Multiple sclerosis - clinical fact sheet and MCQ

Overview

Multiple sclerosis (MS) is a chronic, immune-mediated condition affecting the central nervous system (CNS). It is characterised by inflammation, demyelination, and neurodegeneration, primarily affecting the brain and spinal cord. 

MS manifests in a variety of forms:

• relapsing–remitting MS (RRMS) is the most common at onset (85% of cases)
  • over time, some people with RRMS develop secondary progressive MS (SPMS)
• primary progressive MS (PPMS; 5-15%), is a less common presentation
  • neurodegeneration rather than inflammation is the primary driver of progression
  • typically presents with fewer active lesions on MRI  but more extensive atrophy, particularly in spinal cord and brain
  • more common in middle-aged men
• clinically isolated syndrome (CIS) refers to a single clinical attack of the nervous system that does not meet the criteria of MS

• • not all patients with CIS go on to develop MS

The disease course is highly variable, ranging from benign to rapidly progressive. MS predominantly affects women (3:1 ratio), with a typical onset between 20 and 40 years of age.

In Australia and New Zealand, the prevalence of MS has risen to 131.1 per 100,000 in 2021, a 30% increase from 2017, potentially due to improved diagnosis, increased exposure to risk factors, and improved life expectancy for people with MS. Although MS is incurable, advances in disease-modifying therapies (DMTs), multidisciplinary care, and symptom management have significantly improved long-term outcomes.

Diagnosis of multiple sclerosis

Timely diagnosis is essential in order to initiate DMTs early and minimise irreversible disease progression. The 2017 criteria of MS diagnosis requires proof that inflammatory/demyelinating events have occurred in ≥ 2 separate locations in the central nervous system at ≥ 2 time points. (McDonald criteria of ‘dissemination in time’ and ‘dissemination in space’). 

In 2024, these criteria were revised and are yet to be confirmed. They remove the dissemination in time requirement if more than four areas are affected, and add the optic nerve as a separate affected area as well as providing guidance on incorporation of new MRI technology and biomarkers. These changes may offer clinicians the ability to diagnose MS earlier. 

An attack or a relapse usually has a temporal evolution, often reaching a peak of intensity over one to two weeks then remitting over another one to two weeks. Symptoms may completely resolve or may leave residual deficits.

Relapses occur in distinct regions of the CNS and usually have localised neurological signs.

1. Common presenting symptoms:

• ocular involvement (eg monocular optic neuritis: pain with eye movement, monocular loss or reduction of vision/loss of colour vision)
• sensory symptoms (eg paraesthesia, dysaesthesia, pain)
• altered sensation or pain travelling down the back and sometimes into the limbs when bending the neck forward (Lhermitte’s sign)
• motor dysfunction (eg weakness, spasticity, speech and swallowing difficulties)
• fatigue
• gait or balance disturbances, vertigo
• bladder/bowel dysfunction and incontinence
• cognitive impairment (early or progressive)

2. Differential diagnoses:

• migraine with aura
• stroke/TIA
• neuromyelitis optica spectrum disorder
• acute disseminated encephalomyelitis
• amyotrophic lateral sclerosis
• cerebral neoplasms (primary and secondary)
• peripheral neuropathy (e.g. due to diabetes, B12 deficiency)
• cervical spondylotic myelopathy
• functional neurological disorder
• non-specific symptoms with abnormal MRI 

3. Red flags suggesting an alternative diagnosis:

• peripheral nervous system involvement
• systemic symptoms (fever, weight loss)
• sudden, severe onset of symptoms
• persistent headaches or seizures without other typical MS features

4. Risk factors for multiple sclerosis:

• genetic predisposition (family history of MS)
• female gender (two to three times more likely)
• living in higher latitudes, i.e. further from the equator (thought to be due to reduced UV exposure)
• low serum vitamin D
• Epstein–Barr virus infection
• smoking
• adolescent obesity

5. Initial assessment of multiple sclerosis in general practice

• History: document timing, nature and evolution of neurological symptoms
• Neurological examination: focus on cranial nerves, motor and sensory function, coordination, reflexes and gait
• Basic blood tests: exclude mimics such as vitamin B12 deficiency, infection, autoimmune disease
• Look for the presence of any neurological red flags warranting referral to the emergency department, such as any patients with acute onset or subacute rapidly progressive neurological symptoms, including:
  • • ataxia or gait disorder
    • vertigo 
    • muscle weakness, including limbs, bulbar or neck muscles
    • visual loss or diplopia
• Non-urgent cases of suspected MS should be referred to a neurologist for early assessment and diagnosis
• MRI of brain and spinal cord with post-gadolinium sequences is the investigation of choice for suspected MS (usually requested by a neurologist due to MBS restrictions)
• Other investigations that may be carried out by neurologists to support a diagnosis of MS include lumbar puncture with CSF analysis and evoked potential studies
  
  

Management

Management of multiple sclerosis requires an individualised, multidisciplinary approach focused on disease modification, relapse management, and symptom control.

Role of the GP:

• early identification and referral to a neurologist
• ongoing coordination with specialist and allied health teams
• chronic disease management planning
• monitoring for comorbidities (eg depression, cardiovascular disease)
• preventative health: vaccinations, screening for malignancy, smoking cessation, weight management

1. Disease-modifying therapies (DMTs)

Disease modifying therapies are most commonly prescribed for RRMS. Early initiation is critical as they reduce relapse rates and delay progression in RRMS. Initiated and managed by neurologists, there are escalation and induction strategies depending on disease severity and patient preference. 

Some examples of DMTs include natalizumab, ocrelizumab, ofatumumab and cladribine.

Additional considerations on the use of DMTs including counselling, pre-treatment screening, drug selection, and monitoring, may be found here.

GPs may assist with risk mitigation and monitoring, including:

• monitoring for adverse effects of DMTs (eg GI symptoms, hepatotoxicity, lymphopenia, opportunistic infections)
• monitoring for signs of disease activity (eg acute clinical relapses)
• monitoring for progression of disability 

Cancer screening
For all people with MS receiving DMT, standard age-appropriate national cancer screening guidelines should be followed. This is particularly important as immunosuppressive DMTs may be associated with an increased risk of malignancy.

In addition to this:

• patients on sphingosine-1-phosphate receptor modulators should also be screened at least annually for cutaneous malignancy
• women on immunosuppressive DMTs should also be considered for cervical cancer screening with an HPV test every three years

Vaccinations
While on immunosuppressive DMT, all patients should be up to date with the relevant national immunisation schedule including annual influenza and COVID-19 vaccinations.

In general, live and live-attenuated vaccines should not be administered during treatment with immunosuppressive DMTs. 

2. Relapse management   

Acute relapses should be evaluated with an MRI with gadolinium but should not delay treatment. Relapses may be treated with high-dose corticosteroids (oral or intravenous) once infection has been excluded and after discussion with the treating neurologist.

3. General lifestyle measures and management of comorbidities:

• regular exercise is important and can improve cardiorespiratory fitness and quality of life
• supporting smoking cessation (cigarette smoking is associated with accelerating the progression of MS, higher rates of disability and more frequent relapses)
• cardiovascular risk factor control (BP, lipids, smoking)- as people with MS have a higher risk of cardiovascular disease than the general population
• screening for osteoporosis and promoting bone health through adequate safe sun exposure and Vitamin D supplementation where required (due to increased risk of osteoporosis in people with MS)

4. Symptom management 

GPs may provide advice on symptom management or coordinate referral with other services as appropriate. Support from a multidisciplinary team of allied health professionals with experience in working with people with MS is recommended.

• Fatigue: energy conservation strategies, cognitive behavioural therapy, exercise
• Pain and spasticity: baclofen, gabapentinoids, physiotherapy
• Bladder dysfunction: anticholinergics, referral to urology
• Mood and cognition: regular mental health screening, referral to psychologist and/or antidepressants where appropriate
• Mobility and falls: physiotherapy, occupational therapy input
  
  

References

1. Shipey J, Beharry J, Yeh W , et al. Consensus recommendations for multiple sclerosis management in Australia and New Zealand: part 1. Med J Aust. 2025; 222(7):356-364
2. Shipey J, Beharry J, Yeh W, et al. Consensus recommendations for multiple sclerosis management in Australia and New Zealand: part 2. Med J Aust. 2025; 222(7):365-371.
3. American Academy of Ophthalmology. Multiple Sclerosis. 2024. Available at: https://eyewiki.org/Multiple_Sclerosis. (last accessed June 2025).
4. MS Australia. What is Multiple Sclerosis (MS)? 2025. Available at: https://www.msaustralia.org.au/what-is-multiple-sclerosis-ms/. (last accessed June 2025).
5. MS Australia. Unravelling the causes of MS. 2023. Available at: https://www.msaustralia.org.au/unravelling-the-causes-of-ms/. (last accessed June 2025).
6. Solomon, Andrew J et al.. Differential diagnosis of suspected multiple sclerosis: an updated consensus approach. The Lancet Neurology. 2023;22(8):750 - 768.
7. Garber JY, Beadnall HN, Barnett MH. Multiple sclerosis: the role of the GP in diagnosis and lifetime care. Medicine Today. 2020; 21(12): 14-25.
8. SA Health. Neuroimmunology and Multiple Sclerosis (MS) - Adult CPC. 2024. Available at: https://www.sahealth.sa.gov.au/wps/wcm/connect/public+content/sa+health+internet/services/outpatients/cpc/specialities/neurology/neuroimmunology+and+multiple+sclerosis+ms+adult+cpc#:~:text=Referral%20to%20emergency,visual%20loss%20or%20diplopia. (last accessed July 2025). 
9. MS Australia. Key facts & figures about multiple sclerosis. 2021. Available at: https://www.msaustralia.org.au/wp-content/uploads/2023/02/key-facts-and-figures-about-ms_2021.pdf. (last accessed July 2025)

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