Seizures and Epilepsy: Classification, EEG Patterns, and Management

Seizures represent abnormal, excessive, and synchronized neuronal activity in the brain, affecting approximately 1-2% of the global population. Epilepsy is defined as a chronic disorder characterized by recurrent, unprovoked seizures occurring at least 24 hours apart, or a single seizure with high risk of recurrence (>60%).

Pathophysiological Mechanisms: Seizures result from an imbalance between excitatory and inhibitory neurotransmission. Key mechanisms include:

1. Excitatory mechanisms: Increased glutamate activity, enhanced sodium/calcium channel function
2. Inhibitory mechanisms failure: Reduced GABA function, altered chloride channels
3. Network abnormalities: Aberrant synaptic connections, altered neuronal migration

The seizure threshold varies among individuals based on genetic factors, metabolic state, and structural brain abnormalities. Provoked seizures occur due to acute precipitants (hypoglycemia, electrolyte imbalances, toxins), while unprovoked seizures suggest underlying epileptogenic processes.

Neuronal Synchronization: Normal brain function requires balanced excitation and inhibition. During seizures, large populations of neurons fire synchronously, overwhelming normal regulatory mechanisms. This synchronization can remain localized (focal seizures) or spread throughout both hemispheres (generalized seizures).

Epileptogenesis: This process transforms normal brain tissue into epileptogenic tissue through molecular, cellular, and network changes. Key factors include:

• Neuronal death and gliosis
• Aberrant neurogenesis
• Altered ion channel expression
• Modified synaptic connectivity

Understanding these mechanisms is crucial for targeted therapeutic interventions and explains why some patients develop epilepsy after brain injury while others do not.

The International League Against Epilepsy (ILAE) 2017 classification system categorizes seizures based on onset type, awareness level, and motor features.

Seizure Classification Framework:

Focal Seizures (70% of adult seizures):

• Focal Aware: Consciousness preserved, may have aura, motor symptoms, or sensory phenomena
• Focal Impaired Awareness: Altered consciousness, automatisms common
• Focal to Bilateral Tonic-Clonic: Secondary generalization

Generalized Seizures:

1. Tonic-Clonic:

   • Tonic phase: Sustained muscle contraction (10-20 seconds)
   • Clonic phase: Rhythmic jerking movements
   • Postictal confusion and fatigue

2. Absence:

   • Brief (5-10 seconds) episodes of impaired consciousness
   • Blank stare, may have subtle motor features
   • No postictal confusion
   • Common in childhood

3. Myoclonic: Brief, shock-like muscle jerks

4. Tonic: Sustained muscle contraction without clonic phase

5. Atonic: Sudden loss of muscle tone ("drop attacks")

Clinical Assessment Algorithm:

Witness History → Seizure Description → Classification ↓ Onset type identification ↓ Motor vs Non-motor features ↓ Awareness assessment ↓ Duration and recovery pattern ↓ Final classification

Red Flag Symptoms:

• Focal neurological deficits
• Prolonged postictal confusion
• Status epilepticus
• New onset in adults >40 years

Electroencephalography (EEG) is essential for seizure diagnosis, classification, and monitoring. Understanding characteristic patterns helps differentiate seizure types and guide treatment decisions.

Normal EEG Background:

• Alpha rhythm: 8-13 Hz, posterior dominant
• Beta activity: >13 Hz, frontocentral
• Theta: 4-8 Hz (normal in sleep/children)
• Delta: <4 Hz (abnormal when awake)

Ictal EEG Patterns:

Interictal Abnormalities:

1. Spikes: <70 ms, high amplitude
2. Sharp waves: 70-200 ms
3. Spike-and-wave complexes: Spike followed by slow wave
4. Focal slowing: Localized delta/theta activity

Generalized Spike-Wave Patterns:

• 3-Hz spike-wave: Typical absence seizures
• 4-6 Hz spike-wave: Atypical absence, Lennox-Gastaut syndrome
• Polyspike-wave: Juvenile myoclonic epilepsy

Focal EEG Findings:

• Temporal lobe: Rhythmic theta activity, often maximal at T1/T2
• Frontal lobe: Fast activity, bilateral synchrony
• Parietal/occipital: Variable patterns, often with focal slowing

Activation Procedures:

1. Hyperventilation: Activates absence seizures
2. Photic stimulation: Triggers photosensitive epilepsy
3. Sleep deprivation: Increases seizure likelihood
4. Sleep recording: Increases interictal discharge detection

EEG Interpretation Pitfalls:

• Muscle artifacts mimicking seizure activity
• Normal variants (benign epileptiform transients)
• Psychiatric seizures (normal EEG during event)
• Medication effects on background activity

Video-EEG Monitoring: Gold standard for definitive diagnosis, especially useful for:

• Differentiating epileptic vs. non-epileptic events
• Seizure localization for surgical planning
• Medication adjustment in refractory cases
• Quantifying seizure frequency

Status epilepticus (SE) is a neurological emergency defined as continuous seizure activity lasting ≥5 minutes or recurrent seizures without return to baseline consciousness. Early recognition and aggressive treatment are crucial to prevent permanent neurological damage and death.

Classification of Status Epilepticus:

1. Convulsive SE:

   • Generalized convulsive SE (most common, highest mortality)
   • Focal motor SE with preserved consciousness

2. Non-convulsive SE:

   • Absence SE: Prolonged confusional state
   • Complex partial SE: Altered consciousness without convulsions

Pathophysiology:

• Initial phase (0-5 min): Compensatory mechanisms active
• Transition phase (5-30 min): Compensation begins to fail
• Refractory phase (>30 min): Systemic complications emerge

Emergency Management Protocol:

Seizure >5 minutes ↓ ABC Assessment IV access, glucose, vitals ↓ First-line (0-5 min): Benzodiazepines • IV lorazepam 0.1 mg/kg • OR midazolam 10 mg IM • OR diazepam 0.15 mg/kg IV ↓ Continue seizure activity? ↓ Second-line (5-20 min): • Phenytoin 20 mg/kg IV • OR valproate 40 mg/kg IV • OR levetiracetam 60 mg/kg IV ↓ Continue seizure activity? ↓ Third-line (>20 min): Anesthetic agents + ICU • Propofol 1-2 mg/kg bolus • OR midazolam 0.2 mg/kg bolus • OR pentobarbital 5-15 mg/kg

Critical Care Considerations:

1. Systemic Complications:

   • Hyperthermia, rhabdomyolysis
   • Cardiac arrhythmias, hypotension
   • Respiratory depression, aspiration
   • Metabolic acidosis, electrolyte imbalances

2. Neurological Complications:

   • Cerebral edema
   • Increased intracranial pressure
   • Hippocampal sclerosis
   • Cognitive impairment

Refractory Status Epilepticus: Defined as SE continuing despite adequate doses of first and second-line medications. Management requires:

• ICU admission with continuous EEG monitoring
• Anesthetic coma with burst suppression pattern
• Investigation for underlying causes
• Consideration of experimental therapies

Monitoring Parameters:

• Continuous EEG to assess seizure termination
• Cardiac monitoring for arrhythmias
• Frequent neurological assessments
• Laboratory monitoring (glucose, electrolytes, drug levels)
• Temperature regulation

Prognosis: Mortality rates vary by type:

• Generalized convulsive SE: 15-25%
• Non-convulsive SE: 5-15%
• Refractory SE: 30-50%

Outcome depends on underlying etiology, duration before treatment, and patient age.

Antiepileptic drug (AED) selection requires consideration of seizure type, patient factors, side effect profile, and drug interactions. Modern AED therapy aims for seizure freedom with minimal adverse effects.

Mechanism-Based AED Classification:

First-Line AED Selection:

1. Focal Seizures:

   • Carbamazepine: 400-1200 mg/day (Level 50-100 μmol/L)
   • Lamotrigine: 100-400 mg/day
   • Levetiracetam: 1000-3000 mg/day

2. Generalized Tonic-Clonic:

   • Valproate: 15-60 mg/kg/day (Level 350-700 μmol/L)
   • Lamotrigine: 100-500 mg/day
   • Levetiracetam: 1000-3000 mg/day

3. Absence Seizures:

   • Ethosuximide: 500-1500 mg/day
   • Valproate: 15-60 mg/kg/day
   • Lamotrigine: 100-400 mg/day

Special Populations:

Women of Childbearing Age:

• Avoid valproate (teratogenic risk)
• Prefer lamotrigine or levetiracetam
• Folic acid supplementation (5 mg daily)
• Monitor drug levels during pregnancy

Elderly Patients:

• Start low, titrate slowly
• Consider drug interactions
• Monitor for falls risk
• Prefer lamotrigine or levetiracetam

Pediatric Considerations:

• Weight-based dosing
• Age-specific seizure syndromes
• Developmental considerations
• Family education essential

AED Selection Algorithm:

Seizure Classification ↓ Patient Factors Assessment (age, gender, comorbidities) ↓ First-line AED Selection ↓ Titration to target dose ↓ Seizure control achieved? ↙ ↘ YES NO ↓ ↓ Continue Optimize dose therapy Check levels ↓ Still refractory? ↓ Add second AED (rational polytherapy) ↓ Consider epilepsy surgery evaluation

Therapeutic Drug Monitoring: Indicated for:

• Narrow therapeutic index drugs (phenytoin, carbamazepine)
• Suspected non-compliance
• Breakthrough seizures
• Dose optimization
• Drug interactions

Common Drug Interactions:

• Enzyme inducers: Carbamazepine, phenytoin (decrease levels of other drugs)
• Enzyme inhibitors: Valproate (increases levels of other drugs)
• Protein binding displacement: High protein-bound drugs

Treatment Failure Management:

1. Confirm diagnosis and compliance
2. Optimize monotherapy dosing
3. Consider rational polytherapy
4. Evaluate for epilepsy surgery
5. Consider newer AEDs or experimental treatments

Accurate seizure diagnosis requires systematic evaluation to differentiate epileptic seizures from mimicking conditions and identify underlying etiologies. The diagnostic approach varies based on presentation and clinical context.

Diagnostic Algorithm for First Seizure:

First Seizure Presentation ↓ History & Physical Exam (witness account crucial) ↓ Immediate Labs: • Glucose, electrolytes • CBC, liver function • Toxicology screen ↓ Neuroimaging: • Non-contrast CT (acute) • MRI brain (subacute) ↓ EEG (within 24-48 hours) ↓ Risk stratification for recurrent seizures

Essential History Elements:

1. Preictal Phase:

   • Aura description (sensory, emotional, autonomic)
   • Precipitating factors (sleep deprivation, stress, illness)
   • Warning signs or prodromal symptoms

2. Ictal Phase:

   • Level of consciousness
   • Motor manifestations (focal vs. generalized)
   • Duration and progression
   • Automatisms or behavioral changes

3. Postictal Phase:

   • Recovery time and pattern
   • Confusion, weakness, or other deficits
   • Todd's paralysis (transient focal weakness)

Physical Examination Focus:

• Neurological assessment for focal deficits
• Signs of head trauma or tongue biting
• Skin examination for neurocutaneous syndromes
• Developmental assessment in children

Differential Diagnosis:

Psychogenic Non-Epileptic Seizures (PNES):

• Account for 15-20% of referrals to epilepsy centers
• Clinical features:
  • Prolonged duration (>2 minutes)
  • Fluctuating intensity
  • Side-to-side head movements
  • Pelvic thrusting
  • Eye closure during event
  • Normal EEG during typical events

Laboratory Investigations:

Routine Studies:

• Complete blood count
• Comprehensive metabolic panel
• Liver function tests
• Thyroid function
• Magnesium, phosphate
• AED levels (if applicable)

Specialized Tests:

• Lumbar puncture (if CNS infection suspected)
• Autoimmune encephalitis panel
• Genetic testing (specific epilepsy syndromes)
• Toxicology screening

Neuroimaging Protocols:

1. Emergency CT: Rule out hemorrhage, mass lesions
2. MRI Brain with Epilepsy Protocol:
   • FLAIR sequences for hippocampal sclerosis
   • T2-weighted for cortical dysplasia
   • Post-contrast for inflammatory/neoplastic causes

Risk Factors for Seizure Recurrence:

• Abnormal EEG
• Structural brain abnormality
• Nocturnal seizures
• Family history of epilepsy
• Developmental delay

When to Start AED After First Seizure: Consider treatment if:

• High recurrence risk (>60%)
• Patient preference
• Occupational considerations
• Driving restrictions impact

Special Diagnostic Considerations:

Status Epilepticus Workup:

• Urgent head CT
• Lumbar puncture if febrile
• Comprehensive toxicology
• AED levels
• Metabolic panel

Refractory Epilepsy Evaluation:

• Video-EEG monitoring
• High-resolution MRI
• Neuropsychological testing
• Surgical evaluation if indicated

The diagnostic process should be individualized based on clinical presentation, patient age, and suspected underlying etiology.

Epilepsy syndromes represent distinct clinical entities with characteristic seizure types, EEG patterns, and outcomes. Recognition of specific syndromes guides prognosis and treatment decisions, including surgical interventions for medically refractory cases.

Common Epilepsy Syndromes:

Pediatric Syndromes:

1. Infantile Spasms (West Syndrome):

   • Age: 3-12 months
   • Seizures: Epileptic spasms in clusters
   • EEG: Hypsarrhythmia
   • Treatment: ACTH, vigabatrin
   • Prognosis: Often severe developmental delays

2. Lennox-Gastaut Syndrome:

   • Age: 1-8 years
   • Seizures: Multiple types (tonic, atonic, absence)
   • EEG: Slow spike-wave (1.5-2.5 Hz)
   • Treatment: Broad-spectrum AEDs, ketogenic diet

3. Childhood Absence Epilepsy:

   • Age: 4-8 years
   • Seizures: Typical absence seizures
   • EEG: 3-Hz spike-wave
   • Treatment: Ethosuximide, valproate
   • Prognosis: Good, often remits in adolescence

Adolescent/Adult Syndromes:

1. Juvenile Myoclonic Epilepsy:

   • Age: 12-18 years
   • Seizures: Myoclonic jerks, generalized tonic-clonic
   • EEG: 4-6 Hz polyspike-wave
   • Treatment: Valproate, levetiracetam
   • Prognosis: Lifelong treatment usually required

2. Temporal Lobe Epilepsy (TLE):

   • Most common focal epilepsy in adults
   • Seizures: Complex partial with automatisms
   • Associated: Hippocampal sclerosis
   • Treatment: Carbamazepine, surgical resection

Surgical Evaluation Algorithm:

Medically Refractory Epilepsy (failed ≥2 appropriate AEDs) ↓ Preoperative Assessment: • Video-EEG monitoring • High-resolution MRI • Neuropsychological testing • Functional imaging (PET/SPECT) ↓ Localization Studies: • Invasive monitoring (if needed) • fMRI for language/memory • Wada testing (if needed) ↓ Multidisciplinary Review ↓ Surgical Candidacy Assessment ↙ ↘ Resective Palliative Surgery Procedures

Surgical Indications:

1. Medical Refractoriness: Failed ≥2 appropriate AEDs
2. Localized Seizure Onset: Focal epilepsy with identifiable focus
3. Acceptable Risk-Benefit Ratio: Low morbidity risk
4. Patient Motivation: Understanding of risks and benefits

Types of Epilepsy Surgery:

Resective Procedures:

• Anterior temporal lobectomy (70-80% seizure freedom)
• Lesionectomy for structural abnormalities
• Frontal/parietal resections
• Hemispherectomy (catastrophic epilepsy)

Palliative Procedures:

• Vagus nerve stimulation (VNS)
• Responsive neurostimulation (RNS)
• Deep brain stimulation
• Corpus callosotomy (drop attacks)

Preoperative Localization:

1. Non-invasive Studies:

   • Scalp video-EEG
   • High-resolution MRI
   • FDG-PET (interictal hypometabolism)
   • Ictal SPECT

2. Invasive Monitoring:

   • Subdural grids/strips
   • Depth electrodes (stereoEEG)
   • Indicated when non-invasive studies inconclusive

Functional Mapping:

• Essential to preserve eloquent areas
• Language mapping (fMRI, Wada test)
• Motor mapping (direct cortical stimulation)
• Memory assessment (neuropsychological testing)

Surgical Outcomes:

Engel Classification:

• Class I: Seizure-free or rare auras only
• Class II: Rare disabling seizures
• Class III: Worthwhile improvement
• Class IV: No worthwhile improvement

Factors Predicting Success:

• Concordant localization studies
• Structural lesion on MRI
• Temporal lobe location
• Unilateral EEG abnormalities

Complications:

• Neurological deficits (2-5%)
• Infection (<1%)
• Bleeding (<1%)
• Memory problems (especially dominant temporal resection)

Alternative Therapies:

• Ketogenic diet (especially pediatric)
• Cannabis-based treatments
• Responsive neurostimulation
• Experimental approaches

Successful epilepsy surgery can be life-changing, with 60-80% of appropriate candidates achieving seizure freedom. Early referral for surgical evaluation is crucial in refractory cases.