Toward a Neuroimaging Consensus for the Work-up of Adult Genetic Leukoencephalopathies on Behalf of the White Matter...

Adult-onset genetic leukoencephalopathies are frequently misdiagnosed due to their overlap with more common acquired white matter diseases. The White Matter (WM) Rounds Network includes clinicians and scientists from more than 15 centers around the world who meet monthly to discuss undiagnosed white matter diseases. A key barrier to optimizing diagnosis that arose during these monthly discussions was the lack of MRI protocol standardization between institutions. We aimed to: 1) assess the state of practice of current MR protocols for investigating suspected genetic leukoencephalopathies and 2) propose a core standard protocol.

We used a Delphi method to facilitate group judgements. We submitted a survey for feedback to a panel of neuroimaging experts whose final version was circulated to the entire WM Rounds Network. The results were analyzed, and specific recommendations were put forward during Delphi rounds, for which the stop criterion was 75% agreement.

The MR protocols had an average magnet time of 40 minutes (range 25-60) and included: 3-dimensional (3D) T1 MPRAGE and 3D FLAIR obtained in the sagittal plane, axial T2 and T2-FLAIR, axial DWI/ADC, and axial SWI. Cervical and thoracic spine imaging were also frequently performed. A standardized core imaging protocol inclusive of the above-listed sequences would help harmonize sequence acquisition across institutions and promote cost-effective optimization of the imaging work-up of adult-onset leukoencephalopathies. Four additional recommendations were proposed: 1) contrast-enhanced T1 sequences should be performed for patients with strong clinical and/or radiologic suspicion of adult genetic leukoencephalopathy; 2) cervical and thoracic spine MRI may provide diagnostic value; 3) head CT is of little added value and should not be included routinely; and 4) MR spectroscopy, diffusion tensor imaging, and other advanced imaging techniques are not yet ready to be implemented in the protocol but may be helpful in supporting a working diagnosis.