What is the recommended treatment for a patient presenting with new onset seizures and diagnosed with limbic encephalitis?

From the Guidelines

The recommended treatment for a patient with new onset seizures due to limbic encephalitis includes both antiseizure medications and immunotherapy, with first-line antiseizure medications such as levetiracetam or lamotrigine and immunotherapy starting with high-dose corticosteroids, as supported by the most recent guidelines 1. The treatment approach should be dual, targeting both symptom management (seizures) and the underlying autoimmune pathology causing inflammation in limbic structures.

• First-line antiseizure medications such as levetiracetam (starting at 500 mg twice daily, increasing as needed to 1500-3000 mg/day) or lamotrigine (starting at 25 mg daily with slow titration to 100-400 mg/day) should be initiated promptly to control seizures.
• Concurrently, immunotherapy should be started, typically beginning with high-dose corticosteroids (methylprednisolone 1000 mg IV daily for 3-5 days, followed by oral prednisone 1 mg/kg/day with gradual taper over weeks to months), as recommended by recent studies 1. If the patient shows inadequate response to steroids within 1-2 weeks, second-line immunotherapy with intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days or plasma exchange (5-7 exchanges over 10-14 days) should be considered, based on expert opinions and survey results 1. For refractory cases or antibody-positive limbic encephalitis, rituximab (375 mg/m² weekly for 4 weeks) or cyclophosphamide may be necessary, as suggested by previous studies 1. Treatment response should be monitored through clinical improvement, EEG findings, and repeat imaging, with immunotherapy potentially continuing for months depending on the specific antibody and clinical response. Key considerations include:
• Prompt initiation of treatment, as it confers the best recovery, especially when started within 4 weeks of symptom onset 1.
• Tumour screening should be performed annually for several years, particularly if the treatment response is poor or relapses occur 1.

From the FDA Drug Label

The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day.

The patient presenting with new onset seizures and diagnosed with limbic encephalitis may be treated with valproate, with a recommended initial dose of 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week until seizures are controlled or side effects preclude further increases, with a maximum recommended dosage of 60 mg/kg/day 2.

• Key considerations for treatment include:
  • Monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events, particularly in elderly patients
  • Regular monitoring of serum valproic acid concentrations, especially when initiating carbapenem therapy
  • Weighing the therapeutic benefit of higher doses against the possibility of a greater incidence of adverse effects, such as thrombocytopenia 2.

From the Research

Treatment for Limbic Encephalitis

The treatment for limbic encephalitis typically involves immunotherapy, with the goal of reducing inflammation and modulating the immune system.

• First-line treatment often includes high-dose steroids, such as methylprednisolone, as seen in the case of nivolumab-induced limbic encephalitis, where very high-dose methylprednisolone was used 3.
• Other first-line treatments may include intravenous immunoglobulin and therapeutic plasma exchange, as mentioned in the context of NMDA-R encephalitis 4.
• Second-line therapy for refractory cases may include intravenous rituximab and cyclophosphamide, as noted in the treatment of NMDA-R encephalitis 4 and limbic encephalitis in a patient with systemic lupus erythematosus 5.

Antiepileptic Drug Treatment

For patients presenting with new onset seizures, antiepileptic drug monotherapy may be considered.

• A network meta-analysis of individual participant data found that levetiracetam, lamotrigine, and sodium valproate were effective treatments for partial onset seizures and generalized tonic-clonic seizures 6.
• Levetiracetam has been shown to be effective in the treatment of idiopathic generalized epilepsies, with a favorable safety profile and minimal drug interactions 7.

Specific Considerations

It is essential to note that the treatment of limbic encephalitis and seizures should be individualized, taking into account the underlying cause and the patient's specific needs.

• Measuring anti-neuron antibodies, including anti-GluRs, may be important in diagnosing and managing limbic encephalitis, particularly in patients with systemic lupus erythematosus 5.
• The use of very high-dose corticosteroids, such as methylprednisolone, may be necessary in some cases, as seen in the treatment of nivolumab-induced limbic encephalitis 3.