Fale com a SBCe Highlights on the 58th Annual Scientific Meeting, American Headache Society.
By Maike Blaya, MD
The American Headache Society organizes this annual meeting that brings headache experts together for 4 days from all over the world. Other than learning and updating your knowledge in Headache it is also a great opportunity to network with other neurologists interested in “Headache” and share patient’s experiences.
The meeting grows larger every year; this past June in San Diego we had 850 participants.
The American headache Society has 1122 members and 298 are UCNS certified.
The most important topic in this conference was, in my opinion, the new treatments on the horizon for migraine headaches and other primary headache syndromes. Like Dr Goadsby said, “It is a great time to be in the field of HEADACHE.”
We will finally have drugs designed specifically for migraine patients, the CGRP receptor antagonists. Another breakthrough is the non-drug therapy options. Many transcutaneous devices have been presented, 2 of them already approved in the US.
The features below highlight some of the studies that emerged from the conference.
Neuromodulation Devices
1- Noninvasive vagal nerve stimulator (nVNS, GammaCore, ElectroCore
Approved in Canada and UK. GammaCore is not currently FDA approved and not available in the United States. Limited by US law of investigational use.
Picture from Medscape.com
Possible a great adjunct therapy for migraine and cluster headaches.
Patients with migraine possible have thalamocortical dysrhythmia with deficient habituation to cortical responses.
nVNS with GammaCore can normalize the visual evoked potential habituation in migraine patients, suggesting that the device may potentially modulate corticothalamic responsivity. Is this modulation predictive of therapeutic response? We will need more studies to define that.
PREVA study: randomized prospective controlled study of nVNS for the prevention of chronic cluster headache. One group received standard of care for the treatment of cluster with nVNS. After 2 weeks of treatment the attack frequency was significantly lower in the group that received nVNS with standard of care treatment compared to the patients that were treated with standard of care alone.
Animal model of acute intracranial head pain demonstrated the potential mechanism for the efficacy of this device. The stimulation of the cervical branch of the vagus nerve inhibits the acute nociceptive activation of the central trigeminovascular neurons.
Vagus nerve stimulation inhibits acute intracranial dural-nociceptive activation of central trigeminovascular neurons. Akerman, S; Simon B; Romero-Reyes, M.
2- External Trigeminal Nerve Stimulation (E-TNS, CEFALY)
This transcutaneous device is placed over the forehead over the supraorbital nerve for the acute treatment of migraine.
FDA approved.
3- VESTIBULAR STIMULATOR
Another device presented in the conference under investigation uses time varying caloric vestibular stimulation, this non-invasive device possible helps headache though neuromodulation.
This device has the potential to provide substantial clinical benefit for the prevention of episodic migraines.
4- SPHENOPALATINE GANGLION STIMULATION (SPGs, Pulsante)
This is an implantable device that requires a prior surgical trans-oral procedure. A microstimulator is inserted near the maxillary nerve in the pterygopalatine ganglion. It has been shown to be effective in the treatment of medically refractory cluster patients.
The microstimulator is activated by an external easy to use remote controller that provides on-demand patient-controlled therapy.
Only implantable device marked in Europe for the treatment of Cluster headaches.
?5- Single Pulse Transcranial Magnetic Stimulator (sTMS, Spring TMS)
This device provides a single pulse that feels like a small shock, used for the acute treatment of migraine with aura. Approved in UK and FDA approved in US.
The Eye and Migraine
We know migraine patients have autonomic features and photophobia during the migraine attacks. One of the abstracts published and presented during the conference, provided evidence that patients with migraine, especially patients with chronic migraines, had a lower photophobia threshold also between the migraine episodes. Pupillary responses to light were delayed in migraine patients with reduced constriction velocity.
Other abstract assessed visual quality of life in migraine patients using different questionnaires.
Visual quality of life scores in migrainours were as low as other neuro-ophtalmic disorders such as myasthenia gravis, intracranial idiopathic hypertension, multiple sclerosis and optic neuritis.
Dr Straumann presented a plenary session on the most frequent causes of eye pain in the population of 3.409 patients seen in 2 hospitals.
Causes of eye pain in the neurology office: the primary diagnosis in 51% of the patients was headache/migraine; followed by optic neuritis 22.5%.
Trigeminal neuralgia and other cranial neuralgias was 4%
Causes of eye pain in the ophthalmologist: Conjunctivitis/keratitis 30%; dry eye/blephalitis 19%; Migraine was the 6th cause, 3% of the patients.
The Glymphatic System:
Scientists Discover Previously Unknown Cleansing System in Brain.
“Waste clearance is of central importance to every organ, and there have been long-standing questions about how the brain gets rid of its waste,” said Maiken Nedergaard, M.D., D.M.Sc., senior author of the paper and co-director of the University’s Center for Translational Neuromedicine, University of Rochester Medical Center.
The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system. Besides waste elimination, the glymphatic system also facilitates brain-wide distribution of several compounds, including glucose, lipids, amino acids, growth factors, and neuromodulators.
The glymphatic system functions mainly during sleep and is largely disengaged during wakefulness and is only present and possible visible in vivo, reason why it has not been seen or discovered before.
Biological need for sleep across all species may reflect that the brain must enter a state of activity that enables elimination of potentially neurotoxic waste products.
Interestingly, different factors during sleep may affect the glymphatic system, for example, lateral decubitus during sleep may provide a more effective “clearance of waist” compared to prone.
First author Jeffrey Iliff, Ph.D., a research assistant professor in the Nedergaard lab at the University of Rochester Medical Center, took an in-depth look at amyloid beta, the protein that accumulates in the brain of patients with AlzheimerÂ’s disease. He found that more than half the amyloid removed from the brain of a mouse under normal conditions is removed via the glymphatic system.
During degenerative disease or post head trauma the system becomes inneffective.
“Understanding how the brain copes with waste is critical. In every organ, waste clearance is as basic an issue as how nutrients are delivered. In the brain, it’s an especially interesting subject, because in essentially all neurodegenerative diseases, including Alzheimer’s disease, protein waste accumulates and eventually suffocates and kills the neuronal network of the brain,” said Iliff.
NEW TARGETS FOR TREATING MIGRAINE
Calcitonin gene-related peptide (CGRP) was certainly one of the main “hot topics” of the AHS58 meeting this year.
CGRP is integrally involved in the pathophysiology of migraine, it is a key driver of migraine pain.
Investigational calcitonin gene-related peptide (CGRP) monoclonal antibodies show significant efficacy in preventing migraine attacks with no major safety issues.
They appear to reduce the elevated levels of CGRP.
These are a new class of preventive migraine treatment. AHS president Lawrence C Newman mentioned: “We are excited because there hasn’t been a new medicine designed specifically to prevent migraine in over 50 years.”
CGRP- There are four pharmaceutical companies currently in Phase II trials of an anti-CGRP drug. This new class of drug shows extreme promise in being used as the first preventative medication developed specifically for migraine patients. While still 2-5 years away from being on the market, studies are showing great results in the reduction of migraine attacks. Each one of these antibodies are different in their properties and possible clinical differences may be seen between them.
TEV-48125 (TEVA) is a monoclonal antibody against CGRP, showed efficacy in chronic migraine as early as one week after starting treatment. This is a once a month injection.
LV2951742 is also a monoclonal antibody against CGRP. A study showed that a single injection every 2 weeks of this drug could completely stop the migraine attacks in about one-third of the patients with migraine
AMGEN 334 (Novartis and Amgen in collaboration)
The drug met primary end point confirming efficacy and safety over 12 weeks of treatment.
There was also a head to head study published in the meeting comparing the CGRP binding kinetics of different monoclonal antibodies; ALD403, TEV-48125 and LV2951742.
ALD403 had a more rapid engagement of the CGRP to inactivate the peptide and extremely slow dissociation explaining the rapid onset and long duration of clinical activity.
PACAP receptors
The neuropeptide pituitary adenyl cyclase-activating peptide is an emerging player in the migraine pathology.
NEW DELIVERY SYSTEMS!
AVP-825 - ONZETRA recent FDA approved low-dose Sumatriptan that has a novel bi-directional breath powered technology of intranasal delivery. It is better tolerated than the current nasal spray triptans available with less nasal discomfort and abnormal taste.
AVP-825 Demonstrated faster delivery than the traditional liquid nasal spray and tablets. COMPASS Trial: Migraine suffers taking 22 mg of new product had more rapid relief of symptoms compared to placebo and sumatriptan tablets.
Also reduces migraine-associated nausea faster than Sumatriptan tablets.
Better option than tablets since the gastric emptying is delayed during the migraine attacks.One of the new medications just in the market, Zecuity, was the first and only transdermal triptan.
The FDA was investigating the risk for serious burns and potential permanent scarring with the use of this patch.
The product was approved by the FDA in 2013 and since the product came to the market a large number of patients have reported these side effects.
After polemic discussion during the meeting, Teva pharmacelticus voluntary suspended the sales, marketing and distribution o the product.
Stress and Migraine
Migraine is as disabling as other chronic neurologic conditions. Migraine was considering one of the top 10 most disabling conditions in the world (WHO).
There is also evidence that mental health comorbidities are intricately tied to chronic pain.
Patients bad attitude towards their condition may worsen the pain. Patients should not “catastrophize”. Cognitive behavior therapy, neurobiofeedback can be as effective as oral medications in the treatment and control of migraine headaches.
Stress is the biggest trigger in migraine attacks and woman are more susceptible to stress in the perimenstrual period.
When Mom has Migraine, What it is the Family to Do?- 17% of the US has episodic migraines, while 1.29% have chronic migraines. This can cause parent/ child role reversal, parents feeling guilty, it was shown that family arguments are more prevalent when a parent suffers from migraine.
Comments from Katie M. Golden writer and patient advocate, owner of the website Migraine.com