Multiple Sclerosis Multiple Sclerosis ImagingImaging

ClinicalClinical

Onset Onset – 20 to 35 year old in female 20 to 35 year old in female – 35 to 45 year old in male 35 to 45 year old in male – rare before 14 or after 60 year old rare before 14 or after 60 year old

70 to 75% of patients are female 70 to 75% of patients are female PrevalencePrevalence

– female:male 2:1female:male 2:1– more common in white more common in white

Genetic: Genetic: – first degree relative 10-20X increased riskfirst degree relative 10-20X increased risk

Poser Criteria (1983)Poser Criteria (1983)

  Clinically definite MS Clinically definite MS – 2 attacks and clinical evidence of 2 separate lesions 2 attacks and clinical evidence of 2 separate lesions – 2 attacks, clinical evidence of one and paraclinical evidence of another 2 attacks, clinical evidence of one and paraclinical evidence of another

separate lesion separate lesion Laboratory supported Definite MS Laboratory supported Definite MS

– 2 attacks, either clinical or paraclinical evidence of 1 lesion, and CSF 2 attacks, either clinical or paraclinical evidence of 1 lesion, and CSF immunologic abnormalities immunologic abnormalities

– 1 attack, clinical evidence of 2 separate lesions & CSF abnormalities 1 attack, clinical evidence of 2 separate lesions & CSF abnormalities – 1 attack, clinical evidence of 1 and paraclinical evidence of another 1 attack, clinical evidence of 1 and paraclinical evidence of another

separate lesion, & CSF abnormalities separate lesion, & CSF abnormalities Clinically probable MS Clinically probable MS

– 2 attacks & clinical evidence of 1 lesion 2 attacks & clinical evidence of 1 lesion – 1 attack & clinical evidence of 2 separate lesions 1 attack & clinical evidence of 2 separate lesions – 1 attack, clinical evidence of 1 lesion, and paraclinical evidence of 1 attack, clinical evidence of 1 lesion, and paraclinical evidence of

another separate lesion another separate lesion Laboratory supported probable MS Laboratory supported probable MS

– 2 attacks & CSF abnormalities2 attacks & CSF abnormalities

Clinical TypesClinical Types

AsymptomaticAsymptomatic SymptomaticSymptomatic

– 85% start out as relapsing remitting. 85% start out as relapsing remitting. About 10% remains benign at 20 years About 10% remains benign at 20 years 55% RR-MS: Relapsing remitting MS - attacks 55% RR-MS: Relapsing remitting MS - attacks

occurring average once per year occurring average once per year 30% SP-MS: Secondary Progressive MS 30% SP-MS: Secondary Progressive MS About 50% of RR-MS will become SP-MS. About 50% of RR-MS will become SP-MS.

– 10-15% starts as progressive disease. 10-15% starts as progressive disease. 10% PP-MS: Primary progressive MS. Most 10% PP-MS: Primary progressive MS. Most

commonly first develop symptom at age 40-60. commonly first develop symptom at age 40-60. 5% PR-MS: Progressive relapsing5% PR-MS: Progressive relapsing

PrognosisPrognosis

Overall prognosis of untreated MS at fifteen years Overall prognosis of untreated MS at fifteen years (Minden et al 1993; Weinshenker 1995). (Minden et al 1993; Weinshenker 1995). – 70 to 80%: of patients have impaired ability to work 70 to 80%: of patients have impaired ability to work – 50% need an assistive device to walk 50% need an assistive device to walk – 30%: are wheelchair bound  30%: are wheelchair bound 

Better for female, and those with predominantly Better for female, and those with predominantly sensory symptoms sensory symptoms

Kurtzke 5 year rule: absence of significant motor or Kurtzke 5 year rule: absence of significant motor or cerebellar dysfunction at 5 years correlates with cerebellar dysfunction at 5 years correlates with limited disability at 15 years. limited disability at 15 years.

MS is active in most patients MS is active in most patients Only a small minority have true benign disease Only a small minority have true benign disease Disease abnormalities are widespread and clinically Disease abnormalities are widespread and clinically

underestimatedunderestimated

MRI in MSMRI in MS

MRI findings that strongly suggestive of MS MRI findings that strongly suggestive of MS – 4 or more white matter lesions (each > 3mm) 4 or more white matter lesions (each > 3mm) – 3 white matter lesions, 1 periventricular Lesions 3 white matter lesions, 1 periventricular Lesions – 6 mm diameter or greater 6 mm diameter or greater – Ovoid lesions, oriented perpendicular to Ovoid lesions, oriented perpendicular to

ventricles ventricles – Corpus callosum lesions Corpus callosum lesions – Brainstem lesions Brainstem lesions – Open ring appearance of gadolinium Open ring appearance of gadolinium

enhancementenhancement

Diagnosis MRDiagnosis MR

SupportiveSupportive– 3-4 scattered lesion 3-4 scattered lesion

without mass effect without mass effect throughout white throughout white matter matter

SpecificSpecific– >6mm >6mm – Oval shape in Oval shape in

parasagital regionparasagital region– Infratentorial and Infratentorial and

spinalspinal

MethodsMethods

Gadolinium Gadolinium – BBB breakdownBBB breakdown

PDPD– InflammationInflammation

T2T2– Established lesionEstablished lesion

MRSMRS– Loss of NAA for DDLoss of NAA for DD

Magnetization transfer imagingMagnetization transfer imaging– Lesion in otherwise normal appearing white matterLesion in otherwise normal appearing white matter

Prognosis SensitivityPrognosis Sensitivity

Gad – Twice sensitive than T2 monthly MR Gad – Twice sensitive than T2 monthly MR (0.1mmol/kg)(0.1mmol/kg)

Weekly Gad MR more sensitiveWeekly Gad MR more sensitive Spinal imagingSpinal imaging Triple load Gad (0.3mmol/kg) 70% more Triple load Gad (0.3mmol/kg) 70% more

sensitive and 50%more new lesionssensitive and 50%more new lesions Magnetization transfer T1 Magnetization transfer T1 Delayed scanningDelayed scanning Thinner slices 3mmThinner slices 3mm Fast flair 1mm and 3mm 3D increases 30% Fast flair 1mm and 3mm 3D increases 30%

lesion in sub cortical and cortical lesion.lesion in sub cortical and cortical lesion.

MRI:Prognostic MRI:Prognostic indicatorindicator MRI as a prognostic indicator in clinically isolated MRI as a prognostic indicator in clinically isolated

syndromes: syndromes: – MRI normal at presentation MRI normal at presentation

5 years follow-up: 6% with clinically definite MS 5 years follow-up: 6% with clinically definite MS 10 years follow-up: 10% with clinically definite MS 10 years follow-up: 10% with clinically definite MS

– MRI with 1.2 cc or greater T2 involvement MRI with 1.2 cc or greater T2 involvement 5 years follow-up: 96% with clinically definite MS 5 years follow-up: 96% with clinically definite MS 10 years follow-up: 86% with clinically definite MS (some 10 years follow-up: 86% with clinically definite MS (some

patients in the 5 year cohort not included in 10 year cohort) patients in the 5 year cohort not included in 10 year cohort) Patients with early, relapsing-remitting MS studied by Patients with early, relapsing-remitting MS studied by

monthly MRIs over several months monthly MRIs over several months – approximately 70% have at least one enhancing lesion approximately 70% have at least one enhancing lesion

during a 3 month period. during a 3 month period. – frequency of contrast enhancing lesion activity fluctuates frequency of contrast enhancing lesion activity fluctuates

from month to month.from month to month.

CSF in MSCSF in MS

Cell count: Cell count: – RBC usually none. RBC usually none. – WBC: 1/3 has 5 to 50 lymphocytes WBC: 1/3 has 5 to 50 lymphocytes

Protein: 1/4 of patients has mild elevation Protein: 1/4 of patients has mild elevation Myelin basic protein: Myelin basic protein:

– presence indicates demyelination presence indicates demyelination – can be found in first 2 weeks after a substantial exacerbation in 50-90% can be found in first 2 weeks after a substantial exacerbation in 50-90%

of patients of patients – can be seen in other neuro disease, such as infarct, infection etc can be seen in other neuro disease, such as infarct, infection etc

Immunoglobulin: IgG synthesis rate Immunoglobulin: IgG synthesis rate – Indicates activity of Plasma cells Indicates activity of Plasma cells – >3 in 80-90% of MS >3 in 80-90% of MS – elevated in 12% of normal individual, and 30-50% of CNS infections elevated in 12% of normal individual, and 30-50% of CNS infections

Immunoglobulin: IgG index Immunoglobulin: IgG index – >0.7 in 86-94% of MS first CSF abnormality in early MS >0.7 in 86-94% of MS first CSF abnormality in early MS

Oligoclonal bands Oligoclonal bands – present in over 90% of definite MS present in over 90% of definite MS – seen in other inflammatory diseases seen in other inflammatory diseases – seen in 7% of normal controlseen in 7% of normal control

Evoked potentialEvoked potential

% prolonged in possible MS probable MS definite MS

VEP 40 60 85

SSEP 50 70 80

BAEP 30 40 70

Clinical correlationClinical correlation

Kurtzke Expanded disability status scale Kurtzke Expanded disability status scale (KDSS) (KDSS) – SubjectiveSubjective– Poor reproducibilityPoor reproducibility– Lack of representation of all facets of Lack of representation of all facets of

functional impairmentfunctional impairment– Insensitive to changeInsensitive to change– No correlation with MRNo correlation with MR

Locomotor disability scale reflects spinal Locomotor disability scale reflects spinal cord involvementcord involvement

Neuropsychological scale better Neuropsychological scale better correlationcorrelation

Lesion extentLesion extent

Poor correlation between lesion load and Poor correlation between lesion load and EDSS EDSS

Total extent of brain lesion correlate only Total extent of brain lesion correlate only moderately with locomotor disabilitymoderately with locomotor disability

Clinically isolated syndrome on Brain Clinically isolated syndrome on Brain stem better correlationstem better correlation

No of brain lesion in MR predicts No of brain lesion in MR predicts progress to definite MS in next 1-5years, progress to definite MS in next 1-5years, Poor correlation in next 5years (5-10) Poor correlation in next 5years (5-10)

Lesion siteLesion site

Locomotor disability correlate with Locomotor disability correlate with spinal and post fossa lesionspinal and post fossa lesion

T2 lesion load in post fossa and spinal T2 lesion load in post fossa and spinal cord do not correlate with EDSScord do not correlate with EDSS

Asymptomatic cord lesion with isolated Asymptomatic cord lesion with isolated optic neuritis in 40% casesoptic neuritis in 40% cases

Extensive lesion in clinically eloquent Extensive lesion in clinically eloquent pathway without functional pathway without functional consequenceconsequence

Pathologic naturePathologic nature

Acute lesionAcute lesion– inflammation (perivascular lymphocytes, inflammation (perivascular lymphocytes,

macrophage, infiltrate edema, active macrophage, infiltrate edema, active myelin breakdown and axonal damage)myelin breakdown and axonal damage)

Subacute lesionSubacute lesion– Variable remyelinationVariable remyelination

Chronic lesionChronic lesion– Complete demyelination with marked Complete demyelination with marked

astrocytic gliosis, and axonal lossastrocytic gliosis, and axonal loss– Inflammation at the edegeInflammation at the edege

Acute lesionAcute lesion

Correlates with Gad enhancement Correlates with Gad enhancement in RR and SP MS for 2-6weeksin RR and SP MS for 2-6weeks

More common during relapse More common during relapse than remissionthan remission

Most of them are asymptomaticMost of them are asymptomatic Cord lesion are symptomaticCord lesion are symptomatic Optic nerve lesion correlates with Optic nerve lesion correlates with

visual lossvisual loss

Subacute lesionsSubacute lesions

Magnetizing transfer imagingMagnetizing transfer imaging T1 hypointense lesionT1 hypointense lesion MR spectroscopyMR spectroscopy Measurement of atrophyMeasurement of atrophy Diffusion tensor imagingDiffusion tensor imaging Myelin imaging by T2 decay Myelin imaging by T2 decay

analysisanalysis

Normal appearing White Normal appearing White matter with microscopic matter with microscopic changeschanges T1, T2 MT ratio and NAAT1, T2 MT ratio and NAA Clinical importance not clearClinical importance not clear

Cortical pathology and Cortical pathology and synaptic adaptationsynaptic adaptation Synaptic adaptation by functional Synaptic adaptation by functional

MRMR Cortical plaque not yet studiedCortical plaque not yet studied