Mostrando postagens com marcador autismo. Mostrar todas as postagens
Mostrando postagens com marcador autismo. Mostrar todas as postagens

terça-feira, 26 de julho de 2016

Detalhes sobre autismo

Ressonância magnética para detectar autismo

Embora os primeiros sinais do espectro autista apareçam a partir do primeiro ano de vida, os processos cerebrais ligados à comunicação sofrem alterações que desencadeiam o transtorno muito antes disso. É o que sugere os resultados preliminares de uma pesquisa recente conduzida pelo pesquisador Jason Wolff, da Universidade Chapel Hill, Carolina do Norte, publicada pelo American Journal of Psychiatry.

Para chegarem a essa conclusão, os pesquisadores investigaram o desenvolvimento cerebral de 92 bebês, todos com um irmão mais velho autista, e acompanharam as mudanças na organização neurológica ao longo do tempo por meio de exames de ressonância magnética. Quando as crianças estavam com 2 anos, 28 haviam desenvolvido o autismo, enquanto 64 não. A incidência do transtorno entre irmãos sugere correlação genética, segundo os especialistas. 

Os pesquisadores observaram também que a substância branca (componente sólido do sistema nervoso central responsável pela transmissão de sinais entre regiões do cérebro) se formou lentamente em crianças que posteriormente desenvolveram a patologia, enquanto que nas saudáveis essa estrutura se constituiu rapidamente. Além disso, notaram alterações no desenvolvimento das fibras nervosas que conectam áreas cerebrais.

Esses indícios sugerem que o transtorno seja um fenômeno que atinge o cérebro inteiro, e não uma região específica como se acreditava anteriormente. Apesar de ser muito cedo para dizer o que causa essas diferenças, a descoberta indica uma interação complexa entre os genes e as experiências da criança com o mundo. “Futuros tratamentos poderão ser administrados em fases precoces da maturação cerebral para diminuir o impacto do autismo ou até mesmo para interromper seu desenvolvimento”, diz Wolff.

 “As pessoas pensam que sou idiota.” “É realmente frustrante não conseguir falar.” “Eu me expresso através de comportamentos negativos que ninguém pode entender.” Essas são algumas frases de crianças com autismo, digitadas em aplicativos touch screen (telas sensíveis ao toque) e exibidas no curta-metragem documentário Eu quero dizer (I want to say, sem legendas em português). O filme mostra como esses programas, criados por desenvolvedores das empresas HP e Intel, se tornaram um canal de comunicação para pessoas com o transtorno. A ideia surgiu quando um executivo da HP levou um computador com tela touch à casa de um amigo, pai de um autista, para ver se o garoto se interessaria pelo equipamento. O menino começou a usar a interface intuitivamente e se comunicou com sua família. Em uma cena, uma mãe relata sua emoção ao ver a filha, que não fala, digitar que a amava. O vídeo, de 30 minutos, está disponível no canal Autism Speaks, no Youtube: I want to say.


O elo do silêncio


 Quando comparamos a linguagem humana aos sistemas de comunicação de outros animais, nossa complexidade salta aos olhos. Combinando com grande liberdade um repertório de poucas dezenas de fonemas, somos capazes de produzir milhares de palavras para nomear tudo que nossa mente consegue perceber, fazer e pensar. Os defensores do excepcionalismo humano argumentam que nada parecido existe em nossos parentes mais próximos, os símios africanos. Apesar de limitado, nosso repertório fonêmico é grande o bastante para gerar uma explosão de possíveis combinações, o que só é possível por causa de um aparato fonador especializado. Ainda que bonobos, chimpanzés, gorilas e orangotangos vocalizem durante suas interações sociais, não apresentam um repertório de palavras capaz de representar a variedade de objetos do mundo. Eles contam, claro, com sinais vocais relacionados ao humor, além de muitos gestos e expressões faciais para comunicação de curta distância. No excêntrico teatro símio, o silêncio é de ouro.

Grande parte da elite acadêmica, das ciências biomédicas às humanas, sustenta que a linguagem é a principal linha divisória entre nós e todos os outros animais. Isso faz da expressão verbal humana um mistério evolutivo, sem elos filogenéticos com qualquer outro sistema de comunicação animal. Segundo uma teoria alternativa, defendida há décadas pelo biólogo Peter MacNeilage, a linguagem vocal humana evoluiu através da modificação de movimentos rítmicos faciais realizados por nossos ancestrais primatas. Infelizmente as estruturas necessárias para a produção da fala não se fossilizam, fazendo da abordagem comparativa uma necessidade. Entre os primatas do velho mundo, destaca se uma expressão facial de afiliação chamada abre-fecha labial. Caracterizado por movimentos verticais da mandíbula, esse comportamento quase inaudível é dirigido a outro indivíduo durante interações face a face, envolvendo troca de turnos como num diálogo.

Uma característica fundamental da fala humana é um ritmo em torno de 5 Hz (hertz) relacionado com a taxa de produção de sílabas. Se a fala evoluiu de movimentos faciais rítmicos, seria de esperar que o abre-fecha labial também apresentasse um ritmo próximo a 5 Hz. Para investigar a questão, pesquisadores das Universidades de Princeton e Viena filmaram em raios X os movimentos bucais de macacoscaranguejeiros enquanto realizavam abre-fecha labial ou mastigação.

Embora à primeira vista o abrefecha labial pareça envolver simplesmente a abertura e o fechamento dos lábios, a pesquisa mostrou que o comportamento requer movimentos rápidos e coordenados dos lábios, língua, mandíbula e do osso hioide. Os autores, entre os quais o médico, matemático e neurocientista brasileiro Daniel Takahashi, descobriram que esses movimentos ocorrem 5 vezes por segundo, quase o dobro da velocidade dos movimentos de mastigação. Além disso, análises matemáticas mostraram que os distintos componentes do aparato fonador se articulam durante o abre-fecha labial de modo muito semelhante ao da fala humana. Considerando que os macacos-caranguejeiros são primatas asiáticos que divergiram de nossa linhagem há quase 30 milhões de anos, os resultados sugerem que a fala humana evoluiu a partir de uma linguagem primata ancestral, baseada menos no som do que nas expressões faciais. Talvez a excepcionalidade do Homo sapiens não seja a linguagem e sim o barulho.
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Outgrowing Autism? A Closer Look at Children Who Read Early or Speak Late

The headlines read “New study suggests autism can be outgrown”, or “outgrowing autism: a doctor’s surprise and wonder.” The stories are based on studies reporting that 7-9% of children with a documented early autistic syndrome disorder (ASD) have no symptoms of the disorder on follow-up later in childhood or adolescence. That is good news. The question is how to account for it.
Is it possible to simply “outgrow” autism? Was the initial diagnosis wrong? Did some interventions work? Or might there be other explanations for this welcome news?
"In an earlier column titled “Oops. When “autism” isn’t autistic disorder,” I outlined three types of hyperlexia, or precocious reading ability, which is sometimes an element of a diagnosis of ASD. Type 1 are neurotypical children who simply read way ahead of their chronological age. Listening to a 4 year old reading books to his or her nursery school classmates is a startling experience.
Type 2 are children in which intense fascination with letters and numbers, along with early reading and remarkable memory represent ‘splinter skills’ as a part of autistic syndrome disorder (ASD)
Type 3 are children who likewise show intense fascination and preoccupation with numbers and letters very early, along with precocious reading skills and remarkable memory. They do have “autistic-like” symptoms or behaviors but those disappear over time as the child gets older. The outcome in these children is much more positive than those with ASD to their benefit and the great relief of their parents.
Following the “Oops” article I received numerous reports from parents who identified with hyperlexia 3. “You just described my child,” the puzzled, and relieved parents would write as they read the case examples in my Wisconsin Medical Journal article in December, 2011. I reviewed those reports and recently did an analysis of 165 of them with the following findings:
  • In all the cases there had been a confusing journey of various diagnoses, sometimes ASD/Aspergers or its variants, or else a wide range of others from hyperactivity to anxiety disorder to speech delay.
  • Age of onset of hyperlexia skills was 24.6 months
  • Age of first professional contact was 44 months
  • Certain features caught the parent’s attention in the hyperlexia 3 group as being different from ‘autism’ as usually described. For example their child demonstrated less withdrawal, more eye contact, the ability to seek and give affection and in general overall increased social proficiency.
  • Additionally while some “autistic-like” behaviors were present such as repetitive behaviors, insistence on sameness, occasional stimming, echolalia and increased sensory sensitivity, those symptoms disappeared as the child grew older
  • 11 cases that mentioned adult outcomes indicated 9 persons were attending college and having successful, independent lives. They continued to be exceptional readers which helped their collegiate performance and aided their careers. 2 cases were described as needing supervision because of continued autistic characteristics
  • Having an ASD diagnosis applied to their child at any point was a source of great distress for all parents.
It is impossible, of course, to make a diagnosis of the child based only on parent description. But from reading those reports, many of them very detailed, there was a clear impression that in some cases the hyperlexia was indeed a “splinter skill” manifestation of autism spectrum disorder (hyperlexia 2). But in many others, the increased social proficiency particularly, and disappearance of many “autistic-like” symptoms along with more positive outcomes suggested placement in a separate, hyperlexia 3 group.
In all of medicine the first step in treatment is to make the correct diagnosis. The only way to do that is with an in-person comprehensive evaluation by a multi-disciplinary team, including developmental specialists, neuropsychologists, and speech, language and occupational therapists, to name some. That will be the follow-up to this present study.
In the meantime, unfortunately, there continues to be a misconception in the literature and on the internet, that hyperlexia is always part of autism spectrum condition. That same misconception applies to children who speak late (“Einstein syndrome”), as vividly pointed out in Stephen Camarata’s book “Late-Talking Children: A Symptom or a Stage?” His experience with children who speak late mirrors my experience with children who read early.
While early diagnosis and intervention is to be applauded for children with developmental issues of all sorts, caution is warranted when applying an ASD diagnosis to children who read early or speak late, and at least a differential diagnosis by those familiar with hyperlexia or Einstein syndrome should be used until the natural history of the disorder reveals, finally, its true nature.
When a child exhibits hyperlexia 2 or 3, the same intervention tools are used to deal with the autistic, or autistic-like symptoms to the extent they are present. But the distinction between hyperlexia 2 and 3 becomes a critical one when it comes to vital educational decisions and placements. Hyperlexia 3 children do not do well in typical “special education” classes, and require instead different placements. Hence the cautious, informed diagnostic route.
Some will argue that the various interventions and treatments are responsible for that 6-7% of children who “outgrow” their autism. That may be true in some instances, but among my 165 cases are a number of children, now adult, with sufficient outcome and follow-up to conclude that those with what turned out to be hyperlexia 3 did not have ASD in the first place, the initial diagnosis notwithstanding. In these follow-up cases were a number of ‘success stories’ of very positive outcomes from grateful parents. But one was a first person account from a woman, now an adult, who recounted her journey with hyperlexia 3, asking now that she is rid of the symptoms of autism, how does she get rid of the medical history of “autism” that follows her.
My position is that “outgrowing” autism is most often the situation in which a diagnosis of ASD was prematurely and mistakenly applied, especially in children who read early or spoke late. Granted that early distinction can be a very difficult one since separating ‘’autistic-like” symptoms from ASD itself can be difficult in those early years. Hopefully as we study more children with hyperlexia or speaking late, we will become better at that.
In the meantime a cautious differential diagnostic approach, along with careful, watchful observation over time is advised especially when early reading or late speaking are the presenting symptoms.
Those children who are in the hyperlexia 3 group do not “outgrow” their autism. They did not have ASD in the first place. That is a meaningful distinction between the two groups. Fortunately hyperlexia 3 children do very well over the long term and that, of course, is very good news for them, their parents and the rest of us as well.
Meanwhile I will keep collecting reports from parents, which come to me almost daily, for further analysis and study because the success stories are very relevant and encouraging indeed.
References:
Camarata, S. (2015) Late-talking children: A symptom or a stage? MIT Press Cambridge, MA
Fine, D et al (2013) Optimal outcome in individuals with a history of autism Journal of Child Psychology and Psychiatry 54:195-205
Shulman, L Outgrowing autism: A doctor’s surprise and wonder The Doctors Blog, Albert Einstein College of Medicine May 5, 2015
Treffert, D (2011) Hyperlexia 3: Separating ‘autistic-like’ behaviors from Autistic Disorder; assessing children who read early or speak late WMJ 110:281-286

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For Children with Autism, Multiple Languages May Be a Boon

Oscar, 6, sits at the family dinner table and endures the loneliest hour of his day. The room bustles with activity: Oscar’s sister passes plates and doles out broccoli florets. His father and uncle exchange playful banter. Oscar’s mother emerges from the kitchen carrying a platter of carved meat; a cousin pulls up an empty chair.

“Chi fan le!” shouts Oscar’s older sister, in Mandarin Chinese. Time for dinner!
“Hao,” her grandfather responds from the other room. Okay.
Family members tell stories and rehash the day, all in animated Chinese. But when they turn to Oscar, who has autism, they speak in English.
“Eat rice,” Oscar’s father says. “Sit nice.”
Except there is no rice on the table. In Chinese, ‘eat rice’ can refer to any meal, but its meaning is lost in translation.
Pediatricians, educators and speech therapists have long advised multilingual families to speak one language — the predominant one where they live — to children with autism or other developmental delays. The reasoning is simple: These children often struggle to learn language, so they’re better off focusing on a single one.
However, there are no data to support this notion. In fact, a handful of studies show that children with autism can learn two languages as well as they learn one, and might even thrive in multilingual environments.

LOST IN TRANSLATION:

It’s not just children with autism who miss out when parents speak only English at home — their families, too, may experience frustrating miscommunications. Important instructions, offhand remarks and words of affection are often lost in translation when families swap their heritage language for English, says Betty Yu, associate professor of special education and communicative disorders at San Francisco State University.
Yu, who is fluent in both English and Chinese, detailed Oscar’s experience in the Journal of Autism and Developmental Disorders earlier this year. (The details of dinner and other interactions from Oscar’s everyday life described in this article are from Yu’s case report.) The report hits home for researchers who study bilingual families of children with autism.
“One mother said to me, ‘Italian is the language of my heart and my home.’ She was obviously very sad that she couldn’t share that aspect of her identity with her daughter,” says Sue Fletcher-Watson, chancellor’s fellow in developmental psychology at the University of Edinburgh in the United Kingdom.
The advice to stick with a language that the family doesn’t speak well only intensifies the alienation experienced by these children, Fletcher-Watson and others say. “You’re taking a child who is already socially isolated and you’re making them even more isolated,” she says.

THE KIDS ARE ALL RIGHT:

The science — what little exists — in fact suggests that these children should embrace multilingualism.
“There are few studies on bilingualism in children with developmental disorders, and even fewer with appropriate control groups,” says Napoleon Katsos, lecturer in linguistics at the University of Cambridge in the United Kingdom.
In typical children, learning a second or third language hones critical thinking and executive function — a set of skills that includes attention, self-control and mental flexibility. It also gives them an edge in reading and writing.
Children with developmental delays might reap those same benefits. Bilingual children with autism have language skills on par with monolingual childrenwith the condition, and they acquire social and cognitive skills at the same rate. But these children are twice as likely as monolingual children with autism to use gestures such as pointing when they communicate, according to a 2012 study. This finding suggests that they have a strong command of joint attention and are adept at nonverbal communication.
The standard tools for evaluating a child’s social and communication skills are in English, and may underestimate the skills of bilingual children with autism, says Kruti Acharya, assistant professor of disability and human development at the University of Illinois at Chicago.
At the 2016 International Meeting for Autism Research in Baltimore, Acharya’s team presented preliminary results showing that a picture book a child narrates in his native language can more accurately assess his communication skills.
This approach could be particularly useful for autism clinicians in Europe, where dozens of languages are spoken, says Fletcher-Watson.
“There are some good reasons to be optimistic about the potential benefits of bilingualism,” Fletcher-Watson says. “There’s a big overlap between the areas that we think are helped by bilingual exposure and the areas where children with autism struggle.”

THINGS LEFT UNSAID:

Oscar, now 7, was born in California a few years after his family emigrated from China. At the time, the other members of his household, like more than 24 million other children and adults in the United States, spoke little English at home.
But when Oscar was diagnosed with autism at age 2, pediatricians, speech therapists, neighbors and friends all advised his family to pick a single language to communicate with him. And that language, they all agreed, should be English.
English is the ticket to success in school, Oscar’s teachers said. A prerequisite to participating in state-funded therapies, his therapists said. The predominant language of Oscar’s suburban neighborhood and of the children who play there, his neighbors said.
By the time Oscar turned 3, his family had committed to interacting with him only in English. Yet they sometimes seemed to be at a loss when trying to communicate with him. “There were things that the family didn’t know how to say very smoothly or at all in English, so they had to talk around the issue or just drop it,” Yu says.
The better scenario would have been to speak to Oscar in Chinese and let him learn English from the outside world, says Johanne Paradis, professor of linguistics at the University of Alberta in Canada. Retaining strong cultural and family ties will only help parents connect with their children later on, she says.
“It’s easy to say when a child is diagnosed with autism at age 3 that the family should switch to English at home,” Paradis says. “But when that child is 12, they’re going to have more complex ideas to express and the parent won’t be able to talk with them freely.”
After dinner, Oscar and his grandfather are seated a couple of feet apart on the living room floor, playing with a train set. But they might as well be separated by 2 miles, for all that they can say to each other.
It’s 8 o’clock — time to decide which family member will sleep in Oscar’s room and make sure he is safe.
The grandfather leans in and shakes Oscar’s hands, waiting for the boy to look up. “Oscar, with who sleep?” he asks.
Oscar pauses; glances down at the trains. “Oscar sleep,” the boy echoes, as he does when he struggles to understand.
The grandfather tries again. “You want with who sleep?”
“With Daddy,” Oscar says, finally.
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    segunda-feira, 14 de março de 2016

    Unraveling a pathway to autism - Desvendando um caminho para o autismo


    J. Peter H. Burbach

    + Author Affiliations
    1. E-mail: j.p.h.burbach@umcutrecht.nl
    Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders with shared symptoms in the area of communication and language, restricted interests, and stereotyped and social behaviors. Causes lie in perturbations of brain development, which can be manifold, but genetic factors are prominent among these. Genetic studies have pointed to hundreds of causative or susceptibility genes in ASD, making it difficult to find common underlying pathogenic mechanisms. Careful dissection of molecular and cellular mechanisms are needed to define the molecular targets that can translate into therapeutic strategies. On page 1199 of this issue, Bidinosti et al. (1) uncover defects in a molecular machinery of a genetic ASD mouse model. This allowed the authors to design specific chemical interventions that relieve cellular and behavioral autistic-like features. In addition, Yi et al. (2) report a channelopathy in neurons that may predispose to autism. The discoveries raise hope for developing new drugs that help patients with ASD.
    ASD pathway.
    In glutaminergic neurons, the AKT-mTORC1 pathway transduces signals from neurotransmitter and growth factor receptors and ion channels into several responses through scaffold proteins, including SHANK3. SHANK3 deficiency in a mouse model of ASD decreases the degradation of CLK2. This increases protein phosphatase 2A (PP2A) activity, which reduces AKT activity. As a consequence, protein synthesis decreases, leading to neuronal dysfunction. Drugs that activate AKT or inhibit CLK2 may adjust the AKT-mTORC1 pathway in ASDs. PI3K, phosphatidylinositol 3-kinase.
    ILLUSTRATION: V. ALTOUNIAN/SCIENCE
    Current thinking about pharmacological therapies for ASDs has been stimulated by two scientific milestones. One major advance has been the large number of genes associated with risk for autism (from human genetic studies). This has extended the clinical notion that ASDs include heterogeneous conditions ranging from severe intellectual disability to high-functioning forms (3). Furthermore, identified gene variants in ASDs all appear to be rare, and recurrence is very low (less than 1%) in sporadic cases. However, a number of syndromes with autistic-like features—in addition to fragile X and Rett syndromes—have been recognized. One of these is the Phelan-McDermid syndrome.
    Considering the human genetics of ASDs, the spectrum of properties of proteins encoded by ASD genes can be aggregated in a number of molecular and cellular functions. Thus, protein synthesis and degradation, signal transduction, transcription, and synaptic transmission emerge as major cellular processes from which ASDs may originate (3, 4). These processes are not independent of each other. For example, transcription, translation, and degradation together control the quantity and quality of the total pool of proteins of the cell. Signal transduction couples extracellular chemical signals, such as neurotransmitters and growth factors, to intracellular responses including protein synthesis and degradation, and transcription. These are all essential activity-dependent pathways that remain highly dynamic in adult stages. At an integrated level, these cellular pathways are apparent in biological functions relevant for ASDs, in particular synaptogenesis, axon guidance, dendritic and spine morphology, and synaptic plasticity. This has led to the hypothesis that abnormal synaptic homeostasis could play a key role in the pathogenesis of ASDs (3, 4).
    The other milestone in the field is the notion that neurodevelopmental defects are not necessarily permanent, but may be reversible. There has been a long-standing view that neurodevelopmental disorders are congenital inborn errors of brain development that leave the patient with irreversible defects. This traditional view was first challenged by the reactivation of a silenced gene encoding methyl CpG-binding protein 2 (MeCP2) in a mouse model of Rett syndrome (5). Induction of Mecp2 expression dramatically reversed behavioral and electrophysiological abnormalities in developing and adult mice. Selective reversal of abnormalities was also observed in other ASD models. For example, phenotypes in mice lacking the gene encoding the protein tuberous sclerosis 1 (TSC1) could be reversed by the small molecule rapamycin. Rapamycin blocks mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which controls protein synthesis. The TSC1-TSC2 complex controls mTORC1 activity (6). In mouse models of fragile X syndrome [mice that lack the gene encoding fragile X mental retardation protein 1 (FMRP1)], treatment with an antagonist of the metabotropic glutamate receptor 1/5 class (mGluR1/5) also reversed disease characteristics (6). Signaling by mGluR1/5 is coupled to synaptic response involving FMRP1. Moreover, insulin-like growth factor I has been successfully used to ameliorate autistic-like phenotypes in mouse models of Rett syndrome and Phelan-McDermid syndrome. SHANK3 is the prime gene culprit causing the latter disorder. Interestingly, selective rescue of autistic-like phenotypes in a mouse model was established by reexpression of Shank3 (7).
    SHANK3 is a synaptic scaffolding protein in the postsynapse that connects receptors and ion channels in the membrane with intracellular signaling proteins and downstream processes (see the figure). Yi et al. propose that through direct interaction, SHANK3 may enrich hyperpolarization-activated cyclic nucleotide–gated channels at postsynaptic sites. SHANK3(haplo)deficiency severely impaired hyperpolarization-activation (Ih) current conductance, explaining increased input resistance, a neuronal phenotype in Phelan-McDermid syndrome. Bidinosti et al. generated cells with a genetic defect reminiscent of SHANK3 variants seen in Phelan-McDermid syndrome and sporadic ASD, and encountered a deregulated pathway that has been implicated in other forms of ASD. The AKT-mTORC1 signaling pathway is a hub for many cellular processes and is down-regulated as a consequence of Shank3 deletion in mice. This is opposite of the effect of several other ASD gene mutations on the AKT-mTORC1 pathway. Apparently, an imbalance in this pathway in either direction can elicit autistic-like features. Bidinosti et al. discovered that the down-regulation involves a cascade of events tracing back to an increase in Cdc2-like kinase (CLK2); this is attributed to reduced CLK2 degradation by the ubiquitin-proteosome pathway. How mutated Shank3 affects ubiquitination remains unclear. This may result from a loss-of-function of SHANK3 protein, or perhaps a gain-of-function of other SHANK3 isoforms as a consequence of genetic interference. An intriguing speculation is that it relates to Ih-channel impairment.
    The findings of Bidinosti et al. suggest that small molecules that activate AKT or inhibit CLK2 may be used to adjust the activity of a critical signaling pathway in ASDs. Indeed, Bidinosti et al. reversed abnormalities at the molecular level (AKT phosphorylation) and cellular level (density of dendritic spines; miniature excitatory postsynaptic currents) with such compounds in Shank3-deficient neurons, and also reversed abnormal social behaviors inShank3-deficient mice. These are important proofs of principle for drug targets to be taken further in the direction of drug development.
    Previously, mGluR1/5 antagonists that successfully rescued phenotypes in genetic animal models of fragile X syndrome had disappointing results in patients with the disorder (8). Other candidate compounds are in queue to take this translational route, like compounds related to the mTORC1-inhibitor rapamycin. Bidinosti et al. add new targets to intervene with the pathogenesis of ASDs. The decade to come will show whether this finding can reach patients.

    References

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