Nevada Osteopathic Medical Association Essentials of ...€¦ · Multiple Sclerosis: Diagnosis § Diagnosis is extremely important since there are now 17 medications on the market

Michael J. Olek, DOAssociate Professor of Neurology

Touro University NevadaCollege of Osteopathic Medicine

Nevada Osteopathic Medical AssociationEssentials of Multiple Sclerosis Care

August 2, 2019: 2PM

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§ MS History§ MS Essentials§ MS Diagnosis

§ MRI, CSF, Evoked Potentials, Serum labs§ Diagnostic Criteria§ Mis-Diagnosis

§ MS Treatment§ Disease Modifying Therapies (DMT’s)§ Relapse Treatments§ Symptomatic Treatments

§ MS Monitoring§ MS Care Concerns

§ MS patients and Vaccines§ Coordination of Care Professionals

Essentials of MS Care

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1396: Sister Lidwina van Schiedam (Dutch)-Earliest recorded case of MS

Multiple Sclerosis: History

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Multiple Sclerosis: History

§ First described clinically by Charcot and pathologically by Vulpian in 1866§ Characterized by inflammation, myelin destruction that leads to sensory, motor and cognitive dysfunction § Early inflammation and destruction of myelin leads to dysfunction§ Secondary axonal loss leads to permanent disability and brain atrophy

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Multiple Sclerosis: Essentials

§ Autoimmune disease of the CNS§ 400,000 US patients and 2.3 million worldwide§ 10,000 new cases/year-Prevalence increases further from equator§ Young females ages 15-40 of Northern European ancestry§ F:M ratio is 3-4:1§ Twin studies: Monozygotic-30% and Dizygotic-5%§ 15% of patient with MS have one or more family relatives with MS§ Presenting symptoms-ON, INO, Sensory/Motor or Ataxia§ 85% initially have relapsing-remitting course

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Multiple Sclerosis: Essentials

§ Smoking makes MS Worse§ Relative Risk of developing MS is 1.5 for smokers§ Risk of developing SPMS was more than three times higher in smokers

§ Many MS patients have low vitamin D levels§ I always check vitamin D levels and supplement as needed§ Large study underway to investigate large doses of vitamin D

§ Obesity in adolescence has been linked to MS§ Diagnosed through History and Physical as well as serum Labs to

rule out other autoimmune diseases, MRI, CSF, Evoked Potentials§ 17 Immunomodulating treatments available-ONLY for MS

(Except Tysabri-Also FDA approved for Crohn’s Disease)

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Multiple Sclerosis: Diagnosis§ Diagnosis is extremely important since there are now 17

medications on the market for MS and they all have various side effects

§ Key Diagnostic Variables§ History: 2 episodes in time and space§ 85% have relapsing-remitting course initially§ Physical exam clues (APD, INO)§ CSF clues (OCB, IgG Index)§ Serum to rule out mimickers§ Evoked Potentials (VER > BAER > SSEP)§ MRI Brain and Spinal Cord with and without Gd

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Multiple Sclerosis: DiagnosisClinical Features suggestive of MS

§ Relapses and Remissions§ Onset between 15 and 50§ Northern European Ancestry§ Female§ 20% present with Optic Neuritis (APD on exam)§ 20% present with double vision (INO on exam)§ Other symptoms include

§ Fatigue§ Uhthoff’s phenomenon§ L’hermitte’s sign

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Multiple Sclerosis: Diagnosis

Clinical Features NOT suggestive of MS§ Steady Progression§ Onset before 10 or after 50§ Cortical deficits such as aphasia, apraxia,

alexia, neglect§ Rigidity, dystonia§ Convulsions§ Deficit developing within minutes

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Multiple Sclerosis: Diagnosis-MRI35 OTHER Causes of White Matter Abnormalities on MRI

Toxic/Metabolic§ Atherosclerosis§ Diabetic Microangiopathy§ Hypertension§ Migraine-12-47%§ CADASIL-Cerebral Autosomal Dominant

Arteriopathy with Subcortical Infarcts and Leukencephalopathy: An inherited small vessel disease (NOTCH-3 gene test)

§ Amyloid Angiopathy

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Toxic/Metabolic§ Cocaine§ B12 Deficiency (Subacute Combined Degeneration)§ CO Intoxication§ Osmotic Myelinolysis (Central Pontine Myelinolysis:

CPM)§ Post-CHEMO§ Post-RADIATION§ Hyperhomocystemia

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Inflammatory§ Multiple Sclerosis§ Vasculitis

§ SLE§Behcet’s§ Sjogrens§ Sarcoid

§ Inflammatory Bowel Disease§ (Crohn’s, Ulcerative Colitis, Caeliac-20%)

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Infectious§ HIV (36%)§ Lyme§ Syphilis§ PML§ Post-infectious ADEM§ Toxoplasmosis§ CMV

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Traumatic§ Post Radiation§ Post Concussion

Hereditary Leukodystrophies§ MLD§ ALD§ Globoid Cell§ Mitochondrial

Normal§ Enlarged Virchow-Robin Spaces§ Normal Aging 15


Others§ Stroke§ Multi-Infarct Dementia (Binswanger’s)§ Lymphoma§ Meningitis§ NPH§ Bi-Polar Disease (18-55% with subcortical

hyperintensities)

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MRI in MS

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Typical MS Brain Lesions

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Typical MS Cord Lesions

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Multiple Sclerosis: CSF Analysis

IgG Index Differential§ MS (80-90% sensitive/94% specific)§ Aseptic meningitis§ Lymphoma§ Neurosyphilis§ GBS§ Cerebral Lupus

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Multiple Sclerosis: CSF Analysis

Oligoclonal banding§ MS-83-94% specific§ Encephalitis§ Meningitis§ Polyneuritis§ Headache§ SSPE

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Multiple Sclerosis: Evoked Potentials

§ VER-80-85% abnormal in definite MS

§ SSEP-65-80%§ BAER-50-65%

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Multiple Sclerosis Laboratory Work-up:(partnersmscenter.org)

§ Vasculitis Labs: [CRP, ESR, C3, C4, ACE]§ HIV, HTLV 1-2§ Vitamin D§ RPR, VDRL§ CADASIL: [Notch 3 mutation]§ Thyroid Panel§ Lupus Panel§ ANA, Rheum Factor§ Anticardiolipin Ab§ Lyme§ B12/Folate

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Multiple Sclerosis Specialized Laboratory Work-up: (partnersmscenter.org)

For Atypical cases:§ WBC Arasulfatase A (MLD)-Mayo Lab, yellow top§ Very Long Chain Fatty Acids (ALD, AMN)-Mayo Lab, green top§ Hexosaminidase A (Tay Sachs)§ Galactocerebrosidase C (Gal-C)§ Fasting blood lactate, Quantitative plasma AA, and Urine organic acid analysis

(MELAS)§ Palmitoyl Protein Thioesterase 1 (adults), tripeptidyl peptidase 1, CLN3, and CLN5

(Neuronal Ceroid Lipofuscinoses-NCL)§ NPC-1 (Niemann Pick)-Buccal or rectal mucosa biopsy for EM or skin biopsy for

fibroblast culture or peripheral blood smear (look for vacuolated monocytes)§ HIV§ Special Vasculitis W/U:

§ Behcet’s-Pathergy skin test or skin biopsy and/or derm/rheum referral§ Brain Biopsy:

§ NCL shows fingerprint profiles and curvilinear bodies as well as diffuse white matter gliosis. This is helpful in identifying Systemic Histiocytosis or Whipple’s or Lymphoma

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Multiple Sclerosis Differential Diagnosis

§ Metabolic§ B6 or B12 Deficiency§ CPM§ Hypoxia§ MELAS§ MLD, ALD

§ Infectious§ HIV, HTLV-1, Lyme, PML

§ Neoplastic§ Paraneoplastic§ Spinal cord tumor§ CNS Lymphoma

§ Vascular§ Spinal Dural AVF§ CADASIL§ Susac’s syndrome

§ Psychiatric§ Conversion Disorders§ Malingering 26

§ Spinal Cord Abnormalities§ Cervical Spondylosis§ Arnold-Chiari

§ Genetics§ Hereditary Ataxias§ Leber’s

§ Autoimmune§ Sjogren’s§ Behcet’s§ NMO-SD§ ADEM§ Vasculitis§ Sarcoid§ CT disorder

§ Variants of MS§ CIS such as ON§ Marburg’s

Updated MS Diagnostic Criteria

§ Update McDonald Criteria for 2017§ Now able to use CSF OCB > 4 more than

serum OCB as clinical evidence of a lesion§ Now MRI lesions can be symptomatic or

Asymptomatic§ The main purpose of the revision is to

diagnose and treat MS Early

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Pocket Diagnosis Card for Multiple Sclerosis available online through the National MS Society

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Multiple Sclerosis: Diagnosis/NOTMIS-Diagnosis

4 Academic MS Centers over 13 months§ 110 patients MIS-Diagnosed with MS

§ 22% Migraine§ 15% Fibromyalgia§ 12% Abnormal MRI with non-focal exam§ 11% Psychogenic § 6% NMOSD

§ Time of carrying misdiagnosis:§ 3-9 Years-29%§ 10-20 Years-26%

Andrew Solomon, MD-UVermont; Neurology 2016;87:1-7 29

Multiple Sclerosis: Diagnosis/NOT

MIS-Diagnosis§ 70% of patients had taken DMT’s

§ Tysabri-13%§ Mitoxantrone-2%§ Cyclophosphamide-1%

§ 4% of patients had participated in a MS Study§ Earlier missed opportunity to Dx MS-72%§ Unnecessary morbidity due to misdiagnosis-31%


Multiple Sclerosis: Diagnosis/NOTMIS-DiagnosisUnnecessary Morbidities-31%

§ DMT immunomodulatory effect and DMT side effects§ Steroids and side effects§ Delay in treatment of cervical spondylosis§ Psychological harm due to anxiety/depression§ Worsening of NMOSD with interferon§ Autologous Bone Marrow Transplants§ Death from Fulminent NMO


Multiple Sclerosis: Diagnosis/NOTMIS-Diagnosis§ Update on MS MIS-Diagnosis§ Article from May 2019§ 2 Academic MS centers (UVM and Cedars-Sinai)§ Almost 1 in 5 were MIS-Diagnosed with MS§ Most common alternatives:

§ Migraine-16%§ Radiologically Isolated Syndrome (RIS)-9%§ Spondylopathy-7%§ Neuropathy-7%

§ The MIS-Diagnosed patients received 110 patient years of Unnecessary MS Disease Modifying Therapy (DMT)

Marwa Kaisey and Andrew Solomon, et al in MS and Related Disorders (May 2019): Incidence of MS misdiagnosis in referrals to two academic centers

Preventing Misdiagnosis of MS

§ Detailed History and Physical§ Vigilance for RED FLAGS

§ Nonspecific sx with MRI abnormalities§ Hx of neurological dysfunction without objective signs§ Normal CSF

§ Evaluation of CSF-OCB and IgG index (87-95%)§ Careful review of MRI and other diseases which

may contribute to MRI lesions§ Serum markers for diseases mimicking MS

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Multiple Sclerosis

§ Once the diagnosis of Multiple Sclerosis (MS) has been made, the process of choosing the best disease modifying therapy (DMT) is the next crucial step since the all have their own advantages and disadvantages

§ The basic fact is that every patient with MD taking a DMT for does better than those patient NOT on a DMT

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Natural History of Untreated Multiple Sclerosis

§ 30% to 50% of patients worsen by 1.0 EDSS unit within 2 to 3 years (1)

§ Up to 44% of patients need an assistive device for walking within 5 years (1)

§ Relapsing MS leads to progressive MS after 10 years in 50% of cases (2)

§ 54% to 65% of patients with MS experience cognitive impairment, affecting employment, social life, and daily functioning (3)

1. Munschauer FE, Stuart WH. Clin Ther.1997;19:868-882.2. Weinshenker BG et al. Brain.1989;112:133-146. 3. Rao SM et al. Neurology. 1991;41:685-691.

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Multiple Sclerosis: Goals of Treatment

§ Reduce frequency of relapse

§ Slow progression of disability

§ Reduce MRI activity

§ Prevent morbidity from symptoms and provide palliative care

§ Maintain adherence

§ Provide long-term efficacy and safety

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Multiple Sclerosis Medications 2019§ Injectable medications

§ Avonex (interferon-beta-1a) IM q week§ Betaseron (interferon beta-1b) SQ QOD§ Copaxone (GA-glatiramer acetate) SQ Daily§ Extavia (generic interferon beta-1b)§ Glatopa (generic equivalent of GA both 20mg and 40 mg doses)§ Plegridy (peginterferon-1a) SQ every 14 days§ Rebif (interferon beta-1a) SQ 3x/week§ Zinbryta (daclizumab)-Taken off the market March 2, 2018 due to liver damage and

encephalitis§ Oral Medications

§ Aubagio (teriflunomide) QD§ Gilenya (fingolimod) QD§ Tecfidera (dimethyl fumarate) BID§ Mavenclad (cladribine) variable dosing schedule§ Mayzent (siponimod) variable dosing schedule

§ Infused Medications§ Lemtrada (alemtuzumab) Weekly treatments on a yearly basis§ Novantrone (mitoxantrone) Every 3 months§ Ocrevus (ocrelizumab)-2 initial infusions then every 6 months-ONLY FDA-Approved

medication for PPMS§ Tysabri (natalizumab) Every 30 days

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Multiple Sclerosis Medications 2019§ Medications approved for CIS

§ Avonex§ Betaseron/Extavia§ Mayzent

§ Medications approved for RRMS§ Avonex§ Betaseron/Extavia§ Copaxone/Glatiramer Acetate generic/Glatopa§ Plegridy§ Rebif§ Aubagio§ Gilenya (Approved for those patients > 10 years old)§ Mavenclad§ Mayzent§ Tecfidera§ Lemtrada (Should fail > 2 Other MS Medications)§ Ocrevus§ Tysabri (Must be used as Monotherapy)

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Multiple Sclerosis Medications 2019

§ Medications approved for Worsening RRMS§ Novantrone

§ Medications approved for PPMS§ Ocrevus

§ Medications approved for SPMS§ Novantrone

§ Medications approved for ACTIVE SPMS§ Mavenclad§ Mayzent

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Note: There is a 29 Page PDF file from the National MS Society detailing the basic information, side effects and warnings of ALL the MS Medications

MS Medications-Decisions, Decisions

On current therapy doing well (?): No ChangeNew diagnosis of RRMS:

§ JC Virus Ab Neg-Tysabri§ JC Virus Ab Pos-Tecfidera/Consider Tysabri x 12

months then switch to Tecfidera

On current therapy NOT doing well (?):§ Switch to Other DMT§ Add immunosuppressant§ Switch to IVIG or IV Cytoxan

40What exactly is “Doing Well”?

[These are MY Guidelines]

Potential Indicators of Suboptimal ResponseClinical Indicators§ Relapse frequency: ≥1 severe relapse or ≥2 relapses of any severity in 1 year§ Relapse frequency that has not decreased after the patient has been on DMT for ≥6 to

12 months versus the pretreatment rate§ Incomplete recovery at 6 months from one or more attacks§ Involvement of multiple neurologic systems or functional domains Functional Indicators§ Progressive motor or cognitive impairment that interferes with daily activities (after

ruling out contributing factors such as depression, concurrent medications, and co-morbid diseases)

§ Increasing EDSS score or permanent residual disability§ Change in EDSS at scores <3.0 should not be used in isolation to define treatment

failure § Annual increase in EDSS of ≥1 point from a previous score of 3.0–5.5 or a ≥0.5 point

increase from a score of ≥6.0 may indicate transition from RRMS to SPMS, or only partial response to treatment in SPMS)

Radiologic Indicators§ New or recurrent brain stem or spinal cord lesions§ Increasing lesion number (eg, ≥3 enhancing lesions, or >3 new T2 lesions in 1 year,

or ≥2 new T2 lesions on each repeated scan performed at no less than quarterly intervals) and lesion size on MRI, especially if increase in >2 types of lesions or in the presence of EDSS worsening independent of attacks 41

Multiple Sclerosis: MY Rationale for use of Tysabri

§ 68% Relapse Rate Reduction§ 42% Slowing of Confirmed Disability§ 92% Reduction in MRI Gd Lesions§ 83% Reduction in MRI T2 Lesion§ 76% Reduction in MRI T1 Lesions

[Limiting Factor is PML: Progressive Multifocal Leukoencephalopathy]

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2018 Study of Worldwide Occurrence of JC virus in patients diagnosed with MS or NMO

Paz SC, Branco LP, Pereira MAC, Spessotto CV, Fragoso YD. Systematic review of published data on the worldwide prevalence of John Cunningham virus (JCV) in patients with multiple sclerosis. Epidemiol Health. 2018. doi: 10.4178/epih.e2018001.

PURPOSE:The John Cunningham virus (JCV) is a polyoma virus that infects humans mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies has been described to be between 50% and 90% in human serum. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish real-life values of JCV seropositivity in these individuals.

METHODS:The present review followed the PRISMA guidelines using the following search terms: "JCV" OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica" AND "prevalence". These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, Medline, SciELO, LILACS, Google Scholar and EMBASE.

RESULTS:After initial selection, 18 papers were included in the review. These articles reported on the prevalence of JCV antibodies in serum of patients with MS or NMO living in 26 countries. The systematic review identified data on over 29,000 patients with MS/NMO and found overall that 57% of them (16,730 individuals) were seropositive for anti-JCV (range 40% to 69.5%).

CONCLUSION:

The median worldwide prevalence of JCV among adults with MS or NMO was 57% 43

https://www.ncbi.nlm.nih.gov/pubmed/29370683

Updated Risk of PML with Tysabri: JCV Ab Status

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Clinical Factors Predictive for Aggressive MS

§ Male§ African-American§ Onset > 40§ Motor SX or Ataxia at onset§ Incomplete recovery from relapses§ Frequent early relapses [> 2 in first 2 years]

The Science of MS Management Winter 2017/2018. Vol7 Number 3

Trials of MS Medications in Aggressive MS

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Agent Trial Design Active Definition OutcomesNatalizumab(Tysabri)

70 Active Pts Ø2 relapses AND Ø1 EDSS point > 6 months

48% disease free at 1 year and baseline EDSS < 3 predicted disease free patients

Fingolimod(Gilenya)

Post-HOC Ø1 relapse ANDØ1 Gd lesion or > 9 T2 lesions

67% reduction in RR over 2 years versus placebo

Alemtuzumab(Lemtrada)

Extension of DBPC Trail

Ø2 relapses prior ANDØ> 1 Gd lesion

49.4% reduction in RR versus IFN and 85% of those patients were relapse free at 5 years

Daclizumuab(Zinbryta)

Subgroup of DBPC Trail

Ø2 relapses prior ANDØ> 1 Gd lesion

50% RR reduction versus placebo and 76% reduction in new/enlarging T2 lesions

MS Medications-Decisions, Decisions§ PPMS

§ Ocrevus§ SPMS

§ Do NOT use RRMS medications (Except ACTIVE SPMS-see below)§ Trial of immunosuppression:

§ MTX, Imuran, Cellcept, Cytoxan (CTX), IV steroids§ Intravenous Immunoglobulin(IVIG)§ Plasma Exchange§ Bone Marrow Treatment (BMT)

§ Active SPMS§ Mavenclad§ Mayzent

§ Acute Attacks§ IV steroids or Achtar Gel§ Possible Plasma Exchange or IV Cytoxan

§ NMO§ Rituxan 47


Managing MS Attacks

Steps when assessing an MS Attack:§ Examine the patient if possible§ Obtain Vital Signs§ Obtain urinalysis§ Obtain CBC with differential§ Consider CXR if symptoms are consistent with pneumonia§ NOTE: Infections can make MS patients feel worse and simulate an attack.

If an MS patient calls on a Friday with symptoms and cannot get in to see me, I always get labs first because:§ STEROIDS make infections WORSE§ NO clear evidence that treating attacks impacts the overall disease course

of MSUsual Medication for a MS Attack:

§ IVMP 1000g Daily x 5 with or without oral taper§ Corticotropin injction gel (Achtar) can be substituted for those that do not

tolerate IVMP or those with poor IV access or those who prefer self-injections§ Plasma Exchange can be used in poor responders to IVMP 48


Managing MS Symptoms

Spasticity Dizziness/Vertigo§ Baclofen (lioresal)§ Zanaflex (tizanidine)§ Dantrium (dantrolene)§ Valium (diazepam)§ Klonopin (clonazepam)§ Baclofen Pump-

Neurosurgery§ Botox-Neuro or PMR

§ Physical Therapy§ Antivert (meclizine)

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Bladder Dysfunction

§ Ditropan (oxybutynin)§ Detrol (tolterodine)§ Vesicare (solifenacin)§ Tofranil (imipramine)§ Sanctura (tropsium chloride)§ DDAVP Nasal Spray (desmopressin)§ Enablex (darifenacin)§ Flomax (tamsulosin)§ Hytrin (terazosin)§ Minipress (prazosin)§ Pro-Banthine (propantheline)§ Myrbetriq (mirabegron)§ Intermittent urinary catheter§ Botox into the bladder-URO§ Bladder stimulator-URO

Bladder Infections

§ Bactrim; Septra(sulfamethoxazole)

§ Cipro (ciprofloxacin)§ Macrodantim (nitrofurantoin)§ Hiprex (methenamine)§ Pyridium (phenazopyridine)

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Bowel Dysfunction§ Colace (docusate)§ Dulcolax (bisacodyl)§ Enemeez (docusate stool softener laxative)§ Fleet Enema (sodium phosphate)§ Mineral Oil§ Metamucil (psyllium hydrophilic musilloid)§ Phillips Milk of Magnesia (magnesium hydroxide)§ Sani-Supp suppository (glycerin)§ High Fiber Diet§ Possible referral to GI

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Depression§ Cymbalta (duloxetine hydrochloride)§ Effexor (velafaxine)§ Paxil (paroxetine)§ Prozac (fluoxetine)§ Wellbutrin (bupropion)§ Zoloft (sertraline)§ Psychotherapy§ Psychiatrist§ Group meetings

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Fatigue§ Amantidine§ Provigil (Modafinil)§ SSRI’s such as Prozac

Pseudo-Bulbar Affect§ Nuedexta (Dextromethorphan and Quinidine)

Tremors Walking/Gait Difficulties§ Ampyra (dalfampridine)§ Physical Therapy

§ Klonopin (clonazepam)§ Laniazid, Nydrazid (isoniazid)§ Weighted Wrist Bracelets§ Occupational Therapy§ Deep Brain Stimulation (DBS)

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Pain/Itching Sexual Problems

§ Neurontin (gabapentin)§ Pamelor (nortriptyline)§ Tegretol (carbamazepine)§ Elavil (amitriptyline)§ Klonopin (clonazepam)§ Dilantin (phenytoin)§ Atari (hydroxyzine)

§ Viagra (sildenafil)§ Cialis (tadalafil)§ Levitra (vardenafil)§ Vacuum Pump-UROLOGIST§ Papaverine injections-UROLOGIST§ MUSE transurethral (alprostadil)-URO

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Multiple Sclerosis Monitoring: Biomarkers

MRIONTT: 15 years-50% developed MS

§ No Lesions on Baseline MRI-25% developed MS

§ >1 Lesion on Baseline MRI-72% developed MS

Clinically Isolated Syndrome (CIS) Study§ Initial MRI: No Lesions: 19% MS in 14 years§ Initial MRI: > 1 lesion: 88% MS in 14 years§ Initial MRI: No Lesions: 6% EDSS > 6 in 20 years§ Initial MRI: > 10 lesions: 45% EDSS > 6 in 20 years

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IFN Neutralizing Antibodies§ Avonex-5%§ Rebif-25%§ Betaseron-38%

Aquaporin-4 [NMO]§ Serum: 91% specific and 73% sensitive§ CSF: 60% predictive in patient’s with Optic Neuritis

JC Virus Antibodies

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IQuity Labs§ RNA Microarray Gene Chip Analysis

Mayo Labs§ CDS1-CNS Demyelinating Disease Evaluation, Serum

§ AQP4 (Aquaporin-4-IgG titer) [Typically seen in NMO-SD patients]§ MOG (Myelin Oligodendrocyte Glycoprotein)

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These tests support providers in earlier diagnosis of diseases such as:•Multiple Sclerosis

–Cost: Approximately $1250–Result turn-around time: One week

•IBS•Crohn’s Disease•Ulcerative Colitis•Fibromyalgia•Lupus•Rheumatoid Arthritis•Other challenging autoimmune diseases and related conditions

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Mayo Clinical Labs:§ CDS1: CNS Demyelinating Disease Evaluation, Serum

using FACS (Fluorescence-Activated Cell Sorting)§ AQP-4§ MOG§ Sensitivity > 80% and Specificity > 99%

§ NMO Patients§ 80% are seropositive for NMO§ Of the 20% sero-negative, 1/3 are MOG seropositive


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MOG Seropositivity in disorders such as:§ (NMO-SD, ON, TM, ADEM)§ MOG associated Inflammatory Demyelinating

Disorder (IDD)§ Antibody mediated diseases such as AQP-4

NMO and MOG mediated IDD should NOTbe treated with MS disease modifying therapies (DMT)

Overlap of CNS Demyelinating PhenotypesNeurological Manifestation Frequency of AQP4 Frequency of MOG

NMO 80% 7%

Recurrent LETM (Longitudinally Extensive Transverse Myelitis)

60-80% < 5%

Onetime LETM 40% 20%

Recurrent Optic Neuritis 15% 25%

CRION: Chronic Relapsing Inflammatory Optic Neuropathy

< 5% 25%

Onetime ON < 5 % < 5%

Area Postrema Syndrome < 5% < 5%

ADEM or PRES < 5% 40%

New medication FDA approved for NMO-SD

June 2019

§ Alexion Receives FDA Approval Of SOLIRIS® (Eculizumab) For The Treatment Of Adults With Neuromyelitis Optica Spectrum Disorder (NMOSD) who Are Anti-Aquaporin-4 (AQP4) Antibody Positive

§ SOLIRIS is a first-in-class complement inhibitor that works by inhibiting the C5 protein in the terminal part of the complement cascade

§ Prevalence of NMO-SD is 0.5-10/100,000§ NMO-SD is seen predominantly in women§ SOLIRIS reduced the number of relapses by 94%§ SOLIRIS is also approved for Atypical Hemolytic Uremic Syndrome

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MS and VaccinesBasic Points:

Data updated 2017 (J Neurol 264:1035-1050)§ Screen for TB before starting several MS medications§ No LIVE vaccines§ No LIVE Attenuated vaccines if on immunosuppressants§ Some DMT’s require vaccination for Herpes prior to start§ Delay vaccine if patient has an active relapse§ No change in the risk of developing MS after vaccinations

against seasonal influenza, Hep B, HPV, MMR, Variola, Tetanus, BCG, Polio or Diphtheria

§ No increased risk of relapse following vaccination against seasonal influenza

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2017 Guide for MS and Vaccines

Vaccine Vaccine Type Safe for MS patients on medication?

MMR Live attenuated Yes except if on Immunosupressants

OPV Live attenuated NO

Varicella Live attenuated Yes except if on Immunosuppressants

Inactivated Polio Inactivated YES

Inactivated Flu (Fluarix) Inactivated YES

Influenza Nasal (Flumist) Live attenuated NO

DPT Toxoid YES

H. Influenza B (Hibrix) Component YES

Hepatitis B vaccine Component YES

Hepatitis A vaccine Inactivated YES

Pneumococcal vaccine Component YES

Meningococcal vaccine Toxoid conjugate YES

Yellow Fever vaccine Live attenuated NO

Typhoid vaccine Live attenuated NO

HPV (Guardasil) Component YES

Tetanus toxoid Toxoid YES

Rotavirus Live attenuated NO

Malaria Live attenuated NO65

MS Treatment Team

• Primary Care Physician• Neurologist• Urologist• Nurse• Physiatrist • Physical Therapist• Occupational Therapist• Speech/language pathologist

• Psychiatrist• Psychotherapist• Neuropsychologist• Social worker/Care manager• Pharmacist• Nutritionist

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Multiple Sclerosis Information

Most information for physicians and patients can be found at the National

MS Society website:www.nationalmssociety.com

orwww.partnersmscenter.org

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Thank You

Questions? 68

Documents

Nevada Osteopathic Medical Association Essentials of ...€¦ · Multiple Sclerosis: Diagnosis § Diagnosis is extremely important since there are now 17 medications on the market