1	eSE#: Paper 38
2	Non-Traumatic Neurological Emergencies of The Brain Andrew Goldberg MD Vikas Jain MD MetroHealth Medical center, Cleveland
3	Disclosures None
4	Acute stroke Stroke is actually a lay term denoting a sudden loss of neurological function. Broadly categorized into ischemic (more common, approximately 85%) and hemorrhagic ( 15%). Clinical examination is incorrect in more than 10% of cases. These pts of suspected stroke have a cause other than ischemic or hemorrhagic stroke. It could be neoplastic, infectious, inflammatory, metabolic or vascular. Common cause of morbidity and mortality. Third leading cause of death in USA.
5	Acute stroke, continued Ability to treat some pts in acute settings with thrombolytics has created a pressing need for rapid detection and improved evaluation. First step after stabilization and neurological examination is unenhanced CT of Head. Subsequent workup includes MRI w/ diffusion & perfusion imaging along w/ MRA or CTP (CT perfusion) & CTA in selected patients depending on results of unenhanced CT and clinical evaluation. The exact protocols differ in different institutions depending on various factors.
6	Acute stroke, continued Role of imaging is to answer four key questions Is there hemorrhage? Is there intravascular thrombus that can be targeted for thrombolysis? Is there a core of critically ischemic/ irreversibly infarcted tissue? Is there a penumbra of severely ischemic but potentially salvageable tissue?
7	Role of unenhanced CT Exclude hemorrhage before thrombolytic therapy. A greater than one-third middle cerebral artery (MCA) territory hypodensity at presentation is considered by most to be a contraindication to thrombolysis. Evaluate for any other causes of sudden neurological deficit.
8	Role of Advanced Imaging CTP or MR diffusion & perfusion imaging tells about the size of infarcted tissue, presence or absence of penumbra and the amount of mismatch b/w the two. Pts w/o mismatch are not candidates for thrombolytics. CTA or MRA tells about the state of blood vessels and presence of any thrombus.
9	“Time is Brain” Emphasis is on rapid performance and interpretation of imaging so that Rx can be initiated early to improve outcome and decrease chances of hemorrhage. Intravenous TPA (tissue plasminogen activator) is used for suitable candidates if presentation is within 3 hrs. Intra-arterial (IA) TPA is used for the suitable candidates between 3-6 hrs. IA TPA also used in “wake up stroke” pts whose time of onset of stroke is unknown but have diffusion/perfusion mismatch and meet other criteria.
10	Acute Ischemic Infarct Interruption in blood supply to the brain causes depletion of ATP which leads to failure of sodium-potassium pump leading to cytotoxic edema. CT is insensitive in diagnosing acute infarcts in first 24 hrs and may be normal. Subtle early indicators are “Hyperdense artery sign” due to thrombus Insular ribbon sign loss of gray-white matter differentiation Mild sulcal effacement due to swelling Subtle hypodensity in a wedge shape involving both gray & white matter Respect of arterial vascular territory.
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14	Acute Infarct, MRI Diffusion weighted imaging (DWI) is the most sensitive sequence and usually shows restricted diffusion (RD) as early as 30 min. FLAIR and T2 WI may be normal in first 3-6 hrs, then they show subtle hyperintense signal intensity (SI), cortical swelling, loss of gray white borders. FLAIR images show intra-arterial signal in the affected area and T1C+ images show intravascular enhancement due to slow flow and collaterals.
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23	Complications after infarct Large infarcts develop more vasogenic edema which peaks in 3-5 days and can cause herniation and hydrocephalus. Posterior fossa infarcts can cause life threatening mass effect and hydrocephalus due to a smaller compartment, and may require shunt placement and/ or craniectomy. Massive mass effect and herniation can even cause new infarcts by compression of vessels against tentorium or falx. Hemorrhagic transformation is more common w/ thrombo-embolic infarcts, reperfusion and TPA
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26	Venous infarct Wide spectrum of predisposing causes: trauma, infection, inflammation, pregnancy, dehydration, hematological disorders. Thrombus initially forms in the dural venous sinus and then propagates in cortical veins and other sinuses. Venous pressure rises due to obstruction. Results in breakdown of blood brain barrier (BBB) w/ vasogenic edema and hemorrhage. Then cytotoxic edema and venous infarct develops. Venous infarct develops in nearly 50% cases of sinus thrombosis. Don’t follow typical arterial distribution. Can be reversible in some cases.
27	Venous infarct, continued Commonly presents as headache, nausea, vomiting w/ or w/o neurological deficit CT: hyperdense dural sinus or cortical vein (cord sign) on noncontrast CT and empty delta sign on CECT. Hemorrhage more common than arterial infarcts Look for predisposing causes like trauma, mastoiditis, infection/inflammation, hypercoagulable states.
28	"MR" MR: acute thrombus is isointense on T1 and hypointense on T2 & GRE; however, it distends the sinus (unlike normal flow void)
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32	Sinus thrombosis-pitfalls Early imaging findings often subtle Acute thrombus is hypointense on T2 and can mimic normal sinus flow void---look for distension, and also review GRE (thrombus will be hypointense and normal sinus is slightly hyperintense) Chronic sinus thrombosis can enhance due to organised fibrous tissue Blood in vessels is slightly hyperdense on NECT Arachnoid granulations ( are round or oval rather than long and tubular shape as in clot) False empty delta sign due to SDH, subdural empyema Hypoplastic segment ( small caliber, acute clot distends); usually seen in proximal left transverse sinus
33	Global hypoxia
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35	Hemorrhagic stroke 15% cases of stroke CT is excellent in diagnosing bleed and is a straightforward diagnosis Familiarity with MR appearance of hyperacute and acute hemorrhage important, as Pt may be scanned directly by MR in certain situations, due to increasing use of MR
36	Intraparenchymal Hematoma MRI SI varies depending on numerous factors like age of hematoma, Hgb oxidative state, RBC morphology, pulse sequence and field strength. Hyperacute hematoma is isointense on T1 WI and slightly hyperintense on T2 WI Acute hematoma is isointense on T1 WI and hypointense on T2 WI (more common pattern than hyperacute) Hematoma shows high SI on DWI in hyperacute and late subacute stage, ADC is decreased or normal in hyperacute and increased in late subacute stage. T2 and T2* GRE are normal in hyperacute ischemic stroke but shows heterogenous hyperintensity with dark rim in hematoma.
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38	Common causes of hemorrhage Hypertensive hemorrhage Amyloid angiopathy Vascular malformation Aneurysm Tumors (primary or secondary) Drugs and anticoagulants Vasculitis Prematurity (germinal matrix hemorrhage)
39	Hypertensive hemorrhage Occurs in hypertensive elderly pts Common locations are putamen, external capsule, thalamus, pons and cerebellum HTN most common cause of spontaneous ICH b/w 45-70yrs. DSA almost always normal in setting of old age and deep ganglionic site CTA useful if atypical features or atypical hematoma on MR Subarachnoid extension of hematoma on CT strongly indicates a non-hypertensive cause
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43	Amyloid Angiopathy Common cause of spontaneous lobar hemorrhage (hge) in elderly. Diagnostic clue Normotensive demented pt Lobar hge of different ages Multifocal chronic microbleeds on T2*, particularly in subcortical WM (gray/white junction) Associated WM disease Less common in brainstem, basal ganglia, thalami & cerebellum
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45	Arteriovenous malformation Vascular malformation w/ arteriovenous shunting w/o intervening capillary bed. Most common symptomatic cerebral vascular malformation. Peak presentation b/w 20-40 yrs w/ headache/ hemorrhage/ seizures/ neurological deficit. 98% are solitary & sporadic. Differentiate from GBM w/ AV shunting which shows enhancing intervening parenchyma, mass effect, edema & heterogeneity. CT---iso/hyperdense serpentine vessels, ca++ in 25-30%, strong CE, variable hge, no/minimal mass effect. MR—multiple flow voids, blooming on T2* if hge present, strong CE, little or no brain parenchyma inside AVM. CTA/ MRA/ Conventional angio— enlarged arteries, nidus of tightly packed vessels, draining veins. Especially look for aneurysms and dual blood supply. Essential to examine ECA, ICA & vertebrals completely.
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49	Vasculitis Inflammatory vasculopathy, heterogenous group of CNS disorder characterized by nonatheromatous inflammation and necrosis of blood vessel walls. Can be primary or secondary, caused by broad spectrum of infectious, inflammatory causes & drugs. Imaging features are very nonspecific. Atherosclerosis is the most common cause of a vasculitis like angiographic pattern in older adults. Multifocal areas of smooth or irregularly shaped stenosis alternating with dilated segments is characteristic. CT & MR may show multifocal hyperintensities due to ischemia or infarction, hemorrhage or patchy areas of enhancement. CTA/MRA are useful for screening, but spatial resolution may be insufficient for subtle disease.
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51	Aneurysmal SAH Aneurysmal SAH causes 5% of “strokes”. 85% of nontraumatic SAH due to ruptured aneurysm. Presents w/ sudden severe headache (“thunderclap”) , worst headache of life, peak in 40-60 yrs, F>M. Complicated by Rebleed Vasospasm & ischemia Metabolic and hemodynamic disturbance
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55	Infections Various microbial agents can cause Meningitis Cerebritis Encephalitis Abscess Ventriculitis (Ependymitis) Subdural empyema
56	Abscess Focal infection of brain showing a capsule w/ central liquefied necrosis &inflammatory debris. T2 shows hypointense rim surrounding the hyperintense cavity. Abscess cavity shows restricted diffusion (RD) due to thick viscous pus. The walls show complete ring of intense CE and are relatively smooth w/o solid component or significant nodularity ( helps to differentiate from necrotic tumors which have thick nodular walls w/ solid component; necrotic cavity typically does not show RD, although the solid component may show RD). Surrounded by vasogenic edema, has mass effect. Commonly due to complicated sinusitis, mastoiditis or otitis media. May be hematogenous.
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58	Meningitis Inflammatory infiltrate of pia and arachnoid mater, may be hematogenous or from contiguous spread from sinusitis, mastoiditis or orbital cellulitis. Imaging in early meningitis is often normal & it is mainly a clinical diagnosis supported by LP. Predominant role of imaging is to evaluate for complications like hydrocephalus, abscess and empyema
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60	Ventriculitis Ventricular ependyma infection due to meningitis, ruptured abscess or VP shunts. Look for hydrocephalus, debris levels due to pus, periventricular hyperintensity due to transependymal flow & smooth ependymal CE. Subependymal tumor spread and lymphoma will show nodularity, some solid component and different clinical picture. The debris levels show RD due to pus. Subdural empyema and epidural abscess will also show RD.
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62	Cavernous sinus thrombosis Infection of CS is rare and occurs secondary to venous spread of septic embolus from perinasal or periorbital infection/abscess/boil that results in CS thrombophlebitis Causes edema of lids, chemosis, proptosis, papilledema, retinal vein engorgement CT/MR reveals convex lateral margins of the CS and filling defects in CS after contrast administration. Cavernous ICA may be narrowed in advanced cases due to inflammation.
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64	Herpes encephalitis Brain parenchyma infection caused by HSV type 1 in immunocompetent adults due to reactivation. Acute presentation w/ fever, headache, seizures, viral prodrome, altered mental status, neurological deficit. Commonly causes abnormal SI & enhancement in medial temporal, inferior frontal lobes, insula & cingulate gyri. Basal ganglia usually spared. Typically bilateral disease, but asymmetrical. Hemorrhage is a late feature; cases often show restricted diffusion (unlike limbic encephalitis) PCR of CSF most useful for diagnosis. Mortality ranges from 50-80%, start intravenous acyclovir on suspicious MR findings w/ compatible clinical picture.
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67	Empyema Empyema is loculated collection of pus in extraaxial space w/ rim enhancement; subdural is more common than epidural. Usually secondary to complication from sinusitis, mastoiditis or meningitis. DWI shows restricted diffusion. Differential diagnosis are chronic hematoma, subdural effusion, subdural hygroma or dural metastases.
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69	Others Some other disorders from different categories can also lead to acute deficit where pt presents emergently Osmotic demyelination Posterior reversible encephalopathy syndrome Wernicke encephalopathy Multiple sclerosis
70	Osmotic demyelination Acute demyelination caused by rapid shift in serum osmolality. New name for central pontine myelinolysis as these changes can also be seen elsewhere as in thalami and basal ganglia. 50% in pons, central pontine hyperintensity w/ sparing of periphery. Basal ganglia & cerebral white matter may also be involved in bilateral symmetric manner. Occasionally enhance. More commonly shows RD. Frequently, but not always, resolves completely.
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72	Posterior reversible encephalopathy syndrome (PRES) Disorder of cerebrovascular autoregulation w/ multiple etiologies, predominantly causing acute severe hypertension. Usually patchy, bilateral, asymmetrical, cortical & subcortical WM involvement of predominantly parieto-occipital region. Holohemispheric pattern also recognized, as well as isolated abnormalities in cerebellum and basal ganglia. Appears bright on T2, Petechial hemorrhages and mild punctate CE less common. DWI usually normal, may be restricted in a few cases indicating irreversible ischemia.
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74	PRES: Imaging Patterns* Holohemispheric watershed pattern – vasogenic edema spanning frontal, parietal and occipital lobes, relative temporal lobe sparing. Superior frontal sulcus pattern “Typical” dominant parieto-occipital pattern Partial or asymmetric expression of the primary pattern “Atypical” lesions not uncommon
75	Additional Clinical and Imaging Features Presenting symptoms include headache, visual disturbance, decreased cognition, and especially seizure ( 70% ); significant hypertension in more than half the patients Acute focal parenchmal hemorrhage in 8% “ Atypical “ involvement of the brainstem, basal ganglia and deep white matter seen more in the setting of eclampsia and organ transplantation, possibly due to earlier recognition than with cases of sepsis or shock
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77	Wernicke Encephalopathy Uncommon disorder presenting with ataxia, cognitive and ocular dysfunction 50% may NOT have history of alcohol abuse* T2/Flair hyperintensity in medial thalami, tectal plate, mamillary bodies and periaqueductal area Contrast enhancement most often seen in mamillary bodies, and more often in alcoholics Prompt recognition important for initiation of intravenous thiamine therapy
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79	Multiple Sclerosis Demyelinating disease affecting young adults (20-40yrs). Multiple perpendicular linear or ovoid periventricular T2 & FLAIR hyperintensities. Sagittal FLAIR sequence shows characteristic involement at callosal-septal interface. Acute lesions may show concentric ring pattern w/ hyperintense rim on DWI and transient semilunar, incomplete ring of CE. Large mass like enhancing lesions (tumefactive MS) are rare & may mimic neoplasm. Some lesions may present w/ sudden neurological deficit and clinically mimic stroke.
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82	Tumors Primary malignant tumors and metastatic tumors can occasionally give rise to sudden neurological deficit due to hemorrhage and edema and may cause life threatening hydrocephalus and or herniation. Colloid cyst and intraventricular neurocysticercosis can also give rise to sudden severe obstructive hydrocephalus by obstruction at foramen of monro or aqueduct of sylvius.
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85	Tumors in fourth ventricle Medulloblastoma and ependymoma are the two common tumors seen in fourth ventricle in children. Some of these patients can deteriorate suddenly with worsening life threatening hydrocephalus requiring emergent VP shunt placement.
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87	Bibliography Osborn AG et al. Diagnostic Imaging: Brain. Amirsys; 2005 Atlas SW. Magnetic Resonance Imaging of the Brain and Spine, Lippincott, 2002 Shetty SK, Lev MH: CT Perfusion in Acute Stroke. Neuroimag Clin N Am 15 (2005) 481-501 Rumboldt Z, Thurnher MM, Gupta RK: Central Nervous System Infections. Seminars in roentgenology. 2006; 62-90 Hoeffner EG, Case I, Jain R, Gujar SK et al: Cerebral Perfusion CT: Techniques and Clinical Applications. Radiographics: 2004; 231: 632-644 Yock DH. Magnetic Resonance Imaging of CNS Disease: A Teaching File, St Louis, Mosby; 2002 Grossman RI, Yousem DM. Neuroradiology: The Requisites. St Louis, Mo: Mosby; 1994;114-16
88	Author correspondence Vikas Jain, M.D. MetroHealth Medical Center 2500 MetroHealth Drive Cleveland, Ohio, 44109 Vjain@metrohealth.org