top of page
  • Jason Steadman, Psy.D.

Autoimmune neurology: When the body attacks the brain and sends it haywire

Updated: Sep 14, 2021

In 2012, journalist Susannah Cahalan published her memoir, Brain on Fire, which would eventually become a NY Times Best Seller and be made into a 2016 movie starring Chloe Grace Moretz. Through the book, Cahalan brought national attention to a rare, newly discovered neurological disorder, anti-NMDA receptor encephalitis, that caused her to have severe psychiatric symptoms including hallucinations, sharp behavioral changes, movement problems, and a slew of other intense, mysterious challenges. This disease, first discovered and researched by Dr. Josep Dalmau, a neuro-oncologist (he studies brain cancer) is just one of what is now considered to be a group of neurological disorders under the category of autoimmune encephalitis or autoimmune neurology. This group of diseases occurs when a person’s antibodies begin attacking healthy brain tissue, similar to what happens in Multiple Sclerosis (MS), with differences in presentation depending on which neurons or synaptic proteins are attacked.

Some neuroscience – the advanced version

Cahalan’s condition, anti-NMDA receptor encephalitis, attacks NMDA receptors. NMDA stands for N­-methyl-D-aspartate. For advanced readers, the NMDA receptor (NMDAR) is one of four types of ionotropic glutamate receptors (the other three are AMPA, kainate, and delta receptors). Glutamate is by far the most abundant excitatory neurotransmitter in our nervous system, and accounts for over 90% of neuron connections in the human brain. Glutamate is also especially important for helping us form and train new synapses (called synaptic plasticity), and thus, has a vital role in memory and learning. The term ionotropic means the receptor acts as a “gate” for ions, opening when an “agonist” binds to it and closing when it is blocked by an “antagonist”. The ions that can pass through a gate when it is open include Ca2+, Mg2+, Zn2+, Na+, K+, or Cl-. The NMDA-receptor allows only positively charged ions (e.g. Calcium, Zinc, Sodium, Potassium) through, and it is non-selective (it lets pretty much any positively charged ion through). However, Magnesium and Zinc ions bind to specific sites on the receptor and can block other ions from getting through.

The picture below shows this a bit more clearly, but you’ll notice a few other things in the picture as well. First, NMDA receptors also need Glycine to bind in order for them to open. Glutamate alone is not enough; so, in the picture you can see a binding site for Gly (glycine) as well. Second, you’ll notice PCP labeled in there as well. The recreational drug PCP (phencyclidine) is just one of several NMDA receptor antagonists (meaning, again, that they block the channel). Some others include ketamine, dextromethorphan, and nitrous oxide. In the image, then, PCP is just given as an example of an NMDA receptor blocker – it’s not the only one, and isn’t necessary for NMDAR to work. Lastly, you’ll also see polyamine labeled. Polyamine in this case is similar to glycine – it modulates the effects of glutamate on the receptor. It’s not super important for our purposes here though.

The picture above also shows non-NMDA receptors (such as kainate or AMPA). They have similar action as NMDA, but work in subtly different ways, and are much less complex. Let’s just say that those of use who went to graduate school and studied neuroscience really preferred the non-NMDA receptors when we had to draw and label them on tests. =) They were just a lot easier.

To wrap back around, though, to the point of this blog, new findings in autoimmune neurology have discovered that sometimes our bodies can actually attack the NMDA receptor and/or other non-NMDA receptors, causing them to function improperly. I suspect we will continue, over time, to discover more autoimmune conditions that affect brain receptors.

Some neuroscience in laymen’s terms

This is all very complicated neuroscience, so let me break it down for you in a meaningful way. Let’s say you live on a large farm filled with fences and gates that let you get to and from where you need on the farm. In order for your farm to work optimally, your workers need to be able to pass through gates in the fences to get to and from each part of the farm. Let’s say, also, that you have a very valuable farm and need a lot of security to keep things working like they should. So, at each gate, you’ve installed security measures to make sure you can control which workers go where and when. The conditions we’re exploring in this blog can be considered to be faulty security systems. In fact, what happens is that the shepherds of the farm (the people responsible for keeping predators our and protecting the resources) get confused and start attacking the security measures. This causes all kinds of chaos with workers going where they don’t belong and just messing everything up. If left unchecked for long enough, the farm starts to break down everywhere.

So, in this metaphor, the farm is your brain, the fence gates are NMDA (or other types of receptors), the shepherds are antibodies, and the workers are ions and neurotransmitters.

What are some other conditions in autoimmune neurology?

You’ve probably heard already of at least one autoimmune neurological condition – Multiple Sclerosis, or MS. Because MS does not present with primary psychiatric symptoms, I am not focusing heavily on it here, but the classic pathophysiology of MS is considered to be autoimmune in nature.

Another condition of which most pediatric clinicians are at least somewhat aware, but is not well known to the general public, is Pediatric Acute-onset Neuropsychiatric Syndrome (or PANS), which is a from of abrupt onset OCD triggered by an immune response to some sort of viral or bacterial infection. Classically, the condition was first called PANDAS – Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus – because it was first identified in patients infected with strep. However, over time, we’ve found patients can develop the syndrome from a number of different infections. PANS has specific diagnostic criteria based on a well-agreed-upon clinical presentation:

  1. An abrupt, acute, dramatic onset of obsessive compulsive disorder or severely restricted food intake. The telltale sign here is that the change is like night and day. Parents often say their previously “normal” child just woke up one day and was suddenly afflicted with fairly severe OCD. This often differentiates PANS OCD from classic OCD.

  2. Concurrent (meaning at the same time as symptom 1) of additional neuropsychiatric symptoms with similarly sever and acute onset from at least 2 of the following categories:

    1. Anxiety

    2. Emotional lability (mood swings) and/or depression

    3. Irritability, aggression, and/or severe oppositional behaviors

    4. Behavioral (developmental) regression

    5. Sudden deterioration in school performance

    6. Motor or sensory abnormalities

    7. Somatic signs and symptoms, including sleep disturbances, enuresis (wetting themselves), or urinary frequency

  3. Symptoms are not better explained by something else

  4. Although this condition is seen more often in younger children, there is no age requirement for the condition

Though not outlined in the clinical definition, PANS is also, as noted above, associated with infection. In almost all cases of PANS, the syndrome is preceded by an infection within the last 5-6 months (though it can be longer). In my clinical practice, I have most often seen PANDAS – the form associated with strep – but I am also aware of presentations associated with Lyme Disease, Coxsackie virus, and other viral infections. It should be noted, though, that in PANS (and other autoimmune conditions), the symptoms are not a direct result of the infection, but rather are triggered by the immune response to the infection. It’s like your immune system got a jumpstart from the infection and now hasn’t turned off properly.

How does someone know if their psychiatric symptoms may be autoimmune related?

It’s complicated to answer this simply, because the conditions are all first identified by symptoms, which will vary depending on what part of the brain the autoimmune conditions are attacking. There is a delightful review of several types of presentations (and their treatments) here, for the advanced reader. For our purposes, I’ll keep it relatively short in sweet below.

In PANS, for example, the presentation is an abrupt OCD. NMDAR encephalitis, however, presents most commonly with confusion, memory problems, hallucinations, and movement problems which, like PANS, are abrupt (acute-onset) and often fast-deteriorating. Patients present as if they have advanced Alzheimer’s or other types of dementia. They may also appear to have severe schizophrenia. Other conditions can present with other, primarily psychiatric symptoms. To most people, and even to many good clinicians, the clinical presentations don’t present much differently than other, well-known psychiatric conditions. For this reason, there is often a delay (and a lot of doctor visits) in between initial presentation and ultimate diagnosis with a condition of autoimmune neurology. Autoimmune neurological conditions are rare, and as such they are not at the top of most doctor’s list of things to consider in a standard evaluation. It usually takes something “weird” to make your doctor say, “I think this is different enough that we run some more tests.”

Those “more tests,” in this case, are lab tests that evaluate specific immune functioning. They aren’t standard lab tests. Autoimmune neurological conditions are rarely going to show on a standard CBC (Complete Blood Count) or CMP (Comprehensive Metabolic Panel). Instead, the doctors have to order a special (and often expensive) set of other blood tests to help see if inflammatory or other immune markers associated with the diseases are present. Describing each test is beyond the scope of this blog, but the important thing to understand is that the laboratory markers are typically only found when someone specifically goes looking for them. In other words, lab findings won’t occur incidentally from routine blood work – you have to order, and then interpret correctly, specialized tests.

It’s from these lab results that ultimately a firm diagnosis of an autoimmune neurological condition can be confirmed. So, the only way to know, for sure, if your symptoms may be autoimmune related is 1) have a doctor who spends enough time with you to catch something “weird” in your psychiatric presentation, 2) have that same doctor refer you to a specialist (a neurologist) for specialized testing, 3) get labs (blood work, perhaps some urine) drawn and wait for results, 4) see specific autoimmune markers in the lab work.

What is the treatment for autoimmune neurological conditions?

Neurological treatments are outside my field of expertise, and so I hesitate to outline a clear treatment protocol for these conditions. From a psychiatric/behavioral perspective, psychotherapy can often be offered to help with symptoms. In PANS, for example, PANS OCD is treated the same way as classic OCD, through a type of cognitive behavioral therapy called exposure and response prevention (ERP). Sometimes, medication is added too, to help with anxiety and OCD. However, what’s different from classic psychiatric treatment is that medical treatments are also offered to help correct the immune response that caused the condition. For example, if there is an active infection, that infection is treated (with antibiotics or antivirals). If those do not work after a sufficient course, then oral corticosteroids may be added. If those are unsuccessful, sometimes patients are then pushed up to higher level treatments, like plasmapheresis (a plasma transfusion) or an IVIG infusion (IV means intravenous and IG means Immunoglubulin – basically, you are given an IV of healthy antibodies). Similar to other autoimmune conditions, autoimmune encephalitis can likely also be treated with other immunomodulators, though the specifics of this approach to treatment are still under investigation.

This article summarizes both the diagnosis and treatment of autoimmune encephalitis.

What’s the take home message here?

For clinicians

The take-home message for clinicians is to simply be aware that there are some autoimmune, neurological conditions that can present similarly to psychiatric conditions. The key differences to watch for are that the neurological conditions will typically have an acute onset, whereas true psychiatric conditions are more insidious, with a clearer history of problems leading up to the onset of more acute, concerning symptoms. Second, similarly, encephalitis also gets worse much more quickly than most true psychiatric conditions. So, not only is there an acute onset, but progression of symptoms after onset is also much more rapid. Third, autoimmune encephalopathies can be diagnosed through specialized lab testing, which are ordered by someone with a medical license. Thus, autoimmune conditions can be ruled in or our through specialized testing. It is important, then, to be aware of local, reputable clinicians (neurologists) who can treat the medical aspects of these conditions.

For parents/clients

Similar to the above, parents/clients should be aware that some psychiatric symptoms can be activated directly by an immune response, usually triggered by infection with a bacterial or viral illness. Thus, when you’re thinking about your symptoms, it’s important to consider whether or not you had an infection prior to the onset of symptoms. Rarely, this infection could explain the symptoms.

At the same time, parents/clients should also know that immune-triggered psychiatric symptoms are rare and it’s much more likely that your symptoms/issues are explainable by well-established, traditional psychiatric diagnoses. So, just because you did get an infection prior to the onset of your symptoms does NOT automatically mean your symptoms are infection/immune-related. In fact, bacterial and viral infections are very common, and almost every person who has ever had any psychiatric diagnosis will have had some sort of infection also in their history. So, it’s important not to become over-focused on some “miracle cure” for your psychiatric symptoms. Instead, remind yourself that psychiatric conditions are treatable! Even if your symptoms are not due to an autoimmune encephalitis, you can still get treatment and there is still good reason to be optimistic about outcome.

Recent Posts

See All


bottom of page