Amyloid imaging by 18F-florbetaben PET in a patient with isolated microbleeds and leukoencephalopathy

A 65-year-old man with treated hypertension and hypercholesteremia presented with subacute left-sided leg pain and weakness. A clinical/electrophysiological/radiologicalbased diagnosis of L5-radiculopathy was made while brain MRI (Fig. 1) showed asymptomatic diffuse leukoencephalopathy (preserving basal ganglia and brainstem) and innumerable cortical microbleeds in the absence of acute infarction/hemorrhage, chronic lobar hemorrhage or cortical superficial siderosis. Eye fundus examination was normal. There were no cognitive changes. Mini Mental State examination was 28/30. NOTCH3 gene analysis was normal. CSF analysis showed normal total and phosphorylated tau levels (130 and 26 pg/ml, respectively, for normal values\400 and\60 pg/ml) and very low amyloid b (Ab)-42 and -40 levels (390 and 2041 pg/ml, respectively, for normal values [700 and [7000 pg/ml). Fflorbetaben PET showed diffuse amyloid deposition (Fig. 1). The patient’s cognitive state was stable 1 year later. Increased C-Pittsburgh compound B (PiB) binding (other ligands for cerebral fibrillar s-amyloid imaging have never been tested in cerebral amyloid angiopathy [CAA] to the best of our knowledge) has been reported in patients with classical CAA (i.e., with lobar hematoma) [1]. Although associated preclinical and asymptomatic Alzheimer disease cannot be excluded completely in our patient, the presence of innumerable cortical microbleeds, diffuse leukoencephalopathy, low CSF Ab-42 and Ab-40 levels, and stable cognitive state favor CAA as the most probable diagnosis [2]. Disorders presenting with leukoencephalopathy and microbleeds include hypertensive cerebral small vessel disease, cerebral autosomal dominant/recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL and CARASIL), COL4A1/COL4A2-related disorders, CAA, and amyloid-related angiitis of the CNS (CAA-I). Topography of leukoencephalopathy and microbleeds, together with genetic analyses, CSF analysis, and brain amyloid PET imaging may all help to differentiate between these disorders. In hypertensive cerebral small vessel disease, leukoencephalopathy and microbleeds preferentially involve brainstem and basal ganglia. In CADASIL and CARASIL, leukoencephalopathy preferentially involve temporal poles, external capsules, basal ganglia and thalami, whereas microbleeds can be found in various locations. In COL4A1/ COL4A2-related disorders, other brain abnormalities can be seen including porencephaly, hemorrhage, infarction, dilated perivascular spaces, dolichoid carotid siphons, and aneurysms. In CAA, leukoencephalopathy is typically posterior while microbleeds are often cortical–subcortical, & Dimitri Renard dimitrirenard@hotmail.com