Myelination progresses in a predictable manner caudocranially , back to front ,and central to peripheral (deep to superficial) and sensory then motor.

Fig. 1: Myelination progresses in a predictable manner (posterior to anterior), and central to peripheral (deep to
References: modified from Bonekamp D, Jacobs MA, El-Khouli R, et al. Advancements in MR imaging of the prostate: from diagnosis to interventions. Radiographics 2011;31(3):677.

Fig. 2: Progression of Myelination and Myelination milestones.
References: Kodur, V. (2015, July 22). Neonatal MRI Brain. Retrieved from https://www.slideshare.net/VinayakKodur/mri-in-neonates.

Fig. 3: Myelination progress on MRI.Normal T2-weighted (A–D) and T1-weighted (E–H) images at term (A, E), and at the ages of 5 months (B, F), 1 year (C, G), and 5 years (D, H). Myelin deposition is represented by a low signal on T2-weighted images and high signal on T1-weighted images. Note that myelination consistently looks more advanced on T1-weighted images than on T2-weighted images.
References: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677542/

Differentiating Normal Myelination from Hypoxic-Ischemic Encephalopathy on T1-Weighted MR Images:

• At one year of age, T1 contrast pattern would be similar to that of an adult, although the myelination process is still on going. Hence, T1-weighted images are of little value after the first year.

• The thalamic nuclei and globus pallidi will start to myelinate at 24-25 weeks of gestation while the cortico-spinal tracts will myelinate by 36 weeks, best appreciated along the peri-rolandic cortex and posterior limb of the internal capsules (Figure 4 a - g). Hence, absence of T1 hyperintense and T2 hypointense signal within the ventrolateral thalami and posterior portion of the posterior limb of the internal capsule in a term neonate would be abnormal .

Fig. 4: Structures of the brain that are myelinated at birth in a term infant. Axial T1-weighted images demonstrate normal T1 hyperintense signal within the (a) posterior limb of the internal capsule, (b) optic tracts, (c) optic radiations, (d) peri-rolandic cortex, (e) superior cerebellar peduncles and (f) dorsal brainstem. (g) Axial T2-weighted image shows the normal hypointense signal within the posterior portion of the posterior limb of the internal capsules. Faint T2 hypointense signal is also appreciated within the ventrolateral thalami and far lateral posterior putamen. These hypointense landmarks would be lost in the basal-ganglia-thalamus pattern of HIE.
References: Tan AP (2017) Pediatric MRI Brain: Normal or abnormal, that is the question. Radiol Diagn Imaging 1: DOI: 10.15761/RDI.1000112.

Differentiating Normal Myelination from Periventricular leukomalacia (PVL) on T1-Weighted MR Images:

• Periventricular leukomalacia (PVL) is a subtype of the HIE and the commonest white matter brain injury in preterm infants.
• It has a typical distribution at the watershed areas adjacent to the lateral ventricles. PVL occurs because of ischemic injury to periventricular oligodendrocytes of the developing brain.
• Terminal zones of myelination at the peritrigonal regions are present normally .
• The presence of these should not be mistaken for periventricular leukomalacia. A thin rim of normally myelinated T2 hypointense white matter may be seen between the ependymal surface and terminal zone of myelination, a useful clue to search for .
• High T2 signal related to terminal zone of myelination is also almost always confined to the supero-posterior aspects of the posterior horns .
• Another helpful clue is the triangular configuration of the terminal zones of myelination on coronal images, with the apex of the triangle directed superiorly . (Figure 5 a-c).

Fig. 5: (a) Axial T2-weighted and (b) coronal FLAIR images show the normal terminal zone of myelination, posterior and superior to the occipital horns. Note the triangular configuration of the terminal zones of myelination on coronal image, with the apex of the triangle directed superiorly. (c) Axial T2-weighted image shows abnormal periventricular T2 hyperintense signal extending anteriorly around the bodies of the lateral ventricles, in a child with periventricular leukomalacia
References: • Tan AP (2017) Pediatric MRI Brain: Normal or abnormal, that is the question. Radiol Diagn Imaging 1: DOI: 10.15761/RDI.1000112.

 Bilateral signal abnormalities within the neonatal brain without clinical evidence of hypoxic-ischemic insult should raise the suspicion of underlying inborn errors of metabolism such as Leigh syndrome (Figure 6), Alexander disease (Figure 7) and metachromatic leukodystrophy (Figure 8).

Fig. 6: Leigh Syndrome :T2- Axial, Symmetrical and bilateral hyperintense lesions in the basal ganglia
References: • Cuellar, R. J. C. (n.d.). Leigh syndrome: Radiology Case. Retrieved from https://radiopaedia.org/cases/leigh-syndrome?lang=us.D'souza PC, Vignesh A, Subaschandra K, Mathai P J. Metachromatic leukodystrophy. Muller J Med Sci Res 2013;4:113-5

Fig. 7: Alexander disease : Axial T1/T2-weighted image demonstrates confluent and symmetrical signal abnormalities within the cerebral white matter, predominantly involving the frontal lobes. Involvement of subcortical U-fibers is seen in the frontal lobes
References: Messing, A., Brenner, M., Feany, M. B., Nedergaard, M., & Goldman, J. E. (2012, April 11). Alexander Disease. Retrieved from http://www.jneurosci.org/content/32/15/5017.

Fig. 8: Metachromatic leukodystrophy. Axial T2-weighted image demonstrates confluent and symmetric signal abnormalities within the periventricular and deep white matter. Note the sparing of the subcortical U-fibers
References: http://www.mjmsr.net/article.asp?issn=0975-9727;year=2013;volume=4;issue=2;spage=113;epage=115;aulast=D%27souza

A simplified approach and the findings of common  white matter disorders in children matter disorders in children

  Hereby, we discuss leukodystrophies in terms of their clinical manifestations, and magnetic resonance (MR) imaging characteristics. We focus on the MR imaging features of some of the more common leukodystrophies.

Fig. 9: A simplified approach and the findings of common white matter disorders in children matter disorders in children.
References: author

Canavan  disease: fig10

• Manifests in early infancy as hypotonia followed by spasticity, cortical blindness, and macrocephaly.
•  T1-weighted MR imaging demonstrates symmetric areas of homogeneous, diffuse low signal intensity throughout the white matter, whereas T2-weighted imaging shows nearly homogeneous high signal intensity throughout the white matter.
•  The subcortical U fibers are preferentially affected early in the course of the disease. In rapidly progressive cases, the internal and external capsules are involved, and the cerebellar white matter is usually affected as well.

Fig. 10: Canavan disease in a 6-month-old boy with macrocephaly. (a) T2-weighted MR image shows extensive high-signal-intensity areas throughout the white matter, resulting in gyral expansion and cortical thinning. Striking demyelination of the subcortical U fibers is also noted. (b) T1-weighted MR image shows demyelinated white matter with low signal intensity
References: • Cheon2, J.-E., & Author Affiliations1From the Departments of Radiology (J.E.C. (2002, May 1). Leukodystrophy in Children: A Pictorial Review of MR Imaging Features. Retrieved from https://pubs.rsna.org/doi/full/10.1148/radiographics.22.3.g02ma01461.

Van der Knapp disease:fig11

•   Typically present with megalencephaly during the first year of life associated with mild motor developmental delay and seizures . There is also a gradual onset of ataxia, spasticity, dysarthria, and sometimes extrapyramidal findings. 
•  The hallmarks of radiological diagnosis are:

 o  Megalencephaly

 o Diffuse, bilateral and symmetric T2-weighted hyperintensity and  T1-weighted hypointensity in the cerebral white matter, giving a characteristic 'swollen' appearance
 o  Subcortical white matter involved early in course of disease with involvement of the subcortical U-fibers
 o Relative sparing of the deep and cerebellar white matter
 o Bilateral subcortical cysts affecting the anterior temporal regions and frontoparietal lobes
 o Eventual cerebral atrophy with increase in size of the subcortical cysts.

Fig. 11: Bilateral extensive deep white matter T2 hyperinsity is seen involving the subcortical white matter as well as the subcortical U-fibers with relatively large subcortical cysts of CSF signal intensity are seen predominantly in the bilateral frontal as well as anterior temporal lobes. The lesions are seen sparing the basal ganglia as well as both thalami. No pathological enhancement. •Mild to moderate dilatation of the ventricular system as well as prominent cortical sulci and basal cisterns. •No significant infra-tentorial abnormality.
References: Weerakkody, Y. (n.d.). Megalencephalic leukoencephalopathy with subcortical cysts: Radiology Reference Article. Retrieved from https://radiopaedia.org/articles/megalencephalic-leukoencephalopathy-with-subcortical-cysts-1.

Vanishing white matter disease :fig12

• Vanishing white matter disease (VWM) is one of the most prevalent inherited childhood leucoencephalopathies. The classical phenotype is characterised by early childhood onset of chronic neurological deterioration, dominated by cerebellar ataxia.

• MRI findings are diagnostic in almost all patients and are indicative of vanishing of the cerebral white matter. as shown in fig 12.

Fig. 12: MRI Brain demonstrates bilateral, symmetrical and diffuse cystic changes, with areas of confluence, involving the cerebral periventricular white matter and corpus callosum. There is sparing of subcortical white matter. No sub-cortical cysts. Optic nerves were normal and symmetrical.showing  diffuse involvement, extending from periventricular white matter to the subcortical arcuate fibers. Over time the white matter vanishes replaced by near-CSF intensity fluid (i.e. it attenuates on FLAIR) .
References: Gaillard, F. (n.d.). Vanishing white matter disease: Radiology Reference Article. Retrieved from https://radiopaedia.org/articles/vanishing-white-matter-disease.

Galactosemia:fig13

· Hypomyelinating disorders are a heterogeneous subset of white matter disorders characterized by abnormally low amounts of myelination.

• Clinical findings are non-specific but patients often present with developmental delay, cerebellar signs or spasticity. 

• The imaging diagnosis of hypomyelination is made on the basis of :

 o  Unchanged myelination pattern not appropriately progressed for the patient's corrected gestational age on two successive brain MRI scans carried out at least 6 months apart.

Fig. 13: Galactosemia with delayed subcortical white matter myelination on T2WI.
References: Nazeer, A. (2016, November 5). Presentation1, radiological imaging of pediatric leukodystrophy. Retrieved from https://www.slideshare.net/abd_ellah_nazeer/presentation1-radiological-imaging-of-pediatric-leukodystrophy.

Krabbe disease :fig 14 

• Krabbe disease is an autosomal recessive disorder.

• The clinical manifestation of Krabbe disease varies with patient age at onset.The infantile form is the most common and manifests as hyperirritability, increased muscle tone, fever, and developmental arrest and regres-sion. Disease progression is characterized by cognitive decline, myoclonus and opisthotonus, and nystagmus. Typically, Krabbe disease is rapidly progressive and fatal .

• When diffuse white matter involvement develops, MRI features are characterized by:

 o T2: may show high signal involving periventricular white matter 2 centrum semiovale and deep grey matter; subcortical U-fiber may be spared until late in the course of the disease 5

 o T1 C+ (Gd): no contrast enhancement in these areas .

Fig. 14: Krabbe disease in a 2-year-old boy. T2-weighted MR image demonstrates symmetric high-signal-intensity areas in the deep white matter. The internal and external capsules are also involved (arrowheads). Note the bilateral areas of abnormal signal intensity in the thalami (arrows
References: • Cheon2, J.-E., & Author Affiliations1From the Departments of Radiology (J.E.C. (2002, May 1). Leukodystrophy in Children: A Pictorial Review of MR Imaging Features. Retrieved from https://pubs.rsna.org/doi/full/10.1148/radiographics.22.3.g02ma01461.

X-linked adrenoleukodystrophy :fig15

• Is an inherited metabolic peroxisomal disorder and one of the more common leukodystrophies in both children and adults.

• It is characterized by  severe inflammatory demyelination typically of the periventricular deep white matter with posterior-predominant pattern and early involvement of the splenium of the corpus callosum and parietal white matter changes.

• MRI of the brain demonstrates increased T2 signal and reduced T1 signal in the white matte of the cerebral hemispheres posteriorly. There is faint enhancement at the anterior margin of the signal abnormality.

Fig. 15: MRI of the brain demonstrates increased T2 signal and reduced T1 signal in the white matte of the cerebral hemispheres posteriorly. There is faint enhancement at the anterior margin of the signal abnormality.
References: Weerakkody, Y. (n.d.). X-linked adrenoleukodystrophy: Radiology Reference Article. Retrieved from https://radiopaedia.org/articles/x-linked-adrenoleukodystrophy-1?lang=us.

Mucopolysaccharidoses :fig16

• Represent a heterogeneous group of inheritable lysosomal storage diseases. 

• The typical symptoms include organomegaly, dysostosis multiplex, mental retardation and developmental delay.

• CT and MR imaging usually reveal delayed myelination, atrophy, varying degrees of hydrocephalus, and white matter changes. These changes manifest as diffuse low-attenuation areas within the cerebral hemispheric white matter at CT and as focal and diffuse areas of low signal intensity on T1-weighted MR images and high signal intensity on T2-weighted images (fig17). The sharply defined foci are commonly present in the corpus callosum, basal ganglia, and cerebral white matter. They are isointense relative to cerebrospinal fluid with all imaging sequences and probably represent mucopolysaccharide-filled perivascular spaces . As the disease progresses, the lesions become larger and more diffuse, reflecting the development of infarcts and demyelination.

Fig. 16: Mucopolysaccharidosis in a 4-year-old boy with Hurler disease. (a) T1-weighted MR image shows multiple well-defined areas of low signal intensity in the central and subcortical white matter. (b) T2-weighted MR image demonstrates multiple well-defined areas of high signal intensity in the deep and subcortical white matter.
References: Cheon2, J.-E., & Author Affiliations1From the Departments of Radiology (J.E.C. (2002, May 1). Leukodystrophy in Children: A Pictorial Review of MR Imaging Features. Retrieved from https://pubs.rsna.org/doi/full/10.1148/radiographics.22.3.g02ma01461.