Epilepsy: USMLE Decision Tree

STEP 1 — Is It a Seizure? Rule Out Mimics

STEP 2 — ILAE 2017 Seizure Classification

SEIZURE
│
├── FOCAL ONSET (single hemisphere)
│   ├── Focal Aware (old: Simple Partial)
│   │    └── consciousness preserved
│   ├── Focal Impaired Awareness (old: Complex Partial)
│   │    └── impaired consciousness + automatisms
│   └── Focal → Bilateral Tonic-Clonic (old: Secondary Generalization)
│
├── GENERALIZED ONSET (both hemispheres simultaneously)
│   ├── Motor
│   │    ├── Tonic-Clonic (Grand Mal) — loss of consciousness, tonic then clonic, postictal state
│   │    ├── Myoclonic — brief, sudden jerks (<100 ms), no postictal state
│   │    ├── Tonic — sustained muscle stiffening
│   │    ├── Clonic — rhythmic jerking
│   │    └── Atonic (Drop Attack) — sudden loss of tone → falls
│   └── Non-Motor
│        ├── Typical Absence (Petit Mal)
│        │    └── 4–20 sec stare, abrupt onset/offset, NO postictal state
│        └── Atypical Absence — longer, less abrupt (Lennox-Gastaut)
│
└── EPILEPTIC SPASMS — West syndrome (infantile)

Katzung's Basic and Clinical Pharmacology, 16th Ed. — Table 24-1; Adams and Victor's Principles of Neurology, 12th Ed.

STEP 3 — Identify the Epilepsy Syndrome

STEP 4 — Drug of Choice by Seizure / Syndrome

SEIZURE TYPE
│
├── FOCAL (any type) ─────────────────────────────────────────────────
│   First-line:  Levetiracetam, Lamotrigine, Oxcarbazepine
│   Alternatives: Carbamazepine, Phenytoin, Lacosamide, Zonisamide
│   Note: Lamotrigine needs slow titration; Levetiracetam/Oxcarbazepine
│         can be started at effective dose quickly
│
├── GENERALIZED TONIC-CLONIC (Primary/IGE) ──────────────────────────
│   First-line:  Valproate*, Levetiracetam, Lamotrigine
│   (*Valproate: avoid in women of childbearing age — teratogen)
│
├── TYPICAL ABSENCE ──────────────────────────────────────────────────
│   First-line:  Ethosuximide (best efficacy + tolerability)
│   If also has GTC: Valproate (covers both)
│   Alternative: Lamotrigine
│   ⚠ AVOID: Carbamazepine, Phenytoin (worsen absence!)
│
├── MYOCLONIC (JME) ──────────────────────────────────────────────────
│   First-line:  Valproate, Levetiracetam
│   Alternative: Lamotrigine, Topiramate
│   ⚠ AVOID: Carbamazepine (worsens myoclonus!)
│
├── ATONIC / LENNOX-GASTAUT ──────────────────────────────────────────
│   Valproate, Lamotrigine + Valproate (synergistic), Rufinamide,
│   Clobazam, Topiramate, Felbamate
│
├── INFANTILE SPASMS (West Syndrome) ────────────────────────────────
│   First-line:  ACTH or Vigabatrin (TSC: Vigabatrin preferred)
│   Alternative: Prednisolone, Pyridoxine (if B6 deficiency)
│
└── DRAVET SYNDROME ──────────────────────────────────────────────────
    Valproate, Clobazam, Stiripentol, Cannabidiol (Epidiolex)
    ⚠ AVOID: Lamotrigine, Carbamazepine (Na-channel blockers → worse)

Bradley and Daroff's Neurology in Clinical Practice — "Initiating Therapy"; Katzung's 16th Ed.; Adams and Victor's Principles of Neurology

STEP 5 — Pharmacoresistant Epilepsy

• Defined as failure of ≥2 appropriate AEDs at adequate doses
• Refer for epilepsy surgery evaluation
  • Temporal lobectomy: best outcomes for mesial temporal lobe epilepsy
  • Lesionectomy: for tumors, vascular malformations, cortical dysplasia
• Non-pharmacologic options:
  • Vagus nerve stimulator (VNS) — open-loop; approved for refractory focal + LGS
  • Responsive neurostimulation (RNS) — closed-loop; detects + aborts focal seizures
  • Deep brain stimulation (DBS) — anterior nucleus of thalamus; focal with/without secondary generalization
  • Ketogenic diet — especially effective in myoclonic epilepsies, infantile spasms, Dravet, GLUT1 deficiency (first-line for GLUT1)

Katzung's 16th Ed., p. 640

STEP 6 — Status Epilepticus (SE) Protocol

Seizure duration ≥5 min (GTC) or ≥10 min (non-convulsive) → STATUS EPILEPTICUS

PHASE 1 — Immediate (0–5 min)
  • ABCs, IV access, glucose check
  • Thiamine 100 mg IV (if alcoholism suspected) → then Dextrose

PHASE 2 — Benzodiazepine (5–20 min) ← FIRST-LINE
  • IV lorazepam 0.1 mg/kg (preferred — longer CNS duration vs. diazepam)
  • IM midazolam (if no IV access) — equally effective prehospital
  • Rectal diazepam or intranasal midazolam (prehospital alternatives)
  Note: Diazepam redistributes to fat rapidly → shorter CNS duration
        Lorazepam has less peripheral redistribution → longer effective duration

PHASE 3 — 2nd-line (20–40 min, if benzo-refractory)
  All equally effective (ESETT trial):
  • Levetiracetam IV
  • Valproate IV
  • Fosphenytoin IV (prodrug of phenytoin; less phlebitis/arrhythmia risk)
  • Phenytoin IV (slower; cardiac monitoring required)

PHASE 4 — Refractory SE (>40 min)
  • Intubate
  • Propofol, Midazolam infusion, or Pentobarbital
  • Continuous EEG monitoring mandatory
  • Phenobarbital IV (highly effective but causes prolonged sedation, respiratory depression)

ABSENCE STATUS EPILEPTICUS:
  • IV benzodiazepine → IV valproate
  • Long-term: oral ethosuximide or valproate

Katzung's 16th Ed. — "Status Epilepticus"; Tintinalli's Emergency Medicine

HIGH-YIELD USMLE PEARLS