Annemieke Aartsma-Rus

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Authors outline that more work is needed especially in studying ways to support the caregivers and reduce their burden.

Authors discuss the limitations of the study, which suffers from a selection bias, based on the physicians involved. Also for some of the subgroups, samples were very small, e.g. the employed caregivers in Japan. Still the work is important.

Furthermore the health status of patients and caregivers did not differ between ambulatory and non ambulatory patients. This has been reported before, where even though physically patients have less function, they rate their health the same as when they were ambulatory.

Authors speculate that perhaps the increased anxiety and depression might have influenced the way caregivers rated their perceived health. Overall there were little difference between geographic regions.

Authors also discuss the discrepancy between the visual scale and the EQ-5D-5L scales, where caregivers reported reduced health on the visual scale, while this did not become apparent from the questionnaire. Such discrepancies have been reported before.

Authors discuss that caregiving is very essential for Duchenne patients. They also discuss that the age of diagnosis in Japan is significantly lower than in Europe and USA. This could be due to increased awareness in Japan or due to better/earlier genetic testing.

However, about 30% had anxiety or depression of various severity. Notably authors used both the EQ-5D-5L tool for self reported health but also a visual scale. On the visual scale caregivers did report their health as lower than average.

Some caregivers made adjustments for the caregiving, usually working less hours but sometimes also changing jobs. There was no difference in absenteeism between geographic regions or ambulatory status. Most caregivers did not report reduced health for themselves.

Caregivers were youngest in the USA and (as expected) caregivers of non ambulant patients were older. Most of the caregivers were women and mothers. About 50% of caregivers was employed part time or full time. Percentages were highest in USA for employment and lowest in Japan.

The age of the patients cared for was higher in Japan and (as expected) higher for non ambulatory patients. The age of diagnosis was lowest in Japan. Authors report on the health status of the Duchenne patients, but as that is not the focus of the paper and as expected, I will skip this.

Caregivers were recruited via physicians who confirmed the Duchenne diagnosis and ambulatory status of the patient. 216 caregivers participated, 46% from Europe, 42% from the USA and 12% from Japan. 54% of the patients cared for were ambulatory.

This caregiving can have an impact on the caregiver. Studies into caregiver burden have been done, but usually only in single countries. Here authors aimed to do a more global analysis: USA, Europe (Spain, France and Germany) and Japan.

Duchenne patients lose functions due to muscle wasting, which means they rely on help for most daily activities progressively. Most of this help/care is provided by non-professional caregivers, usually family members.

#apaperaday Today's pick is from BMC Neurology by Strober et al on an analysis of caregiver burden for Duchenne muscular dystrophy in 3 different regions (USA, Europe and Japan). Usually these studies focus on only one country. doi: 10.1186/s12883-025-04531-8

Other aspects that might have impacted the worsening at 6.5 follow up are the pandemic, where everyone was less active. Author stress that studying women with pathogenic variants is important. Note that when directly asked these women may have symptoms that they do not volunteer by themselves.

Interestingly there was no difference in severity for Duchenne or Becker mutations, while in men Duchenne patients have a more severe pathology. Authors discuss that some aspects are expected to get worse with age anyway and it is not clear if the general increase seen if not part of this.

Authors discuss that there was little progression in general, but for a subset there was. Also, worse baseline levels for fat fraction were predictive for a more severe progression. Of these women, 4 had symptoms already in childhood.

There was a minor decrease in myoglobin levels, CK (creatine kinase, muscle damage marker) was stable. The 6 minute walk distance remained stable as well, but for 10% of the women the distance walked was lower than predicted. The forced vital capacity was reduced at follow up only for 1 woman.

A clinical assessment revealed no increased fatigue at the follow up visit for most women, though 7 had a decline. 2 of those had symptoms already at baseline, while 5 developed symptoms during the follow up time. The most prominent symptom was difficulties climbing stairs

Strength decreased as well over time but there was no difference between Duchenne and Becker mutations (also not for MRI fat fraction) and also no correlation with the fat fraction increase and the 4 women who progressed quicker for fat fraction did not show increased muscle strength decline.

This happened mainly in the posterior parts of the muscles and for most the increase was small (1% per year). However, for 4 women increase was much more prominent with 15.4% increase over 6.5 years. These women had a higher fat fraction at baseline.

Others did not have time, or could not be contacted and 1 was misdiagnosed. The variability of symptom severity in the 19 women not having a follow up was similar to those who did have a follow up. First MRI analysis: fat fraction increased in all women after 6.5 years.

All women had a genetic diagnosis of a dystrophin mutation and they had family members with Duchenne or Becker. 53 women were measured at baseline and 34 came for a follow up visit (where 31 women had an MRI analysis twice). Of the 19 women not doing the follow up, 2 had died

Women with dystrophin mutations also are at an increased risk for developing cardiomyopathy and should be checked for this regularly. Authors here wanted to study a cohort of females with dystrophin mutations in a follow up study where there was 6.5 years between the 2 time points.

Woman thus have not 50% of dystrophin in all the cells but rather 50% of their cells can make dystrophin. If X-inactivation is skewed into the wrong direction this % can be lower. How many women with dystrophin mutations have symptoms is not really known: estimates vary between 2.5-81%

Women have 2 X-chromosomes, so when one has a pathogenic variant in the dystrophin gene (located on the X-chromosome) there is a back up copy. However, due to X-inactivation each cell will either express dystrophin (mutated copy inactive) or not (normal copy inactive).

Pathogenic variants in the dystrophin gene in men will result in Duchenne or Becker muscular dystrophy. In women often the perception is that this is not pathogenic, but the more we study this, the more we realize that more women have symptoms than assumed.

#apaperaday Today's pick is about a long term follow up study of women with pathogenic variants in the dystrophin gene by Lyu et al in @journalnd.bsky.social Very good to study these women in more detail. doi: 10.1177/22143602251408549

Authors end by saying that more work is needed. I agree and have given some pointers already. Furthermore, I appreciate that authors do dive into this in more detail and they show that the deletion of the ratchet site does not prevent splicing, but it does make it less efficient.