Cerebrovascular disease and stroke
- important causes of morbidity and mortality in children
- one of the top 10 causes of childhood death
- 2–5/100 000 children/year for childhood stroke (at least 300 a year in the United Kingdom),
- Neonatal stroke is more common, with an incidence of up to 63 per 100 000 live births.
- Boys are at higher risk than girls
- Peak incidence in the first year of life
- intracerebral haemorrhage (ICH) is the commonest form under 
- subarachnoid haemorrhage (SAH) is more common in teenagers.
 Morbidity and Mortality
- 20% mortality and a high recurrence rate, at least half of the survivors of these events have permanent cognitive or motor disability.
- Compared with ischaemic stroke , mortality is higher (8–40%) and recurrence is lower (in a population-based study, 13% for those with medical aetiologies, mainly acutely, and a 5-year cumulative recurrence rate of 13% for those with unoperated AVMs or tumours9), although functional outcome may be better, although only a quarter of patients have no physical or cognitive impairment.
- AIS and VST are associated with death in 6–16% and 3–8% of patients,respectively, higher in those with premorbid conditions and in the critically ill,while 40–60% of both groups have significant disability.
- Recurrence rates are age and diagnosis dependent: 3% in neonates, 6% (3% cerebral) after VST in children 2 years of age with no evidence for recurrence after neonatal VST, and 10% stroke with an additional 20–35% transient ischaemic events (TIAs) after AIS in childhood.
 Risk Factors
- Certain chromosomal (Down syndrome) and single gene disorders (SCD, homocystinuria)
- Intermediate risk factors include infections, hypertension, anaemia (including iron deficiency),hyperhomocysteinaemia26 and dyslipidaemias including elevated lipoprotein(a). Thrombophilias such as protein C deficiency, anticardiolipin antibodies and the factor V Leiden and prothrombin 20210 mutations are more frequent in ischaemic stroke populations than in controls27 but may be more commonly associated with VST rather than AIS, although some appear to be independent risk factors for recurrent cryptogenic AIS.
- At least a third of cases of childhood stroke occur in the context of infection,and the importance of prior varicella infection as a risk factor for cryptogenic AIS and haemorrhage has recently been recognised and is apparently secondary to direct infection of the arterial wall, although secondary pathophysiologies, including transient protein C and S deficiency, may play a synergistic role.
- High leukocyte count is a risk factor for first haemorrhagic stroke in SCD, as well as being a risk factor for recurrent AIS.
 Haemorrhagic Stroke
 Arterial ischemic stroke
 Venous sinus thrombosis
 Haemorrhagic stroke Cavernous angiomas probably result from venous hypertension and are multiple lesions (intra- or extracranial) in 13% of sporadic and 50% of familial cases. Aneurysms are relatively rare in children; 10–15% are post-traumatic and a similar proportion are mycotic. VST may also cause intracerebral and subarachnoid haemorrhage. For haemorrhagic strokes, underlying conditions which may require active exclusion include hereditary haemorrhagic telangiectasia, polycystic kidney disease, Ehler-Danlos syndrome type IV, anaemia and hypertension as well as bleeding disorders.
 Arterial ischaemic stroke (AIS)
 Extra/intracranial dissection While most anterior dissections are intracranial (60%), most posterior dissections arise extracranially (60%).
 Intracranial arteriopathy TCA probably represents an inflammatory response to infections such as varicella, Borrelia or tonsillitis. MR typically shows small subcortical infarcts with multifocal arterial wall lesions. Moyamoya is the Japanese for “puff of smoke” and describes a cerebral arteriopathy with bilateral severe stenosis/occlusion of the terminal internal carotid arteries (ICAs) associated with the development of basal collateral vessels. It may be primary or secondary to SCD, Down syndrome or cranial irradiation. Moyamoya is an independent risk factor for recurrent stroke and TIA, which are probably reduced after extracranial-intracranial revascularisation.
 Venous sinus thrombosis (VST)VST may lead to venous hypertension, focal cerebral oedema, haemorrhagic infarction, hydrocephalus and pseudotumour cerebri. Although these sinuses may recanalise spontaneously with conservative management (rehydration, antibiotics), acute anticoagulation may be considered, as two trials in adults showed reduced mortality and morbidity and a cohort study in children showed reduced recurrence. Those in whom the risks may be outweighed by the benefits of anticoagulation during periods of risk, for example after relapse of nephrotic syndrome, include children over the age of 2 or with the prothrombin 20210 mutation.
- Also see Cerebral venous sinus thrombosis
 Vein of Galen malformation (VGAM)
Vein of Galen malformation (VGAM)is an embryonic arterio-venous fistula occasionally presenting with catastrophic neonatal heart failure which within centres with an experienced multidisciplinary team may be endovascularly palliated; it is usually inappropriate to manage any associated hydrocephalus separately.
 Sturge Weber syndrome (SWS)
Sturge Weber syndrome (SWS)is characterised by a facial capillary haemangioma and venous angiomata of the leptomeninges/choroids associated with intractable epilepsy (which may require hemispherectomy) and episodic stroke-like episodes leading to progressive hemiplegia and learning disability (reduced with prophylactic aspirin  ).
 Stroke Mimics
- Diagnoses of exclusion
 Hemiplegic migraine
In hemiplegic migraine there may be a family history. EEG usually shows unilateral slow background activity.
 Acute disseminated encephalomyelitis (ADEM)
The demyelination is usually obvious on MRI. Intravenous methyl prednisolone probably reduces the duration of the illness and perhaps improves long term outcome.
- characterised by seizures, disorders of consciousness, visual abnormalities and headaches associated with posterior white matter abnormalities on CT/MRI and has been described after acute chest syndrome in SCD,  after hypertensive encephalopathy and during immunosuppression.
- The majority of patients make a full clinical and radiological recovery after careful treatment of their underlying condition, although infarction in the parieto-occipital or watershed can occur.
- If RPLS is associated with hypertension, the blood pressure should be reduced very slowly to avoid precipitous drops and infarction. *Vertebrobasilar dissection, which may present with ataxia, visual disturbance or coma rather than hemiparesis and which is much commoner in boys,and VST are part of the differential diagnosis and should be excluded on emergency imaging as their treatment and prognosis are different.
 Metabolic stroke
There are often clinical clues to the aetiology of metabolic stroke, for example persistent vomiting, hypoglycaemia or diabetes. Organic acidaemias, urea cycle disorders and mitochondrial disorders can cause stroke-like episodes with imaging abnormalities in an atypical vascular distribution. Homocystinuria and Fabry disease are usually associated with cerebrovascular disease.
 Clinical Presentation
Although stroke in childhood is relatively rare, its clinical presentation is usually obvious to the paediatrician, who can investigate both obvious and subtle presentations and initiate emergency medical management. Hemiplegia, headache, seizure or altered levels of consciousness may all herald a potentially reversible or lethal medical or surgical stroke emergency.
Although stroke is traditionally defined as a neurological deficit lasting for [gt-or-equal, slanted]24 h, many children with a TIA lasting [less-than-or-eq, slant]24 h have had a recent cerebral infarction/haemorrhage on imaging.
In addition to the underlying diagnosis , the time from onset of symptoms to presentation is very useful diagnostically, for example arteriopathy is more likely to present with a stuttering onset, suggesting the need for imaging to exclude dissection , and “thunderclap” headaches may be indicative of a subarachnoid haemorrhage warranting lumbar puncture even if neuroimaging is normal.
Stroke mimics may be benign and require no treatment, but in some cases timely intervention prevents neurological disability or death. Emergency MR provides information that can guide management in individual children.
Children may present in coma, status epilepticus, or with signs of intracranial hypertension or imminent herniation
 Management and investigations
Diagnosis independent management
No studies have specifically examined the effect of the loss of cardio-respiratory integrity on stroke outcome in children. However, based on principles which would be applied to the care of any acutely ill child (ABCD, airway, breathing, circulation, disability) including the maintenance of adequate oxygenation (non-invasively estimated by pulse oximetry), cardiac output, systemic and cerebral perfusion pressure, and tight control of blood glucose and body temperature should be the aim.
- Hypertension should not be treated unless intracranial pressure is monitored if there is a space-occupying lesion, and should only ever be lowered slowly.
- Neurosurgical intervention may be necessary for drainage of a haematoma, ventriculostomy for hydrocephalus or craniectomy for intractable intracranial hypertension.
- Management may be guided by intracranial pressure monitoring, which should be considered in children who remain sedated and in whom there is radiological/clinical suspicion of a space-occupying lesion.
- Seizures in the acute phase should be managed aggressively in accordance with conventional algorithms and local guidelines as they significantly increase the cerebral metabolic rate for oxygen and can thus unfavourably affect the substrate supply–demand balance. *Consideration should be given to continuous cerebral function monitoring in paralysed children.
- Haemorrhagic stroke or AIS with mass effect should be excluded by emergency CT, which might also show some evidence of focal ischaemic damage but often only from 24 h after presentation. If CT is not available immediately at the local site, discussion with a tertiary centre is mandatory and urgent consideration should be given to transfer of the child, even if this can only be achieved safely by intubation and ventilation. The regional PICU should be involved in this decision, as this is an emergency.
- If immediately available, MR with diffusion weighting has advantages over CT as haemorrhage can be diagnosed or excluded , RPLS , hemiplegic migraine and ADEM can be distinguished from ischaemic stroke and venous or arterial pathology can usually be identified and this may alter acute management, which in turn may reduce the extent of the eventual infarct.
- VST may be accompanied by infarction (sometimes haemorrhagic), typically in a parietal, occipital , frontal or thalamic distribution  ; if the diagnosis is not obvious on plain CT or MR, emergency CT or MR venography should be considered for all strokes unless there is obvious arterial pathology, so that anticoagulation can be considered .
- For AIS, if MRA is not diagnostic, T1-weighted spin echo of the neck with fat saturation should be performed to exclude dissection as, again, these patients should be considered for anticoagulation.
- Although there is a 1% risk of stroke, highest with intracranial stenosis , conventional angiography may be required for the diagnosis of small vessel vasculitis, cortical venous thrombosis and sometimes for the diagnosis of dissection , particularly in the posterior circulation, as well as for the pre-surgical anatomical definition of moyamoya , AVM or aneurysm.
 Specific measures
 Haemorrhagic stroke
- ensure optimal intravascular volume, normothermia and normoglycaemia.
- Neurosurgical intervention if necessary for haematoma drainage and the management of complications, including hydrocephalus, vasospasm, perihaematomal oedema and brain shift.
- Intracranial pressure monitoring and osmotherapy targeted at maintaining an adequate cerebral perfusion pressure may be required. *Fluid restriction is not advisable initially but may be initiated if there is evidence of inappropriate ADH release.
- Vasospasm may complicate subarachnoid haemorrhage, is detectable by transcranial Doppler (TCD) and treatable with calcium channel antagonists.
- Blood pressure control is a controversial topic as perfusion pressure must be maintained while the risk of recurrent haemorrhage may mandate avoidance of hypertension before definitive vascular treatment. If there is an underlying AVM or aneurysm, the recurrence risk  means that a vascular team with considerable experience should evaluate and decide between the management options (neurosurgery, neuroradiology or stereotactic radiotherapy) once the patient has recovered from the acute phase.
 Ischaemic stroke
Transfusion for acute stroke in sickle cell disease The population with sickle cell disease provides an ideal model for proactive stroke prevention as the majority of strokes are predicted by TCD. Blood transfusion is a mainstay of stroke prevention  as well as acute stroke management. Transfusion should commence within 2–4 h of presentation with neurological deficit; emergency exchange, rather than top-up, transfusion at the time of first stroke appears to be associated with a reduced risk of recurrence.  The aim is to reduce the HbS % to [less-than-or-eq, slant]30% with a haematocrit of >30%.
Pathology can include haemorrhage,VST, RPLS, acute necrotising encephalitis and arterial dissection as well as territorial infarction secondary to arterial stenosis and “silent” or covert injury, generally in the watershed regions and often associated with transient neurological symptoms and signs rather than overt stroke. If available, emergency MR may guide management.
Thrombolysis with tissue plasminogen activator (tPA)
- Despite a little published experience, which is almost certainly biased in favour of positive outcomes, there is no evidence to support the use of tPA in the acute management of childhood stroke.
- Although children may present <3 h after stroke, its rarity, the low sensitivity of CT for acute infarction and the wide differential in this age group means that very few children are diagnosed in the time window described in adult trials of acute intervention in stroke.
- Generally, thrombolysis is contraindicated. Very occasionally, and only as part of a strict research protocol, thrombolysis, with intravenous tissue plasminogen activator (tPA) within 3 h or intra-arterial tPA within 6 h, may be considered for middle cerebral artery occlusion, or for basilar occlusion, within 12 h, perhaps with balloon angioplasty.
Acute anticoagulation or aspirin
- The use of anti-coagulation remains controversial. Children are probably at less risk of haemorrhage than adults and there is a case for acute anticoagulation in AIS. .
- Anticoagulation with low molecular weight heparin followed by warfarin should certainly be considered in children with confirmed VST (for 3–6 months or until complete recanalisation) or extracranial arterial dissection associated with AIS (for 3–6 months or until evidence of vessel healing).The use of anticoagulation in patients with cardiac embolism is controversial and management should involve expert advice from cardiologists and neurologists.
- The use of aspirin probably reduces AIS recurrence  ; aspirin at a dose of 5 mg/kg/day should be considered acutely after AIS, except where there is evidence of haemorrhage, with subsequent long term prophylaxis, particularly if there is persistent vasculopathy, at 3–5 mg/kg/day.
Management of intractable intracranial hypertension If intracranial hypertension persists or there is evidence of impending herniation despite maximal medical therapy, decompressive craniectomy should be considered for AIS, VST and stroke mimics. Patients with hydrocephalus secondary to large cerebellar infarcts may need ventriculostomy or cerebellectomy.
Rehabilitation and follow-up Physio-, occupational and speech therapists should be available for children soon after stroke as part of the multidisciplinary team. Long term rehabilitation should include cognitive, as well as physical, domains.
 Management flow charts
 Future Research
Further multi-centre, multi-national studies of epidemiology and risk factors for primary and secondary stroke should be urgently undertaken through collaborations such as the International Paediatric Stroke Study. We must then use these observational data to encourage and adequately power randomised interventional studies to establish appropriate evidence based guidelines for the treatment of this potentially salvageable paediatric emergency.
 More resources
- ↑ 1.0 1.1 Zahuranec DB, Brown DL, Lisabeth LD, Morgenstern LB (2005). "Is it time for a large, collaborative study of pediatric stroke?". Stroke 36 (9): 1825-9. doi:10.1161/01.STR.0000177882.08802.3c. PMID 16100029. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16100029.
- ↑ 2.0 2.1 Laugesaar R, Kolk A, Tomberg T, Metsvaht T, Lintrop M, Varendi H et al. (2007). "Acutely and retrospectively diagnosed perinatal stroke: a population-based study.". Stroke 38 (8): 2234-40. doi:10.1161/STROKEAHA.107.483743. PMID 17585082. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17585082.
- ↑ Liu AC, Segaren N, Cox TS, Hayward RD, Chong WK, Ganesan V et al. (2006). "Is there a role for magnetic resonance imaging in the evaluation of non-traumatic intraparenchymal haemorrhage in children?". Pediatr Radiol 36 (9): 940-6. doi:10.1007/s00247-006-0236-9. PMID 16841210.
- ↑ 4.0 4.1 4.2 Fullerton HJ, Wu YW, Sidney S, Johnston SC (2007). "Recurrent hemorrhagic stroke in children: a population-based cohort study.". Stroke 38 (10): 2658-62. doi:10.1161/STROKEAHA.107.481895. PMID 17761928. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17761928.
- ↑ Telfer P, Coen P, Chakravorty S, Wilkey O, Evans J, Newell H et al. (2007). "Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London.". Haematologica 92 (7): 905-12. PMID 17606440.
- ↑ 6.0 6.1 Blom I, De Schryver EL, Kappelle LJ, Rinkel GJ, Jennekens-Schinkel A, Peters AC (2003). "Prognosis of haemorrhagic stroke in childhood: a long-term follow-up study.". Dev Med Child Neurol 45 (4): 233-9. PMID 12647924.
- ↑ 7.0 7.1 Jordan LC, van Beek JG, Gottesman RF, Kossoff EH, Johnston MV (2007). "Ischemic stroke in children with critical illness: a poor prognostic sign.". Pediatr Neurol 36 (4): 244-6. doi:10.1016/j.pediatrneurol.2006.12.014. PMID 17437907. PMC PMC1895601. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17437907.
- ↑ 8.0 8.1 8.2 deVeber G, Andrew M, Adams C, Bjornson B, Booth F, Buckley DJ et al. (2001). "Cerebral sinovenous thrombosis in children.". N Engl J Med 345 (6): 417-23. doi:10.1056/NEJM200108093450604. PMID 11496852.
- ↑ 9.0 9.1 9.2 9.3 9.4 Kenet G, Kirkham F, Niederstadt T, Heinecke A, Saunders D, Stoll M et al. (2007). "Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study.". Lancet Neurol 6 (7): 595-603. doi:10.1016/S1474-4422(07)70131-X. PMID 17560171. PMC PMC1906729. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17560171.
- ↑ 10.0 10.1 10.2 10.3 10.4 Sébire G, Tabarki B, Saunders DE, Leroy I, Liesner R, Saint-Martin C et al. (2005). "Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome.". Brain 128 (Pt 3): 477-89. doi:10.1093/brain/awh412. PMID 15699061. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15699061.
- ↑ 11.0 11.1 11.2 Askalan R, Laughlin S, Mayank S, Chan A, MacGregor D, Andrew M et al. (2001). "Chickenpox and stroke in childhood: a study of frequency and causation.". Stroke 32 (6): 1257-62. PMID 11387484.
- ↑ Sträter R, Becker S, von Eckardstein A, Heinecke A, Gutsche S, Junker R et al. (2002). "Prospective assessment of risk factors for recurrent stroke during childhood--a 5-year follow-up study.". Lancet 360 (9345): 1540-5. doi:10.1016/S0140-6736(02)11520-0. PMID 12443591. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12443591.
- ↑ 13.0 13.1 Sébire G, Meyer L, Chabrier S (1999). "Varicella as a risk factor for cerebral infarction in childhood: a case-control study.". Ann Neurol 45 (5): 679-80. PMID 10319896.
- ↑ 14.0 14.1 14.2 14.3 Miravet E, Danchaivijitr N, Basu H, Saunders DE, Ganesan V (2007). "Clinical and radiological features of childhood cerebral infarction following varicella zoster virus infection.". Dev Med Child Neurol 49 (6): 417-22. doi:10.1111/j.1469-8749.2007.00417.x. PMID 17518925. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17518925.
- ↑ 15.0 15.1 Danchaivijitr N, Miravet E, Saunders DE, Cox T, Ganesan V (2006). "Post-varicella intracranial haemorrhage in a child.". Dev Med Child Neurol 48 (2): 139-42. doi:10.1017/S0012162206000302. PMID 16417671. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16417671.
- ↑ 16.0 16.1 16.2 Strouse JJ, Hulbert ML, DeBaun MR, Jordan LC, Casella JF (2006). "Primary hemorrhagic stroke in children with sickle cell disease is associated with recent transfusion and use of corticosteroids.". Pediatrics 118 (5): 1916-24. doi:10.1542/peds.2006-1241. PMID 17079562. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17079562.
- ↑ 17.0 17.1 17.2 17.3 17.4 17.5 Ganesan V, Prengler M, Wade A, Kirkham FJ (2006). "Clinical and radiological recurrence after childhood arterial ischemic stroke.". Circulation 114 (20): 2170-7. doi:10.1161/CIRCULATIONAHA.105.583690. PMID 17075014. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17075014.
- ↑ 18.0 18.1 18.2 18.3 18.4 18.5 18.6 18.7 Roach ES, Golomb MR, Adams R, Biller J, Daniels S, Deveber G et al. (2008). "Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young.". Stroke 39 (9): 2644-91. doi:10.1161/STROKEAHA.108.189696. PMID 18635845. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18635845.
- ↑ 19.0 19.1 Rafay MF, Armstrong D, Deveber G, Domi T, Chan A, MacGregor DL (2006). "Craniocervical arterial dissection in children: clinical and radiographic presentation and outcome.". J Child Neurol 21 (1): 8-16. PMID 16551446.
- ↑ Ganesan V, Prengler M, McShane MA, Wade AM, Kirkham FJ (2003). "Investigation of risk factors in children with arterial ischemic stroke.". Ann Neurol 53 (2): 167-73. doi:10.1002/ana.10423. PMID 12557282.
- ↑ 21.0 21.1 Maguire JL, deVeber G, Parkin PC (2007). "Association between iron-deficiency anemia and stroke in young children.". Pediatrics 120 (5): 1053-7. doi:10.1542/peds.2007-0502. PMID 17974743. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17974743.
- ↑ Fullerton HJ, Johnston SC, Smith WS (2001). "Arterial dissection and stroke in children.". Neurology 57 (7): 1155-60. PMID 11601431.
- ↑ 23.0 23.1 23.2 23.3 Ganesan V, Chong WK, Cox TC, Chawda SJ, Prengler M, Kirkham FJ (2002). "Posterior circulation stroke in childhood: risk factors and recurrence.". Neurology 59 (10): 1552-6. PMID 12451196.
- ↑ Chabrier S, Rodesch G, Lasjaunias P, Tardieu M, Landrieu P, Sébire G (1998). "Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke.". J Child Neurol 13 (1): 27-32. PMID 9477245.
- ↑ 25.0 25.1 Danchaivijitr N, Cox TC, Saunders DE, Ganesan V (2006). "Evolution of cerebral arteriopathies in childhood arterial ischemic stroke.". Ann Neurol 59 (4): 620-6. doi:10.1002/ana.20800. PMID 16450385.
- ↑ Fung LW, Thompson D, Ganesan V (2005). "Revascularisation surgery for paediatric moyamoya: a review of the literature.". Childs Nerv Syst 21 (5): 358-64. doi:10.1007/s00381-004-1118-9. PMID 15696334.
- ↑ 27.0 27.1 Heller C, Heinecke A, Junker R, Knöfler R, Kosch A, Kurnik K et al. (2003). "Cerebral venous thrombosis in children: a multifactorial origin.". Circulation 108 (11): 1362-7. doi:10.1161/01.CIR.0000087598.05977.45. PMID 12939214. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12939214.
- ↑ 28.0 28.1 28.2 28.3 28.4 Royal College of Physicians Paediatric Stroke Working Group (2010 (accessed 13 Feb)). Stroke in childhood: clinical guidelines for diagnosis, management and rehabilitation. http://www.rcplondon.ac.uk/pubs/books/childstroke/childstroke_guidelines.pdf.
- ↑ 29.0 29.1 29.2 29.3 29.4 29.5 Monagle P, Chalmers E, Chan A, DeVeber G, Kirkham F, Massicotte P et al. (2008). "Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).". Chest 133 (6 Suppl): 887S-968S. doi:10.1378/chest.08-0762. PMID 18574281. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18574281.
- ↑ Fullerton HJ, Aminoff AR, Ferriero DM, Gupta N, Dowd CF (2003). "Neurodevelopmental outcome after endovascular treatment of vein of Galen malformations.". Neurology 61 (10): 1386-90. PMID 14638960.
- ↑ 31.0 31.1 Maria BL, Neufeld JA, Rosainz LC, Drane WE, Quisling RG, Ben-David K et al. (1998). "Central nervous system structure and function in Sturge-Weber syndrome: evidence of neurologic and radiologic progression.". J Child Neurol 13 (12): 606-18. PMID 9881531.
- ↑ 32.0 32.1 32.2 Henderson JN, Noetzel MJ, McKinstry RC, White DA, Armstrong M, DeBaun MR (2003). "Reversible posterior leukoencephalopathy syndrome and silent cerebral infarcts are associated with severe acute chest syndrome in children with sickle cell disease.". Blood 101 (2): 415-9. doi:10.1182/blood-2002-04-1183. PMID 12393443. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12393443.
- ↑ Braun KP, Rafay MF, Uiterwaal CS, Pontigon AM, DeVeber G (2007). "Mode of onset predicts etiological diagnosis of arterial ischemic stroke in children.". Stroke 38 (2): 298-302. doi:10.1161/01.STR.0000254484.10680.c6. PMID 17194885. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17194885.
- ↑ Braun KP, Kappelle LJ, Kirkham FJ, Deveber G (2006). "Diagnostic pitfalls in paediatric ischaemic stroke.". Dev Med Child Neurol 48 (12): 985-90. doi:10.1017/S0012162206002167. PMID 17109788. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17109788.
- ↑ Shellhaas RA, Smith SE, O'Tool E, Licht DJ, Ichord RN (2006). "Mimics of childhood stroke: characteristics of a prospective cohort.". Pediatrics 118 (2): 704-9. doi:10.1542/peds.2005-2676. PMID 16882826. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16882826.
- ↑ Adams RJ, Brambilla D, Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) Trial Investigators (2005). "Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease.". N Engl J Med 353 (26): 2769-78. doi:10.1056/NEJMoa050460. PMID 16382063. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16382063.
- ↑ Hulbert ML, Scothorn DJ, Panepinto JA, Scott JP, Buchanan GR, Sarnaik S et al. (2006). "Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia.". J Pediatr 149 (5): 710-2. doi:10.1016/j.jpeds.2006.06.037. PMID 17095350. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17095350.
- ↑ Janjua N, Nasar A, Lynch JK, Qureshi AI (2007). "Thrombolysis for ischemic stroke in children: data from the nationwide inpatient sample.". Stroke 38 (6): 1850-4. doi:10.1161/STROKEAHA.106.473983. PMID 17431210. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17431210.
- ↑ Sträter R, Kurnik K, Heller C, Schobess R, Luigs P, Nowak-Göttl U (2001). "Aspirin versus low-dose low-molecular-weight heparin: antithrombotic therapy in pediatric ischemic stroke patients: a prospective follow-up study.". Stroke 32 (11): 2554-8. PMID 11692016.
- ↑ King AA, White DA, McKinstry RC, Noetzel M, Debaun MR (2007). "A pilot randomized education rehabilitation trial is feasible in sickle cell and strokes.". Neurology 68 (23): 2008-11. doi:10.1212/01.wnl.0000264421.24415.16. PMID 17548550. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17548550.