White matter diseases

Dr. Hytham Nafady

Metabolic disorders

White matter Grey matter

Cortical grey matter

Deep grey matter

Clinical information is often very useful to get started on the right track.

•Seizures.

•Dementia (early stage).

Cortical grey matter

•Chorea.

•Athetosis.

•Dystonia.

Deep grey matter

•Spasticity.

•Hyper-reflexia.

•Ataxia.

White matter

Radiological manifestations

•Sulcal enlargement.

•Cortical thinning.

•Cortical abnormal T2 bright signal.

Cortical grey matter

•Basal ganglia abnormal signal.

•Basal ganglia atrophy.

Deep grey matter

•Marked signal abnormality (before volume loss).

•Inflammatory component.

•Local predominance with progressive spread.

•Cavitation & necrosis of involved white matter.

White matter

Cortical grey matter disorders

• Neuronal lipofuscinoses.• Mucolipidoses.• Glycogen storage disease.• GM1 Gangliosidosis.

Neuronal lipofuscinosis

Deep grey matter

Globus pallidus

Corpus striatum

Globus pallidus

Hallervorden spatz syndrome

Wilson disease

Fucosidosis

DDKernicterus

NF1CO

Corpus striatum

Leigh disease

Wilson disease

Glutaric aciduria Gangliosidosis

Urea cycle disorders

DDHypoxiaHypoglyemiaPRESSOsmotic myelinolysis Encephalitis

White matter disorders

Lysosomal storage diseases

MLD

GLD Krabbe’s disease

Fabry disease

Gangliosidosis

Muco-poly-saccharidosis

Peroxisomal disorders

X linked adreno-

leukodystrophy

Zellweger syndrome

Refsum disease

Mitochondral disorders

Leigh disease

MELAS

MERRF

Kearns Sayer

Amino-acidopathies and

organic acidopathies

Canavan disease

Glutaric aciduria

Urea cycle disorders

Defects of myelin proteins

Pelizaeus Merzbacher syndrome

18 q syndrome

Unknown etiology

Alxander disease

Van Der Knapp encephalopathy

White matter disorders

De-myelination

Destruction of normal myelin

Dys-myelination

formation of abnormal

myelin

Hypo-myelination

Reduction of the amount

of myelin

Delayed myelination

Leuko-encephalopathy Leuko-malaciaLeuko-dystrophy

MRI based approach for diagnosis of white matter metabolic disorders

1. Is it de-myelination or dys-myelination?2. Is it dys-myelination or hypo-myelination?3. Is it permanent hypo-myelination or delayed

myelination?4. Is there a predominant localization (frontal,

parieto-occipital, periventricular, subcortical or diffuse)?

5. Special features.

Special features

• Macrocephaly Canvan, Alexander, Van Der Knapp encephalopathy.

• Enhancement adrenoleukodystrophy, Alexander.• Infarcts MELAS, Urea cycle disorders.• Cortical dysplasia Zellweger syndrome.• Hyperdense thalami Krabbe’s disease.• Associated Addison disease adrenoleukodystrophy.

De-myelination Vs Dys-myelination

De-myelination:• Multifocal & asymmetrical.Dys-myelination:• Confluent & symmetrical.

Dys-myelination Vs De-myelination

ADEMMLD

Dys-myelination Vs De-myelination

MLD ADEM

Dys-myelination Vs hypo-myelination

Dysmyelination:• Prominent T2 hyperintensity.• Prominent T1 hypointensity.

Hypomyelination:• Mild T2 hyperintensity.• Variable T1 signal (hypo, iso or hyperintense).

Dys-myelination

Hypo-myelination

Delayed myelination Vs hypomyelination

• Repeat MRI after 6 months.• Delayed myelination myelination progression.• Hypomyelination no myelination progression.• DD in these 2 conditions is quite different.

Delayed myelination

• Delayed myelination is a non specific finding associated with global developmental delay.

Causes:• Chromosomal abnormalities (e.g. trisomy 21).• Metabolic disorders (e.g. phenylketonuria).• Acquired causes (e.g. HIE).

Leukodystrophy

Genetic diseases with white matter morphological changes.

1. Myelin dysfunction due to enzymatic abnormality2. Demyelination – destruction of normally formed myelin3. Dysmyelination – loss of defective myelin

Enzymatic defects can be in:

• Peroxisomes• Mitochondria• Lysosomes.

Hypomyelination

Myelination

PNS CNS

DD of leukodystrophiesLeukodystrophy

Diffuse white matter

Canavan

Alexander

Van Der Knapp

Organic acidurias

Subcortical white matter

Hydroxyglutaricaciduria

Deep white matter

Krabbe’s

Gangliosidosis

MLD

Phenyl ketonuria

Peroxisomal

Frontal predominance

Alexander

Occipital predominance

ALD

Diffuse white matter

With macro-cephaly

Canavan disease

Alexander disease

Megaloencephalic encephalopathy

Without macro-cephaly

Organic acidurias

Kearns Sayer

Deep white matter

Thalami abnormal

Krabbe’s disease

GM2 gangliosidosis

Thalami normal

Brain stem specific tract involvement

Peroxisomal disorders

Brain stem normal

Vanishing white matter

Metachromatic leukodystrophy

Phenylketonuria

Subcortical white matter

Hydroxyglutaric aciduria Kearns Sayer

End stage disease

• End stage white matter disease of any cause results in diffuse (superficial and deep), bilateral white matter damage that is completely nonspecific.

• End stage cortical grey matter disease will often have abnormal white matter appearance, as Wallerian degeneration of axons causes diminished white matter volume and mild to moderate hyperintensity on FLAIR and T2 weighted images

Most common leukodystrophies

… Adult onset leukodystrophies

• Metachromatic Leukodystrophy

• Krabbé globoid cell leukodystrophy

• Adrenoleukodystrophy

• Refsum disease

• Pelizaeus-Merzbacher disease

• Alexander disease

Role of MRS

Normal myelinationAt birth 1 year6 month 2 years

follow up of a case of Zellweger syndrome

At 8 months the baby could not see toys or strong light (notice the conjugate deviation of the eyes).

At 3 years she could look at herself in the mirror.

Leukodystrophies with macro-cephaly

• Canavan.• Alxander.• Van Der Knapp encephalopathy

Canavan disease• Subcortical white matter.• Globus pallidus.• Thalami.• Dorsal brain stem.

Alexander disease

Adult form of Alexander disease

Van Der Knapp criteria for diagnosis of Alexander disease

• Extensive cerebral white matter changes with frontal predominance,

• Periventricular rim with high signal on T1-WIs and low signal on T2-WIs,

• Abnormalities of basal ganglia and thalami, • Brain stem abnormalities, and • Contrast enhancement of particular gray and

white matter structures.

Hypomyelination syndromes

Hypomyelination with congenital cataract (HCC)

HCC

HCC

HCC

HCC

Diffuse hypomyelination

4 years

11 years

Hypomyelination with cerebellar atrophy

Hypomyelination with cerebellar atrophy

4 H syndrome

• Hypomyelination.• Hypoodontia. • Hypogondatrophic Hypogonadism.

Pelizaeus Merzbacher disease

PMD

Krabbe’s disease

Hydroxy glutaric aciduria

• White matter: subcortical white matter with centripetal deeper confluent progress.

• Bilateral basal ganglia abnormal T2 bright signal.

Hemolytic uremic syndrome

• Bilateral globus pallidus abnormal T2 bright signal.

• Bialateral external & extreme abnormal T2 bright signal surrounding the claustra.