Late Onset Autism and Anti-NMDA Receptor Encephalitis

Lun, 01/08/2011 - 08:25

In Part 1 of our examination of Anti-NMDA Receptor Encephalitis, I presented a late-onset case of autism.  Similar cases have been shown to be caused by antibodies against NR1–NR2 heteromers of the NMDA receptor. There was really very little about the precipitating event that explained why the 9 year-old boy became a victim of such an extreme medical and behavioral illness.  Because of its acute psychiatric manifestation, Anti-NMDA Receptor Encephalitis is often misdiagnosed as a psychiatric issue rather than a neurological-medical disease.  Its apparent increase in cases has been debated as -- a true increase or just better diagnosing?  I have to say it -- we, in the autism community, really dislike that phrase as it has become a mantra of ignorance in the face of truth.

Some further investigating brought me to another case of Anti-NMDA Receptor Encephalitis that presents with some more tangible facts.  Here is the Pubmed excerpt:

J.Neurol 2011 Mar;258(3):500-1. Epub 2010 Sep 30.  Anti-NMDA receptor encephalitis after TdaP-IPV booster vaccination: cause or coincidence?  Hofmann C, Baur MO, Schroten H.

And that's it.  There was no abstract but after some searching, I did find a link:

Anti-NMDA receptor encephalitis after TdaPIPV booster vaccination .


Anti-NMDA receptor encephalitis after TdaP–IPV booster vaccination: cause or coincidence?
Caroline Hofmann • Marc-Oliver Baur • Horst Schroten
Received: 5 September 2010 / Accepted: 13 September 2010 / Published online: 30 September 2010

Springer-Verlag 2010

Dear Sirs,

Anti-NMDA receptor encephalitis is a recently described autoimmune disorder mediated by antibodies to the NR1 subunit of the N-methyl-D-aspartate receptor. It was first
recognized as a paraneoplastic syndrome in young women with ovarian teratoma [1]. Further studies have shown that about 40% of the patients with anti-NMDA receptor
encephalitis do not have a clinically detectable tumor, and men and children are also affected [2]. The mechanisms triggering the disorder, especially in patients without an
associated neoplasm are unknown. The high incidence of prodromal viral-like symptoms suggests a possible infection triggering the autoimmune response [3]. We report about a 15-year-old female patient who was diagnosed with anti-NMDA receptor encephalitis after receiving a booster vaccination against tetanus/diphtheria/pertussis and polio (TdaP-IPV). Within the first 24 h after the injection she developed a low-grade fever and general fatigue. During the following weeks, her family observed an unusual need for sleep. Psychiatric symptoms became apparent 5 weeks after the immunization and included disorganized thinking and hallucinations. Within a few days she became increasingly agitated with orofacial dyskinesia, opistotonic posturing, and choreic movements of the upper extremity. She grew unresponsive to verbal commands and required intensive care treatment due to autonomic instability. The unique pattern of clinical symptoms led to the consideration of anti-NMDA receptor encephalitis, which was confirmed by the detection of anti-NMDAR antibodies in plasma and cerebrospinal fluid. Other possible causes of encephalopathy including intoxication,infectious and metabolic diseases were ruled out; repetitive brain scans showed no abnormalities. After confirming the diagnosis, an extensive tumor search was performed without any proof of malignancy; biopsy of a prominent ovarian cyst revealed no teratoma. The onset of prodromal symptoms shortly after the immunization is intriguing and suggests the vaccination as a possible trigger of anti-NMDA receptor encephalitis. Neurological adverse events including autoimmune disorders have been discussed in literature for many years; a definite causal association between vaccination and disease was seldom established. For example, the 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barre Syndrome (GBS) [4]. A recent study about the safety of TdaP vaccination in adolescents revealed no increased risk of neurological adverse events [5], even though rare cases of GBS have been reported. To our knowledge, this is the first possible case of vaccination associated anti-NMDA receptor encephalitis. Therefore, not only infectious agents and tumor antigens but also vaccines should be considered as a possible trigger of immune response in this recently described disorder.
Conflict of interest None.

1. Dalmau J, Gleichmann AJ et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effect of antibodies. Lancet Neurol 7(12):1091–1098 C. Hofmann (&)
University Children’s Hospital Heidelberg, Heidelberg, Germany e-mail: M.-O. Baur H. Schroten Department of Pediatrics, University Hospital Mannheim, Mannheim, Germany 123 J Neurol (2011) 258:500–501 DOI 10.1007/s00415-010-5757-3

2. Vincent A, Bien CG (2008) Anti-NMDA-receptor encephalitis: a cause of psychiatric, seizure, and movement disorders in young adults. Lancet Neurol 7(12):1074–1075

3. Florance NR, Davis RL et al (2009) Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 66(1):11–18

4. Toplak N, Avcin T (2009) Influenza and autoimmunity. Contemporary challenges

Cause or Coincidence?  Again, for many of us who have seen an increase in not only autism, but corresponding autoimmune disorders, it is not a difficult question to answer but it is a hot topic for researchers to present, so I applaud these researchers for putting the facts out there, including vaccines as a source of causation.  They do mention that  Anti-NMDA Receptor Encephalitis is "recently described."  Another sign of it's new and increasing occurrence - "Anti-NMDAR encephalitis are associated with tumours (commonly teratomas) in about 60% cases 3. Recent studies have however shown that this disorder can occur even in the absence of teratomas and is increasingly recognized in adolescents and children 4." 

And here: "Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms."

"Behavioral and speech problems, seizures, and abnormal movements", sounds much like the world most of us live in with our children who have an autism diagnosis.  There are also others.  In looking for more answers, I saw that these cases of vaccine injury also resulted in Anti-NMDA Receptor Encephalitis - for example:

Cevarix vaccine and anti--NMDA Receptor Encephalitis

Gardasil vaccination and Anti-NMDA Receptor Encephalitis

I was able to correspond with the mother of a teen girl injured by Cervarix, who now has a diagnosis of Anti-NMDA-Receptor Encephalitis. This family has been through hell trying to get proper care after finally getting the correct diagnosis. I big thank you to them for allowing me to share the horrors of their daughter's descent into Anti-NMDA-Receptor Encephalitis. This is a short synopsis of their initial 3 month nightmare, post-vaccine:

"..her first HPV vaccination on 15/11/08 .....After approximately one week ---  become very emotional. After the third injection on 16/05/09 ,,,,,was very agitated all night...the next day .. she said that she hadn’t had any sleep and felt  exhausted.  When I arrived home --- was sobbing her heart out saying that this headache was driving her mad...she was having a full blown seizure and at one point she stopped breathing.   The paramedics had put an oxygen mask on and took her downstairs to the ambulance. The paramedics took us to the Hospital --- started to have what I described as vacant episodes, I was soon to learn that these were partial seizures.  At approximately 5.30am --- had a seizure and wet herself. She had a high  temperature , a cannular was fitted and iv anti viral drugs were started.  --- had gone missing off the ward twice during the night ... I had a voicemail message at 4am asking us if we could get back to the hospital because they couldn’t control her ...temperature was still high. Partial seizures were still continuing .... She then asked for a knife because she wanted to kill everyone...remained very agitated and very disorientated ...

had a panic attack on the way back to the hospital. For the rest of the week --- was up and down. She had become obsessed with the man in the next room and kept trying to get into his room. She said that he was always talking about her and telling her to do things.  She started pulling her hair out...  --- attacked me.  The nurses pulled her off had been called because --- was very aggressive... increased her medication. Tuesday 28th July: one of the blood results had come back and it was showing that something was still attacking her, something to do with the autoimmune system. ... this took 6 weeks to come back. Dr XXX came to see us at 2.30pm. He thinks that there is a link to the injection. The aggression that --- had was what the encephalitis left her with but Dr XXX was adamant that it was a psychiatric problem despite Dr XXX telling him that it wasn’t. We have spent the last six weeks fighting for the correct treatment. Her EEG’s were showing signs of activity in her brain but all the other tests came back negative except the one which showed that she had got anti- NMDA receptor encephalitis.  Dr. XXX is convinced that the vaccine had something to do with --- becoming ill. Dr XXX also believes that there is a link to ---'s  illness from the vaccines. "

Difficult to read as the amount of suffering is just so painful.  What this shows is that Anti-NMDA-Receptor Encephalitis is not only an autoimmune disease associated with females and cancer, but an increasingly diagnosed autoimmune disease in males and females, children and adults.  Vaccines are now being seen as a potential fuse to the explosion of symptoms.  Does the apparent increase in diagnoses of Anti-NMDA-Receptor Encephalitis have anything to do with increases in the vaccine schedule or marketing of them?  How many cases are being misdiagnosed and victims not getting the proper medical treatment? Is there a government agency investigating this?

Some compelling facts:
1.Most autoimmune encephalitides cause psychiatric symptoms and CSF inflammatory abnormalities.

2.Antibodies to NR2 subunits of the NMDAR have been reported in several other disorders...The major antigen is NR1/NR2B, which is predominantly expressed in the hippocampus and forebrain.
3.NR­1 and NR2b glutamate receptor immunoreac­tivity patterns are abnormal in the hippocampi of thimerosal treated SJL mice

4.Preceding infectious illness -often: Sore throat then "strange behaviour", Cognitive deterioration, mutism

5.Brain imaging was normal and EEG showed a diffuse and generalized slowing.... evidence of an inflammatory process was often documented
6.Seizures - Partial complex or generalized seizures

7.Autonomic instability - Hyperthermia (sometimes alternating with hypothermia), hypoventilation, fluctuations of blood pressure, tachycardia, bradycardia, constipation, ileus

8.The concept of epilepsy and seizure disorders caused by autoantibodies to specific neuronal membrane proteins has developed significantly during the past few years.

9.There are a growing number of specific antibodies associated with new onset epilepsy. These patients are likely to have an immune-mediated disorder that may benefit from immunotherapies. Many of these patients do not show a good response to conventional antiepileptic drugs.

10.In anti-NMDA-receptor encephalitis the high prevalence of prodromal viral-like symptoms is intriguing. Direct viral pathogenesis is unlikely because extensive studies of CSF samples, brain biopsies, and autopsies were negative for viruses (data not shown). Whether the prodromal symptoms form part of an early immune activation, or result from a non-specific infection that facilitates crossing of the blood–brain barrier by the immune response is unknown.

There are some potent similarities with autism and I hope these researchers involved will continue to explore all roads that can lead to Anti-NMDA-Receptor Encephalitis, including vaccines.  Thirty years ago, some were looking at regression into autism as medical.  We need that now more than ever:

Arch. Neurology  1981 Mar;38(3):191-4.

Acquired reversible autistic syndrome in acute encephalopathic illness in children.

Delong GR, Bean SC, Brown FR 3rd.


In seeking the neurologic substrate of the autistic syndrome of childhood, previous studies have implicated the medial temporal lobe or the ring of mesolimbic cortex located in the mesial frontal and temporal lobes. During an acute encephalopathic illness, a clinical picture developed in three children that was consistent with infantile autism. This development was reversible................

Teresa Conrick is Contributing Editor to Age of Autism.

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