Headache and Migraine Awareness Week

Dr Michael Eller - Migraine Management and Treatment Options

Dr Eller is a Neurologist at Neurology Network Melbourne, and gave a presentation at The Alfred Hospital on Tuesday 11th September. 
His talk focussed on a number of emerging treatment options for migraine. There were some interesting results first two based on electrical stimulation and the other was the new CGRP monoclonal antibody (mAb).

The first part of Dr Eller's talk was to discuss an often overlooked visual symptoms experienced my many migraineurs - visual snow. Visual snow is an effect where normally consistent colours look pixellated, or blotchy, or grainy in stead of clear and smooth. Sometimes the snow is coloured sometimes black or white, affecting parts of or the whole visual field. 
Other interesting visual phenomena are palinopsia (trailing or ghosting as objects move through the visual field), black floaters (white blood cells passing through capillaries across the retina) and nyctalopia (impared night vision). A number of these phenomena are 'normal' such as floaters (I can see them right now!) however they are enhanced in migraineurs. 

---

Dr Eller then went onto the part of the talk that he thought would be the most dry, but I found the most interesting. He went on to describe what a migraine is. I found this interesting because of his thoughts on the official classification rather than hearing something that I know by heart. Take from the ICHD-3 (International Classification of Headache Disorders version 3), Dr Eller described the familiar traits of a migraine attack according to the classification: Moderate to severe pain lasting 4-72 hours, containing two of - pulsatile pain, one sided, aggravated by routine activity and moderate to severe intensity. It must also have one of the following: nausea and/or vomiting, photpphobia or phonophobia.

Having laid this out he then described it as 'a bit silly' which might strike many as odd, but a sentiment I could not agree with more. The reason of course is that peoples symptoms change from one episode to the next, and despite clearly having migraine, the pain might be moderate, bilateral and aching instead of throbbing, yet if you get nausea with it its not a tension-type headache but not a migraine either - so what is it? The fact is they are all slightly different expressions of the same problem, a sensitised brainstem.
​The classification system is not reflective of hundreds of different pathological problems, but slightly different variations of the same problem. Imagine if we said two ankle sprains were totally different depending on were the bruising comes out?
Dr Eller pointed out that migraine is a 'primary headache disorder'. The way he defined primary was 'you scan the brain, its fine, do blood tests, they're fine.........its just a part of you'. It's another description which defies science now, assuming there is no 'faulty bit' we can test. In fact there are a number of faulty bits. Common to all so called 'primary headache disorders' is a sensitised trigeminal nucleus - the part of the brainstem receiving input from the head and face nerve (trigeminal nerve). We know this is overactive all the time (with or without symptoms) in migraine, tension-type headache and cluster headache. The nerves from the top of the neck feed directly into this area - making them candidate number 1 for a cause of this overactivity.

Dr Eller went on to describe migraine as a 'pathological brain state in which headache is only one possible feature along with visual, sensory, language, motor, cognitive symptoms, nausea, yawning, fatigue, dizziness, cutaneous allodynia, photophobia, phonophobia, osmophobia.
Dr Eller didn't mention the trigeminal nucleus, which is constantly irritated, but did talk about the hypothalamus, which is otherwise normal, but starts to become overactive at the start of the premonitory phase, incorrectly concluding that maybe its the generator. The hypothalamus is important in our bodies homeostasis - sleep wake cycle, body temperature regulation, 
If it was the generator it would precede the premonitory phase - not coincicde with it. Only the trigeminal nucleus along with the upper cervical nerves is constantly overexcited.
​

---

Migraine - New Treatment Options

Dr Eller referred to two new forms of electrical stimulation that have been approved for use in migraine.

The first is called the eNeura, pictured here on the left. It differs from the cephaly which many people may be aware of in that instead of sending electrical impulses across the surface of the head, this generates electrical impulses inside the brain, in an attempt to disrupt the evolving electrical storm that leads to a migraine attack.  The device is like a plastic pillow that you hold to the back of your head (pictured) and has shown similar success rates to CGRP mAbs (see below). That is 46% of the treatment group achieved a 50% or greater reduction in symptom frequency. Cost is in the vicinity of $1000 over 3 months.

---

The 'gammaCore' is a vagal nerve stimulator, which is the nerve that goes down to the stomach and internal organs. Children with seizures sometimes have a vagal nerve stimulator implanted and in some of those that also had headaches they found in some cases their headaches got better as well. That led to the development of a hand held device that is pressed against the neck (pictured) that delivers an impulse to the vagal nerve as it descends in the neck. The results were similar to the above, but interestingly this also had a significant effect in cluster headache, which is often recalcitrant to treatment. 

I spoke to the supplier of these products at he recent AHS scientific meeting in San Fransisco. I managed to hide my shock at the pricetag and the way they have montetised the product. There are two vairites - one can give you 30 charges a day for 3 months, the other gives you 30 days worth of charges.
Either way you then have to order another. $1000 every 3 months approximately. What annoyed me was that if I ordered one (which I can't anyway) they would send a demo to me that I can simply recharge. In other words, it expires each month and you order a new one not for any limitation in the device, but just so you have to buy another one - instead of offering a rechargabale option as well. This speaks greatly to the midset of those developing medical products (devices and drugs) in this space. Why offer you a cure if we can offer you something that makes you a customer for life?

---

Speaking of customer for life, Erenumab the new CGRP mAb was the last topic of the talk. This was approved in the USA in May and approved in Australia in July. The cost is going to be $750-850 per month. I have written extensively on this in previous Blogs, but pleasingly, Dr Eller presented it warts and all. Initially saying 'There's some impressive and not so impressive figures related to this Erenumab. The impressive relates to the side effects profile. Almost identical to placebo. One question on the night Dr Eller wasn't able to answer - what were the SAE's for the medications (SAE = serious adverse event). There were 8 in the treatment group and 7 in the placebo group. This can seem alarming until you understand that any adverse event you have during the trial duration is counted. In other words if you had a car accident, or brooke your ankle playing football during the trial, you are counted as an SAE. The researchers then have to investigate each SAE afterwards and see if there is any probability that the SAE is attributable to the treatment. In the case of Erenumab the SAE's attributed to the medication was 0.

The 'not so good' figures relating to Erenumab is the cost and effectiveness. It is marginally more effective than topiramate and botox. The cost at $750-$850 per month for something you will need for life it significant.
Just last week the Pharmaceutical Benefits Advisory Committee (PBAC) provided a statement in their review of Erenumab:
The evidence used for the basis of the clinical claim that erenumab was more effective than botulinum toxin had significant limitations, resulting in a clinical effectiveness and cost-effectiveness estimates that were highly unreliable for decision making. In addition, the PBAC considered that the cost to Government was underestimated by the submission, both because the number of patients with chronic migraine was underestimated by the submission and because of the significant risk of leakage outside the proposed limited PBS listing (for example, patients with episodic migraine)

It is highly likely that it will be approved but the PBAC will await preliminary data to see if a narrower target treatment group emerges. 
Interestingly Norvatis, who manufacture Erenumab will provide 3 doses at no charge to see if it works for you. Dr Eller was of the belief that you would know in that time if it would be effective. After that initial period you would then revert to full price should you wish to continue. 
Erenumab will only be available by Neurologist prescription (not GP), but the amazing thing here is that every Neurologist, not just the headache specialists but all of them, as a part of a familiarisation protocol, can sign up 10 clients to use the drug for free........forever!
Dr Eller didn't elaborate and seemed a little bashful when asked about it, but you may be able to access it free for life!

---