Botulinum Toxin in the Treatment of Chronic Migraine

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Ezra Benson
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1 Botulinum Toin in the Treatment of Chronic Migraine ERIC L. FRY, MD ASSOCIATE PROFESSOR OF OPHTHALMOLOGY UNIVERSITY OF KANSAS FRY EYE ASSOCIATES, GARDEN CITY, KS History of Botulinum Toin Justinus Kerner, a German physician, first described the link Sausage poison Coined the term botulism (Botulus Latin for sausage) 1897 Emile van Ermengem found bacterium responsible Clostridium botulinum 1928 P. Tessmer Snipe and Hermann Sommer purified toin 1949 Arnold Burgen discovered the mechanism of action 1973 Alan Scott used monkey eperiments for therapeutic uses of toin st used of BTX-A to treat strabismus and blepharospasm H con t 1989 Boto (BTX-A) approved by the FDA for treatment of strabismus, blepharospasm, hemifacial spasm 1992 FDA approval for treatment of glabellar frown lines 1993 Used treat hyperhidrosis 2010 FDA approval to treat chronic migraines 1

poison Coined the term botulism (Botulus Latin for sausage) 1897 Emile van Ermengem found bacterium responsible Clostridium botulinum 1928 P.

2 What is BTX Botulinum toin is the most acutely toic substance known Produced by Clostridium botulinum Inhibits the release of acetylcholine from nerve terminals Lasts 3-6 months Boto (onabotulinumtoina) 2

3 Botulinum Toin OnabotulinumtoinA Boto RimabotulinumtoinB Myoblock AbobotulinumtoinA Dysport IncobotulinumtoinA Xeomin Headache Primary Headaches Migraines Tension-type headaches Cluster headache and other trigeminal autonomic cephalagias 3

Xeomin Headache Primary Headaches Migraines Tension-type

4 Secondary Headaches Trauma Cranial or cervical vascular disorder Substance or its withdrawal Infection etc Migraine 10% of the population suffer from migraines 18% are women 6% are men 113 million lost work days $13 billion in lost earning Moderate to sever HA Usually unilateral but can be bilateral Onset usually around puberty or young adult Associated with nausea and vomiting Phonophobia Photophobia Strong family h Usually has a prodrome Migraine 4

billion in lost earning Moderate to sever HA Usually unilateral but can be bilateral Onset usually around puberty

5 Migraine with Aura Visual prodome Fortification spectrum (scintillating scotoma) Small scotoma near fiation which gradually enlarges and moves to the periphery Almost always hemianopic (frequently perceived by the pt as monocular) Lasts minutes follow by HA usually on the contralateral side Migraine Without Aura Can be a global headache not strictly unilateral Accompanied by other symptoms (nausea, vomiting, phonophobia, photophobia) Acephalgic Migraine Visual symptoms of migraine with aura, but with out the associated headache More common in the elderly Episodic diplopia 5

side Migraine Without Aura Can be a global headache not strictly unilateral Accompanied by other symptoms (nausea, vomiting, phonophobia,

6 Chronic Migraine 15 or more headache days a month Each HA lasting for 4 hours or more Evaluation History is the most important part *ocular eam is normal in vast majority of pts Nature of HA (sharp, dull, constant, throbbing) Pattern (daily, morning, evening, wake from sleep) Location (unilateral, bilateral, localized) Associated phenomenon (scotoma, nausea, vomiting, ptosis, tearing) Family H Evaluation New onset or have they had HA like this in past HA always in same spot or does the pain move 6

morning, evening, wake from sleep) Location (unilateral, bilateral, localized) Associated phenomenon (scotoma, nausea,

7 Eam Complete dilated ophthalmic eam Cranial nerve eam Visual field testing Point tenderness CRP, ESR, platelets (if indicated) Neuro imaging (if indicated) Neuro Imaging What constitutes imaging?* New onset HA after age of 40 Permanent homonymous visual field deficit One sided HA which always occurs on same side and does not ever switch sides Awakens pt from sleep Neurological deficit associated with HA Papilledema Migraine Treatment Abortive treatment (pain relieving meds) NSAIDS Caffeine Triptans (Imatre, Maalt, Zomig) Ergots (Ergotamine and caffeine) Opioids Glucocorticoids Preventative Treatment Beta-blockers (propranolol) Ca+ channel blockers TCA s (amitriptyline) SSRI s OnabotulinumtoinA (Boto) 7

* New onset HA after age of 40 Permanent homonymous visual field deficit One sided HA which always occurs on same side and does not ever switch sides Awakens pt from sleep

8 PREEMPT Phase III REsearsch Evaluating Migraine Prophylais Therapy 1384 pts with on average of 20 headache days per month Most pts had a 50% reduction in headache days per month Adverse Reactions Seen in Trial Boto Placeb o Boto Place bo Headache Migraine Facial paresis 5% 4% 2% 3% 2% 0% Eyelid ptosis 4% <1% Bronchitis 3% 2% Neck pain Musculoskeletal stiffness Muscular weakness Myalgia Musculoskeletal pain Muscle spasms 9% 4% 3% 3% 3% 2% 3% 1% <1% 1% 1% 1% Injection sight pain 3% 2% Hypertension 2% 1% Boto FDA approved for the treatment of chronic migraine 15 or more headache days a month Headache lasting 4 or more hours 8

Bronchitis 3% 2% Neck pain Musculoskeletal stiffness Muscular weakness Myalgia Musculoskeletal pain Muscle spasms 9% 4% 3% 3% 3% 2% 3% 1% <1% 1% 1% 1%

9 Why Does It Work? Nobody really knows Not thought to work by relaing overactive musculature Has been shown to reduce pain in a number of conditions Cervical dystonia Neuropathic pain Lower back pain Myofacial pain cgrp Glu Sub P Hypothesis Boto is believed to block nociceptive neurotransmitters cgrp Sub P Glutamate Act by causing vasodilatation and inflammatory cascade Sensitize peripheral and central neurons to pain 9

in a number of conditions Cervical dystonia Neuropathic pain Lower back pain Myofacial pain cgrp Glu Sub

10 Long Term Use of Botulinum Toin Very well tolerated Acute pain medication was reduced by 53% Emergency room visits reduced by 61% Only additional side effect not listed in the PREEMT study was possible muscle atrophy Was noted in two patients that were treated for >5 yrs *Cernuda-Morollon E., Ramon C., Larrosa D., Alvarez R., Riesco N., Pascual J. Long-term eperience with onabotulinumtoina in the treatment of chronic migraine: What happens after one year? Cephalalgia doi: / What am I Doing? Neurotoin comes in a crystallized form Reconstitute with 2mL of preserved saline *off label Injected in 2.5 to 5 unit aliquots 0.05mL 0.1mL per needle poke Recommended Injection Sites * units per treatment 10

Long-term eperience with onabotulinumtoina in the treatment of chronic migraine: What happens after one year? Cephalalgia. 2014 doi: 10.1177/0333102414561873. What am I Doing?

11 What I m Currently Doing 11

12 What am I Doing? I currently use units per treatment Why Use Botulinum Toin? Fatigue Somnolence Depression Gastric ulcers Inability to concentrate Addiction Hypertension Kidney problems etc Why Use Botulinum Toin? Boto s biggest advantage is the lack of side effects, especially when compared to other medications It is etremely safe and very effective for some people 12

Kidney problems etc Why Use Botulinum Toin?

HEADACHE. as. MUDr. Rudolf Černý, CSc. doc. MUDr. Petr Marusič, Ph.D.

HEADACHE. as. MUDr. Rudolf Černý, CSc. doc. MUDr. Petr Marusič, Ph.D. HEADACHE as. MUDr. Rudolf Černý, CSc. doc. MUDr. Petr Marusič, Ph.D. Dpt. of Neurology Charles University in Prague, 2nd Faculty of Medicine Motol University Hospital History of headache 1200 years B.C.