818 SECTION VI Pediatric Critical Care Neurologic appropriate Seizures have been reported in more than half of children with CSVT 53 Children with acute symptomatic CSVT should be cared for in the PIC[.]
818 S E C T I O N V I Pediatric Critical Care: Neurologic TABLE 66.3 Guideline for Anticoagulation in CSVT Guideline Population Recommendation ACCP guidelines, 201213 Children Initial UH or LMWH, then LMWH or VKA for minimum months plus another months if occlusion persists or symptoms ongoing For children with CSVT with significant hemorrhage, anticoagulation as above or follow-up neuroimaging at to days and anticoagulation if thrombus propagation has occurred AHA Guidelines for Management of Stroke in Infants and Children, 201944 Children Anticoagulation is the primary treatment, except for otogenic lateral sinus thrombosis, with agent, dose, and duration of treatment to be determined by clinical team Diagnosis and Management of Cerebral Venous Thrombosis, AHA, 201186 Adults Initial UH or LMWH in full anticoagulant doses is reasonable, followed by VKAs, regardless of the presence of ICH With provoked CSVT, VKAs may be continued for to months With unprovoked CVT, VKAs may be continued for to 12 months ACCP, American College of Chest Physicians; AHA, American Heart Association; CSVT, cerebral sinus venous thrombosis; ICH, intracranial hemorrhage; LMWH, low-molecular-weight heparin; UH, unfractionated heparin; VKA, vitamin K antagonists appropriate Seizures have been reported in more than half of children with CSVT.53 Children with acute symptomatic CSVT should be cared for in the PICU, particularly while anticoagulation is being initiated Both UH and LMWH are recommended in adults with CSVT.83 With close monitoring, UH and LMWH can be administered to children, which likely improves outcome.67,84–86 Recommendation from the International Paediatric Stroke Study (IPSS) group is that older children without hemorrhage should receive anticoagulation In a recent single-center study, worse clinical outcome and propagation of thrombus was associated with lack of anticoagulation Hemorrhagic complications were relatively rare (5%); however, children with “significant intracranial hemorrhage” were excluded from anticoagulation treatment (Table 66.3).86 Thrombolysis, thrombectomy, or surgical decompression may be considered in children with severe CSVT in whom there is no improvement with UH.87,88 Studies of thrombolysis and thrombectomy for CSVT have not been performed However, case reports and series exist, particularly of children who are comatose or have declining mental status.56,89 Many patients with CSVT have increased ICP and are at risk for vision loss.54 Lumbar puncture is the most effective way to lower ICP However, it requires interruption of anticoagulation to decrease the risk of bleeding Prognosis The mortality rate following CSVT in childhood is approximately 4% to 7%,52,90 and CSVT is frequently associated with long-term neurologic sequelae.60 Recurrence has been reported in 6% of children at an average follow-up of 36 months Predictors of recurrence included persistent occlusion from CSVT, presence of heterozygosity for G20210A mutation, lack of anticoagulant therapy, and initial thrombosis occurring after years of age.84 Vision loss can occur due to elevated ICP after CSVT.54 Accordingly, ophthalmic follow-up is warranted Children with ongoing thrombophilia are at increased risk of recurrent pathologic thrombosis, particularly with triggers such as immobilization, pregnancy and puerperium, prolonged plane travel, and oral contraceptive use Preventive precautions should be discussed with the patient and family Recurrent thrombosis can occur in the absence of identified thrombophilia as well.84 Spontaneous Intracranial Hemorrhage Although spontaneous ICH, or hemorrhagic stroke, accounts for less than 20% of strokes in adults, it accounts for almost half of all pediatric strokes.91–93 Spontaneous ICH includes intraparenchymal hemorrhage, accounting for approximately 75% of cases92; intraventricular hemorrhage (IVH); and subarachnoid hemorrhage (SAH) of nontraumatic origin Following ICH, approximately 10% to 25% of children will die94,95 and over 70% will have neurologic deficits.96 The three most common vascular malformations of the CNS are arteriovenous malformations (AVMs), cerebral cavernous malformations (CMs), and venous malformations AVMs account for approximately half of intraparenchymal ICH.67,84 CMs account for approximately one-quarter of ICH, with higher numbers found in later studies that included MRI assessment Other vascular malformations, brain tumors, and coagulation defects (thrombocytopenia, hemophilia, hepatic failure, anticoagulation) account for most of the remaining cases of spontaneous ICH in childhood Arteriovenous Malformations AVMs are abnormal tangles of vessels (Fig 66.5) that connect arteries directly to veins, resulting in abnormally high flow and pressures in vessels with weak walls This disrupts normal blood flow and leads to hemorrhage and formation of aneurysms Eighty percent of AVMs are supratentorial and three-quarters of those that become symptomatic present with ICH Children with ruptured AVMs present with altered mental status, including coma and seizures In one series, 12% of hemorrhages in previously undiagnosed AVMs were fatal, with a higher mortality associated with infratentorial bleeds.97 Multiple AVMs are more common in children than adults and suggest hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu),98 familial AVMs, and Wyburn-Mason syndrome Vein of Galen malformation is a distinct AVM that appears in newborns and is associated with congestive heart failure due to left-to-right cardiovascular shunting The risk of hemorrhage in children with known AVMs is 2% to 4% per year; 25% of the hemorrhages are fatal.99–101 Although children have a lower annual risk of hemorrhage than adults, they have a greater lifetime risk While AVMs are traditionally considered CHAPTER 66 Pediatric Stroke and Intracerebral Hemorrhage A 819 B • Fig 66.5 A 7-year-old girl presented with a small intracranial hemorrhage A Sylvian fissure arteriove- nous malformation is seen on left carotid injection during conventional cerebral angiogram (A) Head computed tomography shows a large hemorrhage requiring emergent evacuation month following the initial angiogram (B) A small residual was treated with radiosurgery and the lesion was obliterated at 10year follow-up to be congenital without the potential for growth, recurrence of AVM has been reported in children following complete obliteration Thus, long-term follow-up is indicated.102 Larger AVMs may be less likely to hemorrhage than small AVMs, perhaps because of increased pressure in the smaller malformations.103–105 As AVMs are often diagnosed at the time of hemorrhage, there may be a bias toward diagnosis of lesions with a higher incidence of hemorrhage The incidentally found AVM may have a different natural history; however, there is insufficient data to make that determination.106 MRI will demonstrate AVMs, and cerebral catheter angiogram will establish the arteriovenous shunt, as well as feeding arteries and draining veins The Spetzler-Martin grading system accounts for size, involvement of eloquent brain, and pattern of venous drainage.107 AVMs smaller than cm in maximal diameter, with superficial drainage and away from critical areas (e.g., language, motor, and visual areas) have the lowest risk associated with intervention and the best overall prognosis When possible, AVM should be treated with total surgical resection The annual risk of rebleeding following AVM hemorrhage is 20% in children, approximately fourfold the risk in adults.108 Deep-seated AVMs and AVMs with recent (5-year) history of hemorrhage are at higher risk of bleeding.106 Surgical treatment is associated with a very high success rate but is not universally curative A recent series109 of pediatric AVMs resected surgically found about a 1% recurrence at years, suggesting that some degree of postoperative surveillance is warranted Several series have demonstrated a 7% to 13% recurrence on longer-term follow-up.102,110,111 Partial treatment with embolization does not decrease risk of hemorrhage.112 Complete obliteration with embolization is not possible but embolization has been used as an option to reduce the size prior to surgical resection or radiosurgery Gamma knife has been used to treat pediatric AVM, with an obliteration rate of 71.3% after one treatment and 62.5% for patients requiring another treatment The mean time to obliteration was 32.4 and 79.6 months, respectively.113 AVMs with a nidus diameter less than 2.5 cm and with a single draining vein were most likely to respond completely to radiosurgery,114 but these same characteristics also predispose to a favorable outcome with microsurgical resection Ischemic changes presenting as clinical stroke at the site of radiation can occur following radiation Aneurysms Aneurysms account for 10% of hemorrhagic strokes in childhood115 and usually have symptomatic onset in children less than years or greater than 10 years of age.116 Ruptured aneurysms usually present with SAH but can present with IVH and/or intraparenchymal hemorrhage The most common location for aneurysm in children is a saccular aneurysm at the internal carotid artery bifurcation followed by middle cerebral artery bifurcation.117 Infants and children are more likely than adults to have giant aneurysms and posterior circulation involvement and less likely to have aneurysms of the anterior communicating artery and posterior communicating artery,118 although most giant aneurysms in infants involve the middle cerebral artery.119 Approximately 5% of children with aneurysms have multiple aneurysms as opposed to 20% in adults There are multiple genetic disorders associated with the development of aneurysms, including coarctation of the aorta,120,121 fibromuscular dysplasia,122,123 Ehlers-Danlos syndrome,124 pseudoxanthoma elasticum,125 autosomal dominant polycystic kidney disease, connective tissue disorder,126 and a family history of aneurysms Aneurysms can also be associated with AVMs127,128 and can form following radiation for pediatric brain tumors and AVMs 820 S E C T I O N V I Pediatric Critical Care: Neurologic Intracerebral hemorrhage, as opposed to SAH, suggests an aneurysm due to infection or mycotic aneurysms Infective endocarditis, meningitis, chronic pulmonary infection, and intravenous drug use are common predisposing infections Mycotic aneurysms tend to be more distal and are often multiple Cerebral catheter angiography is the study of choice for cerebral aneurysms, although CTA is often the initial imaging study performed with head CT on presentation and may be useful in emergency situations when urgent operative decompression of the hemorrhage is needed Head MRI and MRA can be used for screening of aneurysms but are less sensitive than angiography, which provides more detail of the vascular anatomy.129 Cerebral catheter angiography can be diagnostic and preparatory for endovascular treatment as well The annual risk of aneurysmal rupture is estimated at 0.1% to 8%, with larger aneurysms at higher risk In patients with unruptured aneurysm, symptoms can be related to expanding size Common symptoms include third nerve palsy, afferent pupillary defect, and other cranial nerve deficits, depending on the location of the aneurysm Frank rupture of an aneurysm results in catastrophic ICH, with sudden severe headache, altered mental status, nausea and vomiting, and loss of consciousness The mortality rate in children following aneurysmal rupture is 20%.130 Some patients will have a recent history of “sentinel bleed” with a severe headache Sudden onset of severe headache requires neuroimaging evaluation for possible SAH The most common complication following SAH is cerebral vasospasm resulting in ischemic stroke Vasospasm usually presents within to 10 days following the hemorrhage but can present for up to weeks In adults, euvolemia and nimodipine, a calcium channel blocker, are recommended following aneurysmal SAH to prevent delayed cerebral ischemia (DCI), with induction of hypertension if DCI has occurred.131 Nimodipine has been used to prevent and/or minimize vasospasm, with conflicting data on the benefit of adding statins such as pravastatin Hypervolemia using intravenous fluids has not been shown to be effective in preventing vasospasm Currently, maintaining patients in a euvolemic state is recommended, with hypovolemia carefully avoided Hypertension has been used historically in treating symptomatic vasospasm, but its use has been questioned.132 Normotension, euvolemia, and nondilution are increasingly being considered Approximately one-third of patients will exhibit cerebral salt wasting; as such, serum sodium should be monitored Hydrocephalus is common and CSF diversion often necessary As recurrent hemorrhage from a ruptured aneurysm is a frequent and early event, with 15% of adults suffering a recurrent hemorrhage in the first 24 hours,133 treatment of the aneurysm must be prompt Options for treatment include endovascular therapy, ligation, and clip placement Long-term follow-up is indicated, as over 40% of children with aneurysms will develop new aneurysms later in life.134 For adults, the 10-year risk of SAH in a patient with one first-degree relative with SAH was 0.8%; with two first-degree relatives, the 10-year risk is 7.1%.135 The risk to other family members of children with nonsyndromic aneurysms is unknown Cavernous Malformation Cerebral CMs are vascular malformations with thin-walled sinusoidal spaces lined with endothelial tissue without intervening parenchyma, often containing calcifications CMs cause approximately one-fifth of ICH in childhood.91,136 For untreated CMs, the risk of recurrent hemorrhage is 4% to 5% per year CMs occur in approximately in 200 adults and account for approximately 10% of vascular malformations of the CNS Most occur in the brain, usually supratentorially, although infratentorial and brainstem involvement can occur Less frequently, the spinal cord is involved There is no arteriovenous shunting; thus, the degree of hemorrhage tends to be smaller than with AVMs, often with hemosiderin staining in the absence of a clinical hemorrhage Most CMs are asymptomatic, with 20% to 30% of patients having symptoms CMs can present with headache, seizures, focal neurologic deficit, and hemorrhage Seizures are the most common presenting symptom, especially with involvement of the frontal and temporal lobes (Fig 66.6) CMs often increase in size over time, with a progressing and regressing course due to resorption of blood and reorganization followed by recurrent hemorrhage Although CMs are low-flow lesions, severe hemorrhage can occur One study of patients age 25 years and younger found that the hemorrhage rate was 1.6% per patient-year and 0.9% per cavernoma-year The hemorrhage rate in the symptomatic group was 8.0% annually and 0.2% in the asymptomatic group where a CM was found incidentally.137 In a series of 292 patients diagnosed at age 3.5 to 88.9 years (mean age, 45.8 years), 74 presented with hemorrhage The annual risk of hemorrhage in patients presenting with hemorrhage was 6.2%, with risk decreasing over time The risk of hemorrhage increased in the setting of multiple CMs.138 CM can be either familial or sporadic, and the incidence of CM on imaging increases during childhood with age Multiple CMs occur in 13% of sporadic cases and half of familial cases,139 with greater number of lesions predicting familial CM Multiple genetic mutations have been associated with familial CM, including CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10, accounting for 75% or more of families.140 In one series of 92 children with CM, 30% had multiple CMs and 9% had a family history of CMs.137 In another series of 66 children with CM, (11%) had multiple CMs.141 On MRI, CMs are described as having a “popcorn” appearance due to the mixture of high and low T1 and T2 signal surrounded by hemosiderin from chronic, recurrent hemorrhage Findings on CT are nonspecific, and CMs are not detectable on catheter angiography However, CMs can be associated with developmental venous anomalies, which are seen on angiography If complete resection of a particular CM lesion is possible, this is curative Most patients with symptomatic localization epilepsy associated with the CM will be seizure free following resection as well, especially if the associated hemosiderin rim is also removed (see Fig 66.5) Functional considerations may limit surgery and/ or define the surgical approach Preoperative assessment may include functional MRI or other mapping tools if the location is suspected to be near the motor or language cortex Such mapping tools are possible in patients as young as age or years.142 Resection is not always an option and can be associated with increased neurologic deficit Brainstem CMs in childhood are particularly problematic, as they tend to be larger with a higher rate of recurrence following incomplete resection as compared with that seen in adults.143 Radiosurgery has been considered for patients in whom surgery is not an option Radiosurgery does not appear to be curative and can be associated with significant complications In a large series of 331 adults with CM, radiosurgery reduced the annual risk of symptomatic hemorrhage to 3%, with CHAPTER 66 Pediatric Stroke and Intracerebral Hemorrhage A B one treatment-associated mortality.144 Recent adaptation of stereotactic laser ablation has also been applied to the treatment of CMs, though the experience with this approach is extremely limited to date,145 being applied particularly for the treatment of CM-associated epilepsy.146 The risk of intervention needs to be balanced against the risk with natural history Posterior fossa CM is associated with a greater risk of hemorrhage as well as rebleeding than in other locations Brainstem CMs are high risk if untreated although surgical resection is also high risk in this location, often requiring skull base approaches to access the lesion where it comes to the surface Surgical management of patients with multiple lesions—particularly, familial CM, in which lesions may be numerous—is possible if the symptomatic lesion is identified and resectable In these cases, there is the possibility of a risk of recurrence or of a new lesion in adjacent or distant areas The role of genetic screening for patients with familial CM has been debated Currently, identified genes account for 96% of 821 C • Fig 66.6 Left frontal cavernous malformation (A) resected in an 8-year-old with intractable focal motor seizures, resulting in 10 years of seizure freedom The lesion was entered from within the sulcus (B) Seizures recurred in the setting of a new lesion superior to the first (C), along with a new lesion in the right cerebellum (not shown) familial cases; if a causative gene is found in a pedigree, this could be used to screen other family members Family members of patients with CMs should be imaged if there are any symptoms concerning for CM, such as headache, seizures, or neurologic deficit Symptomatic epilepsy will need appropriate antiepileptic treatment Seizures may be medically refractory or intractable Followup MRI should be pursued every to years to assess for growth or hemorrhage of the CM Coagulation Disorders Hemophilia A and B can result in spontaneous ICH, as can severe thrombocytopenia and coagulopathy due to liver failure ICH associated with vitamin K deficiency occurs in infants who not receive vitamin K prophylaxis at birth due to omission or parental choice.147 Late ICH associated with vitamin K deficiency peaks at to weeks and can be catastrophic.148 822 S E C T I O N V I Pediatric Critical Care: Neurologic General Care of the Child With Intracerebral Hemorrhage A child with ICH can present with emesis, severe headache, seizures, and declining mental status, and can deteriorate rapidly to coma and death Rapid diagnosis and stabilization of the child with ICH is critical Head CT can detect ICH as well as mass effect and impending herniation A CBC, coagulation profile and type, and hold or cross should be sent Initial stabilization will include ensuring control of the airway and ventilation, treatment of seizures with antiepileptic drugs, and prevention of fever Specific coagulopathy should be identified and corrected Urgent evacuation of hemorrhage may be indicated as well as decompressive hemicraniectomy Management of elevated ICP may include hyperosmolar therapy, such as mannitol or hypertonic saline, hyperventilation for induced hypocapnia and cerebral vasoconstriction, and elevation of the head of the bed up to 30 degrees Ventriculostomy drain allows drainage of CSF as well as ICP monitoring and is indicated in the setting of obstructive hydrocephalus as a consequence of IVH Prognosis Prognosis following ICH depends on the etiology and severity of the initial hemorrhage, risk of recurrence, and morbidity associated with treatment of the underlying lesion A study of 56 children followed for a mean of 10 years after ICH found that 13 children died acutely; suffered recurrent hemorrhage, which was fatal in children; and only a quarter of the survivors were without neurologic or cognitive deficit.149 Conclusion Childhood stroke—including AIS, CSVT and ICH—is a significant cause of childhood morbidity and mortality Children presenting with acute stroke require intensive care able to address urgent management, supportive care, neuroprotection, and prevention of early recurrence and complications Key References Al-Holou WN, O’Lynnger TM, Pandey AS, et al Natural history and imaging prevalence of cavernous malformations in children and young adults J Neurosurg Pediatr 2012;9(2):198-205 Amlie-Lefond C, Shaw DWW, Cooper A, et al Risk of intracranial hemorrhage following intravenous tPA (tissue-type plasminogen activator) for acute stroke is low in children Stroke 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Niazi TN, Klimo Jr P, Anderson RC, Raffel C Diagnosis and management of arteriovenous malformations in children Neurosurg Clin N Am 2010;21(3):443-456 Sellers AR, Nguyen AT, Betensky M, Mills K, Goldenberg NA, Shimony N Risk factors for pediatric cerebral sinovenous thrombosis: a casecontrol study with pediatric neuroradiologist case validation Blood 2019;134(suppl 1):2427 Wasay M, Bakshi R, Bobustuc G, et al Cerebral venous thrombosis: analysis of a multicenter cohort from the United States J Stroke Cerebrovasc Dis 2008;17(2):49-54 The full reference list for this chapter is available at ExpertConsult.com ... patients with unruptured aneurysm, symptoms can be related to expanding size Common symptoms include third nerve palsy, afferent pupillary defect, and other cranial nerve deficits, depending on the... complication following SAH is cerebral vasospasm resulting in ischemic stroke Vasospasm usually presents within to 10 days following the hemorrhage but can present for up to weeks In adults, euvolemia and... questioned.132 Normotension, euvolemia, and nondilution are increasingly being considered Approximately one-third of patients will exhibit cerebral salt wasting; as such, serum sodium should be monitored