Lucan · Conditions

Multiple sclerosis

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Australian guidance: eTG Neurology — MS + MS Australia clinical resources

1. Definition and epidemiology

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system characterised by inflammation, demyelination, axonal loss, and gliosis occurring at multiple sites and at different points in time. Australia has one of the highest MS prevalence rates globally, with approximately 33,000 Australians affected; the prevalence increases with distance from the equator, consistent with a latitude gradient attributable in part to vitamin D insufficiency and reduced ultraviolet B exposure. Onset typically occurs between 20 and 40 years of age and MS is approximately twice as common in women as in men.

2. Pathophysiology

Per Robbins Ch 28, MS is characterised by perivenular infiltrates of T lymphocytes and macrophages that breach the blood-brain barrier and mount an autoimmune attack against myelin and oligodendrocytes in the white matter of the brain, spinal cord, and optic nerves. CD4+ Th1 and Th17 cells are the principal effectors; they release interferon-gamma, interleukin-17, and tumour necrosis factor, which activate microglia and promote oligodendrocyte apoptosis. The resulting demyelinating plaques, which are sharply demarcated from surrounding white matter, impair saltatory conduction along affected axons, producing the clinical deficits of an acute relapse. Early plaques are hypercellular and show partial sparing of axons; with repeated attacks, chronic plaques develop in which axons are lost as well, producing irreversible neurological disability. Remyelination can occur in the early stages of disease, partly explaining clinical recovery after a relapse, but becomes progressively less effective as oligodendrocyte precursor pools are depleted. The predilection sites for plaques are periventricular white matter, corpus callosum, optic nerves, brainstem, cerebellum, and spinal cord dorsal columns.

3. Clinical presentation and diagnostic criteria

MS presents with episodic or progressive neurological deficits reflecting the anatomical location of plaques. Common presenting features include optic neuritis (painful monocular visual loss with a relative afferent pupillary defect), internuclear ophthalmoplegia (impaired adduction ipsilateral to the lesion with nystagmus of the contralateral abducting eye), spastic paraparesis or monoparesis, sensory disturbance (tingling, numbness, or the Lhermitte phenomenon, an electric shock sensation radiating down the spine on neck flexion), cerebellar ataxia, and bladder dysfunction. The McDonald 2017 criteria, used in Australia and internationally, require demonstration of dissemination in space (DIS) and dissemination in time (DIT) using clinical episodes, MRI lesion characteristics, or cerebrospinal fluid (CSF) findings. Clinically isolated syndrome (CIS) is a first demyelinating episode that does not yet fulfil MS criteria; the risk of conversion to MS is substantially higher when MRI lesions are present at the time of CIS.

4. Investigations and AU-specific cutoffs

Investigations aim to confirm the diagnosis per McDonald 2017 criteria and to exclude mimics:

  1. MRI brain and spine: The single most important investigation. Gadolinium-enhancing lesions indicate active inflammation and fulfil DIT when combined with non-enhancing T2 lesions at the same scan; T2/FLAIR hyperintensities in at least two of four characteristic locations (periventricular, cortical or juxtacortical, infratentorial, spinal cord) fulfil DIS. MS Australia and eTG support MRI as the primary diagnostic tool.
  2. CSF analysis: Oligoclonal IgG bands (OCBs) on isoelectric focusing are present in over 90% of patients with MS and absent from serum; their presence can fulfil DIT in a patient with DIS on MRI. A mildly elevated total protein and pleocytosis of fewer than 50 white cells per microlitre are supportive but non-specific.
  3. Visual evoked potentials (VEPs): Delayed P100 latency documents previous demyelination of the optic nerve when MRI does not show a corresponding lesion, helping to fulfil DIS.
  4. Serum AQP4-IgG (aquaporin-4 antibody) and MOG-IgG (myelin oligodendrocyte glycoprotein antibody): Mandatory to exclude neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease before committing to an MS diagnosis and initiating disease-modifying therapy (DMT). AQP4-IgG is highly specific for NMOSD; a positive result changes management substantially. These tests are available through major Australian laboratories including PathWest, Melbourne Pathology, and Sullivan Nicolaides.
  5. Bloods: Full blood count, ESR, CRP, ANA, anti-dsDNA, ANCA, B12, folate, syphilis serology (RPR/TPPA), HIV, and thyroid function to exclude systemic lupus erythematosus, vasculitis, B12 deficiency, neurosyphilis, and HIV-associated neurological disease as MS mimics. Vitamin D (25-OH-D) is checked at baseline given the epidemiological association between low vitamin D and MS risk and activity.

5. Management

Management of MS in Australia follows eTG Neurology and MS Australia clinical guidance and encompasses acute relapse treatment, long-term disease-modifying therapy, and symptomatic management.

Acute relapses causing functional impairment are treated with a short course of high-dose corticosteroids, typically methylprednisolone 1 g intravenously daily for 3 to 5 days; this hastens recovery but does not alter the degree of ultimate neurological recovery or long-term disease trajectory. Oral methylprednisolone at equivalent high dose is an acceptable alternative for selected patients per MS Australia guidance. Plasmapheresis (plasma exchange) is used as a rescue therapy for severe steroid-refractory relapses.

Disease-modifying therapy should be initiated early after a definitive MS diagnosis, or after a CIS episode with high-risk features such as multiple MRI lesions, in line with the treat-to-target strategy endorsed by MS Australia. The choice of DMT depends on disease activity, patient values, family planning, comorbidities, and the risk tolerance for adverse effects. Regular MRI surveillance (typically 6 to 12 monthly during initial treatment) and clinical assessment guide dose escalation or switching if breakthrough disease occurs.

6. Pharmacology and AU PBS notes

Disease-modifying therapies are funded through the PBS under authority prescriptions requiring a confirmed MS diagnosis; specialist (neurologist) initiation is required for most agents.

Moderate-efficacy DMTs (first-line): - Interferon beta-1a (Avonex 30 micrograms IM weekly; Rebif 44 micrograms SC three times weekly): PBS Authority. Reduce relapse rate approximately 30%. Adverse effects include injection-site reactions and flu-like symptoms. - Glatiramer acetate (Copaxone 20 mg SC daily or 40 mg SC three times weekly): PBS Authority. Induces regulatory T cells. Adverse effects include injection-site lipoatrophy. - Teriflunomide (Aubagio 14 mg orally once daily): PBS Authority. Teratogenic; mandatory cholestyramine washout before pregnancy. - Dimethyl fumarate (Tecfidera 240 mg orally twice daily): PBS Authority. Monitor lymphocyte count; PML risk with severe lymphopenia.

High-efficacy DMTs (second-line or highly active disease): - Natalizumab (Tysabri 300 mg IV monthly): PBS Streamlined Authority. Anti-VLA4 integrin; blocks lymphocyte trafficking across the blood-brain barrier. JCV antibody index monitored every 6 months; extended interval dosing reduces PML risk in seropositive patients. - Ocrelizumab (Ocrevus 600 mg IV every 6 months): PBS Authority for relapsing and primary progressive MS. Anti-CD20 B-cell depleting. Screen hepatitis B and tuberculosis before initiation. - Fingolimod (Gilenya 0.5 mg orally daily): PBS Authority. Sphingosine-1-phosphate receptor modulator. First-dose cardiac monitoring required for bradycardia; ophthalmology review for macular oedema. - Alemtuzumab (Lemtrada 12 mg IV 5 days year 1, 3 days year 2): PBS Authority after failure of at least one other DMT. Monthly monitoring for autoimmune thyroid disease, immune thrombocytopenia, and nephritis for 48 months after last dose.

7. Complications and monitoring

Secondary progressive MS (SPMS) develops in approximately 65 to 80% of patients with relapsing-remitting MS over 25 years, characterised by a gradual accumulation of disability without clear relapses; most available DMTs have limited efficacy once the progressive phase is established. Primary progressive MS (PPMS) occurs in approximately 15% of patients and is treated with ocrelizumab, the only DMT with demonstrated efficacy in PPMS.

Key complications requiring surveillance include:

Practise this in Lucan

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.