What is Idiopathic (Genetic) Generalized Epilepsy?
When someone has a seizure, this means the nerve cells in their brain, also known as neurons, are firing off too many signals at once. This causes temporary changes in behavior, movement, or consciousness. Epilepsy is a brain disorder where a person has a long-term tendency to have seizures, and it can impact a person’s learning, emotional state, and social life. To be diagnosed with epilepsy, a person needs to have at least one seizure.
Epilepsy could be considered in these situations:
* If a person has had two seizures that were not triggered by a specific cause and happened more than 24 hours apart.
* If a person had one seizure without a specific trigger and there is a high risk for more seizures in the future (like if they had abnormal results from a brain scan).
* If the seizures fit a certain pattern that is considered an epilepsy syndrome.
In recent years, the way epilepsy and seizures are classified has changed. These classifications help doctors understand where the seizure starts in the brain and how it behaves which is important for treatment and research.
There are two types of seizures: focal seizures and generalized onset seizures. Focal seizures start in a specific area of the brain and could affect one part of the body or spread, affecting wider areas. They can be split into two categories: motor onset (related to movement) and non-motor onset (not related to movement). Each category has different subtypes:
Motor onset seizures can cause actions like: accidental movement, loss of muscle strength, muscle spasms or jerking, repetitive movements, or sustained stiffening of the body.
Non-motor onset seizures can cause autonomic responses (changes in body functions that you can’t control) like changes in heart rate or body temperature, behavior, cognition, emotion, or sensory perceptions (like hallucinations).
Generalized onset seizures start in a widespread area of the brain affecting both sides of the body and can cause various motor (movement-related) and non-motor signs and symptoms, depending on the type.
We need to remember that seizures can take different forms and have overlapping features, and they may appear differently depending on the observer’s perspective. That’s why we come up with a framework or system for how to classify seizures. According to the latest guidelines from the International League Against Epilepsy, we first identify where the seizure begins (a particular area, in many areas, or unknown), then what type of seizure (focal, generalized, both, or unknown). We then determine if the seizure is a part of an epilepsy syndrome (which are specific types of epilepsy with their particular characteristics).
Over the years, these classification systems and terms have evolved and adapted. For example, “partial” seizures are now called “focal” seizures, a person’s awareness during a seizure now helps to classify focal seizures, and we’ve stopped using terms like “simple partial” or “complex partial” seizures.
Seizures can be a part of generalized epilepsies, where seizures seem to be initiated in all parts of the brain at the same time. We could think of them as a group of syndromes, including juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), childhood absence epilepsy (CAE), and generalized tonic-clonic seizures, where the seizures seem to start in all areas of the brain at once.
What Causes Idiopathic (Genetic) Generalized Epilepsy?
The latest way of classifying epilepsy takes into account the cause of the condition as it’s critical for diagnosing, advising on the outlook, and treating the disease. It also aids in estimating the odds of experiencing more seizures and in distinguishing between epilepsy and seizures caused by something other than a brain disorder. It’s important to remember that some patients might have more than one contributing cause, and this should be considered along with the classification.
The cause of epilepsy is categorized into six subgroups:
1. Structural: problems with the physical form or arrangement of something.
2. Genetic: caused by one or more abnormalities in the genome.
3. Infectious: caused by a disease spread through direct or indirect contact.
4. Metabolic: owing to the chemical reactions in the body that keep the body alive.
5. Immune: related to the immune system.
6. Unknown: cause is not known or identifiable.
People with idiopathic (genetic) generalized epilepsy typically show no signs of structural brain damage when scanned with an MRI. There are also no symptoms or signs between seizures, ruling out most of the cause categories.
Studies on twins have suggested a genetic component to epilepsy, as identical twins show a higher likelihood of sharing an epilepsy diagnosis than non-identical twins. Research into certain type of epilepsies has pointed to certain chromosomes. However, most epilepsy cases are not linked to known genetic changes.
Another factor connected to idiopathic generalized epilepsies is the quality and pattern of sleep. Studies have shown that a lack of sleep and underlying abnormal sleep patterns are strong triggers for seizures. However, effective epilepsy treatments can improve sleep patterns and also decrease the likelihood of seizures.
Risk Factors and Frequency for Idiopathic (Genetic) Generalized Epilepsy
Epilepsy is a condition that affects a staggering 65 million people across the globe, but unfortunately, many of these individuals lack access to necessary medical care. Research from the CDC suggests that even in western countries, we’re likely underestimating the amount of people affected by epilepsy. In fact, one review of global studies found that for every 1,000 individuals, about 6.38 are currently living with epilepsy, and 7.6 have had it at some point in their lives. Interestingly, the condition doesn’t favor one particular gender or age group.
The most common types of seizures and epilepsy seen are generalized seizures, which are seizures affecting both sides of the brain, and epilepsy of unknown cause. In the U.S., there are about 7.7 new cases of generalized epilepsies per 100,000 people each year. One condition, known as JME or Juvenile Myoclonic Epilepsy, is the most common type of genetic generalized epilepsy. This form of epilepsy accounts for about 3% to 11% of epilepsy cases among adolescents and adults.
Signs and Symptoms of Idiopathic (Genetic) Generalized Epilepsy
Idiopathic Generalized Epilepsy (IGE) presents without any focal neurological indications during a typical clinical examination. There aren’t usually signs of cognitive setbacks in children with the condition, and they generally perform as well as their peers without seizures. However, in-depth cognitive testing may reveal some deficits, particularly in higher cortical functions. In fact, children with IGE, especially those with absence seizures, can exhibit language impairments. Studies have identified a particular neuropsychological profile among IGE patients that features slow psychomotor speed and compromised executive functions, but normal memory. Activities that can induce seizures in these patients include fatigue, lack of sleep, and alcohol consumption.
Juvenile Myoclonic Epilepsy (JME) is commonly observed in people between the ages of 8 and 26, usually peaking between 12 and 16 years. This form of epilepsy can potentially lead to three types of seizures:
- Myoclonic jerks
- Generalized tonic-clonic seizures
- Typical absence seizures
Myoclonic seizures are rapid and brief jerks affecting various parts of the body, such as arms, legs, face, or the entire body. These are more likely to occur when a person is tired or just after waking up. Around two-thirds of patients experience generalized tonic-clonic seizures while one-third may suffer from typical absence seizures, which happen more likely during mornings. Some patients with JME, approximately 30%, also show photosensitivity. Although patients with IGE usually have normal cognitive function, those with JME typically perform lower in advanced cognitive function tests. To manage JME effectively, supplemental cognitive function tests and functional neuroimaging studies are recommended. With appropriate medication, the prognosis can be good for these patients, with 85% to 90% of them able to live without seizures.
Childhood Absence Epilepsy (CAE) typically occurs in early childhood, peaking between the ages of 4 to 7. Noticeable symptoms include stepping and altered consciousness. Diagnosis usually reveals that patients have less than twenty absence seizures per day. A hyperventilation test can provoke seizures in these patients. Medication such as ethosuximide is commonly the first line of treatment and is effective more than 50% of the time. However, if the patient is diagnosed with another type of seizure, valproate is the preferred medication.
Moving on to Juvenile Absence Epilepsy (JAE), this usually occurs between the ages of 7 and 16, peaking between 10 to 12 years. These patients predominantly experience absence seizures sometimes coupled with generalized tonic-clonic seizures and rarely with myoclonic seizures. Hyperventilation can trigger an absence seizure, but this is less likely than in CAE.
Lastly, Generalized Tonic-Clonic Seizures, formerly known as grand mal seizures, tend to occur shortly after waking and can happen at any time. These seizures, characterized by a tonic phase followed by clonic muscle contractions, quickly affects bilateral cortical, subcortical, and brainstem networks. Factors such as fatigue, lack of sleep, and excessive alcohol consumption can induce these types of seizures.
Testing for Idiopathic (Genetic) Generalized Epilepsy
When it comes to identifying idiopathic generalized epilepsy (IGE), the main method involves looking at a patient’s medical history. However, there are also many diagnostic tools that aid in identifying this condition. For patients who’ve had a seizure, a brain MRI/MRA test with a dye is usually done to check for any unusual brain structures and visualize the brain’s lining and blood vessels.
If there are any indications of an infection, like high white blood cell count, fever, stiffness in the neck, or if a patient’s immune system is compromised, then a lumbar puncture (LP) should be performed. This procedure, also known as a spinal tap, involves taking a small sample of the fluid that surrounds the brain and spinal cord to test for infection. Doctors prefer to do this before starting antibiotic treatment. If meningitis is suspected, treatment should not be delayed due to its serious health risks. The cerebrospinal fluid from the LP will be tested for specific markers of infection, including white and red blood cells, protein levels, and microbiology. Certain tests for conditions like fungal infections or tuberculosis may require additional lab work.
An electroencephalogram (EEG) is an important tool for locating possible areas in the brain that might be causing seizures and understanding the type of epilepsy. EEGs measure and record the electrical activity of your brain. Up to 30% of initial seizures are not classified correctly, so EEGs can help in identifying the type of seizure. The EEG test will show unusual brain activity, known as epileptiform discharges, in about 10% to 50% of patients the first time it’s performed. By doing more EEGs and longer tests, like 24-hour ambulatory EEGs, doctors can get a more complete picture of a patient’s brain activity, including changes associated with the sleep-wake cycle and circadian rhythms.
When it comes to IGE, the EEG typically shows abnormal signal patterns containing spikes and waves, usually seen more in the frontal region of the brain. Hyperventilation and light stimulation can increase the chances of detecting these patterns. For Childhood Absence Epilepsy (CAE) and Juvenile Absence Epilepsy (JAE), the severe seizure activity is characterized by high amplitude ictal spike-wave discharges that last longer than 4 seconds. Recent studies on CAE have shown interictal findings related to focal polyspike discharges. Juvenile Myoclonic Epilepsy (JME) on the other hand, shows generalized spike-wave discharges at a frequency of 3 to 6 Hz. EEGs on patients with JME demonstrate photosensitivity about 30% of the time. The presence of a series of spike wave patterns is a strong indication of drug-resistant IGE.
Treatment Options for Idiopathic (Genetic) Generalized Epilepsy
The treatment for IGE, or idiopathic generalized epilepsy, primarily involves the use of anti-seizure medications and educating patients about the factors that may trigger their seizures. The goal is to strive for good control of seizures with as little medication as possible, ideally just one type of medication. Currently, there are many medications approved by the FDA to treat epilepsy, but 9 are most commonly used for IGE.
One widely used medication is Valproate, often the chosen treatment for IGE. It is particularly effective in controlling generalized seizures, which involve the entire brain. It has been found to help around 75% of patients stay seizure-free. Side effects of Valproate include weight gain, hair loss, tremors, stomach issues, and potential harm to an unborn baby if taken by pregnant women. It can also affect the liver and interact negatively with other medications.
Another medication, Ethosuximide, is typically used for absence seizures, which appear as brief lapses in awareness. However, it doesn’t prevent other types of seizures such as generalized tonic-clonic or myoclonic seizures, so it’s largely used in patients with childhood absence epilepsy (CAE). Side effects include weight loss, fatigue, headache, stomach upset and it can cause behavioral changes.
Lamotrigine is also a first-choice medication as it can control absence seizures and generalized tonic-clonic seizures, although it has varying effectiveness with myoclonic seizures. Side effects include headache, upset stomach, dizziness, loss of coordination, and tremor.
There are other medications used when the condition is resistant to these treatments, including Levetiracetam, Clonazepam, and a new treatment called Brivaracetam.
Cenobamate, a recently approved medication, has shown promise in reducing the frequency of seizures in patients with generalized epilepsy.
Perampanel, a different class of drug, works by reducing the activity of glutamate, which is the principal cause of spreading seizures in the brain. Currently, it’s used to treat tonic-clonic seizures and is generally well-tolerated, with side effects including fatigue, dizziness, and behavioral changes.
Another important part of IGE treatment is neuromodulation interventions – these alter nerve activity by delivering electrical or pharmaceutical agents directly to a target area. One widely used device for this purpose is a Vagus Nerve Stimulator (VNS), a device implanted under the skin that sends electrical signals to the brain to prevent seizures. It has been effective and well-tolerated in children with hard-to-treat epilepsy.
Occasionally, dietary changes like a ketogenic diet (a high-fat, low-carb, adequate protein diet) may be used to manage seizure control, particularly when the seizure is resistant to medication. The diet, which must be followed strictly, is thought to limit fluctuations in blood sugar levels, providing another way to manage seizures.
What else can Idiopathic (Genetic) Generalized Epilepsy be?
If you’re being assessed for genetic generalized epilepsy, doctors will consider the potential for other conditions that might cause similar symptoms. Here are a few examples:
- Focal epilepsy with impaired awareness: This is usually associated with longer seizures, between 30 seconds to 2 minutes, and often comes with an aura.
- Syncope: A condition where the brain doesn’t receive enough blood due to low blood pressure or irregular heartbeat. This can cause seizures but isn’t related to epilepsy. This is particularly common if someone is secured in an upright position (e.g., wearing a seatbelt) during a fainting episode. An ECG (a test that measures the electrical activity of the heart) is often necessary to confirm this.
- Non-epileptic seizures: These episodes look like epileptic seizures, although there is no equivalent abnormal brain activity. They might be motor (voluntary movement), sensory (sensations), cognitive (thought related), or autonomic (involuntary body functions) events. These seizures often happen alongside a history of abuse or trauma and are sometimes considered a conversion disorder. Interestingly, about 20%-30% of epileptic patients have these non-epileptic seizures and can be on strong anti-epileptic drugs causing side effects.
- De Novo Absence Status Epilepticus of Late-onset: This occurs in elderly individuals and resembles late-onset general epilepsy. If an elderly person suddenly becomes confused, it’s critical to do a thorough investigation to check for seizures and nonconvulsive status epilepticus. A sudden stop in taking benzodiazepines or starting a new antibiotic are common causes of this type of epilepsy.
- Jeavons Syndrome: This is a type of epilepsy that may account for up to 13% of all generalized epilepsies but is frequently not reported or recognized. It is often diagnosed late and generally presents as generalized epilepsy with symptoms such as eyelid twitching, seizures caused by closing the eyes, abnormal brain activity, and sensitivity to light. Most people with this condition develop epilepsy that is difficult to treat and seizures often continue throughout their lives.
What to expect with Idiopathic (Genetic) Generalized Epilepsy
The outlook for Childhood Absence Epilepsy (CAE) is generally quite positive, with the majority of children (80% to 90%) seeing their symptoms disappear by the time they’re 12 years old. Recent research has found that symptoms can disappear completely after 27 years of treatment, leading to the belief that getting over Idiopathic Generalized Epilepsy (IGE) mainly depends on time. Adults who develop IGE later in life also tend to have positive outcomes, as they often go into remission sooner compared to those who develop it at a younger age.
The common “absence seizures” seen in CAE usually respond well to one or two types of Antiepileptic Drugs (AEDs). However, if other types of seizures occur, the prognosis may not be as favorable. Whether these cases actually represent other forms of IGE, like Juvenile Absence Epilepsy (JAE) or Juvenile Myoclonic Epilepsy (JME), is still an area of ongoing debate. With the right treatment, more than 80% of people with CAE and JAE go into remission.
Normally, if someone with CAE goes a long period without any seizures, their doctor might try to reduce or gradually stop the AEDs to lessen any potential side effects. The right time to do this is still open to debate and must be done carefully and under close monitoring to ensure it’s achieved safely.
Possible Complications When Diagnosed with Idiopathic (Genetic) Generalized Epilepsy
Seizures and epilepsy present significant health risks. Over a year, people who experience recurring seizures face a 40% to 60% chance of physical injuries such as burns, fractures, and concussions. Therefore, controlling seizures is crucial.
A severe form of seizure, known as status epilepticus (SE), lasts longer than five minutes or involves multiple seizures within a 5-minute interval without full recovery between them. This condition can occur in all types of epilepsy, manifesting either as convulsive also known as ‘shaking’ or non-convulsive. Surprisingly, in inherited generalized epilepsy or IGE, the convulsive status is rare and usually responds to treatment with medication given directly into a vein (IV) such as benzodiazepines. In contrast, non-convulsive SE, which often starts and ends abruptly, is more common in IGE, often ending with a jerking seizure. It also responds quickly to treatment with IV benzodiazepines or a medication known as valproate. Convulsive SE, if unchecked, can cause death and is a medical emergency. The after-effects of non-convulsive SE are still under research.
A sudden unexplained death in epilepsy, known as SUDEP, is a fatality that cannot be attributed to a specific illness, injury, drowning, or status epilepticus. The cause remains unclear, but research suggests that it is less common in inherited epilepsy and that women generally have a lower risk.
If epilepsy becomes resistant to medication, it might be time to reevaluate the initial diagnosis and consider other treatment options. It’s also essential to acknowledge if the seizure or epilepsy type was inaccurately classified at first or if the seizures are non-epileptic in origin.
Potential complications of seizures and epilepsy:
- Physical injuries such as burns, fractures, concussions
- Status epilepticus (SE), a severe form of seizure
- Non-convulsive status epilepticus
- Sudden unexplained death in epilepsy (SUDEP)
- Drug resistance
- Potential misdiagnosis
Preventing Idiopathic (Genetic) Generalized Epilepsy
Epilepsy is a condition that can affect people for their entire lives, and it can pose a substantial health challenge. It requires careful management with medication. The quality of life for people with epilepsy can be impacted by poor control of seizures, mental health issues, unemployment, and other negative consequences.
Patient education is crucial in managing epilepsy. Patients and their families need to learn about safety precautions and changes they might need to make in their daily life. They should avoid doing dangerous activities unsupervised such as swimming, working at high levels or operating heavy machines. It’s also important to have good habits such as maintaining a consistent sleep schedule and taking epilepsy medication correctly. It is strongly advised against consuming alcohol and using illicit drugs.
Depending on where they live, people with epilepsy might have certain limitations about driving. It is important that both patients and caregivers are familiar with these restrictions in their country or region.
