PEM Adventures Chapter 1

Stories are powerful vehicles for education. Combine a story with some active participation, and you have the recipe for great learning. And so, it’s with great delight that we bring you Chapter 1 of PEM Adventures.

First presented at EuSEM 2018 and then again with some spectacular twists by Dan Lumsden, Paediatric Neurologist extraordinaire, Dani has a particular soft spot for Tomas, a little boy who dreams of being a footballer. Join us on a journey (with an inbuilt time travel machine) to manage Tomas, a little boy with a dream…

Meet Tomas, an 8-year-old boy who dreams of playing professional football. He’s been completely well until an ill-fated shopping trip for new football boots. At 2 o’clock, while trying to persuade his mother that he needed the new Premier League football to add to the collection, he developed sudden-onset right-sided facial drooping. His mum bundled him into the car and drove him directly to your ED. You look at your watch: it’s now 3.30 p.m.

Your assessment is as follows: Tomas is alert and seems orientated. He has right-sided facial weakness and weakness in both his right arm and leg. He has no obvious sensory changes but is struggling to communicate with you as he has global aphasia.

Suspecting the worst, you have a critical decision to make. But what are you going to do?

Call neurology

You bleep neurology.

And wait…

They don’t answer so you bleep again…

But they still don’t answer…

You bleep a third time…

But they still don’t answer. So you give up and call radiology instead.

Call radiology

You call radiology. And they ask… What imaging do you want?

CT? CT with contrast? CTA?

The radiologist says, “Sure, imaging sounds like a good idea. Let’s do a combination of both a CT brain with CTA to look for blood and clots.”

The CT scanner is available at 16:00.

“But,” she adds, “if you’d like MR imaging, we could do that at 18:00.”

Do you…

Proceed with CT and CTA

Tomas’ CT and CTA show evidence of an arterial ischaemic stroke with a thrombus occluding the middle cerebral artery. There is no intracranial haemorrhage.

It is now 16:15, two ¼ hours after the onset of Tomas’ symptoms.

You’re doing great. Close the toggles and move on to the next part of Tomas’ case.

Say, actually, I’ll have MR imaging please.

Tomas has an MRI and MRA.

It shows an arterial ischaemic stroke with a thrombus occluding the middle cerebral artery.

It is now 18:45, almost five hours after symptom onset—something tells you this is a bit too late.

Luckily for you, the inbuilt time machine whizzes you back to make that last decision again.

This time, when you’re told you can have an MR and MRA at 18:00 or CT and CTA you say… “I’ll have a CT and CTA now please.”

MRI? MRV? MRA?

The radiologist says, “Sure, imaging seems like a good idea. Let’s do a combination of an MRI and MRA to check the brain and look for clots.”

You phone MR. They say they can do the MR at 18:00. The CT scanner, however, is free now.

Do you…

Proceed with MR at 18:00?

Tomas has an MRI and MRA. It shows an arterial ischaemic stroke with thrombus occluding the middle cerebral artery. It is now 18:45, almost 5 hours after symptom onset – something tells you this is a bit too late.

Let’s travel back in time…

This time when you’re told you can have an MR and MRA at 18:00 or CT and CTA now you say… “I’ll have a CT and CTA now please.”

Say, no thanks, I’ll have a CT and CTA please.

Tomas has a CT and CTA. It shows evidence of an arterial ischaemic stroke with thrombus occluding the middle cerebral artery. There is no intracranial haemorrhage.

It is now 16:15, 2 ¼ hours after the onset of Tomas’ symptoms.

You’re doing great. Close the toggles and move on to the next part of Tomas’ case.

With a little luck, Tomas has now had neuroimaging, and you know he’s had an arterial ischaemic stroke with a thrombus occluding the middle cerebral artery without intracranial haemorrhage.

So, what now? You haven’t managed to get hold of a neurologist for love or money. So do you…

After your shift, you do a quick Google search to look at the evidence around using tPA in children, and you stumble across this paper:

Rivkin, M.J., deVeber, G., Ichord, R.N., Kirton, A., Chan, A.K., Hovinga, C.A., Gill, J.C., Szabo, A., Hill, M.D., Scholz, K. and Amlie-Lefond, C., 2015. Thrombolysis in pediatric stroke study. Stroke. 2015: 46(3); 880-885.

Rivkin’s team were part of a huge multi-state stroke research team in North America. They designed the incredibly well thought out and well put together TIPS (Thrombolysis in Paediatric Stroke) study to look at (A) the safety of and (B) dose of tissue plasminogen activator (tPA) in children presenting with an arterial ischaemic stroke (AIS). They set out to recruit children aged 2 – 17 with acute AIS and PedNIHSS scores between 4 – 24 to receive tPA if initiated within 4.5 hours of symptom onset. Centres were given protocols to manage complications such as intracranial haemorrhage, systemic bleeding, hypotension or angioedema.

Sounds good, right?

Well, in principle, yes.  The study opened in April 2012 but closed only 20 months later, in December 2013, because only one child had been enrolled and hadn’t been treated due to complications following extubation before tPA administration. 

93 children had been screened, with 43 having confirmed AIS and the other 50 having a stroke mimic such as migraine, seizure or tumour, etc. 

Of the 43 children with AIS, about half had medical contraindications to tPA (including moyamoya disease and anticoagulation treatment); 10 were outside the treatment window (including 1 who missed the treatment window by 15 minutes due to a delay at the scanner); some had a PedNIHSS that was too low; 1 had a PedNIHSS that was too high; and a couple didn’t have arterial occlusion on imaging.

But it wasn’t a total disaster. Preparing for TIPS also led to the development of Paediatric Stroke Networks in North America, and designing the TIPS study led to consensus guidelines on the management of stroke in children.

These consensus guidelines derived from the TIPS study design have been extrapolated to the 2017 RCPCH Stroke in Childhood guideline based on expert opinion and the best available evidence. In addition to the full guideline, there’s a simple, easy-to-follow pathway poster that can be grabbed for quick reference whenever a child presents with potential stroke symptoms.

The poster gives a list of potential stroke presentations, from an unexplained persistent drop in GCS, through acute focal neurology (even if resolved), focal seizures, headaches, ataxia, dizziness, speech disturbance and a prompt to consider stroke in children with sickle cell disease.

It includes a simple, easy-to-follow Paediatric National Institute of Health Stroke Scale (that PedNIHSS we’ve talked about), a bit like a Glasgow Coma Scale but specific for paediatric stroke.  The PedNIHSS makes up a vital part of the neurological assessment, a way of scoring the severity of the stroke. It is vitally important that the PedNIHSS is calculated because if the score is very low, with a minimal deficit at the outset, the risk of thrombolysis outweighs the potential benefit. And suppose the PedNIHSS score is very high. In that case, the child likely has a very large area of brain damage, with a high risk of bleeding into that infarcted territory, again making the risk-benefit ratio too risky. The child’s PedNIHSS score guides your subsequent management.

The pathway lists investigations (which must include coagulation profile and group and save because of the risk of bleeding), monitoring and neuroimaging. Timing of imaging is key. The guideline states that children should be scanned within 1 hour of presentation to the ED. Pragmatically, this is usually CT with CTA (the angiography component to look at the arteries), because organising an MRI with MRA takes longer. But, if you’re in an institution with great access to MR and can get your imaging within an hour of presentation, then it’s worth discussing with the radiologist.

If a child has a confirmed AIS, what do we do? The guideline offers two either/or treatments: EITHER aspirin 5mg/kg within an hour, as long as there is no parenchymal haemorrhage OR thrombolysis. The guideline suggests that thrombolysis may be considered in children aged 2-8 and could be considered in children over 8 (some careful wording there because extrapolating evidence from adult studies to an 8-year-old is easier than to a 2-year-old) provided the PedNIHSS is between 4 and 24. TPA can be administered within 4.5 hours of symptom onset. There must be either MRA evidence of thrombus or normal or only minimal ischaemic changes on CTA (no huge areas of ischaemia because the risk of bleeding into it is too high), with or without evidence of thrombus. As the biggest risk of giving tPA is haemorrhage, there must be no contraindications, such as abnormal clotting, an underlying bleeding disorder, malignancy, hypertension or moyamoya disease.

It’s crucial to note that the treatment for AIS is not the same as for a child with a haemorrhagic stroke (these children need urgent discussion with a neurosurgeon for consideration of evacuation) or a child with an ischaemic stroke secondary to sickle cell disease (pick up the phone, call a haematologist and organise an exchange transfusion). Although not included in the poster, the guideline summary and full guideline give indications for surgical and endovascular interventions in stroke and those nuggets for managing stroke in a child with sickle cell disease or haemorrhagic stroke.

And what about thrombectomy? This is a very active area of interest. In the world of adult AIS, there has been a big move towards primary clot removal by thrombectomy rather than clot-busting with thrombolysis. In the world of paediatric stroke, although there are some published case series and case reports, we don’t have a clear evidence base or national guidance yet.

So, what is the take-home from Tomas’ case? Although stroke is rare in children, it does occur. Thrombolysis is a potential management option given the right conditions, as long as it’s given within the 4.5-hour window. So, next time you see a child with stroke-like symptoms, send bloods early, get early neuroimaging with angio, and pull out the RCPCH Stroke in Childhood poster.

With special thanks to Dr Dan Lumsden, Paediatric Neurologist at the Evelina London Children’s Hospital, who inspired the creation of Tomas’ case and presented him so fabulously at the Royal Society of Medicine. Thank you, Dan.