The University Hospital of Brno, which includes the Children’s Hospital and its Department of Pediatric Neurology, has a center dedicated to neurodevelopmental disorders, which include autism. The multidisciplinary team diagnoses and supports patients. Several research projects are also currently being conducted there, in partnership with Masaryk University. Brno Daily, as part of a series to mark Autism Acceptance Month, went there to interview the medical team. Image Credit: Freepik
The center for neurodevelopmental disorders at the Children’s Hospital of Brno was created in the early 1990s. It is part of the pediatric neurology department. “There is the Epilepsy Center, which is about 50% of all the patients who come here, then we have the Neuromuscular Center, and finally the third center is this neurodevelopmental unit,” explains Senad Kolář, a PhD student who studied medicine and specialises in pediatric neurology. He is now involved in autism research with the Children’s Hospital.
Neurodevelopmental disorders include developmental dysphasia, intellectual disability, ADHD and autism. Here, they “mostly do the autism diagnostics, and, if ASD is ruled out, we then try our best to find out if there are any other neurodevelopmental disorders”. In this hospital, the usual diagnostic procedure is carried out during a five-day hospitalisation, to ensure that it is as complete as possible. “The first two days are for the autism diagnostic,” explains Kolář. “Then Wednesday is for the polysomnography, to see if they have any sleep disturbances”. This examination consists of closely monitoring several parameters during sleep, such as the breath or the electrical activity of the brain. Finally, “Thursday is for magnetic resonance imaging. Usually, on Thursday or Friday, they go home.”
During the first two days of the autism diagnostic process, there is a medical part, which consists of a physical examination and an interview with parents about their medical history and the child’s medical history. Then follows a psychological part, which includes a battery of cognitive tests and the diagnostic test called ADOS-2 (Autism Diagnostic Observation Schedule), which takes place in a dedicated room. They present children who may be autistic with some stimuli and observe how they react. “We observe the quality and quantity of social contact, the coordination and quality of the components of communication: eye contact, non-verbal communication, speech or vocalisation, and also the way they use the toys and test materials. We are also looking for any signs of stereotypical, repetitive or sense-motivated behavior.”
Indeed, the main specificities of autistic people are deficits in communication, which can be verbal or non-verbal, difficulties in social contacts, perseverative thinking and narrow fields of interests, which can manifest themselves by a tendency to develop passions of an unusual intensity or over-focusing on something, as well as peculiarities in sensory processing, which can lead to pervasive hypersensitivities or unusual behaviors. This is not an exhaustive list, as the symptoms are very diverse and vary greatly from person to person, but are the first points that professionals look for during a diagnostic procedure.
“We use these cameras, so that we can watch it later, Frame by frame, second by second. Then we score it to see if there are significant ASD symptoms.” And do they sometimes still have doubts? “Yes, sometimes it is on the verge of autism or not autism… then we can repeat the test after some time or do some other tests”. There are indeed more tests available which they can somehow combine to reach a diagnosis. Also, “The case history provides us with key information as well. To determine the diagnoses it is important that the whole case picture corresponds with ASD,” adds Lucie Stroupkova, the neuropsychologist of the team. “Sometimes we are not 100% sure about the diagnoses even after the whole process is complete because the symptoms are mild or we suspect some comorbidities that could also explain the symptoms. Then it is useful to let the child mature for a while and repeat the diagnostics again in a year.”
“Sometimes it is stressful for them”, says Kolář, but the diagnostic process requires all these steps. “We try to make it the best for them: they can go outside and they have separate rooms.” Then there is the question of accepting the diagnosis, both for the parents and for the children themselves. Stroupkova was recently talking with a young boy who just received a diagnosis of high-functioning autism and asked her: “I have Asperger’s, am I mentally ill?” She told him that autism is not a disease, but a way he sees the things around him. “You might see them a bit differently than the other kids. But it is ok, we all are different, it’s alright to be yourself. Someone decided that the way you see the world is called Asperger’s. Some people who have it might be very good and successful in specific fields, like science, fishing or languages. But some other things might be more difficult for them than for the other kids: understanding people or trying new things, for example. You just might need to try harder than the others in some situations.” The boy said he believed he could fit into society. “Why wouldn’t you?” Stroupkova replied. “The fact that something is more difficult does not mean that you cannot manage that in your own way.”
The way of thinking about autism has indeed largely evolved towards a less negative and more inclusive vision. For Kolář, even if associations denounce persistent discrimination and stigmatisation, a gradual improvement in the acceptance of autism in the Czech Republic can be observed both among professionals and the general public. “I think in the general public it is getting better because lots of documentaries and series on TV focus on autism, and that helps.” Also, professionals in contact with children, especially pediatricians and teachers, are better trained and informed about autism. The latter are particularly important because they are the first interlocutors with families. They are also often the ones who sound the alarm when a child has features that could suggest an autism spectrum disorder. “There are several people in a child’s life who can send the patients here. Usually it is a pediatrician, sometimes it is school teachers, and sometimes other specialists such as child neurologists.”
Rise in children being diagnosed
“There are more children being diagnosed, (…) the prevalence is on the rise, now it is 1 in 44, so that is around 2% of the population who are probably autistic,” estimates Kolář. However, this does not mean that incidence of the condition is actually rising as much as the official numbers, since many cases were simply not being identified before. “The diagnostic is more accessible than before, there are more specialists carrying out the autism diagnostic and the condition itself is more known to the public.” In addition, the tests are conducted in a more systematic way. A few years ago Czech pediatricians were instructed to carry out the screening test at 18 months of age. For Kolář, neither is it because the criteria have become broader that the number of children diagnosed is increasing. “We see more of all of the profiles, not just more of Asperger’s syndrome.” Historically, lots of doctors misdiagnosed patients with autism with something else. This led to a misunderstanding of the difficulties encountered by the individual and to inadequate medical follow-up.
Furthermore, even if the prevalence is still much higher in boys, there are more girls coming for the diagnosis. “I don’t have the numbers, but we see more girls than in the past,” observes Kolář. Autism was once thought to be a predominantly male condition, but research in recent years has called this into question. It appears that women were more often affected by the condition than was previously thought, but that they present a different symptomatology, sometimes also more subtle, which can easily go unnoticed or be mistaken for something else. The reasons for these differences in presentations between male and female autism, however, remain unclear. The explanation could come from social constructs and differences in education, which would push young girls to hide their symptoms better, but could also have biological reasons, or a mixture of both.
As a consequence of the rising prevalence, there is a long waiting list, sometimes up to six months, for the diagnostic procedure at Brno children’s hospital. “Another common cause of long waiting lists is the general lack of clinical psychologists specialising in kids,” adds Stroupkova. “There are hospitals and public institutions, like us, who do the diagnostics which are paid by the public health insurance and then there are private institutions where diagnostics are a paid service,” adds Kolář. As the waiting list is long, parents sometimes fall back on the second option. With regard to care after diagnosis, Kolář finds that the situation, in terms of accessibility and amount of structures, “is getting better, but it is still not ideal”.
Diagnostics were shut down during the quarantine
“There are studies that show that if the intervention is started early, the outcome later in life is better,” adds Kolář. “If the diagnostic is delayed then there is an aftercare delay and all the intervention that can be provided for the autistic children is also delayed…” Unfortunately, this is exactly what happened during the lockdowns aimed at containing the COVID-19 pandemic. For the safety of families, many appointments and diagnostic procedures had to be postponed. Just a few months of delay can have a lifelong effect for the patient, as the brain becomes less and less flexible and adaptable over time. The implementation of support from an early age is essential, in order to allow children to adopt strategies to compensate for their difficulties. In addition, facing the challenges inherent to autism alone and without explanation can be extremely distressing for patients and their families. Children need understanding from others but also the self-understanding that a proper diagnosis allows.
It is for all these reasons that the Czech government is funding a research project at the Children’s Hospital in Brno, to study the alternatives to in-person diagnostics if new pandemic episodes should arise. “If in the future there will be something like this pandemic again, we don’t want to shut down diagnostics because it would introduce a lot of problems. Thus, we are now reflecting on the possibilities of using computer telehealth options to diagnose autism from a distance,” explains Kolář. They are therefore testing a new diagnostic procedure, developed by the same scientists as the ADOS test, but which can be done through a computer.
“The first data from the developers show that it could be a reliable method of evaluating ASD symptoms online, but we want to try it and validate it by ourselves, to consider if it could be used even in our context.” If families agree to be part of the study, they will therefore double test. “When someone is referred to our center for diagnostics, we will give the families the option to also try the distance test, before the hospitalisation.” If the parents wish to participate, “before the test, we send to them a set of toys that are used for the usual diagnostic.” Then, the whole test is done via computer. The medical team observes the child’s behaviour through the video call that is recorded and the parents go through the different steps of the process, presenting the different stimuli to the child. To conclude the study, the team from the Brno children’s hospital will take into account the results from both tests, in person and distance, and compare them in order to assess the reliability of the distance test.
How gut microbiota can affect the brain
Three other research projects are also currently ongoing in the neurodevelopmental disorder unit. One focuses on gut microbiota, which form in children in the first few months of life. The Children’s Hospital got a grant from Masaryk University and is working on this project with the CEITEC, the research center of Masaryk University, which does the analysis and interpretation. Autistic children experience more gastrointestinal issues than the average population. The studies found that there is a link between brain and gut microbiota, which can affect how the brain works and even symptoms of autism.
But is it the cause of autism or its consequence? “No-one knows actually! (…) Autism is mostly a genetic disorder, but also the environment affects the gut microbiota, and gut microbiota affects the brain,” says Kolář. Certain bacteria in the gut microbiota create molecules that can promote inflammation. These cross the barrier of the intestine and reach the brain. “But there are a lot of other factors which may influence the brain. The brain has to also present some vulnerabilities to this. With the same gut microbiota as in patients with autism, not everyone would develop the condition,” he explains. “This is quite well described already, but we don’t know how it fits in the whole autism pathophysiology.”
Are you a bit lost? To make it more simple, having a bad gut microbiota can lead to an increase in brain inflammation in children if they are vulnerable to it, and then this can increase autism symptoms. But the why and how remain quite mysterious for the moment and are the reasons why the team is investigating. “We are analysing the stool samples, the microbiota samples, of the children who have autism, but also of neurotypical (non-autistic) children. And then we compare it. We hope to find the differences. It is quite hard since the human gut microbiome consists of thousands of different strains and we don’t have full analysis done yet. There is a lot of work to do!”.
If they manage to get a better understanding of the mechanism, of the relations between microbiota and brain inflammation in autism, the team would also like to try to develop a therapy based on this. “Now we are having talks with the state institute for drug control, we need their approval.” The plan is to make clinical observations of gut microbiota transplantation. “We will observe how it affects the core symptoms of autism.”
Autism and sleep disorder
Other ongoing research in Brno’s neuropaediatric unit focuses on analysing the data collected during the autism diagnostic, especially during the sleep monitoring. Up to 80% of children with ASD suffer from sleeping disorders. “They might sleep very little and wake up very early,” says Kolář. Sleep, especially the deep stages, is essential for brain maturation, cognitive development and the storage of memories necessary in the learning process. The goal of the project is to improve the knowledge of sleeping disorders in autistic children. “We are trying to see how the sleep patterns are different in autistic children from neurotypical children,” says Kolář.
Finally, the last research project which just started is the specificities of autism in the hearing process. “The functional magnetic resonance imaging study that is being set up right now, we are doing the protocol, is in cooperation with CEITEC. It focuses on how autistic children and young adults process auditory stimuli. One of the core symptoms of autism is difficulties in social communication and interaction, where hearing is quite important.” If you need a little review of brain structure, each sense has its own processing center. After this primary analysis, the information from other senses is then brought together to create a global perception. In autistic patients it is observed that differences in perception exist, but they are still poorly understood from a neurological point of view. “We are trying to measure this response in special stimuli. We don’t know how it is different from neurotypical controls, or how the auditory centers are activated differently. We want to find out how the hearing process is different from the neurotypical controls.” Specifically this is done by magnetic resonance imaging, which allows us to see the structure of the brain, and then there is the functional magnetic resonance, which helps us to see how the brain functions. It can see the increase of the blood flow in a part of the brain. If a part of the brain is activated, the blood flow increases. Patients would therefore wear headphones and listen to auditory stimuli, which would be white noise, and the research team would later analyse brain activation after hearing the stimulus.
“The protocol we are preparing has not been carried out before on autistic patients, so there are no preliminary results.” 10 autistic people and 10 neurotypical boys or men, from 10 to 20 years old, will be involved in the study. “It is quite a common problem in autism research since participation of girls introduces heterogeneous factors. We cannot yet account for the fact that autism physiology might be different,” says Kolář, with regret. “In the future though, we would like to include girls and women.”
Causes still poorly understood
There is still a lot to discover about autism. Not only its mechanisms, but also its causes are still poorly understood. “You can’t always find some specific genes that do that,” says Kolář. But could it be that all cases of autism are the result of genetics? “It might be…that’s hard to say! There is a huge part that is environmental, but also hereditary. By environmental factors, we must understand biological factors here. Parental education or attitude, contrary to some beliefs, has nothing to do with it. There are a lot of environmental factors. Most of them are present during pregnancy. It could be hypoxia (low oxygen level), higher age of parents, substance use during pregnancy, the use of certain medications, and so on… It is only in 20% or 30% of the cases that we can say yes, this gene is responsible for autism,” he concludes.
