MDCP Review of the Year: Why should subacute sclerosing panencephalitis be on our radar?

Dr. Sankhla is a neurologist from Hinduja National Hospital in Mumbai, India. Congratulations Dr. Sankhla, and thank you for agreeing to talk with us. 

Dr. Charulata Sankhla: Thank you so much for the nice introduction.

Dr. Sarah Camargos: Many of our listeners, including myself, have actually never seen a patient with measles since it's been eliminated in several countries. Thanks to strong vaccination programs. For those who might not be familiar, could you tell us what, so  subacute sclerosing panencephalitis, SSPE is and what first got you interested in this topic?

Dr. Charulata Sankhla: SSPE is actually a chronic measles infection, which settles in the brain, and it's because the virus either has mutated or the [00:02:00] vaccination is inadequate because of the breakage in the cold chain. In such a big hot country like India, we do see the measles outbreak now and again. In India, in fact, the age of onset of the measles is much earlier a t the age of six months or so. So the vaccination program actually has included two vaccines. One is at the younger age and one is at the slightly later age so that they don't miss this vaccine. But in spite of that, we still see this chronic infection called SSPE.

And we feel it's because either the virus is mutated and that's the reason the host response, immune response is not able to eradicate it completely, and it settles in the brain and it's the iniquity of the host response to eradicate this virus that leads to this chronic infection in the way.

And, the host does build up the response. That means the measles antibodies are positive in the CSF, and you make a [00:03:00] diagnosis. That means the response is there, but it's not adequate. And I feel that it's because the virus is at the constant change, which leads to its persistence and it escapes the immune checkpoint.

And that's the reason we see the consistency of the SSPE. If you are an Indian neurologist, you will see SSPE in your residency, you'll see as an attending, you'll see as a faculty more commonly in the government center where the poorer, lower social economic patients come a little less commonly in the academic center.

Dr. Sarah Camargos: And how difficult is to diagnose SSPE and what are the most challenging 

differentials?

Dr. Charulata Sankhla: So we do see the patients with SSPE present with the cognitive decline, and usually that's the first presentation of the SSPE. The parents of the child will come to you saying that he's not doing well in this school, or he's behaving in a [00:04:00] very odd manner, the things he could do earlier h e's not able to do his school homework or schoolwork, or sometimes we see it in the older children and there also we start noticing that they have a problem with their cognition and that's the usual symptom in most of the patients. We do see movement disorders as a presenting symptom, but if when we see these patients, the cognition, if we check it properly, is always slightly affected.

So it's a combination of movement disorders, usually hyperkinetic movement disorders, cognitive decline, and a very typical myoclonus that we see in this particular patient. It's almost diagnostic to this particular patient, and it's time locked with the EEG. So if you get the EEG correlate, then the diagnosis is very easy.

Then the penny drops. But if you don't have the EEG correlate, then usually we follow these patients and we repeat the EEG at the subsequent follow up. And then we do get these very classical periodic complexes that we [00:05:00] see in the the patients with SSPE. The second step that we do is we do the CSF because it's a subacute presentation.

So usually in the subacute presentation you are thinking of inflammation and subacute infection. So inflammation is also another part of the encephalitic symptoms. So the CSF measles antibody titers are elevated in these particular patients, and that's the additional clue to your diagnosis. Brain path is usually not done in India, but then I've seen the reports, case reports, particularly in the article of brain biopsy.

From the rest of the parts of the world as well, and isolating the measles virus from the brain as well. So that is the classical presentation. But we do see the atypical presentation when it gets a little difficult because then we to wait and see what's happening to the patient. Is he going to develop that classical myoclonus, or is he not develop the classical myoclonus.

Dr. Sarah Camargos: So there are patients that [00:06:00] don't have myoclonus.

Dr. Charulata Sankhla: It may not be the presenting symptom, and that's when it becomes a little challenging. I'll give you an example of a girl, which whose video has been mentioned is this particular paper, this young girl came with a poor scholastic performance and she had choreiform movements and we didn't know what was causing this.

Everyone, and she was HIV positive since birth. So everyone thought this is a chorea related to HIV. And we investigated her and we did everything that was possible. And she came for a subsequent, we put her on the deutetrabenazine for the chorea, she came for a subsequent follow-up. She become slightly slow, and then the penny dropped.

We saw the myoclonus when she was walking, for a transient moment she paused when she was walking. The chorea paused, and then she had that chill. So immediately we took her to the EEG room and we had the EEG periodic complexes. So this is how the diagnosis is made. Sometimes we don't get it at the first concert, but subsequently we start seeing [00:07:00] the myoclonus in majority of the patients.

Dr. Sarah Camargos: So myoclonus is one of the core symptoms of the SSPE and is really important for the diagnosis and how it shows up in patients and what we know about the origin of the myoclonus. 

Dr. Charulata Sankhla: So the myoclonus in SSPE is very unusual. If you have seen the videos that we put up in this review article, it's a slow myoclonus, it's a slow held up myoclonus. That's what makes it different than the usual myoclonus. And it is timelock with the EEG, but the time locking is variable in different studies that have been put up.

So the myoclonus at times is associated with the eye deviation, and this eye deviation precedes the EEG correlate. That's the reason they thought it could be originally from the brainstem [00:08:00] where the eye movements occur and then the subsequent EEG changes occur. So they thought that the origin is from the brainstem, but then there are many studies which have looked at the EEG correlates and they've got the EEG correlates coming from the cortex and subcortical region as well.

But eventually it goes down to the brain stem, and it's a very unique myoclonus. If you see it, it's slow. It has a rapid component and then it's slow. 

Dr. Sarah Camargos: There is a slow component.

Dr. Charulata Sankhla: There's a slow component. 

Dr. Sarah Camargos: Yes. And your paper took me on an interesting journey through movement disorders and SSPE. I think you evaluated more than 400 people. 

Through the papers, in 98 papers, is that correct? 

Dr. Charulata Sankhla: Correct. Yes. Yes. 

Dr. Sarah Camargos: And what movement disorders did you collect other than myoclonus?

Dr. Charulata Sankhla: So the other disorders are mainly [00:09:00] hyperkinetic. They're much more common. So we see ataxia, we see dystonia. As I said, this patient had chorea and we do see tics as well as stereotypies, and repetitive movements, either their hand movement or their leg movement. And occasionally the patient may have paroxysmal movement as well.

Rarely we see hypokinetic movement disorder as a presenting symptom of the SSPE. But as the SSPE progresses, these patients become hypokinetic and they become rigid. And the end stage that is a stage three and four is actually akinetic rigid, leading to akinetic mutism and then coma. And then the subsequent. So they do die.

Some of them have a prolonged course. Some of them have a very rapid course making you suspect the diagnosis again. Whether you are dealing with another viral encephalitis, which is an acute viral encephalitis, or you are actually dealing with SSPE.

Dr. Sarah Camargos: How do you [00:10:00] see these patients in long terms? For example they stay chronically with the disease like years?

Dr. Charulata Sankhla: Yes, majority of them are chronically with this particular disease. But there is a very surprising thing that happens to these patients. Some of them undergo remission, a spontaneous remission. To the extent that they completely are normal clinically. So we had a patient when I was doing my residency who had an SSPE, and he reversed his, all the symptoms.

He was akinetic and he went back to college only to come back after a year. Again, manifesting their same symptoms in subsequently succumb. So they do have the spontaneous remission. We do not know what causes the virus to suddenly go into the remission or whether it's a response of the host that goes into remission.

We have no idea. But SSPE does go into remission and [00:11:00] in few patients, but all the patients subsequently die. So we have stages 1, 2, 3, and then the stage three is usually hypokinetic, akinetic. 

Dr. Sarah Camargos: Wow. And, it seems that SSPE it can happen even people that who never had measles or only had incomplete vaccination. I also saw one of your reports that the case of a 20-year-old woman who got measles as a baby was later fully vaccinated and still developed SSPE passing away to three months after symptoms begun.

How do you make sense of cases like this? 

Dr. Charulata Sankhla: So that, that's the thing, that's what intrigues us because some of our patients are fully vaccinated. It's not that the vaccination status is incomplete. This patient that I mentioned to you with HIV, she was fully vaccinated, but [00:12:00] I guess the HIV status may have compromised, but her counts were normal and HIV was very stable.

She had normal CD and yet she got SSPE and that's what killed her rather than the HIV itself. So I think it's a host immune response which decides what's going to happen. And again, I feel that the regional variations are also there in the virus. So I guess we are seeing a mutant virus, which is probably not allowing to the host to build up the adequate immune response in spite of the vaccination.

And majority of these children almost 50% of them are fully vaccinated, and India has a double vaccine program. So if you miss one vaccine, you have the second vaccine. So it's difficult to explain this in a fully vaccinated child.

Dr. Sarah Camargos: We have a lot to learn. Is there a treatment? 

Dr. Charulata Sankhla: So we do try [00:13:00] isoprinosine and we do give interferon, but it, doesn't reverse the syndrome. It continues to progress. It may give you a period where the disease seems to stabilize with all these treatments that we have used. I have a pediatric neurologist whom I work with, and we used to give a lot of these, a combination of the drugs, but only to stabilize the patient for few months and then the patients will worse and move, eventually succomb.

So it's similar to what we see with a CD or seeing the slow virus disease.

Dr. Sarah Camargos: Yes, so the experience, your experience for treating these patients are not very encouraging. 

Dr. Charulata Sankhla: Not very, n ot very encouraging. They, but the moment disorders do respond like this chorea would respond to tetrabenazine. Some of the akinetic patients did respond to levodopa for a short while, but it's not the [00:14:00] long term. Like levodopa will help them for few, few months to a year, I say. But eventually they will, they will become more and more akinetic. They would lose their cognition. They become slow and eventually comatose.

So very heartbreaking.

Dr. Sarah Camargos: Yeah. Do you have a special message for us to diagnose and treat these patients. 

Dr. Charulata Sankhla: Yes. The special message is that a lot of developed countries have given up on measles vaccination because of the fear of it causing autism or various other disorders, and I think this resurgence of the measles will eventually lead to the SSPE cases being seen in those countries as well. And this is what I was discussing with the colleagues from movement disorders, that giving up of the measles vaccine would be a problem eventually.

[00:15:00] And I think this is a diagnosis that one should keep when you see a young child or an adolescent with cognitive decline and movement disorders, particularly hyperkinetic movement disorders. And if you have that myoclonus, then you must do the EEG to make the diagnosis, and you can do the CSF studies to look at the basis antibody titers, and that will give you a clue without the brain biopsy to the accurate diagnosis.

Fairly accurate.

Dr. Sarah Camargos: Yeah, perfect. I actually encourage all the listeners to check out the video presentations of the cases included in the article. They are really fascinating and add a lot of depth into the discussion. Dr. Sankhla, thank you so much for being here with us and congratulations again on your paper. 

Dr. Charulata Sankhla: Thank you. Thank you so much. [00:16:00]