Clinically Isolated Syndrome: Diagnostics and Treatment

00:01 So when we think about clinically isolated syndromes and patients presenting with any of those constellation of symptoms, what's the workup? What is our diagnostic approach? Well, here the goal is to stratify the risk of presenting with another attack or looking for a prior attack.

00:17 Clinically isolated syndrome is one attack.

00:20 If there have been prior episodes of autoimmune attack on the brain, spinal cord or optic nerve, or risk of future attacks, we start to worry about a recurrent syndrome MS, NMO, anti-MOG disease And so our workup is to look at other areas of the neuro axis to look for prior episodes or the potential for future attacks.

00:39 We can do that with MRI of the brain, MRI of the spine, evoked potentials.

00:44 Typically visual evoked potentials of somatosensory evoked potentials can also be performed and lumbar puncture.

00:50 And in the lumbar puncture, we're looking for signs of CNS and CSF inflammatory changes.

00:59 First, let's talk about typical MRI findings that we can see in these patients.

01:03 50 to 80% of patients will have findings on their MRI at the time of their initial clinically isolated syndrome.

01:10 And so these patients, we begin to be more concerned about the risk of a recurrent syndrome.

01:17 The presence of these lesions confers a 70 to 90% chance of clinically definite MS over the next 14 years.

01:24 And so many of these patients, particularly those who have pre-existing MRI findings will go on to develop MS or recurrent syndrome.

01:33 In many fields that number matters, although it's unclear.

01:37 The more lesions that are present on the brain, the more concerned we become about the potential for future attacks, and the more likely we are to treat those patients at their presentation with an initial clinical event.

01:51 So first, let's walk through some of the MRI brain findings that we can see in patients presenting with a clinically isolated syndrome.

02:00 Here you can see typical MRI of the brain, an axial FLAIR on the left and a sagittal FLAIR on the right.

02:06 And we really like the FLAIR sequences when evaluating CNS autoimmunity or MS, or clinically isolated syndromes.

02:14 we're looking for white matter lesions.

02:16 So those are white areas on the T2 or FLAIR that are in the white matter.

02:21 The white matter on the FLAIR is darker.

02:23 And what we tend to see is white matter lesions around the ventricles, periventricular white matter lesions.

02:29 And you can see that really well on the sagittal FLAIR, These white matter lesions that are emanating away from the ventricles, they course along the perivenular pathways emanating away from the ventricles and give us an appearance of what's been termed Dawson's fingers.

02:47 Finger like projections away from the ventricle, which is very commonly seen in patients with MS and other inflammatory disorders of the nervous system.

02:59 How about MRI of the spine? What are the typical findings that we see on the MRI of the spine? Here we're looking at two sagittal T2 weighted MRI demonstrating a very typical appearance of a lesion that would be consistent with a transverse myelitis.

03:14 A short segment of T2 hyperintensity that is suggestive of an area of acute inflammation.

03:21 These lesions often will enhance, there may be patchy enhancement present in these lesions indicative of acute blood-brain barrier breakdown, particularly early in the presentation within that first couple of weeks from symptom onset.

03:38 How about evoked potentials? Historically, this was a very commonly used diagnostic tool.

03:44 And increasingly other tools are, have higher resolution and more specificity and sensitivity for a diagnosis.

03:50 But occasionally, we'll will do visual evoked potentials.

03:54 This is the presentation of a visual stimulus and recording of the time it takes for that stimulus to move through the optic pathway and be recorded back in the occipital cortex.

04:05 We're looking for the time it takes to get there and looking for an asymmetry between the signals coming in from the left eye and the right eye.

04:13 That would be indicative of a lesion somewhere along the visual pathway.

04:19 This is really an extension of our physical exam.

04:21 It's another way of doing that swinging flashlight test looking for an afferent pupillary defect.

04:28 And so this can be useful when the patient has a really suggestive story of an optic neuritis, or a clinically isolated transverse myelitis.

04:36 And we're looking to establish some other evidence that there has been a CNS attack.

04:41 In a patient who has transverse myelitis where there's an abnormal visual evoked potential that then separates those lesions in space and can separate them in time to establish a diagnosis of MS.

04:53 This can also be useful in patients who present with an atypical story where it just doesn't sound like the classic optic neuritis.

05:02 We don't have evidence of an afferent pupillary defect on exam and it's unclear whether there is truly a lesion of the optic nerve and visual evoked potentials can be helpful as objective evidence of lesions that may be subclinical in those patients.

05:20 And then lastly, the lumbar puncture.

05:22 This is a critical aspect of evaluating any immune attack in the central nervous system and often incorporated into the evaluation of patients with clinically isolated syndrome.

05:32 When we're performing a lumbar puncture, we do so with a patient in the lateral decubitus position.

05:37 You can see that here the patient lying on their side.

05:40 We take a spinal needle and that's inserted into the L4-L5 or occasionally L3-L4 spinous process spaces.

05:48 As you can see here and access that thecal sac area where we can gain access to cerebrospinal fluid.

05:55 And typically we draw off 10 to 20 ml of spinal fluid and we'll perform a range of tests to look for signs of infection, inflammation, malignancy, or other potential explanations for the patient's presentation.

06:08 Routine studies performed on essentially all spinal taps performed in neurology includes cell count, glucose, and protein.

06:15 The cell count guides us in terms of whether to be concerned for infection or for cancer.

06:20 An elevation in a cell count is called pleocytosis.

06:23 Pleocytosis gives us concern for a possible infectious process or occasionally malignancy, that when some inflammatory conditions we can see mildly elevated cell count or a mild pleocytosis.

06:36 Glucose levels should really be normal and patients presenting with inflammatory conditions, but maybe abnormal in cancer or acute bacterial or fungal processes affecting the spine or spinal cord.

06:49 And Protein. Protein is really important.

06:51 This is an inflammatory marker, we see elevation in protein in the spinal fluid in conditions that result in inflammation.

06:58 So normal cell count and elevated protein is called an albuminocytological dissociation, and that signature is highly suggestive of an inflammatory process.

07:09 In addition, we can look at some more specific markers for evidence of CNS inflammation, including oligoclonal bands, IgG index, and kappa free light chains.

07:18 And here we're comparing the findings in the spinal fluid to those in the blood looking for evidence of inflammation that is specific to the spinal fluid specific to the central nervous system.

07:29 An increase in oligoclonal bands present in the spinal fluid and not in the serum is suggestive of an active inflammatory process in the nervous system.

07:37 An increase an IgG index and that's immunoglobulins IgG that's increased in the spinal fluid and not in the serum is also supportive of an inflammatory process, as well as increased kappa free light chains.

07:50 These findings should raise strong suspicion for a CNS autoimmune condition, clinically isolated syndrome MS, NMO, anti-MOG disease but can also be seen in other conditions that rev up the immune system in the nervous system, including rarely some cancers and rarely some infectious processes.

08:10 How do we treat clinically isolated syndrome? Well, we treat it the same way we do any acute CNS inflammatory attack, and that's with corticosteroids, IV methylprednisolone or solu-medrol is typically the workhorse in treating these patients.

08:25 Patients will receive one gram of IV methylprednisolone daily for anywhere between three and five days.

08:32 There are a number of studies looking at the length of treatment of IV methylprednisolone, in a famous optic neuritis treatment trial, three days was used typically in clinical practice.

08:43 We may see five days of treatment use.

08:45 The key is to treat that acute CNS inflammatory attack with strong and powerful anti-inflammatories and corticosteroids is the treatment of choice.

08:55 Importantly, steroids do not stop the attack, but reduce the continued progression of the attack and of symptoms and reduce the nadir, reduce the likelihood of reaching as severe a clinical deficit, as we would see.

09:12 Patients with CNS autoimmune conditions will recover spontaneously, and the goal of steroids is to speed that recovery.