Neurol Sci (2006) 27:S52–S54 DOI 10.1007/s10072-006-0549-3
NEUROLOGICAL EMERGENCIES
F. Minicucci • A. Bellini • G. Fanelli • M. Cursi • C. Paleari • S. Dylgjeri • G. Comi
Status epilepticus
Abstract Status epilepticus (SE) is a medical emergency. It requires prompt and adequate diagnosis and treatment, as it may induce CNS injury. It is mainly distinguished into generalised and partial SE on the basis of its major clinical features. There are very few data about SE physiopathology, but it is generally characterised by increasing unresponsiveness to treatment. SE diagnosis is based on EEG recording, associated with neuroimaging techniques and laboratory assays to detect underlying pathologies. During SE we distinguish three different conditions: initial, defined and refractory. Benzodiazepines represent first-line treatment, followed by phenytoin. Refractory SE requires ICU treatment to perform general anaesthesia.
Introduction
Key words Status epilepticus • Seizure • EEG • AEDs
Definition
In the past centuries, status epilepticus (SE) was probably considered as a prolonged “repetition of seizures”, but it was not recognised as a specific disease. Nevertheless, SE requires proper description and specific diagnostic definition. It is associated with severe systemic accidents [1], thus requiring aggressive therapeutic strategies. SE often occurs as a symptom of an underlying disease, but it may also represent a disease per se. SE is a self-sustained process, with a progressive course.
During the Marseilles Colloquium in 1962, Gastaut collected 237 cases of abnormally prolonged or repeating seizures. In 1967 Gastaut [2] defined SE as “a condition characterised by epileptic seizures that are sufficiently prolonged and repeated at sufficiently intervals so as to produce an unvarying and enduring condition”. Not only generalised convulsive or complex partial seizures, but every kind of seizure, had to be recognised as a SE, whenever it repeated for sufficient time to constitute a stable epileptic condition. Shorvon [3] defined SE as “a condition in which epileptic activity persists for 30 minutes or more, causing a wide spectrum of clinical symptoms, and with highly variable pathophysiological, anatomical and aetiological basis”. American Authors reduced the epileptic activity duration required to define SE to 10 min. They aimed to justify praecox treatment.
F. Minicucci () • A. Bellini • G. Fanelli M. Cursi • C. Paleari • S. Dylgjeri • G. Comi Ospedale San Raffaele Servizio di Neurofisiologia Clinica Via Olgettina 60, I-20132 Milan, Italy e-mail:
[email protected]
Physiopathology In experimental settings, the same triggers are able to generate both seizures and SE, but they must be applied at different intensities. In human experience, some conditions
F. Minicucci et al.: Status epilepticus
appear more strongly associated to SE (e.g., anticonvulsant treatment withdrawal, fever and metabolic derangements). During SE the mechanisms that generally limit a seizure fail for unknown reasons. Lothman proposed a reduction in GABA inhibition and a higher sensitivity to extra-cell ion concentrations as a possible explanation [1].
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infections. Low plasmatic levels of antiepileptic drugs in epileptic population, alcohol intoxication and traumatic brain injury predict a better outcome.
Aetiology
In animal models of SE different mechanisms have been demonstrated to be able to induce CNS injury. Our knowledge of SE in human pathology is even more limited. There are a few data clearly demonstrating that a partial SE may induce CNS injury [4], even though it is strongly suspected, justifying an aggressive treatment.
Aetiology depends on age. The most common aetiologies are stroke (10%), traumatic brain injury (10%), cerebral neoplasms (7%), CNS infections (9%), metabolic or toxic encephalopathies and electrolyte disorders (14%). No clear aetiology can be identified in 20% of the cases, especially in patients with a previous diagnosis of epilepsy [3]. In the epileptic population more than 50% of SE depends on voluntary or accidental withdrawal of chronic anticonvulsant treatment. Aetiology is the major prognostic factor in SE [8].
Classification
Diagnosis
A generally accepted classification of SE does not exist. It is commonly classified according to its major clinical features. We usually distinguish generalised and partial SE. The lack of correlation with the general clinical conditions limits the utility of this distinction as a prognostic tool. Partial or generalised motor manifestations of the epileptic cerebral activity constitute the major criteria in different classifications. In the literature the term “non convulsive status epilepticus” is often used, defining both “absence SE” and complex partial SE. It is also used to define particular clinical conditions in which comatose patients present an electrographic status with or without myoclonic jerks. Myoclonic SE in anascic-ischaemic patients is associated with poor prognosis [5]. It must be distinguished from myoclonic encephalopathy and acute intoxications.
SE diagnosis mainly depends on clinical evaluation. Nevertheless, partial SE may be difficult to recognise, especially in ICU comatose patients or in the presence of significant motor impairment. EEG represents the main tool for SE diagnosis, in strict association with clinical features. EEG monitoring is also essential to verify SE course and response to treatment. Neuroimaging techniques are also required to understand SE aetiology and to detect potential underlying pathologies.
Neuropathology
Epidemiology There are no final data about SE incidence, partly because it is not always recognised, particularly in comatose patients [6]. The annual incidence estimate of SE varies according to the different surveys, ranging from 9.9/100 000 to 41/100 000. SE mortality varies from 1 to 22% in different series. Hauser [7] indicates 2% as the higher mortality value actually depending only on SE. There are no studies demonstrating different mortality rates for the different clinical presentation of seizures but a higher morbidity for GCSE is commonly accepted. Prognostic indicators of poor outcome are: SE lasting more than one hour, anoxic aetiology, old age and CNS
Treatment Pharmacological treatment must be associated with general management procedures to guarantee ventilation and cardiovascular functions. General blood screening is required. During SE we distinguish three different conditions [1]: 1. initial (within 20–30 min); 2. defined (within 60–90 min); 3. refractory (longer than 60–90 min). First-line treatment is represented by benzodiazepines [9] - lorazepam 0.05–0.1 mg/kg i.v. - diazepam 0.1 mg/kg i.v. If full doses of benzodiazepines fail in controlling seizures, a second-line treatment is required [10]: - phenytoin: 15–18 mg/kg i.v. If contraindicated [11]: - sodium valproate 15 mg/kg i.v. followed by 1–2 mg/kg/h continuous infusion; - phenobarbital: 10–20 mg/kg i.v.
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Refractory SE requires a more aggressive treatment, which has to be performed in the ICU. EEG monitoring is required [12]: - Thiopentone 5–7 mg/kg i.v. followed by 50 mg boluses at intervals of 2–3 min until EEG “suppression burst” pattern is obtained. Subsequent continuous infusion (3–5 mg/kg/h) for 12–48 h. - Propofol 2–5 mg/kg i.v. followed by continuous infusion (till 5 mg/kg/h) for one hour or more. - Midazolam 5–10 mg i.m. or rectal route; 0.1–0.3 mg/kg bolus i.v., 10 mg buccal instillation, 0.05–0.4 mg/kg/h. i.v. Inhaled anaesthetics (isoflurane) and lidocaine must be used only in ICU by trained physicians and in selected patients.
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