[Vascular leukoencephalopathy in patients without vascular risk factor or NOTCH3 mutation: clinical and radiological...

White matter lesions seen on MR scan reflect small vessel disease of the brain; increasing age and high blood pressure are the main risk factors. In young patients without vascular risk factors, screening for CADASIL mutation has to be done. Our aim was to describe clinical as well as radiological features of a series of patients without NOTCH3 mutation with severe vascular leukoencephalopathy not explained by the presence of vascular risk factors.

Inclusion criteria were grade 3 leukoencephalopathy according to the Fazekas scale, age<70years at onset, and negative screening for NOTCH3 gene. Patients with severe vascular risk factors or atherosclerosis were excluded. Clinical and MRI findings were analysed.

Eight patients (four men) were included, five did not have any vascular risk factor. Mean age at onset was 59.5years. Initial symptoms were progressive in six cases of eight cases. They consisted of astasia-abasia and progressively worsened; of note one patient died 4years after disease onset. Cerebral MRI disclosed marked atrophy in five patients out of eight, temporal lobe (two out of eight) and external capsule (five out of eight) involvement was moderate. Four patients did not have any other atherosclerosis lesion. Seven out of eight had no retinal microangiopathy. High blood pressure was identified in two patients.

The identification of vascular leukoencephalopathy in young patients without any vascular risk factors should lead the clinician to perform a complete work-up to search for treatable conditions including high blood pressure. Patients with vascular leukoencephalopathy usually present with astasia-abasia. In this context, cerebral MRI, cannot perfectly discriminate between patients with CADASIL from those with acquired small-vessel disease of the brain so that sequencing of NOTCH3 gene exons 2-24 is recommended.