MS Brain Health Seminar: A Review

October 24, 2024 | Education, Event, Progressive, Research, Webinar

On 12th July 2024 Multiple Sclerosis New Zealand (MSNZ) co-hosted our MS Brain Health seminar in Auckland with the NZ MS Research Trust and MS Auckland. Thank you to all attendees that came to hear from our special guest speaker, Professor Helmut Butzkueven. Professor Butzkueven captured the audience’s attention, providing updates on the MS Brain Health Initiative, the role of Vitamin D and what’s new for Progressive MS.  

Professor Butzkueven is currently the Head of the Neuroscience Department at Monash University in Melbourne, as well as Managing Director of MSBase Foundation, Director of Neurology at Alfred Health, a Steering Committee Member with MS Brain Health and a leading MS Specialist Neurologist. 

His last visit was in 2018, a pivotal moment in NZ’s MS history. His support was critical in MSNZs 8 years of advocacy calling on Pharmac to widen access to DMTs, achieving the criteria we see today. 

Brain Health Initiative Update 

MS Brain Health was launched in 2015 to establish and improve global standards of care for people with MS and provide tools for benchmarking and evaluation. A tremendous feat of co-design at its finest, involving over 60 clinical experts, Neurologist, Nurses, Allied Health specialists, people affected by MS and patient organisation representatives. MS Brain Health continues to strive to be an organisation that lobbies for improving standards of care globally for people with MS (PwMS) and by PwMS. At MSNZ we proudly endorse MS Brain Health whose work has played a critical role in much of our advocacy as we strive to lead advances in best practice MS care. 

MS Brain Health recommends principles for clinical and self-management, grounded in the concepts of monitoring, which, Professor Butzkueven recommends, should be considered a team approach between clinicians and patients. Monitoring is important in MS for several reasons: 

1. MS is a chronic condition and unique to each person. As such personalised management plans and strategies are required to maximise Brain Health.  
2. If left to ‘sit and forget’ the risk of progression and worsened brain health and quality of life outcomes increase. 
3. Monitoring is essential as progression is often invisible, particularly in the early stages. 

“To measure is to know. If you cannot measure it, you cannot improve it” Lord William Thompson Kelvin 

Professor Butzkueven recommends several ways for patients to actively participate in their own health monitoring: 

1. Ensure your medical team has a management plan including regular MRI. 
2. Ask about your results – do I have new lesions? Is that a lot? What’s the plan? 
3. Understand what a treatment can and can’t do. 
4. Discuss with your clinical team whether your treatment is working or if it needs reviewing. 
5. Ask if and how your care team are recording your data (MRI, clinical examination, relapses and treatments). Are they recording it in a systematic way so that they and you can easily look at it to see changes over the years. 

You might find our guide “Preparing for your Neurologist Appointment” useful: Preparing for Your Neurologist Appointment.pdf   

He also strongly recommends that patients be proactive in managing and maximising their own Brain Health and quality of life: 

• Understand that time matters in MS and there is no time to wait. 
• Devise a plan that YOU are in charge of. 
• Stop smoking. Studies clearly show that smoking increases the speed and risk of progression.  
• Get some sun (safely) and check Vitamin D levels to ensure you are not deficient. If you are supplementing don’t take too much (more on this later). 
• Eat a healthy balanced diet. Adapt your diet to get healthier in stages, if preferred. 
• Prevent accelerated aging and progression by managing your comorbidities/other medical conditions (high blood pressure, diabetes). These can have a considerable effect on the impact of your MS. 
• Discuss concerns about depression, anxiety, bladder and bowel issues and sleep disturbance with your care team. They can significantly impact quality of life, but can often be helped. Depression can make MS 30% worse, so it’s important to seek help and support. Your MS Community Advisor is a good first contact for help, and can assist you in accessing additional support your need. 
• Exercise is important for all people with MS as it improves cognition and brain function. Try to exercise at least 4 times a week at high intensity (Heart rate over 80% max, minimum 15 minutes, ideally 30 minutes). Neuro Physiotherapist Gilly Davy gives a good overview of the recommended levels of exercise for PwMS: https://msnz.org.nz/webinar-managing-your-ms-symptoms-when-things-heat-up/  

MSNZ previously funded two NZ Neurology departments to use the MS Brain Health tool, alongside 12 other international centres, to benchmark services against the recommended standards. The consensus agreed standards provide Core, Achievable and Aspirational timelines for access to diagnosis, treatment and ongoing management.  

Results showed that globally there was room for improvement. This has helped inform patient advocacy organisations like MSNZ to identify areas where we can lobby for improved access based on international best practice. The standards have also been useful in highlighting to clinical teams opportunities for continuous improvement, such as questions they should be asking patients, or areas to provide further education or emphasis on. 

Work has been underway to review the Brain Health Standards which were released at ECTRIMS in Copenhagen in September 2024. The new standards highlight the importance of proactive management of exercise, diet, smoking and depression to improve brain health and quality of life. Read the new report here: https://www.msbrainhealth.org/  

Vitamin D 

The role that Vitamin D plays in MS has long been a source of interest. Particularly since Prevalence Studies, including our own in 2006, highlight a significant latitudinal gradient in MS. Essentially, the further you live from the equator, the higher the risk of MS. In NZ there is a higher prevalence of MS in the south, compared to the north. The hypothesis has been that due to a lack of sunlight, lower vitamin D levels increase the risk of MS.  

To test the hypothesis, 204 participants from Australia and New Zealand participated in the PREVANZ trial to understand whether oral vitamin D supplementation could prevent new MS disease activity in people who had had their first MS attack.  

Each person taking part in the trial was then randomised to one of three different daily doses of vitamin D (1000 IU (international units), 5000 IU or 10000 IU), or a placebo (no vitamin D). Vitamin D was used as a standalone therapy meaning the participants were not on other disease-modifying drugs for their MS. Participants were then followed for 48 weeks to determine whether their MS developed. 

Disappointingly, the results showed conclusively that Vitamin D supplementation had no effect on reducing disease activity. Higher doses even increased the risk of relapse. The results showed the percentage of participants who developed new lesions within 1 year and conversion to MS: 

• Placebo – 54%  

• 1000 IUD – 51% 

• 5000 IUD – 65% 

• 10000 IUD – 63% 

Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome – PubMed (nih.gov) 

Progressive MS – what’s new? 

At MSNZ we are acutely aware of how frustrating it can be for those with Progressive MS to hear about new treatments for relapsing MS regularly becoming available. Professor Butzkueven shared his insights into what we should be on the lookout for when it comes to research and treatments for those with Progressive MS. The trials he discussed are still in the research/trial phase with no proven benefit for MS, yet. 

1. The Octopus/Platypus trial in the UK and Australia is an extremely exciting development to follow. This multi-arm multi-stage (MAMS) study looks to change the way in which clinical trials are performed, making them cheaper, faster and better. https://www.msaustralia.org.au/news/platypus-a-new-clinical-trial-for-progressive-ms/ The study randomly assigns patients to receive placebo, Metformin or Alpha-lipoic acid. Alpha-lipoic Acid is relatively cheap and safe (some skin rashes) and given as a 600mg dose twice daily. The strongest evidence to date is a 2-year small (60 patients) placebo-controlled randomised study in Secondary Progressive MS (SPMS) where it reduced brain volume loss by 2/3, with a strong trend towards better walking speed in the active group: https://pubmed.ncbi.nlm.nih.gov/28680916/
2. In October 2023, NZ became the first country in the Asia-Pacific region, and only one of four English speaking countries to have funded access of Ocrelizumab for Primary Progressive MS (PPMS). Roche are currently studying the safety and efficacy of a double dose of ocrelizumab to understand the impacts on PPMS. 
3. There is a significant interest in CAR (Chimeric Antigen Receptors) T-cells and how these may impact those with Progressive MS. These one-time treatments are similar to stem cell therapy, however in this case, T-cells are genetically engineered and reprogrammed to kill B-cells in the brain.  
4. Other treatments being studied for Progressive MS are Bruton Tyrosine Kinase Inhibitors (BTKs). Clinical trials for Tolebrutinib and Fenebrutinib are underway for non-relapsing secondary progressive MS and PPMS. This is very exciting as there are no treatments in NZ for non-relapsing SMPS. In these studies, tablets are taken once or twice a-day and results are showing they have reasonable tolerability, but as yet unknown effectiveness. 
5. Professor Butzkueven also discussed a passion area of his, how technology can be optimised to measure progression and cognition. He discussed the important role that technology plays in both active and passive self-monitoring of MS progression. Using smartphone-based applications, he sees a future where progression can be measured for worsening or improvement and applicable both for trials or enhancing care. 

PERLs and SELs 

Understanding Progressive MS has long been a mystery. What has never been clear is why some people have no new lesions on their MRI scans but are clinically worsening. Researchers are making significant headway to understanding what can happen to existing lesions and how this impacts progression. 

When you look at a lesion, it can be full of different types of immune cells. These immune cells attack the myelin sheath damaging it. When the attack stops, the inflammation disappears and becomes inactive. However, what researchers are now identifying, is that sometimes, immune cells sit around the edge of the lesion and slowly continue to attack it and slowly expand the iron rim that surrounds it. These are called PERLs, or Paramagnetic Rim Lesions. These are identified on an MRI by their iron rim.  

Slowly Expanding Lesions (SELs) are lesions which can slowly grow over a significant amount of time, 8-10 years. While the number of SELs are often low, they present a huge opportunity to understand more about underlying progression. The identification of PERLs and SELs may provide a biomarker for understanding and predicting progressive MS, and research a target to stop growth. 

While there are no new treatments for progressive MS, research is becoming more focussed in this space. New trial approaches and designs, alongside improved imaging to identify and monitor SELs is setting researchers on the path to better understand and treat progressive MS. 

In conclusion, the MS Brain Health seminar was a resounding success, providing valuable insights into the current state of MS research and care. The collaboration between MSNZ, the NZ MS Research Trust, and MS Auckland is vital in the ongoing effort to improve the lives of those affected by MS.

We thank Professor Helmut Butzkueven for taking the time to visit us in NZ and giving us an insightful update into the developments in MS research. 

Our sincere thanks to our sponsors the NZ MS Research Trust, Roche, Merck and Novartis for their funding of the seminar.

Together, we can continue to advocate for better standards of care and support for the MS community.