Adult-onset genetic leukoencephalopathies (AGL) are frequently misdiagnosed due to overlap with more common acquired white matter (WM) diseases. The WM Rounds Network includes clinicians/scientists from more than 15 centers around the world who meet monthly to discuss undiagnosed WM diseases. MRI remains a central tool in narrowing the differential diagnosis of WM diseases; however, a key barrier to optimizing diagnosis was the lack of protocol standardization between institutions. We aimed to 1. assess the state of practice of current protocols for investigating suspected AGLs and 2. propose a core standard protocol.

We used a modified Delphi method to facilitate group judgements. We developed a survey and submitted it for feedback to a panel of neuroimaging experts. The final survey 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 average summed sequence time of our MR protocols was 40 minutes (range 25-60) and included the following sequences: 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 (T1 sagittal, T2 sagittal and axial) 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 workup of AGLs. Four additional recommendations were proposed: 1) Contrast-enhanced T1 sequences should be performed for patients with demonstrable clinical or radiological evidence of AGL. 2) Lumbar MR spine imaging has limited utility. 3) Head CT is of little added value and should not be included routinely. 4) MRS, DTI, and other advanced imaging techniques are not yet ready to be implemented in the protocol but may be helpful in supporting a working diagnosis.