Friday 26 August 2011

Adrenoleukodystrophy MRI

A 10 y o male with learning disabilities. Poor hearing. 
Here is MRI Brain Axial T2w and Dw images. 
This MRI study of Brain shows T2 hyper intensity involving splenium of corpus callosum, adjacent peri trigonal white matter and along cortico spinal tract. Bilateral symmetrical involvement with restricted diffusion on Dw images.

Imaging diagnosis : Adrenoleukodystrophy.


Syn : X-linked adrenoleukodystrophy (X-ALD) a severe progressive form usually affecting pre-teen males.
An inherited disorder of peroxisome metabolism, there is defect in VLCFA importers leading to impaired Beta-oxidation of Very Long Chain Fatty Acids (VLCFA) which then accumulate in WM leading to brittle myelin.

VLCFA accumulate in all tissues of body
Symptomatic accumulation occurs in CNS myelin, adrenal cortex, Leydig cell testes.
Adrenal failure associated with skin bronzing.
Testes involvement associated with early androgenetic alopecia in adults.

X-ALD: X-linked recessive, Xq28; mutations ABCDI gene.

X-ALD and variants: 1 per 16,800 births in North America

Clinical Presentation
Most common signs/symptoms: Skin bronzing, behavioral difficulties, hearing problems
Pre-teen male (3-10 years): Behavioral, learning, gait, hearing, vision difficulties.
Diagnose of "Addison/adrenal insufficiency" (skin bronzing, nausea & vomiting, fatigue) may predate diagnose of X-ADL
Age: Pre-teen males.

Gender: Males in classic X-ALD. Female carrier.
predominates in North America and France.

Imaging wise diagnostic clue is Peri trigonal white matter demyelination. 
Pattern of involvement is confluent, bilateral symmetrical, typically posterior involvement. Frontal pattern involvement is rare.
Predominantly involves Splenium and adjacent Peri trigonal WM followed by Corticospinal tracts/fornix/commissural fibers/visual and auditory pathways. Typically spares subcortical U-fibers.
MRI is the investigation of choice shows confluent T2 hyper intensity with restricted diffusion. On PC T1w images, leading edge (intermediate zone) enhances. Contrast-enhancement and diffusion restriction strongly linked to progression of disease process.
MRS, increased NAA even in normal appearing White matter predicts progression; High Cho, myo-inositol (ml), lactate peaks between 0.9 and 2.4 ppm probably represent VLCFA macromolecules.

Staging, Grading or Classification Criteria : Loes' MRI scoring system
Severity score based upon location and extent of disease and atrophy
o Pattern 1: Parieto-occipital WM (rapid progression if contrast-enhancement present and very young)
o Pattern 2: Frontal WM (same as pattern 1)
o Pattern 3: Corticospinal tract (adults, slower progression)
o Pattern 4: Corticospinal tract and cerebellar WM (adolescents, slower progression)
o Pattern 5: Concomitant parieto-occipital and frontal WM (mainly childhood, extremely rapid)

Imagingwise DDs
Periventricular leukodystrophy / Leukomalacia shows Periventricular gliosis and volume loss following hypoxia of prematurity, hypoglycemia ; doesn't enhance on post contrast T1.
Alexander disease
Enhances, but frontal predominance, not peri trigonal WM. Macrocephaly clinically.
White matter disease with lactate (WML)
Involves splenium, peri trigonal WM and corticospinal tracts, but doesn't enhance.
Metachromatic leukodystrophy
Involves fronto parietal white matter equally. Doesn't enhance.

Natural History & Prognosis
Progresses to spastic quadriparesis, blindness,deafness, vegetative state

Vegetative state, death in 2-5 years without bone marrow transplantation.
Cholesterol-lowering drugs, dietary VLCFA restriction, glycerol trioleate/trierucate intake, plasmapheresis, interferon, immuno-ablation
Early bone marrow transplantation (BMT) stabilizes demyelination.

Reference : Osborn Diagnostic imaging.

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