Seizures and Epilepsy¶
Chapter 436 | Part 13: Neurologic Disorders
KEY CLINICAL POINTS¶
- Seizures are transient episodes of abnormal neuronal activity, while epilepsy is a chronic condition with recurrent seizures due to underlying neurological dysfunction.
- The ILAE 2017 classification system categorizes seizures as focal (with or without impaired awareness) or generalized, based on onset and propagation patterns.
- Genetic mutations (e.g., SCN1A, CDKL5) underlie many epilepsy syndromes, including Dravet syndrome and CDKL5 deficiency disorder.
- Antiseizure drugs (ASMs) target ion channels, neurotransmitter systems, or synaptic plasticity, with first-line agents varying by seizure type (e.g., valproic acid for generalized seizures, lamotrigine for focal seizures).
- Status epilepticus requires immediate treatment with benzodiazepines, followed by second-line agents like phenytoin or levetiracetam, with surgical or neurostimulation options for refractory cases.
1. DEFINITION & OVERVIEW¶
A seizure is a transient occurrence of abnormal electrical activity in the brain, while epilepsy is a chronic disorder characterized by recurrent seizures. Seizures may be focal (localized) or generalized (bilateral). The ILAE 2017 classification system replaces older terminology (e.g., partial vs. generalized seizures) with a focus on seizure onset and propagation patterns. Epilepsy syndromes are distinct conditions with specific clinical, EEG, and genetic features.
Table 436-1: Classification of Seizures¶
| Seizure Type | Clinical Features | EEG Characteristics |
|---|---|---|
| Focal with impaired awareness | Motor or autonomic symptoms, postictal confusion | Focal spikes, slow waves |
| Focal without impaired awareness | Simple motor or sensory symptoms | Focal spikes |
| Generalized tonic-clonic | Loss of consciousness, generalized motor activity | Generalized spike-and-slow wave |
| Absence | Brief loss of awareness, no motor activity | 3-Hz spike-and-slow wave |
1.1 Seizure Definition¶
A seizure is a sudden, transient episode of abnormal electrical activity in the brain, often with clinical manifestations such as motor, sensory, or autonomic symptoms. Focal seizures may retain awareness, while generalized seizures involve both cerebral hemispheres.
1.2 Epidemiology¶
Global epilepsy prevalence is 5–30 per 1000, with ~5–10% of the population experiencing at least one seizure. Febrile seizures are common in children, while generalized tonic-clonic seizures are more prevalent in adults. Risk factors include genetic predisposition, brain injury, infections, and metabolic disorders.
2. EPIDEMIOLOGY¶
Epilepsy affects ~5–30 per 1000 globally, with higher prevalence in children and older adults. Febrile seizures occur in 2–5% of children, while generalized seizures are more common in adults. Risk factors include genetic predisposition, head trauma, CNS infections, and metabolic disorders. Seizures are more common in individuals with neurodevelopmental disorders or structural brain abnormalities.
2.1 Age-Specific Causes¶
Neonates: Hypoxic-ischemic encephalopathy, metabolic disorders. Children: Febrile seizures, genetic syndromes. Adults: Trauma, stroke, tumors, infections. Elderly: Degenerative diseases, cerebrovascular disease.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Seizures result from imbalances in excitatory/inhibitory neurotransmission. Genetic mutations (e.g., SCN1A, CDKL5) cause channelopathies leading to hyperexcitability. Structural abnormalities (e.g., hippocampal sclerosis) or metabolic disturbances (e.g., hypoglycemia) can also trigger seizures. Epileptogenesis involves long-term changes in neuronal networks following CNS injury.
Table 436-2: Genes Associated with Epilepsy Syndromes¶
| Gene | Clinical Syndrome | Key Features |
|---|---|---|
| SCN1A | Dravet syndrome | Severe myoclonic epilepsy of infancy |
| CDKL5 | CDKL5 deficiency disorder | Early-onset seizures, developmental delay |
| KCNQ2 | Benign familial neonatal seizures | Transient, self-limited |
| DEPDC5 | Benign focal epilepsy | Focal seizures with centrotemporal spikes |
| GRIN2A | Benign childhood epilepsy | Focal seizures with speech arrest |
3.1 Genetic Causes¶
Genetic mutations in ion channels (e.g., SCN1A for Dravet syndrome) or synaptic proteins (e.g., CDKL5) cause inherited epilepsy syndromes. De novo mutations are common in early-onset epilepsies.
3.2 Pathophysiology¶
Seizures arise from abnormal synchronization of neuronal firing, often due to disrupted ion channel function, neurotransmitter imbalances, or structural brain lesions. Epileptogenesis involves long-term changes in synaptic connectivity and excitability.
4. CLINICAL FEATURES¶
Focal seizures may present with motor (e.g., jerking movements), sensory (e.g., numbness), or autonomic symptoms (e.g., sweating). Generalized seizures include tonic-clonic (grand mal), absence (petit mal), or atonic seizures. Postictal confusion, automatisms, or focal neurological deficits may follow. Status epilepticus is a medical emergency with prolonged seizure activity.
4.1 Focal Seizures¶
May involve motor (e.g., unilateral twitching), sensory (e.g., tingling), or autonomic symptoms. Focal seizures with impaired awareness often have motor manifestations (e.g., unilateral movements), while those without awareness may present with olfactory hallucinations or complex automatisms.
4.2 Generalized Seizures¶
Tonic-clonic seizures involve generalized muscle contractions and loss of consciousness. Absence seizures are brief (5–30 seconds) with staring and no motor activity. Myoclonic seizures involve sudden muscle jerks, while atonic seizures cause sudden loss of muscle tone.
5. DIFFERENTIAL DIAGNOSIS¶
Conditions mimicking seizures include syncope, migraine, psychogenic nonepileptic seizures, and movement disorders. Key differentiators include: (1) Aura or postictal confusion in seizures vs. sudden onset in syncope, (2) Motor activity in seizures vs. transient loss of consciousness in syncope, (3) EEG abnormalities in epileptic seizures vs. normal EEG in nonepileptic events.
Table 436-7: Features Distinguishing Seizures from Syncope¶
| Feature | Seizure | Syncope |
|---|---|---|
| Immediate precipitating factor | Usually none | Emotional stress, Valsalva, orthostatic hypotension |
| Posture at onset | Variable | Usually erect |
| Duration of unconsciousness | Minutes | Seconds |
| Duration of tonic/clonic movements | 30–60 s | Never >15 s |
| Facial appearance | Cyanosis, frothing | Pallor |
| Disorientation | Many minutes to hours | Minutes |
5.1 Mimicking Conditions¶
Syncope (e.g., vasovagal, cardiac arrhythmia), migraine (e.g., basilar, confusional), psychogenic seizures, and movement disorders (e.g., tics, paroxysmal dyskinesia).
5.2 Differentiation Criteria¶
Table 436-7 outlines key features distinguishing seizures from syncope, including duration of unconsciousness, motor activity, and EEG findings.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic workup includes EEG (to detect epileptiform discharges), MRI (to identify structural lesions), and genetic testing for syndromic epilepsy. Video-EEG telemetry is essential for ambiguous cases. Laboratory tests assess metabolic causes (e.g., hypoglycemia, electrolyte imbalances).
Table 436-3: Characteristics of Mesial Temporal Lobe Epilepsy¶
| Clinical Feature | Findings |
|---|---|
| History | Febrile seizures, family history of epilepsy |
| Clinical Feature | Findings |
|---|---|
| Clinical Observations | Aura, automatisms, postictal confusion |
| EEG | Anterior temporal spikes, hypometabolism on PET |
| MRI | Small hippocampus, T2 hyperintensity, hippocampal sclerosis |
6.1 Diagnostic Tests¶
EEG: Detects focal or generalized epileptiform activity. MRI: Identifies hippocampal sclerosis, tumors, or malformations. Lumbar puncture: For CNS infections. Genetic testing: For syndromic epilepsy (e.g., SCN1A, CDKL5).
6.2 EEG Findings¶
Focal seizures show localized spikes, while generalized seizures exhibit generalized spike-and-slow wave patterns. Absence seizures have 3-Hz spike-and-slow wave activity.
7. MANAGEMENT & TREATMENT¶
Antiseizure drugs (ASMs) are first-line therapy, with selection based on seizure type. Status epilepticus requires immediate benzodiazepines, followed by second-line agents. Surgical options include resection, vagus nerve stimulation (VNS), or responsive neurostimulation (RNS).
Table 436-8: Antiseizure Drug Selection¶
| Seizure Type | First-Line Drugs | Alternatives |
|---|---|---|
| Generalized tonic-clonic | Valproic acid, lamotrigine | Phenytoin, carbamazepine |
| Focal seizures | Lamotrigine, carbamazepine | Levetiracetam, oxcarbazepine |
| Absence seizures | Ethosuximide, valproic acid | Levetiracetam |
| Myoclonic seizures | Valproic acid, levetiracetam | Zonisamide |
Table 436-9: Dosage and Adverse Effects¶
| Drug | Dosage | Adverse Effects |
|---|---|---|
| Valproic acid | 750–2000 mg/d | Ataxia, hepatotoxicity, weight gain |
| Levetiracetam | 1000–3000 mg/d | Dizziness, sedation, anorexia |
| Carbamazepine | 600–1800 mg/d | Dizziness, ataxia, rash |
| Phenytoin | 300–400 mg/d | Diplopia, hirsutism, osteomalacia |
| Lamotrigine | 150–500 mg/d | Rash, Stevens-Johnson syndrome |
7.1 Antiseizure Drug Selection¶
Focal seizures: Carbamazepine, lamotrigine, levetiracetam. Generalized seizures: Valproic acid, levetiracetam. Status epilepticus: Lorazepam, midazol(stats), phenytoin.
7.2 Treatment Algorithms¶
Figure 436-5 outlines management of generalized tonic-clonic status epilepticus: initial benzodiazepines, then IV antiseizure drugs, followed by continuous infusion of phenytoin or propofol.
8. SURGICAL TREATMENT¶
Resective surgery (e.g., temporal lobectomy, amygdalohippocampectomy) is effective for focal epilepsy. Neurostimulation (VNS, RNS) is used for refractory cases. Surgical candidates must have localized seizure foci with no critical brain function.
8.1 Surgical Options¶
Temporal lobectomy for mesial temporal sclerosis. Hemispherectomy for hemispheric dysplasia. Laser ablation for focal seizures. VNS/RNS for refractory epilepsy.
8.2 Preoperative Evaluation¶
Video-EEG, MRI, PET, and Wada test to localize seizure focus. Functional mapping to preserve language and motor areas.
9. STATUS EPILEPTICUS¶
Continuous seizures or repetitive seizures with impaired consciousness require immediate treatment. Management includes benzodiazepines, then IV antiseizure drugs, and continuous infusion for refractory cases. Neurostimulation or surgery may be required for prolonged status.
9.1 Treatment Algorithm¶
Figure 436-5: Initial lorazepam or midazolam, followed by phenytoin or valproic acid. For refractory cases, use propofol or pentobarbital. Consider VNS/RNS for long-term management.
10. SPECIAL CONSIDERATIONS¶
Pregnancy requires careful ASM management to minimize fetal risks. Breastfeeding is generally safe with most ASMs. Women with catamenial epilepsy may need adjusted dosages around menstruation. Psychosocial support is critical for quality of life.