Featured Content:
Featured Categories:
Lyme Disease
Diagnosis
GF/CF pecan pie
Development
The hardest hit
Home Education for Autism
Autism Advocacy
Science
Education
Diet
Health
Autism
Latest Content:
Neuroborreliosis
Neuroborreliosis refers to the Lyme infection of the nervous system. The Lyme spirochetes actively invade the cerebrospinal fluid (CSF), the meninges, and the brain shortly after infection. The severity of the symptoms that occurs following the Central Nervous System (CNS) infection depends on the health of the individuals, particularly the immune system. CNS complications in neuroborreliosis generally involve an inflammation initiated by the Lyme spirochete.
There is a growing interest in the possibility that some children diagnosed with autism could in fact have a diagnosis of Lyme disease. You only need to google Lyme and Autism to see numerous entries on the subject.
I will flag a few links of interest here:
Is there a connection between Lyme and autism?
Doctors find link between Lyme disease and autism
Additionally please take a look at a leaflet made by the International Lyme and Associated Disease Society ILADS- Psychiatric Lyme Disease: What psychiatrists should know about Lyme. The leaflet can be seen here:
What I would like to stress is that autism has previously been linked to a number of infections, Herpes, Measles, Mycoplasma for example. Fundamentally speaking, whether it is caused by one pathogen or another is not very different. In fact post-mortem brain Lyme Borreliosis resembles very much the images obtained from post-mortem autistic brain samples. There is wide spread microglial activation, indicative of brain inflammation. To view some pictures of Neuroborreliosis brain you can download the Miklossy et al 2008 paper here, or alternatively view Figure 4 here, I will at a later stage review the literature concerning some autism post-mortem brain studies.
We can very well have a scenario in which the brain will be affected both through direct infection and through indirect inflammatory processes. One could even push this scenario further by saying that the inflammation might not even resides primarily in the brain to cause brain dysfunction, but instead anywhere in the periphery, in the digestive system for example. After all, it is well known that the brain, the hippocampus in particular is sensitive to an immune deregulation. The brain must have this sensitivity in order to control the beahviour of a living organism, to respond more effectively to the immune challenge. It is very possible that with such a scenario, autism is unique in its presentation due to the developmental stage during which the organism is affected.
Autism
When my little boy lost his ability to speak at the age of 6 years old, becoming withdrawn within 2 weeks, unable to function at school, being overwhelmed in most public settings, he received, plugged out of the air, the magical diagnosis of autism. This was based on 10 min observation in school conducted by an autism expert. That is all what he received. No investigations were made. My son was autistic and an alternative school placement with other autistic children was given in compensation. The novel symptoms he presented with, his great health fragility, the sudden development of his epilepsy, which progressively worsened over the years, his gut problems, his immune impairment, nothing received any kind of attention, unless I forcefully requested for some tests to be done, mostly unsuccessfully. We had a brand new label and there was no question to ask about this. Asking questions was seen as being a difficult parent.
Unfortunately, his case is not unique. Nearly 6 years later, I am working to assist other parents to access to the medical investigations my son should have received minute one after becoming unwell. I can report that in a group of 400 children seen at the Autism Treatment Trust in Edinburgh, 60% present with similar sudden regression and occurrence of novel autistic behaviours. Whilst many have experienced this regression around the age of 18 months, other children become affected in later years, at the age of 2, 3, 4, 6, 8 or even 9, years old. Christopher Gillberg has reported other cases of regression in autism at age 14, 30 and 31 years old (Gillberg 1991,Gillberg 1986 ). The difference in these cases, was that Prof. Gillberg had the genuine interest to investigate the cause of their novel behavioural traits right at the onset of their regression. And what he found was in all 3 cases reported was viral herpes encephalitis. A condition that is reversible because Herpes can be treated with anti-viral drugs. Did these people really have autism? No, they had viral encephalitis. Not autism. Christopher Gillberg has reviewed in his book, the Biology of the Autism Syndromes, coauthors with Dr. Mary Coleman the many genetic, environmental, viral, metabolic conditions that come with the features of autism. Are these conditions really autism? How could a condition come with so many different unrelated etiologies? Does autism actually exist?
To make matter worse still, we have some individuals who suddenly decide on day, that they are also autistic, most notoriously Donna Williams, whom I had the opportunity to meet in Edinburgh last Sept 08. Donna Williams was to me a very puzzling character right from the outset, though I must acknowledge that the concerns over her diagnosis were raised to me by others. But indeed there seems to be a great inconsistency with the symptoms she was reporting to experience and her ability to discuss and report them. Something that is rather hard for people with autism to actually do. A very demonstrative set of investigations questioning the validity of her diagnosis can be found here. I have since met other adults who also claim a diagnosis of autism, and present with similar puzzling social and emotional abilities very uncommonly seen in autism.
Michael Fitzgerald (in his book the Genesis of Artistic Creativity) and others have argued that many notorious historical figures, such as Beethoven, Handel, Van Gogh were also autistic. Equally scientists such as Einstein, T. Edison have also been presented as being autistic. But are these retrospective diagnoses a myth or a reality?
So Autism: What the hell is that about?
I am calling for the support of parents and professionals to request that proper medical and psychological investigations are conducted on all children receiving a diagnosis of autism today. Autism as defined by Kanner in 1943 is a different condition than the ones we see today in as many as 1 child in 100. To conveniently hide the true reality of the problem with an incorrect diagnosis of autism is an hypocrisy that can only delay the urgent need we have to deal appropriately with the issues.
Treating Lyme with antibiotics
Somehow I reverted again to a traditional approach to treating disease: Lyme is a spirochete bacteria, therefore we must treat it by killing it with antibiotics. I knew though there were challenges ahead of us, because the spirochete exists in three different stages (Spirochete, cyst, and spirochete colonies), is intracellular, evade the immune system, has the ability to mutate, and can affect essentially any organ. For a microscopic view of this pathogen in human brain samples of Lyme neuroborreliosis and in vitro culture of chicken and rat neurons as well as rat and human astrocytes, please check this paper from Miklossy et al. 2008 (see illustrative figures 1-4). The different forms which this pathogen can adopt require the use of several antibiotics simultaneously. The Cyst form in particular is most resistant. Ninety-five percent of Lyme spirochete can encyst within one minute and remain viable for up to 10 months, survive several cycles of freezing and thawing. Reconversion to motile can occur rapidly within one hour given the right conditions. The cysts survive quite happily in the digestive system from which they can spread throughout the body.
Figure: 1: Characteristic morphology of Borrelia burgdorferi (Dark field microscopy images of Borrelia burgdorferi strain B31 showing the usual spiral form of spirochetes (A) and their agglomeration into colony-like masses (B)
Figure 2: Rolled and cystic forms of Borrelia burgdoferi spirochetes observed after one week of culture in medium to which Thioflavin S had been added.
F-H: Atomic force microscopy (AFM) images of Borrelia cysts. Rolled spirochetes are clearly visible in F (strain B31) and G (strain ADB1). Arrow in G shows that the cyst is formed by two spirochetes rolled together. H: The cystic form is entirely covered by a thickened external membrane masking the content of the cyst (strain B31).
Figure 3: Atypical and cystic Borrelia forms following 1 week exposure of primary neuronal and astrocytic cultures to Borrelia burgdorferi. C: OspA positive Borrelia spirochetes closely surrounding neurons (strain B31). D: Atypical filamentous and ring-shaped cystic, apparently intra-cellular spirochetes in a neuron (strain B31).
Figure 4: Chronic neuroinflammation in the frontal cortex of a patient with Lyme neuroborreliosis. First column (A, D and G): Accumulation of HLA-DR (A) and CD68 (D) immunoreactive microglia forming clumps, and GFAP (G) positive large reactive astrocytes in the frontal cortex of a patient with Lyme neuroborreliosis.
A further complexity related to the fact that my son’s health is extremely fragile and that he is very prone to seizure, especially following an immune challenge. Treating Lyme with antibiotics is known to cause a Heirxheimer reaction, which is essentially equivalent to an increased release of bacterial toxins, with inflammatory consequences. This is very similar to the Lipopolysaccharide (LPS) model of rheumatoid arthritis caused by injection of collagen molecules followed by LPS injection. LPS are molecules found in the outer membrane of Gramm negative bacteria. They acts as potent endotoxins leading to the secretion of pro-inflammatory cytokines and Nitric Oxide. They will cause an endotoxic shock, increasing the auto-immune response to collagen. What happens during antibiotic use is very similar. There is an acute release of a wide range of bacterial endotoxins which drain the immune system, pushing it towards inflammatory stress and potentially auto-immune response. Causing such reaction is a challenge to affected individuals. The reaction is notoriously severe with people describing all the symptoms returning all together concentrated during the reaction. The problem is in the case of my son, that it causes him an increase in epilepsy. Each time his symptoms are clear unwellness, epilepsy, raised lymphocyte count and fever. I have not yet managed to control this reaction (see separate section on Heirxheimer).
We have tried many antibiotics, azythromycin, doxycyclin, Zinnate, Ciflox, Flagyl, Bactrim, Rifampicin, Bactrim, minocyclin and ceftriaxone i.v. Ceftriaxone is the antibiotic that appears to lead to immediate benefits, however, within 10 days of treatment, my son was too unwell with epilepsy to continue. Ceftriaxone is thought to have the best penetrance in the Central Nervous System (CNS), however, it does not work on all the Lyme stages. It has also anti-inflammatory function, which was making this antibiotic a prime candidate. The second best choice was minocycline, again because of CNS penetrance and anti-inflammatory properties.
I am not sure if it makes a great deal of sense to detail the treatments proposed, but for the sake of illustration, I will show what has been suggested to us. However, as I said, we have not managed to do this for more than a few weeks in total and not for any longer than 2 weeks without interruption.
An alternative protocol (oral antibiotics only) was proposed:
I might consider these treatments again, but for now, I feel a much more gentle approach is required. This is where I started to investigate the potential use of plants. The information compiled below come from reading Healing Lyme and also looking at some protocols written by Dr. Klinghadt.
Lyme Disease
Introduction: Realising that medicine does not have all the answers
A lot has already been written about Lyme Disease, so I will avoid repeating, focusing instead on our own experience: symptoms, diagnosis, treatments, failures, hopes, doubts, and other emotions that flow throughout the process.
To step back in time though and in ways of introduction, let me explain that I started my quest in science as a student, holding a very naive view of what it was about. I thought science’s main purpose was to solve problems, mysteries and focus on making people’s life better, either through providing greater knowledge, or by directly alleviating people’s suffering. I thought, science was above vile, it was the closest to truth, that it was immune of jealousy, greediness, manipulation and corruption. I soon realised as a student working in the HIV field, that science was no different than any other area of human activity; there was some good about it yes, but there was also a lot of less good. Essentially, all too often research was directly driven by the funding opportunities which in turn were directly related to market values. Market values are not driven by knowledge or greater good, they are only driven by whether or not they can generate an economy.
It is one thing to come to realise this as a student and fumble in the hope that this would come to make greater sense one day, that somehow there would be ways to reconcile all the conflicting views and bypass the unethical influences. But it is yet another thing, a far worse realisation still, to appreciate that these great limitations had a direct impact on the health of our children. Hitting a brick wall was exactly how it felt, when I ask for support in understanding why my son was sick. I only received in response, preconception, further misunderstanding, and arrogance. To put it bluntly, traditional medicine could not care less for what we were experiencing. In a way, it was as if this was outside their remit. They had made hastily their diagnosis, Autism, and there was nothing to do about. The least they would hear from us, the happier they were. We were actively discouraged to look for answers, arguing that one day, I should come to term with the fact that my son was disabled and that in many ways, I should feel grateful that he was not more affected, as some unfortunate children can indeed be. Was I going to settle with these views?
I later came to appreciate that traditional medicine can deal with simple health issues, most acute problems in fact can be addressed effectively (appendicitis, bone fracture, classic infections and so on). However, the situation is very different when it comes to a range of chronic and pervasive conditions, especially as I came to realise, when brain function and behaviour are affected. I had also realised, ages ago in fact, that medicine particularly was incredibly compartmentalised. Each consultant having some understanding within their own field of expertise but having little understanding or even appreciation of how other organs, physiology, body function influence their own system. Isn’t it obvious though that biology is all about integration and most health problems, especially if chronic, are about deregulating this integration?
Dr. Stephen Buhner in his book “Healing Lyme” describes western medicine as technological medicine, stating that they are rather blunt. “They are concerns with kill (antibacterial), remove (surgery), reduce pain (opiates or the equivalent), reduce inflammation (corticosteroids), or force it to do what you want (hypotensives and so one). Subtle understanding of the complexity of physiological interactions and knowledge of how to enhance the response of the body to disease are underdeveloped. “
So, no the diagnosis of Autism was not the correct answer: It was absolutely not explaining my son’s developmental history and it was not explaining his symptoms either.
Related sections:
A more accurate diagnosis: Lyme Disease
Treating Lyme
Diagnosis
A more accurate diagnosis: Lyme Disease
A much more relevant diagnosis was found much later, in fact 9 years after my son’s initial regression: Lyme’s. This diagnosis was not found by our NHS consultants, as I said earlier, as far as they were concerned, our case was closed. In despair, I had returned to France, hoping that I would get more answers from a series of lab tests conducted by Prof. Montagnier, following the advice of Dr. Skorupka. Other tests were made on the same day, as well as an electro-encephalogram (EEG). The other tests did not show any particular relevant information, though the EEG, showed a classic low frequency wave (theta activity 4-7Hz, regular, widely spread over the whole scalp area, bilateral and symetrical), without epileptic activity which was interpreted in a different light than the one I was used to in the UK. I will discuss this in another section on this web site.
The presence of Borrelia burgdorferi was initially detected by Polymerase Chain Reaction (PCR). Now, let me tell you a little more about this method of detection as I have come to understand that there is a lot of misunderstanding about what this technique is about, even from medical doctors themselves. For those who want to skip the explanation on PCR skip to Confirmation of the initial diagnosis below.
PCR allows the detection of genomic material, either RNA (with a prior step of reverse transcription) or DNA, using a set of primers specific to the target DNA sequence. Primers are short oligonucleotide sequences of 10-25 base pairs that will specifically hybridize (bind) to the target DNA sequence, by complementary base pairing. The primers are then extended by the DNA polymerase in the presence of nucleotides. This cycle is repeated several times, 30-50 times depending on the conditions, in order to generate sufficient amplification for detection. The band is then analysed on a gel by electrophoresis to compare its size to DNA markers. The size is initially used as way of identifying the product and confirming its identity, but often the amplified product is further analysed for example by enzyme restriction digest (using an enzymes that is expected to cut the target at specific sequences leading to the expected digestion products according to their size), or by cloning and sequencing.
There are several potential artefacts to a PCR. One is that the product obtained can be a contamination, leading to a false positive result. This is in fact something that is extremely common in labs. The reason is that a PCR is really sensitive and can pick up minutes amounts of DNA. If the target DNA is around in the lab, which is the case as prior PCR have been performed, either as ongoing testing or to establish the assay, the chances are very high that other reaction tubes could get contaminated. Good laboratory practice requires that absolute care is being taken when performing a PCR assay. Generally you work with gloves, filtered tips (to avoid contamination from the pipette), under a hood, with absolutely clean reagents and material. You also use water as control (No DNA control), and it should remain totally clear of any amplification if there is no contamination. With practice, you can get a very good sense of whether or not the results come from a contamination or are genuine. Repeating the assay and finding the same pattern or positive and negative products should also confirm that the results. In short, if no proper care is taken, a PCR can give rise to false positive results.
The second type of problem is that the PCR can be negative, either because the assay is not working reliably (primers or detection of very low target number), or because the biological sample from which the assay is ran does not contain the target. We have to keep this in mind, that the body is complex. Often we only have access to blood sample to run a PCR, if the blood does not contain any material, because say for example the pathogen is not found in the blood, then the PCR will be negative. Regarding the detection of Lyme’s pathogen, it has been estimated that only 25% of the cases (who have developed a classic erythema migrans rash together with the symptoms of the disease) are positive by PCR. This indicates that indeed the spirochete genomic material is rarely present in blood sample, so a negative PCR result does not rule out an infection.
A further clarification I wish to make is that even though PCR can detect trace amounts of genomic material, it does not mean that the result is benign in terms of its significance. The genomic material of Borrelia burgdorferi should not be present in people, full stop. If it is, even if it is at low level, it indicates an earlier infection. And this is sufficient to demonstrate Lyme disease.
Now having explained all of this, the results we initially obtained indicated a positive result, which was confirmed 3 times. The PCR product was sequenced and its identity: Borrelia burgdorferi was confirmed by its sequence.
I felt none the less that it was important to confirm this result with further independent testing.
Confirmation of the initial diagnosis
The confirmation was made using a test called Borrelia burgdorferi (Bb) Elispot LTT. Basically a blood sample was placed in presence of Bb full antigen, a Bb peptide mix or Bb LFA-1 (LFA-1 stands for Leukocyte function-associated antigen 1- and it refers to the immunodominant epitote of Outer Surface Protein A (Ospa). This epitope is similar to human LFA-1, which leads to possible auto-immune reaction). This Elispot measures the release of interferon gamma by reacative lymphocytes. It is a test of T-cellulal immune response. If the organism has not been in prior contact with a given antigen, there will be no reactivity. These tests were conducted at the Borreliose Centrum Augsburg in Germany.
The test showed:
Borrelia burgdorferi Elispot LTT
Borrelia Full Antigen + 4 SI < 2
Borrelia Peptide Mix + 3 SI < 2
Borrelia LFA-1 2 SI < 2
The results of the Elispot-Lymphocyte-Transformation-Tests are an indication for an actual cellular activity against Borrelia burgdorferi.
There was also measurement of IgM and IgG against Bb by immunoblot. This is a test that is known to frequently be negative because the host immune system is not easily capable of developing an humoral (antibody-mediated) immune response against this pathogen. The results were indeed negative.
Borrelia burgdorferi antibodies (immunoblot)
Borrelia-Blot-IgG-antibodies negative negative|
Borrelia-Blot-IgM-antibodies negative negative
Further, a CD 57 (Natural Killer cell- type 1) flow cytometry was performed and showed the typical immune suppression of NK-1 (CD57) cell count seen in Lyme disease.
CD 57 Flow Cytometry
Leucocytes 6.41 /ul 2.6-10.0
Peripheral Lymphocytes 49.1 % 18.0-51.0
Lymphocytes 3147 /μl 468-5100
Natural killer cells 9.54 % 6-29
Natural killer cells 300 /μl 60-700
CD 57 positive NK-cells 3.02 % 2-77
CD 57 positive NK-cells – 95 /μl 100-360
The CD57-cell-count is an indication for a chronic immune-suppressive situation caused by Borrelia burgdorferi.
Other co-infections were also screened for as a tick bite can also transmit other pathogen, Ehrlichia was borderline positive whilst none of the other pathogens were found.
Ehrlichia Elispot LTT
Ehrlichia-Elispot LTT 2 SI < 2
The result of the Elispot-Lymphocyte-Transformation-Test is an indication for a borderline actual cellular activity against Ehrlichia.
Yersinia antibodies
Yersinia-IgA-antibodies (immunoblot) negative negative
Yersinia-IgG-antibodies (immunoblot) negative negative
The specific Yersinia-IgA- and –IgG-antibodies are no indication for a humoral immuneresponse against Yersinia spp.
Bartonella antibodies
Bartonella henselae-IgG-IFT < 1:320 Titer < 1:320
Bartonella quintana-IgG-IFT < 1:320 Titer < 1:320
Serological no evidence for an infection with Bartonella henselae or Bartonella quintana.
Babesia divergens antibodies
Babesia divergens-IgG-antibodies < 1:16 < 1:16
No serological evidence for an infection with Babesia divergens.
Toxoplasma gondii antibodies
Toxoplasma gondii-IgG-antibodies 0.3 IE/ml < 1.60
Toxoplasma gondii-IgM-antibodies negative negative
No serological evidence for an infection with Toxoplasma gondii.
Anaplasma phagocytophilum antibodies
Anaplasma phagocytophilum < 1:64 < 1:64
IgG-antibodies
Anaplasma phagocytophilum < 1:20 < 1:20
IgM-antibodies
No serological evidence for an infection with Anaplasma.
The presence of auto-antibodies was also assessed. No antinuclear antibodies were detected.
ANA (EIA) 0.07 Ratio < 1.0
Included are auto-antibodies (IgG) against the following antigens: Chromatin (dsDNA,
Histones), Sm/RNP, SS-A, SS-B, Scl-70, Centromer, PCNA, Jo-1, Mitochondria (M-2),
Ribosomes, nuclear extracts.
There is no evidence for antinuclear antibodies.
Together with the symptoms presentation, these results indicate conclusively a Lyme diagnosis.
I would like to take this opportunity to thank Dr. Skorupka, Prof Montagnier, Dr. Nicolaus, Dr. Schwarzbach and the wonder staff at the BCA.
Recent Comments