Chap

ter

49Gul Moonis, MD, and

Laurie A. Loevner, MD

Brain: inflammatory, infectious, and Vascular diseases

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1. How is multiple sclerosis (MS) diagnosed?MS is the most common of the acquired demyelinating disorders. The disease has a characteristic relapsing-remitting course and usually manifests between the third and fifth decades of life with a female predominance. On magnetic resonance imaging (MRI), the demyelinating lesions of MS are ovoid and hyperintense (bright) on T2-weighted images and occur predominantly in the white matter, especially in the periventricular location (usually perpendicular to the ventricular surface) (Fig. 49-1). The corpus callosum, white matter around the temporal horns of the lateral ventricles, and middle cerebellar peduncles are other favored locations of MS plaques. There may be enhancement of the plaques (ringlike or solid) that denotes active disease. Occasionally, MS plaques can be large and masslike (tumefactive MS), in which case differentiation from a tumor may be difficult.

2. What is the differential diagnosis of MS based on imaging findings?The diagnosis of MS is a clinical one (neurologic symptoms spaced over time and in multiple distributions), with supporting radiologic findings. The diagnosis cannot be made on imaging findings alone because other inflammatory and vascular processes can manifest with similar imaging findings. White matter lesions similar to MS can be seen with a spectrum of inflammatory conditions, including Lyme disease, sarcoidosis, and vasculitis.

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Figure 49-1. MS in a young patient. Axial fluid-attenuated inversion recovery (FLAIR) MR image shows numerous ovoid, periventricular lesions characteristic of MS plaques. These are oriented along the perivascular spaces, and the appearance has been referred to as “Dawson’s fingers.”

3. What are the causes of intracranial abscesses?Infectious agents gain access to the central nervous system (CNS) by direct spread from a contiguous focus of infection, such as sinusitis, otitis media, mastoiditis, orbital cellulitis, or dental infection. Infection from these locations may also spread to the intracranial compartment by retrograde venous reflux. Hematogenous spread of infection can also occur from a distant nidus of infection, such as the lung. Polymicrobial infection is common with brain abscesses. Four stages have been described in abscess evolution: early cerebritis, late cerebritis, early capsule formation, and late capsule formation. A mature abscess is characterized by a “ring-enhancing” lesion on cross-sectional imaging.

4. What is the imaging differential diagnosis of a ring-enhancing lesion in the brain?The following disease processes can have an imaging presentation identical to brain abscess: metastatic disease, primary CNS glioma, resolving hematoma, and demyelinating disease. Interpreting the radiologic findings in conjunction with the clinical history is usually helpful in differentiating among these possible etiologies.

5. What advanced MRI techniques may be useful in distinguishing brain abscess from neoplasm?Differentiating a subclinical brain abscess from cystic or necrotic tumor with conventional

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A B

Figure 49-2. A, Frontal lobe abscess secondary to frontal sinusitis. Axial contrast-enhanced T1-weighted MR image shows two ring-enhancing lesions in the left frontal lobe (arrow) and enhancing soft tissue within and anterior to the frontal sinus. B, On the corresponding diffusion-weighted image, there is restricted diffusion (high signal intensity) within these lesions that is compatible with abscesses.

computed tomography (CT) or MRI can be difficult. 1H magnetic resonance spectroscopy and diffusion-weighted MRI can be useful in this regard (Fig. 49-2). Typically, on diffusion-weighted MRI, an abscess is hyperintense (bright).

6. What anatomic location in the brain is preferentially involved by herpes simplex encephalitis?In adults, type 1 herpes simplex virus is responsible for fulminant, necrotizing encephalitis. The virus preferentially involves the temporal lobes, but involvement of the frontal lobes (especially the cingulate gyrus) is common. Often, there is bilateral temporal lobe involvement, although this is usually asymmetric. On MRI, there is T2-weighted hyperintensity in the temporal and frontal lobes with enhancement (Fig. 49-3). Clinically, the patient presents with acute confusion, disorientation, or seizures progressing to stupor and coma. Most cases are a result of reactivation of dormant virus in the trigeminal ganglion. There is commonly asymmetric temporal lobe involvement. Hemorrhage in the affected area is common.

7. What is the differential diagnosis of an intracranial mass in a patient with human immunodeficiency virus (HIV) infection?It is crucial to determine whether the cause of HIV-related brain mass is neoplastic or infectious because these entities are managed differently. Among infectious etiologies, toxoplasmosis and brain abscesses secondary to fungal or bacterial etiologies have to be considered. The major neoplastic consideration is primary CNS lymphoma. Toxoplasmosis is the leading cause of focal CNS disease in acquired immunodeficiency syndrome (AIDS) and results from infection by the intracellular parasite Toxoplasma gondii. It is usually caused by reactivation of old CNS lesions or by hematogenous spread of a previously acquired infection. On imaging, single or multiple ring-enhancing lesions in the white matter or basal ganglia or both with mass effect may be observed. A single lesion favors the diagnosis of lymphoma over toxoplasmosis (Fig. 49-4). Occasionally, progressive multifocal leukoencephalopathy, a demyelinating disease caused by a viral infection, may result in ring-enhancing lesions. Progressive multifocal leukoencephalopathy is caused by a virus that infects the oligodendrocytes in immunocompromised patients.

8. What is a stroke?A stroke occurs when the blood supply to a vascular territory of the brain is suddenly interrupted (ischemic stroke), or when a blood vessel in the brain ruptures, spilling blood into the spaces surrounding the brain cells (hemorrhagic stroke). Ischemic stroke is the more common form, responsible for approximately 80% of vascular accidents. In adults, these blockages are usually associated with two conditions: atherosclerosis-related occlusion of vessels (60%) and cardiac embolism (20%).

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A B

Figure 49-3. A, Herpes simplex encephalitis. Axial FLAIR MR image shows abnormal T2 hyperintensity in the left medial temporal lobe involving gray and white matter. B, Axial enhanced T1-weighted MR image shows mild patchy enhancement (arrow) that is consistent with cerebritis.

A B

Figure 49-4. A, Toxoplasmosis in an HIV-positive patient. Axial FLAIR MR image shows extensive signal abnormality involving the left basal ganglia and adjacent frontal and temporal lobes with mass effect. B, Axial enhanced T1-weighted MR image at the same axial level as A shows a rim-enhancing lesion in the center of the left basal ganglia (arrow) with extensive surrounding edema and midline shift from left to right.

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9. What are the common causes of stroke that one must consider in children and young adults?Only 3% of cerebral infarctions occur in patients younger than 40 years old. The most common causes of stroke in young patients are cardiac disease, hematologic diseases (hypercoagulable states), and vascular dissection (from trauma or disease of the vessel wall). Other causes include CNS vasculitis, fibromuscular dysplasia, and venous sinus thrombosis.

10. What are the imaging manifestations of ischemic stroke in the acute stage?Commonly, in the acute setting, a CT scan of the head may be normal. The earliest signs (≤6 hours) of an acute infarct on CT are loss of the gray-white differentiation with obscuration of the lateral lentiform nucleus. There may be a high density noted in the proximal middle cerebral artery, representing acute thrombus or calcified embolus; this is referred to as the “hyperdense artery” sign (Fig. 49-5A). Within 12 to 24 hours, there is low density in the appropriate vascular distribution, with increasing mass effect. Mass effect peaks between 3 and 5 days. Findings of acute ischemia are detected earlier on MRI. With the use of diffusion-weighted imaging, acute ischemic changes can be seen within minutes of onset of the ictus. High signal intensity is noted within the involved vascular territory on T2-weighted images, with characteristic restricted diffusion (also hyperintense) on diffusion-weighted images (Fig. 49-5B and C). Swelling of the involved cortex and arterial enhancement are noted early in the time course.

11. How can one differentiate acute from chronic stroke on imaging?Chronic stroke is manifested by encephalomalacic change in the involved vascular territory with accompanying dilation of the sulci and cisterns. There is also ex vacuo dilation of the ipsilateral ventricle. There is absence of mass effect. If it is difficult to distinguish the age of a stroke on CT, MRI that includes a diffusion-weighted sequence can be invaluable.

12. What are watershed infarctions?Also known as “border zone infarcts,” watershed infarctions occur in the vascular watersheds (the distalmost arterial territory with connection between the major arterial branches). In severe hypotension or shock, the systemic blood pressure is insufficient to pump arterial blood to the end arteries. In the cerebrum, not enough blood gets to the “watershed zones” between the anterior and middle cerebral arteries or the middle and posterior cerebral artery territories, and in those areas infarcts are likely to develop. Some other causes of cerebral watershed infarcts include heart failure, decreased systemic perfusion pressure, and low blood pressure in the setting of a high-grade stenosis of a major artery (internal carotid) supplying the brain.

13. What are lacunar infarctions?Lacunar infarctions are small infarcts caused by occlusion or disease of the perforating arteries (arteriolar lipohyalinosis). Initially, these are slightly hypodense on CT. By 4 weeks, sharply circumscribed, cystic lesions develop. These lesions are most commonly seen in the deep gray matter (basal ganglia, thalami), brainstem, internal capsule, and corona radiata. These small infarctions are usually 1 cm or smaller.

A B C

Figure 49-5. Hyperdense middle cerebral artery consistent with acute thrombus or calcified embolus. A, Axial unenhanced CT scan of the head shows hyperdensity in the left middle cerebral artery (arrow) that is compatible with acute thrombus. B and C, Corresponding axial FLAIR and diffusion-weighted MR images shows diffuse hyperintensity involving gray and white matter in the left middle cerebral artery territory, which is characteristic of stroke. The hyperintensity on the diffusion-weighted image represents restricted diffusion, which is compatible with acute ischemia.

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14. What are the risk factors for venous sinus thrombosis and venous infarction?Venous sinus thrombosis is associated with many systemic conditions, including acute dehydration, hypercoagulable states, chemotherapeutic agents (l-asparaginase), sinusitis and mastoiditis, hematologic malignancies, pregnancy, and trauma. Unenhanced CT reveals the presence of high density and enlargement of the dural venous sinuses. The “empty delta” sign, which refers to enhancement around the clot in a dural venous sinus, may also be present (Fig. 49-6A). The diagnosis of venous thrombosis is improved significantly with MRI. On unenhanced T1-weighted images, high signal intensity clot is noted within the venous sinuses (Fig. 49-6B). There may be associated venous infarction. Venous infarctions have a high rate of hemorrhagic transformation compared with arterial infarctions.

15. What is the most common cause of nontraumatic subarachnoid hemorrhage (SAH)?An aneurysm rupture is the most common cause of nontraumatic SAH. An aneurysm is a focal dilation of an artery, most commonly encountered at branching points in the intracranial vasculature. Aneurysms are usually due to a congenital weakness in the media and elastica of the arterial wall, but can be acquired in the setting of trauma or mycotic infections. The approximate relative frequency of aneurysm formation in the intracranial vasculature is as follows: anterior communicating artery (30%), distal internal carotid artery and posterior communicating artery (30%), middle cerebral artery (25% to 30%), and the posterior vertebral-basilar circulation (10% to 15%). Multiple aneurysms are seen in approximately 15% of cases. There is increased incidence of intracranial aneurysms in patients with polycystic kidney disease, Marfan syndrome, and fibromuscular dysplasia (and other rarer entities, including moyamoya disease, Ehlers-Danlos syndrome, and Takayasu arteritis).

16. What is the work-up of a patient presenting with SAH?If the patient presents with the classic history of “the worst headache of my life,” a CT scan should be obtained to look for SAH. If the results of the CT scan are negative, but there is high clinical suspicion for SAH, a lumbar puncture should be performed to look for red blood cells or xanthochromia or both in the cerebrospinal fluid (CSF). If CSF analysis is positive for subarachnoid blood, a diagnostic conventional catheter angiogram is the next step to find the aneurysm, providing an anatomic road map for the neurosurgeon. Increasingly, CT angiography is being used rather than conventional catheter angiography for aneurysm detection.

17. If multiple aneurysms are seen on catheter angiography in a patient with SAH, which one most likely bled?If multiple aneurysms are identified, greater suspicion falls on the aneurysm that is the largest in size, on the aneurysm with a lobulated contour (nipple sign), or on the aneurysm closest to the largest clot on CT. Extravasation of contrast agent from the aneurysm is rarely seen, but is diagnostic.

A B

Figure 49-6. A, Venous sinus thrombosis. Axial contrast-enhanced T1-weighted MR image shows acute clot in the superior sagittal sinus. Note the characteristic “empty delta” sign (arrow) that represents nonenhancing clot within the superior sagittal sinus. B, Sagittal unenhanced T1-weighted MR image taken in the midline shows relative high signal intensity in the superior sagittal sinus (arrows), which is consistent with acute thrombosis.

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Figure 49-7. Left thalamic hypertensive hemorrhage. Axial unenhanced CT scan of the head shows a large focus of hemorrhage centered in the left thalamus (arrow) with extension into the ventricular system and hydrocephalus.

18. What are common locations for hypertensive intraparenchymal hemorrhages?In adults who present with nontraumatic intraparenchymal hemorrhage in the brain, hypertension is the most common etiologic factor. The arteries in the brain injured by chronic hypertension typically are the perforating arteries, which supply the basal ganglia, thalami, and pons (Fig. 49-7). Other areas that may also be affected by hypertensive bleeds include the centrum semiovale and, occasionally, the cerebellum.

19. What is amyloid angiopathy?Amyloid angiopathy results from deposition of amyloid in the media and adventitia of small and medium-sized vessels of the superficial layers of the cortex and leptomeninges. Amyloid deposition increases with age. Pathologically, there is loss of elasticity and increased fragility of the vessels that cause hemorrhages that are usually lobar and most often in the frontal and parietal lobes. These parenchymal hemorrhages may be associated with subdural hemorrhage and SAH. The usual course is multiple hemorrhagic incidents spaced over time.

20. Review the MRI signal characteristics of intracranial hemorrhage.See Table 49-1.

21. What are the imaging features of cerebral hypoxia/anoxia?Hypoxia refers to a lack of oxygen supply to the cerebral hemispheres. Hypoxia can have a multifactorial etiology, including drowning, asphyxiation from smoke inhalation, severe hypotension, strangulation, perinatal hypoxic insult, cardiac arrest, and carbon monoxide poisoning. On MRI, there is increased T2 signal in the perirolandic and occipital cortex and the basal ganglia (Fig. 49-8). The watershed zones between major vascular territories and the hippocampi are also prone to hypoxic-ischemic damage. Layers three, four, and five of the cortex are sensitive to global hypoxia-ischemia and may become necrotic and hemorrhagic (laminar necrosis).

Table 49-1. MRI Signal Characteristics of Intracranial Hemorrhage

AGE T1-WEIGHTED T2-WEIGHTED

Hyperacute Hours old, mainly oxyhemoglobin with surrounding edema

Hypointense Hyperintense

Acute Days old, mainly deoxyhemoglobin with surrounding edema

Hypointense Hypointense, surrounded by hyperintense margin

Subacute Weeks old, mainly methemoglobin

Hyperintense Hypointense, early subacute with predominantly intracellular methemoglobin

Hyperintense, late subacute with predominantly extracellular methemoglobin

Chronic Years old, hemosiderin slit or hemosiderin margin surrounding fluid cavity

Hypointense Hypointense slit or hypointense margin surrounding hyperintense fluid cavity

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A B

Figure 49-8. Hypoxic injury in a patient who was found in respiratory arrest. A and B, Axial FLAIR (A) and diffusion-weighted (B) MR images show abnormal hyperintensity in the bilateral caudate heads and the right putamen (arrows on A). The diffusion hyperintensity is consistent with acute hypoxic-ischemic injury.

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