multiple sclerosis diagnostics dr c bourque
TRANSCRIPT
Multiple SclerosisMultiple SclerosisDiagnostic IssuesDiagnostic Issues
Christopher BourqueChristopher Bourque
AcknowledgementsAcknowledgements
American Academy of NeurologyAmerican Academy of Neurology Continuum seriesContinuum series
Multiple SclerosisMultiple Sclerosis Vol 10, #6, Dec. 2004Vol 10, #6, Dec. 2004
Elsevier SaundersElsevier Saunders Neurologic ClinicsNeurologic Clinics
Multiple SclerosisMultiple Sclerosis Vol 23 # 1 Feb. 2005Vol 23 # 1 Feb. 2005
MS in 1 SlideMS in 1 Slide
Manifestations due to CNS Manifestations due to CNS Slowing or failure of transmissionSlowing or failure of transmission
Inflammatory demyelinationInflammatory demyelination Axonal damageAxonal damage
Mostly damage of white matter tractsMostly damage of white matter tracts Optic neuritis, weakness, sensory loss, ataxia nystagmus, Optic neuritis, weakness, sensory loss, ataxia nystagmus,
bladder dysfunction, cognitive impairmentbladder dysfunction, cognitive impairment
Diagnosis based on clinical and laboratory Diagnosis based on clinical and laboratory evidence ofevidence of
Dissemination in timeDissemination in time Dissemination in spaceDissemination in space
Patterns of MSPatterns of MS Relapsing - remittingRelapsing - remitting
Attacks with complete/incomplete recoveryAttacks with complete/incomplete recovery Stable between attacksStable between attacks
Secondary - progressiveSecondary - progressive Initially relapsing-remittingInitially relapsing-remitting Then progression +/- attacksThen progression +/- attacks
Progressive - relapsingProgressive - relapsing Initial gradual detioriationInitial gradual detioriation Subsequent episodesSubsequent episodes
Primary progressivePrimary progressive Gradual declineGradual decline No attacksNo attacks
Schumacher Clinical CriteriaSchumacher Clinical CriteriaMS Diagnosis 1965MS Diagnosis 1965
Age (onset 10-50 years)Age (onset 10-50 years) CNS white matter diseaseCNS white matter disease Lesions disseminated in time and spaceLesions disseminated in time and space Objective abnormalities on examObjective abnormalities on exam Consistent time courseConsistent time course
Attacks lasting > 24 hrs., spaced at least 1 month Attacks lasting > 24 hrs., spaced at least 1 month apartapart
Slow or stepwise progression for > 6 monthsSlow or stepwise progression for > 6 months No better explanationNo better explanation Diagnosis by experienced clinicianDiagnosis by experienced clinician
Poser Criteria for the Poser Criteria for the Diagnosis of MS 1983Diagnosis of MS 1983
Widely used for last 20 yearsWidely used for last 20 years Definite or probableDefinite or probable Laboratory supported MSLaboratory supported MS Replaced by McDonald criteria 2001Replaced by McDonald criteria 2001
Technical advances enable quicker dx.Technical advances enable quicker dx. ControversialControversial
McDonald CriteriaMcDonald CriteriaClinical (attacks) Objective
LesionsAdditional Requirements to Make Diagnosis
2 or more 2 or more None
2 or more 1 Dissemination in space by MRI or positive CSF and 2 or more MRI lesions consistent with MS or further clinical attack involving different site
1 2 or more Dissemination in time by MRI or second clinical attack
1 monosymptomatic 1 Dissemination in space by MRI or positive CSF and 2 or more MRI lesions consistent with MS and dissemination in time by MRI or second clinical attack
0 (progression from onset)
1 Next slide
McDonald CriteriaMcDonald CriteriaClinical (attacks)
Objective Lesions
Additional Requirements to Make Diagnosis
0 (progression from onset)
1 Positive CSF and Dissemination in space by MRI evidence of 9 or more T2 brain lesionsor 2 or more cord lesions or 4-8 brain and 1 cord lesionor positive VEP with 4-8 MRI lesionsor positive VEP with less than 4 brain lesions plus 1 cord lesionandDissemination in time by MRI or continued progression for 1 year
Clinical ManifestationsClinical Manifestations DemographicDemographic
FemaleFemale Women make up to 70%-75% MS patientsWomen make up to 70%-75% MS patients
Young ageYoung age Onset before age 16: 5% of casesOnset before age 16: 5% of cases Peak onset post puberty, early 20’sPeak onset post puberty, early 20’s
Relapsing MS 28-30 yearsRelapsing MS 28-30 years
SymptomsSymptoms Recent onsetRecent onset Frequently progressiveFrequently progressive
Coming on over 1-several daysComing on over 1-several days Very acute symptoms possibleVery acute symptoms possible
The MS EventThe MS Event
Attack/relapse/exacerbationAttack/relapse/exacerbation Acute episode of CNS dysfunctionAcute episode of CNS dysfunction Lasting at least 24 hoursLasting at least 24 hours In absence of fever or metabolic In absence of fever or metabolic
derangementderangement All events within 30 days are unitaryAll events within 30 days are unitary
MS SymptomsMS Symptoms
Deficit reported Presenting%
During course %
Visual/oculomotorParesisParesthesiasIncoordinationGenitourinary/bowelCerebral
49424123104
1008887826339
Source: Whitaker JN, Mitchell GW 1997
Clinical ManifestationsClinical Manifestations MotorMotor
Weakness, spasticity, ataxiaWeakness, spasticity, ataxia Rarely radicularRarely radicular
lesion ant. horn, root entry zonelesion ant. horn, root entry zone painfulpainful atrophyatrophy
SomatosensorySomatosensory 1st sx. in 43% patients1st sx. in 43% patients
Includes visualIncludes visual Any anatomic distributionAny anatomic distribution Any combinationAny combination
Loss pain, temp, light touch, vbn, positionLoss pain, temp, light touch, vbn, position Positive sx. commonPositive sx. common
Paresthesiae, hyperpathia, allodynia, dysesthesiasParesthesiae, hyperpathia, allodynia, dysesthesias
Nonspecific Associated Features Nonspecific Associated Features That Suggest MSThat Suggest MS
Excessive unexplained fatigueExcessive unexplained fatigue Temperature sensitivityTemperature sensitivity
Hot, humid weatherHot, humid weather Relatively recent symptomsRelatively recent symptoms History of Lhermitte’s signHistory of Lhermitte’s sign History of bandlike sensation around the waistHistory of bandlike sensation around the waist Uhthoff’s phenomenonUhthoff’s phenomenon
eg, blurry vision with exercise or heat exposureeg, blurry vision with exercise or heat exposure
Clinical ManifestationsClinical Manifestations FatigueFatigue
One of the most important causes of disabilityOne of the most important causes of disability Several sourcesSeveral sources
Handicap fatigueHandicap fatigue Increased effort to perform routine tasksIncreased effort to perform routine tasks
Secondary fatigueSecondary fatigue Depression, sleep disturbances, medication side-Depression, sleep disturbances, medication side-
effects, other conditionseffects, other conditions Systemic fatigueSystemic fatigue
Chronic lack of energy, tirdness, malaiseChronic lack of energy, tirdness, malaise Etiology unknownEtiology unknown
Clinical ManifestationsClinical Manifestations
Cognitive DisturbancesCognitive Disturbances Common, frequently overlookedCommon, frequently overlooked
Estimated 50-75%Estimated 50-75% Most commonMost common
Impaired attention, slow info processing, short term memory Impaired attention, slow info processing, short term memory loss, reduced visuospatial skills, impaired executive functionloss, reduced visuospatial skills, impaired executive function
Impaired driving skillsImpaired driving skills Important impact QoL, ADLImportant impact QoL, ADL Can occur independentCan occur independent
of disease courseof disease course other manifestationsother manifestations
MRI in MSMRI in MS Brain lesionsBrain lesions
CharacterCharacter Large Large >> 3 mm 3 mm OvoidOvoid Oriented perpendicular to ventriclesOriented perpendicular to ventricles EnhancingEnhancing
Open-ring enhancementOpen-ring enhancement Multifocal homogeneousMultifocal homogeneous
LocationLocation Multiple white matterMultiple white matter Brainstem, infratentorialBrainstem, infratentorial JuxtacorticalJuxtacortical Corpus callosumCorpus callosum
Pointing awayPointing away Moth eatenMoth eaten Callosal atrophyCallosal atrophy
Evoked PotentialsEvoked Potentials
Visual evoked potentialsVisual evoked potentials Not auditory or somatosensoryNot auditory or somatosensory May point to subclinical involvement of optic May point to subclinical involvement of optic
nervenerve Quality control issuesQuality control issues
Principal Differential Diagnosis of Principal Differential Diagnosis of Multiple SclerosisMultiple Sclerosis
InfectionInfection Lyme, Syphilis, Progressive Multifocal Lyme, Syphilis, Progressive Multifocal
Leukoencephalopathy, HIV, HTLV-1Leukoencephalopathy, HIV, HTLV-1
InflammatoryInflammatory SLE, Sjogren syndrome, vasculitis, Sarcoidosis, Bechet’s SLE, Sjogren syndrome, vasculitis, Sarcoidosis, Bechet’s
diseasedisease
MetabolicMetabolic B12 deficiency, lysosomal disorders, adrenoleukodystrophy, B12 deficiency, lysosomal disorders, adrenoleukodystrophy,
mitochondrial disorders, other genetic diseasesmitochondrial disorders, other genetic diseases
NeoplasticNeoplastic CNS lymphomaCNS lymphoma
Spine diseaseSpine disease Vascular malformations, degenerative spine diseaseVascular malformations, degenerative spine disease
Cerebrospinal FluidCerebrospinal Fluid Useful, not diagnosticUseful, not diagnostic
Other conditionsOther conditions Chronic CNS infections, viral syndromes, neuropathiesChronic CNS infections, viral syndromes, neuropathies
Immunoglobulin abnormalitiesImmunoglobulin abnormalities Production of immunoglobulinProduction of immunoglobulin
By plasma or B cells in CNSBy plasma or B cells in CNS Oligoclonal bands of immunoglobulin (IgG) (OCB)Oligoclonal bands of immunoglobulin (IgG) (OCB)
In CSF, not serumIn CSF, not serum Isoelectric focusing techniqueIsoelectric focusing technique
Elevated IgG indexElevated IgG index Ratio of IgG/protein in serum and CSFRatio of IgG/protein in serum and CSF index = index = (csf IgG/csf albumin)(csf IgG/csf albumin)
(serum IgG/serum (serum IgG/serum albumin)albumin)
Cerebrospinal FluidCerebrospinal Fluid First event - chance of progression to MSFirst event - chance of progression to MS
In 3 yearsIn 3 years OCB +ve: 25%OCB +ve: 25% OCB -ve: 9%OCB -ve: 9%
CIS:clinically isolated syndromeCIS:clinically isolated syndrome 62.5% cases +ve OCB62.5% cases +ve OCB
Clinically definite MSClinically definite MS 90% +OCB90% +OCB
MRI in MSMRI in MS Spinal cord lesionsSpinal cord lesions
CharacterCharacter Asymptomatic lesionsAsymptomatic lesions Focal T2/proton density hyperintense lesionsFocal T2/proton density hyperintense lesions Diffuse proton density abnormalitiesDiffuse proton density abnormalities AtrophyAtrophy Asymmetric involvementAsymmetric involvement
Multiple scattered lesionsMultiple scattered lesions Edema with acute plaquesEdema with acute plaques
Often enhancingOften enhancing
LocationLocation Cervical and thoracicCervical and thoracic
Especially midcervicalEspecially midcervical PeripheralPeripheral Less than 2 vertebral segmentsLess than 2 vertebral segments Less than 50% cross-sectional areaLess than 50% cross-sectional area Lateral, dorsal cordLateral, dorsal cord
Paroxysmal Symptoms in MSParoxysmal Symptoms in MS
Trigeminal neuralgia (and others)Trigeminal neuralgia (and others) Tonic “seizures”Tonic “seizures” Paroxysmal dysarthriaParoxysmal dysarthria Hemifacial spasmHemifacial spasm Paroxysmal itchingParoxysmal itching Abrupt loss of muscle toneAbrupt loss of muscle tone Paroxysmal aphasiaParoxysmal aphasia Paroxysmal kinesogenic choreoathetosisParoxysmal kinesogenic choreoathetosis Lhermitte’s signLhermitte’s sign
MS SymptomsMS Symptoms
Deficit reported Presenting%
During course %
Visual/oculomotorParesisParesthesiasIncoordinationGenitourinary/bowelCerebral
49424123104
1008887826339
Source: Whitaker JN, Mitchell GW 1997
Clinical ManifestationsClinical Manifestations
Visual symptoms, afferentVisual symptoms, afferent Almost any pattern, related to locationAlmost any pattern, related to location Optic neuritisOptic neuritis
Central scotomaCentral scotoma Mild: color desaturationMild: color desaturation Severe: blindnessSevere: blindness
Vast majority have excellent return by 6 monthsVast majority have excellent return by 6 months Frequent painFrequent pain
Worse on eye movementWorse on eye movement
Optic NeuritisOptic NeuritisRisk of Subsequent MSRisk of Subsequent MS
Higher RiskHigher Risk Young adult (26-40 years)Young adult (26-40 years) Venous sheathingVenous sheathing Recurrent optic neuritisRecurrent optic neuritis Female sexFemale sex History of minor neurologic symptomsHistory of minor neurologic symptoms Brain MRI lesionsBrain MRI lesions CSF oligoclonal bands or intrathecal IgG productionCSF oligoclonal bands or intrathecal IgG production
Lower RiskLower Risk Age < 10Age < 10 Macular star/exudatesMacular star/exudates Retinal or disc hemorrhageRetinal or disc hemorrhage Severe disc edemaSevere disc edema No brain MRI lesionsNo brain MRI lesions Normal CSFNormal CSF
Clinical ManifestationsClinical Manifestations
Visual symptoms, efferentVisual symptoms, efferent Any eye movement abnormalityAny eye movement abnormality INOINO
Internuclear ophthalmoplegiaInternuclear ophthalmoplegia Adductor weaknessAdductor weakness Abduction nystagmusAbduction nystagmus In young adult strongly suggests MSIn young adult strongly suggests MS
NystagmusNystagmus Many typesMany types
Clinical ManifestationsClinical Manifestations
Other Brain Stem StructuresOther Brain Stem Structures Facial weaknessFacial weakness VertigoVertigo Loss of hearing, tasteLoss of hearing, taste Dysarthria, dysphagiaDysarthria, dysphagia
Bulbar musclesBulbar muscles Weakness, ataxia, spasticityWeakness, ataxia, spasticity
Clinical ManifestationsClinical Manifestations
Psychiatric DisturbancesPsychiatric Disturbances DepressionDepression
Also up to 75% of patientsAlso up to 75% of patients Major depression less frequentMajor depression less frequent Suicide: 15% of adult MS deathsSuicide: 15% of adult MS deaths
Risk factorsRisk factors Living aloneLiving alone FH mental illnessFH mental illness Reporting social isolationReporting social isolation PH major depression, anxiety, alcohol abusePH major depression, anxiety, alcohol abuse
Emotional incontinenceEmotional incontinence Frontal lobe involvementFrontal lobe involvement
Clinical ManifestationsClinical Manifestations Bladder dysfunction; the importance of urodynamic studiesBladder dysfunction; the importance of urodynamic studies
Failure to store: detruser hyperactivityFailure to store: detruser hyperactivity Urgency, frequency, nocturiaUrgency, frequency, nocturia
Failure to emptyFailure to empty Detruser-sphincter dyssynergiaDetruser-sphincter dyssynergia Poor detruser contractionPoor detruser contraction
Hesitancy, increased residual vol., retentionHesitancy, increased residual vol., retention
BothBoth Combined Combined
detruser hyperactivitydetruser hyperactivity detruser-sphincter dyssynergiadetruser-sphincter dyssynergia
IncontinenceIncontinence Detruser hyperactivity orDetruser hyperactivity or OverflowOverflow Symptoms may not be accurate indicator of urodynamic pathologySymptoms may not be accurate indicator of urodynamic pathology
Clinical ManifestationsClinical Manifestations Bowel dysfunctionBowel dysfunction
ConstipationConstipation Can be aggrevated by Can be aggrevated by
fluid restrictionfluid restriction Anticholinergic medicationsAnticholinergic medications
Urgency and incontinenceUrgency and incontinence
Sexual dysfunctionSexual dysfunction Erectile dysfunctionErectile dysfunction Women: loss of libido, anorgasmiaWomen: loss of libido, anorgasmia Both sexesBoth sexes
Loss of perineal sensationLoss of perineal sensation Neuropathic painNeuropathic pain SpasticitySpasticity IncontinenceIncontinence Depression, fatigueDepression, fatigue
Pain Syndromes in MSPain Syndromes in MS Primary painPrimary pain
NeuralgicNeuralgic Trigeminal neuralgiaTrigeminal neuralgia Other neuralgiasOther neuralgias
Dysesthetic painDysesthetic pain Most often burning (legs)Most often burning (legs) Other dysesthesiasOther dysesthesias
Radicular painRadicular pain Tonic seizuresTonic seizures SpasticitySpasticity
Flexor spasmsFlexor spasms Extensor spasmsExtensor spasms
Secondary painSecondary pain Low back painLow back pain Osteoporosis with fracturesOsteoporosis with fractures
Neurologic Syndromes Likely for MS Neurologic Syndromes Likely for MS
Optic neuritisOptic neuritis Unilateral eye involvementUnilateral eye involvement Retrobulbar rather than papillitisRetrobulbar rather than papillitis Eye painEye pain Partial vision loss, with at least some recoveryPartial vision loss, with at least some recovery No retinal exudates, disc hemorrhages, macular starNo retinal exudates, disc hemorrhages, macular star
10 years follow-up: 38% develop MS10 years follow-up: 38% develop MS MRI other lesions: risk 56%MRI other lesions: risk 56% MRI normal: risk 22%MRI normal: risk 22%
20 years follow-up: 70% develop MS20 years follow-up: 70% develop MS
Neurologic Syndromes Likely for MSNeurologic Syndromes Likely for MS
Transverse MyelitisTransverse Myelitis IncompleteIncomplete Sensory > motorSensory > motor AssociatedAssociated
Lhermitte’s signLhermitte’s sign Bandlike abdominal or chest pressure Bandlike abdominal or chest pressure
Internuclear OphthalmoplegiaInternuclear Ophthalmoplegia Trigeminal NeuralgiaTrigeminal Neuralgia Hemifacial SpasmHemifacial Spasm
Neurologic Syndromes Likely for MSNeurologic Syndromes Likely for MS
Paroxysmal symptomsParoxysmal symptoms Last seconds to minutesLast seconds to minutes Occur multiple times dailyOccur multiple times daily
Tonic spasmsTonic spasms Dysarthria, ataxiaDysarthria, ataxia Hemiparesis, hypesthesiaHemiparesis, hypesthesia
Polysymptomatic Syndrome Without Mental Polysymptomatic Syndrome Without Mental Status ChangesStatus Changes
Clues to a Misdiagnosis; MSClues to a Misdiagnosis; MS
HistoricalHistorical No disseminationNo dissemination Onset < 10 yrs. or > 55 yrs.Onset < 10 yrs. or > 55 yrs. Genetic red flagsGenetic red flags
+ve FH+ve FH However about 20% of MS patients have FHHowever about 20% of MS patients have FH
Early-age onsetEarly-age onset Unexplained non-CNS diseaseUnexplained non-CNS disease
Progressive course starting before age 35Progressive course starting before age 35 Localized diseaseLocalized disease
Clues to a Misdiagnosis; MSClues to a Misdiagnosis; MS ExaminationExamination
Prominent Prominent fever, headache, uveitis, painfever, headache, uveitis, pain
Abrupt Abrupt hemiparesis, hearing losshemiparesis, hearing loss
NoNo optic nerve/ocular involvementoptic nerve/ocular involvement bowel/bladder involvementbowel/bladder involvement
Progressive myelopathyProgressive myelopathy Without bowel/bladder involvementWithout bowel/bladder involvement
Impaired level of consciousnessImpaired level of consciousness Nonscotomatous visual field defectsNonscotomatous visual field defects Grey matter featuresGrey matter features
Early dementia, aphasiaEarly dementia, aphasia FasciculationsFasciculations Extrapyramidal featuresExtrapyramidal features
Clues to a Misdiagnosis; MSClues to a Misdiagnosis; MS MRIMRI
BrainBrain NormalNormal Small lesions < 3 mm.Small lesions < 3 mm. Subcortical location (internal capsule)Subcortical location (internal capsule) Prominent infratentorial involvementProminent infratentorial involvement Prominent grey matter involvement (basal Prominent grey matter involvement (basal
ganglia)ganglia) Symmetric, confluent hemispheric white matter Symmetric, confluent hemispheric white matter
involvementinvolvement HydrocephalusHydrocephalus Severe cerebellar/brain stem atrophySevere cerebellar/brain stem atrophy No callosal/periventricular lesionsNo callosal/periventricular lesions
Clues to a Misdiagnosis; MSClues to a Misdiagnosis; MS MRIMRI
Spinal cordSpinal cord Large lesion, multiple segments (>2)Large lesion, multiple segments (>2) Severe swellingSevere swelling Full thickness lesionsFull thickness lesions Leptomenengial enhancementLeptomenengial enhancement T1 hypointense lesionsT1 hypointense lesions
Clues to a Misdiagnosis; MSClues to a Misdiagnosis; MS CSFCSF
NormalNormal Disappearance of oligoclonal bandsDisappearance of oligoclonal bands
Normalization of IgG indexNormalization of IgG index
Cell count > 50 wbc/cubic mm.Cell count > 50 wbc/cubic mm. Protein > 100 mg/dlProtein > 100 mg/dl
MS Diagnosis; 1 Final SlideMS Diagnosis; 1 Final Slide
Manifestations due to CNS Manifestations due to CNS Slowing or failure of transmissionSlowing or failure of transmission Mostly damage of white matter tractsMostly damage of white matter tracts Recent appreciation of axonal/grey matter involvementRecent appreciation of axonal/grey matter involvement
Diagnosis based on clinical and laboratory evidence ofDiagnosis based on clinical and laboratory evidence of Dissemination in timeDissemination in time Dissemination in spaceDissemination in space Recent appreciation of role of MRI in assisting diagnosisRecent appreciation of role of MRI in assisting diagnosis
In-office pattern recognitionIn-office pattern recognition Appropriate demographicAppropriate demographic Appropriate clinical eventAppropriate clinical event