What are the recent advances in the management of epilepsy?

Recent Advances in Management of Epilepsy

Vagus nerve stimulation (VNS) is one of the most significant recent advances in epilepsy management, offering effective seizure reduction for patients with refractory epilepsy who don't respond to antiepileptic drugs (AEDs). 1

Pharmacological Advances

First-Line Treatment Options

• Approximately 47% of patients achieve seizure freedom with the first attempted AED, with an additional 14% responding to a second or third AED 1
• For focal seizures, lamotrigine and levetiracetam show the best profiles in terms of treatment failure and seizure control as first-line treatments 2
• For generalized tonic-clonic seizures, sodium valproate remains the most effective first-line treatment, with lamotrigine and levetiracetam as suitable alternatives 2

Management of Status Epilepticus

• Benzodiazepines remain the first-line treatment for status epilepticus 1
• For patients with generalized convulsive status epilepticus who continue to have seizures despite benzodiazepines, several second-line options are available:
  • Valproate (30 mg/kg IV) has shown efficacy in 88% of cases within 20 minutes of infusion 1
  • Levetiracetam (30 mg/kg IV) demonstrates similar efficacy to valproate (73% vs 68%) 1
  • Phenytoin/fosphenytoin remains a traditional option but has drawbacks including hypotension in 12% of patients 1

Neuromodulation Therapies

Vagus Nerve Stimulation (VNS)

• FDA-approved in 1997 as an adjunctive therapy for patients with refractory epilepsy 1
• Approximately 51% of patients experience a 50% or greater reduction in seizure frequency with VNS 1
• VNS involves implanting helical cuff electrodes on the left cervical vagal trunk connected to an implanted pulse generator 1
• Recent advances in VNS include:
  • Optimization of stimulation parameters to improve outcomes 1
  • Evidence suggesting that higher duty cycle and/or frequency could improve response rates 1
  • Delivering electrical stimulation closer to the nerve to enhance neural activity 1

Advanced Neuroimaging

Nuclear Medicine Imaging

• Molecular neuroimaging has significantly impacted presurgical management of epilepsy patients 1
• Techniques include:
  • Interictal [18F]fluorodeoxyglucose (FDG) PET 1
  • Ictal perfusion SPECT 1
  • Ictal subtraction perfusion SPECT (interictal SPECT fused, normalized, and subtracted from ictal SPECT) 1
• These techniques are particularly valuable for:
  • Non-lesional epilepsy cases 1
  • Patients with multifocal structural cerebral abnormalities 1
  • Localizing seizure onset for tailored resection that preserves critical brain functions 1

Surgical Advances

• Surgical resection of epileptogenic areas can be highly effective, with 52% of patients remaining seizure-free 5 years post-surgery 1
• Advanced imaging techniques help improve surgical outcomes by better identifying the epileptogenic zone 1
• Surgical approaches are increasingly tailored to preserve motor, visual, language, or temporal lobe functions 1

Personalized Medicine Approaches

• Treatment decisions are increasingly individualized based on:
  • Precise classification of seizure type and epilepsy syndrome 1
  • Patient characteristics including age, sex, and comorbidities 3
  • Genetic factors that may influence drug response 1
• For refractory epilepsy (30% of cases), combination therapy approaches are being refined 4

Common Pitfalls and Considerations

• Refractory epilepsy affects 20-40% of newly diagnosed patients and requires special consideration 1
• Not all patients are candidates for surgical resection due to:
  • Disease etiology 1
  • Location of seizure initiation zone in critical brain regions 1
  • Susceptibility to complications associated with invasive surgery 1
• Most commonly reported adverse events across AEDs include:
  • Drowsiness/fatigue 2
  • Headache or migraine 2
  • Gastrointestinal disturbances 2
  • Dizziness/faintness 2
  • Rash or skin disorders 2
• When using VNS, a challenge remains in achieving selective activation of targeted therapy-producing nerve fibers without co-activation of non-targeted fibers 1

Future Directions

• Improved characterization of the relationship between VNS stimulation parameters and fiber recruitment will likely expand its therapeutic applications 1
• Additional VNS applications being investigated include treatment of chronic heart failure, tinnitus, post-traumatic stress disorder, stroke, and inflammatory diseases 1
• Continued development of evidence-based guidelines for nuclear medicine imaging procedures in epilepsy management 1