They say every seizure-free day is a great day, but if we were asked what a seizure is, what would we say? Here’s our definition of one. A seizure is a paroxysm of abnormal neural activity which can have motor, sensory, autonomic and/or cognitive manifestations, and it occurs because of a transient brain dysfunction.
There are many different types of seizures, and when we think of seizures, we don’t always have to think of someone with their eyes rolled upwards and secretions frothing out of their mouth as they convulse uncontrollably. Let’s hear about Stanley.
Table of Contents
Case scenario
Stanley, the 6-year-old son of a fellow doctor, is brought to the hospital and admitted as requested by his anxious parents. The attending doctor takes a look at him and finds an apparently well child, with a regular pulse of 100 bpm, a saturation of 96% on air, and a steady respiratory rate of 30 per minute. He is conscious, rational, and responds enthusiastically to questions. His parents, however, appear anxious and tachypneic. They relate the story of how Stanley has “episodes” of seeming disconnected. They last for less than ten seconds and they involve him gazing vacantly into the distance with no response to his name. The only noticeable abnormality was his eyelids fluttering excessively during the episode. Once the ten seconds have elapsed, he regains usual activity with no recollection of anything unusual. They are increasingly worried as these episodes have been occurring over 30 times in a single day.
Although the attending doctor has the option of advising the new parents of an only child and letting them take the little guy home, he has some knowledge about absence seizures, and refers the child to a pediatrician for further follow-up.
It was with good reason too! Not more than five minutes into the referral, Stanley develops yet another episode where a vacant expression crosses his face, he begins nodding his head gently and blinking his eyes and would no longer respond to anyone calling out to him. The whole episode ends within ten seconds, but it is certain that there is something wrong with Stanley.
If you were faced with a similar scenario, would you do the same? Before you answer that question; let’s try to tackle the topic of absence seizures and delve a little deeper into the matter.
Let’s begin with some basic terms that may help us as we familiarize ourselves with the topic.
A convulsion is a seizure with motor components. This could be stiffening (tonic), a massive jerk (myoclonic), jerking (clonic), trembling (vibratory) or thrashing (hypermotor).
An epilepsy is a disorder which makes the brain more vulnerable to seizures. Generally, there have to be two or more seizures to diagnose epilepsy.
What are absence seizures?
To answer that, it is important to realize that there are three types of seizures according to the International League Against Epilepsy (ILAE). They are
- Partial seizures
- Generalized seizures
- Unclassified seizures
Generalized seizures too may be convulsive or non-convulsive. Absence seizures are a form of generalized non-convulsive seizure and because they happen so frequently, they are a type of epilepsy.
How do absence seizures present?
Absence seizures or petit-mal seizures almost always occur in childhood. There are three types of absence seizures divided according to the age group and clinical presentations.
- Childhood Absence Epilepsy (CAE) (Typical absence seizures)
These typically present around 4-8 years and last for 10-20 seconds. Because they last for such a short period, they are also called pyknoleptic seizures. During the seizure, there is marked impairment of consciousness and hardly any activity suggestive of a seizure. The only features would be mild eyelid blinking, head nods, and mild clonic movements around the mouth. They can have tens to hundreds of seizures per day, but most often, these attacks go unnoticed. The patients present with other complaints such as behavioral problems and a decline in school performance, but the good news is that these seizures usually remit in adolescence.
- Juvenile Absence Epilepsy (JAE)
They occur in older age groups ranging from 7-16 years and they present with typical absences lasting longer than CAE. These have a less severe impairment of consciousness and occur much less frequently (about 1-10 per day). They are called non-pyknoleptic or spanioleptic seizures, and many of these will progress into adult life and become generalized convulsive epilepsies.
- Juvenile Myoclonic Epilepsy (Atypical Absence seizures)
These are slightly different from the two other presentations. Although they occur in a similar age group to JAE (7-16 years), they cause a triad of seizure types which include typical absences in one third of patients, myoclonic jerks on awakening or induced by action in some, and in still others; they may cause generalized tonic clonic seizures. These may lead to a developmental delay and even mental retardation. The past medical history should be questioned in detail, including previous hypoglycemic episodes and previous hospitalizations for otherwise mild illnesses. It may be important to take a careful family history to look for genetic disorders such as inborn errors of metabolism and some neurocutaneous diseases. The birth history can also give important clues and any complications during pregnancy can point us in the right direction. It is also important to ask about consanguinity and previous unexplained neonatal or infantile deaths in the family.
Lucky for Stanley, he appears to be suffering from CAE, and with proper treatment, may not have to continue medication after adolescence.
With an idea of how absence seizures present, let us try to think up some differential diagnoses which we may have to exclude before progressing into our examination.
Your Differential Diagnoses
Absence seizures are typically mistaken for temporal lobe seizures as they too cause a transient alteration in awareness. However, these last for about 1-2 minutes and there is no associated loss of awareness but there may be memory impairment and an aura (which is now called focally aware).
Sometimes, absence seizures are confused with complex partial seizures. But they usually last longer than 30 seconds and are more gradual in both onset and ending.
They may also be confused with migraine attacks, breath holding and staring spells and some types of panic and anxiety attacks. If the absence seizures are complicated with fever, they may even be confused for febrile seizures.
Some children, may present with features mimicking an atypical absence seizure upon ingestion of a drug or
On examination
A complete neurological examination is often warranted for a child presenting with any form of seizures. Usually, the neurological examination will be normal in a child presenting with a typical absence seizure (CAE). Physical examination is also normal, and the child may appear apparently well.
In a busy clinic setting, the child can be provoked into having an absence seizure by asking him/her to hyperventilate for 3-5 minutes. During the seizure, the child will not respond to any commands, and if he is walking, he may continue to do so, or may stand motionless, staring into space. Once the episode is over, he will have no recollection of it whatsoever.
However, if a child presents with an atypical absence seizure, further examination may show a developmental delay, or even mental retardation on general examination, and more specifically, it may reveal a cerebral palsy or spastic paresis. There may also be an underlying genetic disorder such as a neurocutaneous disease (such as tuberous sclerosis) or an inborn error in metabolism. Remember the mnemonic ASHLEAF when looking for tuberous sclerosis.
A – Ashleaf spots
S – Shagreen patches
H – Heart rhabdomyosarcoma
L – Lung hamartoma
E – Epilepsy (from cortical tubers)
A – Angiolipoma of kidneys
F – Facial angiofibroma
How would you investigate this patient?
If the clinical history is clear enough, an EEG (Electro-Encephalogram) may be all we need to make a diagnosis of absence seizures, but we can exclude some of the differentials and also get an idea of what may have caused the absence seizures. This would include investigations to look for metabolic abnormalities, such as elevated levels of blood lactate, ammonia and hypoglycemia. A panel of biochemical tests can also be run with a sample of urine, to look for other inborn errors of metabolism. At the same time, it may be important to exclude ingestion of a drug or toxin which may have led to a presentation of this nature.
Once the lab tests are out of the way, we can focus on the single investigation which will be diagnostic of absence seizures, and that is the EEG. During an EEG, we place metal electrodes on the scalp and use them to detect brain waves.
To prepare the child for the EEG, we may have to give the following instructions to the parents.
The night before the EEG, ask the mother to wash the child’s hair and avoid applying any products (even baby oils, shampoos and soaps!). If the child is on any medications that may interfere with the test, they may have to be temporarily stopped. Also, it is important to tell the parents not to give anything that may contain caffeine or chocolate before the test as it might interfere with the EEG results.
EEGs can be taken with the patient awake (awake recording), asleep (sleep recording) or when they have been sleep-deprived (sleep-deprived recording).
A normal EEG report will usually contain the following terms:
- Background activity is normal (here they are talking about the alpha frequency)
- No abnormalities (nothing stands out in the background)
- No changes in the EEG provoked by photic stimulation or hyperventilation
- No asymmetry
For typical absence seizures, especially CAE, an awake recording may be pathognomonic. The EEG will have normal background activity and bursts of 3 Hz spike-and-wave complexes mostly in the frontal cortex during the seizure. The spike frequencies can range from 2.5-6 Hz and the faster waves are usually seen at the beginning of the seizure and also with older groups of children. These children may have seizure episodes as short as 3 seconds, and the shorter they are; the less likely they are to have any clinical manifestations. Also, the clinical features occur after the EEG changes have occurred (lag).
In atypical seizures, it may be hard to differentiate the beginning and the end of the seizure but background activity is usually abnormal. A spike-and-wave recording of 2.5Hz may be noted classically but there may also be poly-spike-and-wave complexes.
To realize the number of seizures a patient may be having each day, ambulatory EEG monitoring (which is a fancy term for 24-hour EEG monitoring) may be helpful.
What about the role of neuroimaging? Generally, neuroimaging is not indicated for absence seizures as there may not be any neurological abnormalities. But it can hint towards the etiology of seizures (like a primary structural defect). Therefore, doctors usually prescribe neuroimaging to support their diagnosis and exclude differentials. The imaging method of choice is an MRI of the brain, although the CT scan may also be used.
Diagnosis
Now that we have an EEG report to support the clinical picture, we can make a diagnosis of typical absence seizures in Stanley, and move on to the treatment.
How will we treat Stanley?
First off, we must clarify why it is important that Stanley gets treatment if he has been diagnosed with absence seizures. Any form of epilepsy must be treated, with some form of Anti-Epileptic Drug (AED). This is because even though a typical absence seizure may not cause hypoxic damage to the brain unlike other epilepsies, they can significantly interfere with both a child’s education and his behavior. Untreated absence seizures may lead to various psychological disturbances and can affect his personality.
On the other hand, JAE and other atypical myoclonic absence seizures can cause both physical and neurological damage leading to mental retardation and developmental delays, so prompt intervention is necessary.
A word of caution prior to beginning AED is warranted; all AED are toxic and have numerous side effects. Doses must always be titrated to suppress all epileptiform activity, but it should be balanced against minimum side effects.
AED for typical absence should be initiated by a pediatrician/ pediatric neurologist. It is usually not recommended after a first unprovoked tonic-clonic seizure and monotherapy should be used wherever possible. If monotherapy with the first drug fails, monotherapy should be tried again after changing the drug. If monotherapy fails even after the maximum dose, a second drug should be added and if possible, taper off the dose with the first drug and only continue the second.
If monotherapy continues to fail, consider the possibilities of an alternate diagnosis, a lack of patient compliance and the quality of the drug before shifting to combination therapy.
For CAE, our first option would be Ethosuximide or Sodium Valproate. Ethosuximide is effective against absence seizures only, but Sodium Valproate can be used for absence, tonic-clonic and myoclonic seizures. The second choice is usually Topiramate or Lamotrigine but research has shown these to have greater side effects and a lower efficacy compared to first line treatment.
In the treatment of JAE, Sodium Valproate is indicated as first-line treatment, and only if it is not tolerated or proves ineffective, we can consider topiramate or lamotrigine. In both these types of seizures, it is important to avoid drugs like Phenytoin, Carbamazepine and Vigabatrin as they may worsen the seizures.
For symptomatic Juvenile myoclonic epilepsy, we begin with Sodium Valproate or lamotrigine, depending on whichever is better tolerated and in case of a second option, we can fall back on Clobazam, Clonazepam or Topiramate. This may be necessary on many occasions as the children are refractory to the initial treatment, but it must be kept in mind that although these drugs reduce seizure frequency, they have limited efficacy. Under special circumstances, even acetazolamide can be given to these children. Newer drugs include Levetiracetam as adjunctive therapy, but the drug doesn’t seem to work any marvels.
It is important to caution Stanley’s parents to the adverse effects of the treatment he may be taking. Sodium Valproate can cause GI disturbances, including dyspepsia and nausea, as well as an impaired glucose tolerance which may lead to weight gain. It can also cause hair loss, tremor and raise liver enzymes. Ethosuximide has far fewer adverse effects. Patients mostly complain of dyspepsia, ataxia and imbalance. Almost all AED can cause dizziness and sedation, so it is important that Stanley is not left alone for long periods. However, it is important not to unnecessarily handicap the child. He should be free to engage in outdoor activities. Even activities that may be considered dangerous for an epileptic patient, such as swimming and skateboarding may be allowed under supervision. However, a patient with absence seizures cannot drive unless they are completely seizure-free both clinically and on EEG.
Follow-up
The remission rates of absence seizures vary depending on the seizure type. The worst type is Juvenile Myoclonic absence seizures, and patients may suffer from recurrences even after they achieve good control. So, patients should be followed up for a long seizure-free interval until therapy can be discontinued.
Some patients may progress to generalized epilepsy despite treatment, especially with Juvenile myoclonic seizures and generally need treatment for life. They will also have to abstain from alcohol and have a healthy sleep.
Luckily, remission is good with typical absence seizures; sometimes reaching as much as 80%, but this usually depends on the duration of follow-up. Generally, early-onset, quick response to treatment and normal EEG background are good prognostic signs.
References
Kumar & Clark’s Clinical Medicine – Edition 10 [Cited March 28, 2021]
Illustrated Textbook of Paediatrics – Edition 5 [Cited March 28, 2021]
https://www.healthline.com/health/eeg#procedure
https://neurology.med.wayne.edu/pdfs/how_to_interpret_and_eeg_and_its_report.pdf
https://reference.medscape.com/article/1183858-overview#a1
https://www.webmd.com/epilepsy/understanding-temporal-lobe-seizure-symptoms