EFrohman cocktail for reducing side effects of tecfidera

1. 0.5 to 1 mg of glycopyrrolate (Robinul) for GI

2. Baby ASA + 10mg of Zyrtec for flush, hot, etc. 

Above taken 30-60 minutes before both doses (NOT concomitantly). 

Then take Tecfidera with a cup of applesauce (or more food). 

2-4 weeks of this then attempt to withdraw. Some can, some cannot. 

I will tell you all, the above has been magic in a number of our "ready to jump ship" patients. It's reduced our 30% down to less than 10% withdrawal. Perhaps our percentage of intolerant patients is higher than most, but Bob Lisak told me last night, this was his number as well. 

Pearls on mitoxantrone related leukemia and toxicity

review article  Chan A and LoCoCo F.  MTX related acute leukemia in MS. An open or closed book>
Neurology 2013; 80"1529-33.

Pearls

1. Current therapy related risk is 0.81 % but varies widely among countries.  It still is current therapy in many parts of Europe with different protocols in different countries.

2. Therapy related leukemia is specifically acute promyelocytic leukemia (the "other" PML). This may be due to preferential attachment to DNA breaks at the PML gene site locus.

3.  Genetic variants of dna repair genes  BRCA 2 (rs1801406) and XRCC5 (rs207906) and detoxification enzyme CYP384(rs2740574) may predispose to apml. Combinations of first two lead to 50 fold increase in risk of MTX associated leukemia in MS patients.

4.  Early MTX cardiotoxicity is associated with a rare ABC transporter genotype leading to increased intracellular MTX levels.

5.  aPML is aggressive and often fatal within hours or days if NOT recognized, but a very treatable form of leukemia if recognized and diagnosed promptly.  80 % curable with all trans retinoic acid and arsenic trioxide together with anthracycline chemotherapy, which is true also for MTX related forms.

6.  Presentations of aPML: bruising, petechiae, anemia, thrombocytopenia, infections related to neutropenia and immune dysfunction,  lymphadenopathy and splenomegaly,  and systemic symptoms including fever and weight loss.  Leukocyte nadir occurs 10-14 days after treatment and returns after 21 days, monitoring is crucial.

7.  Other tests that hav potential value in assessing include blood smear, aPTT, fibronogen, d-dimer, LDH, and bone marrow biopsy.

8.  aPML may occur up to five years after therapy so vigilance in surveillance is indicated.

Pearls Frohman's talk on symptom management AAN 2013

1.  70 % of MS patients have impaired sweating, or delayed sweating.  This complicates efforts to manage heat intolerance.

 

2.   Pulfrich's sign after optic neuritis is very common and can present as dizziness or sensation of discomfort with moving cars, roller coasters, etc.  It is easily treatable with tinted lenses.

 

3.   Uhtoff's sign and L;Hermitte's sign each have many and varied analogues in systems throughout the body besides just the visual and c spine areas.

 

4.  Calls "MS hug" the "anaconda sign"

 

5.  Beware of infections in MS patients, compare temperature against their true baseline temp.  If they run 97 degrees, then 98.2 can represent a fever and an infection.

 

6.  Reverse Uhtoff's occurs when MS patients are sensitive to cold temperatures.

 

7.  Bronson's vitamins, available online are effective in some patients with fatigue and contain carnitine

 

8.  Before prescribing anticholinergics, check a PVR if high check for pelvic floor abnormalities, allow patients to double and triple urinate if needed to relax and get the number down.

 

 

IRIS and Tysabri related PML

Tan IL, McArthur JC, Clifford DB, et al.  Immune reconstitution syndrome (IRIS) in natalizumab associated PML.  Neurology 2011; 77: 1061-1067

Patients in literature (42) were generally managed with discontinuation and PLEX/IA.   17 patients had contrast enhancement at time of discontinuation (early PML-IRIS) and 20 developed it later(late PML-IRIS).  load All patients developed IRIS.  Among early IRIS patients, JC virus load increased tenfold, among late IRIS patients, load increased  lesthan two fold.  All patients had worsening EDSS after discontinuation of natalizumab, but early IRIS patients did far worse. Mortality was about the same in early IRIS and late IRIS groups  20-30 %, slightly worse in early group.  Corticosteroid therapy was associated with better EDSS outcome/score.  

Conclusion:  PLEX may accelerate IRIS, corticosteroids may be beneficial and may require a larger study to confirm.

Notes
there are also 2 forms of IRIS in HIV literature
there is no effect of prior immunosuppression

mefloquine and mirtazepine did not seem to help although this was not purpose of study
adjuvant steroids help another iris like syndrome, TB meningitis in HIV negative patients that helps survival.