Seizures in the ICU: Recognition, Evaluation, and Management with Special Emphasis on Non-Convulsive Seizures and Status Epilepticus

Dr Neeraj Manikath ; claude.ai

Introduction

Seizures represent a significant neurological complication in critically ill patients, occurring in approximately 8-34% of ICU patients. The incidence varies depending on the underlying pathology and comorbidities. While convulsive seizures are relatively easy to recognize, non-convulsive seizures (NCS) and non-convulsive status epilepticus (NCSE) present unique diagnostic challenges due to their subtle clinical manifestations. These conditions are associated with increased morbidity, mortality, and prolonged ICU stays if not promptly recognized and managed. This review focuses on the recognition, evaluation, and management of seizures in the ICU setting, with special emphasis on non-convulsive presentations.

Epidemiology and Etiology of ICU Seizures

Incidence

• Overall incidence of seizures in ICU: 8-34%
• Non-convulsive seizures: 10-20% of all ICU seizures
• Non-convulsive status epilepticus: 8-19% of comatose ICU patients without overt seizure activity

Common Etiologies in ICU Patients

1. Primary Neurological Conditions

   • Traumatic brain injury (TBI)
   • Ischemic or hemorrhagic stroke
   • Subarachnoid hemorrhage (10-26% develop seizures)
   • Central nervous system infections
   • Primary epilepsy syndromes

2. Systemic Disorders

   • Metabolic derangements (hyponatremia, hypoglycemia, uremia)
   • Toxic-metabolic encephalopathy
   • Sepsis and systemic inflammatory response syndrome
   • Hepatic or renal failure
   • Autoimmune disorders

3. Iatrogenic Causes

   • Medication effects (particularly antibiotics, antipsychotics)
   • Medication withdrawal (benzodiazepines, antiepileptics, alcohol)
   • Anesthetic agents

Clinical Presentation and Recognition of Non-Convulsive Status Epilepticus (NCSE) in the ICU

Clinical Manifestations of NCSE

NCSE presents with a remarkably heterogeneous clinical picture, making it one of the most challenging neurological conditions to diagnose in the ICU setting. The presentation can range from subtle behavioral changes to profound alterations in consciousness without the classic motor manifestations seen in convulsive status epilepticus.

Spectrum of Mental Status Changes

1. Altered Consciousness

   • Fluctuating levels of awareness (waxing and waning pattern)
   • Unexplained or disproportionate coma
   • Delayed recovery from anesthesia or sedation
   • Failure to regain consciousness after convulsive seizures

2. Behavioral Abnormalities

   • Acute confusion or delirium not explained by metabolic derangements
   • Inappropriate responses to commands
   • Perseveration or echolalia
   • Abnormal behavior including agitation, aggression, or withdrawn states
   • Psychosis-like symptoms (hallucinations, delusions) in previously lucid patients

3. Speech and Language Disturbances

   • Aphasia, particularly if intermittent or fluctuating
   • Speech arrest or mutism inconsistent with structural lesions
   • Garbled speech or paraphasic errors
   • Forced speech or pressured verbal output

4. Cognitive Changes

   • Acutely impaired attention and concentration
   • Memory deficits (particularly short-term)
   • Executive dysfunction disproportionate to underlying condition
   • Disorientation despite resolution of metabolic causes

Subtle Motor Manifestations

Unlike convulsive seizures, motor activity in NCSE is minimal but can include:

1. Ocular Signs

   • Nystagmus (horizontal, vertical, or rotatory)
   • Sustained eye deviation or subtle gaze preference
   • Abnormal or fluctuating pupillary responses
   • Eyelid fluttering or subtle blinking (>3 Hz)
   • Sustained eye opening or closing

2. Facial Movements

   • Facial twitching (particularly perioral or periorbital)
   • Subtle jaw movements or rhythmic chewing
   • Grimacing or facial automatisms
   • Lip smacking or oral automatisms

3. Extremity Findings

   • Subtle rhythmic movements of fingers or toes
   • Asymmetric posturing
   • Minimal clonic activity in distal extremities
   • Automatisms (e.g., picking at bed clothes, fumbling)
   • Tremor-like movements distinct from metabolic tremors

4. Autonomic Disturbances

   • Fluctuating vital signs unrelated to medication effects
   • Tachycardia out of proportion to fever or distress
   • Hypertension refractory to standard management
   • Hypersalivation
   • Diaphoresis
   • Pupillary changes (often subtle and asymmetric)
   • Temperature dysregulation

Specific NCSE Syndromes and Presentations

Subtle Status Epilepticus

• Occurs following overt convulsive status epilepticus
• Cessation of overt convulsions but continued electrical seizure activity
• Often seen in deeply comatose patients
• Characterized by subtle motor signs that may be limited to eye movements or toe twitching

Absence Status Epilepticus

• More common in patients with pre-existing generalized epilepsy
• Clouding of consciousness with blank staring
• May maintain responsiveness to basic stimuli
• Patients appear "disconnected" from environment
• Can last hours to days if unrecognized

Complex Partial Status Epilepticus

• Often presents with confusion, behavioral changes
• May exhibit automatisms (lip smacking, chewing, swallowing)
• Associated with temporal or frontal lobe dysfunction
• Can have prolonged postictal states with persistent confusion

Aura Continua

• Prolonged sensory symptoms (olfactory, visual, or auditory hallucinations)
• Patient may remain conscious and describe ongoing abnormal perceptions
• Limited response to environment due to continuous abnormal sensations

Clinical Settings and High-Risk Populations for NCSE

Post-Convulsive Status

• NCSE occurs in up to 14-48% of patients after apparent resolution of convulsive status
• Persistent altered mental status after convulsive seizures warrants EEG monitoring
• Particularly common when benzodiazepines alone used to terminate convulsions

Post-Neurosurgical States

• Incidence of 3-17% in post-neurosurgical patients
• Particularly common after tumor resection, aneurysm clipping, or traumatic brain injury surgery
• May be misattributed to postoperative delirium or medication effects

Critical Illness-Related NCSE

• Particularly common in septic encephalopathy (9-22%)
• Often seen in multi-organ failure with metabolic derangements
• Can be precipitated by medication adjustments or withdrawal
• More common in patients requiring mechanical ventilation

Vulnerable Neurological Populations

• Patients with acute brain injuries (stroke, TBI, hypoxic injury)
• Those with pre-existing epilepsy, particularly with antiepileptic drug withdrawal
• Patients with autoimmune encephalitis
• Elderly patients with acute neurological changes

Diagnostic Challenges and Mimics

Common Misdiagnoses

• Metabolic encephalopathy
• Psychiatric disorders (particularly in patients with preserved consciousness)
• Post-ictal states
• Medication effects (particularly sedatives, antipsychotics)
• Neurodegenerative processes with rapid decline
• Toxic-metabolic delirium

Differential Diagnostic Features

• Fluctuating symptoms (often cycling over minutes to hours)
• Lack of improvement despite correction of metabolic abnormalities
• Poor response to typical delirium management
• Subtle motor phenomena observable with careful examination
• Response to benzodiazepine challenge (diagnostic trial)

Clinical Assessment Approaches

Structured Clinical Evaluation

1. Four-Score Coma Assessment

   • More sensitive than GCS for detecting subtle neurological changes
   • Includes eye response, motor response, brainstem reflexes, and respiration

2. Standardized Mental Status Examination

   • Serial assessments to detect fluctuations
   • Attention tasks particularly sensitive (digit span, months backward)
   • Language assessment (naming, comprehension, repetition)

3. Richmond Agitation-Sedation Scale (RASS) Fluctuations

   • Unexplained changes in RASS scores
   • Particularly relevant in sedated patients

Provocative Testing

1. Noxious Stimuli Response Assessment

   • Asymmetric or unusual responses
   • Facial grimacing without appropriate motor withdrawal

2. Benzodiazepine Challenge

   • Administration of IV lorazepam (1-2 mg) or midazolam (2-5 mg)
   • Temporary improvement in mental status suggests NCSE
   • Both clinical and EEG improvement may be observed
   • False negatives possible in refractory cases

Specialized Physical Examination Techniques

1. Oculomotor Testing

   • Passive eye opening and observation for eyelid myoclonia
   • Testing for oculocephalic reflexes (subtle abnormalities may be present)
   • Assessment for subtle nystagmus with directional changes

2. Systematic Motor Examination

   • Observation for minimal appendicular myoclonus
   • Assessment of tone fluctuations
   • Testing for subtle asymmetries in reflexes or tone

3. Autonomic Evaluation

   • Heart rate variability assessment
   • Pupillary dynamics (subtle asymmetries or fluctuations)
   • Skin temperature changes (may have thermal asymmetries)

Electroencephalographic Features

While EEG remains the gold standard for diagnosis, understanding the clinical correlation with specific patterns is essential:

Classic EEG Patterns in NCSE

1. Rhythmic Delta Activity (RDA)

   • Often seen in moderate to severe encephalopathy
   • May evolve into clear seizure activity
   • Particular significance when asymmetric or changing over time

2. Periodic Discharges

   • Lateralized Periodic Discharges (LPDs) - associated with focal structural lesions
   • Generalized Periodic Discharges (GPDs) - often seen in toxic-metabolic states
   • Bilateral Independent Periodic Discharges (BIPDs) - highly epileptogenic

3. Continuous 2-3 Hz Spike-Wave Discharges

   • Classic pattern in absence status epilepticus
   • May be modified by medications

4. Evolving Rhythmic Activity

   • Changes in frequency, amplitude, or distribution over time
   • Evolution is key diagnostic feature distinguishing seizures from artifact

Salzburg Consensus Criteria for NCSE (2015)

These clinical and EEG criteria have improved standardization in diagnosis:

1. EEG criteria (one must be present):

   • Epileptiform discharges >2.5 Hz
   • Epileptiform discharges ≤2.5 Hz with clinical improvement after IV AED
   • Rhythmic delta/theta activity (>0.5 Hz) with evolution in frequency, morphology, or location

2. Clinical criteria (associated with EEG changes):

   • Altered mental status
   • Decreased responsiveness
   • Subtle motor phenomena

Multimodal Detection Approaches

Combined Monitoring Strategies

1. EEG with Video Recording

   • Correlation of subtle clinical signs with electrographic activity
   • Detection of behavioral changes missed on routine examination

2. Quantitative EEG Trending

   • Detection of subtle changes in frequency composition
   • Identification of seizure patterns that may be missed on visual review

3. Neuromonitoring Integration

   • Brain tissue oxygenation changes during seizures
   • Microdialysis showing metabolic shifts (increased lactate/pyruvate ratio)
   • Cerebral blood flow alterations on transcranial Doppler

Neuroimaging Correlates

1. MRI Findings

   • Restricted diffusion on DWI in affected regions
   • FLAIR hyperintensities in prolonged cases
   • Perfusion changes (hyperperfusion during ictal activity)

2. Functional Imaging

   • PET/SPECT showing hypermetabolism in active seizure foci
   • ASL perfusion MRI demonstrating increased regional blood flow

Practical Approach to Recognition in ICU Setting

High-Risk Clinical Scenarios Requiring Vigilance

1. Post-Cardiac Arrest

   • Up to 12-22% develop NCS/NCSE
   • Often masked by therapeutic hypothermia or sedation
   • Associated with worse neurological outcomes

2. Unexplained Neurological Deterioration

   • New focal deficits without structural explanation
   • Failure to wean sedation
   • Increasing vasopressor requirements without clear cause

3. Fluctuating Glasgow Coma Scale Score

   • Changes of ≥2 points without clear explanation
   • Particular attention to eye opening component

4. Persistent Altered Mental Status Despite Treatment of Presumed Cause

   • Failure to improve after correction of metabolic derangements
   • Persistent delirium despite appropriate interventions

Screening Protocols

1. Routine EEG Screening

   • Brief (30-minute) EEG for high-risk patients
   • Continuation to continuous monitoring if suspicious patterns found

2. Standardized Nursing Assessment Tools

   • Nursing checklists for subtle seizure signs
   • Regular documented assessments for eye movements, facial twitching

3. Triggered EEG Protocols

   • Clinical criteria that automatically trigger EEG evaluation
   • Integration into ICU bundles of care

Clinical Pearls for Recognition

1. Fluctuating Symptoms: The hallmark of NCSE is often a waxing and waning pattern of neurological findings.

2. Delayed Recovery: Unexplained delays in regaining consciousness after sedation withdrawal should prompt consideration of NCSE.

3. Eye Movements Matter: Subtle ocular findings are often the only clinical manifestation in deeply comatose patients.

4. Autonomic Instability: Unexplained vital sign variability or autonomic storms can be manifestations of ongoing seizure activity.

5. Refractory Symptoms: When standard treatments for delirium or encephalopathy fail, consider NCSE.

6. Systematic Examination: Brief but systematic evaluation for subtle motor phenomena should be part of routine ICU neurological assessment.

7. Risk Stratification: Certain conditions (TBI, subarachnoid hemorrhage, encephalitis) carry particularly high risk and deserve lower threshold for EEG evaluation.

8. Monitoring after Convulsions: Prolonged altered mental status following convulsive seizures warrants EEG evaluation.

This expanded section provides a comprehensive overview of the clinical presentation and recognition of NCSE in the ICU setting, emphasizing the importance of systematic assessment and high clinical suspicion in appropriate contexts.

Risk Factors for Developing NCS/NCSE in ICU Patients

1. Pre-existing conditions

   • Prior history of epilepsy
   • Structural brain lesions
   • Advanced age

2. Acute conditions

   • Sepsis and systemic inflammatory response syndrome
   • Acute brain injury (stroke, trauma, surgery)
   • Metabolic derangements

3. Pharmacological factors

   • Sedation interruption or withdrawal
   • Use of pro-convulsant medications
   • Insufficient antiepileptic drug levels

Diagnostic Evaluation

Clinical Assessment

• Thorough neurological examination
• Identification of subtle clinical signs (eye movements, autonomic changes)
• Glasgow Coma Scale (GCS) assessment and tracking
• Richmond Agitation-Sedation Scale (RASS) monitoring

Electroencephalography (EEG)

EEG remains the gold standard for diagnosing NCS and NCSE:

1. Conventional EEG:

   • Should be performed in any ICU patient with unexplained altered mental status
   • Minimum 30-minute recording recommended
   • Sensitivity increases with recording duration

2. Continuous EEG Monitoring (cEEG):

   • Recommended for high-risk patients
   • Duration of 24-48 hours captures 90-95% of seizures
   • Essential for monitoring treatment response

3. Common EEG Patterns in ICU Seizures:

   • Electrographic seizures with evolution in frequency, amplitude
   • Periodic discharges (PDs) with evolution
   • Lateralized periodic discharges (LPDs)
   • Generalized periodic discharges (GPDs)
   • Rhythmic delta activity (RDA)

Laboratory Investigations

• Complete metabolic panel
• Toxicology screening
• Inflammatory markers
• Antiepileptic drug levels (if applicable)
• CSF analysis when infection suspected

Neuroimaging

• CT brain (for acute pathology)
• MRI brain (superior for identifying structural abnormalities)
• Advanced imaging (perfusion, spectroscopy) in selected cases

Management Approaches

General Principles

1. Stabilization:

   • Airway protection
   • Hemodynamic support
   • Prevention of secondary injury

2. Treatment of Underlying Causes:

   • Correction of metabolic abnormalities
   • Treatment of infections
   • Management of increased intracranial pressure
   • Discontinuation of offending medications

Pharmacological Management

First-Line Agents

1. Benzodiazepines:

   • Lorazepam (0.1 mg/kg IV)
   • Midazolam (0.2 mg/kg IV bolus, followed by 0.1-0.4 mg/kg/hr infusion)
   • Diazepam (0.15-0.2 mg/kg IV)

2. Loading Antiseizure Medications (ASMs):

   • Phenytoin/Fosphenytoin (20 mg/kg IV, target level 10-20 μg/mL)
   • Valproic acid (40 mg/kg IV, target level 50-100 μg/mL)
   • Levetiracetam (60 mg/kg, up to 4500 mg IV)
   • Lacosamide (400 mg IV)

Second-Line Agents (Refractory Status)

1. Continuous Infusions:
   • Propofol (1-2 mg/kg bolus, followed by 1-10 mg/kg/hr)
   • Midazolam (0.2 mg/kg bolus, followed by 0.1-2 mg/kg/hr)
   • Ketamine (1-3 mg/kg bolus, followed by 1-10 mg/kg/hr)
   • Pentobarbital (5-15 mg/kg bolus, followed by 0.5-10 mg/kg/hr)

Third-Line Approaches (Super-Refractory Status)

• Ketogenic diet
• Immunotherapy (steroids, IVIG, plasmapheresis)
• Surgical interventions (in focal cases)
• Novel antiseizure medications (perampanel, brivaracetam)

Special Considerations for NCSE

1. Treatment Aggressiveness:

   • Should be tailored to clinical context and EEG patterns
   • Less aggressive approach may be warranted compared to convulsive status
   • EEG-guided titration of medications

2. Monitoring Response:

   • Continuous EEG monitoring essential
   • Clinical correlation with EEG findings
   • Treatment targets may include:
     • Complete resolution of seizures
     • Burst suppression pattern
     • Suppression of periodic discharges

3. Duration of Therapy:

   • Acute treatment: 24-48 hours of seizure control
   • Maintenance therapy: Individualized based on etiology

Monitoring and Prognostication

Continuous Monitoring

• Vital signs with attention to autonomic changes
• Neurological examination trends
• Continuous EEG when available
• ICP monitoring in selected cases

Outcome Predictors

• Etiology (structural vs. metabolic)
• Duration of status before treatment
• Age and comorbidities
• Response to initial therapy
• EEG patterns (evolution, background activity)

Long-term Management

• Transitioning to oral antiepileptic regimens
• Tapering of sedative agents
• Rehabilitation needs assessment
• Seizure precautions after discharge

Prevention Strategies

1. Pharmacological Prophylaxis:

   • Not routinely recommended
   • Consider in high-risk patients (TBI, subarachnoid hemorrhage)
   • Options: Levetiracetam, phenytoin for short-term (7-14 days)

2. Avoidance of Triggers:

   • Careful medication selection
   • Planned weaning of sedatives
   • Metabolic control

3. Optimization of AED Regimens:

   • Therapeutic drug monitoring
   • Consideration of drug interactions
   • Avoid abrupt discontinuation

Conclusion

Seizures, particularly non-convulsive types, represent a significant diagnostic and therapeutic challenge in the ICU setting. A high index of suspicion, appropriate use of EEG monitoring, and prompt multi-modal treatment are essential for improving outcomes. Recognition of risk factors and early intervention can prevent progression to refractory status epilepticus and minimize secondary brain injury. Further research is needed to establish optimal treatment protocols, particularly for NCSE where evidence-based guidelines remain limited.

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