SCHAFER AUTISM REPORT "Healing Autism:

No Finer a Cause on the Planet"

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July 1, 2002 CALENDAR LISTING: EVENTS@doitnow.com

** Publication note: some readers report not receiving their Monday,

July 1, edition of this newsletter, so it is being reissued here.

PUBLIC HEALTH

* Measles Increasing As British Forego Inoculations

* UK Babies Given Toxic Vaccines, Admits Drug Co. Glaxo

* Lancet Editorial: MMR Vax, Ileal Lymphoid Nodular Hyperplasia, & PDD

* Lancet Letters: Autism, Bowel Inflammation, And Measles

On the Building Autism MMR Vaccine Controversy

RESEARCH

* Serological Detection of Measles Virus in Relation to Autoimmunity

in Autism

* Hydrogen Proton Magnetic Resonance Spectroscopy In Autism

* Serotonin PET Scan, Half-Side Paralysis & Neurodevelopmental Delay

* Munchausen by Proxy in an International Context

Measles Increasing As British Forego Inoculations

Controversy Keeps Heating Up in the UK

London - Health chiefs reported Saturday that the number of measles cases have risen dramatically in the first three months of this year in Britain, where parental fears over vaccination has lead to a drop in childhood inoculations.

There were 126 confirmed cases of measles in England and Wales from January to the end of March 2002, compared with only 32 cases in the last quarter of 2001, the Public Health Laboratory Service said.

The steep increase was the result of a single outbreak linked to several nurseries and schools in south London which flared up early this year and has now died down.

Use of the controversial combined measles, mumps and rubella vaccine in London remains lower than in any other region of Britain, the report said, despite government efforts to promote vaccination.

The health agency said 35 of 50 cases in London involved children aged under five who were not vaccinated.

By February of this year, MMR immunization in British 2-year-olds had dropped to a record low of 84 percent, well below the 95 percent specialists say is needed to prevent measles from returning.

The measles, mumps and rubella inoculation is required in 90 other countries.

The fears in Britain appear to be the result of a surge of publicity about one doctor's concerns about the safety of the triple inoculation.

A 1998 British study contended the vaccine could be linked to autism, a severe neurological disorder usually diagnosed around the age of 2 - the same age that the vaccine is given.

Since that study, several authoritative groups of international scientists have examined the evidence - including a panel that reviewed five decades of research on the vaccine's side effects - and concluded there is no evidence of a connection.

However, many parents remain unconvinced and health authorities fear a measles comeback.

The strain of measles that hit the capital is common in Thailand and other southeast Asian countries, but until this year had been very rare in Britain.

* * *

UK Babies Given Toxic Vaccines, Admits Drug Co. Glaxo

British drug giant GlaxoSmithKline has finally admitted that thousands of babies in this country were inoculated with a batch of toxic whooping cough vaccines in the 1970s.

Some experts believe that these Trivax vaccines - which had not passed critical company safety tests - may have caused permanent brain damage and even fatalities in young children.

In 1992, the family of an Irish boy, Kenneth Best, who suffered brain damage from one of these toxic vaccines, was awarded £2.7 million in compensation by the Irish Supreme Court.

Despite a long and fierce battle with the drug giant, the boy's family finally won this historic case after his mother Margaret made a startling find when sifting through tens of thousands of company documents.

She discovered that the Trivax vaccine used on her son, from a batch numbered 3,741, had been released by the company despite it having failed to pass a critical safety test. Documents revealed that the 60,000 individual doses within this batch were known to be 14 times more potent than normal.

At the time the Irish judge accused GlaxoSmithKline - then known as Glaxo Wellcome - of negligence and attacked the company's poor quality control at its Kent laboratory. Immunology experts condemned Glaxo in court for what one US scientist described as an 'extraordinary event'.

Last year an investigation by The Observer found evidence to suggest that vaccines from this faulty batch, which may have wrecked Kenneth Best's life, had also been used in Britain.

Liberal Democrat MP Norman Baker raised questions in the House of Commons, asking whether vaccines from this batch had been given to British babies.

Then Health Minister Yvette Cooper wrote to the company asking for information.

Now, almost a year later, GlaxoSmithKline has replied that it is 'highly probable' the toxic batches had been used in Britain. The Department of Health is under pressure to make efforts to trace the children who received the suspect vaccines.

Last week in the House of Commons, Health Minister Hazel Blears said: 'Unfortunately they no longer have details of the quantitites of vaccine or the places where the vaccine was supplied.

'Since vaccines were not centrally purchased and distributed at that time there are no central records either. Information on individuals who received these vaccines will only exist if the general practioner at the time of the immunisation recorded the batch number and the patient's notes are still available.' Baker will now write to the Minister to demand that she asks health authorities to check the records to find out who received the vaccine. It is believed that at least one boy from Wales died after receiving a jab from toxic batch 3,741, although the parents have never been informed.

A spokesman for GlaxoSmithKline told The Observer : 'We do not accept that these batches were harmful.'

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MMR Vax, Ileal Lymphoid Nodular Hyperplasia, & Perv. Developmental Disorder

_and_review.21444.1

Pervasive developmental disorder (PDD) is an umbrella term used to describe a group of disorders, including autistic disorder, which involve delayed development of communication and social-interaction skills and particular behavioural abnormalities.1 Although both genetic factors and environmental insults have been implicated in the pathogenesis of PDD, the underlying causes remain poorly understood. Some children with PDD present with regression in abilities at age 1-2 years, which has raised concern about environmental exposure during this period. An atypical immune response to measles-mumps-rubella (MMR) vaccine has been suggested as a possible precipitating factor.2,3 Due to the potentially serious public-health implications, this hypothesis has evoked considerable debate, including US congressional hearings. Moreover, organisations including the WHO and the American Academy of Pediatrics have issued statements on this issue.4-7 The widely-held conclusion is that available data do not support a link between MMR vaccine and PDD.

Andrew Wakefield and colleagues have raised the possibility that a subset of children with PDD, particularly those with a history of developmental regression and chronic gastrointestinal symptoms, have a dysregulated immune response to measles antigen associated with intestinal abnormalities.2,3,8 In 1998 Wakefield's group reported on a group of children with PDD and other psychiatric and neurological disorders referred to a gastroenterology clinic for evaluation of a range of chronic gastrointestinal symptoms, including abdominal pain, bloating, and diarrhoea.3 12 children were evaluated, and, strikingly, 11 had ileal lymphoid hyperplasia without granulomas.3 A subsequent study by this group noted ileal lymphoid nodular hyperplasia in 93% of affected children compared with 14% of control children.2 A possible link between ileal lymphoid nodular hyperplasia and MMR vaccination was suggested in these reports based on a temporal association between the administration of vaccine and the onset of symptoms in many cases.2,3 A potentially important sample bias in these investigations is that patients were identified because of referral to a gastroenterology clinic. Of interest would be evaluation of PDD patients with and without gastrointestinal symptoms to determine if features such as a history of developmental regression are more common among those patients with PDD found to have ileal lymphoid nodular hyperplasia.

In a new report by V Uhlmann and colleagues (including Wakefield), intestinal tissues of children with PDD and histologically confirmed ileal lymphoid nodular hyperplasia were assessed.8 Using RT-PCR the investigators identified fragments of measles-virus nucleocapsid fusion-protein, and haemaglutinin DNA in 75 of the 91 study subjects.8 By contrast, RT-PCR for measles virus DNA was positive in only 5 of 70 patients in a heterogeneous control group. Hybridisation of PCR products with probes to fusion protein and haemaglutinin DNA was demonstrated in 4 of the 75 patients, but sequence specificity was not confirmed in any case. Results such as these must be interpreted with caution. For example, amplification of human DNA sequences by papillomavirus primers has been reported, leading to the development of methods for verifying the identity of PCR products.9,10 Nonetheless, even if measles virus DNA is assumed to be present in the tissues evaluated, the significance of the observation remains debatable.

Similar studies have reported detection of viruses, including herpesvirus DNA11 and measles virus DNA,12,13 in diseases that also manifest intestinal lymphoid hyperplasia, such as ulcerative colitis and Crohn's disease. Thus the clinical importance of finding sequences of measles nucleic acid in patients with PDD and ileal lymphoid hyperplasia is unclear. One attractive alternative explanation is that lymphoid hyperplasia is associated with the presence of increased amounts of many antigens and DNA sequences with resultant increases in the detection of cross-reacting antigens and DNA sequences. Consistent with this hypothesis, a measles-virus-related antigen, which is derived from host rather than viral protein, has been reported in patients with a broad spectrum of colitides.14 Wakefield and co-workers have suggested that the pattern of normal behavioural development followed by regression shortly after measles vaccination leading to the diagnosis of PDD is particularly meaningful.2,3,8 However, one study has reported that the age at which parents first noticed symptoms was no different for autistic children with or without a history of regression.15 In addition, age of presentation was no different in a sample of autistic children before and after MMR vaccine was introduced.15 The frequency of gastrointestinal complaints seemed similar among autistic children with or without a history of regression.15 In view of the close temporal association between the age at which MMR vaccine is given and the age at which symptoms typically are recognised in children with PDD, the chance occurrence of cases where MMR vaccination immediately precedes the presentation of PDD is predictable.

Although the causes of PDD are likely to be heterogeneous, the overlap in symptoms among different PDD diagnoses suggests shared underlying factors. In addition, the commonality of some neurotransmitters to the brain and intestine (such as vasoactive intestinal peptide), plus the observation of altered secretin-stimulation responses in PDD patients,16 indicates that a disturbance of the brain-gut axis in PDD patients is biologically plausible. Although far from universal, gastrointestinal complaints appear to be increased among children with PDD compared with the general population.16 Nonetheless, the intestinal complaints of these children are often not investigated by endoscopy, so the existence of a distinct variant of inflammatory bowel disease among children with PDD may not be widely appreciated.

Thus the idea of a PDD-associated inflammatory bowel disease deserves further consideration. In support of this hypothesis, Torrente and colleagues (again with Wakefield) have now reported that IgG and complement C1q were found deposited on the basolateral epithelial in duodenal biopsy specimens from 23 of 25 autistic children, but not in specimens from control cases.17 However, at present, conclusions about a causative association between PDD, intestinal disease, and MMR vaccination are speculative.

*Barbara A Hendrickson, Jerrold R Turner

*Section of Pediatric Infectious Diseases and Department of Pathology, University of Chicago, Chicago, IL 60637, USA bhendric@peds.bsd.uchicago.edu bhendric@peds.bsd.uchicago.edu

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Autism, Bowel Inflammation, And Measles: Lancet Letters

On the Building Autism MMR Vaccine Controversy

dence.21380.1 <- -address ends here.

Sir--John Walker-Smith (Feb 23, p 705)1 states that children have been badly served by the adversarial approach involved in the current legal action against manufacturers, but offers no evidence to explain how and why.

It is the children, via their parents, who have started this action, at huge public expense and at no cost to the families. They will not be exposed to costs in the likely event of the case failing.2 By contrast, health service professionals and the manufacturers have to meet their own costs.2 It shows the generosity of our legal system that this action is publicly funded in the absence of published evidence supporting a causal relation between the measles-mumps-rubella (MMR) vaccine, and mounting evidence to the contrary. In the context of a failing National Health Service, is this good use of scarce public monies? Although I have every sympathy for these children, can they be said to be badly served by the litigation system compared with the defendants? Moreover, it is difficult to see what this litigation will achieve apart from enriching lawyers.

Penelope Elphinstone

Ampthill Square Medical Centre, London NW1 1DR, UK 1 Walker-Smith J. Autism, bowel inflammation, and measles. Lancet 2002; 359: 705-06. [Text </journal/vol359/iss9323/full/llan.359.9307.correspondence.20101.1>] 2 Lord Chancellor's department. Access to Justice Act 1999--section II.

Sir--I am a partner in one of the firms of solicitors coordinating claims on behalf of families who believe their children have developed autism as a result of receiving the MMR vaccine. John Walker-Smith1 says that children have been badly served by the adversarial approach involved in the current legal action against manufacturers. I and my colleagues entirely agree.

The present situation has arisen despite our attempts to encourage research of individual cases, not populations. I agree with Walker-Smith's point that much of the criticism of Wakefield's work has been epidemiological. We deal with hundreds of individual accounts of children's health worsening after receiving the MMR vaccine.

In 1996, I was so concerned about what seemed to be happening that I wrote to chairman of the Committee on Safety of Medicines offering to make available the medical records and other information about children who had apparently been affected by the vaccine.

My offer was put to government representatives on three occasions but was turned down. The only concession was that parents would be sent questionnaires about their children's symptoms. In coordination, we and the Department of Health sent out around 1200 questionnaires.

The Department of Health, without referring to us or our clients, set up a working party to look at the families' questionnaires, and questionnaires they later sent to the treating family physicians. They now use the resulting report2 as part of the evidence to support the assertion that the MMR vaccine and autism are not linked. They describe it as involving a detailed assessment of more than 100 children's records referred to them by solicitors, yet the report itself states that it took into account only evidence derived from the parental and medical questionnaires.3 The report's conclusion is that it is impossible to prove or refute the suggested associations between MMR vaccine and autism, pervasive development disorder, or inflammatory bowel disease because of the nature of the information used.

Few would argue with Walker-Smith's sentiments. Those of us who are involved in the litigation are acting only because the families have no other alternative. Clearly, MMR does no harm to most children. The question mark over safety of the MMR vaccine for a minority of children needs proper investigation.

The real issue is that the UK has no adequate vaccine-damage compensation scheme. A one-off payment, currently of UK£100 000, is paid only if parents can prove that their children have been at least 60% disabled by a particular vaccine. No public help is available to enable parents to present their cases to the Vaccine Damage Payments Unit or Tribunal and the autism is not currently acknowledged as an adverse effect of the MMR vaccine. As a consequence, few payments are made.

If the UK Government were to adopt a more helpful scheme, like that in the USA, the issue raised by Walker-Smith would start to be resolved and some common sense could once again be injected into these important public-health issues.

Richard Barr

1 Walker-Smith J. Autism, bowel inflammation, and measles. Lancet 2002; 359: 705-06. [Text </journal/vol359/iss9323/full/llan.359.9307.correspondence.20101.1>]

Sir--John Walker-Smith1 recognises that epidemiological studies have shown that MMR vaccine is safe in most children,2 but he suggests that further non-epidemiological research is required in the subgroup of children who show features of regression and gut disease.

This suggestion follows a report that measles virus genes were present in the intestinal tissue of children who had gut and developmental disorder more frequently than in a comparison group, in which some children had gut disease but all of whom were developmentally normal.2 Walker-Smith suggests that epidemiological methods are too blunt a tool to solve the newly defined question. We strongly disagree with this opinion.

We agree that if Uhlmann and colleagues' findings2 are confirmed, further molecular research is required to address issues such as the origin of the measles virus markers and whether their presence is specific to this type of autism or is present in other gut pathologies. The latter would suggest the persistence of measles virus markers is a result of disease rather than a cause and, therefore, unrelated to autism.

If a small proportion of cases of autism arise because of exposure to MMR vaccine and those cases cannot be distinguished by their clinical or pathological characteristics from all other cases of autism, epidemiological research may not identify or confirm the association. However, such confirmation is not what is being proposed; the key question is whether exposure to MMR vaccine (or other sources of measles virus) is associated with an increased risk of this relatively rare subtype of autism.

Epidemiological research has not addressed this question so far because the question was not previously posed, not because epidemiology itself is a blunt tool. Research focusing on this subgroup of autistic children compared with a suitable control group will assess association and establish the temporal sequence between exposure to measles virus and onset of the disorder, thus addressing causality.

*Liam Smeeth, Andrew J Hall, Laura C Rodrigues, Claire Cook, Eric Fombonne

Departments of *Epidemiology and Population Health, and Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK; and Department of Psychiatry, McGill University, Montreal Children's Hospital, Montreal, Canada (e-mail:liam.smeeth@lshtm.ac.uk

1 Walker-Smith J. Autism, bowel inflammation, and measles. Lancet 2002; 359: 705-06. [Text </journal/vol359/iss9323/full/llan.359.9307.correspondence.20101.1>]

Sir--In your Feb 23 editorial,1 you somewhat belatedly acknowledge that the publicity surrounding MMR and autism has been mainly negative.

When Wakefield and colleagues' work2 was first reported, many of us doubted the wisdom of the associated hype, for which you must take at least some of the responsibility. Many of us who wrote to point out the real hazards of measles, especially in any child with congenital or acquired immunodeficiency, had our submissions rejected on the grounds that there had been adequate publicity on the topic.

Tensions are inherent in vaccination programmes started for potentially life-threatening diseases, such as measles, or those that can cause severe morbidity, such as rubella in pregnancy. The risk for the individual is balanced against a low but definite risk of abnormal reaction to the vaccine. Therefore, the topic should be handled with maximum objectivity and sensitivity.

One of the great challenges of modern day medicine is to balance the individual's wellbeing against the overall health of the community. You have provided no objective balance in the argument previously, possibly in the search for headline publicity. In contrast to previous attempts, your current editorial does provide such balance. Media hysteria has done a great disservice to many thousands of parents who are anguishing over what is right to do for their children.

I hope in the future you will be more thoughtful in your search for publicity. Your journal is highly respected and widely read, but its content is taken as authoritative and the media rightly or wrongly assume it is sound and objective. I presume you will not publish this letter but perhaps those responsible within the editorial office will ponder on its message.

O B Eden

Department of Paediatric Oncology, Christie Hospital NHS Trust, Withington, Manchester M20 4BX, UK (e-mail:tim.eden@christie-tr.nwest.nhs.uk

1 Editorial. Time to look beyond MMR in autism research. Lancet </journal/vol359/iss9307/full/llan.359.9307.editorial_and_review.20100.1>

2002; </journal/vol359/iss9307/full/llan.359.9307.editorial_and_review.20100.1>359

: </journal/vol359/iss9307/full/llan.359.9307.editorial_and_review.20100.1>

637 </journal/vol359/iss9307/full/llan.359.9307.editorial_and_review.20100.1>.

2 Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998; 351: 637-41. [Text </journal/vol359/iss9323/full/llan.351.9103.original_research.7540.1>]

Sir--John Walker-Smith's call1 for a programme of non-epidemiological research is justified and timely.

The people who overlook these concerns do not observe the first rule in clinical medicine--listen to the patient. Parents of the children in question have described their children's ailment with extraordinarily little effect on the commissioning of clinical research, which suggests to me a deep resistance to hear what they are saying.

The Department of Health is adamant that autism is typically noticed around the time of vaccination, but presents no cases in which autism was acquired after a normal infancy just before MMR, nor seeks to explain autism developing in older children who received MMR after several years of normal development.

Although no evidence of a link between MMR and autism has been reported in reviews, absence of evidence is not evidence of absence. Confusing the two may yet prove to be medicine's fatal error.

Most of the reviews that are quoted as evidence of non-involvement of MMR in acquired autism have since been overtaken by further clinical research. For example, Singh2 reported that, in 75 of 125 autistic children, there was an unusual MMR antibody that was related to the measles haemagglutinin antigen of MMR. None of 92 controls had this feature. In addition, more than 90% of MMR antibody-positive autistic sera were also positive for myelin basic protein autoantibodies, which Singh interprets as suggesting a causal association between MMR and brain autoimmunity in autism.

Such findings suggest that the concerns raised by Walker-Smith, and by Wakefield and co-workers,3 are well founded. These findings are also consistent with the reports of parents.

The US Institute of Medicine's lmmunisation Safety Review Committee has stated that it was unable to address the concern about exposure of susceptible children to multiple immunisations in the developmental period, since no epidemiological study addresses this issue.4 The UK Department of Health does not seem to share their candour about the lack of research. They have slightly increased autism research funding. However, there has been no clinical research. The Scottish Chief Medical Officer, Mac Armstrong, has even stated that calls to fund clinical research into MMR and autism would be resisted.

Increasingly, it has become a battle between the crude science of epidemiology and the forensic science of clinical examination. The cause of those who seek to shore up public confidence in childhood immunisation by placing all their faith in epidemiology, much of it based on children's medical records that probably contain little of relevance to the issue, will be more than ill served if they are eventually proved wrong.

David Thrower

49 Ackers Road, Stockton Heath, Warrington, Cheshire WA4 2DZ, UK (e-mail:David@ThrowerWarrington.freeserve.co.uk

1 Walker-Smith J. Autism, bowel inflammation, and measles. Lancet 2002; 359: 705-06. [Text </journal/vol359/iss9323/full/llan.359.9307.correspondence.20101.1>]

2 Singh VK, Nelson C. Abnormal measles serology and autoimmunity in autistic children. J Allergy Clin Immunol 2002; 109: (abstr 702).

3 Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998; 351: 637-41. [Text </journal/vol359/iss9323/full/llan.351.9103.original_research.7540.1>] 4 National Vaccine Information Center. Press release. 2002; Feb 20.

* * *

Serological Detection of Measles Virus in Relation to Autoimmunity in Autism

102nd General Meeting of the American Society for Microbiology May 19-23, 2002, Salt Lake City, Utah, Presentation V-5

V.K. Singh, R.L. Jensen, J. J. Bradstreet

Utah State University and the International Child Development Resource Center

Abstract: Autoimmunity to brain myelin protein (MBP) secondary to a measles infection may cause autistic regression in some children with this neurodevelopmental disorder.

We hypothesized that measles-mumps- rubella (MMR) immunization is a source of measles infection; hence the serological link between MMR and MBP antibodies might exist in autistic children.

To test the hypothesis, we conducted a serological study of MBP, MMR and neuron- axon filament protein (NAFP) in serum and cerebral spinal fluid

(CSF) of autistic children.

Antibodies were assayed by immunoblotting with MBP, NAFP and MMR as antigens.

We found that a significant number of autistic children had antibodies to MBP (up to 88% positive) and antibodies to MMR (up to 65% positive), but not to NAFP.

Normal children did not harbor these antibodies.

Moreover, the analysis of paired samples (serum and CSF) from 7 autistic children also revealed a high degree of serological association between MMR and MBP: 50% of CSF had MMR antibodies, 86% of CSF had MBP antibodies, 75% of sera had MMR antibodies and 100% of sera had MBP antibodies.

Therefore, as indicated by paired analysis of serum and CSF samples, there is a strong correlation between MMR antibodies and MBP autoantibodies in autism.

By using monoclonal antibodies, we characterized that the MMR antibodies are due to the measles subunit, but not due to mumps or rubella subunits, of the polyvalent vaccine.

Furthermore, the MMR and MBP antibodies are not cross-reactive because the pre-incubation of MBP with MMR did not block the binding of MBP antibodies.

In light of the new evidence presented here, we suggest that the MMR vaccine in some cases of autism might cause autoimmunity and it might do so by bringing on an atypical measles infection that does not produce a typical measles rash but manifests neurological symptoms upon immunization.

Note: The MMR antibody has been previously reported to be the hemaggluttin protein of the vaccine measles virus (MV-HA).

"Immunoblotting analysis showed the presence of an unusual MMR antibody in 60% (75 of 125) of autistic children, but none of the 92 normal children had this antibody. Moreover, by using MMR blots and monoclonal antibodies, we found that the specific increase of MV antibodies or 'MMR' antibodies was related to measles hemagglutinin antigen (MV-HA)" (Singh, VK. Abnormal Measles Serology and Autoimmunity in Autistic Children, Journal of Allergy and Clinical Immunology 109, no. 1, page S232, Jan. 2002.)

It is confirmed here (in an additional population) that this antibody is not typically produced during normal immune response to the vaccine.

* * *

Hydrogen Proton Magnetic Resonance Spectroscopy In Autism Preliminary evidence of elevated choline/creatine ratio.

ds=12088077&dopt=Abstract

Sokol DK, Dunn DW, Edwards-Brown M, Feinberg J.

Department of Neurology, Indiana University School of Medicine, Indianapolis, USA. dksokol@iupui.edu

Hydrogen proton magnetic resonance spectroscopy is only beginning to be studied in autistic individuals.

We report an association between hydrogen proton magnetic resonance spectroscopy choline/creatine ratios and severity of autism as measured by the Children's Autistic Rating Scale (Pearson r = .657, P = .04) in 10 autistic children.

Hydrogen proton magnetic resonance spectroscopy choline/creatine ratio measures the concentration of cytosolic choline including free choline used in the synthesis of acetylcholine.

Elevation in this ratio has been interpreted as a result of membrane degradation such as caused by a tumor or, alternatively, as a result of choline synthesis associated with increased cellular proliferation.

Recent neuropathologic evidence has implicated disruption of acetylcholine transmission in the brains of autistic adults.

A case-controlled study of hydrogen proton magnetic resonance spectroscopy choline/creatine ratios is warranted.

PMID: 12088077 [PubMed - in process]

* * *

Serotonin, Half-Side Paralysis & Neurodevelopmental Delay 'Alpha[11C] methyl-L-typtophan positron emission tomography in patients with alternating hemiplegia of childhood.'

ds=12088079&dopt=Abstract <- - Address ends here.

Pfund Z, Chugani DC, Muzik O, Juhasz C, Behen ME, Lee J, Chakraborty P, Mangner T, Chugani HT. Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit 48201, USA.

Based on previous reports suggesting a role of the neurotransmitter serotonin in the pathomechanism of alternating hemiplegia of childhood and speculation that it may be a migraine variant, we measured brain serotonin synthesis in children with alternating hemiplegia of childhood.

Clinical and neurodevelopmental data, as well as standard uptake values in 25 brain regions and whole-brain serotonin synthesis capacity (unidirectional uptake rate constant or K-complex), were assessed in six patients with alternating hemiplegia of childhood (three girls and three boys; mean age = 7 6/12 years) using alpha[11C]methyl-L-tryptophan positron emission tomography (PET).

The PET studies were performed interictally in three patients, during the ictal state in two patients, and postictally in one patient.

The PET data were compared to those obtained interictally from six age-matched patients with focal epilepsy (two girls and four boys; mean age = 7 8/12 years) and six non-age-matched apparently normal siblings of autistic children (two girls and four boys; mean age = 9 11/12 years).

Patients with alternating hemiplegia of childhood studied in the ictal or postictal state showed increased serotonin synthesis capacity in the frontoparietal cortex, lateral and medial temporal structures, striatum, and thalamus when compared to controls, and subjects with alternating hemiplegia of childhood studied interictally.

The involvement of these brain regions was consistent with the semiology of the hemiplegic attacks.

In patients with interictal studies and in the controls, the PET scans revealed similar and bilaterally symmetric regional patterns of serotonin synthesis capacity.

Increased whole-brain serotonin synthesis capacity (reported in migraine subjects without aura) was not found in the alternating hemiplegia of childhood group.

There was no correlation between the neurodevelopmental scores and regional standard uptake values; however, patients with a larger estimated lifetime attack number showed greater delay in communication (P = .005) and daily living skills (P = .042).

These studies suggest increased regional serotonergic activity associated with attacks in alternating hemiplegia of childhood.

Furthermore, the attack number may have an effect on neurodevelopmental delay, thus supporting the notion that alternating hemiplegia of childhood may be a progressive disorder.

PMID: 12088079 [PubMed - in process]

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Munchausen by Proxy in an International Context

ds=12079087&dopt=Abstract

1: Child Abuse Negl 2002 May;26(5):509-24

Feldman MD, Brown RM.

Department of Psychiatry & Behavioral Neurobiology, University of Alabama at Birmingham, 35294-0018, USA.

OBJECTIVE: The professional literature on Munchausen by Proxy (MBP) abuse consists of more than 400 articles, chapters, and books.

Most have come from a handful of English-speaking industrialized countries.

Our aims were to establish the extent to which published work about MBP has emerged from outside these countries, and to determine the characteristics of any reported cases.

METHOD: Numerous health care computer databases were queried, and the results supplemented by materials accumulated less formally.

RESULTS: We identified 59 articles from 24 countries describing at least 122 cases in 9 different languages.

Among cases in which the information was available, the mother was the sole perpetrator in 86%, the victim was aged between 3 years and 13 years in 52%, and the victim was male in 54%.

The presentations of MBP appear to be similar across the world with the exception of induced apnea, which emerged as notably uncommon in this review.

An extensive table presents the characteristics of each case.

CONCLUSIONS: MBP clearly is not a phenomenon unique to Western or highly medicalized societies.

This form of abuse is being increasingly recognized and reported throughout the world.

The literature from the US, Canada, UK, Australia, and New Zealand often presupposes access to resources, such as subspecialists and social service agencies, that may be seriously constrained in other countries.

The contributions of professionals elsewhere will be vital in ensuring that the efforts in English-speaking industrialized settings to develop standards of care encompass an international perspective.

PMID: 12079087 [PubMed - in process]

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