Secondary Progressive Ms: Symptoms, Types, Causes and Treatment

Secondary Progressive Multiple Sclerosis (SPMS) is a complex and often challenging stage of multiple sclerosis (MS) that follows the initial relapsing-remitting phase. For many, this transition brings new symptoms, evolving disease mechanisms, and a distinct approach to management. In this article, we'll explore the key features of SPMS—its symptoms, types, underlying causes, and the latest treatment strategies—providing a clear, evidence-based resource for patients, families, and healthcare professionals.

Symptoms of Secondary Progressive MS

The symptoms of SPMS are varied, evolve over time, and can significantly impact daily life. Unlike the relapsing-remitting form, SPMS is marked by a steady accumulation of disability, often independent of relapses. Understanding these symptoms is essential for early recognition and proactive management.

Symptom	Description	Prevalence/Impact	Source(s)
Mobility Issues	Progressive walking difficulties, weakness	Most common in SPMS transition	2 4 6
Cognitive Deficits	Problems with memory, processing, attention	Up to 83% in SPMS	1 7
Fatigue	Persistent, often severe tiredness	Strongly associated with SPMS	1 7
Sensory Changes	Numbness, tingling, altered sensations	Frequent in SPMS	1 4
Visual Impairment	Blurred or diminished vision, optic neuritis	May dominate in some SPMS cases	2 4
Bladder/Bowel	Incontinence, urgency, or retention	Common and often disabling	1 4
Spasticity	Muscle stiffness, spasms	Common in progressive stages	1 4

Table 1: Key Symptoms

Overview of SPMS Symptoms

SPMS symptoms are not only numerous but often more severe and persistent than in relapsing-remitting MS (RRMS). The most distinctive feature is a steady worsening of neurological function, often without the clear-cut relapses that characterize earlier disease stages.

Mobility and Physical Disability

• Walking Difficulties: The hallmark of SPMS is a gradual loss of mobility. This can manifest as increased difficulty walking, muscle weakness, and impaired balance. Walking impairment is so common that it's often used as a clinical indicator of progression 2 4 6.
• Spasticity and Muscle Stiffness: Many with SPMS develop muscle tightness or spasms, which can further limit mobility and increase the risk of falls 1 4.

Cognitive and Emotional Changes

• Cognitive Decline: Cognitive symptoms—including problems with memory, attention, information processing speed, and verbal fluency—are reported by up to 83% of SPMS patients, and tend to be more severe than in RRMS 1 7.
• Fatigue: An overwhelming sense of tiredness, unrelated to physical activity, is frequently reported and is strongly linked to cognitive and physical symptoms 1 7.

Sensory and Visual Symptoms

• Sensory Disturbances: Numbness, tingling, or altered sensations in the limbs can become more prominent and persistent as SPMS progresses 1 4.
• Visual Impairment: Some patients experience a progressive decline in vision, which may even be the first sign of transition to SPMS in certain cases 2.

Autonomic and Other Symptoms

• Bladder and Bowel Dysfunction: Issues such as urgency, incontinence, or retention are frequent and can greatly affect quality of life 1 4.
• Other Symptoms: Sexual dysfunction, pain, and coordination problems (ataxia) can also occur, reflecting widespread nervous system involvement 4.

Types of Secondary Progressive MS

SPMS is not a one-size-fits-all condition. Recent research has highlighted important differences within SPMS, particularly regarding disease activity and progression patterns. Recognizing these types helps guide treatment and expectations.

Type	Key Features	Distinction	Source(s)
Active SPMS	Progression with ongoing relapses/MRI activity	Younger patients, more relapses	8 15
Non-active SPMS	Progression without relapses or MRI activity	Older age, longer disease duration	8 15
Other Progression	Gradual worsening, independent of relapses	Disability accrual (PIRA)	8 6

Table 2: SPMS Types

Classification of SPMS

SPMS was historically viewed as a single entity, but now it's recognized as comprising subtypes based on disease activity and progression:

Active vs. Non-active SPMS

• Active SPMS: Characterized by ongoing relapses or new MRI lesions alongside progression. These patients tend to be younger and may respond better to certain treatments 8 15.
• Non-active SPMS: Involves gradual worsening of disability without recent relapses or MRI evidence of new disease activity. This group is typically older and has a longer MS history 8.

Progression Independent of Relapse Activity (PIRA)

A significant finding is that most disability accumulation in SPMS is due to progression independent of relapse activity (PIRA). Both active and non-active SPMS show similar rates of disability progression, emphasizing that ongoing neurodegeneration—rather than relapses—is the main driver of disability in this stage 8 6.

Why Does This Matter?

• Treatment Decisions: Active SPMS may benefit from disease-modifying therapies (DMTs) approved for relapsing disease, while non-active SPMS requires a focus on neuroprotection and symptom management 8 15.
• Prognosis: The distinction helps set realistic expectations for patients and clinicians regarding disease trajectory.

Causes of Secondary Progressive MS

The transition from RRMS to SPMS is complex and not fully understood. However, advances in research have shed light on the underlying mechanisms that drive this change.

Cause/Mechanism	Description	Key Points	Source(s)
Neurodegeneration	Axonal loss and chronic demyelination	Main driver of progression	5 9 10 11
Inflammation	Chronic, less intense inflammation	Shifts from acute to chronic	5 11
Age/Disease Duration	Increased risk with longer disease, older age	Not sole determinants	7 9
Genetic/Environmental	Potential but not clearly defined	Still under investigation	11 12

Table 3: SPMS Causes

The Shift from Inflammation to Neurodegeneration

• Early MS: RRMS is dominated by acute inflammation—immune cells attack myelin, leading to relapses 5 10.
• SPMS Transition: Over time, inflammation becomes more chronic and less pronounced, while neurodegenerative processes—such as axonal loss and chronic demyelination—take over 5 9 10.
• Pathological Changes: Progressive MS is marked by widespread damage in both white and gray matter, microglia activation, chronic oxidative stress, and even abnormal protein accumulation (such as tau), which are linked to irreversible disability 11 12.

What Triggers the Transition?

• The exact triggers for progression are unknown, but cumulative axonal damage, mitochondrial dysfunction, and age-related changes are implicated 9 10 11.
• Biomarkers such as neurofilaments and imaging evidence of brain and spinal cord atrophy are being studied to detect progression early 3 9.

Is SPMS Inevitable?

• Not all RRMS patients will develop SPMS. Early, aggressive treatment of inflammation may delay or reduce the risk of progression 15.
• Disease duration and older age are associated with higher risk, but they are not absolute predictors—many factors interplay to determine progression 7 9.

Treatment of Secondary Progressive MS

Managing SPMS is challenging, but recent advances have brought new hope. While there is no cure, a combination of disease-modifying therapies, symptom management, and rehabilitation can make a substantial difference.

Treatment Type	Examples/Details	Efficacy/Role	Source(s)
Disease-modifying Drugs	Siponimod, cladribine, ocrelizumab, etc.	Benefit in active SPMS	15 16
Neuroprotective Agents	Amiloride, riluzole, fluoxetine (trialed)	Under investigation (MS-SMART)	13 14
Symptom Management	Physical therapy, medications for spasticity etc.	Essential for quality of life	4 16
Rehabilitation	PT, OT, cognitive rehab	Supports function, independence	1 3 16

Table 4: SPMS Treatment Options

Disease-Modifying Therapies (DMTs)

• For Active SPMS: Recent approvals (e.g., siponimod, cladribine) offer options for people with ongoing disease activity. These therapies can slow disability progression and reduce relapses in "active" SPMS 15.
• For Non-Active SPMS: DMTs have limited effect. The main focus here is on symptom control and neuroprotection 16.

Neuroprotective Strategies and Clinical Trials

• Emerging Therapies: The MS-SMART trial and similar studies are investigating drugs (amiloride, riluzole, fluoxetine) that may protect nerve cells from damage in SPMS. Results are awaited, as neuroprotection is seen as a key unmet need 13 14.
• Research Focus: As neurodegeneration is central to SPMS progression, the goal is to find drugs that can slow or halt this process, beyond just controlling inflammation 9 14.

Symptom Management

• Physical Therapy (PT): Helps maintain mobility, balance, and strength.
• Medications: Address specific symptoms such as spasticity, bladder dysfunction, pain, or depression 4 16.
• Cognitive Rehabilitation: Tailored programs can help manage cognitive deficits, supporting memory and executive function 1 3.

Rehabilitation and Support

• Occupational Therapy (OT): Promotes independence in daily activities.
• Multidisciplinary Care: Involving neurologists, therapists, psychologists, and social workers is essential to address the full spectrum of SPMS challenges 3 16.
• Patient Education: Empowering patients with knowledge about disease progression and self-management improves outcomes 3.

Future Directions

• Early Detection: Improved biomarkers and imaging are being developed to identify progression sooner, allowing earlier intervention 3 9.
• Personalized Treatment: As our understanding of SPMS subtypes grows, treatments can be better tailored to individual needs.

Conclusion

Secondary Progressive MS is a multifaceted stage of multiple sclerosis, marked by evolving symptoms, distinct subtypes, complex underlying mechanisms, and emerging treatments. Understanding SPMS empowers patients, families, and clinicians to make informed decisions and advocate for the best possible care.

Key Takeaways:

• SPMS is defined by a steady progression of disability, often independent of relapses.
• Symptoms include mobility issues, cognitive deficits, fatigue, sensory changes, visual impairment, and autonomic dysfunction.
• There are active and non-active types of SPMS, distinguished by the presence or absence of ongoing disease activity.
• The main cause of progression is a shift from inflammation to neurodegeneration; early, aggressive therapy may delay transition.
• Treatment focuses on disease-modifying drugs for active SPMS, neuroprotective research, comprehensive symptom management, and rehabilitation.
• Ongoing research is vital to discovering effective neuroprotective therapies and improving early detection of progression.

Understanding and addressing SPMS takes a collaborative, personalized approach. With continued advances in research and care, there is hope for better outcomes for all affected by this challenging stage of MS.