Absance: what is it, causes, signs, treatment, prognosis

What is absence absence?

Absance (from fr. absence, literally "absence") also called minor epileptic seizure - These are short epileptic seizures (seizures) characterized by a stopping behavior that correlates with generalized 3 Hz spike-wave discharges on the electroencephalogram (EEG). Small seizures occur with multiple genetic generalized epilepsyincluding childhood absence epilepsy (DAE), juvenile absence epilepsy (JAE) and juvenile myoclonic epilepsy (JME). Atypical absence seizures were observed in almost 60% of patients with Lennox-Gastaut syndrome.

Historically, absence epilepsy was known as pycnolepsy. This term comes from the Greek word pyknoswhich means "very often" and Iepsis "attack". The term "minor seizure" was once used to describe absences in the past, but is no longer called that.

The 2017 International Antiepileptic Classification defines absence seizures as “generalized non-seizure (non-motor) seizures”. However, this term is not entirely accurate, since, as discussed below, motor manifestations of absence epilepsy are often observed.

Causes and risk factors

A genetic component exists in all generalized epilepsies and, in particular, in absence epilepsy. In 1951, it was found that 66% of monozygotic twins showed compliance with the EEG pattern in the form of pulses and waves with a frequency of 3 Hz. Later, 252 patients with absence epilepsy with a 3 Hz spike-wave pattern were described. It has been hypothesized that multifactorial inheritance exists. The T-type voltage-gated calcium channel gene, the GABRG2 and GABRG3 receptor subunits, and the CACNA1A gene are thought to be involved in the etiology of this epilepsy syndrome. However, the mode of inheritance and most of the genes involved in childhood absence epilepsy are still unknown.

Triggers that cause seizures (for any type of epilepsy) include:

• non-compliance with the treatment regimen;
• lack of sleep;
• alcohol consumption;
• the use of drugs that lower the seizure threshold, such as isoniazid, antipsychotics;
• refusal from benzodiazepines, alcohol and other drugs for the central nervous system.

Epidemiology

The absence rate ranges from 0.7 to 4.6 per 100,000 in the general population and 6 to 8 per 100,000 among children under 15 years of age.

Childhood absence epilepsy (DAE) is a common syndrome of childhood epilepsy. Among all cases of epilepsy in schoolchildren, 10% to 17% are associated with DAE. The age at onset of DAE is usually 4 to 10 years, with a peak between 5 and 7 years. DAE is more common in girls than in boys.

Pathophysiology

Although several pathways involved in the development of absences have been described, their pathophysiological mechanisms remain to be fully understood. The cortico-thalamo-cortical contour is thought to play an important role in the pathophysiology of absence seizures.

Some of the neurons involved in the cortico-thalamo-cortical system include:

• Cortical glutamatergic neurons originate in the cortical layer VI and project into the reticular nucleus of the thalamus.
• Thalamic relay neurons, which have excitatory projections onto cortical pyramidal neurons.
• Neurons from the reticular nucleus of the thalamus containing inhibitory GABAergic projections that connect with other neurons from the same nucleus and with reticular neurons in the thalamus. These neurons are not directly connected to the cortex.

The neurons in the reticular nucleus of the thalamus can activate an oscillatory pattern (for example, rhythmic bursts, involved in the generation of carotid spindles) or continuously with single impulses (tonic activation during wakefulness). Shifts between these two patterns of excitation in the reticular nucleus of the thalamus are modulated by spines present in the thalamocortical networks and neurons in the reticular nucleus of the thalamus. They are mediated through low-threshold transitional calcium channels known as T-type channels. After depolarization, the T-type channels allow calcium to enter for a short time before becoming inactivated. Reactivation requires relatively prolonged hyperpolarization, facilitated by GABA-B receptors. Consequently, abnormal oscillatory rhythms can occur due to T-channel abnormalities or due to increased GABA-B activity.

As explained by the genetics of absence epilepsy, genes encoding T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medicines that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence medicines. Conversely, drugs that increase GABA-B activity (such as vigabatrin) increase the frequency of absences. In contrast, GABA-A agonists (eg, benzodiazepines), which preferentially increase GABAergic activity in neurons in the reticular nucleus of the thalamus, can suppress absence seizures.

History and physical signs

The age of onset of childhood absence epilepsy (DAE) is usually 4 to 10 years, with a peak between 5 and 7 years. Onset of absence before 4 years of age should raise concerns about type 1 glucose transporter (GLUT1) deficiency.

With regard to his clinical presentation, family members and teachers usually describe short periods when the patient becomes unconscious, unresponsive, and has a delay in behavior. They describe the patient during these periods as if he had a “blank stare”. Episodes occur frequently, 10 to 30 times during the day. Most children quit their activities completely, but some may continue in a slower or unusual way. Some children experience regular flutter of the eyelids at a frequency of 3 Hz. Oral automatisms can also occur, especially with prolonged seizures or during hyperventilation. Children often have mild clonic or tonic movements in the first few seconds of an attack. Pallor is often reported. Urinary incontinence is rare. The seizures usually last 4 to 30 seconds. Hyperventilation, arousal, sleep deprivation, and medication can affect the duration of a seizure. These seizures do not precede the aura and do not have a postictal state.

For juvenile absence epilepsy (JAE), the age of onset is classically 10 to 19 years, with a peak at 15 years. Seizures are less common than with DAE but tend to last longer.

On physical examination, hyperventilation can cause absences. To test this, the examiner asks the child to blow continuously for more than 2 minutes. Using a pinwheel or paper may be helpful because it encourages the child to cooperate more during the examination. If the hyperventilation is successful, the patient will develop seizures that can be seen clinically and / or on the EEG. There is some evidence that absences are easier to provoke when a person is in a seated position.

The absence state consists of generalized non-convulsive seizures characterized by impaired consciousness, and periodically has other manifestations, such as automatism or subtle myoclonic, tonic, atonic or vegetative phenomena. Patients usually have a previous diagnosis of generalized epilepsy. The absence status manifests itself as a non-convulsive seizure lasting from half an hour to several days. It usually ends spontaneously and suddenly, but when diagnosed, it should be treated with anticonvulsants.

Diagnostics

EEG is the main diagnostic tool for assessing absence epilepsy. In the case of absences in childhood, the EEG reveals bilaterally synchronous and symmetric spike-wave discharges of 3 Hz, which begin and end abruptly. These discharges can sometimes have a maximum frontal amplitude or start with one-sided focal bursts. In 50% of attacks in DAE, the initial observed discharges have a typical wave-like morphology. The remaining 50% may show a single spike, polyspike, or an atypical, irregular, generalized spike-and-wave. The background is normal.

Atypical absence seizures have more insidious onset and deviation, slower spike-wave paroxysms (less than 3 Hz), and abnormal interictal background.

Neuropsychological research has shown that patients with DAE have cognitive deficits, especially those related to attention, executive functions, verbal and visual-spatial memory. Difficulties with language and reading are also frequently reported. Depression, anxiety and attention deficit hyperactivity disorder were also more common in patients with DAE.

Because DAE is generalized epilepsy, imaging studies are usually not performed.

With JAE on the EEG, paroxysms of generalized spike-wave or polyspike-wave discharges of 3-4 Hz are observed.

In the absence of the status, the EEG shows continuous or almost continuous generalized spike-wave or polyspike-wave discharges with a frequency of 2-4 Hz.

Treatment

Etosuximide is a first-line treatment for absence epilepsy. A 2010 randomized controlled trial in 446 children with DAE showed that ethosuximide and valproic acid were superior to lamotrigine. However, in this study, the seizure-free rate was low: 53% of patients were taking ethosuximide, 58% were receiving valproic acid, and 29% of patients were taking lamotrigine. The valproic acid group had significantly lower attention scores than the ethosuximide and lamotrigine groups. For this reason, ethosuximide is the preferred treatment for absence epilepsy. The study found that only a quarter of children with absence epilepsy had seizures from levetiracetam. Although effective, leveteriacetam can control absence epilepsy at relatively low doses (usually less than 40 mg / kg / day).

The most common side effects of ethosuximide are stomach pain and nausea. For this reason, ethosuximide should be taken with meals. Other medications that can be used to treat DAE include valproate, lamotrigine, and topiramate. Second-line drugs that can be used as adjunctive therapy include valproic acid, zonisamide, and levetiracetam.

It is important to note that some sodium channel blockers, such as phenytoin, carbamazepine, gabapentin, pregabalin, and vigabatrin, can worsen absences.

Women of childbearing age who do not use contraception should not be given valproic acid; the preferred agent is ethosuximide.

Some experts suggest that a ketogenic or medium chain triglyceride diet may be beneficial, but there is no strong evidence to support their use.

Differential diagnosis

Differential diagnosis for attention seizures (one-point gazing) includes absence epilepsy, focal seizures with altered consciousness and nonepileptic paroxysmal phenomena.

Focal epilepsy with altered consciousness (formerly called complex partial epilepsy) can also manifest as behavioral arrest and automatism. However, these seizures are usually less frequent than absence seizures. Patients may have generalized seizures with focal epilepsy. The semiology of automatisms can vary depending on the area of ​​the cerebral cortex where seizures occur.

A study evaluating non-epileptic gaze seizures using video EEG monitoring showed that these episodes were often characterized by a cessation of all activity, indistinct facial expression and fixation of vision at one point without blinking. When the duration of the events was quantified, the observation episodes lasted from 3 to 74 seconds. For most children, it was difficult to determine the beginning and end of the event. Most parents could not get the child's attention back if they waved their hand in front of him. Other more energetic measures, such as clapping hands or other loud noises, have been successful in stopping events in all children. A significant percentage of children (41%) were inactive at the onset of gazing, and 18% of children watched TV when the seizure began.

A retrospective review of maps performed at a tertiary epilepsy center showed that among 276 patients in the epilepsy department, which needed to track the seizures of their appearance in the main role, only 11% had seizures. Consequently, most attention seizures are not epileptic in nature. When patients are handling gaze seizures, practitioners should exercise caution and not informing parents or other health care providers that these episodes are “absences” until the assessment is complete EEG. The aforementioned study developed a tool to determine the pretest probability of seizures in children with gaze seizures. This tool takes into account patient variables such as previous EEG results, previous use of anticonvulsants or mental health treatments, and the duration seizures.

Forecast

Typical childhood absence epilepsy occurs during childhood and resolves by adolescence. The absence of seizures is observed in 57–74% of patients. Patients with generalized tonic-clonic seizures usually do not respond to initial ethosuximide monotherapy and do not achieve long-term remission.

The risk of accidental injury during absences compared to controls is well known. As previously mentioned, these patients have problems with attention, executive function, verbal and visual-spatial memory. Difficulties with language and reading are also frequently reported. Depression, anxiety, and ADHD were also more common in patients with DAE.