MS diagnostic criteria
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review of diagnostic criteria for Multiple sclerosis till latest revised 2010 MC Donalds criteria.

review of diagnostic criteria for Multiple sclerosis till latest revised 2010 MC Donalds criteria.

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MS diagnostic criteria Presentation Transcript

  • 1. DIAGNOSTIC CRITERIA MULTIPLE SCLEROSIS
  • 2. Overview
    • Introduction
    • Clinical types
    • Why diagnostic criteria?
    • Criteria for MS
    • Clinically isolated syndromes
    • Variants
  • 3. Multiple Sclerosis
    • One of the most common nontraumatic neurologic cause of disability in young adults
    • Onset in the 2 nd to 5 th decades of life with resultant important socioeconomic repercussions
  • 4. Multiple Sclerosis www.library.med.utah.edu
  • 5. Immunopathogenesis
  • 6. Multiple Sclerosis
    • Pathological hallmark- cerebral/spinal plaque
  • 7. Course
    • Most characteristic clinical course- RELAPSE
    • Acute or subacute onset clinical dysfunction
    • Reaches peak from several days to weeks
    • Followed by remission- partial / complete
    • Minimum duration – 24 hours
    • 15% never experience a relapse
  • 8. Course
  • 9. Need for diagnostic criteria
    • No single clinical feature or diagnostic test is sufficient to diagnose MS
    • Earlier criteria - established to select patients for participation in therapeutic trials
    • Later ones – intended for use by practicing physician
    • Therapeutic implications with novel disease modifying drugs
  • 10. Diagnostic criteria
    • Jean-Martin Charcot
    • -first to delineate diagnostic criteria for MS
    • -triad of nystagmus, intention tremor and scanning speech ( 1868)
  • 11. Diagnostic criteria
    • Schumacher 1965
    • Poser 1983
    • McDonald 2001
    • revisions 2005
    • Most recent 2010
    • MRI
    • Paty 1988
    • Fazekas 1988
    • Barkhof 1997
    • Tintore 2000
  • 12. Schumacher criteria
    • Delineated the requirement of dissemination in time and space for the diagnosis of MS
    • The touchstone for all subsequent diagnostic recommendations
    • Six items required to diagnose clinically definite MS
  • 13. Schumacher criteria
    • Onset at appropriate age (10-50 years)
    • CNS disease predominantly reflects white matter involvement
    • Objective abnormalities of CNS dysfunction on examination
    • History indicating involvement of 2 or more CNS sites
    • Course- attacks > 24 hrs, at least 1 month apart or gradual progression over 6 months
    • No alternative diagnosis
  • 14. Schumacher criteria- Limitations
    • Diagnosis is essentially a clinical one
    • No provision was made for incorporating supportive laboratory data
    • To select patients for participation in therapeutic trials
    • Pertain only to definite MS
    • Stringent criteria excluded some patients with MS
  • 15. Poser et al 1983
    • Workshop on Diagnosis of MS, Washington
    • Need for more exact criteria to conduct therapeutic trials in multicenter programs
    • To conduct epidemiological surveys
    • To evaluate new diagnostic procedures
    • To estimate the activity of disease process
  • 16. Poser et al 1983
    • Expanded the age at onset to 59 yrs
    • Use of data derived from laboratory studies-
    • analysis of CSF
    • evoked potentials
    • neuroimaging
    • Developed to ensure that only patients with MS were included in research studies
  • 17. Poser et al 1983
    • Definitions
    • Attack – occurrence of a symptom(s) of neurological dysfunction,+/- objective confirmation, lasting >24 hrs
    • Paraclinical evidence – demonstration of existence of a lesion of the CNS which has not produced signs, but may or may not have caused symptoms in the past
    • Hot bath test, evoked responses, imaging, urological assessment
  • 18. Poser et al 1983
    • Remission- definite improvement of signs, symptoms or both that has been present for at least 24 hours
    • Laboratory support- examination of CSF for oligoclonal bands and increased IgG
    • Two major groups- definite and probable
    • Each with two subgroups- clinical and lab supported
  • 19. Poser criteria
    • Clinically definite MS (CDMS)
    • Two attacks and clinical evidence of two separate lesions
    • Two attacks; clinical evidence of one lesion and paraclinical evidence of another, separate lesion
    • The two attacks must involve different parts of the CNS, must be separated by a period of at least one month, and must each last a minimum of 24 hrs
  • 20. Poser criteria
    • B) Lab-supported definite MS (LSDMS)
    • Demonstration in CSF of IgG oligoclonal bands (OB) or of increased CNS synthesis of IgG. OB must not be present in patient’s serum and serum IgG level must be normal
    • Two attacks; either clinical or paraclinical evidence of one lesion; and CSF OB/IgG
    • One of the episodes must involve a part of the CNS distinct from that demonstrated by clinical or paraclinical evidence
  • 21. Poser criteria
    • 2) One attack; clinical evidence of two separate lesions; and CSF OB/IgG
    • 3) One attack; clinical evidence of one lesion and paraclinical evidence of another, separate lesion; and CSF OB/IgG
    • Historical information cannot be substituted for the clinical evidence. Both lesions must not have been present at the time of first examination and must be separated by at least one month
  • 22. Poser criteria
    • C) Clinically probable MS (CPMS)
    • Two attacks and clinical evidence of one lesion
    • One attack and clinical evidence of two separate lesions
    • One attack; clinical evidence of one lesion and paraclinical evidence of another, separate lesion
  • 23. Poser criteria
    • D) Lab-supported probable MS (LSPMS)
    • Two attacks and CSF OB/IgG
    • The two attacks must involve different parts of the CNS, must be separated by minimum of one month and must each have lasted at least 24 hrs
  • 24. Poser criteria or
  • 25. Poser criteria
    • Reason- to restrict therapeutic trials and other research protocols to patients with definite MS
    • Category of probable- designed for the purpose of prospectively evaluating new diagnostic methods
    • Lab supported MS- extends the limits; making available larger reservoir of patients for investigative purposes
  • 26. Need for new criteria
    • Poser criteria was utilized widely by clinicians for 20 yrs
    • Continuing technological advances, particularly in MRI, led to greater understanding of the biology of MS
    • Enable earlier and more confident diagnosis
  • 27. MRI criteria
    • To predict conversion to clinically definite multiple sclerosis in isolated demyelinating syndromes
    • Paty et al 1988
    • Fazekas et al 1988
    • Barkhof et al 1997
  • 28. MRI criteria
    • Paty et al (1988)
    • ≥ four lesions, or 3 lesions of which one is periventricular
    • Fazekas et al (1988)
    • ≥ three lesions with 2 of the properties
    • infratentorial location
    • periventricular location
    • lesion > 6 mm
  • 29. MRI criteria
    • Barkhof et al (1997)
    • Gadolinium enhanced lesion or the presence of
    • nine or more T2 lesions
    • One infratentorial lesion
    • One juxtacortical lesion
    • Three periventricular lesions
  • 30. Comparison of MRI criteria
    • Tintore et al (2000)
    • MR imaging parameters proposed by Barkhof et al are more specific and accurate than the criteria proposed by Paty et al or Fazekas et al for predicting conversion to clinically definite multiple sclerosis
  • 31. McDonald criteria
    • National Multiple Sclerosis Society and the International Federation of MS Societies convened a committee in July 2000 to reassess existing diagnostic criteria and to recommend, if necessary, appropriate changes
    • The group, led by W. Ian McDonald, published its recommendations in July 2001
  • 32. McDonald criteria
    • Aims
    • To create diagnostic criteria that could be used by the practicing physician and that could be adapted, as necessary, for clinical trials
    • To integrate magnetic resonance imaging (MRI) into the overall diagnostic scheme
    • To include a scheme for the diagnosis of primary progressive disease
    • To clarify certain definitions used in the diagnosis of MS and to simplify the diagnostic classification and descriptions
  • 33. McDonald criteria
    • Conclusions
    • Obtaining objective evidence of dissemination in time and space of lesions typical of MS is essential in making a secure diagnosis
    • Exclusion of other, better explanations for the clinical features
    • Clinical evidence depends primarily on objectively determined clinical signs
  • 34. McDonald criteria
    • Conclusions
    • MRI, CSF, and VEP can add to a clinical diagnosis
    • May be essential in making a diagnosis when clinical presentation alone does not allow a diagnosis to be made
    • The outcome of a diagnostic evaluation is either MS, possible MS, or not MS
  • 35. McDonald criteria
    • Definitions
    • Attack (exacerbation, relapse)
    • an episode of neurological disturbance of the kind seen in MS
    • should last for at least 24 hours
    • event should not be a pseudoattack, such as might be caused by a change in core body temperature or infection
  • 36. McDonald criteria
    • Time Between Attacks
    • To define what constitutes separate attacks
    • For the purpose of documenting separation in time
    • 30 days should separate the onset of the first event from the onset of a second event
  • 37. McDonald criteria
    • Abnormality in Paraclinical tests
    • MRI
    • Three of four of the following:
    • 1) one gadolinium-enhancing lesion or nine T2 hyperintense lesions if gadolinium-enhancing lesions are not present
    • 2) at least one infratentorial lesion
    • 3) at least one juxtacortical lesion
    • 4) at least three periventricular lesions
  • 38. McDonald criteria
    • MRI
    • Lesions will ordinarily be larger than 3 mm in cross section
    • One spinal cord lesion can be substituted for one brain lesion
    • There should be little or no swelling of the cord
    • Spinal lesions should be unequivocally hyperintense on T2- weighted images, be at least 3 mm but under two vertebral segments in length, and occupy only part of the cross section of the cord
  • 39. McDonald criteria MRI Juxtacortical lesions A) T2WI B) T1WI (gado)
  • 40. McDonald criteria MRI Periventricular,callosal/subcallosal lesions (T2WI & postGd T1WI)
  • 41. McDonald criteria MRI Multiple white matter & periventricular lesions (FLAIR)
  • 42. McDonald criteria MRI Infratentorial lesions A) T2WI B) T1WI (gado)
  • 43. McDonald criteria MRI Spinal cord lesions
  • 44. McDonald criteria
    • MRI- Dissemination in time
    • 1) If first scan ≥ 3 months after onset of clinical event
    • -Gd enhancing lesion sufficient (not at the site implicated in original event)
    • -if no Gd enhancing lesion, follow up scan after 3 months  new T2 or Gd enhancing lesion fulfills the criteria
  • 45. McDonald criteria
    • MRI- Dissemination in time
    • 2) If first scan < 3 months of clinical onset, a second scan done 3 months or more after the clinical event showing a new Gd enhancing lesion sufficient.
    • If no enhancing lesion in second scan  further scan not less than 3 months after the first scan that shows a new T2 lesion or an enhancing lesion will suffice
  • 46. McDonald criteria
    • CSF analysis
    • Abnormality on CSF analysis can provide supportive evidence of the immune and inflammatory nature of lesion(s)
    • CSF analysis cannot provide information about dissemination of lesions or events in time or space
  • 47. McDonald criteria
    • CSF analysis
    • CSF abnormality is defined by the presence of oligoclonal IgG bands different from any such bands in serum and/or the presence of an elevated IgG index
    • Preferably using isoelectric focusing
    • Lymphocytic pleocytosis should be less than 50/mm3
  • 48. McDonald criteria
    • VEP
    • Abnormal VEP, typical of MS - delayed but with well-preserved wave form
    • Can be used to supplement information provided by a clinical examination to provide objective evidence of a second lesion
    • Provided that the only clinically expressed lesion did not affect the visual pathways
  • 49. McDonald criteria
    • The Diagnostic Scheme
    • Mode of clinical presentation
    • +
    • Data needed to make an MS diagnosis
    • If criteria indicated are fulfilled, the diagnosis is multiple sclerosis (MS)
    • if the criteria are not completely met, the diagnosis is “possible MS”
    • if the criteria are fully explored and not met, the diagnosis is “not MS”
  • 50. McDonald criteria
    • The additional criteria needed to make a diagnosis of MS become more stringent as the clinical evidence upon presentation becomes weaker
    • Follow-up with additional clinical assessments, laboratory investigation, and in particular MRI is important when a diagnosis cannot be made on clinical criteria alone at first presentation
  • 51. McDonald criteria
    • Two or More Attacks, Objective Clinical Evidence of Two or More Lesions
    • Diagnosis solely on clinical grounds
    • No additional tests required
    • If these tests are undertaken and are not abnormal in a manner typical of MS, extreme caution must be taken in making a diagnosis of MS
  • 52. McDonald criteria
    • Two or More Attacks, Objective Clinical Evidence of One Lesion
    • Dissemination in space, demonstrated by MRI or Two or more MRI-detected lesions consistent with MS plus positive CSF
    • OR
    • 2) Await further attack implicating a different site
  • 53. McDonald criteria
    • One Attack, Objective Clinical Evidence of Two or More Lesions
    • Dissemination in time, demonstrated by
    • MRI
    • or
    • Second clinical attack
  • 54. McDonald criteria
    • One Attack, Objective Clinical Evidence of One Lesion (clinically isolated syndrome)
    • Dissemination in space, demonstrated by MRI or Two or more MRI-detected lesions consistent with MS plus positive CSF
    • and
    • Dissemination in time, demonstrated by MRI or Second clinical attack
  • 55. McDonald criteria
    • Insidious Neurological Progression Suggestive of Multiple Sclerosis (PPMS)
    • 1) Positive CSF and
    • 2) Dissemination in space, demonstrated by
    • Nine or more T2 lesions in brain or
    • 2 or more lesions in spinal cord, or
    • 4–8 brain plus 1 spinal cord lesion or
    • abnormal VEP - associated with 4–8 brain lesions, or
    • with fewer than 4 brain lesions plus 1 spinal cord lesion demonstrated by MRI
  • 56. McDonald criteria
    • Insidious Neurological Progression Suggestive of Multiple Sclerosis (PPMS)
    • 3 ) Dissemination in time, demonstrated by
    • MRI
    • or
    • Continued progression for 1 year
  • 57. McDonald criteria
  • 58. McDonald criteria- 2005 Revisions
    • Value of original criteria in populations other than adults of western European ethnicity
    • Goals-
    • Incorporate new evidence where available
    • Develop refined consensus where evidence is scant
    • Simplify and clarify original definitions
  • 59. McDonald criteria- 2005 Revisions
    • Major revisions
    • MRI criteria for dissemination of dissemination of lesions (space & time)
    • Incorporation of spinal cord lesions into the imaging requirements
    • Diagnosis of PPMS
  • 60. McDonald criteria- 2005 Revisions
    • MRI- Dissemination in time- REVISED
    • Detection of gd enhancement at least 3 months after the onset of initial clinical event, at different site
    • OR
    • b) Detection of a new T2 lesion if it appears a any time compared with a reference scan done at least 30 days after the onset of initial clinical event
  • 61. McDonald criteria- 2005 Revisions
    • MRI- Dissemination in space- original criteria
    • Three of four of the following:
    • 1) one gadolinium-enhancing lesion or nine T2 hyperintense lesions if no gadolinium-enhancing lesions
    • 2) at least one infratentorial lesion
    • 3) at least one juxtacortical lesion
    • 4) at least three periventricular lesions
    • spinal cord lesion = brain infratentorial lesion;
    • enhancing spinal lesion = enhancing brain lesion
    • individual spinal lesions can contribute together with individual brain lesions to reach the required number of T2 lesions
    • l
  • 62. McDonald criteria- 2005 Revisions- PPMS
    • ORIGINAL
    • CSF
    • Space
    • ( ≥9 T2 brain lesions or ≥ 2spinal lesions or 4-8 brain+ 1 spinal lesions or VEP + 4-8 brain lesions orVEP+ ≥4 brain + 1 spinal lesion)
    • Time (MRI or progression > 1yr )
    • REVISED
    • One year of disease progression PLUS
    • Two of the three
    • a) +ve brain MRI
    • (9 T2 lesions / ≥4 T2 lesions with positive VEP)
    • b) +ve spinal cord MRI (two focal T2 lesions)
    • c) +ve CSF
    • (OB/ increased IgG index)
  • 63.  
  • 64. McDonaldCriteria
    • Earlier diagnosis of MS with a high degree of both specificity and sensitivity allowing for better counseling of patients and earlier treatment.
    • need for their simplification to improve their comprehension and utility
    • evaluating their appropriateness in populations that differ from the largely Western Caucasian adult populations from which the Criteria were derived.
  • 65.  
  • 66. McDonalds 2010
    • Patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a CNS inflammatory demyelinating disease
    • Alternative diagnoses are considered and excluded.
    • Correct interpretation of symptoms and signs is a fundamental prerequisite for diagnosis.
    • Key changes in the McDonald Criteria related to the use and interpretation of imaging criteria for DIS and DIT as MAGNIMS research group .
  • 67. Definitions- McDonalds 2010
    • Attack (relapse, exacerbation)
    • Patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the CNS, current or historical, with duration of at least 24 hours, in the absence of fever or infection.
    • Although a new attack should be documented by contemporaneous neurological examination, in the appropriate context, some historical events with symptoms and evolution characteristic for MS, but for which no objective neurological findings are documented, can provide reasonable evidence of a prior demyelinating event .
  • 68.
    • Reports of paroxysmal symptoms (historical or current) should, however, consist of multiple episodes occurring over not less than 24 hours.
    • For definite diagnosis of MS to be made,
    • - at least 1 attack must be corroborated by findings on neurological examination, visual evoked potential (VEP) in patients reporting prior visual disturbance, or MRI consistent with demyelination in the area of the CNS implicated in the historical report of neurological symptoms.
  • 69.  
  • 70.  
  • 71. CSF findings in diagnosis
    • The Panel reaffirmed that positive cerebrospinal fluid (CSF) findings (elevated immunoglobulin G [IgG] index or 2 or more oligoclonal bands) can be important
      • to support the inflammatory demyelinating nature of the underlying condition,
      • to evaluate alternative diagnoses,
      • and to predict CDMS .
    • Panel believes that even further liberalizing MRI requirements in CSF positive patients is not appropriate. (A positive CSF finding could be used to reduce the MRI requirements for reaching DIS criteria 2005)
    • Prospective studies are needed to confirm the additional diagnostic value of CSF .
  • 72.  
  • 73.  
  • 74.
    • The 2010 revisions to the McDonald Criteria allow a more rapid diagnosis of MS
    • equivalent or improved specificity and/or sensitivity compared with past Criteria.
    • clarify and simplify the diagnostic process with fewer required MRI examinations
  • 75. Clinically Isolated Syndromes
  • 76. Clinically Isolated Syndromes
  • 77. Variants of Multiple Sclerosis
    • Balo ’s concentric sclerosis
    • Rare acute variant of MS
    • Large concentric bands of demyelination are separated by intact myelin
    • Acute monophasic progressive course over weeks to months that ends in death within a year
    • Typical age of onset 20 to 50 years
    • Cerebral and increased intracranial pressure symptoms that would be unusual for a first attack of MS
    • Does not involve demyelination within the spinal cord, cerebellum, brain stem, or optic chiasm
  • 78. Variants of Multiple Sclerosis
    • Marburg Variant
    • acute fulminant process, without remissions
    • typically ends in death within a year
    • generally monophasic course
    • death usually result from brain stem involvement
    • most cases are young people who have no prior neurologic history
  • 79. Variants of Multiple Sclerosis
    • Myelinoclastic diffuse sclerosis
    • Schilder’s disease
    • typically affects children
    • bilateral symmetric hemispheric demyelinating lesions
    • Children present with visual problems or even initial blindness, seizures, headache, and vomiting
  • 80. Differentials
  • 81. Differentials
  • 82. Conclusion
    • Core features
    • Objective clinical findings
    • Evidence of dissemination of lesions in time and space
    • Use of supportive and confirmatory paraclinical examination
    • To eliminate better explanations for the diagnosis
  • 83.
    • Thank you
  • 84. references
    • National multiple sclerosis society website
    • Annals of neurology
    • Multiple sclerosis-Olek
    • Neurologic clinics 2005
    • emedicine-MS