|
Absence status epilepticus
by C. P. Panayiotopoulos Date of submission:October 30, 2000 Date of Update: November 2, 2002 Medline SEARCH DATE: October 25, 2002 |
| HISTORICAL NOTE AND NOMENCLATURE Absence status epilepticus is the name proposed by the Commission on Classification and Terminology of the International League Against Epilepsy (Commission of Classification and Terminology of the International League Against Epilepsy 1981; 1989). Absence status is not synonymous with nonconvulsive status epilepticus, which also encompasses complex partial status epilepticus. Petit mal status and various other synonyms have also been used in the past. Classification. Considering that absence status epilepticus
is a prolonged absence seizure, it is reasonable to adopt for this condition
a definition and classification similar to that recognized for epileptic
seizures and syndromes manifested with absences (Commission of Classification
and Terminology of the International League Against Epilepsy 1989; Panayiotopoulos
1997; Engel 2001; Panayiotopoulos 2002). Table 1. Classification of Absence Status Epilepticus
Cryptogenic or symptomatic (atypical) absence status epilepticus of:
Situation-related absence status epilepticus due to:
Adapted from (Panayiotopoulos 1997). Absence seizures are broadly divided into: (a) typical absences of mainly idiopathic generalized epilepsy with generalized, greater than 2.5 Hz spike or polyspike-and-slow waves, and (b) atypical absences of symptomatic or cryptogenic epilepsies with slower, less than 2.5 Hz generalized discharges (Commission of Classification and Terminology of the International League Against Epilepsy 1981). Similarly, absence status epilepticus is divided into typical absence status epilepticus of mainly idiopathic generalized epilepsy|{diagram:asep1.bmp}{caption:Typical absence status epilepticus in idiopathic generalized epilepsy with phantom absences (1)}{label:Top: Video-EEG prior to diazepam. There was continuous spike and occasional polyspike and slow wave activity mainly at 3-Hz that lasted until the administration of diazepam. Note also slower or faster components and some topographic variability of the discharge. Bottom: Relative normalization of the EEG started within a minute from onset of diazepam administration. Note the fragmentation of the discharge and the reappearance of alpha rhythm.}| and atypical absence status epilepticus of symptomatic and cryptogenic generalized epilepsies.|{diagram:asep2.bmp}{caption:Atypical absence status in symptomatic generalized epilepsy}{label:Video-EEG from a 9-year-old girl who had severe mental and physical deficits due to birth related brain anoxia. Slow spike and slow wave activity is continuously recorded.}| Furthermore, to comply with seizure and syndrome classification, absence status epilepticus may be situation-related and caused by the introduction or withdrawal of certain drugs, intoxication, or electrolyte or metabolic disturbances. Symptomatic absence status may also be caused by severe brain anoxia or other brain damage. Absence status epilepticus is a prolonged, generalized absence seizure, which is defined as lasting more than half an hour, but usually lasts for hours and even for days. It is associated with typically regular and symmetrical generalized discharges of 1 Hz to 4 Hz spike or multiple spike-and-slow wave complexes. Though the sharing symptom of absence status epilepticus is impairment of cognition, this is often associated with other clinical manifestations that may be syndrome-related. It should be emphasized that absence status epilepticus, like the brief absence seizure, is not one but many types of a prolonged, generalized, absence seizure (Andermann and Robb 1972; Commission of Classification and Terminology of the International League Against Epilepsy 1981; 1989; Guberman et al 1986; Dunne et al 1987; Rohr-Le Floch et al 1988; Shorvon 1995; Snead et al 1997; Agathonikou et al 1998; Panayiotopoulos 2002). Impairment of consciousness, memory, and higher cognitive functions.
The cardinal symptom shared by all cases of absence status is the altered
content of consciousness in a patient who is usually fully alert.|{video:asep9.avi}{caption:Absence
status epilepticus}{label:Absence status epilepticus of late onset in
idiopathic generalized epilepsies. This woman is unable to remember dates.
She could not remember her date of birth or other significant dates from
her life.}|Memory and higher cognitive intellectual functions such as
abstract thinking, computation, and personal awareness are the main areas
of disturbance (Andermann and Robb 1972; Guberman et al 1986; Agathonikou
et al 1998; Panayiotopoulos 2002). This varies from extremely mild to
extremely severe with intermediate states of severity occurring more often.
Mild impairment of consciousness manifests with slow reaction, behavior,
and mental functioning.
Moderate and severe impairment of consciousness manifest with varying degrees of confusion, global disorientation, and inappropriate behavior, and these are described by witnesses as follows:
Usually, the patient with absence status of idiopathic generalized epilepsy is alert, attentive, and cooperative. Verbal functioning is relatively well preserved, but is often slow with stereotypic and usually monosyllabic answers. Movement and coordination is intact. Although the patient may rarely become completely unresponsive, this author is not aware of any such case with idiopathic generalized epilepsy. It is surprising how often physicians are deceived by the general good appearance, alertness, and cooperation of the patient. Based on previous experiences, patients and relatives usually recognize the condition. However, medical intervention to stop the absence status and prevent an impending GTCS may not be offered because attending physicians may not appreciate this as an emergency. |{diagram:asep3.bmp}{caption:Typical absence status epilepticus in idiopathic generalized epilepsy with phantom absences (2)}{label:EEG (top) of absence status and "interictal video EEG" (bottom) with phantom absences of a woman who had her first absence status epilepticus followed by a generalized clonic-tonic seizure at age 56 years. Initially, we erroneously classified her as de novo absence status epilepticus instead of idiopathic generalized epilepsy with phantom absences. This mistake became apparent when interictal video-EEG demonstrated absences manifested with mild cognitive impairment and eyelid fluttering (bottom). In reviewing this video-EEG with the patient and her daughter, they recognized that these mild absences were occurring many years prior to the absence status epilepticus. Note the similarity between the EEG discharge of absence status epilepticus (top) and typical absence seizure (bottom).}|Basic testing of memory and higher cognitive functions are essential for diagnosis. Behavioral abnormalities and experiential phenomena.
Though the most common behavioral changes refer to daily activities disturbed
by the impairment of consciousness, some patients become depressed, agitated,
and occasionally, hostile. More commonly than usually appreciated are
experiential and sensational phenomena such as: "sensation of viewing
the word through a different medium,” “a feeling of not being
in the same world as everyone else,” “uncontrollable rush
of thoughts,” “a feeling of fear of losing control of my mind,"
"a feeling of closeness," "a funny feeling that I can not
elaborate," "a strange feeling of not being myself," "edgy,
worried, and uncomfortable,” "my character changes completely,
I become extremely snappy…have a severe headache," or "weird"
(Agathonikou et al 1998). Myoclonic jerks. Segmental, usually eyelid or perioral
and less often limb, myoclonic jerks frequently occur during typical absence
status and vary in degree and severity. They are most likely to occur
in syndromes manifesting with similar myoclonic phenomena during brief
absences (Panayiotopoulos 2002). PATHOPHYSIOLOGY Furthermore, we also do not know why and how an absence seizure or status
may progress to a GTCS.|{diagram:asep7.bmp}{caption:Transformation from
absence to a generalized tonic clonic seizure}{label:This is a rare illustration
of the transformation of an absence to GTCS. It is from a video-EEG of
a 23-year-old woman with idiopathic generalized epilepsy and absence seizures.
Upon awakening she had numerous absence seizures with complete recovery
in between, which is not absence status.}| Absence status epilepticus does not appear to cause permanent neurologic
damage from (Drislane 1999). Of neurotransmitters, GABAB receptors play the most prominent role by
eliciting long-standing hyperpolarization required to drive low threshold
calcium channels for the initiation of sustained burst firing. (Snead
1995; Coulter 1997; Danober et al 1998; Futatsugi and Riviello 1998; Pinault
et al 1998). GABAB agonists such as baclofen aggravate, GABAB antagonists
suppress typical absences. GABAergic drugs such as vigabatrin interfering
with the degradation and tiagabine interfering with the reuptake of GABA
are pro-absence substances (Panayiotopoulos et al 1997a; Ettinger et al
1999; Knake et al 1999). The only exception to GABAergic activation inhibiting
absences is that of the reticular thalamic nucleus, with exclusively GABAA
receptors, which function as a pacemaker to synchronize thalamocortical
oscillations (Gibbs et al 1996; Hosford et al 1999). Enhanced activation
of GABAA receptors in this nucleus decreases the pacemaking capacity of
these cells, thus decreasing the likelihood of generating absence seizures. Idiopathic (typical) absence status epilepticus. Idiopathic (typical) absence status epilepticus is easy to diagnose, providing that the associated syndrome of idiopathic generalized epilepsy with typical absences is correctly identified. This is often combined with myoclonic jerks and GTCS. With the possible exception of childhood absence epilepsy, all other syndromes of idiopathic generalized epilepsy with typical absences may manifest with typical absence status, either as a spontaneous expression of their natural course or provoked by external factors or inappropriate treatment maneuvers (Panayiotopoulos 1997; Agathonikou et al 1998). In these conditions, the patient or relatives are well aware of the clinical manifestations of absence status epilepticus, which often heralds GTCS. The most common misdiagnosis is made because absences are not recognized or are misdiagnosed as complex partial seizures (Panayiotopoulos 1997; Agathonikou et al 1998; Panayiotopoulos 2002). A previous or a new EEG invariably shows generalized discharges in idiopathic generalized epilepsy. It may be normal or may show specific focal spikes in partial epilepsies, mainly temporal lobe epilepsy. The clinical manifestations of idiopathic (typical) absence status epilepticus, a lengthened absence seizure, are syndrome-related (Agathonikou et al 1998; Panayiotopoulos 2001; Panayiotopoulos 2002). Though mild or severe impairment of consciousness is the sharing symptom, other associated manifestations such as perioral or eyelid myoclonia depend on the underlying epileptic syndrome (Table 1). Impairment of consciousness and myoclonic jerks. Impairment
of consciousness, memory, and higher cognitive function, as detailed in
the clinical manifestations, may be the same irrespective of idiopathic
generalized epilepsy syndrome. It is not the absence but the other associated
clinical manifestations (ie, myoclonic jerks) that betray the underlying
syndrome of idiopathic generalized epilepsy. These may be segmental (usually
eyelid or perioral and less often limb) myoclonic jerks occurring during
typical absence status. They are of varying degree and severity. They
are most likely to occur in syndromes manifesting with similar myoclonic
phenomena during brief absences. Thus, continuous and disturbing eyelid
myoclonia is a consistent symptom of typical absence status in the syndrome
of eyelid myoclonia with absences. Similarly, perioral myoclonia is the
relevant clinical manifestation of absence status in perioral myoclonia
with absences. Random myoclonic jerks of the limbs or eyelids may be seen
in absence status epilepticus of juvenile absence epilepsy. In juvenile
myoclonic epilepsy, absence status epilepticus is rare as opposed to the
frequently occurring long series of myoclonic jerks and myoclonic status
epilepticus prior to a generalized convulsion. It is possible that in
juvenile myoclonic epilepsy, absence status epilepticus consists of a
mixture of myoclonic jerks interspersed with absences. Absence or poverty
of segmental or other jerks is rather characteristic of the syndrome of
phantom absences. Only rarely, there may be some mild eyelid fluttering
markedly different from that of the eyelid myoclonia. The relation of
the typical absences and typical absence status epilepticus is epitomized
as follows by the presented illustrative patient:
Her first overt seizure occurred at age 30 years. She was moderately confused for 12 hours prior to a GTCS.|{diagram:asep1.bmp}{caption:Typical absence status epilepticus in idiopathic generalized epilepsy with phantom absences (1)}{label:Top: Video-EEG prior to diazepam. There was continuous spike and occasional polyspike and slow wave activity mainly at 3-Hz that lasted until the administration of diazepam. Note also slower or faster components and some topographic variability of the discharge. Bottom: Relative normalization of the EEG started within a minute from onset of diazepam administration. Note the fragmentation of the discharge and the reappearance of alpha rhythm.}||{video:asep9.avi}{caption:Absence status epilepticus}{label:Absence status epilepticus of late onset in idiopathic generalized epilepsies. This woman is unable to remember dates. She could not remember her date of birth or other significant dates from her life.}|Despite an EEG showing brief discharges of 3 Hz spike-and-slow waves|{diagram:asep6.bmp}{caption:Interictal EEG of idiopathic generalized epilepsy with phantom absences}{label:From interictal video-EEG. Brief generalized discharges of 3 Hz spike and slow waves lasting 2 to 3 seconds without apparent clinical manifestations. Similar abnormalities were recorded in 1972 and again in 1997. Note the similarity of the discharge with the ictal and immediately post-diazepam EEG. The only significant difference is duration, brief interictally, continuous for hours ictally.}|and no clinical evidence of brief complex partial seizures of temporal lobe symptomatology, she was misdiagnosed as having temporal lobe epilepsy and was treated with high doses of primidone and sulthiame until her referral to this author’s clinic in 1990. Through the years, she had at least 30 episodes of absence status, lasting from 3 hours to 10 days and often progressing to GTCS. Also, questioning revealed that she frequently had brief episodes of 2 seconds to 5 seconds, wherein she experienced a lack of concentration (phantom absences) or of memory for a few seconds, which could be misinterpreted as normal variations in daily life. She was free of seizures for the previous 9 years on monotherapy with sodium valproate 1000 mg daily. Her last EEG in 1997 still showed some brief generalized discharges of 3 Hz spike-and-slow waves on overbreathing without clinical manifestations. Syndromic classification of this illustrative case. We initially categorized this woman amongst the unclassified cases suggesting that "she may be a case of late onset absence status, absences, and GTCS” (Panayiotopoulos et al 1992). Later, on the basis of another 12 similar cases, we concluded that she suffered from a previously unrecognized syndrome of idiopathic generalized epilepsy with phantom absences, GTCS with onset in adulthood, and frequent absence status epilepticus (Panayiotopoulos et al 1997b). In some patients with idiopathic generalized epilepsy, there may be brief tonic spasms of facial muscles (Agathonikou et al 1998).|{diagram:asep4.bmp}{caption:Absence status epilepticus with repetitive discharges of unclassified generalized epilepsy}{label:Continuous recording from video-EEG of a 48-year-old woman with unclassified absences and GTCS from age 11 years. Video-EEG was recorded 7 hours from onset of symptoms, which ended with a generalized tonic clonic seizure one hour later.}| This patient realized from previous experiences that she was in absence status epilepticus when she felt “weird, like in a trance, missing pieces of conversation,” and she went to the hospital. Despite written instruction, no diazepam was administered. She was alert, attentive, cooperative, and well-behaved, but she seemed depressed. Movement and speech were normal. She was able to count with no errors except when the discharges between arrows occurred. During these discharges, eyes, and sometimes mouth, would tonically open with a slight retropulsion of the head. Onset, duration, and evolution. Though of sudden onset, the severity of symptoms may be initially mild and inconspicuous. The patient or relatives, with the experience of previous episodes, recognize this state that may progress to more serious disturbances and probably a generalized convulsion. These initial symptoms may be mild slowness of thought and mental functioning, an increasing number of perioral or eyelid jerks interspersed with mild impairment of concentration, or just a familiar, habitual personal feeling heralding the status. Soon after this initial phase, half of the patients reach a more or less steady state that, mild or severe and with or without clinical manifestations other than impairment of consciousness, is stereotype for each patient. In another one-fourth of patients, the impairment of consciousness deteriorates with time. For the remaining one-fourth, severity shows marked fluctuations in the course of the absence status epilepticus. It is important to remember that more than half of the patients are aware of the situation when entering or during absence status epilepticus, which is of great practical significance regarding termination of this state and prevention of the impending GTCS by self-administration of appropriate medication. Generalized tonic-clonic seizures associated with idiopathic typical absence status. Ending with a GTCS is probably the rule irrespective of syndrome (Andermann and Robb 1972; Guberman et al 1986; Agathonikou et al 1998). However, in only one-third of patients does absence status epilepticus end with GTCS when untreated. In the remaining patients, it may also terminate spontaneously without GTCS. It is exceptional for GTCS to precede or intersperse with typical absence status (Fagan and Lee 1990; Agathonikou et al 1998). It is also exceptional for more than one GTCS to occur following absence status epilepticus. Duration and frequency. Idiopathic (typical) absence status epilepticus usually lasts for an average of 3 hours to 4 hours, rarely a minimum of half an hour, often exceeding 6 hours to 10 hours, and occasionally enduring for 2 days to 10 days. Frequency also varies from 1 in a lifetime to an average of 10 to 20 or catamenial. This depends on treatment strategies and syndromic classification (Agathonikou et al 1998). Postictal state. Amnesia of the event is exceptional. The patient is usually aware of what happens during the absence status; some are able to write down their experiences, even when in status, and others have a patchy recollection of the events, usually missing the last part prior to GTCS. Following a GTCS, the patient feels tired, has a headache, and is confused for a varying duration of time. Age at onset and sex. It is rare for absence status epilepticus in idiopathic generalized epilepsy to start before the first decade. Other types of seizures such as absences, myoclonic jerks, and GTCS may predate the first occurrence of absence status epilepticus for many years. In the study of Agathonikou and colleagues, mean age at onset of absence status epilepticus was 29 years with a range of 9 years to 56 years (Agathonikou et al 1998). In 7 of 21 patients, absence status epilepticus was the first overt type of seizure; this was mainly the case in the syndrome of phantom absences with GTCS. Twelve of the 21 patients were women. Precipitating factors. These are also syndrome- and treatment-related. Inappropriate use or discontinuation of anti-absence medication is the most common precipitant of idiopathic absence status epilepticus. Sleep deprivation, stress, and excess of alcohol consumption, alone or usually combined, are common precipitating factors. Some patients may have catamenial precipitation. In others, this mainly starts on awakening. Lights precipitate absence status epilepticus in eyelid myoclonia with absences, a mainly photosensitive type of epilepsy. Cryptogenic or symptomatic (atypical) absence status epilepticus. Cryptogenic or symptomatic (atypical) absence status epilepticus is clinically characterized by fluctuating impairment of consciousness, often with other ictal symptoms such as repeated serial tonic or atonic seizures and segmental or generalized jerks. The ictal EEG pattern is of slow, less than 2.5 Hz spike and slow wave generalized activity (Commission of Classification and Terminology of the International League Against Epilepsy 1981; 1989; Aicardi 1994; Shorvon 1994; 1995). Both the clinical patterns and the EEG abnormalities are more variable than of the typical absence status epilepticus. The main distinction of atypical from typical absence status is that it occurs mainly in children with symptomatic or cryptogenic generalized epilepsies who also have a plethora of other types of frequent seizures such as atypical absences, tonic and atonic seizures, myoclonic jerks, and GTCS. Most of them also have moderate or severe learning and physical handicaps. In addition, interictal EEG is often abnormal with slow background and frequent brief or long runs of slow generalized spike-and-slow waves, paroxysmal fast activity, and paroxysms of polyspikes. It is often difficult to define the boundaries, onset, and termination of atypical absence status epilepticus because these children frequently have alterations of behavior and alertness as well as long interictal slow spike-and-slow wave discharges.|{diagram:asep2.bmp}{caption:Atypical absence status in symptomatic generalized epilepsy}{label:Video-EEG from a 9-year-old girl who had severe mental and physical deficits due to birth related brain anoxia. Slow spike and slow wave activity is continuously recorded. Despite video-EEG monitoring, it was difficult to detect overt clinical manifestations. The girl was probably less communicative and quieter during the discharge, which ended when she was alerted by the pain from inserting the drug infusion tube.}|As Aicardi stated, “No doubt, Lennox-Gastaut syndrome is commonly associated with distinct episodes of absence status, but in this condition all transitions may be found between distinct episodes of absence status and prolonged bad periods during which paroxysmal EEG activity is permanent and mental efficiency is fluctuating, at times, only in certain specific tasks” (Aicardi 1994). Atypical absence status epilepticus occurs in more than two-thirds of patients with Lennox-Gastaut syndrome. It may last days, weeks, or months and is highly resistant to treatment. "The EEG often becomes hypsarrhythmic and these status-like seizures constitute a reversible aggravation of the interictal symptomatology" (Beaumanoir and Dravet 1992). Additional discriminating features of atypical absence status epilepticus are:
Situation-related absence status epilepticus. De novo absence status epilepticus is often misdiagnosed as a psychotic state or dementia. EEG is probably mandatory in adults on neuroleptic drugs or withdrawal of diazepines who present with a confusional state. Drugs or electrolyte and metabolic disturbances. De novo absence status epilepticus is coined for this condition if it appears in adults, mainly middle age women, without antecedent history of epileptic seizures (Thomas et al 1992; Thomas and Andermann 1994; Thomas 1999). Most of the patients have a history of psychiatric disorders, and the main cause of absence status epilepticus is withdrawal of benzodiazepines. Thomas and colleagues reported absence status epilepticus in 11 middle-aged patients (10 female, 1 male; mean: 58.6 years) without a history of seizures (Thomas et al 1992). Absence status epilepticus coincided with benzodiazepine withdrawal in 8 cases. Cofactors included excessive use of mainly psychotropic drugs, hypocalcemia, hyponatremia, and chronic alcoholism. CT demonstrated mild cerebral atrophy in 6 cases. There was no recurrence, even without chronic antiepileptic treatment. The impairment of consciousness was mild, more often moderate, and rarely reached severe states of the patient becoming bedridden, stuporous, and incontinent. Half of the patients also had mainly facial myoclonic jerks, and one-third had automatisms. One-fourth of patients had GTCS either prior to or during the absence status epilepticus. The EEG pattern varied with continuous or more often short, repetitive recurrent bursts of generalized 0.5 Hz to 4 Hz spike- or polyspike-and-slow waves. Typical absence status manifested as prolonged confusional state with continuous 3 Hz spike-and-slow waves is also well documented after metrizamide myelography in nonepileptic patients (Vollmer et al 1985; Obeid et al 1988). The clinical and EEG features are easily reversible with diazepam intravenously. Hypoglycemia (Lennox 1945), hypocalcemia (Kline et al 1998), and uremia (Tanimu et al 1998) may also induce situation-related absence status epilepticus. Antiepileptic medication. There is an increasing number of reports of absence status epilepticus induced by certain antiepileptic drugs introduced for the treatment of "epilepsy". Vigabatrin and tiagabine are notable examples (Panayiotopoulos et al 1997a; Parker et al 1998; Ettinger et al 1999; Knake et al 1999; Panayiotopoulos 2001; Panayiotopoulos 2002). They even induce "de novo" absence status in patients with partial seizures. Despite their pro-absence effect, these drugs are used for the treatment of idiopathic generalized epilepsy, because the official bodies are casual in appropriately informing physicians regarding treatment and other respects of "epilepsies" (Panayiotopoulos 1999). The treatment of "epilepsy" is different in partial from generalized epilepsies. Absence status epilepticus in comatose or critically ill patients.
Comatose, mainly after severe brain anoxia, or critically ill patients
may have EEG features of absence status with continuous generalized spike
and wave complexes at 1 Hz to 3 Hz. When clinically possible to determine,
this may be associated with additional impairment of consciousness and
segmental facial, trunk, or limb jerking. These features are usually associated
with a fatal outcome. Prognosis does not appear to improve with treatment. DIAGNOSTIC WORKUP In idiopathic (typical) absence status epilepticus, all patients by definition
are of normal physical and mental state and have normal brain imaging.
Ictal EEG confirms the diagnosis with continuous, greater than 2.5 Hz
generalized spike-and-slow wave complexes.|{diagram:asep1.bmp}{caption:Typical
absence status epilepticus in idiopathic generalized epilepsy with phantom
absences}{label:Top: Video-EEG prior to diazepam. There was continuous
spike and occasional polyspike and slow wave activity mainly at 3-Hz that
lasted until the administration of diazepam. Note also slower or faster
components and some topographic variability of the discharge. The patient
was fully alert, attentive, and cooperative. Movements and speech were
normal. There were no abnormal ictal symptoms other than severe global
memory deficit and global diminution of content of consciousness. She
was unable to remember her name, how many children she had, date, and
location. She could not perform simple calculations but could repeat up
to 5 numbers given to her. She could read text correctly, and she wrote
her address correctly, although she could not remember it on verbal questioning.
She did not know where she was, but given the choice between various locations,
she correctly recognized that she was in the hospital. Bottom: Relative
normalization of the EEG started within a minute from onset of diazepam
administration and the patient was able to say the correct date, her address,
the name of the hospital and that she had one child and her name. Note
in EEG the fragmentation of the discharge and the reappearance of alpha
rhythm. She continued having problems with calculations and there were
still some memory disturbances even after the intravenous administration
of another 5 mg of diazepam and 400 mg of sodium valproate. However, she
was sufficiently well to be allowed to leave hospital with her husband
and she recovered completely at home.}||{diagram:asep3.bmp}{caption:Typical
absence status epilepticus in idiopathic generalized epilepsy with phantom
absences}{label:EEG (top) of absence status and "interictal video
EEG" (bottom) with phantom absences of a woman who had her first
absence status epilepticus followed by a generalized clonic-tonic seizure
at age 56 years. Initially, we erroneously classified her as de novo absence
status epilepticus instead of idiopathic generalized epilepsy with phantom
absences. This mistake became apparent when interictal video-EEG demonstrated
absences manifested with mild cognitive impairment and eyelid fluttering
(bottom). In reviewing this video-EEG with the patient and her daughter,
they recognized that these mild absences were occurring many years prior
to the absence status epilepticus. Note the similarity between the EEG
discharge of absence status epilepticus (top) and typical absence seizure
(bottom).}| Ictal EEG during the absence status may consist of repetitive
discharges of multiple spikes and slow waves.|{diagram:asep4.bmp}{caption:Absence
status epilepticus with repetitive discharges of unclassified generalized
epilepsy}{label:Continuous recording from video-EEG of a 48-year-old woman
with unclassified absences and GTCS from age 11 years. She realized from
previous experiences that she was in absence status epilepticus when she
felt “weird, like in a trance, missing pieces of conversation,”
and she went to the hospital. Despite written instruction, no diazepam
was administered. She was alert, attentive, cooperative, and well-behaved,
but she seemed depressed. Movement and speech were normal. She was able
to count with no errors except when the discharges between arrows occurred.
During these discharges, eyes, and sometimes mouth, would tonically open
with a slight retropulsion of the head. Video-EEG was recorded 7 hours
from onset of symptoms, which ended with a generalized tonic clonic seizure
one hour later.}|Interictal EEG of idiopathic generalized epilepsy usually
shows brief discharges with similar characteristics as those of the ictal
EEG.|{diagram:asep6.bmp}{caption:Interictal EEG of idiopathic generalized
epilepsy with phantom absences}{label:From interictal video-EEG. Brief
generalized discharges of 3 Hz spike and slow waves lasting 2 to 3 seconds
without apparent clinical manifestations. Similar abnormalities were recorded
in 1972 and again in 1997. Note the similarity of the discharge with the
ictal and immediately post-diazepam EEG. The only significant difference
is duration, brief interictally, continuous for hours ictally.}| Prognosis depends on the type of absence status epilepticus and syndrome. It may occur only once in a lifetime (situation related); it may be infrequent or preventive (as in most cases of idiopathic generalized epilepsy with typical absences); it may be frequent and intractable (which is often the case with symptomatic generalized epilepsies and atypical absences); or it may be associated with death due to the underlying severe medical condition (as in absence status epilepticus of severe brain anoxia). Absence status epilepticus often terminates spontaneously or with a
generalized tonic-clonic seizure. In most cases of idiopathic absence
status epilepticus, the patient is aware of this condition and the risk
of ending with GTCS. The role of self-administered drugs for its termination
should be addressed. Absence status epilepticus of any cause is treated with intravenous diazepam, other diazepines, or sodium valproate, but this may be available only in hospitalized patients (Panayiotopoulos 2001; Panayiotopoulos 2002).|{diagram:asep1.bmp}{caption:Typical absence status epilepticus in idiopathic generalized epilepsy with phantom absences}{label:Top: Video-EEG prior to diazepam. There was continuous spike and occasional polyspike and slow wave activity mainly at 3-Hz that lasted until the administration of diazepam. Note also slower or faster components and some topographic variability of the discharge. The patient was fully alert, attentive, and cooperative. Movements and speech were normal. There were no abnormal ictal symptoms other than severe global memory deficit and global diminution of content of consciousness. She was unable to remember her name, how many children she had, date, and location. She could not perform simple calculations but could repeat up to 5 numbers given to her. She could read text correctly and she rightly wrote her address though she could not remember it on verbal questioning. She did not know where she was but given the choice between various locations she correctly recognized that she was in the hospital. Bottom: Relative normalization of the EEG started within a minute from onset of diazepam administration and the patient was able to say the correct date, her address, the name of the hospital and that she had one child and her name. Note in EEG the fragmentation of the discharge and the reappearance of alpha rhythm. She continued having problems with calculations and there were still some memory disturbances even after the intravenous administration of another 5 mg of diazepam and 400 mg of sodium valproate. However, she was sufficiently well to be allowed to leave hospital with her husband and she recovered completely at home.}||{video:asep13.avi}{caption:Absence status epilepticus of late onset in idiopathic generalized epilepsy: response to treatment}{label:Sample from video-EEG of a patient immediately after the first intravenous diazepam of 5 mg was administered from 16:33:38 to 16:34:50. EEG shows relative normalization, the patient has significant improvement but complete recovery did not occur until the next day.}|Rectal preparations of diazepines as soon as the first symptoms of absence status epilepticus appear may stop it, but often this is not applicable (Panayiotopoulos 2001; Panayiotopoulos 2002). Some patients may prevent GTCS with sodium valproate (usually double of the daily dose) at the onset of absence status. A new development, which may be the best practical therapeutic option, is that buccal application of midazolam may stop absence status epilepticus and prevent the development of GTCS (Scott et al 1999). Ten milligrams of midazolam solved in a 2 ml peppermint (otherwise it smells and tastes terribly) should be swirled in the mouth for 4 to 5 min and then spat out. The parties involved should be informed that midazolam is not yet licensed for this type of treatment. Absence status epilepticus is syndrome and seizure related. Appropriate treatment of the responsible syndrome will also prevent absence status (Panayiotopoulos 2001; Panayiotopoulos 2002). Sodium valproate, ethosuximide and lamotrigine alone or in combination are the only first line drug agents in absence seizures (Panayiotopoulos 2001; Panayiotopoulos 2002). Choice between them depends on other than absences associated generalized seizures and adverse reactions. Sodium valproate controls absences in 75% of patients, GTCS in 70%, and myoclonic jerks in 75%, but because of adverse reactions may be undesirable for women. Similarly, lamotrigine may control absences in possibly 50% to 60%, GTCS in 50% to 60%, but may worsen myoclonic jerks; skin rashes are common. However, there are reports of patients developing absence status epilepticus after replacement of valproate with lamotrigine (Trinka et al 2002). Ethosuximide controls 70% of absences but has no effect on GTCS. Monotherapy should not be abandoned before making sure that maximum tolerated dose has been achieved if smaller doses have failed. If monotherapy fails or unacceptable adverse reactions appear, then replacement of one by the other is the alternative. Combination of any of these 3 drugs may be needed for resistant cases. The most effective combination treatment is sodium valproate with lamotrigine possibly because of a pharmacodynamic interaction between them. Minute doses of lamotrigine added to sodium valproate have a dramatic beneficial effect; small doses are also mandated because of increased adverse effects. Of the newer drugs, levetiracetam and topiramate appear highly promising (Panayiotopoulos 2002). Clonazepam, particularly in absences with myoclonic components or idiopathic generalized epilepsy with myoclonic jerks is a useful adjunctive drug. Acetazolamide may be also be used as an add-on drug (Panayiotopoulos 2001; Panayiotopoulos 2002). Contraindicated drugs. Carbamazepine (Parker et al
1998; Osorio et al 2000), vigabatrin (Panayiotopoulos et al 1997a), and
tiagabine (Ettinger et al 1999; Knake et al 1999; Kellinghaus et al 2002)
are contraindicated in the treatment of absence seizures, irrespective
of cause and severity (Panayiotopoulos 2002). In particular, vigabatrin
and tiagabine, which are GABA agonists, may induce instead of treat absence
seizures and absence status epilepticus. Similarly, phenytoin, (Osorio
et al 2000), phenobarbitone, and gabapentin should not be used in the
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ILAE ILAE Copyright Notice ABBREVIATIONS SYNONYMS Petit mal status SUBTOPICS Idiopathic (typical) absence status epilepticus MAJOR KEYWORD DESCRIPTORS atypical absences MINOR KEYWORD DESCRIPTORS altered state of consciousness AGE OF PRESENTATION 0-01 month AGE OF TYPICAL PRESENTATION 01-23 months GLOSSARY - ILLUSTRATION CAPTIONS
Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Video-Clips Video clip 2 Video clip 3 Legend for video clip 4. Sample from an interview in 1997 with the patient of the clinical vignette. Legend for video clip 5. Another sample from an interview in 1997 with the patient of the clinical vignette. Video clip 6 PERMUTED TOPIC, SYNONYMS, VARIANTS RELATED TOPICS DIFFERENTIAL DIAGNOSIS
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