Literature Review

Progressive disability in MS explained?


From Neurology

Differences in lesion evolution may help neurologists distinguish between multiple sclerosis (MS) and other demyelinating disorders in new findings that may help explain differences in disease course, particularly progressive disability in MS.

Results from a retrospective study show that complete resolution of brain lesions on MRI was more common among patients with myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD). Complete resolution occurred in 72% of the group with MOGAD, versus 17% of those with MS and 14% of those with aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD).

“What we found was, with MOGAD in particular, many of the lesions resolved completely,” said co-investigator Eoin Flanagan, MBBCh, neurologist, Mayo Clinic, Rochester, Minn. “That fits with MOGAD having a fairly good prognosis and patients not developing much long-term disability with that disease,” he said.

The researchers also studied whether scarring may account for the absence of slowly progressive disability among patients with AQP4+ NMOSD and MOGAD compared with patients with MS. “The differences in scarring that we found will help physicians distinguish these three diseases more easily to aid in diagnosis. More importantly, our findings improve our understanding of the mechanisms of nerve damage in these three diseases and may suggest an important role of such scars in the development of long-term disability in MS,” Dr. Flanagan said in a statement.

The findings were published online July 14 in Neurology.

Lesion evolution

MOGAD, AQP4+ NMOSD, and MS are inflammatory demyelinating disorders that share certain manifestations. However, these disorders differ in important ways, including the severity of attacks and their clinical course.

Although patients with MOGAD and AQP4+ NMOSD generally have severe attacks that bring major disability, the clinical course of these disorders is better than initial attacks would suggest. In contrast, patients with MS have comparatively mild attacks that are associated with a high risk for progressive disability.

Previous studies of these demyelinating disorders have examined the shape and location of lesions but not change over time. Observing these lesions’ development and resolution could provide information about disease course and influence treatment and the monitoring of disease activity, the current researchers noted.

They retrospectively identified consecutive patients with MOGAD, AQP4+ NMOSD, or MS who presented to the Mayo Clinic between January 2000 and August 2019. Data from a cohort of patients with MS in Olmsted County, Minn., were also included.

Eligible participants had experienced a first brain or myelitis attack, had undergone MRI of the brain or spinal cord within 6 weeks of the attack nadir, and had undergone a follow-up MRI 6 months after the attack.

Patients who experienced a relapse during follow-up in the same region as the initial attack were excluded. Concomitant brain and myelitis attacks were analyzed separately.

An index lesion was identified for each patient. The index lesion was defined as an acute lesion that provided an anatomic explanation for the clinical symptoms. If multiple lesions were present, the largest of them was chosen as the index lesion. MRIs were examined by neuroradiologists who were blinded to patients’ diagnoses and serology results.

Among the 156 participants, 67 had MS (76% women), 51 had AQP4+ NMOSD (80% women), and 38 had MOGAD (45% women). The median age at first attack for the groups was 37, 53, and 25 years, respectively.

In addition, 63 patients had relapsing-remitting MS, two had a single attack of progressive MS, and two had clinically isolated syndrome. No patients with NMOSD or MOGAD had developed progressive disease at final follow-up.

Participants experienced a total of 81 brain attacks and 91 myelitis attacks. Sixteen patients had experienced both a brain attack and a myelitis attack.

Symptoms corresponding to the index brain lesions were brainstem or cerebellar syndrome (56), encephalopathy or focal symptoms (12), or combinations of these (13). Among patients with an index myelitis attack, 31 had cervical involvement, 21 had thoracic involvement, and 39 had involvement of both regions.


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