Neuromodulation Devices Webinar

0:00 all right so like the title suggests
0:02 we’re going to be focusing on
0:03 non-invasive strategies for treating
0:05 migraine and you know maybe instead of
0:07 looking at uh pills or injections other
0:10 types of devices and tools that you can
0:11 use as part of your treatment plan
0:13 like ashley internet again we’re just
0:15 providing information and so even though
0:17 if it may seem from my presentation it’s
0:18 a good fit for you i think it’s still
0:20 important to have that discussion with
0:22 your healthcare provider because there
0:23 may be some other reason to think twice
0:28 so let me just advance this here
0:36 it’s freezing on me
0:42 there we go all right so this is me i’m
0:44 a neurologist and i did my training at
0:46 queen’s for medical school i did some
0:48 time at uh western university for
0:50 neurology and then i did a fellowship
0:52 with dr larue mozagar becker over in
0:55 calgary
0:56 right now i operate a community-based
0:58 headache and neurology practice in
1:00 london ontario i’m still doing some
1:02 research so right now i wrapped up a
1:04 cannabis study for migraine and we’re
1:06 looking at now perhaps some silocybin
1:09 related trials to migraine and other
1:11 headache-related disorders as well as
1:13 education-based research and we’re
1:15 focusing on curricular content for the
1:16 residency programs it’s a big project of
1:18 ours to try to increase more
1:20 neurologists who are aware of these
1:21 kinds
1:23 so for my disclosures just so you’re
1:25 aware my fellowship was funded from the
1:27 canadian headache society and uh i
1:30 participated in adwords for various
1:32 pharmaceutical companies that helped to
1:33 deliver migraine medications novartis
1:35 lily lundbeck abbey and tama um
1:38 similarly i give a lot of talks to
1:39 family doctors nurse practitioners other
1:41 people in the community just to help
1:43 spread it and we’ve been lucky enough to
1:45 have some funding to assist with that
1:48 so for tonight what i want to focus on
1:50 is just reviewing the neurostimulators
1:52 that we have available here in canada to
1:54 people who suffer with headache
1:56 we’re going to look over some of the
1:58 purported mechanisms you know a lot is
2:00 still pretty mysterious about neurology
2:01 i tell people we’re really good at
2:03 telling people what things aren’t you
2:05 know ruling things out but there’s still
2:07 a lot of mysterious stuff between
2:08 neurology and psychiatry and migraine
2:11 and some of the other disorders are
2:12 something that fall into that gray zone
2:15 we’re going to look at some of the
2:16 landmark studies for these stimulators
2:17 you know and give you a relative idea of
2:19 you know a reasonable expectation of
2:21 what you can expect from using them
2:23 for the physicians in the audience i
2:25 hope that you’re better able to you know
2:27 pick out maybe the patients that might
2:28 be a good ideal candidate for these and
2:30 think about it when you offer them some
2:32 choice
2:33 in the clinic and for patients uh you
2:35 know at least you’ll have something to
2:36 take back to your headache provider and
2:38 maybe come up with some alternative
2:40 options if you’re reaching some
2:41 difficulty
2:43 so i think a good place to start is
2:45 looking at the current landscape you
2:47 know of headache maybe some of these
2:48 numbers are a little bit older but you
2:50 know i i think a good rule of thumb is
2:52 that maybe one in five canadians will
2:54 suffer from you know a primary headache
2:56 specifically migraine at some point in
2:57 their life
2:59 there’s over a billion people in the
3:00 world who have migraine
3:02 in about 50 percent of these patients
3:04 there’s more than five year delay
3:05 between the first time that they
3:07 manifest the migraine looking back
3:09 and when they finally get that label
3:11 from a provider and so many people go
3:13 for many years not even knowing it’s
3:14 important
3:16 now you’ve reached the hurdle of getting
3:17 the diagnosis about 30 of the people who
3:20 qualify and should be having a
3:21 preventive actually receive it
3:24 and then even worse at one year you know
3:26 fewer than 20 of these people are still
3:29 taking their preventive medicines more
3:31 than 80 of days and i think that speaks
3:33 a lot to you know a lot of the medicines
3:35 that we traditionally use for migraine
3:36 because they have some pretty bizarre
3:38 side effects or you know it’s just
3:40 not practical for some people to take
3:43 you know a pill every day
3:45 so i think it just kind of speaks to a
3:47 need for alternative options for these
3:48 people
3:49 and so that’s where this kind of comes
3:51 in sometimes bills aren’t an option you
3:53 know people are kind of fed up so i’ve
3:56 overheard in the clinic you know i
3:57 prefer to take a natural approach i want
3:59 to focus on vitamins and lifestyle i
4:01 think that’s reasonable to start you
4:03 know
4:04 people are tired of experimenting with
4:06 medications you know they often joke
4:08 that they’re my test subject or guinea
4:09 pig i try to tell them i’m not doing
4:11 tests on you but it is a trial and error
4:12 process you know and that can be very
4:14 frustrating for people
4:16 some people just don’t like the way that
4:18 medications make them feel
4:20 there’s always the crowd where they feel
4:21 that all medicines are you know my body
4:23 resists them and i i don’t you know do
4:26 well on these i want to caution some of
4:28 these patients too because you know we
4:30 all know about the placebo you know
4:32 which is you can have a positive effect
4:34 just by expecting good results but the
4:36 flip side of that coin is the nocebo you
4:39 know and so sometimes if you’re reading
4:41 the monograph where you expect medicines
4:42 to fail you can sometimes you know um
4:46 undercut your benefit sometimes too so
4:47 it’s a double-edged sword
4:50 the other thing is you know the multiple
4:51 chemical sensitivities and things like
4:53 this where they’ve really tried a lot of
4:55 medicines and gave a fair effort but it
4:56 just doesn’t seem to be a fit for them
4:58 so they’re looking for options that
4:59 aren’t systemically absorbed either
5:01 things like injections whether it’s
5:03 botox or a nerve block or maybe other
5:05 things like a stimulator
5:07 so a quick overview of the
5:09 neuromodulatory approaches to headache
5:11 to date from left to right you’ve got
5:13 things that are acting more centrally
5:15 like a deep brain stimulator where they
5:16 actually
5:18 insert a platinum cathode deep into
5:19 centers in the brain and send electrical
5:21 pulses
5:22 you’ve got things where they kind of
5:24 just sit just under the skull cap under
5:26 the lining of the brain and they’re
5:28 sitting right on the surface that’s a
5:29 cortex stimulator
5:30 sometimes we target things in the spinal
5:32 cord or at the occipital nerves which
5:34 are the peripheral nerve stimulators
5:36 and there are other types of unusual
5:38 ones you know for sphenopalatine
5:39 ganglion but these ones i would say
5:42 they’re reserved for patients with the
5:43 most severe disability who have tried
5:45 everything it’s very difficult to find
5:47 some specialty expertise in neurosurgery
5:49 and people who are willing to do these
5:50 things so often patients may face
5:52 barriers like having to travel very long
5:54 distances
5:56 and you know they suffer from a lot of
5:57 complications there can be bleeding
5:59 infection migration of the leaves
6:01 so i mean these are not things to be
6:04 considered lightly
6:06 for the purposes of our talk here today
6:07 we’re going to focus on the non-invasive
6:09 stimulators and what’s nice about these
6:11 is that you know some of them are even
6:13 available without a prescription and
6:15 they’re available to people you know in
6:17 the community without having to go to a
6:18 tertiary medical center
6:20 so i think that’s kind of exciting
6:23 so
6:24 focusing on canada you know i would say
6:27 here are kind of the four big ones that
6:28 we think about there are there’s been an
6:30 explosion of devices you know more
6:31 recently and a lot of them are in the
6:33 states in canada i think we have two
6:35 main ones and we’re going to focus on
6:36 these for tonight
6:38 the first is cephali which is a type of
6:40 external trigeminal nerve stimulation
6:42 device and that’s working on branches of
6:43 lubricant
6:44 and then the second is the gamma core
6:46 which some of you may be familiar with
6:48 and this is a non-invasive bagel nerds
6:50 familiar
6:51 the other ones nervio and inura
6:52 unfortunately are not available in
6:54 canada but we’ll take a quick peek at
6:55 them just so you’re aware of what’s
6:57 brewing
6:59 so
7:00 this is cephaly uh and you can see the
7:03 device is attached to his forehead by a
7:04 little
7:05 adhesive patch there
7:07 and so
7:08 it’s called the cephalic duo because it
7:10 has kind of two programs that you can
7:12 use it for it’s a transcutaneous nerve
7:14 stimulator like i mentioned so it’s
7:16 sending little electrical pulses kind of
7:18 like a tens machine and it’s hitting
7:20 those two branches of nerves uh here on
7:22 your forehead
7:23 it’s the first device that of its kind
7:25 that was approved by the fda for the
7:27 treatment of migraine and like i
7:29 mentioned it’s the dual because it’s got
7:30 two paradigms you can use it both as an
7:32 acute medication which is on demand as
7:34 you need it when pain is bad and also as
7:37 a preventive so you can actually use it
7:39 in a way every day to try to prevent
7:40 headaches from happening
7:42 so for acute it’s indicated in patients
7:44 18 plus migraine with or without aura
7:47 and you can use it you know 60 to 120
7:50 minutes so studies looked at both
7:52 paradigms and maybe it’s a little bit
7:53 better with a prolonged
7:55 application but you know then you have
7:57 to deal with parasitus for two hours as
7:59 well
8:00 preventive treatment uh which is kind of
8:02 nice also in episodic migraine patients
8:04 18 plus uh and this is for people taking
8:07 it maybe 20 minutes each evening you
8:09 know but you can probably do it a
8:10 different time
8:12 it’s available over the counter without
8:13 a prescription which is nice it’s a
8:15 little bit easier to obtain
8:17 um and so we talked about the acute
8:19 treatment
8:20 it’s a higher frequency and longer
8:22 stimulation period compared to some of
8:24 its uh you know competitors
8:27 but the way we think this works is by
8:28 exhausting pain signals in the fibers so
8:31 you know these
8:32 nerves communicate with different
8:33 chemicals called neurotransmitters and
8:35 you can actually use some of it up
8:36 that’s called tachyphylaxis and it takes
8:38 some time to regenerate so it may be
8:40 working through that way um you know i
8:43 think the studies have touted pain
8:44 freedom pain relief you know maybe not
8:47 complete absence but it’s better and
8:49 resolution of the most bothersome
8:50 symptom which could be like photophobia
8:52 the sensitivity to light nausea or
8:55 vertigo or something
8:56 so i think we’ll we’ll take a quicker
8:59 closer look rather at the data for that
9:01 in a second
9:02 the preventive option 20 minutes each
9:04 evening or morning like i mentioned
9:06 it’s a lower frequency and it’s
9:07 something you do on a daily basis and
9:10 instead of just kind of hammering the
9:11 nerve you know for a long time to try to
9:13 deplete the signal they’re thinking
9:14 maybe this is working indirectly through
9:16 some uh both peripheral and central
9:18 mechanisms to change the way the
9:20 migraines happen and the threshold
9:22 you know the studies for this one showed
9:24 some reduction in migraine days any kind
9:26 of headache days so you know you don’t
9:28 necessarily have all the features of a
9:29 migraine and also showed over time to
9:31 reduce the use of acute medications
9:35 so safety and contraindications uh you
9:37 know
9:38 important to point out compared to
9:39 something like the pyramid or other oral
9:41 medications no serious adverse events in
9:43 the trials
9:44 mild adverse events were things like
9:46 sleepiness fatigue
9:48 insomnia local pain and paresthesia may
9:50 be worsening of headache um but in
9:53 general it’s pretty well tolerated
9:55 the people who definitely should not use
9:57 this are people who have metallic
9:58 implants in their head you know cochlear
10:00 implants plates any kind of stimulator
10:02 that’s already embedded
10:04 and anybody with kind of cardiac
10:06 implanted lines or pacemakers
10:09 so how does it work you got to make sure
10:11 that you clean your forehead every time
10:13 whether that’s like nicely with soap and
10:14 water or they’ve got wipes that come
10:16 along with this and then you can see
10:17 this lady here she’s applying the patch
10:19 to her forehead you kind of want to
10:21 center it there in the glabella and then
10:23 you’re going to make sure it’s firmly
10:24 attached by rubbing your fingers over it
10:27 and then embedded in that patch is
10:29 actually a little magnet and that’s
10:31 where the cephaly itself attaches
10:33 and then you can program the device and
10:35 you can uh you know use that power
10:36 button to get it started
10:38 and you leave it in place so attaches
10:40 using the self-adhesive electrode each
10:42 electrode is actually designed to last
10:44 for about 20 applications so you know
10:47 you do end up having to replace them so
10:48 there’s a little bit of a cost with
10:50 ongoing use
10:51 but it’s pretty reasonable given that
10:52 you can reuse it so many times
10:55 so how does it work okay so you can see
10:57 the woman here she’s you know attached
10:59 it to her head it seems to be pulsing uh
11:02 so these stimulate both super orbital
11:04 and supratrochlear nerves you can see
11:05 some of the
11:06 depiction of this in the middle here and
11:08 these feedback through v1 which is you
11:11 know the first division of the
11:12 trigeminal nerve the ophthalmic it goes
11:14 all the way back through various holes
11:16 in your skull feeds back into the brain
11:18 stem into the trigeminal nucleus
11:20 caudalis which is the kind of generator
11:22 of migraine this thing integrates the
11:25 three branches of your trigeminal nerve
11:27 from your face it does auricular
11:28 temporal nerve from the sides occipital
11:30 nerves and even upper cervical roots
11:33 so all these kind of sensory inputs are
11:35 feeding back into this area where
11:36 migraine happens and you know chronic
11:38 pain from there can bleed both ways so
11:40 that’s why people often have neck
11:41 stiffness pain in their face you know
11:43 all over the head it can migrate
11:45 so it’s feeding back to the brain stem
11:47 and there it causes changes both in
11:49 peripheral nerves as it goes along but
11:52 also in brain stem pain centers where
11:53 the migraine resides and then over time
11:55 it even causes central changes
11:58 so this is going to be the change in the
11:59 pain and salience matrices
12:01 that are involved in the pain
12:02 dysregulation that’s a little bit beyond
12:05 the scope of our talk tonight i don’t
12:06 think we have enough time to get into it
12:08 but i will just for the sake of interest
12:10 go over a couple interesting points you
12:12 know
12:13 i think the truth is that we don’t fully
12:15 understand even the full mechanism of
12:16 migraine you know we’ve made a lot of
12:18 interesting advances recently
12:20 uh and the mechanism by which these
12:23 stimulators work is even more mysterious
12:24 to be honest but there are some
12:26 important clues i think that are very
12:28 exciting areas to continue researching
12:31 first is that you know external
12:33 transcutaneous stimulation
12:34 it changes that trigeminal nucleus you
12:37 know and it changes the threshold to
12:38 alter the pain response
12:41 when we look at ftg pet studies you know
12:44 you may see some of these colorful brain
12:45 scans with different areas that are
12:46 lighting up different colors
12:48 you know migraineers tend to have less
12:51 metabolism in the frontal temporal area
12:53 compared to healthy controls with no
12:55 headaches and you can actually see
12:57 normalization of this over time with
12:58 chronic use of the preventive
13:01 another type of imaging which is bold
13:03 you know and it looks like when we have
13:04 people do tasks in the mri
13:07 their brain uses amounts of sugar
13:09 differently and extracts oxygen
13:11 differently
13:12 and so as a result we can try to see
13:14 what are the areas of the brain that are
13:16 active when you’re doing a different
13:17 test
13:18 and so for migranters when we actually
13:20 stimulate them with a heat like a
13:23 painful stimulus called the noxious
13:24 stimulus uh you know they light up in a
13:26 particular way that’s different from
13:27 healthy controls
13:29 and they have much greater reaction and
13:31 when we use etns the nerve stimulator it
13:34 actually kind of returns that closer to
13:36 normal compared to healthy controls so
13:38 it suggests that we’re kind of shifting
13:40 the brain to behave a lot more like
13:41 someone who doesn’t have headaches
13:44 another interesting one is this idea of
13:47 or cortical reverberations so the
13:49 thalamus are like these two things
13:51 sitting in the middle of your brain atop
13:52 the brainstem and they’re essentially
13:54 the relay station for everything in your
13:56 brain
13:56 so they go back and forth from spinal
13:58 cord to the cortex to the deep gray
14:00 structures
14:01 very very complicated circuitry
14:04 but what’s interesting is that there’s
14:05 many loops that go back and forth to the
14:07 cortex and we think that it stores
14:09 different types of sensory memory
14:10 there’s all sorts of information that
14:11 reverberates there
14:13 in people with
14:15 migraine we’re able to kind of normalize
14:17 the function of those reverberations so
14:19 it’s almost like maybe perhaps you know
14:21 you’re trapped in a sensory with pain or
14:23 something and by repetitively
14:25 stimulating you and kind of coursing
14:26 your brain and returning to a normal
14:28 pattern perhaps we can get rid of those
14:30 dysfunctional rhythms
14:32 and so that can be seen in something
14:33 called the somatosensory evoked
14:35 potential
14:36 so you know if we’re doing this talk
14:38 maybe in a more academic setting we can
14:40 go through all the evidence piece by
14:41 piece and it’s kind of exciting to parse
14:44 but for the interest of time you know i
14:45 don’t think we can do tonight
14:47 so let’s take a peek at the first study
14:49 and this one is called acne
14:52 and it’s looking at acute data for 60
14:54 minutes of stimulation
14:56 and so this was prospective double blind
14:57 randomized shame controlled study people
15:00 were given little units that looked
15:01 identical you know but maybe the pulse
15:03 strength and width and frequency is
15:05 lesser than the the stimulator
15:08 and so this was an american-based study
15:10 and it recruited 106 people they were
15:12 divided one to one to have virum which
15:14 means like the true treatment uh versus
15:17 the sham which is kind of the fake one
15:19 that’s not as powerful and so they
15:21 recorded their pain scales using the
15:22 visual analog and they were
15:24 recorded at baseline before they started
15:27 then after uh one hour two hour and 24
15:30 hours
15:31 so to get into the study you could be
15:33 male or female anyone from the age of
15:35 age 18 to 65
15:37 you had to have a diagnosis of migraine
15:39 with or without aura
15:41 and then you had to experience an attack
15:44 with or without aura lasting at least
15:45 three hours they wanted to make sure it
15:46 wasn’t just a brief attack or a false
15:48 alarm and they wanted to see that the
15:50 pain severity was essentially stable for
15:52 about an hour prior
15:53 so you know a little bit specific but i
15:56 think it’s good to try to narrow down
15:57 your population to make sure you can
15:59 detect a signal
16:00 what was nice about this is that it
16:02 included both episodic and chronic
16:03 migraines
16:05 and you know i if you’re keeping a pulse
16:07 on the evolution of our research i think
16:09 we’re trying to move away from the
16:10 episodic and chronic paradigm because uh
16:13 perhaps it isn’t as relevant
16:15 people that were excluded included those
16:17 who are pregnant people have had botox
16:19 or super open mirror blocks if they had
16:21 other types of headache other than
16:23 medication ovaries or migraine
16:26 and so
16:27 you know again it’s important to make
16:28 sure that we’re getting a good sample
16:30 for the study to see that it works you
16:32 don’t want to confound it with too many
16:33 other variables
16:34 but also sometimes you know if you’re
16:36 too stringent it can limit the
16:37 generalizability to your population
16:41 so what did they look for
16:43 they were concerned with pain intensity
16:44 at one hour compared to baseline as a
16:46 major thing the other key
16:48 kind of secondary endpoints to look at
16:50 were things like pain freedom at one
16:52 hour uh change in the intensity of pain
16:55 at two hours uh intensity of pain at 24
16:57 hours so they wanted to make sure that
16:58 this was a sustained benefit not just
17:00 like you know it’s helping for a little
17:02 while and it’s masking the symptoms
17:04 and then they also looked at how many
17:06 times patients had to use rescue
17:07 medication in addition to the stimulator
17:09 compared to baseline
17:12 so what they found uh you know there was
17:14 a significant difference you know
17:16 looking at 59 reduction uh in pain
17:19 intensity of one hour compared to the
17:21 sham and this is sound to be
17:22 statistically significant uh more than
17:25 double of note like i mean
17:27 if you’re familiar with the trial data
17:28 for migraine look at the size of the
17:30 placebo uh 30 is pretty huge and this is
17:34 actually you know standard for for a lot
17:36 of pain medications and stimulators and
17:39 you know i think that just goes to show
17:40 like i think sometimes people don’t
17:42 understand what placebo is and it’s not
17:44 that it’s fake i think it’s a very
17:46 powerful response and it shows kind of
17:48 the higher cortical centers that are
17:49 involved in pain processing
17:51 so you know the power of your
17:52 expectation
17:54 these things are impacted by anxiety
17:56 mood all these things and so it’s
17:58 important not to neglect that
18:00 but i think this is clearly showing is
18:02 demonstrating a superiority over placebo
18:04 for sure
18:06 so looking at their data over time this
18:08 is looking at the severity again and
18:10 there’s a 29 gain at the one hour
18:13 sustained again over two hours and 24
18:15 hours and this retains the statistical
18:18 significance
18:20 so there was a twenty nine percent
18:22 reduction in average migraines that are
18:24 in the two treatment groups after one
18:25 hour aimed at two hours and for 24 hours
18:28 after treatment
18:29 and pain freedom at one hour was five
18:31 times higher in the treatment group
18:32 compared to sham
18:34 the migraine responders uh those are the
18:36 people who had more than a 50 reduction
18:38 in pain severity was nearly twice the
18:41 rate in the stimulation group compared
18:42 to chef and so i think that’s very
18:44 promising for a lot of people who’ve had
18:46 bad experience with traditional acute
18:48 medications
18:52 so this is the follow-up then where they
18:55 looked at a two-hour protocol they
18:56 thought oh can we potentially you know
18:58 get better results
19:00 out of a more prolonged use of it
19:02 so again uh doing a very similar type of
19:05 study but they had more patients so
19:06 improved statistical significance and
19:08 they looked at a two hour
19:10 so this one they recruited 538 patients
19:13 again split one to one with a sham
19:15 and again court recording the visual
19:17 analog scale and most bothersome
19:19 symptoms this is a baseline two hours 24
19:21 hours
19:22 a similar inclusion criteria um you know
19:25 just maybe a little bit more stringent
19:27 making sure it wasn’t onset after 50
19:29 which should be a red flag anyway
19:32 and you know exclusion criteria were
19:34 again a little bit more stringent this
19:35 time around so maybe difficulty
19:37 distinguishing migraine attacks from
19:39 tension type headaches and that’s a
19:40 difficult discussion to have in the
19:42 clinic like i think a lot of my patients
19:44 maybe have a common parlance you know
19:46 colloquially they think of something as
19:48 a migraine but maybe doesn’t fit the
19:49 ichd3 criteria so that can be actually
19:52 very difficult to screen
19:55 so that presents a challenge for the
19:56 study
19:57 but these are the people who have more
19:59 than 15 hectares per month excluded so
20:01 that’s my chronic migraine population
20:03 you know i i have only maybe a handful
20:05 of episodic migrators in my clinic um
20:07 unless they’ve improved the medicine i
20:09 gave them uh you know and so i would say
20:12 maybe that’s not as generalizable to a
20:14 neurology clinic
20:16 um and the other issues here they
20:18 excluded people who’ve had a change in
20:19 their migraine prophylaxis in the past
20:21 three months
20:22 so that would be most people in my
20:23 practice
20:24 but i still think it’s important to
20:25 limit them into study group
20:28 so this study looked at percentage of
20:30 pain freedom at two hours and then the
20:32 resolution of the most bothersome
20:33 symptom like i mentioned that could be
20:34 anything to the patient so that’s
20:36 whether it’s the nausea or the light
20:37 sensitivity you know vertigo or
20:39 something like that
20:41 secondary endpoints looking at reduction
20:43 in the severity of two hours how many
20:45 people have sustained pain freedom you
20:46 know at 24 hours which is pretty
20:48 relevant
20:49 and then the resolution of all migraine
20:51 associate symptoms so who’s really
20:52 feeling good after this
20:55 so
20:56 here are some data on the pain freedom
20:57 and most bothersome symptoms
20:59 as you can see again sham still has
21:01 pretty significant contribution with
21:03 placebo there
21:05 but
21:06 you know still a pretty significant
21:08 statistical gain
21:10 and so there were 7.2 percent higher
21:12 rates of
21:13 pain freedom among the people at two
21:15 hours in the stimulation group
21:16 competition
21:17 uh 14.1 percent you know had resolution
21:20 of their most bothersome symptom
21:22 compared to sham
21:23 and sustained pain freedom at 24 hours
21:25 was you know significantly higher so uh
21:28 and pain relief rather
21:30 in the stimulation group
21:33 the people who had a
21:34 good response they had 14.3 reduction of
21:36 migraine pain severity and so all of
21:39 these met nice statistical significance
21:40 with that large group that they
21:42 recruited
21:43 the people who were lucky with complete
21:45 resolution of all their nausea vomiting
21:47 light and sound sensitivity uh 8.4
21:49 percent higher in the stim group
21:51 so just for comparison you know you
21:53 can’t really compare apples to oranges
21:55 and the trials are all different they
21:57 all slightly define everything slightly
21:58 differently
21:59 but you know if you’re looking at uh
22:01 [Music]
22:02 hemotropin approximate combination pill
22:04 which is out there or just zuma trypton
22:07 or naproxen alone
22:08 you know these are kind of comparable to
22:11 some of the the results of these other
22:13 traditional medicines
22:16 uh then it comes to like side effects so
22:19 you know if we are thinking about trip
22:20 downs you have things like chest
22:21 tightness sedation you know weird
22:23 feeling sometimes i think it’s like a
22:25 angina almost
22:27 you know but generally well tolerated so
22:29 for these stimulators they can cause
22:31 some you know more discomfort locally so
22:33 some people really just don’t like the
22:34 sensation of a tens machine
22:37 you know it feels like it’s a buzz or a
22:39 paresthesia and it can give them a
22:40 little bit of sore skin locally or make
22:42 them feel dizzy tired um you know maybe
22:45 they’re getting some radiation into the
22:46 jaw or elsewhere
22:48 but in general it’s like pretty
22:50 comparable to the sham
22:52 except for forehead discomfort and the
22:54 nausea and vomiting
23:00 so
23:01 next up we moving away from the acute
23:03 which is kind of the as needed paradigm
23:05 and we’re looking at a preventive so
23:06 using it on a regular basis to try to
23:08 stop your headaches
23:10 so
23:11 this one was again looking at the the
23:13 cephali for this purpose it was a bit of
23:16 a smaller study 67 patients enrolled
23:19 and again double blind randomized
23:21 and sham-controlled
23:23 so in this case they’re comparing the
23:25 truth
23:26 intervention which is 20 minutes daily
23:28 for three months
23:30 versus a sham stimulation and this one
23:32 was looked at in belgium
23:34 so again male or female 18 to 65 you had
23:37 to have episodic migraine under the 15
23:39 per month mark um and having at least
23:42 two attacks per month
23:44 people who are excluded from this are
23:45 those who had any migraine preventive in
23:47 the past three months um so they’re not
23:49 contaminated with other treatment
23:52 and then people who were refractory you
23:54 know they have tried three you know
23:56 adequate drug trials before of a good
23:59 duration two to three months and
24:00 adequate therapeutic dose
24:02 anybody with medication overuse headache
24:04 frequent chronic tension type headaches
24:06 in addition or other kind of severe
24:09 neurologic and psychiatric disorders uh
24:11 which again you know kind of stretches
24:13 the generalizability to my my clinic for
24:15 sure
24:17 in this study the primary endpoint was
24:20 the number of people who have a 50 or
24:22 more reduction in headache days and that
24:24 includes all days of migraine and other
24:26 types
24:27 uh secondary endpoints we’re looking at
24:28 the intake the use of medic acute
24:30 medications how many discrete migraine
24:33 days or attacks they had and the reduce
24:35 in the number of headache days
24:38 so for the study data
24:41 we had 67 subjects like i mentioned only
24:43 59 subjects actually completed the study
24:46 um
24:47 changing the monthly migraine days it’s
24:49 you know minus 2.1 versus 0.3 actually
24:52 maybe increase the mission a little bit
24:54 uh
24:54 just kind of going over the statistical
24:56 uh
24:58 cutoff for first significance uh so it’s
25:00 not quite meeting it um
25:03 the 50 response rate however did do
25:06 quite well so you know maybe not
25:08 migraine specifically
25:10 uh reducing but when we look at it at a
25:12 different way you know reduction in the
25:13 other types of headaches that come along
25:15 uh many people think that
25:17 you know they spend a lot of time kind
25:18 of parsing their headaches out you know
25:20 i have six types of headaches this one’s
25:21 the migraine this one’s the tension this
25:23 one’s whatever i mean pragmatically
25:25 speaking i think of it more like a
25:26 continuum and so you know sometimes it’s
25:29 hard to tell like you may not think
25:30 you’re photosensitive but you’re
25:32 preferring to lay in a dark room you
25:34 know so i think it can be hard to
25:35 identify those migraine days so i think
25:38 for me a useful surrogate is really just
25:40 the 50 production
25:44 migraine medication use was reduced by
25:46 over a third in the treatment group um
25:48 and there was also kind of 29
25:51 reduction overall in any kind of
25:53 headache
25:54 days oh there we go uh so how do people
25:58 actually like it you know i guess that’s
26:00 the most important thing because we’re
26:01 talking about adherence and giving
26:02 people options um so there was a good
26:04 survey uh where they looked at all the
26:06 patients who had been refilling their
26:08 their uh you know their adhesive things
26:10 over time and had purchased the
26:12 subscription to it
26:14 and then they asked them all to
26:15 participate and like any kind of survey
26:17 um you know i think they got like a 56
26:20 response rate because not many people
26:21 want to write in especially if they’re
26:22 doing well and so what they found was
26:25 that
26:26 um out of all the people using the
26:28 device that wrote back
26:30 um not all of them use it to treat
26:32 acutely you know like there were a chunk
26:34 that were mostly using it for prevention
26:37 only but i would say 88.6 is pretty good
26:40 that they’re using it for acute in
26:41 addition to preventatives
26:45 42.6 percent of people believe that they
26:48 were reducing their use of acute
26:49 medications as a result
26:51 which is nice you know if your
26:52 interactions with other things maybe
26:54 you’re saving some money in the long run
26:55 uh which we’ll get to in a second
26:57 and then there were the people who said
26:59 no i don’t use it to treat attacks when
27:01 we prevent it and so parsing them down
27:03 why didn’t they like use it again i
27:06 think it goes back to that adverse side
27:08 effects like you know some people don’t
27:09 like the sensation on the skin it makes
27:11 it feel sore or a buzzing weird feeling
27:14 some people just feel it doesn’t help
27:15 for acute but it is still useful as a
27:17 preventive for them
27:19 and so i think you know in general it
27:21 seems well tolerated and people do like
27:23 it
27:24 so on to the cost and i think this is
27:26 the barrier for a lot of people to be
27:27 honest um if you look at amazon you can
27:30 find this on sale it has a little bit of
27:32 a coupon code
27:33 and you’ll have to buy those replacement
27:35 pads like we talked about they each are
27:37 good for about 20 applications
27:39 and it’s a very comparable price if you
27:41 go onto the actual cephali website which
27:44 is probably the better place to purchase
27:45 it
27:46 to be honest but the nice thing about it
27:48 is it has a 90-day money-back guarantee
27:51 uh you know i’m not paid by these people
27:53 so i can say it pretty nicely i think
27:55 it’s a great option because it gives
27:56 people who are hesitant to commit a big
27:58 chunk of cash
27:59 uh you know to to give it a fair shake
28:02 and to see if it really helps them um so
28:04 i think that’s actually pretty generous
28:06 and it is given a three-year limited
28:08 warranty so you know if it does
28:10 fail because of a you know manufacturing
28:12 defect or something you can get it a
28:14 replacement easily
28:16 so like i mentioned each uh electrode is
28:19 good for 20 uses so
28:21 uh you know it’s 32 for a replacement
28:23 pack
28:25 what other kind of options do we have
28:28 so another one that’s available here in
28:30 canada is the gamma core and if you’ve
28:32 been all around for a while you may
28:34 recognize this is like the new modern
28:36 version of this uh the other one was
28:38 kind of a circular one with two
28:39 electrons and it was a blue one
28:41 um
28:43 so this is in a contrast to the cephali
28:45 which was kind of a external
28:47 transcutaneous stimulator working on the
28:49 forehead this is a non-invasive vagal
28:51 nerve stimulator so the vagus is the
28:52 tense nerve
28:54 and this one’s acting on your neck
28:56 and so it’s targeting that cervical
28:58 portion and so it has actually quite a
29:01 few indications they’re very good at
29:03 studying it for use in different types
29:05 of primary headache disorders um so it’s
29:07 you know primarily indicate i would say
29:09 for preventive and acute use uh in
29:11 migraine
29:12 in
29:13 both you know adolescents and and adult
29:15 patients
29:16 but it also has some
29:18 demonstrated use for cluster you know
29:20 and so i’ve had some cluster patients
29:22 who have tried everything they’ve done
29:24 the verapamil the lithium you know maybe
29:26 dipping into psilocybin in an
29:29 unregistered way and you know i i found
29:32 that maybe this was a useful tool for
29:33 them to avoid additional medications
29:36 um other types of unusual cousins of
29:39 cluster things like hemicrania
29:41 continuous or paroxysmal hemicrania
29:43 there’s also some data to support use in
29:45 these people too
29:48 you know the cephaly you can kind of
29:50 just purchase yourself over the internet
29:51 this one you know you may require a
29:53 letter of authorization and it doesn’t
29:56 necessarily have to be from a specialist
29:57 or a neurologist you can be your family
29:59 doctor a nurse practitioner a nurse
30:02 you know
30:02 just physiotherapist even just someone
30:04 who kind of has that expertise and they
30:06 feel comfortable to go through the
30:08 contraindications and everything with
30:10 you and decide if it’s a good fit for
30:12 you
30:14 this device you know it is private sale
30:15 but the company provides some training
30:17 to you at the end at the initial purpose
30:20 just to make sure you’re using it
30:21 correctly and that you get a good
30:22 outcome
30:23 and then you know if you need support as
30:25 you go you can always contact the the
30:26 patient support
30:28 system and they’ll help you with any
30:30 questions
30:31 so how is it used um this is a little
30:34 bit different from the cephali so where
30:36 cephaly was 60 to 120 minutes
30:40 you’re going to start this one as soon
30:41 as you feel the pain you know two minute
30:43 stimulations and you do two in a row
30:46 then you wait 20 minutes
30:48 if you’re still having a headache uh
30:49 that’s unfortunate hopefully you got rid
30:51 of it already uh but you do the same
30:53 thing again so a two minute run you take
30:56 a pause you do another two minutes and
30:58 then you’re kind of in a refractory
30:59 period you gotta wait two hours um of
31:02 note it’s important that you apply the
31:04 gel so there’s a conductive gel that you
31:06 actually have to apply to your neck for
31:08 the electrodes each time
31:09 you wouldn’t want to put it directly it
31:11 won’t work as well
31:12 and treatment three so again you waited
31:15 your two hours if you’re still getting a
31:16 little bit of rebound or it didn’t
31:17 happen you know that you’re feeling
31:19 better
31:20 then you do you repeat the course one
31:22 more time
31:23 in the preventive it’s kind of similar
31:26 but you’re taking this on a daily basis
31:28 and you’re just
31:29 you know spacing it out throughout the
31:30 day so first thing when you wake up
31:32 you’re going to do two two-minute
31:34 stimulations you’re going to wait four
31:35 to six hours to do uh you know by
31:37 mid-day or so two more stimulations
31:40 and then again before bed you can do it
31:42 again
31:44 so people that should not be using this
31:46 one similar to cephali you know any kind
31:48 of implanted device but again it kind of
31:50 harkens back to like where exactly are
31:52 stimulating in these people you don’t
31:54 want anything like a pacemaker any
31:56 implanted metal devices plates screws
31:58 anything in your neck in the area
32:00 cochlear implants hearing aids etc
32:03 you know the other thing is you can’t
32:04 use other devices at the same time so
32:06 you know you don’t want to be on your
32:07 cell phone with one hand while you’re
32:09 stimulating on the other just to make
32:10 sure
32:12 and
32:13 safety and efficacy you know
32:15 probably may be safe but we just don’t
32:16 have the safety data to recommend it for
32:18 people who have other significant
32:20 medical issues so this would be
32:22 uncontrolled hyper hypotension you know
32:24 arrhythmias either fast or slow
32:26 um adolescent patients who have
32:28 congenital cardiac issues i mean you
32:31 know probably the likelihood of causing
32:33 an arrhythmia is
32:34 low but uh you know it’s still something
32:36 to consider and be cautious with
32:39 people who have a lot of coronary artery
32:41 disease atherosclerosis
32:43 angina or issues like that
32:45 people who have already undergone
32:47 vagotomy where they’ve severed the nerve
32:49 so you know it may not even be an
32:51 effective option for them
32:53 um it’s unfortunately under 12 we don’t
32:55 have the data to support the use just
32:57 yet and as always it’s going to be
32:59 difficult to do any kind of registered
33:01 trials in pregnant women so i i would
33:03 say i would avoid that you know for now
33:06 so what exactly is biggest nerve
33:08 stimulation i think it sounds kind of
33:10 weird uh the vagus nerve you know if you
33:13 think of all your cranial nerves you got
33:14 12 of them
33:16 and we talked about trigeminal already
33:18 which is the three branches each side of
33:19 your face vegas is the tenth nerve and
33:22 it’s called vagus because it is a
33:23 wanderer like a vagrant
33:25 so it goes all around your body it
33:27 innervates all sorts of different organs
33:28 tissues and has a lot of different
33:30 functions
33:32 it does brain
33:33 heart regulating your heart rate you
33:34 know your digestive system moving your
33:36 bowels along and
33:38 that probably is the basis for a lot of
33:40 the gi symptoms of things you experience
33:41 with migraine you know the change in the
33:43 motility of the gut the nausea and the
33:44 vomiting um so it’s a key part of
33:47 parasympathetic nervous system and if
33:50 you think back you know we have fight
33:51 and flight which is the sympathetic you
33:53 know and you have the rest and digest
33:55 which is the parasympathetic and so
33:58 these two systems are constantly have
33:59 balance in each other in your body and
34:01 when they’re out of whack you know they
34:02 can cause a lot of bizarre symptoms
34:05 so vagus nerve stimulation has already
34:07 been demonstrated to be useful in a
34:08 couple of different important conditions
34:10 headache migraine cluster and others
34:12 like we talked about it’s useful for
34:14 patients with epilepsy in select cases
34:17 refractory depression and they may be
34:21 using stimulators at different sites
34:22 even in the arm
34:23 and it’s being investigated for use in
34:26 bowel and motility issues you know
34:27 gastroparesis alias things like that
34:31 so you know it is an interesting target
34:33 for therapy and it has a lot of
34:34 potential uses for different conditions
34:37 so the gamma how does it work
34:40 again i’m going to give you that line
34:41 that you know it’s a mysterious
34:42 mechanism when we haven’t quite elicited
34:44 everything
34:46 but
34:47 you know it’s not to kind of modulate
34:49 that same trigeminal nucleus center that
34:50 we talked about um and what’s
34:53 interesting is even just stimulating on
34:54 one side it’s actually
34:56 affecting changes bilaterally you know
34:58 the brain has a lot of kind of bilateral
35:01 connections that affect both half of
35:03 your brain
35:04 and brainstorming
35:06 so the first thought is that you know we
35:07 have this nucleus in the pons this is
35:09 kind of the ball sitting underneath your
35:11 brain right on top of the the medulla in
35:14 the brainstem and there’s an area there
35:16 called nucleus tracted solitarius or
35:18 solidarity and so we think that perhaps
35:21 this is feeding into the vagus nerve and
35:22 that then goes back down to the
35:24 trigeminal complex another way is
35:26 perhaps coming up through that nucleus
35:28 going to the para hippocampal gyrus so
35:30 you think of like the brain infection
35:32 you’ve got the areas that curl
35:33 underneath or your memories happen
35:35 and there’s an adjacent area which helps
35:37 to process pain you know time to memory
35:39 and then that goes back down to the
35:41 medulla so maybe taking the longer home
35:44 and then we have uh top down modulation
35:46 so this is thinking about higher centers
35:48 in your brain hypothalamus is a center
35:50 that does everything from day night
35:52 cycle you know thermoregulation
35:56 it has a lot of different regulatory
35:58 functions homeostasis which is that
35:59 balance inside your body um and so you
36:02 know we’re thinking there’s also
36:03 indirect connections modulated through
36:05 there
36:08 so you know we’ll go quickly over over
36:10 some of the kind of interesting pieces
36:11 of evidence again if if there’s any
36:13 interest we can do a more academic talk
36:15 and look at the specific study
36:17 vagal nerve stimulation was able to kind
36:19 of stop the effect of you know we take
36:22 the dura which is the lining of the
36:24 brain in rats and then we would give
36:27 them a noxious stimulus you know whether
36:29 it’s heat or chemical
36:31 and also just study how it works in rats
36:34 that have migraines and when you gave
36:36 them the vagus nerve stimulation it
36:37 actually slowed the rate of that firing
36:39 and stopped that signal
36:42 interestingly we have other studies
36:44 where we look at you know giving people
36:45 a painful
36:46 heat stimulus and measuring you know the
36:49 amount of tears that are produced which
36:50 sounds pretty horrific when you say the
36:52 lab
36:53 and by doing vagus nerve stimulation
36:55 you’re actually able to stop the reflex
36:57 of lacrimation and that’s a that’s a
36:59 brainstem mediated thing through the
37:00 trigeminal complex
37:03 people who are familiar with aura you
37:05 know
37:05 the kind of basis of that on the brain
37:07 is something called cortical spreading
37:09 depression
37:10 and we can measure the electrical
37:11 activity spreading over your brain and
37:12 how it burns out and that causes some of
37:14 the symptoms of aura
37:16 so they were able to raise the threshold
37:18 that you triggered aura and also stop
37:20 the spread of it going farther you know
37:22 which could progress to other more
37:24 you know severe symptoms of aura
37:26 and so vagus nerve stimulation was able
37:28 to attenuate that
37:30 the other method they think it works is
37:32 actually more like neural humeral so you
37:34 it’s not japal electricity there’s a lot
37:36 of chemicals at play here um and so it’s
37:39 not to have an anti-inflammatory effect
37:41 you know by by inhibiting cytokines
37:43 which are some of your inflammatory
37:44 chemicals um the messengers uh again
37:47 this is a generalized
37:49 from a rat study but you know there’s
37:51 some good basis that it’s conserved in
37:52 people too
37:55 uh the other one is you know linking the
37:56 two kind of together so uh the aura
37:59 basis the spreading depression uh as it
38:01 spreads over the brain it leaves kind of
38:03 a in its wake a nasty chemical soup of
38:05 inflammation and so it’s thought that
38:08 you know they’re able to measure this
38:09 actually with microbial thing and uh you
38:12 know vagus nerve stimulation reduces the
38:14 magnitude of that release
38:17 so on to the study data um so the first
38:20 study for for gamma core is presto
38:22 looking at acute acute treatment
38:25 and um
38:26 so this is again a multi-center study
38:28 but this one’s focused in italy they
38:30 recruited 248 patients and they were
38:32 randomized either to the stimulator or
38:34 to sham uh within 20 minutes of their
38:36 headache onset and then they were told
38:38 that they could repeat the treatment
38:40 again if they weren’t better
38:41 in a quarter of an hour
38:43 and so there were
38:44 three four-week periods they had a
38:46 run-in period where they’re just uh you
38:47 know recording all their headaches and
38:48 their diary to get a good baseline
38:51 then a double blind period where they
38:52 actually did the sham or the the vagal
38:55 nerve stimulator followed by an open
38:56 label period where they knew what was
38:58 going on and they were able to use the
38:59 actual stimulator even if they’re in the
39:01 placebo group
39:03 so primary endpoints for this one
39:05 they were concerned with you know they
39:07 want pain freedom for the first migraine
39:08 attack um so what proportion of the
39:10 patients were free from their headache
39:13 at 120 minutes and they they were not
39:15 using any kind of trip down or
39:18 secondary endpoints how was it sustained
39:21 pain freedom of 30 and 60 minutes and
39:23 then uh relief which could just be any
39:25 reduction in the severity of 30 60 and
39:27 125.
39:28 they looked at the mean percentage
39:30 change in pain score across these times
39:32 and also the absence of you know the
39:34 associated migraine features like we
39:36 talked about before
39:38 so now we’re kind of upping the anti we
39:40 are including some of our elders which
39:42 is always good to see because we don’t
39:44 have a lot of quality data on people up
39:46 to 75 and beyond
39:48 these are people who have
39:50 you know typical migraine episodic or
39:52 chronic
39:54 with or without aura
39:55 and and very comparable to the other
39:57 studies
39:58 people who are excluded again people
40:00 with psychiatric or cognitive disorders
40:02 another significant pain disorder uh
40:04 substance use i think these are all
40:06 reasonable exclusions because they can
40:08 confound the result but like i mentioned
40:11 limits generalizability a bit
40:14 so on to the data
40:16 so this is looking at
40:18 uh the number of patients who are
40:19 achieving uh that pain and freedom at
40:22 the time after treatment um
40:24 you know they reached significance for
40:26 reduction in pain severity at 30 and 60
40:29 minutes but with the initial analysis
40:31 unfortunately did not reach statistical
40:33 significance uh in the first past two
40:35 hours
40:37 but you know what they did do was they
40:39 reanalyzed the data and using a multiple
40:42 comparisons measure they were actually
40:43 able to determine that it was still a
40:45 significant uh sustained benefit of two
40:48 hours
40:49 but again this is a post-hoc analysis so
40:52 it would probably bear repeating uh you
40:54 know the study with greater statistical
40:56 power to confirm it
41:00 uh so for the preventive study data this
41:02 is now on to the premium two um and this
41:06 is looking at
41:07 you know how good is this legal nerve
41:09 stimulator for preventing headaches on a
41:11 regular basis
41:12 again multi-centered double-blind
41:14 randomized sham-controlled trial uh
41:16 looking at patients with or without aura
41:18 so they initially recruited 336 patients
41:21 but you know they wanted to make sure
41:23 about adherence and so with a modified
41:25 intention to treat protocol they
41:27 included only the people who you know
41:29 were adherent to the treatment at least
41:31 66 of the time uh which i think is fair
41:34 um but again that speaks to like what
41:36 are the reasons in a true intention to
41:38 treat what are the reasons why people
41:39 are not continuing um you know so i
41:42 think that’s important to consider
41:44 um so again this study had a four week
41:45 diary run-in period where they get a
41:47 good idea of people’s baseline amount of
41:49 headaches and then the patients were
41:51 randomized to receive either the actual
41:52 stimulator or a sham over a 12-week
41:54 double blind period
41:56 so for this one we already covered the
41:58 treatment protocol
41:59 three sessions based out equally through
42:01 the day of two stimulations uh each for
42:04 22 minutes
42:06 waking midday and before sleep um and
42:09 you know for the sake of the protocol it
42:10 had to be delivered on the same side of
42:12 the neck you know usually on the same
42:14 side where you have the most pain
42:17 primary endpoints included the number
42:19 changing the number of migraine days
42:21 from the run-in period that they were
42:22 measuring that diary um to the last four
42:24 weeks of the double-blind period they
42:26 also looked at other key endpoints like
42:28 50 responder rate for migraine
42:30 the mean change in the number of
42:32 headache days uh and also you know
42:34 reducing the amount of medication used
42:37 uh people included in this one episodic
42:39 or chronic
42:40 uh you know they had to make sure that
42:42 they weren’t over 50 at the time of
42:43 onset which like i mentioned is a red
42:45 flag
42:46 and people who are excluded you know
42:48 people who are already on to migraine
42:50 preventive therapies you know receiving
42:52 ongoing botox or cjrp monoclonal
42:54 antibodies and people who have had a
42:56 previous diagnosis of medication overuse
42:59 headache which you know i would struggle
43:01 to recruit patients from my clinic i
43:02 think
43:04 and any preceding history or suspicion
43:06 of a secondary headache disorder
43:09 so in this slide we’re looking at the
43:11 change in the number of migraine days
43:13 from that running period to the last
43:14 four weeks of the 12
43:16 week period
43:18 and you can see that there was a
43:20 difference you know
43:21 .83 days fewer
43:24 and not quite statistically significant
43:26 the issue with this study was that it
43:28 happened during the pandemic and so they
43:30 weren’t able to reach their statistical
43:32 significance for the primary outcome due
43:34 to a lack of uh you know
43:36 recruiting patients and maintain them in
43:38 the study so they had to terminate it
43:40 earlier
43:42 unfortunately
43:43 and that affected the statistical power
43:46 and you know
43:47 there’s a lot of talk in medicine about
43:49 re-examining p-values and intervals and
43:52 what it truly means and you know on the
43:54 other flip side of this issue you can
43:56 size a study with 10 000 patients and
43:59 prove the most minuscule difference is
44:01 statistically significant
44:02 so i think we’re trying to look at other
44:04 ways statistically as well
44:06 so i think it’s an encouraging result
44:08 that still shows you know some
44:10 improvement but perhaps it needs to be
44:12 uh re-analyze the greater central before
44:15 um so in contrast to this you know i
44:18 think there were also other endpoints
44:20 where there were significant differences
44:22 uh that suggests that it is a very
44:24 useful therapy
44:26 so for instance this is the 50 responder
44:28 rate uh for all headache days and you
44:30 know you’re looking at the people who
44:32 received the stimulator uh you know it’s
44:35 forty four point eight percent as
44:36 opposed to twenty six point eight one
44:38 percent uh you know and so i think
44:40 that’s pretty significant uh odds ratio
44:42 of two point two two so that means
44:43 you’re two times more likely to have a
44:46 you know a positive response reach the
44:48 threshold
44:50 and this one this is the change in the
44:51 number of headache days you know all
44:53 types of headaches whether it’s migraine
44:55 or otherwise um and again a
44:57 statistically significant difference and
44:59 i think this is important sometimes
45:01 these numbers seem a little small but
45:03 you’re looking at episodic migrators so
45:05 the difference of a day or two can be a
45:07 huge difference for your life for
45:08 productivity for working uh you know
45:11 even presenteeism when you’re at work
45:13 and you’re still not doing your best
45:15 so i think it’s an important important
45:17 difference
45:18 this is looking at the medication use
45:21 again significant reduction um
45:23 however it didn’t meet statistical
45:25 thresholds
45:27 and another important way of looking at
45:29 this is the impact on disability and
45:31 quality of life
45:32 so we measure this a number of different
45:34 ways on these scales you know where all
45:36 have their own difficulties and
45:37 limitations but uh
45:39 for now i think we’re stuck with hit six
45:41 and midas for better or worse for
45:42 insurance purposes and things
45:44 and with the hit six score again a
45:47 significant reduction there uh and uh
45:50 with the migraine disability score which
45:52 we commonly use uh also showing a good
45:55 change that right uh statistic threshold
45:59 so what are the side effects um you know
46:01 listed in the monograph probably the
46:02 most common are things like discomfort
46:05 of the site of application similar to
46:07 the cephaly you may get a little bit of
46:08 skin irritation or redness it may kind
46:11 of hurt in the area where you apply it
46:13 but usually it’s pretty mild um
46:15 sometimes it can even radiate into the
46:17 teeth uh for some individuals to report
46:19 this
46:20 muscle twitching or contractions makes
46:22 sense i mean it’s an electrical
46:23 stimulator and you can kind of hijack
46:25 the mechanism there that’s usually only
46:27 when you’re applying the actual
46:28 stimulation um it’s not like it’s gonna
46:30 keep twitching typically uh you know
46:33 some people actually feel worse with
46:34 headache uh and you know that’s
46:36 interestingly listed as a side effect of
46:38 every oral medication is potentially
46:40 headache and botox injection even often
46:43 causes a worsening of headache so that’s
46:45 not anything specific
46:47 some people feel a little dizzy or you
46:49 know paresthesia pins a needle feeling
46:51 where you apply the device but again
46:53 that makes sense because you’re
46:54 stimulating it so these side effects you
46:56 know they typically resolve uh very
46:58 quickly and it’s important to note that
47:00 throughout the whole uh of all the
47:02 trials you know no really serious uh
47:04 device related events were found and
47:07 nothing was significantly really greater
47:08 than
47:11 so just looking at the adverse events it
47:13 doesn’t list them specifically here
47:15 but what you can see is that when you
47:17 compare it to the sham the numbers are
47:19 fairly comparable for mostly
47:23 so how are you going to get it yeah so
47:25 rsk medical is the company that’s
47:27 licensed to distribute electric core for
47:29 electric core in canada and i’ve left it
47:32 up here if you want to take a peek you
47:33 can either reach them by telephone
47:35 they’ve got an email or a website which
47:36 you can visit
47:38 like i mentioned before you would
47:40 require a letter of authorization
47:43 how much does it cost so you know you
47:45 can buy a couple different options
47:47 for a 31 day starter kit that’s about
47:49 655 dollars and so you can use up to uh
47:54 32-minute stimulations daily
47:56 you do have to continue to replace it on
47:58 a monthly basis so it is a subscription
48:00 service
48:01 the other issue is that you could you
48:03 know stock up if you find it’s effective
48:05 and you want to get a little bit of a
48:07 price benefit
48:08 you can lock in for 93 days and it ends
48:11 up being 975
48:13 canadian so the issue is it’s not
48:15 covered by public payers you know which
48:17 is a significant barrier to many people
48:19 here in ontario on
48:22 you know odfb or
48:24 who are applying to the eap program for
48:26 various issues
48:28 but you know if you have a private payer
48:30 like you know one of the many insurance
48:32 companies through your work or benefits
48:34 it might be possible every plan is a
48:36 little bit different
48:38 and it probably depends on what your
48:39 adjuster rate for breakfast
48:41 but i would say reach out to them and
48:43 see if they’re they’re willing to
48:44 consider it you can always ask
48:47 your your provider for a letter of
48:49 support
48:51 so providers how do you go about helping
48:54 your patient to get this
48:56 so you know there’s a very easy and
48:58 convenient prescribing process you can
48:59 find it online at their website like i
49:01 list and there’s also a form and it’s
49:03 easy to enter it into your emr and you
49:05 can auto populate everything um so you
49:08 just kind of
49:09 indicate whether you’d like to do the 93
49:11 or 31 day trial kind of thing and you
49:14 can also if you prefer to write a little
49:16 letter of support indicating um
49:19 for insurance
49:20 so a quick overview of the things that
49:23 unfortunately are not available in the
49:25 north um
49:27 there are a couple but we’ll focus on
49:30 two but neurivio is a really interesting
49:32 one um and so this device is an armband
49:35 that’s controlled from your smartphone
49:37 and you just wear it on your arm it’s a
49:39 remote electrical neuromodulator which
49:41 is also targeting the vagus nerve but a
49:43 branch that’s you know innervating
49:45 elsewhere
49:46 and so uh you know this can be used for
49:49 acute treatment of migraine with or
49:51 without aura and adolescence or or older
49:54 again this one requires prescription
49:57 but you do administer it yourself at
49:58 home
50:00 and you would put it on right at the
50:01 onset of the attack
50:03 and it’s been shown to be useful for
50:05 acute uh decrease in migraine related
50:07 pain currently available in u.s
50:11 inura is another very interesting one
50:12 and i think this technology has a lot of
50:14 potential for applications outside of
50:16 migraine it’s a transcranial magnetic
50:18 stimulator um and so you may have seen
50:22 some interesting setups with all the
50:23 weird coils and everything you go to a
50:26 psychiatrist or a physiatrist’s office
50:28 and they will fix the coil somewhere to
50:30 your head and pulse you with magnetic
50:32 waves and the magnets actually induce
50:35 an electrical
50:36 signal in your brain and so it’s a kind
50:38 of way of getting deep past the skull
50:40 without actually inserting any
50:42 electrodes or anything
50:43 it can be used as a preventive four
50:45 pulses of this on a twice a day basis or
50:48 as an acute uh medication a treatment
50:51 rather with three pulses during a single
50:53 attack
50:54 so again requires a prescription and
50:56 it’s a subscription service where you
50:58 return the device or charge it um and
51:01 again you would administer this to
51:03 yourself at home
51:04 only available in the states for now but
51:06 perhaps you know they may expand
51:08 in the future
51:10 uh just a quick overview i kind of
51:12 mentioned already using the magnets to
51:14 induce an electrical current uh blocks
51:16 the cortical spreading depression which
51:18 is a commonality to the mechanisms
51:19 already discussed
51:21 kind of calms down that trigeminal
51:23 complex and its connections to the
51:25 thalamus which we talked about already
51:27 it stops the spread of cortical
51:29 spreading depression which is the aura
51:30 type symptom
51:32 and also modulates those corticothalamic
51:35 reverberation those loops
51:37 and so all of this kind of feeds in to
51:38 calm down that brainstorm where we think
51:40 the migraine comes from so very
51:41 interesting that all these devices share
51:43 a lot of common pathways
51:45 but they’re looking at modulating the
51:48 the brain and the axis at different
51:50 entry points uh so it’s kind of an
51:52 exciting time with all these devices
51:54 emerging and i think it’s given a lot of
51:56 hope to people who you know are eager to
51:58 see how it evolves because they’re eager
52:00 to try therapies that you know are
52:03 alternatives to what has not worked for
52:05 them so far
52:06 so in summary
52:08 i think these non-invasive neural
52:09 stimulators for migraine they may be
52:11 useful for both acute and preventive
52:13 treatment of migraine
52:14 which is nice it’s a non-medication
52:17 option which i think is useful for those
52:19 who are hoping to avoid systemic effects
52:21 and interactions or maybe have
52:22 contraindications from other medical
52:24 conditions
52:25 and you know it’s not an either or
52:27 situation you know like this is
52:29 complementary to existing therapies so
52:31 you can you know take it in conjunction
52:33 with your other modalities if you’re not
52:35 quite happy with how things are coming
52:36 along
52:37 so it can be used with or without oral
52:38 medications injections like botox or grp
52:41 labs
52:42 it’s safe and well tolerated
52:45 and there are a few contraindications to
52:47 use you know like unless you have some
52:48 sort of implanted device or
52:51 certain medical conditions like we
52:52 talked about
52:53 and that’s why i think it’s kind of
52:55 useful
52:56 access may be limited in some areas
52:58 okay and of course i think the initial
53:00 startup cost of it represents a barrier
53:02 to many um but
53:05 you kind of have to think about the long
53:06 game too if you are sparing yourself a
53:08 lot of the communication use um you know
53:10 this may actually potentially save you
53:12 money in the long run um but that’s a
53:14 you’ll have to sit down and crunch the
53:16 numbers
53:17 so with that i want to thank you for
53:19 your attention
53:20 and i’ll turn it back to ashley maybe
53:21 we’ll take some questions from the
53:22 audience