[MUSIC] [COUGH] So, why are we talking about multiple sclerosis or MS, and epilepsy, and traumatic brain injury? [COUGH] Well, the reason we're talking about MS is that it is one of the first conditions or indications that was targeted by GW Pharma in the marketing and development of Sativex, which is a one-to-one plant-derived preparation of THC and CBD. So equal amounts of THC in CBD. And so, a lot of cleaner pieces of evidence, the phase three clinical trials of a cannabis preparation, those were done with Sativex and MS. So that's where a lot of our knowledge comes from. So a logical place to start this lecture on brain disorders is with MS. [COUGH] So then with epilepsy, we're going to talk about epilepsy because while Sativex was approved in Europe for the indication of MS pain and MS spasticity, here in the US, Epidiolex, which is a purified form of CBD derived from plants, was recently approved for epilepsy. So again, a clear indication from a governmental authority that a cannabinoid is effective for a given disorder. And finally, we'll talk about TBI, or traumatic brain injury. [COUGH] And for this disorder ,there isn't as much evidence, but it's a serious injury with chronic implications, and very important especially for veteran groups and active military people. And, though it has not been studied as much in terms of cannabis, I think we're going to see a very significant interest in the development of research in this area. Okay, so, what is MS? MS is multiple sclerosis. It involves an abnormal immune system response which basically leads to attacking the central nervous system. Specifically involves the damage to nerve fibers and even more predominately the myelin that surrounds those nerve fibers. [COUGH] And as inflammation occurs and damage occurs along these fibers and on the myelin, basically, you start to see effects on the central nervous system, negative effects and symptoms. And so this damage produces neurological effects that vary widely from person to person. People with MS typically experience of four disease courses, different types of MS. And, it's also worth noting, there are over a dozen treatments to help modify the disease process, to slow it down, for example, and/or for symptomatic relief. We'll talk more about those in one of the lectures. And this is just a graphic showing you the for the normal nerve and then, the nerve affected by MS. You can see the this outer layer of myelin is damaged and exposes the nerve fiber which also can be damaged. And that's the predominant mechanism that underlies the negative CNS effects of MS. So what are the effects, what are the signs and symptoms of MS? Symptoms often involve problems with movement. So numbness or weakness in one or more limbs, the sensation of electric shock that can occur, certain neck movements, tremor, lack of coordination and steady gait. Vision problems, so partial or complete loss of vision, usually in one eye at a time. And oftentimes with pain during eye movement or double vision or blurry vision. Some other symptoms might include things like slurred speech, fatigue, dizziness. Tingling or pain in parts of the body, and problems with sexual, bowel and bladder function. And importantly, it also involves pain and muscle spasms and spasticity, and problems with sleep are also common. And we'll talk more about this too, because as you've seen with other disorders, in terms symptomatic relief from cannabis, these are some of the key targets. Okay, so, [COUGH] what's the clinical course of MS? Most people with MS have intermittent relapse and then long periods of remission. Sometimes long, sometimes not so long. About 60 to 70% of people with relapsing-remitting MS eventually develop a steady progression of symptoms. And, that can occur with or without periods of remission. This is known as secondary-progressive MS. The worsening of symptoms usually include problems with mobility and gait and which amass over time. And the rate of disease progression can vary considerably from one person to another. And with people with secondary progressive MS. Some people with MS experience a gradual onset. And, slow, steady progression of signs and symptoms without any relapses and that's known as primary progressive MS. Okay, so that's kind of the rundown on MS, but what about epilepsy, what is epilepsy? Epilepsy is a central nervous system, neurological disorder in which brain activity becomes abnormal and leads to seizures. Now seizures can vary widely, some people with epilepsy maybe involved staring blankly for a few seconds during a seizure, others might involve twitching in arms and legs. [COUGH] And it is important to note to having a single seizure doesn't initially mean someone has epilepsy. It's also important to note that epilepsy is not one condition. So, epilepsy refers to a variety of different disorders that have some commonalities. And one of those commonalities is that there's an underlying brain dysfunction. And, that brain dysfunction, though, can result from many different causes. Another important point is that not all seizures are epileptic seizures. An epileptic seizure has a clear start and a clear finish. And, [COUGH] a clinical manifestation that might involve a sensory, motor, and autonomic function, a change in consciousness, change in emotional state, memory cognition or behavior. Epileptic seizures have abnormal enhanced synchrony of neuronal activity. So what are some symptoms of epilepsy? Well, as we mentioned, it's caused by abnormal activity in the brain. And so obviously, it can affect any kind of a process that the brain coordinates. So some signs and symptoms may involve things like temporary confusion, I mentioned staring already. Uncontrollable movement in arms and legs, loss of consciousness or awareness. And, some psychiatric symptoms like fear, anxiety or deja vu. And, some of those can vary depending on the type of seizure. But, a person with epilepsy will tend to have the same type of seizure each time. Symptoms also are typically similar from episode to episode. So different types of epilepsy, there's hundreds of different types of epilepsy. Some common ones, Dravet Syndrome, is the result of a rare genetic dysfunction of the brain. It typically begins in the first year of life in an otherwise healthy infant, and then is a lifelong disorder. Frontal lobe epilepsy produces brief seizures, start in the frontal lobes. It's the second most common type of focal epilepsy and tends to run in the families. Temporal lobe epilepsy is the most common type of focal epilepsy. And in this type, there's a high risk for memory and mood difficulties. [COUGH] This type usually begins at the end of a first or second decade of life. So that's the summary of epilepsy, let's talk about traumatic brain injury, or TBI, for a second. TBI is defined as an alteration of brain function that manifest as confusion or altered level of consciousness, or involve seizure or coma, or focal sensory or motor neurologic deficits. And these are basically a TBI result from a blunt or penetrating force to the head. In mild TBI, there are subtle behavioral and neuropsychological change that may be the only symptoms, right? So for mild, maybe these are minimal symptoms. And TBI in general has considerable morbidity, mortality, and also itself is a major cause of epilepsy. So this graphic shows you some of the major types or types of traumatic brain injury. And so what you see here is a direct impact injury, where there's a blunt impact on the skull, causing injury to the brain. This is an example of an acceleration-deceleration injury. And finally, this shows you a shock wave injury. And so, the typical thing for the acceleration-deceleration is a car accident where the head is accelerated and decelerated very quickly. For the shock wave injury is typically an explosion. And obviously, this is particularly relevant to veterans who may have experienced an explosion from an IED that caused a shock wave injury to the brain. Of course, also the same veterans may have suffered from direct impact or penetrating injuries as well. Okay, so symptoms of mild TBI, we sort of talked about this for a minute already, but this is an expanded list of symptoms. And, including things like nausea or vomiting, fatigue and drowsiness, problems with speech, difficulty sleeping. And some sensory problems as well as some cognitive or mental symptoms. [COUGH] When we get into more moderate to severe TBI, we're talking about things like a loss of consciousness from several minutes to hours. Typically, involves persistent headache and/or headaches that worsen, and vomiting, and nausea, seizures dilation of the pupils of the eyes, clear fluids draining from the nose or ears, inability to awaken from sleep. So clearly, this is definitely moving up in terms of the severity of TBI. And then on the cognitive and mental side, profound confusion, agitation, slurred speech, etc. So, another important point of TBI is that it often involves chronic pain and sleep disturbance. So, when you look at individuals with TBI, what you find is that about 50 to 70% of them also report chronic pain. The typical types of chronic pain reported by individuals with TBI, headaches or the probably the most common type of chronic pain, which makes sense obviously, but then followed by neck, shoulders back and upper limb pain. Also, as we've noted a couple of times in this course, veterans typically have comorbid. It's quite common to have TBI as well as chronic pain, co-occur with PTSD and depression. So that's kind of a typical mix that we see in the veteran population. And on sleep, it's important to note that sleep disturbance is also common in TBI patients. So, about 50% report insomnia or poor sleep, in also about 50%. And also a fair number report delayed sleep onset. So some conclusions, starting off this first part of brain disorders. MS is a chronic disease. State that most damage to the protective layer of the nerve fibers also involves pain and muscle spasticity. Epilespy is a term that refers to a variety of disorders with different causes that result in brain dysfunction and seizures. And traumatic brain injury or TBI is common, especially among veterans, and often involves comorbid chronic pain, as well as sleep disturbance.
