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MS brain lesions appear identical to those for optic neuropathy associated with MS


 

FROM THE JOURNAL OF NEUROLOGY, NEUROSURGERY, AND PSYCHIATRY

References

Conventional MRI brain images of patients with multiple sclerosis are "indistinguishable to the expert eye" from those of patients who have an MS-like disease associated with Leber’s hereditary optic neuropathy, according to a retrospective, case-control study.

Leber’s hereditary optic neuropathy (LHON), a mitochondrial abnormality inherited through the maternal line, is characterized by painless, subacute bilateral loss of vision that usually occurs in early adulthood. Very rarely, it is associated with a coexisting MS-like disease, which is often referred to as Harding’s disease. If the brain-imaging traits of these two disorders were found to be similar, it would suggest that they share a common pathophysiologic mechanism, said Dr. Lucy Matthews of the Nuffield Department of Clinical Neurosciences at Oxford (England) University, and her associates.

In what they described as "the first blinded observational study of the MRI features of LHON and LHON-associated MS," Dr. Matthews and her colleagues reviewed brain MRIs from patients treated at six clinical sites in Oxford; Milan and Siena, Italy; London; Bochum, Germany; and Copenhagen. A total of 31 patients had LHON, including 11 with LHON-associated MS. Their MRIs were compared with those from 30 age-matched control subjects who had MS alone (J. Neurol. Neurosurg. Psychiatry 2014 July 22 [doi:10.1136/jnnp-2014-308186]).

Three experts in the field of MRI and MS who were blinded to patients’ clinical and demographic data independently reviewed these MRIs. They found that the morphology and location of cerebral lesions were identical in LHON-associated MS and MS. Brain atrophy and hypointense T1 lesions were observed in both disorders.

In contrast, patients who had LHON alone showed T2 hyperintense white matter lesions, notably fewer oval lesions, and no Dawson’s fingers or diffuse-type lesions. Most of their lesions were 2-5 mm in size, while most of the lesions in the MS and LHON-associated MS patients were larger, some as big as 25 mm.

In addition, T2 lesions showed a similar distribution between patients with MS and patients with LHON-associated MS, while T2 lesions in the LHON-only group were uncommon in the corpus callosum and nonexistent in the cerebellum.

A total of 90% of the patients with MS and 73% of those with LHON-associated MS fulfilled McDonald’s criterion for the spatial dissemination of brain lesions, compared with only 6.7% of the patients who had LHON alone.

These findings support the idea that "MRI changes in LHON-associated MS are due to MS pathology and not a separate Leber’s mitochondrial-related process." They also suggest that mitochondrial pathways may be important in the development of MS, the investigators said.

The researchers also observed an "intriguing" influence of gender in these disorders. "The penetrance of LHON in women is much lower than in men. However, it appears that once a woman develops LHON clinically, she has a very high risk of developing either radiological or clinical MS. It is [neither] clear whether those with asymptomatic lesions at the time of MRI will develop clinical features in the future, nor what the risk is in asymptomatic female carriers of Leber’s mutation," they added.

This study was supported in part by the U.K. Medical Research Council. Dr. Matthews’s associates reported numerous ties to industry sources.

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