 Visually evoked potentials were first noticed in EEG recordings in the 1930s. Clinical EEG's date from just fairly recently, not 100 years ago, from a German neurologist named Berger, and about 1929 was the publication. And by the early 1930s, they were recording EEG's in the United States. As you know, the visual part of the brain is at the back of the head. Everything at the back of the head is visual, and the primary visual area that visually evoked potentials are recorded from mostly is the central area, which if you feel up the back of your head to your Indian and go up about three or four centimeters, that's the center of the primary visual area area 1701-02 Indian. This is a functional MRI of the visual area stimulated with a check pattern similar to what is commonly used in visually evoked potentials. And I want to show you this to show you the variation between hemispheres. This is recorded here, not at Moran, but in MRI unit here at the university. Note the asymmetry. The hottest area is red. Notice the asymmetry at the cortical level between where you can record visual activities to a pattern. In his case, the hottest area is buried deep down three or four centimeters. This is why using electrodes lateral from the central area are very poor at detecting hemispheres. For one thing, once the signal leaves the cortical surface, the polarity fields start to tilt and you get false lateralization on your visually evoked potential, whether it's coming from the right or the left side. Although commonly in the world, people put an array across the back of the head, which is just a waste of time for everybody, but they do it anyway. If you present a sensory stimulus, that's this blip, flash a light, a changing pattern, a click in the ear, and then take a period of the EEG from the brain following that click, repeat it, take another period, save each atom to the next, atom to the next, atom to the next, that's how evoked potentials are recorded, whether they're visual, auditory or somatosensory. They come from the EEG or extracted from the EEG. This is the chronological order of visually evoked potentials, the way they were done until how in the middle 60s was a strobe flash only. Then they start adding pattern to the top of a strobe and then the original invention of the pattern reversal visually evoked potential stimulus was a mirror system. It was really cute. One of the advantages of being older than dirt like me is that I knew most of these pioneers when they were alive 50 years or 60 years ago. The originator of the pattern reversal response took two Kodak slide projectors and he had a pattern of a checkerboard in one and then the reverse of it in the other and he put a camera shutter in front of them. That was the stimulus. He back projected onto a translucent screen a pattern that the checks were in one position and then the next fraction of a second later it was reversed and that's how he did it. There were even these cute little suitcase systems that you open the suitcase and it exploded out and it had two of these little projectors shining in on a screen. This is how that was done before television monitors were used to do it. I had one. It would be wonderful to have it and somebody without asking me threw it away. Then the pattern onset offset is the pattern comes on and then goes to gray. I'll show you each of these. This is the stimulator, an old one of what's used for photic driving by neurologists and this was the original stimulator for visually evoked potentials. This is what I was trained on. Even for ERGs, when I learned ERGs, this strobe lamp was put on an articulated arm and patients were tested lying down with this over their face, foot away or so. Then mid-60s people starting adding a static pattern and then the pattern reversal is this. The visual system really likes this. It likes sharp edges, what are called stop lines and high contrast. The great thing about pattern reversal response is if I test everyone in this room, I get the same looking visually evoked potential whereas with a flash or pattern onset response, they're quite variable between individuals and more reflect individual fine differences in anatomy of individuals. This is the normal pattern reversal visually evoked potential which is the handout. If you use the televisions until the modern ones that are faster and brighter, this is what you get. This is the classic. You get this response that peaks around a positive wave that peaks around 100 and everyone in this room would look like this. I'm not going to go into this, as I'll mention that the visually evoked potential is present at birth but because your system is not myelinated, things are much slower. You can just watch if you would sequentially test an infant from a few months of age all through up into at least grade school, you could just watch the quote P100 start out around 180 or so and then improve 10 or more milliseconds a year so that by the time they're about first grade, it looks like an adult. You get full pattern responses by about six months of age, although with continued myelination of the optic pathways, the speed increases like I said for the first six or seven years. This is a thesis done by a person who's still here that was a friend of mine, has been a friend of mine for 50 years. He took about 20 people of each of these average age groups on the left and recorded the responses and the only significant change you get until after age 55 is about a one millisecond slowing of the response. The biggest difference for people after 55 is look at the standard deviation jump. That's because of the big differences in aging between individuals and the same is true on the development end in the big differences between the maturation of a 2, 3, 4, 5-year-old. This is a scattergram of all those patients I just showed you. Note you get a big variation in lower grade school and it's even greater than that before age six or seven. Things tighten up through young adulthood and then the variation goes up again when you get over 65 or 70. The pattern offset response is what I mentioned was from a blank gray pattern, a pattern appears, goes back to gray, pattern appears, goes back to gray. This is the preferred stimulus for any person that has nystagmus as part of their symptoms. The pattern onset visually evoked response is best for poor fixation, eye movement, lingering, deliberate defocusing and nystagmus as I mentioned. There are choices that have to be made. This display is inverted as from that same study that I mentioned showing the similarity in responses with no significant difference until after age 55. You can estimate visual acuity by using different sizes of pattern in the pattern evoked potential, but you can't do a better job than you can do. Even though it's cute that you can estimate a person's acuity or an infant's acuity by using two or three different sizes of patterns and creating a linear, compute a linear distribution of the response speeds and amplitudes you can determine acuity. No. No. Use malingers. In fact, that's the end that you really get asked for is malingers. So if they're not so sociopathic that they've researched it and know that not to cooperate, if they cooperate and I use different sizes of checks, then you have evidence that they're really not the acuity they're trying to tell you. But I don't get asked for infants or anything. Back. What? No. Good. Good. For one thing, they have the attention period of a NAT and they will, unless you can somehow force them to watch it, you can't get them to fixate for long enough and maintain fixation to get a response. Like ERGs, you cannot fake unless you refuse to do it. Like it's running a strip of your electrocardiogram. That visually evoked potentials for pattern require the patient cooperates and fixates. So I've had, through the years, a lot of patients in malingers that come in and they know to pretend, but to either consciously defocus or look at the bottom of the screen instead of the screen or something like that. One of my, I guess I got to tell you this one. He was a VA patient brought in and he just came into the room like this. This was a long time ago when he used EEG machines to provide the amplification of the EEG and he just came in like this and we recorded the results and as he was leaving the room like this, the EEG machine goes over there and he went, are those my EEGs? And his wife hit him. He was trying to get a blind compensation from the VA. Are those my EEGs? He had another guy that had a white cane and he was like this and he said, you know, where are we going? And I said, well, we're going right to the floor, right below where we are right now. But the closest elevators down there in the middle of the building, so we have to go down there and down the elevator and come back and he said, is there a shorter way? And I said, well, yeah, there's some stairs right over here. And so he went to the top of the stairs like this. He folded up a stick and went down the stairs like this and then opened up a stick again and continued on with this charade. The classic use of visually evoked potentials, at least the pattern reversal visually evoked potential, similar to the classic use in full field ERGs, which was ferretinitis pigmentosa, the classic use was to quantitate optic neuritis in multiple sclerosis patients. The pattern reversal VEP was invented at Queens Square, London, the National Center for Neurology and Stroke for Great Britain. It was a neurologist named Martin Halliday visited his lab in the 70s there when he was using the Kodak projectors to create the pattern reversal. In classic optic neuritis, usually one nerve starts before the other. So whenever I quiz patients that, and I always ask them, is it one eye or both? And of course, people think both is worse, but that's not true. One is worse. Even if having one nerve only is poorer prognosis at that point than having both. Classically, if you get a perfect patient like this, there's no amplitude difference. You just have significant slowing of one nerve. I'm going to run through some different examples. Sometimes there's a bilateral one. Just look at that middle column where it says P100. If you took a classic multiple sclerosis patient that onset was, say, 25 or 30 years old and then you followed them and tested them every five years or so until they were 60 or 70, you would see first one nerve slowing, then the other one kicking in in six months or a year and also slowing, and then getting slower and slower as they demyelinate more and more through the decades. After they say 50 or 60 years old, there's enough demyelination going on that you also start to lose amplitude. That's definitely abnormal. Standard deviation is six to seven. When you get past about 112, you're pretty sure that you're beyond two standard deviations. Especially in a woman, because women in general have a little faster responses than men. This is not part of your high school graduation, so you don't have normative data, so you don't know when you see a person, they're 30 or 40, if when they were 18 or 20, what it was. Women can be as fast as the mid-90s. Men can be also occasionally at least upper 90s. The typical male is around 100 or just a little bit slower. Typical female is around 100 or faster. Neurofibromatosis type one, we see a lot of those here, and the VEP looks just like a patient with demyelination. If you show me VEPs of an affected neurofibromatosis patient, I couldn't tell you if it was an MS patient with the opti-neuritis or because for completely different reasons, it produces the same thing. Same thing early on, amplitude loss later on, but that's caused by the gliomas, not by demyelination. You get the same looking response, essentially all neurofibromatosis patients type one have slow responses by grade school, even if they don't have gliomas. There's just something else going on metabolically that slows the response, a little slow, not necessarily significantly slow, but say 110 or something like that. Well, it's like MS. Usually the presentation, one nerve is more affected than the other, which is usually related to the gliomas. But you don't have to have the gliomas to get the slowing. I've tested, I don't keep count, way more than 50. I'm probably following 30 now, something between all the pediatric specialists we have here. I followed some that have come and gone, I started when there were three, I watched them grow up, and then last saw them when they were 16 or 18 years old or something. They drove in themselves, and I tested them. Okay, here's the bad news, initial VEP of a patient, just slow one eye only. Four years later, with growth of gliomas on both nerves, and four years later just really nothing, no recordable visually woke response on the left and just the semblance of one on the right. But this is not common, the typical average patient will have slowing but don't develop the gliomas to the extent that this happens. So I'm going to run through some different other diagnoses. Anything that messes with the optic nerve pathways, the central projections through the geniculate and thalamus, projections to the visual cortex or the cortical area itself such as from meningitis or anoxia, near death drowning, birth anoxia, anything along there will affect the visually woke response. The differential interpretation depends on the history. You're not going to mix up a meningitis patient with a hydrocephalus patient, et cetera. It's an orbital mass, this was a patient of Dr. Patel's, let's see if I have a follow up on this one. Oh yeah. So beforehand there was essentially no recordable response on the right side and a tiny one on the left, and then after decompression a little bit of a visually woke response came back on the right, and I didn't follow these people forever so I don't know, because I just, I do what I'm told to do, so usually just one recording is done a few months after or something like that and I don't see them anymore. So the visually woke response like the ERG and the multifocal ERG can be used to quantitate progression in either direction, either recovery or pathology progression. Neuroblastoma, left side, orbital fracture left, paleoptic nerve, slow and loss of amplitude, ethambiotal nerve toxicity, this was a 30-something year old adult I believe, it doesn't have his age on here. Again if you're showing this, oh it could be optic neuritis, so you can't make the, you can't say what the etiology is from visually woke potentials, because again this one looks just like demyelination or neurofibromatosis, slowing to 114, 116, meningial tuberculosis, then just slowing, not much amplitude, little or no amplitude loss. Cardi syndrome, nasty, really poor on one side. The other side is really okay, this was a small child that shows you the slow VEP even though it has normal form and amplitude to it, really, really normal amplitude, you would only get numbers this size in children. Okay and I've talked about multifocal ectoretnograms, you can also do multifocal visually woke potentials where you get 60 to 100 depending on the protocol, again, same system is used, but the target is different, the target is this, I don't have a video of it moving, they don't move, none of them move, they pop off and on in reverse, so this dart board kind of pattern, again this was invented by the same guy Eric Sutter and the other companies that provide these systems use the same stimulus patterns. Normal responses, here's normal multifocals, red is for right, right and left eyes, test one eye at a time. This is coming up as an episode of severe acute optic neuritis obliterating the multifocal VEPs and then they recover in amplitude but the time delay remains. Once you have these episodes of demyelination it's during the episodes that the VEPs will be the slowest and then they will recover and get better but they don't speed back up again because once you lose the myelin you've lost the speed. So the red trace, the very small trace in most cases is this during this episode of acute optic neuritis and then here's the recovery, notice the amplitudes come back almost completely but that the time, the red trace is a little bit further to the right in each case and that's slowing because time goes by left to right. Eschemic optic neuropathy, this shows this area there where there's a big difference between the traces. Optic nerve glioma shows the difference between the traces there. Just want to get you a feeling for all of this electrophysiology that there's lots of applications that you can use. In the case of the retina the great is you can quantitate what's going on in the retina or confirm your expected diagnosis and multifocals are really useful to follow, map, detect and determine if it really is in the retina because you can get almost the same field issues at each level in the system, the retina, the nerve, the central pathways, the projections, the cortex and at the cortex. One of the great things about the multifocal that I didn't mention is you can tell immediately is it in the retina or not because people with just complete hematopsias or large field loss if it's not in the retina the multifocal is going to be normal and that's really useful to individuals especially the neuro ophthalmology patients when they got these dumps from the other specialties because we can't find it, send it to neuro, let them figure it out. We don't want to waste our time on it. Again there's chapters in web vision on visually evoked responses that include this and other diseases and in general the internet's a great source. There must be like ten videos out there that are on either ERGs or visually evoked potentials by different people or different companies so if you get interested enough and you need a cure for insomnia you can look at some of these or if you end up in one of the specialties where it's important to you like pediatrics or retina or neuro ophthalmology. Again switch, how are we doing on time? Forty-five. Okay, let me do dark adaptation for sure, dark adaptation should be somewhere there. Dark adaptations rarely used, I use it most in studies, just research studies. Until the last year or so I've used the Goldman Weaker's dark adaptometer which was the classic way to measure a person's dark adaptation curves. Just like this and inside the patient views this pattern which can be rotated 90 degrees to make sure the patient's not guessing so just randomly the tester would rotate this stripe. The stripe, the white of the stripes blinks about once per second. You start off at zero at complete blackness and test the patient's one eye at a time. The fixation point is ten degrees off center which is the peak of your rods. Even though you're dominated by cones right in the fovea and out to about ten degrees the rods actually peak out within ten degrees. It's not true that you know the rods keep getting more and more and more and more. They just dominate more and more and more as you get out but so a person can see this stripe best if they fixate on the red spot and just pay attention to what's going on right below it. The patient is asked to tell or tap a coin when they see it, stop tapping the coin or tell the tester when it appears and disappears. And over a period of 30 to 45 minutes an individual will after the first six or seven minutes get a sharp break. This is called the cone break even though it's the rods it's called the cone break and improve about three logs over the next 30 to 40 minutes. This is the dark adaptation if you're just working on your cones. The principle of using colors is what I mentioned last time about ERGs. If you limit the stimulus to a really deep red you can isolate the cones. If you limit the stimulus to a really dim deep blue or peaking around 450 nanometers you can just nick the rods. So you can also do dark adaptations for just the rods and the cones separately. So this would be the target, the blue target below for the rods and the red target below for just the cones. This shows the differences if you use a red target versus a blue target in the dark adaptation. Now these programs are done with LED stimulation and the modern Gonsfels instead of the Goldman Weekers which was just a brightness and a blinking light and these are completely automated you just get the patient going they push a button like doing a Humphrey field when they see it and the program knows if the patient pushes a button and sees it it knows to make it a little dimmer and then when the patient quits pushing the button that they don't see it it makes it a little bit brighter and it just changes this and produces the same kind of curves over whatever time period you wish most people use a minimum of 30 minutes some use as long as an hour. Do I have one here? This is the system I'm using currently it gives you two different curves because they stimuli alternate between red and green or blue and these are the the the person pushing the pushing their automated buttons over a period of an hour. As a patient with liver disease this is a patient of Bernstein's and he had not very much small intestine and it's not the same patient I talked about last week in the ERGs this is another individual. But prior to vitamin A therapy he essentially had no night vision the red curve is the normal curve and those the other two curves are two months on vitamin A therapy and four months on vitamin A therapy. He had essentially a completely dysfunctional liver he was on the liver transplant list and he also had very very little small intestine so he couldn't absorb well what is this? Oh that's an albino that grew up here lives in San Francisco now used him for a lot of studies in fact the names albinos have better night vision than normal individuals more light gets in their eye. He told me a story that he was with friends they hiked up Mill Creek Canyon at dusk so they were by the time they got up at the top where they were headed it was completely dark and they decided for fun they would race back to the car well he was back at the car eating sandwiches before anybody else because everybody else was running into tree limbs and falling off the running off the trail and to him it was like dusk and he would just run down the trail just like he came up the trail and these are some individuals of the old classification of the tie tie negative albinos and type positive those the tie negative are the really white kind like Dale. He was exceptional a lot of ways you see he's got not exceptional that he has a little store business but his vision was 2040 or better and he was this type of albino it's really rare for this type of albino to have that good a vision and be able to get a driver's license. He finally did give up driving when he got older he's now oh he's at least over 50 now and he's quit driving that's it okay