Progressive MS (PMS), including primary progressive MS (PPMS) and secondary progressive MS (SPMS), remains one of the most challenging forms of multiple sclerosis to understand and treat. In this episode, I speak with neurologist Dr. Thomas Knoll about the mechanisms behind disease progression, current treatment limitations, and what people living with PMS can actively do to maintain their quality of life.
In both PPMS and SPMS, neurodegeneration is the dominant process, which so far can hardly be treated with medication. This makes an active lifestyle and acceptance of the diagnosis all the more important. With the help of symptomatic therapies, assistive devices, and support from social and healthcare services, quality of life can be maintained as much as possible.
Dr. Knoll shares his experience from 30 years as a neurologist, much of which he has spent focusing on MS.
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Introduction – Who is Dr. Thomas Knoll?
I am 57 years old and have been working independently for 20 years in a large neurologist-owned practice in downtown Munich. We are three partners, and a total of eight physicians work in our practice. Many of the doctors have specialized in multiple sclerosis for years.
We offer specialized outpatient care within the German ASV system (ambulatory specialized medical care which is specific to Germany for complex diseases.) and are part of the NeuroTransData network. Within this framework, we advocate for improved patient care. I personally serve as a medical advisor within the network.
A brief note about my personal life: I am married, have three children aged 11 to 24, and we have a dog. I think the dog is the only family member who treats me with respect. 😉
In my free time, I am interested in many things—especially opera.
Personal motivation for choosing this profession
Originally, I had a strong interest in the natural sciences.
Among them, I found the nervous system the most fascinating.
Having my own practice gives me a certain degree of creative freedom. My decisions are based on exchanges with patients on equal footing.
Basic Knowledge About Primary Progressive Multiple Sclerosis (PPMS)
What are the typical symptoms and characteristics of PPMS compared to other forms of MS?
This is defined in the McDonald Criteria 2017 as follows:
If progressive symptoms persist for at least one year, and MS-specific abnormalities are found in the brain or spinal cord MRI, and/or MS-specific changes are found in the cerebrospinal fluid, and there is no more plausible alternative diagnosis, then PPMS can be diagnosed.
How many patients are diagnosed with PPMS and what is the natural course without treatment?
Worldwide, about 10–15% of patients are affected, amounting to approximately 20,000–30,000 new diagnoses per year.
The ratio of men to women is about 1:1.
According to data published by Stefan Braune, 480 PPMS patients are treated within the NeuroTransData network, representing about 5% of all MS patients in that network.
The most common symptom is slowly progressive gait disturbance. Acute relapses are rare.
The disease course varies greatly—as is typical in MS—up to the point where assistive devices such as wheelchairs may become necessary.
Analysis of the NTD data showed that symptoms are often initially nonspecific, and it may take up to 10 years from disease onset to diagnosis. Around 15% of patients are initially diagnosed with relapsing-remitting MS.
Are there factors influencing the course of PPMS?
PPMS patients are typically older at onset—around 40 years of age, which is about 10 years later than in relapsing-remitting MS.
Genetics appear to play an important role. Certain genetic variations increase both the risk and severity of the disease.
Within epigenetics (environmental influences on gene expression), key factors include:
- Epstein-Barr virus (EBV)
- Smoking
- Obesity
- Vitamin D deficiency
- High salt intake
Since only limited medication options are currently available, an active approach to the disease is particularly important. This includes maintaining an active lifestyle and minimizing risk factors.
However, it should be noted that influencing factors in PPMS are less well studied than in relapsing MS.
What are the biggest challenges in living with PPMS?
- Gait disturbances
- Access to assistive devices
- Motor impairments of the upper limbs
- Spasticity
- Pain
- Bladder and bowel dysfunction
- Depression
- Fatigue
- Cognitive impairment
Overall, these often lead to reduced quality of life.
Treatment and Intervention in PPMS
What treatment options are currently available?
In MS, two disease processes occur:
- Focal inflammation (visible in relapses and MRI lesions)
- Diffuse neurodegeneration
Currently, medications primarily target inflammation, which dominates in relapsing MS.
Diffuse neurodegeneration—more prominent in progressive MS—is still largely untreatable.
B-cell therapies such as Ocrelizumab and Rituximab can treat inflammatory aspects of PPMS, especially in:
- Younger patients (<45–50 years)
- Short disease duration
- Low disability
- Evidence of inflammatory activity on MRI
Treatment may also be attempted in patients over 50 for about two years, but side effects must be monitored closely.
Repeated steroid treatments (once common practice) lack scientific evidence.
What progress has been made in recent years?
Previously, steroid pulses were routinely used.
Since 2018, Ocrelizumab has been approved, though with limitations.
Better understanding of disease mechanisms is key to developing new therapies.
How important is early intervention?
Ocrelizumab is more effective in younger patients with lower disability scores (EDSS).
For patients over 50, there is little evidence of effectiveness.
What about autologous stem cell therapy?
In Germany, autologous hematopoietic stem cell transplantation (aHSCT) is not yet approved for MS.
The concept of “resetting” the immune system is appealing.
It primarily targets lymphocyte-driven inflammation and is most relevant for highly active relapsing MS.
There is some evidence of benefit in early SPMS with inflammatory activity
(Burt 2022). However, PPMS patients are generally not ideal candidates.
How important is it to measure the progression of PPMS in order to understand what works for individual patients and to identify patterns at the group level? Which assessments and patient data are particularly important in this context?
At the individual level, measuring disease progression helps to better assess both limitations and remaining potential.
In addition to pharmacological treatment approaches, physiotherapy, occupational therapy, cognitive training, regular physical activity, and a healthy diet play a crucial role.
The following assessments are commonly used in clinical practice and research:
- EDSS (Expanded Disability Status Scale)
- T25FW (Timed 25-Foot Walk – assessment of walking ability)
- 9HPT (9-Hole Peg Test – assessment of fine motor skills)
- SDMT (Symbol Digit Modalities Test – assessment of cognitive function)
- FSMC (Fatigue Scale for Motor and Cognitive Functions – assessment of fatigue impact on motor and cognitive abilities)
- PROs (Patient-Reported Outcomes – health outcomes reported directly by patients)
In addition, social and occupational factors play an important role in supporting people with PPMS, such as workplace adaptations, equal opportunity considerations, and the evaluation of disability status.
Group-level effects have been well analyzed in the scientific work by Stefan Braune.
Quality of Life and Patient Support
How can people with PPMS improve their quality of life?
People living with PPMS can improve their quality of life by making use of rehabilitation services, empowering themselves, and taking an active approach to managing their condition.
Everyone should try to make the most of the aspects of the disease they can influence, while also recognizing their limits, accepting the “new normal,” and learning how to live with it. Make use of available assistive devices, consider adapting your workplace, and ensure an appropriate disability status, which can help compensate—at least to some extent—for the disadvantages caused by MS.
What role do rehabilitation programs and physiotherapy play in supporting people with PPMS?
They are very important given the limited pharmacological treatment options.
What advice would you give to people with PPMS and their families to help them cope with the disease?
All those directly and indirectly affected should try to accept the diagnosis, including the specific disease concept of primary progressive multiple sclerosis (PPMS).
It is extremely important to stay active and to maintain one’s resources.
Build a strong support network, including a good neurologist, skilled therapists, and a reliable rehabilitation clinic. And stay informed—for example, by following a good podcast. Research is continuously advancing, and as a well-informed patient, you may be able to benefit earlier from new insights.
Are there support groups or resources that people with PPMS can use to access help and information?
Make use of resources offered by your local MS patient organization, as well as international organizations like the Multiple Sclerosis International Federation and the European Multiple Sclerosis Platform, in addition to social media, blogs, and podcasts.
You should be cautious with forums, as the most sensational stories tend to receive the most attention and may be completely untrue.
Future Developments and Research Directions
What promising developments or research directions do you see for the future of understanding and treating PPMS?
Disease mechanisms—especially neurodegeneration—are being understood better and better. This also opens up new possibilities for influencing the disease.
New treatment options are just around the corner and theoretically have the potential to address PPMS more effectively. However, we still need to wait for the results of ongoing studies.
Quickfire Round
Please complete the sentence: “For me, multiple sclerosis is…”
…a success story of neurology.
I have been a neurologist for 30 years. Understanding and treatment options have changed dramatically. And I hope that in the future we will be able to offer even better options for people with progressive MS.
What breakthrough in research and/or treatment of PPMS would you like to see in the next five years?
Exactly that: being able to treat progressive MS more effectively.
And that digitalization, with its many possibilities for support, will play a greater role.
Which website would you recommend on the topic of MS?
Further information & networks:
- NeuroTransData: https://www.neurotransdata.com
- NeuroTransConcept: https://www.neurotransconcept.com
- Neuromuenchen (Dr. Knoll): https://www.neuromuenchen.de
Farewell
Would you like to share a final message with the listeners?
I see what a difference it makes whether patients engage with their condition or not.
This helps to develop a realistic understanding, reduces fear, and creates perspective.
Thank you to Dr. Thomas Knoll for his insights into progressive MS and for repeatedly emphasizing how important it is to actively engage with the disease in order to shape everyday life—even with progressive MS.
See you soon and try to make the best out of your life,
Nele
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