A conversation with Dr. Eric Jouvent, MD, PhD, Professor of Neurology at Paris University. He is involved in acute stroke care in the stroke unit in Lariboisière Hospital in Paris. He holds a PhD in image processing.
Interviewed by Dr. Stephanie Lyden, MD, BS, a vascular neurology fellow at the University of Utah.
They will be discussing the article “Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Lessons From Neuroimaging.” Published in the January 2020 issue of Stroke, it is part of a Focused Updates in Cerebrovascular Disease series of articles on topics related to cerebral small vessel diseases.
Dr. Lyden: First of all, thank you for taking the time to discuss this important topic. What led you to become interested in studying CADASIL?
Dr. Jouvent: It was not really a choice at first. Residency in France is different than in the United States, where we first choose a city and then we move from department to department in that city. At the end of that time period, you hope to match in a department or with a team. At the end of my cycle, I matched with a team headed by Dr. Bousser, who identified the first family with CADASIL, in part because I was not only interested in stroke, but also in cognitive and behavioral alterations and in advanced MRI techniques, which are key aspects in small vessel diseases. This was how I started to become involved in CADASIL research.
Dr. Lyden: You mentioned that in the future, different imaging algorithms may help identify patients with a likelihood for NOTCH3 mutations. What do you think would be the best radiographic sequences and algorithms to obtain this?
Dr. Jouvent: There is not a single imaging sequence that can differentiate specific small vessel diseases; rather, we need to consider data from various sequences, such as quantitative data looking at cerebral atrophy, susceptibility weighted imaging (SWI) or gradient echo (GRE), to assess the number and specific distribution of microbleeds and diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences to assess for lacunes, respectively. The aggregation of all the information with specific machine learning tools may help better stratify the risk of a given patient to have CADASIL.
Dr. Lyden: Do you think DTI could be important?
Dr. Jouvent: We have been studying this, and it may not be helpful in diagnosis, but it could be helpful with prognosis based on the location of the white matter disease as lesions of white matter tracts that have higher interconnection may cause more significant deficits than those with less. Additionally, the nature of the lesion affecting the white matter tract is important in assessing prognosis. For example, incomplete infarcts (while also translating into white matter hypertintensities) may be associated with more disability than vasogenic edema in the same area. There is some belief that the white matter disease affecting the anterior temporal lobe may correlate with edema. Overall, we have to take into consideration the multi-faceted nature of these factors when we are trying to understand this disease and its associated prognosis.
Dr. Lyden: What radiographic factors do you think help to estimate disease severity the most?
Dr. Jouvent: I think the degree of cerebral atrophy and number of lacunes may be the most important factors to estimate disease severity. This might be different at the earliest stages when patients have no or only mild symptoms (in this case, diffusion metrics might be more interesting).
Dr. Lyden: Do you think 7 Tesla (7T) MRIs can help advance our understanding of CADASIL and other small vessel disorders?
Dr. Jouvent: There are advantages and disadvantages to using 7T MRIs, and at this point, I do not think the advantages outweigh the disadvantages. We have been using 7T MRIs for over 10 years and have found that they can see things with more precision, but there are many technical drawbacks, such as increased imaging artifacts and distortions that you have to reconcile, and it is harder to process. Furthermore, the 7T MRIs compared to standard MRIs cause more side effects in patients. For example, if a patient moves their head in the scanner, they can experience significant vertigo.
Dr. Lyden: What is the main take-home point you would like readers to leave with after reading your paper?
Dr. Jouvent: When I was a resident and fellow, we were looking for specific aspects on MRI brain that would be specific for CADASIL, but I have come to find that there is no specific aspect detectable with the naked eyes. We are now looking for specific imaging aspects detectable by specific computerized algorithms including data from all the different sequences. An important take-home point should be that if there is a discrepancy between a low vascular risk profile in a patient and a high white matter lesion burden on MRI, then patients should be tested genetically (including NOTCH3 and other known mutations), even in the absence of familial history.
Dr. Lyden: What do you think are the important next steps in this field for advancing our understanding of CADASIL?
Dr. Jouvent: I think we need further therapeutic trials. We are expecting preliminary data with exon skipping and immunotherapy with antibodies against NOTCH 3 in animal models.
Dr. Lyden: Thank you so much for completing this interview!