372.3 🏥 內科專科考前版

372.3.1 Mechanistic Deep Dive

372.3.1.1 Channels + Receptors

Sodium: phenytoin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine Calcium (T-type): ethosuximide, valproate (partial) GABA enhancement: benzodiazepines, barbiturates, vigabatrin, tiagabine Glutamate: perampanel (AMPA), topiramate, felbamate SV2A vesicle: levetiracetam, brivaracetam Mixed: valproate, topiramate, zonisamide

372.3.1.2 Cenobamate Mechanism

  • Sodium channel inactivation
  • GABA-A positive allosteric modulator
  • Highly effective for focal refractory

372.3.1.3 Cannabidiol Mechanism

  • Not via CB1/CB2
  • Multiple targets (TRPV, GPR55, adenosine)
  • Effective in Dravet, LGS, TSC

372.3.2 Recent Trials & Updates

372.3.2.1 Cenobamate (Xcopri)

  • FDA 2019
  • Very high response rate in refractory focal
  • DRESS risk (slow titration mandatory)

372.3.2.2 Fenfluramine (Fintepla)

  • FDA 2020 Dravet, 2022 LGS
  • Serotonin release
  • Effective for drop attacks (LGS)
  • Cardiac monitoring

372.3.2.3 Ganaxolone (Ztalmy)

  • Neuroactive steroid
  • FDA 2022 CDKL5 deficiency disorder

372.3.2.4 Carfilzomib for Anti-LGI1

  • Autoimmune encephalitis with seizures
  • Specific antibody-driven

372.3.2.5 Gene Therapies

  • AAV-delivered
  • Trials for Dravet (SCN1A)
  • Limited availability

372.3.2.6 Anti-Inflammatory Approaches

  • Targeted for autoimmune epilepsies
  • NORSE/FIRES (febrile infection-related epilepsy syndrome)
  • Immunotherapy + ketogenic + anakinra

372.3.2.7 Stereo-EEG (sEEG)

  • Replacing subdural grids
  • Less invasive
  • Better deep structures
  • Localizes seizure onset zone for surgery

372.3.2.8 Laser Interstitial Thermal Therapy (LITT)

  • Minimally invasive ablation
  • For specific epileptogenic foci (mesial temporal, hypothalamic hamartoma)
  • Shorter recovery vs craniotomy

372.3.3 High-Yield Specialist Points

372.3.3.1 Mesial Temporal Sclerosis

  • Most common pathology in epilepsy surgery
  • Hippocampal sclerosis on MRI
  • History of febrile seizures often
  • Excellent surgical outcomes (70%+ seizure free)

372.3.3.2 Cortical Dysplasia

  • Common in pediatric epilepsy surgery
  • Various types (Type I, II, III)
  • FCD type IIb associated with TS

372.3.3.3 Tuberous Sclerosis Complex (TSC)

  • TSC1, TSC2
  • Cortical tubers
  • Subependymal nodules + giant cell astrocytomas
  • Epilepsy common (often refractory)
  • Everolimus (mTOR inhibitor) — FDA approved for SEGA + refractory epilepsy in TSC
  • Vigabatrin first-line for TSC-related infantile spasms

372.3.3.4 Dravet Syndrome

  • SCN1A mutation
  • Refractory infantile-onset
  • Avoid sodium channel blockers (worsen)
  • Valproate + clobazam first-line
  • Stiripentol, cannabidiol, fenfluramine

372.3.3.5 Lennox-Gastaut Syndrome

  • Multiple seizure types (atonic, tonic, atypical absence)
  • Slow spike-wave on EEG
  • Cognitive impairment
  • Drug-resistant
  • Valproate, lamotrigine, clobazam, rufinamide, cannabidiol, fenfluramine, vagus nerve stim
  • Corpus callosotomy for drop attacks

372.3.3.6 Genetic Epilepsies

  • Sodium channelopathies (SCN1A — Dravet, SCN8A)
  • Potassium channelopathies (KCNQ2)
  • Glutamate receptor (GRIN2A, GRIN2B)
  • Synapse-related (STXBP1, SYNGAP1)
  • Pyridoxine-dependent (ALDH7A1) — try B6 in neonatal
  • Glucose transporter (SLC2A1) — DEET-1; ketogenic diet

372.3.3.7 Autoimmune Epilepsy

  • Anti-NMDA-R (psychiatric + seizures + movement)
  • Anti-LGI1 (faciobrachial dystonic seizures pathognomonic!)
  • Anti-CASPR2
  • Anti-GAD65
  • Anti-Ma2 (paraneoplastic)
  • Immunotherapy + ASMs

372.3.3.8 Faciobrachial Dystonic Seizures

  • Pathognomonic of anti-LGI1
  • Brief unilateral facial + arm dystonia
  • Many per day
  • Detect early → immunotherapy → prevent encephalitis

372.3.3.9 Photosensitive Seizures

  • JME often
  • Stroboscopic stimulation triggers
  • Avoid TV close, video games (some)
  • ASMs as for syndrome

372.3.3.10 Pyridoxine-Dependent Epilepsy

  • ALDH7A1
  • Neonatal refractory seizures
  • Trial of pyridoxine 100-500 mg IV
  • Lifelong B6

372.3.3.11 EEG Interpretation

  • Generalized 3 Hz spike-wave: absence
  • Generalized polyspike-wave: JME
  • Slow spike-wave (< 2.5 Hz): LGS
  • Hypsarrhythmia: West syndrome (infantile spasms)
  • Focal sharp/spike: focal epilepsy
  • PLEDs: focal lesion, HSV
  • Triphasic: metabolic
  • Burst-suppression: deep encephalopathy

372.3.4 Pearls

  • Seizure ≠ epilepsy (provoked vs unprovoked)
  • Witnessed account critical for history
  • ILAE 2017: onset (focal vs generalized) + awareness + motor vs non-motor
  • ASM by type — choose appropriately
  • Pregnancy: lamotrigine + levetiracetam safest
  • **HLA-B*1502** screen for CBZ in Asians
  • Refractory: 2 ASM failure → surgery/VNS/RNS/DBS/diet/cannabidiol
  • Mesial temporal sclerosis: excellent surgical outcome
  • Cenobamate (2019) high response in refractory focal
  • Cannabidiol for Dravet, LGS, TSC
  • Fenfluramine for Dravet, LGS
  • Anti-LGI1 + faciobrachial dystonic seizures — autoimmune, immunotherapy
  • SUDEP counsel patients