Write a short note on multiple sclerosis.

Definition

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system, characterised pathologically by plaques of demyelination with relative axonal preservation, and clinically by episodes disseminated in time and space. It is the commonest cause of non-traumatic neurological disability in young adults in Western countries; it is less common but well recognised in India, where neuromyelitis optica spectrum disorder is relatively more frequent and must be distinguished.

Aetiology

Multifactorial: genetic susceptibility (HLA-DRB1*15:01) interacting with environment — latitude (increasing prevalence with distance from the equator), low vitamin D, Epstein–Barr virus infection, smoking, and obesity in adolescence. Female to male ratio is about 3:1, with peak onset between 20 and 40 years.

Clinical Features

Any CNS white matter site may be affected, so presentations are protean. Characteristic ones are:

• Optic neuritis — the presenting feature in about 20%: subacute unilateral visual loss with pain on eye movement, a relative afferent pupillary defect, and central scotoma. The disc is normal early ("the patient sees nothing and the doctor sees nothing") and becomes pale later.
• Brainstem: diplopia from internuclear ophthalmoplegia (impaired adduction of one eye with nystagmus in the abducting eye — bilateral INO in a young adult is virtually diagnostic of MS), vertigo, facial numbness, trigeminal neuralgia in a young patient.
• Spinal cord: partial transverse myelitis — sensory level, paraparesis, sphincter disturbance, Lhermitte's phenomenon (an electric shock sensation down the spine on neck flexion).
• Cerebellar: ataxia, intention tremor, scanning speech — with nystagmus forming Charcot's triad.
• Sensory: paraesthesiae, numbness, the "useless hand" of Oppenheim.
• Other: fatigue (the commonest and most disabling symptom), bladder urgency and incontinence, sexual dysfunction, cognitive impairment, depression, spasticity and pain.
• Uhthoff's phenomenon — transient worsening of symptoms with a rise in body temperature (hot weather, fever, exercise, hot bath); not a true relapse.

Clinical Course

Diagnosis

Based on demonstrating dissemination in space and time, with no better explanation — the McDonald criteria, which allow MRI evidence to substitute for a second clinical attack, permitting earlier diagnosis.

Investigations:

• MRI brain and spinal cord with gadolinium — the key investigation. Ovoid periventricular lesions perpendicular to the ventricles (Dawson's fingers), juxtacortical, infratentorial and spinal cord lesions. Gadolinium enhancement indicates an active (< 6 weeks old) lesion, and the coexistence of enhancing and non-enhancing lesions demonstrates dissemination in time on a single scan.
• CSF examination: oligoclonal bands present in CSF but not in serum (intrathecal IgG synthesis) in 85–95%; raised IgG index; mild lymphocytic pleocytosis. The presence of oligoclonal bands supports the diagnosis and predicts conversion from a clinically isolated syndrome.
• Visual evoked potentials — delayed latency with preserved amplitude, giving evidence of a previous subclinical optic neuritis.
• Exclude mimics: anti-aquaporin-4 (NMO) and anti-MOG antibodies, vitamin B12, ANA and ENA, ACE (sarcoidosis), HIV, syphilis serology, and where relevant HTLV-1 and Behçet's disease.

Management

1. Acute relapse

• High-dose corticosteroids (intravenous methylprednisolone, or high-dose oral) for 3–5 days — shortens the duration of the relapse but does not alter long-term disability, an important point to state.
• Plasma exchange for severe steroid-refractory relapses.
• Exclude and treat infection (especially urinary), which commonly causes a pseudo-relapse.

2. Disease-modifying therapy (relapsing disease)

• Moderate efficacy: interferon-beta, glatiramer acetate, teriflunomide, dimethyl fumarate.
• High efficacy: natalizumab (risk of progressive multifocal leukoencephalopathy with JC virus positivity), ocrelizumab and rituximab (anti-CD20; ocrelizumab is also approved for primary progressive MS), alemtuzumab, cladribine, fingolimod and siponimod.
• Early use of higher-efficacy therapy is increasingly favoured over escalation.

3. Symptomatic management — where most of the day-to-day benefit lies

• Spasticity: physiotherapy, baclofen, tizanidine, botulinum toxin, intrathecal baclofen.
• Fatigue: exercise, sleep hygiene, treat depression and anaemia; amantadine or modafinil.
• Bladder: anticholinergics for urgency, intermittent self-catheterisation for retention, treat infection.
• Neuropathic pain: gabapentin, pregabalin, carbamazepine (for trigeminal neuralgia), amitriptyline.
• Depression and cognitive impairment; tremor and ataxia; sexual dysfunction; constipation.
• Vitamin D supplementation, smoking cessation, exercise, and vaccination.
• Multidisciplinary rehabilitation, occupational therapy, mobility aids, and carer support.