7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Hemorrhagic stroke in children : Evelyn K Shih, MD, PhD, Lauren A Beslow, MD, MSCE : Scott E Kasner, MD, Douglas R Nordli, Jr, MD : Richard P Goddeau, Jr, DO, FAHA All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 17, 2022. INTRODUCTION Although less common than in adults, hemorrhagic stroke can affect children, resulting in significant morbidity and mortality. An overview of hemorrhagic stroke in children beyond the newborn period is provided here. Other clinical aspects of stroke in neonates and children are reviewed elsewhere: (See "Stroke in the newborn: Classification, manifestations, and diagnosis".) (See "Stroke in the newborn: Management and prognosis".) (See "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors".) (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis".) (See "Ischemic stroke in children: Management and prognosis".) (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease".) (See "Prevention of stroke (initial or recurrent) in sickle cell disease".) (See "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis".) (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".) CLASSIFICATION https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 1/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate Hemorrhagic stroke encompasses spontaneous intracerebral hemorrhage (ICH), isolated intraventricular hemorrhage, and nontraumatic subarachnoid hemorrhage [1]. ICH is defined by intraparenchymal hemorrhage or a combination of intraparenchymal and intraventricular hemorrhage ( image 1). Despite its common usage, the term hemorrhagic stroke remains confusing. It has also been used to denote hemorrhagic transformation of arterial ischemic stroke or of cerebral venous sinus thrombosis, but it does not encompass those entities, strictly speaking. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Subsequent imaging'.) EPIDEMIOLOGY Although stroke in children is relatively rare compared with adults, it is a significant cause of childhood death and lifelong disability. A stroke suffered within the first decade may cause functional sequelae for multiple decades to follow. Hemorrhagic stroke is a notable contributor to childhood morbidity and mortality, as it accounts for about half of all childhood strokes, compared with <20 percent of adult strokes [2,3]. The estimated incidence of all types of stroke (ischemic and hemorrhagic) in children ranges 2 to 13 per 100,000 children per year in the developed world [4,5]. A study of a California-wide hospital discharge database for first stroke admission for children ages 1 month through 19 years found an annual incidence rate of 1.1 per 100,000 children for hemorrhagic stroke and 1.2 per 100,000 children for ischemic stroke [4]. Similarly, a retrospective cohort study of 2.3 million children (age <20 years) followed for more than a decade revealed an average annual incidence rate of 1.4 per 100,000 children for hemorrhagic stroke [6]. Among hemorrhagic stroke subtypes, the estimated annual incidence of intracerebral hemorrhage in developed countries ranges from 1.1 to 5.2 per 100,000 children [4,5], while the estimated annual incidence of subarachnoid hemorrhage is 0.4 per 100,000 children [4]. ETIOLOGY AND RISK FACTORS Ruptured vascular malformations are the most common cause of intracerebral hemorrhage (ICH) in children. In contrast, hypertension and amyloid angiopathy are the most frequent causes of ICH in adults. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Risk factors'.) https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 2/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate Aneurysms are the most common cause of nontraumatic subarachnoid hemorrhage in both adults and children. (See "Aneurysmal subarachnoid hemorrhage: Epidemiology, risk factors, and pathogenesis".) The etiology and risk factors of perinatal hemorrhagic stroke are reviewed separately. (See "Stroke in the newborn: Classification, manifestations, and diagnosis", section on 'Hemorrhagic stroke'.) Vascular malformations Depending on the series, vascular malformations are responsible for 18 to 90 percent of childhood ICH cases [3,7-9], with arteriovenous malformations (AVMs) being the most common type and cavernous malformations and aneurysms found less frequently ( image 2) [10]. AVMs consist of abnormal direct connections between arteries and veins without intervening capillaries that give rise to high-flow lesions extremely prone to rupture (see "Brain arteriovenous malformations"). The incidence of cerebral AVMs in adults has been estimated to be 1 per 100,000 person-years [11]. Many AVM lesions are thought to be congenital, so this estimate may reflect the incidence in children as well; however, only a small percentage of AVMs (estimated 8 to 20 percent) become symptomatic under the age of 15 years [12,13]. The risk of hemorrhage from a cerebral AVM in children has been estimated at 2 percent per year [14]. AVMs account for 14 to 46 percent of ICH in children and nearly 50 percent of intraparenchymal hemorrhage [15-17]. Although most AVMs are isolated developmental lesions, there are genetic causes that predispose to multiple AVMs. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder of vascular dysplasia associated with mucocutaneous telangiectasias and AVMs. AVMs in patients with HHT most often occur in the pulmonary, hepatic, and cerebral circulations [18,19]. Multiplicity of brain AVMs is highly predictive of the diagnosis of HHT [20]. Incidence of HHT is reported to be 1 in 5000 to 8000 individuals per year [21], although this is likely to be an underestimate due to the variability in clinical manifestations. Approximately 20 percent of adults with HHT have cerebrovascular malformations [22]. The prevalence of cerebrovascular malformations in children with HHT is unknown but believed to approximate that of adult [23]. In one of the largest case series of pediatric patients with confirmed HHT, 11 of 115 children had cerebral AVMs and >50 percent developed symptomatic ICH [19]. Arteriovenous fistulas differ from AVMs because there is an absence of a discrete nidus between the arterial feeder and draining vein. Arteriovenous fistulas are worth noting as these also carry a significant risk of hemorrhage of 1.5 percent per year. However, arteriovenous fistulas are much rarer, comprising only 4 percent of pediatric cerebral vascular malformations [24,25]. https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 3/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate Cavernous malformations (cavernomas or cavernous angiomas) have an estimated annual incidence of 0.56 per 100,000 people, which is approximately one-half that of AVMs [26]. Cavernous malformations consist of dilated sinusoidal vessels lined by endothelium without intervening neural parenchyma. "Leaking" of blood into surrounding tissue can occur due to dysfunctional endothelial cell connections. These are considered to be low-flow lesions. Cavernous malformations have been found to have a prevalence of 0.5 percent in autopsy studies [27,28] and are estimated to account for 20 to 25 percent of pediatric intraparenchymal hemorrhage [3,16,29]. While symptoms may manifest in all age groups, affected children tend to cluster in two age groups: infants and toddlers under the age of 3 years and children in early puberty, ages 12 to 16 years [30,31] While aneurysms are one of the most common vascular anomalies of the central nervous system, they are far less common in children than in adults, with a reported prevalence ranging from 0.5 to 5 percent of the total prevalence of intracranial aneurysms in the general population [32-39]. Aneurysms in children are felt to be different from those in adults in the following respects [33,39-41]: Pediatric aneurysms tend to be larger in size There is a higher incidence of giant aneurysms in children There tends to be a male predominance in children The most common cause of nontraumatic subarachnoid hemorrhage in children and adolescents is rupture of a cerebral aneurysm [6]. Ruptured aneurysms can also cause intraparenchymal hemorrhage or can present with nonhemorrhagic symptoms like headaches or seizures. Hematologic In reports from developed countries, hematologic abnormalities (including thrombocytopenia or platelet dysfunction, hemophilia and other congenital or acquired coagulopathies, and sickle cell disease) were the major risk factor for pediatric hemorrhagic stroke, found in 10 to 30 percent of cases [42]. In resource-limited countries, ICH secondary to underlying hematologic disorders occurs more frequently than hemorrhage due to vascular malformations. A retrospective study of 50 children with ICH at a single institution in Pakistan demonstrated that 52 percent had bleeding disorders compared with 14 percent with vascular malformations [43]. Similarly, a retrospective analysis of 94 children with hemorrhagic stroke in China found that 88 percent of patients had a bleeding diathesis compared with 14 percent with AVM [44]. Special populations with hematologic abnormalities include children with immune thrombocytopenia (ITP), hemophilia, and sickle cell disease: https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 4/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate With ITP, intracranial hemorrhage is estimated to occur in up to 1 percent. (See "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis", section on 'Intracranial hemorrhage'.) With hemophilia, the reported ICH prevalence in children is 3 to 12 percent [45-47]. (See "Clinical manifestations and diagnosis of hemophilia", section on 'Intracranial bleeding'.) With sickle cell disease (SCD), affected individuals are at risk for ischemic and hemorrhagic stroke. One report suggested that children with SCD had a >200-fold higher risk of hemorrhagic stroke compared with children without SCD [48]. In other reports, specific factors associated with hemorrhage in children with SCD included premorbid hypertension, transfusion within the last 14 days, treatment with glucocorticoids, low steady-state hemoglobin concentration, high steady-state leukocyte count, and late effects of moyamoya-type vasculopathy [49-51]. (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease" and "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis".) Cancer A smaller proportion of hemorrhagic stroke in children is attributable to cancer. In one case series of 69 children with intraparenchymal hemorrhage, brain tumors accounted for 13 percent cases [7]. In another case series from a tertiary cancer center, ICH occurred in 3 percent of over 1000 children with brain tumors and in 1 percent of nearly 1600 children with acute leukemia [52]. [53,54] Other Although much less common than in the adult population, hypertension has also been associated with ICH in children. In one small retrospective cohort study, 45 percent of children th with ICH had elevated blood pressure above the 90 percentile at presentation; however, only 14 percent continued to have persistently elevated blood pressure on follow-up, and none required antihypertensive treatment [55]. Another cause of hemorrhagic stroke in childhood is moyamoya disease. Ischemic cerebrovascular events, either transient ischemic attack or infarction, are more prevalent than hemorrhagic events in children with moyamoya, while hemorrhagic stroke is more common in adults. However, moyamoya can cause either ICH or subarachnoid hemorrhage in children. (See "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis", section on 'Clinical presentations'.) Drugs of abuse, coagulopathies secondary to liver dysfunction, and porphyria are rare causes of hemorrhagic stroke in children. https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 5/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate Cohort studies have shown that 9 to 23 percent of childhood ICH remains cryptogenic without a definitive risk factor identified despite extensive evaluation [8,56,57]. However, some proportion of these cryptogenic cases may be due to vascular malformations that have self-obliterated at the time of the incident hemorrhage [58]. CLINICAL FEATURES AND PRESENTATION Among all children who present outside the perinatal period, headache is the most common symptom of hemorrhagic stroke, affecting 46 to 80 percent [7,8,10,17]. Other common presenting symptoms in children include: Nausea and emesis in nearly 60 percent [8] Seizures (either generalized or focal) in 20 to 40 percent [7,8,59] Focal neurologic deficits such as hemiparesis or aphasia, which range in frequency from 13 to 50 percent [8,17,55,58] Neck pain Altered level of consciousness in 50 percent or more [7,8,56,58] The clinical presentation of hemorrhagic stroke can vary based upon the age of the child; younger children are most likely to present with only nonspecific features (eg, altered mentation, seizures, vomiting) while older children are more likely to present with headache, mental status change, and focal neurologic deficits. There is overlap between symptoms in pediatric hemorrhagic stroke, pediatric arterial ischemic stroke, and pediatric cerebral sinovenous thrombosis. All can present with headache, altered mental status, focal neurologic deficits, and seizures. Therefore, neuroimaging is required to differentiate among these entities. However, severe sudden headache with rapid alteration in level of consciousness may be more indicative of a hemorrhage. In a retrospective review of 85 children with nontraumatic intracerebral hemorrhage (ICH) at a tertiary pediatric hospital, the most common clinical signs in young children (<6 years of age) were mental status change, seizures, or vomiting [55]. In contrast, older children ( 6 years of age) often presented with headache and focal neurologic deficits in addition to symptoms of mental status change and nausea/vomiting, allowing clinicians to quickly narrow the differential diagnosis. Another cohort study found that children younger than three years of age at time of hemorrhage onset (n = 9) presented with vague symptoms of general deterioration, increased crying and sleepiness, irritability, feeding difficulty, vomiting, and sepsis-like symptoms with cold extremities [17]. https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 6/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate The onset of clinical symptoms due to hemorrhagic stroke is variable and ranges from rapid occurrence over minutes to insidious progression over several hours to days. In a cohort study of 22 children with ICH, the median time to hospital presentation was 70 minutes, but 23 percent of children presented after 24 hours [8]. A prospective study of 53 children with ICH found that acute symptomatic seizures, defined as those occurring from presentation to seven days after onset, occurred in 36 percent [59]. Thus, acute symptomatic seizures with ICH may be more common in children than in adults, where the corresponding rate is estimated to range from 5 to 30 percent (see "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Clinical presentation'). Further, children with ICH may present with seizures more commonly than children with arterial ischemic stroke, in whom seizures at stroke onset have been reported in 22 percent [60]. Cortical involvement of ICH, which is an important predictor of acute symptomatic seizures in adults [61,62], was not related to acute symptomatic seizures in the pediatric ICH cohort [59]. The pace of symptom onset may be related to the underlying etiology, with aneurysm rupture expected to correlate with sudden onset, while other mechanisms may allow for subacute onset, at least in some cases. However, data are sparse. In a small cohort study of children with spontaneous ICH, approximately half had acute onset of symptoms while the other half had a subacute course [17]. Among children with a known onset, there were four with aneurysms, and the presentation was acute in three; among 16 children with arteriovenous malformation and known onset, an acute presentation occurred in 10 cases (63 percent). Other factors that could affect the rapidity of symptom development are size and location of hemorrhage, intraventricular extension, and presence of hydrocephalus. INITIAL EVALUATION AND DIAGNOSIS The diagnosis of hemorrhagic stroke requires confirmation by brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI) [63]. Therefore, clinical suspicion for hemorrhage in the setting of a compatible presentation (eg, headache, mental status changes, seizure, vomiting, or focal neurologic deficits) as described above should prompt urgent imaging. (See 'Clinical features and presentation' above.) For children of school age or older, the acute onset of headache, particularly when severe, (eg, sometimes reported as the "worst headache of life") should prompt evaluation for intracerebral or subarachnoid hemorrhage. However, the diagnosis of hemorrhagic stroke in children can be difficult because the presentation is often nonspecific and subacute. In one small study, most cases with delayed diagnosis (7 of 11) had subacute onset [17]. https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 7/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate The initial evaluation should center on rapid diagnosis of the hemorrhage, assessment for presence of elevated intracranial pressure, and identification of easily correctible risk factors such as thrombocytopenia or coagulopathy. Children with hemorrhagic stroke are also at increased risk of subsequent ischemic stroke due to compression of blood vessels from mass effect from the intracerebral hemorrhage, vasospasm after subarachnoid hemorrhage, or underlying vasculopathy (such as moyamoya or cocaine-induced vasculopathy) [64]. Urgent neuroimaging Neuroimaging with CT or MRI as the initial study is necessary to determine the cause, to distinguish hemorrhagic stroke from ischemic stroke, and to distinguish stroke from stroke mimics. In a stable patient, MRI is preferred because of the lack of radiation and the better resolution of the parenchyma. MRI with gradient echo and/or susceptibility- weighted sequences is equally sensitive for acute hemorrhage and more sensitive for chronic hemorrhage than CT [65]. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Brain MRI'.) However, MRI is not universally available and may require sedation [65]. Noncontrast head CT should be performed if a patient with suspected hemorrhage is unstable or if obtaining an MRI might delay diagnosis. CT is quick, widely available, does not require sedation in most cases, and is highly sensitive for acute hemorrhage. Noncontrast head CT reveals the diagnosis of subarachnoid hemorrhage in more than 90 percent of cases if performed within 24 hours of bleeding onset; the sensitivity of modern head CT for detecting SAH is highest in the first six hours after subarachnoid hemorrhage (nearly 100 percent when interpreted by expert reviewers). Limited data suggest that proton density and fluid-attenuated inversion recovery (FLAIR) sequences on brain MRI may be as sensitive as head CT for the detection of acute subarachnoid hemorrhage. If neuroimaging is negative for blood and there is high clinical concern for subarachnoid hemorrhage, lumbar puncture should be performed to detect red blood cells or xanthochromia if there are no contraindications (eg, large hemorrhage with significant edema causing impending herniation). (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Evaluation and diagnosis'.) Laboratory studies First-line laboratory studies should include electrolytes, blood urea nitrogen and creatinine, glucose, complete blood count with platelets, coagulation studies (prothrombin time, international normalized ratio, and activated partial thromboplastin time) [63]. Type and screen should be sent for any child who will undergo surgery. https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 8/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate DIFFERENTIAL DIAGNOSIS Hemorrhagic stroke must first be differentiated from other types of acute intracerebral vascular events, such as arterial ischemic stroke and cerebral sinovenous thrombosis, both of which may have concomitant hemorrhagic transformation [66]. (See "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors" and "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis" and "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".) The differential diagnosis for hemorrhagic stroke ( table 1) also includes a broad list of diagnoses that can mimic stroke syndromes. The most common childhood stroke mimics are: Migraine syndromes (see "Types of migraine and related syndromes in children" and "Migraine-associated stroke: risk factors, diagnosis, and prevention", section on 'Forms of migraine with aura') Postictal (Todd) paralysis (see "Differential diagnosis of transient ischemic attack and acute stroke", section on 'Transient neurologic events') Other conditions that may mimic stroke include the following: Brain tumors (see "Clinical manifestations and diagnosis of central nervous system tumors in children") Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (see "Reversible posterior leukoencephalopathy syndrome") Intracranial infections including abscess, encephalitis, and meningitis White matter diseases ( algorithm 1) including multiple sclerosis, acute disseminated encephalomyelitis, and leukodystrophies (see "Pathogenesis, clinical features, and diagnosis of pediatric multiple sclerosis" and "Acute disseminated encephalomyelitis (ADEM) in children: Pathogenesis, clinical features, and diagnosis" and "Differential diagnosis of acute central nervous system demyelination in children") Metabolic derangements such as hypoglycemia (see "Approach to hypoglycemia in infants and children") Organic or amino acidurias (see "Inborn errors of metabolism: Classification" and "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features") https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 9/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate Mitochondrial diseases such as mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) (see "Mitochondrial myopathies: Clinical features and diagnosis", section on 'MELAS') Methotrexate and other chemotherapeutic agent neurotoxicity (see "Overview of neurologic complications of conventional non-platinum cancer chemotherapy" and "Overview of neurologic complications of platinum-based chemotherapy") Bell's palsy (see "Facial nerve palsy in children") Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (see "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)") Conversion disorders Musculoskeletal conditions Neuroimaging is required to diagnose hemorrhagic stroke and to distinguish stroke from mimics. (See 'Initial evaluation and diagnosis' above.) MANAGEMENT Once diagnosis of hemorrhagic stroke is confirmed (see 'Initial evaluation and diagnosis' above), the focus should shift to stabilization of the patient, treatment of elevated intracranial pressure (if present), and close monitoring for brain herniation. There are currently no established evidence-based diagnostic or management guidelines for children with hemorrhagic stroke. The American Heart Association (AHA) scientific statement for the management of stroke in infants and children includes recommendations for children with hemorrhagic stroke [67], which are mostly extrapolated from adult guidelines or are based on expert opinion derived from small retrospective pediatric studies. Immediate consultations Immediate consultations should be obtained from neurosurgery and neurology; hematology should also be consulted if hematologic abnormalities are present on laboratory studies (eg, activated partial thromboplastin time [aPTT], prothrombin time [PT], international normalized ratio [INR], complete blood count [CBC]) or are suspected. Platelet transfusion may be required if there is thrombocytopenia or concern for platelet dysfunction. Coagulopathy may require intravenous vitamin K and/or fresh frozen plasma, and children with factor VIII or IX deficiency typically require urgent factor replacement. Any child on an anticoagulant medication who presents with hemorrhage should receive blood products, https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 10/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate protamine, or vitamin K as warranted. (See "Reversal of anticoagulation in intracranial hemorrhage".) Potential need for decompressive hemicraniectomy and hematoma evacuation should be discussed with neurosurgery. (See 'Surgical management' below.) Supportive measures Subsequent supportive medical management of children with hemorrhagic stroke centers on preventing the progression of brain injury, with primary goals of reducing metabolic demand on brain tissue and avoiding hematoma expansion [63]. Isotonic fluids without glucose should be immediately started to maintain euvolemia, and normothermia should be maintained with acetaminophen and cooling blankets, as temperature elevation >37.5 C increased the likelihood of poor outcome in adult intraparenchymal hemorrhage [68]. Children who present with seizures should be treated with appropriate antiseizure medication (see "Seizures and epilepsy in children: Initial treatment and monitoring"). Prophylactic antiseizure medication treatment is unproven, though there are no high-quality studies of prophylactic antiseizure medication administration in pediatric hemorrhagic stroke. The AHA pediatric stroke guidelines make no recommendations regarding prophylactic antiseizure medication treatment in intracerebral hemorrhage (ICH) [67]. We agree with the AHA guidelines for management of ICH, which recommend against prophylactic antiseizure medications [69]. While treatment of hypertension is a mainstay of hemorrhagic stroke management in adults [63], no clear evidence for managing hypertension after ICH exists in children. It may be a th reasonable goal to lower a child's blood pressure to the 95 percentile for age and sex if elevated after hemorrhage to help prevent hematoma expansion. However, this is not evidence based and may cause a reduction in cerebral perfusion, thereby exacerbating secondary brain injury, particularly if there is elevated intracranial pressure. Any use of antihypertensive medication should be used cautiously. Intracranial pressure Medical management General measures for children with increased intracranial pressure include: Rapid treatment of hypoxia, hypercarbia, and hypotension Elevation of the head of the bed to at least 30 degrees Maintenance of the head and neck midline to facilitate venous drainage Aggressive treatment of fever with antipyretics and cooling blankets Control of shivering in intubated patients with muscle relaxants (eg, vecuronium, rocuronium) https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 11/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate Maintenance of adequate analgesia to blunt the response to noxious stimuli Intracranial pressure (ICP) may become precipitously elevated in hemorrhagic stroke due to mass effect from the hemorrhage or from obstructive or communicating hydrocephalus from intraventricular hemorrhage. This contrasts with acute ischemic stroke, in which increased ICP typically develops several days after the incident event as infarcted brain tissue become edematous. To help reduce or prevent elevated ICP, the head of the bed should be elevated to at least 30 degrees, and the neck should be maintained in a midline position to promote venous drainage. Signs and symptoms of elevated ICP should be frequently reassessed, including presence of positional headache, vomiting, irritability or combativeness, declining mental status, sixth nerve palsies, and papilledema. While Cushing's triad (ie, hypertension, bradycardia, and respiratory depression) is highly suggestive of elevated ICP, this is typically a late finding. For any neurologic deterioration, a head computed tomography (CT) should be obtained promptly to assess for worsening hemorrhage, hydrocephalus, edema, or herniation. Direct ongoing measurement of ICP may require placement of an intraventricular catheter, which can also aid in ICP reduction via direct cerebrospinal fluid drainage, or a subdural bolt if an intraventricular catheter is not technically feasible due to small size of a child's ventricles or other reasons. Nonsurgical interventions for management of increased ICP include hyperventilation to PCO of 2 25 to 30 mmHg (if the child is intubated) and hyperosmolar therapy with intravenous mannitol (bolus 1 g/kg, given as an intravenous infusion through an in-line filter over 20 to 30 minutes, followed by infusions of 0.25 to 0.5 g/kg as needed, generally every six to eight hours) or hypertonic saline to promote osmotic diuresis (see "Elevated intracranial pressure (ICP) in children: Management", section on 'Hyperosmolar therapy'). If hyperosmolar therapy is administered, close monitoring of plasma osmoles and electrolytes is required to avoid hypovolemia, hypotension, and renal failure. Glucocorticoids should be avoided because they did not improve outcomes in randomized controlled trials of adults with ICH [70,71], and the resultant hyperglycemia may lead to worse outcomes [72,73]. Surgical management Ultimately, medical interventions for elevated ICP are only temporizing measures, and surgical evacuation of a parenchymal hematoma or decompressive craniectomy may be necessary to control refractory elevations in ICP and/or mass effect. Surgical hemorrhage evacuation for supratentorial ICH is controversial, and no high-quality studies in children have evaluated early surgical hematoma evacuation or hemicraniectomy. In adults, randomized trials have not conclusively demonstrated benefit. (See "Spontaneous https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 12/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate intracerebral hemorrhage: Acute treatment and prognosis", section on 'Surgical approaches for selected patients'.) As children typically lack the baseline cerebral atrophy found in older adults that permits expansion of the hematoma without consequent compression of the surrounding parenchyma, it is biologically plausible that children may benefit from hematoma evacuation to reduce ICP. If a child is undergoing resection of an underlying vascular malformation that is at high risk for acute rebleeding, it may be optimal to concurrently evacuate the hematoma. Surgical evaluation also might be warranted if a child is comatose, has elevated intracranial pressure that is refractory to medical management, or a worsening neurological examination. As in adults, cerebellar hemorrhages >3 cm in diameter in a child who is deteriorating or in whom brainstem compression and/or hydrocephalus is developing due to compression on the ventricular system should also be considered for surgical evacuation. If a cerebellar hemorrhage is evacuated, suboccipital craniectomy is typically performed at the same time. While hemicraniectomy has not been studied in the setting of pediatric hemorrhagic stroke, there are some series in which hemicraniectomy was associated with improved function and survival in pediatric arterial ischemic stroke [74,75]. In a child who undergoes surgical hematoma evacuation due to a supratentorial hemorrhage causing elevated intracranial pressure that is refractory to medical management, the surgeon may elect to perform a concomitant hemicraniectomy, particularly if the intracranial pressure remains elevated after hematoma evacuation or if there is herniation out of the craniotomy defect. Identifying the etiology Obtaining dedicated cerebrovascular imaging in the acute setting is critical to guide appropriate interventions given the high rate of vascular malformations underlying hemorrhagic stroke in children. Cerebral angiography is a minimally invasive modality that may be used for diagnosis and treatment of vascular causes of ICH [76]. While conventional cerebral angiography remains the gold standard, many institutions opt to first use noninvasive modalities. One retrospective study found that a combination of magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and magnetic resonance venography (MRV) images accurately identified the cause of ICH in 66 percent of subjects, which was statistically equivalent to the diagnostic yield of conventional cerebral angiography alone (61 percent) [77]. However, another retrospective case series of children with nontraumatic ICH reported identification of the cause of bleeding in 97 percent of children who underwent conventional cerebral angiography compared with 80 percent of children who did not have angiography [7]. Another alternative is CT angiography (CTA), which can be rapidly obtained without the need for sedation in some children, is more widely available than MRA, and may offer superior https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 13/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate angioarchitectural visualization compared with MRA [78]. CTA also has a higher sensitivity for detecting aneurysms up to 2 mm in size. However, CTA exposes the child to both ionizing radiation and an iodinated contrast agent, requires a large bore intravenous line, and may be nondiagnostic if the child moves during the study. For children with hemorrhagic stroke and no identified cause despite a thorough evaluation, including appropriate noninvasive vascular imaging, we suggest conventional cerebral angiography. As an acute hemorrhage with large hematoma and significant cerebral edema can obscure visualization of an underlying vascular malformation, vascular studies that are initially nondiagnostic should be repeated weeks to months later once the clot has been reabsorbed if no other cause for the hemorrhage (eg, tumor, coagulopathy) is found [76]. The yield of an extensive evaluation for a bleeding diathesis in children with hemorrhagic stroke is not well-studied. A rational approach is to obtain the screening laboratory studies suggested above (see 'Laboratory studies' above) (ie, a complete blood count with platelets, coagulation studies, prothrombin time, international normalized ratio, and activated partial thromboplastin time) and to pursue additional testing if the screening studies are abnormal or if an underlying vascular lesion or tumor is not found. Higher-level studies may include factor VIII, IX, and XIII levels and von Willebrand disease studies and should be ordered in consultation with a hematologist. (See "Approach to the child with bleeding symptoms" and "Approach to the child with unexplained thrombocytopenia" and "Clinical manifestations and diagnosis of hemophilia" and "Clinical presentation and diagnosis of von Willebrand disease".) Treatment of vascular lesions Endovascular and/or surgical management of vascular malformations may be required in the acute setting depending on the location and vascular anatomy of the lesion in conjunction with the clinical status of the child. Multidisciplinary consultation with neurosurgery, interventional radiology, and neurology is advised to choose the optimal approach to treatment of these lesions [67]. Vascular malformations other than aneurysm typically have a low risk of acute rebleeding (although they may rebleed at later times) [79-81]. Therefore, many centers will await hematoma resolution prior to definitive treatment so that the full extent of the vascular malformation can be elucidated. However, if hematoma evacuation is needed, a vascular malformation may be addressed at the same time. Some arteriovenous malformations that cannot be treated with endovascular or surgical techniques may be amenable to gamma knife or proton beam therapy once the hematoma has retracted. Aneurysms have a higher rate of acute rebleeding [82]. Therefore, aneurysm repair typically occurs in the acute setting. AVMs with an aneurysmal component that may cause acute https://www.uptodate.com/contents/hemorrhagic-stroke-in-children/print 14/33 7/7/23, 11:29 AM Hemorrhagic stroke in children - UpToDate rebleeding also may require earlier intervention. Follow-up imaging Due to the high risk of recurrence, we suggest follow-up imaging for most children with hemorrhagic stroke due to a vascular malformation. In addition, we suggest follow-up imaging in cases where a vascular cause is not found but is suspected. Even when complete resection of an arteriovenous malformation is achieved, there is a substantial risk of recurrence. In one retrospective report of 28 children who underwent surgical resection of arteriovenous malformations, 4 had recurrence leading to repeat resections [83]. Of note, two of the children in this cohort had arteriovenous malformations that were not detected until 17.7 and 25 months after the incident hemorrhage. While the frequency and modality of follow-up imaging is center-dependent, our suggested protocol is to obtain brain MRI with MRA at three to six months after the first hemorrhage, and/or a conventional angiogram between three and six months. Additional follow-up imaging at later points is typically necessary. In children with an unresected cavernous malformation, periodic imaging with MRI is suggested if the child is having frequent symptoms such as headaches or seizures. Genetic screening Genetic screening may be reasonable if multiple vascular malformations are found on imaging or if there is a suggestive family history [67]. The most common genetic cause of brain AVMs is hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant condition. Patients with HHT may have cerebral or spinal cord involvement with telangiectasias, brain AVMs, aneurysms, or cavernous malformations. (See