Treating Migraines with Botox A presentation with a short video on injection technique Dr Chris Blatchley chrisblatchley@doctors.org.uk www.capital-aesthetics.com www.london-migraine-clinic.co.uk

Botox for Migraines More than 1 in 10 women suffer from migraines You will primarily see aesthetics patients who also have migraines Botox can be enormously effective It is not difficult to optimise your injection technique for migraine treatment See the article in this month’s Aesthetic Medicine Magazine for the science

What is Migraine? Migraine is a Primary Headache diagnosed from the history.

How does Botox Work? Transcytosed through gut epithelium Endocytosed by neurons - as the vesicles are reabsorbed after releasing their neurotransmitter load BoTN-A is cleaved as it crosses the vesicle wall. The light chain becomes active Seven serotypes of BoNT – act in different ways. BoTN-A blocks the SNAP25 complex, which prevents vesicle binding and any further neurotransmitter release Some evidence that the active light chain is transported centrally, but little that it can then jump across synapses to other neurons

How does Botox work? Peripheral Free Nerve Endings Botox blocks the release of Neuropeptides from the vesicles in the free nerve endings by the same process as at the Neuro-Muscular Junction

The pain is largely linked to the distribution of the Greater Occipital Nerve (C2) in the neck and ophthalmic branch of the Trigeminal Nerve (V1) around the eye Their pain centres overlap in the Trigemino-Cervial Tract in the brainstem and send info to trigger the migraine in higher centres

Injecting the glabella with 60 units (100U Botox/Xeomin in 2 Injecting the glabella with 60 units (100U Botox/Xeomin in 2.5ml Preserved Saline = 1.5ml) green dots 10 units (0.20ml) yellow dots 4 units (0.10ml) - blue dots 2 units (0.05ml)

How do we inject the botulinum? 60U Botox/Xeomin (150U Dysport) directly into the Corrugators and 20-30U into the Forehead 100U diluted with 2.5ml preserved saline Most patients don’t need injections into the neck

Danger of Lid Ptosis?? Botulinum Toxin is a large 1000Kdalton molecule specially adapted to piggy-back onto natural neuro-synaptic endocytosis processes It is too big to: cross cell membranes by passive diffusion enter neurons along their axon length cross the Blood Brain Barrier or fascial septa

Injecting the Corrugators to avoid Ptosis Anatomy – X-section of upper eyelid

Fascial compartment of the Corrugators Anatomy – Forehead layers showing glide layer during surgical brow lift – free nerve endings are in fascial aponeurosis Forehead peeled forward exposing glide layer Brow incl corrugators Hair line Periosteum on forehead

Injecting the glabella with 60 units (100U Botox/Xeomin in 2 Injecting the glabella with 60 units (100U Botox/Xeomin in 2.5ml Preserved Saline = 1.5ml) green dots 10 units (0.20ml) yellow dots 4 units (0.10ml) - blue dots 2 units (0.05ml)

Injecting the brow without lateral brow lift blue dots 2 units (0 Injecting the brow without lateral brow lift blue dots 2 units (0.05ml) - red dots 1-2 unit (0.025-0.05ml)

Injecting the high-acting Frontalis and reducing brow lift blue dots 2 units (0.05ml) - red dots 1-2 unit (0.025-0.05ml)

Where did the PREEMPT Protocol come from? In 2000’s Allergan were being investigated in the USA for making claims they couldn’t substantiate so they needed a controlled trial. Allergan tell me they were worried about lid ptosis so a decision was made to keep away from the corrugators in the trial designed by a team of neurologists working with them After several attempts they got approval from the FDA in Oct 2010. In Sept 2010, presumably knowing they were to get FDA approval, they settled the previous Department of Justice investigation for $600million because “it was in the interests of the shareholders to do so” as they were selling $billions of Botox a year Allergan tell me there are no plans for further studies to improve on the PREEMPT Protocol. Apparently they have also managed to patent Botox for migraine use making it difficult for other manufacturers to do migraine research.

Almost no Botox goes into the Glabella

Injecting the brow with lateral brow lift blue dots 2 units (0.05ml)

Injection Plan Combine Surgeon’s and PREEMPT Protocols Inject Glabella and Forehead only Will be adequate for the majority of patients and will keep the costs down to something the patient can afford If the neck needs to be done then this can be done later

Why the difference? Turf war between the Surgeons and Neurologists Neurologists refused at first to believe that Botox could work and certainly not that surgery could help, let alone ‘cure’ migraines This trenchant disagreement has kept both sides from exploring the positive sides of each others’ theories/methods and has slowed down improvement in treatment protocols

Avoiding Lid Ptosis – Anatomy of the Glabella Botox is too big to pass through Fascia The glabella and eye socket have a series of fascial compartments designed to reduce spread of infection. The Botox has to be injected within each compartment to have any action Free Nerve Endings are present in skin, muscles, tendons and facia, particularly in the aponeuroses of muscle attachments:- bony attachments of the small muscles to the vertebrae and the base of the skull Non-bony attachments of glabellar muscles to the fascial aponeuroses

How do we inject the Botox? Surgeon’s approach – 50U Botox into the corrugators Neurologist’s approach - 150U Botox everywhere except the corrugators - the PREEMPT Protocol designed by Allergan Combined approach – 50-60 U to corrugators and 20- 30U to the forehead. If necessary the neck can be injected later, but generally not necessary.

The headache in migraine comes from the meninges which are innervated primarily by V1 and C2/3, which may account for why there is pain in the temples even though the external anatomy is innervated by V3. The Vagus nerve is also involved

Botox? I’m using “Botox” as a generic name for Botulinum Toxin A (BoTN-A) All 3 commercial varieties can be used I use Xeomin by Merz because you don’t need to store it in a fridge

What is Migraine? Migraine is a Primary Headache diagnosable from the history We don’t generally have to worry about secondary headaches caused by tumours etc because the migraine sufferers we see will have had it for years

What is Migraine? Migraine is a Primary Headache diagnosable from the history We don’t generally have to worry about secondary headaches caused by tumours etc. because the migraine sufferers we see will have had them for years If the headache is new or the pattern has changed markedly then they need to be seen by their GP

What is Migraine? Migraine is a Primary Headache diagnosable from the history We don’t generally have to worry about secondary headaches caused by tumours etc. because the migraine sufferers we see will have had them for years If the headache is new or the pattern has changed markedly then they need to be seen by their GP You don’t need to know too much about migraines - just enough that you sound as though you know what you’re talking about!

What is Migraine? Migraine and other Primary Headaches result from an imbalance of the normal excitatory and inhibitory control processes within the brain Usually associated with N&V, photophobia etc – closely linked to autonomic control systems Set off by the fall in Estrogens just before the period visual patterns and flashing lights strong smells, loud sounds and visual patterns Food is surprisingly unimportant Some people have a visual or other sensory aura an hour or so before the headache starts

What we’ll talk about What are Migraines? How does Botox work? How and where do you inject it for Migraines? Do you want to join a research project? A download will be available with a guide to the migraine consultation and an injection plan chrisblatchley@doctors.org.uk

What is Migraine? Often genetic – Women > Men - can start in childhood Associated with N&V, photophobia etc Migraines FEEL different to other headaches but some neurologists feel that ALL primary headaches have the same migrainous process So common that everyone thinks they have THE treatment Osteopaths – a neck problem Dentists – a TMJ problem Neurologists – a brain problem They’re all right … to a degree

What is Migraine? The trigeminal nerve carries a mixture of somatic and autonomic sensory information.

What is Migraine? The trigeminal nerve carries a mixture of somatic and autonomic sensory information. Diffuse pain can perhaps be considered part of the autonomic process and travels from Free Nerve Endings in muscles and fascia via unmyelinated fibres to a complex array of nuclei in the Trigemino-cervical tract in the brain stem

What is Migraine? The trigeminal nerve carries a mixture of somatic and autonomic sensory information. Diffuse pain can perhaps be considered part of the autonomic process and travels from Free Nerve Endings in muscles and fascia via unmyelinated fibres to a complex array of nuclei in the brain stem There’s a suggestion that migraines are an aberration of the avoidance reflex close eye and turn head

How does Botox work? Neurologists dismissed migraine surgery, favouring the explanation that it acts on the pain pathways, either peripherally from Free Nerve Endings or centrally. Peripheral Free Nerve Endings Botox blocks the release of Neuropeptides from the vesicles in the free nerve endings by the same process as at the Neuro-Muscular Junction

None of the theories are mutually exclusive How does Botox work? None of the theories are mutually exclusive Paralysing the muscles will reduce the mechanical stimulation of the free nerve endings Direct action on the free nerve endings reduces afferent pain signal There is some evidence of central axonal flow which may affect the central synapse of that neuron, there is no definite evidence of inter-neuronal spread

Injection Instructions for Botox/Xeomin 100u in 2.5ml preserved saline Inject using 8mm 30g insulin syringe, held at 30 degrees to the skin, in line with the corrugator to avoid injecting outside the fascial compartment. Now for the video…

How effective is Botox for Migraines? 10% total cessation of migraines 10% no effect 80% patient is happy with improvement Less pain for shorter time Fewer migraines Less feeling that the next migraine is about to happen (people are often happiest with this)

Would you like to be part of a research project?

Thank you….