La storia dei disturbi dello spettro autistico (ASD) ? unica rispetto ad altri disturbi in quanto pochi hanno visto un tale aumento inspiegabile nel tempo, tensione sulle risorse personali e sanitarie, aumento dell'attivismo sociale e organizzazioni di difesa e approcci terapeutici controversi. Segnalato per la prima volta nel 1943, l'autismo pone particolari sfide ai ricercatori, visti i numerosi potenziali fattori che contribuiscono. Sebbene curabile, ? considerato un disturbo incurabile e multifattoriale che ? influenzato da aspetti genetici, neurologici, ambientali e immunologici.1 Detto questo, i recenti sviluppi hanno contribuito a creare una migliore comprensione dell'eterogeneit? dell'ASD e dei suoi fenotipi variabili.2
Autism itself is a biologically based disorder of brain development. This neurodevelopmental disorder is characterized by variable degrees of social and language deficits. Children with ASD demonstrate stereotypically restricted and repetitive behavior. Variants of ASD include conditions such as pervasive developmental delay (PDD) and Asperger disorder (AD). A 2012 Centers for Disease Control and Prevention (CDC) report estimates that of all autism diagnoses in the United States, 47% were PDD and 9% were AD.3 Comorbid conditions such as ADHD on the other hand are separate but appear to have a higher prevalence in ASD.
L'incidenza di ASD ? aumentata di 10 volte negli ultimi 25 anni. Nel 1990, la prevalenza stimata era di 5 su 10.000 bambini. Un rapporto pubblicato dal Dipartimento della salute e dei servizi umani degli Stati Uniti indica che tra i bambini di et? compresa tra 6 e 17 anni, la prevalenza di autismo ? aumentata da 1.16% nel 2007 a 2.00% nel 2012,4, sebbene il CDC stima che uno su 110 bambini ora nati nel Gli Stati Uniti hanno ASD.5
Sebbene vi siano controversie sui vari fattori che possono contribuire alla prevalenza e alla gravit? dell'ASD, forse l'aspetto pi? frustrante dell'ASD sia per i genitori che per gli operatori sanitari ? che le sue cause rimangono sconosciute. Detto questo, la maggior parte degli esperti concorda sul fatto che l'ASD ? un disordine geneticamente predisposto che sembra richiedere un innesco ambientale (o trigger) ambientale. Per la maggior parte dei casi di ASD, nessun singolo gene o gruppo di geni ha dimostrato definitivamente di avere un impatto significativo sul suo sviluppo. Tuttavia, esiste una concordanza 90% tra gemelli identici vs 30% nei gemelli fraterni.6
The pathophysiology of autism is without surprise not well understood. A genetic cause can be identified in only 20% of ASD cases, involving genes that converge on common pathways that alter synaptic homeostasis.7 There is good evidence to support the understanding that autism is characterized by inflammatory and abnormal neural connections, particularly underconnectivity of cortical systems leading to abnormal interhemispheric communication. With corroborating advanced imaging from fMRI, this abnormal brain function correlates well with many of the stereotypical behaviors seen in ASD.8
One of the most widely debated aspects of ASD is gastrointestinal (GI) dysregulation specifically conditions known as dysbiosis and increased intestinal permeability. However, the exact cause for increased prevalence of GI abnormalities in ASD is unknown. Up to one-third of children with autism exhibit some form of GI disorder clinically (e.g., constipation, abdominal pain, diarrhea, gastroesophageal reflux disease). The human gut is home to a dynamic and complex community of microbes that can profoundly influence nervous system growth and development.9 Many of the behavioral challenges associated with autism likely can be explained by gut dysfunction, noting that many autistic children have communication barriers and have challenges expressing their discomfort.
Uno studio ha scoperto che i bambini con ASD trattati con vancomicina hanno visto un miglioramento sia dei batteri intestinali anormali che dei sintomi gastrointestinali, osservando anche miglioramenti nel comportamento autistico.10 Il test del lattulosio-mannitolo rivela che la maggior parte di questi bambini mostra una permeabilit? intestinale anormale, che si pensa possa indica atrofia della mucosa intestinale e lesioni alle giunzioni intercellulari. Si ritiene che questa alterata permeabilit? intestinale consenta l'assorbimento di peptidi digeriti in modo incompleto che si comportano come agonisti del recettore portando a una neuroattivit? cerebrale anomala che provoca cambiamenti comportamentali.11
Along these lines, duodenal biopsies from 25 autistic children show increased lymphocytic proliferation and other immune abnormalities, indicating a possible autoimmune etiology.12 A separate study of 36 autistic children reported significantly higher levels of IgG, IgM, and IgA to food proteins such as casein and lactoglobulin compared to controls.13 An autoimmune etiology in ASD is supported by an epidemiological study showing that families affected by autism had 1.87 relatives with autoimmune disorders, which is significantly more common when compared to the general population, and surprisingly even more common than families affected by other common autoimmune diseases such as lupus and rheumatoid arthritis.14 Another study even found that 36.7% of autistic patients and 21.2% of their direct relatives demonstrated active leaky gut syndrome as compared to 5% of controls.15 These findings suggest an inheritable predisposition for ASD that, when triggered by environmental events, may play a key role in prevalence and severity.
DIETA SENZA GLUTINE / SENZA CASEINA
The majority of published studies show a statistically significant benefit of a gluten-free/casein-free (GFCF) diet in ASD. However, specific characteristics of best and non-responders to GFCF intervention have not yet been elucidated. That some children benefit from this dietary intervention and others do not is likely due to variable ASD phenotypes.16 One striking case report in the literature reported significant benefits in a child with severe ASD, morbid obesity, and epilepsy, who after limited response to other interventions, was placed on a GFCF-ketogenic diet that used medium-chained triglycerides and a high intake of vegetables. Over the course of a few years, the child's Autism Rating Score went from severe to non-autistic, her intelligence quotient increased 70 points, and she became seizure-free with normal follow-up EEGs.17 Needless to say, in keeping with the favorable benefit-harm ratio, it is entirely reasonable for families affected by ASD to implement a GFCF diet.
Inoltre, molti studi dimostrano la necessit? di integrare la dieta dei pazienti autistici con acidi grassi omega-3, probiotici, vitamine e minerali in combinazione con altri interventi medici e psicologici.18 Tuttavia, buoni dati che dimostrano il beneficio clinico conclusivo di queste aggiunte in gran parte mancano e ci sono state chiamate per indagare sul probabile ruolo benefico dei probiotici nell'ASD.19
TOSSINE DEL MERCURIO E DELL'AMBIENTE
Un altro popolare sospetto di ASD ? il thimerisol (etilmercurio), precedentemente contenuto nelle vaccinazioni infantili. Questo, forse pi? di ogni altro aspetto della storia dell'autismo, ? stato oggetto di accesi dibattiti. Una revisione della FDA ha rilevato che prima del 1999, la somma aggiuntiva delle vaccinazioni infantili superava i limiti EPA per un'esposizione sicura del metilmercurio. Sebbene gli studi epidemiologici non siano riusciti a trovare una connessione tra le piccole quantit? di mercurio nei vaccini e l'incidenza dell'ASD, 20 uno studio ha dimostrato un aumento associato del 61% nel tasso di incidenza dell'autismo per ogni 1000 libbre di mercurio rilasciato dall'inquinamento industriale.21
There is ongoing concern about the growing chemical milieu that children are exposed to early in life. A well-known source of mercury exposure comes from amalgam fillings. However, whether there are any adverse health effects from this remains a subject of debate.22 While mercury is a well-known neurotoxin with no acceptable level of exposure, it is unproven as a significant cause of autism by itself. However, mercury may just be the tip of the iceberg. Children today are exposed to thousands of synthetic chemicals, with at least 200 being known neurotoxins and another 1000 demonstrating neurotoxicity in laboratory tests. According to the CDC s biomonitoring program, there are more than 100,000 chemicals commonly used every day in household cleaners, solvents, pesticides, food additives, lawn care, and other products. Every year another 1000 chemicals are introduced that do not take into account the mixtures and various combinations of commercial and consumer products to which people are exposed.23
Another alarming study found nearly 300 environmental toxins in the umbilical blood of neonates.24 Animal models show that even low levels of these toxins can negatively affect neurodevelopment. Indirect human evidence points to the sensitivity of the developing brain to lead, mercury, and other toxins. The strongest proof-of-concept evidence comes from research linking ASD to various chemical exposures in early pregnancy.25 Given this information, it is reasonable for parents and practitioners alike to follow the precautionary principle that states, When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically. 26
Detto questo, ? stato postulato che difetti metabolici ereditari precedentemente non rilevati predispongono coloro che alla fine verrebbero diagnosticati con ASD a causa di sistemi di disintossicazione compromessi che non sono adeguatamente in grado di gestire lo stesso basso livello di esposizione tossica dei bambini in via di sviluppo. Ad esempio, in uno studio su oltre 200 bambini autistici trattati con l'agente chelante DMSA, i livelli urinari di mercurio erano significativamente pi? alti rispetto ai controlli neuro-tipici.27 Ulteriori studi supportano l'ipotesi che, sebbene i bambini con autismo e neuro- entrambi i bambini tipici hanno esposizioni simili, 28 quelli con ASD mostrano livelli di porfirina urinaria anormali, che indicano un metabolismo e un'eliminazione anomali del mercurio.29
Although children with ASD may be susceptible to even normal levels of mercury exposure, and although there are some data showing increased urinary output of toxic metals with use of chelating agents,30 evidence showing clinically beneficial outcomes from the use of chelating agents such as EDTA and DMSA is lacking.31 What s more, NIH-funded trials were halted prematurely due to ethical concerns.32 However, there are reasonable lifestyle approaches to help reduce toxic body burden for would-be-mothers and families with young children (see EWG link in resources).
VACCINARE O NON VACCINARE: IL CASO DI MMR
Il vaccino MMR ? stato implicato da molti genitori come un evento scatenante per l'autismo. Sebbene ci siano state preoccupazioni iniziali, non ? stato trovato alcun legame tra la vaccinazione MMR e l'autismo.33 In effetti, uno studio recente ha scoperto che i bambini con ASD hanno livelli simili di anticorpi contro il vaccino MMR rispetto ai controlli neuro-tipici della stessa et?.34 famigerato studio pubblicato nel Lancetta in 1998 that suggested a link in ASD with colitis and MMR vaccination35 was retracted in 2010 by the journal due to serious irregularities.36 An 8-year U.S. federal court process that finally ended in 2010 concluded that ASD was not caused by an adverse reaction to vaccination.37 To the contrary, it is now estimated that MMR vaccinations administered in the United States from 2001-2010 helped prevent more than 16,000 cases of congenital rubella syndrome a known cause of ASD which in turn helped prevent more than 6000 new cases of ASD during that 10-year period.38
Le retrazioni degli studi e le sentenze del tribunale hanno appena trasformato il pensiero di molti gruppi di difesa antivaccina. Una recente storia della CNN ha riferito che le infezioni da morbillo, una volta considerate sradicate negli Stati Uniti, sono aumentate.39 Ad esempio, un'altra storia dell'NPR ha riportato che 21 parrocchiani scettici con vaccino di una chiesa del Texas del Nord che non erano stati adeguatamente immunizzati con MMR erano infetti in un focolaio di morbillo.40 Per riferimento, si stima che 1 su 1000 bambini alla fine muoiano per infezioni da morbillo, anche con la migliore cura.39 Di conseguenza, ci sono state chiamate a mettere da parte le controversie filosofiche e invece rispondere con empatia e aprire un dialogo incentrato sulla famiglia per affrontare la disinformazione e le preoccupazioni sulle vaccinazioni.41
Alternative childhood immunization schedules (ACIS) are one approach for families that refuse standard CDC vaccine schedules. Despite controversy of a well-known ACIS (the Sears alternative vaccine schedule42), a recent survey of 517 families in Washington found that this approach did not predominate, with only 9.4% of parents reporting use of ACIS.43 The real advantage of offering ACIS to concerned parents is not about efficacy or promoting a better or worse vaccination schedule, but rather in establishing a trusting relationship while ensuring eventual full immunization and protection for children.
TERAPIE DI COMPORTAMENTO E DI DISCORSO PER L'ASD
Although the cause(s) of autism are unknown, there are reasonable and effective treatments for ASD. The most common, and arguably the most effective approaches address behavioral, communication, and social deficits. Early screening during routine well-child exams can identify signs of ASD, which in turn should lead to initiation of speech-language therapy (see NICHCY link in resources). Effective services should vary with individual children, depending on the child's age, cognitive level, language skills, behavioral needs, and family priorities. With some children, it is appropriate to incorporate augmentative and alternative communication (AAC), such as the Picture Exchange Communication System, other high- and low-tech assistive technology tools, and/or sign language. A meta-analysis of single-case research studies indicates strong effects for the use of AAC on communication skills. Although effect sizes should be interpreted cautiously due to the small number of studies, social skills, challenging behaviors, and spelling also appear to be positively affected.44
Although behavioral intervention methods appear to have a positive impact on learning, communication, and behavior in children with ASD, intervention studies suffer from methodological problems that make it difficult to form definitive conclusions regarding efficacy. That being said, there is evidence to support the use of applied behavioral analysis for functional skills development, and there are clear benefits of Lovaas therapy compared to no treatment. Furthermore, increased therapy intensity is known to be more effective than no- or low-intensity therapy. The National Research Council suggests that young children with ASD should receive at least 25 hours of individualized and structured intervention per week, 12 months a year.45 In general though, as no definitive behavioral or developmental intervention improves all symptoms for every child, it is recommended that therapy management be guided by each child's needs and availability of resources.46
Other common and effective behavioral therapies include Greenspan s Floortime and Developmental Individual Difference Relationship Model, which incorporates play activities with an emphasis on emotional development. Relationship Development Intervention is a parent-based treatment approach that works to improve social skills, adaptability, and self-awareness skills. Social Communication/Emotional Regulation/Transactional Support uses practices from a variety of other approaches in order to promote child-initiated communication and skills in a variety of settings.
Although there are anecdotal reports of benefits from sensory motor interventions, such as sensory integration therapy or use of a sensory diet, results are limited and inconsistent. A review of auditory integration therapy by the American Speech-Language and Hearing Association concluded that efficacy standards for use by audiologists and speech-language pathologists are not yet available. At this time, families should pursue these therapies with some skepticism until further research can be conducted.47 n
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La sig.ra Stuntebeck ? professore assistente clinica, Dipartimento di Scienze e disturbi della comunicazione, Universit? del Wisconsin-Madison. Il dott. Fortney ? medico di medicina di famiglia integrativa, Meriter Medical Group, Madison, Wisconsin.