Excerpt from Focal Status Epilepticus

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Classification

All forms of status epilepticus are historically defined as continuous seizure activity lasting longer than 30 minutes or recurrent seizures without interval neurologic recovery. Over the last decade, this definition has been operationally revised to reduce the required seizure duration for status down to about 10 minutes. This change was motivated by findings demonstrating that most seizures spontaneously end in 2 minutes or less. This definition of status does not specify whether the seizure activity is clinical, electrographic, or both. Although not always required for the diagnosis of status, electroencephalography (EEG) can be extremely useful to validate the diagnosis and often helps in categorizing the type of status.

Status epilepticus occurs in 2 broad forms; convulsive and nonconvulsive. Both types can be subdivided into focal and generalized subtypes, just as isolated seizures can be focal or generalized. Clinical, semiologic, and EEG data may aid in the categorization of status. In light of this schema, focal status epilepticus (FSE) is encountered in both convulsive and nonconvulsive forms. By extension from the broad definition of status, FSE can be continuous or repetitively recurrent without interval neurologic recovery. EEG can be especially helpful in the diagnosis of FSE, as nonconvulsive instances account for many cases.

Any region of cortex can generate focal epileptic activity, which, if sustained or recurrent, may constitute FSE. When motor cortex is affected, it is termed epilepsy partialis continua (EPC), which characteristically involves repetitive, often rhythmic, unilateral focal motor twitching of the limbs and/or face, usually with preservation of consciousness. This sparing of consciousness subcategorizes EPC as a form of simple partial status epilepticus (SPSE). EPC may be considered a form of convulsive FSE.

Other regions of cortex beyond motor cortex similarly may generate FSE. FSE associated with these regions of cortex are characterized by predictable phenotypes depending on the function of that particular region. For example, episodes of FSE involving primary sensory cortex are expected to be associated with focal sensory symptoms, and occipital FSE causes focal visual symptoms (eg, flashing spots of light, colorful visual hallucinations). FSE of language cortex typically causes aphasia, termed ictal aphasia.

Perhaps most important because of its relative frequency, is FSE of the limbic cortex (eg, mesial temporal lobe), which causes protracted signs and symptoms associated with complex partial seizures: staring, unresponsiveness, automatisms, atypical anxiety, rising abdominal symptoms, déjà vu, or more profound stupor. This entity commonly is termed complex partial status epilepticus (CPSE). FSE of frontal-lobe origin may produce clinical symptoms indistinguishable from FSE of temporal-lobe origin.

Some authors prefer to group the nonmotoric forms of FSE under the rubric of nonconvulsive status epilepticus (NCSE) because of their phenotypic similarities, and reserve the label of FSE for EPC alone. Another way to categorize these disparate forms of status is to use the pattern of seizure onset and/or the ictal EEG as the defining criterion. Thus, focal onset forms of status epilepticus, whether motoric (eg, EPC) or nonmotoric (eg, CPSE), are grouped together and contrasted with purely generalized forms of status (eg, absence status, generalized convulsive status). Because this article focuses on EEG correlates of FSE, the author uses this last definition. Topics included are SPSE, including EPC, and CPSE.

Categorization of status cases is no simple matter because they often exhibit characteristics of both focal and generalized processes. This has been the focus of considerable literature over the last 30 years, beginning with Geier et al in 1976²⁰, Ellis and Lee in 1978¹⁶, and Niedermeyer et al in 1979⁴⁴.

Several investigators have suggested that the bulk of these indeterminate examples are instances of focal onset episodes of status that have secondarily generalized in the same manner as many focal onset seizures. EEGs of patients with these conditions fail to capture the onset of status; therefore, this critical element is lost. Some of these instances are characterized by diffuse, slow (<3 Hz) spike-and-wave activity, albeit with focal predominance. In many instances, interictal recordings demonstrate focal discharges that further implicate a focal process. Whether such cases are best grouped with focal status remains controversial.

For simplicity, this article provides an overview of the purest forms of FSE. It concentrates on focal nonmotor status epilepticus, emphasizing CPSE of temporal-lobe origin, as it dominates this category much as temporal-lobe seizures predominate among focal seizures. Focal motor status (ie, EPC) is also highlighted. The article examines the distinctions (or lack thereof) of continuous focal seizure activity versus recurrent focal seizures among the forms of focal status.

Pathophysiology

The pathophysiology of FSE is analogous to the physiology of focal seizures. The precise pathophysiologic mechanisms underlying focal seizure activity are still largely unknown. Researchers widely believe that focally enhanced excitatory and/or focally depressed inhibitory neural mechanisms enable focal seizures and that diverse focal neural injuries can catalyze their formation. The net effect of the initial CNS insult and later neural remodeling, attendant to still-unknown feed-forward mechanisms, is to foster the development of neural circuits that with enhanced hypersynchronous firing behavior. Diverse mechanisms likely play pivotal roles in individual patients.

The diverse mechanisms that support focal epileptogenesis are unknown, as are the precise mechanisms leading to seizure initiation and termination. If most focal and generalized seizures self-terminate in 2 minutes or less, why then do episodes of status epilepticus, including focal status, fail to terminate? Intrinsic inhibitory mechanisms are believed to play a major role in seizure termination. However, the fundamental mechanisms responsible for seizure termination are still unknown, as are the reasons why they fail to occur in status epilepticus, focal or generalized. Patients who have had status epilepticus are more apt to have further episodes of status than others. Most of the data refer to generalized status epilepticus, but it is reasonable to surmise a similar pattern in FSE.

Frequency

More information is available concerning the frequency of convulsive status epilepticus and by extension NCSE than concerning FSE. In their prospective evaluation of patients with status, DeLorenzo et al (1996) determined a rate of 60 cases per 100,000 per year in the United States.¹² In 1994, Shorvon estimated cases of NCSE at a rate of 15-20 per 100,000 per year, of which only 3-4 were clearly instances of CPSE.⁵² This finding is in accordance with Celesia's early estimates in 1976.⁸ The above-mentioned intermediate category of secondarily generalized NCSE has been appreciated more than CPSE; this attention may account for the bulk of cases of NCSE.

True absence status (ie, generalized, ongoing, 3-Hz spike-and-wave activity) may account for fewer patients with NCSE than previously believed. NCSE, and by extension FSE, is believed to be frequently overlooked. EPC, or focal motor status, is rare by comparison, even in pediatric epilepsy referral centers, though it is overwhelmingly a syndrome of children. In the author's series of 41 patients with FSE who were referred from a tertiary referral center that treated adults over 15 years, only 3 had EPC.

Mortality and morbidity

Risks of mortality and morbidity in FSE are not as ominous as they are for generalized convulsive status epilepticus. NCSE has been examined more than FSE, per se. Evidence from experimental models of partial epilepsy demonstrated profound and long-lasting neurologic changes after experimental status. In human studies, occasional patients have reportedly had profound memory and behavioral changes after episodes of CPSE. In some reports, the duration of the status was linked with these lasting memory deficits. However, most cohorts of patients with NCSE did not undergo prestatus and poststatus neuropsychologic testing to permit direct comparison.

In some cohort studies, recurrent episodes of CPSE were observed, though without convincing neurologic deterioration. Krumholz and colleagues described 10 patients with CPSE associated with serious morbidity.³² However, the study was criticized because many subjects had severe neurologic or medical insults in addition to status, which may have been pivotal in the genesis of their residual neurologic deficits. Nonetheless, 3 patients prolonged memory and/or other cognitive deficits, which their FSE may have provoked. Data from available studies suggest that NCSE alone usually does not cause irreversible neurologic injury, though rare instances may occur. However, NCSE appears so often in the company of serious neurologic or medical injury that clinically significant morbidity and mortality are common.

Patients with focal motor status (ie, EPC) have a particularly poor prognosis if they are untreated in the setting of Rasmussen encephalitis. Focal seizures and EPC characterize this progressive epileptic syndrome, often with progressive focal or unilateral deficits (sensory, motor, language) associated with unilateral hemispheric atrophy (see Media file 1). Seizure activity is difficult to suppress with standard anticonvulsants, even in combination. Surgical resection of the affected hemisphere (hemispherectomy) remains the definitive treatment for this progressive illness. The morbidity of other causes of EPC varies depending on the etiology and speed of their recognition and whether they are vascular, infectious, metabolic, or drug induced.

The author's series of patients with FSE revealed that patients with new neurologic insults (eg, acute stroke) or those whose status appeared postoperatively had a mortality rate of 67%. Those with a history of epilepsy did well overall. This group usually had a new toxic and/or metabolic or other medical aggravator that precipitated their status but that left little to no lasting neurologic effect after its resolution. The author compared patients with recurrent seizures with those who had ongoing, continuous seizure activity. No difference in outcome was observed between the subgroups of FSE.

Patient characteristics

Status is not overrepresented in male or female individuals, nor is it believed to have a predilection for any particular racial or ethnic group. The age frequency of status epilepticus probably follows the same curve for the incidence of seizures with age. This J-shaped curve reflects the high frequency in the young and the increasing incidence with advancing age, though status clearly occurs across a wide age range. FSE probably obeys a similar age relationship, though the data are understandably limited. Because of the special relationship of EPC with childhood epilepsy, this entity is distinctly predominant in children. In the author's study of adults with FSE, the age range was 15-91 years with a mean age of 62 years. Most available studies are retrospective; therefore, prospective data on the age-related incidence of FSE are still lacking.

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