Multiple sclerosis

Multiple sclerosis (MS) is an acquired chronic immune-mediated inflammatory condition of the central nervous system, affecting both the brain and spinal cord (1,2,3):

• affects more than 150,000 people in the UK (4)
  • 1 in 400 people living in MS and 135 people each week / 7100 people a year diagnosed on average within the United Kingdom
• is the most common cause of serious physical disability in adults of working age (1,2,3)
• people with MS typically develop symptoms in their late 20s, experiencing visual and sensory disturbances, limb weakness, gait problems, and bladder and bowel symptoms
  • may initially have partial recovery, but over time develop progressive disability
• the cause of MS is unknown
  • is believed that an abnormal immune response to environmental triggers in people who are genetically predisposed results in immune-mediated acute, and then chronic, inflammation
    • the initial phase of inflammation is followed by a phase of progressive degeneration of the affected cells in the nervous system
• MS is a potentially highly disabling disorder with considerable personal, social and economic consequences
  • people with MS live for many years after diagnosis with a significant impact on their ability to work, as well as an adverse and often highly debilitating effect on their quality of life and that of their families
    
    
• there are four types of MS (revised in 2013) (5):
  • Clinically isolated syndrome (CIS)
  • Relapsing-remitting MS (RRMS)
  • Primary progressive MS (PPMS)
  • Secondary progressive MS (SPMS)
    
• the most common pattern of disease is RRMS where periods of stability (remission) are followed by episodes when there are exacerbations of symptoms (relapses)
  • about 85 out of 100 people with MS have RRMS at onset (3)
  • around two-thirds of people who start with RRMS may develop secondary progressive MS MS: this occurs when there is a gradual accumulation of disability unrelated to relapses, which become less frequent or stop completely (3)
    
• about 10 to 15 out of 100 people with MS have primary progressive MS where symptoms gradually develop and worsen over time from the start, without ever experiencing relapses and remissions (3)
  
• definition of relapse (6):
  
  • a relapse is defined as the onset of new symptoms or the worsening of pre-existing symptoms attributable to demyelinating disease lasting for more than 24 hours and preceded by improving or stable neurological status for at least 30 days from the onset of the previous relapse in the absence of infection, fever or significant metabolic disturbance
  • clinically significant relapse
    • any motor relapse
    • any brainstem relapse
    • any sensory relapse if it leads to functional impairment
    • relapse leading to sphincter dysfunction
    • optic neuritis
    • intrusive pain lasting more than 48 hours
      
      
  • disabling relapse
    • a disabling relapse is defined as any relapse which fulfills one or more of the following criteria:
      • affects the patient’s ability to work
      • affects the patient’s activities of daily living as assessed by an appropriate method
      • affects motor or sensory function sufficiently to impair the capacity or reserve to care for themselves or others as assessed by an appropriate method
      • needs treatment/hospital admission
        
        
• highly active disease (7)
  • patients with an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year despite treatment with beta interferon
    • “defined as 1 relapse in the previous year and magnetic resonance imaging (MRI) evidence of disease activity”
      
      
• rapidly evolving severe (RES) relapsing–remitting disease (7):
  • defined by two or more disabling relapses in one year and one or more gadolinium-enhancing lesions on brain MRI or a significant increase in T2 lesion load compared with a previous MRI
    
    
• Clinically isolated syndrome (CIS) was not included in the initial MS clinical descriptors
  • now recognized as the first clinical presentation of a disease that shows characteristics of inflammatory demyelination that could be MS, but has yet to fulfill criteria of dissemination in time
  • natural history studies and clinical trials of MS disease-modifying therapies have shown that CIS coupled with brain MRI lesions carries a high risk for meeting diagnostic criteria for MS
    
    
• cause of MS is unknown
  • believed that an abnormal immune response to environmental triggers in people who are genetically predisposed results in immune-mediated acute, and then chronic, inflammation
  • initial phase of inflammation is followed by a phase of progressive degeneration of the affected cells in the nervous system

Treatment aims to:

• reduce the severity and frequency of relapses
  • possible treatment options for relapsing and remitting multiple sclerosis include beta interferon, glatiramer acetate, fingolimod, natalizumab and teriflunomide
  • siponimod is an option for treating secondary progressive multiple sclerosis
• limit persistent disability
• relieve symptoms
• promote tissue repair

Reference:

1. Murray TJ. Diagnosis and treatment of multiple sclerosis. BMJ 2006; 332: 525-7.
2. NICE (June 2022).Multiple sclerosis in adults: management
3. NICE (November 2019). Teriflunomide for treating relapsing-remitting multiple sclerosis
4. MS Society Multiple Sclerosis Incidence, and Prevalence in the UK’. 2024
5. Lublin FD et al. Defining the clinical course of multiple sclerosis - The 2013 revisions.Neurology. 2014 Jul 15; 83(3): 278–286.
6. NHS England (2014). Clinical Commissioning Policy: Disease Modifying Therapies for Patients with Multiple Sclerosis (MS)
7. NHS England (June 2023). Treatment Algorithm for Multiple Sclerosis Disease-ModifyingTherapies