What is the management and treatment for Rasmussen syndrome?

Management and Treatment of Rasmussen Syndrome

Functional hemispherectomy or hemispherotomy remains the only definitive cure for Rasmussen syndrome, though immunomodulatory therapy should be considered as initial treatment in early-stage disease, particularly in young children without advanced MRI lesions, to potentially preserve cognitive function and delay or avoid surgery. 1, 2

Understanding Rasmussen Syndrome

Rasmussen syndrome is a chronic, progressive autoimmune encephalopathy characterized by:

• Unihemispheric brain atrophy 3
• Refractory focal epilepsy with epilepsia partialis continua 4
• Progressive hemiparesis and cognitive/language decline 3
• Affects previously neurologically normal individuals 1

Diagnostic Workup

The majority of providers pursue the following investigations 3:

• Cerebrospinal fluid analysis for autoimmune encephalitis antibodies (82% of providers) 3
• Serum autoimmune encephalitis panels (78% of providers, with higher rates in US/Europe at 85% versus 67% elsewhere) 3
• Genetic and metabolic studies are obtained by approximately one-third of providers (36-38%), though US and European providers pursue genetic testing more aggressively (56% and 47% versus 14% elsewhere) 3
• Brain biopsy is performed by 36% of providers when patients otherwise meet diagnostic criteria, with US providers significantly more likely to recommend this (73% versus 14-41%) 3

Treatment Algorithm

Early-Stage Disease (No or Minimal MRI Lesions)

Initiate immunomodulatory therapy first 2:

1. Regular steroid pulse therapy as first-line treatment 2

   • Methylprednisolone 30 mg/kg/day in children or 1000 mg/day in adults for 3 days 2
   • Achieves 81% response rate for seizure control 2
   • Preserves IQ ≥80 in 100% of patients without MRI lesions 2
   • Motor function deteriorates in only 10% of patients 2

2. Switch to tacrolimus after several months of steroid therapy 2

   • Initial dose: 0.1 mg/kg/day in children 2
   • Achieves 42% seizure response rate 2
   • Preserves IQ ≥80 in 29% of patients 2
   • Motor function deteriorates in 0% of patients (data not explicitly stated but implied) 2

3. Intravenous immunoglobulin (IVIG) as alternative or adjunctive therapy 2, 4

   • Dose: 100 mg/kg/day 2
   • Achieves 23% seizure response rate 2
   • US providers favor IVIG as first-line (67%) compared to other regions (28-32%) 3
   • Long-term maintenance every 4 months has shown benefit in preventing disease progression 4

4. Mycophenolate mofetil (MMF) may be considered 5

   • Demonstrated reduction in seizures and stability of radiological findings in case reports 5
   • Represents a potential steroid-sparing option 5

Advanced Disease (Progressive MRI Lesions, Severe Deficits)

Proceed to surgical intervention 1, 2:

• Functional hemispherectomy or hemispherotomy is the standard of care (90% consensus) 3
• Achieves 71% seizure-free rate 2
• Critical caveat: 100% of surgical patients experience motor function deterioration, and 0% maintain IQ ≥80 2
• Surgery remains the only definitive cure despite inevitable functional consequences 1

Timing Considerations

Early surgery versus prolonged immunotherapy remains controversial 1, 3:

• Not all patients have rapidly progressive disease; some may benefit from extended immunomodulatory treatment 1
• Careful evaluation of clinical course is essential to identify patients who would benefit most from early surgery 1
• Practice patterns vary significantly internationally regarding prioritization of hemispherectomy versus immunotherapy based on neurologic deficit severity 3

Cognitive and Motor Outcomes Comparison

Immunomodulatory therapy preserves function better than surgery 2:

• IQ ≥80 preservation rates: Regular steroid pulse (50%) > Regular IVIG (43%) > Tacrolimus (29%) > Functional hemispherectomy (0%) 2
• Motor function improvement: Only observed with immunomodulatory therapy, never with surgery 2
• Motor function deterioration rates: Functional hemispherectomy (100%) > Regular IVIG (62%) > Regular steroid pulse (10%) 2

Common Pitfalls

• Delaying immunotherapy in early disease: Patients without advanced MRI lesions have 100% chance of preserving IQ ≥80 with steroid pulse therapy versus 0% with surgery 2
• Rushing to surgery in slowly progressive cases: Some patients respond well to long-term immunomodulation and may avoid or significantly delay surgery 1, 4
• Inadequate trial of immunotherapy: Response to steroids may take several months; premature surgical referral may sacrifice cognitive function unnecessarily 2
• Underestimating surgical morbidity: 100% of surgical patients experience motor deterioration and complete loss of higher cognitive function (IQ <80) 2