 cases very often of each individual each individual case very often but few of these cases all of us are certainly going to encounter in our daily routine practice whether we are practicing in a big city or a small town or anywhere in between. Hence in this presentation I'll quickly talk about the different types of white matter disorders which are both inherited and acquired because of the multiple different types the diagnostic process is different while MRI is exquisitely sensitive for detecting the presence of white matter pathology because of the overlap of imaging findings because of the overlap of imaging findings and the white spectrum of imaging findings in many of these disorders the establishing of specific diagnosis is often delayed. In this presentation we will briefly discuss how to distinguish normal and abnormal white matter in children and formulate an approach to evaluation of white matter disorders radiologically using a pattern recognition approach. We will also briefly see the role of your imaging techniques like diffusion and spectroscopy. So the normal myelinated white matter has shorter t1 and t2 relaxation in that in the normal myelinated white matter on t1 whiteed images the white matter is whiter than the gray matter and on t2 whiteed images the white matter is grayer than the gray matter. In unmyelinated white matter the contrast is reversed while most of us most commonly see older children and adult patients in our routine practice the in the younger children the myelination when the myelination is not complete and the contrast is reversed it may sometimes be mistaken for pathology. So now I will talk about how myelination progresses in the in an orderly manner in the developing brain. This is a dynamic process that starts during the intrauterine life and continues after birth in a well-defined and predetermined manner. So here we have a 26-weeker in which the white matter is almost hyper intense completely hyper intense on t2 weighted images and as time passes the white matter becomes progressively darker on t2 weighted images. The awareness of this changing appearance of the brain on MRI as a result of this maturation process is important to minimize misinterpretation of normal changes. The general rule is that myelination progresses from caudal to rostral from posterior to anterior and from the central to the peripheral regions from the central to the peripheral regions. It begins during the fifth month of life and continues throughout life in an orderly manner. However on imaging typically we will see the slight amount of myelin myelin appearing in the brain by around 36 weeks or around turn and then we see habit progresses. CT has very limited role in evaluation of myelination. Here we see the more watery content of the unmyelinated brain. It may be sometimes mistaken for edema or some other pathology also. So CT has limited role. MRI is a workhorse for evaluation of myelination and we see both t1 and t2 weighted images because they produce differential contrast and we evaluate the brain in different planes. In the neonates the sagittal plane is most useful because we are evaluating the dorsal brain, the dorsal brainstem and the posterior fulsar structures for the presence of myelin. In the terminal stages of myelination we evaluate the coronal images because we are seeing the subparticle u-fibers. For example here the subparticle u-fibers in the temporal lobes are not myelinated in an almost two-year-old child. In the intermediate state of myelination we will evaluate the axial planes because we are seeing the posterior limb of the internal capsules, the corticospinal tracts, the optic radiations, etc. On t1 weighted images, in a term neonate the parts that are myelinated are the dorsal, the brainstem, the cerebellar hemisphere, the posterior limb of the internal capsule, the ventrolateral thalamus and the corticospinal tracts and the perirolandic areas. By four months the myelination in these areas becomes more robust. We are seeing more obvious myelination in the optic radiations and in the centrum semi-oval and the perirolandic regions. We are also seeing myelination that is just beginning in the anterior limbs of the internal capsules at four months of age and myelination is also appearing in the basal ganglia and in the rest of the thalamine. By eight to nine months myelination is almost complete on t1 weighted images. We see myelination is spread in most of the white matter and it extends almost up to the subcortical ufibers and after 12 months there is hardly any change in the myelination on t1 weighted images. On t2 weighted images myelination follows a few weeks later. By four months we are seeing that there is some myelination and myelination is just beginning to appear in the anterior limbs of the internal capsule. By eight months myelination is appearing but it is not yet seen in the frontal subcortical ufibers. More robust myelination is seen in the posterior subcortical ufibers in the paritoxial lobes. By 12 months we are seeing that the frontal frontal and the temporal subcortical ufibers are not myelinated. The rest of the white matter is almost completely myelinated including this plenium of the body of the corpus callusum and the anterior limbs of the internal capsule and by two years myelination is complete even in the subcortical ufibers of the anterior temporal lobes which are the last two myelination on t2 weighted images. So in the initial period up to maybe around six months we will evaluate t1 weighted images and from six to eighteen months we will evaluate t2 weighted images to see how to see the progression of myelination. Nowadays we use fast pinnico t2 weighted images with longer eco-trail lengths, eco times and recovery images and myelination is seen earlier on these fsc t2 weighted images rather than the conventional t2 weighted images which are generally not even used now. So here we have a case of four month old child with vest syndrome and MRI was done outside and was sent for review and it was outside it was reported as vanishing white matter disease but we know that in a four month old child on t2 weighted images the subcortical ufibers are not going to be myelinated. So these are just normally unmyelinated normal for age subcortical ufibers and should not be mistaken for any white matter pathology like vanishing white matter disease etc. Apart from t1 and t2 weighted images we will see terminal zones of myelination up to a which are unmyelinated in the peritrigonal white matter up to a longer period. So there are three main types of white matter disorders. One is the demyelinating disorder in which there is destruction of intrinsically normal myelination. These are typically acquired disorders and are beyond the purview of this talk. We see that these these areas are patchy and almost always bilaterally asymmetric. The myelin has already formed normally and then it is destroyed. These are conditions like ADM etc. We will talk about this in another talk. In this presentation we will discuss more of the dysmyelinating disorders in which there is abnormal formation destruction or turn or round of myelin. These come in the white matter disorder bracket or hypomyelinating disorders in which there is decreased formation of otherwise normal myelin. So in the first major discriminator is the myelination complete or not? Is it a hypomyelination? Is it a hypomyelinating disorder or a dysmyelinating disorder? So we have to remember it is abnormal for the cerebral white matter to have hyper intense signal in a child beyond beyond 1.5 years on T2 weighted images. And if we are seeing hyper intense signal, we have to rule out delayed myelination or permanent hypomyelination or some other pathology within the white matter. So how do we define deficient myelination? In a patient with deficient myelination, the white matter will be hypo or iso intense on T1 weighted images. And on, it may almost look normal on T1 weighted images. In fact, on T2 weighted images the abnormalities are diffused. There is no focality and this is not very intensely hyper intense. MRI basically looks like a normal MRI of a very young child. And to define permanent hypomyelination, we need an unchanged pattern of deficient myelination on two MRIs performed more than six months apart and a child more than one year of age. So we need at least two MRIs. One MRI we cannot diagnose hypomyelinating disorders. So here we have a 15 month old child. When we study this MRI on T1 weighted images on T2 weighted images, it looks almost normal like an MRI of a six, maybe a six month old child. This is actually a 15 month old child. So if we are seeing only one MRI, we will call it delayed myelination. If we do a follow-up scan and see that it does not progress, then we will call it hypomyelination. So here we have this hypomyelinating disorder. And how do you distinguish it from other dysmyelinating disorders or leukodystrophies? There is no gradient in hypomyelinating disorder and the white matter abnormality is very homogeneous and diffuse, as I said. While in leukodystrophies or dysmyelinating disorders, either there is a gradient here, we have a patient with Alexander's with a gradient from anterior to posterior, or we will have very intense white matter disorders and volume loss in this patient with Krabbi's disorder. Here I have another patient, a six month old child. We see on T2 weighted images, there is hardly any myelinated white matter supra-tentorially or infratentorially. On T1 weighted images, at least in the posterior white matter structures, there is some myelination. And this turned out to be Pelusius-Mersbecher disease. I'm showing only one MRI, this patient had a follow-up MRI also. White matter, hypomyelinating white matter disorders may have or may not have peripheral nervous system involvement in the form of neuropathies. I'll just show another case. Here we have a six month old with delayed myelination and we see that with delayed milestones and we see that on T2 weighted images, there is hardly any myelin. On T1 weighted images, myelination looks almost normal for age, maybe slightly delayed. So this was diagnosed as delayed myelination for age. This is a T2 weighted coronal and surgical image which shows the delayed myelination for age. At 23 months of myelination, we see that myelin has appeared in the posterior limbs of the internal capsule, anterior limbs of the internal capsule, in the corpus callusum, both this plenium and the genu of the corpus callusum in the deep white matter. And on T1 weighted images also, there is robust myelination that has appeared, which looks pretty good for the age. Incidentally, we are seeing a cavernous hemangioma in the right parietal lobe. So patient underwent MRI because the patient had delayed myelination and patient was unable to sit. So this delayed myelination progressed over time. We are seeing the corpus callusum, almost the entire white matter is pretty well myelinated for age and this was diagnosed, this patient was diagnosed to have MCT-8 deficiency. Other causes of delayed myelination include this patient and with the basal ganglia are almost not seen. So this is hypomyelination with atrophy of atrophy of the basal ganglia and the cerebellum, the cerebellum is reduced in size. And this was confirmed to have this tuba mutation. Then we can have cerebellar hypoplasia with hypomyelination and hypodontia, in which the teeth will be abnormal and the white matter is diffusely hypomyelinated. Apart from normal or abnormal myelination, the second MRI discriminator is the distribution of the MRI signal abnormalities, whether it is confluent, multifocal, symmetric, bilaterally asymmetric. We have already reviewed this, I will repeat it again. In a white matter disorder or a leukodystrophy, in an inherited white matter disorder or leukodystrophy, the signal abnormality will be confluent and almost certainly bilaterally symmetric, like in this patient with vanishing white matter disease. While patients with acquired white matter disorders or demyelinating disorders will have patchy, multifocal and almost certainly asymmetric signal abnormality, like here we have this patient with tuberous sclerosis. Apart from the distribution of white matter, whether it is symmetric, asymmetric, we also evaluate whether it is predominantly white matter involvement or gray matter involvement. If it is predominantly white matter involvement, the way brain will be typically swollen in the earlier period, and in the late stage there will be volume loss. While it is a gray matter disorder, like ECHID syndrome maybe, the cortex is thinned out with enlarged sulci and there is secondary valerian regeneration of the white matter and the cerebral volume loss appears at a slightly earlier age. The third MRI distribution is the localization of the white matter abnormalities, whether it is frontal, parieto-excipital, periventricular, etc. We will evaluate each as an example. If the white matter signal abnormality is more frontal than posterior, then we have to consider Alexander's like in this case or frontal variant of adrenal leukodystrophy. In patients with excellent adrenal leukodystrophy, we will see parieto-excipital signal abnormality. Other differentials of parieto-excipital signal abnormality include crevice, peroxysmal disorders, etc. Periventricular signal abnormality is seen in patients with metachromatic leukodystrophy, among others. Then we have diffuse cerebral white matter in this patient with Canavan's disease. Deep white matter involvement can include involvement of the thalamus brainstem or we not have brainstem or corticostinal tract involvement. Here we have a patient with ganglioncytosis GM2 steroid disorders and with the thalamus is diffusely hypo intense, the basal ganglia are hyper intense and this gives a clue to white matter steroid disorder. Here we have a patient with brainstem corticostinal tract involvement, in which there is hyper intensity in the brainstem. Now we have to see whether the cortical ufibazine involved or the central periventricular white matter is involved. If the subcortical ufibazine are involved with macrocephaly, we have to consider Alexander's megalencephalic leukoencephalopathy with cysts or mlc and Canavan's. Patients may or may not have striatis basal ganglia involvement, so if patients have both gray and white matter involvement, we have to see if the deep gray matter is involved, whether it is striatin, globus pallidus or cortex. Here we have a patient with lase disease with striatal involvement, Canavan's with pallidal involvement and thalamic involvement, which is quite typical, methylvalonic acidemia with globus pallidus involvement and we also evaluate other specific MRI characteristics like cystic degenerative changes in this patient with lowest syndrome. This was a patient who also had cataract, we can see the patient has undergone excision of the cataract surgery and multiple periventricular cysts are seen in this patient with consanguinity. Then we can see multiple enlarged perivascular spaces like this patient with mucopalicecarylosis, other gray matter changes like polymicrogyria in this patient with Zellweger's, calcification in echidicuteus, spinal cord involvement like this patient with complex one deficiency and also we see evolution over time. In the late stage, because most leukodystrophies are generally progressive, there is diffuse white matter signal abnormality and atrophy and even highly characteristic imaging findings in the earlier period, like in the earlier period it's very easy to diagnose, relatively easy to diagnose metachromatic leukodystrophy but in the later stage the patterns become non-specific and it's really difficult to say what the pathology is. Also there is a white spectrum of severity depending on the degree of the functional gene product remaining. The same pathology, the same disease may present in the neonatal period, infantile period, here we have a patient with infantile crevice with typical imaging findings of periventricular signal abnormality and cerebral white matter volume loss and then we have another child with juvenile crevice, this girl at juvenile crevice in which the signal abnormality was typically peritrigonal and this could very well have be mistaken for x-link adrenal leukodystrophy except that this was a girl and not a boy and adrenal leukodystrophy is an x-link disorder. So Vandernapp and all have given a computerized pattern recognition system for differentiating these white matter disorders. They studied a large number of patients and it's a very interesting article you can look at up online. With this I'll come quickly to a few cases. Here we have a four month old child with extensive white matter signal abnormalities. So infratentorially involving the upper cervical cord, involving the cerebellar hemispheres and the middle cerebellar peduncles and the periventricular white matter and extensive restricted diffusion was also seen in these involved areas and long segment signal abnormality. So when we are seeing these changes this helps us to narrow down, this is complex one deficiency which was proven genetically. Here we have an other patient with extensive periventricular signal abnormalities, similar appearance with restricted diffusion and we are seeing a lactate pig. This is an other patient with mitochondrial disorder. Coming to the third patient we are seeing basal ganglia signal abnormality enlarged to sylvian fissures with incomplete apricula hystia of the sylvian fissures and this is eutoric aciduria type one. We also see dentate signal abnormalities. Here we have another patient with difficulty in walking white matter delayed development generalized hypotonia. So we are seeing white matter signal abnormalities, malformation of cortical development, polymicrogyria and we are also seeing some periventricular cysts and this was Zellweger's disease. Here we have another patient with white matter signal abnormality two-year-old with difficulty in walking delayed motor milestones and we also see cobblestone lisencephaliae white matter abnormality. The ventricles are enlarged. This can mimic Zellweger's but this turned out we see that brainstem abnormality and pontine hypoplasia and this turned out to be congenital muscular dystrophy mericin positive type. And another patient with extensive white matter abnormality with normal appearance of the brain stem and the posterior posa structures and this was the mericin negative congenital muscular dystrophy. Here we have a child with only brain stem signal abnormality and gliosis and neuro regression and this is the latest stage of mitochondrial disorder. This is a in this patient the genetic testing showed mitochondrial translation release factor mutation, MTFR mutation. I'll share another case a six-month six-year-old child born of congenital parentage when which EMG was done which showed polyneuropathy extensive white matter signal abnormality was done spectroscopy was also done which shows reduction in NA and increase in the choline peak and seroleno biopsy was done which showed enlarged neurons so this was confirmed to be giant axonal neuropathy based on the seroleno biopsy. So this is how the peripheral nervous system involvement helps us to come to a diagnosis. Now I'll share another patient a two-year-old male with neuro regression and spasticity extensive white matter volume loss with supratentrial white matter volume loss with expected dilatation of the lateral ventricles and extensive periventricular signal abnormality. At this in this condition it's very it's really very difficult to come to a diagnosis and this was proven to be NCL6, neuronal seroid lekofuccinosis. Here we have a one-year-old girl with again consanguinity with silvery hair we can see abnormal hair, delayed development neuro regression and delayed decreased vision and we see the periventricular signal abnormality and this was grizzly syndrome type one. Another patient with abnormal hair and delayed development with periventricular signal abnormality was phenyl ketonegia. They performed these urine test TMS studies which confirmed the phenyl ketonegia. Here we have another child with delayed development scan looks almost normal patient but we have other clues skin lesions and deafness when we see skin lesions and we are seeing white matter signal abnormalities and patient is having spasticity diplasia this is biotinitis deficiency which was proven genetically. Apart from T1 and T2 weighted images we also evaluate diffusion weighted images in which diffusion weighted signal changes may represent cytotoxic edema or sometimes which may be irreversible but not necessarily. It can also be myelin vaculation in which the diffusion weighted changes may sometimes reverse. Here we have a patient with classic maple syrup urine disease and another patient with similar distribution in the brainstem in the myelinated white matter which was proven to have beta ketothiolase deficiency. Spectroscopy also plays an important role in most conditions it is non there is a nonspecific increase in the choline to creatinine ratio and reduction in NA but in some metabolic disorders there are specific characteristics like canavans or congenital creatinine deficiency or non ketothi hyperglycinemia or MSUT. Here we have a patient with metachromatic leukodystrophy in which there is just nonspecific reduction in NA and increase in the choline to creatinine ratio. In late syndrome we are seeing this characteristic lactate peak. Here we have a patient with extensive supratentorial and infratentorial signal abnormality diffuse and also involving the globus pallidus and thalamus and we are seeing a very large NA peak prominent NA peak and this was confirmed to be canavans disease. Okay apart from spectroscopy diffusion also look at other changes like we saw one patient with biotinidase deficiency with skin changes. Here we have another patient with skin changes with ichthyosis also spasticity and developmental delay. We see extensive periventricular signal abnormalities and on spectroscopy we see large lipid peaks on short as well as intermediate T spectroscopy and skin changes along with lipid peaks on the spectroscopy help us to diagnose Jogren Larson syndrome. Then we have a 17 month old child with neuro regression with periventricular signal abnormalities and diffuse signal loss and diffuse volume loss in the cerebral white matter. Otherwise on T1 and T2 weighted images finding are nonspecific. However we see Icardi Gutierre syndrome we see that Icardi Gutierre syndrome was diagnosed on the basis of the presence of calcification or subtle calcifications were also seen on the SWI images which were actually missed initially and were picked up more easily on the CT. Here we have another patient with volume loss here and MRI was performed at 17 months and follow-up MRI after 4 months at 21 months shows progressive volume loss and this was another patient with Icardi Gutierre syndrome. These are these follow under the bracket of interferinopathies in which there is refractory calcification white matter abnormalities in the very young with white matter volume loss and CSF pleocytosis. So just to sum up first we have to approach these patients with white matter disorders we evaluate hypomyelination we see whether the involvement is diffuse versus multifocal the distribution of signal changes whether it is frontal predominance periventricular paritoxibital subcortical diffuse or whether the posterior foci is involved brainstem is involved and other findings like cis calcification spinal cord involvement and this helps us this pattern recognition approach will help us with an organized approach to formulate a narrow differential diagnosis. Thank you very much. Thank you so much ma'am. Just a couple of questions. Is MRI useful before complete the myelination before the age of 2 years in the case of delayed milestones? Yes we should do MRI just to make sure that first we are not missing any structural abnormality second we are not missing any other gross metabolic disorder for example zelvegas or any other peroxisomal disorder the other indication to do an MRI often if she patients with just delayed milestones we do MRI to rule out congenital creatinine deficiency the scan may be normal absolutely normal but the if we do spectroscopy we will not see the creatinine peak we will only see the two large peaks colline and nAA rather than three large peaks hence MRI should be done for in patients with delayed milestones. And the next one is how to differentiate between cytotoxic edema in an encephalitis and infarction on a vision. Infarction will always have specific vascular distribution that is how we can distinguish the white med the cytotoxic edema because of infection versus infection infection will never be in a vascular territory while infarction will always be in a vascular territory. Thank you ma'am. If I can ask you to hang around for a few minutes in case more questions come up in the chat room. I will do that. Thank you. Thank you ma'am. Thank you. Bye. Have a nice day.