INTRODUCTION: 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.
MATERIAL AND METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.