Approach to New-Onset Seizures in the Elderly: Not Always Epilepsy

A Comprehensive Review for Critical Care Postgraduates

Dr Neeraj Manikath ,Claude.ai

Abstract

New-onset seizures in elderly patients (≥65 years) represent a complex clinical challenge in critical care settings, with underlying etiologies differing substantially from younger populations. Unlike pediatric and adult seizures, elderly-onset seizures are more commonly secondary to acute medical conditions rather than primary epilepsy. This review provides a systematic approach to evaluation and management, emphasizing the critical distinction between structural and metabolic causes. Key etiologies include cerebrovascular disease (40-50% of cases), metabolic derangements (particularly hyponatremia), neoplasms, autoimmune encephalitis, and medication toxicity. A structured diagnostic approach incorporating targeted neuroimaging, electroencephalography, and laboratory investigations is essential for optimal outcomes. Early recognition and treatment of underlying causes can be life-saving and may prevent progression to status epilepticus.

Keywords: Elderly seizures, status epilepticus, stroke, hyponatremia, autoimmune encephalitis, critical care

Introduction

The incidence of new-onset seizures demonstrates a bimodal distribution, with peaks in early childhood and after age 65 years. In the elderly population, the annual incidence ranges from 85-140 per 100,000, representing the highest age-specific incidence across all age groups. Unlike younger patients where idiopathic epilepsy predominates, elderly-onset seizures are overwhelmingly symptomatic, with identifiable underlying causes in 70-80% of cases.

The critical care physician must approach elderly seizures with heightened suspicion for acute, potentially reversible conditions. The mantra "not always epilepsy" reflects the reality that many elderly patients presenting with apparent seizures have underlying medical emergencies requiring immediate intervention beyond anticonvulsant therapy.

Epidemiology and Pathophysiology

Age-Related Changes Predisposing to Seizures

The aging brain undergoes several changes that lower seizure threshold:

Structural alterations: Cortical atrophy, white matter changes, and increased blood-brain barrier permeability
Neurotransmitter imbalance: Decreased GABA-ergic inhibition and increased excitatory amino acid activity
Reduced seizure threshold: Enhanced susceptibility to metabolic derangements
Polypharmacy effects: Increased risk of drug interactions and toxicity

Clinical Pearl 🔹

Elderly patients may present with subtle seizure manifestations. Simple partial seizures and complex partial seizures are more common than generalized tonic-clonic seizures, often leading to delayed recognition and misdiagnosis as confusion or dementia.

Etiology: The Big Five Categories

1. Cerebrovascular Disease (40-50% of Cases)

Stroke represents the most common cause of new-onset seizures in the elderly, with seizures occurring in 2-23% of stroke patients.

Acute vs. Remote Stroke:

Early seizures (within 24 hours): Often related to cortical ischemia, hemorrhage, or metabolic factors
Late seizures (>7 days): Associated with gliosis and scar formation

High-Risk Stroke Subtypes:

Cortical infarcts (especially MCA territory)
Hemorrhagic stroke (intracerebral and subarachnoid)
Large vessel occlusions
Posterior circulation strokes affecting thalamus

Clinical Hack 🔧 In elderly patients with new-onset seizures, always consider "silent" strokes. Up to 20% of elderly individuals have evidence of prior subclinical infarcts on neuroimaging that may serve as epileptogenic foci.

2. Metabolic Derangements

Metabolic causes are particularly important as they are often rapidly reversible with appropriate treatment.

Hyponatremia (Most Common Metabolic Cause):

Seizure risk increases when sodium <120 mEq/L or with rapid changes
Common causes in elderly: SIADH, diuretics, SSRIs, hypothyroidism
Oyster Alert 🦪: Rapid sodium correction can cause osmotic demyelination syndrome

Other Critical Metabolic Causes:

Hypoglycemia (<40 mg/dL)
Uremia (BUN >100 mg/dL)
Hepatic encephalopathy
Hypoxia/hypercarbia
Hypocalcemia, hypomagnesemia

Clinical Pearl 🔹 The "metabolic seizure" often presents with altered mental status preceding the ictal event. Always check fingerstick glucose and basic metabolic panel immediately in any elderly patient with altered consciousness.

3. Neoplasms (10-15% of Cases)

Brain tumors, both primary and metastatic, are significant causes of elderly-onset seizures.

Primary Brain Tumors:

Glioblastoma multiforme (most common primary tumor >65 years)
Meningiomas (often asymptomatic until large)
Primary CNS lymphoma (increasing incidence)

Metastatic Disease:

Lung, breast, melanoma, renal, GI primary tumors
Multiple metastases more likely to cause seizures than single lesions

Paraneoplastic Syndromes:

Anti-NMDA receptor encephalitis
Anti-LGI1 antibody syndrome
Can occur without detectable tumor on imaging

4. Autoimmune Encephalitis

An increasingly recognized cause of new-onset seizures in elderly patients.

Key Syndromes:

Anti-LGI1 encephalitis: Faciobrachial dystonic seizures, hyponatremia
Anti-NMDA receptor encephalitis: Psychiatric symptoms, movement disorders
Anti-GABA-B encephalitis: Temporal lobe seizures, memory impairment
Hashimoto's encephalopathy: Thyroid antibodies, steroid-responsive

Clinical Hack 🔧 Consider autoimmune encephalitis in elderly patients with new-onset refractory seizures, especially if accompanied by psychiatric symptoms, movement disorders, or hyponatremia. These conditions are often steroid-responsive.

5. Medication-Related Seizures

Polypharmacy in elderly patients increases seizure risk through multiple mechanisms.

Direct Pro-convulsant Medications:

Tramadol, bupropion, theophylline
Fluoroquinolones, beta-lactam antibiotics
Contrast agents (especially with renal impairment)

Withdrawal Syndromes:

Benzodiazepines, barbiturates, alcohol
Baclofen, gabapentin (often overlooked)

Medication Interactions:

Warfarin-antibiotic interactions causing drug level fluctuations
CYP450 inhibitors affecting anticonvulsant metabolism

Diagnostic Approach

Initial Assessment Framework

Step 1: Stabilization and Immediate Labs

ABCs, fingerstick glucose, IV access
Basic metabolic panel, magnesium, phosphorus
CBC with differential, liver function tests
Arterial blood gas if altered mental status

Step 2: Rapid Neurological Assessment

Glasgow Coma Scale
Focal neurological deficits
Meningeal signs
Evidence of head trauma

Step 3: Medication Review

Complete medication reconciliation
Recent medication changes or discontinuations
Over-the-counter medications and supplements

Neuroimaging Strategy

Emergent CT Head (Within 30 minutes):

Rule out hemorrhage, mass effect, hydrocephalus
Indicated for all elderly patients with new-onset seizures

MRI Brain (Within 24 hours):

Superior sensitivity for acute infarcts, small lesions
FLAIR, DWI, and T2* sequences essential
Contrast enhancement for suspected neoplasm/infection

Advanced Imaging Considerations:

CT angiography: If stroke suspected
MR venography: For cerebral venous thrombosis
PET scan: For suspected autoimmune encephalitis or occult malignancy

Clinical Pearl 🔹 In elderly patients, a normal CT head does not rule out acute stroke. MRI with DWI is essential for detecting acute infarcts, which may present with seizures as the primary manifestation.

EEG Strategy

Timing and Duration:

Emergent EEG: If status epilepticus or persistent altered mental status
Routine EEG: Within 24-48 hours for diagnostic evaluation
Prolonged monitoring: If subclinical seizures suspected

EEG Patterns Suggesting Specific Etiologies:

Triphasic waves: Metabolic encephalopathy (uremia, hepatic)
Periodic lateralized epileptiform discharges (PLEDs): Acute structural lesion
Extreme delta brush: Anti-NMDA receptor encephalitis
Focal slowing: Structural lesion (tumor, stroke)

Oyster Alert 🦪 EEG in elderly patients may show age-related changes that can be misinterpreted. Temporal slowing and decreased amplitude are normal findings. Focus on asymmetries and epileptiform discharges.

Distinguishing Structural from Metabolic Causes

Clinical Clues for Structural Causes

Historical Features:

Focal onset seizures
Progressive neurological symptoms
Recent head trauma
Known cancer history

Examination Findings:

Focal neurological deficits
Papilledema
Asymmetric reflexes
Persistent confusion after seizure

Investigational Findings:

Focal abnormalities on neuroimaging
Focal slowing or PLEDs on EEG
Elevated protein in CSF

Clinical Clues for Metabolic Causes

Historical Features:

Generalized seizures
Recent medication changes
Systemic illness symptoms
Multiple seizure types

Examination Findings:

Symmetric neurological examination
Signs of systemic illness
Rapid improvement with correction
Asterixis or myoclonus

Investigational Findings:

Normal or symmetric imaging
Generalized EEG abnormalities
Specific metabolic abnormalities

Clinical Hack 🔧 Use the "MATCH" mnemonic for rapid metabolic screening: - Magnesium, Ammonia, Toxins, Calcium, Hypoglycemia

Laboratory Investigations

Tier 1 (Emergency Department):

Complete metabolic panel
Magnesium, phosphorus
Complete blood count
Liver function tests
Thyroid stimulating hormone
Urinalysis

Tier 2 (If Indicated):

Ammonia level
Vitamin B12, folate
Blood cultures
Toxicology screen
Anti-epileptic drug levels

Tier 3 (Specialized Testing):

Autoimmune encephalitis panel
Paraneoplastic antibodies
CSF analysis (if infection/autoimmune suspected)
Tumor markers

Management Pearls

Acute Management Priorities

Treat the Underlying Cause: This is paramount and may be more important than anticonvulsant therapy
Cautious AED Selection: Start low, go slow; consider drug interactions
Avoid Polypharmacy: Single-agent therapy preferred when possible

Anticonvulsant Selection in Elderly

First-Line Options:

Levetiracetam: Minimal drug interactions, renal clearance
Lamotrigine: Well-tolerated, requires slow titration
Valproic acid: Broad spectrum, but multiple interactions

Avoid in Elderly:

Phenytoin (nonlinear kinetics, drug interactions)
Carbamazepine (hyponatremia, cardiac effects)
Phenobarbital (sedation, falls risk)

Clinical Pearl 🔹 In elderly patients with new-onset seizures, consider starting anticonvulsant therapy at 25-50% of standard adult doses and titrate slowly. Age-related changes in pharmacokinetics increase risk of toxicity.

Special Considerations

Status Epilepticus in the Elderly

Higher mortality rate (20-40% vs. 10-15% in younger adults)
Often nonconvulsive; high index of suspicion needed
More likely to be symptomatic (underlying acute illness)
Aggressive treatment warranted but with attention to cardiopulmonary status

Mimics of Seizures in Elderly

Common Mimics:

Syncope (cardiac, orthostatic)
Transient ischemic attacks
Migraine with aura
Psychiatric disorders
Medication toxicity

Oyster Alert 🦪 Transient global amnesia can mimic complex partial seizures in elderly patients. Key distinguishing feature: preserved personal identity and lack of automatisms in TGA.

Prognosis and Long-term Management

Factors Affecting Prognosis

Good Prognosis Indicators:

Metabolic cause identified and corrected
Normal neuroimaging
No cognitive impairment
Single seizure episode

Poor Prognosis Indicators:

Multiple seizures at presentation
Status epilepticus
Structural brain lesions
Cognitive impairment

Long-term Anticonvulsant Therapy

Duration Considerations:

Metabolic causes: Often can discontinue after correction
Structural causes: Usually require long-term therapy
Single unprovoked seizure: Individual risk-benefit assessment

Future Directions and Research

Emerging areas of research include:

Biomarkers for autoimmune encephalitis
Advanced neuroimaging techniques for seizure localization
Precision medicine approaches to anticonvulsant selection
Telemedicine applications for EEG monitoring

Summary and Key Takeaways

High index of suspicion: New-onset seizures in elderly patients are usually symptomatic
Systematic approach: Use structured evaluation to identify treatable causes
Imaging is essential: All elderly patients with new seizures need neuroimaging
Metabolic causes are reversible: Rapid identification and treatment can be life-saving
Medication review is critical: Both causative and therapeutic drug considerations
EEG timing matters: Early EEG can guide diagnosis and treatment
Think beyond epilepsy: Consider stroke, tumors, autoimmune conditions, and medications

Final Clinical Pearl 🔹 The elderly patient with new-onset seizures requires a medical detective approach. The seizure is often the symptom, not the disease. Focus on finding and treating the underlying cause while providing appropriate symptomatic management.

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Sunday, July 20, 2025