'Raisin bread sign' feature of pontine autosomal dominant microangiopathy and leukoencephalopathy

Pontine autosomal dominant microangiopathy and leukoencephalopathy is one of hereditary cerebral small vessel diseases caused by pathogenic variants in COL4A1 3 ' UTR and characterized by multiple small infarctions in the pons. We attempted to establish radiological features of this disease. We performed whole exome sequencing and Sanger sequencing in one family with undetermined familial small vessel disease, followed by clinicoradiological assessment and a postmortem examination. We subsequently investigated clinicoradiological features of patients in a juvenile cerebral vessel disease cohort and searched for radiological features similar to those found in the aforementioned family. Sanger sequencing was performed in selected cohort patients in order to detect variants in the same gene. An identical variant in the COL4A1 3 ' UTR was observed in two patients with familial small vessel disease and the two selected patients, thereby confirming the pontine autosomal dominant microangiopathy and leukoencephalopathy diagnosis. Furthermore, postmortem examination showed that the distribution of thickened media tunica and hyalinized vessels was different from that in lacunar infarctions. The appearance of characteristic multiple oval small infarctions in the pons, which resemble raisin bread, enable us to make a diagnosis of pontine autosomal dominant microangiopathy and leukoencephalopathy. This feature, for which we coined the name 'raisin bread sign', was also correlated to the pathological changes. Kikumoto et al. detected a characteristic radiological feature of pontine autosomal dominant angiopathy and leukoencephalopathy, which enables more accurate evaluations of patients with undetermined juvenile cerebral vascular disorder. This feature is multiple oval small infarctions in the pons resembling raisin bread, for which they coined the name 'raisin bread sign'. Graphical Abstract

Automated summary

Pontine autosomal dominant microangiopathy and leukoencephalopathy is a hereditary cerebral small vessel disease caused by pathogenic variants in COL4A1 3' UTR. The appearance of multiple oval small infarctions in the pons resembling raisin bread, known as the 'raisin bread sign', is a characteristic radiological feature of this disease. The discovery of this sign has important implications for accurate diagnosis and evaluation of patients with undetermined juvenile cerebral vascular disorder.