According to the World Health Organization, approximately 50 million people worldwide have epilepsy, making it one of the most common neurological diseases.
Epilepsy is a chronic disorder of the brain characterized by recurring seizures, which are brief episodes of involuntary movement of the body sometimes accompanied by loss of consciousness. The disorder spans all age groups, and to onlookers it can instill fear, misunderstanding and discrimination.
November is National Epilepsy Awareness Month. VCU News spoke with Victor Gonzalez-Montoya, M.D., co-medical director of the Epilepsy Monitoring Unit at VCU Medical Center to better understand the disorder. Gonzalez-Montoya is also an assistant professor in the Department of Neurology in the Virginia Commonwealth University School of Medicine.
What causes epilepsy and how can it be treated?
Epilepsy is a disorder in the brain in which there are spontaneous episodes of uncontrolled and excessive electrical activity that often disrupt its function. It can be pretty dangerous.
There are multiple causes, like lesions in the brain due to an injury, tumors, strokes, infections, genetic conditions and others. Sometimes we can find the direct cause for epilepsy, and other times it’s difficult.
But the way we diagnose and treat seizures has changed dramatically, thanks to research. The majority of time, we treat epilepsy with medication. If someone resists medication, they may seek treatment at a Level 4 Epilepsy Center, which is the highest level. VCU Medical Center is a Level 4 Epilepsy Center, and therefore we typically provide diagnostic and treatment techniques that are not widely available; techniques that help us localize the problem in the brain and see if a surgical procedure or brain stimulation is an option.
Surgery in the brain can scare people, but that too has come a long way. If surgery is an option, there are different types, depending on the patient: epilepsy resective surgery, minimally invasive laser surgery, responsive neurostimulation and deep-brain stimulation. Every patient’s brain is like a different universe, so we model the treatments to the patient.
How does epilepsy affect one’s daily life?
The disease is horrible. There are many variables that determine how a seizure affects the brain, and that determines how it appears in someone’s life. It could be anything from a twitch in one hand to someone losing complete consciousness, falling and having a convulsion that leads to injury.
If you have epilepsy, you don’t know when any of these things will happen. So as a patient, you live under the assumption that at any given time you cannot function normally. There are plenty of activities a patient with epilepsy cannot do. For example, someone with epilepsy cannot drive. So if they don’t have a good public transportation system nearby, they rely on someone to take them anywhere they need—like going to the market to get milk.
In many cases, epilepsy by itself is associated with depression, and all of these social limitations worsen the depression because they cannot take part in activities that the rest of us can. It’s a perpetuation. Epilepsy has a 360-degree effect on someone’s life.
What don’t people understand about epilepsy?
We don’t realize it, but as a society, we demand a high level of functionality. We indirectly punish those with epilepsy, when in reality they need a lot of support—from their coworkers, family, friends and the community.
Family impacts vary by culture. Some families are very hard on someone with epilepsy, which can lead to worsening of depression. Sometimes they’re not allowed out of their houses. They may not be able to go on dates like their friends. There have been reports of people losing friends because of the social effects of their disorder.
At work, people sometimes won’t tell their employers they have epilepsy. The law protects them, but since they don’t have the same functionality as someone without epilepsy, they fear their employers may find another reason to fire them.
At school, epilepsy requires the teachers to be educated on the disorder. Really, patients become the teachers of their condition because they need to share with people the correct actions to take if there is a seizure.
Why do you think National Epilepsy Awareness Month is important?
It is extremely important. This is a month that you have the chance to reach out to the community and say: Listen, wake up. If you know someone with epilepsy, there are things you can do to change or improve how you interact with them. Let’s have a conversation about it.
It’s a good start in not only alleviating the stigma, but also sharing what to do and what not to do if you see someone having a seizure. At the end of the day, it is about improving the lives of those suffering from the disorder in every way we can.
Researchers from the University of California, Irvine School of Medicine, have found that a rare gene mutation alters brain development in mice, impairing memory and disrupting the communication between nerve cells. They also show memory problems could be improved by transplanting a specific type of nerve cell into the brain. The findings were published today in Neuron.
“Mutations in hundreds of genes have been linked to neurodevelopmental disorders, many of which have devastating behavioral consequences that cannot be managed with available treatment options,” explained Robert Hunt, Ph.D., assistant professor of Anatomy & Neurobiology, who led the study with Young Kim, Ph.D., a postdoctoral fellow. “Now, a major challenge in the field is to identify the underlying cause for each of these rare genetic disorders so that new, disease-specific therapies can be developed.”
The UCI team focused on the gene CHD2, which scientists believe modifies the structure of chromatin—the coiled complex of DNA and proteins—and controls expression of hundreds of other genes. Normally, humans have two copies of the CHD2 gene. However, in some cases, one copy is lost, which can lead to developmental disorders such as intellectual disability, epilepsy or autism.
To mimic the human disorder and better understand how CHD2 is involved in brain development, Hunt and his colleagues created mice that possess only one functioning copy of the CHD2 gene. Remarkably, the mice had severe memory problems and an increase in electrical oscillations in the brain, features similar to the condition in people.
A closer look at the animals’ brains revealed an abnormal development of brain circuitry, including changes in the way neurons communicate with each other, and fewer inhibitory interneurons, which control the activity of brain circuits. The mouse neurons also showed differences in the expression of more than 100 other genes associated with neurodevelopmental disorders. In the embryo, many of the altered genes are involved in critical biological processes like neurogenesis, but in adult animals, genes associated with neuronal activity and synapse function were changed. That insight indicated CHD2 may play different roles in early brain development and adulthood.
The findings prompted Hunt’s team to transplant embryonic progenitor cells capable of generating inhibitory internerneurons into the brains of the mutant mice. They targeted the hippocampus, a brain region critical for learning and memory, for cell transplantation.
“Inhibitory neurons regulate oscillatory rhythms that are required for memory functions,” Hunt said. “We’ve been developing a similar interneuron cell therapy for epilepsy, so we naturally thought of trying this approach in mice with CHD2 mutation.”
In the UCI study, the transplanted inhibitory cells migrated throughout the hippocampus and generated new interneurons, in effect replacing the brain cells that were missing in the mutant mice. In addition to having more inhibitory nerve cells, the treated mice showed a dramatic improvement in hippocampal-dependent memory.
“At least in principle, it should be possible to develop targeted therapies for genetic disorders like CHD2 mutation,” Hunt said. “That would be great, because in many cases, the medications that are currently available offer no therapeutic value at all.”
While the new research offers an important step toward understanding the role of CHD2 in brain development and function, further studies are necessary before interneuron progenitors can be used for cell therapy in the clinic. The Hunt lab next aims to evaluate brain wiring in the mouse model more closely and to explore how CHD2 mutations affect different neuronal pathways.
A large international research team has discovered a new genetic cause for a severe, difficult-to-treat childhood epilepsy syndrome. Spontaneous mutations in one gene disrupt the flow of calcium in brain cells, resulting in epileptic overactivity. The team’s research in patients also found clues to potential medical treatments for the rare condition.
“Even though variants in this gene were only just discovered to cause disease, we already have a good understanding of how changes in the gene’s associated protein affect brain function—causing neural overactivity in epilepsy,” said first author Katherine L. Helbig, MS, CGC, a research genetic counselor in the Neurogenetics Program in the Division of Neurology at Children’s Hospital of Philadelphia (CHOP). “Furthermore, although much follow-up research remains to be done, we found that there is a possibility that specific anti-seizure medications could reduce this overactivity in some patients.”
The senior authors of this large international study, published online today in the American Journal of Human Genetics, were Heather C. Mefford, MD, Ph.D., of the University of Washington, and Holger Lerche, MD, of the University of Tuebingen, Germany. The full research team included nearly 100 scientists, from Europe, Canada, China, Australia, New Zealand and the United States.
Katherine L. Helbig, MS, LCGC, is a genetic counselor in the Division of Neurology at Children's Hospital of Philadelphia. Credit: Children's Hospital of Philadelphia
The research team focused on disease-causing changes in the CACNAIE gene, long suspected to play a key role in how neurons regulate their electrical activity, but not previously known to cause human disease. This study was the first to link the gene to human epilepsy. By doing next-generation sequencing in 30 infants and young children with severe epilepsy, the team pinpointed disease-causing variants in CACNA1E. In most cases, the gene variants were de novo—present in the affected children, but not found in their parents. De novo variants are being increasingly found in severe childhood epilepsies.
“The fact that we were able to identify 30 patients at this stage of research indicates that we could be looking at a more common cause of genetic epilepsy than we would have initially assumed,” said Helbig. She added, “This research enables us to give some families an answer as to why their child has severe epilepsy. It also offers the potential that we can build on this knowledge to find new strategies for treatment.”
In addition to having difficult-to-treat epilepsy, most of the affected children had severe developmental delays, low muscle tone, contractures starting at birth and movement disorder. “Many of the children were initially thought to have a severe muscular condition because of their contractures,” said Helbig. “We were surprised to find that a genetic epilepsy had such severe symptoms.” Helbig is a specialist genetic counselor in CHOP Neurology, which has deep experience in investigating and treating genetic epilepsies.
The de novo mutations disrupt a calcium channel in brain cells, causing the channel to activate too easily or to inactivate too slowly, and giving rise to epilepsy. In some cases, the study team found the increase in calcium current was too high to measure.
Most of the 30 patients did not respond to any anti-epileptic medications, except for a few who responded to the medication topiramate, known to target the CACNA1E channel. Further systematic work, said Helbig, will investigate this finding and other aspects of their research, with the aim of translating their knowledge into targeted precision therapies for children with severe genetic epilepsy.
Epilepsy is the most common neurological disorder affecting children, and may be characterized by sudden, recurrent episodes of uncontrolled motor activity and, in some cases, impaired consciousness (seizures). Any condition that triggers disruptive electrical discharges in the brain can produce epilepsy. Although the underlying abnormality may not be correctable, seizures themselves can usually be controlled through drug therapy. There are a number of relatively benign genetic epilepsies of childhood, some but not all of which may be outgrown.
Common Causes of Epilepsy
Seizures may develop as a result of a head injury, brain infection, brain tumor, drug or alcohol withdrawal or intoxication, stroke, birth trauma or metabolic imbalance. In most cases, the underlying cause of a child’s epilepsy is never discovered.
Types of Epileptic Seizure
Epileptic seizures fall into two broad categories: generalized and partial. Generalized seizures, which involve the whole brain, fall into several subtypes. The least dramatic of these are absence seizures (also known as petit mal seizures), which consist of brief episodes of altered awareness during which the child may appear to be daydreaming. During an absence seizure, all motor activity stops, and the child stares blankly or blinks rhythmically and does not respond when touched or called by name. Absence seizures may last five to ten seconds and recur many times a day.
The Two Main Types of Seizure
At the other extreme are generalized tonic-clonic seizures (also known as grand mal seizures) during which the child abruptly ceases activity, falls and loses consciousness. During the initial phase of the seizure, lasting only a few seconds, the muscles stiffen. In the subsequent phase, the muscles undergo rhythmic, alternating contractions and partial relaxations, causing uncontrollable jerking motions (tonic-clonic seizures). Breathing may become irregular. After the seizure, which usually ends in less than five minutes, muscles relax, and the child may be confused and sleepy.
Partial seizures are categorized as simple or complex. A simple partial seizure may involve abnormal twitching, tingling and sensory hallucinations. Consciousness is preserved and the child can often recount details of the seizures, which generally last several minutes. Complex partial seizures have a variety of manifestations, including staring, complex involuntary movements and hallucinations. They may involve a loss of consciousness.
Tonic-clonic seizures are impossible to miss. Some of the more subtle types of seizures, however, may occur several times before parents or teachers recognize them. If the child occasionally seems unaware of his surroundings or experiences involuntary muscle contractions in one area of the body, he may have a seizure disorder.
It is important to note that the seizures some children have in association with fever do not constitute epilepsy. In addition, febrile seizures in early childhood are not usually associated with the later development of epilepsy.
Diagnosis of Epilepsy
After an initial seizure, the pediatrician (or pediatric neurologist) may order several tests, the most important of which is an electroencephalogram (EEG), a painless test that record the brain’s electrical activity. It is often necessary to perform several EEG’s in different circumstances (while the child is sleeping and while the child is looking at flashing lights, for example) to identify the type of seizure disorder present.
Treatment of Epilepsy
In the majority of cases, children’s seizures can be satisfactorily controlled or reduced in frequency with drug therapy. The success of the therapy depends chiefly on the severity of the seizure disorder, as well as on the child’s compliance in taking his medication, and on careful monitoring of blood levels by the physician.
One or more of about six different agents, called antiepileptic drugs, are generally prescribed for the treatment of epilepsy in children. Each of the drugs is useful in specific types of seizure disorders, and each has different dosage requirements and side effects that the physician takes into consideration before deciding which one to prescribe. In many cases, finding the proper medication and correct dosage level takes some time. Recent developments in specific types of brain surgery for intractable seizures offer new hope for very severe cases of epilepsy.
Looking After a Child with Epilepsy
A child who has a seizure disorder should be treated the same way you would treat any other child. Certain precautions should be taken while the threat of seizures exists.
Make sure the child is well supervised in the bathtub, and at the beach or swimming pools.
Teach the child to recognize the signs of an impending seizure and seek help.
Have the child wear a MedicAlert bracelet that identifies his condition.
Most important, be sure the child continues to take medication at the prescribed doses, even after seizures are under control. The doctor may recommend tapering off the medication after the child has been free of seizures for two or three years, but close medical supervision is needed for this process.
Epilepsy is a disorder in the central nervous system characterized by recurrent seizures. An unexpected rush of electrical activity inside the brain leads to a seizure. Brain activity becomes abnormal and leads to periods of unusual behaviour with loss of awareness at times.
Seizures do not always include unusual muscle movements or convulsions. Untreated seizures can seriously affect the lives of children having them. Epilepsy affects both men and women regardless of their ethnic background and age.
Signs of Epilepsy:
A staring spell
Loss of consciousness
Jerking movements of arms and legs.
Panic or anxiety
Kinds of Seizures:
Seizures are normally classified as focal or generalized depending on the commencement of abnormal brain activity.
Focal (partial) seizures result from abnormal activity in a particular area of the person’s brain. Simple partial seizures may change emotions or the way things smell, appear, feel, sound or taste. It is characterized by tingling and dizziness.
Complex partial seizures or focal seizures with impaired awareness entail a modification of or loss of awareness and consciousness. Repetitive movements are performed during such seizures such as hand rubbing, walking in circles or swallowing.
Thorough testing is needed to differentiate epilepsy from other neurological disorders such as narcolepsy, migraine or mental illness.
Generalized seizures normally affect all areas of the brain and consist of:
Tonic seizures lead to muscle stiffness and normally affects muscles in the person’s back, legs and arms.
Atonic seizures or drop seizures lead to a loss of muscle control which makes a person abruptly collapse or fall down.
Myoclonic seizures are visible as short jerks or twitches of a person’s arms and legs.
Clonic seizures are characterized by repetitive or rhythmic jerking muscle movements.
Tonic-clonic seizures cause sudden loss of consciousness, quivering and body stiffening.
Absence seizures might take place in clusters and lead to momentary loss of awareness.
Symptoms of Epilepsy:
The main symptoms of epilepsy are seizures and it differs from one person to another.
Symptoms of Focal (partial) seizures include:
Change or modification in the sense of smell, taste, hearing, sight or touch.
Twitching and tingling of limbs.
Symptoms of Complex partial seizures include:
Performing repetitive movements
Loss of awareness or consciousness
Genetics may provide a person with a natural seizure threshold as a person who is susceptible to seizure triggers is said to have inherited a low seizure threshold. A higher threshold conversely makes a person less liable to have seizures.
Epilepsy is a comparatively common neurological disorder that affects innumerable people worldwide and treatments range from medication to surgery.