Overview of CNS Inflammatory Diseases

00:01 So let's walk through some of the types of CNS inflammatory conditions we can see the monophasic illnesses, the recurrent illnesses.

00:09 And let's think a little bit more about the predominant cell type that's involved and the typical conditions that we see.

00:16 Let's start with monophasic conditions.

00:19 These are our clinically isolated syndromes.

00:22 Patients present with a single attack, subacute onset of neurologic deficits that peaks over the course of a couple of weeks and then returns typically back to normal.

00:31 We call these the clinically isolated syndrome because there is a isolated syndrome that doesn't recur.

00:37 This syndrome can be categorized based on the area of the nervous system that's involved.

00:43 So clinically isolated optic neuritis is an optic neuritis that occurs with one attack.

00:48 The patients develop new vision changes or vision loss often with red or color desaturation and pain with eye movements.

00:55 Those are the classic symptoms of an optic neuritis.

00:58 We may do an MRI and see enhancement of the optic nerve or an LP and see inflammation within the nervous system.

01:04 Because again, the optic nerves are an extension of the brain and they're connected to that same spinal fluid space.

01:10 In clinically isolated optic neuritis, there's one event it's a monophasic illness.

01:14 We worry in a patient's first presentation that they could develop new events and watch closely for those and look for signs of evidence of possible or recurrence or risk of recurrence.

01:26 When the brainstem is affected is a clinically isolated brainstem syndrome.

01:31 When the spinal cord is affected is a clinically isolated transverse myelitis.

01:36 And when there are no symptoms and we see it just with imaging, that is coined radiographic isolated syndrome.

01:45 Those are the clinically isolated syndromes where there is a single area of brain that is involved and not a diffuse or multifocal area that's involved.

01:53 We can also see monophasic inflammatory disorders where there's dissemination of symptoms over nearly the entire neuro axis or central nervous system.

02:03 The most common of those is the acute demyelinating encephalomyelitis, which is called ADEM.

02:09 This is a diffuse multifocal process that involves the brain and the spinal cord.

02:14 That's why it's an encephalomyelitis.

02:17 It's an inflammatory disorder.

02:18 That's why the name ends with itis.

02:20 There's inflammation in the nervous system.

02:23 And there's demyelination.

02:24 We see demyelination on MRI and spinal cord.

02:28 MRI of the spine and MRI of the spinal cord.

02:31 We see increased protein with the spinal fluid and with an LP.

02:35 And those are all suggestive of an underlying autoimmune condition and demyelination.

02:40 It's follows a monophasic course with sub acute onset, peaking in several weeks, and then often improving back to normal and rarely recurs, but can and in various rare exceptions.

02:52 And then there's a second condition called Acute hemorrhagic leukoencephalitis or Hurst encephalitis, which is just a hyperacute and fulminant form of ADEM.

03:00 And again, these are where there's an attack all over the central nervous system one time as a monophasic course.

03:09 Those monophasic conditions are different from the recurrent conditions.

03:14 And we can categorize recurrent inflammation in the nervous system based on the predominant cell type that's involved.

03:21 There are recurrent T cell predominant syndromes, and this is where there's recurrent episodes of relapses and remissions.

03:29 And the predominant cell type that's involved that we see is a T cell process.

03:33 Now when the immune system is activated, there's always some degree of T cells and B cells and a lot of other things in between.

03:40 But the primary cell type that's mediating this problem are T cells.

03:44 The classic example of this is multiple sclerosis.

03:47 And there are a number of types or categories of multiple sclerosis that we can see.

03:52 We can see relapsing remitting MS, which is depicted on the schematic on the left.

03:56 We can see relapsing progressive MS, where there's not returned to baseline.

04:01 Patients develop persistent fixed deficits during their remissions.

04:06 We can see secondarily progressive MS, which you see in the depiction on the right, where patients have a period of relapses followed by progression over time.

04:14 And that's where this inflammatory disorder is taking on a degenerative flavor.

04:21 And Primary Progressive MS doesn't start with relapses and remissions at all it just progresses steadily over time.

04:29 MS is driven by a T cell activation, and it is our produce a prototypical T cell predominant recurrent CNS autoimmune condition.

04:41 What about recurrent B cell predominant disorders? And again, these are primary CNS neuroinflammatory disorders where the problem is really with the B cells.

04:49 B cells have to be turned on by T cells and they do interact with the T cells but we can measure the antibodies and that's what gives these conditions their name and diagnostic testing.

05:00 There are two classic examples.

05:01 One, is NMO or neuromyelitis optica.

05:05 And the second is MOG antibody disorder.

05:08 We think about those and some of the typical diseases are NMO or Devic's disease, which is another name for that condition.

05:15 There is NMO spectrum disorders, which are some of the secondary CNS autoimmune conditions that we'll talk about, in MOG antibody disorder.

05:23 And these should be the three things you think about when we're thinking about recurrent B cell predominant, CNS autoimmune conditions.

05:31 And then there's also another or also other CNS neuroinflammatory disorders that don't fall strictly in those other categories.

05:38 There are some macrophage mediated, macrophage predominant conditions like neurosarcoidosis Erdheim-Chester, Histocytosis, and Rosai-Dorfman disease.

05:48 Here, macrophages are activated.

05:50 There's also T and B cells that are a part of that process, but the primary immune mediator that infiltrates into the brain are the macrophages.

05:58 We can also see some T cell variants or variants of multiple sclerosis, There's a Marburg, Schider's, Balo's concentric sclerosis variant, chronic myelopathy, and progressive ataxia that can also be observed.

06:11 And then some other conditions that are CNS autoimmune condition, Neuro-Behcet's, and connective tissue disease associated CNS-autoimmunity.

06:19 We can see some mixed polyclonal B/T cell.

06:22 This disease is an example. There is Castleman's disease and primarily B cell mediated disorders, like a plasma cell granuloma would also be a consideration.

06:31 And these are significantly less common than the other disorders that we discussed.

06:35 And I really encourage you to focus on things like MS, NMO, and MOG antibody disease as well as the clinically isolated syndromes.