Nancy A. Melville

September 30, 2015

CHICAGO — Despite being asymptomatic, a significant percentage of patients with cerebral X-linked adrenoleukodystrophy (ALD) show signs of early lesion development and progression on MRI, new research suggests.

"We have shown that when ALD patients are asymptomatic they can indeed have a lesion in the brain — a lot of people don't realize that, and when the lesions are present, they can show contrast enhancement," first author Afonso P. Liberato, MD, from Massachusetts General Hospital (MGH), Boston, Massachusetts, told Medscape Medical News.

"So with this unique cohort we can better understand which patients can benefit from crucial rescue therapies in the early stages."

Their results were presented here at the American Neurological Association (ANA) 2015 Annual Meeting.

For the study, Dr Liberato and his colleagues evaluated 193 MRIs performed at MGH between 2001 and 2015 from 44 boys with ALD who were asymptomatic, established by a score of 0 on the Neurologic Functional Scale. Patients had a mean age of 7.8 years and had not undergone hematopoietic stem cell transplantation/gene therapy.

Most of the patients were siblings of patients who had a lesion and had been diagnosed with ALD, Dr Liberato said.

Results from two investigators blinded to the patients' clinical status showed MRI abnormalities on FLAIR sequence in 26 (59%) patients.

Among the T1-weighted postcontrast sequences from initial MRI that were available for 26 patients, 22 (85%) showed contrast enhancement at baseline or follow-up MRI.

Eleven of the 22 patients (50%) had contrast enhancement at presentation.

Twelve (48%) of 25 boys had lesion progression, with a Loes score increase of 1 point or more, and 10 patients presented with normal baseline MRI but subsequently converted to a cerebral form of the disease at a mean age of 6.6 years.

Most of the lesions found were small, but even in the few that were larger, patients were still asymptomatic, Dr Liberato noted.

The novel study offers insights that could be important in providing appropriate treatment as early as possible, he added.

"ALD patients are getting imaged earlier and earlier in life, yet we don't have any data to guide treatment in these early stages," Dr Liberato explained.

"So we're trying to better understand how the disease progresses. MRI is already very useful in patients with symptomatic and more developed stages, but to be able to show progression from this earlier stage can help in the determination of when to initiate treatment and to follow after the gene therapy."

Commenting on the study, Thomas Sutula, MD, PhD, professor and chair of the Department of Neurology at the University of Wisconsin School of Medicine and Public Health, Madison, agreed the findings are of clinical significance.

"While ALD is relatively infrequent, the reported sensitivity of the imaging application is an advance for early diagnosis and as a tool to assess effects of treatment in future clinical trials," he told Medscape Medical News.

Dr Liberato and Dr Sutula have disclosed no relevant financial relationships.

American Neurological Association (ANA) 2015 Annual Meeting Abstract M307WIP. Presented September 28, 2015.

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