SPMS: Causes, Risk Factors, and Complications

SPMS: Causes, Risk Factors, and Complications

Multiple Sclerosis (MS) is a debilitating and unpredictable neurological condition that affects the central nervous system of an individual. It can cause worsening symptoms over time such as fatigue, pain, vision problems and cognitive issues. Although it is not curable at the present time, treatments have improved for managing symptoms and preventing further damage to neurologic function by dampening the underlying mechanisms of the condition. As scientific research continues to help researchers recognize the potential medical advances in treating MS, there are already numerous resources available to support those living with the disease.

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Secondary Progressive MS

Multiple sclerosis (MS) is a chronic autoimmune disease, the severity and nature of which can vary greatly from case to case. According to Johns Hopkins Medicine, around 90 per cent of people with MS tend to be diagnosed initially with the relapsing-remitting form of the disease (RRMS).

Secondary progressive MS often results when disease progression leads to neuron loss, cellular atrophy and other changes in disease activity. If one notices signs that their symptoms are becoming worse without any notable relapse or remission taking place, then an MRI scan may be recommended in order to assess disease development and further measure the level of cell death and brain atrophy within the patient.

Generally speaking, the increased contrast will show up during an attack due to leaking capillaries absorbing more of the gadolinium dye used during an MRI scan.

Diagnosing SPMS

Diagnosing SPMS can be difficult as disease progression, disease activity, and disease onset may not always be obvious. MRI scans are a useful tool for diagnosis and can provide valuable insight into the disease.

They can help demonstrate the level of cell death and brain atrophy associated with this disease and also enable evidence of disease activity during an attack. MRI scans are especially helpful in an attack situation where the extra uptake of gadolinium dye due to leaking capillaries further highlights disease activity.

Treating SPMS

While periods of remission are fewer or less frequent in Secondary Progressive Multiple Sclerosis, they still occur and can be exacerbated by heat or humid weather. MS Patients with SPMS are more likely to experience mobility problems in walking and with balance than individuals with RRMS.

While RRMS symptoms are thought to be driven by inflammation and damage to brain cells, SPMS symptoms are assumed to be driven by the loss or atrophy of these damaged nerve cells.

Modern disease-modifying treatments (DMTs) can markedly reduce the number of RRMS patients who do on to develop SPMS while also extending the time for that transition.

Without MS treatment, roughly half of Relapsing-remitting MS patients will go on to develop SPMS within 10 years of disease onset. But, with DMTs, these MS patients will not progress to SPMS for 25 years. And, by current estimates, 10% of MS patients will not progress to SPMS within three decades.

Medications for SPMS

While the majority of disease-modifying treatments (DMTs) are indicated by the Food and Drug Agency for relapsing forms of MS. Patients with secondary progressive MS still experiencing relapses can be suitable for treatment.

These treatments are not specifically aimed at SPMS but can still reduce relapse frequency and delay disease progression in clinical trials. They include:

  • Aubagio (teriflunomide)
  • Avonex (interferon beta 1a)
  • Bafiertam (monomethyl fumarate)
  • Betaseron (interferon beta 1b)
  • Copaxone (glatiramer acetate injection)
  • Extavia (interferon beta 1b)
  • Gilenya (fingolimod)
  • Kesimpta (ofatumumab)
  • Lemtrada (alemtuzumab)
  • Mavenclad (cladribine)
  • Mayzent (siponimod)
  • Ocrevus (ocrelizumab)
  • Plegridy (peginterferon beta-1a)
  • Ponvory (ponesimod)
  • Rebif (interferon beta-1a)
  • Tecfidera (dimethyl fumarate)
  • Tysabri (natalizumab)
  • Vumerity (diroximel fumarate)
  • Zeposia (ozanimod)

Symptomatic Treatments

Treatments that deal with physical or mental symptoms without treating the underlying cause are known as symptomatic treatments. Physiotherapy may help ease muscle stiffness and muscle spasms.

Cognitive Behavioural Therapy can improve pain, anxiety and depression. Although some therapies can make symptoms worse before they get better.

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SPMS Meaning

Secondary-progressive MS is one of the progressive forms of active MS and can lead to significant disability when compared with relapsing MS. MRI scans will show further brain lesions and the disease course will have disability worsening.

If you can detect progression in your symptoms you should consult the health professionals in your MS team.

The progressive forms of MS will always cause progressive disability worsening.

Factors linked to a faster onset of SPMS include:

  • older age at MS onset
  • longer disease duration
  • smaller brain volume
  • being male
  • a larger number of brain lesions

Secondary Progressive Multiple Sclerosis

Progressive forms of Multiple Sclerosis (MS) tend to possess symptoms that are distinct from more typical types of the condition, such as impairments in motor and visual functions, both of which may lead to significant disability over time. The underlying causes for these progressive types are then different and incompletely understood, making it difficult to identify appropriate and effective therapeutic interventions.

A variety of potential explanations have been put forward including mitochondrial injury and oxidative stress, microglial activation, increased strain on demyelinating axons, and a potential role for the kynurenine pathway leading to excitotoxic degeneration. However, there is still no clear agreement on precisely how each mechanism contributes.

Recent developments in MRI have shown that tissue pathology can often be detected with characteristic shifts away from active plaques towards inactive ones across cortical gray and white matter with progression; thus imaging technology could provide useful biomarkers to better understand these changes.

What are the challenges of conducting Clinical Trials?

Randomized clinical trials are of vital importance when assessing the efficacy of any new drug used in the treatment of multiple sclerosis. The changing definitions of progressive MS over time make the patient selection less uniform.

Multiple Sclerosis type classification

In 1996, those with multiple sclerosis (MS) were referred to simply as having chronic progressive MS. However, the terminology was later expanded to include secondary progressive MS (SPMS), primary progressive MS (PPMS) and progressive-relapsing MS (PRMS) due to its inadequacies in defining this condition.

In an effort to accurately specify the progression of this illness, another proposal was put forth in 2014 where they classified these phenotypes according to disease activity over the span of 12 months; This could be either active or inactive. Furthermore, it further classified these phenotypes as being either progressive or nonprogressive by taking into account the history of previous activity over the course of the last year.

Lorscheider et al have proposed a definition of secondary progressive multiple sclerosis (SPMS) that disease progression should be determined annually using an objective measure such as the Expanded Disability Status Scale (EDSS). This measure enables healthcare professionals to identify deterioration in a reliable and repeatable way, as it takes into account physical, cognitive, and functional errors. A worsening of one point is indicative of disease progression into SPMS.

Measuring disease progress annually gives doctors and their patients a better understanding of the disease and more personalized treatment options.

Primary Progressive Multiple Sclerosis

Primary Progressive Multiple Sclerosis (PPMS) is considered to be a distinct type of MS, with an onset of progressive neurological dysfunction and disability from disease onset, in the absence of the relapses that characterize Relapsing-Remitting MS (RRMS).

While episodes of relapse may eventually begin following PPMS onset, some evidence suggests that PPMS may represent a separate, noninflammatory or less inflammatory form of the disease compared to Secondary Progressive MS (SPMS) and RRMS. While PPMS was only recently classified as a discrete subtype of MS, ongoing studies are beginning to offer more insight into possible diagnostic biomarkers and therapeutic approaches unique to this category.

Despite this progress, much still remains unknown in regards to reliably identifying primary progressive MS and developing effective treatments specifically targeted at it.

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The View that PPMS is not a distinct entity from SPMS

Recent studies have revealed that, as opposed to its separate labelling as an entity distinct from SPMS, PPMS may in fact represent progression after an unrecognised or subclinical inflammatory injury.

This notion is supported by data showing that around 10 per cent of people with Radiologically Isolated Syndrome (RIS) – a condition comprising MRI-visible lesions but no clinical signs or symptoms of MS – can transition to PPMS without passing through a relapsing phase.

Collectively, this evidence suggests that some individuals may unknowingly progress from the relapsing form of MS to the progressive one and are then diagnosed with PPMS upon further investigation.

Progressive MS

Secondary Progressive Multiple Sclerosis (SPMS) and Relapsing-Remitting MS (RRMS) are both forms of Multiple Sclerosis, but there are some major distinctions between the two. While a few treatments have been developed to slow the progression of RRMS, treatments proven to halt progression in Secondary Progressive MS have not yet been available—thus it is critical for physicians to adapt treatment plans based on which phase of the disease the patient is in for optimal outcomes.

Recently, a few treatments have demonstrated efficacy in slowing disability worsening for Secondary Progressive Multiple Sclerosis, offering hope that more efficient therapies can be developed in the future.

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Pathology of SPMS

Secondary Progressive Multiple Sclerosis (SPMS) and Relapsing-Remitting MS (RRMS) are both forms of Multiple Sclerosis, but there are some major distinctions between the two.

While a few treatments have been developed to slow the progression of RRMS, treatments proven to halt progression in Secondary Progressive MS have not yet been available—thus it is critical for physicians to adapt treatment plans based on which phase of the disease the patient is in for optimal outcomes.

Recently, a few treatments have demonstrated efficacy in slowing disability worsening for Secondary Progressive Multiple Sclerosis, offering hope that more efficient therapies can be developed in the future.

Secondary Progressive Multiple Sclerosis (SPMS) is the next phase of Multiple Sclerosis that occurs after the initial Relapsing-Remitting MS (RRMS). There is one theory that suggests that MS starts as an inflammatory disease during RRMS and then progresses to a neurodegenerative state as it transitions into SPMS.

These differences in the transition time between the diagnosis of RRMS and the diagnosis of SPMS may be due to individual patient differences in functional reserve capacity within the brain.

Therefore, neurodegeneration associated with progressive clinical disease can occur when preexisting brain damage exceeds the patient’s individual functional reserve capacity.

Understanding Secondary Progressive MS greatly aids in helping diagnose and treat patients sooner, which can potentially slow down the progression of this debilitating condition.

Symptoms of Secondary Progressive MS

Multiple Sclerosis (MS) is an unpredictable and complex condition that can affect individuals in a variety of ways. Depending on where MS has damaged the brain and central nervous system, symptoms can vary immensely.

Secondary Progressive MS (SPMS) is a form of MS that often results in more debilitating effects than relapsing-remitting MS. Secondary Progressive Multiple Sclerosis (SPMS) is characterized by gradually worsening neurological symptoms with or without periods of relapse or stabilisation.

It’s important to note that no two cases are alike; symptoms vary in each individual person depending on the location and extent of damage caused to the brain and spinal cord.

The transition from RRMS to SPMS

Transitioning from Relapsing-Remitting MS to Secondary Progressive MS can be an unsettling experience – one of the first symptom indicators is difficulty walking. Some people may experience stiffness, weakness or a heavy feeling in their legs that gradually gets worse, while others may have unsteadiness or problems with balance and coordination.

Falling on kerbs or stumbling when trying to go up steps are just some of the dangers associated with Secondary Progressive Multiple Sclerosis, so it is important to seek medical advice as soon as possible if you notice any changes in your mobility.

For people living with Secondary Progressive Multiple Sclerosis, the transition from Relapsing-Remitting MS (RRMS) to Secondary Progressive MS (SPMS) may be difficult. One of the first signs that this transition is taking place is an increase in difficulty with walking.

This might manifest as stiffness and weakness in the legs, a feeling of heaviness when walking and increased difficulty when stepping up or over obstacles such as curbs or stairs. Additionally, instability and coordination issues can lead to further trouble when walking. While this change in mobility can seem daunting, it is important to remember that there are many treatments and therapies available to help individuals manage Secondary Progressive MS and its associated symptoms.

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Common Symptoms

Some of the common symptoms of Secondary Progressive MS are:


Fatigue can be a debilitating symptom that affects people in many different ways. It’s much more than just feeling tired after a day at work or a long run.

It’s exhaustion which is completely out of proportion to the circumstances. This type of fatigue can be either physical, mental or both.

It can make it difficult to engage in any type of activity, whether physical or mental tasks become too overwhelming even when seemingly minor.

Even simple things such as getting up in the morning and taking care of basic daily responsibilities can be a struggle due to the overwhelming mental or physical fatigue caused by multiple sclerosis. For those dealing with fatigue, recognizing it for what it is and getting support are important steps towards navigating it effectively.

Spasticity or Spasms

Spasticity and spasms are uncomfortable yet frequently seen symptoms among those with musculoskeletal disorders or chronic pain.

Spasticity is characterized by muscle stiffness, whereas spasms are a common reflex resulting from hyperactive neurons. Many people with MS struggle with spasticity and/or spasms on a daily basis, often alleging that the discomfort can make everyday tasks difficult to undertake.

It is important to note that exercises designed to gently stretch the affected muscles may help alleviate this symptom; if this does not prove to be a lasting solution, further medical intervention may be pursued in order to manage it more effectively.

Cognitive Problems

Cognitive problems can have a profoundly negative impact on daily functioning, especially when it comes to tasks that require concentration and attention to detail, such as studying or working.

They can also interfere with important activities like remembering appointments, meetings, or deadlines.

Furthermore, they may result in difficulty organizing tasks or planning complex activities.

Fortunately, cognitive problems can be managed through education and lifestyle changes. For instance, eating a healthy diet that is rich in antioxidants and omega-3s has been linked with improved and protected mental health.

Additionally, engaging in regular physical activity encourages brain health by boosting oxygen flow and stimulating nerve growth factors – both of which aid in improving cognitive performance. 

Finally, taking steps to reduce stress by engaging in calming activities like yoga or mindfulness meditation can help alleviate mental distress associated with cognitive problems.

Emotional Difficulties

Emotional difficulties such as feelings of anxiety and altered moods can be difficult to manage. 

However, there are ways to help cope with these issues. Taking a mental health break, talking to friends or family about how you’re feeling, taking prescribed medications, engaging in physical exercise, and practising relaxation techniques can all make a significant difference in improving emotional health.

Consulting with a mental health professional is also an effective way of getting personalized advice on managing different kinds of emotions. It’s important to remember that if you’re feeling like your mental well-being is compromised, then taking measures to improve it, however small they may be, is extremely beneficial in the long run.

Altered Sensations

Altered sensations are an all-too-familiar experience for many. These unusual feelings, ranging from numbness to tingling and even burning sensations, can be especially common among people with progressive MS.

Neuropathic or nerve pain is also a type of pain associated with progressive MS as well as other neurological conditions.

Altered sensations can be quite disruptive to day-to-day activities and interfere with sleep, but there are treatments available to help reduce them. It’s important for those who suffer from these sensory disruptions to seek out qualified medical advice so that they can receive the best possible care directed at their individual needs.

MS Symptoms Recap

For those living with multiple sclerosis know that some of its symptoms can be difficult to convey to family, friends, and coworkers even though they may have a major effect on everyday life.

These kinds of symptoms are labelled as invisible symptoms, which include fatigue and changes in sensations. People who don’t suffer from multiple sclerosis may not understand how these invisible symptoms can be draining and often painful, making regular tasks or activities more challenging and sometimes even impossible to complete.

It is important for those with progressive MS to find ways to explain their invisible symptoms so that others can learn to better comprehend and support them.

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Treatments for Multiple Sclerosis

People living with multiple sclerosis (MS) in the secondary progressive phase often mistakenly believe that there is no effective treatment available. It is important to understand that there are multiple options when it comes to managing MS symptoms, from medications to lifestyle modifications.

Additionally, some individuals with early or active secondary progressive multiple sclerosis may be eligible to receive a disease-modifying drug (DMD). Living with multiple sclerosis is challenging, but through research and accessible treatments, those affected by secondary progressive multiple sclerosis can find ways to cope and live their best lives.

Symptomatic Treatments

Multiple Sclerosis (MS) is the most common acquired chronic neurological disorder among young people, and there are multiple treatments to help manage its symptoms. Symptomatic treatments can be used to help ease symptoms, such as fatigue, spasticity, muscle weakness and blurry vision; however, they are unable to change the course of the condition itself.

Secondary progressive MS is when the symptoms have no clear remission periods and patients experience a steady decline growing worse over time. Symptomatic treatments for this form of multiple sclerosis include physical therapy, anti-spasticity medications, medications to reduce fatigue, antidepressants and immunomodulatory drugs to slow down disease progression.

While these treatments do not cure multiple sclerosis or alter the course of the condition directly, they can assist those suffering from MS in managing their symptoms on a daily basis.

Drug Treatments

For people suffering from multiple sclerosis, drug treatments can provide relief from a variety of MS symptoms, like pain, spasticity and bladder issues.

Some medications act as a defence against attacks on the nervous system, slowing down disability progression and providing some symptom relief. Others can be targeted to specific needs, such as reducing pain or improving mobility. These treatments help patients manage multiple sclerosis more effectively, giving them a better quality of life.


Therapies can be an effective way to manage brain and spinal cord diseases like multiple sclerosis (MS). MS is a chronic illness with unpredictable symptoms which can last for many years. Active secondary progressive MS is an advanced form of disease where physical and mental impairments increase over time.

In order to lessen the burden of dealing with MS, therapists seek to improve mobility, reduce pain and address psychological issues such as depression or anxiety. Therapies such as physiotherapy, speech-language therapy and cognitive behavioural therapy are proven treatments to help individuals struggling with MS cope better.

The science behind these therapies is essential in maintaining healthy minds and bodies for those with active secondary progressive MS.

Management Techniques

Managing your energy levels and minimising fatigue is often a top priority for people living with a brain and spinal cord impairment, such as multiple sclerosis. Applying effective management techniques such as pacing yourself – which involves balancing periods of activity and rest in order to conserve energy – can be an invaluable way to minimise the MS symptoms associated with this condition.

Doing so helps you carry out desired activities without feeling overwhelmed, frustrated or too tired to continue. Working towards a balanced life by pacing yourself enables those with brain or spinal cord impairments to make positive progress in many aspects of their daily routines and activities.


Rehabilitation helps individuals live life to the fullest while providing practical support to overcome personal barriers. A national multiple sclerosis society can support with referral services, education and other resources to help with certain areas such as attending clinical trials.

Depending on an individual’s needs, different services might be obtained such as physiotherapy, speech and language therapy, cognitive rehabilitation therapy, or occupational therapy which looks at activities that are difficult and finds ways of simplifying them through lifestyle changes or by using aids, equipment or adaptations.

Ultimately, rehabilitation programs help individuals better their lives with improved physical ability and overall cognitive functioning.

Disease Modifying Therapies

Disease-modifying drugs (DMDs) are a form of treatment used to reduce disability progression and combat relapsing forms of multiple sclerosis. The primary goal of disease-modifying therapies is to decrease the number and severity of relapses, as well as slow down disability progression that can accumulate if patients do not completely recover from these relapses.

Until recently, DMDs have only been prescribed for people with MS who experience relapses; however, they are also now used in secondary progressive MS (SPMS) when there is still evidence of active disease. Ultimately, usage may be discontinued if the patient stops having relapses or their activity levels become nonexistent.

Effective disease-modifying therapy can reduce disability accumulation in remitting multiple sclerosis and can help in reducing disability progression.

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