Stroke in Children

Paediatric Clinical Guideline Emergency: 4.8 Stroke in Children

Short Title: Stroke in Children

Full Title: Guideline for the management of stroke in children and young people

Date of production/Last revision: January 2008

Explicit definition of patient group This guideline applies to all children and young people under the age of 19 to which it applies: years.

Name of contact author Dr Bhupendra Singh, Paediatric SpR Dr William Whitehouse, Consultant Paediatric Neurologist Ext: 64476 Revision Date January 2011

This guideline has been registered with the Trust. However, clinical guidelines are 'guidelines' only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date. Stroke in Children

Introduction Cerebrovascular disease or stroke in children is uncommon. The incidence is 5/100,000 children/year.1 The diagnosis can often be established with modern neuroimaging techniques. Identification of an underlying cause is essential and evaluation should proceed in an organised fashion to identify any potentially treatable disorder. 2

Definitions

 Stroke is a focal or global neurological deficit lasting more than 24 hours having a vascular basis.3,4  Transient Ischaemic Attack (TIA) is a similar episode, but lasting for a shorter period of time.4  Stroke-like-episode is a focal neurological deficit lasting more than 24 hours for which a vascular component cannot be excluded.4

Stroke should be suspected in all cases of acute onset focal neurological deficit unless there is another cause evident clinically.

Predisposing Conditions/Aetiology

Cryptogenic- in around 10% of the cases no cause or predisposing factor is identified despite extensive investigations.

Ischaemic Stroke  Heart disease- congenital or acquired  Sickle cell disease  Trauma e.g. arterial dissection  Infection, e.g. tuberculous or bacterial meningitis, Herpes simplex encephalitis (HSV), HIV, Mycoplasma, Chlamydia pneumoniae.  Dehydration  Metabolic, e.g. homocysteinuria and other causes of homocysteinaemia, Mitochondrial Encephalopathy with Lactic Acidosis and Stroke like syndrome (MELAS)  Moyamoya

Bhupendra Singh Page 1 06/04/2018 Paediatric Clinical Guideline Emergency: 4.8 Stroke in Children  William syndrome, Down’s syndrome (both associated with Moyamoya and aortic arch anomalies)

Haemorrhagic Stroke  Coagulation Disorders- congenital or acquired  Immune thrombocytopenic purpura (ITP)  Cerebrovascular structural anomalies, e.g. arterial aneurysms, arteriovenous malformations

Differential Diagnoses  Tumour  Traumatic extradural or subdural haemorrhage  Focal encephalitis  Demyelinating conditions e.g. acute disseminated encephalomyelitis (ADEM)  Todd’s paralysis following focal epileptic seizures  Hemiplegic migraine

Clinical Presentation

Stroke in children can present with specific symptoms and signs indicating involvement of a particular vascular territory (e.g. anterior circulation or posterior circulation). Generally the impairment is very acute (sudden), e.g. on waking from sleep, or with a collapse. But it can also present with a wide range of non-specific signs and symptoms e.g. headache, seizures with or without an associated focal neurological deficit, altered consciousness etc.

Features of anterior circulation stroke Features of posterior circulation stroke Acute hemiplegia +/- numbness Acute hemiplegia +/- numbness Apraxia Hemianopia Hemianopia (spared in capsular stroke) Ataxia Dysphasia (spared in capsular stroke and Vertigo usually in right hemisphere/cortical stroke) Diplopia Headache Squint Nausea Dysphasia Hemichorea Dysarthria Thalamic pain Headache Nausea

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Neuroimaging  Discuss urgently with the Neuroradiologist.  Some cases of ischaemic arterial stroke (IAS), who present within a certain time from the onset of stroke (see appendix) may require urgent intra-arterial thrombolysis; hence time can be crucial in their management.  The algorithm on the following page is recommended as a guide for neuroimaging:

Urgent CT Head to identify significant haemorrhage

MRI/MRA T1 weighted spin echo of the neck with fat saturation sequence to identify dissection within 24hours

Anterior Posterior Venous Vertebrobasilar Circulation Circulation Infarction Infarction Infarction in child Infarction in >10yrs Child >10yrs presenting within presenting within 3 hrs of onset 24hrs

Urgent catheter MRV with Lateral C spine angiogram/ VENDI X-ray to screen thrombolysis sequence for arcuate

Figure 1 - Guide to Neuroimaging in Stroke in Children

 Repeat neuroimaging: each case needs to be discussed with Neuroradiologist and Paediatric Neurologist. General recommendations are as follows: - Repeat MRI and MRA after 6 months in cases of arterial dissections - Repeat MRI with contrast after 3 months in haemorrhagic stroke

Other investigations:  Thrombophilia screen should be performed on all children with ischaemic stroke.3,8  Thrombophilia screening should not be routinely requested in patients with TIAs.  MTHFR TT677 gene to be done only when Homocysteine is raised.

Type/colour of bottle Priority/urgency Investigations FBC, ESR, Haemoglobin 1 full paediatric EDTA On admission electrophoresis (if appropriate) (purple top) U & E 1 paediatric Li-heparin On admission (green top) Thrombophilia screen 2 adult citrate On admission/ before Coagulation profile (blue top) commencing Protein C & S Antithrombin 3 + 1 paediatric clotted anticoagulation Factor V Leiden mutation (red top) (otherwise will be Prothrombin 20210 gene, Thermo labile methylene to haematology delayed till 6 weeks after tetrahydrofolate reductase stopping) gene (MTHFR TT677) *, Lupus anticoagulant Anticardiolipin antibodies, 1 paediatric clotted Can be done next day Autoantibodies screen (red top) to immunology Total homocysteine 1 Paediatric Li-heparin Can be done next day Fasting cholesterol (green top) Triglycerides to clinical chemistry Lp(a) lipoprotein Antibody titres for 1 full paediatric clotted Can be sent next day Herpes (red top) Mycoplasma sample to microbiology Chlamydia pneumoniae, Helicobacter pylori Borrelia burgdorferi 2,8 These are only indicated, when infection is suspected Urine analysis (if clinical Bed side dip-stick suspicion of nephrotic syndrome) ECG, Cardiology south Within 48 hrs Precordial echocardiography

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General measures  Maintain ABC  Use Glasgow Coma Scale (GCS) or child’s GCS 9 while assessing level of consciousness (see appendix 1)  Admit to PICU if consciousness is deteriorating or in coma (GCS 8 or less)  Control seizures  Maintain temperature between 36.5 – 37.0 0C 3,8  Monitor BP and optimise it  Minimal handling  Fluid therapy- Restrict to 60% of normal fluid requirements if there are concerns about cerebral oedema or SIADH; otherwise normal maintenance. For sickle cell disease patients discuss with Paediatric Haematologist and Paediatric Neurologist as fluid management may vary from case to case.

Immediate anticoagulation Indications include  Ischaemic arterial stroke (IAS) due to extracranial or intracranial dissection  Venous infarction - can be considered even if haemorrhagic (discuss with on-call Paediatric Neurologist through QMC switch board. If no on-call local neurologist, contact Sheffield or other centres).  IAS with cardiac source of embolus - discuss with Cardiologist and Neurologist as there is risk of intracranial haemorrhage  Cerebral venous sinus thrombosis  Patients with known prothrombotic disorders

Systemic anticoagulation: We suggest low molecular weight Heparin (Enoxaparin) for 3-6 months, as this is possibly safer and easier to manage.

Age Dose of subcutaneous Enoxaparin 10 < 2months 1.5 mg/kg twice a day > 2 months 1 mg/kg twice a day

Alternatively, full heparinization acutely (see separate guideline) followed by Warfarin for 3-6 months (aim for INR 2.0-2.5).

Antiplatelet therapy Indications:  IAS where anticoagulation is not used  Available agents: o Aspirin: 1- 5 mg/kg/day (maximum 75 mg).3, 8 o Dipyridamole: in addition or as an alternative as a second line after discussion with Neurologist. 10 . 2.5 mg /kg bd for 1month – 12 years and . 100-200 mg 3 times a day for 12 –18 years old (also available as modified release 200 mg capsules, to be used as twice a day)  Clopidogrel- being used in combination with Aspirin in adults. It can be considered in older children in discussion with the Neurologist.

Stroke in sickle cell disease 3,8  See Sickle cell protocol for more detailed information.  Fluid management: normal or hyperhydration - discuss with consultant Haematologist and Neurologist.  Urgent exchange transfusion to reduce HbS <30% and raise Hb to 10-12.5 gm/dl

Bhupendra Singh Page 5 06/04/2018 Paediatric Clinical Guideline Emergency: 4.8 Stroke in Children  If the patient has had a neurological event in the context of severe anaemia (e.g. splenic sequestration or aplastic crisis), or if exchange transfusion is going to be delayed for more than 4 hours, urgent top up blood transfusion should be considered.  (please see sickle cell disease policy)

Those with haemorrhage: May need neurosurgical advice  Discuss conventional 4 vessel angiography, if no bleeding diathesis, with the Neurosurgeon and Neuroradiologist.  Will still need to consider causes e.g. infection or haemorrhagic infarction (as above)  Repeat MRI with contrast 3 months later

Urgent Neurosurgical referral: for consideration of decompression or drainage if  Haemorrhagic stroke  Cerebellar stroke presenting in coma

Those with no infarct:  Discuss with Neurologist, consider post-epileptic seizure (Todd’s paresis especially in pre-school age group) or hemiplegic migraine.  Please note: Cases with initial normal MRI could still have ischemic stroke or TIA, unless DWI was definitely normal.

Secondary Prevention of Stroke Risk of recurrence is 6-20% in AIS and up to 60% in children with Sickle Cell disease.3

Aspirin prophylaxis: Patients with cerebral arteriopathy other than arterial dissection or Moyamoya syndrome or those with Sickle Cell disease should receive Aspirin (1-5 mg/kg/day, up to a maximum dose of 75 mg/day). 3, 4, 8 Length of treatment to be discussed with Paediatric haematologist and Neurologist on case to case basis.

Continuing anticoagulation: should be considered (length to be discussed with Paediatric haematologist and Neurologist on case to case basis), i) until there is evidence of vessel healing, or for 3-6 months in patients with arterial dissection ii) if there is a recurrence of AIS stroke despite treatment with aspirin and /or dypyridamole iii) in children with a cardiac source of embolism, following discussion with the Cardiologist managing the patient iv) until there is evidence of recanalisation or for 3-6 months after cerebral venous sinus thrombosis

Secondary prevention children with Sickle Cell disease 3,8 Discuss with their Haematologists.

Preventable risk factors:  Advice should be offered regarding preventable risk factors for arterial disease in adult life, particularly smoking, exercise and diet.3,8  Blood pressure should be measured annually to screen for hypertension. 3,8  Patients with prothrombotic disorders: should be referred to a Haematologist. 3,8

Early Disability Assessment and Management 3,8 As soon as possible after admission, all children following stroke should have an evaluation of:  swallowing safety  feeding and nutrition  communication  pain  moving and handling requirements  positioning requirements  risk of pressure ulcers  All children affected by stroke should have a multidisciplinary assessment at about 3- 4 weeks.

References 1. De Veber G. In pursuit of evidence-based treatments for paediatric stroke: the UK and chest guidelines. Lancet Neurology 2005; 4:432-6.

2. Anthony R Riela, E Steven Roach. Aetiology of Stroke in Children, Journal of Child Neurology, 1993; 201-220

3. Intercollegiate working party for paediatric stroke. Clinical guidelines for diagnosis and management of acute stroke in childhood. 2004, Royal College of Physician, London.

4. F J Kirkham. Stroke in Childhood, Archives of Diseases in Childhood, 1999; 81-89

5. Steven G Pavlakis, Peter B Kingsley, Martin G Bialer. Stroke in Children: Genetic and Metabolic Issues, Journal of Child Neurology, 2000; 15: 308-314

6. Fenella J Kirkham, M P Prengler, D K M Hewes, V Ganesan. Risk factors for arterial iscaemic stroke in children, Journal of Child Neurology 2000; 15: 299-307.

7. K E Cushing, V Ramesh, N V Todd, A Gholkar, P Baxter. Tethering of the vertebral artery in congenital arcuate foramen of atlas vertebra: possible cause of vertebral artery dissection in children: Developmental Medicine & Child Neurology 2001; 43 :491-496

8. RCPCH guideline appraisal. Clinical guidelines for diagnosis and management of stroke in children, 2004; www.rcpch.ac.uk/publications/clinical_docs/stroke

9. A Tatman, A Warren, A Williams, JE Powell, W P Whitehouse. Development of a modified paediatric coma scale in intensive care clinical practice. Archives of Diseases in Childhood 1997; 77; 519-521.

10. BNF for children 2005, BMJ Publishing Group Limited, London.

11. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. New England Journal of Medicine.1995; 333: 1581-1587 .

Dr Bhupendra K Singh (SpR) Dr WP Whitehouse (Paediatric Neurologist)

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Modified Glasgow Coma Scale

Pain as nail bed pressure with pencil or press on supra-orbital notch with thumb; score best response

Adult and child > 5 years Child < 5 years

Eye opening E4 spontaneous As older child E3 to verbal stimulus As older child E2 to pain As older child E1 no response to pain As older child Verbal V5 orientated Alert, babbles, coos, words or sentences to usual ability V4 confused Less than usual ability or spontaneous irritable cry V3 inappropriate words Cries to pain V2 incomprehensible sounds Moans to pain V1 no response to pain No response to pain VT intubated Intubated Grimace G5 spontaneous normal As older child facial/oromotor activity, for example sucks tube, coughs G4 less than usual spontaneous ability As older child or only responds to touch G3 vigorous grimace to pain As older child G2 mild grimace or some change in As older child facial expression to pain G1 no response to pain As older child Motor M6 obeys commands Normal spontaneous movements M5 localises to pain stimulus As older child or withdraws to touch M4 withdraws from pain As older child M3 abnormal flexion to pain As older child M2 abnormal extension to pain As older child M1 no response to pain As older child

Arch. Dis. Child. 1997; 77; P 519

Appendix 2 IV or intra-arterial anticoagulation: For IAS of <3 hours duration (anterior circulation) and <24 hours duration (posterior circulation), IV or intra-arterial tPA can be considered.11 Urgent discussion with Paediatric Neurologist and Neuroradiologist is needed. If the patient is in a peripheral hospital, will need transfer to the QMC as soon as possible.

Appendix 3 Infarction in atypical distribution 4 .  CSF (when safe to LP) for lactate, glucose, protein, microscopy, culture and sensitivity, viral cultures and antibody titres, in particular for Varicella zoster, HSV  Plasma ammonia and amino acids (2 ml Li Heparin)  DNA for mitochondrial mutations i.e. MERFF, MELAS and NARP (2 ml EDTA)  Urine organic and amino acids  Consider MR spectroscopy

Appendix 4 Surgical revascularisation: Children with Moyamoya syndrome (including those with Sickle Cell disease) should be referred to the Paediatric Neurosurgeons for evaluation for surgical revascularisation.3,8

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