What are the typical presentation, differential diagnosis (DDx), investigations (InvX), and management (Mx) of Multiple Sclerosis (MS)?

Multiple Sclerosis: Clinical Presentation, Diagnosis, and Management

Multiple sclerosis (MS) typically presents in young adults (20-30 years) with unilateral optic neuritis, sensory disturbances, partial myelitis, or brainstem syndromes developing over several days, with a female predominance of nearly 3:1 1. Early recognition of MS symptoms is crucial, as prompt diagnosis and treatment with disease-modifying therapies can potentially slow disease progression and improve long-term outcomes 2.

Clinical Presentation

Common Initial Symptoms

• Sensory symptoms:

  • Distal paresthesias or sensory loss starting in one area before progressing to others
  • Often begins in legs and may progress to arms and cranial muscles
  • Typically asymmetrical 2

• Visual disturbances:

  • Optic neuritis occurs in 20-31% of initial MS presentations
  • Associated with visual impairment, scotoma, red-green desaturation
  • Characteristic pain on eye movement 2, 3

• Motor symptoms:

  • Typically start in legs and progress to arms and cranial muscles
  • May include asymmetrical weakness (predominantly proximal or distal) 2

• Other presentations:

  • Internuclear ophthalmoplegia (failure of ipsilateral eye adduction with contralateral eye abduction nystagmus) 3
  • Severe and diffuse pain may precede weakness 2
  • Children under 6 may exhibit nonspecific features (poorly localized pain, refusal to bear weight, irritability) 2

Differential Diagnosis

MS must be distinguished from several conditions that can mimic its clinical or radiological presentation:

1. Neuromyelitis optica spectrum disorders (NMOSD):

   • More severe visual loss with preferential altitudinal field loss
   • Chiasmal and tract lesions more common
   • Requires AQP4-IgG antibody testing 2, 3

2. Acute disseminated encephalomyelitis (ADEM) 2

3. Small vessel disease (especially in patients >50 years) 2

4. MOG-associated encephalomyelitis:

   • Requires MOG-IgG antibody testing 2

5. Leber's hereditary optic neuropathy:

   • Affects young males
   • Painless, subacute visual loss
   • Typically involves both optic nerves 3

6. Chronic relapsing inflammatory optic neuropathy 3

7. Giant cell arteritis (in older patients) 3

Caution: Bilateral simultaneous sensory disturbances are less common in MS and may suggest other conditions. Isolated cranial nerve involvement is rare in MS (10.4%), and isolated eighth nerve palsy is extremely rare (<1%) 2.

Diagnostic Evaluation

McDonald Criteria

Diagnosis requires evidence of:

1. Dissemination in space: Damage in different parts of the nervous system
2. Dissemination in time: Damage occurring at different times
3. No better explanation for the clinical presentation 2

MRI Findings

• Brain lesions:

  • T2-hyperintense lesions (periventricular, juxtacortical, or infratentorial)
  • Gadolinium-enhancing lesions (nodular or ring-enhancing)
  • At least one typical MS lesion in at least two characteristic regions 4, 2

• Spinal cord lesions:

  • Small (≥3mm), covering less than two vertebral segments
  • Usually located in periphery of spinal cord (lateral or dorsal columns)
  • Cigar-shaped on sagittal images and wedge-shaped on axial images 2

MRI Protocol

• Mandatory sequences:
  • Axial T1-weighted sequences
  • Axial T2-weighted and proton-density sequences
  • Sagittal 2D or isotropic 3D T2-FLAIR sequences
  • Single dose gadolinium-based contrast with minimum 5-minute delay 2
  • MRI studies should be performed on scanners with minimum field strength of 1.5T 4

Laboratory Tests

• Basic laboratory tests:

  • Complete blood count, comprehensive metabolic panel
  • Erythrocyte sedimentation rate, C-reactive protein
  • Urinalysis (to rule out infection and alternative diagnoses) 2

• Lumbar puncture (when diagnosis is uncertain):

  • Tests for oligoclonal bands
  • Elevated IgG index
  • Normal cell count and protein levels 2

• Additional testing:

  • Optical coherence tomography (sensitive for detecting subclinical optic nerve changes) 3

Management

Disease-Modifying Therapies (DMTs)

• Nine classes of DMTs available for relapsing-remitting MS and secondary progressive MS with activity
• One DMT (ocrelizumab) approved for primary progressive MS
• DMTs reduce clinical relapses by 29-68% compared to placebo or active comparators 2, 1

Available DMT Classes

1. Interferons
2. Glatiramer acetate
3. Teriflunomide
4. Sphingosine 1-phosphate receptor modulators
5. Fumarates
6. Cladribine
7. Monoclonal antibodies (3 types)
8. Mitoxantrone 1, 5

Relapse Management

• High-dose corticosteroids for acute relapses 3

Symptom Management

• Fatigue and weakness: Rehabilitation, energy conservation strategies
• Spasticity and gait problems: Physical therapy, medications
• Depression and cognitive issues: Counseling, cognitive rehabilitation
• Bladder, bowel, and sexual deficits: Targeted therapies
• Neuropathic pain: Pain management strategies 6

Rehabilitation

• Physical therapy, occupational therapy, and speech therapy to maintain function and independence
• Speech and language therapy, especially communication partner training and intensive treatment approaches 2

Monitoring and Prevention

• Regular monitoring for disease progression and treatment response
• Screening for dysphagia (swallowing difficulties) to prevent complications like aspiration pneumonia
• Early recognition and treatment of flares to prevent long-term disability 2

Important: MS treatments may have adverse effects on vision, including central serous retinopathy with corticosteroid therapy and macular edema with fingolimod 3. Regular monitoring is essential.