Paediatric multiple sclerosis

What it is

Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system, in which the immune system targets oligodendrocyte myelin in the brain, spinal cord and optic nerves. POMS shares the underlying biology with adult-onset MS — including the genetic risk loci (HLA-DRB1*15:01 most prominent), the environmental risk factors (low vitamin D, Epstein-Barr virus, smoking exposure, obesity) and the relapsing-remitting natural history — but with some differences: a higher early relapse rate, more brainstem involvement at onset, less involvement of the spinal cord at onset, and a slower transition to secondary progressive MS.

How it presents

Adolescents most often present with one of:

• Optic neuritis — pain on eye movement followed by visual loss; usually unilateral
• Transverse myelitis — sensory level, sphincter disturbance, weakness; usually short rather than longitudinally extensive (which would suggest MOGAD or AQP4-NMOSD)
• Brainstem or cerebellar syndrome — diplopia (internuclear ophthalmoplegia in the older adolescent), vertigo, ataxia, facial sensory disturbance
• Hemiparesis or sensory disturbance from a single white-matter lesion
• Fatigue, cognitive symptoms (concentration, memory) and depression — common but often missed early
• Encephalopathy is rare in adolescent POMS — its presence should prompt re-evaluation for ADEM, MOGAD or autoimmune encephalitis

Diagnosis

The 2017 McDonald criteria require dissemination of demyelinating lesions in space and time, which can now be established at a single MRI (if multiple lesions of different ages are present and oligoclonal bands are detected in CSF). The 2013 IPMSSG paediatric modifications give specific guidance for the under-18s: dissemination in time can be met with a follow-up MRI showing new lesions, or a positive CSF (oligoclonal bands/elevated IgG index) in the absence of typical alternative diagnoses.

Key differential — MOGAD and AQP4-NMOSD — should always be excluded with cell-based assays. Increasingly, MOG-IgG-positive disease accounts for many cases that previously would have been labelled paediatric MS or relapsing-remitting ADEM.

Investigations: MRI brain and spine with contrast, optical coherence tomography (OCT) of the retinal nerve fibre layer, CSF (cells, protein, oligoclonal bands, IgG index), MOG-IgG and AQP4-IgG by CBA, vitamin D, B12, basic autoimmune screen.

Treatment of relapses

Acute relapse management is similar to adult MS:

• IV methylprednisolone 30 mg/kg/day (max 1 g) for 3–5 days, with or without short oral taper. Long oral tapers (used in MOGAD and ADEM) are not needed in MS
• Plasma exchange or IVIG in steroid-refractory severe relapses

Disease-modifying therapy (DMT)

DMT choice in POMS has shifted dramatically in the last 5 years from a 'start low, escalate if needed' approach to a 'start high if disease is active' approach. The PARADIGMS Phase 3 trial (Chitnis et al. 2018) showed fingolimod superior to interferon beta-1a in paediatric MS, and observational data from international cohorts now support high-efficacy first-line treatment.

• First-line for active disease: high-efficacy agents — ocrelizumab (B-cell depletion, IV every 6 months), ofatumumab (subcutaneous monthly), natalizumab (IV monthly, only if JCV-antibody-negative), fingolimod (oral daily, paediatric-licensed for ages 10+)
• Older first-line options (interferons, glatiramer acetate) — increasingly reserved for mild disease
• Other oral DMTs (teriflunomide, dimethyl fumarate, diroximel fumarate, ponesimod) — less paediatric data; used as second-line in some regions
• Cladribine — used in some centres for highly active disease in older adolescents; rebound is a concern
• Stem cell transplantation (autologous haematopoietic) — reserved for severe, treatment-refractory POMS; emerging evidence

Multidisciplinary care

Modern POMS care goes well beyond the DMT:

• Cognitive and educational assessment at diagnosis and periodically; Educational Health Care Plan / IEP when needed
• Mental-health screening at every visit — anxiety and depression rates are at least double the general adolescent population
• Physiotherapy and occupational therapy
• Vitamin D — supplement to maintain serum 25-OH-D above 75 nmol/L (some specialists target higher)
• Lifestyle — smoking avoidance, healthy weight, regular exercise; all influence long-term outcome
• Vaccinations — bring up to date before starting B-cell-depleting therapy; live vaccines should be avoided during these treatments
• Transition planning to adult MS services from age 16

Prognosis

With high-efficacy DMT and modern multidisciplinary care, most adolescents with POMS achieve very low annualised relapse rates and stable MRIs over the first decade. However, even with controlled relapses, cognitive symptoms and fatigue can affect education and quality of life; the long-term concern remains the eventual transition to secondary progressive disease — which now appears later, but at a younger absolute age than adult-onset MS. Mental health and family support are central.

How an educational review can help

POMS families have to make rapid, high-stakes decisions about DMT choice in the first weeks after diagnosis. An educational review can pull together the current evidence for high-efficacy first-line treatment, summarise where the trials stand, and help you prepare focused questions for your treating MS team — particularly around treatment choice, monitoring, vaccinations and cognitive/educational support.

It is an educational second opinion — not a diagnosis, treatment or prescription — and it does not replace the care of your child's own clinicians.