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Diagnosis:

  • McDonald Criteria (2017)
  • MRI McDonald Criteria:
    • Dissemination in space: >1 or 1 T2 lesions in at least 2/4: periventricular, juxtacortical, infratentorial, spinal cord
    • Dissemination in time (at least one point):
      • 1. A new T2 and/or gad-enhancing lesion on follow-up MRI, with reference to a baseline scan, irrespective of the timing of the baseline MRI.
      • 2. Simultaneous presence of asymptomatic gad-enhancing and nonenhancing lesions at any time.
  • EDSS Form

 



Mimics:

  • Diagnoses to consider: NMO, sarcoid, B12 deficiency, Whipple, mitochondrial disorder, CADASIL, antiphospholipid antibody syndrome, Lupus, Sjogren's, Wilsons, Adrenoleukodystrophy, histiocytosis, vasculitis, Susac syndrome, lymphoma, Behcet, Lyme, CLIPPERS
  • Labs to send: Lyme antibody, B12, HIV, ANA/ENA, ACE, rarely HTLV-1, consider NMO Antibody (miscellaneous lab sendout to Mayo)


Treatment: 

Generic Name

Brand Name

Mechanism

Dosing

Monitoring

FDA Approval

Relapse Rate Reduction (compared to placebo)

Side Effects

Risks

Other

Interferon 1a/1b

Betaseron, Avonex, Rebif

Enhancement of suppressor T cell activity, reduction of proinflammatory cytokines, down-regulation of antigen presentation, and reduced trafficking of lymphocytes

Daily to weekly injections

CBC/comp every 6 months

1993+

~30%

Flu-like symptoms, injections site reactions, depression, headaches

Rare hepatotoxicity, leukopenia

Can develop neutralizing antibodies

Glatiramer

Copaxone

Mixture of random synthetic polypeptides, similar to myelin basic protein, competition for MHCII presenters to T cells

20mg daily injection or 40mg 3x/week injection

None

1996

~30%

Injection site reactions, injection systemic symptoms (flushing, diaphoresis), lipoatrophy

None.


Dimethyl fumarate

Tecfidera

Fumaric acid ester. Mechanism unclear. Also called BG-12.

120mg BID x 7 days, then 240mg BID, PO

CBCPD, LFTs every 6 months

2013

44-51%

Flushing, diarrhea, nausea, abdominal pain

Lymphopenia

Daily baby aspirin may help side effects. Case reports of PML in formulation for psoriasis.

Teriflunomide

Aubagio

Inhibits dihydro-orotate dehydrogenase, interfering with pyrimidine synthesis

7-14mg daily PO

LFTs and CBC every 6 months

2012

31%

GI upset, hair thinning

teratogen, hepatotoxicity


Fingolimod

Gilenya

Sphingosine-1-phosphate receptor modulator, sequesters lymphocytes in lymph nodes

0.5mg daily PO

CBC, LFTs, EKG, Ophthalmology (start and 3 months), ensure previous exposure to VZV

2010

54%

Well tolerated, rare headache, influenza, diarrhea, back pain, elevated liver enzymes, and cough

Arrhythmia, bradycardia, rare death, macular edema, LFTs, VZV, teratogen, 2 cases of PML

Requires 6 hour cardiac monitoring during first dose.

Natalizumab

Tysabri

Monoclonal antibody that binds alpha4-integrin and blocks interaction of alpha4beta1-integrin on leukocytes with vascular cell adhesion molecules, inhibiting migration of leukocytes from blood into CNS

Monthly 400mg infusion

JC Virus every 6 months

2004

68%

Well tolerated. Rare anxiety, fatigue, edema, infusion-related symptoms.

PML - risk table below

Rare neutralizing antibodies.

Alemtuzumab

Lemtrada

Monoclonal antibody against CD52, depleting lymphocytes and monocytes

IV infusion 12mg daily x 5 days and then 12mg daily x 3 days every year

CBCPD, probably monitor urine, renal function, and thyroid function

2014

~50% (compared to IFN beta 1a)

Infusion-related symptoms

Infections (URI, UTI, oral herpes). Autoimmune disorders (thyroiditis, ITP, Goodpasture syndrome), bone marrow suppression


Mitoxantrone

Novantrone

Anthracycline analogue, inhibits DNA/RNA synthesis.

12mg/m2 every 3 month infusion

TTE, CBCPD, Comp,

2000

66%?

Alopecia

Cardiotoxicity (systolic dysfunction, CHF), acute leukemia, amenorrhea, infections

Used rarely for progressive or refractory MS. Avoid in old or significantly disabled patients

Ocrelizumab

Ocrevus

Monoclonal antibody against CD20, binds to a different, but overlapping epitope than rituximab

IV infusion every 6 months, first cycle is day1 and day15, subsequent cycles are day 1

CBC, CMP, IG Quant

TB Quant, Hepatitis panel, HIV, VZV serology, +/- JCV index

2017

70-80%, 50% compared to interferon

Infusion-related symptoms

One patient died due to inflammatory reaction


Natalizumab:
  • To send JC virus in Michart - miscellaneous send-out - JC virus stratify through Quest. 3mL Lavender top. 
  • 50% patients with MS will be JC virus positive. 2-3% yearly conversion rate.

    JC Virus Antibody Results

    Past Immunosuppressants?

    Overall Risk

    Risk Up to 24 Months of Therapy

    Risk After 24 Months of Therapy

    Negative

    No

    1:9,505

    1:45,890

    1:5,725

    Negative

    Yes

    1:3,352

    1:16,184

    1:2,019

    Positive

    No

    1:238

    1:1,147

    1:143

    Positive

    Yes

    1:84

    1:405

    1:50

Source: http://www.neurology.org/content/78/6/436


 Symptomatic Treatments

  • Gait
    • Dalfampradine (Ampyra) - potassium channel blocker, improves conduction across demyelinated axons.
      • 10mg BID
      • Risks: seizure, trigger trigeminal neuralgia, don't take if CrCl <50
  • Fatigue
    • Amantadine (Symmetrel) - 100mg BID. Caution in seizures or renal dysfunction
    • Modafanil (Provigil) - 100mg daily up to 100mg twice daily or 200mg daily. Expensive.
    • Methylphenidate - 10-60mg daily
  • Depression
    • Fluoxetine (especially with fatigue) - 10-20mg daily -> BID
    • other SSRIs
  • Spasticity
    • Baclofen
    • Tizanidine (Zanaflex)
    • Diazepam (Valium)
    • Dantrolene
    • Botulinum toxin (Botox)
  • Urinary urgency
    • Oxybutynin (Ditropan) - 5mg BID, 10mg daily, up-titrate as needed
    • Tolterodine tartrate (Detrol)
  • Urinary retention
    • Doxazosin (Cardura)
    • Tamsulosin (Flomax)
  • Paroxysmal Symptoms
    • Carbamazepine
    • Valproic acid
    • Oxcarbazepine
    • Gabapentin

How to set up an outpatient infusion (from Inpatient service or from ED)

  • Consider giving patient 1,250mg of PO prednisone daily to finish the three day course as similar efficacy and easier to set up.
  • Otherwise, on Michart. send an encounter to Nursing (TC NEU CLIN SUP) to arrange, next available solumedrol infusion. Nursing will set up orders and forward to MIST (infusion scheduling-phone734-232-2655) and they will arrange in next available location. 5TACU (on 5C-transplant), Taubman, East Ann Arbor, Northville or Canton infusion Center. 



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