Place de l’électroencéphalogramme dans l’état de mal épileptique

Recordings of the electroencephalogram (EEG) play a major role in the management of patients with status epilepticus (SE). The EEG contributes to the diagnosis of SE, can be used to identify differential and syndromic diagnoses, and sometimes provides the etiologic diagnosis. EEG is helpful in monitoring therapeutic management and is an essential component of the follow up. The interpretation of the EEG in a patient with refractory SE is difficult, requiring clinical experience in this domain. We discuss the different modalities of EEG recording and their indications in emergency situations.     

Recherche étiologique lors d’un état de mal épileptique

Because of the wide range of etiologies which may provoke status epilepticus (SE), physical examination, laboratory tests and neuroimaging must be conducted according to a well-designed hierarchical system. While implementing intensive care management, clinicians must of course search for curable causes but also consider the possible interaction of multiple factors and hidden diseases favoring or triggering SE. Causes of SE in idiopathic or cryptogenic epilepsy and new-onset SE do not correlate but careful analysis of serum chemistry and neuroimaging abnormalities must nevertheless be conducted with the specific objective of establishing an etiological diagnosis.     

Bases physiopathologiques des états de mal épileptiques

The mechanisms that induce epileptic activity and make it durable, leading to status epilepticus (SE), are poorly known. They probably result from an imbalance between the activating systems of neuronal depolarisation (excitatory amino acids release with postsynaptic N-methyl-d-aspartate [NMDA] receptor activation, spreading depolarisation following abnormal progression) and the inhibiting systems (GABAergic synapses). Status epilepticus leads to many direct and indirect cerebral disorders, as well as systemic disorders, with intertwined mechanisms and consequences. These disorders are more frequent in case of convulsive SE with generalized tonic-clonic seizures. Direct neuronal damage (selective neuronal loss and epileptogenesis) results mostly from excitotoxicity, which arises from enhanced and extended neuronal activation. Indirect neuronal damage results from the inability of the circulatory system to supply sufficient oxygen and glucose contribution compared to the high metabolism level of the highly depolarized and synchronized neurons. This energetic deficit is usually patent after 30 minutes of SE, when systemic compensation mechanisms (cardiac output increase) are exhausted. Understanding these pathophysiologic aspects is essential for effective treatment of SE.     

Diagnostics différentiels des états de mal épileptiques

The diagnosis of status epilepticus can be retained, wrongly, in several circumstances. Nonepileptic pseudoseizures from a psychiatric origin and some movement disorders can mimic convulsive status epilepticus. Encephalopathy of various causes (post-anoxic, metabolic, toxic, Creutzfeldt-Jakob disease) can be wrongly taken for non-convulsive status epilepticus, mainly due to inadequate interpretation of the electroencephalogram (EEG). In these encephalopathies, the existence of (non-epileptic) myoclonus and the abolition of the EEG abnormalities with the use of a benzodiazepine (without correction of the clinical symptoms) are additional confounding factors, leading to false diagnosis. Nevertheless, in general, the diagnosis of status epilepticus can be confirmed or rejected base on a combined analysis of the clinical data and the EEG.     

Prise en charge non spécifique de l’état de mal épileptique convulsif

The systemic consequences of status epilepticus occur in two stages: the first stage is a hyperadrenergic period (high blood pressure, tachycardia, arrhythmia, hyperventilation, hypermetabolism, hyperthermia), the second stage a collapsus period, sometimes with acute circulatory failure, and hypoxemia. Symptomatic resuscitation aimed at restoring vital functions should be undertaken. Resuscitation must be started immediately before hospital transfer, by a trained emergency team. Respiratory care includes at least oxygen intake, but it can also require oral intubation (crash induction) and mechanical ventilation. The arterial blood gas objectives are SaO₂ ≥ 95%, and 35 mmHg ≤ PaCO₂ ≤ 40 mmHg. Fluid and electrolyte care includes intravenous infusion of normal saline, with control of sodium and calcium levels as well as blood pH within normal limits. Heart rate and blood pressure must be monitored. Mean blood pressure must be kept between 70 and 90 mmHg, first by means of plasma volume expansion, and then norepinephrine if necessary. Hyperthermia must be corrected to prevent further neuronal damage. Cerebromeningeal sepsis should be ruled out. Capillary glucose (most often elevated) must be corrected using a pre-established insulin infusion algorithm. Rhabdomyolysis is rare, but can result in hyperkaliemia, acidosis, and acute renal failure. In case of associated intracranial hypertension (traumatic, vascular or infectious injury), status epilepticus is considered as a secondary insult for the brain, that can worsen neuronal damage. Numerous compounds have experimental neuroprotective properties, but none have proven significant efficacy in clinical conditions. Nevertheless, convulsion cessation is considered as a neuroprotective measure.     

L’épreuve d’anticipation, une étude de cas

In the field of psychology, very few studies deal with anticipation, the latter being defined as a paradoxical conduct. This paper describes a specific instrument elaborated by Mr Berta. The examined person is asked to imagine what he would wish to become in other life. Thus, he describes this imagery life that is located between two poles; one is rejected, the other ardently desired. Usually, this double attitude is illustrated by imagery. The negative pole (i.e. what the person is fighting) is actually what he does not want to become but as he struggles he actually develops in himself this unwanted, negative pole. The writers provide a clinical vignette, a woman called Mrs B. hospitalized for a depressive state consecutive to her husband’s death. Her protocole shows that she still is strong enough to integrate the bereavement. This way of organizing the psyche between the two poles thus having recourse to deep ethic values provides with innovating psychotherapeutic strategies.     

Traitement pharmacologique de l’état de mal réfractaire

Status epilepticus (SE) refractory to benzodiazepines and other antiepileptic agents is managed with intravenous anesthetic compounds, such as thiopental, propofol or midazolam. These drugs display quite different pharmacodynamic and pharmacokinetic properties, but have not been prospectively compared to date. Their use is clearly advocated for the treatment of generalized convulsive SE, whereas partial-complex, or absence SE are generally managed less aggressively, in consideration of their better prognosis. The most important aspect seems to be related to the correct use of these anesthetics in the right context, rather than the choice of one specific compound. An electroencephalographic burst-suppression should be targeted for about 24 hour, before progressive weaning of the dosage under EEG monitoring. If this approach proves unsuccessful, the use of other drugs, including inhalational anesthetics, has been described.     

Pronostic de l’état de mal chez l’adulte

Most investigations on prognosis of status epilepticus (SE) have focused on mortality, and suggest that outcome basically depends on the etiological and biological background. However, some recent studies also suggest that SE itself could be an independent predictor of death. Conversely, very little work has been published concerning the impact of SE on cognition. As compared with a first brief epileptic seizure, an incident SE episode seems to increase the risk of developing epilepsy.     

Prise en charge d’un état de mal épileptique de l’enfant (nouveau-né exclu)

Convulsive status epilepticus in childhood is a life threatening condition with serious risk of neurological sequelae which constitutes a medical emergency. Clinical and experimental data suggest that prolonged seizures can have immediate and long-term adverse consequences on the immature and developing brain. So the child who presents with a continuous generalized convulsive seizure lasting greater than five minutes should be promptly treated. The outcome is mainly determined by the underlying etiology, age and duration of status epilepticus. In children the mortality from status epilepticus ranges from 3 to 5% and the morbidity is two-fold higher. Mortality and morbidity are highest with status epilepticus associated with central nervous system infections, which is the most important cause of status epilepticus. There are few evidence-based data to guide management decisions for the child with status epilepticus. Immediate goals are stabilization of airways, breathing and circulation and termination of seizures. Benzodiazepines remain the first-line drugs recommended for prompt termination of seizures. As intravenous lorazepam is not available in France, we suggest clonazepam as the best choice for initial therapy. Rectal diazepam or buccal midazolam remain important options. Intravenous phenytoin/fosphenytoin and phenobarbital are the second-line drugs. Phenytoin is being increasingly substituted by fosphenytoin, but pediatric data are scarce and fosphenytoin is not authorized for use in France below five years old. In children, phenytoin is often preferred to phenobarbital, even though no comparative studies have demonstrated a better efficacy. To manage status epilepticus refractory to a benzodiazepine and administration of phenytoin and/or phenobarbital, many pediatricians today prefer high-dose midazolam infusion rather than thiopental to minimize serious side effects from barbiturate anesthesia. There is no benefit/risk ratio to support the use of propofol for children with refractory status epilepticus.     

Pharmacologie des agents utilisés dans l’état de mal épileptique

The pharmacokinetics and pharmacodynamics of major antiepileptic agents are presented. The onset of action and the factors leading to extraction across the blood brain barrier are described as well as the mechanism and extent of metabolism, and the main interactions with other drugs. For each class, the dosing scheme and practical issues related to administration are described, based on evidence when available in the literature.     

États de mal épileptiques non convulsifs

Non convulsive confusional status epilepticus is classically divided on the basis of the ictal EEG into absence status (AS) and complex partial status epilepticus (CPSE). The clinical presentation is often insufficient to establish diagnosis and emergency EEG is required. AS is a polymorphic condition that can complicate many epileptic syndromes. In half of cases, confusion of varying intensity is associated with bilateral periocular myoclonias. Clinical and EEG normalization is obtained after intravenous benzodiazepine injection. From a nosographic point of view, four types of AS may be recognized. Typical AS occurs as part of an idiopathic generalized epilepsy. Atypical AS occurs in patients with symptomatic or cryptogenic generalized epilepsies. “De novo” AS of late onset is characterized by toxic or metabolic precipitating factors in middle-aged subjects with no previous history of epilepsy. AS with focal characteristics occurs in subjects with a preexisting or newly developing partial epilepsy, most often of extratemporal origin. Most cases are transitional forms between these four entities. CPSE is characterized by continuous or rapidly recurring complex partial seizures which may involve temporal and/or extratemporal regions. Cyclic disturbance of consciousness is characteristic of CPSE of temporal lobe origin, which requires vigorous treatment to prevent recurrence or cognitive sequelae. CPSE of frontal lobe origin is a diagnostic challenge: it is rare, the symptoms are unusual, and extensive documentation is required. A focal, frontal lesion is discovered in one third of cases.