Autoimmune Encephalitis is treated with immunotherapy. Immunotherapy slows down the over excited immune system. By slowing down the immune system it slows down and attempts to stop the attack that is occurring. Initially, high dose steroids are used to slow down the immune system and bring down the inflammation in the brain in a broad way.
Immunotherapy treatment is the combination of treatments that include first-line therapies: steroids, IVIG, plasma exchange (plasmapheresis) and second -line therapies: Rituxamab (Rituxan) and cyclophosphamide(Cytoxan), followed in many cases by steroid-sparing agents such as cellcept or azathioprine in the long-term. The fact that patients who receive second line immunotherapies have fewer relapses, is leading many physicians to use rituximab initially as a first line treatment.
If the clinician suspects autoimmune encephalitis, treatment is often given without delay based on clinical observations of symptoms, a history of how the disease developed, and the results of medical evaluations and tests performed. Experts in the field recommend beginning treatment immediately and not waiting 7-10 days for specific antibody test results to come in as, in general, prompt treatment, and escalation of treatment in patients who remain ill, is associated with better outcomes.
In the case, of ‘probable’ or ‘possible’ autoimmune encephalitis being suspected, treatments may include steroids and/or IVIG
IVIG offers an important advantage of being unlikely to make infectious encephalitis worse. Plasmapheresis is also unlikely to significantly worsen infectious encephalitis. Clinicians need to also consider that treatment with steroids, rituximab, or cyclophosphamide could complicate tumor diagnosis in the case of tumors like lymphoma.
If a cell-surface/synaptic antibody disorder is diagnosed, (remember those are the extracellular antibodies which are exposed on the OUTSIDE of the brain cell it is attacking). Initial immunotherapy treatments may include IVIG, plasmapheresis, and/or steroids. Immunotherapy is mostly targeting the B cell response which is why positive outcomes are seen in these more commonly occurring antibodies in autoimmune encephalitis.
The response to immune therapy is generally good, particularly if the more effective treatments are used promptly. However, powerful immune suppression may be needed for weeks or months in difficult cases and treatment may take many months to reach its full effects. Some patients, an estimate of 35-42% have persistent deficits, especially in the domains of memory and cognition. Autoimmune encephalitis may relapse, so follow-up care is important.
Many forms of autoimmune encephalitis are paraneoplastic, and each of these conveys a distinct risk profile for various tumors. Tumor screening and, if necessary, tumor removal is essential to proper management of treatment.
Special Thanks to Autoimmune Encephalitis Alliance who sponsored
the symposium from which this video was taken.
New Treatments for Refractory Cases:
As research continues to unfold, alternative treatments for cases that have been resistant to the prior mentioned immunotherapies have come to the forefront. More prominently: Bortezomib, Tocilizumab, Ofatumumab and Inebilizumab
Early Treatment and Outcomes:
The case that early treatment provides the best outcomes, has been made in several studies. A small case series reported that 4 of 5 children treated with combinations of first-line immunotherapy within 6 days of symptom onset recovered fully with no relapses. The strongest evidence in favor of early treatment comes from the largest observational cohort published, January 2011 Dr. Josep Dalmau and Dr. Eric Lancaster’s co-hort study of 577 patients followed over a 2-year period. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis.
In that study, approximately 50% of patients respond to first line immunotherapies (intravenous immunoglobulins (IVIG), steroids, or plasma exchange) and the other 50% require second line therapies, such as rituximab or a combination of rituximab and cyclophosphamide. Relapses occur in 12–20% of cases (12% during the first 24 months of the disease), often presenting as fragments of the syndrome (perhaps due to prompt diagnosis), and respond to immunotherapy. Patients who do not respond to treatment, or who have relapses, should be reassessed for the presence of an underlying contralateral (opposite side) or recurrent teratoma with anti-NMDAr and tumor search in other variants where this may occur.
In the July 2016 study, Anti-LGI1-associated cognitive impairment: Presentation and long-term outcome, Drs. Dalmau and Graus were surprised to discover in their study of the most common Limbic encephalitis, that follow up after 2 years shows 35% were fully recovered but not able to return to their previous jobs or function as they had previously due to lasting brain injury. Of the patients who received treatment within 3 months 27% relapsed. Relapse usually occurs when immunotherapies are tapered early. The final outcome for those with LGI1 antibodies is far from optimal. Improvement occurs but they acknowledge that there is a lot more that needs to done to get better improvement for these patients.
The associated syndromes often respond to immunotherapy, resulting in substantial or complete recovery particularly if the more effective treatments are used promptly. However, treatment may take many months to reach its full effects, and some patients have persistent deficits, especially in the domains of memory and cognition.
Prior to these disorders being identified, and taking into account the severity and duration of symptoms, the clinical recovery of similar patients was not expected. Unaware of how the disorders worked and that they could respond to a treatment, they were thought to be untreatable and the disease was allowed to progress. These patients eventually died of status epilepticus or coma. The discovery of the first antibody, NMDAr, and subsequent antibodies since, has changed the concepts about supportive therapy today in cases that would have been considered futile in the past.
Click to read the paper below which contains treatment overview and the above Table 4
Dr. Dalmau & Dr. Graus discussing their paper:
Anti-LGI1-associated cognitive impairment final outcomes
Modified Ranking Scale:
Most studies have used the modified Rankin Scale (mRS) to measure outcome. The is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered an illness that caused neurological disability. The Dalmau and Lancaster co-hort study of 577 patients, demonstrated that early treatment, the lack of need for intensive care admission, and maximum mRS score of ≤ 3 were independently associated with good outcome. In that study, about half the patients who received first-line immunotherapy improved within 4 weeks of treatment, and 97 % of these patients went on to have a good outcome (mRS 0–2) at 24 months of follow-up.
Even in those patients classified as having good outcome in Autoimmune Encephalitis, (mRS 0–2), incomplete recovery with deficits in executive function and memory are common and are more severe in those with delayed treatment. This would suggest that the initial part of the illness may be critical in terms of neuronal damage and long-term disability which is why it is so important to be aware of this syndrome during its earlier psychiatric presentation. As it progresses into the the later neurologic stages, the potential for a long term deficit increases.
In addition, the associated syndromes often respond to immunotherapy, resulting in substantial or complete recovery in 70–80% of the patients. Physicians should be aware that isolated psychiatric symptoms can last for months before neurological symptoms and should remain hopeful for a good prognosis because continuous immunotherapy can achieve a favorable outcome despite delayed diagnosis. Owing to the severity and duration of symptoms, before these disorders were known the clinical recovery of similar patients was not expected, thus changing our concepts about supportive therapy today in cases that would have been considered futile in the past.
