Absence seizure

The incidence of absence seizures in the United States is 1.9–8 cases per 100,000 population. The morbidity from typical absence seizures is related to the frequency and duration of the seizures, as well as to the patient's activities; effective treatment ameliorates these factors. Educational and behavioral problems often result from frequent, unrecognized seizures. No deaths result directly from absence seizures. However, if an individual suffers an absence seizure while driving or operating dangerous machinery, a fatal accident may occur. ==Cause==

An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), GABRG3, and CACNA1A2 genes. ==Signs and symptoms==

The clinical manifestations of absence seizures vary significantly among patients. • Absence with impairment of consciousness only as per the above description. The head may tonically draw to one or another side. • Absence with automatisms. Purposeful or quasi-purposeful movements occurring in the absence of awareness during an absence attack are frequent and may range from lip licking and swallowing to clothes fumbling or aimless walking. If spoken to, the patient may grunt, and when touched or tickled may rub the site. Automatisms are quite elaborate and may consist of combinations of the above described movements or may be so simple as to be missed by casual observation. • Absence with autonomic components. These may be pallor, and less frequently flushing, sweating, dilation of pupils and incontinence of urine. Mixed forms of absence frequently occur. These seizures can happen a few times a day or in some cases, hundreds of times a day, to the point that the person cannot concentrate in school or in other situations requiring sustained, concentrated attention. ==Risk factors==

Typical absences are easily induced by hyperventilation in more than 90% of people with typical absences. This is a reliable test for the diagnosis of absence seizures: a patient suspected of typical absences should be asked to hyperventilate for three minutes, counting breaths. During hyperventilation, the oxygen and carbon dioxide level will become abnormal. This results in weakening of electrical signal which leads to a reduction in the seizure threshold. Intermittent photic stimulation may precipitate or facilitate absence seizures; eyelid myoclonia is a common clinical feature. A specific mechanism difference exists in absence seizures in that T-type Ca++ channels are believed to be involved. Ethosuximide is specific for these channels and thus it is not effective for treating other types of seizures. Valproate and gabapentin (among others) have multiple mechanisms of action including blockade of T-type Ca++ channels, and are useful in treating multiple seizure types. Gabapentin can aggravate absence seizures. ==Pathophysiology==

The corticothalamic circuit plays an important role in the pathophysiology of absence seizures. Specific neuron groups implicated include: • Cortical glutamatergic neurons • Thalamic relay neurons • Neurons of the thalamic reticular nucleus Abnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low-threshold T-type calcium channel. This explains how the inheritance of the gene code for the T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as gabapentin, tiagabine, and vigabatrin cause inhibition of GABA, resulting in exacerbation of absence seizures. ==Diagnosis==

The primary diagnostic test for absence seizures is electroencephalography (EEG). However, brain scans such as by an MRI can help rule out other diseases, such as a stroke or a brain tumor. During EEG, hyperventilation can be used to provoke these seizures. Those most susceptible to this are children, and the first episode usually occurs between 4 and 14 years old. Absence seizures have two essential components: • Clinical the impairment of consciousness (absence) • EEG the EEG shows generalized spike-and-slow wave discharges Absence seizures are broadly divided into typical and atypical types: • Typical absence seizures usually occur in the context of idiopathic generalised epilepsies and an EEG shows fast >2.5 Hz generalised spike-wave discharges. The prefix "typical" is to differentiate them from atypical absences rather than to characterise them as "classical" or characteristic of any particular syndrome. • Atypical absence seizures: • Occur only in the context of mainly severe symptomatic or cryptogenic epilepsies of children with learning difficulties who also have frequent seizures of other types, such as atonic, tonic and myoclonic. • Have slower onset and termination and changes in tone are more pronounced. • Have particular ictal characteristics: EEG is of slow (less than 2.5 Hz) spike and slow wave. The discharge is heterogeneous, often asymmetrical and may include irregular spike and slow wave complexes, fast and other paroxysmal activity. Background interictal EEG is usually abnormal. Syndromes Absence seizure syndromes are childhood absence epilepsy, epilepsy with myoclonic absences, juvenile absence epilepsy and juvenile myoclonic epilepsy. Other proposed syndromes are Jeavons syndrome (eyelid myoclonia with absences), and genetic generalised epilepsy with phantom absences. Absence seizures are also known to occur to patients with porphyria and can be triggered by stress or other porphyrin-inducing factors. Childhood Absence Epilepsy Childhood absence epilepsy (CAE) is a type of idiopathic epilepsy characterized by its non-convulsive, generalized nature and a genetic origin influenced by multiple factors Epilepsy with Myoclonic Absences Myoclonic Absence Epilepsy is an infrequent type of childhood epilepsy characterized by a high occurrence of intellectual impairments and resistance to treatment. Juvenile Absence Epilepsy Juvenile Absence Epilepsy is considered an Idiopathic GED (Idiopathic Major Epilepsy) Syndrome and is officially categorized as Idiopathic Generalized Epilepsy by the ILAE. This condition typically begins in adolescents during the puberty stage and is distinguished by the occurrence of absence seizures and Generalized Tonic-Clonic Seizures. Juvenile Myoclonic Epilepsy Juvenile Myoclonic Epilepsy (JME), also referred to as Janz Syndrome and Impulsive Petit Mal, is a form of epilepsy that is characterized by absence, Myoclonic, and Generalized Tonic-Clonic Seizures. This epilepsy variant is marked by its idiopathic and hereditary characteristics, as well as its generalization across seizures. The initial documentation of JME dates back to 1867 by Herpin, followed by Janz and Christian labeling it as 'Impulsive Petit Mal' in 1957, and Lund's 1975 designation of 'JME'. Jeavons Syndrome Reflex Epilepsy (JS) is a form of epilepsy usually categorized within the spectrum of genetically linked Generalized Epilepsy (GGE). While EM (Epileptic Myoclonus) is commonly acknowledged as a type of seizure, the formal recognition of JS as a separate medical entity by the International League Against Epilepsy (ILAE) has not yet occurred. ==Treatment==

Treatment of patients with absence seizures only is mainly with ethosuximide or valproic acid, which are of equal efficacy in controlling absences in around 75% of patients. Lamotrigine monotherapy is less effective, controlling absences in around 50% of patients. This summary has been recently confirmed by Glauser et al. (2010), who studied the effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug dosages were incrementally increased until the child was free of seizures, the maximal allowable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine. There were no significant differences between the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide. If monotherapy fails or unacceptable adverse reactions appear, replacement of one of the three antiepileptic drugs with another is the alternative. Adding small doses of lamotrigine to sodium valproate may be the best combination in resistant cases. Although ethosuximide is effective in treating only absence seizures, valproic acid is effective in treating multiple seizure types, including tonic-clonic seizure and partial seizure, suggesting it is a better choice if a patient is exhibiting multiple types of seizures. Similarly, lamotrigine treats multiple seizure types, including partial seizures and generalized seizures, and it is also an option for patients with multiple seizure types. Clonazepam (Klonopin, Rivotril) is effective in the short term but is not generally recommended for treatment of absence seizure because of the rapid development of tolerance and high frequency of side effects. Roughly 70% of children experiencing absence seizures will see these seizures naturally cease before they reach the age of 18. In such instances, the need for medications might no longer be relevant in adulthood. It is worth noting that children who develop absence seizures prior to turning 9 are more inclined to outgrow them compared to those whose absence seizures commence after the age of 10. ==Prevention==

Appropriate medication is the best way to manage absence seizures, but prevention can be considerably enhanced by life-style changes such as exercise, stress reduction, good sleep hygiene, and healthy diet. Medications that should not be used Carbamazepine, vigabatrin, and tiagabine are contraindicated in the treatment of absence seizures, irrespective of cause and severity. This is based on clinical and experimental evidence. Similarly, oxcarbazepine, phenytoin, phenobarbital, gabapentin, and pregabalin should not be used in the treatment of absence seizures because these medications may worsen absence seizures. Nor is it easily known how long a medication must be continued before an off-medication trial should be conducted to determine whether the patient has outgrown the absence seizures, as is often the case in children. To date there have been no published results of any large, double-blind, placebo-controlled studies comparing the efficacy and safety of these or any other medications for absence seizures. A 2019 Cochrane review found that ethosuximide was the best mono-therapy for children and adolescents but noted that if absence seizures co-exist with tonic-clonic seizures then valproate should be preferred. == References ==