35-year-old man presents by EMS with seizures. According to family at the scene, he has a history of seizures but has not been taking his medication recently. He has been seizing for 30 minutes, despite treatment of intravenous lorazepam by EMS. On arrival, he is obtunded, foaming at the mouth, and exhibiting generalized tonic-clonic seizure activity.

Clinical Question

» How should status epilepticus be diagnosed?

The diagnosis and management of status epilepticus are essential skills for emergency physicians. Should emergency physicians rely on standard textbooks for diagnostic and treatment regimens? Or should recent literature guide diagnosis and management?

Status epilepticus has previously been defined as seizure(s) greater than or equal to 30 minutes in which the patient does not regain normal mental status between seizures. Alternatively, the Neurocritical Care Society defines it as a seizure with five minutes or more of continuous clinical or EEG seizure activity, or recurrent seizure activity without recovery between seizures.¹

History and physical examination have been the cornerstone of seizure diagnosis in the emergency department (ED). History taking, which relies on patient or witness accounts of the seizure event, can provide critical clues to differentiate seizures from other episodic disorders; however, its sensitivity is limited by the accuracy and completeness of the recollection, which can be affected by the patient’s postictal state or the observer’s understanding of seizure manifestations. Physical examination, including the assessment of postictal signs such as Todd’s paralysis, tongue bite marks, or loss of bladder control, offers additional diagnostic clues but also lacks specificity for seizure diagnosis.

These issues are compounded in the diagnosis of nonconvulsive seizures in critically ill patients. This subset of seizures lacks the dramatic convulsive movements typically associated with seizures, instead manifesting with either subtle clinical signs or altered mental status without any overt seizure-like activity. These seizures are detectable only with EEG monitoring and, similar to convulsive seizures, nonconvulsive seizures that are prolonged or repetitive can present a neurological emergency termed nonconvulsive status epilepticus.² A study of routine EEG in the ED in 2013 found that five percent of ED patients with altered mental status had nonconvulsive seizures (of whom 75 percent were in nonconvulsive status epilepticus).³ A systematic review of nonconvulsive seizures and status epilepticus in the intensive care unit (ICU) reported a pooled prevalence of 15 percent using continuous EEG; however, this prevalence varied considerably according to the clinical context or underlying etiology (eight percent among patients with coma, 10 percent in sepsis, 15 percent in stroke, 23 percent post-cardiac arrest, 33–48 percent following treatment of convulsive status epilepticus).⁴ With the increasing utilization of EEG, especially continuous EEG, nonconvulsive seizures have been increasingly recognized and diagnosed as a cause of altered mental status in critically ill patients.

Although they may not appear as physically injurious as convulsive seizures, nonconvulsive seizures can significantly impact the neurological outcomes and overall prognosis of patients in critical care settings. Especially in the case of status epilepticus, delayed treatment can lead to a phenomenon known as pharmacoresistance, in which the effectiveness of anti-seizure medications diminishes over time due to neurobiological changes that alter drug targets (e.g., reduced surface expression of postsynaptic GABAA receptors) and drug transport mechanisms (e.g., increased expression of drug efflux transporters) to enable self-sustaining ictal rhythms.^5,6 This underscores the importance of being vigilant and integrating clinical findings with advanced diagnostic tools like EEG to improve diagnostic accuracy for seizures and refine the management of critically ill patients to ensure comprehensive neurological care.⁷

Several studies have demonstrated the importance of EEG monitoring in the management of seizures.^8–11 Although continuous EEG monitoring would be the gold standard for diagnosing and managing nonconvulsive seizures, it is either unavailable or delayed at many centers, and it is rarely performed in the ED. This is because conventional EEG requires a large machine, a qualified technologist, and a significant amount of time for setup, and the output data must be reviewed and interpreted by a neurologist. Some institutions have the capability to perform real-time EEG monitoring and interpretation by a neurologist in the ED. Other devices have demonstrated potential use as an alternative to traditional EEG monitoring. For example, other modes of EEG monitoring may be used in the operative setting, including bispectral index monitoring (BIS) and SEDline device, to monitor depth of sedation.¹² A point-of-care (POC) EEG system has been developed to provide real-time EEG data.¹³ Preliminary data suggest that among 157 adult patients, POC EEG enabled acquisition of EEG data within 90 minutes of ED arrival, identified epileptiform activity in 36 percent of patients, and impacted treatment decisions.¹⁴ Future research is needed to determine the sensitivity and specificity of this device, particularly in the ED environment, where patients may have taken medications or recreational drugs, or may have received sedative or antiepileptic medications.

Diagnostic studies useful in determining the etiology may include POC glucose, serum electrolytes, and complete blood count. Other considerations dependent on the clinical setting and history may include CT scan, MRI, or lumbar puncture.

Management of status epilepticus includes stabilization of airway, breathing, and circulation. If a patient is obtunded or unable to protect the airway, endotracheal intubation is indicated. Following stabilization, pharmacologic therapy should be initiated with first-line therapy of a benzodiazepine, such as lorazepam. Appropriate dosing is associated with seizure termination and reduced complications.^15-17 Anti-epileptic medication may be administered concurrently, such as fosphenytoin, phenytoin, levetiracetam, or valproic acid.^18–21 Refractory status epilepticus may be treated with a continuous infusion of an antiepileptic medication, such as propofol, ketamine, midazolam, or pentobarbital.

Consultation with neurology should be sought to guide therapy. Patients with status epilepticus require hospital admission, often to an intensive care setting.

Case Conclusion

Following stabilization of airway, breathing, and circulation, antiepileptic therapy is indicated. This patient has already received first-line treatment with a benzodiazepine. Specific antiepileptic therapy should be initiated with another agent, such as fosphenytoin, phenytoin, levetiracetam, or valproic acid. Neurology consultation should be initiated, and the patient should be admitted to the ICU.

Disclaimer

This article is not a comprehensive review of diagnosis and treatment of status epilepticus but an overview of management and future directions. Authoritative sources should be used for diagnostic and treatment decisions.

References

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