How urgent is the treatment of nonconvulsive status epilepticus?
Article first published online: 30 OCT 2007
Volume 48, Issue Supplement s8, pages 44–45, November 2007
How to Cite
Thomas, P. (2007), How urgent is the treatment of nonconvulsive status epilepticus?. Epilepsia, 48: 44–45. doi: 10.1111/j.1528-1167.2007.01347.x
- Issue published online: 30 OCT 2007
- Article first published online: 30 OCT 2007
Status epilepticus may be classified for practical purposes into convulsive status epilepticus, which must be rapidly stopped to prevent death or neurologic sequelae, and nonconvulsive status epilepticus (NCSE), which is usually characterized by some degree of clouding of consciousness. This latter condition constitutes a diagnosis challenge, because it often goes unrecognized or is mistaken for behavioral or psychiatric disturbances. Emergency EEG is the key feature for diagnosis. NCSE are classically divided on the basis of the ictal EEG into absence status (AS), with predominantly symmetrical synchronous ictal discharges and complex partial status epilepticus (CPSE), with continuous or rapidly recurring complex partial seizures that may involve temporal and/or extratemporal regions (Shorvon, 1994).
NCSE should obviously be rapidly treated because of the acute neurologic impairment of the patients, because of the attendant morbidity including physical injury, and because it may evolve on to generalized convulsions. There is reasonable concern about possible long-term effects, but long-term permanent neurologic damage from NCSE occurring in ambulatory patients has not yet been firmly documented as a mandate for aggressive treatment (Drislane, 1999).
Despite its high recurrence rate, typical AS occurring in idiopathic generalized epilepsies almost always present a rapid and spectacular response to intravenous benzodiazepines. Anecdotal case reports in which AS lasted as long as weeks or even months recovered without any sequelae. Despite the lack of long-term follow-up studies, there is no scientific evidence that typical AS has any effect either on cognitive functions, or on the natural history of the underlying epileptic syndrome (Drislane, 1999). The influence of atypical AS on the cognitive prognosis in cryptogenic or symptomatic generalized epilepsies is not as clear. In most instances, AS does not appear to have any significant effect. This is, however, a subject of debate. Doose and Völzke believe that repetitive AS may aggravate intellectual deterioration in children with myoclonic-astatic epilepsy (Doose and Volzke, 1979). Manning and Rosenbloom reported 13 children with atypical AS followed by a deterioration of their mental handicap, suggesting aggressive treatment for their epilepsy (Manning and Rosenbloom, 1987). However, in these reports, formal premorbid neuropsychological evaluation was lacking, and deterioration may also have been induced by the progression of the underlying disease.
Although experimental partial SE of the limbic system, using pilocarpine, kainic acid, or various protocols using electrical stimulation can cause neuronal damage, the great majority of patients with CPSE are successfully treated without sequelae, even after several recurrences or a very long duration. Transient disturbances of memory, cognitive function, or personality are, however, common and in our experience resolve after days to weeks. Despite the fact that most documented reports of CPSE reveal favorable outcome with or without prompt medical treatment (Kaplan, 1999; Kaplan, 2000a), there is still a strong debate regarding the morbidity of CPSE (Krumholz, 1999; Kaplan, 2000b). However, unfavorable outcomes in patients without underlying comorbid factors have been only exceptionally documented: patients reported by Treiman et al. (1981) and Engel et al. (1978) had severe and prolonged amnesia which was permanent in one case. Similar unfavorable outcome was documented in a personal, unpublished observation with limbic CPSE of very long duration. On the contrary, patients with an acute brain lesion causative of CPSE may have a much more unfavorable progonis: Krumholz et al. reported a series of 10 consecutive patients with three deaths, four patients with permanent memory disturbance (two of which were severe), and three with memory and cognitive disturbances lasting longer than three months (Krumholtz et al., 1995). However, most of these patients had lesions that could produce in themselves permanent sequelae, such as viral encephalitis or acute stroke. Another problem is that CPSE occurring with an acute brain lesion may cause long-term worsening of the associated neurologic dysfunction (Hilkens and De Weerd, 1995). Significant increase in neurospecific enolase, a marker of neuronal damage, has been reported in a series of 8 consecutive adult patients with CPSE (DeGiorgio et al., 1996), but can also result of the seizure activity by itself. These reports argue in favor of vigorous treatment, especially when CPSE complicates an acute brain lesion, because seizures and lesion may act synergistically to worsen brain damage: in a retrospective assessment of acute morbidity and mortality in NCSE (Shneker and Fountain, 2003), mortality rates were higher in patients with an actute medical etiology (27%) versus the epilepsy (3%) and the cryptogenic (18%) groups. However, early and agressive treatment with intravenous anticonvulsants (e.g., benzodiazepines or phenytoin) can confer morbidity and must be put in balance in ambulatory patients with a relatively benign outcome. A staged approach that avoids overtreatment is probably the best option.
In the recent years, many studies tend to lump together NCSE, subtle SE, myoclonic SE in coma, and EEG patterns suggestive of SE in comatose patients (Towne et al., 2000; Mayer et al., 2002). In this group, the overall prognosis is poor, with a low response to antiepileptic drugs, but it may be particularly difficult to separate co-morbidity to consequent morbidity. Post–hypoxic-ischemic encephalopathy, a life-threatening condition that can express itself in the form of coma, EEG changes and myoclonus illustrates such methodological problems: in the Veterans Affairs study (Treiman et al., 1998), 24% of the patients had subtle SE with a death rate of 65%, with hypoxic-ischemic encephalopathy as the cause in 38% of cases, whereas in the EPISTAR study (Coeytaux et al., 2000), which excluded hypoxic-ischemic encephalopathy, only 1.2% of patients had subtle SE. We believe that this conceptual extension may increase nosographic problems, and that in most instances, these cases may not represent NCSE per se.
- 2000) Incidence of status epilepticus in French-speaking Switzerland: (EPISTAR). Neurology 55:693–637. , , , . (
- 1996) Neuron-specific enolase, a marker of acute neuronal injury, is increased in complex partial status epilepticus. Epilepsia 37:606–609. , , , , , . (
- 1979) Petit Mal status in early childhood. Neuropediatrie 10:10–14. , . (
- 1999) Evidence against permanent neurologic damage from nonconvulsive status epilepticus. J Clin Neurol 16:323–331. . (
- 1978) Prolonged partial complex status epilepticus: EEG and behavioral observations. Neurology 28:863–869. , , . (
- 1995) Non-convulsive status epilepticus as cause for focal neurological deficit. Acta Neurol Scandinvia 92:193–197. , . (
- 1999) Assessing the outcomes in patients with nonconvulsive status epilepticus: nonconvulsive status epilepticus is underdiagnosed, potentially overtreated, and confounded by comorbidity. J Clin Neurophysiol 16:341–352. . (
- 2000a) Prognosis in nonconvulsive status epilepticus. Epileptic Disord 2:185–193. . (
- 2000b) No, some types of nonconvulsive status epilepticus cause little permanent neurologic sequelae (or: “the cure may be worse than the disease”). Neurophysiol Clin 30:377–382. . (
- 1995) Complex partial status epilepticus accompanied by serious morbidity and mortality. Neurology 45:1449–1504. , , , , , . (
- 1999) Epidemiology and evidence for morbidity of nonconvulsive status epilepticus. J Clin Neurophysiol 16:314–322. . (
- 1987) Non-convulsive status epilepticus. Arch Dis Child 62:37–40. , . (
- 2002) Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 59:205–210. , , , , , . (
- 2003) Assessment of acute morbidity and mortality in nonconvulsive status epilepticus. Neurology 61:1066–1073. , . (
- 1994) Complex partial status epilepticus. In: ShorvonS. (Ed) Status epilepticus, its clinical features and treatment in children and adults. Cambridge University Press, Cambridge , pp. 116–130. . (
- 2000) Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 54:340–345. , , , , , , . (
- 1981) Impairement of memory following complex partial status epilepticus. Neurology 31(Supp 4):S109. , , . (
- 1998) A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med 339: 792–798. , , , , , , , , , , , . (