AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Clinical Characteristics and EEG Manifestations
• Clinical Description
• Differential Diagnosis
• Workup
• Treatment
• Medication
• Follow-up Care
• Multimedia
• References

CLINICAL CHARACTERISTICS AND EEG MANIFESTATIONS

Section 2 of 10  

• Authors and Editors
• Clinical Characteristics and EEG Manifestations
• Clinical Description
• Differential Diagnosis
• Workup
• Treatment
• Medication
• Follow-up Care
• Multimedia
• References

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.

CLINICAL DESCRIPTION

Section 3 of 10  

• Authors and Editors
• Clinical Characteristics and EEG Manifestations
• Clinical Description
• Differential Diagnosis
• Workup
• Treatment
• Medication
• Follow-up Care
• Multimedia
• References

Diverse clinical histories and examination findings accompany cases of FSE, as is predicted on the basis of its varying forms and sites of cortical involvement. A discussion of the respective historical features and clinical manifestations follows.

Nonmotor simple partial FSE

By clinical history, nonmotor simple partial FSE involves subjective sensory disturbances, including focal or unilateral paresthesias or numbness; focal visual changes usually characterized by flashing lights, focal visual obscuration or focal colorful hallucinations; olfactory or gustatory hallucinations; or atypical rising abdominal sensations. These focal phenomena with preserved consciousness are not uncommon as self-limited seizures, and they most often occur as auras associated with complex partial and secondarily generalized seizures. However, in rare cases, they persist in an ongoing or recurrent fashion that fulfills the criteria for FSE.

Because these particular forms of status involve sensory disturbances with preserved consciousness, no helpful clinical signs are associated with them. The gradual evolution of nonmotor SPSE into overt complex partial or generalized seizures helps provide clinically apparent confirmation of these rare forms of FSE. In rare instances, a focal or generalized seizure may precede such an episode of status. However, maintain a high index of suspicion that long-lasting focal sensory disturbances after convulsive seizures represent a transient postictal correlate (a relatively common sequence) rather than FSE. EEG often helps in making this clinical distinction.

Epilepsy partialis continua

FSE of the motor cortex, known as EPC, may occur in various contexts. Some subdivide EPC into type I and type II, where type I refers to a nonprogressive form and type II refers to a progressive syndrome. Type I classically occurs after acute insults to the sensorimotor cortex, which may be infectious (eg, Russian spring-summer encephalitis), neoplastic, traumatic, metabolic, or vascular. Nonketotic hyperglycemic diabetes, particularly that linked to hyponatremia, occasionally causes EPC, often, though not always, with a preexisting focal CNS lesion (eg, stroke). Mitochondrial disorders (eg, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes [MELAS]; myoclonic epilepsy with ragged-red fiber disease [MERRF]) may include EPC.

The syndrome of childhood epilepsy with rolandic spikes (ie, benign rolandic epilepsy) may occasionally involve EPS. Patients have prolonged speech arrest, facial twitching, and sialorrhea, in episodes that are clinically similar to those of the syndrome, though more prolonged than usual.

Patients with type I EPC develop intermittent, semirhythmic, and involuntary twitching involving a discrete subset of muscles. Although any group of muscles may exhibit these features, it is observed most commonly in the face and ipsilateral distal hand musculature. Myoclonus of this variety may evolve into a partial or generalized convulsion. Many other attendant historical symptoms may be present depending on the nature of the focal insult; these symptoms heavily influence the ultimate clinical outcome in this setting.

In the converse, type II EPC, the progressive form, is usually linked with Rasmussen encephalitis, a unique and rare epilepsy syndrome that predominantly affects children. Children with Rasmussen encephalitis historically had a variety of seizures, including simple and complex partial seizures with occasional secondary generalization. EPC is yet another seizure type these patients have. In addition to seizures, patients have gradual loss of unilateral function, and in parallel, imaging studies show focal or unilateral hemispheric atrophy. The typical age of onset is 5-10 years, though the range is broad, and rare cases are reported in adults. Intellectual skills may become impaired to various degrees, and language skills may be affected, depending on the age of onset and the laterality of the process. Pathologic findings include cortical atrophy, reactive gliosis including microglial nodules, and some perivascular lymphocytosis, occasionally with necrotic features.

Although the subject of intense scrutiny, the etiology of Rasmussen encephalitis remains unknown. Numerous attempts to identify a consistent viral pathogen have failed. An autoimmune hypothesis based on a glutamate receptor subtype has been suggested, but this remains unproven in humans.

Complex partial status epilepticus

CPSE often begins with a history of recurrent or prolonged simple partial seizures, or it may follow or precede a generalized convulsive seizure. Patients with CPSE are often confused and have variable responsiveness. Memory of the event is usually impaired. Behavior may fluctuate or be bizarre. Many patients have clinical automatisms, as with typical complex partial seizures, including repetitive lip-smacking, fumbling, or swallowing movements. Subtle nystagmus may be observed. The range of confusion can be great, with some patients having mildly diminished responsiveness and with others in frank stupor or in a catatonic state. Aphasia and other localizing signs and symptoms (eg, focal weakness) may accompany CPSE (see Media files 2-3).

Type I CPSE refers to recurrent recognizable complex partial seizures without interval recovery. Type II CPSE represents continuous, ongoing complex partial seizure activity. Clinical cycling may be most indicative of type I, though this clinical inference may not be highly reliable. Clinically distinguishing CPSE from absence (generalized) NCSE may be problematic; EEG showing focal or lateralized features may be helpful. EEG is a particularly valuable tool in this setting because treatment options may partly depend on this distinction. Knowledge of the patient's interictal EEG and clinical syndrome, when possible, may also help make this important clinical distinction.

Many causes of FSE have already been enumerated. Patients often have an established history of epilepsy, typically characterized by a focal onset. In the author's series, approximately 25% of patients had such a history. In these individuals, subtherapeutic anticonvulsant levels or other new metabolic or systemic stressors were implicated in the expression of FSE. However, acute or chronic focal cerebral injuries of various kinds may provide the substrate for new-onset focal seizures and FSE. As expected, vascular insults account for most focal CNS insults that are believed to be pivotal for the expression of FSE. Approximately 50% of the author's cohort with FSE had a history of acute or chronic vascular CNS injury.

In addition to focal ischemic stroke, diffuse hypoxic-ischemic injury and intracranial hemorrhage (eg, subdural hematoma, parenchymal hemorrhage) account for some patients with vascular FSE. Other occasional underlying causes of FSE include trauma, neoplasia, focal demyelination, and infection (eg, abscess, meningitis, encephalitis, HIV related). In several patients, the focal CNS injury that provides the substrate for FSE is chronic, with FSE triggered by a superimposed medical stressor ranging from metabolic derangements (eg, hyponatremia), infections, hypoxemia, or proconvulsant medications (eg, lithium, cyclosporin). On occasion, no focal cause is found, though a systemic process can often be implicated in such situations.

The partial list described herein accounts for patients with SPSE and CPSE. As mentioned already, the list of causes for EPC also includes entities such as nonketotic hyperglycemic diabetes mellitus, mitochondrial disorders (eg, MELAS, MERRF), benign rolandic epilepsy of childhood, and Rasmussen encephalitis in EPC with a progressive course.

DIFFERENTIAL DIAGNOSIS

Section 4 of 10  

• Authors and Editors
• Clinical Characteristics and EEG Manifestations
• Clinical Description
• Differential Diagnosis
• Workup
• Treatment
• Medication
• Follow-up Care
• Multimedia
• References

Diagnosing FSE often requires a high index of suspicion. EEG can be pivotal in solidifying the diagnosis. Instances of EPC are rarely misdiagnosed, but consider possible alternative diagnoses, even for this unique entity.

Simple partial status epilepticus

The list of alternative diagnoses for SPSE is a subset of the list associated with CPSE. Consider transient ischemia attack (TIA) and stroke early in cases resembling simple partial status. Migraine and its attendant neurologic phenomena (eg, sensory, visual) can mimic simple partial status. Transient postictal phenomena analogous to Todd paresis may mimic SPSE. Ophthalmic disorders, such as retinal detachment, may mimic visual simple partial (occipital) status. Peripheral neurologic syndromes and vestibulopathies may uncommonly masquerade as SPSE. As always, psychogenic processes, including somatoform disorders, should be on this list. Diagnosing SPSE is understandably easiest when it arises in a patient with an established history of focal epilepsy. Evolution of SPSE from or to a clinically overt complex partial or secondarily generalized seizure also permits accurate diagnosis.

Complex partial status epilepticus

CPSE is associated with more differential diagnoses than SPSE because of its variable clinical manifestations and associated altered consciousness. In addition to TIA, stroke, and migraine, other key disturbances of CNS function that mimic CPSE include toxic or metabolic encephalopathy, delirium of diverse etiologies, and transient global amnesia. In the category of epileptiform processes, absence status (persistent generalized 3-Hz spike-and-wave activity) may be clinically indistinguishable from CPSE. Prolonged postictal states may closely resemble, and are more common than, CPSE. Psychiatric causes of decreased responsiveness resembling CPSE are familiar to many tertiary epilepsy referral centers. These include severe mood disorders, psychotic disorders, and related nonepileptic phenomena (ie, pseudo-CPSE).

Periodic lateralized epileptiform discharges (PLEDs) may occur with and without FSE. In FSE, PLEDs may represent an ictal correlate. This interpretation is supported by an overt clinical correlate (ie, focal twitching) or by improvement in the patient's findings on neurologic examination after PLED resolution, as may occur after treatment. However, such clinical improvement may lag the disappearance of PLEDs by hours owing to residual postictal CNS dysfunction. Marked evolution of PLEDs, such as abrupt frequency or amplitude changes, may also signify an ictal correlate. Whether the absolute discharge frequency reliably differentiates interictal from ictal PLEDs remains controversial.

Single-photon emission CT (SPECT) may assist in distinguishing ictal and interictal PLEDs in the setting of possible FSE. In such instances of PLEDs in FSE, SPECT may show focal hyperperfusion. Apart from FSE, PLEDs often represent an interictal finding associated with acute structural CNS lesions (eg, infarct, tumor, infection) or a chronic CNS lesion with a new, superimposed systemic disturbance. In this setting, PLEDs are still associated with seizures in 70-80% of cases. Both FSE and PLEDs arise from similar clinical contexts, and both imply an increased risk of future seizures and epilepsy.

Epilepsy partialis continua

For EPC, with its associated semirhythmic, repetitive muscle twitching, the differential diagnosis is a bit different from that of SPSE and CPSE. Other entities to consider include nonepileptic forms of myoclonus, such as those of basal ganglia, brainstem, or spinal origin. The coexistence of other overt complex partial and secondarily generalized seizures and epileptiform changes in the EEG help make this distinction. A finding of a bilateral or multifocal myoclonic process argues against focal epilepsy.

Multifocal myoclonus is frequently encountered in very ill, hospitalized patients, often after systemic hypoxemia, though it is occasionally related to medications or metabolic derangements. Other movement disorders (eg, choreiform disorders, hemiballismus, tic disorders, opsoclonus-myoclonus syndrome) might theoretically be confused for EPC. Careful evaluation of the movements, EEG, and accompanying history may assist in differentiation. Finally, a psychogenic process may emulate EPC in rare cases.

A partial list of the differential diagnoses for SPSE, CPSE, and EPC follows:

• Nonmotor SPSE
  • Transient cerebral ischemia and/or ischemic stroke
  • Intracranial hemorrhage
  • Migraine
  • Postictal states
  • Ophthalmic disorders
  • Vestibulopathies
  • Psychiatric syndromes
• Complex partial status epilepticus
  • Transient cerebral ischemia and/or ischemic stroke
  • Intracranial hemorrhage
  • Transient global amnesia
  • Migraine
  • Toxic and/or metabolic encephalopathies
  • Delirium
  • Absence status epilepticus
  • Postictal states
  • PLEDs
  • Psychiatric syndromes
• Epilepsy partialis continua
  • Myoclonic disorders, nonepileptic forms
  • Choreiform disorders
  • Tic disorders
  • Hemiballismus
  • Opsoclonus-myoclonus
  • Psychiatric syndromes

WORKUP

Section 5 of 10  

• Authors and Editors
• Clinical Characteristics and EEG Manifestations
• Clinical Description
• Differential Diagnosis
• Workup
• Treatment
• Medication
• Follow-up Care
• Multimedia
• References

The approach to potential FSE should be conducted similarly to that for any self-limited seizure, but clearly in an expeditious fashion. A speedy diagnosis facilitates medical intervention to abort or limit FSE. However, as reviewed in Treatment, the risk of lasting morbidity and mortality of FSE is usually less ominous than for generalized convulsive status. This feature affords extra opportunities to pursue diagnostic tests to confirm the diagnosis of FSE, reveal associated etiologic processes (some of which may be morbid), and provide insight into fruitful treatment strategies.

Simple partial status epilepticus/epilepsy partialis continua

In patients with preserved consciousness and sensory or motor symptoms compatible with FSE, a history of epilepsy may help focus the workup tremendously. Patients with previous epilepsy, particularly prior FSE, known to co-localize with the presumptive localization of the ongoing FSE, are not apt to have a newly acquired CNS lesion but are likely to have a systemic stressor that is aggravating their epilepsy. The episode may reflect subtherapeutic anticonvulsant levels, new toxic or metabolic derangements, intercurrent infection (usually outside of the CNS), recent stress, or sleep deprivation, as in any breakthrough seizure in a patient with known epilepsy. In some situations, no new precipitant can be found, though one should be sought aggressively.

Expedient testing should be performed to determine routine levels of electrolyte, CBC, glucose, BUN, creatinine, calcium, magnesium, and anticonvulsant and to complete liver function tests, pulse oximetry, arterial blood gas measurements (if needed), urinalysis, and toxicology screens. Fever should prompt a thorough search for sources of infection. Lumbar puncture (LP) should be ordered if a CNS infection seems plausible.

In patients without a previous diagnosis of epilepsy, an aggressive search for a new or preexistent focal CNS lesion is paramount. Because patients with established epilepsy are not immune to new CNS lesions, a search for a new CNS process should be considered if their established epileptic focus does not seem to account for the ongoing FSE.

This search should include brain imaging, preferably with MRI (or CT if MRI is unavailable) to look for a new lesion (eg, new stroke, mass lesion). Today, many centers offer advanced MRI, such as diffusion-weighted, perfusion, and susceptibility-weighted imaging. These newer methods can be particularly helpful in identifying acute cerebral ischemia. The physician often does not know if the patient has a newly acquired focal CNS lesion, FSE, or both. Search for a new focal lesion early because certain acute processes pose high rates of morbidity and may require treatment independent of FSE. For example, quickly finding a new cardioembolic stroke due to atrial fibrillation is pivotal because this condition must be dealt with swiftly, in parallel with FSE, if both apply.

After imaging is complete, evaluate the CSF (unless contraindications to LP are present) in patients whose findings prompt a high index of suspicion of CNS infection (eg, meningitis, encephalitis). Fever, stiff neck, headache, and photophobia are signs and symptoms that may suggest such infection.

When feasible, EEG is often helpful in solidifying the diagnosis of FSE, and it may be crucial in differentiating FSE from some of the other mimics (see Differential Diagnosis). Simple partial seizure activity occasionally lacks an EEG correlate. The absence of ongoing epileptiform activity does not completely exclude SPSE. However, absence of an EEG correlate should at least call the diagnosis of FSE into question. Many patients with EPC have a repetitive discharge on EEG that is time-locked to the motor activity. In many hospitals, EEG is frequently unavailable for the acute workup of new FSE, and presumptive treatment strategies for FSE must occasionally be started before EEG confirmation becomes available.

Complex partial status epilepticus

The approach to a patient with a confusional or stuporous picture that suggests CPSE is similar to the approach in SPSE and EPC. The first pivotal step is including CPSE in the differential diagnosis. Numerous authors report that CPSE is often overlooked and that correct diagnosis is often considerably delayed. This problem stems from the close clinical overlap between CPSE and other, more common encephalopathies in hospitalized patients. When CPSE occurs in the setting of previous epilepsy, search for new medical stressors (eg, toxins, metabolic derangements, alcohol, proconvulsant medications, subtherapeutic anticonvulsants, intercurrent illness, hypoxemia) that may trigger its expression.

Another common clinical scenario leading to CPSE, especially in patients without previous epilepsy, involves overt yet self-limited generalized convulsion, often in the context of a new serious medical illness, after surgery, or after an acute CNS process. In this familiar scenario, the patient does not have the expected timely recovery to neurologic baseline after the brief convulsion. Anticonvulsants are often started in response to the overt seizure, though frequently with inconsistent attention to blood levels. The patient's persistent stupor is initially misattributed to the concomitant medical illness or a diminished recuperative ability (in older patients) to the newly acquired CNS process. Potentially diagnostic EEGs may be wrongly deferred after that new-onset convulsion in this setting because the overt seizure is long over and the diagnosis of CPSE is overlooked.

Numerous authors have highlighted the frequent association of CPSE with previous or late generalized convulsive seizures. This constellation of features includes (1) serious medical, surgical, or neurological illness; (2) a brief convulsive seizure; and (3) protracted stupor with fluctuating neurologic findings, subtle nystagmus, or focal twitching. The presence of these elements should prompt consideration of CPSE and expedient EEG evaluation.

After EEG results confirm CPSE, the workup proceeds as outlined in Simple partial status epilepticus/epilepsy partialis continua.

Head imaging, preferably MRI, may reveal an acute or chronic focal structural basis for the status. Interpretation of acute MRIs may be problematic in FSE because seizures and FSE themselves can cause a wide range of MRI abnormalities, many of which are transient. Repeat imaging over weeks to months may be helpful to clarify their interpretation. LP, after appropriate head imaging to ensure safety, may be helpful in patients with a suspected CNS infection, particularly when complicated by fever of unknown source. A thorough battery of blood and urine testing, as enumerated for SPSE and EPC, can be ordered to address many of the frequent comorbid conditions or mimics of CPSE. Because recurring complex partial seizures without interval neurologic recovery constitutes CPSE, a single EEG lacking ongoing partial seizure activity does not entirely preclude the diagnosis; the study may have been performed between seizures. Repeated or prolonged EEG recordings may be crucial in confirming CPSE (see Media files 2-3).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Clinical Characteristics and EEG Manifestations
• Clinical Description
• Differential Diagnosis
• Workup
• Treatment
• Medication
• Follow-up Care
• Multimedia
• References

After FSE is diagnosed, treatment may be started. Most treatments entail various antiepileptic drugs (AEDs), though general supportive measures must be remembered. Surgical strategies are an uncommon approach in FSE, as outlined below. Specific information concerning the most commonly used anticonvulsants follows in Medication.

Focus status epilepticus/epilepsy partialis continua

In motor FSE, specifically EPC, the treatment approach parallels that for generalized convulsive status epilepticus, though the urgency of treatment and the extremes to which a physician may elect to go to terminate the seizure are tempered. After EPC is presumptively diagnosed with or without EEG confirmation, treatment should begin. Airway, breathing, and circulation (ABCs) of emergency treatment still apply. Although generalized convulsive status frequently jeopardizes these systems, they infrequently are imperiled with EPC.

In concert with early treatment measures, diagnostic studies (as outlined in Workup) should be performed rapidly. Rapid turnaround of anticonvulsant drug levels may be particularly helpful in guiding treatment choices in patients with well-established epilepsy who are taking AEDs over the long term. Emergent glucose assessment is particularly important because hyperglycemia and hypoglycemia can be associated with focal seizures and FSE. In patients with recent trauma or a suspected new intracranial process (eg, stroke), urgent head CT or MRI also may be useful and may uncover pathology that takes precedence over EPC.

Well-established treatments for status can and should be attempted to interrupt EPC. Of course, the first major concern is to limit the seizure and inhibit its threat of generalization. Then, the aim is to abolish recurring or ongoing focal seizure activity. Benzodiazepines are the preferred first line agents. Although diazepam is familiar to paramedics and emergency physicians, a consensus has evolved among neurologists and epileptologists that lorazepam may be preferred in this setting because of its long distribution half-life.

Administration of intravenous (IV) lorazepam should be followed by a longer-acting AED, as in convulsive status. This is where knowledge of the patient's usual regimen and current levels may be pivotal. Oral supplementation of their routine medication (guided by stat AED levels) or, when possible, intramuscular (IM) or IV supplementation, may help suppress EPC. In patients who are naïve to AEDs, administration of phenytoin or fosphenytoin may help deter seizure recurrence after the lorazepam is cleared. Fosphenytoin provides the advantage of a potentially rapid rate of administration with less risk of venous irritation (eg, to avoid the risk of purple-glove syndrome with phenytoin).

Most cases of EPC can be terminated with these measures and/or with correction of metabolic derangements when applicable. In rare instances, EPC may slow but fail to abort with high or even supratherapeutic levels of phenytoin. Those uncommon instances may warrant judicious use of barbiturates (eg, phenobarbital) to augment the effects of phenytoin and lorazepam. Use caution when adding barbiturates to benzodiazepines because their coadministration may potentiate ventilatory failure. For this reason, especially in the setting of partially treated EPC, in which the morbidity of the underlying illness is less than in generalized convulsive status, a tempered approach may be preferred. Incremental doses of phenobarbital may offer satisfactory efficacy in these uncommon settings and may be safer than full IV loading doses, which increase the risk of respiratory suppression.

As an alternative to phenobarbital, one may consider advancing doses of other concomitant adjunctive medications to high or near-maximal doses to help terminate EPC. One might even consider rapid oral loading of 1 of the newer AEDs (eg, topiramate), depending on the ongoing clinical urgency. Anecdotal reports describe the beneficial use of topiramate in some cases of FSE. Low-frequency transcranial magnetic stimulation was recently helpful in disrupting EPC, but this nonpharmacologic approach remains investigational in this setting. Other highly potent treatments for refractory convulsive status (eg, pentobarbital, propofol, IV midazolam) are always an option for EPC, but their risk must carefully be weighed against the morbidity of the process.

Simple partial status epilepticus

In SPSE (consciousness preserved), an approach similar to that just outlined for EPC applies. Given the relatively mild morbidity of this form of status, use caution and give considerable thought before using overly aggressive approaches (eg, coadministration of barbiturates with benzodiazepines, IV loading of barbiturates, barbiturate coma). Because SPSE is often more difficult to confirm on clinical grounds alone than EPC, EEG validation may be especially important. However, the yield of EEG in detecting simple partial seizure activity is variable and certainly lower than for complex partial seizures or generalized processes.

Given the relative rarity of SPSE, maintain a high degree of skepticism before considering this diagnosis. Other common processes (eg, vascular CNS insult) and other focal processes may mimic this rare entity; keep these well in mind, especially when tempted to apply increasingly risky treatment strategies. Invest more time in confirming the diagnosis and in deliberately observing the effect of each successive treatment.

Complex partial status epilepticus

CPSE may be harder to diagnose than EPC because of its close resemblance to other, more common encephalopathic states. Although still unproven and controversial, morbidity may last longer than previously believed. Given this background, keeping the possibility of CPSE in mind and aggressively screening for it with EEG seems critical, especially when suggestion of a previous convulsive seizure or a background of epilepsy is present. Treatment algorithms for CPSE should be akin to those outlined above for EPC and slightly more aggressive in terms of tempo and AED selection than those for SPSE. Infrequent cases of refractory CPSE may require the use of iatrogenic coma (eg, pentobarbital, propofol, midazolam) with attendant ventilatory support.

Although prompt clinical alerting after the administration of lorazepam (or other benzodiazepines or AEDs) tends to corroborate the diagnosis of status, the absence of clinical alerting by no means excludes the diagnosis. Most patients remain sleepy or stuporous after a prolonged episode of status, focal or otherwise, that lorazepam interrupts. For this reason, bedside EEG assessment can be invaluable in guiding treatment decisions for FSE. This is true not only early in the treatment paradigm but also late to help gauge the patient's recovery and to ensure that he or she is not having repeated subclinical seizures. Portable computer-aided EEG monitoring (LTM system) can be particularly helpful in this task.

Frequent recurrent complex partial seizures without interval neurologic recovery constitute a form of CPSE; approach them in much the same way as outlined in Focal status epilepticus/epilepsy partialis continua. Repeated doses of lorazepam after recurrent partial seizures can be used to diminish the likelihood of immediate recurrence. Doses of long-acting agents may need to be raised to high therapeutic or supratherapeutic ranges or started anew to sustain this protective effect. Repeated doses of lorazepam, like repeated doses of other benzodiazepines, can cause important cumulative effects (eg, prolonged sedation). This may be especially true for patients (eg, elderly patients) with impaired drug clearance.

Other ancillary strategies that should be used to treat FSE are the same as for any seizure-prone patient. Protective padding for the bed rails may help avert falls. Bed alarms may help alert nursing staff if the patient wanders away from bed, as he or she may do when confused or postictal. IV access is essential. Supplemental oxygen may be necessary; perform pulse oximetry at least once. IV fluids are indicated when the patient is in prolonged stupor and unable to take food by mouth. Provide attention to other associated medical issues (eg, infection, new CNS injury or process). Prophylaxis against deep venous thrombosis (eg, pneumatic boots) may be helpful for particularly prolonged cases in stuporous patients.

Surgical approaches to the treatment of FSE are rare and reserved for the most refractory examples. Brain biopsy or resection is applicable only under extraordinary circumstances. In rare instances, surgery may help in defining and treating a new focal CNS lesion (eg, brain abscess) that may be instigating the FSE. Hemispherectomy occasionally is indicated for the definitive treatment of highly selected individuals (usually children) with Rasmussen encephalitis, as described in Mortality and morbidity. However, this procedure is elective and planned after exhaustive workup. Medical management is the mainstay of treatment for FSE.

MEDICATION

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• Clinical Description
• Differential Diagnosis
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• Medication
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• References

This section outlines pertinent attributes and guidelines for administration of the most commonly used AEDs in the treatment of FSE. This section elaborates on the treatment strategies and AEDs enumerated in Treatment. The article serves as a useful starting point; readers are encouraged to find supplemental information on these and other AEDs from other sources, some of which appear in the bibliography.

Drug Category: Benzodiazepine

These are first-line agents for treating FSE. They rapidly achieve therapeutic CNS concentrations after IV administration and act to potentiate action of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, and rapidly abrogate ongoing seizure activity. Their effect is temporary, which is a limitation; diazepam begins to redistribute out of CNS within minutes. Because the effect is time limited, loading of a traditional AED, such as phenytoin, is recommended soon after administration to help mitigate seizure recurrence.

Drug Category: Anticonvulsant

These agents terminate clinical and electrical seizure activity. They are the first-line treatment of status.

Drug Name	Fosphenytoin (Cerebyx)
Description	Prodrug hydrolyzed rapidly and completely to phenytoin by endogenous phosphatases soon after delivery. Highly soluble in aqueous solutions at physiologic pH. IV administration can be more rapid than that for phenytoin. Eliminates risk of phlebitis and purple-glove syndrome. Achieves therapeutic CNS levels as quickly as phenytoin.
Adult Dose	15-20 mg PE/kg IV; not to exceed 150 mg PE/min
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome; history of cardiac disease or arrhythmia (at minimum, administer slowly and monitor pressures and heart rhythm and rate)
Interactions	Long-term administration can induce hepatic enzyme systems, which may accelerate metabolism of other coadministered medications, including AEDs (not relevant acutely in FSE)
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Risk of hypotension and cardiac arrhythmias in susceptible patients (ie, older patients, those with known cardiac disease); rate of administration can dramatically influence cardiovascular toxicity (tailor infusion rate accordingly); perineal paresthesias often accompany rapid infusion but not known to be injurious

Drug Name	Phenobarbital (Solfoton, Luminal, Barbita)
Description	Generally used after phenytoin or fosphenytoin fails, though can be used in lieu of phenytoin in certain circumstances. Works at CNS GABA receptors to potentiate CNS inhibition.
Adult Dose	20 mg/kg IV; not to exceed 100 mg/min; slow rate of infusion if hypotension observed Alternate dose: Small IV aliquots (eg, 2-3 mg/kg) and assess for effect; may repeat over hours to suppress status while minimizing risk of respiratory depression
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis
Interactions	Long-term use may decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients whose coagulation parameters stabilized with anticoagulants may require dosage adjustments if added to or withdrawn from regimen) Alcohol may produce additive CNS effects and death; addition to benzodiazepines can promote respiratory suppression; chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraception to prevent unwanted pregnancy); menstrual irregularities may occur
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	EEG monitoring may help (many patients become sedated, making clinical assessment problematic); risks include sedation, respiratory depression, and (infrequently) hypotension; often wise to administer in intensive care unit (ICU) to increase monitoring of vital signs and respiratory status and facilitate rapid airway control if necessary (many intubate patients before treatment because of risk of respiratory depression); exercise appropriate caution when considering therapy for FSE because morbidity less with FSE than with generalized convulsive status and diagnosis often less secure) May be appropriate for some instances of CPSE or EPC but may be inappropriate for most cases of SPSE; rare aplastic anemia and hepatitis may occur; may be teratogenic in pregnancy (statistically small effect in population studies; risk of inadequately treated CPSE or EPC may outweigh risks in pregnancy, particularly in urgent and time-limited use)

FOLLOW-UP CARE

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• Differential Diagnosis
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• References

Once the acute episode of FSE is terminated by using methods enumerated above, further inpatient care is required to ensure that seizure activity does not recur quickly. Close observation to ensure recovery to neurologic baseline is essential. Follow-up EEG or EEG monitoring (in the ICU, on neurology unit, or in a monitored unit) may be extremely helpful in assessing recovery. This is especially true for cases complicated by prolonged stupor, which may be drug induced, which may signify persistent seizure activity, or both. Once the patient is breathing without ventilatory assistance and is less lethargic than before, he or she may be transferred from the ICU.

Administer anticonvulsants according to maintenance dosing regimens to deter seizure recurrence. If the patient cannot take medications by mouth, administer maintenance AEDs IV or per nasogastric tube if needed. Phenytoin, phenobarbital, and valproate can be dosed IV, as can benzodiazepines, such as lorazepam. Fosphenytoin can be administered IM if desired. Once the patient can take medications orally, adjust the regimen appropriately.

If the patient was taking AEDs at the onset of FSE, those drugs may be resumed, with some interval of AED overlap to ensure a smooth transition to the desired long-term regimen. Periodically track AED levels to optimize therapy and decrease the risk of FSE recurrence. Additional workup may be completed if the episode of status is symptomatic of a newly acquired CNS process. Determine transfer to a rehabilitation facility or home in the usual fashion, depending on any residual symptoms and their functional impact.

Late outpatient care focuses on tracking the patient's progress in terms of seizure activity and adverse effects. Obtain AED levels if they may not be optimal for the particular patient. Within an episode of FSE, this scrutiny may be more vigilant than usual in outpatient follow-up care. Educate family members about the early recognition and treatment of FSE. Diastat, a formulation of rectally administered diazepam, can be useful for home treatment of prolonged or clustered seizures, as in recurrent FSE. Its availability to families may help terminate such episodes and prevent hospital visits.

One should identify contributors to FSE (eg, medication noncompliance, intercurrent stressors, sleep deprivation, new provocative medications) and minimize these, where possible. Importantly, patients and their families must know that FSE can, and often does, recur (as does status in general).

Complications of FSE can be variable. SPSE usually poses little risk of lasting sequelae. Compared with SPSE, EPC may pose a more credible potential for more persistent CNS risks. However, most instances of EPC arise from new CNS injury or from a progressive process, such as Rasmussen encephalitis. Determining the portion of CNS injury attributable to EPC alone is problematic. CPSE is infrequently associated with cognitive, behavioral, and memory deficits. However, pre-FSE and post-FSE neuropsychologic tests are available in few instances.

In many reported patients with FSE and long-lasting neurologic deficits, a concomitant CNS process confounded the interpretation of the morbidity caused by FSE. This remains a topic of some controversy. Most authors concur that prolonged FSE, particularly CPSE, poses a risk of long-lasting neurologic injury to affected neural structures, frequently the mesial temporal regions, with risk of attendant difficulties with memory.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Clinical Characteristics and EEG Manifestations
• Clinical Description
• Differential Diagnosis
• Workup
• Treatment
• Medication
• Follow-up Care
• Multimedia
• References

Media file 1:  Focal status epilepticus. Electroencephalograph (EEG) in a patient with epilepsia partialis continua caused by Rasmussen encephalitis before hemispherectomy. The patient had long-standing, intractable partial epilepsy since the first decade of life. Seizures included complex partial with occasional secondary generalization and repetitive myoclonus involving the left body. Note the frequent epileptiform discharges at 1-2 Hz involving the right frontocentral channels. These were evident on many of the patient's routine EEGs. Clinical myoclonus is often correlated with high-voltage bursts of such activity.
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Media type:  Photo

Media file 2:  Focal status epilepticus. Electroencephalograph (EEG) in a 35-year-old patient with a history of intractable partial epilepsy, in complex partial status epilepticus. The patient underwent a rapid antiepileptic drug taper as an inpatient for long-term video/EEG monitoring as a presurgical candidate. On clinical observation, the patient abruptly stopped and stared, exhibiting automatisms. This first of 2 EEG fragments covers approximately 30 seconds and illustrates the start and evolution of a seizure in the right temporal lobe. The onset appears to be at Sp2 and T4. Note the time of the event, 18:35 on May 9. (See Image 3).
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Media type:  Rhythm Strip

Media file 3:  Focal status epilepticus. This electroencephalographic (EEG) fragment, in the same patient as in Image 2, was obtained at approximately 12:39 on May 10, 18 hours after the first fragment. Other EEG acquisitions over the interval were identical. On clinical observation, the patient was lethargic, sluggish, and vague, with variable responsivity to examiners. Note the persistent epileptiform discharges at 1.5-2.5 Hz with phase reversal mainly at Sp2 though infrequently shifting to Sp1 and F7. The bulk of the discharges are maximal at Sp2, reflecting their mesial temporal origin, with rare, subtle, and low-amplitude reflection from lateral neocortical channels (F8). Background activities are slow with admixed beta frequencies. This finding corresponds to complex partial status epilepticus.
	View Full Size Image
Media type:  Rhythm Strip

REFERENCES

Section 10 of 10

• Authors and Editors
• Clinical Characteristics and EEG Manifestations
• Clinical Description
• Differential Diagnosis
• Workup
• Treatment
• Medication
• Follow-up Care
• Multimedia
• References

1. Alexopoulos A, Lachhwani DK, Gupta A, et al. Resective surgery to treat refractory status epilepticus in children with focal epileptogenesis. Neurology. Feb 8 2005;64(3):567-70. [Medline].
2. Assal F, Papazyan JP, Slosman DO, et al. SPECT in periodic lateralized epileptiform discharges (PLEDs): a form of partial status epilepticus?. Seizure. Jun 2001;10(4):260-5. [Medline].
3. Ballenger CE 3d, King DW, Gallagher BB. Partial complex status epilepticus. Neurology. Dec 1983;33(12):1545-52. [Medline].
4. Bensalem MK, Fakhoury TA. Topiramate and status epilepticus: report of three cases. Epilepsy Behav. Dec 2003;4(6):757-60. [Medline].
5. Blumkin L, Lerman-Sagie T, Houri T, et al. Pediatric refractory partial status epilepticus responsive to topiramate. J Child Neurol. Mar 2005;20(3):239-41. [Medline].
6. Borchert LD, Labar DR. Permanent hemiparesis due to partial status epilepticus. Neurology. Jan 1995;45(1):187-8. [Medline].
7. Cascino GD. Nonconvulsive status epilepticus in adults and children. Epilepsia. 1993;34 Suppl 1:S21-8. [Medline].
8. Celesia GG. Modern concepts of status epilepticus. JAMA. Apr 12 1976;235(15):1571-4. [Medline].
9. Cockerell OC, Walker MC, Sander JW, Shorvon SD. Complex partial status epilepticus: a recurrent problem. J Neurol Neurosurg Psychiatry. Jul 1994;57(7):835-7. [Medline].
10. Cury RF, Wichert-Ana L, Sakamoto AC, Fernandes RM. Focal nonconvulsive status epilepticus associated to PLEDs and intense focal hyperemia in an AIDS patient. Seizure. Jul 2004;13(5):358-61. [Medline].
11. DeLorenzo RJ, Garnett LK, Towne AR. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia. Feb 1999;40(2):164-9. [Medline].
12. DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. Apr 1996;46(4):1029-35. [Medline].
13. Dinner DS, Lueders H, Lederman R, Gretter TE. Aphasic status epilepticus: a case report. Neurology. Jul 1981;31(7):888-91. [Medline].
14. Drislane FW. Evidence against permanent neurologic damage from nonconvulsive status epilepticus. J Clin Neurophysiol. Jul 1999;16(4):323-31; discussion 353. [Medline].
15. Drislane FW, Blum AS, Schomer DL. Focal status epilepticus: clinical features and significance of different EEG patterns. Epilepsia. Sep 1999;40(9):1254-60. [Medline].
16. Ellis JM, Lee SI. Acute prolonged confusion in later life as an ictal state. Epilepsia. Apr 1978;19(2):119-28. [Medline].
17. Engel J Jr, Ludwig BI, Fetell M. Prolonged partial complex status epilepticus: EEG and behavioral observations. Neurology. Sep 1978;28(9 Pt 1):863-9. [Medline].
18. Fazekas F, Kapeller P, Schmidt R, et al. Magnetic resonance imaging and spectroscopy findings after focal status epilepticus. Epilepsia. Sep 1995;36(9):946-9. [Medline].
19. Feinberg TE, Roane DM, Cohen J. Partial status epilepticus associated with asomatognosia and alien hand- like behaviors [corrected] [published erratum appears in Arch Neurol 1999 Jan;56(1):24]. Arch Neurol. Dec 1998;55(12):1574-6. [Medline].
20. Geier S, Bancaud J, Bonis A, Enjelvin M. Tele-E.E.G. recordings of three epileptic attacks classified as episodes of PM status [in French]. Rev Electroencephalogr Neurophysiol Clin. Apr-Jun 1977;7(2):201-2. [Medline].
21. Granner MA, Lee SI. Nonconvulsive status epilepticus: EEG analysis in a large series. Epilepsia. Jan-Feb 1994;35(1):42-7. [Medline].
22. Hamilton NG, Matthews T. Aphasia: the sole manifestation of focal status epilepticus. Neurology. May 1979;29(5):745-8. [Medline].
23. Henry TR, Drury I, Brunberg JA, et al. Focal cerebral magnetic resonance changes associated with partial status epilepticus. Epilepsia. Jan-Feb 1994;35(1):35-41. [Medline].
24. Hong KS, Cho YJ, Lee SK, et al. Diffusion changes suggesting predominant vasogenic oedema during partial status epilepticus. Seizure. Jul 2004;13(5):317-21. [Medline].
25. Hosain SA, Solomon GE, Kobylarz EJ. Electroencephalographic patterns in unresponsive pediatric patients. Pediatr Neurol. Mar 2005;32(3):162-5. [Medline].
26. Husain AM, Horn GJ, Jacobson MP. Non-convulsive status epilepticus: usefulness of clinical features in selecting patients for urgent EEG. J Neurol Neurosurg Psychiatry. Feb 2003;74(2):189-91. [Medline].
27. Juul-Jensen P, Denny-Brown D. Epilepsia partialis continua. Arch Neurol. Dec 1966;15(6):563-78. [Medline].
28. Kaplan PW. Nonconvulsive status epilepticus. Semin Neurol. Mar 1996;16(1):33-40. [Medline].
29. Kaplan PW. Nonconvulsive status epilepticus in the emergency room. Epilepsia. Jul 1996;37(7):643-50. [Medline]. [Full Text].
30. Kapur J, Lothman EW, DeLorenzo RJ. Loss of GABAA receptors during partial status epilepticus. Neurology. Dec 1994;44(12):2407-8. [Medline].
31. Kristiansen K, Kaada BR, Henriksen GF. Epilepsia partialis continua. Epilepsia. Sep 1971;12(3):263-7. [Medline].
32. Krumholz A, Sung GY, Fisher RS, et al. Complex partial status epilepticus accompanied by serious morbidity and mortality. Neurology. Aug 1995;45(8):1499-504. [Medline].
33. Kutluay E, Beattie J, Passaro EA, et al. Diagnostic and localizing value of ictal SPECT in patients with nonconvulsive status epilepticus. Epilepsy Behav. Mar 2005;6(2):212-7. [Medline].
34. Lee SI. Nonconvulsive status epilepticus. Ictal confusion in later life. Arch Neurol. Aug 1985;42(8):778-81. [Medline].
35. Lowenstein DH. Status epilepticus: an overview of the clinical problem. Epilepsia. 1999;40 Suppl 1:S3-8; discussion S21-2. [Medline].
36. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. Apr 2 1998;338(14):970-6. [Medline].
37. Manford M, Shorvon SD. Prolonged sensory or visceral symptoms: an under-diagnosed form of non- convulsive focal (simple partial) status epilepticus [published erratum appears in J Neurol Neurosurg Psychiatry 1992 Dec;55(12):1223]. J Neurol Neurosurg Psychiatry. Aug 1992;55(8):714-6. [Medline].
38. Markand ON, Wheeler GL, Pollack SL. Complex partial status epilepticus (psychomotor status). Neurology. Feb 1978;28(2):189-96. [Medline].
39. Meldrum BS, Brierley JB. Prolonged epileptic seizures in primates. Ischemic cell change and its relation to ictal physiological events. Arch Neurol. Jan 1973;28(1):10-7. [Medline].
40. Meldrum BS, Vigouroux RA, Brierley JB. Systemic factors and epileptic brain damage. Prolonged seizures in paralyzed, artificially ventilated baboons. Arch Neurol. Aug 1973;29(2):82-7. [Medline].
41. Misawa S, Kuwabara S, Shibuya K. Low-frequency transcranial magnetic stimulation for epilepsia partialis continua due to cortical dysplasia. J Neurol Sci. Jul 15 2005;234(1-2):37-9. [Medline].
42. Mitchell WG. Status epilepticus and acute repetitive seizures in children, adolescents, and young adults: etiology, outcome, and treatment. Epilepsia. 1996;37 Suppl 1:S74-80. [Medline].
43. Ng YT, Kim HL, Wheless JW. Successful neurosurgical treatment of childhood complex partial status epilepticus with focal resection. Epilepsia. Mar 2003;44(3):468-71. [Medline].
44. Niedermeyer E, Fineyre F, Riley T, Uematsu S. Absence status (petit mal status) with focal characteristics. Arch Neurol. Jul 1979;36(7):417-21. [Medline].
45. Oguni H, Andermann F, Rasmussen TB. The syndrome of chronic encephalitis and epilepsy. A study based on the MNI series of 48 cases. Adv Neurol. 1992;57:419-33. [Medline].
46. Rasmussen T, Olszewski J, Lloyd-Smith D. Focal seizures due to chronic localized encephalitis. Neurology. 1958;8:435-45.
47. Rasmussen T. Further observations on the syndrome of chronic encephalitis and epilepsy. Appl Neurophysiol. 1978;41(1-4):1-12. [Medline].
48. Rogers SW, Andrews PI, Gahring LC. Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis. Science. Jul 29 1994;265(5172):648-51. [Medline].
49. Scholtes FB, Renier WO, Meinardi H. Simple partial status epilepticus: causes, treatment, and outcome in 47 patients. J Neurol Neurosurg Psychiatry. Jul 1996;61(1):90-2. [Medline].
50. Scholtes FB, Renier WO, Meinardi H. Non-convulsive status epilepticus: causes, treatment, and outcome in 65 patients. J Neurol Neurosurg Psychiatry. Jul 1996;61(1):93-5. [Medline].
51. Schomer DL. Focal status epilepticus and epilepsia partialis continua in adults and children. Epilepsia. 1993;34 Suppl 1:S29-36. [Medline].
52. Shorvon S. Definition, classification and frequency of status epilepticus. In: Shorvon S, ed. Status Epilepticus: Its Clinical Features and Treatment in Children and Adults. Cambridge: Cambridge University Press;1994:21-33.
53. Szabo K, Poepel A, Pohlmann-Eden B, et al. Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. Brain. Jun 2005;128(Pt 6):1369-76. [Medline].
54. Theodore WH, Porter RJ, Albert P, et al. The secondarily generalized tonic-clonic seizure: a videotape analysis. Neurology. Aug 1994;44(8):1403-7. [Medline].
55. Thomas JE, Reagan TJ, Klass DW. Epilepsia partialis continua. A review of 32 cases. Arch Neurol. May 1977;34(5):266-75. [Medline].
56. Tomson T, Svanborg E, Wedlund JE. Nonconvulsive status epilepticus: high incidence of complex partial status. Epilepsia. May-Jun 1986;27(3):276-85. [Medline].
57. Tomson T, Lindbom U, Nilsson BY. Nonconvulsive status epilepticus in adults: thirty-two consecutive patients from a general hospital population. Epilepsia. Sep-Oct 1992;33(5):829-35. [Medline].
58. Toone BK, Roberts J. Status epilepticus. An uncommon hysterical conversion syndrome. J Nerv Ment Dis. Sep 1979;167(9):548-52. [Medline].
59. VanLandingham KE, Lothman EW. Self-sustaining limbic status epilepticus. II. Role of hippocampal commissures in metabolic responses. Neurology. Dec 1991;41(12):1950-7. [Medline].
60. Veggiotti P, Beccaria F, Guerrini R, et al. Continuous spike-and-wave activity during slow-wave sleep: syndrome or EEG pattern?. Epilepsia. Nov 1999;40(11):1593-601. [Medline].
61. Walker MC, Smith SJ, Sisodiya SM, Shorvon SD. Case of simple partial status epilepticus in occipital lobe epilepsy misdiagnosed as migraine: clinical, electrophysiological, and magnetic resonance imaging characteristics. Epilepsia. Dec 1995;36(12):1233-6. [Medline].
62. Young GB, Jordan KG, Doig GS. An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality. Neurology. Jul 1996;47(1):83-9. [Medline].

Article Last Updated: May 4, 2006