| 00:03 | Uh This is lecture 21 of Uh As a reminder, I ask |
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| 00:12 | not turn on the closed caption. me make sure I actually disable |
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| 00:22 | So this first slide that you see the material actually reminds us what we |
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| 00:27 | about when we talked about the somatic system. And when we talked about |
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| 00:31 | in the brain and we talked about paralysis as well. And this describes |
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| 00:37 | experiment with the monkey hand where monkey were exposed to activity and the maps |
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| 00:46 | the primary somatosensory cortex grew for those fingers. We talked about phantom |
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| 00:51 | There is a description description there also very interesting description of how violentness that |
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| 00:57 | left versus right hand will have a anatomical organization and uh different kind of |
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| 01:04 | uh or or areas uh larger areas the brain dedicated to the hand and |
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| 01:11 | that are more active over the hand is less active. So is synaesthesia |
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| 01:18 | common than autism. It's somewhat of dated article from 10 years ago, |
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| 01:22 | in that case, uh this article that uh synaesthesia and adults with autism |
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| 01:32 | almost three times greater than the So that's something to keep in |
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| 01:35 | And if you remember that had to with the cross wiring between the number |
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| 01:40 | the color area or the sound area a particular structure in the brain. |
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| 01:44 | those are the things that are gonna on the quiz uh tomorrow. Uh |
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| 01:50 | that uh due to this cross it's typically was uh associated with the |
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| 01:56 | component, the trimming gene. And , uh I guess in this |
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| 02:03 | uh it, it is more prevalent autism um patients. OK. So |
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| 02:10 | learned a lot so far if you , we looked at a version of |
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| 02:14 | slide very early in the semester. you learned a lot about individual neurons |
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| 02:19 | synapsis and synaptic communication and cell circuits cell structures and their functions and systems |
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| 02:26 | systems. And we talked about how brain is capable of generating activity, |
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| 02:33 | neurons are capable of generating activity, this activity has certain spatial temporal |
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| 02:39 | how it has what we call activity or brain activity map neuronal activity |
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| 02:46 | And that activity will spread through the neuronal circuits in the form of what |
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| 02:53 | would refer as a brain wave. so today, we're gonna talk about |
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| 02:59 | in the brain and to understand uh of the brain and rhythms of the |
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| 03:07 | . Uh We have to understand how record activity in the brain in humans |
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| 03:13 | what relationship this has with epilepsy. , in uh the beginning of the |
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| 03:22 | century, it was Hans Berger in that used this electrical recording technique that |
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| 03:32 | referred to as electrons of foo gram E E G. It's a measurement |
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| 03:37 | electrical activity from the surface of the as noninvasive. So the electrodes are |
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| 03:44 | on the skin of the skull. what Hans Berger noted using this type |
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| 03:51 | electrical recording in 1929 that a person was awake had a very different E |
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| 04:01 | G pattern or electrical pattern versus a that was asleep. And so down |
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| 04:09 | here, you're actually seeing the first published traces of E E G recordings |
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| 04:17 | . OK. And so this is significant. Now, E E G |
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| 04:22 | of holograms have advanced over the last years in their application and uh recording |
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| 04:29 | activity noninvasively in different rhythms as well using E E G for diagnosing uh |
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| 04:37 | and epilepsy or abnormal rhythms is also advanced, taking some advances and we'll |
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| 04:44 | about that a little bit later. , what's interesting is that when the |
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| 04:51 | are placed on the scalp here on skull, these electrodes, this is |
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| 05:00 | the E E G recordings are And what's been noted is that their |
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| 05:07 | G recordings, they will produce these , electrical traces from the underlying activity |
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| 05:16 | neurons in the brain and these electrical will come in certain dominant frequencies and |
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| 05:25 | certain dominant frequencies, for example, as alpha beta delta theta gamma and |
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| 05:34 | fast frequencies that we refer to as , they are dominating in certain behavioral |
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| 05:45 | . So alpha rhythm, for is associated with relaxed wakefulness and it |
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| 05:53 | dominant at about 8 to 10 That means that this rhythm, this |
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| 05:59 | of the rhythm repeats 8 to 10 per second. Now, beta rhythm |
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| 06:05 | a little bit beta rhythm is associated intense mental activity and it will have |
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| 06:16 | different frequency and it has not just particular value of a frequency, but |
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| 06:23 | rhythms actually have a dominant range of we call frequency. So it will |
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| 06:29 | beta intense mental mental activity at 13 30 Hertz delta rhythm will be associated |
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| 06:37 | drowsiness and it will be slow. is associated with drowsiness or pathology. |
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| 06:45 | also it's very important rhythm for learning well as the gamma rhythm. So |
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| 06:51 | of these different traces, beta alpha sleep spindles, delta waves, they |
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| 06:57 | labeled excited, relaxed drowsy as deep sleep. That means that the |
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| 07:04 | rhythmicity, overall rhythm in the brain . And when we talk about these |
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| 07:11 | E G recordings that are taken from scal the rhythms that we can pick |
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| 07:16 | represent synchronized activity of hundreds and thousands cells underneath a particular electrode in a |
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| 07:24 | part of the brain where this grid grid is sitting on below here are |
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| 07:32 | different type of recordings. These are that are done from the surface of |
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| 07:37 | brain. These are very rare and only done in the cases when there |
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| 07:42 | a surgical resection or surgery neurosurgery of brain. And the electrode grid is |
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| 07:48 | that case, it placed intracranially inside cranium where the skull, the skull |
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| 07:55 | removed, the scalp and the dura and the meninges are exposed yet |
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| 08:01 | And the grid is placed in order typically identify very small areas of the |
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| 08:07 | before brain surgery takes place. So not to compromise important functionally areas of |
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| 08:14 | brain or otherwise, that may not involved in pathology. Um Being the |
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| 08:21 | for a particular surgery when we think brain rhythms. This is a very |
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| 08:28 | book that I would recommend for you have a read at leisure. Uh |
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| 08:33 | of the brain by Yogi Boa. what he talks about is the intimate |
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| 08:40 | between space and time. Spatial temporal packed into the concept looks X Y |
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| 08:46 | T. So you have space three dimensions in space. Fourth dimension |
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| 08:51 | time oscillations can be conceived up and in terms of either space or |
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| 08:57 | the phase plane of a sinusoid This is like a sinusoidal away the |
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| 09:02 | plane of the sinusoid harmonic uh oscillates circle. So if you think about |
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| 09:09 | , everything repeats in life in the , what has been is what will |
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| 09:13 | . And what has been done is will be done and there's nothing new |
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| 09:17 | the sun. This is the circle life. And our walk on this |
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| 09:20 | is measured as dislocation from some sort a perimeter, some sort of a |
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| 09:25 | value as an alternative uh to viewing periodicity and this periodicity, this periodicity |
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| 09:33 | nature periodicity. In this case, activity and neuronal rhythmic activity can be |
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| 09:41 | of the universe display periodicity as a of sine waves and oscillations. |
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| 09:48 | we can walk along the trots and off the line without ever returning to |
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| 09:53 | starting point. Although we come back the same date the year later in |
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| 09:57 | same calendar date, but things are exactly the same time here as a |
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| 10:02 | with the cycle as its metric, cycles are identical in shape and the |
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| 10:07 | and end points of the cycles form intimate path into the seemingly endless |
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| 10:13 | OK. So it's a way to about periodicity in life periodicity in |
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| 10:21 | But inevitably periodicity and fast rhythm These rhythmic oscillation, sinusoidal like oscillations |
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| 10:30 | you would see in the brain as recording electrical activity using E E G |
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| 10:37 | . So why uh why are there many rhythms? And here is another |
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| 10:43 | that shows the table that there are very slow rhythms. So the slowest |
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| 10:47 | on the in the brain are diurnal your uh day and night rhythm, |
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| 10:56 | is dictated by the super cosmetic nucleus you learned about, which is the |
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| 11:00 | body clock. And super cosmetic nucleus the night time will express certain transcription |
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| 11:07 | and influence the sleep cycle. And the morning time and daytime, it |
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| 11:12 | express a different subset of transcription factors be turned on and different molecules are |
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| 11:18 | and therefore it was promoting the day . But in general, there are |
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| 11:24 | rhythms, there are metabolic rhythms. we talk about neuronal activity, we |
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| 11:29 | to feature these rhythms like delta theta gamma, fast and ultra fast and |
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| 11:36 | at the ultra fast rhythms. 200 600 Hertz. That means that neuronal |
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| 11:42 | that these hundreds and thousands of cells some point can synchronize in time and |
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| 11:51 | , it's 200 or 600 cycles a . So these are ultra ultra fast |
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| 12:00 | . Why would you have such a of these dominant rhythm frequencies? And |
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| 12:05 | there a system in which we can all of these different dominant frequencies? |
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| 12:11 | do these different rhythms come about? from the very beginning in this |
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| 12:17 | we talked about how different neuronal subtypes slightly different dialect. And what we |
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| 12:25 | that dialect as is the frequencies and patterns and the numbers of the action |
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| 12:32 | that are being produced by different subtypes neurons in the hippocampus alone, we |
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| 12:38 | a great variety of the inhibitor into in cortex, the same way that |
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| 12:43 | capable of producing different firing or action patterns at different speeds, representing their |
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| 12:51 | individual dialect. So a variety of cell subtypes would be contributing to having |
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| 13:00 | variety of these uh network rhythms, and neuro modulators. So, we |
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| 13:10 | about chemical neurotransmitters and we talked about some of them like Gaba and glutamate |
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| 13:15 | have a fast effect on neurotransmission depo polarization. But then we talked about |
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| 13:22 | modulators and we said how neuromodulator will a longer lasting effect but it may |
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| 13:29 | slower. Therefore, a variety of of these chemical interactions and communications within |
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| 13:35 | specific neuronal circuits will also contribute to of these different rhythms, external |
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| 13:43 | which is the stimuli that we are . And the perfect example is hearing |
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| 13:51 | we discussed recently where you have oscillation the air molecules, which translates into |
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| 13:58 | oscillation of the fluids in the inner , which translates into mechanical movement and |
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| 14:06 | of the uh potassium channels and the cells and those hair cells producing oscillations |
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| 14:15 | are representative of the mechanical oscillations. their oscillations are in the form of |
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| 14:21 | depolarizations and hyper polarization. OK. you have a variety of different |
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| 14:30 | the stimuli and train our different sensory , visual auditory and so on. |
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| 14:38 | we have to have brain activity to certain rhythmic activity that is dominant around |
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| 14:45 | . Why would you need to have many oscillatory regimes, so many different |
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| 14:50 | , multiple tasks, some tasks are , some tasks are fast. Sometimes |
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| 14:55 | cells have to be fast. Sometimes have to take care of slow metabolic |
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| 15:00 | . If you have really fast cells can synchronize in a very fast |
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| 15:04 | for example, using the gap so they can perform very precise and |
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| 15:10 | uh collective uh synchronized activity in the . And of course, by having |
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| 15:18 | variety of these different neuronal setbacks by having a variety of these dominant |
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| 15:26 | in our brain. This is what for our ability to have distinct levels |
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| 15:32 | distinct complexities of computation and different neuronal from the primary secondary all the way |
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| 15:39 | the association areas. Now, uh Buja at some point has placed these |
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| 15:47 | rhythms here on their natural uh log here in frequencies and these dominant |
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| 15:55 | delta theta beta gamma fast, ultra . They, they were uh separated |
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| 16:02 | by a whole full integer on this M Hertz scale. Here, the |
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| 16:07 | scale here is frequency and this is classes or descriptions of these different their |
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| 16:12 | of these different rhythms. OK. here's an example of a happy student |
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| 16:18 | with an E E G cap eyes . You can see alpha waves I |
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| 16:24 | the E E G recordings from these change into a different beta wave rhythm |
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| 16:30 | it's not as synchronized. Therefore, not as pronounced on the E E |
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| 16:34 | recordings and the student close his eyes and again, the brain areas where |
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| 16:41 | recordings are done are dominated by the waves. This is just enlarged image |
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| 16:47 | what I was explaining earlier can feel to uh read on your own about |
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| 16:55 | these recordings would be done for the cases for surgical resections or brain surgeries |
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| 17:01 | general. Mhm And epileptic oscillations. talk now about epilepsy. For some |
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| 17:12 | , this image is getting a little cut off. So maybe I'll exit |
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| 17:15 | of this uh presentation so that we have a full image uh view. |
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| 17:22 | . So why are we talking about when we're talking about rhythmic activity? |
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| 17:30 | epilepsy in general is diagnosed quite often using E E G S. Epilepsy |
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| 17:39 | abnormal synchronization of neuronal networks. And abnormal synchronization can be picked up using |
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| 17:47 | E G recordings and epilepsy or epilepsies there's so many different subtypes of epilepsies |
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| 17:56 | general uh are rhythmic brain disorders And when these rhythms become abnormal and |
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| 18:06 | there is abnormal synchrony in the it can start over exciting the |
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| 18:13 | driving the cells to accumulate a lot calcium, uh driving the sauce to |
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| 18:21 | a lot of glutamate, driving glia release a lot of glutamate, thereby |
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| 18:28 | what is known as glutamate excitotoxic and excitotoxic which both lead to apoptosis or |
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| 18:40 | cell death. And this abnormal repeated activity is an abnormal synchrony can be |
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| 18:48 | as sort of a electrical short circuits the brain, therefore, eventually burning |
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| 18:55 | and destroying the regions of the brain seizures are generated. And these E |
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| 19:01 | G caps, a lot of times be placed with the electrodes located in |
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| 19:06 | parts of the scalp. Here picking activity from different parts of the brain |
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| 19:12 | determine where the focus or the origin that seizure is. And as you |
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| 19:20 | see here in a, the person sitting and she has a cap tied |
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| 19:23 | her head. And indeed, this experiences quite often before a person has |
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| 19:31 | pronounced seizure event, they would experience of something about to happen. Sometimes |
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| 19:38 | a really bad feeling. Some people a euphoric very happy feeling of |
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| 19:44 | And even during this period of or can already see that electrodes 12, |
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| 19:52 | through 16 are starting to show what would define as abnormal synchronized electric |
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| 20:01 | OK. And then, and see person is having a full blown |
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| 20:07 | And now you can see at point that this E E electrical activity which |
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| 20:12 | be started in these regions here. through 16. 1st, as this |
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| 20:18 | synchrony and abnormal activity spread as a wave across all of the electrodes in |
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| 20:26 | brain and created what is called a seizure, which basically is abnormal synchrony |
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| 20:32 | abnormal activity, electrical activity throughout the cortex. And uh subcortical areas as |
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| 20:40 | . Hippocampus, a structure that we well that we studied while is highly |
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| 20:45 | to seizures is highly susceptible to And it can neuro degenerate if seizures |
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| 20:52 | in the temporal lobe area or in limbic structures like the hippocampus, hippocampus |
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| 20:59 | also be damaged with other neurodegenerative And it would also be damaged in |
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| 21:06 | , but uh it is highly susceptible damage and epilepsy as well. |
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| 21:12 | So this is a reminder how you the cells from Ramon Coal's drawings that |
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| 21:19 | placed in certain locations within the cortex certain connectivity. There are different sub |
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| 21:24 | that speak all of these different dialects the ability of the inhibitor and excitatory |
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| 21:31 | to exchange these patterns and frequencies of potentials is what allows for these diverse |
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| 21:39 | behaviors of individual cells and the synchronization diverse electrical behaviors of neuronal networks and |
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| 21:49 | of the brain in general. So when you're recording, uh this |
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| 21:56 | a recording uh example where you would these E G electrodes and you would |
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| 22:01 | exactly the areas where they would play play. So you can see this |
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| 22:05 | occipital lobe. OK. This is , frontal. OK. We have |
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| 22:11 | three, temporal five. So this covering over temporal lobe. So you |
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| 22:15 | the location and now you can identify origin of abnormal activity in the brain |
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| 22:21 | how it spreads, spreads throughout the networks. So what in reality is |
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| 22:29 | E G picking up this activity E G in reality is picking up activity |
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| 22:35 | from the surface of the cortex and really activity from these excited to parameter |
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| 22:42 | . And when they're very active, electrically active, they also generate magnetic |
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| 22:48 | . And that information from the of parameter cells can be picked up by |
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| 22:55 | E E G electrodes that are placed the scalp. They go through the |
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| 23:03 | E G amplifier that will amplify that and allow us to detect these different |
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| 23:12 | and abnormal rhythms in the brain as . But imagine this. So this |
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| 23:17 | the electrode that's sitting on the So that means the signal electrical signal |
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| 23:22 | is synchronized. We have to synchronize and thousands of cells for this electrode |
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| 23:26 | pick up the activity here. So from a single cell is not gonna |
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| 23:30 | anything for this E E G But then when you have the synchronization |
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| 23:35 | activity of these thousands of cells that activity in these mag electromagnetic fields have |
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| 23:43 | cross through P subarachnoid dura Aloma skull . Essentially all of this acts as |
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| 23:53 | low pass filter and filters out a of the activity that gets picked up |
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| 24:00 | the level of the G at the of the scalp. So that's why |
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| 24:06 | preoperatively would wanna do these intracranial recordings the surface of the brain because they |
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| 24:11 | be more precise in detecting normal or activity. This is exactly what I'm |
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| 24:18 | about. So, if you have E E G recording and you have |
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| 24:22 | activity amongst these six cells, and can imagine that there's six cells that |
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| 24:28 | involved here in reality will be the or thousands of cells involved, let's |
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| 24:32 | 600 cells involved in this, but getting a different input, this inputs |
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| 24:38 | in and it's uh exciting them at times. And each one of |
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| 24:42 | 12 through six seem to have their distinct pattern of depolarization and hyper polarization |
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| 24:49 | activity. And therefore, in some E G picks up what you would |
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| 24:54 | this some signal, which would be irregular signal. There, there is |
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| 24:58 | a distinct or dominant rhythm. One argue that would be picked up. |
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| 25:03 | once these cells, they could be a common input. But once these |
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| 25:09 | and if they get activated at the time, so there's a very strong |
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| 25:15 | coming in and 123456 is gonna be depo about the same time. And |
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| 25:20 | synchronization across this network of cells now be picked up on the sun E |
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| 25:26 | G recording as something that is meaningful relevant rather than something that is just |
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| 25:31 | background noise or background irregular activity that have a dominant frequency rhythm to |
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| 25:40 | OK. Now, neurons in those foci or in those the locations that |
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| 25:48 | seizures have characteristic behaviors. Those character behaviors is that they produce intracellular spiking |
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| 25:58 | and interictal spiking activity. So a of cells would synchronize and they would |
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| 26:05 | these what are called spiking and bursting that are referred to as peral depolarizing |
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| 26:13 | that typically last 50 to 200 they have very large 20 to 44 |
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| 26:19 | N S neurons depolarizations with a number burst of action potentials riding on top |
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| 26:26 | this depolarization. So this repetitive synchronized . Typically, the bursts represent repetitive |
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| 26:36 | activity. It comes about because of intrinsic neuronal membrane properties, such as |
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| 26:47 | subtypes of voltage gated sodium potassium and channels itself express as well as their |
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| 26:57 | connectivity and synoptic signaling Cytra versus inhibitor so on and so forth. |
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| 27:04 | in epilepsy, you have enhanced There is too much or enhanced signaling |
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| 27:10 | glutamate glutamate signals glutamatergic system. Ample A too much of glutamate release. |
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| 27:19 | could be impairments also in Gaba B which uh could be lacking hyper |
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| 27:27 | Other channels, calcium dependent potassium channels also involved. Glia may play a |
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| 27:39 | roll here because glia if you recall buffering and spatially distributing abnormal rises and |
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| 27:50 | concentrations such as potassium, they're also in neurotransmitter reuptake. In particular glutamate |
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| 27:59 | and glutamate cycling, they produce calcium and they, they, they may |
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| 28:07 | other uh things like glycine that serves an MD A co factor. Uh |
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| 28:15 | gli again, is very likely very involved in these epileptic processes. If |
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| 28:22 | have epilepsy or epilepsy is defined if having repetitive seizures. But these are |
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| 28:29 | cellular mechanisms of the cellular substrates of activity. These synchronized bursts, Baros |
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| 28:36 | polarizing shifts that represent synchronized activity, increase in excitation, a decrease in |
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| 28:44 | and abnormal glial signaling epilepsy. In incidents of epilepsy cases for 100,000 on |
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| 28:59 | Y axis and age in years. here on the X axis, |
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| 29:06 | epilepsy affects 1 to 2% of the . It's most prevalent in early |
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| 29:14 | And again, it has this U curve where it becomes more pronounced. |
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| 29:20 | epilepsy is more incidences of epilepsy and elderly people seems to be rising again |
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| 29:28 | the age of about 55 or Now, epilepsy is more common in |
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| 29:35 | countries. Um uh epilepsy is very because there could be untreated childhood |
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| 29:47 | infections or pre and post natal Uh And because it occurs most often |
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| 29:55 | , in young Children, it's it's critical now to have all of this |
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| 30:00 | post natal care and early childhood care well as elderly care where a lot |
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| 30:07 | 2nd and 3rd world countries do not the systems cannot afford or the elderly |
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| 30:12 | afford to be a part of the homes and such to take care of |
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| 30:18 | , which can then be where elderly go and shack them develop certain diseases |
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| 30:25 | epilepsy. Childhood epilepsy is usually It's caused by genes or disease or |
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| 30:33 | that is present at birth. Elderly to acquire epilepsy as a consequence of |
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| 30:41 | and other disorders of conditions such as tumors or even Alzheimer's disease. So |
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| 30:49 | with Alzheimer's disease are way more prone have epilepsy or seizures. And in |
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| 30:55 | case, epilepsy becomes a comorbidity. disease is already killing a person and |
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| 31:02 | now contributes to co killing that person as a comorbidity to potentially depriving this |
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| 31:10 | of their uh future years of Epilepsy is more a symptom of a |
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| 31:17 | than the disease itself. Uh Seizures really a symptom of the disease. |
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| 31:23 | are many different types of epilepsies. can be caused by tumors in particular |
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| 31:30 | , reactive gliosis, tissue scar formation to tissue blood vessels. So, |
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| 31:36 | glial networks, trauma to the brain components, metabolic dysfunctions, infections, |
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| 31:45 | disease, environmental and in many cases of epilepsy is unknown. So there |
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| 31:54 | many different types of epilepsies. The different causes of epilepsies from infection to |
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| 32:01 | to to genetic dysfunction and in many , it's unknown, but let's talk |
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| 32:09 | this. There are several mutations, ? There's several mutations that are famous |
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| 32:18 | causing epilepsy in childhood epilepsy in So here what is highlighted is mutated |
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| 32:28 | channels. You can also have mutations potassium channels. You can also have |
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| 32:33 | in calcium channels. But in this case, remember we talked about these |
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| 32:38 | gated sodium channels early on in the while these voltage gated sodium channels, |
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| 32:45 | is the remember they have four Each subunit has six transmembrane segments. |
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| 32:55 | 123456 S four is a voltage sensor S five and S six. You |
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| 33:02 | the four loop which is the selectivity area of this voltage gated sodium |
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| 33:09 | And what are all of these different . So everywhere where you see a |
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| 33:14 | dot that means that a mutation in gene that goes for this channel and |
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| 33:21 | mutation that would be represented in this in this particular location or that particular |
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| 33:26 | in multiple locations on this voltage gated channel can lead in green to gaps |
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| 33:34 | stands for generalized epilepsy with febrile seizures generalized epilepsy, febrile seizures plus. |
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| 33:45 | if mutations on that same gene that the same voltage gated sodium channel occurs |
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| 33:52 | the areas where there are amino acid corresponding to these red dots. |
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| 33:59 | multiple red dots. A person is to develop a different subtype of |
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| 34:07 | It's also a very severe subtype of , developmental congenital genetic form of |
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| 34:13 | Again called severe mylo epilepsy of infancy sme I severe chronic epilepsy of |
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| 34:24 | otherwise known as drive A syndrome. you can have this is sodium channel |
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| 34:32 | sodium channel. And you can see if fortunately, a person has a |
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| 34:38 | in the gene that codes for these channels. And there is uh mutations |
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| 34:46 | these amino acid sequences in green or . It could lead to these two |
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| 34:51 | severe forms of epilepsy, generalized febrile seizures, febrile seizures are actually |
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| 34:58 | most common type of seizures that occurs many little babies. That's why it's |
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| 35:04 | if somebody's temperature goes up, uh child's temperature goes up about 100 and |
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| 35:10 | F to place them and even ice bath to cool them off. Uh |
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| 35:19 | febrile seizures are hyperthermia induced seizures. means when the body temperature goes up |
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| 35:26 | fever with infections. Uh A child experience febrile seizures and if a child |
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| 35:32 | one seizure due to an infection and has a seizure again, they're not |
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| 35:37 | . But the Children that are born these mutations here, they experience generalized |
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| 35:44 | with feb seizures or severe Marchionni epilepsy infancy. And in both instances, |
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| 35:51 | very sensitive to internal temperature rises. these Children, if they have just |
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| 35:56 | small fever or 100 F 101 they start having a seizure. So it |
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| 36:04 | them very susceptible to hypothermia. This mutation and voltage gated sodium channels, |
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| 36:11 | are found in in the neurons into and exci cells as well. So |
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| 36:17 | is an image of some of these . Unfortunately, some of them passed |
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| 36:23 | or severe myronic epilepsy of infancy sme is a catastrophic form of epilepsy. |
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| 36:31 | 30% or about 30% of the Children respond to the existing pharmaceutical treatments and |
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| 36:39 | medications. Uh, about 20% of Children die from what is called severe |
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| 36:49 | or unexpected death and epilepsy, PSE unexplained death and epilepsy which typically happens |
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| 36:57 | night. And that's why these severe of epilepsies that are very hard to |
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| 37:03 | . Also referred to as intractable forms epilepsy because uh intractable, the patient |
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| 37:09 | respond to pharmaceutical drug treatments and cocktails these treatments. It's catastrophic if the |
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| 37:17 | dies and it's catastrophic for the whole . And these kids have a mutation |
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| 37:24 | voltage gated sodium channel. Uh One these mutations that we're talking about that |
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| 37:30 | in red here that will cause severe epilepsy of infancy. Now, these |
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| 37:39 | are quite often given cocktails of drugs they're given cocktails of of many |
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| 37:46 | And this is an image of a that is testifying in front of the |
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| 37:53 | showing them what type of cocktails of and the amount of drugs some of |
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| 37:58 | Children have to take in order to seizures and he had over 30% of |
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| 38:05 | seizures would not be controlled by all these medications. Think about that. |
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| 38:12 | we talked about different kind of a pharmacological and medication like approaches in this |
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| 38:22 | already. But how difficult it might on that child to metabolize to process |
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| 38:31 | different pills a day. What uh it may have on their liver, |
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| 38:37 | effect it may have on their what side effects it may have on |
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| 38:41 | digestive system and all of these And so this is where we start |
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| 38:47 | discussion about medical phenomenons and medical calendars . And Charlotte Figgy pictured here was |
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| 38:56 | girl and fortunately she passed last but Charlotte Figgy was a girl was |
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| 39:03 | of the syndrome kids that were not to all of the pharmaceutical medication. |
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| 39:09 | had quite conservative parents that were uh military both but they heard about medical |
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| 39:19 | and they moved their family to Colorado Charlotte Figgy worked with neurologist Edward Ma |
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| 39:29 | neurologist uh gave her T H C , which is one of the phyto |
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| 39:37 | and cannabis plants and CBD or And the Charlotte seizure frequency from nearly |
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| 39:48 | convulsive seizures per day, went to to 3 nocturnal convulsions per month. |
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| 39:57 | is a huge, huge difference. this child in drive A syndrome was |
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| 40:03 | to phyto Komal treatment. You see CBD over the cocktails of previously supplied |
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| 40:10 | . And in fact, they, , they slowly weaned her off or |
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| 40:15 | her off the pharmaceutical medications. most of the epilepsy drugs remember Gabba |
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| 40:21 | receptor channel, it increases inhibition, promotes chloride flux. It has a |
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| 40:31 | side for Gaba, it has a side if you recall for diazePAM and |
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| 40:37 | lot of anti seizure drugs will be to Gaba receptors. And if you |
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| 40:43 | Gaba receptor also has a binding side ethanol alcohol. And so when Children |
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| 40:51 | these pharmacological preparations, the target Gaba like diazePAM, for example, or |
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| 40:59 | the side effect, one of the is that they feel as if they |
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| 41:04 | intoxicated, drunk, like state and act almost like drunk, uh |
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| 41:12 | losing the gate and ability to, control their motor functions. So this |
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| 41:20 | a very successful case. Unfortunately, I said, Charlotte piggy has |
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| 41:26 | but she started something that uh allowed many United States States and also countries |
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| 41:35 | the world to start looking at cannabis cannabinoids from maybe a more positive and |
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| 41:43 | medicinal uh perspective. And there were number of articles since 2014 that uh |
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| 41:52 | and corroborated that indeed uh cannabinoids in cannabidiol or CBD is very helpful for |
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| 42:01 | treatment of seizures and epilepsy. And in this course, we'll also talk |
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| 42:06 | then the cannabinoid system and pharmaceutical drugs CBD is a uh is an approved |
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| 42:13 | preparation for treatment of seizures in particular syndrome and uh or severe myronic epilepsy |
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| 42:21 | infancy. Now, the United States which is only now uh allowing sort |
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| 42:30 | uh for the United States individual states decide their pathway for the use of |
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| 42:40 | or medical cannabis in their different programs in the State of Texas um United |
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| 42:46 | government, the United States of America of Health and Human Services has this |
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| 42:53 | pattern published since 2003 that says that act as antioxidants and neuroprotectant. So |
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| 43:02 | is not just a myth and all these, you know, probably what |
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| 43:08 | states or 40 states now um uh to say hundreds of millions of patients |
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| 43:16 | medical programs, not recreational, adult use, cannabis are seeing benefits |
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| 43:24 | cannabinoids. And so we will talk the next couple of lectures about what |
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| 43:29 | be developed as a future neuropharmacology treatments on the basis of cannabinoids, for |
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| 43:36 | . But this is an interesting view have uh because while the government had |
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| 43:42 | patent on antioxidants and neuroprotectant cannabinoids. here, Alzheimer's disease, Parkinson's disease |
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| 43:50 | dementia um in a positive way, also is on a federal level. |
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| 43:57 | as a criminalized substance, cannabis in , and it's only on a state |
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| 44:03 | but it is allowed. And there's you know, some questionable issues about |
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| 44:09 | uh whether cannabis is all positive it also has some negative effects. |
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| 44:14 | for some people in certain conditions, cannabinoids like T H C are not |
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| 44:21 | , especially in the cases of the negative effects of cannabinoids and cannabis |
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| 44:26 | well. And the point is that really need to start understanding what these |
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| 44:31 | combinations of T H C and different preparations, different methods of |
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| 44:37 | taking it as a pill versus inhalation it into the lungs, how all |
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| 44:43 | these different combinations of cannabinoids can treat specific diseases. And I think this |
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| 44:49 | gonna be a question that gets slowly over the next 23 decades. And |
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| 44:53 | going to be very exciting as the industries again and going to draw on |
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| 45:00 | natural molecules, natural compounds and hopefully these phyto compounds in the final preparations |
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| 45:07 | uh uh as final treatment products for . So if you want to learn |
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| 45:14 | over the weekend, um you can watch a series that was produced by |
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| 45:22 | Gupta. He's a chief medical correspondent CNN, but he's an interesting guy |
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| 45:29 | in cannabis is, is not a issue. It's really a bipartisan |
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| 45:34 | I think it's a health regulation, issue of anything and criminal uh activity |
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| 45:40 | as well. Now Sanjay Gupta actually not believe in medical cannabis. So |
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| 45:46 | story is quite interesting because he came this like everybody else. Oh, |
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| 45:50 | heard somebody said anecdotally. Oh, heard it, it helps, you |
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| 45:55 | , but you know this guy the president of the United States, |
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| 45:59 | said, so I inhaled, I it. Um Montel Jordan here got |
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| 46:04 | off is really famous for using it his condition. He has multiple sclerosis |
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| 46:09 | Sanjay Gupta uh met all of these people and changed his mind on the |
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| 46:18 | benefits of cannabis, not just medical cannabinoids, but cannabis in general and |
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| 46:26 | up with this series called Weed Weed , I think it's all up to |
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| 46:31 | now, if I'm not mistaken. it's something uh interesting to watch over |
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| 46:35 | weekend if you fancy. Ok. this uh as I mentioned is gonna |
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| 46:41 | a little bit shorter lecture. We'll back and talk about some of the |
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| 46:45 | preparations from cannabinoids and the cannabinoid system the treatment of uh epilepsy in that |
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| 46:51 | as well and other neurological disorders because interesting that cannabinoids are typically targeted for |
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| 46:58 | nausea, uh weight, uh uh control, weight, uh wasting control |
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| 47:07 | uh neurodegenerative or neurological disorders prevalent. And not surprising because you will learn |
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| 47:15 | cannabinoid receptors. C B two are most abundant G protein coupled receptor in |
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| 47:20 | brain. OK. So this will our lecture. Thank you very much |
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| 47:25 | joining me with a short notice on zoom. This is very helpful for |
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| 47:30 | . You can do that today. will see everyone in class live next |
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| 47:37 | . We'll be ending the scores fairly . Good luck tomorrow on the quiz |
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| 47:43 | I will see everyone back on Thank you everyone and have a good |
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