doctor injecting medicine into an IV

Initial, short-term treatments for autoimmune epilepsy include high dose intravenous (IV) corticosteroid therapy, plasma exchange (PLEX) and intravenous immunoglobulin (IVIG).

Autoimmunity is now recognized as a potentially treatable cause of epilepsy. Treatment of people with autoimmune epilepsy includes therapies to inhibit the immune system (called immunotherapy) and removal of immunologic triggers where possible.

Immunotherapy can be further divided into two phases: acute and maintenance.

Major Principles of Immunotherapy

  • Immunotherapy should be started as soon as a diagnosis of autoimmune epilepsy seems probable and alternative causes, especially infections, are excluded. Infections that can mimic autoimmune epilepsy include viral infections.
  • The main goal of immunotherapy is to reduce acute inflammation and minimize irreversible neuronal dysfunction (brain cells that do not work correctly).
  • Initial immunotherapy needs to be aggressive. After the acute phase of treatment, immunotherapy doses are a gradually reduced over weeks to months.
  • If there is no significant response to initial immunotherapy, other causes should be reconsidered before increasing immunosuppression. Furthermore, if antibodies associated with cancers are identified (called paraneoplastic), a thorough search for an underlying tumor is recommended.
  • After acute treatment, maintenance therapy is started. The goals of maintenance therapy are to prevent disease progression and relapses.
  • People with autoimmune epilepsy may have clinical problems in addition to their seizures, including psychiatric difficulties, cognitive problems, balance impairment, sleep disorder and autonomic (involuntary actions like breathing or heartbeat) dysfunction. It is important to identify and manage these symptoms as they may significantly affect quality of life.

Acute Phase Treatment

Acute treatment options for autoimmune epilepsy include high dose intravenous (IV) corticosteroid therapy, plasma exchange (PLEX) and intravenous immunoglobulin (IVIG).

  • In critical care cases, such as people admitted to an intensive care unit, acute therapy is intravenous methylprednisolone (IVMP) at 1 gram per day for 5 days combined with or followed by PLEX (5-7 cycles; one exchange every other day spread over 10-14 days) or IVIG (0.4g/kg per day for 5 consecutive days). If both PLEX and IVIG are used, it is best to do PLEX first to avoid removing the immunoglobulins from the blood circulation.
  • In outpatient management, treatment is typically 12 weeks of immunotherapy using IVMP or IVIG.
    • IVMP treatment includes 1 g per day for 3-5 days followed by once weekly for 5 weeks, followed by once every 2 weeks for 6 weeks.
    • If the person has contraindications for IVMP or cannot tolerate high-dose corticosteroids due to side effects, 12 weeks of IVIG may be considered. This includes 0.4 g/kg IVIG daily for 3-5 days followed by 0.4 g/kg every week for 6 weeks, then every 2 weeks for 6 weeks.

Maintenance Phase

Studies looking at how effective maintenance immunotherapy are unfortunately limited.

  • In most cases, chronic immunotherapy decisions are based on response to the acute immunotherapy regimen and on any specific autoantibodies identified.
  • In cases that do not respond completely to acute treatment, second line immunosuppressive agents are sometimes started early in the disease course. Rituximab, cyclophosphamide, mycophenolate mofetil, and azathioprine medications that are commonly used in these cases.
  • In some cases, chronic IVIG or plasmapheresis once every 2 to 3 weeks can be used for maintenance therapy.
  • If mycophenolate mofetil or azathioprine are used, an overlapping 2-3 month course of corticosteroids should be considered due to their delayed therapeutic effect.

Personalized Maintenance Treatment Options

The type of autoimmune epilepsy a person has can determine treatment strategies.

  • For example, those due to classic paraneoplastic antibodies, such as anti-Hu IgG, usually require treatments that affect T-cell immune responses, such as cyclophosphamide and mycophenolate mofetil.
  • However, B-cell targeted therapies are preferred in conditions due to antibodies targeting antigens on the neural cell surface or synapses, such as NMDA-R IgG and LGI-1 IgG, to reduce abnormal antibody production.

What does long-term maintenance look like?

How long a person needs to stay on maintenance immunotherapy is not known.

  • The person’s epilepsy team may try to stop or withdraw maintenance immunotherapy after two years of clinical stability without any relapses.
  • Some people continue to have chronic drug-resistant epilepsy despite aggressive immunotherapy and antiseizure drugs.

Managing autoimmune epilepsy can be challenging. Therefore, people with autoimmune epilepsy should follow up regularly with their provider team, which should include both an epileptologist (a neurologist who specializes in epilepsy) and a neuroimmunologist (a specialist in both the nervous and immune systems).

References

Authored By: 
Divyanshu Dubey MD
Authored Date: 
02/2020
Reviewed By: 
Jeffrey W. Britton MD
Andres M. Kanner MD
on: 
Saturday, February 15, 2020