Ep. 212: Reversible Cerebral Vasoconstriction Syndrome

00:00:00: Welcome to EANcast, your weekly source for education research and updates from the European Academy of Neurology.

00:00:16: Hello!

00:00:17: And welcome to EENcast Weekly.

00:00:19: Neurolegy.

00:00:20: My name is Irgita Valeikiyane.

00:00:21: I am a clinical neurologist and neurosanologist at Vilnius University Center of Neuralogy Lesienia.

00:00:28: The topic today is Neurosanology.

00:00:30: In this episode we are going be talking about reversible cerebral laser construction syndrome.

00:00:37: My guest today is Theodoros Mavridis.

00:00:40: He's a consultant neurologist, stroke and headache specialist at the Department of Neurology, Dalat University Hospital, Adelaide and Mid-Hospital Dublin Highland, also Scientific Research Associate at First Neurolegy Department, Agenation Hospital Medical School National and Kapodistrian University of Athens, Greece and Chair of the Irish Headache Society at Migraine, Ireland.

00:01:10: Welcome to your doors!

00:01:11: Thank you for joining us today.

00:01:22: Many clinicians might still be confused by the various names this condition has had over the years.

00:01:30: Would you clarify what RCBS is and how their terminology hasn't evolved?

00:01:37: Thank-you, Gita, for your nice question!

00:01:39: Let's start with a basic.

00:01:40: So RCBS was basically a clinical radiological syndrome that was classically defined which will talk more about them when they appear where they're not appearing.

00:01:53: Multifocal segmental vasoconstriction of the intracranial, of course, arteries and as the name suggests reversibility of these changes within approximately twelve weeks.

00:02:03: maybe a bit longer may be a bit less so it had many names previously called called Fleming syndrome or As we are seeing often after pregnancy like postpartum angiopathy other names like migranus spasospasm and benign angiopathy of the CNS.

00:02:23: But in two thousand seven it was proposed that these entities should be unified under a single umbrella.

00:02:30: basically, The term reversible cerebral vasoconstriction syndrome are serious because they share the same clinical course an imaging patterns And today has even its own ICD-TAN code and basically ICD-Eleven code.

00:02:49: And we know now it's an entity on its

00:02:54: own.".

00:02:55: Let's talk

00:02:56: about the biological.

00:02:57: why!

00:02:58: What is actually happening in this Cerebral Vessels during the RCDS episode?

00:03:04: Yes, that... This is very important because these are basics of pathophysiology is underlying this problem.

00:03:13: So basically it involves a transient multifocal dysregulation of the cerebral vascular tone, basically confined mostly in the medium and small vessels.

00:03:25: This we think its likely driven by sympathetic overactivity And temporal impairment on the blood brain barrier.

00:03:33: so It's important these states to say regarding the pathophysiologist that it's not inflammatory and is not atherosclerotic.

00:03:42: It's functional disturbance of their tone rather than structural or inflammatory disease, like for example vasculitis.

00:03:51: so this mechanism of dysregulation in the vascular tone leads what we know as the string-of beads appearance other parts that are constricting and other parts about dilating.

00:04:06: And usually it has in the distal vessels, but it can in severe forms migrate to more proximal segments of the turquoise well over several weeks.

00:04:19: Okay thank you!

00:04:21: As CDS as explained is a relatively benign condition by recent data from the reverse network suggests especially here in Europe.

00:04:32: What

00:04:32: did that data reveal?

00:04:34: Yeah, this is something... I think it's a bit of misunderstanding.

00:04:38: we think that RCBS has been nine but its not exactly what the term says reversible.

00:04:46: so the latest findings from the reverse network say it's not always a benign condition, so large school cohorts specifically from Europeans.

00:04:56: we see that they have high rates of brain lesions.

00:05:00: Specifically ischemic stroke or intrahanial hemorrhage Or even the other part of their CVS which is the press.

00:05:07: I'm going to talk more about this.

00:05:09: and there are differences between European and Asian populations.

00:05:15: brain parenchyma lesions appear in around twenty nine to thirty percent in the Europeans and only two six percent in Asian population.

00:05:22: So there is a difference between those ethnicities.

00:05:26: now, The other thing that's not in the European Population we have secondary or what would call triggered associated our CVS.

00:05:33: it's far more frequently Europe and appears more than fifty percent of cases.

00:05:37: so We have some trigger factors which Is Not Very very typical for the asian population.

00:05:43: And another thing that needs to be said regarding the classical presentation of RCVS being the Thunder Club headache, it's not a very classic for Europeans.

00:05:55: So around thirty-to-thirty two percent of European population can actually present without the classical Thunder Club Headache which makes the diagnosis even more difficult.

00:06:07: We have to know there is also different Outcome between European and Asian population, so the unfavorable three month outcome is have high risk in the European population.

00:06:20: And there's also as I told you a secondary trigger more often.

00:06:28: And if the presentation can be atypical, how can we reliably distinguish ACVS from other serious conditions like primary andritis of CNS or Moyamoya disease syndrome?

00:06:43: How do you explain that.

00:06:44: Yeah

00:06:46: this is something very important as we discussed before.

00:06:49: there are other presentations are typical specifically in European populations.

00:06:58: So we have afocal neurological signs like seizures, visual disturbances.

00:07:02: And we know that patients who present without the Thunderclap headache... ...have even a worse outcome than those who present with the Thanderclaps headache.

00:07:12: so it's very important.

00:07:13: That is why there was a tool made to help us distinguish RCBS from other mimics Like you said primary angiitis of CNS or MoyaMoya which is the R-CVS II score.

00:07:29: So this basically it's a clinical score that gives or takes out points to have an approximation, so for example if you have recurrent thunderclapedics these gets up to five points.

00:07:40: If you have a carotid D-R-III involvement This subtracts two points.

00:07:44: It's minus two points and there are presences of vasoconstrictive trigger.

00:07:48: It has three point.

00:07:49: female sex one point Or some background hemorrhage One point.

00:07:52: Basically You get a total score And we know now from not many cohort, but we know that the score of five or higher it gives us a specificity of ninety nine percent for our CVS.

00:08:08: If you have scored two or less then the specificity is one hundred percent and the sensitivity eighty-five percent.

00:08:17: The problem lies if there's three or four scores which are indeterminate.

00:08:23: So basically the specificity drops around eighty three percent and the sensitivity goes way down, around ten percent.

00:08:30: And that's why you need more investigation and more imaging data to make sure that you have an RCBS Now.

00:08:40: keep that in mind that RCBS II score is very good for using clinical practice.

00:08:46: but be careful because this was a big single standard retrospective study And we know now that you have to be very careful in those three or four scores.

00:08:58: If you've got more than five, then it's our CVS.

00:09:01: if you can't less them two and its not a CVS but the three-and-four has been very careful and use more tools like imaging tools.

00:09:10: I agree this is important.

00:09:13: We had several modalities at our disposal CT MRI DC analyzer sound.

00:09:19: How should we navigate this?

00:09:21: for diagnosis and monitoring?

00:09:27: We need those tools, so basically let's start with the CT and CTA.

00:09:34: Of course it is not very specific to parenchyma lesions but CTAs are useful in assessing that string of beads.

00:09:45: We can also use it very often in the emergency department just to see if there's an aneurysmal subarchloric hemorrhages or other things.

00:09:52: And of course MRI is much better for perechymal lesions, Or if we have e.g.

00:09:58: a press and water-centered infarcts.

00:10:02: It has more sense now.

00:10:04: In terms of MRA and CTA It's very important to remember that if you do it very, very early You might miss the string of beads because this is something that evolves over The duration of two or three weeks.

00:10:23: So If you did too early again... ...you might miss those strings of beads even though we have a clinical thought and suspicion That these are CVS.

00:10:35: so possibly to re-standard Now, the digital subsequent geography.

00:10:40: It is a gold standard for vessel resolution and but it's in vape.

00:10:44: We don't usually use its too often.

00:10:47: we used when we have A doubt that this is our CVS or not our CVs?

00:10:53: And again if you do to early You might miss.

00:10:55: so you need to wait up until you do?

00:10:57: Of course as say, you know your guitar yourself here in your sonologist and Transcranial Doppler, and TCCD is very useful specifically in the hands of experienced physicians.

00:11:12: And we can see with a TCD that evolution of those vessels... We'll see how it evolves because if it's non-invasive It could be bedside.

00:11:22: so you measure the velocities and ratios to see whether it gets worse or better.

00:11:31: Which ratios you have mentioned?

00:11:36: Yes.

00:11:38: This is very important, so I personally do two things.

00:11:42: first of all... Of course i don't do one measurement but a series because as we discussed before RCDS is something that evolves.

00:11:52: So I do measurements and try to be more specific at week two or four.

00:11:59: I do two things.

00:12:00: First of all, I measure the MCA velocities.

00:12:03: we know that if you have higher MCA middle cerebral artery sorry velocity is more than one hundred and twenty then You see an evolution that increases the stenosis of the arteries.

00:12:16: The other ratio where are discussing is the Lindergaard index.

00:12:20: So basically it's the index between the MCA versus the ICA And if it is, of course below three the ratio then you don't have significant vaso spasm.

00:12:33: If you have three to four point five some people say more than two points seven but more than four point Five You have moderate to severe vaso Spassler.

00:12:43: Of course More Than six.

00:12:45: It's and its something that points up to severe Vaso Spasm.

00:12:48: so if see a velocity off The Ratio of them say Velocity to the IC velocity is more than six is a severe values problem.

00:12:57: This is very interesting because it's a bedside investigation, you can monitor the patient and also see what we call the high mode dynamic trends.

00:13:07: so if you give the patients specific treatment like the calcium channel blockers that they have I don't say there are the best but one of the only things for R-CVS specifically for their headache if you give modipping for example of the RCBS.

00:13:28: I think it's a very useful tool, i won't tell that its best one but something to do on bedside and if physician is trained.

00:13:42: That's very interesting.

00:13:45: You mentioned the Linda guard index and sometimes it is a problem to differentiate subrachnoidal haemorrhage in case of CT negative Subrachnodal hemorrhages.

00:13:57: have you had such cases?

00:14:00: Yes, this is very difficult because we go back to what we call chicken and egg.

00:14:08: so Sometimes in severe RCVS or in areas that are not very, very certain.

00:14:17: If the RCBS caused a subarchlorine hemorrhage... ...or the subarachloride hemorrhoids cause vasoconstriction because we know that in severe subarchioline hemorages.. ..we have vasocostrictions and then we've got lindegadration.

00:14:30: It's really difficult to be honest.

00:14:33: I had two of those cases And i needed all the tools together To see how it evolved.

00:14:41: So basically what did And I don't say that this is what everyone should do.

00:14:47: Is, i try to treat for the worst case scenario which was the Sambaracan hemorrhage and tried to find if there's an aneurysm?

00:14:55: When it didn't find any reason then i relaxed and searched for R-CVS or the triggers... ...and everything else!

00:15:08: I totally agree with you.

00:15:11: That is a problem.

00:15:14: we should collaborate and have more examples, more cases for the exact answer to this question.

00:15:24: that's difficult

00:15:26: also

00:15:27: yeah.

00:15:28: Also i find the rule of ultrasound particularly useful.

00:15:32: how can Poccus specifically in the management of these patients, point-of-care ultrasound exactly.

00:15:39: Yes this is what we discussed and I think it's as i told you...I know that your neurosanologist and uh..i think its very nice ,its accessible.

00:15:49: It's a noninvasive tool That You can do As many times as you want .You don't need to be thinking about The radiation are About To Be invasive like the DSA.

00:16:01: All advantages, it has limitations.

00:16:03: For example its not a standalone for diagnosis.

00:16:07: It also has segmental coverage.

00:16:08: so you cannot see the whole spectrum of the MCA if want to find those parts because as we discussed before Its string of beads So isnt really easy to find their segmental narrowing and high velocities And off course As we discuss this operation and window dependence.

00:16:28: So if the patient doesn't have a really good window, you cannot find anything And If your not trained operator You reduce their reliability.

00:16:37: But it's very nice because... ...you can see the clinical improvement specifically with extended release verapamil or nipodipine.. ..You can see resolution of those vessels even if you administrate it intravenously or in very, very severe cases interarterially.

00:16:58: And I haven't done this myself but from the literature that is severely fractured cases.

00:17:03: You can use ultrasound for a stale ganglion block as guidance to rescue therapy.

00:17:11: It's useful tool and neurologist should be trained on ultrasonic ultrasound because as we discussed before it's accessible and non-invasive dead site tool that you can use every minute.

00:17:23: So, we don't need to be restricted about moving the patient through CT or MRI of course not as a standalone test.

00:17:31: That's perfect thank-you!

00:17:33: We must also discuss the triggers.

00:17:36: what should we be looking for particularly regarding pregnancy and medications?

00:17:43: Yes... As we discussed before Europeans have more trigger based associated with RCBS and agents.

00:17:52: So there are some vasoactive substances that have been recognized in more than sixty percent of the cases, The most common one is the serotoningic adidipresence either SNRIs or SSRI's.

00:18:04: And tryptans are very-very-very common over-the counter decongestants like the nose decongests.

00:18:10: Of course lacy drugs such as cocaine and cannabis are major triggers.

00:18:16: Then there is the postpartum period, which is a major trigger and accounts for about seven to twenty-one percent of cases often picking around two weeks after delivery.

00:18:31: Among Postpartum or CVS cases hemorrhagic presentations are common – about fifty three are hemorrhagic with the intracerable haemorrhage being more frequent than subrachnal hemorrhages.

00:18:51: There is also a very tight overlap between postpartum RCVS, preeclampsia-eclampusia antipress likely due to assert mechanism of endothelia dysfunction and impaired vascular toll.

00:19:06: A case control study of forty pregnancy related RCVs cases versus one hundred and twenty controls papioclampsia, eclampsia in seventy-three percent of the cases versus ten percent of their controls with fifty five percent of our CVS cases having intracranial complications like hemorrhage infarction or press.

00:19:26: As well we have other drugs immunosuppressants.

00:19:30: We also have some hormonal agents that are being accused and Of course ,we must not forget the glucocorticoids which it's also going into the differentiation with the primary ansiitis CNS.

00:19:44: It is very important to differentiate from the angiotis because this treatment for the primary anxiatis, but if you give glucocorticoids in an RCBS or mist RCBS case then you might exacerbate and worsen the RCBS because glucocorticoids have been suspected as a possible trigger.

00:20:08: Exactly, thank you.

00:20:10: Are RCBS and PRESS actually the same thing or are they separate diseases?

00:20:17: And this is a very nice question.

00:20:19: so many studies that think we have the shared mechanism between RCBS & PRESS.

00:20:27: So basically if I can answer with one answer would say there's distinct clinical syndrome, clinical radiological syndromes but all of them are on the same spectrum that they have a shared pathophysiological basis and mechanism bases, but there are supposed to be different diseases.

00:20:46: So if we go from the arcygous point of view would say it's more of a vasoconstriction.

00:20:52: so its mostly the vessels whereas in us you will see more problems inside the parenchyma with vagogenic edema.

00:21:00: But infact around thirty-eight or forty percent cases press-like presentation in their scans.

00:21:10: On the other hand, eighty five percent of the press patients in OneSlee so that they have some vasoconstrictions even though they don't have a full string of beads.

00:21:24: we see patients with RCBS having press imaging and many press patients who have RCBS imaging.

00:21:35: they may be the two sides of the same coin and one is emphasizing on the vessels, in other it's emphasizing on result of endothelial failure which is basically brain.

00:21:46: That's interesting!

00:21:48: And now just practical question for these patients are you doing transorbital focus?

00:21:56: Are looking at optical nerve sheet diagram?

00:22:00: Yeah this very interesting because as we know that the brain has a direct connection with the optic nerve.

00:22:08: And we see that in other cases, like idiopathic and chronic hypertension In other types of edema We see the optic nerves C diameter increasing in those cases.

00:22:20: I don't do it routinely in RCBS cases But in cases that have breasts are more interesting to find if there is dilation and increase in the diameter which points to higher opening pressures as well.

00:22:36: I'm not sure how i can use it in the future treatment wise, so if that will help me treatment-wise because we don't have much for the treatment of RCBS and press besides getting out off of the trigger situation or giving a bit of an emoticon on RCBS.

00:22:55: but uh... It's useful too.

00:22:58: But at the moment I don't know how to fully utilize it.

00:23:03: more thoughts about that.

00:23:07: Teodoros, sometimes I found the enlargement of optical nerve sheet diameter and we should continue our research And to wrap up, where is the field heading?

00:23:36: What are future directions for R-CVS research?

00:23:41: So we still as mentioned before have significant gaps.

00:23:45: One of them was as you told me about the optic nerve diameter and how can utilize it.

00:23:50: We need biomarkers that reliable distinguish R-cvs from its mimics As I said earlier specifically when imaging isn't conclusive primary NGIDs of the central member system or a Moya-Moya.

00:24:06: We also lack randomized control trials to confirm if early initiation, for example, calcium channel blockers actually outters their long term outcomes and it just manages its symptoms.

00:24:18: so we're not quite sure about nemodipine.

00:24:23: The previous physicians were using it but found that there is some evidence against these symptoms.

00:24:29: The other thing that I would like to mention, which is very interesting when we're in this kind of cases.

00:24:37: That there's a difference between the Europeans and Asian population And we might need more research on genetic environmental factors To explain why Europeans seem to face a severe disease or worse outcomes?

00:24:51: Why they have more trigger-based RCBSs than the Asian population.

00:24:58: This is really interesting to do a really nice genetic study on that.

00:25:04: And you have summarized our

00:25:06: talk,

00:25:07: and I think after our talk the listeners will remember that reversible cerebral vasoconstriction syndrome or ACVS is relatively benign condition characterized by recurrent sun-declared headaches and transient segmental vasocostrictions of cerebral

00:25:26: arteries

00:25:27: in younger individuals?

00:25:30: younger than six years, roughly mean forty-years.

00:25:34: And typically resolving within three months.

00:25:37: however in thirty percent cases it may present without typical symptoms or without headache and maybe complicated by stroke and irreversible changes especially In Europe.

00:25:54: you also summarized the triggers associated conditions.

00:26:00: We can thank our listeners for listening to this episode of our series.

00:26:07: And we hope that these insights help you in your clinical practice, and I would like say goodbye!

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