Chapter 18. Stroke

Stroke in the pediatric population is being identified more frequently, and its effects, once thought to be limited, are now being recognized as more serious. Estimates of incidence range between 2 and 8 per 100,000, with neonates being disproportionately affected. A recent population-based study found that perinatal arterial ischemic stroke (PAS) was recognized in 1 in 2300 term infants.1 The rise in diagnosis of stroke is in part attributable to improved diagnostic techniques and to greater survival of susceptible children.2,3 Definitions and epidemiology of specific types of stroke in children are detailed below in the discussion of differential diagnosis.

In the past, it was felt that children generally recover from stroke with minimal long-term deficit (due to plasticity of the young brain). Recent studies reveal, however, that only 31% of children with ischemic stroke recovered to a normal neurological examination. Approximately 17% had persistent cognitive deficits. Disability can include physical, cognitive, behavioral, and psychiatric sequelae. Despite significant advances in management, stroke continues to be one of the leading causes of death among children.

The relative lack of controlled clinical trials significantly limits the current treatment guidelines, and the evidence-based interventions established for adults cannot be directly extrapolated to pediatric patients. Differences in the hemodynamic and coagulation pathways as well as in the significant risk factors that contribute to cerebrovascular events distinguish the two. For instance, atherosclerosis is one of the most common sources of adult stroke but rarely contributes to stroke risk in the pediatric population.3

Ischemic strokes occur secondary to insufficient cerebral oxygen delivery. This may occur because of occlusion of a vessel secondary to plaque formation (more common in adults), fibromyscular dysplasia, or vascular dissection. Cardioembolic sources of stroke are more common in children. Hematologic sources of stroke include hyperviscosity syndromes, sickle cell disease, and leukemia. Each of these disorders is discussed in much greater detail in the following sections.

Intracranial hemorrhage also occurs in several distinct subtypes. Subarachnoid hemorrhage may arise secondary to aneurysm rupture or trauma. Subdural and epidural hematomas often occur secondary to traumatic injury. Parenchymal hemorrhages may be related to a number of etiologies including trauma, abuse, collagen vascular diseases, and ischemic stroke.

In order to know appropriately manage stroke patients (see "Management" later in the chapter), the acutely presenting pediatric stroke patient must be recognized in a timely fashion. Unfortunately, the average delay between symptom onset and first diagnostic study is 28.5 hours, largely prohibiting the institution of hyperacute interventions.4 This delay stems from the often nonspecific symptoms with which pediatric stroke patients present. Neonates with underlying stroke frequently present with seizures as well as lethargy and apnea, whereas older children may present with more focal neurological deficits such as speech abnormalities, visual or sensory changes, or hemiparesis.5

The differential diagnosis can be vast, including infections and metabolic imbalances. A few key stroke masqueraders should also be considered. Familial hemiplegic migraine is characterized by family history and EEG pattern of unilateral slow background rhythm.5 Postictal or "Todd" paralysis is a consideration when focal weakness occurs after a seizure, and can closely mimic stroke. Patients should be treated with the urgency of an acute cerebral infarction until proven otherwise.

Physicians must be aware of predisposing conditions and risk factors to have the index of suspicion required to diagnose stroke. This involves awareness of three main categories of cerebrovascular events: arterial ischemic, hemorrhagic, and sinovenous thrombosis. Risk factors overlap for stroke subtypes, but treatment may differ.

Perinatal Stroke

Definitions and Epidemiology

A number of ischemic and hemorrhagic insults may affect the developing fetal or neonatal brain. It is therefore important for the clinician to be aware of the different types of events that can cause perinatal stroke, as the evaluation, management, and expected outcome may be related to the type of lesion. Perinatal arterial ischemic stroke refers to a cerobrovascular event occurring during fetal or neonatal life, before 28 days after birth, with pathologic or radiologic evidence of focal arterial infarction of brain.6 Sinovenous thrombosis describes thrombosis in one or more of the cerebral venous sinuses and may be associated with secondary hemorrhage.7 Primary hemorrhagic stroke and other types of intracranial hemorrhages that tend to affect near-term and term infants tend to be associated with specific risk factors responsible for the hemorrhage. Periventricular hermorrhagic infarction, a lesion that mainly affects preterm infants, is a serious complication of germinal matrix-intraventricular hemorrhage.

Clinical Presentation

Although these lesions tend to have significant overlap in terms of being hemorrhagic or ischemic, the effects of these types of events on the neonate may result in immediate or eventual death, with other long-term complications including cerebral palsy, epilepsy, blindness, behavioral disburbances, and congnitive dysfunction. Despite the type of lesion, symptoms may be subtle and are often nonspecific. The acute and chronic manifestations of perinatal stroke are reviewed in Table 18-1.

Perinatal Arterial Ischemic Stroke

Definitions and Epidemiology

Perinatal arterial ischemic stroke, occurring more frequently in the near-term and term infant, has a prevalence ranging from 17 to 93 per 100,000 live births.7-10 Most lesions occur in the left hemisphere within the distribution of the middle cerebral artery. Rarely, multifocal lesions occur but tend to be embolic in origin.7

Pathogenesis

A wide range of risk factors have been implicated in the etiology of perinatal arterial ischemic stroke, and these are listed in Table 18-2.7,9,11-13 However, some studies report no finding of an obvious precipitating event in as many as 25% to 77% of cases.14-16 The difficulty with identifying a specific risk factor for the development of the lesion is that neonates often have multiple risk factors present, making it likely that a combination of environmental risk factors interacting with genetic vulnerabilities is often responsible for the ischemic event.6 The exact role of genetic thrombophilias in the pathogenesis of perinatal arterial ischemic stroke is yet to be defined,17 but disorders such as factor V Leiden mutation, the prothrombin 20210 promoter mutation, hyperhomocystinemia, elevated lipoprotein (a) levels, antiphospholipid antibodies, and relative protein C deficiency have been described with increased frequency in infants who have perinatal arterial ischemic stroke when compared with healthy control subjects.18-24 Other genetic thrombophilias have also been implicated and are provided in Table 18-3. Further studies are required to better define the potential role of infantile thrombophilia in the pathogenesis and outcome of perinatal arterial ischemic stroke, but experts in the field do recommend a comprehensive thrombophilia assessment for all infants presenting with perinatal arterial ischemic stroke, regardless of other risk factors present.17,25

Clinical Presentation

The difficulty with identifying perinatal arterial ischemic stroke in the neonate is that symptoms tend to be nonspecific and often are difficult to identify. In many cases, the symptoms may not become evident until quite some time after the stroke. The acute and chronic manifestations of perinatal arterial ischemic stroke are reviewed in Table 18-1. Figure 18-1 reveals a multifocal infarction on diffusion-weighted MRI involving the pons and temporal lobe.

Sinovenous Thrombosis

Clinical Presentation

Most cases of sinovenous thrombosis occur in term infants and present with nonspecific clinical features as listed in Table 18-1. The superficial and lateral sinuses are most frequently involved, and venous infarction has been reported in up to 30% of cases.26 An example of magnetic resonance venography (MRV) in a normal patient is shown in Figure 18-2.

Pathogenesis

Risk factors for the development of sinovenous thrombosis are similar to those for perinatal arterial ischemic stroke and are listed in Table 18-3, although a significant number of cases are reported as idiopathic.16

Hemorrhage

Definitions and Epidemiology

Primary hemorrhagic stroke and other types of intracranial hemorrhage include subdural, primary subarachnoid, intracerebellar, intraventricular hemorrhage, and other miscellaneous types such as focal hemorrhages into the thalamus, basal ganglia, brainstem, or spinal cord.4

Periventricular hemorrhage (PVHI) is a venous hemorrhagic infarct in the drainage area of the periventricular terminal vein.27,28 A complication mainly associated with prematurity, a recent study found that 1% of infants less than 2500 g met the diagnostic criteria for PVHI, with the highest percentage (9.9%) being those less than 750 g.28

Pathogenesis

The majority of these types of hemorrhages tend to be antepartum or during the stresses of delivery and associated with specific risk factors as outlined in Table 18-3. Intrapartum risk factors associated with the development of PVHI include emergent cesarean section, low Apgar scores, and need for respiratory resuscitation; while postnatal factors include pneumothorax, pulmonary hemorrhage, patent ductus arteriosus, acidosis, hypotension requiring pressure support, and significant hypercarbia.28 Although an exact cause/effect relationship of these risk factors and correct knowledge of when these events occur has been difficult to prove, it is felt that disturbances in systemic and cerebral hemodynamics occurring around the intrapartum and early neonatal period are important in the development of PVHI.28

Clinical Presentation

Figure 18-3 shows a hemorrhage in the thalamic region on CT. In general, primary subarachnoid hemorrhages are more frequently seen in the premature infant but tend to be clinically benign; in contrast to intracerebellar hemorrhages which, although also more frequently observed in premature infants, tend to be serious.27 Subdural and other miscellaneous types of hemorrhages tend to affect full-term infants, and their outcome is variable. Although intraventricular hemorrhages tend to predominately occur in premature infants (discussed later), they have been reported to occur in term infants as well.

PVHI usually accompanies a large germinal matrix-intraventricular hemorrhage.28 See Figures 18-4 and 18-5 for examples of PVHI.

Arterial Ischemic Stroke

Definitions and Epidemiology

Arterial ischemic stroke can be related to a number of vascular, hematologic, cardiac, and metabolic risk factors. Potential causes of ischemic stroke in children are presented in Table 18-4.

Pathogenesis

Arterial dissection most commonly occurs after trauma. These injuries occur more frequently in boys than girls. Traumatic dissection can result from head or cervical trauma, including whiplash, shaken baby, or intraoral trauma such as falling with a pencil in the mouth.2 Rarely, dissection occurs atraumatically due to a connective tissue disease such as fibromuscular dysplasia. See Table 18-5.

The C1-2 vertebral level is the most common location for a vertebral artery dissection. Artery to artery embolism from the site of endothelial injury is the usual pathogenic mechanism for infarction.29 In one meta-analysis, 15% of posterior circulation and 5% of anterior circulation dissections were followed by recurrent ischemic events.30

Diagnosis

Diagnosis is made via characteristic findings on MRI and MRA of the head and neck, extracranial vascular ultrasound, or cerebral angiography. Because C1-2 is the most common location for a vertebral artery dissection, findings of a double lumen, intimal flap, or bright crescent on T1 fat suppression images confirm the diagnosis. Also, the finding of occlusion or segmental narrowing of an artery within 6 weeks of a known trauma, or of vertebral artery occlusion at the C2 vertebral level even without trauma, should raise the possibility of dissection.31

Cardiac Causes of Stroke

Definitions and Epidemiology

Cardiac risk factors rise in importance in pediatric stroke relative to the adult population. Congenital heart disease is one of the major risk factors for stroke in pediatric patients. The Canadian Pediatric Ischemic Stroke Registry reported that 19% of children with arterial ischemic stroke had heart disease.2 The risk is particularly high during surgical procedures.32 Right-to-left shunting can lead to hypoxia and polycythemia, creating a hyperviscous state. Infective endocarditis additionally poses risk for embolic stroke, and patent foramen ovale is a risk for thromboembolic strokes due to venous-arterial communication. PFO (patent foramen ovale) is three times more prevalent in pediatric stroke patients than in the general population.2

Vasculitis

Definitions and Epidemiology

Vasculitis is another source of stroke risk in the pediatric population. Primary vasculitides include those affecting large and medium vessel such as Takayasu arteritis, and those affecting small vessels such as primary CNS angiitis and Wegener. Unique to children is the importance of secondary, postinfectious vasculitis. Varicella zoster infection was detected in the preceding 12 months in 31% of children in one study of acute ischemic stroke as opposed to 9% of healthy controls.33

Clinical Presentation

Strokes caused by postinfectious vasculitis typically involved the basal ganglia with typical vascular abnormalities of focal stenosis of the distal internal carotid and proximal segments of anterior cerebral (A1), middle cerebral (M1), and posterior cerebral artery (P1).31,33 Other pathogens including HIV and CMV may produce similar vasculitis and stroke risk. Radiation to the brain can also be a risk factor for secondary vasculitis.2

Moyamoya

Moyamoya is a vascular condition with risk of recurrent stroke. Primary moyamoya disease is an autosomal dominant disease most common in Japanese patients, hence the Japanese name meaning "puff of smoke." This describes the angiographic blush that occurs due to extensive collateralization in response to occlusion of large intracranial arteries, often with bilateral carotid artery occlusion. Moyamoya syndrome can also occur secondary to sickle cell disease, Down syndrome, cranial radiation, or neurofibromatosis.2,5,31

Sickle Cell Disease

Definitions and Epidemiology

Sickle cell disease (SCD) is one of the most prevalent hematologic risk factors for pediatric stroke. An astounding (9%) of patients with SCD will have an acute ischemic stroke by the age of 14, and approximately 20% will have MRI evidence of silent ischemic insults.31 Risk is greatest in the younger years (ages 2-8), and two-thirds will have a recurrent event if untreated.34,35

Pathogenesis

The sickled erythrocytes can cause thrombosis in large blood vessels or occlusion of small blood vessels leading to hypoperfusion in watershed areas.2

Other Hematologic Conditions

Further hematologic variables relevant to ischemic stroke include high concentrations of lipoprotein (a), protein C deficiency, and factor V Leiden mutation.36 These hypercoaguable states are most highly associated with risk of recurrent stroke.35,36 Other prothrombotic states include positivity for antiphospholipid antibodies including anticardiolipin antibodies and lupus anticoagulant, protein S deficiency, factor V Leiden mutation, prothrombin gene mutation (G20210A), and antithrombin III deficiency.2 Extensive discussion of each of these is beyond the scope of this chapter. Hyperviscosity or "sludging effect" can also be caused by dehydration, thrombocytosis, and polycythemia. Malignancies including leukemia and lymphoma can also create hypercoaguable states with increased risk of stroke. Several chemotherapeutic agents have also been implicated in cerebral infarction, including adriamycin, asparaginase, and methotrexate. Severe anemia, often seen in developing countries, can result in cerebral infarction secondary to the poor oxygen-carrying capacity.

Other etiologies to consider are toxic or iatrogenic sources such as cocaine or oral contraceptive pills. Metabolic sources of stroke risk include homocysteinuria, ornithine transcarbamylase deficiency, and MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes). CADASIL and hyperhomocyteinemia can lead to endothelial damage and platelet aggregation and are treated with folate and vitamin B.2 MELAS is a heritable mitochondrial disease that presents in childhood with proximal muscle weakness, episodic vomiting and lactic acidosis, migraine headaches, and stroke-like episodes. The areas of infarction can be inconsistent with any single vascular distribution. Diagnosis is made by muscle biopsy finding ragged red fibers, and the disease is usually progressive. Hearing and visual loss may occur as well.2 Neurocutaneous diseases of childhood such as (Sturge-Weber and NF1) can be associated with increased risk of stroke.

Hemorrhagic Stroke

Hemorrhagic stroke in children, in contrast to adults, occurs with equal frequency to ischemic stroke.2 Trauma and bleeding diathesis are important risk factors for hemorrhagic stroke. Risk factors for hemorrhagic stroke are outlined in Table 18-6. Vascular malformations such as aneurysm or AVM may result in an intracerebral hemorrhage (see Figure 18.6).

Aneurysm in Subarachnoid Hemorrhage

Definitions and Epidemiology

Intracranial aneurysms are common in the general population. The prevalence of unruptured intracranial aneurysms has been largely determined through autopsy studies and through angiographic series. In adults, the prevalence ranges from 0.2% to 9%, with a mean of approximately 2%. The prevalence is thought to be lower in children.

The incidence of aneurysm rupture or subarachnoid hemorrhage (number of aneurysm ruptures/ 100,000 population/year) varies depending upon factors such as the population being studied (Finnish and Japanese persons have a greater disposition) or the age distribution of the population (a younger population will have a lower incidence). The incidence of aneurysmal subarachnoid hemorrhage ranges from approximately 7 to 21 per 100,000 persons per year, with an average of 10 per 100,000 persons per year. In the United States alone, there are approximately 28,000 new patients with subarachnoid hemorrhage each year. The incidence of subarachnoid hemorrhage has remained stable over the last three decades.

Aneurysms are relatively uncommon in children and become more common with increasing age, with a peak incidence occurring between the ages of 50 and 60. There is a clear female gender predilection (approximately 1.6 times higher incidence in females). Smoking and hypertension may predispose to aneurysm formation and/or rupture.

Although most cases of subarachnoid hemorrhage are sporadic, in those families with a history of subarachnoid hemorrhage in more than one family member, the prevalence of unruptured aneurysms in other family members is markedly increased (a fourfold to tenfold increased prevalence). Autosomal polycystic kidney disease is unequivocally associated with a higher prevalence of intracranial aneurysms. Other conditions that may predispose to intracranial aneurysm formation include connective tissue disorders such as Ehlers-Danlos syndrome type IV, Graphic Jump Location

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Clinical Presentation

ICH is suggested by the rapid onset of neurological dysfunction and signs of increased intracranial pressure (ICP), such as headache, vomiting, and decreased level of consciousness.

The symptoms of ICH are related primarily to the anatomic location and pressure resulting from the expanding hematoma. Findings such as hypertension, tachycardia, or bradycardia (Cushing response), and abnormal respiratory patterns, are common effects of elevated ICP and brainstem compression.

Diagnosis

Confirmation of ICH cannot rely solely on the clinical exam and requires the use of emergent CT scan or MRI. Widespread use of non-enhancing CT scan of the brain has dramatically changed the diagnostic approach of this disease, becoming the method of choice to evaluate the presence of ICH. CT scan evaluates the size and location of the hematoma, extension into the ventricular system, degree of surrounding edema, and anatomic disruption. Contrast-enhanced CT scan is not done routinely in most centers, but may prove helpful in predicting hematoma expansion and outcome. MRI techniques such as gradient-echo (GRE, T2*) are highly sensitive for the diagnosis of ICH but may be more difficult to obtain in the pediatric patient (often requiring sedation). Sensitivity of MRI for ICH is 100%. MRI and CT are equivalent for the detection of acute ICH, but MRI is significantly more accurate than CT for the detection of chronic ICH.

Further discussion of unruptured aneurysms and subarachnoid hemorrhage is undertaken in the chapters on these disorders.

The child presenting with acute stroke will require careful history and physical examination including perinatal history and developmental milestones. As mentioned above, diagnosis of acute stroke in childhood can be challenging. The physician must have a high index of suspicion. Stroke should not be considered an "adult disease" but a neurological disorder with different manifestations in different age groups. Table 18-7 highlights many of the physical findings associated with stroke in the pediatric age group.

Two sets of guidelines have recently been proposed that may help guide neurologists and generalists treating pediatric stroke. In the United States, the ACCP guidelines (American College of Clinical Pharmacy) published in Chest addressed both neonatal and childhood arterial ischemic stroke and cerebral sinus venous thrombosis.37 The Scottish Intercollegiate Guidelines from the UK (UK Royal College of Physicians pediatric working group) addressed pediatric patients 1 month to 18 years of age.38 Both sets of guidelines contain review of the literature and input from pediatric hematologists. The UK guidelines add the involvement of pediatric neurologists. The two sets of guidelines have several areas of agreement, and also variation on several points.

Initial Stabilization

Clearly the most crucial initial interventions are those of stabilizing airway, breathing, and circulation. Adequate oxygenation and ventilation are crucial to reducing the metabolic demand of the ischemic brain. Oxygen should be applied via 100% mask and intubation performed for hypoxia, failure to protect airway, decompensated shock, status epilepticus, or GCS less than 8.39 Core temperature should be kept between approximately 36°C and 37°C.39 Normoglycemia should be maintained, and seizures should be treated aggressively. Cardiac monitoring with telemetry or Holter monitor should be applied, and initial laboratories sent to evaluate glucose, electrolytes, liver function tests, complete blood count (WBC, Hct, platelets), coagulation profile (PT/PTT/INR), erythrocyte sedimentation rate, ANA, and toxicology screen. This can help identify a metabolic acidosis, which can be seen in MELAS; a concurrent infection; or gross hematologic abnormalities. Generally, a chest radiograph and electrocardiogram are obtained due to the significance of cardiac disease to risk of pediatric stroke.

Because a key initial branch point in the approach to stroke is the distinction between a hemorrhagic and an ischemic event, CT of the head should be performed immediately. Although MRI with diffusion-weighted imaging is better equipped to detect the acute ischemic event, the study takes longer and often requires sedation of the child. CT, although insensitive to infarction in the first 2 days and inferior for evaluating the posterior fossa, is more readily available and quickly obtained. A negative CT scan acutely does not rule out ischemia, however, and requires follow-up imaging in 24 to 48 hours.

Imaging

When MRI is performed after the CT, diffusion imaging helps age the stroke. Perfusion and proton magnetic resonance spectroscopy images are variations that can help determine the territory of ischemia in addition to infarction (Table 18-8). MR angiography is a noninvasive way to detect vascular occlusions or abnormalities, but may overestimate the degree of stenosis (Table 18-9). MRI and MRA should be obtained in arterial ischemic or hemorrhagic strokes. In the latter, arterial venous malformations or aneurysms may be detected and possibly amenable to treatment. When dissection is suspected, fat suppression MRI of the neck or MRA of the cervical arteries can make the diagnosis. Carotid Doppler ultrasonography can quickly evaluate for dissection in suspected cases. Conventional angiography is the "gold standard," as therapeutic interventions may be possible with the procedure, but due to it being more time-consuming and invasive, it is usually reserved for those cases in which MRA is nondiagnostic. MR venography is useful for detecting cerebral sinus thromboses, especially in patients with unexplained lethargy, seizures, or infarction with headache.

Cardiac Evaluation

An echocardiogram should be obtained to evaluate for congenital heart disease or for an embolic source arising from valvular abnormalities, dilated cardiomyopathy, or abnormalities involving the proximal great vessels. A bubble contrast study with agitated saline should be part of the evaluation to detect intracardiac shunting due to a PFO. A transthoracic echocardiogram is less invasive, but a transesophageal echocardiogram allows visualization of the aortic arch and ascending aorta.2

Laboratory Evaluation

If the initial tier of investigations fails to identify a cause for stroke, further evaluation is indicated for known hypercoagulable states (Table 18-4). These investigations should be made 3 to 6 months after the acute stroke.5 Hemoglobin electrophoresis is used to detect sickle cell disease; and arterial pyruvate, CSF, and arterial lactate are used to evaluate for mitochondrial disease. Lipid profile and serum and urine homocysteine can help detect a predisposition to thrombosis. HIV testing should also be considered.2

Sickle Cell Disease Management

Sickle cell disease (SCD) is the only area of pediatric stroke for which clear evidence-based guidelines exist. In patients with sickle cell disease, both guidelines suggest exchange transfusion to HbS less than 30%, and intravenous hydration is indicated. Transcranial Doppler ultrasound is used to screen periodically for increased cerebral flow suggesting need for exchange. The STOP trial in 1998 was aborted early due to a clear demonstration of 92% relative risk reduction in stroke with exchange transfusion for cerebral blood flow velocities greater than 200 mL/sec on transcranial Doppler.34,40 This has led to clear recommendations by the American Academy of Neurology for screening SCD patients with transcranial Doppler ultrasound.41 The frequency of screening has not been established. Sicklers with frequent transfusions are at risk for iron overload, and alternative therapies including hydroxyurea can also be considered in the chronic maintenance of patients with sickle cell disease.

Anticoagulants

In general, the treatment guidelines suggested in Chest recommend unfractionated or low molecular weight heparin for 5 to 7 days regardless of etiology, and the UK guidelines suggest aspirin 5 mg/kg acutely. Neither guideline recommends the use of alteplase. Specific situations merit further interventions as follows:33

Perinatal Arterial Ischemic Stroke

Management of perinatal arterial ischemic stroke is mainly supportive. Current guidelines from the American College of Chest Physicians suggest that neonates with proven cardioembolic stroke should receive treatment with unfractionated heparin or LMWH.37 The guidelines do not recommend anticoagulant therapy for neonates with non-cardioembolic stroke. However, the guidelines do not mention if the number of blood vessels affected should be taken into consideration or if noncardiac-related embolism warrants anticoagulation. In addition, there is a lack of information on how to properly anticoagulate neonates who are found to have a genetic thrombophilia.

Sinovenous Thrombosis

Management of neonates with sinovenous thrombosis is controversial and limited by the fact that there are no current clinical trials evaluating the use of anticoagulation. Current guidelines from the American College of Chest Physicians recommend the use of either low-molecular weight heparin or unfractionated heparin only for neonates with sinovenous thrombosis but without large ischemic infarctions or evidence of intracerebral hemorrhage due to the theoretical risk of bleeding. Radiologic monitoring and initiation of anticoagulation only if extension occurs is recommended for the remainder of cases.38 Longer-term anticoagulation with warfarin for at least 3 to 6 months may be necessary for older patients with venous thrombosis. Follow-up imaging of the venous thrombosis is necessary prior to discontinuation of treatment.

Arterial Dissection

Both guidelines recommend anticoagulation for 3 to 6 months after dissection. The Chest guidelines specify 5 to 7 days of unfractionated (UFH) or low molecular weight heparin (LMWH) followed by LMWH or warfarin for 3 to 6 months, while the UK guidelines generally suggest anticoagulation for up to 6 months or until vessel healing.

Vasculitis

Vasculitis is usually acutely treated with steroids, with consideration for long-term immunosuppression. The Chest guidelines suggest aspirin 2 to 5 mg/kg/day after initial UFH or LMWH for 5 to 7 days in patients with other vasculopathies. The UK guidelines recommend continued aspirin 1 to 3 mg/kg/day after 5 mg/kg on the first day.

Cardiogenic Embolism

The guidelines both support anticoagulation for cardiogenic embolism, and the Chest guidelines recommend UFH or LMWH for 5 to 7 days followed by LMWH or warfarin for 3 to 6 months. The doses of UFH and LMWH for the treatment of stroke are not fully developed for adults, much less for children. In general, the usual weight-based nomograms are used in adults, and this would seem reasonable in the treatment of children as well. The most important consideration is to avoid bolus therapy. Bolusing these agents results in a transient but severely elevated PTT, which could in turn increase the risk of intracranial hemorrhage.

Hemorrhagic Stroke

Hemorrhagic stroke or intracerebral hemorrhage requires close observation, likely in the intensive care unit. Tight control of blood pressure is vital. The target blood pressure should be identified after consultation between the neurologist and the neurosurgeon. If significant mass effect is present, surgical evacuation or craniotomy for decompression may be indicated. Children should be emergently transported to a tertiary care center if necessary.

Eeg Monitoring

Continuous electroencephalographic (cEEG) monitoring has been shown to detect nonconvulsive seizures or status epilepticus in 28% of stuporous or comatose ICH patients, a finding consistent with studies of patients with other types of severe acute brain injury. Moreover, ictal activity detected by cEEG after ICH is associated with neurological deterioration and increased midline shift. It is our practice to perform surveillance cEEG monitoring for at least 48 hours in all comatose ICH patients.

Anticonvulsant Therapy

The 30-day risk of clinically evident seizures after ICH is approximately 8%. Convulsive status epilepticus may be seen in 1% to 2% of patients, and the risk of long-term epilepsy ranges from 5% to 20%. Lobar location is an independent predictor of early seizures. Acute seizures should be treated with intravenous lorazepam (0.05-0.1 mg/kg) followed by an intravenous loading dose of fosphenytoin (20 mg/kg). Critically ill patients with ICH may benefit from prophylactic antiepileptic therapy, but no randomized trial has addressed the efficacy of this approach. Some centers prophylactically treat ICH patients with large supratentorial hemorrhages and depressed level of consciousness during the first week, based on evidence that this practice reduces the frequency of seizures from 14% to 4% during the first 7 days after severe traumatic brain injury. The AHA guidelines recommend antiepileptic medication for up to 1 month, after which therapy should be discontinued in the absence of seizures. This recommendation is supported by the results of a recent study that showed that the risk of early seizures was reduced by prophylactic AED therapy. Further detail regarding the selection of appropriate antiepileptic medications is reviewed in Chapter 3.

Temperature Management

Fever after ICH is common, particularly after IVH, and should be treated aggressively. Sustained fever after ICH has been shown to be independently associated with poor outcome, and even small temperature elevations have been shown to exacerbate neuronal injury and death in experimental models of ischemia. As a general standard, acetaminophen and cooling blankets should be given to all patients with sustained fever in excess of 38.3°C (101.0°F), but evidence for the efficacy of these interventions in neurological patients is meager. Newer adhesive surface cooling systems (Arctic Sun, Medivance, Inc.) and endovascular heat exchange catheters (Cool Line System, Alsius, Inc.) have been shown to be much more effective for maintaining normothermia. However, clinical trials are needed to determine if these measures improve clinical outcome.

Nutritional Support

As is the case with all critically ill neurological patients, enteral feeding should be started within 48 hours to avoid protein catabolism and malnutrition. A small-bore nasoduodenal feeding tube may reduce the risk of aspiration events.