gMG tends to be more aggressive with onset at age 65 or older
But these older patients may have more favorable outcomes, per a study
People who begin experiencing symptoms of generalized myasthenia gravis (gMG) at the age of 65 or older tend to have a more aggressive initial disease course — but a more favorable prognosis over the following two years.
That’s according to a new study from Greece that investigated the short-term prognosis of so-called very-late-onset myasthenia gravis, or vloMG, compared with that of early- and late-onset MG.
The results showed that older individuals with generalized vloMG required more respiratory support than people with either early-onset gMG or generalized late-onset MG — when symptoms start in patients after the age of 50.
However, people with vloMG also were found to have better outcomes over the next two years while being less reliant on corticosteroids, the researchers noted.
Based on these findings, the scientists concluded that “vloMG has a more severe, potentially life-threatening onset and a more favorable prognosis, thereafter.”
Their study, “The short-term prognosis of very late onset generalized myasthenia gravis: a single-center retrospective cohort study,” was published in the journal Frontiers in Neurology.
In myasthenia gravis, or MG for short, the immune system mistakenly attacks the proteins that help nerve and muscle cells communicate, causing symptoms of muscle weakness and fatigue. In most cases, the self-reactive antibodies that drive the disease target acetylcholine receptor (AChR) proteins on muscle cells.
In gMG, a more severe and widespread form of the disease, symptoms of muscle weakness and fatigue affect different muscle groups across the body. Often, the disease first affects the ocular muscles that control eye and eyelid movements. It can also affect muscles in the face and neck, causing issues with speaking, swallowing, and chewing. These are called bulbar symptoms.
Symptoms starting after age 65 dubbed ‘very late-onset MG’
While MG symptoms can arise at different time points throughout a person’s life, including during childhood and adolescence, onset is usually in early or later adulthood. When symptoms start between the ages of 18 and 50, the disease is defined as early onset; it’s known as late onset if signs of the condition are seen when a person is older than 50.
Early-onset MG is more common in women, while late-onset MG is more common in men.
But “lately, due to the phenotypic [clinical manifestations] and biological differences of MG occurring above the age of 65, a new MG subgroup is widely recognized; very late-onset MG,” the researchers wrote.
In this study, the team sought to assess the symptoms and short-term prognosis of vloMG. To that end, they compared data from people with vloMG with that of those they dubbed as having eloMG — the other adult-onset types, both early and late. Analyses accounted for changes in participants’ condition over time and biological differences between disease types.
Lately, due to the phenotypic [clinical manifestations] and biological differences of MG occurring above the age of 65, a new MG subgroup is widely recognized; very late-onset MG.
The study involved 42 eloMG and 26 vloMG participants. Patients in the vloMG group had a significantly shorter interval between symptom onset and diagnosis compared with those in the eloMG group (mean of 3.5 vs. 9.6 months).
Further, a significantly greater proportion of vloMG patients tested positive for antibodies targeting AChR compared with eloMG participants (89% vs. 57%).
Initial symptoms also differed between the groups. Tumors or enlargement in the thymus gland, which can contribute to MG autoimmune processes, were significantly more common in the eloMG group than in the vloMG group (40% vs. 0%). Ocular and bulbar symptoms were also more common in the vloMG group, but these differences weren’t statistically significant.
Five participants in the vloMG group (19%) required placement of a breathing tube to support respiratory function within one month of diagnosis. In comparison, none in the eloMG group needed this procedure. Bulbar symptoms “probably [explain], at least partly, the need for respiratory support due to the risk of aspiration,” the researchers wrote. Aspiration refers to the accidetal inhalation of foods, including liquids, or mucus into the lungs.
Respiratory support may be needed for patients with vloMG
In an initial analysis, the MG relapse rate in the two years after diagnosis was about 50% lower in the vloMG group. In agreement with this, vloMG participants had about double the odds of having milder disease features. This was seen despite a significantly lower intake of corticosteroids — a class of immune-suppressing medications — in the vloMG group, according to the researchers.
The team hypothesized that the greater prevalence of anti-AChR antibodies in the vloMG group contributed to these differences. The researchers noted that in their experience, individuals with these antibodies responded more positively to treatment.
Considering this, the team adjusted the analysis to account for the difference in AChR-targeting antibodies. They also corrected other key biological differences between the two groups, including thymus problems. After these corrections, prognosis differences were no longer statistically significant.
“This suggests that at least part of the variability of the short-term prognosis is explained by the aforementioned well-established biological differences,” the team wrote.
Together, these results indicated that people with very late-onset gMG have disease characteristics associated with better short-term outcomes. However, in early disease stages, people with vloMG may have severe symptoms, more frequently requiring respiratory support.
Researchers noted that future studies could expand these analyses to larger groups, potentially strengthening the findings.
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