Faculty Bibliography

RATIONALE: Natalizumab is a monoclonal antibody (mAb) indicated for treatment of multiple sclerosis. Natalizumab has special attributes which must be addressed when planning rapid desensitization for immediate hypersensitivity reactions (HSR.) Immediate HSRs during rapid desensitization are common, with consequent need to hold the infusion, treat the HSR, and possibly maintain a slower infusion rate. Complete infusion could require more than 8 hours, however, per FDA approved instructions, each bag of natalizumab solution must be infused within 8 hours of preparation or be discarded. Natalizumab is only supplied as 300 mg singledose vials. One published 3-bag, 12-step rapid desensitization protocol wastes approximately 10% of the drug, by discarding most solution in the first 2 bags. Accordingly, one must open another vial of natalizumab, costing approximately $3,000, or the patient will only receive approximately 90% of the typical intended dose. METHODS: Report of two patients with history of immediate HSR to natalizumab, and adaptation of a 3-bag, 12-step, rapid desensitization protocol as follows: Bag #1-0.6 mg in 50ml; Bag #2-6 mg in 50ml; Bag #3 and Bag #4-each 146.7 mg in 122.25ml. Bag #4 was not prepared until Bag #2 was mostly infused. Bags #2, #3 and #4 were infused completely. RESULTS: 99.8% of the intended dose was infused, without immediate HSR. CONCLUSIONS: With adaptation of a published protocol, rapid desensitization to natalizumab 300 mg is possible, utilizing only one single-dose vial, and with minimal chance of exceeding the FDA-approved eight hour infusion window from the time of preparation of each bag

We review the evidence for a link between multiple sclerosis (MS) and two of the most common primary headache disorders: tension-type headache and migraine. We argue that the association between migraine and MS is biologically plausible and is confirmed by most studies. We discuss possible explanations for the association. First, we consider the possibility that the association is spurious. Next, we consider unidirectional causal models in which one of the conditions increases the risk of the other. A bidirectional model would suggest that each disease predisposes to the other. Alternatively, genetic or environmental risk factors shared by each condition may account for the association between them. We also address the question of whether coexisting migraine or tension-type headache in a patient with MS affects the symptom profile, clinical course, and radiographic characteristics of MS

The objectives of this study were: (1) to assess relative frequency of migraine in multiple sclerosis (MS) patients using the validated self-administered diagnostic questionnaire, and to compare the migraine rates in MS outpatients to age- and gender-matched historical population controls; (2) to compare clinical and radiographic characteristics in MS patients with migraine and headache-free MS patients. We conducted a cross-sectional study to assess the demographic profiles, headache features and clinical characteristics of MS patients attending a MS clinic using a questionnaire based on the American Migraine Prevalence and Prevention (AMPP) study. We compared the relative frequency of migraine in MS clinic patients and AMPP cohort. We also compared clinical and radiographic features in MS patients with migraine to an MS control group without headache. Among 204 MS patients, the relative frequency of migraine was threefold higher than in population controls both for women [55.7 vs. 17.1%; prevalence ratio (PR) =3.26, p<0.001] and men (18.4 vs. 5.6%; PR=3.29, p<0.001). In a series of logistic regression models that controlled for age, gender, disease duration, beta-interferon use, and depression, migraine in MS patients was significantly associated (p<0.01) with trigeminal and occipital neuralgia, facial pain, Lhermitte's sign, temporomandibular joint pain, non-headache pain and a past history of depression. Migraine status was not significantly associated with disability on patient-derived disability steps scale or T2 lesion burden on brain MRI. Migraine is three-times more common in MS clinic patients than in general population. MS-migraine group was more symptomatic than the MS-no headache group