Subtle status epilepticus

Lawrence J Hirsch MD (Dr. Hirsch of Yale University School of Medicine received consultation fees from Ceribell, Marinus, Monteris, Neuropace, Sun Neuroscience, Sunovion, and Upsher Smith; research support from Lundbeck, Acorda, Upsher Smith, Eisai, and Sunovion; and honoraria for speaking from Neurospace.)
Daniel Friedman MD (Dr. Friedman of the New York University Comprehensive Epilepsy Center has no relevant financial relationships to disclose.)
Jerome Engel Jr MD PhD, editor. (Dr. Engel of the David Geffen School of Medicine at the University of California, Los Angeles, has no relevant financial relationships to disclose.)
Originally released August 20, 2007; last updated September 3, 2015; expires September 3, 2018

This article includes discussion of subtle status epilepticus, subtle generalized status epilepticus, electrographic status epilepticus, status epilepticus in coma, nonconvulsive status epilepticus, nontonic-clonic status epilepticus, subclinical status epilepticus, status myoclonus, and status epilepticus terminans. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

As a subgrouping of status epilepticus, subtle status epilepticus is used to describe the clinical and electroencephalographic findings in a comatose patient after prolonged convulsive status epilepticus who has subtle or no movements, but periodic discharges on EEG. In this article, the authors describe the current thinking and controversies surrounding the classification, diagnosis, and treatment of subtle status epilepticus. The term “status epilepticus terminans” is defined and suggested as a less ambiguous and more specific term for this phenomenon.

Key points

 

• Subtle status epilepticus describes the condition after a period of tonic-clonic activity where obvious convulsive activity has ceased, but the patient remains comatose, with periodic discharges on EEG. We have termed this specific scenario “status epilepticus terminans,” and use the more general term for any status epilepticus with subtle clinical signs.

 

• Subtle status epilepticus is among the spectrum of disorders associated with rhythmic or periodic EEG discharges, altered mental status, and without overt motor manifestations. This spectrum includes nonconvulsive seizures, nonconvulsive status epilepticus, and the ictal-interictal continuum.

 

• Patients may be comatose with or without eye deviation or nystagmus and subtle focal or multifocal myoclonic face or limb movements; none of these signs is specific for ongoing ictal activity. EEG is required for diagnosis.

 

• Subtle status epilepticus, often refractory to treatment, is associated with significant morbidity and mortality. There is no consensus on the best treatment strategy.

Historical note and terminology

The first mention of subtle status epilepticus appeared in an abstract by Dr. David Treiman and colleagues from UCLA (Treiman 1984). They defined subtle status epilepticus as consisting of “nystagmus, eye blinking, and/or mild motor movements…with marked impairment of consciousness and continuous or nearly continuous, usually bilateral, ictal patterns on the EEG.” They also noted that 3 of their 10 patients continued to have ictal EEG activity after all movements ceased. Five of the patients had severe encephalopathy. The abstract also states that although the ictal patterns were usually bilateral, all 10 patients had periodic, lateralized, epileptiform discharges. Resolution of the EEG discharges seemed to be associated with better outcome. Late 19th- and early 20th-century writers, however, were well acquainted with this later phase of status epilepticus lacking convulsive activity, which they termed the “meningitic” or “stuporus” stage (Neligan and Shorvon 2009). Treiman has expanded on his definition in multiple subsequent articles. He points out that some patients may have had only an isolated convulsion (rather than convulsive status epilepticus) prior to being in subtle status epilepticus and that some may have never had a recognized convulsion. Although most patients probably have a focal component at some point, Treiman notes that periodic discharges tend to become bilateral even if generated from a single focus (Treiman 1995). In his landmark publication of the Veterans Affairs Status Epilepticus Cooperative Study, Treiman noted that subtle status epilepticus was considered present in patients with coma and ictal discharges (it is unclear if periodic discharges were included, but presumably they were) “with or without subtle movements (rhythmic twitching . . .; tonic eye deviation; or nystagmoid eye jerking)” (Treiman et al 1998). Thus, even patients with no clinical manifestations other than coma were included as having subtle status epilepticus. In other papers, he refers to this situation as “electrographic status epilepticus” once the clinical manifestations (other than coma) have progressed from subtle to absent. Thus, he describes a continuum of status epilepticus from convulsive to subtle to electrographic.

The literature since then has evolved significantly as more intensive care unit patients undergo prolonged digital EEG monitoring. Many authors have described the above phenomenon at the end of convulsive status epilepticus with a variety of terms (or no specific term at all), and many authors (including the authors of this article) have used the term subtle status epilepticus in a less specific way, including any electrical status epilepticus with subtle (and sometimes no) clinical manifestations (Simon and Aminoff 1986; Drislane and Schomer 1994; Privitera et al 1994; So 1995; Jaitly et al 1997; DeLorenzo et al 1998; Lowenstein and Alldredge 1998; Nei et al 1999; Brenner 2002; Husain et al 2003; Mirski 2005; Jirsch and Hirsch 2007). Subtle status epilepticus is sometimes considered a subset of nonconvulsive status epilepticus and sometimes a subset of convulsive status epilepticus.

In 2005, the Epilepsy Research Foundation published a report detailing a discussion on a classification scheme for nonconvulsive status epilepticus where subtle status epilepticus was described as nonconvulsive status epilepticus in a comatose patient after convulsive status epilepticus with electrographic seizure activity demonstrating unilateral or bilateral periodic discharges (Walker et al 2005). Later in the report, the authors state that subtle status epilepticus is “otherwise known as status epilepticus in coma” and is probably more similar to refractory convulsive status epilepticus than nonconvulsive status epilepticus (Walker et al 2005). Meierkord and Holtkamp define subtle status epilepticus as “a form of nonconvulsive status epilepticus that develops from generalized convulsive status epilepticus if the latter has been treated insufficiently or not treated at all”; they further suggest that this term be applied only when there are documented EEG findings (not further defined) and prior overt convulsive seizure activity (Meierkord and Holtkamp 2007).

Thus, there is clearly no current consensus on terminology in this area; in fact, there is no consensus on any of the key features: the clinical scenario to which it applies, the clinical correlates or lack thereof, or the EEG findings and whether they are a necessary component of the definition.

The ILAE Classification Core Group (Engel 2006a; Engel 2006b) now lists subtle status epilepticus as a subclassification of status epilepticus in general and gives the following description:

 

…an end stage of prolonged generalized tonic-clonic status epilepticus characterized by focal or multifocal myoclonic movements, coma, and periodic lateralized epileptiform discharges against a slow, low-voltage background on EEG. The myoclonic movements reflect severe brain damage caused by prolonged status epilepticus and may not be epileptic in nature (Engel 2006a; Engel 2006b).

Although this description does not consider all of the features cited by Treiman and others (eg, generalized periodic discharges, ictal nystagmus without myoclonic movements, or the same situation after an isolated convulsion), it was not meant to be an all-inclusive definition and would accept these scenarios as well (J Engel, personal communication).

Kaplan and Sutter described the electrographic features associated nonconvulsive status epilepticus, which they subdivided into different entities with distinct (though often overlapping) clinical and electrographic features (Sutter and Kaplan 2013). For purposes of discussion in this article, we will suggest and use the following definition for the concept of subtle status epilepticus in the aftermath of convulsive seizure activity. To distinguish this from the nonspecific use of the term when referring to any situation when electrographic status epilepticus or periodic discharges are associated with subtle or no clinical manifestations, we suggest the term “status epilepticus terminans” as defined below.

 

Status epilepticus terminans: a condition after overt convulsive seizure activity in which the patient is comatose for at least 30 minutes, has periodic epileptiform discharges on EEG, and has subtle or no clinical correlate other than coma. The preceding convulsive seizure activity can be of any duration, and the periodic discharges can be lateralized or generalized.

When referring to the nonspecific use of the term for any situation with subtle or no clinical manifestations of ictal EEG activity, we will use the phrase “broad definition.”

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