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Court Clarifies: Hannah Poling case “does not afford any support to the notion that vaccinations can contribute to the causation of autism”

8 Jul

One of the most common arguments in the “vaccines-cause-autism” discussion involves the case of Hannah Poling. Miss Poling is autistic and was compensated by the government through the vaccine-court system. Online discussions usually end up going around in circles with people explaining why the concession doesn’t mean the government has stated that vaccines cause autism, and the other side saying “but it does”.

Well, the Court has clarified the situation. Here is a footnote from the decision in Brian Hooker’s case.

I am well aware, of course, that during the years since the “test cases” were decided, in two cases involving vaccinees suffering from ASDs, Vaccine Act compensation was granted.
But in neither of those cases did the Respondent concede, nor did a special master find, that there was any “causation-in-fact” connection between a vaccination and the vaccinee’s ASD. Instead, in both cases it was conceded or found that the vaccinee displayed the symptoms of a Table Injury within the Table time frame after vaccination. (See Section I above).

In Poling v. HHS, the presiding special master clarified that the family was compensated because the Respondent conceded that the Poling child had suffered a Table Injury–not because the Respondent or the special master had concluded that any vaccination had contributed to causing or aggravating the child’s ASD. See Poling v. HHS, No. 02-1466V, 2011 WL 678559, at *1 (Fed. Cir Spec. Mstr. Jan. 28, 2011) (a fees decision, but noting specifically that the case was compensated as a Table Injury).

Second, in Wright v. HHS, No. 12-423, 2015 WL 6665600 (Fed. Cl. Spec. Mstr. Sept. 21, 2015), Special Master Vowell concluded that a child, later diagnosed with ASD, suffered a
“Table Injury” after a vaccination. However, she stressed that she was not finding that the vaccinee’s ASD in that case was “caused-in-fact” by the vaccination–to the contrary, she
specifically found that the evidence in that case did not support a “causation-in-fact” claim, going so far as to remark that the petitioners’ “causation-in-fact” theory in that case was “absurd.” Wright v. HHS, No. 12-423, 2015 WL 6665600, at *2 (Fed. Cl. Spec. Mstr. Sept. 21, 2015).

The compensation of these two cases, thus does not afford any support to the notion that vaccinations can contribute to the causation of autism. In setting up the Vaccine Act
compensation system, Congress forthrightly acknowledged that the Table Injury presumptions would result in compensation for some injuries that were not, in fact, truly vaccine-caused. H.R. Rept. No. 99-908, 18, 1986 U.S.C.C.A.N. 6344, 6359. (“The Committee recognizes that there is public debate over the incidence of illnesses that coincidentally occur within a short time of
vaccination. The Committee further recognizes that the deeming of a vaccine-relatedness adopted here may provide compensation to some children whose illness is not, in fact, vaccine related.”

While the arguments may still not convince those who wish to believe, the conclusion is clear: The compensation of these two cases, thus does not afford any support to the notion that vaccinations can contribute to the causation of autism.

The Special Masters (basically the judges in this special court) are not only the experts in the decisions (they work every day in the court and write the decisions), they are legally bound by the decisions. If a case sets a precedent, they must follow it. Or they will be overturned by higher courts.

I agree that following the logic takes time and effort, but, again, if you don’t have the time to go through that, the conclusion is very clear. And repeated again for emphasis

The compensation of these two cases, thus does not afford any support to the notion that vaccinations can contribute to the causation of autism.

—
By Matt Carey

The next Hannah Poling. Not vaccine injured. No mitochondrial disease.

27 Jun

One of the main talking points for the idea that autism is a “vaccine induced epidemic” is the case of Hannah Poling. Hannah Poling was chosen as one of the test cases for the Omnibus Autism Proceeding (OAP). But before the case went to hearing, the Department of Health and Human Services conceded her case on the grounds that she met the criteria for a table injury. If you want more details there are a lot of discussions online, including a lot of misinformation. But basically a table injury means that Miss Poling met certain criteria in a prescribed time frame after receiving vaccines, so she is presumed vaccine injured. One can go into length about how this isn’t “the vaccine court decided vaccines caused her autism”, but that’s another story (if you are interested, Prof. Dorit Reiss discusses it in Vaccine Injury Compensation and Mitochondrial Disorders).

At the time, the Poling concession was big news, on CNN and elsewhere. The story broke when David Kirby released some of the details of the concession (the Rule 4c report, a report written by Department of Justice attorneys on behalf of HHS describing the concession.) Kirby was journalist/PR man working with groups promoting the idea that vaccines cause autism. Much of his writing was problematic at best, much more PR than journalism. Kirby stayed with the Poling story for some time, pushing the idea that mitochondrial disorders are highly prevalent in the autistic population and suggesting that these disorders were caused by vaccines. As part of that PR effort, he wrote this article:

The Next Vaccine-Autism Newsmaker: Not Isolated, Not Unusual

Which begins:

In February, I leaked news of the Federal government’s admission that vaccines had triggered autism in a little girl named Hannah Poling. The stunning revelation, though still reverberating around the world, was roundly downplayed by US officials, who insisted that Hannah had an extremely rare, genetic case of “aggravated” mitochondrial disorder, with zero bearing on other autism cases.

Dr. Julie Gerberding, Director of the US Centers for Disease Control and Prevention (CDC), rushed to the airwaves, exhorting parents to adhere to the nation’s intensive and virtually mandatory immunization schedule, and brushing off their legitimate anxieties by saying: “We’ve got to set aside this very isolated, unusual situation.”

Well, the days of setting aside are over: Hannah Poling is neither isolated nor unusual.

In fact, the boy who was selected to replace Hannah Poling as the first-ever thimerosal “test case” in so-called Vaccine Court, has just been found with many of the same unusual metabolic markers as… you guessed it, Hannah Poling.

You see, Hannah Poling was supposed to be a test case for the OAP. One of the arguments the families and attorneys were going to argue in the OAP was that autism is a form of mercury poisoning caused by thimerosal (which used to be in infant vaccines as a preservative.) That idea (and the Wakefield inspired MMR causes autism and bowel disease) failed to even come close to the rather lenient standard of proof of the vaccine court. No one knew for sure before the OAP hearings that the thimerosal argument would fail so completely. Those involved actually had a great deal of confidence. But even with this confidence, some families decided to leave the OAP when the Poling concession was made public.  Most notably Robert Krakow (an attorney and activist in the autism-is-vaccine-injury community) pulled his son’s case from the OAP. His son was to be one of the three thimerosal test cases and is the one Mr. Kirby was discussing in his “Not Isolated, Not Rare” article quoted above.

In many ways it was a strange decision on the part of Mr. Krakow. The expert report on the Krakow boy (made public as part of the OAP and since pulled) made no mention of mitochondrial dysfunction. Also, the court hadn’t decided that the idea that vaccines aggravate mitochondrial disorders causes autism. While many deny this, as an attorney Mr. Krakow must have known this point. Miss Poling was compensated because she showed signs of an encephalopathy soon after vaccination, so it was presumed that encephalopathy was caused by the vaccines. The Krakow boy’s history did not show this.

In another recent case, a vaccine court Special Master noted,

In Poling v. HHS, the presiding special master clarified that the family was compensated because the Respondent conceded that the Poling child had suffered a Table Injury–not because the Respondent or the special master had concluded that any vaccination had contributed to causing or aggravating the child’s ASD.

So the situation for the Krakow boy (and Hannah Poling)  was very, very different than David Kirby painted (as was often true). This wasn’t another Poling case. Mr. Krakow and his attorneys and experts would have to show that (a) his son had real signs of mitochondrial dysfunction, (b) the hypothesis that vaccines vaccines contribute to causing autism was valid (recall, it hadn’t been decided by hearing), (c) this hypothesis applied to his son even though his son didn’t show signs of encephalopathy following vaccination.

As you will see, none of these points were valid.

Mr. Krakow pulled his son’s case  in 2008. The case dragged on for 7 years as the Krakows tried to put together their argument. And it appears that they did not win. Based on the facts presented, these documents appear to be the final decision and a ruling on motions in the Krakow case. These have been anonymized so it is possible that these are not a discussion of the Krakow case, but since the facts so closely match, I will write as though it is the Krakow case for brevity and clarity.

The decisions are lengthy. This case is as involved–if not more–than those in the OAP itself. It’s as if this is the test case for a third OAP argument.

Here is a key paragraph from the documents:

“Petitioners have failed to show that A.K. had an underlying mitochondrial disorder. They have also failed to show that the onset of A.K.’s ASD was in any way related to his influenza vaccinations. Indeed, respondent persuasively presented significant evidence indicating that A.K.’s ASD onset predated his vaccinations. Nor did petitioners establish by preponderant evidence that A.K. experienced any regression of skills related to his ASD or his vaccinations””

The Krakow boy’s history is in no way similar to that of Hannah Poling. Since her case was conceded, we don’t know if she showed signs of autism before vaccination. We do know now that the Krakow boy did show signs of autism. Poling regressed. Krakow didn’t. Poling has evidence of mitochondrial disease. Krakow doesn’t.

There are other interesting statements in these documents. Here are a few. First:

“The measles, mumps, and rubella [“MMR’] vaccines are ordinarily administered in a combined MMR vaccination, but A.K. received his in three separate vaccinations administered on December 1, 2000 (mumps); December 19, 2000 (measles), and January 2, 2001 (rubella), when he was between 13-14 months of age”

Yes. The Krakow family was following the Wakefield-recommended “separate the MMR into single vaccines” schedule. Didn’t prevent autism. This seems like valuable information for the autism community, but Mr. Krakow chose to hold this information back.

The Special Master took on the general idea that vaccines trigger regression in people with mitochondrial disorders. The evidence is very much lacking and “remain speculative”.

Here, petitioners’ experts strained to stretch the idea of mitochondrial regression to encompass vaccines as triggers of such regression. As described above, that extension is completely unsupported by any scientific literature; it was presented in this case almost entirely through the opinion of Dr. Kendall, supported by one case report (Poling, Res. Ex. MM, Tab 14). Doctor Kendall’s and Dr. Shafrir’s further reliance on the Shoffner and Weissman papers was misplaced and their opinions that vaccines can act as triggers of mitochondrial regression were unpersuasive. Evidence that regression in ASD, a well-described phenomenon involving the loss social communication and behavior, “looks like” mitochondrial regression was also nearly non-existent. “Mitochondrial autism” may someday be accepted as a descriptor for co-morbid autism and mitochondrial disorder diagnoses, but there is little evidence that autism itself is caused by such disorder, and no evidence that autism causes mitochondrial disorders. While Dr. Kendall is one of the few mitochondrial disorder specialists in the U.S., her opinion that vaccines can trigger either onset of a mitochondrial disorder with symptoms looking like ASD, or ASD via a mitochondrial regression are insufficiently supported and remain speculative.

We parents are often hit with testimonials about how alternative medicine works wonders on autistic kids. With the OAP cases we heard about a child who had adverse reactions to chelation. In this case we hear that these alternative therapies just didn’t work:

Doctor Boris recommended a gluten-free, casein-free diet for A.K. and began therapies such as chelation, supplements to counteract the effects of his MTHFR gene defect, and autoimmune medications. Tr. at 168-69. He testified that A.K. “did not respond very well to most of the treatments [he] administered.”

In an interesting twist, The Krakow boy’s geneticist  recommended he get vaccinations:

I [the special master] noted that the geneticist who had been seeing A.K. had specifically recommended that he continue to receive vaccinations and indicated that he was a “good candidate” to receive seasonal vaccinations, such as influenza.

Many people have been trying to characterize the “vaccine court” (the Court of Federal Claims) as highly adversarial. But Mr. Krakow writes that “The tenor of VICP proceedings is exceptionally hostile and adversarial”. The record show the Court was far from hostile and adversarial.

Consider this. The record shows that Robert Krakow (an attorney who appears in the vaccine court) and the attorney he chose to take over his son’s case were not proactive in prosecuting their case:

Other than the filing of medical records, petitioners did little to advance their claim during the period in which [A.K.’s father] was attorney of record.

and

However, the glacial pace of progress toward a causation hearing continued for many months thereafter. Mr. McHugh’s representation has been marked with missed deadlines, repeated requests for delays, late filings, and difficulties in properly designating and filing exhibits. His failure to meet deadlines nearly cost petitioners the opportunity to fully litigate their son’s claim.

That last sentence refers to the fact that after years of delays and missed deadlines, the court was finally forced to dismiss the case for inaction:

Accordingly, after petitioners missed the deadlines set forth in my August 18, 2010 order, I ordered them to show cause why their case should not be dismissed for failure to prosecute and comply with court orders. See Order to Show Cause, issued Sept. 3, 2010 (ECF No. 98). After petitioners ignored the deadline in the show cause order, I dismissed their petition on October 13, 2010.

The Court allowed the family to petition and re-enter the vaccine program. Not only that, but the Court granted the motion to redact parts of the dismissal. The dismissal was available on the vaccine court website (where I found and read it) but was pulled.

Many in the “autism is a vaccine epidemic” community call for a repeal of the vaccine act and a return to the time when vaccine manufacturers could sued directly.  How many cases in regular court are dismissed and allowed back in?

We could go on as the decisions are lengthy but instead let’s get back to the key points above.  When David Kirby wrote his article he concluded “And there are many more Hannah’s out there, waiting to be counted.”  Just not so.  First off, the real Hannah Poling case isn’t what Kirby claimed. The Court has stated that neither they nor the government  “…concluded that any vaccination had contributed to causing or aggravating the child’s ASD.”  More importantly, this new  case isn’t about a child with mitochondrial disorder, or even regression. It is a case of a child who showed signs of autism before the vaccines the parents claim caused autism.

This is a case of one of the most vocal proponents of the idea that vaccines cause autism misleading the public.  Mr. Krakow probably believes the story he tells of his child’s development.  He probably believes the story about how contentious the vaccine court is. But the facts tell a very different story.

I am often asked why I can not support the idea that vaccines cause autism.  Thousands of parents tell the same story, I’m told.  The problem is that the parents stories don’t match the facts. We saw this with Jenny McCarthy. We saw this with the Omnibus Autism Proceeding test cases.  We’ve seen this with more vaccine court cases.  We’ve seen this with parent stories shifting in online discussions. And now we’ve seen this with “the next Hannah Poling”.

—

By Matt Carey

The Next Vaccine-Autism Newsmaker…5 years later

6 Feb

Years back, much focus in online autism parent community discussions focused on the Omnibus Autism Proceeding (OAP). This was the large “vaccine court” proceeding to explore if people could be compensated for autism as a vaccine injury. Those hearings were held in 2008, and the decisions went against the families.

A year ago I wrote (The Omnibus Autism Proceeding: effectively over), and while, yes, as an “Omnibus” it is effectively over, there is still activity for those who filed claims and were included in the Omnibus Autism Proceeding. Statistics as of today show there were 5,635 claims included in the Omnibus, and 4,564 have been dismissed. 2 claimants have been compensated, with the caveat given that “**HHS has never concluded in any case that autism was caused by vaccination.” This leaves 1,069 cases still pending. A relatively small fraction of the original Omnibus, but a large number nonetheless.

Another way to look at this is the Omnibus proceedings are over, the docket hasn’t been updated for quite some time but there are still individual cases to be decided. Including one case that was rather prominent in the Omnibus: that of A. Krakow. He was intended to be one of the test cases for the thimerosal but was pulled out to pursue another argument: that metabolic dysfunction is involved. David Kirby referred to him as “The Next Vaccine-Autism Newsmaker”, following the supposed game-changer of Hannah Poling.

That was in 2008. As it’s been nearly 5 years, I checked the status of the case. It turns out the first hearing was held in December (a hearing on fact) and a second hearing is set for expert witnesses to testify in April of this year. One way to explore the arguments the family may be taking is to review the experts that are testifying. For example, the family has chosen Richard Deth as an expert. His work has not focused on mitochondria. On the other hand, Yuval Shafir is also listed as an expert and has listed many articles on mitochondria with his report. Richard Frye’s CV was submitted (he also has some work on mitochondria and autism), but I don’t see that an expert report from him has been submitted.

Other experts date from 2008 (from when he was going to be an Omnibus test case) include: Elizabeth A. Mumper, Robert S. Rust, Richard Deth and Sander Greenland.

(edit to add, I see a report in the docket from Marcel Kinsbourne in 2010).

So, is this going ahead as a “mitochondrial autism” case? The “Next Hannah Poling” as David Kirby claimed in Spectrum Magazine? Well, even Hannah Poling wasn’t the game-changer some people predicted. Probably the most we can say is that is 10 years old, with a docket 16 pages long, will finally be heard.

edit to add: For the curious, here is the docket.
—
By Matt Carey

The Omnibus Autism Proceeding: effectively over

21 Jan

The Omnibus Autism Proceeding (OAP) was held in the U.S. Court of Federal Claims to group the large number of claims filed involving autism and vaccines. The Docket was opened on July 3, 2002, nearly 10 years ago. The last entry was placed 1 year ago. Since then many cases have been dismissed. About half the cases are left to hear, but the fact that the two causation theories presented (that the MMR vaccine causes autism and that Thimerosal causes autism) were both found to have no merit (“not even close” one special master put it) and no new theory is proposed by the Petitioners’ Steering Committee (the attorneys who presented the case for the petitioners) makes it clear that the group claim, the omnibus, is effectively over.

That is not to say that other claims are not proceeding through the court, or that new cases will not be presented. There is at least one case pursuing the idea of mitochondrial dysfunction and autism, as with the Hannah Poling case. ([edit to add–the case ongoing, which was briefly closed, is not the Hannah Poling case. See the comments below). The case was actually dismissed for lack of action by the petitioners but the special master allowed it to continue again).

Looking back, the Omnibus peaked in 2003 when 2,437 cases were filed (close to 1/2 of the total that would eventually be filed).

Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder.

12 Apr

Autism and mitochondrial medicine have become a very hot topic in recent years. What the connections are between autism and mitochondrial disorders has yet to be clarified. Mitochondria are little structures within cells that produce much of the energy required. Mitochondria have their own DNA (mtDNA) in addition to the nuclear DNA (nDNA) of the cell. nDNA is what most people think of when we hear “genes” or DNA. Given the focus on mitochondrial dysfunction and autism, it is natural to consider the question: are there mutations in the mtDNA which increase the risk of autism?

A new paper takes a look at the question. They studied 148 patients with ASD and found, well, no support for a link to mtDNA mutations. Here is the abstract:

BMC Med Genet. 2011 Apr 6;12(1):50. [Epub ahead of print]
Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder.
Alvarez-Iglesias V, Mosquera-Miguel A, Cusco I, Carracedo A, Perez-Jurado LA, Salas A.
Abstract
ABSTRACT:
BACKGROUND: There is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850). A significant proportion of ASD cases display biochemical alterations suggestive of mitochondrial dysfunction and several studies have reported that mutations in the mitochondrial DNA (mtDNA) molecule could be involved in the disease phenotype.

METHODS: We analysed a cohort of 148 patients with idiopathic ASD for a number of mutations proposed in the literature as pathogenic in ASD. We also carried out a case control association study for the most common European haplogroups (hgs) and their diagnostic single nucleotide polymorphisms (SNPs) by comparing cases with 753 healthy and ethnically matched controls.

RESULTS: We did not find statistical support for an association between mtDNA mutations or polymorphisms and ASD.

CONCLUSIONS: Our results are compatible with the idea that mtDNA mutations are not a relevant cause of ASD and the frequent observation of concomitant mitochondrial dysfunction and ASD could be due to nuclear factors influencing mitochondrion functions or to a more complex interplay between the nucleus and the mitochondrion/mtDNA.

PMID: 21470425 [PubMed – as supplied by publisher]Free Article

This is consistent with previous studies, as noted in a recent review article which was itself summarized at The Thinking Person’s Guide to Autism by Emily Willingham as Mitochondrial Disease and Autism: Linked?

Ms. Willingham noted there:

Thus, tracking down mitochondrial dysfunction in the context of ASD to a specific mutation has remained an elusive goal. Two scenarios are likely for this lack of mutational findings: (1) there are mutations, but we just haven’t found them yet; or (2) the environment is largely responsible for any mitochondrial dysfunction that abnormal marker levels might indicate.

This paper is available as a free manuscript online. Here is the

Although it is widely accepted that some forms of ASD appear concomitantly with the impairment of mitochondrial energy metabolism, there are reasons to believe that the cause of these mitochondrial disorders does not systematically rest on mutations or variants in the mtDNA molecule. Pathogenic mtDNA mutations have been reported in ASD patients, but this seems to be the exception rather than the rule. It is more likely that the real causes of mitochondrial deficiencies in some ASD cases are due to the intervention of several nuclear factors acting alone (additively or epistatically) or through a complex interplay with mtDNA variants. For the time being, while the cause for mitochondrion dysfunction in ASD remains unclear, there is no reason to indicate systematic screening for mtDNA mutations in ASD patients unless a mitochondrion disorder is suggested by a clear phenotype.

What is also interesting to me is the table of characteristics of the study subjects. In particular, there is a big difference in the percentage with epilepsy and dimorphism between adults and children:

Mitochondrial dysfunction is listed as mild and somewhat infrequent (about 10%). Not the very high prevalences of mitochondrial dysfunction that some have suggested are present in autitics. This does beg the question: should this genetic study be performed on those with some measure of mitochondrial dysfunction?

This doesn’t mean that mitochondrial dysfunction isn’t an important area for autism research, or that a genetic study such as this shouldn’t be done on a larger group with some measure of mitochondrial dysfunction.

Of course it would be great to hear that there is something definitive in this study. As in, “this is it!” rather than “this probably isn’t it”. Mitochondrial DNA mutations “probably isn’t it” when it comes to the etiology of ASD in most people.

Robert F. Kennedy Jr. not holding a press conference on Monday

9 Apr

My guess is that you are reading this thinking: this is news? Doesn’t pretty much every day go by without Robert F. Kennedy holding a press conference? Well, yes. But there was a press conference planned for Monday. Yes, the man who brought you “Deadly Immunity” (an article promoting the mercury/autism link that was so flawed that it was retracted by Salon.com and quietly removed from the Rolling Stone website) has something so new and important that he wants to tell the world about it from in front of the White House.

The subject? A study purportedly showing that many autistic kids have been compensated over the years by the National Vaccine Injury Compensation Program (a fact that has been public knowledge for 9 years or more). The article, under review by his University’s law journal, appears to be the one which was touted as ongoing a few years ago (I recall this being on a piece by David Kirby on the Huffington Post before he focused on his new project of food safety).

That press conference, from what I’ve heard, has been put off until after the paper is actually accepted and published.

Here’s the background history:

1) The US adopts a National Vaccine Injury Compensation Program in the mid-late 1980’s.

2) Autistic kids are amongst those compensated.

3) The concept of a vaccine-induced autism epidemic gains momentum in the late 1990’s.

4) Enough cases are submitted to the Program that an Omnibus proceeding is started to cover all the cases.

5) The first item added to the docket, Autism General Order #1, tells attorneys to be aware that autistics with table injuries should be handled outside the Omnibus for faster processing. (year 2002)

One important caveat, however, is drawn to the attention of all petitioners and their counsel! There may be cases involving autistic-like disorders which manifested following an injury defined in the Vaccine Injury Table. That is, a vaccine may have suffered an episode involving a severe acute encephalopathy within 72 hours after a pertussis vaccination (DTP or DTaP), or 5 to 15 days after an MMR vaccination. If so, such an acute encephalopathy and any residual effects thereof would be presumed to be vaccine-caused pursuant to the Vaccine Injury Table.

and

Autism cases involving Table Injuries have been compensated under the Program. If in a particular case there exist medical records demonstrating that such a qualifying “acute encephalopathy” occurred within the appropriate time frame, petitioner or counsel should bring that to the assigned special master’s attention so that, if appropriate, the case can be processed without delay as a Table Injury.

6) The government concedes Hannah Poling’s case as a table injury (late 2007) and the Hannah Poling concession was leaked while still in process. (Feb. 2008).

7) Given the news focus generated, then Chief Special Master Gary Golkiewicz was quoted:

“Years ago, actually, I had a case, before we understood or knew the implications of autism, that the vaccine injured the child’s brain caused an encephalopathy,” he said. And the symptoms that come with that “fall within the broad rubric of autism.”

And there are other somewhat similar cases, Golkiewicz says, that were decided before autism and its symptoms were more clearly defined.

8) Kathleen Siedel found a number of cases which were in the public record involving vaccine injury cases compensated. This list then appeared in many places, including a journal paper.

9) it was signaled that a new study was in the works where the prevalence of autism was notably higher amongst people compensated in the vaccine-injury program.

10) The autism prevalence estimate in the US was increased to 1 in 100, up from 1 in 150. Whether this had an impact on the apparent delay of (9) I can’t say.

Short form: we’ve been waiting for years for the study which will show us that the fraction of kids compensated by the Court is higher than expected. Now it appears that the study is in process and in a law journal. And that Robert F. Kennedy wanted to tell us all about it on Monday. But that won’t happen now, apparently. Apparently even law journals have embargoes.

Even though the press conference seems to be canceled for now, I guess that sometime in the near future Robert F. Kennedy will confirm what is and has been public knowledge. This will be followed by a blog storm acting as though this is news. Perhaps I’ll be surprised and something new will be in the announcement.

So far, the fraction of children with ASD diagnoses who have been compensated by the Autism Omnibus Proceeding is 1 in 838. This isn’t a fair estimate of what the final fraction will be, as many of those cases dismissed are for procedural issues like failure to prosecute and timeliness of filing. For that one compensated case, there is the note:

*May include case(s) that were originally filed and processed as an OAP cases but in which the final adjudication does not include a finding of vaccine-related autism.

**HHS has never concluded in any case that autism was caused by vaccination.

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder.

16 Mar

A study published today looks for mitochondrial dysfunction in autistic children. In specific, the researchers are looking directly at the brains of autistic children. The team, from the University of Washington, used both MRI (Magnetic Resonance Imaging) and proton magnetic resonance spectroscropic imaging (HRMS). MRI gives structural information on soft tissues. HMRS is a “spectroscopic” techinque: it gives chemical information on
Here’s a good reference with a discussion of HMRS on brain tissue (as a spectroscopy, not an imaging technique): Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy

With that background in hand, here is the abstract from the recent study on autism:

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder.

Corrigan NM, Shaw DW, Richards TL, Estes AM, Friedman SD, Petropoulos H, Artru AA, Dager SR.

Department of Radiology, University of Washington, Seattle, WA, USA.
Abstract

Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ((1)HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally in typically developing (TD) children at 3-4, 6-7 and 9-10 years-of-age. A total of 239 studies from 130 unique participants (54ASD, 22DD, 54TD) were acquired. (1)HMRS and MRI revealed no evidence for brain mitochondrial dysfunction in the children with ASD. Findings do not support a substantive role for brain mitochondrial abnormalities in the etiology or symptom expression of ASD, nor the widespread use of hyperbaric oxygen treatment that has been advocated on the basis of this proposed relationship.

Does this mean that mitochondrial dysfunction never occurs in autistics? No. But it makes it very unlikely that more than a fraction of autistics have mitochondrial dysfunction in their brains.

Beyond that, the use of spectroscopic imaging is very impressive to me. MRI structural data is quite valuable on its own, but adding chemical information is very powerful.

Mitochondrial Disease and Autism: Linked?

11 Mar

Mitochondrial disease and autism. I don’t read about it as much as during the peak of the Hannah Poling story, but it is a big topic. Emily Willingham at
Thinking Person’s Guide to Autism has put together an excellent post on the subject. Here’s the first paragraph:

Hannah Poling’s family entered the national spotlight when they revealed that Hannah’s autism-like symptoms may have been linked to a reaction to several childhood vaccines at once in combination with her mitochondrial dysfunction. Her case was not the first revelation of a possible mitochondrial disorder (MD)-autism spectrum disorder (ASD) link, but because of her ultimately successful vaccine injury suit, she became the avatar of the vaccines-cause-harm movement — which almost eclipsed the real scientific and therapeutic feature of her case: the mitochondria.

I’d love to do a wholesale copy of the post, but that’s hardly fair now, is it? So, I’ll send you all to the Thinking Person’s Guide to Autism and Mitochondrial Disease and Autism: Linked?

Mitochondrial Dysfunction in Autism

22 Dec

A recent paper from the MIND Institute, published in the Journal of the American Medical Association (JAMA) entitled Mitochondrial Dysfunction in Autism caused a bit of a stir. One which is far beyond what is supported by the paper’s conclusions or data, I will add.

The study is very small: 10 autistic children and 10 controls. The authors used a very nonstandard methodology. Perhaps the best summary of this study so far can be found on the Simons Foundation blog SFARI (Defects in mitochondria linked to autism). Deborah Rudacille discusses the methodology and brings in quotes from the study’s lead author (Cecilia Giulivi) as well as established experts in the field of mitochondrial disease and autism such as Jay Gargas.

Before I get too far ahead of myself, here is the abstract:

Context Impaired mitochondrial function may influence processes highly dependent on energy, such as neurodevelopment, and contribute to autism. No studies have evaluated mitochondrial dysfunction and mitochondrial DNA (mtDNA) abnormalities in a well-defined population of children with autism.

Objective To evaluate mitochondrial defects in children with autism.

Design, Setting, and Patients Observational study using data collected from patients aged 2 to 5 years who were a subset of children participating in the Childhood Autism Risk From Genes and Environment study in California, which is a population-based, case-control investigation with confirmed autism cases and age-matched, genetically unrelated, typically developing controls, that was launched in 2003 and is still ongoing. Mitochondrial dysfunction and mtDNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls.

Main Outcome Measures Oxidative phosphorylation capacity, mtDNA copy number and deletions, mitochondrial rate of hydrogen peroxide production, and plasma lactate and pyruvate.

Results The reduced nicotinamide adenine dinucleotide (NADH) oxidase activity (normalized to citrate synthase activity) in lymphocytic mitochondria from children with autism was significantly lower compared with controls (mean, 4.4 [95% confidence interval {CI}, 2.8-6.0] vs 12 [95% CI, 8-16], respectively; P = .001). The majority of children with autism (6 of 10) had complex I activity below control range values. Higher plasma pyruvate levels were found in children with autism compared with controls (0.23 mM [95% CI, 0.15-0.31 mM] vs 0.08 mM [95% CI, 0.04-0.12 mM], respectively; P = .02). Eight of 10 cases had higher pyruvate levels but only 2 cases had higher lactate levels compared with controls. These results were consistent with the lower pyruvate dehydrogenase activity observed in children with autism compared with controls (1.0 [95% CI, 0.6-1.4] nmol × [min × mg protein]?1 vs 2.3 [95% CI, 1.7-2.9] nmol × [min × mg protein]?1, respectively; P = .01). Children with autism had higher mitochondrial rates of hydrogen peroxide production compared with controls (0.34 [95% CI, 0.26-0.42] nmol × [min × mg of protein]?1 vs 0.16 [95% CI, 0.12-0.20] nmol × [min × mg protein]?1 by complex III; P = .02). Mitochondrial DNA overreplication was found in 5 cases (mean ratio of mtDNA to nuclear DNA: 239 [95% CI, 217-239] vs 179 [95% CI, 165-193] in controls; P = 10?4). Deletions at the segment of cytochrome b were observed in 2 cases (ratio of cytochrome b to ND1: 0.80 [95% CI, 0.68-0.92] vs 0.99 [95% CI, 0.93-1.05] for controls; P = .01).

Conclusion In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than typically developing children.

As the abstract states, the MIND Institute study methodology involved: “Mitochondrial dysfunction and mtDNA abnormalities were evaluated in lymphocytes from 10 children with autism and 10 controls”. Lymphocytes (a type of white blood cell). Children were concecutively recruited and genetically unrelated. Mitochondrial function was tested first, and given the results seen, children were brought back for a second blood draw where mitochondrial DNA (mDNA) and nuclear DNA (nDNA) were examined.

As shown in the figure below, they found that the autistic children had different mitochondrial activity levels than their controls. Note that “low” activity is not referenced to any standardized norms, but to the 10 control children.

They also performed genetic testing. Table 3 from the paper is reproduced below:

They show that, by their methodology, 7 of their 10 autistic kids have some form of genetic signature for mitochondrial dysfunction. 2 of 10 of their controls meet their criteria as well.

The Simons blog quotes the study author, Prof. Giulivi on this choice:

“Lymphocytes do not rely as heavily on mitochondria as the brain does,” she says, “so if this is happening in cells that don’t use mitochondria as much, it’s likely to be happening in cells that rely more heavily on mitochondria, like neurons.”

They also quote Dr. Fernando Scaglia, of the Baylor Clinic:

However, the unconventional decision to use lymphocytes should have been validated, says Fernando Scaglia, associate professor of molecular and human genetics at Baylor College of Medicine in Houston. “I’m not saying that studies done in lymphocytes are useless,” says Scaglia, an expert in inherited metabolic disease. “But they should be validated in other tissue.”

and Prof. Gargas of the University of California at Irvine:

“Lymphocytes are fine to study chromosomal DNA, but they are a horrible source for studying mitochondrial DNA,” he says.

Cells have hundreds of mitochondria, each with multiple copies of the DNA. In people with mitochondrial disease, some cells have healthy DNA and others have the mutated copies, he notes. In a blood sample, defective lymphoctyes tend to get lost among rapidly proliferating healthy cells.

“The best source for studying mitochondria are post-mitotic cells such as muscle,” he says. “That way you are sampling the set of cells the child was born with.”

In the end, if we stick to the idea that this is a very preliminary report and relies on a new unproven methodology at that, we can consider the study as posing interesting questions. Is mitochondrial dysfunction more prevalent in autistics than the general population? Are there ways to test this in a faster, less intrusive manner than is often used? If we take this study in context, there may be some value. Unfortunately as Seth Mnookin has already pointed out, this study has already been used to promote ideas that are clearly outside of the study and conclusions. This is the unfortunate world of autism research: it is hard for people to push the boundaries and risk being wrong. Not because it may cause the researchers some embarrassment, but because there are a multitude of people waiting to misuse information and mislead.

Commentary on Mitochondrial Dysfunction in Autism

22 Dec

I recently wrote about the paper Mitochondrial Dysfunction in Autism by the MIND Institute. It is difficult to write about the topic of mitochondrial dysfunction and mitochondrial disorders and autism without discussing vaccines. Even the Simons Foundation blog mentioned vaccines in their treatment of the paper, even though the paper makes no comments about vaccines.

Why? Because the case of Hannah Poling and, especially, the way David Kirby presented it to the public has linked autism–mitochondrial dysfunction–vaccines into one neat package. With posts like “NEW STUDY – “Mitochondrial Autism” is Real; Vaccine Triggers Cannot Be Ruled Out” and “The Vaccine-Autism Story: Trust Your Government, or Be a Patriot and Get on Google”. In the latter post he wrote:

“Google “autism and mitochondria,” (96,900 hits) and then Google “mercury and mitochondria,” (169,000 hits) and draw your own, informed conclusions. “

It was very much in David Kirby’s style. Don’t come out and say something directly (like, “mercury is the cause of mitochondrial disease”) but lead the reader along with a series of, well, leading statements.

A more responsible approach would be that one needn’t trust the government nor seek advice on google. A more responsible approach for Mr. Kirby would be to suggest that perhaps, just perhaps, parents of autistic kids should seek out the advice of experts in mitochondrial medicine. Mr. Kirby clearly had an agenda, and it wasn’t the well being of autistics. He was promoting the idea that vaccines caused an autism epidemic.

Mr. Kirby thankfully appears to have moved on from focusing his attention on promoting the vaccine-autism hypotheses. And yet, there is obviously a hunger amongst his old readers for this discussion. This can be seen in Mark Hyman’s blog post at the Huffington Post, “Autism Research: Breakthrough Discovery on the Causes of Autism” which has nearly 1,900 comments. Where David Kirby was promoting himself and the interests of groups like SafeMinds and Generation Rescue, Dr. Hyman uses the MIND Institute paper to promote himself and his own business.

What is worse is the way he goes about doing this. Dr. Hyman is even less capable of covering his obvious mistakes than was David Kirby.

Dr. Hyman writes:

While we don’t have all the answers, and more research is needed to identify and validate the causes and treatment of autism, there are new signs of hope. A study just published in The Journal of the American Medical Association by researchers from the University of California, Davis called “Mitochondrial Dysfunction in Autism” (i) discovered a profound and serious biological underpinning of autism — an acquired loss of the ability to produce energy in the cells, damage to mitochondria (the energy factories in your cells), and an increase in oxidative stress (the same chemical reaction that causes cars to rust, apples to turn brown, fat to become rancid, and skin to wrinkle). These disturbances in energy metabolism were not due to genetic mutations, which is often seen in mitochondrial problems, but a condition the children studied acquired in utero or after birth.

The statement is amazing. Not in a good way. It is amazing that someone could write such an irresponsible paragraph and attribute it to a paper which clearly doesn’t make or support these claims.

The very title of Dr. Hyman’s post (Autism Research: Breakthrough Discovery on the Causes of Autism) is in error. The study makes no claims about the causes of autism. Dr. Hyman didn’t have to look any farther than the paper itself which clearly states as one of the limitations:

Sixth, inferences about a cause and effect association between mitochondrial dysfunction and typical autism cannot be made in a cross-sectional study.

Given this, we can also throw out Dr. Hyman’s wild claim that the study’s authors “discovered a profound and serious biological underpinning of autism”.

Since it is already clear that Dr. Hyman is using the paper to promote his own ideas, regardless of the facts in the paper, I won’t posit as to why he claims that the mitochondrial dysfunction is “acquired”, or that this is due to “damage” to mitochondria. The paper does not support either of these conclusions as fact.

He makes the claim that “These disturbances in energy metabolism were not due to genetic mutations, which is often seen in mitochondrial problems, but a condition the children studied acquired in utero or after birth.”

I am unsure how Dr. Hyman reached this conclusion. The paper notes differences in the mtDNA of many of the children studied. It does not provide evidence as to when or how these genetic differences arose.

Table 3 clearly shows the genetic measures the MIND Institute researchers used. Question the method as you may (or some experts have), there are differences in the mtDNA. The methodology doesn’t allow one to state if these difference were present at birth or not.

The MIND Institute hosts an interview with Prof. Giulivi
At about 3:30 into Prof. Giulivi’s interview, she states clearly that they can not conclude if the mitochondrial dysfunction they claim causes autism or is a result of it.

It is hard for me to decide if Dr. Hyman is more irresponsible than David Kirby or if it is the other way around. David Kirby was certainly doing some self promotion, but his impact was largely as a publicist for the autism-as-vaccine-injury groups like SafeMinds and Generation Rescue. Dr. Hyman is clearly focused on promoting his own services as a practitioner of alternative medicine.

The problem is that in the end, rather than being a leader in treatment, as Dr. Hyman presents himself, such irresponsible actions hinder advancement.

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