doi:10.1038/301520a0

Seizure-related brain damage induced by cholinergic agents

John W. Olney, Taisija de Gubareff & Joann Labruyere

Department of Psychiatry, Washington University School of Medicine, 4940 Audubon Avenue, St Louis, Missouri 63110, USA

Distinctive acute brain damage involving limbic and related brain regions develops in adult rats following sustained limbic seizures induced by systemic administration of kainic acid or dipiperidinoethane (DPE) or by intra-amygdaloid injection of kainic acid or folic acid1−4. This seizure-brain damage (S-BD) syndrome is of particular interest because it tends to parallel the type of seizures and brain damage seen in human temporal lobe epilepsy5,6. We have observed that DPE induces the S-BD syndrome by systemic but not intra-mygdaloid injection2, whereas an oxidized DPE derivative which structurally resembles the cholinergic agonist oxotremorine is effective when injected into the amygdala7. Prompted by this finding, we injected known acetylcholine (ACh) agonists and cholinesterase (ChE) inhibitors into the rat amygdala and found that either class of agent reproduces this type of S-BD syndrome. These and related findings8 suggest that ACh mechanisms might have a more important role in human epilepsy and epileptic brain damage than has generally been appreciated.

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