1. بسم اللة الرحمن الرحيم

2. Presented by Yasser Hamed MD Neurology
In Children Stroke
Presented by Yasser Hamed MD Neurology

3. Pediatrics is the branch of medicine that deals with the medical care of infants, children, and adolescents, and the age limit up to 18 (in some places until age 21 as in the United States)
Pediatric stroke is an important cause of long-term disability, with children often living for many years with significant neurological deficits.
In children, 55% of strokes are ischemic, in contrast to adults in whom 80–85% of all strokes are ischemic.

4. Strokes in children differ from those in adults in three important ways:
Predisposing factors (In children, congenital and acquired heart disorders, hematologic conditions are common causes. In contrast, hypertension, smoking and hypercholesterolemia are more common predispositions in adults..
Clinical evolution (children often improve much more than an adult with a comparable lesion because of the abundant collateral circulation or because of the differences in response of the immature brain to the lesion).
Anatomic site of pathology (children commonly show occlusion of the intracranial portion of the internal carotid artery, whereas adults more frequently show extracranial occlusions of the internal carotid).

5. Epidemiology
The reported incidence of pediatric stroke ranges from 1.2 to 13 cases per 100,000 children under 18 years of age.
In Egypt (Al kharga District), the incidence of pediatric stroke was 4/100,000 and prevalence was 26/100,000 children under 20 years of age..
However, pediatric stroke is likely more common than that reported as it is thought to be frequently undiagnosed or misdiagnosed.
In one report, 19 out of 45 children with a stroke did not receive a correct diagnosis until 15 hours to 3 months after initial presentation.

6. Stroke is more common in boys than girls.
Stroke is appear to be more predominant in black children.
This difference may be attributed to sickle cell anemia.

7. Risk Factors and Causes
Cardiac (CCHD, VSD, ASD and RHD) are the most common cause of stroke in childhood, accounting for up to a third of all AIS.
Hematologic
Sickle cell disease (SCD) is a very common cause of stroke.
AIS is more common in the younger age whereas hemorrhagic strokes occurs more frequently in older children and adults.
Children with SCD develop all types of ICH

8. Hypercoagulable disorder including antithrombin III, protein C & S deficiencies, factor V Leiden mutation, elevated levels of lipoprotein (a) and antiphospholipid antibody syndrome.
It is suspected in individuals with recurrent DVT, recurrent pulmonary emboli, or a family history of thrombotic events or if thrombotic events occur during childhood or adolescence.
Hemophilia A (factor VIII deficiency) and B (factor IX deficiency) are the two most common hereditary bleeding disorders that cause intracranial hemorrhage.
Vitamin K deficiency results in decreased factors II, VII, IX, and X.
Thrombocytopenia results from either immune thrombocytopenic purpura (ITP) or the combined effects of leukemia or its treatment. Nontraumatic brain hemorrhage does not usually occur with platelets counts above 20,000 to 30,000,

9. Infection
Varicella infection within the past year can result in basal ganglia infarction.
HIV infection can cause stroke secondary to HIV-induced vasculitis, vasculopathy with subsequent aneurysms, or hemorrhage in the context of immune thrombocytopenia
Vascular
Arteriovenous malformations (AVM) are the most common cause of hemorrhagic stroke, but can also cause thrombotic stroke. AVM may be associated with neurocutaneous syndromes such as Sturge-Weber disease, tuberous sclerosis and neurofibromatosis.
Moyamoya is another important vascular cause of childhood stroke and is associated with conditions such as Down syndrome, neurofibromatosis, and sickle cell disease.

10. Syndromes and Metabolic Disorders
Marfan syndrome are at risk of ischemic stroke.
Homocysteinuria can cause AIS and should be suspected in the presence of mental retardation associated with lens dislocation and occasionally pectus excavatum.

11. Vasculitis
Cerebral vasculitis is a less common cause of stroke in children, and is more common in children older than 14 years of age. Although idiopathic vasculitis is most often diagnosed, signs and symptoms of systemic vasculitides with Kawasaki disease, Henoch-Schnlein Purpura (HSP), polyarteritis nodosa, Takayasu’s arteritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, sarcoidosis, Sjogren syndrome, or Behcet disease should be considered

12. Oncologic
Children with cancer are at increased risk for AIS as a result of their disease, subsequent treatment, and susceptibility to infection.
Intracranial hemorrhage may complicate an intracranial tumor.
Leukemia and lymphoma create a hypercoagulable state.
L-asparaginase decreases antithrombin levels, and may trigger venous thrombosis.
Radiation therapy for brain tumours can cause vasculopathies.

13. Trauma
Dissection of the carotid or vertebral arteries resulting from hyperextension or rotational injuries of the neck.
Symptoms of traumatic arterial dissection can be delayed by 24 hours, and the risk is greatest within a few days of the vascular injury.
Drugs
Cerebral infarcts and hemorrhage have been reported in patients abusing drugs such as amphetamines, cocaine and glue sniffing.
Stimulants and heroin can also cause vasculopathies.
Adolescent girls using oral contraceptives are at higher risk of cerebral venous thrombosis.
Overuse of ergot alkaloids are also associated with increased risk of ischemic events.

14. Clinical Presentation
AIS most often presents as a focal neurologic deficit. Hemiplegia is the most common focal manifestation, occurring in up to 94% of cases.
Hemorrhagic strokes most commonly present as headaches or altered level of consciousness.
Seizures are common in both ischemic and hemorrhagic strokes.

15. There can be significant differences in the clinical presentation based on the child’s age.
Neonatal strokes present with focal seizures or lethargy.
Infants present with lethargy, apnea spells, or hypotonia.
Toddlers present with deterioration of their general condition, increased crying and sleepiness, irritability, feeding difficulty, vomiting, and sepsis-like symptoms with cold extremities.
Older children demonstrate more specific neurological defects similar to adults.

16. Differential Diagnosis
Hemiplagic migraine.
Focal seizures associated postictal hemiparesis (Todd’s Paresis).
Intracranial neoplasms.
Trauma as extradural, subdural, SA and intracerebral haematoma.
Intracranial infections such as meningitis, brain abscess, and herpes simplex encephalitis.
Metabolic abnormalities like hypoglycemia, CADASIL and MELAS syndrome.

17. Diagnostic Evaluation Ischemic Stroke:
A- Imaging
Noncontrast head CT to exclude a hemorrhagic stroke.
Diffusion-weighted MRI of the brain is the most sensitive method to diagnose acute AIS.
MRA head, neck.
MR Venogram (especially consider with sickle cell disease).
CT angiography. MRA may be preferable to CTA
Other investigations as ultrasound to evaluate the extracranial carotid circulation, ECG, chest radiograph, and transthoracic or transesophageal echocardiography.

18. B- Laboratory: Prothrombin time and concentration, INR.
Antithrombin, factor V Leiden, protein C&S.
Lipid profile, CBC and C-reactive protein levels.
Tests for vasculitis (ESR, antinuclear antibodies, antidouble strand antibodies, lupus anticoagulant and anticardiolipin antibodies).

19. A- Recommended universal supportive measures
Fever control (hypothermia should not be used in children with stroke);
Normalization of serum glucose;
Maintenance of normal oxygenation;
Ameliorate increased intracranial pressure;
Treat dehydration;
Correct anemia;

20. B- Blood pressure management
The AHA guidelines suggest “control of systemic hypertension” in children with AIS and hemorrhagic stroke.
Specific guidelines for blood pressure values are absent.

21. C- Anticonvulsants and EEG monitoring
Seizures are a common complication of pediatric stroke, affecting up to 25% with AIS and up to 20% with ICH. When they occur, seizures should be treated aggressively.
Prophylactic anticonvulsants are often used in the setting of intraparenchymal or subarachnoid hemorrhage in adults, although this approach is not evidence-based practice.
The AHA pediatric stroke guidelines recommend against prophylactic anticonvulsant use in ischemic stroke but do not make recommendations in the setting of hemorrhagic stroke.

22. D- Management of intracranial pressure
Nonsurgical methods
Keeping the head of a patient’s bed at 30°.
Hyperventilation to a pCO2 of 25–30 mmHg.
Hyperosmolar therapy—with either mannitol or hypertonic saline.
In some cases, sedation may be required to help manage elevated ICP.
Corticosteroids should be avoided.

23. Surgical
An intraventricular catheter (IVC) providing both a means to measure ICP and, via drainage of cerebrospinal fluid.
Hemicraniectomy may be both life-saving and function- sparing in adults with a large AIS who progress to signs and symptoms of impending herniation.
In children, study of 10 children with malignant middle cerebral artery infarction, seven underwent hemicraniectomy, all of whom survived and had moderately good recovery.

24. AIS-specific treatments
A- Antiplatelet
I- Aspirin
For all older children with ischemic stroke except kids with sickle cell disease
Typical dose is 3-5 mg/kg/day. This dose can be reduced to 1 to 3 mg/kg for long-term prophylaxis.
Risk of Reye’s syndrome is very low. It recommend to discontinue or reduce dose to half during febrile illness.
It recommend to vaccinate for varicella and give an annual influenza vaccine.
II- Clopidogrel
For children unable to take aspirin.
Typical dose is 1mg/kg/day.

25. B- Anticoagulant
I - UH with loading dose 75 units/kg IV followed by 20 units/kg/hour for children over 1 year of age or 28 units/kg/hour below 1 year of age. The target APTT is 60 to 85 seconds.
II- LMWH doses of 1 mg/kg every 12 hours or in neonates, 1.5 mg/kg every 12 hours.
III- Warfarin with target of INR 2.5 to 3.5.

26. Consider if suspicion high for cardioembolic stroke, arterial dissection, posterior circulation stroke.
According to the Australian AIS treatment guideline, for children with confirmed AIS, UH or LMWH is recommended in the first 5 to 7 days until the evaluation for underlying etiologies and risk factors is completed.
Children are continued on either oral or subcutaneous anticoagulants for 3-6 months and then switched to an antiplatelet agent, usually aspirin.
Platelet count should be monitored

27. C- Thrombolytic therapy
Use of thrombolytic therapy for patients aged <18 years is much more controversial. The current AHA guidelines recommend that tPA use in young children is limited to a clinical trial.
Evidence for the safety and efficacy of thrombolysis in children with stroke is extremely limited. The existing studies of this treatment suggest a high risk of hemorrhagic complications.

28. Recommendations for stroke and heart disease
Therapy for congestive heart failure is indicated.
When feasible, congenital heart lesions, especially complex heart lesions with a high stroke risk, should be repaired.
Resection of an atrial myxoma is indicated.
Surgical repair or transcatheter closure is reasonable in individuals with a major atrial septal defect.

29. In children with a risk of cardiac embolism, it is reasonable to continue either LMWH or warfarin for at least 1 year or until the lesion responsible for the risk has been corrected.
Anticoagulant therapy is not recommended for individuals with native valve endocarditis
Surgical removal of a cardiac rhabdomyoma is not necessary in asymptomatic individuals.

30. Recommendations for children with SCD
Risk factors for stroke include high blood flow velocity on TCD, low hemoglobin value, high white cell count, hypertension, silent brain infarction, and history of chest crisis.
Acute management of ischemic stroke resulting from SCD should include optimal hydration, correction of hypoxemia, and correction of systemic hypotension.

31. Periodic transfusions to reduce the percentage of sickle hemoglobin are effective for reducing the risk of stroke in children 2 to 16 years of age.
For acute cerebral infarction, exchange transfusion designed to reduce sickle hemoglobin to <30% total hemoglobin.
Hydroxyurea may be considered in children and young adults with SCD and stroke who cannot continue on long- term transfusion.
Bone marrow transplantation.
Surgical revascularization procedures.

32. Recommendations for treatment of coagulation disorders
Antithrombin deficiency is resistant to heparin.
After a thrombotic event, lifelong warfarin is indicated.
Patients with protein C or S deficiency or factor V Leiden mutation and stroke are treated with anticoagulation.
The prophylactic anticoagulation for asymptomatic patients is controversal.

33. Sinus thrombosis
The antithrombotic therapy is aimed at preventing the clot propagation and recurrence within the cerebral venous system.
For children without evidence of significant intracranial haemorrhage, anticoagulation for 3-6 months is recommended, with reassessment of re-canalization at 3-months.
With significant intracranial haemorrhage, monitoring with serial neuroimaging is advised.
In case of clot propagation, treatment with anticoagulation is advised.

34. Recommendations for treatment of hemorrhage in Children
Children with brain hemorrhage should undergo a thorough risk factor evaluation, including cerebral angiography when noninvasive tests have failed to establish an origin.
Children with a severe coagulation factor deficiency should receive appropriate factor replacement therapy, and children with less severe factor deficiency should receive factor replacement after trauma.
Given the risk of repeat hemorrhage from congenital vascular anomalies, these lesions should be identified and corrected whenever it is clinically feasible.
Stabilizing all supportive measures.

35. Individuals with SAH may benefit from measures to control cerebral vasospasm.
Surgical evacuation of a supratentorial intracerebral hematoma is not recommended. However, surgery may help selected individuals with developing brain herniation or extremely elevated intracranial pressure.
There are no data to indicate that periodic transfusions reduce the risk of ICH caused by SCD.

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