Stroke in Children:Clinical Guidelines

Prof Dr Hussein AbdeldayemProf of Ped Neurology, Alex Univ

CASE STUDY

• 4 YS DS with TF• Sudden onset of

hemiplegia

WHO DEFINITION OF STROCK 2004

• “A clinical syndrome in which there is rapidly developing signs of focal or global disturbance of cerebral functions, lasting more than 24 hours or leading to death, with no apparent causes other than of vascular origin”

Definition

• Transient ischaemic attacks (TIAs): ‘where the neurological deficit resolves within 1 hr (previously 24 hours).

Differs from Adult Stroke

• In adult: chronic risk factors • In children: 1- congenital and developmental risk factors 2- rare 3-subtle presentation* 4- wide DD 5- no established tt

*Among neonates, signs of hemiparesis are generally not seen before the first six months to one year of life

incidence

-2.5 – 3.0 children out of 100,000 affected every year. -Newborn babies can develop a stroke 28/100,000- More in boys- Nearly half are hgic stroke

One of the top ten causes of childhood deaths world wide

types

• A hemorrhagic stroke: a ruptured blood vessel bleeding into the brain.

with: headache, disturb consc, vomiting • An ischaemic stroke: +++

51% isch, 49% hgic

80% isch and 20% hgic (adult)

Hgic Stroke

Types (cont. )

• An ischaemic stroke : an embolism or thrombus blocks a blood vessel in the brain ++

EMBOLI: sec thrombus: minutes warning: TIA

Arterial ischaemic stroke: ‘a clinical stroke syndrome due to cerebral infarction in an arterial

distribution’ .

Ischemic Stroke

Thrombus

Embolus

types of stroke

ischemic hemorrhagic

thrombosis embolusStenosisSpasm intraparenchymalsubarachnoid

arterial venous

I Ventricular

Fate Fate

• About 10% of childhood strokes are fatal.

Fate Fate

• Recurrence ( 20-30%)• Motor impairment• Seizures (10-20%)• Language, Communication• Cognition• Headache (30%)• Social interaction• Learning

Motor impairment

• Hemiparesis/hemiplegia• Spasticity (?CP)• dystonia • a mixed pattern

Language and communicationdefects

• language input :(receptive aphasias)• language processing (word-finding problems,

grammatical problems and other aphasias),• speech production ( dysarthria ) • written language (dyslexia).• Mutism: problems of social interaction and the

willingness to communicate

Blood supply of brain

pathophysiology

• Blood supply of the brain

• In children ischemic stroke has been most commonly reported in the distribution of the middle cerebral artery.

Types of stroke (2)

According to time of onset :1- prenatal 2- perinatal2- pediatric

Prenatal and Perinatal stroke

• 17 times more common than pediatric stroke beyond the newborn period. 

• Arterial ischemia occurring during the 3 days surround birth is reported to be responsible for 50% to 70% of congenital hemiplegic cerebral palsy.

• Germinal matrix hge : prone with increase BP

Pathophysiology

• Features of perinatal period that influence coagulation state– Presence of fetal hemoglobins– Fetal proteins– High hematocrit and blood viscosity– Concentrations of procoagulant and anticoagulant

proteins change with gestational and postnatal age

Risk Factors for Perinatal Arterial Stroke

• Infants : Antiprothrombin factors• in the mothers, antiphospholipid antibodies :

anticardiolipin (aCL) antibodies and lupus anticoagulant (LA).,

Prenatal Stroke

• Focal cerebral infarction (stroke) secondary to intrauterine or perinatal thromboembolism related to thrombophilic disorders, especially anticardiolipin antibodies, is an important cause of hemiplegic CP

Nelson Textbook of Pediatrics 18th ed

Prenatal Stroke

• Family histories suggestive of thrombosis and inherited clotting disorders may be present and evaluation of the mother may provide information valuable for future pregnancies and other family members.

Nelson Textbook of Pediatrics 18th ed

Perinatal stroke and the risk of developing childhood epilepsy.

• Childhood epilepsy is frequent after perinatal stroke. Evidence of infarction on prenatal ultrasonography and a family history of epilepsy predict earlier onset of active seizures

J Pediatr. 2007 Oct

Stroke Awareness

• Survival from risky disease : PMT, LK, Cyanotic CHD

• Improving of radiography

CPNeonates - <6 months • Seizures• Irritability, drowsiness, bulge AF, jitterness,

apnea• Focal motor defect ( hemiparesis): >6 mo age

CP> 6 months• As adult: focal motor, ataxia, aphasia

sensation troubles• ICHge: severe headache• SAH: meningism• Developmental delay (17%- SCD)

Potential signs

• Motor Disorder• Sensory • Reflexes

- focal weakness - initial hypotonia then spasticity - Abnormal plantar reflex ( Babinski’s)

Aetiology Cong/Acq/ IdiopathicCONGENITAL: Cardiac, SCD, Coag abnACQUIRED:• 1- TRAUMA/ drug induced• 2-VASCULAR• 3-INFLAMMATORY/autoimmune• 4-NEOPLASM• 5-systemic: METABOLIC, DEHYDRATION &

DEGENERATIVE

Coagulopathies andHematologic Disorders

RBC: SCD, polycythemiaPlatelets: ITP-Thrombocytosis,Protein C deficiency Protein S deficiency Factor V (Laiden) mutationAnticardiolipin antibodiesLupus anticoagulant antithrombin III deficiencyCong coagulation defects 8-9-VWFDICLiver dysfunction with coagulation defects,Vit K defeciencyMalgnancy: Leukemia

Metabolic/syndrome

HomocystinuriaMitochondrial disordersSulfite oxidase deficiencyFabry’s syndromeDSEhler’s – Danlos-Moyamoya syndrome

Hematologic causes

• Sickle cell disease:Overt or silent strokes1-Occlusion of small vessels by deformed sickled

cells2-Membranes of SRC are abnormal ,so have a

pro coagulant activity3-VWF enhances adherence of sickle red cells to

endothelium in cases of high rates of flow (linear sheer stress)

Consequences of Arterial Occlusive Stroke in Sickle Cell Disease

Age: 5 y (1-18y)1-disturbed learning and intellectual problems2 -Neovascularization occurs in the areas that

are left underperfused by the stroke. The network of small, delicate vessels that appear as cloud-like puffs on an arteriogram are called "moyamoya

Moyamoya disease

Basal arterial occlusion with telangectasia

Chronic , progressive, non inflammatory vasculopathy Bilateral slowly progressive occlusion of ICA As occlusion is slowly progressive multiple anastomosis

between external & internal carotid New vascular net work at the base of the brain composed of collaterals(basillar meningeal& choroidal

arteries)

• It is not a disease but secondary to other disorders

Sickle cell anaemiaVSDDown syndromeTOFNFI

MR angiography :telangectasis produces hazy appearance like a puff of smoke ( japanese word :moyamoya)

Moyamoya disease in a 9-year-old boy.

©1999 by Radiological Society of North America

Disorders of coagulation:

1- anticoagulant deficiency Protein cProtein sAT III2- Factor v leiden3- prothrombin mutation

Protein C, Protein S, AntithrombinIII deficiency• Protein C and protein S are inhibitors of factor

V(Leiden) and antithrombin III opposes the normal procoagulant activity of factors II, IX, X, XI, and XII by promoting the irreversible formation of inactive complexes of these factors.

• inherited or acquired

Congenital Heart Disease

Acquired Heart Disease

VSD, ASD, PDAAortic stenosisMitral stenosisCoarctationCardiac rhabdomyomaComplex congenital heart defects as FT

Rheumatic heart diseaseProsthetic heart valveLibman-Sacks endocarditisBacterial endocarditisCardiomyopathyMyocarditisAtrial myxomaArrhythmia

Cardiac causes

Cyanotic heart disease (<2 years)1. Venus sinus thrombosis: polycythemia,

dehydration ,viral illness and iron deficiency anaemia

2. Embolic arterial occlusion in children due to vegetations or RT to LT shunt

Cardiomyopathy , prothetic valve ,endocarditis, cardiac cath and surgical repair

Vasculitis

Meningitis/encephalitisSystemic infection, SLEPolyarteritis nodosaGranulomatous angiitisTakayasu's arteritisRheumatoid arthritisDermatomyositisIBD, HUSDrug abuse (cocaine, amphetamines), Drug induced

Systemic Vascular Disease

Systemic hypertensionVolume depletion or systemic hypotensionHypernatremiaSuperior vena cava syndromeDiabetes

VasoSpastic Disorders

Structural Anomalies of the Cerebrovascular System

MigraineErgot poisoningVasospasm with subarachnoid hemorrhage

Arterial fibromuscular dysplasiaAgenesis or hypoplasia of the internal carotid orvertebral arteriesArteriovenous malformation AVMHereditary hemorrhagic telangiectasiaSturge-Weber syndromeIntracranial aneurysm

Trauma

Child abuseFat or air embolismForeign body embolismCarotid ligation (e.g., ECMO)Vertebral occlusion following abrupt cervical rotationBlunt cervical arterialTrauma: Neck trauma, intraoral trauma

Posttraumatic arterial dissectionArteriographyPosttraumatic carotid cavernous fistulaCoagulation defect with minor traumaAmniotic fluid/placental embolismPenetrating intracranial trauma

Drugs:

AmphetaminesCocaine SympathomimeticsL asparginase

Inflammatory

• Meningitis• Encephalitis (due to vasculitis, venous thrombosis or parenchymal necrosis)( bacterial & varicella)• Local head and neck infection

Sebrie et al 1999

Metabolic

MELAS• 1. Mitochondrial emcephalopathy, lactic acidosis, and

stroke• 2. Point mutation of mitochondrial DNA• 3. Normal developmental milestones in first few years

of life.• 4. Episodic vomiting, lactic acidosis, and proximal

muscle weakness• 5. Stroke syndromes - migranous HA, seizures, or

hemiplegia• 6. Encephalopathy/dementia are progressive.• 7. Hearing loss, visual defects, and

short stature are typical•

Systemic DisorderMetabolic

• Mitochondrial disorder(MELAS):Mitochondrial accumulations and abnormalities

in sm of intramuscular vessels , brain arterioles and in blood vessels of choroid plexus

(mitochondrial angiopathy)

• Fabry’s disease X-linked, defniciency of alpha-galactosidase

angiokeratomas, corneal and lenticular opacities, and painful acroparesthesias ,hypohydrosis,

Vascular complications:(renal failure, cerebral thrombosis.?

Homocystinuria:

Thromboembolic episodes involving both large and small vessels specially brain

Damage to the vascular endothelium and increased platelet adhessivness 2ry to elevated homocystine level

Metabolic Hyperhomocysteinemia

• HC is a highly reactive amino acid toxic to vascular endothelium– Pro-atherogenic and pro-thrombotic effect on

blood vessels• HC can potentiate the auto-oxidation of

LDL• HC is emerging as a potentially modifiable

risk factor for atherosclerosis

prothrombin gene G20210A mutation.

• Prothrombin G20210A mutation is an important prothrombotic condition for venous thrombosis. Recently, some studies have also considered it to be a risk factor for arterial ischemic stroke in children.

J Child Neurol.2007 Mar;22(3):329-31

Clinical presentation

• F:M = 3:2• Girl + headache+ bilateral UMNL signs 1. Sudden hemiplegia of face and limbs associated

with hemianopia ,hemianaesthesia and aphasia recovery may occur followed by new episodes of

focal neurological findings on same or other side2-recurrent TIA with episodic hemiparesis for min or hrs

with no loss of consciousness

Scope of the guidelinesScope of the guidelines

• the diagnosis, investigation and management of acute arterial ischaemic stroke in children beyond the neonatal period

Stroke Guidelines 1st • Families/carers should be given actual

information about their child’s condition as soon as possible after diagnosis . This should be simple and consistent, avoiding technical terms and jargon

• Children should be given information about their condition at an appropriate level .

Stroke Guidelines 2nd Presentation and diagnosis

• All children with acute stroke should be referred to, or have their management discussed with, a consultant paediatric neurologist

Stroke Guidelines 3rd Brain Imaging• Cross-sectional brain imaging is mandatory in

children presenting with clinical stroke • Brain magnetic resonance imaging (MRI) is

recommended for the investigation of children presenting with clinical stroke

Stroke Guidelines 4th

• If brain MRI will not be available within 48 hours, computed tomography (CT) is an acceptable initial alternative

Stroke Guidelines 5th

Further Non-invasive cerebrovascular imaging :- M R Angiography- CT angiography- ultrasound with Doppler techniques- combination

MRV (magnetic resonance venography)

Stroke Guidelines 6th

• All children with clinical stroke should have regular assessment of conscious level and vital signs

• Brain imaging should be undertaken urgently in children with clinical stroke who have a depressed level of consciousness at presentation or whose clinical status is deteriorating

History

Subsequent Lab

• CBC (WBC, RBC*, Platelets)• Electrolytes• PT/PTT• Liver functions• Lipid profiles• ESR• Echocardiograph: Transthoracic cardiac

echocardiography • * CSF examination

Initial Lab

*Hemoglobin electrophoresis

Stroke Guidelines 8th

Echocardigram: - for congenital and acquired cardiac disease- Transthoracic cardiac echocardiography should

be undertaken within 48 hours after presentation in all children with arterial ischaemic stroke

A lumbar puncture

• LP will screen for metabolic derangements and CNS inflammatory and infectious disorders.

• Prothormbic tendency factors• Other relevant tests

SubsequentLab

prothrombotic Factors• protein C deficiency • protein S deficiency• Antithrombin III• Factor V Leiden• antiphospholipid antibodies:anticardiolipin (aCL) antibodies and lupus anticoagulant (LA)., • activated protein C resistance • lipoprotein-associated phospholipase A2 (Lp-PLA2)*• high-sensitivity C-reactive protein (hs-CRP) * • increased plasma homocysteine ( & urine)• prothrombin G20210A and MTHFR TT677 mutations and A

1298C

*FDA approved for stroke recurrence

• homocysteine levels, levels of protein C,S,and antithromin III, Leiden factor V, RPR, C reactive protein/ESR,lipid panel, troponin, creatinine kinase, electrolytes, glucose, HbA1C, diffusion weighted and perfusion weighted MR, transesophageal echocariogram, EKG with rhythm strip, CBC with platelets, chest X ray?

Other relevant tests

• ANA• HIV• Lactic acid, pyruvic acid ( blood , CSF)

Acute careAcute care

• General measures• Specific measures• Prevention/prophylaxis

Recovery after stroke depends on the severity of the stroke and the speed of treatment

• General measures• Specific measures• Prevention/prophylaxis

Recovery after stroke depends on the severity of the stroke and the speed of treatment

Acute caregeneral measures Stroke Guidelines 9th

Acute caregeneral measures Stroke Guidelines 9th

• Hospital• ABCD care• Temperature should be maintained within

normal limits• Oxygen saturation should be maintained

within normal limits

Acute caregeneral measures Stroke Guidelines 10th

Acute caregeneral measures Stroke Guidelines 10th

• i - swallowing safety • ii-feeding and nutrition• iii-communication • Iv- pain• v-moving and handling requirements • vi- positioning requirements• vii- risk of pressure ulcers

Acute caregeneral measuresAcute caregeneral measures

Pain:• Children affected by stroke should be assessed

for the presence of pain using non verbal technique

• All pain should be treated actively, using appropriate measures including positioning, handling, and medication

Reduce intracranial tension : mannitol IV

Specific treatment

Acute care specific medical treatments (cont.)Acute care specific medical treatments (cont.)

If diagnosed within 3 hrs: • Thrombolytics: streptokinase, tissue

plasminogen activator (tPA)

Acute care specific medical treatmentsAcute care specific medical treatments• Aspirin (5 mg/kg/day)* should be given once

there is radiological confirmation of arterial ischaemic stroke, except in patients with evidence of intracranial haemorrhage on imaging and those with sickle cell disease

- LMWH (1 week) - Warfarin ( for 6 months)

*max 300 mg

• Aspirin (5 mg/kg/day)* should be given once there is radiological confirmation of arterial ischaemic stroke, except in patients with evidence of intracranial haemorrhage on imaging and those with sickle cell disease

- LMWH (1 week) - Warfarin ( for 6 months)

*max 300 mg

SCD stroke

1- exchange transfusion2- prevention: repeat transfusion 4-6 weeks to keep

hemoglobin S <20- 30%

• Neonate + noncardioembolic AIS do not use anticoagulant or aspirin

• Neonate+cardioembolic AIS use anticoagulant therapy (UFH or LMWH ) for 3 months

• Child+AIS treat with anticoagulant for 5-7 days or until cardio-embolic or vascular dissection has been excluded.

Antithrombotic therapy in children: the Seventh ACCP Conference on Antithrombotic Chest 2004 Sep;126 (3 Suppl):645S-687S.

Acute care specific medical treatments (cont.)Acute care specific medical treatments (cont.)

• Treatment of underlying cause

A Cardiac Source of Embolism and AIS

• The decision to use anticoagulation should be discussed with a consultant paediatric

cardiologist and paediatric neurologist

3- prevention Stroke recurrence3- prevention Stroke recurrence

• Arterial ischaemic stroke recurs in between 6% and 20% of all children.

• The risk of recurrence* is increased in children with multiple risk factors and in those with protein C deficiency, increased levels of lipoprotein (a) and vascular disease

*(Lanthier et al2000)

Stroke recurrence Stroke Guidelines 11th 1- Aspirin

Stroke recurrence Stroke Guidelines 11th 1- Aspirin

• Patients with cerebral arteriopathy other than arterial dissection or moyamoya syndrome or those with sickle cell disease should be treated with aspirin (1–3 mg/kg/day)

Stroke recurrence prevention 2- AnticoagulationStroke recurrence prevention 2- Anticoagulation

• should be considered:1- until there is evidence of vessel healing, or for a

maximum of six months, in patients with arterial dissection

2- if there is recurrence of arterial ischaemic stroke despite treatment with aspirin

3- in children with cardiac sources of embolism, following discussion with the cardiologist managing the patient

4- until there is evidence of recanalisation or for a maximum of six months after cerebral venous sinus thrombosis

Stroke recurrence In children with sickle cell disease:Stroke recurrence In children with sickle cell disease:

• should be considered:1- regular blood transfusion (every three to six weeks)

should be undertaken to maintain the HbS% <30% and the Hb between 10–12.5 g/dl (C)

2- transfusion may be stopped after two years in patients who experienced stroke in the context of a precipitating illness (eg aplastic crisis) and whose repeat vascular imaging is normal at this time (C)

3- after three years a less intensive regime maintaining HbS <50% may be sufficient for stroke prevention(C)

Stroke recurrence Stroke Guidelines 12th moyamoya syndrome

Stroke recurrence Stroke Guidelines 12th moyamoya syndrome

• Children should be referred for evaluation to a centre with expertise in evaluating patients for surgical re-vascularisation

Stroke recurrenceStroke recurrence

• Advice should be offered regarding preventable risk factors for arterial disease in adult life, particularly smoking, exercise and diet

• Blood pressure should be measured annually to screen for hypertension

• Advice should be offered regarding preventable risk factors for arterial disease in adult life, particularly smoking, exercise and diet

• Blood pressure should be measured annually to screen for hypertension

DD of stroke like events

1- Alternating hemiplegia:2-18 month, intermittent episodes of hemiplegia from

one side to the other associated with choreoathetosis and dystonia for min or weeks and then resolve ,occasionally associated with migrain

Progressive MR and developmental disabilities , poor prognosis

Radiology & lab are free

• Todds paralysis• Stroke like episodes: migraine • Focal post viral encephalitis, ADAM, HIV• hyperlipidemia• Familial hemiplegic migraine

Rehabilitation Use of assessment measures

• The assessment tools selected should be appropriate for the child’s age and developmental and functional level

Goal of Rehabilitation

• Help children with physical disabilities improve FUNCTION and PARTICIPATE more fully in family, social, educational and recreational activities.

Rehabilitation Tools

• Motor and cognitive exercises• Medications• Injections• Braces• Adaptive equipment• Referral to therapies• Referral to surgeries• Recreational involvement

• Child +AIS+cardioembolic treat with anticoagulant 5-7 days followed by oral anticoagulant for 3-6 mon

• ALL children +AIS TREAT WITH aspirin 2-5 mglkglday after the anticoagulant therapy

- Prevention of recurrence:Low dose aspirin or oral anticoagulant for long

term prophylaxis in certain conditions?

1. Cardiac emboli2. Disecting aneurysm3. Severe prothrombotic conditions4. High grade cerebral artery stenosis

3 -treatment of underlying cause

a) For SCD:Exchange transfusionFrequent transfusionBone marrow transplantHydroxy urea

• Moyamoya: consider revascularization

• Prothrombotic :consider anticoagulant

• For others :low dose asprin

• 4- rehabilitation therapy:Speech , physiotherapy, occupational

&psychotherapy