New-Onset Seizure in an Adult: A Focused Evaluation Plan

Dr Neeraj Manikath, Claude.ai

Abstract

New-onset seizures in adults represent a critical neurological emergency requiring systematic evaluation and prompt management. This review provides a structured approach to the diagnostic workup of adult-onset seizures, emphasizing the key role of metabolic derangements, structural abnormalities, infections, and autoimmune conditions. We present evidence-based strategies for utilizing neuroimaging, cerebrospinal fluid analysis, and electroencephalography in the acute setting, along with practical pearls for critical care physicians managing these challenging cases.

Keywords: Adult seizure, status epilepticus, metabolic encephalopathy, autoimmune encephalitis, neuroimaging

Introduction

The incidence of new-onset seizures in adults peaks in the elderly population, with approximately 120,000 new cases annually in the United States¹. Unlike pediatric seizures, adult-onset seizures carry a higher likelihood of underlying structural or metabolic pathology, making rapid and systematic evaluation crucial for optimal patient outcomes. Critical care physicians must be equipped with a focused diagnostic approach that balances thoroughness with clinical urgency.

Metabolic Derangements: The Great Mimickers

Hyponatremia: The Silent Culprit

Hyponatremia remains the most common electrolyte abnormality precipitating seizures in hospitalized patients. Seizures typically occur when serum sodium drops below 120 mEq/L, particularly with rapid onset².

Clinical Pearl: The rate of sodium decline is more critical than the absolute value. A drop of >10 mEq/L in 24 hours can precipitate seizures even at "normal" sodium levels.

Diagnostic Approach:

Measure serum and urine osmolality simultaneously
Calculate fractional excretion of sodium (FENa)
Assess volume status clinically
Consider SIADH in euvolemic patients with concentrated urine

Management Hack: For symptomatic hyponatremia with seizures, aim for correction of 1-2 mEq/L per hour initially, then 0.5 mEq/L per hour to avoid osmotic demyelination syndrome³.

Hypocalcemia: Beyond the Chvostek Sign

Hypocalcemia-induced seizures are often overlooked, particularly in critically ill patients receiving multiple medications.

Clinical Pearl: Always check ionized calcium, not total calcium, especially in patients with hypoalbuminemia or acid-base disorders.

High-Risk Scenarios:

Post-thyroidectomy (hypoparathyroidism)
Massive blood transfusion (citrate toxicity)
Pancreatitis with fat saponification
Proton pump inhibitor use (chronic magnesium depletion)

Oyster: Magnesium deficiency must be corrected before calcium replacement will be effective. Hypomagnesemia causes functional hypoparathyroidism⁴.

Glucose Dysregulation: The Biphasic Challenge

Both hypoglycemia and hyperglycemia can precipitate seizures, often presenting diagnostic challenges.

Hypoglycemic Seizures:

Threshold varies (typically <40 mg/dL in adults)
May occur with rapid glucose decline from higher baseline
Consider factitious hypoglycemia in healthcare workers

Hyperglycemic Seizures:

Nonketotic hyperosmolar state (glucose >600 mg/dL)
Focal seizures more common than generalized
May present as epilepsia partialis continua

Clinical Hack: Always perform bedside glucose testing in any altered mental status patient, regardless of known diabetes history.

Neuroinfection: The Fever May Be Absent

Bacterial Meningitis in Adults

Adult bacterial meningitis presents with the classic triad (fever, neck stiffness, altered mental status) in only 44% of cases⁵. Seizures occur in 20-30% of patients and may be the presenting feature.

High-Risk Pathogens:

Streptococcus pneumoniae (most common)
Neisseria meningitidis
Listeria monocytogenes (elderly, immunocompromised)

Diagnostic Pearl: Obtain blood cultures before antibiotics when possible, but never delay treatment for lumbar puncture in suspected bacterial meningitis.

Viral Encephalitis: HSV and Beyond

Herpes simplex virus (HSV) encephalitis remains the most treatable cause of viral encephalitis, with mortality reducing from 70% to 20% with acyclovir therapy⁶.

Clinical Characteristics:

Temporal lobe predilection
Personality changes, aphasia
Hemorrhagic necrosis on imaging
CSF: lymphocytic pleocytosis, elevated protein, normal glucose

Diagnostic Hack: Start acyclovir empirically if HSV encephalitis is suspected. PCR results may take 24-48 hours, and treatment delay worsens outcomes.

Opportunistic Infections in Immunocompromised Hosts

Toxoplasmosis: Ring-enhancing lesions, especially in AIDS patients with CD4 <200 Cryptococcus: Indolent course, may lack typical CSF findings Progressive Multifocal Leukoencephalopathy (PML): JC virus in immunosuppressed patients

Structural Abnormalities: The Hidden Masses

Primary Brain Tumors

Seizures are the presenting symptom in 60-70% of patients with low-grade gliomas and 30-40% of high-grade gliomas⁷.

Clinical Pearl: New-onset seizures in adults >40 years warrant neuroimaging, even with normal neurological examination.

Tumor-Associated Seizure Characteristics:

Focal seizures with secondary generalization
Progressive frequency and severity
Resistance to standard antiepileptic drugs

Metastatic Disease

Brain metastases are 10 times more common than primary brain tumors. Most common primary sources:

Lung (50%)
Breast (20%)
Melanoma (10%)
Renal cell carcinoma (5%)

Oyster: Melanoma metastases are particularly epileptogenic due to their tendency to cause microhemorrhages.

Autoimmune Encephalitis: The New Frontier

Anti-NMDA Receptor Encephalitis

This condition has revolutionized our understanding of autoimmune seizures, particularly in young women.

Clinical Progression:

Prodromal phase: Flu-like symptoms
Psychotic phase: Psychiatric symptoms, memory problems
Hyperkinetic phase: Seizures, movement disorders
Catatonic phase: Stupor, autonomic instability
Recovery phase: Gradual improvement

Diagnostic Pearl: Consider paraneoplastic screening, particularly ovarian teratoma in young women.

Limbic Encephalitis

Associated with various antibodies (anti-Hu, anti-Ma2, anti-LGI1, anti-CASPR2).

Clinical Features:

Subacute memory impairment
Personality changes
Seizures (often temporal lobe)
MRI: T2 hyperintensity in medial temporal lobes

Clinical Hack: Serum antibody testing is more sensitive than CSF for most autoimmune encephalitis antibodies⁸.

Neuroimaging: Choosing the Right Tool

Magnetic Resonance Imaging (MRI)

MRI remains the gold standard for evaluating new-onset seizures.

Optimal Sequences:

T1-weighted with gadolinium
T2-weighted and FLAIR
Diffusion-weighted imaging (DWI)
Susceptibility-weighted imaging (SWI) for microhemorrhages

Clinical Pearl: FLAIR sequences are most sensitive for detecting hippocampal sclerosis and cortical dysplasia.

Contraindications for Emergency MRI:

Unstable vital signs
Need for continuous monitoring incompatible with MRI
Metallic implants (case-by-case basis)

Computed Tomography (CT)

While less sensitive than MRI, CT remains valuable in emergency settings.

Indications for Emergent CT:

Hemodynamically unstable patients
Suspected intracranial hemorrhage
Trauma history
Focal neurological deficits

Oyster: Non-contrast CT misses up to 50% of structural abnormalities that cause seizures. Always follow with MRI when clinically stable.

Cerebrospinal Fluid Analysis: The Window to the Brain

Indications for Lumbar Puncture

Absolute Indications:

Suspected meningitis or encephalitis
Fever with new-onset seizures
Immunocompromised patients

Relative Indications:

Unexplained altered mental status
Suspected autoimmune encephalitis
Normal neuroimaging with persistent symptoms

CSF Interpretation Pearls

Normal Values:

Opening pressure: 10-20 cmH₂O
White blood cells: <5/μL
Protein: 20-45 mg/dL
Glucose: 40-80 mg/dL (CSF:serum ratio >0.6)

Bacterial Meningitis:

Elevated opening pressure (>30 cmH₂O)
Neutrophilic pleocytosis (>1000/μL)
Elevated protein (>100 mg/dL)
Low glucose (<40 mg/dL)

Viral Encephalitis:

Normal to mildly elevated pressure
Lymphocytic pleocytosis (50-500/μL)
Moderately elevated protein (50-100 mg/dL)
Normal glucose

Clinical Hack: Always send CSF for cell count with differential, protein, glucose, Gram stain, culture, and hold additional sample for further testing based on clinical suspicion.

Electroencephalography: Capturing the Electrical Storm

Indications for EEG

Emergent EEG:

Suspected non-convulsive status epilepticus
Persistent altered mental status post-seizure
Comatose patients

Routine EEG:

Characterizing seizure type
Monitoring treatment response
Prognostic assessment

EEG Interpretation for Non-Neurologists

Seizure Patterns:

Generalized spike-and-wave (3 Hz in absence, variable in tonic-clonic)
Focal spikes or sharp waves
Rhythmic delta activity

Status Epilepticus Patterns:

Continuous seizure activity
Frequent discrete seizures
Periodic lateralized epileptiform discharges (PLEDs)

Clinical Pearl: EEG should be performed within 24 hours of seizure onset when possible, as yield decreases significantly after 48 hours⁹.

Drug-Related Seizures: The Iatrogenic Challenge

Seizure-Inducing Medications

Antibiotics:

Beta-lactams (especially high-dose penicillin)
Fluoroquinolones
Carbapenems (particularly imipenem)

Psychiatric Medications:

Tricyclic antidepressants
Buproprion (dose-dependent)
Lithium (toxicity)

Other Common Culprits:

Tramadol (especially with serotonergic drugs)
Theophylline
Local anesthetics (systemic toxicity)

Clinical Pearl: Always review medication history, including over-the-counter drugs and supplements. Pay special attention to recent changes or overdoses.

Withdrawal Seizures

Alcohol Withdrawal:

Onset: 6-24 hours after last drink
Peak: 24-48 hours
May progress to delirium tremens

Benzodiazepine Withdrawal:

Onset: Variable (hours to days)
Risk factors: High-dose, long-term use
May be life-threatening

Antiepileptic Drug Withdrawal:

Abrupt discontinuation of any AED
Particularly dangerous with short-acting drugs

Clinical Decision-Making Algorithm

Immediate Assessment (0-15 minutes)

Airway, breathing, circulation
Bedside glucose
Vital signs and neurological examination
Brief history (witnesses, medication list)

Acute Management (15-60 minutes)

Laboratory studies: Complete metabolic panel, CBC, liver function tests, toxicology screen
Neuroimaging: CT head (emergency), MRI when stable
Lumbar puncture if indicated
Initiate antiepileptic therapy if recurrent seizures

Extended Evaluation (1-24 hours)

EEG monitoring
Expanded laboratory testing based on clinical suspicion
Autoimmune markers if indicated
Paraneoplastic workup in appropriate cases

Treatment Pearls for Critical Care

First-Line Antiepileptic Drugs

Levetiracetam:

Loading dose: 20-30 mg/kg IV
Advantages: Minimal drug interactions, renal clearance
Disadvantages: Psychiatric side effects

Phenytoin/Fosphenytoin:

Loading dose: 15-20 mg/kg IV
Advantages: Well-established efficacy
Disadvantages: Cardiac monitoring required, drug interactions

Valproic Acid:

Loading dose: 15-20 mg/kg IV
Advantages: Broad spectrum, mood stabilization
Disadvantages: Hepatotoxicity, teratogenicity

Status Epilepticus Management

First-line: Benzodiazepines (lorazepam 4-8 mg IV) Second-line: Phenytoin, levetiracetam, or valproic acid Third-line:Continuous infusion (midazolam, propofol, or pentobarbital)

Clinical Hack: Don't delay second-line treatment. Seizures become increasingly refractory to treatment the longer they continue¹⁰.

Prognosis and Long-term Management

Recurrence Risk Factors

High-risk features:

Structural brain abnormality
Abnormal EEG
Focal seizures
Family history of epilepsy

Low-risk features:

Metabolic cause (corrected)
Drug-induced seizures (drug discontinued)
Isolated seizure with normal workup

Long-term Antiepileptic Therapy

Generally recommended after:

Two or more unprovoked seizures
Single seizure with high recurrence risk
Structural brain abnormality

Conclusion

New-onset seizures in adults require a systematic approach emphasizing rapid identification of treatable causes. Metabolic derangements, particularly hyponatremia and hypoglycemia, should be corrected immediately. Neuroinfection, especially HSV encephalitis, demands urgent recognition and treatment. The emerging field of autoimmune encephalitis has expanded our therapeutic options for previously untreatable conditions. Neuroimaging with MRI, targeted CSF analysis, and EEG monitoring form the diagnostic triad for comprehensive evaluation. Drug history remains crucial, as both intoxication and withdrawal can precipitate seizures. Early recognition and appropriate management of these conditions can significantly improve patient outcomes and prevent progression to status epilepticus.

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Author Information

Conflicts of Interest: None declared

Funding: None

Ethical Approval: Not applicable (review article)

Tuesday, July 8, 2025