Paediatric Stroke by Shree Basu
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Shree Basu is a Paediatirc Intensivist in Sydney. These slides from the Brain Symposium 2023 accompany the talk she gave. She discusses how Paediatric stroke presents, what neuroimaging is required and what interventions are available, including thrombolysis and the role of endovascular thrombectomy.
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Paediatric Stroke by Shree Basu
- 2. PAEDS STROKE By Shree Basu
- 4. The other 80%? How do they present? What neuroimaging do they need? What interventions are available?
- 5. How many? Between 58 and 390 kids in Australia each year Ischaemic > Haemorrhagic, CVST ~ 1 in 4 NSW: 166 AIS over 10 years
- 6. Which kids have strokes? 50% previously well Known RF: CHD/endocarditis Arteriopathy Traumatic Prothrombotic SCD
- 7. Presentation Age and cause dependent AIS: Focal neuro deficits + seizures HS: Headache, vomiting, ↓LOC
- 8. Diagnostic Delay Unfortunately common Suspicion and sense of urgency needed Time = brain
- 9. Which pictures? CT v MRI? - CT: No sedation, poor sensitivity in AIS - MRI: Sedation and timely access
- 10. Australian Clinical Consensus Guideline: diagnosis and acute management of childhood stroke Int J Stroke, 2019 14 (1)
- 12. What can we do? tPA Endovascular Thrombectomy Disease specific therapies
- 13. tPA Dose? Efficacy? TIPS trial – unsuccessful Limited data
- 14. Endovascular Thrombectomy No RCTs Growing data set Needs discussion early
- 15. JAMA Neurol. 2020;77(1):25-34 Save ChildS Study 63 AC strokes 10 PC strokes 16 with IV tPA + ET
- 17. Local Experience 166 AIS in 10 years in NSW 23.5% large vessel occlusion (LVO) 1/3 underwent thrombectomy LVO no ET = 73% severe disability or death LVO post ET = 67% mRS <3 at final timepoint
- 18. Bottom Line re ET Feasible Low* complication rate Long term outcomes seem good
- 19. ICU Management Neuroprotection - Normothermia, normoglycaemia, normovolaemia, norm-O2-Co2-pH, seizure control
- 20. ICU Management ‘Normotension’ - Target SBP > 50th centile for age - Treat > 15% over 95th centile
- 21. Take Home Know the risk factors BUT no risk factors ≠ no risk Support efficient systems for diagnosis and imaging Retrieve to closest paediatric stroke service ASAP
- 22. The neurons you save have decades more work to do
- 23. References 1. Management of Stroke in Infants and Children. Stroke. 2008;39:2644–2691 2. Australian Clinical Consensus Guideline: diagnosis and acute management of childhood stroke. Int J Stroke, 2019 14 (1) 3. TIPS Study: Stroke. 2015;46:880–885 4. Save ChildS Study: JAMA Neurol. 2020;77(1):25-34 5. Incidence and Natural History of Pediatric Large Vessel Occlusion Stroke: A Population Study. JAMA Neurol. 2022 May 1;79(5):488-497.
Editor's Notes
- Lets call this guy Jack. Jack is the poster boy for the Berlin heart – an extracorporeal ventricular assist device which as you can see in this picture, Jack has two of. Along with his Berlin, historically he has about a 30% risk of stroke. This is Hayden. Hayden came to us at CHW on VA-ECMO and during his run, his stroke risk was a somewhere in the range of 10-20%. And this is Poppy who you can see has recovered well from her cardiac surgery, but still has a 10 to 100 fold increased stroke risk depending on her underlying cardiac pathology and repair. Now, I can imagine you thinking “Sure Shree – but those kids are your problem” and you’re right – stroke associated with cardiac disease occurs predominantly in the inpatient setting and these are the ones I worry about most. In reality though, this group makes up about 20% of paediatric strokes so today I want to talk to you about the other 80% that you’re more likely to see outside of a tertiary centre.
- We’re going to talk about How they present What neuroimaging they need And what interventions are available for them
- But first, how many kids have strokes? Extrapolating from international data, there are somewhere between In our own fairly recent NSW paediatric data identified 166 ischaemic strokes in 10 years which is more than one a month for just this subtype. This thankfully isn’t common, but it also isn’t rare and requires us to know what we’re doing when they present.
- 50% of children who present with stroke will have no established risk factors and so no features that raise either family or clinician suspicion that this uncommon event might occur The other 50% have risk factors many of which will be familiar CHD as we’ve mentioned or endocarditis as in adults Arteriopathies for example moya moya disease Traumatic strokes for example associated with dissection And then lastly the haematological risk factors in children with prothrombotic disorders or sickle cell disease where in some cases patients and families will be aware of the heightened stroke risk and may alert clinicians to this concern on presentation
- - Diagnosis of childhood stroke begins with know- ledge of the signs and symptoms. Clinical presentation varies depending on stroke type, vessels involved, and the child’s age. Focal neurological deficits and seizures are more common presenting features of AIS, whereas headache, vomiting, and altered mental status are more common in HS which is also less likely to show focal deficits The signs and symptoms you should be looking for, as in adults, are hemiparesis and hemifacial weakness, speech and language disturbance, visual disturbance, ataxia, altered mental status and seizures. Seizures at stroke onset are more common in children than adults and affect up to 25% of children, particularly in the <6 age group. Peak age for both ischemic stroke and intraparenchymal brain hemorrhage is the first year of life, with a third of the cases presenting in this age group, whereas SAH is more common among teenagers. What neurological signs you can elicit is also highly age dependent and in young children sometimes difficult to demonstrate with certainty – so listen to parents and engage your friendly local paediatrician early if you’re uncertain.
- Diagnostic delay in these patients is unfortunately common Most children with acute ischaemic stroke present within 6 h but data worldwide demonstrates that in-hospital diagnostic delays are frequent An index of suspicion and a sense urgency cf adult stroke codes needed Time = brain
- So now that you have a clinical concern, what pictures do you need? Diagnosis must be confirmed on brain imaging in children before considering reperfusion therapies as stroke is an uncommon and accounts for less than one- third of cases with focal neurological symptoms The advantages of CT are that most children will not require sedation and it is readily available in most emergency departments. However, these benefits are largely outweighed by the evidence showing that CT has poor sensitivity for early detection of ischemic infarction and can further delay diagnosis. As a result, magnetic resonance imaging (MRI) is recommended as the imaging modality of choice for suspected AIS, recognising the challenges of sedation and timely access In contrast, CT imaging and appropriate MRI sequences are equally sensitive for the detection of intraparenchymal blood. Therefore, where signs and symptoms suggest hemorrhagic stroke, and access to sedation or MRI is delayed, a CT should be performed.
- This is the summary from the Australian Clinical Consensus Guideline on paediatric stroke, published in 2019 As you can see, once there is a clinical suspicion of stroke, the next priority is the decision around imaging and transfer. Where an urgent MRI +/- GA is not available, then for hyperacute presentations that is within 6h of symptom onset, primary transfer is recommended. If not, a low radiation CT +/- CTA and transfer.
- If the MRI is feasible and the patient presents within 6h of symptom onset, then a rapid MRI sequence is recommended and should be discussed with your radiologist. Reperfusion therapies are time dependent – hence rapid MRI protocols to accurately diagnosis stroke are imperative As you can see – what is recommended is a group of axial sequences in addition to a time of flight MRA and this protocol is estimated to take 10-15 minutes. It’s acknowledged that accessing urgent MRI is a major challenge in the pediatric emergency department, particularly with the added requirement for sedation in younger children. Nevertheless, with interdepartmental acknowledgement of its importance, it’s something we can probably do better both in peripheral and tertiary paediatric hospitals.
- So for a patient diagnosed with a stroke, once they get to a paediatric stroke centre, what can we do? For AIS – as in adults, we consider tPA and endovascular thrombectomy In other conditions, like arteriopathy and sickle cell disease, we might need to consider disease specific therapies which I won’t talk more about right now.
- The tPA question for stroke in children remains fairly much unanswered with a lack of data despite concerted international efforts. Things we do know – dosing in children is likely different to adults. The fibrinolytic system of younger children includes lower levels of endogenous tPA and higher levels of plasminogen activator inhibitor-1 ithan are found in adults. In addition, children have an increased volume of distribution and more rapid hepatic clearance, suggesting that they will clear tPA more quickly. This raises the possibility that a higher dose of tPA may be needed to promote thrombolysis in children who present with acute AIS than that used in adults. The TIPS trial was a major multicentre study aimed to assess safety, best dose and feasibility of treatment but despite NIH funding and a robust set up was closed about 18 months later due to lack of accrual. As a result, we still have very limited data so consensus guidelines acknowledge and support that adult treatment strategies are likely reasonable to apply to older children presenting within the usual 4.5h window. How tPA should be used in younger children remains unclear.
- Considering endovascular thrombectomy, we similarly have no RCTs. However, we have a growing data set that demonstrates potential utility. As for other specialized treatments, such therapies need to be deployed within a time period and so potential ET needs discussion early.
- The biggest single study we have is the Save ChildS study which was a retrospective, observational, multicenter cohort study, conducted between 2000 and 2018 and synthesising data from 27 European and US stroke centers. The overall results of this study were encouraging. You can see from the graph on the left that for a majority of treated patients, the stroke scale scores reduced after treatment with endovascular thrombectomy with median score of 14 at admission reducing to 4 at day 7.
- The same study also plotted their results against the outcome assessments in adult trials included in the Hermes Meta-analysis trial. You can see here that outcomes are summarized by modified rankin score from 0 to 6 where 0 = no deficit to 6 = death. Noting different end points – discharge and 180 days for the paediatric study and 90 days for the adult study, results in the Save ChildS study suggest that children have potentially better outcomes than adults after ET with almost 90% had a mRS of < 3 at 180 days.
- Looking at our local experience and data, a retrospective study performed in our NSW kids health network identified 166 AIS in NSW. 23.5% large vessel occlusion ie potentially suitable for thrombectomy 1/3 underwent thrombectomy (noting substantial practice change considerations over the studied decade) LVO no ET = poor outcome (73% severe disability or death) LVO with ET = better (ped-mRS all <3, but small sample size)
- The bottom line re endovascular thrombectomy is that from the limited but growing data with have endovascular thrombectomy in pediatric patients with ischemic stroke and large-vessel occlusion is feasible ccomplication rates were low in children undergoing mechanical recanalization treatment (relevant intracerebral hemorrhage in 1 patient only) long-term neurologic outcomes were good in most patients (median mRS score, 1 and median PSOM score, 0.5 at 6 and 24 months) A word on the complication rate. There are increased technical challenges under 5 and more particularly under 2 Morbidity from femoral access in small children is higher than in older children or adults. Post-angiography Doppler–determined arterial occlusion rates are sig- nificantly higher in children weighing less than 10 kg (16%). Increased risk of vasospasm, dissection, and coagulopathic states during angiography are also concerns in young children, particularly those weighing less than 15 kg. Nevertheless, these may be worthwhile risks depending on the clinical picture and we should at least create the conditions that allow us consider it with an expert multidisciplinary stroke team assessment and a discussion with the local IR expert about suitability and technical feasibility.
- In terms of ICU management, the principles are in line with other neuroprotective bundles and principles that apply in adults apply equally in children. These will be applied in various ways depending on the clinical condition of the patient, severity of stroke and interventions that have been performed.
- One area worth a mention is blood pressure management, the approach to which is based on physiological principles rather than outcome based data. Some retrospective data correlates hypertension with in hospital mortality and increased length of hospitalisation and certainly we intend to avoid significant hypertension. Nevertheless, the general approach is to ensure adequate brain oxygenation while mitigating risk of secondary injury and haemorrhagic complications, so the target is somewhere between normotension and mild permissive hypertension with most major centres and consensus guidelines targeting SBP > 50th and treating hypertension 15% over the 95th centile for age. So really, for all aspects of ICU management, the same physiological principles and targets apply other numerical modifications to age appropriate targets.
- Diagnostic delay is not only because the clinical presentations can be subtle and confusing. It’s also because pathways to imaging have been challenging or uncertain, particularly in non tertiary paediatric facilities