Absence seizure

Absence seizures are one of several kinds of seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dating from the late 18th century ).

Absences seizures are brief (usually less than 20 seconds), generalized epileptic seizures of sudden onset and termination. They have 2 essential components: Absence seizures are broadly divided in typical and atypical absence seizures. Typical absence seizures usually occur in the context of idiopathic generalised epilepsies and 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.
 * clinically the impairment of consciousness (absence)
 * EEG generalized spike-and-slow wave discharges.

Atypical absence seizures:
 * occur only in the context of mainly severe symptomatic or cryptogenic epilepsies of children with learning difficulties who also suffer from frequent seizures of other types such as atonic, tonic and myoclonic.
 * onset and termination is not so abrupt and changes in tone are more pronounced
 * ictal 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.

Clinical Presentation
The clinical manifestations of absence seizures vary significantly among patients. Impairment of consciousness is the essential ictal element and may be the only clinical symptom, but this is often combined with other manifestations. The hallmark of the absence seizures is abrupt and sudden onset impairment of consciousness, interruption of ongoing activities, a blank stare, possibly a brief upward rotation of the eyes. If the patient is speaking, speech is slowed or interrupted, if walking, he or she stands transfixed; if eating, the food will stop on his way to the mouth. Usually the patient will be unresponsive when spoken to. In some, attacks are aborted when the patient is spoken to. The attack lasts from a few seconds to half a minute and evaporates as rapidly as it commenced. 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 other situations requiring sustained, concentrated attention.
 * 1) Absence with impairment of consciousness only as per the above description
 * 2) Absence with mild clonic components.  Here the onset of the attack is indistinguishable from the above, but clonic components may occur in the eyelids, at the corner of the mouth, or in other muscle groups which may vary in severity from almost imperceptible movements to generalised myoclonic jerks. Objects held in the hand may be dropped.
 * 3) Absence with atonic components.  Here there may be a diminution in tone of muscles subserving posture as well as in the limbs leading to drooping of the head, occasionally slumping of  the trunk, dropping of the arms, and relaxation of the grip.  Rarely tone is sufficiently diminished to cause this person to fall.
 * 4) Absence with tonic components.  Here during the attack tonic muscular contraction may occur, leading to increase in muscle tone which may affect the extensor muscles or the flexor muscles symmetrically or asymmetrically.  If the patient is standing the head may be drawn backward and the trunk may arch. This may lead to retropulsion. The head may tonically draw to one or another side.
 * 5) Absence with automatisms.  Purposeful or quasipurposeful 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 or to the spoken voice 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 causal observation.
 * 6) Absence with autonomic components.  These may be pallor and less frequently flushing, sweating, dilatation of pupils and incontinence of urine.

Precipitating factors
Typical absences are easily induced by hyperventilation in more than 90% of the patients. This is a reliable test for the diagnosis of absence seizures: a patient suspected of typical absences should be asked to overbreathe for 3 min, counting his or her breaths. Intermittent photic stimulation may precipitate or facilitate absence seizures; eyelid myoclonia is a common clinical accompaniment.

Syndromes of idiopathic generalised epilepsies with absence seizures
These are childhood absence epilepsy, juvenile absence epilepsy, epilepsy with myoclonic absences and juvenile myoclonic epilepsy. Other proposes syndromes are Jeavons syndrome (eyelid myoclonia with absences) and idiopathic generalised epilepsy with phantom absencesPrecipitating factors of absence seizures.

These types of seizures are also known to occur to patients suffering with Porphyria, and can be triggered by stress or other Porphrin-inducing factors.

Treatment
Treatment of patients with absence seizures only is mainly with sodium valproate or ethosuximide, which are of equal efficacy controlling absences in around 75% of patients. Lamotrigine monotherapy is less effective with nearly half of the patients becoming seizure free. This view has been recently confirmed by Glauser et al. (2010) who performed a double-blind, randomized, controlled clinical trial, to compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable 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. Differential drug effects were determined by means of pairwise comparisons. The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03). If monotherapy fails or unacceptable adverse reactions appear, replacement of one by the other of the other three antiepileptic drugs is the alternative. Adding small doses of lamotrigine to sodium valproate may be the best combination in resistant cases.

In a study published in the March 2010 Pakistan Journal of Medicine it was found that ethosuximide was the most effective treatment for childhood absence epilepsy. The study group enrolled 453 children newly diagnosed with childhood absence epilepsy from July 2004 to October 2007. Study participants were randomly assigned to ethosuximide, valproic acid or lamotrigine. Drug doses were incrementally increased until the child was seizure-free. After 16 weeks of therapy, the researchers found ethosuximide and valproic acid were significantly more effective than lamotrigine in controlling seizures, with no intolerable side effects. They also determined ethosuximide was associated with significantly fewer negative effects on attention.

Although ethosuximide is often effective in treating absence seizures, valproate is much more effective in treating tonic-clonic seizure, and so it may be a better choice if a patient is exhibiting both types of seizures. Clonazepam (Klonopin, Rivotril) is effective in the short term but is not generally recommended for treatment of absence seizure due to the rapid development of tolerance and high frequency of side effects.

Contraindicated drugs
The treatment of idiopathic generalized epilepsy is demanding because many antiepileptic drugs are either ineffective or exaggerate absences and myoclonic jerks. An antiepileptic drug is contraindicated not only when it exaggerates seizures but also when it is ineffective in controlling the seizures that it is supposed to treat. It may cause unnecessary adverse reactions and deprives the patient of the therapeutic effect that could be provided by another antiepileptic drug. 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. In particular, the GABA agonists vigabatrin and tiagabine are used to induce, not to treat, absence seizures and absence status epilepticus. The error of prescribing these drugs in the treatment of absence seizures may be of the same magnitude as prescribing a gluten-rich diet in the treatment of celiac disease. Similarly, phenytoin, phenobarbital, gabapentin, and pregabalin should not be used in the treatment of absence seizures.

Data limitations and research directions
In the treatment of absence seizures there is often insufficient evidence for which of the available medications has the best combination of safety and efficacy for a particular patient. Nor is it easily known how long a medication must be continued before an off-medication trial should be conducted to determine whether the individual 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. The studies that exist have been small and not produced clear conclusions.