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Multiple sclerosis imaging

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  • 1. Multiple Sclerosis Imaging
  • 2. Clinical
    • Onset
      • 20 to 35 year old in female
      • 35 to 45 year old in male
      • rare before 14 or after 60 year old
    • 70 to 75% of patients are female
    • Prevalence
      • female:male 2:1
      • more common in white
    • Genetic:
      • first degree relative 10-20X increased risk
  • 3. Poser Criteria (1983)
    •   Clinically definite MS
      • 2 attacks and clinical evidence of 2 separate lesions
      • 2 attacks, clinical evidence of one and paraclinical evidence of another separate lesion
    • Laboratory supported Definite MS
      • 2 attacks, either clinical or paraclinical evidence of 1 lesion, and CSF immunologic abnormalities
      • 1 attack, clinical evidence of 2 separate lesions & CSF abnormalities
      • 1 attack, clinical evidence of 1 and paraclinical evidence of another separate lesion, & CSF abnormalities
    • Clinically probable MS
      • 2 attacks & clinical evidence of 1 lesion
      • 1 attack & clinical evidence of 2 separate lesions
      • 1 attack, clinical evidence of 1 lesion, and paraclinical evidence of another separate lesion
    • Laboratory supported probable MS
      • 2 attacks & CSF abnormalities
  • 4. Clinical Types
    • Asymptomatic
    • Symptomatic
      • 85% start out as relapsing remitting.
        • About 10% remains benign at 20 years
        • 55% RR-MS: Relapsing remitting MS - attacks occurring average once per year
        • 30% SP-MS: Secondary Progressive MS
        • About 50% of RR-MS will become SP-MS.
      • 10-15% starts as progressive disease.
        • 10% PP-MS: Primary progressive MS. Most commonly first develop symptom at age 40-60. 5% PR-MS: Progressive relapsing
  • 5. Prognosis
    • Overall prognosis of untreated MS at fifteen years (Minden et al 1993; Weinshenker 1995).
      • 70 to 80%: of patients have impaired ability to work
      • 50% need an assistive device to walk
      • 30%: are wheelchair bound 
    • Better for female, and those with predominantly sensory symptoms
    • Kurtzke 5 year rule: absence of significant motor or cerebellar dysfunction at 5 years correlates with limited disability at 15 years.
    • MS is active in most patients
    • Only a small minority have true benign disease
    • Disease abnormalities are widespread and clinically underestimated
  • 6. MRI in MS
    • MRI findings that strongly suggestive of MS
      • 4 or more white matter lesions (each > 3mm)
      • 3 white matter lesions, 1 periventricular Lesions
      • 6 mm diameter or greater
      • Ovoid lesions, oriented perpendicular to ventricles
      • Corpus callosum lesions
      • Brainstem lesions
      • Open ring appearance of gadolinium enhancement
  • 7. Diagnosis MR
    • Supportive
      • 3-4 scattered lesion without mass effect throughout white matter
    • Specific
      • >6mm
      • Oval shape in parasagital region
      • Infratentorial and spinal
  • 8. Methods
    • Gadolinium
      • BBB breakdown
    • PD
      • Inflammation
    • T2
      • Established lesion
    • MRS
      • Loss of NAA for DD
    • Magnetization transfer imaging
      • Lesion in otherwise normal appearing white matter
  • 9. Prognosis Sensitivity
    • Gad – Twice sensitive than T2 monthly MR (0.1mmol/kg)
    • Weekly Gad MR more sensitive
    • Spinal imaging
    • Triple load Gad (0.3mmol/kg) 70% more sensitive and 50%more new lesions
    • Magnetization transfer T1
    • Delayed scanning
    • Thinner slices 3mm
    • Fast flair 1mm and 3mm 3D increases 30% lesion in sub cortical and cortical lesion.
  • 10. MRI:Prognostic indicator
    • MRI as a prognostic indicator in clinically isolated syndromes:
      • MRI normal at presentation
        • 5 years follow-up: 6% with clinically definite MS
        • 10 years follow-up: 10% with clinically definite MS
      • MRI with 1.2 cc or greater T2 involvement
        • 5 years follow-up: 96% with clinically definite MS
        • 10 years follow-up: 86% with clinically definite MS (some patients in the 5 year cohort not included in 10 year cohort)
    • Patients with early, relapsing-remitting MS studied by monthly MRIs over several months
      • approximately 70% have at least one enhancing lesion during a 3 month period.
      • frequency of contrast enhancing lesion activity fluctuates from month to month.
  • 11. CSF in MS
    • Cell count:
      • RBC usually none.
      • WBC: 1/3 has 5 to 50 lymphocytes
    • Protein: 1/4 of patients has mild elevation
    • Myelin basic protein:
      • presence indicates demyelination
      • can be found in first 2 weeks after a substantial exacerbation in 50-90% of patients
      • can be seen in other neuro disease, such as infarct, infection etc
    • Immunoglobulin: IgG synthesis rate
      • Indicates activity of Plasma cells
      • >3 in 80-90% of MS
      • elevated in 12% of normal individual, and 30-50% of CNS infections
    • Immunoglobulin: IgG index
      • >0.7 in 86-94% of MS first CSF abnormality in early MS
    • Oligoclonal bands
      • present in over 90% of definite MS
      • seen in other inflammatory diseases
      • seen in 7% of normal control
  • 12. Evoked potential 70 40 30 BAEP 80 70 50 SSEP 85 60 40 VEP definite MS probable MS possible MS % prolonged in
  • 13. Clinical correlation
    • Kurtzke Expanded disability status scale (KDSS)
      • Subjective
      • Poor reproducibility
      • Lack of representation of all facets of functional impairment
      • Insensitive to change
      • No correlation with MR
    • Locomotor disability scale reflects spinal cord involvement
    • Neuropsychological scale better correlation
  • 14. Lesion extent
    • Poor correlation between lesion load and EDSS
    • Total extent of brain lesion correlate only moderately with locomotor disability
    • Clinically isolated syndrome on Brain stem better correlation
    • No of brain lesion in MR predicts progress to definite MS in next 1-5years, Poor correlation in next 5years (5-10)
  • 15. Lesion site
    • Locomotor disability correlate with spinal and post fossa lesion
    • T2 lesion load in post fossa and spinal cord do not correlate with EDSS
    • Asymptomatic cord lesion with isolated optic neuritis in 40% cases
    • Extensive lesion in clinically eloquent pathway without functional consequence
  • 16. Pathologic nature
    • Acute lesion
      • inflammation (perivascular lymphocytes, macrophage, infiltrate edema, active myelin breakdown and axonal damage)
    • Subacute lesion
      • Variable remyelination
    • Chronic lesion
      • Complete demyelination with marked astrocytic gliosis, and axonal loss
      • Inflammation at the edege
  • 17. Acute lesion
    • Correlates with Gad enhancement in RR and SP MS for 2-6weeks
    • More common during relapse than remission
    • Most of them are asymptomatic
    • Cord lesion are symptomatic
    • Optic nerve lesion correlates with visual loss
  • 18. Subacute lesions
    • Magnetizing transfer imaging
    • T1 hypointense lesion
    • MR spectroscopy
    • Measurement of atrophy
    • Diffusion tensor imaging
    • Myelin imaging by T2 decay analysis
  • 19. Normal appearing White matter with microscopic changes
    • T1, T2 MT ratio and NAA
    • Clinical importance not clear
  • 20. Cortical pathology and synaptic adaptation
    • Synaptic adaptation by functional MR
    • Cortical plaque not yet studied