815CHAPTER 66 Pediatric Stroke and Intracerebral Hemorrhage is an important predictor for primary and recurrent arterial ischemic stroke in childhood; depending on etiology, treatment with antithrombo[.]
CHAPTER 66 Pediatric Stroke and Intracerebral Hemorrhage • BOX 66.2 Initial Laboratory Studies in a Child With Possible Acute Stroke Complete blood count Coagulation studies: PT, PTT, INR For child on anticoagulation: • LMWH activity and anti-Xa for LMWH • PT/INR for warfarin Electrolyte panel Glucose ESR Renal and liver function studies If clinically indicated: • Pregnancy test • Urine or serum toxicology • Blood gas • Fibrinogen, if intravenous t-PA being considered Type and screen or cross if intracranial hemorrhage is suspected, the child has sickle cell disease, or thrombolysis or thrombectomy is being considered ESR, Erythrocyte sedimentation rate; INR, international normalized ratio; LMWH, low-molecular-weight heparin; PT, prothrombin time; PTT, partial thromboplastin time; t-PA, tissue plasminogen activator is an important predictor for primary and recurrent arterial ischemic stroke in childhood; depending on etiology, treatment with antithrombotic medications, immunosuppressive agents, and antiviral medication may be indicated Laboratory Evaluation Initial laboratory studies include complete blood count (CBC), electrolytes, blood urea nitrogen (BUN), creatinine, glucose, prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), ESR, blood gas and type, and screen or cross-match if ICH is suspected, the child has SCD, or thrombolysis or thrombectomy is being considered (Box 66.2) Initial Laboratory Studies in Child With Possible Acute Stroke If the child is on anticoagulation, studies to assess therapeutic range include low-molecular-weight heparin (LMWH) activity and anti-Xa for LMWH, PTT for unfractionated heparin (UH), and PT/INR for warfarin Other Tests of Hypercoagulability (eTable 66.1) Laboratory tests considered in childhood AIS not need to be sent urgently when maintaining an optimal hematocrit is critical, and not all patients require exhaustive testing Urgent evaluations may include screen for systemic inflammatory disease (ESR, CRP, antinuclear antibodies [ANAs]), and lupus inhibitor screen, antiphospholipid panel, and pregnancy test Lumbar puncture may be indicated if there are concerns about infection However, it may need to be delayed until risk of intracranial hypertension has passed If a cardioembolic etiology is suspected, urgent echocardiogram is indicated Treatment Initial management includes optimizing cerebral perfusion and preventing hypoxemia, rescuing and minimizing expansion of the 815 penumbra, and preventing complications Children with acute stroke should be admitted to the pediatric intensive care unit (PICU) for a minimum of 48 hours for neurologic and medical monitoring and aggressive management of complications Neurologic status should be followed by the bedside nurse (hourly pediatric Glasgow Coma Scale and pupils until stable) as well as by medical staff Ideally, the pediatric NIHSS38 should be used to serially assess the patient Urgent neuroimaging should be obtained for any neurologic deterioration Supportive Therapy For the most part, therapy for childhood stroke is based on extrapolation from adult-based guidelines Endotracheal intubation and mechanical ventilation are indicated for children with inadequate oxygenation and/or respiratory drive or inability to protect their airway and may be needed to facilitate diagnostic or therapeutic procedures Keeping the head of the bed flat may optimize cerebral perfusion Blood pressure should be maintained, with careful attention to adequate blood volume to avoid hypotension Many children have transient hypertension following stroke, possibly representing a compensatory mechanism to maintain CBF, and permissive hypertension is usually recommended If hypertension requires treatment, blood pressure should be lowered cautiously, with close attention to worsening of neurologic status Clinical and electrographic seizures should be treated, but there are no data to support seizure prophylaxis with antiepileptic medications Fever should be treated aggressively to decrease metabolic demands on the brain Cooling blankets should not be used in patients with sickle cell anemia Recanalization Therapies There is minimal data on the use of recanalization therapies in acute childhood stroke; currently the American Heart Association (AHA) notes that “hyperacute therapies for AIS remain controversial.”44 Due to the challenge of determining time of stroke onset and limitations of extrapolation from adult data to very young children, t-PA for AIS should be used with great caution in children younger than years and avoided in neonates For older children and adolescents, data on safety and efficacy is limited, but t-PA could be considered in selected patients Published consensus-based guidelines and safety monitoring recommendations exist.36 The risk of symptomatic intracranial hemorrhage following intravenous t-PA for appropriately selected children with AIS appears to be low.45 Mechanical thrombectomy is the standard of care in appropriately selected adults within hours of AIS due to proximal largevessel occlusion (LVO), with the treatment window for mechanical thrombectomy in anterior circulation LVO in acute AIS with salvageable penumbra on perfusion imaging extended to 24 hours.46–48 Mechanical thrombectomy is increasingly performed in children, with literature reports of good outcome, but no controlled studies Recently published AHA guidelines note that it would be reasonable to limit mechanical thrombectomy to children with LVO and disabling deficit in larger children by an experienced team but not address the time window for treatment or the role of perfusion-based imaging in childhood.44 If the child was last seen at baseline within hours and MRA or CTA shows occlusion in the internal carotid or M1 segment of the middle cerebral artery or the vertebral and basilar artery, the possibility of thrombectomy should at least be discussed, particularly 815.e1 eTABLE Laboratory Tests Considered in Childhood Arterial Ischemic Stroke 66.1 Laboratory Tests Caveat Hemoglobin S percentage If child with known or suspected sickle cell disease Iron and total iron binding capacity Severe iron deficiency anemia is a risk factor for stroke Antinuclear antibodies Rheumatoid factor a If clinical concern about underlying rheumatologic disease a If clinical concern about underlying rheumatologic disease Antiphospholipid antibody studies Includes anticardiolipin antibody IgM, IgG, and IgA; anti-b2 glycoprotein IgM, IgG, IgA; and lupus anticoagulant FVL mutation Most common cause of activated protein C resistance; 3%–8% of people with European ancestry carry one copy of the mutation Prothrombin gene mutation (Factor II/G20210A)a More common in white population Protein C activity and antigen Can be lowered by warfarin, vitamin K deficiency, liver disease, DIC Protein S activity and free antigen Can be lowered by warfarin, vitamin K deficiency, liver disease, DIC, pregnancy Only the free protein S is functional as a cofactor for protein C APCRa Rarely indicated, as FVL accounts for most cases of APCR 5,10-methylenetetrahydrofolate reductase a Needs to be sent only if homocysteine is elevated PT, aPTT, and INR PT and INR measure extrinsic pathway of coagulation PTT measures intrinsic pathway of coagulation AT III activity Heparin and direct thrombin inhibitors can affect results AT III should be checked if a patient is requiring higher heparin doses than expected, as anti-Xa activity is dependent on patient’s AT III level D-Dimer May reflect clot burden C reactive protein Acute phase reactant to inflammation Erythrocyte sedimentation rate Nonspecific measure of inflammation Homocysteinea Fasting sample preferred b-human chorionic gonadotropin (pregnancy test) Strongly consider in any female of childbearing age Toxicology screen Cocaine, methamphetamine, other vasoactive drugs, and cannabis associated with stroke Lipoprotein (A) a Does not need to be a fasting sample a Rarely indicated in the acute period APCR, Activated protein C resistance; aPTT, activated partial thromboplastin time; AT III, antithrombin III; DIC, disseminated intravascular coagulation; FVL, Factor V Leiden; Ig, immunoglobulin; INR, international normalized ratio; PT, prothrombin time; PTT, partial thromboplastin time 816 S E C T I O N V I Pediatric Critical Care: Neurologic A B • Fig 66.3 Head computed tomography scan of a 17-year-old girl with complete left middle cerebral infarct before (A) and after (B) decompressive hemicraniectomy for an older adolescent An extended time window may be indicated, particularly for basilar artery occlusion However, this procedure should be approached with caution, including full disclosure of the lack of data in children, and should be performed only by neurointerventionalists or interventional radiologists with pediatric experience Urgent neurosurgical consultation for possible decompressive hemicraniectomy should be obtained promptly in children with malignant middle cerebral artery infarct (Fig 66.3) Suboccipital craniectomy with dural expansion should be considered in patients with neurologic deterioration due to edema from cerebellar infarct In malignant infarction, monitoring of intracranial pressure (ICP) has not been shown to be helpful and may delay surgical treatment in these patients Antithrombotic Therapy A full review of the use of antithrombotic therapies in children is available in the Chest guidelines.13 Anticoagulation is typically used in children with acute AIS without hemorrhage pending complete workup of potential etiologies to prevent recurrent stroke, which can occur early, particularly in the setting of dissection or cardioembolic stroke Anticoagulation is usually initially achieved with continuous intravenous heparin, which can be reversed if necessary by protamine or fresh frozen plasma, with transition to LMWH when the child is stable LMWH has more predictable pharmacokinetics and reduces the risk of heparininduced thrombocytopenia, a serious antibody-mediated complication of heparin.49 However, LMWH cannot be reversed rapidly and has renal clearance, necessitating dosage adjustment in the setting of impaired renal function For long-term anticoagulation, LMWH or warfarin is used Warfarin has difficult-to-manage pharmacokinetics; thus, LMWH often is the anticoagulant of choice, despite the need for subcutaneous injection Newer anticoagulants are currently being studied in adult stroke but have not been used widely in pediatric stroke Anticoagulation is usually continued in children with presumed cardioembolic stroke and significant thrombophilic, states such as antiphospholipid syndrome.44,50 Chest guidelines recommend anticoagulation for cervical artery dissection, while AHA guidelines consider this to be controversial.44,50 Aspirin inhibits platelet activity by irreversibly inhibiting cyclooxygenase-1 and is used based on consensus for stroke prevention in children not felt to require anticoagulation A dose of to mg/kg per day is recommended after contraindications such as ICH have been excluded.44 Aspirin is often continued for long-term stroke prophylaxis in children However, optimal duration is unknown The doses used for stroke prophylaxis are less than those associated with Reye syndrome (Table 66.2).51 Cerebral Sinus Venous Thrombosis CSVT occurs when thrombosis is present in the major venous sinuses draining the brain Headache is the most common presenting symptom of CSVT CSVT can result from multiple processes, including venous stasis, hypercoagulable state, dehydration, and direct damage to the vessel wall in the venous system, which has slower blood flow CSVT can involve the dural venous sinuses (superior sagittal, transverse, or sigmoid sinus), deep venous system (internal cerebral veins) or cortical dural veins Multiple sinuses are involved in most children, with the transverse sinus most commonly affected, followed by the sagittal sinus.52 Potential complications due to CSVT include venous infarction, which occurs secondary to venous outflow obstruction, intracranial hypertension, cranial nerve palsies, and cerebral hemorrhage The incidence of CSVT in children age month to 18 years is approximately 0.4 in 100,000 per year,53 although with advances in neuroimaging, this reported incidence may rise Children with CSVT often present with nonspecific findings, such as headache, seizures, increased ICP, and lethargy, although localizing signs such as cranial nerve palsies and hemiparesis may be present CHAPTER 66 Pediatric Stroke and Intracerebral Hemorrhage 817 TABLE 66.2 Published Guidelines for Treatment of Childhood Acute Arterial Ischemic Stroke Indication ACCP guidelines, 201213 American Heart Association Guidelines for Management of Stroke in Infants and Children, 201944 Initial treatment UH or LMWH or aspirin 1–5 mg/day until cardiac etiology or arterial dissection ruled out UH or LMWH until etiology determined Aspirin 3–5 mg/kg/ day for children without known risk of recurrent embolism or severe hypercoagulable disorder Cardiac embolism with risk of recurrence (excluding native valve endocarditis) LMWH UH or LMWH Extracranial cervicocephalic arterial dissection LMWH Anticoagulation considered controversial Sickle cell disease Exchange transfusion with goal HbS ,30% Simple or exchange blood transfusion, depending on baseline hemoglobin Intravenous t-PA Not recommended for children outside of research protocol No recommendations provided ACCP, American College of Chest Physicians; HbS, hemoglobin S; LMWH, low-molecular-weight heparin; t-PA, tissue plasminogen activator; UH, unfractionated heparin Etiologies and Risk Factors Most children with CSVT have underlying risk factors identified, and multiple risk factors are often present.52–58 Prothrombotic disorders are found in approximately half of children with CSVT.53,54,58,59 The AHA recommends a thorough evaluation for risk factors, including thrombophilia in children with CSVT.44 Laboratory studies should be directed based on the medical history, and a family history of thrombophilia and thrombosis should be obtained An abbreviated thrombophilia screen may be adequate in children with triggered CSVT, for example, following surgery involving the dural sinuses or following head trauma (eBox 66.3) Neuroimaging CSVT can be seen in some cases on CT scan—in particular, contrast-enhanced CT scan; however, the sensitivity is poor A clot may be visible on nonenhanced CT scan as a dense clot sign The delta sign, a triangular area of high-contrast enhancement with a low attenuating center, may be present on enhanced CT scan This is best seen with sagittal sinus thrombosis CT venography is sensitive for CSVT but requires radiation and does not assess parenchyma well for venous congestion or infarct Head MRI and magnetic resonance venography (MRV) are the preferred diagnostic modality MRI is the best modality to detect associated parenchymal abnormalities The head MRI and MRV should be ordered with and without contrast, with the caveat that contrast is not needed if the radiologist is satisfied with the noncontrast images Contrast may be particularly helpful in borderline or unusual cases or with suspected infection as the etiology Rarely, high-resolution CT venography or catheter angiogram will be indicated Laboratory Evaluation Initial laboratory studies include CBC, electrolytes, BUN, creatinine, glucose, PT/PTT, ESR, and antithrombin III activity in preparation for possible heparin administration, as well as a pregnancy test in females of child-bearing age Urgency of evaluation for risk factors for CSVT will be determined by history and presentation • Fig 66.4 Magnetic resonance image of a 15-month-old boy with a week of irritability who presented with a generalized tonic-clonic seizure followed by sleepiness, with extensive thrombosis of the inferior sagittal sinus, straight sinus, internal cerebral veins, and vein of Galen Laboratory studies showed severe iron deficiency (hemoglobin 6.2 g/dL, microcytic anemia, and high total iron binding capacity) There is symmetric T2 hyperintensity within the bilateral thalami associated with involvement of the deep venous system Treatment Supportive measures include adequate ventilation, hydration, treatment of infection if indicated, and control of seizures Children with CSVT may rapidly progress to obtundation, particularly when the deep venous system is involved (Fig 66.4), and even death Signs and symptoms of infection of the head and neck should be sought and broad-spectrum antibiotics started when 817.e1 • eBOX 66.3 Risk Factors Reported in Pediatric CSVT Inherited Thrombophilias 58 G20210A mutation Factor V Leiden58,63 Protein C deficiency58,63 Protein S deficiency58,63 Antithrombin III deficiency57,58,63 MTHFR57 Homocysteine64,65 Elevated Factor VIII level57 Acquired Thrombophilias Asparaginase56,61,66 Exogenous estrogen (BCP)55,56 Infection55,57 Sinusitis61,67 Otitis media55 Mastoiditis55,63,67 Lemierre syndrome68 Primary varicella61,69 Thyrotoxicosis/hyperthyroidism74 Elevated anticardiolipin immunoglobulin G56,57 Antiphospholipid antibodies63 Lupus anticoagulant58 Behỗet disease75 Acute Illness56 Dehydration56,57 Meningoencephalitis58 Chronic Illness56 Nephrotic syndrome55,56,76 Anemia57,77 Thrombocytosis78,79 Protein losing enteropathy57 Hematologic malignancy55,60,80 Autoimmune hemolytic anemia81 Obesity82 Hemoglobinopathy Autoimmune/Inflammatory Disorders Sickle cell disease55,57 b-Thalassemia major57 Systemic lupus erythematosus55,56,70,71 Inflammatory bowel disease (ulcerative colitis, Crohn disease)61,72 Celiac disease73 Head67,83,84 Head and neck surgery85 Trauma ... adolescent An extended time window may be indicated, particularly for basilar artery occlusion However, this procedure should be approached with caution, including full disclosure of the lack of data... guidelines recommend anticoagulation for cervical artery dissection, while AHA guidelines consider this to be controversial.44,50 Aspirin inhibits platelet activity by irreversibly inhibiting cyclooxygenase-1... to 18 years is approximately 0.4 in 100,000 per year,53 although with advances in neuroimaging, this reported incidence may rise Children with CSVT often present with nonspecific findings, such