Multiple sclerosis is an acquired, chronic, immune-mediated, inflammatory disease of the brain and the spinal cord characterized by the presence of multiple discrete areas of myelin loss within the CNS and subsequent axonal degeneration.
It affects more women than men; however, men are more likely to have a malignant clinical course.
A multiple sclerosis attack is usually characterized by any neurological disturbance with minimum 24 hours duration in the absence of fever or infection.

Multiple%20sclerosis Diagnosis


  • Consider sending patient to a neurologist who is experienced in diagnosing multiple sclerosis
  • There is no single test diagnostic for multiple sclerosis
    • Differential and succeeding workup must be directed by the atypical clinical or paraclinical findings or red flags which are specific to each condition
  • Multiple sclerosis is defined clinically by:
    • Evidence from history and examination
    • Neurological investigations show lesions within the central nervous system that are disseminated in time and space

McDonald Criteria for Demonstration of Dissemination in Space and Time by MRI in a Patient with a Clinically Isolated Syndrome (CIS)1

  • Dissemination in space is demonstrated by ≥1 symptomatic or asymptomatic T2-hyperintense lesion(s) in ≥2 of 4 CNS areas: Periventricular, cortical or juxtacortical, infratentorial, spinal cord
  • Dissemination in time is demonstrated by:
    • A new T2-hyperintense and/or gadolinium-enhancing lesion on follow-up MRI, compared to a reference or a baseline MRI, irrespective of the timing of the baseline scan or
    • Simultaneous presence of gadolinium-enhancing and non-enhancing symptomatic or asymptomatic lesions at any time

McDonald Criteria for Diagnosis of Multiple Sclerosis 2017 in Patients with an Attack at Onset1

  • Should only be applied to patients presenting with a typical CIS suggestive of multiple sclerosis or patients presenting with symptoms consistent with central nervous system inflammatory demyelinating disease


  • ≥2 attacks and objective clinical evidence of ≥2 lesions; no additional tests are required to demonstrate dissemination in space and time
  • ≥2 attacks and an objective clinical evidence of 1 lesion with historical evidence of a prior attack implicating a different site; no additional tests are required to demonstrate dissemination in space and time
  • ≥2 attacks and an objective clinical evidence of 1 lesion and dissemination in space demonstrated by 1 of these criteria:
    • Magnetic resonance imaging based on McDonald Criteria or
    • Further clinical attack implicating a different site
  • 1 attack and objective clinical evidence of  ≥2 lesions and dissemination in time demonstrated by 1 of these criteria:
    • Magnetic resonance imaging based on McDonald Criteria or
    • Demonstration of cerebrospinal fluid-specific oligoclonal bands or
    • Second clinical attack
  • 1 attack and an objective clinical evidence of 1 lesion and with dissemination in space and time
    • Dissemination in space demonstrated by 1 of these criteria:
      • Magnetic resonance imaging based on McDonald Criteria or
      • Second clinical attack implicating a different central nervous system site 
    • Dissemination in time demonstrated by 1 of these criteria:
      • Magnetic resonance imaging based on McDonald Criteria or
      • Demonstration of cerebrospinal fluid-specific oligoclonal bands or
      • Second clinical attack

McDonald Criteria for Diagnosis of Primary-Progressive Multiple Sclerosis (PPMS) 20171

  • 1 year of disease progression plus
  • 2 of 3 from the following brain imaging criteria:
    • ≥1 T2-hyperintense lesions in at least 1 area characteristic for multiple sclerosis (periventricular, cortical or juxtacortical or infratentorial)
    • ≥2 T2-hyperintense lesions in the spinal cord
    • Evidence of cerebrospinal fluid-specific oligoclonal bands

 1 Modified from: Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162-173.


Clinical Types of Multiple Sclerosis

Clinically Isolated Syndrome (CIS)

  • An episode of neurological symptoms which are suggestive of multiple sclerosis usually involving the cerebral hemispheres, optic nerves, cerebellum, brainstem or spinal cord 

Relapsing-Remitting Multiple Sclerosis (RRMS) 

  • Patient experiences cycles of relapse and remission
    • Relapses are characterized by acute worsening of neurologic function
    • Relapses are followed by periods of remission with no or minimal disease progression
  • Patient may suffer residual deficit from relapse

Secondary-Progressive Multiple Sclerosis (SPMS)

  • At onset of multiple sclerosis, patient experiences relapsing-remitting multiple sclerosis
  • This is followed by progression with or without sporadic relapses, plateaus and minor remissions
  • Most patients who start with relapsing-remitting multiple sclerosis  will eventually convert to progressive disease

Primary-Progressive Multiple Sclerosis (PPMS)

  • Patients present with continuous worsening of disease
  • Patient may have temporary minor improvements, acute relapses or plateaus
  • Further characterized at different points in time as either:
    • Primary-progressive multiple sclerosis with active disease in patients with progressive disease from onset with acute attack and/or evidence of new magnetic resonance imaging activity or 
    • Primary-progressive multiple sclerosis not active disease with progressive disease from onset without acute attacks or relapses and no magnetic resonance imaging activity

Phenotype Classification of Multiple Sclerosis

  • Disease activity is defined as clinical relapses and/or neuroimaging changes (new/unequivocally enlarging T2 lesions or gadolinium-enhancing lesions) evaluated at least once yearly
  • Progressive disease spectrum includes both primary and secondary-progressive multiple sclerosis
    • Progressive multiple sclerosis can be at onset or transitioned from relapsing forms
    • Progression is determined by at least once yearly clinical evaluation

Clinically Isolated Syndrome (CIS)

  • Active or Not active

Relapsing-Remitting Multiple Sclerosis (RRMS)

  • Active or Not active

Progressive Multiple Sclerosis 

  • Active with or without progression
  • Not active with or without progression (stable)


History and Physical Exam

  • Identify multiple sclerosis-related events
  • Evaluate mental, emotional, language functions, balance, vision, hearing, sense of smell, sense of touch, sense of taste


Magnetic Resonance Imaging (MRI)

  • Preferred imaging of brain to detect the presence of lesions, plaques or scars caused by multiple sclerosis
  • More sensitive and specific for predicting evolution to clinically definite multiple sclerosis than other studies (eg computed tomography scan, evoked potential studies, cerebrospinal fluid analysis)
  • Confirms dissemination in space and time typically found in multiple sclerosis

Computed Tomography

  • Used only to exclude alternative diagnosis


Evoked Potential Studies 

  • Visual evoked potential (VEP) is the initial and most useful method; clinically silent lesions are identified in the visual, brainstem and spinal cord pathways 
  • May identify patients with clinically definite multiple sclerosis and may also confirm dissemination in space 
  • Considered positive if visual evoked potential is delayed but with well-preserved wave form

Lumbar Puncture 

  • Usually needed to establish diagnosis in atypical presentations  
  • Considered positive for multiple sclerosis if evidence of ≥2 oligoclonal bands is present in the cerebrospinal fluid (CSF) and not in serum
  • Positive findings can provide supportive evidence that the underlying disorder is inflammatory demyelinating


  • Relapse of acute attack of multiple sclerosis is suspected if the patient develops a new symptom or has worsening of existing symptoms which last for >24 hours in the absence of infection or not attributable to other cause after a stable period of at least 1 month
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