Nonconvulsive Status Epilepticus: Overlooked and Undertreated

Table of Contents

 

When a patient presents to the ED with new-onset altered mental status or unusual behavior without visible convulsive activity, how can you tell if it is nonconvulsive status epilepticus? Prompt treatment can prevent neurologic sequelae.

Definitive diagnosis is by EEG, but what are the clinical clues that will help determine what’s causing the behavior changes if EEG is unavailable?

Do patients in NCSE always have impaired consciousness?

What are the possible causes of NCSE?

What are the risk factors that could point to NCSE?

Is CT scan recommended for all patients who have a seizure?

What are the first-line, second-line, and third-line drugs to use?

How should you manage alcoholic patients who present with seizure?

What are the cautions you should exercise when managing elderly patients with NCSE?

1. Abstract
2. Case Presentations
3. Abbreviations of Types of Status Epilepticus
4. Introduction
5. Classification and Taxonomy of Status Epilepticus
6. Critical Appraisal of the Literature
7. Etiology and Pathophysiology
8. Differential Diagnosis
9. Prehospital Care
10. Emergency Department Evaluation
    1. History
    2. Physical Examination
11. Diagnostic Studies
    1. Laboratory Studies
    2. Neuroimaging
    3. Lumbar Puncture
    4. Electroencephalography
12. Treatment
    1. Pharmacologic Therapy
       1. First-Line Treatment
       2. Second-Line Treatment
       3. Third-Line Treatment
13. Special Populations
    1. Patients Abusing Alcohol
    2. Elderly Patients
14. Controversies and Cutting Edge
    1. Bedside Electroencephalography
    2. Additional Treatment Options
15. Disposition
16. Summary
17. Time- and Cost-Effective Strategies
18. Risk Management Pitfalls for Patients With Nonconvulsive Status Epilepticus in the Emergency Department
19. Case Conclusions
20. Clinical Pathway for Management of Nonconvulsive Status Epilepticus
21. Tables
    1. Table 1. Clinical Features of Nonconvulsive Status Epilepticus
    2. Table 2. Clinical Subtypes and Features of Nonconvulsive Status Epilepticus
    3. Table 3. Common Etiologies of Nonconvulsive Status Epilepticus
    4. Table 4. Differential Diagnosis for Nonconvulsive Status Epilepticus
    5. Table 5. Clinical Findings and Risk Factors in Nonconvulsive Status Epilepticus
    6. Table 6. Treatment Approach in Nonconvulsive Status Epilepticus, by Subtype
    7. Table 7. Pharmacotherapy for Nonconvulsive Status Epilepticus
    8. Table 8. Indications for Continuous EEG to Diagnose Nonconvulsive Status Epilepticus in the Critically Ill Patient
22. References

Abstract

Nonconvulsive status epilepticus (NCSE) is characterized by persistent change in mental status from baseline lasting more than 5 minutes, generally with epileptiform activity seen on EEG monitoring and subtle or no motor abnormalities. NCSE can be a difficult diagnosis to make in the emergency department setting, but the key to diagnosis is a high index of suspicion coupled with rapid initiation of continuous EEG and early involvement of neurology. Benzodiazepines are the mainstay of first-line therapy, with antiepileptic drugs and anesthetics as second- and third-line therapies, respectively. The few established guidelines on the treatment of NCSE are highly variable, and the objective of this comprehensive review is to create a standardized evidence-based protocol for the diagnosis and treatment of NCSE.

Case Presentations

An 81-year-old woman presents with 1 day of behavioral changes. On examination, she is disoriented, with no focal neurologic findings and no evidence of seizure activity. Her medical history is remarkable for anxiety, arthritis, and hypertension; she has no history of stroke, trauma, or immunocompromise. Her medications include furosemide, lorazepam, and acetaminophen. After an extensive workup in the ED including ECG, CBC, CMP, UA, and brain CT, all of which were normal, she was admitted to the floor. You wonder: Is there something you forgot to consider in your differential diagnosis?

A 35-year-old man with unknown history is brought to the ED following a 10-minute witnessed seizure. EMS administered 4 mg of lorazepam IV and fosphenytoin 1200 PE IVPB, which terminated the seizure; however, the patient remained altered. Brain CT was normal. ECG, CBC, CMP, VBG, UDS, and UA were unremarkable other than an elevated lactate that quickly cleared. You admit him to the ICU, but wonder: Is he is altered because he is postictal? Is it from the lorazepam, or could there be another etiology to consider?

A 42-year-old homeless man with bipolar disorder arrives by EMS after being found on a park bench. He has a temperature of 38.1°C (100.6°F) but otherwise normal vital signs. He smells of alcohol and has abrasions on his hands and face. GCS score is 10, and he is mumbling inappropriate but comprehensible words. Brain CT and cervical spine were normal. Laboratory testing demonstrated elevated BUN, Cr, CPK, and alcohol levels; mild leukocytosis; and normal UA and UDS. When his mental status did not improve, you order a lumbar puncture, but you wonder: Could another test could be diagnostic?

Abbreviations of Types of Status Epilepticus

Introduction

Seizures are classified as partial or generalized, and they can generate motor, sensory, psychiatric, or autonomic disturbances. A partial seizure denotes abnormal neuronal firing within a limited area of 1 brain hemisphere, whereas a generalized seizure constitutes abnormal firing diffusely across both hemispheres. Partial seizures are simple when they do not involve a change in mental status, and complex when consciousness is impaired. Seizures with altered mental status (AMS) but without motor activity are classified as nonconvulsive seizures.

Status epilepticus has been traditionally defined as a continuous seizure that lasts > 30 minutes, or multiple seizures in a 30-minute period without return to baseline. This definition was based largely on pathophysiologic observations that long-term consequences, including neuronal injury and death, result from seizures that last > 30 minutes. In practice, individual seizures that last > 5 minutes are prone to persist or recur before full recovery is made and, in all likelihood, represent status epilepticus.¹

By definition, nonconvulsive status epilepticus (NCSE) presents with a persistent alteration in behavior or consciousness in the absence of convulsive activity, but the range of possible symptoms is broad. (See Table 1 and Table 2.) Although overt convulsions are absent, subtle motor signs such as twitching or blinking, extrapyramidal signs, or myoclonus may be seen.² Despite the lack of convulsive activity, NCSE may still result in neuronal injury, making early recognition and treatment critically important.

NCSE is underdiagnosed, especially in patients without antecedent convulsive seizures.³ Many of these patients are not diagnosed in the emergency department (ED), either due to failure to consider the diagnosis or to lack of access to emergent encephalography (EEG), which confirms NCSE.^4,5 The role of EEG in the ED is evolving, and newer portable technologies are being developed that may increase access and allow rapid confirmation of suspected NCSE.⁶

This issue of Emergency Medicine Practice provides an evidence-based review of the diagnosis and management of NCSE. An emphasis is placed on increasing awareness in order to initiate timely therapy and prevent neurologic sequelae.

Risk Management Pitfalls for Patients With Nonconvulsive Status Epilepticus in the Emergency Department

3. “Benzos didn’t work. I was starting a second-line agent, and the nurse came to tell me that the sodium was 118.”

NCSE represents a final common pathway for numerous pathologies. Seizures can be precipitated by various chemical and metabolic insults, with or without structural central nervous system abnormality. It is important to consider all possible causes and focus medical management on identifying a correctable etiology before escalating therapy (ie, seizures brought on by hypoglycemia, pre-eclampsia, isoniazid overdose, and drug toxicity).

6. “Everything is back and all the tests are normal, but the patient is still altered. We can’t get an EEG. Should we give a benzo?”

When NCSE is suspected and EEG is unavailable, consider an early trial of benzodiazepines and observe for clinical improvement. Benzodiazepine efficacy decreases the longer a seizure persists, so the initial agent should be started as quickly as possible; however prior to empiric treatment, coordination with neurology is ideal.

10. “He stopped convulsing, but I’m not sure whether he is still seizing.”

The only way to truly know whether a patient is in NCSE is to monitor brain activity with cEEG. Failure to initiate cEEG early can lead to delayed recognition of clinical deterioration and diminished efficacy of antiepileptic therapy. Emergency clinicians must advocate at an institutional and specialty level for timely access to cEEG, initiated as soon as possible when the diagnosis of NCSE is considered.

Tables

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

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