Status epilepticus (SE) is the term given to prolonged seizure activity that is of sufficient duration to produce a “fixed and lasting epileptic condition” or neuronal injury and has a substantially increased risk of death.¹ SE has been formally defined as seizures lasting longer than 30 minutes. The most common and easily understood form is generalized convulsive status epilepticus (GCSE), which is characterized by continuous or recurrent convulsive motor seizures of more than 30 minutes’ duration (see Chapter 24). All other forms are grouped under the rubric of nonconvulsive status epilepticus (NCSE). NCSE is fundamentally divided into complex partial status epilepticus (CPSE) and absence status epilepticus (a form of generalized status epilepticus; see Chapter 26). This chapter focuses on CPSE, but it includes some discussion of absence SE because of inevitable overlap.

CPSE describes a variety of clinical entities in which impairment due to focal seizure activity persists for at least 30 minutes. The clinical presentations and natural history of CPSE are diverse. The diagnosis usually is straightforward when epileptic behavior and electroencephalographic (EEG) activity are evident. For example, in its pure form, there is the obvious recurrence of complex partial clinical and electrographic seizures (Figure 25-1). However, evidence of CPSE may be difficult to observe because it can occur in subtle forms within a spectrum of manifestations.

The diagnosis is usually contingent on the presence of focal seizure activity on EEG. EEG at the onset of CPSE shows focal discharges and seizures with complex partial symptomatology. It is the usual pattern of prolonged SE that discharges eventually appear generalized on the EEG even if they were focal at the onset. The EEG discharges of CPSE often generalize by the time an EEG is obtained. Thus, scalp EEG may show generalized or bilateral discharges, often with lateralized features, even when seizures are primarily occurring or originating in one region of the brain. If only the EEG is considered, then some patients with SE of focal origin will be considered to have generalized NCSE. To resolve this, the remainder of the clinical picture must be considered. Thus, presentation of CPSE varies by degree of symptoms, EEG focality, and presence of focal brain disease or epilepsy.

There is clearly a high incidence of CPSE within NCSE case series.² The largest case series of NCSE published to date examined 100 unselected patients and found that ~40% had lateralized EEG discharges, classifying these cases as CPSE.³ Most investigators now apply the more general term NCSE instead CPSE to avoid this type of confusion.

The incidence of all forms of SE in the general population is 30 to 50 per 100,000 population based on a prospective epidemiologic incidence study in Richmond, Virginia.⁴The incidence of CPSE has not been determined precisely because it is grouped with other types of NCSE. Nevertheless, the incidence of all types of NCSE is 2.2 per 100,000 in a retrospective epidemiologic case series.⁵

The incidence of CPSE in specific situations is probably more clinically useful than its incidence in the general population. Towne et al. found that 8% of patients with encephalopathy had NCSE.⁶ About 20% of patients with epilepsy will have SE at some time in their lives.⁷ This takes the form of GCSE in two thirds, but one third of patients will have at least one episode of NCSE. CPSE does not have any age or gender predilection except that imposed by some conditions that predispose to certain types of epilepsy. The incidence of CPSE in children is difficult to determine because there are few case series.⁸

The natural history of CPSE has not been studied in detail but is undoubtedly dependent on the underlying etiology or associated epilepsy syndrome.^9,10 It is often easily treated when it occurs in outpatients with established focal epilepsy because it is often due to inadequate treatment. The cause of inadequate treatment may be poor treatment adherence (noncompliance), ineffective medications, or purposeful drug withdrawal. In these cases, seizures usually stop with benzodiazepine use, and acute morbidity and mortality are avoided. Memory deficits can follow CPSE.¹¹ Krumholz et al. reported 10 patients with prolonged CPSE, lasting at least 36 hours: 3 died, 5 had cognitive impairments (primarily transient memory loss), and 3 had cognitive impairments with motor or sensory deficits.¹² This certainly demonstrates that CPSE can have serious sequelae, but it should be noted that these patients had very prolonged and intractable CPSE, so whether similar outcomes occur with more common brief CPSE is unknown.

There are a few case reports of CPSE in specific epilepsy syndromes. Frontal CPSE can appear with generalized EEG discharges, so it may be included with generalized NCSE.¹³ Occipital SE most often either secondarily generalizes or remains simple partial SE with continuous visual images, which can be very refractory to treatment, but can also present with CPSE.

When CPSE is accompanied by a severe medical problem or causes severely altered mental status, then there is a risk of serious morbidity and mortality (Figure 25-2).¹⁴ Mortality of all causes of NCSE in an unselected series of 100 patients was 18% and 27% when NCSE was due to an acute medial problem.³ SE occurring in the comatose patient is frequently nonconvulsive and usually shows focal EEG features, thus presenting as a type of CPSE. In this case, mortality is very high because the underlying conditions have a high mortality.¹⁵. For example, mortality is > 90% when NCSE accompanies subarachnoid hemorrhage or head trauma.^16–19 When due to limbic encephalitis, the mortality is very high.²⁰

The long-term outcome of patients who survive CPSE due to an acute medical illness is not well studied. The only long-term outcome study of NCSE reported the rate of later seizure recurrence after resolution of NCSE from the 100 patients noted earlier.²¹ Approximately 40% had recurrence of seizures, excluding those who did not die in the hospital and did not have epilepsy as the cause of their first episode of NCSE. A recurrent episode of NCSE was the most common type of subsequent seizure, but complex partial seizures also developed in some patients who had presentations most similar to CPSE as defined here.

The most common cause of CPSE is preexisting epilepsy, accounting for 30 to 50% of cases. It accounted for 3 of 10 cases with prolonged CPSE¹² and 31% of 100 cases of NCSE, which also included generalized NCSE.³ Epilepsies most commonly associated with CPSE include temporal lobe, frontal lobe, and occipital lobe, although seizure onset at any location is possible. Drug withdrawal or otherwise subtherapeutic antiepileptic drug (AED) dosing is often the cause, but CPSE can occur without provocation.

When encephalitis presents with SE, it is most often of the convulsive type, but 13% of the episodes are CPSE.²² Limbic encephalitis of paraneoplastic or other origin can present with a malignant form of CPSE that is very resistant to treatment. Herpes encephalitis frequently affects the temporal and frontal lobes to cause seizures but only rarely causes CPSE.²³

CPSE occurring in comatose patients is often due to brain insults, including stroke, tumor, intracranial hemorrhage, and trauma.^3,24 It can also occur in patients with acute systemic medical conditions, especially if there is a preexisting brain injury, such as a prior stroke, as a remote symptomatic cause.

A few metabolic conditions can cause CPSE, which is surprising, because metabolic conditions would not be expected to cause focal brain pathology resulting in seizures. Hypothyroidism has been frequently reported to cause encephalopathy, and in some cases of Hashimoto encephalopathy, the altered mental status is due to CPSE.²⁵

Pathologic Substrates

The pathophysiology of limbic CPSE has been studied extensively in animal models.²⁶ It seems to be similar to the pathophysiology of GCSE, which has been well studied in animal models and humans. It is clear in animal models that ongoing neuronal epileptic activity injures neurons in limbic CPSE. Excess neuronal excitation during CPSE causes prolonged depolarization of neurons, which activates the N-methyl-d-aspartate (NMDA) type of glutamate neurotransmission. NMDA-mediated neurotransmission causes neuronal injury through acute injury to neurons and through delayed apoptosis.²⁷ These processes are independent of systemic physiological changes and excessive motor activity. Thus, neuronal injury can occur even when pulse, blood pressure, glucose, and oxygenation are controlled and kept in a normal range.²⁶

Neuronal injury is most likely to affect the hippocampus in the temporal lobe because NMDA receptors are concentrated there with only little distribution elsewhere in humans.²⁸ Thus, acute hippocampal injury is replaced subsequently by hippocampal neuronal loss and gliosis (hippocampal sclerosis). Edema from the acute injury manifests on neuroimaging initially as an enlarged hippocampus with increased T2 signal, but later this is replaced by hippocampal atrophy and increased T2 signal on magnetic resonance imaging (MRI). This results in findings identical to other forms of mesial temporal lobe epilepsy with hippocampal sclerosis.²⁹

The proportion of patents with CPSE who suffer neuronal injury is unknown because prospective long-term studies have not been done. It might be reasonable to consider that the risk of neuronal injury is different depending on the context in which CPSE develops. For example, temporal lobe epilepsy (TLE) commonly follows limbic encephalitis, but TLE does not commonly develop following NCSE resulting from a neocortical source. It is remarkable that TLE did not follow any cases of NCSE in one long-term follow-up study.²¹

Ictal Behavior

The ictal manifestations of CPSE are highly variable, as is true for all forms of complex partial seizures and NCSE.³⁰The uniformly present symptom is altered mental status. The most subtle manifestation is confusion without other obvious symptoms or signs. Some patients have typical complex partial seizure manifestations, such as staring, unresponsiveness, oral or manual automatisms, or repetitive or automatic behaviors. This is typically seen in epilepsy monitoring units where individual complex partial seizures crescendo into CPSE. For patients whose seizures start prior to hospital presentation, the later stages of confusion and altered consciousness are present by the time video EEG monitoring (VEM) begins. At this stage, patients are often difficult to arouse and have only intermittent or isolated motor manifestations, such as an occasional limb or face twitch or intermittent limb posturing (Figure 25-3).

Overall, it is most clinically useful to consider CPSE as fitting into just a few clinical patterns of occurrence. Table 25-1 outlines the clinical categorization of CPSE based on etiology, mental status, EEG and situation. The easiest pattern to understand is when it occurs in a patient with focal epilepsy. This usually presents with recurrent clinical complex partial seizures and discharges that remain focal. Waxing and waning of mental status correlate with the occurrence of seizures (Figure 25-4). One prototypical form occurs in TLE, but it can arise from any brain region, especially the frontal lobes (Figure 25-5). Although discrete seizures may persist for many days, it is also common for the seizures to merge and become less discrete and less focal. The history of epilepsy and clinical evolution are the hallmarks of this situation. If patients present late in CPSE, they may have similar clinical symptomatology but EEG discharges that are asymmetrically generalized, giving the impression that seizures started focally, especially if there is a history of focal epilepsy (Figure 25-6).