What clinical symptoms and diagnostic findings should be sought in a patient with multiple sclerosis?

Clinical Symptoms and Diagnostic Findings in Multiple Sclerosis

Multiple Sclerosis (MS) diagnosis requires evidence of dissemination in space and time, with no better explanation for symptoms, as outlined in the McDonald criteria and MAGNIMS consensus guidelines. 1

Key Clinical Symptoms to Seek

Neurological Presentations

• Visual Disturbances

  • Unilateral optic neuritis with pain on eye movement
  • Blurred vision or vision loss
  • Prominent papilledema/papillitis during acute episodes 2
  • Internuclear ophthalmoplegia (failure of ipsilateral eye adduction and contralateral eye abduction nystagmus) 3, 4

• Motor and Sensory Symptoms

  • Weakness in limbs (typically asymmetric)
  • Numbness and tingling sensations
  • Partial myelitis
  • Spasticity 5

• Balance and Coordination Issues

  • Incoordination
  • Imbalance and gait dysfunction (present in 50-80% of patients) 6
  • Cerebellar symptoms (ataxia, tremor)

• Brainstem Symptoms

  • Internuclear ophthalmoplegia
  • Nystagmus (gaze-evoked or pendular) 4
  • Dysarthria
  • Vertigo

• Bladder and Bowel Dysfunction

  • Urinary urgency, frequency, or incontinence
  • Erectile dysfunction (may become permanent after myelitis) 2

• Other Characteristic Symptoms

  • Fatigue (common and often debilitating)
  • Heat sensitivity worsening symptoms
  • Lhermitte's sign (electric shock sensation down spine with neck flexion)
  • Cognitive impairment
  • Area postrema syndrome (intractable nausea, vomiting, or hiccups) 2

Diagnostic Findings

Imaging

• Brain MRI (mandatory sequences) 1

  • Axial T1-weighted sequences
  • Axial T2-weighted sequences
  • Proton-density or T2-FLAIR sequences
  • Sagittal 2D or isotropic 3D T2-FLAIR sequences
  • Gadolinium-enhanced T1-weighted sequences (5-minute delay after injection)
  • Look for:
    • Periventricular lesions
    • Juxtacortical lesions
    • Infratentorial lesions
    • Spinal cord lesions

• Spinal Cord MRI (indicated for) 1

  • Patients with spinal symptoms
  • Inconclusive brain MRI findings
  • Strong clinical suspicion with normal brain MRI
  • Primary progressive MS presentation
  • Look for:
    • Longitudinally extensive spinal cord lesions (≥3 vertebral segments)
    • Conus medullaris lesions (especially at onset) 2

Laboratory Tests

• Cerebrospinal Fluid Analysis 1

  • Cell count and differential
  • Protein and glucose
  • Oligoclonal IgG bands (positive in 85-95% of MS patients)
  • IgG index
  • Neutrophilic pleocytosis or WCC > 50/μl may suggest MS 2
  • Absence of CSF-restricted oligoclonal bands may argue against MS diagnosis in European populations 2

• Evoked Potentials

  • Visual evoked potentials (VEP) - characteristic delayed but well-preserved waveform 1
  • Can provide objective evidence of a second lesion when clinical examination doesn't show evidence of visual pathway involvement

• Other Laboratory Tests

  • Complete blood count
  • Comprehensive metabolic panel
  • Inflammatory markers (ESR, CRP) to rule out infection and other conditions 1
  • MOG-IgG and AQP4-IgG testing to rule out other demyelinating disorders 2

Diagnostic Algorithm

1. Establish clinical evidence of CNS demyelination

   • Document at least one typical MS attack
   • Objective clinical evidence of at least one CNS lesion

2. Demonstrate dissemination in space

   • MRI evidence of lesions in at least two of four areas: periventricular, juxtacortical, infratentorial, or spinal cord
   • Or additional clinical attacks implicating different CNS sites

3. Demonstrate dissemination in time

   • New T2 or gadolinium-enhancing lesions on follow-up MRI
   • Simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions
   • Or a second clinical attack

4. Rule out alternative diagnoses

   • Consider MOG encephalomyelitis, neuromyelitis optica, ADEM, and other MS mimics
   • Look for "red flags" that suggest alternative diagnoses 2

Important Considerations

• Disease Patterns to Recognize

  • Relapsing-remitting MS (most common): discrete episodes with stable periods between attacks
  • Primary progressive MS: insidious worsening without discrete relapses
  • Secondary progressive MS: initial relapsing course followed by steady progression 7

• Complications to Monitor

  • Progressive multifocal leukoencephalopathy (PML) risk with certain treatments 8, 9
  • Macular edema (especially with fingolimod) 8
  • Increased risk of infections 1
  • Hypothalamus-pituitary-adrenal axis dysfunction 1
  • Vitamin D deficiency 1

• Follow-up Recommendations

  • Neurology follow-up within 1-2 weeks of diagnosis
  • Repeat MRI in 3-6 months to assess for new lesions and treatment response 1
  • Regular monitoring for treatment complications

By systematically evaluating these clinical symptoms and diagnostic findings, clinicians can effectively diagnose MS and differentiate it from other demyelinating disorders.