INSIGHTS | 20. The Link Between Autism & Inflammation

Neuroimaging allows us to look inside that infinitely complex structure we call the brain. Unfortunately, this isn't routinely done for those with Autism.

Article: Normal Rates of Neuroradiological Findings in Children with High Functioning Autism

Photo by Peter Burdon on Unsplash

Background

In recent years, people have become justifiably skeptical about Big Pharma and vaccines. With recent covid policies, the definition of “anti-vaxxer” has expanded as well.

When I was in school, an anti-vaxxer was characterized as someone who thought the MMR vaccine caused autism. But recently, our regulators have expanded this definition to include anyone opposed to vaccine mandates.

Quite the range of beliefs for one derogatory term.

But, this article is not about vaccines.

This piece is about the role of inflammation in neurological disease, with attention on autism.

What is Autism?

The definition and diagnostic criteria for autism should help illustrate how incomplete and uncertain a condition it really is. Initially, people would refer to those with difficulties in language & social interaction as autistic.

Now, we refer to it as autism spectrum disorder (ASD) because, over time we learned that it wasn’t as simple as we thought.

The most recent Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has very elaborate diagnostic criteria:

• Persistent deficits in social communication and interaction

• Restricted or repetitive patterns of behavior, interest or activities

• Symptoms must be present in early developmental period

• Symptoms cause impairment in social, occupational, and life settings

• Not better explained by intellectual disability or global developmental delay…

  • But, intellectual disability frequently co-occurs with ASD (go figure)

The DSM goes on to state that the doctor must specify if there is:

• Intellectual impairment

• Language impairment

• Developmental, mental, or behavioral disorders

• Catatonia - abnormal muscle tone

• Associated with medical or environmental factors

It’s all a bit complicated.

What is Autism, really?

One of the best descriptions I have come across was from Karl Deisseroth, who was a guest on the Lex Fridman podcast. Karl is best known for his pioneering work on optogenetics, but is also a psychiatrist.

In Karl’s view, autism is an inability to appropriately process new information.

You may be wondering ‘what is the connection between social interactions and processing new information?’

As Karl points out, since autistic people have difficulty processing novel information, the domain within which that would manifest the greatest is social dynamics. There is nothing as unpredictable, chaotic and idiosyncratic as interactions with other humans.

Thus, it would make sense for the most apparent ‘deficiency’ within autism to be social interaction. A natural extension of this would be language fluency and intellectual disability.

What causes Autism?

You can find an extensive list of possible causes for Autism, but fundamentally we do not know. It is almost certain that if ASD represented a unique disease, it would have multiple causes.

If you think about the fundamental problem (as described by Deisseroth), slow processing of novel information, it isn’t difficult to imagine the possible causal or contributory factors.

For example: maternal nutritional status, pre-natal and perinatal factors, complications during birth, immunologic & inflammatory stress during infancy, exposure to toxins, lack of cognitive support & nourishment during early years, poor behavior modelling, and so on.

I believe there are two factors that are often ignored with autism:

1. Poor behavioral modeling, and its impact across generations - to be written about in a future article.

2. Overall inflammatory state and the impact this has on anatomy and physiology of the brain - the topic of this article.

The Normal Brain

An MRI is useful because it allows us to look at the brain with exceptional contrast resolution. The stronger the magnetic field, the higher the resolution - generally speaking.

Here we have a T2-weighted image of a normal brain:

Notice a couple of things:

• Gray matter is gray (ribbon of cortex along the periphery)

• White matter is really dark - especially near the top of the image (which corresponds to the frontal lobes)

• Normal cerebrospinal fluid is bright white - in the sulci between the cortical gyri, and within the lateral ventricles at the center of the image.

The problem with a T2-weighted image is that all fluid will be bright, making it difficult to differentiate between normal fluid and pathological fluid.

This is what a FLAIR sequence is for. It suppresses normal fluid, so all that is left is pathologic fluid, if there is any.

Notice in the above normal FLAIR sequence:

• Gray and white matter are whitish-gray and dark, respectively - like T2 image

• This time, the normal CSF within the sulci and ventricles are suppressed - so they appear dark

The above images were most likely taken with a 1.5 Tesla strength magnet.

Bonus: Look what happens when we crank this up to 7 Tesla - beautiful isn’t it?

The Inflamed Brain

If you are looking for a pathologic lesion, you are most definitely getting a FLAIR sequence. A common location for chronic lesions is the white matter - the connective tracts of the brain.

Rarely is there a pathologic diagnosis of the brain which does not manifest with lesions in the white matter, which are visible on FLAIR.

But, what does it mean for there to be a white matter lesion?

They can result from several things:

• Demyelination - like with multiple sclerosis

• Gliosis - fancy word for scarring

• Infarction - such as from strokes or bleeds

• Disease of the veins which alters perfusion and drainage

• Inflammation - systemic or focal

• Infection

• Tumor

As the brain experiences inflammation the person will manifest neurological symptoms. If it is acute and severe, the person may become comatose.

If the inflammation is low-grade and persists chronically, then corresponding regions of the brain will start to develop features like scarring, volume loss (prolonged ischemia), bleeding, demyelination, and swelling.

Exhibit A. FLAIR sequence of a person with multiple sclerosis - a demyelinating disorder:

Look at all those white blotches in locations including: surrounding the ventricles, in the deep white matter, and the subcortical (more specialized regions) white matter.

Imaging Autism

Since genes are a common way to look at illness, outdated perspectives on autism included assumptions about its genetic basis and heritability.

So, the early attempts at characterizing the imaging findings of ASD looked at major heritable anatomic differences. This early research was often done with computed tomography or low resolution MRIs - making finer anatomic differences difficult to distinguish, if not impossible.

Consequently, the American Academy of Neurology, the American Academy of Child and Adolescent Psychiatry, and the American Academy of Pediatrics have independently concluded that imaging is not indicated as part of the routine evaluation of children with autism.

More recent research, which has not made its way into diagnostic or management algorithms within fiat medicine, uses higher resolution imaging.

These studies reveal more interesting pictures.

For example, Boddaert et al look at MRI of 69 children with ASD and 77 normal. In ASD, distinct abnormalities were found including: 27.5% had white matter lesions and 29% subcortical lesions & infarcts within the temporal lobes.

Boddaert et al 2009

Granted, not all studies show similar frequency of these lesions. The article linked at the top did not find a difference in kids with ASD. But, they also have differences in imaging technique and age-range, which may account for these observations.

Regardless, my assertion is not that these lesions explain all cases of ASD.

I argue that some of the symptoms may be explained by these lesions. They may even point to multiple contributing causes, which manifest in the global picture of ‘autism.’

Why White Matter Lesions?

The brain is a highly energy-intensive organ in a very confined space that happens to be on one polar end of your body - very far from the heart.

Source: https://www.frontiersin.org/articles/10.3389/fnmol.2018.00216/full

As you can imagine, it has a very finely balanced and regulated mechanism to maintain a robust supply of energy, metabolites, and oxygen to the brain. In addition, it also has a complex mechanism to clear waste from the brain.

We cannot have fluids & waste build up in such a confined space.

Consider how relatively simple the combustion engine in your car is compared to the brain. Now consider all the maintenance that needs to be done to make sure that the car is ‘firing on all cylinders.’ At minimum, you need to provide adequate fuel, have an efficient exhaust system, and make sure the engine lubricant is free of debris, waste, and degradation products.

In the brain, even chronic low-grade inflammation can impact the functioning of neurons as well as the integrity of the vasculature which nourishes and clears waste from the brain.

One of the factors which can have a significant impact on this, is diet.

However, anything that can impact the optimal functioning of the brain can:

1. Result in symptoms related to the region of the brain that is underperforming

2. If chronic, the pathology can result in chronic changes to brain structure

Implications

Practically, what does this mean?

For one thing, children are diagnosed with ASD very early in life. Timing matters. The sooner you intervene, the better.

The earlier the onset of symptoms or diagnosis, the more likely it is that a change in lifestyle may reduce symptoms and long-term consequences.

If we can pull a clot out of an artery fast enough, we can minimize the volume of infarcted brain in the event of a stroke. This is a very short time-horizon event.

Chronic low-grade inflamation provides a longer window of intervention.

So, the sooner you stop giving things to your children which can induce, prolong or worsen inflammation…the sooner you can stop progression and maybe recover some function.

But, what about vaccines?!

I am not here to argue about individual vaccines causing autism.

But, every vaccine depends on an immune response to work. They induce inflammation, both local & systemic, by necessity.

How many and how often do you need to vaccinate your child before the recurrent inflammatory cycles result in impact on the brain which may manifest with neurological symptoms?

How long until these structural changes become permanent?

At what age do you want to minimize this stress to optimize the uptake of social intelligence?

We haven’t even started talking about environmental toxins, diet, low activity, and social behavioral modelling.

These are the important questions.

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Thank you for your support.