History
Generalized convulsive status epilepticus (SE) is usually easy to diagnose, but an understanding of its evolution from overt convulsions through subtle SE is important. Patients may present with an undramatic clinical picture if they have subtle SE at the time of presentation.
Treiman and coworkers [48, 49, 50] described the clinical and electroencephalographic (EEG) changes accompanying generalized convulsive SE. The event usually begins with a series of generalized tonic, clonic, or tonic-clonic seizures that often are dramatic. Each seizure is discrete; the motor activity stops abruptly, coincident with the end of the electrographic seizure. Each convulsion is followed by gradual recovery, and then the next seizure occurs.
If the condition is not treated or is treated inadequately, SE persists, and the motor manifestations become less dramatic than before. Eventually, only subtle movements (eg, nystagmoid jerks of the eyes or twitching of the shoulder) may be seen—that is, subtle SE. If SE continues, all motor activity may stop, though EEG seizures persist (ie, electrical generalized convulsive SE).
The paradoxical evolution of apparent clinical improvement is important to understand. The clinician unfamiliar with this phenomenon may stop treatment because of the apparent improvement. Treatment should be continued until the EEG seizure activity has resolved completely.
In some patients, the underlying encephalopathic insult is so severe that only a few (or no) generalized convulsions occur before subtle convulsive activity develops. Finally, as the patient evolves from generalized tonic-clonic SE into subtle and then electrical generalized tonic-clonic SE, the manifestations become less intermittent and more continuous than before.
Persons accompanying the patient may be able to provide important information. A history of epilepsy frequently is elicited. Among patients with established epilepsy, noncompliance with medications is the rule rather than the exception. In roughly one third of cases, status epilepticus is the initial presentation of a seizure disorder.
In those without epilepsy, the history may suggest associated injuries, such as a fall or involvement in a motor vehicle accident. A history of systemic or CNS neoplasms, infections, metabolic disorders, toxic ingestions, alcohol cessation, and many other conditions may give clues to the precipitating cause of seizures.
Nonmotor simple partial status epilepticus
By clinical history, nonmotor simple partial SE involves subjective sensory disturbances, including the following:
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Focal or unilateral paresthesias or numbness
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Focal visual changes, usually characterized by flashing lights
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Focal visual obscuration or focal colorful hallucinations
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Olfactory or gustatory hallucinations
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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 focal SE.
Because these particular forms of SE involve sensory disturbances with preserved consciousness, no helpful clinical signs are associated with them. The gradual evolution of nonmotor simple partial SE into overt complex partial or generalized SE 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 SE. However, long-lasting focal sensory disturbances after convulsive seizures often represent a transient postictal phenomenon rather than focal SE. EEG often helps in making this clinical distinction.
Epilepsy partialis continua
Focal SE of the motor cortex, known as epilepsy partialis continua, may occur in various contexts. Some authors subdivide epilepsy partialis continua into type I (nonprogressive) and type II (progressive).
Type I epilepsy partialis continua features 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.
Type I classically occurs after acute insults to the sensorimotor cortex. These insults may be infectious (eg, Russian spring-summer encephalitis), neoplastic, immune mediated, structural, traumatic, metabolic, or vascular.
Nonketotic hyperglycemic diabetes, particularly in association with hyponatremia, occasionally causes epilepsy partialis continua, often in patients with a preexisting focal CNS lesion (eg, stroke). Epilepsy partialis continua may be a feature of mitochondrial disorders such as mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and myoclonic epilepsy with ragged-red fiber disease (MERRF). [51]
The syndrome of childhood epilepsy with rolandic spikes (ie, benign rolandic epilepsy) may occasionally involve epilepsy partialis continua. 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.
Type II epilepsy partialis continua, 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; epilepsy partialis continua 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
Complex partial SE often begins with a history of recurrent or prolonged simple partial seizures, or it may follow or precede a generalized convulsive seizure. Patients 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 complex partial SE.
Type I complex partial SE refers to recurrent, recognizable complex partial seizures without recovery between seizures. Type II 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 complex partial SE from absence (generalized) nonconvulsive SE may be problematic; an 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.
As in generalized SE, patients with focal SE often have an established history of epilepsy, and subtherapeutic anticonvulsant levels or other new metabolic or systemic stressors may be implicated in the expression of FSE. Alternatively, acute or chronic focal cerebral injuries of various kinds (especially, vascular insults) may provide the substrate for new-onset focal seizures and SE.
Refractory and super-refractory status epilepticus
Refractory status epilepticus is defined as recurrent seizures in spite of treatment with two anticonvulsants (including a benzodiazepine); super-refractory status epilepticus is defined as recurrent seizures in spite of anticonvulsants and anaesthetic therapy beyond the 24-hour mark. [52] Mechanisms behind these two conditions are thought to involve internalization of GABA receptors and increase in the number of glutamate receptors on the cell surface, among other factors. Also at the cellular level, refractory and super-refractory status epilepticus is characterized by a change in the ion concentration surrounding the cell; mitochondrial dysfunction; changes in the vasculature and opening of the blood-brain barrier. [53] These changes, along with excitotoxicity (glutamatergic excess), contribute to cerebral injury with status epilepticus—and in particular, refractory and super-refractory status epilepticus.
Physical Examination
Generalized convulsive status epilepticus often is recognizable to the clinician at the bedside when typical rhythmic tonic-clonic activity is present. Consciousness is impaired. Rarely, status epilepticus may present as a persistent tonic seizure.
A number of features on physical examination may provide information about the underlying cause of SE. Needle track marks might suggest SE secondary to the use of illicit, or street, drugs. Features on neurologic examination can also be helpful.
Papilledema, a sign of increased intracranial pressure, suggests a possible mass lesion or brain infection. Lateralized neurologic features, such as increased tone, asymmetric reflexes, or lateralized features of the movement during SE itself, are suggestive of the seizures beginning in a localized region of the brain, and they may suggest a structural brain abnormality.
Rapid repeated extensor or flexor posturing may be confused with convulsive activity by a casual observer. Repetitive myoclonus in a comatose patient following diffuse hypoxic brain injury may simulate generalized seizures. The physiologic origin of the myoclonic jerks may not be cortical. The myoclonus usually is limited in duration to several hours.
Suspect subtle status epilepticus or transformed status epilepticus in any patient who does not have improving level of consciousness within 20-30 minutes of cessation of generalized seizure activity. The motor expression of the abnormal cortical electrical activity may change so that a flicker of an eyelid or twitch of an extremity is the only sign of the ongoing generalized electrical discharges. Motor activity may be absent even in the presence of ongoing electrical status epilepticus.
Associated injuries that may be present in patients with seizures include tongue lacerations (typically lateral), shoulder dislocations, head trauma, and facial trauma.
Complications
Complications of status epilepticus are many. Systemic complications include the following:
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Hyperthermia
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Acidosis
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Hypotension
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Respiratory failure
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Rhabdomyolysis
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Aspiration
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Treatment algorithms for convulsive status epilepticus.
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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 side of the 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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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.
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Focal status epilepticus. This electroencephalographic (EEG) fragment was obtained at approximately 12:39 on May 10, 18 hours after the onset of complex partial status epilepticus originating in the right temporal lobe, in a 35-year-old patient with a history of intractable partial epilepsy. 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.
