This study looked at five men with a rare genetic brain disease (cerebral ALD) whose brain lesions stopped growing on their own, but later started growing again. It shows that these lesions can pause and then reactivate, and that early stem‑cell transplants are needed to stop damage, but many patients miss the chance because the disease can be silent for a while.

X-linked adrenoleukodystrophy (ALD) is the most common genetic peroxisomal disorder with an estimated prevalence of 1:15,000. Approximately two-thirds of males with ALD manifest the inflammatory demyelinating cerebral phenotype (cALD) at some disease stage, in which focal, inflammatory lesions progress over months to years. Hematopoietic stem-cell transplantation can permanently halt cALD progression, but it is only effective if initiated early. Although most cALD lesions progress relentlessly, a subset may spontaneously arrest; subsequent reactivation of these arrested lesions has not been previously detailed. We describe a novel arresting-relapsing variant of cALD. Salient clinical and radiographic studies were reviewed and summarized for cALD patients with episodic deteriorations. We report a series of five unrelated men with spontaneously arrested cALD lesions that subsequently manifested signs of clinical and radiologic lesion progression during longitudinal follow-up. In three of five patients, functional status was too poor to attempt transplant by the time the recurrence was identified. One patient experienced reactivation followed by another period of spontaneous arrest. These cases emphasize the need for continued clinical and radiologic vigilance for adult men with ALD to screen for evidence of new or reactivated cALD lesions to facilitate prompt treatment evaluation.