Multiple Sclerosis (MS)

Definition

• Textbook of Family Medicine 9e, p. 1252
• Bradley and Daroff's Neurology in Clinical Practice, p. 167

Classification / Types

1. Relapsing-remitting MS (RRMS)
   • Most common at onset.
   • Clear attacks (relapses) followed by complete or partial recovery (remission).
2. Secondary progressive MS (SPMS)
   • Initially RRMS, later gradual worsening of disability with or without relapses.
3. Primary progressive MS (PPMS)
   • Continuous neurological deterioration from onset, without distinct relapses.
4. Clinically isolated syndrome (CIS)
   • First episode suggestive of CNS demyelination, for example optic neuritis or transverse myelitis. May later develop into MS.
5. Radiologically isolated syndrome (RIS)
   • MRI lesions typical of MS in a person without neurological symptoms.

Causes / Risk Factors

• Genetic susceptibility, including association with HLA-DRB1
• Autoimmune dysregulation
• Previous Epstein-Barr virus infection
• Low vitamin D level and low sunlight exposure
• Smoking
• Female sex
• Young adult age, usually 20-40 years
• Higher prevalence in temperate regions

Pathophysiology

1. In genetically susceptible individuals, environmental triggers activate autoreactive T lymphocytes and B lymphocytes.
2. These immune cells cross the blood-brain barrier.
3. They attack myelin and oligodendrocytes in the CNS.
4. Inflammation causes demyelination, edema, and plaque formation.
5. Repeated inflammation causes axonal transection, neuronal loss, gliosis, and permanent disability.

• Periventricular white matter
• Optic nerve
• Brainstem
• Cerebellum
• Spinal cord

Clinical Features

Common symptoms

• Optic neuritis: painful loss of vision, impaired color vision, central scotoma
• Diplopia due to internuclear ophthalmoplegia
• Nystagmus
• Limb weakness, spasticity, hyperreflexia
• Numbness, tingling, sensory loss
• Ataxia, tremor, unsteady gait
• Vertigo
• Fatigue
• Lhermitte sign: electric shock-like sensation down spine on neck flexion
• Bladder dysfunction: urgency, frequency, retention, incontinence
• Constipation and sexual dysfunction
• Cognitive slowing, memory impairment
• Depression, anxiety, emotional lability
• Heat sensitivity: symptoms worsen with heat, called Uhthoff phenomenon

• Textbook of Family Medicine 9e, p. 1252

Diagnosis

Principle

• Dissemination in space (DIS): lesions in different CNS regions.
• Dissemination in time (DIT): lesions occurring at different times, or evidence of old and new lesions.

Investigations

1. MRI brain and spinal cord with gadolinium
   • Best investigation.
   • T2/FLAIR: hyperintense demyelinating plaques.
   • Gadolinium-enhancing lesions indicate active inflammation.
   • Common locations: periventricular, juxtacortical/cortical, infratentorial, and spinal cord.
2. CSF analysis
   • Oligoclonal IgG bands
   • Raised IgG index
     These support intrathecal inflammation.
3. Evoked potentials
   • Visual evoked potential may reveal subclinical optic nerve demyelination.
   • Somatosensory and brainstem auditory evoked potentials may also be used.
4. Optical coherence tomography (OCT)
   • Can show retinal nerve fiber layer loss after optic neuritis.
5. Blood tests to exclude mimics
   • Vitamin B12, thyroid profile, ANA, HIV, syphilis testing where appropriate
   • Serum AQP4-IgG and MOG-IgG to exclude neuromyelitis optica spectrum disorder or MOG-associated disease.

• Textbook of Family Medicine 9e, p. 1252

Management

1. Treatment of acute relapse

• High-dose corticosteroids, usually IV methylprednisolone for 3-5 days, or high-dose oral methylprednisolone in selected patients.
• Steroids shorten relapse duration but do not cure MS or prevent long-term progression.
• Plasma exchange may be used for a severe steroid-resistant relapse.

2. Disease-modifying therapy

• Interferon-beta
• Glatiramer acetate
• Teriflunomide
• Dimethyl fumarate
• Fingolimod and other S1P modulators
• Natalizumab
• Ocrelizumab
• Ofatumumab
• Alemtuzumab
• Cladribine

3. Symptomatic treatment

• Spasticity: physiotherapy, stretching, baclofen or tizanidine
• Neuropathic pain: gabapentin, pregabalin, duloxetine, or amitriptyline
• Bladder symptoms: timed voiding, pelvic-floor therapy, antimuscarinic drugs or intermittent catheterization when required
• Fatigue: energy conservation, sleep management, exercise, treat depression or anemia
• Depression/anxiety: counseling and antidepressants where indicated
• Constipation: fluids, fibre, exercise, laxatives if needed
• Sexual dysfunction: counseling and targeted treatment

4. Rehabilitation and preventive care

• Physiotherapy, occupational therapy, speech therapy
• Regular exercise and fall prevention
• Stop smoking
• Adequate vitamin D and balanced nutrition
• Vaccination and infection prevention
• Psychological, social, vocational, and family support

Complications

• Permanent motor disability and wheelchair dependence
• Spasticity and contractures
• Falls and fractures
• Chronic pain
• Neurogenic bladder, recurrent UTI, urinary retention
• Renal damage in severe long-standing bladder dysfunction
• Constipation and fecal incontinence
• Sexual dysfunction
• Cognitive impairment and dementia-like decline
• Depression, anxiety, and suicide risk
• Dysphagia, aspiration pneumonia in advanced disease
• Pressure sores in immobile patients
• Osteoporosis due to immobility and steroid exposure
• Adverse effects of immunosuppressive disease-modifying therapies, including infection risk

One-line conclusion for exam