1	Stroke: Etiology and CT/MR Imaging in Neonates, Infants, Children and Young Adults B. Henriquez, MD¹; C. Ferretti, MD¹; D. Reede, MD¹; W. Smoker, MD²; D. Lefton, MD³ Department of Radiology of ¹Long Island College Hospital, ²University of Iowa Health Care and ³Saint Luke’s-Roosevelt Hospital Center.
2	Stroke in the Adult Focal neurologic abnormality due to disturbance in blood flow to the brain by any cause Third leading cause of death after heart disease and cancer and a leading cause of long-term disability Typically caused by atherosclerotic disease Patients often have a history of hypertension, diabetes mellitus, hyperlipidemia and/or smoking
3	Stroke in Pediatric Patients and Young Adults
4	Imaging Findings In Stroke Cytotoxic edema Efflux of K⁺ with influx of Ca⁺⁺, Na⁺, and H20 Cellular ‘cytotoxic edema’ à detection of infarct Smaller component of ‘vasogenic edema’ as capillary endothelial cells lose integrity MRI 1^st few hours: swelling of cortex on T1WI and FLAIR By 8 hours: high signal intensity on T2WI At 16 hours: low signal intensity on T1WI Diffusion-weighted MRI (DWI) Cellular swelling associated with cytotoxic edema causes restricted diffusion Gradient applied to sensitize images to Brownian water motion Brain water diffusion rates fall rapidly during acute ischemia Early infarct: high signal Changes seen hours earlier than on T2WI
5	Stroke: Table of Contents Neonates and Infants: slides 6-24 Children: slides 25-31 Young Adults: slides 32-40 Summary: slide 41
6	Neonates and infants (birth-1yr) Imaging is essential in neonates and infants because the clinical signs of stroke are often subtle Congenital cyanotic heart disease is the most common cause of embolic cerebral infarct in neonates Etiologies Hypoxia-ischemia Thrombo-embolism Infection Metabolic disease Trauma
7	Periventricular Leukomalacia Most common ischemic brain injury in premature infants Occurs in white matter adjacent to ventricles, the watershed zone of the premature infant Periventricular white matter lesions ànecrosis and cavitation à shrinkage of cavities with focal enlargement of adjacent ventricle Ultrasound: periventricular echoes or cysts MRI: expansion of posterior portions of ventricles from decreased posterior white matter volume; scalloping of lateral margin of ventricle; atrophy of splenium of corpus callosum; periatrial high T2 white matter signal
8	Hypoxia-ischemia, premie
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12	Seizures and DWI Apparent diffusion coefficients are reduced during the initial phase then are normal or increased in the later phase of prolonged status epilepticus (SE) This effect is caused by cytotoxic edema induced by excitotoxicity defined as a pathology common to many neurological disorders. It is caused by an excess of, or excessive sensitivity to, glutamate—the main excitatory neurotransmitter. Excitotoxicity triggers a cascade of events including membrane polarization, ending in cell death. DWI can be used to localize a seizure focus, predict the prognosis of the affected tissue and research the basic pathophysiology of SE.
13	Neonatal Seizures
14	Neonatal Hypoglycemia Glucose is vital to normal brain function; it is accepted that profound hypoglycemia will result in significant brain damage. Acute signs include jitteriness, seizures, and vomiting. Significant hypoglycemia: Glucose < 20-40 mg/dL in premature infants Glucose < 30-35 mg/dL in first 24 hrs in term infants Glucose < 40-45 mg/dL after 24 hours in term infants Imaging studies reflect diffuse brain damage: Most severe in parietal and occipital lobes bilaterally Acute phase: Reduced diffusion with edema of cerebral cortex and underlying white matter Lack of gray/white matter distinction Chronic phase: cortex and white matter show cystic encephalomalacia à atrophy
15	Neonatal Hypoglycemia
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18	Protein C/S Deficiency
19	Protein C Deficiency
20	Protein S Deficiency
21	Meningitis
22	Disruption of Cerebellar Development in Extreme Prematurity Proposed mechanisms: Acquired asymmetric pontocerebellar hypoplasia, as has been reported after fetal drug exposure, secondary to vascular undersupply Disruption of cerebellar development in extreme prematurity – selective vulnerability of developing cerebellum in window of 24-30 weeks combined with perinatal risk factors (i.e. drug exposure) Cerebellar infarction in very low birth weight
23	Cerebellar Reduction Volume and In-Utero Drug Exposure
24	Vein of Galen Malformation
25	Children (1 yr-14 yrs) Etiologies Congenital heart disease Blood dyscrasias Metabolic disease Vasculitis Trauma Venous thrombosis
26	Vertebral Artery Dissection
27	Fibromuscular Dysplasia (FMD) Commonly seen in adult women, rarely seen in children Affects medium and large arteries -- unknown etiology Overgrowth of smooth muscle and fibrous tissue in the vessel wall Different appearances: Type I “String of beads” (classic), type II long tubular stenosis, type III confined to portion of arterial wall Renal artery (60%) > ICA or vertebral arteries (35%) > iliac arteries (3%) > visceral arteries (2%) Fibromuscular dysplasia is a well-recognized cause of stroke and transient ischemic attacks in adults but a seldom-recognized cause of stroke in children.
28	Fibromuscular Dysplasia
29	Thrombocytosis with Ulcerative Colitis
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31	Sickle Cell Disease
32	Young Adults (15-23 years old) Etiologies Cardiac emboli Arterial dissection Coagulopathy Vasculitis Drug abuse
33	Moyamoya from Sickle Cell Disease
34	Vasculitis Diagnosis of exclusion Caused by wide range of entities Collagen vascular disease (systemic) CNS infection: Meningitis, encephalitis Drugs Autoimmune disorder (i.e. primary angiitis of CNS) Angiography: Long segments of multiple focal arterial narrowing Sensitivity = 70% CT/MRI – nonspecific findings Single or multiple infarcts of various sizes Hyperintense white matter lesions on T2WI Leptomeningeal enhancement MRI advocated as sensitive screening tool with high negative predictive value
35	Primary Angiitis of the CNS A necrotizing vasculitis with a predilection for the central nervous system (CNS), histologically referred to as granulomatous angiitis of the CNS, of unclear etiology Nonspecific symptoms include headache, malaise, mental status change, focal neurological deficits and seizure. Rapidly progressive and frequently fatal Commonly involves vessels of brain parenchyma and leptomeninges with predilection for small arteries and arterioles Arteriogram Focal or multifocal segmental stenoses of small and medium sized vessels in parenchyma and leptomeninges May be abnormal in approximately 85% of cases May be negative in 15% of cases – when disease involves precapillary arteriole
36	Primary Angiitis of the Central Nervous System
37	Patent Foramen Ovale (PFO)
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39	Venous Thrombosis
40	ICA Dissection
41	Summary: Etiologies of Pediatric and Young Adult Stroke Hypoxia-ischemia Premature newborn with perinatal distress Full term newborn with perinatal distress Newborn with hypoglycemia Infant with hypoperfusion (e.g. viral myocarditis with hypotension) Thrombo-embolism Cardiac causes (congenital heart disease, vascular dissection, patent foramen ovale, mitral valve prolapse) Polycythemia Trauma Vasculopathy (Sickle cell disease, Moyamoya, FMD, Kawasaki) Infection (viral or bacterial meningitis) Coagulopathy (Protein C/S deficiency, Factor V Leiden, antiphospholipid antibody syndrome) Maternal drug abuse Migraine Vascular malformation (Vein of Galen malformation, AVM) Metabolic disorders (mitochondrial disorders, hyperhomocysteinemia, lysosomal storage disorders, hyperlipoproteinemia, disorders of cholesterol and triglyceride metabolism)