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Alexander Disease


KEY FACTS

Terminology

  • Rare inherited leukoencephalopathy characterized by Rosenthal fibers (eosinophilic intracytoplasmic inclusions)

  • 3 clinical forms

    • Infantile (most common)

    • Juvenile

    • Adult

Imaging

  • Infantile: Symmetric ↑ T2 bifrontal white matter (WM) including subcortical U fibers

  • Juvenile/adult: ↑ T2 brainstem (especially medulla), cerebellum, cervical cord

  • Other findings: ↓ T2, ↑ T1 enhancing nodular periventricular rim

    • 1 of few metabolic disorders that enhance

Top Differential Diagnoses

  • Canavan disease

  • Megaloencephalic leukoencephalopathy with subcortical cysts

  • Other: Glutaric aciduria type 1, mucopolysaccharidoses

Pathology

  • Dominant mutations GFAP (17q21) (> 95% of cases)

Clinical Issues

  • Clinical profile: Infant with macrocephaly, seizures

  • Natural history: Variable rate of progression ultimately leading to death in all forms

  • Treatment: Supportive

Diagnostic Checklist

  • Enhancing, symmetric bifrontal WM disease in macrocephalic infant highly characteristic of Alexander disease (AD)

  • Consider adult AD if ↑ T2 signal and atrophy in medulla (inferior olives and gracile nuclei) and cervical cord

Axial NECT shows the typical appearance of infantile Alexander disease. The striatum and periventricular rim
are hyperdense. Note the symmetric, frontal predominant, white matter (WM) hypodensity.

Axial T2WI MR shows a nodular, hypointense, periventricular rim
with symmetric, mild hyperintensity in the striata and thalami
. The cerebral WM is diffusely hyperintense, greatest in the frontal lobes, where it extends from the ventricular margin to the subcortical U fibers.

Axial T1WI MR shows diffusely hypointense, swollen-appearing WM with a frontal to occipital gradient. Only the occipital WM appears myelinated. The nodular periventricular rim
is hyperintense. The lateral ventricles are abnormally enlarged.

Axial T1WI C+ MR shows enhancement of the periventricular rim, the caudate heads, and the putamina bilaterally. The nodular, rabbit ear appearance of the frontal periventricular rim
is typical of Alexander disease.

TERMINOLOGY

Abbreviations

  • Alexander disease (AD)

Synonyms

  • Fibrinoid leukodystrophy

Definitions

  • Rare leukoencephalopathy characterized by Rosenthal fibers (RFs), intracytoplasmic astrocytic inclusions

  • 3 clinical forms: Infantile (most common), juvenile, adult

  • Caused by dominant mutations in gene encoding GFAP

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