A retrospective review of the 302 patients discussed in the Queen Square Adult Leukodystrophy Group (QSALG); a tertiary-centre, multidisciplinary team (MDT) of neurologists, neuroradiologists and metabolic physicians who review the clinical presentations, investigations, and neuroimaging of adults with suspected inherited white matter disorders referred from throughout the UK and abroad.

When extensive white matter abnormalities are detected on MRI scans it represents the start of a common and occasionally complex diagnostic challenge for even the most experienced neurologist. While straightforward investigations can reveal an acquired cause, many cases have a genetic aetiology (a leukodystrophy) and regardless, specialist input is often needed to advance diagnosis. Here, we describe the experience of our UK-wide MDT; our recommended approach including when to suspect a genetic disorder, and outcomes following MDT discussion.

A review of all patients with white matter abnormalities discussed in the QSALG MDT from February 2012 to October 2022.  

Following MDT discussion and follow-up investigation, a definitive diagnosis was made in 179 cases (59.3%) and 37 cases (12.3%) were thought of as unsolvable. 86 patients (28.5%) have ongoing, open investigations. Of those receiving a diagnosis, a genetic diagnosis was made 42.46% of the time and the most common leukodystrophies diagnosed were CSF1R-related ALSP, adrenoleukodystrophy and vanishing white matter disease. Acquired causes were common, in particular small-vessel disease (aSVD) and multiple sclerosis (MS).

Here we report our experience and lessons learned in diagnosing difficult white matter disorders in the largest European cohort of such patients, with a doubling of the cohort since last reporting (ABN, 2019). Less than half of those referred as suspected leukodystrophy are then genetically confirmed. We describe a high instance of diagnosing acquired causes, emphasising that though most neurologists are of course familiar with these diagnoses, difficulties still arise with atypical presentations, or in end-stage disease.