L'autisme : une forme particulière
d'intoxication au mercure (2)

Etude comparative des symptômes de l'autisme et de ceux de l'intoxication au mercure

Extraits de l'étude
"Autism: A unique type of Mercury Poisoning",

disponible dans son intégralité à l'adresse
http://www.autismwebsite.com/ari/vaccine/mercurylong.htm 

Sallie Bernard*
Albert Enayati, B.S., Ch.E., M.S.M.E.**
Teresa Binstock
Heidi Roger
Lyn Redwood, R.N., M.S.N., C.R.N.P.
Woody McGinnis, M.D.

*Contact : sbernard@nac.net
**Contact : (201) 444-7306
njcan@aol.com

Copyright (c) 2000 ARC Research

14 Commerce Drive
Cranford, NJ 07016
21 avril 2000

N. d. T. : Les pages qui suivent sont extraites de l'étude "Autism: A unique type of Mercury Poisoning". Les tableaux ont été traduits au complet, mais pour des raisons pratiques, les textes intercalés sont en revanche des extraits ou des résumés de la version initiale en langue anglaise.

Le texte d'origine a été toutefois conservé à la suite des passages en français. Il présente les très nombreuses références d'études étayant le propos des auteurs.

Tableau A :
Similitudes entre les symptômes de
l'autisme et ceux de l'intoxication au mercure

Introduction

Autisme

Considéré comme un syndrome neuro-développemental, l'autisme ou spectre autistique se caractérise par une altération qualitative des aptitudes relationnelles, un déficit de la communication verbale et non verbale, ainsi que la présence de comportements et intérêts répétitifs et restreints. Il convient toutefois d'évoquer d'autres traits tels que les troubles de la motricité, des dysfonctionnements sensoriels, des difficultés cognitives, ainsi que des anomalies sur les plans gastro-intestinal et immunitaire. Pour être qualifiés d'autistiques, les troubles doivent apparaître avant l'âge de trois ans ; apparents dans certains cas dès la naissance, ils succèdent le plus souvent à plusieurs mois de développement normal suivis d'une régression ou d'une incapacité nette à progresser normalement. Initialement considéré comme une affection rare, l'autisme concernerait actuellement un enfant sur 500, voire 1 sur 100 si l'on considère l'ensemble des sujets répondant aux caractéristiques d'un "spectre autistique" au sens large.

Les symptômes autistiques peuvent être associés à différentes affections connues telles que la sclérose tubéreuse, les syndromes de Rett, de Landau-Kleffner et de l'X fragile ainsi que diverses maladies métaboliques. Dans la grande majorité des cas toutefois (70 à 90%), l'étiologie et la pathogenèse demeurent inexpliquées. La thèse d'une atteinte environnementale précoce sur un terrain génétiquement prédisposé tend toutefois à s'imposer.

Mercure

Le métal lourd qu'est le mercure (Hg) est considéré comme l'une des substances les plus toxiques au monde. Des cas d'empoisonnement sont évoqués depuis l'époque de l'empire romain. Citons en particulier la "maladie du chapelier", ainsi que des empoisonnements à grande échelle au cours du 20^e siècle : la maladie de "Minamata" (empoisonnement au Japon dû à la consommation de poisson contaminé), empoisonnements en Iraq, au Guatemala et en Russie suite à l'ingestion de graines contaminées, ou encore, durant la première moitié du 20^e siècle, l'acrodynie ou "maladie rose", empoisonnement par des poudres destinées à atténuer les douleurs de la percée dentaire chez le jeune enfant. De nombreux cas d'empoisonnement isolés ou de groupes plus restreints ont été par ailleurs documentés.

Les symptômes, qui varient d'un individu à l'autre en fonction de différentes variables, sont recensés Tableau  I. Parmi ces variables il faut citer l'âge, les doses et la durée de l'exposition, le type de mercure, le mode d'exposition – par inhalation, sous-cutanée, orale, intramusculaire - ainsi que, et surtout, le terrain immunitaire et génétique de chacun.

Autism, or Autistic Spectrum Disorder (ASD), is considered a neurodevelopmental syndrome, emerging early in life and exhibiting a constellation of seemingly unrelated features and a wide variation in symptom expression and level of severity by individual (Filipek et al, 1999; Bailey et al, 1996). The diagnostic criteria for autism are qualitative impairments in social relatedness, deficits in verbal and nonverbal communication, and the presence of repetitive and restricted behaviors or interests (APA, 1994). As will be cited below, other traits associated with autism are movement disorder, sensory dysfunction, and cognitive impairments as well as gastrointestinal difficulties and immune abnormalities (Gillberg & Coleman, 1992; Warren et al, 1990; Horvath et al, 1999). Onset must occur before age 36 months (APA, 1994); although in some instances deficits are apparent at birth, in the great majority of cases there are at least several months of normal development followed by clear regression or failure to progress normally (Gillberg & Coleman, 1992; Filipek et al, 1999; Bailey et al, 1996). Formerly regarded as a rare disease, autism is now said to affect one in 500 children (Bristol et al, 1996), with some estimates suggesting one in 100 for a broader phenotype often labeled as the "autism-spectrum" of disorders and which includes both higher and lower functioning individuals (Arvidsson et al, 1997; Wing, 1996).

Autism and autistic symptoms can arise from a number of known disorders, most notably tuberous sclerosis, Rhett syndrome, Landau-Kleffner syndrome, Fragile X, Phenylketonuria, purine autism, and other purine metabolic diseases such as PRPP synthetase defects and 5'-nucleotidase superactivity. The etiology and pathogenesis of the vast majority of autism cases - 70% - 90% (Gillberg and Coleman, 1992; Bailey et al, 1996) - remain unexplained, however, despite ASD being "one of the most extensively studied disorders in child psychiatry today" (Malhotra and Gupta, 1999). Nevertheless, there is general agreement that most cases of autism arise "from the interaction of an early environmental insult and a genetic predisposition" (Trottier et al, 1999; Bristol et al, 1996).

Tableau I : variables de l'exposition au mercure et  
symptômes divers et non spécifiques observés

Si ces variations en termes d'exposition, de terrain et de génotype produisent des phénotypes cliniques variables, tous les troubles d'origine mercurielle présentent des caractéristiques communes : dans presque tous les cas des troubles moteurs qui pourront revêtir la forme d'une simple maladresse ou au contraire de mouvements involontaires invalidants ; ou encore des troubles psychologiques qui pourront se traduire chez certains par de l'anxiété ou chez d'autres par de l'agressivité ou de l'irritabilité.

Diagnostic de l'empoisonnement au mercure chez les sujets atteints d'autisme

Difficile à diagnostiquer, l'empoisonnement au mercure est souvent interprété par les cliniciens comme une pathologie psychiatrique, en particulier si aucune exposition n'est suspectée. La principale difficulté est inhérente à deux caractéristiques de ce métal lourd : la possibilité d'une longue période de latence entre le moment de l'exposition et l'apparition des symptômes, et les manifestations variables de la maladie qui permettent difficilement au clinicien d'établir un lien précis entre les symptômes spécifiques de son patient et ceux décrits dans d'autres études de cas.

Face à ces difficultés, les critères suivants ont été établis :

1. Anomalies dans la plupart des domaines suivants :
   (a) difficultés motrices,
   (b) anomalies sensorielles,
   (c) troubles psychologiques et du comportement,
   (d) déficits neurologiques et cognitifs,
   (e) altération du langage, de l'audition et de la vision, et
   (f) manifestations physiques telles que irritations ou réflexes inhabituels.
   
   
2. Exposition connue au mercure :
   (a) à un niveau identifié comme ayant entraîné des séquelles chez des sujets comparables dans des circonstances similaires, et 
   (b) à un moment compatible avec l'apparition des symptômes, compte tenu de la période de latence.
   Il faut noter les différences de vues des toxicologistes quant à la définition des doses "toxiques" ou "sûres", certains chercheurs estimant que le mercure est toxique à quelque dose que ce soit.
   
   
3. Niveaux de mercure décelables dans les urines, le sang ou les cheveux.
   L'éventuelle absence de mercure dans les échantillons analysés avant même l'apparition des symptômes ne permet pas de conclure à l'absence d'intoxication ; inversement, des niveaux détectables ont été observés chez des personnes ne présentant aucun trouble.
   
   
4. Amélioration des symptômes après chélation.
   Il faut toutefois noter l'absence d'amélioration chez certains sujets clairement empoisonnés ou au contraire l'amélioration spontanée d'autres sujets.

Aucun de ces critères n'est en soi suffisant pour établir avec certitude un diagnostic et la conjonction de deux ou trois de ces critères est généralement nécessaire. En faisant la synthèse de la masse de littérature disponible tant pour les troubles du spectre autistique que le mercure, ce document met en évidence le fait que, sur la base de ces quatre critères de diagnostic, de nombreux si ce n'est la majorité des cas d'autisme répondent aux critères de l'empoisonnement mercuriel.
Cette étude :
(i) met en lumière un mécanisme unique auquel peut être imputé l'ensemble des troubles et anomalies biologiques de l'autisme, en tenant compte de sa composante génétique, des niveaux de prévalence et du sexe ;
(ii) impute ce mécanisme à "l'attaque environnementale" que constitue l'exposition précoce des enfants. Le principal mode d'exposition est le thimoséral, conservateur des vaccins infantiles composé à 50% d'éthylmercure.

Le propos n'est pas d'affirmer que les cas d'intoxication au mercure documentés par le passé étaient des cas d'autisme, mais que le spectre autistique inclut une forme spécifique d'intoxication au mercure, de même que l'acrodynie, la maladie de Minamata et la "maladie du chapelier fou" correspondent à des formes comparables d'intoxication au mercure. Une expression spécifique s'imposerait pour l'autisme, sachant que les effets de l'administration répétée d'éthylmercure aux nourrissons et jeunes enfants lors des vaccinations n'ont encore jamais été décrits dans la littérature consacrée au mercure.

Nous maintenons que le phénotype divers qu'est l'autisme correspond au phénotype divers qu'est l'intoxication au mercure dans des proportions beaucoup trop importantes pour que l'on puisse envisager la moindre coïncidence. Considérés l'exposition connue au mercure des enfants autiste et la présence de mercure dans les échantillons biologiques d'un certain nombre de sujets autistes, nous sommes certains de la validité de nos conclusions.

I. Comparaison des symptômes

La similitude des symptômes des  troubles du spectre autistique et de l'empoisonnement au mercure est frappante. Les tableaux de synthèse fournis à la fin de chaque partie en facilitent la comparaison.

a. Affect/profil psychologique

Depuis la définition établie en 1943 par le psychiatre Leo Kanner, l'autisme a été initialement défini comme relevant de la psychiatrie. L'une des conditions requises pour évoquer le diagnostic est le déficit des interactions sociales avec recherche de la solitude, des difficultés pour entrer et demeurer en relation, entretenir une conversation, des difficultés en matière de reconnaissance des visages et de "théorie de l'esprit ", ainsi que l'évitement du regard.

La seconde condition requise est la présence d'activités répétitives et stéréotypées, une aversion pour le changement et des tendances obsessionnelles compulsives. La plupart des sujets se caractérisent également par leur anxiété.

Les troubles du spectre autistique peuvent également s'assortir de tendances dépressives, de "passivité", avec un affect plat, l'absence d'expressions faciales, un manque d'initiative, une inhibition des réactions émotionnelles, une instabilité d'humeur, et souvent un langage psychotique. Par le passé l'autisme a souvent été considéré à tort comme une schizophrénie infantile. Des peurs irrationnelles, des comportements agressifs et des crises de colère intenses sont également courants, ainsi qu'une irritabilité chronique, des pleurs ou des rires inexpliqués.

L'empoisonnement au mercure, avant d'être identifié, est souvent initialement diagnostiqué comme une pathologie psychiatrique aux vues de symptômes classiques tels que :

(a) la dépression, y compris le "manque d'intérêt" et la "confusion mentale",
(b) une "extrême timidité", le manque d'empathie et la recherche de la solitude,
(c) l'irritabilité chez l'adulte et les crises de colère chez l'enfant, ainsi que
(d) l'anxiété et la peur.
Des névroses incluant des traits schizophrènes et obsessionnels compulsifs ont été également signalées.

Les jeunes singes exposés avant leur naissance au mercure présentent des déficits relationnels, des comportements passifs ainsi qu'un déficit dans la reconnaissance des visages. Les humains exposés aux vapeurs du mercure rencontrent également des difficultés aux tests de reconnaissance faciale et peuvent présenter un visage "impassible" et une instabilité émotionnelle. Les enfants irakiens exposés au méthylmercure ont par exemple tendance à pleurer, rire ou sourire sans raison apparente, à la manière des enfants autistes décrits par Wing et Attwood (1987).

While these variations in exposure, individual status, and genotype give rise to a diverse clinical phenotype, there are nevertheless obvious commonalities across all mercury-caused disorders. Thus, for example, victims will almost always develop a movement disorder, but in some individuals this may manifest as mere clumsiness, while others will develop severe involuntary jerking movements. Likewise, psychological disturbances are usually present, but in some individuals these might manifest as anxiety while in others it might present as aggression or irritability.

Diagnosing Mercury Poisoning in Autism

Mercury poisoning can be difficult to diagnose and is often interpreted by clinicians as a psychiatric disorder, especially if exposure is not suspected (Diner and Brenner, 1998; Frackelton and Christensen, 1998). The difficulty in diagnosis derives primarily from two notable characteristics of this heavy metal. First, there can be a long latent period between time of exposure and onset of overt symptoms, so that the connection between the two events is often overlooked. The latency period is discussed in more detail below. Second, the diverse manifestations of the disease make it difficult for the clinician to find a precise match of his particular patient's symptoms with those described in other case reports (Adams et al, 1983, Kark et al, 1971; Florentine and Sanfilippo, 1991; Matheson et al, 1980; Frackelton and Christensen, 1998; Warkany & Hubbard, 1953).

Due to the difficulty of diagnosing mercurialism based on presentation of non-specific symptoms alone, clinicians have come to rely on the following criteria (Warkany & Hubbard, 1953; Vroom and Greer, 1972).

1.        Observation of impairments in many but not all of the following domains: (a) movement/motor disorder, (b) sensory abnormalities, (c) psychological and behavioral disturbances, (d) neurological and cognitive deficits, (e) impairments in language, hearing, and vision, and (f) miscellaneous physical presentations such as rashes or unusual reflexes (Adams et al, 1983; Snyder, 1972; Vroom & Greer, 1972).

2.        Known exposure to Hg (a) at a level that has been documenting as causing impairment in similar individuals under similar circumstances, and (b) at approximately the same time as the symptoms emerge, with allowances given for the latency period (Ross et al, 1977; Amin-Zaki et al, 1978). It should be noted that the dose which is considered "toxic" vs. "safe" is unresolved among toxicologists; some researchers feel that any amount of exposure is "unsafe" (see EPA, 1997, pp.6-47 to 6-59, for dose discussion).

3.        Detectable levels of mercury in urine, blood, or hair (Florentine and Sanfilippo, 1991; Frackelton and Christensen, 1998; EPA, 1997, p.ES-2). Importantly, because mercury can clear from biologic samples before the patient feels symptoms or is tested, the lack of detectable mercury is not cause for ruling out mercury poisoning; and conversely, detectable levels have been observed in unaffected individuals (Adams et al, 1983; Warkany & Hubbard, 1953; Cloarec, 1995).

4.        Improvement in symptoms after chelation. While many patients' symptoms resolve with chelation, some clearly poisoned individuals do not improve. Other exposed subjects have also been known to improve without intervention (Vroom & Greer, 1972; Warkany & Hubbard, 1953).

Thus, none of these criteria is sufficient on its own for a certain diagnosis. Rather, observed effects within two or three domains are generally required. This paper, which reviews and compares the extensive literature available on both ASD and mercury, provides citations documenting that, based on these four diagnostic criteria, many if not most cases of autism meet the requirements for mercury poisoning. In fact, this review and its citations (i) delineate a single mechanism for inducing all of the primary domains of impairment and biological abnormalities in autism, including its genetic component, prevalence levels, and sex ratios; and (ii) identify that mechanism as arising from the "environmental insult" of early childhood exposure to mercury. Furthermore, the route of exposure is thimerosal, which is 50% ethylmercury by weight and which is a preservative used in many childhood vaccines.

We are not suggesting that the previous reports of mercurialism described in the literature are in fact cases of autism; rather, we claim that autism represents its own unique form of Hg poisoning, just like acrodynia, Minamata disease, and Mad Hatter's disease represent distinct yet closely related presentations of mercurialism. A unique expression would be expected in cases of autism, given that the effects of repeated vaccinal administration of ethylmercury to infants and toddlers have never been described before in mercury-related literature. We maintain that the diverse phenotype that is autism matches the diverse phenotype that is mercurialism to a far greater degree that could reasonably be expected to occur by chance. Given the known exposure to mercury via vaccination of autistic children and the presence of mercury found in biologic samples from a number of autistic subjects, also described here, we are confident that our claim is substantiated. Our paper discusses some important medical and societal ramifications of this conclusion.

I. Symptom Comparison

The overt symptoms of ASD and mercury poisoning, described in the literature and presented here, are strikingly similar. Summary tables have been provided after each section to aid in symptom comparisons.

a. Affect/Psychological Presentation

Since its initial description in 1943 by Leo Kanner, a psychiatrist, autism has been defined primarily as a psychiatric condition. One of the three requirements for diagnosis is a severe deficit in social interactions (APA, 1994). Self and parental reports describe children and adults who prefer to be alone and who will withdraw to their rooms if given the chance (MAAP, 1996-1999). Even high functioning autistics tend to be aloof, have poor social skills, are unable to make friends, and find conversation difficult (Tonge et al, 1999; Capps et al, 1998). Face recognition and what psychologists call "theory of mind" are impaired (Klin et al, 1999, Baron-Cohen et al, 1993). Poor eye contact or gaze avoidance is present in most cases, especially in infancy and childhood (Bernabei et al, 1998).

The second psychobehavioral diagnostic characteristic of autism is the presence of repetitive, stereotyped activities and the need for sameness (APA, 1994). Traits in this domain strongly resemble obsessive-compulsive tendencies in both thought and behavior (Lewis, 1996; Gillberg & Coleman, 1992, p.27), especially as the individual becomes more high functioning (Roux et al, 1998): "it [is] very difficult.to distinguish between obsessive ideation and the bizarre preoccupations so commonly seen in autistic individuals" (Howlin, 2000). Serotonin uptake inhibitors known to be effective for OCD also reduce repetitive behaviors in some autistic patients (Lewis, 1996). Most autistic subjects - 84% in one study - show high levels of anxiety and meet diagnostic criteria for anxiety disorder (Muris et al, 1998).

ASD has been linked to depression, based on symptoms, familial history of depression and the positive response to SSRIs among many autistics (Clarke et al, 1999; DeLong, 1999; Piven and Palmer, 1999). One subset of autistics has been described as "passive", with flat affect, "absence of facial expression," lack of initiative, and diminished outward emotional reactions. Some autistics have a strong family history of manic depression and mood swings, and, among those who are verbal, psychotic talk is frequently observed (Plioplys, 1989). Autism is also said to strongly resemble childhood schizophrenia. In the past it was often misdiagnosed as such (Gillberg & Coleman, 1992, p.100), and there are a number of instances of dual ASD-schizophrenia diagnoses in the literature (Clarke et al, 1999). Furthermore, irrational fears, aggressive behaviors, and severe temper tantrums are common (Muris et al, 1998; McDougle et al, 1994), as are chronic hyperarousal and irritability (Jaselskis et al, 1992). "Inexplicable changes of mood can occur, with giggling and laughing or crying for no apparent reason" (Wing & Attwood, 1987).

Mercury poisoning, when undetected, is often initially diagnosed as a psychiatric disorder in both children and adults (Fagala and Wigg, 1992). Common psychiatric symptoms are (a) depression, including "lack of interest" and "mental confusion;" (b) "extreme shyness," indifference to others, active avoidance of others or "a desire to be alone"; (c) irritability in adults and tantrums in children; and (d) anxiety and fearfulness. Neurosis, including schizoid and obsessive-compulsive traits, has been reported in a number of cases (Fagala and Wigg, 1992; Kark et al, 1971; O'Carroll et al, 1995; Florentine and Sanfilippo, 1991; Amin-Zaki, 1974 and 1979; Matheson et al, 1980; Joselow et al, 1972; Smith, 1972; Lowell, 1996; Tuthill, 1899; Clarkson, 1997; Camerino et al, 1981; Grandjean et al, 1997; Piikivi et al, 1984; Rice, 1996; Vroom & Greer, 1972; Adams et al, 1973; Hua et al, 1996).

Juvenile monkeys prenatally exposed to mercury exhibit decreased social play and increased passive behavior (Gunderson et al, 1986, 1988), as well as impaired face recognition (Rice, 1996). Humans exposed to mercury vapor also perform poorly on face recognition tests and may present with a "mask face" (Vroom & Greer, 1972); emotional instability can occur in children and adults exposed to Hg. For instance, Iraqi children poisoned by methylmercury had a tendency "to cry, laugh, or smile without obvious provocation" (Amin-Zaki et al, 1974 & 1979), like the autistic group described by Wing and Attwood (1987).

Tableau II : troubles psychiatriques
communs à l'autisme et à l'intoxication au mercure

L'autisme ayant été traditionnellement défini et étudié par les chercheurs à la lumière de la psychiatrie, il s'avère nécessaire de partir de cas pour illustrer les aspects psychiatriques similaires entre les troubles du spectre autistique et l'intoxication au mercure. Il convient de rappeler que le retrait social et l'altération des facultés de communication sont des caractéristiques (i)  inhérentes à l'autisme et (ii) clairement associées à l'intoxication au mercure qui revêtent les formes suivantes :

 (a) interprétation littérale rigide de la signification des mots ; erreurs de sens et pragmatiques qui perturbent la communication sociale ;
 (b) déficits sociaux, difficultés de perception des règles de comportement social, perçues comme un manque d'éducation ;
(c) incapacité à prendre part à une conversation ; difficultés de compréhension de la conversation ; pensées exclusives.

b. Langage et audition

Le troisième critère de diagnostic de l'autisme est l'altération qualitative de la communication, qui est également l'un des principaux symptômes de l'empoisonnement au mercure.

Le retard d'apparition du langage fait souvent partie des premiers signes annonciateurs d'un trouble du spectre autistique. Globalement la moitié des personnes atteintes d'autisme classique ne parvient pas à développer un langage cohérent et souffre de difficultés de motricité buccale (pour mâcher ou avaler, par exemple). Lorsque le langage se développe, il peut s'accompagner de troubles neuromoteurs spécifiques tels que dyspraxie verbale ou dysarthrie. L'écholalie et l'inversion des pronoms sont classiques chez le jeune enfant. Beaucoup de sujets obtiennent aux tests de QI verbaux des résultats inférieurs à ceux obtenus aux tests de QI performance. Les sujets de haut niveau tels que ceux atteints du syndrome d'Asperger peuvent disposer d'un langage fluide assorti d'erreurs sémantiques et pragmatiques.

Les troubles de l'audition sont également courants : déficit léger à profond de l'audition chez 24% des sujets, hyperacusie, otites et perte de l'audition chez certains sujets, indépendamment du QI, qui conduisent généralement à des tests d'audition avant même qu'un diagnostic d'autisme soit envisagé. Des réactions atypiques aux stimuli auditifs ainsi qu'un babillage inhabituel sont quasiment systématiques dans l'autisme, qu'il s'agisse d'un manque de réaction ou de réactions excessives. Les difficultés de compréhension du langage ou de perception du langage sur fond sonore sont courantes.

En ce qui concerne le langage et l'aspect auditif, les similitudes entre l'autisme et l'intoxication au mercure sont frappantes. Les premiers signes de l'empoisonnement au mercure sont la dysarthrie (articulation déficiente) et des troubles de l'audition allant jusqu'à la surdité. Dans certains cas, ces troubles de l'audition se traduisent plus par une inaptitude à comprendre le langage qu'à une réelle incapacité auditive. L'empoisonnement au mercure peut également se traduire par de l'aphasie, incapacité à comprendre ou à prononcer des mots.

Les enfants exposés au mercure, y compris in utero, présentent des difficultés de langage. Les bébés irakiens exposés in utero se caractérisaient par l'absence de langage ou des troubles sévères du langage, des réactions excessives au bruit et une audition réduite. Les enfants exposés par la consommation de pain contaminé au méthyl ou à l'éthylmercure présentaient des problèmes d'articulation ou un langage incohérent. La plupart présentaient une altération de l'audition voire une surdité.

Les symptômes constatés chez des adultes intoxiqués sont similaires, qui s'agisse des adultes irakiens ayant consommé du pain contaminé au méthylmercure, ou d'adultes intoxiqués par le thimoséral, du diméthylmercure ou des vapeurs de mercure.

Since traditionally autism has been characterized and studied by researchers primarily in psychiatric terms, providing case studies illustrating the psychiatric aspects of ASD and of mercurialism are necessary in establishing the similarities of the two disorders on this critical domain. Also included is a comparison of "Lenny," an autistic adult described by Rhea Paul (1987), and the Mad Hatter from Alice in Wonderland, considered to be an accurate portrayal of victims of the disease. Of particular relevance in all these cases are social withdrawal and deficits in social communication, traits (i) always prominent in autism and (ii) clearly associated with mercurialism.

Case Studies: Autism
"I am 18 years old. My parents found out I was autistic when I was 18 months old. My parents said I banged my head a lot when I got frustrated when I was young. Head banging motions help me deal with nervousness. I also take 2 medications to help me cope with stress. I have very few friends. It is also somewhat painful for me to look people in the eye. This sometimes makes people think I am not paying attention" (The MAAP, Vol. II, 1997).

"I have a high-functioning autistic eight-year-old boy. My mistake was putting him in the second grade with a teacher who was determined to 'socialize' him. After three months, the anxiety proved to be too great for him. He spent a lot of time crying, withdrawing to his room, becoming compulsive and belligerent. In another era, he would have been seen as having a 'nervous breakdown'" (The MAAP, Vol. II, 1997).

"I am writing regarding our 25 year old son who was diagnosed only a few months ago as having Asperger's Syndrome. All his life he displayed the 'classic' symptoms of Asperger's (lack of social skills, disorganization, anxiety, etc.). A few months ago, he became clinically depressed, phobic about being around people for fear of more rejection or being laughed at. He now has obsessive thoughts that our home is electronically 'bugged' and all his actions are being observed and belittled" (The MAAP, Vol. II, 1997).

"Several people have asked me what it's like to have Asperger's Syndrome. Today, I still prefer to work on my computer or with electronics rather than socialize. I've never been able to tolerate any kind of physical contact or intimacy. I like wrestling and rough-housing, but I hate being caressed or held." (The MAAP, Vol. II, 1997).

"My son Brian is a 6-year-old with high functioning autism. Our main problem now is his rigidity and obsessive/compulsive behaviors. He gets extremely upset when activities don't go as he thinks they should. He first gets mad, screaming and yelling, then begins to obsessively talk about how he can remedy the situation, then often begins to cry uncontrollably. These tantrums can go on for hours" (The MAAP, Vol. IV, 1996).

"[I'm] age 12r. I have Autism/PDD. I don't really know any real social skills, though my brother Isaiah says I am a social outcast. I do have trouble making new friends because I get real shy and nervous" (The MAAP, Vol. IV, 1997).

"I am the mother of three autistic boys. Nate was considered very shy. Poor eye contact but very smart and doing well in school. Nate was also diagnosed with Hypotonia of the face (which answered all the mumbling he did wasn't just shyness) and extremities" (The MAAP, Vol. III, 1999)

"I spent many hours sitting in the trees or under the bed or in a dark closet. I had a loud flat voice. Socialization has always been beyond me" (The MAAP, Vol. II, 1998).

"I sit in my room a prisoner to my autism. Mom and sis doing their loving best to get me out. I wanted to get out - really get out. I wanted to love, to feel, to connect. But, I couldn't. I was stuck. I was slowly dying. There were days I truly wanted to end it all. If any days were good, I didn't deserve it. I shouldn't be happy. Autism teaches you that - because it's a life sentence" (The MAAP, Vol. VI, 1996).

Case Studies: Mercury Poisoning
A 12 year old girl with recent mercury vapor poisoning was initially diagnosed as having a psychiatric disturbance. Her behavior was more normal when she was unaware of being watched. She became upset when people were around, was reluctant to speak when others were present, spoke in a soft, mumbling voice, lacked eye contact, had a flat affect, was sometimes tearful, experienced auditory hallucinations of voices laughing at her, wished to stay alone in her room with the lights off and her head covered, and had frequent temper tantrums (Fagala and Wigg, 1992).

Sufferers of Mad Hatter's disease, arising from prolonged mercury vapor exposure, were known to suffer from depression, lassitude, acute anxiety, and irrational fears. They also became nervous, timid, and shy. They blushed readily, were embarrassed in social situations, objected to being watched, and sought to avoid people. They felt a constant impulse to return home. They were easily upset, and were prone to agitation, irritability, anger, and aggressive behavior (O'Carroll et al, 1995).

A survey on an Internet site of adult acrodynia victims, which compared the symptoms of adults who suffered from acrodynia as children with controls, reported the following symptoms as seen to a greater degree in acrodynia sufferers than in controls: dislikes being touched or hugged, is a loner, lacks self confidence, feels nervousness and has a racing heart, has depression and suicidal feelings (Farnesworth, 1997). One acrodynia victim described his own situation: "not having learnt normal social skills I spent a lot of my time alone.Gradually by age 11 or so, I was becoming 'normal'.But, I have never overcome the headache problem, irritability, shyness with real people, not wanting to be touched, depression, fear of doctors, great anxiety." (Neville's Recollection, Pink Disease site)

A doctor from the 19th century described several cases of mercury poisoning from dental amalgams: "There is mental excitability as well as mental depression; perplexing events cause the highest degree of excitement, ordinary conversation sometimes causes complete confusion, headache, palpitation, intense solicitude, and anxiety, without reason for it. Such are some of the symptoms attending these cases." As an example he cites the case of a young woman who "had come to be melancholic and to withdraw herself from her family and friends, seeking the seclusion of her room -- refusing to go out or to associate with others, or even with the members of her own household." (Tuthill, 1899)

Nearly a century later, initial questioning of a 28 year old woman, subsequently found to have mercury vapor poisoning, "elicited the fact that she had become increasingly withdrawn from social activities and had felt most uncomfortable when with strangers. She also felt that her friends had turned against her. She had a repetitive disturbing dream of electric fire around the frames of the windows in her bedroom." (Ross et al, 1977)

Lenny and The Mad Hatter
(a) Rigid literal interpretation of word meaning; word meaning and pragmatic errors which interfere with social communication

Lenny - "He was very literal minded, and words spoken to him became matters of immutable fact. For example, he was trying on new shoes. His mother asked him if they slipped up and down. He said they didn't, and when asked again if he were sure, he replied, 'No, they don't slip up and down; they slip down and then they slip up.' "

The Mad Hatter - "Take some more tea," the March Hare said to Alice, very earnestly.
"I've had nothing yet," Alice replied in an offended tone: "so I ca'n't take more."
"You mean you ca'n't take less," said the Hatter: "It's very easy to take more than nothing."

(b) Social deficits, inability to interpret social rules, leading to perceived rude behavior

Lenny - "Although he tried working in his father's business for a time, his immaturity, self-centered behavior, and lack of social judgment required his return to a sheltered setting."

The Mad Hatter - "Your hair wants cutting," said the Hatter. He had been looking at Alice for some time with great curiosity, and this was his first speech.
"You should learn not to make personal remarks," Alice said with some severity: "it's very rude."
The Hatter opened his eyes wide upon hearing this; but all he said was "Why is a raven like a writing desk?"

(c) Inability to engage in meaningful social conversation; poor conversational interpretation skills; perseverative thoughts

Lenny - "During one interview he engaged in a 20 minute monologue about a broken washing mashine. The interviewer momentarily dozed off. Upon rousing, the interviewer exclaimed, 'Oh, Lenny, I'm sorry!' 'It's all right,' Lenny replied calmly, 'the washing machine got fixed."

The Mad Hatter (who talks obsessively/perseveratively about Time for a good portion of the chapter) - "What a funny watch!" she remarked. "It tells the day of the month, and doesn't tell what o'clock it is!"
"Why should it?" muttered the Hatter. "Does your watch tell you what year it is?"
"Of course not, " Alice replied very readily: "but that's because it stays the same year for such a long time altogether."
"Which is just the case with mine," said the Hatter.
Alice felt dreadfully puzzled. The Hatter's remark seemed to her to have no sort of meaning in it, and yet it was certainly plain English.

b. Language and Hearing

The third diagnostic criterion for autism is a qualitative impairment in communication (APA, 1994), and such impairment is a primary feature of mercury poisoning.

Delayed language onset is often among the first overt signs of ASD (Eisenmajer et al, 1998). Historically, half of those with classic autism failed to develop meaningful speech (Gillberg & Coleman, 1992; Prizant, 1996); and oral-motor deficits (e.g. chewing, swallowing) are often present (Filipek et al, 1999). When speech develops, there may be "specific neuromotor speech disorders," including verbal dyspraxia, a dysfunction in the ability to plan the coordinated movements to produce intelligible sequences of speech sounds, or dysarthria, a weakness or lack of control of the oral musculature" leading to articulation problems (Filipek et al, 1999). Echolalic speech and pronoun reversals are typically found in younger children. Many ASD subjects show poorer performance on tests of verbal IQ relative to performance IQ (Dawson, 1996; Filipek at al, 1999). Higher functioning individuals, such as those with Asperger's Syndrome, may have language fluency but still exhibit semantic (word meaning) and pragmatic (use of language to communicate) errors (Filipek et al, 1999).

Auditory impairment is also common. Two separate studies, for example, both found that 24% of autistic subjects have a hearing deficit (Gillberg & Coleman, 1992). More recently Rosenhall et al (1999) have diagnosed hearing loss ranging from mild to profound, as well as hyperacusis, otitis media, and conductive hearing loss, in a minority of ASD subjects, and these traits were independent of IQ status. Among the earliest signs of autism noted by mothers were strange reactions to sound and abnormal babble (Gillberg & Coleman, 1992), and many ASD children are tested for deafness before receiving a formal autism diagnosis (Vostanis et al, 1998). "Delayed or prompted response to name" differentiates 9-12 months old toddlers, later diagnosed with autism, from mentally retarded and typical controls (Baranek, 1999). In fact, "bizarre responses" to auditory stimuli are nearly universal in autism and may present as "either a lack of responsiveness or an exaggerated reaction to auditory stimuli" (Roux et al, 1998), possibly due to sound sensitivity (Grandin, 1996). Kanner noted an aversion to certain types of sounds, such as vacuum cleaners (Kanner, 1943). Severe deficits in language comprehension are often present (Filipek et al, 1999). Difficulties in picking out conversational speech from background noise are commonly reported by high functioning ASD individuals (Grandin, 1995; MAAP, 1997-1998).

In regard to language and auditory phenomena, autism's parallels to mercurialism are striking. Emerging signs of mercury poisoning are dysarthria (defective articulation in speech due to CNS dysfunction) and then auditory disturbance, leading to deafness in very high doses (Clarkson, 1992). In some cases, hearing impairment manifests as an inability to comprehend speech rather than an inability to hear sound (Dales, 1972). Hg poisoning can also result in aphasia, the inability to understand and/or physically express words (Kark et al, 1971). Speech difficulties may arise from "intention tremor, which can be noticeable about the mouth, tongue, face, and head, as well as in the extremities" (Adams et al, 1983).

Mercury-exposed children especially show a marked difficulty with speech (Pierce et al, 1972; Snyder, 1972; Kark et al, 1971). Even children exposed prenatally to "safe" levels of methylmercury performed less well on standardized language tests than did unexposed controls (Grandjean et al, 1998). Iraqi babies exposed prenatally either failed to develop language or presented with severe language deficits in childhood. They exhibited "exaggerated reaction" to sudden noise and some had reduced hearing (Amin-Zaki, 1974 and 1979). Iraqi children who were postnatally poisoned from bread containing either methyl or ethylmercury developed articulation problems, from slow, slurred word production to the inability to generate meaningful speech. Most had impaired hearing and a few became deaf (Amin-Zaki, 1978). In acrodynia, symptoms of sufferers (vs. controls) include noise sensitivity and hearing problems (Farnesworth, 1997).

Adults also exhibit these same Hg-induced impairments. There is slurred or explosive speech (Dales, 1972), as well as difficulty in picking out one voice from a group (Joselow et al, 1972). Poisoned Iraqi adults developed articulation problems (Amin-Zaki, 1974). A 25 year old man with elemental mercury poisoning had reduced hearing at all frequencies (Kark et al, 1971). Thimerosal injected into a 44 year old man initially led to difficulty verbalizing, even though his abilities in written expression were uncompromised; he then progressed to slow and slurred speech, although he could still comprehend verbal language; and he finally lost speech altogether (Lowell et al, 1996). In Mad Hatter's disease, there were word retrieval and articulation difficulties (O'Carroll et al, 1995). A scientist who recently died from dimethylmercury poisoning demonstrated an inability to understand speech despite having good hearing sensitivity for pure tones (Musiek and Hanlon, 1999). Workers exposed to mercury vapor showed decreased verbal intelligence relative to performance IQ (Piikivi et al, 1984; Vroom and Greer, 1972).

Tableau III : troubles de la parole, du langage et de l'audition
dans l'intoxication au mercure et l'autisme

c. Perception sensorielle

Les anomalies sensorielles et sensori-motrices sont considérées comme l'une des caractéristiques de l'autisme : aversion pour le toucher, manque d'attention visuelle, objets portés à la bouche, retards dans la réaction au nom chez le jeune enfant. Il est envisageable que ces anomalies soient à la base des difficultés de sociabilisation ultérieures et permettent de différencier les personnes porteuses d'un TED de celles présentant un retard mental ou neurotypiques. Outre la sensibilité au bruit, les troubles du spectre autistique s'accompagnent souvent d'une insensibilité à la douleur, ou au contraire de réactions excessives à des stimuli tels que la luminosité ou le toucher. Des sensations anormales au niveau des extrémités et de la bouche sont courantes, ainsi que la marche sur la pointe des pieds. Les enfants autistes présentent souvent des troubles de la déambulation et des difficultés d'orientation dans l'espace.

Ces anomalies sensorielles se retrouvent dans presque tous les cas d'intoxication au mercure. La paresthésie, ou sensation anormale, des sensations de chatouillement ou une insensibilité autour de la bouche et aux extrémités, sont généralement les premiers symptômes sensoriels de l'intoxication au mercure. Les japonais qui ont consommé du poisson contaminé présentaient une insensibilité des extrémités, du visage et de la langue. Les enfants irakiens qui avaient consommé du pain contaminé présentaient une insensibilité de la bouche, des mains et des pieds, associée à une impression de "fourmillements sous la peau", de picotements. Une perte des capacités d'orientation dans l'espace a également pu être notée. Les personnes atteintes d'acrodynie font état de douleurs intenses dans les membres lorsqu'elles se heurtent, de zones insensibles et de problèmes de circulation. Les bébés irakiens exposés in utero se caractérisaient par des pleurs, une irritabilité et des réactions intenses à des stimuli tels qu'un bruit soudain ainsi qu'au toucher.

c. Sensory Perception

Sensory impairment is considered by many researchers to be a defining characteristic of autism (Gillberg and Coleman, 1992; Williams, 1996). Baranek (1999) detected sensory-motor problems - touch aversion, poor non-social visual attention, excessive mouthing of objects, and delayed response to name - in 9-12 month old infants later diagnosed with autism, and suggests that these impairments both underlie later social deficits and serve to differentiate ASD from mental retardation and typical controls. Besides sensitivity to sound, as previously noted, ASD often involves insensitivity to pain, even to a burning stove (Gillberg & Coleman, 1992), while on the other hand there may be an overreaction to stimuli, so that even light to moderate touches are painful. Pinprick tests are usually normal. Children with autism have been described as "stiff to hold," and one of the earliest signs reported by mothers is an aversion to being touched (Gillberg & Coleman, 1992). Abnormal sensation in the extremities and mouth are common. Toe-walking is frequently seen. Oral sensitivity often results in feeding difficulties (Gillberg & Coleman, 1992, p.31). Autistic children frequently have vestibular impairments and difficulty orienting themselves in space (Grandin, 1996; Ornitz, 1987).

As in ASD, sensory issues are reported in nearly all cases of mercury toxicity, and serve to demonstrate the similarities between the two conditions. Paresthesia, or abnormal sensation, tingling, and numbness around the mouth and in the extremities, is the most common sensory disturbance in Hg poisoning, and is usually the first sign of toxicity (Fagala and Wigg, 1992; Joselow et al, 1972; Matheson et al, 1980; Amin-Zaki, 1979). In Japanese who ate contaminated fish, there was numbness in the extremities, face and tongue (Snyder, 1972; Tokuomi et al, 1982). Iraqi children who ate bread experienced sensory changes including numbness in the mouth, hands and feet, and a feeling that there were "ants crawling under the skin." These children could still feel a pinprick (Amin-Zaki, 1978). Loss of position in space has also been noted (Dales, 1972). Acrodynia sufferers describe excessive pain when bumping limbs, numbness, and poor circulation (Farnesworth, 1997). One adult acrodynia victim described himself as a boy as "shying away from people wanting to touch me" due to extreme touch sensitivity (Neville Recollection, Pink Disease Support Group). Iraqi babies exposed to mercury prenatally showed excessive crying, irritability, and exaggerated reaction to stimulation such as sudden noise or when touched (Amin-Zaki et al, 1974 and 1979).

Tableau IV : anomalies sensorielles
dans l'intoxication au mercure et l'autisme

d. Mouvement/ motricité

L'autisme s'accompagne dans presque tous les cas de troubles moteurs. Qu'il s'agisse de la position allongée ou de se retourner, s'asseoir ou marcher à quatre pattes, le jeune enfant autiste se comporte de manière inhabituelle. Assis, il tombe faute d'utiliser l'un de ses bras, plus tard, sa démarche est anormale, asymétrique le plus souvent du côté droit. Parmi les autres caractéristiques, l'absence de marche à quatre pattes, l'absence d'anticipation lorsque l'on s'apprête à le prendre dans les bras, une agitation des bras, des postures inhabituelles, des sauts et des mouvements maniérés des doigts. On retrouve chez de nombreux sujets Asperger des difficultés de coordination et une maladresse dans le mouvement. Il faut également évoquer dans l'autisme des problèmes de praxis (mouvement intentionnel), les stéréotypies, les mouvements de déplacement en cercle ou de rotation sur place, les balancements, la marche sur la pointe des pieds, des mouvements saccadés, des difficultés pour déglutir et mâcher, écrire, l'apraxie des membres et une mauvaise coordination oculomotrice.

L'intoxication au mercure est également essentiellement caractérisée par des troubles moteurs, y compris dans le cas des enfants intoxiqués in utero. Ces troubles revêtent différentes formes : chez les bébés et enfants irakiens intoxiqués, une ataxie allant de la maladresse à une réelle incapacité à marcher ou à se tenir debout.

Nearly all cases of autism include disorders of physical movement. Movement disturbances have been detected in infants as young as four to six months old who were later diagnosed as autistic: Teitelbaum et al (1998) have observed that these children do not lie, roll over, sit up or crawl like normal infants; impairment in motor control sometimes caused these babies to fall over while sitting, consistently to avoid using one of their arms, or to rest on their elbows for stability while crawling. Later, when trying to walk their gait was abnormal, and some degree of asymmetry, mostly right-sided, was present in all cases studied. Kanner noted in several of his subjects the absence of crawling and a failure to assume an anticipatory posture preparatory to being picked up in infancy (Kanner, 1943). Arm flapping, abnormal posture, jumping, and hand-finger mannerisms (choreiform movements) are common (Tsai, 1996). Many individuals with Asperger's syndrome are typically characterized as uncoordinated or clumsy (Kugler, 1998). Other autism movement disorders include praxis (problems with intentional movement), stereotypies, circling or spinning, rocking, toe walking, myoclonal jerks, difficulty swallowing and chewing, difficulty writing with or even holding a pen, limb apraxia, and poor eye-hand coordination (Caesaroni and Garber, 1991; Gillberg and Coleman, 1992; Filipek et al, 1999).

Like ASD, movement disorders have been a feature of virtually all descriptions of mercury poisoning in humans (Snyder, 1972). Even children prenatally exposed to "safe" levels of methylmercury had deficits in motor function (Grandjean et al, 1998). The movement-related behaviors are extremely diverse: Iraqi infants and children exposed postnatally, for example, developed ataxia that ranged from clumsiness and gait disturbances to an "inability to stand or even sit" (Amin-Zaki et al, 1978). The various movement behaviors are listed more fully in Table V (Adams et al, 1983; Kark et al, 1971; Pierce et al, 1972; Snyder, 1972; O'Carroll et al, 1995; Tokuomi et al, 1982; Amin-Zaki, 1979; Florentine and Sanfilippo, 1991; Rohyans et al, 1984; Fagala and Wigg, 1992; Smith, 1977; Grandjean et al, 1998; Farnesworth, 1997; Dales, 1972; Matheson et al, 1980; Lowell et al, 1996; O'Kusky et al, 1988; Vroom and Greer, 1972; Warkany and Hubbard, 1953).

Noteworthy because of similarities to movement disorders in autism are reports in the Hg literature of (a) an infant with "peculiar tremulous movements of the extremities which were principally proximal and can best be described as flapping in nature" (Pierce et al, 1972; Snyder, 1972); (b) "jerking movements of the upper extremities" in a man injected with thimerosal (Lowell et al, 1996); (c) "constant choreiform movements affecting the fingers and face" in mercury vapor intoxication (Kark et al, 1971); (d) myoclonal jerks, associated with epilepsy among Iraqi subjects (Amin-Zaki et al, 1978); (e) poor coordination and clumsiness among victims of acrodynia (Farnesworth, 1997); (f) rocking among infants with acrodynia (Warkany and Hubbard, 1953); (g) "unusual postures" observed in both acrodynia and mercury vapor poisoning (Vroom and Greer, 1972; Warkany and Hubbard, 1953); and (h) toe walking among less severely poisoned children in the Minamata epidemic (Minamata Disease, 1973). In animal studies, cats exposed to mercury by eating fish developed "circling movements" (Snyder, 1972), and subcutaneous administration of methylmercury to rats during postnatal development has resulted in postural disorders (O'Kusky et al, 1988).

As summarized in Table V, movement similarities in autism and Hg poisoning are clear.

Tableau V : troubles moteurs
dans l'intoxication au mercure et l'autisme

e. Cognition/capacités mentales

Presque toutes les personnes porteuses d'autisme présentent une altération des fonctions mentales, même si les autres fonctions cognitives demeurent intactes. Le QI peut être révélateur d'un retard mental ou au contraire normal ou supérieur à la moyenne. Le tableau est identique dans le cas de l'intoxication au mercure. Les capacités affectées sont par ailleurs identiques dans les deux cas.

Pour ce qui est de l'autisme :
(a) mémoire à court terme ou mémoire de travail et mémoire auditive et verbale ;
(b) concentration et attention, en particulier aptitude à reporter son attention ;
(c) aptitudes visuomotrices et de la perception, y compris la coordination oculomotrice ;
(d) langage, expression et compréhension ; et
(e) exploitation de l'information visuelle en temps limité.

Domaines relativement peu affectés : la mémoire à long terme, la reconnaissance de schémas, la mise en correspondance, l'organisation perceptuelle et la discrimination de stimuli.

Les compétences sollicitées pour des tâches requérant un traitement plus complexe sont généralement affectées :
(a) traitement et filtrage de stimuli multiples ;
(b) exécution de consignes multiples ;
(c) mise en séquence, planification et organisation ;
(d) pensée abstraite et conceptuelle, compréhension de la symbolique.
Les enfants les plus jeunes ou les plus atteints peuvent présenter des difficultés en matière de jeu symbolique, de compréhension de la permanence des objets ou de la pensée d'autrui. Certains sont hyperlexiques sans pour autant comprendre ce qu'ils lisent. Le QI verbal est le plus souvent inférieur au QI performance.

A l'instar de l'autisme, l'exposition au mercure se caractérise par des difficultés dans les domaines suivants :
(a) mémoire à court terme et mémoire auditive et verbale ;
(b) concentration et attention, en particulier inhibition des réactions ;
(c) aptitudes visuomotrices et perceptuelles, dont la coordination oculomotrice ;
(d) langage, expression verbale et compréhension ; et
(e) temps de réaction.

Les personnes intoxiquées peuvent sembler avoir perdu la mémoire ou souffrir de confusion. Les résultats de QI performance peuvent être supérieurs aux résultats de QI verbal.

L'altération des "aptitudes mentales supérieures" se traduit par :
(a) des difficultés pour exécuter des consignes multiples ;
(b) des anomalies de la pensée abstraite et symbolique ;
(c) un déficit des compétences d'abstraction (construction et concepts).
On observe également parfois une alexie, incompréhension de la signification des mots lus.

Les enfants exposés in utero à des niveaux réputés "sûrs" de méthylmercure présentent des scores inférieurs à certains sous-tests cognitifs, en particulier ceux portant sur la mémoire et l'attention. Chez le jeune singe exposé, on constate un retard dans le développement de la compréhension de la permanence de l'objet et la capacité à conceptualiser un objet caché.

Les recherches menées en matière de retard mental dans l'autisme donnent des résultats contradictoires selon la nature des tests utilisés : le recours à des tests spécifiquement conçus fait apparaître un retard mental chez 20% des enfants autistes, contre 70%-80% avec les tests classiques. Contrairement à d'autres troubles assortis de retard mental, les sujets autistes présentent également des résultats particulièrement hétérogènes. En outre, contrairement aux cas classiques de retard mental, le plus souvent identifiés dès les premiers moments de la vie, les parents d'enfants du spectre autistique évoquent un développement relativement normal ultérieurement qualifié de retardé à l'occasion de tests.

De même que pour l'autisme, les sujets présentant les symptômes de l'intoxication au mercure peuvent présenter un QI normal, limite ou un  retard mental ; lorsqu'une altération de l'intelligence est notée, elle est toujours précédée d'une détérioration évidente chez des personnes dotées auparavant d'une intelligence normale. Une fois le mercure éliminé, la plupart de ces patients "recouvrent" leur QI normal, ce qui laisse supposer que le "vrai" QI n'a pas été affecté.

Nearly all autistic individuals show impairment in some aspects of mental function, even as other cognitive abilities remain intact. Most individuals may test in the retarded range, while others have normal to above average IQs. These characteristics are true in mercurialism. Moreover, the specific areas of impairment are similar in the two disorders.

The impaired areas in autism are generally in (a) short term or working memory and auditory and verbal memory; (b) concentration and attention, particularly attention shifting; (c) visual motor and perceptual motor skills, including eye-hand coordination; (d) language/verbal expression and comprehension; and (e) using visually presented information when constraints are placed on processing time. Relatively unimpaired areas include rote memory skills, pattern recognition, matching, perceptual organization, and stimuli discrimination. Higher level mental skills requiring complex processing are typically deficient; these include (a) processing and filtering of multiple stimuli; (b) following multiple step commands; (c) sequencing, planning and organizing; and (d) abstract/conceptual thinking and symbolic understanding (Rumsey & Hamburger, 1988; Plioplys, 1989; Bailey et al, 1996; Filipek et al, 1999; Rumsey, 1985; Dawson, 1996; Schuler, 1995; Grandin, 1995; Sigman et al, 1987). Younger or more mentally impaired children may have difficulties with symbolic play and understanding object permanence or the mental state of others (Bailey et al, 1996). Some autistic children are hyperlexic, showing superior decoding skills while lacking comprehension of the words being read (Prizant, 1996). As mentioned before, for most autistic individuals verbal IQ is lower than performance IQ.

As in autism, Hg exposure causes some level of impairment primarily in (a) short term memory and auditory and verbal memory; (b) concentration and attention, including response inhibition; (c) visual motor and perceptual motor skills, including eye-hand coordination; (d) language/verbal expression and comprehension; and (e) simple reaction time. Hg-affected individuals may present as "forgetful" or "confused." Performance IQ may be higher than verbal IQ. "Degeneration of higher mental powers" has resulted in (a) difficulty carrying out complex commands; (b) impairment in abstract and symbolic thinking; and (c) deficits in constructional skills and conceptual abstraction. One study mentions alexia, the inability to comprehend the meaning of words, although reading of the words is intact (Yeates & Mortensen, 1994; O'Carroll et al, 1995; Pierce et al, 1972; Snyder, 1972; Adams et al, 1983; Kark et al, 1971; Amin-Zaki, 1974 and 1979; Davis et al, 1994; Grandjean et al, 1997 & 1998; Myers & Davidson, 1998; Gilbert & Grant-Webster 1995; Dales, 1972; Fagala and Wigg, 1992; Farnesworth, 1997; Tuthill, 1899; Joselow et al, 1972; Rice, 1997; Piikivi et al, 1984; Vroom and Greer, 1972). Even children exposed prenatally to "safe" levels of methylmercury show lower scores on selective subtests of cognition, especially in the domains of memory and attention, relative to unexposed controls (Grandjean et al, 1998). In exposed juvenile monkeys, tests have revealed delays in the development of object permanence, or the ability to conceptualize the existence of a hidden object (Rice, 1996).

Research on mental retardation in autism is contradictory (Schuler, 1995). The finding that "mental retardation or borderline intelligence often co-exists with autism" (Filipek et al, 1999) is based on using standard measures of intelligence (Gillberg & Coleman, 1992, p.32; Bryson, 1996); other intelligence tests, designed to circumvent the language and attentional deficits of autistic children, show significantly higher intelligence test scores (Koegel et al, 1997; Russell et al, 1999). One study using such a modified rating instrument has found 20% of autistic children to be mentally retarded (Edelson et al, 1998), rather than the 70%-80% so scored on standard tests. ASD individuals also show "strikingly uneven scores" on IQ subtests, "unlike other disorders involving mental retardation, in which subtest scores seem to be more or less even" (Bailey et al, 1996). Also unlike typical cases of mental retardation, which is nearly always noted in the peri- or neonatal periods, most parents of ASD children report infants of seemingly normal appearance and development who were later characterized as mentally retarded on tests. For example, one study compared early developmental aberrations in mentally retarded children with and without autism. Findings indicated that, whereas nearly all parents of the non-autistic mentally retarded study group were aware of their child's impairment by age 3 months, nearly all parents of the autistic children failed to notice any developmental delays or issues until after 12 months of age (Baranek, 1999). Finally, there are several case reports of autistic adults who were labeled mentally retarded as children based on tests, who later "emerged" from their autism and had normal IQs (ARI Newsletter, 1993, review).

As in autism, symptomatic mercury-poisoned victims can present with normal IQs, borderline intelligence, or mental retardation; some may be so impaired as to be untestable (Vroom and Greer, 1972; Davis et al, 1994). When lowered intelligence is found, it is always reported as an obvious deterioration among previously normally functioning people; this includes children exposed as infants or toddlers (Dale, 1972; Vroom and Greer, 1972; Amin-Zaki, 1978). Once the Hg-exposure source is removed, many (although not all) of these patients "recover" their normal IQ, suggesting that "real" IQ was not affected (Vroom and Greer, 1972; Davis et al, 1994). Infant monkeys given low doses of Hg, while clearly impaired in visual, auditory, and sensory functions, had intact central processing speed, which has been shown to correlate with IQ in humans (Rice, 1997).  

Tableau VI : altération des capacités mentales
dans l'intoxication au mercure et l'autisme

f. Comportement

L'autisme s'accompagne de troubles du sommeil, d'hyperactivité, d'hyperactivité avec déficit d'attention, ainsi que de comportements automutilateurs tels que se frapper la tête contre les murs, y compris en l'absence de tout retard mental. Agitation, cris, pleurs, regards dans le vide, comportements stéréotypés et grimaces sont courants. Les problèmes d'alimentation – alimentation sélective, vomissements ou anorexie sont également fréquents.

Les humains et les animaux exposés au mercure développent des comportements inhabituels : reniflements stéréotypés chez le rat exposé au mercure pendant la gestation, agitation, faible inhibition des réactions, agitation, pleurs, grimaces et insomnie chez le bébé et le jeune enfant ; les symptômes de l'acrodynie chez le bébé et le jeune enfant sont, entre autres, les pleurs, l'anorexie et l'insomnie ; le priapisme, érection permanente, a pu être également noté chez les garçons empoisonnés au mercure. Les adultes quant à eux présentent des insomnies assorties d'agitation et de perte de l'appétit. Les adultes atteints d'acrodynie dans leur enfance présentent des particularités sur le plan alimentaire telles qu'une préférence marquée pour les aliments salés, peut-être parce que le mercure entraîne une excrétion excessive de sodium.

Autism is associated with difficulties initiating and/or maintaining sleep; hyperactivity and other ADHD traits; and self injurious behavior such as head banging, even in the absence of mental retardation. Agitation, screaming, crying, staring spells, stereotypical behaviors, and grimacing are common (Gaedye, 1992; Gillberg and Coleman, 1992; Plioplys, 1989; Kanner, 1943; Richdale, 1999; Stores & Wiggs, 1998). Kanner (1943) made a point of noting excessive and open masturbation in two of the eleven young children comprising his initial cases. Feeding and suckling problems are typical (Wing, 1980), and restricted diets and narrow food preferences "are the rule rather than the exception" (Gillberg and Coleman, 1992; Clark et al, 1993); some autistics show a preference for salty foods (Shattock, 1997). Kanner, in his 1943 article, noted feeding problems from infancy, including vomiting and a refusal to eat, in six of the eleven autistic children he described. There are case studies of anorexia nervosa occurring in ASD patients, as well as an increased likelihood of this eating disorder in families with ASD (Gillberg & Coleman, 1992, p.99).

Humans and animals exposed to mercury develop unusual, abnormal, and "inappropriate" behaviors (Florentine and Sanfilippo, 1991). Rats exposed to mercury during gestation have exhibited stereotyped sniffing (Cuomo et al, 1984) and hyperactivity (Fredriksson et al, 1996). "Restlessness" has already been noted, and Davis et al (1994) found poor response inhibition in their human subjects; both of these behaviors are closely associated with ADHD in children. Babies and children with Hg poisoning exhibit agitation, crying for no observable reason, grimacing, and insomnia (Pierce et al, 1972; Snyder, 1972; Kark et al, 1971; Amin-Zaki, 1979; Florentine and Sanfilippo, 1991; Aronow and Fleischmann, 1976). An 18 month old toddler with otitis media, exposed to thimerosal in ear drops, had staring spells and unprovoked screaming episodes (Rohyans et al, 1984). Symptoms of acrodynia in babies and toddlers include continuous crying, anorexia and insomnia (Matheson et al, 1980; Aronow and Fleischmann, 1976). These children were said to bang their heads, have difficulty falling asleep, be irritable, and either refuse to eat or only eat a few foods (Neville Recollection, Pink Disease Support Group Site; Farnesworth, 1997). The frequent temper tantrums of a previously normal 12 year old, poisoned by mercury vapor, included hitting herself on the head and screaming; furthermore, she had extreme genital burning and was observed to masturbate even in front of others (Fagala and Wigg, 1992). Similarly, priapism, persistent erection of the penis due to a pathologic condition resulting in pain and tenderness, has been noted in boys with mercury poisoning (Amin-Zaki et al, 1978).

Adults with mercury poisoning present with insomnia, agitation, and poor appetite (Tuthill, 1899; Adams et al, 1983; Fagala and Wigg, 1992). Relative to controls, more adults who had acrodynia in childhood have eating idiosyncrasies, particularly a preference for salty foods to sweet ones (Farnesworth, 1997), possibly because mercury causes excessive sodium excretion, as shown in studies of dental amalgam placed in monkeys and sheep (Lorscheider et al, 1995).

Tableau VII : comportements inhabituels dans
l'intoxication au mercure et dans l'autisme

g. Vision

L'un des premiers symptômes de l'autisme est le manque de contact oculaire et d'attention conjointe. Il faut également noter des anomalies ou un ralentissement des saccades visuelles. Malgré dans certains cas une acuité visuelle hors normes, deux études ont identifié des troubles de la vision dans 50% des cas, dont une altération des bâtonnets et un voile rétinien qui conduisent de nombreux sujets à privilégier la vision périphérique. L'hypersensibilité à la lumière et une vision floue sont par ailleurs courantes.

Le mercure peut s'assortir de différents troubles de la vision : des enfants ayant absorbé de fortes doses de mercure en consommant du porc contaminé sont devenus aveugles, des enfants irakiens ont pu présenter des troubles allant d'une vision trouble ou d'un champ visuel retréci à une cécité complète. Les victimes de l'acrodynie présentent des troubles tels que la myopie et une sensibilité accrue à la lumière. Des troubles comparables ont été notés auprès des populations nippones et de mères irakiennes exposées.

Chez des chiens exposés à des doses quotidiennes de méthylmercure, on a pu observer une distorsion du potentiel visuel évoqué ; des singes exposés dès la naissance à de faibles doses de méthylmercure ont présenté des troubles de la vision spatiale et de l'acuité visuelle vers 3 et 4 ans.

In autism, one of the earliest signs detected by mothers is a lack of eye contact (Gillberg & Coleman, 1992), and an early diagnostic behavior is failure to engage in joint attention based on the ability to "look where you are pointing" (CHAT, Baron-Cohen et al, 1992). Of 11 autistic children studied, ten had inaccurate or slow visual saccades (Rosenhall et al, 1988). Although some adults with ASD report exceptional visual acuity, visual problems are common, with two separate studies reporting 50% of ASD subjects having some type of unusual visual impairment (Steffenburg, in Gillberg & Coleman, 1992). Ritvo et al (1986) and Creel et al (1989) found decreased function of the rods in a study of autistic people, including a retinal sheen, and noted that many such individuals tend to use peripheral vision because of this. A number of case reports describe over-sensitivity to light and blurred vision (Sperry, 1998; Gillberg & Coleman, 1992, p.29; O'Neill & Jones, 1997).

Mercury can lead to a variety of vision problems, especially in children (Pierce et al, 1972; Snyder, 1972). Children who ate high doses of mercury from contaminated pork developed blindness (Snyder, 1972). In Iraqi babies exposed prenatally there was blindness or impaired vision (Amin-Zaki, 1974 and 1979). Iraqi children exposed postnatally developed visual disturbances, which ranged from blurred or hazy vision to constriction of the visual fields to complete blindness (Amin-Zaki et al, 1978). Two girls with mercury vapor poisoning were found to have visual field defects (Snyder, 1972), and, as previously noted, one child with Hg poisoning developed gaze avoidance (Fagala & Wigg, 1992). Acrodynia sufferers report vision problems, including near-sightedness and light sensitivity or photophobia (Diner and Brenner, 1998; Neville Recollection, Pink Disease site; Farnesworth, 1997; Matheson et al, 1980; Aronow and Fleischmann, 1976). A 25 year old man with elemental mercury poisoning exhibited decreased visual acuity, difficulty with visual fixation, and constricted visual fields (Kark et al, 1971). In Japanese victims, there was blurred vision as well as constriction of visual fields (Snyder, 1972; Tokuomi et al, 1982). Iraqi mothers exposed to Hg had visual disturbance (Amin-Zaki, 1979).

In dogs exposed to daily doses of methylmercury, distortion of the visual evoked response from the visual cortex was the first sign. Damage occurred in the preclinical silent stage, demonstrating that CNS damage is occurring before overt symptoms appear (Mattsson et al, 1981). Monkeys treated at birth with low level methylmercury exhibited impaired spatial vision and visual acuity at age 3 and 4 years (Rice and Gilbert, 1982). Disturbances caused by methylmercury in rat optic nerves were observed (Kinoshita et al, 1999).

Tableau VIII : troubles de la vision

dans l'intoxication au mercure et l'autisme

h. Condition physique

Le nombre de cas d'autisme chez les enfants atteints de paralysie cérébrale n'est pas dû au hasard. Nombre de ces enfants présentent un tonus musculaire anormal ainsi que des problèmes d'incontinence. Les faiblesses musculaires sont généralement plus marquées dans la partie supérieure du corps. Les difficultés pour mâcher et avaler sont également fréquentes.

Ces symptômes sont également constatés dans l'intoxication au mercure. Dans les populations irakiennes et nippones atteintes, de nombreux enfants ont développé une paralysie cérébrale clinique avec perte de tonus et de contrôle musculaire, voire une paralysie complète dans certains cas.

Irritations, dermatites et eczéma sont courantes chez les sujets atteints d'un syndrome autistique.

Les irritations et démangeaisons sont également des symptômes classiques de l'intoxication au mercure.

Des signes de troubles de l'autonomie, tels que transpiration, respiration irrégulière et accélération du pouls peuvent  être notés de temps à autre. On a également noté des anomalies de la circulation sanguine, de la transpiration et de la régulation thermique chez les sujets Asperger.

Les anomalies de la transpiration, du pouls et de la circulation sanguine sont également courantes dans certaines formes d'intoxication au mercure. Ces anomalies peuvent être liées à un déséquilibre en acétylcholine, souvent insuffisante chez les sujets autistes et personnes intoxiquées au mercure (voir ci-après la section consacrée aux neurotransmetteurs).

There is a much higher rate of autism among children with cerebral palsy than would be expected by chance (Nordin and Gillberg, 1996). Many autistic children have abnormal muscle tone including hyper- and hypotonia, and many are incontinent or have difficulty being toilet trained (Filipek et al, 1999; Church and Coplan, 1995). Several of the infants which Teitelbaum and colleagues (1998) observed showed decreased arm strength, and Schuler (1995) describes greater muscle weakness in the upper than the lower body. Impairments in oral-motor function, including problems chewing and swallowing, are common, as noted previously.

These impairments are seen in mercurialism as well. In the Iraqi and Japanese epidemics, many children developed clinical cerebral palsy (Amin-Zaki, 1979; Myers & Davidson, 1998; Gilbert & Grant-Webster 1995; Dale, 1972). Amin-Zaki et al (1978) reported muscle wasting and lack of motor power and control in most cases, complete paralysis in several cases, and athetotic movements in 2 cases, of postnatally exposed children. In the Iraqi babies and children, some had increased muscle tone, while others had decreased muscle tone. Abnormal reflexes, spasticity, and weakness were common. One child said "my hands are weak and do not obey me" (Amin-Zaki et al, 1974 and 1978). The 12 year old who inhaled mercury vapor exhibited weakness and decreased muscle strength (Fagala and Wigg, 1992). As in autism, muscle weakness from mercury poisoning is most prominent in the upper body (Adams et al, 1983). Acrodynia, for example, is marked by poor muscle tone in general and loss of arm strength in particular (Farnesworth, 1997). Finally, difficulty in chewing and swallowing, salivation, and drooling are common in children as well as adults; incontinence was observed in children in the Iraqi Hg-crisis (Amin-Zaki, 1974 and 1978; Pierce et al, 1972; Snyder, 1972; Joselow et al, 1972; Smith, 1977).

The presence of rashes and dermatitis is sometimes reported in descriptions of ASD subjects. Whiteley et al (1998) found that 63% of the ASD children had a history of eczema or other skin complaints. "Some children with autism are frequent scratchers. Gentle rubbing and scratching can become a calming self-stimulation; but when it becomes clawing, and there are rashes and open scrapes on the skin, a tactile intolerance can be responsible" (O'Neill, 1999).

Rashes and itching are common disturbances in mercury toxicity as well (Kark et al, 1971). A 4 year old with Hg poisoning developed an itchy, peeling rash on the extremities (Florentine and Sanfilippo, 1991). Mercury vapor inhalation caused a rash and peeling on the palms and soles of a pre-adolescent (Fagala and Wigg, 1992). An acrodynia victim described himself as a child as having severe itching and a constant burning sensation at the extremities, resulting in him rubbing his hands and feet raw (Neville Recollection, Pink Disease Support Group). Acrodynia symptoms in an adult poisoned by ethylmercury injection included pink scaling palms and soles, flushed cheeks, and itching (Matheson et al, 1980). In acrodynia the skin may be rough and dry, and the soles and palms are usually but not necessarily red (Aronow and Fleischmann, 1976). Thimerosal ingested by 44 year old man led to dermatitis (Pfab et al, 1996).

In autism, "signs of autonomic disturbance may be noticed at times, including sweating, irregular breathing, and rapid pulse" (Wing and Attwood, 1987). There may be elevated blood flow and heart rate (Ornitz, 1987). An increased incidence of acrocyanosis has been observed in Asperger's syndrome. Acrocyanosis is an uncommon disorder of poor circulation in which skin on the hands and feet turn red and blue; there is profuse sweating; and the fingers and toes are persistently cold (Carpenter and Morris, 1991).

Sweating and circulatory abnormalities are also common in some forms of mercury poisoning. Acrodynia in adults and children results in excessive sweating, poor circulation, and rapid heart rate (Farnesworth, 1997; Matheson et al, 1980; Cloarec et al, 1995; Warkany and Hubbard, 1953). The 12 year old with mercury vapor poisoning sweated profusely, especially at night (Fagala and Wigg, 1992), and elevated blood pressure has been reported in exposed workers (Vroom and Greer, 1972). Autonomic system abnormalities can be caused by disturbances in acetylcholine levels, known to be deficient in both autism and Hg poisoning (see neurotransmitter section below).

Tableau IX : troubles physiques
dans l'intoxication au mercure et l'autisme