Brain MRI can detect early signs of autism. Necessary medical research in the treatment of autism What MRI shows in autism

US researchers believe that by scanning the brains of infants who have older siblings with autism, it is possible to make a fairly accurate prediction of whether the children under study will also develop autism or not.

The results of a recent study give scientists hope that there is a real opportunity Diagnose children with autism spectrum disorder (ASD) before they show the first symptoms. Previously, this goal seemed unattainable.

Moreover, the study opens up possibilities and perspectives in the diagnosis and possibly even treatment of autism.

But first, let's figure out why it is so difficult to diagnose autism in children. Typically, a child will show symptoms of an autism spectrum disorder (such as difficulty making eye contact) after the age of two. Experts believe that the brain changes associated with ASD begin much earlier—perhaps even in the womb.

But various methods that measure human behavior cannot predict who will be diagnosed with autism, says study lead author Joseph Piven, a psychiatrist at the University of North Carolina at Chapel Hill.

“Children who show signs of autism at the age of two or three do not look like they have autism in their first year of life,” Piven explains.

Many wonder if there are any genetic "signatures" or biomarkers that could help predict the development of autism. It is noted that there are some rare mutations associated with autism spectrum disorder, but the vast majority of cases cannot be associated with one or even more genetic risk factors.

Back in the early 1990s, Piven and other researchers noticed that children with autism tend to have slightly larger brains than their peers. This suggested that brain growth might be a biomarker for autism spectrum disorder. But Piven and colleague Heather Cody Hatzlett, a psychologist at the University of North Carolina at Chapel Hill, note that it's not at all clear exactly when such overgrowth occurs.

Statistically, autism occurs in about one in 100 children in the general population. But babies who have older siblings with autism run a big risk: a 1 in 5 chance of developing ASD.

As part of the NIH funded Infant Brain Imaging Study program, Piven and colleagues scanned the brains of 106 children from the high risk. The age of the babies at the time of the study was 6, 12 or 24 months.

Experts used magnetic resonance imaging (MRI) to see if they could "catch" what they call brain growth in action. In addition, they studied 42 low-risk children.

15 high-risk children were diagnosed with autism at 24 months of age. MRI scans showed that the brain volume of these children increased more rapidly between 12 and 24 months compared to children who had not been given a similar diagnosis. The researchers say that this increase occurred at the same time that the behavioral signs of autism appeared.

The researchers also found brain changes at 6 and 12 months of age, before the onset of ASD symptoms. Cortical surface area - an indicator of the size of the folds on outside brain - grew faster in infants who were later diagnosed with autism. Again, compared with those children who were not given a similar diagnosis.

Arises, perhaps main question: Is it possible to focus on these brain changes and use them to predict autism in children? A group of scientists led by Hatzlett and Piven further entered the MRI scan data (changes in brain volume, surface area and cortical thickness at the age of 6 and 12 months), as well as the sex of children into a special computer program. The goal is to find out which babies at 24 months of age are most likely to have autism.

It turned out that brain changes recorded at 6 and 12 months (among children who have older brothers and sisters with autism) helped to successfully identify 80 percent of all babies who were diagnosed with ASD at the age of 24 months.

In other words, the researchers were able to correctly identify which infants were diagnosed with autism at two years of age 80 percent of the time.

The authors clarify that their results still need to be confirmed in future studies. scientific works and with a large number of high-risk newborns. In addition, they intend to use other imaging techniques to help detect early brain changes.

Other experts point out that even if the results are reliable, clinical application such a technique can be rather limited. Specialist Cynthia Schumann of the University of California at Davis says the findings only apply to infants from high group risk, and not to the general population as a whole. She notes that other studies will be needed to test whether it is possible to predict the development of autism in children not at risk.

Shilov G.N., Krotov A.V., Dokukina T.V. GU "RSPC mental health»

In the literature (Pandey A. et all, 2004), the question of the use of one or another method of neuroimaging (primarily CT and MRI, as the most common and available methods) to identify diseases with impaired development of the central nervous system (CDNS), which, in particular, include autism spectrum disorders (ASD), usually supervised by psychiatric practice.

From literary sources it is well known (Shalock R.L. et all 2007, Gillberg C., 2000; Bashina V.M., 1999) that autism is a disease with significant deviations in reciprocal relationships (i.e. in the development of communication), as well as limited behavior, interests, imagination and early onset of the disease, usually up to 3-5 years (Morozov S.A., 2002; Lebedinskaya K.S., Nikolskaya O.S., 1991; Shchipitsyna L.M., 2001) . Currently (according to ICD-10), autism in its clinical manifestation is classified into: childhood autism; atypical autism; Rett syndrome; other disintegrative disorder childhood; hyperactive disorder, combined with mental retardation and stereotyped movements; Asperger's syndrome (see Chart 1).

It is believed that a child with RCCNS has impaired brain functions, which are probably based on developmental disorders in the form of pathological morphogenesis or histogenesis. It is believed that with the help of MRI it is possible to determine small and large malformations of the brain, which indicate the participation of the identified structural changes in the pathogenesis of NADNS (Decobert F. et all, 2005). However, it is possible to make an etiological and/or syndromic diagnosis based only on MRI data only in a small group of patients (0-3.9%). SRTSNS is defined by many different etiological factors which greatly complicates the diagnosis. At the same time, the significance of the results of neuroimaging studies, such as magnetic resonance imaging(MRI), in the analysis of patients with RRCNS remains uncertain, given that in children with RRCNS pathological changes, which are usually detected, are not specific enough.

Meanwhile, the range of recommendations for MRI varies from conducting a study in all patients with RCCNS (Shaefer G.B., 1998) to studying only patients with indications for clinical examination using MRI (van Karnebeek C.D. et all, 2005). It is considered that the most important indications for neuroimaging are pathological changes in the size of the head, the presence of signs of various kinds of anomalies of the central nervous system, certain neurological and mental symptoms and syndromes that are detected during the collection of anamnestic data and / or physical examination, indicating a high probability of structural pathology of the brain.

As for the RAS itself, it is currently accepted to believe that in most cases the occurrence of this pathology is the result of a combination genetic predisposition and trigger exogenous factors due to a number of reasons, such as viruses, toxins, immune-allergic stress, etc. (Van Gent et all, 1997; Comi A.M. et al., 1999; Warren, R. P., et al., 1996; M. Kontstantareas et al., 1987; Gassen A. N., 1999; Singh V. K. et al. ., 1997).

MRI of the child's brain

The purpose of the study was to identify the role and significance of MRI (as the most harmless and informative method for the study of the CNS in children) in the diagnosis of ARCNS, as well as to identify the most important trigger exogenous factors in the occurrence of ASD.

Materials and methods

The studies were carried out on the tomograph "Obraz 2 M" (RF, 1998) with intensity magnetic field 0.14 T in the sequence T1W, T2W in the axial and sagittal planes (according to indications - using intravenous anesthesia or sedation).

A total of 61 children with ASD aged 3 to 15 years were examined. Children with ASD were diagnosed in accordance with ICD-10 criteria and on the basis of a detailed clinical examination: the psychological, psychiatric and neurological status was studied, a mandatory examination by a pediatrician and consultations of other specialists, magnetic resonance imaging (MRI) and electroencephalogram (EEG) were carried out. AT clinical picture RAS dominated: qualitative violation social interaction, repetitive limited stereotypical behavior, cognitive impairment, regardless of the presence or absence of mental retardation, the onset of the disease, as a rule, was noted in the first 3 years of life. The range of diagnostic pathology included: childhood autism - 28 people; atypical autism - 25 people; Rett syndrome - 1 person; Heller's syndrome - 2 people; Asperger's syndrome - 5 people.

Results and discussion

The results of MRI scanning of the brain were evaluated according to the detected structural disorders, taking into account their relationship with characteristic clinical symptoms and signs (see Diagram 2 - most quantitatively represented significant groups from the entire RAS spectrum).

In the group examined with a diagnosis of childhood autism, which included 28 patients (which accounted for 46% of total patients with ASD), MRI signs of structural abnormalities were found, which were regarded as: 1. consequences of a neuroinfection (including asymmetry of the lateral ventricles) - in 9 (32.1%) cases 2. inflammatory changes in paranasal sinuses nose and structures of the temporal bones - in 5 (17.9%) cases 3. changes corresponding to the combination of signs of the consequences of a neuroinfection and signs of inflammation in the paranasal sinuses and structures of the temporal bones were determined in 4 (14.3%) cases 4. cysts of the middle lines - in 3 (10.7%) cases 5. changes corresponding to the totality of signs of the consequences of neuroinfection with midline cysts in 1 (3.6%) case 6. changes corresponding to the totality of signs of inflammation in the paranasal sinuses and structures of the temporal bones with cysts midline in 1 (3.6%) case. At the same time, a normal MRI picture was determined in 5 (17.9%) cases.

Magnetic resonance imaging in autism

In the group of patients diagnosed with atypical autism, which included 25 children, which accounted for 41% of the total number of patients with ASD, MRI signs of structural abnormalities were found, which were regarded as: 1. consequences of a previous neuroinfection (including asymmetry of the lateral ventricles) - in 9 (36%) cases 2. inflammatory changes in the paranasal sinuses and in the structures of the temporal bones - in 5 (20%) cases 3. changes corresponding to the combination of signs of the consequences of a neuroinfection and signs of inflammation in the paranasal sinuses and in the structures of the temporal bones bones were determined in 4 (16%) cases 4. changes corresponding to the totality of signs of the consequences of a neuroinfection with midline cysts in 2 (8%) cases. At the same time, a normal MRI picture was determined in 5 (20%) cases.

Rett syndrome was diagnosed in 1 child (MRI was normal).

The group with a diagnosis of childhood disintegrative disorder was also small - 2 cases, which accounted for 3% of the total number of patients with ASD: in 1 case, signs of the consequences of a neuroinfection (including asymmetry of the lateral ventricles) were revealed, in 1 case - changes corresponding to a combination of signs of the consequences of a neuroinfection and signs of inflammation in the paranasal sinuses and structures of the temporal bones.

In the group examined with a diagnosis of Asperger's syndrome, which included 5 patients (which is 8% of the total number of patients with ASD), the following MRI signs of structural abnormalities were found: (40%) cases 2. changes corresponding to the totality of signs of the consequences of a neuroinfection and signs of inflammation in the paranasal sinuses and in the structures of the temporal bones were determined in 1 (20%) case 3. midline cysts in 1 (20%) case. At the same time, a normal MRI picture was determined in 1 (20%) case.

Of the study group of 61 people, 21 (34.4%) patients showed signs of the consequences of a neuroinfection; in 24 (39.3%) - signs of inflammation in the paranasal sinuses and structures of the temporal bones; in 8 (13.1%) - the presence of midline cysts was determined; 12 (19.7%) had an MRI picture without signs of pathology in the brain and paranasal sinuses, as well as structures of the temporal bones.

Thus, in 45 patients (which accounted for 73.7% of the total) diagnosed with childhood autism and atypical autism, MRI signs of the consequences of a neuroinfection and MRI signs of inflammatory changes in the paranasal sinuses and/or cells of the mastoid processes were revealed temporal bone(see diagram 2.).

MRI of the child's brain

The data obtained indicate that more than 70% of the examined patients with ASD had either inflammatory processes in history, which proceeded with complications characteristic of neuroinfection (see Fig. 7), or signs of a chronic inflammatory focus (including at the time of examination) in the structures facial skull, anatomically associated with different parts of the brain (see Fig. 1,2), which, apparently, could be the cause of intoxication and allergization of various parts of the central nervous system.

This fact is also confirmed by the fact that in 40 patients out of 61 examined, signs of hypertrophy of the adenoid tonsils were found, which accounted for 65% of total number patients (see Fig. 3)

Also noteworthy is the almost equal ratio of MRI-detected changes in the group of patients with childhood and atypical autism (see Diagram 2), which once again indicates the possible trigger role of the infectious-allergic factor in the etiology of the development and course of these forms of autism.

In turn, the presence of such changes as midline cysts and dysgenesis corpus callosum(in 37% of cases), related to anomalies in the development of the central nervous system (see Fig. 4,5,6), are more indicative of a genetically determined cause of autism.

Findings:

From the above it follows:

1. Apparently, against the background of genetic predisposition (taking into account the presence of key phases and stages in the formation of interneuronal connections in the CNS), it is the infectious-allergic factor that is the fundamental trigger in the mechanism of the onset of ASD.

2. MRI examination of the CNS should be used as early as possible in all children with RCCNS and, in particular, ASD, not only as the most informative, but also as the most harmless in order to early detection infectious-allergic focus that can adversely affect normal development CNS and hence the onset of ASD

3. An almost equal ratio of structural changes in the brain and facial skull in childhood and atypical autism may indicate a common etiology and exogenous trigger mechanism for these types of ASD.

4. Until now, the problem remains, if not to eliminate, then at least to reduce the toxic effects of anesthesia or sedation on the CNS in children with ASD during an MRI study (which is extremely necessary to eliminate motor artifacts that prevent obtaining a high-quality image).

Literature:

1. Comi A.M. et al., “Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism,” Jour. child. Neurol. 1999 Jun; 14(6):338-94.

2. Decobert F., Grabar S., Mercoug V. et al. Unexplained mental retardation: is brain MRY useful? Pediatric radiol 2005; 35:587-596. web of science.

3. Gillberg, C. and Coleman, Mary. “The Biology of the Autistic Syndromes”, 3rd Edition, 2000 Mac Keith Press, Chapter, Clinical diagnosis

4. Kontstantareas M. and Homatidis S., "Ear Infections in Autistic and Normal Children, Journal of Autism and Developmental Diseases, Vol. 17, p. 585, 1987.

5. Pander A., ​​Phadke S.R., Gupta N., Phadke R.V. Neuroimaging in mental retardation. Indian J Pediatr 2004; 71:203-209

6. Schalock R.L., Luckasson R.A., Shorgen K.A. et al. The renaming of mental retardation: understanding the change to the term intellectual disability, Intellect Dev Disabil 2007; 45:116-124

7. Shaefer G.B., Bodensteiner J.B., Radiological findings in developmental delay. Semin Pediatric Neurol 1998; 5; 33-38

8. van Karnebeek C.D., Jansweijer M.C., Leenders A.J., Offringa M., Henntkam R.S. Diagnostic investigation in individuals with mental retardation: a systemic literature review of their usefulness. Europe J Hume Genet 2005; 13:6-25. web of science.

9 Van Gent et al. Autism and immune system. J children psychology and psychiatry march 1997, p. 337-49.

10 Warren, R. P., et al. (1996). “Immunogenetic studies in autism and related disorders”. Molecular and Chemical Neuropathology, 28, pp. 77-81.

11. Bashina V.M. Autism in childhood. - M., Medicine, 1999.

12. Gassen A. N. et al. Neuroimmunotoxicology: the humoral aspect of neurotoxicity and autoimmune mechanisms environment", Volume 107, October 5, 1999

The journal Science Translational Medicine published the results of a study of the possibilities of magnetic resonance imaging (MRI) in the diagnosis of autism in 6-month-old children. It turned out that an MRI study of connectivity in the brains of infants at high risk of autism successfully identified nine of 11 children who were subsequently diagnosed with autism spectrum disorder (ASD) at the age of two. Moreover, neuroimaging data made it possible to correctly diagnose the norm in all 48 infants, in whom the diagnosis of ASD was subsequently rejected. Currently, there are no generally accepted methods for diagnosing ASD before the onset of behavioral symptoms, but these new data support the hypothesis that brain developmental patterns predisposing to autism are present in children long before they develop typical ASD by about 2 years of age. behavior. According to the authors of this paper, this opens up opportunities for early intervention, which can be much more effective than current correction strategies, which, as a rule, begin after two years, when atypical brain characteristics have long been formed.

This study was sponsored by the National Institute child health and Human Development and the US National Institute of Mental Health. As part of this work, a team of scientists from the University of North Carolina and the University of Washington School of Medicine tested a 15-minute scanning protocol called functional connectivity MRI (fcMRI) on 59 sleeping children with a high hereditary risk of ASD, namely those with older siblings with RAS. It is known that having a sibling with autism increases a child's risk of developing ASD by up to about 20%, while for children without siblings with ASD, this risk is approximately 1.5%.

Assessed in this study the functional connectivity of the brain makes it possible to judge how different parts of the brain can function synchronously during the performance of certain tasks or at rest. As part of a larger project that has been ongoing for 10 years, researchers have collected a large number of data on 26,335 pairs of functional relationships between 230 different zones brain. After scanning, the authors used a self-learning computer program to decipher the fcMRI data, with the help of which algorithms were developed to identify the patterns that were chosen as predictors of ASD. At the same time, among all functional relationships, those were selected that correlated with at least one ASD-related behavioral feature that appeared in the study participants during the examination at 24 months (among them were the skills social behavior, speech, motor development and repetitive behavior). According to the comments of the authors of the work, the picture obtained with fcMRI at rest can be used to judge how different parts of the brain will interact under the most various types activities ranging from limb movements to social interaction, and the very complex patterns that emerge can be both typical and atypical.

Overall, the diagnostic accuracy of a self-learning program for identifying infants who subsequently develop ASD using fcMRI was 96.6% (95% confidence interval [CI], 87.3% - 99.4%; P<0,001), с положительной предсказательной ценностью 100% (95% ДИ, 62,9% - 100%) и чувствительностью 81,8% (95% ДИ, 47,8% - 96,8%). Более того, в исследовании не было ложноположительных результатов . Все 48 детей, у которых впоследствии не было выявлено РАС, были отнесены в правильную категорию, что соответствовало специфичности 100% (95% ДИ, 90,8% - 100%) и отрицательной предсказательной ценности 96% (95% ДИ, 85,1% - 99,3%).

Of course, these are very early results that will later need to be confirmed in larger populations. In fact, one such study, the European Autism Interventions study, is already underway, also performing brain scans on at-risk infants to better understand the biology of ASD and eventually develop pharmacological treatments.

In addition, according to the authors of the now published work, the fcMRI technique they used, followed by the interpretation of the results by a self-learning computer program, is unlikely to ever be suitable for routine mass screening of infants. Most likely, in the future, some cheaper method (for example, DNA detection in the saliva of a child) will be used as a screening to identify a high-risk group, and neuroimaging techniques will be used as early as the second stage to confirm a very high risk of autism.

From a medical point of view, autism is a complex medical condition with an unclear etiology (i.e. causes). In my practice, I try to learn as much as possible about each of my patients. This requires a thorough examination of the child himself, detailed communication with parents about the medical history, as well as extensive laboratory tests.

Here's where I start my research:

• The actual admission of the patient: The standard ten minutes that the pediatrician graciously grants to the patient is not enough here. Among other things, the conversation should include a detailed description of the drugs taken during pregnancy, a description of the food the child takes, and a story about older relatives: do grandparents and older parents have any quirks?
• Audiology: I had a patient from Canada who had no hearing test. The boy was deaf, but not autistic.
• MRI: I'm not a big fan of this procedure. First of all, you need to take into account the risks that general anesthesia creates (without it, this study will not work, since complete immobility of the child is required). The main practical value of MRI often comes down to the fact that parents cheer up a little: according to external signs, everything is in order with the brain.
• EEG: often the child does not show any visible epileptic seizures (loss of consciousness or muscle twitching). However, prominent autism doctors believe that checking brain rhythms (especially if it is also performed during sleep) can be of great importance in identifying peaks in activity that can harm the brain.
  And now the fun begins: you need to somehow convince the child to cooperate with you during the procedure. Then you need to find a good pediatric neurologist who will help decipher the data. The next step is to decide whether to treat the areas of increased electrical excitability, since no anticonvulsant drug is completely safe. A very difficult and time-consuming process.
• Detailed blood test: very often pediatricians ignore this simple test. If we are striving to ensure that the brain is sufficiently saturated with oxygen, we first need to understand whether the child is suffering from anemia.
  
• Assessment of lead and mercury levels in the patient's blood: the theory that heavy metals can somehow be “locked up” in the brain is controversial and has been the subject of much debate in the medical community. But such a check often helps to calm anxious parents. I oppose the introduction of a special provocateur into the body, which will make heavy metals stand out, without first finding out their baseline.
• Other metals: magnesium, calcium and zinc are very important for many chemical reactions taking place in the body. Picky eaters often miss out on essential nutrients. Micronutrient deficiencies can lead to skin rashes and digestive problems.
• Assessment of the thyroid gland: I offer you a logical construction. We have a patient who demonstrates hyperactivity or, conversely, lethargy and loss of energy. How can we know that this condition is not related to thyroid health if we don't get it checked? Correct answer: none.
• Chromosomal analysis: conventional doctors too often tell parents that autism is a genetic disease and that it is useless to treat it in any way other than classes like ABA. So why not check the chromosomes themselves? If they are all right (at least to the extent that modern genetics can claim it), then obviously biomedical intervention has a much better chance of success than is commonly believed.
• Gastrointestinal health: I prefer to see a detailed coprogram and check feces for dysbacteriosis in order to know for sure if there is a pathological overgrowth of pathogenic microorganisms (including yeast fungi) in the intestines, and how the process of digesting proteins, fats and carbohydrates is going. By the way, it will be much easier to potty train a child when intestinal health is restored.
• Food allergies: when the body reacts to an agent coming from the external environment by secreting immunoglobulins, an inflammatory process takes place, which undermines the overall energy of the body. Avoiding foods that are known to be hypersensitive will help clear the haze and improve eye contact and communication.
  A gluten-free, casein-free diet usually doesn't work in two ways: 1) The patient is not allergic to either gluten or casein; 2) The child continues to receive some third (fourth, fifth ...) product to which he has an allergic reaction.
  We check children sensitivity to a very wide range of foods and we advise not some general diet, but a diet specially selected for a particular patient. It is also necessary to test urine for traces of substances like opiates, which are associated with poor absorption of gluten and casein in the intestine.
• Vitamin levels: it is especially important to know if the patient is getting enough vitamins A and D from food. This is easy to find out and just as easy to solve with multivitamin supplements.
• Knowledge about metabolism: information about how well a patient's kidneys and liver are working should be familiar to the attending physician, as this determines the tolerability of many medications.
• Lipid panel: both high and low cholesterol levels can lead to health problems. If cholesterol is very low, it is easily corrected with medication, often leading to improvements in eye contact and communication. Also, this information can affect the composition of the diet used.