All right, so ready to go to start our session. Our first speaker is going to be Dr. Shelley Shearn from Tel Aviv, and we're very much looking forward to her presentation on pediatric stroke. Thank you, Shelley. I hope everybody can hear me. And unfortunately, kids do suffer from stroke. And when we come to talk about stroke in children, we need to define it by the age of occurrence, as well as the etiology. For today, I chose to bring cases concentrating on arterial ischemic stroke in children and some diagnostic details. So let's assume for a moment that we live in a perfect world where a child with a stroke is immediately recognized and rushed to the emergency room, where a good diagnostic algorithm for pediatric stroke is present, as well as a stroke team. And you know the minute they hit that stroke protocol button, imaging is needed. And in many cases, CT and CTA will be the initial study, as it is a wide availability throughout the world and in the emergency setting. And of course, it can exclude hemorrhage or mass effect as a cause for the child's symptoms. However, there is a known limited sensitivity of CT for detecting arterial ischemic stroke in the acute phase, as well as to detect stroke mimics, which in the pediatric population are several. For that reason, MRI is the modality of choice to assess a suspected stroke in a child. However, time is also important. And if there is one thing that is similar between adults and children when it comes to stroke, it is that time is brain. So if you are lucky to have a child present in the hyperacute phase, and you have that MRI capability in the emergency setting, it's good to have installed a rapid MRI protocol with diffusion-weighted imaging, T2 FLIR, SWI, and time-of-flight MRI just to make the diagnosis. However, you don't want to delay the study in that hyperacute phase, so in many cases, you will still send the patient to the CT, especially if a child is medically unstable, if there is contraindication to MRI, or if the need for sedation will delay the study. However, whichever scenario this is, you will still need to go ahead and have a full diagnostic MRI, including vascular imaging tailored to the diagnosis. And that should be done in the acute phase within the first few days since symptoms started. And we do the MRI, and you know, the diagnosis is really easy. You do the diffusion-weighted imaging, and there it is, high signal. In the restricted areas, you have a stroke diagnosis. But basically, this is only where our work begins, because we need to go to our vascular imaging to assess for the etiology. And correct etiology in children is extremely important, both for prognosis and treatment. So look not just at the diagnosis of stroke, but also at the territory. And for MCA territory, when you have basal ganglia sparing and kind of distal large stroke, then you can expect the cutoff in the distal M1 segment, as opposed to basal ganglia stroke, where you can expect an abnormality in the proximal MCA M1 segment. When you have multifocal infarcts, you need to think about the thromboembolic event. And in a child who is previously healthy and doesn't have any cardiac condition, a dissection, arterial dissection, is a very strong possibility. And then when you get a stroke which is more like a watershed stroke area, in the central semivalve, for example, you need to think about moyamoya-type of scolopathy. So let's move to the first two cases, both of children presenting with acute basal ganglia stroke, in this case on the right. And the first one is a two-year-old boy with acute onset left hemiparesis, who actually was rushed to the ER early on and had an MRI study, four hours since he was last seen well. And the MRI study, the diffusion-weighted imaging, demonstrated the stroke. And then the time-of-flight MRA, both I'm showing you here, the maximal intensity projection reformat and the 3D volume rendering reformat, demonstrate nicely this narrowing and irregularity in the distal M1 proximal M2 segments on the right. Vessel wall imaging was performed. And although easier to assess in the supracellular cistern, sorry, because of the CSF around the arteries, you can still use it also for more distal arteries. And you can see here, you can see here this enhancement along the affected vessels compared to the normal other side. And this can even be better seen in additional planes, like here, you can see the enhancing walls of the affected vessels. And this child was diagnosed with focal cerebral arteriopathy, inflammatory type. This is a companion case to the first one, basically a child with a few days of symptoms that arrived to the ER. And the CT showed hypodensity suspicious of stroke in the left basal ganglia. And the CTA study showed the narrowing and irregularity of the distal supraclinoid ICA and the M1 segment MCA. Child didn't have an MRI because of dental hardware and was taken to the angiography suit, where you can clearly see a very nice beating pattern within the abnormal left MCA. And this pattern is basically protognomonic for focal cerebral arteriopathy inflammatory type. However, I brought this case because you can see that although you see the narrowing and irregularity on the CTA and in many cases also in the MRI, you cannot really see that typical beating. And that should not exclude this diagnosis, as was also shown in this study from the VIPS study group, that although protognomonic, only 25% of their patients with FCAI had the typical beating appearance. So do not exclude this diagnosis based on not finding that pattern. The next case, a 5-and-a-half-year-old girl with acute onset left central facial neuropalsy and progression to left hemiparesis within first 48 hours. She had an MRI, MRI study on the third day showing the acute stroke in the basal ganglia. And then the MRI study demonstrated a focal significant narrowing in the middle M1 segment on the right. Vessel-world imaging was performed and demonstrated this focal nodular thickening of the wall of the artery that enhances after contrast administration. And this is typical of focal cerebral arteriopathy dissection type. So basically, focal cerebral arteriopathy per definition is a unilateral stenosis irregularity of the large intracranial arteries of the anterior circulation. But we need to remember that there are different etiologies, and it's very important to differentiate between those because the treatment protocols differ. For example, for FCA inflammation type, which is basically a focal vasculitis, steroid treatment protocols are being built. So I find that vessel-world imaging is very useful in helping us differentiate between the different etiologies. And it's basically a high-resolution 3DT1-weighted sequence with blood and CSF suppression before and after gadolinium injection. And of course, there are great sources in the literature regarding the technique. So our next two cases are children presenting with multifocal infarcts. And this is a seven-and-a-half-year-old boy with acute onset right hemiparesis and vision blurring following a breakdance lesson. And the CT already showed hypodensity in the right occipital lobe with blurring of gray and white matter differentiation, as well as a small focus in the left thalamus. CTA study was performed and initially read as normal. MRI study on the same day demonstrated the full extent of the infarcts with both infratentorial and supratentorial bilateral areas of posterior circulation infarcts. A vessel wall imaging study have demonstrated that there is focal nodular thickening and enhancement. And this was diagnosed as vertebral artery dissection. So we went back to the CT and see why this was initially read as normal. And apparently, when you actually look at the source images only in the axial plane, dissections can be really hard to diagnose. And then if you look in other planes only in the computer-generated maximum intensity projection, you definitely may miss subtle abnormalities. So I urge you to learn to do your own multi-planar reformats at the workstation and use as many planes as possible. And that can help you actually see a subtle dissection within the vertebral artery on the left, as in this case. The next case is an 8-year-old boy with sleepiness, confusion, slurred speech, ataxia, a day after falling with blunt-hand trauma. So CT showed hypodensity within the right thalamus. And then next day, MRI on the diffusion-weighted images, we saw bilateral thalamic infarcts, which was acute as seen below ADC. But then also, there were findings consistent with chronic infarct in the cerebellum infertentorially. The time-of-flight MRI was centered on the intracranial arteries and demonstrated nicely these cut-off and irregularities at distal PCA branches. You may appreciate it better if you look at the follow-up study where there was already some reconstitution of flow within those affected vessels. However, in the initial study, the neck vasculature was only assessed with contrast-enhanced MRI, in this case a Kerr-Bolus contrast-enhanced MRI, which unfortunately was delayed and contaminated by venous contrast. So a CTA was performed, which again, unfortunately, was not the best diagnosis quality. However, contrast was seen filling the arteries, and I think initially, this type of impingement seen here between C1 and C2 was not getting attention. Patient was treated, treatment was stopped, and then a few months later, presented with new onset symptoms. Time-of-flight MRI study was performed. It was degraded by motion artifacts, so a subtle abnormality in the left vertebral artery was dismissed. So I think you can already realize this is kind of a case of a series of unfortunate imaging events. But as we continue to follow up this case, patient definitely developed abnormality of the left vertebral artery, and this was a pseudoaneurysm at the dissection site. And when we look again at the coronal plane, we can see and we can appreciate that there is some asymmetry in the position of the lateral mass of C1 compared to C2, and impingement just at the dissection site. And this child was diagnosed with vertebral artery dissection due to rotational arteriopathy, the Bow-Hunter syndrome. So this case of a series of unfortunate events is actually a very good example for what was nicely discussed in this study in radiographics about vertebral artery dissection in children. And basically, when you do have multifocal isolated posterior cerebral arterioschemic strokes, especially if those are of varying age, you really need to think about vertebral dissection, vertebral artery dissection. And the most common place to look for it is at that V3 segment, C1, C2 level. Look always for related bone abnormalities, and remember that 50 percent will progress within the first year. The last case for today is a 3-year-old girl with neurofibromatosis type 1 presenting with normal eye exam. And her initial MRI study showed these typical T2 hyperintensities in the cerebellum, brain stem, and basal ganglia, as you can see here, consistent with NF1 FASI. She also had this enhancing tumor within the optic chiasm consistent with optic glioma. So she was followed up for her optic glioma for many years. Tumor has grown within those years that led to surgical dissection. You can see the tumor here. But what was failed to be noted throughout all her studies was that there were those curvilinear T2 flare hyperintensities within the salt side on the left hemisphere, a bit also in the medial aspect of the right hemisphere. And this is basically consistent with what we're used to see as IV sign in Moyamoya patients. So this patient had NF1-associated Moyamoya syndrome, which basically NF1 patient up to 3 percent can have this kind of a scleropathy. And Moyamoya disease is an idiopathic, non-inflammatory, non-enterosclerotic, progressive vasoclusive disease with creation of multiple collaterals. So Moyamoya syndrome describes Moyamoya-type of scleropathy associated with predisposing condition like NF1, post-radiation, or sickle cell disease. So when you see that type of T2 flare abnormalities in the salt side, I urge you, before you dismiss it as artifact, go to your T2 sequences. Because remember, the T2 can be like a poor man's MRA, and in the T2, you can actually see the asymmetry that developed to full lack of flow void in the supraclinoid ICA in the left MCA, as well as multiple collateral vessels in the CSF basilar cisterns, and a small new focus of T2 hyperintensity in the centrum semiovalve consistent with a focus of ischemic or chronic ischemia. Time-of-flight MRA was performed actually after she had her surgery and showed complete lack of signal in the supraclinoid ICA and left MCA as opposed to the normal side. You can see the lack of signal. But this child also developed spontaneous external carotid artery circulation collaterals through her craniotomy, and luckily for her, did not develop any major stroke during the surgery. So to conclude, my take-home messages are establish imaging protocols as part of institutional stroke protocol in accordance with your medical center ER imaging availability. Make sure a full diagnostic MRI, MRA study is performed within the first day, if not in the hyperacute stage. And diffusion-weighted imaging, make the diagnosis, but then go ahead and look at the ischemic changes pattern to guide your etiology investigation. Do not forget cervical arteries evaluation. And I cannot stress it enough. Use time-of-flight MRA both for head and neck prior to conscious administration. Use vessel wall imaging to help differentiate between different vasculopathies. And pay attention to developing IV sign for early detection of Moyamoya syndrome in predisposing condition to prevent future stroke. And as always, it takes a team. I thank my stroke team in Tel Aviv Medical Center. And I thank you for listening. So hello, everyone. Thank you for being here. I would like to say thank you for the invitation for today to talk about primary neurometabolic disorders. It's a very interesting topic. The purpose of this talk is to bring you some ideas of classification of neurometabolic disorders, help you in the diagnostic rationale for these disorders, and bring you some examples of the most common disorders and the variability of the imaging phenotypes. There are several classifications. I would say the most common one is dividing the cell where the location of the cell of the abnormalities is coming. Sometimes it's very useful to have this classification depending on how this translation of the abnormalities in the internal cell to the neuroimaging phenotype. For instance, for Manx, where you understand these abnormalities, they come to the copper deficiency, the copper translation to the cell. We understand the deficiency of the copper will bring mitochondrial problems, will come with melanin problems, collagen deficiencies, abnormalities in the elastin, as well as anemia in the context of viral transportation deficiencies as well. Knowing these findings, kind of being kind of obvious, or at least straightforward for you, the neuroimaging find is expected. So these patients, they tend to have large cerebral collections, the typical Vormian bones, volume loss of the brain, white matter chains, along with this whole tortuosity of the vessel. So kind of useful to make the translation of the abnormalities inside the cells to the neuroimaging finds. Not always this connection is that easy, but even when not so obvious, the translation from the abnormalities of the cell to the neuroimaging phenotype, we certainly can make other diagnoses. So just to present to you this case, a three-month-old female patient with lack of energy, typical appearance of the urinary. You look for the brain, you see the edema of the brain, areas of increased restrictive fusion in the areas that are getting myelinated to the brainstem, thalami. So putting all these findings together, even not understanding very well how the enzyme defects is translating the neuroimaging finds, you are able to make the diagnosis of maple sugar disease. Same example here. You see a patient with urea cycle disorder. You don't understand how the OC, that's the most common enzyme affecting in this disease, is bringing the phenotype. But you put all these findings together. See a baby with hyperhormonemia, edema of the brain. You see the clasped peak of 2.32 that reflect the glutamine and glutamate. And the ribosome, the areas of restrictive fusion along the insula, if you put all these findings together, even without understanding how the deficiency of the enzyme is coming, you are still able to make the diagnosis. Sometimes even hair disorders like Christian Hansen syndrome, the clinical findings and the clinical data and the imaging finds are so typical, such as, for instance, in Christian Hansen, you see this kind of abnormalities only in the inferior aspect of the cerebellum with atrophy. If you put all these dots together, you don't need to understand how the genes, the defect of the gene and how the metabolic pathways are occurring, but you are able to make the diagnosis. Unfortunately, most of the time, this is not our reality, yes? Our reality is bringing a case of a leukodystrophy and they say, okay, the leukodystrophy was a diagnosis. And you have this whole data of 100 differentials and you start to cry because, of course, there is no straightforward answer for that. And with that, we start to bring a lot of ways of narrowing our rationale. So, patients with thyroid appeasing leukodystrophies are more superficial white matter involved instead of the deep white matter involved, posterior gradient instead of anterior gradient, diffused white matter chains, chains related like presence of calcification or cavitation, subcortical cyst spectroscopy that's extremely helpful for cannabis, and also enhancement of the nerve wound. So, you put all these findings together, you are narrowing, more or less, your differentials, for instance, in the context of leukodystrophies. So, for today, I want to bring to you the most common pattern that you may see in leukodystrophies and also the most common organelle affected in neurometabolic disorders, the mitochondrial diseases. So, let's bring first the thyroid and the leopard pattern. This is the pattern that I want to discuss with you today. I want you to take a look and see if you are able to make a diagnosis of all these patients presenting with the thyroid pattern, the leopard skin pattern. Okay, the top four at the top, all of them are metachromatic leukodystrophy. So, metachromatic leukodystrophy is a phenotype that you need to keep in mind is thyroid, leopard skin. The thyroid are those stripes that you see and the nodularis related to the thyroid pattern. So, thyroid and the leopard skin together. Leopard is nodularis and the thyroid are the linear stripes, okay? Remember that metachromatic leukodystrophy is also associated not only to the central nervous system, but also the peripheral nervous system. So, it's very common to see enhancement of the cranial nerves, enhancement of the caudate quina. When you put all these findings together, you may be able to consider this diagnosis, okay? But of course, there are several variabilities and I decided to bring to you three different examples, all these three patients presenting with metachromatic leukodystrophy, so you may understand the variability of the phenotype. So, here you can see the involvement of the corpus callosum, anterior and posterior, involvement of the posterior limbs of the internal capsule, and minimal involvement of the brainstem, and no involvement of the cerebellum. In this other case, you see again the thyroid and the leopard skin together. You don't see much involvement of the basal ganglia, you don't see involvement of the posterior limbs of the internal capsule, and again, you don't see involvement of the cerebellum. And the third patient, again, with the diagnosis of metachromatic leukodystrophy, you again see the involvement, the typical appearance of the thyroid and leopard skin, the diffuse involvement of corpus callosum, anterior and posterior, and more involvement of the basal ganglia and more involvement of the brainstem, as well the posterior fossa. So involvement of the posterior fossa is not something that define metachromatic leukodystrophy, but if you put again the presence of enhancement of the cranial nerves, enhancement of the caudate quina together with the leopard skin and thyroid pattern, it's kind of reasonable to consider these in your differentials, okay? So putting together, you may see risk diffusion or not, you may see enhancement, and frequently you see the thyroid and the leopard skin together, because these are basically disorder that follows the perivendular distribution. Every time that I think about metachromatic leukodystrophy, you should put in your differential CAR-B, yes? So CAR-B is very similar, may also present with thyroid and leopard skin. In general, you may also see enhancement of cranial nerves for the same reason, it's also involved in the peripheral system. And these enhancements normally associated with increasing thickening of the upper nerves, typical findings, along with the involvement of the hyaline, the dentate. So putting together, kind of good differential to keep in mind. So similar to what I did with metachromatic leukodystrophy, I want to bring three patients with CAR-B, so you may create your own rationale for this diagnosis. So what we are seeing here in this patient with CAR-B, kind of younger patients, actually CAR-B most frequently are younger than metachromatic leukodystrophy, you see the pattern of thyroid and leopard skin, and you may see that the signal changes are a little bit more posterior. So in metachromatic leukodystrophy, in general, you have the whole involvement of the corpus callosum. These patients tend to have more posterior thyroid and leopard skin change, and when you go to posterior fossa, change in the brainstem, as well, change in the hyaline of the dentate, typical for younger patients. Second patient, again, you see the white matter change, kind of sparing the U-fibers, more like the deep white matter. Beautiful example of the leopard skin and the thyroid, so perivenular distribution involvement of posterior limbs of the internal capsule, more posterior, more posterior gradient of involvement of the white matter. And again, the involvement of the brainstem and the hyaline of the dentate. Older patients, like this one, six years old, the white matter change tends to be more and more located in the central, in the peripheral region, the corticospinal tracts, and you may not see the involvement of the hyaline of the dentate. So putting all these findings together, you see classic picture. Enhancement of cranial nerves, increased thickening of the upper nerves, and more selective white matter change when these patients get old, along the corticospinal tracts, and you may not see the increased thickening of the upper nerves, particularly when they're older patients. So there's some variability of these findings. When they are very young, there are also some variability, so there is no enough myelination, so you may not see the thyroid or the leopard skin, but you may see, again, the increased thickening of the upper nerves, and sometimes even increased thickening of other areas, such as the corticospinal tract. Look how thick is this. So these are kind of typical features for Krabbe in all different spectrum of the disease. So now that you learned about Krabbe and metachromatic leukodystrophy, let's jump to this other one, more delicate appearance of the thyroid and leopard skin. Here we are talking about a different entity, the hypomalinating disorder, Pellezius-Myers-Barker. This is a prototype of hypomyelinating disease. They're very more delicate, and they tend to be associated to boys, because X-linked disease. And different from typical leukodystrophies, in this case, you don't have destruction of the myelin. Actually, you don't have a proper formation of the myelin. And this makes the water to be along with the sheets of the myelin, and increases signaling to two. So we have an increased signaling to two, but a normal signaling to one, because the myelin itself is there. The fat component's there. It's just the myelin is not mature enough, so there's a lot of water along with the myelination sheets. And the signal increases to two. The normal volume, and very mild form of thyroid and leopard skin. So let me bring you a challenging case. I want you to take a look and see what you think about this patient. It's 12 years old, kind of older for those other patients that we discussed. It's a severe headache, ataxia, and behavior change. So you're seeing your leopard skin. You're seeing your nodal ligaments. But look how they are more like gross. They don't follow very well the perivenular distribution. You see some signal changes in the brainstem, but brainstems are kind of too effective, it appears. Not very typical for those that we discussed. And where is our thyroid? We see the leopard skin, but I discussed with you, they are like perivenular distribution. So it means that's missing something, yes? And this case was actually a no longer herniated cytosis. No longer herniated cytosis, they mimicked leukodystrophies. Remember putting it all together. The reason of this pattern is because of perivenular distribution. If you see nodal ligaments, OK, it can be a good finding. But keep in our rationale how these lesions, they need to be distributed, OK? Moving on from the other two aspects of thyroid and leopard skin, these are very different. Because, for instance, for cancer, you tend to spare the deep white matter. It's much more peripheral. And you see these stripes, which is kind of unique for cancer. And Alexander, where the white matter chains are more anterior, and the stripes itself are more posterior. For cancer, typical singular skin mitochondrial deletion tends to have multiple systems involved. And these are the features that I want you to keep in mind. Because 90% of them, they represent like this. Involvement of the brain stem, involvement of the basal ganglia, withstanding out the globus pilus, white matter chains involving also the corpus callosum, sparing the leaf, and also the subcortical white matter with these stripes, like more coral leaf, because they're very fine compared to the classic metachromatic leukodystrophy. In the context of Alexander, this patient tends to have a magnizephaly. May see enhancement along the horns of the lateral ventricles, as well in the brain stem. And as I said to you, when you look for the white matter chains, they have more anterior distribution. So you see kind of swollen appears, because this is astrocytopathy. The astrocytes are responsible for controlling those modes. So kind of edema of the brain more anterior. And the stripes, they are more posterior to the white matter. So you see this classic pattern of gradient of distribution. White matter more diffusely anterior, and the stripes are more posterior. So moving on, let's talk very quickly about mitochondrial disorders. As I said, mitochondrial disorders are the most common ones in the neurometabolic disorder that we have. Remember that they are not only related to mitochondrial gene, but also to the nuclear gene. The reason is kind of straightforward. When you think that the importance of these enzymes, some enzymes that are formed in the nucleus, proper function in the mitochondria. So any kind of dysfunction in the nucleus that's responsible for forming enzymes that they go to the mitochondria may cause a mitochondrial disease. And this is the reason why this is the most common neurometabolic disorder in the world. Tends to not be just one system. You see multiple organs involved. So keep in mind, these patients are very complex patients. And of course, the brain is a common location for lesions, for abnormalities. So I want you to take a look. All these are class pictures of mitochondrial disorders. All of them are confirmed and described as forms of presentation of primary mitochondrial disease. So I hope you can make yourself some diagnosis if you look. Okay, so these we have forms of cortical involvement in NILS, OG, more white matter, as we said, basal ganglia, cerebellar, and malformations. I know that I discussed with you about white matter and leukodystrophies in cancer. That's a red mitochondrial disorder. But this is the one that I want you to remember. This is very unique for mitochondrial disorders. Very unusual to see this in any kind of other disease. You may see intoxication, but very, very uncommon. So please keep in mind, these cavitations, they have more lamellar distribution, with restricted diffusion, unique for mitosis. Unfortunately, it does not bring you specific genes, more frequent nuclear genes, and the mitochondrial dysfunction. But if you put together further findings, such as involvement in cerebellum, very typical for complex one, or BPL, when diseases are kind of small and patient presented with cardiomyopathy, you need to think about complex three. If they give you a spectroscopy, and you see this peak in 2.32, the diagnosis is done, 2.36. The succinate deficient, the succinate dehydrogenase deficient, you don't need to struggle anymore. And the white matter are not that cavitated, but follow the cortical spinal tracts, and you see the involvement of the spine, lateral columns, posterior columns, this is DARS-2, okay? So I think we can move on for cortical chains and mitochondrial disorders. Prototype, MILAS. MILAS, kind of mitochondrial disorder, it's very typical for the cortical involvement. Remember, these kids, they tend to not be normal. You need to be proactive in asking some questions. They tend to not hear well, they tend to be smaller for their age, they tend to be wearing glasses for a long time. But if you don't ask, the parents will not tell you that. So you need to keep in mind this. And the classic picture that you see are these cortical lesions that are very large, more posterior, they don't reflect arterial territory. Normally, you see increased ASL perfusion. You may see engorgement of these vessels, such as the posterior cerebral artery here, some engorgement of the veins, and of course, the lactate peak at 1.3. This case is pretty interesting, because we got a follow-up, and you see that there's minimal volume loss on the right, and you don't see signal change anywhere else. And the patient's presenting, again, a stroke-like episode. But when you got an ASL and the MRA, you were able to see the lesion on the left. And also, you see now, the engorgement of the left posterior cerebral artery. So remember about the ASL when you wanna go and really find the lesions that are not that obvious in the structural images, okay? Sometimes, it can be even harder. Some lesions may not that typical. They may be like scattered through the brain. And this diagnosis is sometimes not that easy, but important. So if you see some association with basal ganglia lesions, these patients, they tend to have a worse prognosis, and you should consider that, because it's not that obvious to make this diagnosis. Now that we spoke about cortical and white matter, I just wanna bring Lee very quickly for you. Lee, I would say that's the most complex mitochondrial disorder that we have. The reason that, because we have more than 100 genes related to Lee syndrome. I would say the first step that you need to consider is to divide what genomes affect nuclear genome, mitochondrial genome, white matter chains, more frequently related to nuclear genome, cortical chains, more frequently associated to the mitochondrial genome. So if you do, I write this game in trying to separate. It's already very nice. Remember, we need narrow imaging findings for the diagnosis of Lee syndrome, basal ganglia and brainstem, typical locations, substantial nigra, oculomotor nuclei, peritoneal gray matter, inferior colliculi, inferior vestibular nuclei, and the leaves. When you put this together, with classic appearance of restricted fusion, they are not restricting as strokes. They have heterogeneous components. They may even have a target sign appearance. The location of the brainstem is almost pathogenomonic. White, these lesions, that's not just pericardial, but they extend more laterally. These are all typical features. Sometimes the same gene that caused Lee syndrome, such as PGH, that's more actually for the globus pilus, may also cause malformations. And malformation is another phenotype that you need to keep in mind. Sometimes you may consider this diagnosis in the early stage. This opens a new field for us. So malformations associated with mitochondrial disorder is something that you need to keep in mind, even for fetal MRI. So this is another field that we are considering nowadays, and this is where you wanna go. So with that, I end my talk, and I open for questions. Thanks so much. Thank you. Thank you, Cesar. We have to move on for sake of time. I just want to say, while we are rearranging a little bit here to set up for mitochondrial disorders, metabolic disorders, I'm doing this since more than three decades. It still frustrates me because it's so complex. Be aware, you are part of a team. It's not radiologists only who makes a diagnosis. You sit together with all the other team members, and then you make the diagnosis. And finally, we should also not forget that many metabolic disorders, you have to recognize them as early as possible. We cannot treat it, only if you would change your genomic setup, but we can prevent injury to the brain by taking care of toxic metabolites to take them out of the circulation, et cetera, et cetera. So it is a complex topic, and it's teamwork. Thank you, Cesar. And in the meantime, we are set up. Happy to introduce to you Dr. Laura Hayes. Also, Laura is a very active and very prolific member of the Medical Society of Pediatric Neurobiology. You see, we have a little bit of different setup. She's from Nemours Children's Hospital in Orlando, Florida, and she is an assistant professor at University of Central Florida College of Medicine. Hopefully, by the end of this talk, you'll feel more comfortable interpreting imaging of the spine in children with trauma. Most important, 80% of pediatric spine injuries are in the cervical spine. And in little children, actually, most of the injury is very high up. These are some of the hardest injuries to detect on imaging, and most of them are ligamentous injuries, so they can be very hard for us to identify. Okay. So our first case, I'll show you a two-year-old, status post-MBA. This is the CT scan of the head. Oops, sorry, don't look at that. Well, at least I used arrows. It's working now. Okay. It's working now. Oh, there we go. Okay, good. All right, so sorry, everyone. Okay, so on this head CT, you can see this hyperattenuation at the level of the foramen magnum. So you're seeing blood at the level of the foramen magnum and a retrocollipal hematoma here. So whenever you see blood at the level of the foramen magnum, you have to be very concerned for an injury of the spine. So we ordered a CT scan of the spine, and these are the sequences we're sent to PACS. So I looked at this, I'm like, oh my gosh, what am I gonna do with this? Just bones. And I know that most common injury is ligamentous injury. So, you know, I call the technologist, I say, you know, send me some sagittal soft tissue reformats. But in the meantime, let's look at what we've got with our bone windows. So is this normal? Or does this look abnormal to you? So I just have you look at that for a second, and then we'll come back. So how can we tell without MRI if this is normal or abnormal? Well, we have to know what's normal for age and understand the biomechanical differences in children versus adult. Sometimes, unfortunately, we're gonna have to use measurements, and most importantly, get the soft tissue reformat. So I'm gonna tell you, I'll give you some pearls in this. We're gonna start with C2, because C2 is very complicated. One of the most important things to know is that the body of C2 here fuses with the odontoid process by six years of age, so about kindergarten time. This fusion line you could actually see into adolescence. I saw an 18-year-old boy the other day. That's still, you could see the fusion line. But in general, you should not see an unfused subdental synchondrosis after the age of six. So if you see this in an older child, be very concerned about a synchondrosis injury. Also, before the fusion occurs, I want you to make sure that you look at the alignment of the dens with the body of C2, because that's also very important. Pre-recebral soft tissues. This can be your best friend, or this could be your worst enemy. It can be thick with edema from an injury, but oftentimes, we see this pseudothickening when the child is breathing out during the exposure. So what you can do if you wanna get some further imaging clarification, just repeat the cross-table lateral with mild extension during inspiration. You can roll up some washcloths under the child's shoulders, and that may be helpful. So what I want you to remember here is that normal pre-recebral soft tissues should be less than six millimeters at the level of C3. If you don't wanna remember six millimeters, that's fine. Just remember that it's less than 1 1⁄2 the AP diameter of the vertebral body. Saturatory formats. I can't stress how important these are when you're evaluating the cervical spine in children, because you can see normal ligaments at the craniocervical junction on CT. You can see the tectorial membrane. You can see the apical ligament. You can see this anterior atlanto-occipital membrane, and also the anterior longitudinal ligament. There's fat interposed here, so it's super helpful. Make sure you get those sagittal soft tissue reformats. A pitfall that people fall into in children is pseudosubluxation versus true subluxation. This is pretty common in children under the age of seven years. It's rarely seen into the second decade. So one thing you can do to find out if you think it's real or not is to look at this spinal laminar line. This is also known as the line of Swiss chuck, from the level of C1 to the level of C3. You should not see this widening more than 2 millimeters. By the way, this is a really good paper by McAllister et al. that talks about cervical spine injury. It's super helpful, so if you want more information, I would refer to that article as well. So there are a lot of other helpful guides. All these are helpful guides, but remember in children not to go solely by the numbers, as the measurements can change with age. Age may be exaggerated by positioning, et cetera. This one is very important. This is the Bayesian DENS interval. If the DENS is unossified, it should be less than 12 millimeters. If it's ossified, it should be less than 10 millimeters. Remember this, and also remember 12. 12 is something that we often see in kids. Here's another example of 12. This posterior interspinous distance, very helpful indicator of ligamentous integrity. So it shouldn't be greater than 12 millimeters. If you don't want to remember 12 millimeters, just remember that it shouldn't be more than 1.5 times greater than the interspinous distance one level above or below. This is huge, especially in little, little kids. This is the Atlanto occipital interval. It does change with age. In adults like us, it's gonna be about 2.5 millimeters, but in the younger kids, it should be about three to four millimeters. One of the takeaway points, if you don't want to remember the numbers, is to look at asymmetry, especially on the coronal reef formats. It can be very helpful. And it should be kind of uniform here. It shouldn't be really that much bigger posteriorly than anterior. So the asymmetry is your friend. So let's go back to my case. So if we draw some measurements, we can see actually if there was a measurement here instead of a line. This is slightly greater than 12 millimeters. This interspinous distance is too wide. The Atlanto occipital distance is greater than four millimeters. And look, it's more prominent back here than it is anteriorly. And even at the level of C2-3, we're seeing a widening at that level as well. So we put them in the truth machine, right? And we see this disruption of the ligaments at the cranial cervical junction. You can see the tectorial membrane is stripped. There's prevertebral edema. There's fluid between the joint spaces and this is an occipital atlantoaxial distraction type injuries. These type of distraction type injuries are very common in children, especially if they're in a high speed motor vehicle accident. You can see it on many x-rays as well. We're seeing prevertebral edema. We're seeing widening of that interspinous distance. And even you can get a sense that there is widening between the occiput and C1. Here's another example of an atlanto-occipital distraction injury. This is more than 12 millimeters. And look at the sagittal soft tissue reformats. You can't see any of those beautiful ligaments that we were seeing before. You see a hematoma underneath the tectorial membrane and this extensive prevertebral. We see prevertebral edema. We see blood here. So this is an atlanto-occipital distraction injury here. The MRI tells the tail all the ligaments are torn. You see all this edema posteriorly. And even in this case, we're going to see edema in the brainstem. Here's another case where you have widening between C1 and C2. There's widening of the interspinous distance and all this prevertebral edema. So this is a distraction between C1 and C2. And here it is on MRI where you see there's actually an avulsion of the cartilaginous tip of C2. And again, you're seeing this fluid in the joint space. Here's a really unfortunate case of an eight-year-old girl that was in a motor vehicle accident. Of course, we have this widening of the basion dense interval again. And in older children, you may see associated fractures as well. She has a avulsion fracture here from the occipital condyle. Abusive head trauma. I can't not talk about this and talk about pediatric spine trauma. Important to know that about 60% of children with abusive head trauma have spine injuries. And X-rays and CT are not sufficient to exclude the spinal injury. So it is now recommended to order a complete spine, a complete MRI scan of the spine. And not only is this important for the kids, but this is important when this case goes to court. Okay, next slide. Take a look at this. This is a portable chest on a neonate with respiratory distress. Besides that, you see anything else going on here? Well, there is widening here in the mid cervical spine. This is a distraction type injury. Luckily, it's pretty uncommon birth injury. But if you have an X-ray on a child, a neonate with respiratory distress, really look really closely at that spine because obviously it's something you don't wanna miss. Here is the CT that was performed. Of course, this widened distance. There's a separation at the level of the cartilaginous end plate here and this really horrible cord transection. This is a case that was loaned to me by Dr. Murski. This is a two and a half month old infant that presented with wheezing and irritability. On this X-ray, we're seeing really this obvious thickening of the prevertebral soft tissues and maybe a little bit of hyperattenuation in that region as well. Here's the CT. Again, prevertebral edema, looks like calcification back here as well. Note there's some central lucency within that calcification as well. And here's the MRI. Again, we have that splitting at the level of the cartilaginous end plate. We have this large prevertebral mass-like structure. And here is the T1 images. Here's post-contrast. Again, note that little central lucency there. There's no decreased diffusivity. And this child went on to have a skeletal survey. And what we can see is numerous healing rib fractures here. We see classic CMLs. And this was a case of non-accidental trauma. So this is a case of myositis ossificans circumscripta related to cervical spine trauma. Here's just a case that looks exactly like it from the literature from Pediatric Radiology and Dr. Harmon et al. in 2012. Here's a teenager that presented with a football injury and neck pain. Let's see if you see anything going on here. The key finding in this case is this prevertebral edema. Like I said, about three millimeters at the level of C3, or I'm sorry, less than six millimeters at the level of C3 is normal. Again, less than 1 1⁄2 the width of the vertebral body. And in this case, if you measure it, it's 8.4 millimeters. Here's the CT showing the prevertebral edema. And here's the bone windows where we see widening, but it's not really a fracture. These are really sclerotic margins. So this is actually a separation at the synchondrosis of an incompletely fused anterior arch of C1. And you can see posteriorly, the posterior arch of C1 is also not completely fused. So here on the MRI, fluid there, prevertebral edema like we were seeing. And actually, some people say that these children shouldn't even participate in contact sports, but I really wouldn't put that in my report, but I might relay that to the referring doctor. Real quick, here's a 10-year-old cheerleader, status post-fall. Just, this is the scout for the CT. Don't mind this horrible NG tube, but there is a prevertebral edema, and maybe there's some widening in interspinous distance. Here's the MRI scan showing you the prevertebral edema, this fracture that is impinging on the spinal cord, all this ligamentous injury. I want you to really look closely at this axial T1 and see if there's anything that you think looks abnormal. So there's no flow void at the level, the expected location of the vertebral artery. This child went on to have a CTA, and you can see there is a vertebral artery here, but it's absent at the level of C2-3. So pay close attention to the vertebral arteries, any of the arteries in general, to look for any vertebral artery abnormalities. Here's a teenager with a ground-level fall and weakness. You can see the fusion rods back here, but it may be unbelievable for you to see that the alignment of the cervical vertebral bodies are absolutely misaligned with the rest of the thoracic vertebral bodies. Here is this horrible-looking CT of the cervical spine, and this is a spine dislocation. So this happens when there is a bilateral facet fracture dislocation. In children that don't have spine fusion, this is usually at the thoracolumbar junction, and this is a very unstable injury, as you can imagine, with a very high rate of spinal cord injury. This is one of my last cases. This is a teenage boy that presented with back pain after he was lifting weights. The X-rays are totally normal. You can't see any abnormality. The child continued to have back pain, and finally a CT was performed, where you can see this avulsion fracture at the level of the superior end plate. Went on to have MRI. You can very well see this fracture fragment impinging on the spinal, excuse me, on the cauda equina, and this is an apophyseal ring fracture. This is a fracture that occurs at the level of where the sharpie fibers attach onto the superior end plate, and again, radiographically occult. So if you have a child that has persistent back pain, have a very low threshold for obtaining cross-sectional imaging. So these are my take-home points. Cervical spine injuries in young children are usually high and ligamentous. That atlanto-occipital interval is very sensitive for CCJ injury. Really look really closely at that. Scrutinize the alignment, and look at the soft tissues. Get the sagittal soft tissue reformats on your CT scans, and even consider in children that have trauma, including the upper cervical spine to the level of C3, and have a very low threshold for recommending MRI scans in these children. Thank you.

pediatric stroke

arterial ischemic strokes

rapid diagnostic approach

MRI imaging

acute ischemic strokes

etiology

focal cerebral arteriopathy

moyamoya syndrome

vertebral artery dissection