David Clopton, MD, Department of Radiology, University of Virginia Health Systems, Charlottesville, VA
A 65-year-old female with unknown medical history presents to the emergency department with an altered mental status after a motor vehicle accident. Her family reports she did have some behavioral changes in the preceding weeks.
What is the most likely diagnosis?
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First looking at the computed tomography (CT) examination, there are bilateral thalamic hyperdensities, which without a magnetic resonance imaging (MRI) study could represent calcifications or hemorrhage. The distribution would not be typical for hemorrhage associated with a trauma and raises the possibility of a different etiology (eg, possibly venous infarct). On the MRI, the previously seen areas of hyperdensities show low signal on the susceptibility weighted images, and the pulvinar of the thalami intrinsic has T1 shortening, which is bilateral and symmetric. Additionally, there are numerous low signal foci on susceptibility-weighted images within primarily the subcortical and deep white matter to include the corpus callosum. This is most consistent with chronic micro hemorrhages, which may relate to amyloidosis or chronic hypertension. T2/FLAIR images demonstrate scattered periventricular and deep white matter foci of hyperintense signal. Additionally, there is abnormal FLAIR signal overlying the anterior right frontal lobe sulci, which is low signal on susceptibility images and is consistent with subarachnoid blood.
Fabry disease is an X-linked inborn error of glycosphingolipid catabolism resulting from a deficient activity of the hydrolase α-galactosidase A. Diagnosis of the disease is actually relevant as the disease can be treated with an enzymatic substitutive therapy, which has been available since 2001. In absence of this specific therapy, the life expectancy in men is around 50.
The main mechanism of CNS manifestations is small vessel ischemia, which results in ischemic strokes (most commonly involving the posterior circulation).
On head CT, findings include calcium in the lateral pulvinar, globus pallidus, putamen, substania nigra, and dentate nuclei. As is the case with most things, MRI is more sensitive than CT to detect CNS involvement from the disease. On T2/FLAIR, patients may display nonspecific asymmetric, widespread deep white-matter nodules that are hyperintense and predominantly located in the frontal and parietal lobes. On T1-weighted imaging, hyperintensity of the deep gray nuclei can be observed, particularly in the lateral pulvinar (as is seen in this case). This T1 hyperintensity in the pulvinar is considered pathognomonic. Both T2 and T1 changes have been shown to undergo regression with early institution of treatment. Fabry’s disease has the potential to affect multiple organ systems, not just the brain. The kidneys tend to thin and develop multiple small uniform appearing cysts. End stage renal failure is typical by the fourth decade. Aortic valve thickening is seen in 25% of patients with the disease. AVN of the femoral heads has been described.
Bilateral T1 high signal in the lateral pulvinar with associated calcifications should prompt the addition of Fabry’s to the differential diagnosis.