Metachromatic leukodystrophy:

It is a lysosomal storage disorder with decreased arylsulfatase A leading to sphingolipid accumulation and progressive demyelination. It is the most common inherited leukodystrophy [10] and has three forms

• Late infantile (most common)
• Juvenile
• Adult

Imaging findings:

Centrifugal spread of demyelination

Starts in corpus callosum, splenium and deep parietooccipital white matter and frontal, temporal white matter are affected later and spares subcortical U-fibers and cerebellum.

Classic butterfly pattern

Symmetric hyperintensities around frontal horns, atria (Fig 1 A)

Tiger pattern

Stripes of perivenular myelin sparing in white matter (Fig 1 A).

Adrenoleukodystrophy:

It is a peroxisomal disorder with impaired oxidation of very long chain fatty acids leading to its accumulation in the nervous system, testes, and adrenal gland causing impaired function [2]. The three major categories are

1. Classic X-linked ALD

The most common form (45%) is seen in preteen boys with features of deteriorating cognition and school performance.

2. Adrenomyeloneuropathy (AMN)

The second most common form (35%) is generally in male patients.

3. Addison disease without CNS involvement (20%)

Imaging findings:

• X-linked ALD shows posterior predominance in 80%
  • Earliest finding: corpus callosum splenium hyperintensity
  • Spreads posterior to anterior, center to periphery (Fig 2 A)
  • The affected cerebral white matter is typically split into three different zones on T1W MRI (Fig 2 B)
    • Central zone: (Necrotic "burned out" core)hypointense
    • Intermediate zone: (active demyelination + inflammation) hyperintense
    • Peripheral zone: (Peripheral demyelination) hypointense
  • Variant patterns
    • X-linked adrenoleukodystrophy with anterior predominance (10-15%)
    • Adrenomyeloneuropathy involves corticospinal tracts, cerebellum, cord more than hemispheric white matter.

Subacute Sclerosing Panencephalitis (SSPE)

It is rare progressive, fatal encephalitis that affects primarily children and young adults, caused by measles virus reactivation occurring years after initial infection.

Imaging Findings

In the early stages, imaging may be normaland normal MR does not exclude Subacute Sclerosing Panencephalitis. Gray matter reduction in the frontotemporal cortex may occur before other lesions become apparent.

In later stages bilateral but asymmetric periventricular, cortical and subcortical white matter and basal ganglia hyperintensity on T2/FLAIR sequences (Fig 3 A)

Diffuse atrophy with ventricular and sulcal enlargement indicates the disease progression.

Magnetic Resonance Spectroscopy (MRS) shows decreased NAA and choline with elevated myoinositol and glutamine/glutamate (Fig 3 B)

CT may not demonstrate the findings.

Wilson's disease

Wilson disease is an autosomal recessive disorder with a defect in copper metabolism and abnormal accumulation of copper in various tissues like the liver, brain and eye.

Imaging Findings

High T2 hyperintensity in the putamina is the most common MRI abnormality (Fig 4 A)

Face of the giant panda sign: Involvement of the midbrain, tegmentum on axial images (high T2 signal) (Fig 4 B). 

Signal abnormalities on T1-weighted images are variable, seemingly dependent on the degree of edema and hepatic dysfunction.

CT may demonstrate atrophic changes in the basal ganglia, cortical and cerebellar regions ( Fig 4C).

Ataxia telangiectasia

It is an autosomal recessive disease caused by mutations in the ATM gene, which plays are role in DNA repair processes and cell cycle control.  It is to be suspected in all children exhibiting cerebellar ataxia that arises when the child begins to walk, movement disorders, sino-pulmonary infections and oculocutaneous telangiectasia. [5]

Imaging Findings

Cerebellar volume loss with compensatory enlargement of the 4^th ventricle (Fig 5 A, B)

Magnetic Resonance Spectroscopy (MRS) shows an increased choline signal.

Multiple sclerosis

It is a progressive neurodegenerative disorder characterized by multiple inflammatory demyelinating focal plaques in white matter.  Most commonly seen in a supratentorial location with perivenular extension (Dawson fingers). In children, infratentorial involvement is also seen. Children tend to have more frequent and severe relapses and better recovery as compared to adults with multiple sclerosis.

Imaging Findings

MRI Brain shows high T2 signal multiple small ovoid lesions of varied sizes in the periventricular region, the corpus callosum, brain stem, optic nerves and visual pathway [6].

On T1WI lesions are hypointense with or without faint hyperintense rim and the active plaques will enhance post contrast. (Tumefactive partial rim) (Fig 6B).

On T2WI very hyperintense center with slightly less hyperintense rim (Fig 6 A)

CT may show patchy or confluent hypodensities.

Hellervorden-spatz disease

It is an autosomal recessive, pantothenate kinase associated neurodegenerative disorder characterized by early onset of progressive movement alteration like rigidity, choreoathetosis and mental deterioration or progressive dementia [7].

Imaging findings:

On T2-weighted MRI hypointense changes in the globus pallidi and pars reticulata of the substantia nigra(Fig 7 A) with corresponding low signal in areas from iron deposition on Susceptibility Weighted Imaging (SWI)(Fig 7 B).

Eye of the tiger sign: refers to a central T2 relatively hyperintense spot (block arrows) within the hypointense globi pallidi due to gliosis and vacuolisation.

Alexander disease

Alexander disease is a rare, non-familial fibrinoid leukodystrophy that typically presents with macrocephaly, rapid neurological deterioration, seizures and spasticity [8].The most common form is infantile/childhood-onset.

Imaging findings:

CT Brain (Fig 8 B) axial section shows a large head with symmetric white matter hypoattenuation in the frontal lobes that extends into the caudate nuclei and internal/external capsules.

MRI shows macrocephaly, cerebral white matter changes in the frontal predominance, a periventricular rim with high signal on T1-weighted images and low signal on T2-weighted images (Fig 8 A), abnormalities of caudate nuclei, and anterior putamina, thalami, brain stem abnormalities. [8]

Friedrich ataxia

Most common autosomal recessive hereditary progressive ataxia which is typically present in childhood without gender predilection. It is a disorder affecting both the central and peripheral nervous systems in almost all cases [9].

Imaging findings:

Normal cerebellar volume or mild cerebellar atrophy is seen. 

There will be a decrease in the anteroposterior diameter of the medulla oblongata (Fig 9 A,B) and the cervical spinal cord [9].