Radiological correlates of episodes of acute decline in the leukodystrophy vanishing white matter

Purpose: Patients with vanishing white matter (VWM) experience unremitting chronic neurological decline and stress-provoked episodes of rapid, partially reversible decline. Cerebral white matter abnormalities are progressive, without improvement, and are therefore unlikely to be related to the episodes. We determined which radiological findings are related to episodic decline. Methods: MRI scans of VWM patients were retrospectively analyzed. Patients were grouped into A (never episodes) and B (episodes). Signal abnormalities outside the cerebral white matter were rated as absent, mild, or severe. A sum score was developed with abnormalities only seen in group B. The temporal relationship between signal abnormalities and episodes was determined by subdividing scans into those made before, less than 3 months after, and more than 3 months after onset of an episode. Results: Five hundred forty-three examinations of 298 patients were analyzed. Mild and severe signal abnormalities in the caudate nucleus, putamen, globus pallidus, thalamus, midbrain, medulla oblongata, and severe signal abnormalities in the pons were only seen in group B. The sum score, constructed with these abnormalities, depended on the timing of the scan (χ²(2, 400) = 22.8; p <.001): it was least often abnormal before, most often abnormal with the highest value shortly after, and lower longer than 3 months after an episode. Conclusion: In VWM, signal abnormalities in brainstem, thalamus, and basal ganglia are related to episodic decline and can improve. Knowledge of the natural MRI history in VWM is important for clinical interpretation of MRI findings and crucial in therapy trials.