Children with neurodevelopmental disorders need multidisciplinary care

What percentage of children suffer from neurodevelopmental disorders, and what percentage among these are rare conditions?

Michał Zawadka: According to some estimations, even up to 15% children have neurodevelopmental disorders. Precise assessment is difficult because not all the disorders we are talking about are included in the currently used classifications.

Sylwia Czarnecka: As far as rare diseases are concerned, please be reminded that the rate of occurrence of such conditions in the population is below 1:2000. This criterion is fulfilled by 7000 conditions and one in 15 people suffer from a rare disease, with most of them experiencing neurodevelopmental disorders. This is a huge group which keeps growing, also because we as physicians are learning more about rare conditions and we will more frequently look for them during the diagnostic process.

Do you often have such patients in your clinical practice?

S.Cz.: Neurology is a very broad field. It encompasses epilepsies, autoimmune diseases, neurometabolic and developmental diseases. In every one of these sub-fields, there will be a patient with a rare disease. Right now we have a patient in our ward with a disease diagnosed in just 10 people in Poland. We have another who is the only one in the world with his disease.
Neurodevelopmental conditions are more often diagnosed in prematurely born children - why is this?

M.Z.: Prematurity is in itself a risk factor for nervous system impairment, which may lead to cerebral palsy in the future. On the other hand, rare diseases may be the cause of premature birth.

S.Cz.: Whatever their health issues, premature children are more frequently consulted by doctors, they work with therapists. This increases the probability of early discovery of neurodevelopmental disorders.

When are the first symptoms of such disorders noticeable and what should you watch out for?

M.Z.: At any age, from newborns even to adults. Symptoms of metabolic disorders, for example, which lead to nervous system injury, may appear in the first days of life. These include: decreased muscle tone (hypotonia), convulsions, disturbance of consciousness. Other diseases may seem unremarkable at first. We may observe, for example, non-specific behavioral disorders, or mild intellectual disability, which may in certain cases involve severe acute encephalopathy.

S.Cz.: Generally, we may say that the most common reasons for starting diagnostics are delays in psychomotor development. Children acquire certain skills in certain intervals - these are called milestones. We should emphasize that these are not specific points in time but rather a certain time frame in which you expect the child to acquire a specific skill. Parent should bear this in mind and observe their children. At our clinic, we have seen two-year-olds who were unable to walk, and this kind of delay is really significant.

M.Z.: What I often see in my practice is children several years old who do not speak. In the case of such issues, if we fail to launch neurological speech therapy or auditory-verbal therapy, the impairments may already be irreversible.

What diagnostic tests are undertaken for rare neurodevelopmental disorders?

M.Z.: Whatever the type of neurodevelopmental disorders, diagnostics always starts with a detailed interview and an in-depth assessment of the child’s development, their health condition, exposure to harmful factors from the prenatal period.
Depending on the actual problem which may be discovered, we will suggest more specific tests, such as laboratory tests demonstrating the metabolic factors, activity tests such as electroencephalogram, and imaging tests such as magnetic resonance imaging. Genetic testing is gaining importance as well.

S.Cz.: Let’s assume we have a toddler or a young child with speech issues. We need to start with the simplest tests. The pediatrician should immediately rule out hearing disorders, chronic otitis media, etc. This has to be followed by analyzing whether the child understands other people speaking but cannot speak by themselves, or they neither speak nor understand others. In this area, we work very closely with neurological speech therapists and other speech therapists. More specific diagnostics comes next. At this point, first we try to confirm or reject the disorders for which we can suggest a therapy. The point is that such a therapy needs to be launched as soon as possible, so that the patient is helped more effectively and realistically.

Is genetics often the underlying basis of rare neurodevelopmental disorders?

S.Cz.: Yes. The group of rare neurodevelopmental conditions which are genetic disorders will be increasing because we now have genetic tests for detecting them. Also, there are more specialists capable of carrying out and interpreting such tests. A good illustration of this trend is the category of epilepsies. ¾ of these disorders used to be considered of unknown etiology - we did not know the cause. Now we know that more than half of all epilepsies are genetically based. A smaller percentage is associated with metabolism, and the smallest category comprises epilepsies of unknown origin. The proportions have reversed.

M.Z.: That’s exactly the reason why in our diagnostics of neurodevelopmental disorders, we very often consult a geneticist so as to set our priorities. We decide whether we start with general genetic testing or proceed to more specific tests right away. The tendency today is to start genetic diagnostics with WES testing. In this test, we study all the exons, i.e. all fragments coding a specific part of proteins.  

S.Cz.: Sometimes only one gene can be damaged, or even one nucleotide, the smallest building block of a DNA string. This is particularly true for metabolic disorders. If certain very specific symptoms guide us towards a specific mutation or group of mutations, then we can start with checking for that mutation.

Are we still dealing with a diagnostic odyssey when it comes to diagnostics of rare diseases?

S.Cz.: It depends. The approach to genetic testing is changing. These tests speed up a lot of work. Yet the path to the right diagnosis would be even shorter if this was dealt by teams of specialists. In rare diseases, we may experience symptoms from the digestive system, cardiovascular or nervous system, etc. If the child comes to different doctors without coordination, each doctor will view the patient from the perspective of their specialization and is unable to see the broader perspective. Therefore, it would be best if children no longer visited one specialist after another but were admitted to a ward on one particular day and a group of experts could schedule the tests and discuss treatment strategies.

What kind of treatment strategies are we talking about, how does the treatment proceed?

S.Cz.: First of all, this is multidisciplinary care provided by physical therapists, speech therapists, eye therapists, educational therapists, psychologists. Orthopedic care is needed as well. 
Targeted treatments are available for certain disorders, such as special diets in metabolic disorders, enzyme replacement therapies, genetic therapies or immune modulation therapy in autoimmunization processes.

What are the prognoses for rare neurodevelopmental disorders?

M.Z.: The earlier the diagnosis, the better the prognosis. We already know that in syndromes with intense aggression, a timely intervention by a psychologist will be very helpful in reducing or even getting rid of that aggression altogether. The overall purpose of therapy in neurodevelopmental disorders is to make sure that our patients as adults are capable of functioning normally in the society, working, starting a family. A patient’s independence is what we consider a major success of treatment.

Pediatric neurology is often viewed as a promising field of medicine. Why is that?

M.Z.: A lot is changing in this field. And it’s not just about using genetic testing. Our knowledge about the central nervous system is increasing as well. While we already know the structure of the brain and its neurotransmitters, we are still researching the actual operation of a synapse. This is the most important and extremely dynamic component of the nervous system. It is responsible for the plasticity of the nervous system where we focus all our therapeutic efforts in neurodevelopmental disorders. So the more we know about the synapse, the more we will be able to propose to the patients.

S.Cz.: The direction pediatric neurology is taking indicates that we will be collaborating more closely not just with therapists or doctors of different specializations but also with biologists experimenting on the available material, such as nematodes or rodents. For example, there is a specific rare gene. There are a few people in the world carrying that gene. We don’t know how it works, what the path is, what the gene affects, and we cannot test it on human subjects. But we can ask biologists these questions. The results of such experiments may give us a lot of suggestions in terms of targeted treatments. This is a very interesting path which is just opening.

What are the greatest challenges in terms of treatment of rare neurodevelopmental disorders in children?

M.Z.: At the moment, the greatest challenge in the reality of our healthcare system is the coordination of care over these children, which we have mentioned before. It is hard to diagnose them urgently enough, to have them consulted by one specialist after another, and to finally offer them therapy. In some cases, we had a diagnosis for which we were able to propose effective treatment, yet the diagnostic process took so long that it was already too late to implement the treatment procedure. Naturally, we have a well performing screening program for newborn babies, yet neurodevelopmental disorders cover a significantly broader spectrum of conditions.
Besides, irrespective of coordinated care, effective treatment is not possible without having experts specializing in specific types of disorders in children, and there are personnel shortages practically in every group, doctors (pediatric neurologists, geneticists) as well as therapists.

Interviewed by Iwona Kołakowska
Fot. Michał Teperek
Communication and Promotion Office