Late Onset Autism and Anti-NMDA-Receptor Encephalitis: Part 1
By Teresa Conrick
My daughter, Megan, continues to be severely affected by both the medical and behavioral symptoms of autism. As a result, I continue to read studies and research that correlate with the symptoms that she has. Some of the factors, if we were to list them like they do in a journal, would be -- seizures, autism, nmda/glutamate dysfunction, cancer signalling, encephalopathy, agitation. Surprisingly, there was a current, case study just out that had many of these key words:
Late onset autism and anti-NMDA-receptor encephalitis The Lancet, Vol 378. Issue 9785, Page 98, 2 July 2011
Caroline Creten, MD, Sanne van der Zwaan BSc, Roos J Blankenspoor BSc, Arien Maatkamp, PhD, Prof Jim van Os PhD, Dr Jan NM Schieveld PhD
In December, 2009, a 9-year-old boy was admitted to our hospital with an acute onset of secondary generalised seizures. He had no medical or psychiatric history and functioned very well socially and academically. He presented with speech and swallowing difficulties, which after 10 days developed into a severely agitated catatonic state with opisthotonic posturing, tonic posturing of limbs, insomnia, and dyskinesia. Initially the electroencephalogram showed a normal background pattern with epileptic discharges, and oligoclonal bands were present in cerebrospinal fluid (CSF). Brain MRI and extensive blood tests were normal. The neurological diagnosis was atypical childhood epilepsy with centrotemporal spikes, for which oral corticosteroids and anti-epileptic drugs were prescribed. His catatonia was treated with benzodiazepines. In January, 2010, our patient presented in a robotic state with complete mutism and negativism, and he did not respond to any form of contact. We provisionally diagnosed acute late onset autism with a differential diagnosis of childhood disintegrative disorder or early onset schizophrenia.
Childhood disintegrative disorder, early onset schizophrenia, and late onset autism often share a final common pathway: previous normal development, followed by sudden neuropsychiatric regression of social interaction and communication skills, and a decline in intelligence and daily activities. 1 The disorders are sometimes misrecognised and collectively called as autistic disorder. Although judged to be functional psychiatric diagnoses, the marked deterioration and poor prognosis suggest an organic cause, especially in children with catatonia, a normal development up to at least 5 years of age, or both1,2. In our patient, late onset autism was considered because: it is associated with neurological disorders; 2 it is a known end stage of acquired brain injury; progression of symptoms was fast and severe, unlike in early onset schizophrenia; the absence of positive symptoms made schizophrenia less plausible; the age of onset and rare prevalence made chronic disintegrative disorder unlikely; 1 and accompanying catatonic features were present. 3 After extensive diagnostic assessments, our patient was finally diagnosed with anti-NMDA-receptor encephalitis on the basis of slightly raised anti-NMDA-receptor antibody titres in serum and highly raised titres in CSF. 4 Clinical characteristics of this condition are acute major neuropsychiatric symptoms including anxiety, aggression, agitation, behavioural changes and catatonia, delusional thoughts, progressive speech deterioration, and hallucinations. Neurological symptoms such as dyskinesia, abnormal seizure-like movements, and diffuse and profound autonomic instability have also been reported.4.5 Anti-NMDA-receptor encephalitis can occur in the context of malignant disease; 4 however for our patient extensive oncological investigations were negative. Electroconvulsive therapy was given for the severe catatonic state, and monoclonal antibody treatment (rituximab) was started because of the unsatisfactory response to the initial treatment with benzodiazepines. The acquired autism gradually subsided, he spoke fluently and was able to draw a happy picture (figure). In June, 2011, he only had some mild cognitive dysfunction.
Childhood disintegrative disorder, early onset schizophrenia, late onset autism and all stages of anti-NMDA-receptor encephalitis share core symptoms, as in our patient. We suggest that anti-NMDA-receptor encephalitis might be a possible organic cause underlying these three disorders. Patients previously diagnosed with these diagnoses might need to be re-examined for anti-NMDA-receptor encephalitis. We suggest that forthcoming editions of DSM-5 and ICD-11 exclude and define cases of regressive autism spectrum disorders due to anti-NMDA-receptor encephalitis.
All authors looked after the patient, wrote and contributed equally to the report. Written consent to publish was obtained.
1 Disorders usually first diagnosed in infancy, childhood, or adolescence. In: American Psychiatric Association , ed. Diagnostic and statistical manual of mental disorders. 4th edn, Text revision. Washington DC: American Psychiatric Association, 2000.
2 Van Engeland H, Buitelaar JK. Autism spectrum disorders. In: Rutter M, Bishop DVM, Pine DS, Scott S, Stevenson J, Taylor E, eds. Rutter's child and adolescent psychiatry. UK: Blackwell Publishing, 2008: 759-781.
3 Schieveld JNM. Section IV Case reports with a child psychiatric exploration of catatonia, autism, and delirium. In: Dhossche DM, Wing L, Ohta M, Neumärker KJ, eds. . London: Academic Press, 2006: 195-206.
4 Kayser MS, Kohler CG, Dalmau J. Psychiatric manifestations of paraneoplastic disorders. Am J Psychiatry 2010; 167: 1039-1050. CrossRef | PubMed
5 Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7: 1091-1098. Summary | Full Text | PDF(635KB) | CrossRef | PubMed
a Department of Psychiatry, Maastricht University Medical Centre+, Maastricht, Netherlands
b Department of Neurology, Maastricht University Medical Centre+, Maastricht, Netherlands
Correspondence to: Dr Jan Schieveld, Department of Psychiatry and Psychology, Division of Child and Adolescent Psychiatry, Maastricht University Medical Centre+, P. Debyelaan 25, PO Box 5800 6202 AZ Maastricht, Netherlands
Very interesting and speaks to the paradigm shift that we are seeing. Autism, or as they say, "a known end stage of acquired brain injury," is not some increasing genetic disorder but an increasing medical disorder brought on by an inflammatory process. This study shows it as a process of "anti-NMDA-receptor encephalitis, with acute major neuropsychiatric symptoms." Many of us with children who have an autism diagnosis also are familiar with another disorder of inflammation, movement and OCD issues - PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections. There is very little information on a possible precipitating event that may have caused this boy to become so ill. It is heartbreaking and I hope he continues to improve. From my reading, this is not an isolated case.
The sentence that really blows me away in this Lancet article is when the researchers state that autism is a known result of acquired brain injury. Has anyone else read this type of statement in another mainstream medical journal?
I think that we will begin to see, in the next few months or years, mainstream medical articles casually "inserting" statements like this, as if the sentiment has been standard all along. We'll soon see statements like this from an NEJM article: "Autism is likely more environmentally based than genetically based" or "Since autism most likely originates from an overtaxed immune system..."
It's amazing to see that statements that were ridiculed only a decade or so ago are slowly becoming accepted as fact in the medical community.
Posted by: Patricia Wood | July 26, 2011 at 03:54 PM
There was one more change, I discussed with my husband when he woke up yesterday (referring to his miracle cure of his oxygen and breathing problems). I asked if that was about the time he stopped bothering to take the naispan. It was.
This past spring a heart doctor tried to get my husband back on it. I even sat in that doctor's office and said that anything like that (not a naturally B vitamin, but a B vitamin that has been reworked by pharma) can mess up a already faulty metabolism.
A couple of weeks later out comes a study that said strokes were happening very often to those taking niaspan. So much so, that they discontinued the study because it was unethical to continue when they already had their obvious answer.
Posted by: Benedetta | July 25, 2011 at 10:23 AM
Thanks, apparently these DAN doctors are on the leading edge of some real treatments! Good luck with this and please let us all know how it workds out.
Teresa Conrick :
Thanks for the links. The clinical trials for our area have nothing for this drug, but I did notice that they did have something for Lyrica - which the insurance would only pay for 3 pills a day instead of 4 pills.
I can't blame the insurance company though since it is 350 dollars a month and Pfizer seems to have orginally manufactured this drug for epilepsy (doesn't work) so they are looking for another disease it would be good for. perphial neuropathy /fibromylia seems to be what they are focusing on.
That is what mitochondrial cytopathy has finally developed into for my husband - perphial neuropathy- it took about 25 years to do it though. Scared us when it involved his breathing, and his oxygen levels dropped so very low, he failed a bunch of pulmnary tests, they put him on oxygen, and was discussing ventilators if it dropped more.
Then it just stopped bothering him in that way.
Why that happened is a guess, I think it was the very low carb diet of only 15 carbs a day we had been on for several months, it was the only change we made.
The plumanary doctors were surprised, and since it was a teaching medical center sent all the young interns up to watch the test that were performed when he got better. There were lots of questions they asked us about about the diet and supplements we were taking.
Someone made a snarly comment on this website, that the B vitamins can cause perphial neuropathy - it appears that this immune disease will cause that anyway.
There sure seems to be a lot of names for this one inflammatory/immune/neruro immune - disease so I will add
Anti-NMDA-receptor encephalitis as just one more name to a very long list.
Posted by: Benedetta | July 24, 2011 at 11:15 AM
Hi Benedetta- our DAN doc prescribed it. Also apparently some docs are prescribing it for seizures and it's working well. Teresa's recommendation is a good one altho I haven't joined any group to discuss it as yet.
Posted by: Maurine Meleck | July 23, 2011 at 01:28 PM
Thanks for all of your comments. I just wanted to respond to your question as I saw a good number of websites/ forums where parents posted about Namenda. It looks like neurologists and psychiatrists are prescribing it for autism just as they are for Alzheimer's.
Here also are clinical trials:
Posted by: Teresa Conrick | July 23, 2011 at 10:08 AM
What kind of doctor in what kind of speciality prescribed Namenda a glutaminergic agen and a Alzheimer drug?
We have been to all kinds of docs from rheumatologist on lots of occasions (usless), neurologist (almost usless but did have several seizure drugs that worked well), pain clinic (give you mostly opium to make you lay in bed and waste away), psych (lots of good powerful drugs there, as they GUESSSSSS).
So how did this come about?
Posted by: Benedetta | July 23, 2011 at 08:40 AM
Hi. I guess I need to say that I am just reporting on this study and definitely not a fan of ECT, especially since this is an autoimmune issue. As far as the Rituximab, I saw this -- "In cell lines, rituximab-induced apoptosis has been reported to involve calcium mobilization and protein tyrosine kinase phosphorylation." ...so,yes....sure looks like it has a mechanism to injury.
I do like that the authors are warning strongly that too many children/people are being dx with the DSM labels and they recommend that anti-NMDA-receptor encephalitis be evaluated.
Posted by: Teresa Conrick | July 22, 2011 at 10:31 PM
Taximon and Carolyn M:
You both are so very wonderful to help me on this. Both of you have said about what my 83 year old mother said this afternoon. She said she would not have lost her teeth in front at least, if not for a bridge. She said my son will never miss it when it is gone. She said if it was hurting that dentist needed to pull it now. She talked to my son, he was disturbed about his teeth, but she is a real communicator and she helped him in this. Thank you both for your thoughts and opinions on this subject.
I have often thought though that the missing permanent teeth may not be so much of an sign of who is vunerable to vaccines but be perhaps the cause of the missing teeth. After all they are now saying that certain medications and medical conditions of the mother can cause a cleft palate. The mouth area seems to be very sensitive and easily damaged. anti- inflammatory response, or high fevers may kill the buds. Just guessing of course.
We are like sheep to the dentist too , aren't we. My wisdom and 12 year old molar fused together and they came out together so I have an empty socket and I too was told 35 years ago that the tooth on top would descend - well it has not! Thanks for the information about the bone graft to keep the teeth in place. I never heard of that one.
Also I read in Pub med this afternoon that titanium steel provoked more T cells and B cells in around and throughout the body even more than stainless steel. I also mentioned inflammation to the dentist today and he said that different people react to different stuff that is why when patients come in with lots of metal piercings he thinks that they may be setting themselves up for an allergric reaction if they every do have to have some implant later on.
If Kent is right and it is a virus in B cells then for heaven sakes we sure don't want to provoke any B cells.
Tereasa thanks for letting me horn in on your article about this subject.
I have been reading some articles on R-nase ( a little knowledge is a dangerous thing) but it appears to me that men with prostate cancer have trouble with R-Nase not doing what it should to rid the body of viruses. Where as it could be working too well in the acquired mitochondrial cytopathy. My understanding (which is not great) is that there is a moment when the mitrochondria must decide if it will make energy or make the R-Nase. In the case of Acquired Mitrochondrial Cytopathy it may be the case of not making enough energy and too much R-Nase.
AND the Rituximab; It is manufactured from DNA from both humans and (rats and mice)!!!!! A mouse DNA to kill a mouse virus - it makes sense.
It targets proteins that are specfic for B cells. It kills B immune cells and it is used to kill B immune cells in rheumatoid Artheritis and nonlympathic Hogkins disease. B cells were found to be rather numerous in kids with autism in an autism study that was published in Scientific American about six years back.
Then B cells are in this Anti-NMDA-receptor encephalitis which is suppose to be because of cancer cells - but where were these cancer cells in this child??? There was none.
Posted by: Benedetta | July 22, 2011 at 10:17 PM
This is particularly interesting to me because we have started namenda in the last couple of weeks-
Ten years of OCD , echolalia with no let-up.
Thanks, Teresa. Your research is stupendous. M
Posted by: Maurine Meleck | July 22, 2011 at 09:12 PM
Rituximab has been given for XMRV, which is suspected to be a cause of many cases of autism. The action by which it may work is that it targets a very specific type of B cell where the XMRV retrovirus is believed to hide.
As far as the electroconvulsive therapy, I can say nothing positive.
All the best,
Posted by: Kent Heckenlively | July 22, 2011 at 07:05 PM
Benedetta, I have 3 baby teeth, and I am in my 40's. My son has the same 3 baby teeth, with no secondary teeth underneath to push them out.
I have been under pressure from dentists for literally decades to consider implants, but for now, I refuse to consider them. Mine are molars, and will not be seen.
My father lost a back molar, didn't do anything about it, and he has been just fine for 30 years. No chewing problems, no migrating teeth, no bit misalignment--in spite of the threats from the dentists.
I fear that dentists consider us a captive audience--they can tell us whatever they want ("you have cavities," "you need a crown," "you need implants," and like sheep (the same sheep who vaccinated their babies), we let em do whatever they say we need.
I wonder if the residual baby teeth could be have any significance regarding genetic susceptibility to vaccines--does anyone else here have them?
I have a documented allergy to thimerosal--from when it was in contact lens solution in the 1970's. And I have had major autoimmune reactions to vaccines.
Posted by: Taximom5 | July 22, 2011 at 05:48 PM
I don't know about whether titanium implants can cause health problems. I don't know of any other kind of implant.
What I do know: some of my family members in the past had bridges put in. The teeth that the bridges were attached to became loose and came out. This then required a larger bridge.
Also, once a broken tooth is removed, a bone graft may be used to fill in the hole left; it will be put in as part of the process of getting an implant, and may be put in if an implant is not going to be put in, in order to reduce the possibility of problems with the gum. It was explained to me by a dentist that if the affected tooth is on the lower jaw and is not replaced, that the corresponding tooth on the upper jaw may descend and come out.
I also have a baby tooth without the corresponding permanent tooth.
Sorry not to be of more help.
Posted by: Carolyn M | July 22, 2011 at 05:43 PM
I have spent a small fortune straightening my son's teeth. He is so very proud of them. He cleans them constantly.He is also very careful of what he eats because of them and not so much he has epilepsy and we are on a low carb diet.
Two of his baby teeth are still in his mouth at age 25, because there were no permanent teeth buds under them.
I have been told numerous times that when the time comes when these baby teeth are lost, titanium implants are the best option.
Today we went to the dentist because he is having pain when he bites down, or extreme temperature. He has lost his filling out of one of his baby teeth, and it broke off besides so a filling will not hold.
They would put a bridge in except the teeth on both sides of the baby teeth are beautiful, and to make a bridge they have to file down these beautiful teeth and put caps on them.
So once again I am looking at titanium implants.
Titanium implants; I have been looking at studies on inflammation and all I can find is for knee/joint replacement and yes there is inflammation and bits of metal in the surrounding tissue.
I have a titanium steel piece in my ear. When I was 40 Inflammation of the ear bone caused calcium to build up and it had to be replaced. Worked great, nothing like going from being totally deaf to can hear again in one ear. A few years later I did become very ill, slept all the time, severe headaches, muscles hurting on the back of my legs, constant yeast infection, hypothyroid. (sound familiar?) Only I got over it, it only took five years!
Did it begin from a tetanus shot I had in my early 40's?
Was the ear thing a genetic weakness for calcium buildup on one of my earbones (happened to my sister when she was only 22 years old) and then did the titanium implant cause more problems?
What do I do, about my son's teeth? Do I get implants? Could titanium steel cause him additional problems. After all that DPT shot showed he was perhaps more vunerable than most?
Has anyone out there had any similiar experiences? If you have would you share?
Posted by: Benedetta | July 22, 2011 at 03:55 PM
It would be very informative to know the incidence of childhood disintegrative disorder. Has its incidence also increased "coincident" with increases in the vaccine schedule? Does it occur more commonly in more heavily vaccinated populations?
Here is another article on a similar problem in a young girl--which indicates this is an "increasingly reported" syndrome:
Interestingly, they tested this child for mercury (though they don't say how -- (one would guess with a fairly useless blood test).
How many normally developing children and young adults have this fate in their future?
I, for one, am afraid to know the answer.
Thanks for accessing this article and your thoughts.
Posted by: Sue | July 22, 2011 at 10:47 AM