{ multiple sclerosis: what the family physician should know... michael m.c. yeung, md, frcpc...
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Multiple Sclerosis:Multiple Sclerosis:What the Family Physician What the Family Physician Should Know . . .Should Know . . .
Michael M.C. Yeung, MD, FRCPCMichael M.C. Yeung, MD, FRCPC
Director, MS Clinical Trials Research Director, MS Clinical Trials Research ProgramProgram
Clinical Associate ProfessorClinical Associate Professor
Department of Clinical NeurosciencesDepartment of Clinical Neurosciences
University of CalgaryUniversity of Calgary
October 2, 2014October 2, 2014
Research SupportResearch Support National Institutes of Health, MS Society of Canada, National Institutes of Health, MS Society of Canada,
BiogenIdec, Hoffman-LaRoche, Sanofi-Aventis, BiogenIdec, Hoffman-LaRoche, Sanofi-Aventis, Novartis, Elan, EMD Serono, Neuroscience Canada, Novartis, Elan, EMD Serono, Neuroscience Canada, IMPAX, Bayer, Teva Canada Innovation, Genzyme, IMPAX, Bayer, Teva Canada Innovation, Genzyme, Acorda Therapeutics, Berlex, BioMS Technology,Acorda Therapeutics, Berlex, BioMS Technology,
Protein Design Labs, Genentech, GSK, Abbott, Protein Design Labs, Genentech, GSK, Abbott, NeurocrineNeurocrine
ConsultantConsultant BiogenIdec, Novartis, EMD Serono, Bayer, Teva BiogenIdec, Novartis, EMD Serono, Bayer, Teva
Canada InnovationCanada Innovation Speakers’ BureauSpeakers’ Bureau
MS Society of Canada, BiogenIdec, Novartis, EMD MS Society of Canada, BiogenIdec, Novartis, EMD Serono, Bayer, Teva Canada InnovationSerono, Bayer, Teva Canada Innovation
HonorariaHonoraria MS Society of Canada, BiogenIdec, EMD Serono, MS Society of Canada, BiogenIdec, EMD Serono,
Bayer Teva Canada InnovationBayer Teva Canada Innovation
DisclosuresDisclosures
University of Calgary MS ClinicUniversity of Calgary MS Clinic When Should I Suspect Multiple When Should I Suspect Multiple
Sclerosis?Sclerosis? Diagnostic CriteriaDiagnostic Criteria Is it a Relapse?Is it a Relapse? Disease Modifying TreatmentsDisease Modifying Treatments Symptom ManagementSymptom Management Complementary & Alternative Complementary & Alternative
TreatmentsTreatments
ContentsContents
Established in 1978 as part of Established in 1978 as part of Canadian Network of MS ClinicsCanadian Network of MS Clinics
To provide specialized multi-disciplinary To provide specialized multi-disciplinary care and treatmentcare and treatment
To participate in clinical and To participate in clinical and investigator-driven research trialsinvestigator-driven research trials
University of Calgary University of Calgary MS ClinicMS Clinic
~6000 registered patients~6000 registered patients Foothills Medical Centre and South Health Foothills Medical Centre and South Health
CampusCampus 9 neurologists, 1 physiatrist, 2 neuro-9 neurologists, 1 physiatrist, 2 neuro-
psychiatristspsychiatrists 1 nurse practitioner, 4.5 clinic nurses, 2 1 nurse practitioner, 4.5 clinic nurses, 2
special therapies nurses, 1.5 research special therapies nurses, 1.5 research nursesnurses
3 research coordinators, 3 research 3 research coordinators, 3 research assistants, 4 health outcomes research assistants, 4 health outcomes research assistantsassistants
University of Calgary University of Calgary MS Clinic MS Clinic
OOututppatient atient TTreatment reatment iin n MuMultiple ltiple SSclerosisclerosis
OT, PT, SW, psychology, bowel & OT, PT, SW, psychology, bowel & bladder nursebladder nurse
2 psychiatrists, 2 neuro-psychiatrists2 psychiatrists, 2 neuro-psychiatrists Provides access to co-ordinated rehab Provides access to co-ordinated rehab
servicesservices Entry point is MS ClinicEntry point is MS Clinic
OPTIMUS OPTIMUS
Multidisciplinary Team Approach
Diagnose and confirm MSDiagnose and confirm MS Initiate and monitor disease modifying Initiate and monitor disease modifying
therapiestherapies Give recommendations for symptom Give recommendations for symptom
managementmanagement Initiate referral to rehabilitation servicesInitiate referral to rehabilitation services Organize other community supportOrganize other community support Offer eligible patients the opportunity to Offer eligible patients the opportunity to
participate in clinical trialsparticipate in clinical trials
What the Clinic What the Clinic CanCan DoDo
Provide emergency careProvide emergency care Manage primary care needsManage primary care needs Initiate non-evidence-based treatmentsInitiate non-evidence-based treatments Manage patients without a primary care Manage patients without a primary care
providerprovider Provide services under the mandates of Provide services under the mandates of
other programsother programs
What We What We CannotCannot Do Do
What is MS?What is MS?
What is MS?What is MS?
Auto-immune disorder of CNSAuto-immune disorder of CNS InflammationInflammation Axonal degenerationAxonal degeneration
Genetic predispositionGenetic predisposition CaucasianCaucasian
Environmental triggerEnvironmental trigger Unknown Unknown
EpidemiologyEpidemiology
EpidemiologyEpidemiology
MS is the most common neurological MS is the most common neurological disorder affecting young adults in disorder affecting young adults in CanadaCanada
More common in females (2 - 3:1)More common in females (2 - 3:1) ~50,000 people with MS in Canada~50,000 people with MS in Canada Prevalence 1:500 - 1:1000Prevalence 1:500 - 1:1000 Alberta prevalence 1:300Alberta prevalence 1:300
When Should MS be in When Should MS be in the Differential the Differential Diagnosis?Diagnosis?
Common PresentationsCommon Presentations
VisualVisual Optic neuritisOptic neuritis INOINO
MotorMotor Progressive myelopathyProgressive myelopathy Incomplete transverse myelitisIncomplete transverse myelitis
SensorySensory Lhermitte’sLhermitte’s Incomplete transverse myelitisIncomplete transverse myelitis
CoordinationCoordination AtaxiaAtaxia
GaitGait
Common PresentationsCommon Presentations
Unusual PresentationsUnusual Presentations
PainPain Paroxysmal symptomsParoxysmal symptoms Migratory transient paresthesiasMigratory transient paresthesias Movement disordersMovement disorders Seizures Seizures Peripheral neuropathyPeripheral neuropathy
Unusual PresentationsUnusual Presentations
Structural lesions of brain or spinal cordStructural lesions of brain or spinal cord Cerebral vasculitisCerebral vasculitis Autoimmune diseasesAutoimmune diseases
SarcoidosisSarcoidosis LupusLupus
Metabolic diseasesMetabolic diseases Vitamin B12 deficiencyVitamin B12 deficiency
InfectionsInfections Lyme diseaseLyme disease
Differential Diagnosis Differential Diagnosis of MSof MS
Barkhof’s MRI Criteria
Gd-enhancing T2-hyperintense
Juxtacortical Periventricular
SpinalCord
Infratentorial
Differential Diagnosis Differential Diagnosis of MRI White Matter of MRI White Matter LesionsLesions
AgingAging MigrainesMigraines HypertensionHypertension TraumaTrauma Radiation therapyRadiation therapy Chronic fatigue syndromeChronic fatigue syndrome Cocaine addictionCocaine addiction CADASILCADASILDifferential Diagnosis Differential Diagnosis
of MRI White Matter of MRI White Matter LesionsLesions
CBC & differentialCBC & differential LFTs & renal functionLFTs & renal function Electrolytes, glucose, Ca, Mg, PO4Electrolytes, glucose, Ca, Mg, PO4 Vitamin D levelVitamin D level Serum protein electrophoresisSerum protein electrophoresis Vitamin B12 levelVitamin B12 level RF, ANARF, ANA VDRLVDRL MRI brain and cervical spinal cord +/- MRI brain and cervical spinal cord +/-
contrastcontrast
Work-upWork-up
Diagnostic CriteriaDiagnostic Criteria
2010 revised McDonald criteria2010 revised McDonald criteria Neurological symptoms and/or signs Neurological symptoms and/or signs
separated in time and spaceseparated in time and space MRI can help in diagnosis, but is MRI can help in diagnosis, but is notnot
THETHE diagnostic test diagnostic test
Goodin DS, et al. Neurology. 2002;58:169-178. Craig J, et al. J Neurol Neurosurg Psychiatry. 2003;74:1225-1230.
MS: Clinical SubtypesMS: Clinical Subtypes
Four established clinical courses differ by the time Four established clinical courses differ by the time course of relapse and progressioncourse of relapse and progression
Relapsing-Remitting MS (RRMS) Relapsing-Remitting MS (RRMS) Secondary Progressive MS (SPMS)Secondary Progressive MS (SPMS) Primary Progressive MS (PPMS)Primary Progressive MS (PPMS) Progressive Relapsing MS (PRMS)Progressive Relapsing MS (PRMS)
Lublin FD, Reingold SC. Neurology. 1996;46:907-911.
No disease progression between relapses
Acute relapses with full recovery Acute relapses with sequelae and residual deficit upon recovery
Incr
easi
ngD
isab
ility
Incr
easi
ngD
isab
ility
Time Time
Relapsing-Remitting MSRelapsing-Remitting MS
Patients with an initial RRMS course convert to SPMS, which is characterized by continuous progression
Lublin FD, Reingold SC. Neurology. 1996;46:907-911.
Without relapses With relapses
Time Time
Incr
easi
ngD
isab
ility
Incr
easi
ngD
isab
ility
Secondary Progressive Secondary Progressive MSMS
PPMS is characterized by progression of disability from onset
Lublin FD, Reingold SC. Neurology. 1996;46:907-911.
Without plateaus or remissions With occasional plateaus and temporary minor improvements
Time Time
Incr
easi
ngD
isab
ility
Incr
easi
ngD
isab
ility
Primary Progressive MSPrimary Progressive MS
PRMS is characterized by disease progression from onset withthe occurrence of clear acute relapses
Full recovery following relapse with progression between relapses
Without full recovery following relapse with progression between relapses
Lublin FD, Reingold SC. Neurology. 1996;46:907-911.
Time Time
Incr
easi
ngD
isab
ility
Incr
easi
ngD
isab
ility
Progressive Relapsing Progressive Relapsing MSMS
Clinical Subtypes (at Clinical Subtypes (at Presentation)Presentation)
Jacobs LD, et al. Jacobs LD, et al. Mult Scler.Mult Scler. 1999;5:369-376. 1999;5:369-376.
About 80%–85% of all MS patients initially have RRMS;About 80%–85% of all MS patients initially have RRMS;most will convert to SPMS in 6-10 yearsmost will convert to SPMS in 6-10 years
(N = 3019)
Education and supportEducation and support Optimize overall wellnessOptimize overall wellness Relapse identification and treatmentRelapse identification and treatment Symptom managementSymptom management Disease modifying therapiesDisease modifying therapies
MS TreatmentMS Treatment
WellnessWellness
Healthy and balanced dietHealthy and balanced diet Regular exerciseRegular exercise Smoking cessationSmoking cessation Avoid excessive caffeine & alcoholAvoid excessive caffeine & alcohol Routine screening medical exams and Routine screening medical exams and
attention to other medical conditionsattention to other medical conditions Recognition and treatment of depressionRecognition and treatment of depression Manage stressManage stress Vitamin D3 4000 IU/dayVitamin D3 4000 IU/day Vaccinations (avoid live attenuated Vaccinations (avoid live attenuated
vaccines)vaccines)
WellnessWellness
Vitamin DVitamin DAdapted from Hollis et al., CMAJ 2006
Vitamin DVitamin DAdapted from Mora et al., Nature Reviews immunology 2009
Relapse vs Pseudo-Relapse vs Pseudo-relapse vs Fluctuationrelapse vs Fluctuation
30-yr-old woman with RRMS for 3 years, 30-yr-old woman with RRMS for 3 years, on a DMT, calls the Clinic. Over the last on a DMT, calls the Clinic. Over the last 3 days, she has noted pain in the L eye 3 days, she has noted pain in the L eye with some visual blurring, worse at the with some visual blurring, worse at the end of day. Colours seem less bright. end of day. Colours seem less bright. Her last relapse (Lhermitte’s with Her last relapse (Lhermitte’s with numbness of her R arm) was ~2 years numbness of her R arm) was ~2 years ago prior to starting her DMT.ago prior to starting her DMT.
What would you do?What would you do?
Case Mrs. RRCase Mrs. RR
““a focal disturbance of function, affecting a focal disturbance of function, affecting a white matter tract, lasting for more than a white matter tract, lasting for more than 24 hours. Typically, tends to progress 24 hours. Typically, tends to progress over a period of a few days, reaching a over a period of a few days, reaching a maximum in less than 1 week and then maximum in less than 1 week and then slowly resolving.”slowly resolving.” SchumacherSchumacher
““occurrence of a symptom or symptoms of occurrence of a symptom or symptoms of neurological dysfunction, in the absence of neurological dysfunction, in the absence of fever, with or without objective fever, with or without objective confirmation, lasting more than 24 hours.”confirmation, lasting more than 24 hours.” Clinical trialsClinical trials
What is a relapse?What is a relapse?
Recurrence of old symptomsRecurrence of old symptoms Short durationShort duration Accompanying metabolic or toxic changeAccompanying metabolic or toxic change Disappearance of symptoms and signs Disappearance of symptoms and signs
when aggravating metabolic change has when aggravating metabolic change has been correctedbeen corrected
What is a pseudo-What is a pseudo-relapse?relapse?
Changing neurological function Changing neurological function throughout day.throughout day.
What are fluctuations?What are fluctuations?
Lhermitte’s phenomenon/symptomLhermitte’s phenomenon/symptom Uhthoff’s phenomenon/symptomUhthoff’s phenomenon/symptom Multiple tonic spasms over 24 hoursMultiple tonic spasms over 24 hours Trigeminal neuralgiaTrigeminal neuralgia Dragging foot after shopping for 20 Dragging foot after shopping for 20
minutes; better after having coffee and minutes; better after having coffee and éclairéclair
Increased leg weakness with recent Increased leg weakness with recent URTIURTI
Numbness to waist lasting 3 weeksNumbness to waist lasting 3 weeks
Relapse/pseudo-relapse/Relapse/pseudo-relapse/fluctuation?fluctuation?
To Treat or Not to To Treat or Not to Treat?Treat?
InterferonsInterferons Betaseron®Betaseron® Extavia®Extavia® Rebif®Rebif® Avonex®Avonex®
Glatiramer acetate Glatiramer acetate (Copaxone®)(Copaxone®) Natalizumab Natalizumab (Tysabri®)(Tysabri®) Fingolimod Fingolimod (Gilenya®)(Gilenya®) Dimethyl fumarate Dimethyl fumarate (Tecfidera®)(Tecfidera®) Teriflunomide (Aubagio®)Teriflunomide (Aubagio®) Alemtuzumab (Lemtrada®)Alemtuzumab (Lemtrada®)
Disease Modifying Disease Modifying TherapiesTherapies
Seems to protect from relapses (2Seems to protect from relapses (2ndnd & 3 & 3rdrd trimester); likely related to hormone trimester); likely related to hormone levelslevels Fertility treatments may increase risk of Fertility treatments may increase risk of
relapserelapse Increased relapse rate during 1Increased relapse rate during 1stst
trimester post-partumtrimester post-partum First-line injectable DMTs (GA, IFN-β) First-line injectable DMTs (GA, IFN-β)
considered safe in breast-feedingconsidered safe in breast-feeding
PregnancyPregnancy
Symptom ManagementSymptom Management
Sources of SymptomsSymptoms vary widely in incidence
and severity
Sensory symptoms,Lhermitte’sPainProprioception
Optic neuritis
DiplopiaVertigoDysarthriaINO
Tremor,Ataxia
Cognitive loss
Emotional disinhibition
Bladder dysfunction
SymptomsSymptoms
SpasticitySpasticity Tremor & ataxiaTremor & ataxia FatigueFatigue Sensory symptomsSensory symptoms Bowel and bladderBowel and bladder Sexual dysfunctionSexual dysfunction Cognitive impairmentCognitive impairment
Complementary & Complementary & Alternative TreatmentsAlternative Treatments
CAM WebsitesCAM Websites
Neurologycare.netNeurologycare.net Naturaldatabase.comNaturaldatabase.com
There is no specific diagnostic test There is no specific diagnostic test (imaging, blood, CSF) for MS(imaging, blood, CSF) for MS
There is a differential diagnosis for white There is a differential diagnosis for white matter lesions on MRImatter lesions on MRI
Neurological symptoms in MS patients Neurological symptoms in MS patients are not always related to MS activityare not always related to MS activity
MS patients can develop other diseases MS patients can develop other diseases that may impact their MS symptomsthat may impact their MS symptoms
Take HomeTake Home
Exacerbations do not necessarily require Exacerbations do not necessarily require treatment with corticosteroidstreatment with corticosteroids
There is NO role for low dose There is NO role for low dose corticosteroids in the treatment of MS corticosteroids in the treatment of MS relapsesrelapses
Treatment of symptoms will improve Treatment of symptoms will improve quality of lifequality of life
Take HomeTake Home
Thank you!Thank you!