Extensive Extrapulvinar Calcification in Fabry Disease

A 36-year-old male with no vascular risk factors presented for the evaluation of recurrent posterior circulation strokes. He had a strong family history of acroparaesthesia. On physical examination, he had extensive angiokeratoma over the trunk [Figure 1a]. His blood alpha-galactosidase activity was reduced (0.1 nmol/h/mg), and genetic study confirmed the diagnosis of Fabry disease (FD). His blood metabolic profile was normal. His magnetic resonance imaging brain showed T1 hyperintensity in basal ganglia, pons, and pulvinar region of the thalamus which were hyperdense on computed tomography (CT) Brain, suggestive of calcification. Susceptibility-weighted images showed signal loss in the same areas, with diffusion-weighted imaging revealing an acute infarct in the left lateral medulla [Figure 1b–d]. Invasive cerebral angiogram showed normal vertebrobasilar vasculature [Figure 1e]. Although pulvinar calcification is a pathognomonic sign in FD,[1] extrapulvinar pontine calcification, has not been described before.

Figure 1.

(a) Clinical photograph of torso showing multiple angiokeratoma. (b) Computed tomography head showing calcifications involving bilateral thalami (arrow), basal ganglia and pons (arrow). (c) Magnetic resonance imaging brain diffusion-weighted images showing acute infarcts in the right ventral thalamus (arrow) and left lateral medulla, with (d) T1 sequence showing “pulvinar sign” (arrow). (e) Normal vertebrobasilar vasculature on invasive cerebral angiogram

FD is an X-linked lysosomal storage disorder associated with deficient activity of alpha-galactosidase, causing multisystem accumulation of glycosphingolipids.[2] About 1.5%–4.9% of young patients with cryptogenic stroke were detected to be having FD, thereby reinstating the prevalence of this rare disorder in the cohort of cryptogenic young strokes.[3] The putative pathophysiological mechanisms for recurrent cerebrovascular events (especially posterior circulation) in FD include altered cerebral hemodynamics (related to dolichoectasia), endothelial dysfunction, and upregulation of prothrombotic factors.[2,4] White matter lesions constitute the most common neuroimaging finding in FD cohort (52%),[2] even in those without prior history of stroke or receiving dialysis (44.4%).[5] Yet another pathognomonic MR neuroimaging finding in FD is the abnormal T1 hyperintensity in the posterior thalamus (Pulvinar sign) seen in up to 23% subjects, with corroborating signal changes of calcium deposition on CT brain images.[1] This dystrophic calcification is possibly contributed by the elevated vertebrobasilar cerebral blood flow and hyperperfusion in FD as demonstrated by perfusion studies.[1,2] The pulvinar and extrapulvinar neuroimaging findings in our case highlight the consequences of more widespread alteration in cerebral hemodynamics in FD, which is a novel finding in this hitherto underdiagnosed disease cohort.

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The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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