What is Electrical Status Epilepticus in Sleep?
Electrical Status Epilepticus in Sleep (ESES) is a type of epilepsy that starts in childhood. It is marked by seizures, a decrease in mental abilities, and significant increase in abnormal brain activity that shows on a brain wave test (EEG) during deep sleep. This abnormal brain activity often appears as nearly non-stop spike-wave patterns on the EEG.[1]
While ESES majorly refers to these striking EEG patterns, the International League Against Epilepsy (ILAE), has given it a more descriptive name, Continuous Spikes and Waves during Slow Sleep (CSWS) in 1989. This term better covers the full range of signs and symptoms that you may see.[2][3]
What Causes Electrical Status Epilepticus in Sleep?
Epileptic Encephalopathy with Spike-Wave during Sleep (ESES), a sleeping disorder related to epilepsy, can arise from various causes. This includes both cases where there are structural changes within the brain and cases where there are none. One key event that is associated with ESES is early developmental damage to a part of the brain called the thalamus. This could happen due to issues like stroke, periventricular leukomalacia (damage to the brain’s white matter), and cortical malformation (abnormal brain development). In a study, it was found that 14% of people with epilepsy and sleep-related changes in their brain’s electrical activity (EEG) had early development-related damage to their thalamus.
Recent research has also linked several genetic causes to ESES. This could involve single gene mutations or changes in the number of copies of certain genes. More specifically, mutations in the GRIN2A gene, which possibly affects the signaling of NMDA receptors (proteins that help in the transmission of signals in the brain), have been commonly linked with ESES. Alterations in the number of copies of certain areas within genes, like Xp22.12 deletion and 16p13 deletion, have also been associated with the disorder.
The exact reason behind the abnormal EEG patterns during sleep in ESES is not yet fully understood. Some researchers believe it might have to do with the abnormal over-activity of the brain’s thalamic circuit, which involves a play between inhibitory (reducing activity) and excitatory (increasing activity) cells in the thalamus. The shift in this balance, potentially caused by changes in the type of GABA (an inhibitory neurotransmitter) receptors involved, may increase epileptiform discharges (unusual electrical activity in the brain seen in epilepsy). These discharges can disrupt normal brain processing, which can, in turn, affect a person’s learning and memory.
Risk Factors and Frequency for Electrical Status Epilepticus in Sleep
ESES, or Electrical Status Epilepticus of Sleep, is a rare condition. In a study of children with epilepsy over 20 years in Israel, only 0.2% were found to have ESES. Another study examined nearly 1500 EEG records over five years and found 102 patients with ESES. It’s important to note that children with generalized spike-wave discharges from ESES often have severe developmental issues compared to those with focal epileptiform discharges. Also, children with a spike-wave index of over 50% are more likely to have more widespread developmental disruption.
Signs and Symptoms of Electrical Status Epilepticus in Sleep
Typically, children between 2 and 12 years of age, most frequently between 3 and 5 years, may start experiencing occasional seizures, and their cognitive and physical development may stall or go backwards. Usually, between 2 and 3 years after these initial symptoms, they may further deteriorate and experience more common generalized seizures, like sudden loss of muscle control (atonic) or abnormal gaps in consciousness (atypical absence seizures). While most children affected by this have normal development before the disease begins, others may already have developmental delays or cognitive impairments from the start, depending on what’s causing their symptoms. In rare cases, some children may show signs of intellectual and cognitive decline before showing any obvious signs of seizures. Behavioral changes, such as being hyperactive, are also frequently seen along with this condition.
Testing for Electrical Status Epilepticus in Sleep
ESES, or Electrical Status Epilepticus during Sleep, is diagnosed by looking at the brain’s electrical activities during a certain type of sleep called NREM (Non-Rapid Eye Movement) sleep. The brain waves during this sleep stage are slower, between 1.5 to 3 Hz, and continuous or almost continuous. These waves can be seen all over the brain or on both sides, and they display a specific pattern of abnormal spikes and waves.
When the person is awake or in a different sleep stage called REM (Rapid Eye Movement) sleep, these patterns change. They become intermittent (not continuous) and can be seen in specific parts of the brain. If the brain waves are not adequately examined during NREM sleep, the diagnosis may be missed entirely.
Some people may display unusual spikes and waves in the frontotemporal or centrotemporal parts of their brains, even when they’re awake. However, these abnormal patterns significantly increase during sleep, disrupting their typical sleep patterns.
There is some debate over the minimum amount of abnormal spike-wave activity needed during NREM sleep to formally diagnose ESES. Different studies suggest a range from 25% to 85%, but most commonly, either an 85% or 50% spike-wave index (the measure of these abnormal brain waves) is accepted for diagnosis.
Treatment Options for Electrical Status Epilepticus in Sleep
Due to a lack of specific studies, current options for treating this particular illness are primarily based on past studies and expert advice. The aim of treatment is to improve control of seizures, behavior and cognitive abilities, and this should be established at the time of diagnosis. The most commonly used treatments are primarily anti-seizure medications, including benzodiazepines, corticosteroids, epilepsy surgery, and other non-drug therapies like IVIG and ketogenic diet.
The most common anti-seizure medications used include valproate, ethosuximide, and levetiracetam. It’s been observed that levetiracetam can reduce the abnormal brainwave patterns associated with the illness. Ethosuximide and sulthiame have been reported to improve these patterns, either when used alone or combined with other treatments. Valproate, another common medication, may not exacerbate seizures, but its effectiveness is unclear, so it’s not typically the first choice for treatment.
Benzodiazepines, like diazepam and clobazam, are often used for treatment. Studies show that diazepam can significantly reduce abnormal brainwave patterns within 24 hours. However, temporary side effects like drowsiness, dizziness, slowed breathing, muscle weakness, and paradoxical excitement can occur in about a quarter of patients. Clobazam has also been shown to be effective. However, there have been rare cases of increased absence seizures (where the patient goes “blank” for a few seconds) with clobazam.
Some specific anti-seizure medications, such as phenytoin, phenobarbital, and carbamazepine, can make seizure control worse and need to be stopped if the patient’s seizures worsen.
Corticosteroids, a group of anti-inflammatory medications, have also been used to treat this condition. The treatment course can last for several months, with high doses given at the start and gradually reduced over time. While corticosteroid therapy can improve brainwave patterns and cognition, the response rates can vary, and there is a high rate of relapse. Side effects can also lead some patients to discontinue the treatment early.
Patients with structural brain damage, such as damage from a stroke at birth or abnormal brain development, could potentially benefit from epilepsy surgery.
The ketogenic diet (a high-fat, low-carb diet) and intravenous immunoglobulin infusions (a treatment made from pooled, filtered plasma from many donors) have been studied in a small number of patients, so no specific recommendations can be made about their effectiveness.
What else can Electrical Status Epilepticus in Sleep be?
Patients with Landau-Kleffner syndrome typically experience less frequent seizures and severe problems with understanding or interpreting sounds, which is unique to this syndrome and not a broader issue. The main indicators of this syndrome can usually be found on one side of a brain scan.
Children who have a condition known as benign pediatric focal epileptic syndromes – which includes both benign childhood epilepsy with centrotemporal spikes and late-onset childhood occipital epilepsy (Gastaut type) – usually show a milder version of epilepsy symptoms, and their brain scans show that their seizures become more intense during sleep. However, this increase is less prominent when compared to the almost continuous seizure activities found in cases of ESES.
During the acute stages of ESES, children might experience tough-to-control ‘drop’ and ‘blank stare’ seizures, which can look quite similar to a condition known as Lennox-Gastaut syndrome. However, unlike patients with Lennox-Gastaut syndrome, these children don’t experience ‘stiffening’ seizures.
What to expect with Electrical Status Epilepticus in Sleep
Both seizures and abnormalities in EEG (Electroencephalogram, a test that measures brain waves) naturally improve after puberty. In spite of this, there is just a partial improvement in cognitive function. If ESES (Electrical Status Epilepticus in Sleep, a serious, long-duration epileptic condition) lasts for a longer time, it could result in worse cognitive impairment.
The EEG might continue to indicate abnormalities that are either concentrated in one area (focal) or scattered across various areas (multifocal) even when seizures are not happening.
Possible Complications When Diagnosed with Electrical Status Epilepticus in Sleep
If a diagnosis is not made quickly or treatment is not handled correctly, it could lead to worsening mental abilities.
Preventing Electrical Status Epilepticus in Sleep
After a diagnosis, certain antiepileptic drugs (or AEDs) specifically levetiracetam, clobazam, and ethosuximide, are usually recommended. On the other hand, a few specific AEDs like phenytoin, phenobarbital, carbamazepine, and oxcarbazepine are generally not suggested and should be stopped. If the patient’s brainwave patterns (seen on an EEG test) or mental performance don’t improve after three months of taking these AEDs, doctors may consider prescribing a corticosteroid – a type of medication that lessens inflammation. However, the doctor will carefully weigh the side effects of this medicine.
It has been found that using a combination of medications, as opposed to just one (called polytherapy), works effectively in most patients. There might be a small group of patients who have physical changes in their brain. These patients may need to be evaluated to see if they need epilepsy surgery.
