Showing posts with label Chiari. Show all posts
Showing posts with label Chiari. Show all posts

Tuesday 5 September 2017

Autism MRI

Source: Brain MR Imaging Findings and Associated Outcomes in Carriers of the Reciprocal Copy Number Variation at 16p11.2

In the early days of this blog, one medical reader told me that in cases of autism an MRI scan of the brain should appear normal.
This also fits with the idea that once you have a biological diagnosis, you no longer have a case of “autism”. It is only Autism, when it is of unknown origin.  
People who have a single gene type of autism actually can have significant variations in brain structure that appear clearly on an MRI.  This was the subject of a recent study and the source of the MRI in this post.

Many people with autism have abnormalities at a specific site on the 16th chromosome known as 16p11.2. Deletion or duplication of a small piece of chromosome at this site is one of the most common genetic causes of autism spectrum disorder.
People with deletions tend to have brain overgrowth, developmental delays and a higher risk of obesity.
Those with duplications are born with smaller brains and tend to have lower body weight, but also developmental delays. 
For regular readers of this blog there are some interesting points to note.

Agenesis of the Corpus Callosum

The corpus callosum is a wide, flat bundle of fibers about 10 cm long that connects the left and right sides of the brain.  It facilitates communication between the two sides of the brain.
Agenesis of the corpus callosum (ACC) is a birth defect in which there is a complete or partial absence of the corpus callosum.
ACC leads to behaviors compatible with a diagnosis of autism or Asperger’s in about half of cases.
Symptoms of ACC vary greatly among individuals, as they do in all types of autism.  Seizures are common, some people have poor motor coordination, and some people are non-verbal.  My original post on the subject:-

Agenesis of the Corpus Callosum (ACC)                                                                                 
You may recall that in the film Rain Man, Dustin Hoffman’s character was inspired by a man with ACC called Kim Peak.  It is now thought that Peak had FG Syndrome and this is what caused his ACC. It appears that his brain adapted and made unusual connections leading to his remarkable memory.
The Corpus Callosum is clearly visible on an MRI.
In 16p11.2. deletion you end up with an overgrown (thick) corpus callosum, while in 16p11.2. duplication you end up with a thin corpus callosum, which equates to a partial Agenesis of the Corpus Callosum.                                
At least one reader of this blog has a case of partial Agenesis of the Corpus Callosum and as he told me, it is not autism it is ACC.

Chiari 1 “brain hernia”
Another point of interest on the above MRI has been highlighted as Cerebellar Ectopia. Now if they had called it a Chiari malformation, you might have linked it to an old post on this blog.

In people with brain overgrowth and/or a small skull, what happens when there is no space left for a growing brain? Well it appears that pressure builds up and you get a kind of hernia with the brain expanding downwards into the spine.
This is called a Chiari 1 malformation and it seems to be quite common in the types of autism associated with over active pro-growth signalling pathways.
Since 16p11.2 deletion is associated with too much growth (thick corpus callosum, brain overgrowth and obesity) we should not be surprised that they often present with Chiari 1 “brain hernia”, which is treatable and this should improve symptoms. 


An MRI can sometimes tell you a lot, when you know what to look for and clearly should be carried out on anyone diagnosed with disabling autism.
Undoubtedly there are other areas of the brain where important variances occur.
This would provide useful data to assign individuals with autism into subgroups and hence improve the chance of finding effective therapy.  What works for Peter may help Paul, but what works for Zach probably will not help Amber.

Sunday 30 August 2015

Treatable Chiari 1 “brain hernia” present in 7% of Autism

Today’s post is again prompted by a reader’s comment.

Regular readers will be accustomed to learning here about “rare”, often treatable, disorders that may cause, or just aggravate autism; add Chiari 1 to that list.
The Chiari 1 brain hernia occurs when part of the brain is forced downwards into the spinal column.  It is supposedly very rare, occurring in only one person per thousand.  It is generally not life-threatening and can be surgically repaired.  The symptoms of Chiari 1 do rather overlap with those of autism.

You can diagnose Chiari 1 using an MRI scan.  Very few people with autism ever receive any diagnostic follow up, be it genetic testing, metabolic testing or a scan of their brain.

There have been anecdotal reports associating Chiari with autism, and indeed of the corrective surgery greatly improving autism symptoms.  This goes back to the day of Bernie Rimland (Autism Research Institute and DAN).

Finally we have some genuine data:-

Patients with symptomatic Chiari malformation Type I (CM-I) frequently present with headaches, neck pain, difficulty swallowing, and balance disturbances. In children with autism spectrum disorder (ASD), diagnosing CM-I can be a challenging task. Moreover, even if symptomatic, some patients do not undergo further evaluation or management, as their presentations are attributed to autism and its myriad symptoms. Therefore, cranial MRI findings were reviewed after evaluating and treating patients with coexisting ASD and CM-I. In this paper, the authors report on 5 children with ASD and symptomatic CM-I, including their clinical presentation, imaging studies, management, and outcomes, and discuss the likely under recognized coexistence of these conditions.
All pediatric patients with ASD and cranial MRI conducted for any reason in the period from 1999 to 2013 were considered for analysis. All cases with concomitant symptomatic CM-I were eligible for this retrospective analysis.
One hundred twenty-five pediatric patients diagnosed with ASD had undergone MRI, and 9 of them had evidence of cerebellar tonsillar herniation. Five patients were symptomatic and underwent suboccipital craniectomy, a C-1 or a C-1 and C-2 laminectomy, and duraplasty with bovine pericardium or Type I collagen allograft. There were no intraoperative complications. All patients showed symptom improvement and/or resolution of presenting symptoms, which included headache, dysphasia, speech, and irritability.
There is no identified cause of autism. Children with ASD can be difficult to assess specifically in a neurological examination. Thus, cranial MRI considered when completing a comprehensive diagnostic evaluation. While cranial MRI is not a routine part of ASD evaluation, this study demonstrates that CM-I and ASD may coexist and be underrecognized. The study reinforces the importance of a comprehensive medical evaluation designed to elucidate neurological findings in children with impaired communication abilities and suggests the judicious use of neuroimaging.
ASD = autism spectrum disorder; CM-I = Chiari malformation Type I; Chiari malformation I; autism; autism spectrum disorder; suboccipital craniectomy


We know that in many cases of classic autism there is accelerated brain growth until the age of five (Courchesne, UC San Diego) and frequently this is associated with large heads (Macrocephaly).

As usual in autism, both extremes exist and so Microcephaly (small brains/heads) is also present.  The result is that in studies the average head size is meaningless.  Just as with many other possible markers, like cholesterol levels.  The same is true with signaling pathways like mTOR, Wnt, ERK and BDNF; both hypo function and hyper function exist and both can lead to “autism”.

Data from a series of 126 autistic children ages 2-16 years and referred to an Autism Diagnosis Unit in South-West France were examined. Macrocephaly (head circumference > 97th centile) was observed in 16.7% of the sample, a significantly higher proportion than that expected. Macrocephaly was more frequent among older subjects but was otherwise not associated with gender, developmental level, the presence of epilepsy or of medical disorders, or severity of autistic symptomatology. Microcephaly (head circumference < 3rd centile) was also significantly raised and found in 15.1% of the sample. Microcephaly was significantly associated with the presence of medical disorders. Results support those from recent studies suggesting a raised rate of macrocephaly in autism which, pooling published data, can be estimated to be 20%. It is argued that the raised incidence of microcephaly among low-functioning autistic subjects with medical disorders might have contributed to delay the recognition of an increased head circumference among a minority of subjects with idiopathic autism.

It is not hard to imagine what might happen if the brain is expanding faster than the skull is growing.  It would be reasonable to think that, in some cases, autism might cause Chiari malformation I.

Most people consider Chiari malformation I to be genetic.  In people with no underlying cause(s) of autism, the hernia itself may be the sole cause of the associated symptoms.

Since we know that autism is often caused by multiple “hits”, in some people the Chiari malformation might just be one of those handful of hits/triggers.  Oxidative stress and inflammation are both key drivers and consequences of autism; clearly hernia(s) growing in the spinal column are going to aggravate this.

To Treat or Not?

Surprisingly, some neurologists/neurosurgeons are unwilling to repair Chiari malformation I in children with autism.

If you recall my recent post on the history of autism, the reason becomes clearer.

Those neurologists/neurosurgeon hold the historical view that autism is untreatable and so how could surgery possible help?  It seems that in as many as 7% of autism cases, surgery might indeed help.  That is a surprise to me.

Fortunately, enough people with autism and Chiari 1 have been treated for it to be known that it does improve autism.

Since treatment involved a brain operation, it is not without risks.  Not treating the brain hernia likely also has risks.

Dr. Manuel Casanova on Chiari and Autism

Dr Casanova is a neurologist with a blog and an interest in autism. He is of the opinion that Chiari does not cause autism, but just makes it worse.

I am not a neurologist, but if you accept that autism, like cancer, is often caused by multiple hits, Chiari would seem like quite a dangerous hit, and perhaps more so than an immune over-reaction to childhood vaccines. In my recent autism history post we saw that for Hannah Poling the vaccine was enough to cause profound autism; she had two hits the first being a genetic mitochondrial dysfunction and the second an inflammatory reaction to the vaccines.

Over to Dr Casanova:-

"If you ever do a search through the internet you will find a lot of interest among multiple health boards on the possible correlation between the Chiari malformation and autism. Dr. Neil Felstein, Director of the Pediatric Neurosurgery Division of the Morgan Stanley Children’s Hospital, has seen many children with both conditions ( ). He believes that there is an association but can’t provide an explanation. Although a Chiari malformation is certainly not the cause of autism, it can aggravate the same. It may be worth noting that the Chiari malformation is seen as a comorbidity to both the Ehlers-Danlos and Marfan syndromes (Milhorat et al., 2007).  Both of these conditions manifest autistic symptomatology in a high percentage of cases ( )."

Head Circumference

Since data on head circumference is routinely collected during childhood, it would not be difficult to go back to the 125 cases studied by MRI in the research study, quoted at the start of this post.  You could then look for a correlations between head size, brain size and the Chiari hernia.

This might show that in autism the head was just not big enough at some critical point in time.

More links


It looks like you might want to add an MRI to those metabolic and genetic tests that most children with autism never receive, but perhaps should.

Or, as put in today’s study:-

“The study reinforces the importance of a comprehensive medical evaluation designed to elucidate neurological findings in children with impaired communication abilities and suggests the judicious use of neuroimaging.”