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Desimir Mijatovic, MD, discusses the diagnosis and management of central sensitization syndromes in children.

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Pediatric Central Sensitization Syndromes

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: February 15, 2024

Expiration Date: February 15, 2025

Estimated Time of Completion: 25 minutes

Pediatric Central Sensitization Syndromes

Desimir Mijatovic, MD


Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

  • Review up to date and clinically pertinent topics related to neurological disease
  • Discuss advances in the field of neurological diseases
  • Describe options for the treatment and care of various neurological disease

Target Audience

Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.


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Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

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Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

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Podcast Series Director

Imad Najm, MD

Epilepsy Center

Additional Planner/Reviewer

Cindy Willis, DNP


Desimir Mijatovic, MD

Center for Pediatric Neurology


Glen Stevens, DO, PhD

Cleveland Clinic Brain Tumor and Neuro-Oncology Center


Pediatric Central Sensitization Syndromes

Desimir Mijatovic, MD


In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

Imad Najm, MD


Advisor or review panel participant


Other activities from which remuneration is received or expected: Research Funding

LivaNova, PLC 

Advisor or review panel participant

SK Life Science Inc

Advisor or review panel participant
Teaching and Speaking

Glen Stevens, DO, PhD



 The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Cindy Willis, DNP, Desmir Mijatovic, MD

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.


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Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research, discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD: Central sensitization, a process that occurs when the central nervous system amplifies sensory stimuli may be the underlying mechanism of conditions characterized by unexplained pain. However, because these conditions can also be associated with other symptoms, including fatigue, brain fog, sleep disturbance, and gastrointestinal issues, they're not easily diagnosed, which often means that patients undergo many unnecessary evaluations and treatments. In this episode of Neuro Pathways, we're discussing central sensitization syndromes in children and how clinicians can determine the best treatment approach and help patients and their support systems understand and navigate the condition.

I'm your host, Glen Stevens, neurologist/neuro-oncologist in Cleveland Clinic's Neurological Institute. And joining me for today's conversation is Dr. Desimir Mijatovic. Dr. Mijatovic is a pediatric and adult pain medicine specialist in Cleveland Clinic Neurological Institute's Center for Comprehensive Pain Recovery. Des, welcome to Neuro Pathways.

Desimir Mijatovic, MD: Thank you so much. I'm super glad to be here.

Glen Stevens, DO, PhD: So, Des, for those that don't know you, share a little bit about yourself, where you're from, how you made your way to Cleveland Clinic and what you do at the Cleveland Clinic.

Desimir Mijatovic, MD: So, I actually grew up here in northeast Ohio. I did a lot of my training around here. I did my residency here at Cleveland Clinic in psychiatry. I went to Akron Children's for child psychiatry and Cincinnati Children's for my pain fellowship. Made my way back here. I was already connected with the pain recovery department, and so when I came back, I said, "I'm happy to come back." I absolutely want to set up a program for kids as well because that's really where my passion lies in taking care of kids with these complicated conditions.

Glen Stevens, DO, PhD: Well, I applaud you for what yu do, that's for sure. I alluded to this in the intro but tell us about central sensitization. What is it, what causes it, those types of things.

Desimir Mijatovic, MD: Central sensitization is a process that I think underlies a lot of different conditions, and there are a lot of different conditions that fall into the category of central sensitization syndromes. What I think about and how I talk about it is when the nervous system gets activated on a normal level, let's say an alarm system, and the body goes off like pain. Usually there's some kind of injury that causes it. The nerves will send electrical and chemical signals that signal pain. And then once that injury is healed, those signals stop being sent, and the body clears out those electrical and chemical signals. What can happen though is if you have constant repeated signaling of pain or any of these other problems, alarm systems, the nervous system gets stuck in that on position. Basically, it's long-term potentiation, just like memory formation, everything like that. So, the nerves become activated chronically and send these signals even though that original injury may have healed or may have gone away. So, the patient ends up having all of those same alarm systems as if there was an active acute injury going on, but one usually can't be found. Of course, this gets complicated when the patient already has some other long-term, maybe an inflammatory condition or still has a structural problem going on. And when I talk about it with patients, I talk about it as a whole separate issue that needs to be addressed separately and addressed differently.

Glen Stevens, DO, PhD: So, I can see it as a chronic issue. Can you get it from a single injury?

Desimir Mijatovic, MD: It's possible. Sometimes it's an idiopathic condition where it just develops, and we can't always pinpoint it. There are risk factors that we can see the patients do have. However, in my practice, it's usually multiple different risk factors or multiple different injuries, so to speak, that cause this problem. Usually there's some kind of predisposition to it and then you add on top of it a physical injury or an inflammatory injury like an infection or an autoimmune condition, and then this process develops and continues and can oftentimes be very difficult to treat.

Glen Stevens, DO, PhD: How young can you see this in patients?

Desimir Mijatovic, MD: I see it as young as under 10. So as long as the nervous system is present, it can happen, and it can be a thing.

Glen Stevens, DO, PhD: Now, I recall lots of different names over the years, and I don't know if they're all part of the same thing or not, but this condition called AMPS, is this the same thing? What is AMPS? Is that the same thing we're talking about here?

Desimir Mijatovic, MD: So, when you look up central sensitization syndromes online, there's a lot of different diagrams that will list a lot of other conditions under the central sensitization syndrome. When the nerves or the part of the nervous system that's affected is the musculoskeletal nervous system, well then, it's called AMPS. Or if it's more specifically centered into one limb or two limbs, it can be complex regional pain syndrome or CRPS. If it affects the stomach or the internal organs, it's called visceral hyperalgesia. If it affects the body's wakefulness system, it's chronic fatigue syndrome. If it affects the nerves in the head, then it's chronic migraines or new daily persistent headache. So, I think there's a lot of these conditions that all fall under this category, but that affect patients differently. The thing that they all have in common is those issues that you mentioned at the beginning, fatigue, brain fog, trouble functioning in their daily life. So, all of those things overlap. It just what part of the body does the symptoms affect?

Glen Stevens, DO, PhD: I hadn't really thought about chronic headache as being within the same category, but as you mentioned it makes sense, right?

Desimir Mijatovic, MD: And what we see is that new daily persistent headache or chronic daily headache, it's oftentimes described very differently by patients than somebody who has chronic migraines or intermittent migraines. The pain feels very different. I oftentimes describe it more as a head pain rather than a headache, and patients seem to understand that a little bit more.

Glen Stevens, DO, PhD: So, I'm sure this is a very difficult question to answer because the difficulty in making the diagnosis, but how common is this?

Desimir Mijatovic, MD: It's very common in the patients that I see, I would say about 30 to 50 percent of patients that I see have one of these syndromes in my pediatric clinic. In the adult clinic, central sensitization is a part of chronic pain, so I do believe that any patient who has chronic pain has some degree of central sensitization going on, and so I think it's very common. The significant syndromes where it's full-blown, affects the whole body, multiple different systems of the nervous system. That is a little bit more rare, but it's very common in patients that I see.

Glen Stevens, DO, PhD: So, you've mentioned a couple, but other syndromes associated with the disorder?

Desimir Mijatovic, MD: The most common one that people would probably be familiar with is fibromyalgia. So, fibromyalgia is a condition of central sensitization throughout the whole body, the nervous system of the whole body. That's where you get the sensitivity to touch, the fatigue, brain fog, abdominal issues, headache issues, TMJ, all of these things that come along with that.

Glen Stevens, DO, PhD: And how long has it been linked as this type of a disorder? Because I always sort of looked at it as it was out there as its own thing.

Desimir Mijatovic, MD: The problem with these conditions is that the technology that we have when it comes to testing for these conditions isn't there yet. Oftentimes when you look at labs like lab tests, those are usually done on models that aren't really clinically relevant. So, when I talk to patients about the testing for these, they can look at levels of inflammatory signals and nerves and things like that. However, that would require us to remove large parts of the patient's nervous system and run tests on that, and that's not really clinically viable as an option.

There's also a lot of stigma attached to these conditions, which is really hard. And so, I think in the past they've oftentimes been lumped into that conversion disorder category or psychosomatic where patients tell me all the time, they've been told that, "Oh, it's all in my head. It's just anxiety. I just need to get my anxiety taken care of." And I don't think that that's fair and I don't think that that's accurate. I just don't think our technology is caught up to be able to really test for these conditions at this point. However, that does not mean in the future we won't be able to. I think about it like a lot of these other conditions that used to be "conversion disorder." In the past, things like seizures used to be considered conversion disorder. Diabetes used to be considered conversion disorder, asthma. Once we got the technology to catch up, then we were able to actually identify them more clearly.

Glen Stevens, DO, PhD: Well, sadly, my mother had MS and in the sixties, she was thought to have conversion disorder. I wish she did. It would've been the better option. So, in 2023, we understand some disorders that we didn't before COVID. Is long COVID a type of central sensitization disorder?

Desimir Mijatovic, MD: I believe so. I do categorize it in the sense that it affects the nervous system, it has symptoms all throughout the body, and it's treated the same way that we treat all these other central sensitization syndromes. I would also lump in there, chronic Lyme disease, any of these long-term symptoms after any infectious disorder. I lumped them all into the, I think of post-infectious central sensitization syndromes. Where the infection is most likely gone, but the symptoms are still around, and that's because those symptoms lie in the nervous system, not within some kind of infection in the body.

Glen Stevens, DO, PhD: And if I come see you and you're wondering if I might have this type of a disorder, is there anything specific that you want to hear from me or that you go, "If they have this, they probably, have it?" Or is there anything unique that I would say to you that's common?

Desimir Mijatovic, MD: What is unique is this cluster of symptoms that go along with the central sensitization. So, it's not enough to just have pain. You have to also have that fatigue and brain fog and life dysfunction that comes with all of these symptoms. Oftentimes, I can list some of the other symptoms of patients and they tell me, "Yes, I have those things as well." They didn't even think about it as being connected.

Oftentimes that's when I bring up nausea, when I bring up dizziness, when I bring up all of these other alarm systems that the body has. The patients will tell me that they have those symptoms too. And if all of these symptom clusters are coming together, it makes me more confident that I have a patient who has a central sensitization syndrome. The difficult part is oftentimes patients are told that these are diagnoses of exclusion, and that can be hard. Because oftentimes that is not a satisfying diagnosis when you're told it's a diagnosis of exclusion because it makes you feel like something's missing or that we haven't found the right thing yet. I think about it as more of a positive diagnosis in the sense that yes, you have all of these symptoms that are consistent with this syndrome and that makes me more confident in the treatment.

Glen Stevens, DO, PhD: I seem to recall back in the day with complex regional pain syndrome or RSD, lots of different things they called it. Then it seemed a little easier because they could measure blood flow or look at the skin and there were temperature changes or hair pattern changes, or maybe even bone remodeling changes, those types of things. But a lot of the stuff you described; you wouldn't see a physical change.

Desimir Mijatovic, MD: That's correct. You wouldn't see a physical change. There are some things that we do see on physical exams still, changes in coloring of the skin. So, you'll see mottling of the skin and different things. It can be subtle sometimes. Postural orthostatic tachycardia syndrome, that also to me is a central sensitization syndrome of the cardiovascular nervous system. And so, a lot of times patients develop those type of symptoms as well. So, there are things that they're looking into in terms of testing when it comes to pain sensitivity, testing for allodynia, testing for hyperalgesia. These things are just not done clinically on a regular basis. They're mostly in research.

Glen Stevens, DO, PhD: So, somebody comes to see you and I'm sure its variable depending on exactly what their symptom complaints are. But the general diagnostic workup includes what?

Desimir Mijatovic, MD: Most of the time, by the time they're coming to see me, the diagnostic workup has been done pretty extensively. Most of these patients have seen multiple different specialties, whether it's neurology, gastroenterology, rheumatology, orthopedics. They've seen a lot of different specialists who've done a lot of different tests, usually by the time they see me. If I'm ordering tests, usually it's imaging or studies like EMGs where I'm testing to make sure that the weakness is not due to some structural nerve problem or some other structural problem going on in the nervous system. After that, most of the time patients get this extensive testing and it all ends up being normal or just very slightly abnormal. Nothing that explains the extent of their symptoms. So once all that testing is done, I usually do need the help of the other specialists from the primary area of the body that the symptoms are present in. But once I have that, looking at all of that extensive testing that's done and seeing it being normal really helps me be more confident as well.

Glen Stevens, DO, PhD: So, I imagine it's difficult for a lot of physicians to understand the disorder, and as you've sort of indicated historically there was just negativism associated with this. Just imagine explaining it to the family. So how do you explain the disorder to the patient, to the family so that they understand what they have going on?

Desimir Mijatovic, MD: When I explain these syndromes, I talk about them as disorders of the alarm systems of the body. So, I usually review just the structure and function of the nervous system. I talk about parts of the nervous system that they can control, like the arms, legs, things like that. But then I move into the parts of the nervous system that they can't control, the autonomic system. And within that autonomic system, that's where the alarm systems are. And so what I talk about is how the injury, whether it's the inflammatory injury, structural injury, infectious injury, that causes malfunction in that alarm system which sets the alarms on and never turns off. And so that explains the extent of the symptoms. I review what the alarm systems are, so pain, weakness, fatigue, poor sleep, nausea, vomiting sometimes. All of these things I review with them, and I say, "These are all parts of the body's alarm system, and they all run on the same machinery, so they affect one another." I do talk about the role that anxiety and depression play because anxiety and depression are alarm systems as well. And so I tell them it's not caused by the anxiety, but anxiety makes it worse. And they usually will agree with that and have identified that for themselves.

Glen Stevens, DO, PhD: So how do people react to what you tell them? Are they just relieved that someone's actually listening to them or are they just overwhelmed by the process?

Desimir Mijatovic, MD: Usually there is a big sense of relief of having a name for the condition that they have, having it explained to them in a way that makes sense to them, in the way that it puts everything together. The other thing about it that I talk about is how there is hope that this can get better and that there is a treatment for this. And so that kind of helps me go into the second part of my talk with patients, which is how we use the functional approach to get people feeling better from these conditions.

Glen Stevens, DO, PhD: So, I think that's where we're going next. Tell us about the treatment approach for patients.

Desimir Mijatovic, MD: In general, when I talk to patients about this, the functional approach really means helping their body get back to functioning so that those alarm systems, the body kind of senses, "Hey, everything's working well, the body's functioning okay. We can turn these alarm systems off." And so, I talk about strengthening the body and strengthening the nervous system. Usually by the time patients come to me, they've been unable to move, they've been unable to attend school, they've been unable to do sports for weeks, months, years sometimes. And with that inactivity comes a lot of deconditioning and weakness of the body. So, the first step is getting the body strong again. And so, with that, getting the body functioning again, functioning properly, how it's supposed to be functioning. What we see is that over time, those symptoms will decrease as the body senses that things are actually going OK and we're actually being able to function.

When I talk about medications and injections or procedures that I do for that, I tell them those are really to help with those symptoms that you have so that you can go back to functioning. So, the medicines that we use help decrease the pain. They don't cure the symptoms, they don't cure the syndrome, but they help you feel better so that you can participate in school, in sports and whatever their life entails.

Glen Stevens, DO, PhD: Are there inpatient programs or this is all outpatient?

Desimir Mijatovic, MD: So here at Cleveland Clinic, we have an inpatient pediatric pain rehab program. It's one of only a few in the country, and it's here at our children's rehab hospital. I work as part of that program in doing evaluations for kids who are looking to be admitted into it. I also refer a lot of patients that I see in my outpatient clinic to that program as well. The main thing that we treat there is the central sensitization syndromes. So, AMPS, chronic daily headache, chronic abdominal pain, those are probably the top 80 percent of admissions that come in. And the results are really, really good, especially compared to the fact that a lot of these kids have gone months or years of other types of treatment that hasn't been helpful. And our outcomes for pediatric pain rehab are close to 80-90 percent successful for letting these kids get back to their lives.

Glen Stevens, DO, PhD: So how long are they hospitalized for on average?

Desimir Mijatovic, MD: So, for our program, it's a three-week program where we do two weeks inpatient, one weekday program, which is pretty typical of the other programs that exist, anywhere from three to six weeks. I also work in our adult pain rehab program. Since COVID, it switched to a virtual model now in our adult program. But yes, it's a lot of the same type of functional restoration as the main goal of the program.

Glen Stevens, DO, PhD: How much variances are based on the age of the child for the program?

Desimir Mijatovic, MD: So, most kids that are admitted to the program are eight or above. The average is probably between 13 and 17 years old for the patients that go to that program. Because we can have up to 10 kids at a time, we really do make the program individual for each kid. So, we kind of see where they start, where they're at in terms of their functioning and then what their goals are. And so, the program is very specific for each kid that comes through. It's not a cookie cutter model where we do the same thing for every kid. It's really dependent on what the kid's symptoms are and what they would like to achieve.

Glen Stevens, DO, PhD: And you sort of touched on this, but it's just not a physical thing. It's an emotional thing. And part of that emotional problem probably caused by the medical community and how we've dealt with these individuals previously. So, there must be a lot of comorbidities with... And you kind of mentioned that, and I guess in your specialty it's helpful, but probably co-mingles quite a lot.

Desimir Mijatovic, MD: The statistics show that of kids who have chronic pain, 80% of them have some kind of psychiatric condition diagnosis as well. So, it is something that's very, very commonly comorbid. And so, a big part of functional restoration for these kids is pain psychology or pain-focused psychology, which is different from regular mental health treatment for depression anxiety. It's really medically focused on how to stay functional despite the pain and how kids can keep living their lives even though they have this pain. So absolutely. If there are other conditions, like you mentioned, the medical community, medical PTSD or PTSD-related to medical conditions or medical issues is very common in these kids because they have had a lot of testing, a lot of invasive procedures, surgeries, all of this stuff before they get to that point. And so that needs to be addressed as well.

Glen Stevens, DO, PhD: And the parents' involvement with the rehab, is there some education for the parents separate?

Desimir Mijatovic, MD: Absolutely. Patient and parent involvement are very important. We are a small portion of this kid's life when they come into our program, the parents are going to be there every day. And so, we help teach the parents about these conditions, about what the parents can do to help best support the children, to allow them to kind of get back to their life, to get back to school, to get back to these things. So, the parent portion is a large portion. It's also a large portion of what I do in my clinic is educating the parent as well as the child about what's the best way to approach these things.

Glen Stevens, DO, PhD: So, if I'm sitting out here listening to this and I go, "Holy cow, I've got several of these patients in my practice." How do they get in to see you or somebody in the group?

Desimir Mijatovic, MD: So, in the pediatric world, if it's a pediatric patient, I work in our peds neuro department. So, the referral is actually for peds neurology and pain management is one of the options that comes down there. If it's in an adult patient, then it's our Center for Pain Recovery is the referral. And in the peds world, it's just me and our pain rehab. There are other doctors that do the evaluations too. But in the adult world, we have a small department where we do take care of a lot of people and offer a lot of different services as well.

Glen Stevens, DO, PhD: Sounds like we need another you.

Desimir Mijatovic, MD: That would be great. It would be great to have some support.

Glen Stevens, DO, PhD: And collaboration, right? Well, Des, I would like to thank you so much for joining me today. Always enlightening, and I'm pleased to hear that we're doing something to help these very chronic conditions as opposed to just ignoring it and letting it go through the system. So, I'm really excited about what you're doing. I really hope that we can get some additional help for you. And I hope that individuals listening to this that have patients that they feel could benefit from your program, send them. Because I'm sure, the sooner, the better, right?

Desimir Mijatovic, MD: Absolutely. The sooner we can get involved and start along this functional restoration path for these patients, the better they do and the faster they get better. So, I'm always happy to be of any kind of support, and if anybody has anything for me, I'm happy to always talk about that. And so, thank you so much for having me and allowing me to talk about what I'm passionate about.

Glen Stevens, DO, PhD: All right, thank you.

Desimir Mijatovic, MD: Thank you.

Conclusion: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.

Neuro Pathways

Neuro Pathways

A Cleveland Clinic podcast for medical professionals exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neurorehab and psychiatry. Learn how the landscape for treating conditions of the brain, spine and nervous system is changing from experts in Cleveland Clinic's Neurological Institute.

These activities have been approved for AMA PRA Category 1 Credits™ and ANCC contact hours.

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