SYMPTOMS

Autoimmune encephalitis (AE) can produce a very wide range of neuro-psychiatric symptoms. A major
challenge in diagnosis is that different symptoms may appear at different times and different levels of
intensity, so that the disease may mimic many other disorders. Some patients initially present with either
neurological or psychiatric symptoms, further complicating diagnosis.
Symptoms associated with AE can include:

weakness or numbness of part of the body

loss of balance

slowed or blurred speech or loss of ability to speak

ataxia

involuntary movements

distorted vision

cognitive impairment

memory disturbance

decreased level of consciousness to the point of unresponsiveness, catatonia or coma

seizures (either self-evident, or smaller seizures that show up on an eeg reading)

partial or complete loss of appetite for long periods

food and drink tasting inedible or triggering nausea

excessive eating without feeling sated

agitation

inability to sleep

loss of inhibition

rapid, pressured, or involuntary speech

hallucinations (visual or auditory) and delirium

paranoid thoughts

severe anxiety
An otherwise unexplained mixture of the above neuro-psychiatric symptoms may be a clue that the
underlying cause is autoimmune encephalitis.
DIAGNOSIS

A quick diagnosis allows for early and aggressive treatment, improving the opportunity for quick and
full recovery.
Autoimmune encephalitis (AE) is a complex disease that often requires collaboration among multiple
medical disciplines for effective diagnosis and treatment. Most AE patients can expect to see a team of
doctors that may include neurologists, rheumatologists, psychiatrists, immunologists and others.
AE can be caused by different antibodies. Currently there are 13 known antibodies or triggers for AE but
only one commercially available diagnostic test. Tests for Anti-NMDA Receptor autoimmune encephalitis
is commercially available at Athena Diagnostics or Mayo Clinic. This test should be ordered quickly by
your doctor if AE is suspected.
However, negative test results for anti-NMDA Antibodies and/or teratoma do not rule out AE. A significant
percentage of AE cases are caused by other, still unknown antibodies, or by known antibodies for which a
diagnostic test is not yet available.
In some AE cases an MRI test will show brain inflammation (encephalitis) and/or an EEG test will show
generalized slowing or seizure activity in the brain. These two tests can rule out purely psychiatric causes of
illness. For example, voltage-gated potassium channel complex encephalitis, another form of AE, can be
recognized on MRI, as reported in a recent study by Kotsenas et al.
Too many general practitioners and even many specialists including psychiatrists and neurologists have little
if any experience diagnosing or treating AE. If you suspect AE dont hesitate to share this information with
your medical provider. Disseminating scientific knowledge about diagnosis and treatment of the disease is
one of the primary goals of the Autoimmune Encephalitis Alliance.
TREATMENT
Just as the diagnosis of autoimmune encephalitis (AE) has evolved over the past several years, so have the
treatment options. The following discussion is intended only as an introduction to various treatment
options. ONLY your doctor or medical professional can prescribe an appropriate treatment regime.
Early and aggressive treatment of AE leads to the best outcomes. A number of options are available to treat
AE. These therapies are broken down into what are considered first line and second line treatment
options. One or more first line treatments may be prescribed by your physician as soon as a patient is
diagnosed with AE. The four most common first line treatments include the following:

removal of a teratoma (if present) that could be triggering the autoimmune response;

use of anti-inflammatory drugs (ie. steroids);

use of plasmapheresis to remove harmful antibodies from blood; and

treatment with intravenous immunoglobulin (IVIG) which is believed to occupy the binding sites
where harmful antibodies attach to brain cells.
Early and aggressive therapy has been shown to prevent progression of the disease.
Patients who do not improve on first line treatments may be given a second line treatment. Second line
treatments are drugs that are intended to suppress the immune system. The three most common second
line drugs used for AE are:

Rituximab,

CellCept , and

Cytoxan (cyclophosphamide).
RECOVERY
The recovery process is unique to each patient. Early and aggressive treatment leads to the best recovery. A
recent study in Lancet Neurology by Dr. Titulaer, Dr. Dalmau and colleagues found that 50% of autoimmune
encephalitis (AE) patients show substantial improvement within four weeks of receiving treatment.
According to the same study, patients continue to improve after being discharged from the hospital. Over
80% of patients with autoimmune encephalitis eventually have partial or complete recovery. However, on
average, autoimmune encephalitis patients took up to 14 months for complete recovery.
Many patients have total recovery, including patients who are severely ill. For example, see the memoir by
Susannah Cahalan, Brain on Fire: My Month of Madness. Other patients struggle for years to get the correct
diagnosis and appropriate treatment. Helen and Daniel Eggers blog Light of Sasha details their adolescents
journey with AE.
Persisting Symptoms
After recovery from an acute episode of autoimmune encephalitis, many patients have symptoms of
traumatic brain injury (TBI). Symptoms of TBI can include, but are not limited to, fatigue, difficulty
concentrating, acquired Attention Deficit Disorder (ADD), cognitive challenges, coordination problems,
memory problems, lack of motivation, change of personality, irritability, and depression.
Aggressive treatment for TBI can substantially improve outcomes, especially in young people who have a
great deal of brain plasticity. Doctors recommend that autoimmune encephalitis patients pursue TBI
rehabilitation as appropriate after discharge from hospital.
If neurological symptoms persist, it may be a sign that the underlying disease process is continuing. Ongoing
treatment with immunomodulation drugs on an outpatient basis may be recommended in these cases.
Relapse Frequency
The Lancet Neurology article by Titulaer et al reported that 12% of anti-NMDA receptor encephalitis
patients had at least one relapse within two years. No other studies have followed a sizable patient
population to estimate relapse frequency.
RESOURCES
If you are reading this page, then you or someone you care about has likely been diagnosed with
autoimmune encephalitis. You are not alone. We are here to provide hard won wisdom, connections to a
community living with this disease and tools to navigate the medical system.
After reviewing the following resources, please contact us if you know of other useful resources for patients
and families living with autoimmune encephalitis.
Social Media Support Group
Connect with other families and patients as they share their stories and hard won lessons living with AntiNMDA Receptor Encephalitis, a specific type of autoimmune encephalitis.
NMDA Antibodies Support Group for families and patients.
Information for Parents of School Age Children
School age children are entitled to accommodations under U.S. law, and may qualify for an Individualized
Education Program (IEP) for acquired cognitive problems and/or ADD. Both the National Center for
Learning Disabilities and the National Dissemination Center for Children with Disabilities provide useful
information on IEPs and other resources.
Autoimmune Encephalitis Specific Sites

Current estimates suggest there are 13 known causes or types of Autoimmune Encephalitis. The Alliance is
building a list of the known types of AE and will add resource links where available. Please connect with us
to let us know of additional resources. [NOTE: These are external links. The AE Alliance does not certify
the accuracy of information contained on these sites.]

Anti-NMDA autoimmune encephalitis: This wikipage provides very basic overview and some
research articles.

Hoshimotos Encephalopathy: The Hoshimotos Encephalopathy SREAT Alliance provides

information and support on HE.

Rasmussens Encephalitis: The Encephalitis Society provides a fact sheet on Rasmussens

Encephalitis.

Voltage-gated Potassium Channel Encephalitis: The Encephalitis Society (again) provides a good
fact sheet.
Encephalitis Focused Groups
The Encephalitis Society and Encephalitis Global provide resources to patients and families with a wide
range of encephalitis diseases.
Autoimmune Disease Groups
The American Autoimmune Related Diseases Association Inc (AARDA) provides information on the more
than 100 known autoimmune diseases.
Navigating the Medical System
Anyone who has spent time in a hospital, learns unique processes or ways to be efficient. One thing that
worked for our family was keeping a binder of all our test results and doctors write ups. During the course
of diagnosis and treatment, patients (both young and old) with autoimmune encephalitis will interact with
doctors from different medical disciplines. In order to stay organized with the many different tests and
medical reports, it is important for you to keep your own binder with copies of these reports divided by
medical specialty (i.e. Neurology, Psychiatry, Immunology). This can help eliminate duplicate testing and
hopefully lead to more efficient care
GLOSSARY
An antibody also known as an immunoglobulin, is a large Y-shaped protein produced by B-cells that is used
by the immune system to identify and neutralize foreign objects such as bacteria and viruses.
Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that
coordinate movement.
Autoimmune diseases arise from an inappropriate immune response of the body against substances and
tissues normally present in the body (autoimmunity).
CellCept is an oral immunosuppressant, originally prescribed to patients undergoing organ transplant
surgery, but now is recommended as a possible second line defense in AE. CellCept interferes with the
formation of DNA in certain immune system cells that become overactive in cases of autoimmune disorders.
Most common side effects include nausea, vomiting, diarrhea, headache, dizziness or rash. Less common but
more serious side effects include anemia, and blood clots. Click here for a complete list of side effects.
Cytoxan is a chemotherapy drug that comes in tablet or injectable form. It works by slowing or halting the
growth of immune system cells. Common side effects include nausea, vomiting, and hair loss. Less common
but more serious side effects include damage to the bladder, fertility problems, and bone marrow
suppression. Click here for a complete list of side effects.

EEG is an Electroencephalograph used to record the brains spontaneous electrical activity over a short
period of time usually 2040 minutes, as recorded from multiple electrodes placed on the scalp. A clinical
use of EEG is in the diagnosis of encephalopathy.
Encephalitis is acute inflammation of the brain.
Intravenous immunoglobulin (IVIG) is a blood product administered intravenously consisting of blood
plasma donations from human donors. IVIG contains an antibody called IgG that helps to ward off infection,
modulates immune system, and reduces inflammation, though the full extent of how IVIG works remains a
unknown. One theory in autoimmune encephalitis disorders is that IVIG occupies the binding sites where
harmful autoantibodies attach to brain cells.
Side effects include headaches, dermatitis (peeling of skin on palms and soles), pulmonary edema, and
allergic reactions. Click here for side effects.
Immunologist specializes in the diagnosis and treatment of problems with the immune system, including
immunodeficiency, when the immune system is compromised or impaired, and autoimmunity, when the
immune system attacks its own body.
MRI is a Magnetic Resonance Imaging scan. It can show the brain inflammation characteristic of
encephalitis. Please note that not all autoimmune encephalitis patients have abnormal MRI scans.
Neurologist specializes in the diagnosis and treatment of diseases involving the nervous system, which
includes the brain, spinal cord, and bodys network of nerves.
Plasmapheresis is a blood-cleansing intravenous procedure where blood is removed from a patient, treated,
and then returned to the patient. The procedure works by removing the patients blood plasma, which
contains the disease-causing autoantibodies.
Potential risks, including infection and bleeding, may emerge from the catheter insertion. Procedure side
effects include blood clots and hypotension. Click for a complete list of side effects and more information:
Prednisone, the most common form of corticosteroids prescribed to patients with autoimmune encephalitis,
acts as an immunosuppressant, which suppresses the immune system from making harmful autoantibodies.
Steroids also work as anti-inflammatory agents by reducing swelling in the brain. Side effects include high
blood glucose levels (important to those suffering from diabetes), weight gain, facial swelling, blurred
vision, increased levels of infections, and osteoporosis. Psychiatric side effects also can occur, including
insomnia, mood fluctuations, mania, depression, and anxiety. Click for a complete list of side-effects and
more information.
Psychiatrist specializes in the diagnosis and treatment of mental disorders.
Receptor is a protein on the surface of a brain cell that receives chemical messages and is a key building
block in the brains chemistry. In autoimmune encephalitis, the bodys immune system produces an antibody
that binds to a receptor in the brain and causes cells to respond inappropriately. Treatment of AE involves
eliminating or reducing these antibodies.
Rheumatology is a sub-specialty in internal medicine and pediatrics, devoted to diagnosis and therapy of
rheumatic diseases.
Rituximab is cell-targeted antibody injection that helps the immune system destroy certain blood cells that
may cause the immune system to create autoantibodies.
Common side effects during infusion include fever, shaking, fatigue, or nausea. Other adverse effects
include cardiac arrest, cytokine release syndrome, and types of immune toxicity. For a complete list of side
effects and more information.

Steroids are medications used to treat inflammation. One of the most common prescribed steroid drugs is
called Prednisone.
Teratoma is a tumor comprised of tissue and/or organ components. Teratomas are normally benign, but it is
believed that the teratomas (which sometimes contain brain tissue) act as the trigger in an AE patients
autoimmune response. Surgical removal of the teratomas in autoimmune encephalitis patients with one is the
first step in the recovery process.

What is Autoimmune Encephalitis (AE)?

AE is a serious medical condition in which the immune system attacks the brain, impairing function.
What are the most common symptoms of AE?
Autoimmune encephalitis can produce a wide range of neuro-psychiatric symptoms. Click here for a full
discussion of symptoms.
Is AE considered a new disease? Is it rare?
AEspecifically the anti-NMDA-receptor typewas first described by Dr. Josep Dalmau in 2005. The
field of AE has expanded rapidly since then. Now there are thirteen known types of AE. Initially considered
very rare, the disease is now increasingly recognized as a significant diagnosis in the spectrum of brain
illnesses related to malfunctions of the immune system. These types of disorders may be much more
common than previously thought.
Are you more likely to be diagnosed with AE due to age or gender?
The disease occurs in men, women and children of all ages, but it has historically been diagnosed most
frequently in young women. Out of 100-plus known autoimmune diseases, 75% of people affected are
female.
What kind of doctors treat AE?
Autoimmune Encephalitis is generally treated by four types of specialist doctors: psychiatrists, neurologists,
rheumatologists, and immunologists.
Psychiatrists specialize in the diagnosis and treatment of mental disorders and are key to ruling out
neurological causes of psychiatric symptoms. It is estimated that a majority of patients with AE see
psychiatrists first.
Neurologists specialize in the diagnosis and treatment of diseases involving the nervous system, which
includes the brain, spinal cord, and bodys network of nerves.
Rheumatologists specialize in the diagnosis and treatment of clinical problems that affect the joints and soft
tissue. Since many of the disease rheumatologists treat are immune system related, they are often included
under the banner of immunology.
Immunologists specialize in the diagnosis and treatment of problems with the immune system, including
immunodeficiency, when the immune system is compromised or impaired, and autoimmunity, when the
immune system attacks its own body.
How do clinicians currently recognize, and establish a diagnosis of AE?
Some types of AE can be diagnosed through a specific test measuring the presence of antibodies (ie antiNMDA receptor antibodies) or through the presence of a teratoma.
To rule out other psychiatric illnesses, Psychiatrists could consider administering the following tests:

blood test measuring inflammation markers

EEG (Electroencephalograph)

MRI (Magnetic Resonance Imaging)

Many cases of AE are diagnosed by process of elimination and diagnosis-through-treatment: for example, if
test results for all other diseases are negative and the disease symptoms improve with immune-modulation
therapy.
What are the known causes of AE?
Acute episodes of AE are known to be triggered by:

a teratoma ( a type of tumor, generally found in the ovaries);

the presence in the body of a cancer, that indirectly triggers an autoimmune response (this is called a
paraneoplastic syndrome)

exposure to certain common bacteria, including, but not limited to, streptococcus and mycoplasma
pneumonia, with or without active infection.
A teratoma or cancer is found only in a small minority of AE patients. Active infection is also uncommon in
patients presenting with acute AE. Unfortunately, the immediate trigger of many episodes of AE remains
unknown, though studies on possible viral triggers are currently underway.
Are family members at greater risk of contracting AE?
No research to date shows increased risk of contracting AE among family members of those with the
disease.
What kind of outcomes can we expect from this disease? How long does it take to get better?
A recent Lancet Neurology article by Dr. Titulaer, Dr. Dalmau and colleagues reviewed the study of 577
patients with AE reported that 53% of patients who received immunomodulation therapy showed
improvement within 4 weeks. 81% of patients showed substantial or complete recovery. On average,
patients continued to improve for 14 months after onset of acute AE. 12% of patients who recovered from a
first acute episode had at least one relapse in the next two years. Overall mortality associated with the
disease was approximately 6%. [Titulaer, et. al. Lancet Neurology 2013. Note that this study is limited to
one type of AE anti-NMDA-receptor antibody encephalitis].
How can I determine whether someone Im caring for has AE or not?
If you suspect that you or a family member may have AE, you should consult your primary care physician in
addition to specialists in neurology, psychiatry, immunology, or rheumatology. Workup should include tests
for known antibodies (anti-NMDA-receptor antibody, for example), scans for teratomas, EEG, and MRI.
At least thirteen different types of autoimmune encephalitis have been identified in the laboratory, including
auto-antibodies directed against NMDA, LGI1, CASPR2, VGKC-complex antibodies, AMPA, and GABA.
Commercially available lab tests exist though for only anti-NMDA receptor encephalitis.
In the absence of a positive test for an antibody marker, autoimmune encephalitis must be diagnosed by
process of elimination and diagnosis-through-treatment. When test results for all other diseases that could
explain the observed symptoms are negative, your doctor may initiate immune-modulation therapy to
determine if symptoms improve.
What are the most common treatments for AE?
As soon as a patient is diagnosed with AE, they should receive one or more of the four (4) first-line
treatments.

1.

removal of a teratoma (if present) that could be triggering the autoimmune response

2.

steroids to reduce immune response and inflammation

3.
4.

plasmapheresis to remove harmful antibodies from blood

intravenous immunoglobulin (IVIG), which is believed to occupy the binding sites where harmful
antibodies attach to brain cells.
Second line treatmentsimmunosuppressant drugsshould be started promptly if first-line treatments
fail to improve symptoms. The three most commonly used drugs are:

1.

Rituximab

2.

CellCept

3.

Cytoxan (cyclophosphamide)
What other medications are commonly prescribed to patients with AE? Are there any medications
that specifically should not be taken by someone suffering from AE?
Treatment of symptoms in particular agitation and sleeplessness, using benzodiazepines is common and
appropriate. High-dose Lorazepam (trademark: Ativan) is highly effective for AE patients.
Note that because of the completely different disease mechanism, use of anti-psychotic drugs commonly
used to treat bipolar disorder and schizophrenia such as Clozapine (Clozaril) and Risperidone (Risperidal)
may not be effective, and may actually increase the severity of AE symptoms.
Because individuals with undiagnosed AE are commonly misdiagnosed as having bipolar disorder or
schizophrenia, clinicians and families should be alert to possible deterioration or severe negative reactions in
patients receiving this class of drugs.
Failure to respond to anti-psychotics can be a diagnostic clue that the actual cause of psychosis may be
autoimmune encephalitis.
How long does it typically take to recover for an acute episode of AE? How long should I wait to
determine if one of the first-line or second-line therapies is working? How likely is recovery?
There is good data reporting that 50% of AE patients show substantial improvement within four weeks of
receiving treatment according to a recent Lancet Neurology article. However, on average, AE patients took
up to 14 months for complete recovery.
Generally, patients continue to improve after being discharged from the hospital. Over 80% of patients with
AE eventually have partial or complete recovery. Many have total recovery, including patients who are
severely ill. For one example, see the memoir by Susannah Cahalan, Brain on Fire: My Month of Madness.
What is the frequency of relapse after having an acute episode of AE?
The Lancet Neurology article reported that 12% of patients had at least one relapse within two years.
What social services are available for children (in the U.S.) who have AE?
School age children are entitled to accommodations under U.S. law, and may qualify for an Individualized
Education Program (IEP) for acquired cognitive problems and/or ADD. Both the National Center for
Learning Disabilities and the National Dissemination Center for Children with Disabilities provide useful
information on IEPs and other resources.
My doctor says my family member does not have AE. Should I get a second opinion?
As the patient or family member, it is critical that you have comfort that your medical provider is addressing
all of your medical concerns. The Alliance is working to develop a medical consensus on how to properly
diagnose AE. But in the current state, only a few definitive tests exist. If one medical provider has not
addressed your concerns, then you might want to pursue another opinion.

Is AE related to PANDAS, and if so, how?

PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) is a
disease that results in psychiatric symptoms, including obsessive-compulsive behaviors. Clinical trials are
now underway on use of immunomodulation therapy for PANDAS, and a number of clinicians offer this
type of treatment. PANDAS, like AE, is still poorly understood, but it appears both illnesses are part of a
related continuum of brain disorders triggered by immune system malfunctions and may be under the
umbrella of AE disorders.
What is the mission of the AE Alliance? How can I help?
The Autoimmune Encephalitis Alliance seeks to improve the lives of autoimmune encephalitis patients and
their families through :

Establishing autoimmune encephalitis clinical standards of care across medical disciplines

Coordinating basic and clinical research efforts

Building community awareness connecting families so that nobody faces autoimmune encephalitis
alone.
Please visit our contact page to connect with the AE Alliance and join our mailing list. The events page lists
upcoming activites related to AE.
A family member has recovered from AE, and we would like to reach out to help others coping with
this illness. How can we help?
There are many ways that you can assist the AE Alliance and other families going through the disease. Share
your story with us. In the near future, we plan to establish a patient/family peer-to-peer network. But also
you can host an event in your area or share this information broadly to your network. Keep in touch on
social media. We want to spread the word and help educate a community on this disease. Please visit our
volunteer signup.