27 Viral and Non-Viral Infections in Immuno- competent and Immunocompromised Patients

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27 Viral and Non-Viral Infections in Immuno-

competent and Immunocompromised Patients

Vincent Dousset

V. Dousset

Professor of Radiology, Université Victor Segalen Bordeaux 2, CHU de Bordeaux –Hôpital Pellegrin, Place Amélie-Raba Léon, 33076 Bordeaux, France

CONTENTS

27.1 Introduction 391 27.2 Viral Infections 392

27.2.1 Viruses in Immunocompetent Patients 392 27.2.1.1 Herpes Viruses 393

27.2.1.2 Enterovirus 394 27.2.1.3 West Nile Virus 394

27.2.2 Viruses in Immunocompromised Patients 394 27.2.2.1 HIV Encephalitis 394

27.2.2.2 Progressive Multifocal Leukoencephalopathy 396 27.2.2.3 Cytomegalovirus Infection 396 27.3 Prion Diseases 396

27.4 Bacterial Infections 398 27.4. 1 Bacteria 398

27.4.2 Clinical and Imaging Features 399 27.4.3 Bacterial Meningitis 399

27.4.4 Subdural Empyema 399 27.4.5 Brain Abscesses 400 27.4.6 Mycotic Aneurysms 400 27.5 Parasitic Infections 401

27.5. 1 Cysticercosis (Taenia solium) 402

27.5.2 Hydatid Cysts (Echinococcus granulosus) 403 27.5.3 Echinococcus multilocularis 403

27.5.4 Toxoplasmosis 405

27.5.5 Toxocara canis and Toxocara cati Infections 405

27.6 Mycotic Infections 405 27.6.1 Cryptococcosis 407 27.6.2 Aspergillosis 407 27.6.3 Mucormycosis 407

27.7 Granulomatous Infections and Immunoreactive Diseases 407 27.7.1 Granulomatous Infections 407 27.7.2 Vasculitis 408

27.7.3 Acute Disseminated Encephalomyelitis 408 References 408

27.1

Introduction

Infectious diseases affecting humans have greatly decreased in the past decades thanks to the antibiotics and the level of hygiene in current life. However, the CNS must be seen as a potential target from many external organisms that have the ability to produce severe diseases with striking symptoms.

Imaging technology, CT and especially MRI, have led to an enhanced ability to characterize infectious processes. MRI techniques such as fast imaging T2- weighted images and ﬂ uid-attenuated inversion-re- covery (FLAIR) make it possible to depict lesions in the brain, spinal cord, and the meninges. More recently, techniques such as diffusion weighted imaging (DWI) and magnetic resonance spectroscopy, have been applied to inﬂ ammatory and infectious lesions, bringing new capabilities for in vivo characterization (Zimmerman 2000; Lai et al. 2002; Cecil and Lenkinski 1998; Burtscher and Holtas 1999).

They have an impact on making the positive diagnosis and for the understanding of the disease process.

The appearance of inﬂ ammatory lesions is the mirror of multiple factors, including the type of infectious organism, mode of spread, target and host response.

Infections can spread to the CNS in three ways:

Hematogenously, either through the choroid plexus or through the blood–brain barrier (BBB).

It is now the most frequent origin of infection in the CNS

Direct spread from adjacent structures, such as the sinuses, nasopharynx, or mastoid air cells

Retrograde axoplasmic ﬂ ow along cranial or peripheral nerves by some viral agents such as herpes

The imaging features of CNS infections can be classi- ﬁ ed by the organisms, the location of the lesion and the host response.

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The organisms include viruses, mycotic agents, parasites, bacteria and prions (Gray et al. 2004)

The location of the lesions might be one or several of the following: CSF, meninges, parenchyma, arteries, veins, cranial cavities (sinuses, mastoid).

It is of importance in an imaging study to look at all these locations

The host response:

1. Immunocompetent patients (child and adults): the response is immunologic and most often symptoms and in vivo images are related to the host response rather than to the infectious agent itself.

This means that common imaging features are present for several organisms, making the speciﬁ c diagnosis somewhat difﬁ cult. There is now more evidence for a strong role in the individual genetic background for the development of an organism in the CNS. Not only prions develop in susceptible individuals, but many more organisms are probably infective for some individuals and not others.

A transient decrease in the level of immunity may also be responsible for disease development 2. Immunocompromised patients: this group

includes several causes such as HIV infection – which, without treatment leads to deep im- munodeﬁ ciency – anticancer chemotherapy, diabetes mellitus, long-term steroid adminis- tration and, more rarely, congenital immunode- ﬁ ciency. In these patients, opportunistic agents develop, meaning that these germs might be present in non-immunocompromised people without the ability to develop (Post et al. 1986).

HIV has infected more than 60 million people in the world, with 26 million in Africa. In the CNS of HIV-positive patients, some numerous and very speciﬁ c agents may develop: the HIV virus itself, Toxoplasma gondii, JC virus, tuber- culosis, cytomegalovirus (CMV), and Crypto- coccus are the most frequent (Gray et al. 2004).

CNS type-B lymphoma can also develop. In immunocompromised non-HIV patients, agents such as Candida albicans, mucormycosis or Nocardia may become pathogenic for the CNS 3. Newborns: during birth and for a few weeks after,

babies might be affected by infectious agents that are present in the mother’s birth canal: herpes type 2, Listeria monocytogenes, and urinary germs such as E. coli, Proteus, or Candida albicans 4. Embryo and fetus: several agents may develop

that can lead to death of the embryo or to fetus CNS malformations. The most frequent agents are Toxoplasma gondii, and CMV, rubella, her- pes or HIV viruses (Osborn and Byrd 1991)

5. Finally, the immunologic system may be the origin of CNS manifestations, due to systemic infections of which agents promote a cross-reaction with some constitutive proteins of the CNS cells. The organism is usually absent from the CNS. The most sensitive targets are the myelin proteins, leading to acute disseminated encephalomyelitis (ADEM). This includes cross-reaction to viruses or bacteria following systemic infection or vaccination. Vasculitis may also be of immunologic origin in response to a systemic organism, leading to cerebral infarct. It is also possible to include in this group some granulomatous diseases, which produce normal immunologic-cell abnormal collection in the CNS, mostly in the meninges, facial cavities or cavernous sinus, e.g., inﬂ ammatory pseudo- tumor and sarcoidosis

We now will describe the infections by the type of organisms affecting the CNS: viruses and prions, bacteria, parasites, fungi, and granulomatous or immunologic reaction. The immunologic state of the host and the location will be discussed in each chapter.

27.2

Viral Infections

The two main features are meningitis and encephalitis. Neurological symptoms will depend on the location of the organism.

Meningitis due to viruses, a frequent infectious disease of immunocompetent hosts, has few imaging manifestations. The role of CT or MRI is questionable – waiting for imaging modalities may unnecessarily delay the time for lumbar puncture and treatment.

Enhancement of meninges is rare.

Viral encephalitis is usually associated with seizure or reduced consciousness or focal symptoms such as motor or sensory deﬁ cits. Mild mass effect may be seen during the acute phase of encephalitis.

Enhancement is often absent early on during the course of acute encephalitis, with sometimes an enhancement of the adjacent leptomeninges.

27.2.1

Viruses in Immunocompetent Patients

Some viruses may affect both immunocompetent and immunocompromised patients, children, adults

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or neonates. They belong to the groups of herpes viruses, enteroviruses and arboviruses.

27.2.1.1 Herpes Viruses

Herpes viruses are DNA viruses, and many can cause CNS infections in humans, including herpes simplex viruses 1 and 2, varicella-zoster virus, the Epstein- Barr virus, and cytomegalovirus (CMV) (Tien et al.

1993; Bonthius and Karacay 2002).

Herpes simplex virus 1 is the most common cause of sporadic viral meningoencephalitis. Clini- cal manifestations include fever, headache, neck stiffness, seizures, focal defi cits, and depressed mental state. Because acyclovir therapy is safe, it is recommended that the drug be given on the basis of clinical fi ndings. Encephalitis results from reactivation of latent viral infection of the gas- serian (fi fth cranial nerve) ganglion. From here,

the infection spreads to the parenchyma. The virus has a predilection for the medial area of the temporal lobes, the frontal lobes and the insular lobes (Fig. 27.1). On CT, low densities are seen on affected areas. There is no enhancement, only the adjacent meninges may show some congestive changes, with very little contrast-agent uptake.

On MRI, hyperintensities are encountered in the temporal, frontal or insular areas, and the bilateral nature of the process is frequent. Initially, the infection may appear unilateral on imaging studies, but over time, involvement of the contralateral temporal and frontal lobes will become apparent

Herpes simplex virus 2 is the most common cause of neonatal encephalitis. Infection occurs when the fetus passes through the birth canal of a mother who has genital herpes. Imaging ﬁ ndings reﬂ ect rapid brain destruction. Rare observations have been made on adults with extension to the spinal cord

a b

c d

Fig. 27.1a–d Herpes en- cephalitis. a, b Contrast- enhanced CT. Low density of the temporal and insular lobes without focal enhancement. c, d Flair MR imaging. High signal intensities in both insular lobes and in both temporal lobes

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Varicella-zoster virus produces two distinct clinical syndromes, chicken pox and herpes zoster. Dif- fuse encephalitis is a rare complication of chicken pox, but it is more common in adults. It is usually mild. Herpes zoster may lead to an involvement of peripheral and cranial nerves. The affected cranial nerve will appear edematous and swollen, and it will enhance at MR imaging with gadolinium.

Herpes zoster may also produce small vessel vasculitis, leading to cerebral infarcts

CMV in adults is seen almost exclusively in immunocompromised patients. However, CMV is the most common cause of congenital encephalitis.

It produces massive brain destruction during the ﬁ rst trimester. Infections acquired in the second trimester produce cortical dysplasia

Epstein-Barr virus has been linked to diverse entities, such as Guillain-Barré syndrome, and lymphoma in patients with AIDS. About 5% of the patients with infectious mononucleosis develop an acute, usually self-limited encephalomyelitis. This disorder may be responsible for hyperintensities on T2-weighted images in the deep supratentorial gray matter and central gray matter of the spinal cord. Rapid resolu- tion of the lesions has been reported in this disease

Human herpes virus-6 has been identiﬁ ed as a cause of encephalitis and febrile seizure (Bonthius and Karacay 2002)

27.2.1.2 Enterovirus

Enterovirus may be responsible for meningitis and, rarely, for encephalitis (Zimmerman 2000). In the

latter, the spinal cord, medulla, pons, mesencepha- lon, the dentate nucleus of the cerebellum, and oc- casionally the thalamus may be affected. These structures appear hyperintense on T2-weighted images (Fig. 27.2).

The location in the rhombencephalon and mes- encephalon is also the predilection of the bacteria Listeria monocytogenes.

27.2.1.3 West Nile Virus

This virus has emerged in the United States as a new etiologic pathogen causing encephalitis (Bonthius and Karacay 2002).

27.2.2

Viruses in Immunocompromised Patients The CNS of immunocompromised patients may be affected by the same viruses that affect immunocompetent patients. Additionally, other viruses only develop in immunocompromised patients (Post et al. 1986;

dal Canto 1997). The HIV virus that causes the deple- tion in immunity may be responsible for encephalitis.

Another virus, JC virus, can also cause multifocal encephalitis with destruction of oligodendrocytes.

27.2.2.1 HIV Encephalitis

HIV-1 is the human RNA retrovirus that causes AIDS.

The brain is one of the most commonly affected or-

Fig. 27.2 Viral cerebellitis due to enterovirus. Flair MR imaging showing high signal intensities of the cerebellar cortex

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gans. Almost all patients have the HIV virus in the CNS, and 10–15% may develop a decrease in mental status or dementia.

It has been described that the primary infection to HIV may lead to focal abnormal deep white matter spots recognized as hyperintensities on T2-weighted images (Trotot and Gray 1997). This is a nonspeciﬁ c sign that should be taken cautiously, since it is very frequent in many other conditions such as aging, high blood pressure, tobacco, and diabetes mellitus. The brain parenchyma is one of the sites of residency of the HIV virus for several years. During the phase of latency, before the patient starts to have AIDS, it has been shown that some degree of atrophy may occur. When immunodepression is becoming stronger, the HIV virus itself causes sub-

acute progressive encephalitis. The organism replicates within multinuclear giant cells and macrophages in the white matter (dal Canto 1997). There is atrophy, water accumulation in the interstitium, slight demyelination, but no inﬂ ammatory changes.

The most common ﬁ nding is generalized atrophy on CT or MR without focal abnormalities (Fig. 27.3a).

Some degree of non-atrophic brain shrinkage is caused by systemic effects of the disease. In severe cases, diffuse symmetric hyperintensity is seen in the supratentorial white matter, predominantly in the periventricular region (Fig. 27.3b, c). Mass effect and enhancement are absent (Fig. 27.3d). On T1-weighted images, the white matter appears almost normal or slightly hypointense.

Fig. 27.3a–d HIV encephalitis. a T2 MR imaging. Slight parenchymal atrophy and ventricular enlargement. b T2 MR imaging.

Parenchymal atrophy, ventricular enlargement, bilateral and symmetrical deep white matter abnormal high signal intensities.

c T2 MR imaging. Severe parenchymal atrophy, severe ventricular enlargement, bilateral and symmetrical deep white matter abnormal high signal intensities. d Gadolinium-enhanced MR imaging. Same patients as c. No gadolinium uptake. No notice- able changes on T1-weighted images

a b

c d

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27.2.2.2

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is caused by a papovavirus—the JC virus. This virus is ubiquitous in the adult population. It is present in lymph nodes, and it has been suggested that it resides in the kidneys. When a deep immunodepression is present, usually with blood CD4 cells below 100/mm³, the virus infects the myelin-producing oligodendrocytes, which results in severe demyelination with little inﬂ ammatory reaction. Patients complain of focal and progressive neurological impairment, with motor or visual function loss or cerebellar syndrome. Demyelination starts at the subcortical white matter, in the U-ﬁ bers (Fig. 27.4a–c). Areas of demyelination are seen as hyposignal on T1-weighted images, with a high signal on T2-weighted images and FLAIR images, without mass effect or enhancement (Fig. 27.4d–f) (Post et al. 1986; Dousset et al.

1997). There is always a strong correlation between the symptoms and the location of the abnormalities on MRI.

In the past, PML was inevitably fatal, with death occurring within 6–12 months of the onset. The ad- ministration of drugs developed to treat HIV, such as protease inhibitors, can cause, in some cases, a sta- bilization of the lesions produced by PML, probably by improving the function of the immune system.

Additionally, the incidence of PML, around 5% before the development of antiretroviral drugs, has dropped signiﬁ cantly (Gray et al. 2003).

27.2.2.3

Cytomegalovirus Infection

CMV infection in immunocompromised patients leads to ventriculitis and leptomeningitis. Ventriculitis is diagnosed on MRI by the presence of enhancement of ventricle surfaces. The differential diagnosis is sub- ependymal lymphoma.

27.3

Prion Diseases

A group of CNS diseases called transmissible spongiform encephalopathies (TSE) is characterized by spongiform degeneration of neurons in the cortex and subcortical nuclei. It is known to be transmissible since the 1920s, when it was observed that humans in Borneo eating the CNS of defeated warriors

were affected by a fatal dementia called kuru. Several human and animal diseases produce this distinctive pattern, including kuru, bovine spongiform encephalopathy (mad cow disease) and scrapie (sheep and goat). There are four forms of TSE, according to the way of contamination:

Sporadic Creutzfeldt-Jakob disease (CJD), the most frequent (80%) has a spontaneous and sporadic origin. However, tissues from those patients may transmit the disease to other humans when injected or grafted

Heritable TSE affects families and is known as Gerstmann-Sträussler disease and fatal familial insomnia

Acquired TSE is of medical transmission, when patients are grafted with contaminated tissues from infected donors: blood transfusion, pituitary extracts, dura mater, and corneal transplantation

Variant CJD (vCJD) is believed to affect patients who have eaten meat from bovine spongiform encephalopathy-infected cattle. The epidemic has affected mostly the UK, with more than a hundred deaths and France with at least four deaths since 1996. The epidemia has stopped.

This classiﬁ cation shows the role of an infectious agent that becomes pathogenic in particular genetic settings. Prusiner and others have partially eluci- dated the origin of TSE (Prusiner 1987). Although still controversial, transmissible agents are likely to be proteins called prions. The normal protein PrP^c becomes pathogenic when beta-pleated, thus becoming insoluble and resistant to heat, and is called PrP^res. PrP^res is capable of inserting itself into the cell membrane of neurons and inducing their own repro- duction. It accumulates in the CNS and is neurotoxic.

This results in death of groups of neurons within the brain (Gray et al. 2004).

Patients with CJD usually present late in life (>50 years of age) with rapid onset of dementia and myoclonic jerks (Martindale et al. 2003). Most patients are dead within a year of the onset of symptoms.

MRI is becoming a technique of choice for diagnostic orientation. The earliest MRI signs are symmetric basal ganglia and cortical hyperintensities on FLAIR and/or DWI (Fig. 27.5a, b) (Collie et al. 2001).

In the clinical setting, these MRI signs are quite spe- ciﬁ c, although not constant. In most cases, the MRI abnormalities of CJD are bilateral and symmetric, but they may be unilateral. Bilateral hyperintensity of the basal ganglia may be seen on top of the basilar artery infarct, deep venous thrombosis, in acute ex-

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Fig. 27.4 a–f. Progressive multifocal leukoencepha- lopathy (PML). a T2 MR imaging. High signal intensity of arcuate ﬁ bers under the frontal motor cortex in an HIV-infected man complaining of right- hand paresis. b Flair MR imaging. Same patient as in a. The abnormality is more conspicuous than in part a. The cortex is spared. c T2 MR imaging.

Evolution of PML on the same patient as in a and b. Subcortical high signal intensity extending into the frontal white matter.

No mass effect. d T1 sagit- tal MR imaging. PML of the occipital lobe of an HIV patient with bilateral visual loss. Atrophy and low signal intensity of occipital-lobe white matter indicating destruction of the axonal ﬁ bers. e Flair MR imaging. Bilateral high signal intensity of the subcortical occipital white matter. f Gadolinium-en- hanced MR imaging. No uptake of gadolinium

a b

c d

e f

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position to toxics, and in metabolic disorders such as Wernicke’s encephalopathy. Usually the clinical setting is far different from CJD, making those diagno- ses very unlikely.

Variant CJD shows a peculiar MRI sign, with high signal intensity in the pulvinar of the thalami (Collie et al. 2003). This “pulvinar sign” is, however, sometimes seen on sporadic CJD. Lately, atrophy and white matter high signal intensities are present on MRI studies.

Electric encephalograms may reveal the presence of triphasic waves that strongly suggest the disease.

This sign is, however, of low sensitivity. CSF might be normal or with increased proteins. The 14-3-3 protein might be suggestively high although not speciﬁ c.

In vCJD, the search for the PrP^res protein includes biopsy of lymphoid organs or tonsils.

27.4

Bacterial Infections

Many bacteria may enter the CNS either hematogenously or by contiguity from the paranasal sinuses, the inner and middle ear or through a traumatic or surgical opening in the dura (Zimmerman 2000). The infection may affect one or several compartments of the brain at the same time: subdural (empyema) or CSF spaces (meningitis) and the brain parenchyma

(encephalitis followed by a circumscribed abscess).

Arteries, veins and perivascular Virchow-Robin spaces contribute to the spread of the bacteria from one compartment to another. Furthermore, acute or rapidly progressive thromboses of these vessels lead to additional abnormalities. The infection may also reach the surface of the endothelial wall causing the so-called distal mycotic aneurysms (see section 4.6) that have a high risk of rupture.

27.4. 1 Bacteria

Staphylococci and streptococci pneumonia spread to the CNS either by a hematogenous path or via adjacent cranial structures.

Meningococci follow a hematogenous path and pro- duce acute meningitis with high risk of death.

Koch bacilli causing tuberculosis (TB) usually is of hematogenous origin, leading to acute or subacute meningitis, and/or brain abscesses. TB affects many people worldwide, in underdeveloped countries, including patients with AIDS.

Nocardia affects immunocompromised patients (AIDS or others) and causes many brain abscesses, usually contemporary with chest infection.

Fig. 27.5a,b Creutzfeldt-Jakob disease. a Flair MR imaging. Bilateral and symmetrical high signal in- tensity of the striatum from the basal ganglia. b Diffusion (b=1,000 mm²/s, trace image) MR imaging.

High signal intensity of the two caudate nuclei and high signal intensity of the left frontal and insular cortex

a b

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Listeria monocytogenes may affect newborns or pa- tients eating a high amount of bacteria in contami- nated foods. The distribution of Listeria is usually the meninges and/or the rhombencephalon (brain stem and cerebellum), where it produces microabscesses (Maezawa et al. 2002; Gray et al. 2004).

E. coli or Proteus, bacteria of urinary origin, can cause brain abscesses in neonates.

Tropheryma whippelii causing Whipple disease is a rare infection, usually, but not constantly, encountered in patients with digestive malabsorption. It may appear as small lesions disseminated throughout the entire CNS with a predilection for gray matter (cortex, nuclei) (Gray et al. 2004).

Treponema pallidum causing syphilis is becoming a very rare cause of CNS infection. It produces mostly chronic meningitis, and, in a few cases, granulomatous reactions have been described along the cranial nerves.

Borrelia burgdorferi transmitted to humans by in- sect bytes causes Lyme disease. Involvement of spinal or cranial nerve roots is frequent. An immunological process leading to the involvement of the white matter resembling MS is much rarer.

27.4.2

Clinical and Imaging Features

Systemic signs of infection (e.g., fever and leukocy- tosis) may be present. Signs of CNS contamination include one or several of the following: neck stiffness and photophobia when meninges are affected, seizures and focal deﬁ cit or cerebellar signs when the parenchyma is involved.

Imaging features refl ect the host reaction and are of variable appearance according to the type and location of the bacteria. Imaging techniques such as FLAIR and DWI, including the calculation of apparent diffusion coeffi cient (ADC) maps, are now used routinely in the indication of infl ammatory CNS diseases. On DWI, purulent material is usually hyperintense and the decreased ADC shows the restriction of water motion (Desprechins et al. 1999; Lai et al.

2002). ADC helps in differentiating brain abscesses from CNS tumors. Indeed, necrotic debris from CNS tumors such as glioblastoma or metastases has variable and heterogeneous intensities and usually an increased ADC. There are, of course, some over-

laps, especially in parasitic toxoplasmic abscesses or in punctured bacterial abscesses that may show increased ADC. MR spectroscopy, which is less routinely used, reveals the presence of amino acids from extracellular proteolysis and bacterial metabolism (fermentation products), including succinate, ac- etate, leucine, valine, and alanine, which are not seen in necrotic neoplasms (Lai et al. 2002; Cecil and Lenkinski 1998; Burtscher and Holtas 1999).

27.4.3

Bacterial Meningitis

The diagnosis is conﬁ rmed with lumbar puncture, and imaging does not play a primary role in the de- tection or treatment of this disorder. It is recommended to treat the patients as early as possible, without waiting for unnecessary imaging modalities.

CT may be used to exclude increased intracranial pressure prior to lumbar puncture—only when there are clinical doubts. Meningitis without parenchyma involvement has a normal appearance on CT and MR T2-weighted images.

FLAIR imaging might be helpful in the diagnosis of meningitis, if the clinical presentation is not straightforward. It shows diffuse subarachnoid hyperintensity, while the CSF in the ventricles is dark (Fig. 27.6). However, there are three differential diag- noses when the subarachnoid space appears bright on Flair: (1) a CSF ﬂ ow artifact, (2) a subarachnoid hemorrhage, (3) a hyperoxygenation such as during 100% oxygen supplementation for anesthesia or during a status epilepticus.

In bacterial meningitis, contrast-agent enhancement in the CSF space can be present, although it is unusual when the parenchyma is not involved.

Tuberculous meningitis may be seen as an enhancement in the cisterna and along the sylvian ﬁ ssures.

CSF space enhancement may also evoke granulomatous diseases.

27.4.4

Subdural Empyema

Subdural empyema may be the result of direct spread of infection from the paranasal sinuses or the middle ear, or it can be of hematogenous origin or follow meningitis or cerebritis, through the venous structures. Subdural empyema produces an acute progressive syndrome characterized by fever and rapid development of neurologic abnormalities

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(e.g., seizure and hemiparesis) (Rich et al. 2000).

A complete imaging study of the brain and cranial structures is compelling in cases of subdural empyema. Subdural empyema produces brain complica- tions by retrograde venous thrombosis that leads to cortical venous stasis with marked cortical swelling and brain abscesses.

Subdural empyema can be difﬁ cult to detect, particularly on unenhanced CT images (Fig. 27.7). The collection is typically narrow. There is disproportion- ate mass effect, with diffuse swelling of the hemisphere adjacent to the collection (Zimmerman 2000). The cortex may appear thickened because of venous stasis.

There might be evidence of sinusitis or mastoiditis.

On MR images, the subdural collection is more conspicuous, particularly on FLAIR images, where it appears hyperintense to adjacent brain. On DWI, the content may appear bright, and the ADC values low (Fig. 27.7d). MR spectroscopy reveals the presence of amino acids. Contrast-enhanced CT and MR images reveal thin enhancement of the deep and superﬁ cial membranes of the subdural empyema (Fig. 27.7b, c).

27.4.5

Brain Abscesses

An abscess is the result of the host defense against bacteria, which initially produce a diffuse cerebritis or encephalitis. Macrophages produce a true collag- enous capsule that marks the passage from cerebritis to the abscess phase. On CT, the capsule may appear

with a slight increased density. Contrast enhancement with iodine contrast agents takes a regular ring appearance (Fig. 27.7b). The capsule made of ﬁ brin and collagen has a typical appearance on MRI: low signal intensity on T2-weighted images and FLAIR, and ring enhancement with gadolinium (Fig. 27.7c).

Additionally, on FLAIR and T2-weighted images, vasogenic edema appears as a high signal intensity inﬁ ltrating the white matter (Zimmerman and Weingarten 1991).

The central necrotic region is hyperintense on FLAIR images, and isointense to CSF on T2-weighted images.

On diffusion imaging the center appears bright, which may be due to “T2 shine-through” effects. On ADC maps, the central necrotic material is hypointense, due to the restriction of water motion, because the water molecules move slowly in the dense abscess content, made of thick proteins and mucus (Fig. 27.7d). In at least two circumstances, the ADC may be increased:

in toxoplasmic abscesses and in bacterial abscesses that have been punctured. Nevertheless, the decreased ADC values help to differentiate from brain necrotic tumors or metastases, which have increased ADC values. In brain abscesses, MR spectroscopy with long TR sequences reveals the presence of amino acids that are the proteolytic breakdown and fermentation products unique to bacterial infection. Enhancement will per- sist for up to 8 months.

A peculiar feature of brain abscesses is the miliary (Fig. 27.8). It may happen following the hematog- enous spread of TB or Nocardia. Innumerable, small abscesses are present in the parenchyma.

27.4.6

Mycotic Aneurysms

Intracranial infectious aneurysms are important features that are not rare. They usually occur in patients with staphylococcal endocarditis and are called “mycotic” aneurysms (Phuong et al. 2002). They also develop in intravenous drug abusers (Tunkel and Pradhan 2002). Their imaging presentation is usually a small mass in the subarachnoid space near the cortex with strong enhancement. They may rupture, leading to subarachnoid hemorrhage with high risk of death. They also can be revealed by focal infarcts or seizures (Fig. 27.9). Note that stroke may occur without infective aneurysms in patients with valve endocarditis (Anderson et al. 2003). Non-ruptured aneurysms may disappear under antibiotics.

Ruptured and sometimes non-ruptured aneurysms need endovascular treatment or surgical clipping.

Fig. 27.6 Viral meningitis. Flair MR imaging. High signal in- tensity of the sub-arachnoid CSF space

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27.5

Parasitic Infections

The most common parasitic infections that affect the CNS are (Chang et al. 1991; Gray et al. 2004):

Protozoal infections:

a) Amebiasis b) Cerebral malaria

c) Toxoplasmosis that develops in the CNS of HIV- infected patients

d) Trypanosomiasis

Metazoal infections:

a) Neurocysticercosis (Taenia solium) from pork b) Hydatidosis (Taenia echinococcus / Echinococ-

cus granulosus) from dogs, responsible for hy- datid cysts

c) Echinococcus multilocularis (Taenia multiloc- ularis) from foxes

d) Toxocariasis (Toxocara canis and Toxocara cati), which may produce visceral larva migrans and CNS manifestations in children

e) Paragonimiasis (Paragonimus westermani) from infected crabs or crayﬁ sh

Other parasitic infections including sparganosis, trichinosis (Trichinella spiralis), strongylosis, schis- tosomiasis may also develop in the CNS.

The three taenias, responsible for neurocysticer- cosis, hydatidosis and Echinococcus multilocularis, produce cystic lesions. A cystic wall is completely different from the capsule of a brain abscess. The cystic wall has a parasitic origin, whereas the cap-

Fig. 27.7a–d. Subdural empyema and brain abscess. a CT without contrast media. A careful analysis shows a focal low density in the left frontal lobe and a lack of visibility of the parietal gyri. b Contrast-enhanced CT. Ring enhanc- ing lesion of the left frontal lobe and enhancement of the meninges. c Sagittal contrast-enhanced MR imaging. Focal lesion of the frontal lobe and subdural collection. d Diffusion MR imaging: Apparent diffusion coefﬁ cient (ADC) map. The frontal lobe and meninges lesions show a restriction of water diffusion (low signal intensity). This is consistent with an infectious origin a

d

b

c

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sule of an abscess has a host origin. The cystic wall is not detectable by the host immunologic system till the larva dies. The symptoms often arise after the death of the parasite, when the host response can occur. However, the location of the cyst may be also responsible for symptoms such as seizures, mass effect or CSF occlusion, before the death of the parasite.

27.5. 1

Cysticercosis (Taenia solium)

Cysticercosis is the most common parasitic infection of the CNS and is endemic in all countries, particu-

larly in Latin America (Gray et al. 2004). The larvae enter the intestinal wall and develop in the brain, the subarachnoid space, or the ventricles (del Brutto et al. 2001). Once the scolex is established, it makes itself immunologically invisible to the host and, conse- quently, incites no inﬂ ammatory reaction. Live cysts are isointense to CSF with all pulse sequences. No enhancement is seen within the cyst wall while the organism is alive (Fig. 27.10). The scolex may be seen as a 2-4 mm mural nodule in the cyst wall. There is no associated edema.

When the organism dies, an inﬂ ammatory granulomatous response occurs. The clinical manifestations are seizures or focal deﬁ cits. The wall enhances, and there is associated vasogenic edema (Fig. 27.10a,

Fig. 27.8a–c. Miliary tuberculosis. a Flair MR imaging. Several high signal intensities in the pons and the right cerebellar hemisphere. b Gadolinium- enhanced MR imaging. Focal enhancement of several small lesions of the same size. c Gadolinium-enhanced MR imaging. Numerous small enhancing lesions in the two hemispheres

a b

c

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c, h). The dead cyst commonly calciﬁ es (Fig. 27.10f).

Patients treated with praziquantel may develop acute symptoms because of the simultaneous death of all live cysts (Fig. 27.10c). Subarachnoid cysts may often produce secondary obstructive hydrocephalus (Fig. 27.10d, e).

27.5.2

Hydatid Cysts (Echinococcus granulosus)

Human Echinococcus granulosus contamination oc- curs by accidental ingestion of contaminated dog feces. The disease is endemic in the Mediterranean regions, the Middle East, and Latin America. The

most common sites of development in humans are the liver, lung and bone. The brain is affected in less than 5% of patients. It is usually a single, unilocular and quite large cyst. When the cyst ruptures, it produces an inﬂ ammatory reaction.

27.5.3

Echinococcus multilocularis

This is a rare parasitic infection that usually has a fatal issue. The cysts are recognizable by their resem- blance to wine grapes.

Fig. 27.9a–c. Mycotic aneurysm. a Contrast-enhanced CT.

Small enhancing lesion adjacent to the right parietal cortex. Note the incidental ﬁ nding of a venous angioma on the left hemisphere. b T2* MR imaging. Presence of magnetic susceptibility, probably due to hemosiderin surrounding the mycotic aneurysm. c Selective right carotid-artery an- giogram. The small mycotic aneurysm appears ﬁ lled by the contrast agent on an anterior parietal branch of the middle cerebral artery

a b

c

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Fig. 27.10a–h. Cysticercosis. a Contrast-enhanced CT.

Patient with right arm seizure. Focal ring enhancing lesion in the left frontal cortex. On the right hemisphere, presence of a cystic lesion with a high density on the margin representing a cysticercosis cyst.

b Contrast-enhanced CT. Same patient. Three other non-enhancing cystic lesions in the brain parenchyma.

c Contrast-enhanced CT. The same patient 3 weeks af- ter praziquantel antibiotic. Simultaneous death of all live cysts leading to a ring enhancement of the cystic walls. d Sagittal T2 MR imaging. Cysticercosis cysts in the CSF of the cauda equina. e Gadolinium-enhanced MR imaging. The cystic walls enhance in the CSF of the cauda equina. f CT without contrast agent. Focal high density of the right subcortical occipital lobe cor- responding to a calciﬁ cation. g Flair MR imaging. High signal intensity corresponding to edema surrounding the low signal intensity calciﬁ cation. h Gadolinium-en- hanced MR imaging. Small and unique ring-enhancing lesion corresponding to a dying cyst

a b c

d e

f g h

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27.5.4

Toxoplasmosis

Toxoplasma gondii is distributed worldwide and in- fects more than 500 million humans (Ramsey and Dean 1997). It does not cause clinical intracranial infection in immunocompetent hosts, and, conse- quently, was rarely seen prior to the onset of the AIDS epidemia. However, toxoplasmosis may infect the embryo, producing diffuse necrotic lesions of the cortex, cerebral malformations and intracranial cal- ciﬁ cations, especially in the periventricular regions (Gray et al. 2004).

Toxoplasmosis is the most common cerebral mass lesion encountered in the HIV-positive patient (Ramsey and Dean 1997). This is the fi rst diagnosis to evoke when CNS manifestations occur with rapid progression in HIV-infected patients. The imaging appearance might be ubiquitous, but the antibiotic treatment is very effi cient. Thus, AIDS patients with rapid CNS manifestations should be treated for toxoplasmosis regardless of the imaging features. The diagnosis might be reconsidered if the treatment is ineffi cient. With HAART (highly active antiretroviral therapy) treatment, the incidence of toxoplasmosis has dropped (Gray et al. 2003). Now, toxoplasmosis is encountered in patients who are unaware of their viral status for HIV. It is not rare that patients pre- senting inaugural seizures and several brain lesions are positive for HIV. This diagnosis must be evoked by the radiologist.

Although largely identical to an abscess, the lesion is not encapsulated, which accounts for the histologic classiﬁ cation of encephalitis rather than abscess (Zimmerman 2000; Gray et al. 2004). In the major- ity of cases, multiple mass lesions are present, and they may be located anywhere within the brain. The basal ganglia and the cortical-subcortical junction are more affected.

The imaging ﬁ ndings in the beginning include a mass effect with or without a slight, not well-demar- cated, contrast enhancement (Fig. 27.11a). Later, the enhancement is quite similar to an abscess, like a ring (Fig. 27.11c, d). The central necrosis is typically hyperintense on FLAIR and T2-weighted images. DWI reveals heterogeneous intensity (Fig. 27.11e), and the ADC is usually increased. Hemorrhage is not present at the time of initial diagnosis. Signs of hemorrhage are present when the patient is treated with antibiotics. High signal intensity from methemoglobin is seen on non-enhanced T1-weighted images, leading to conﬁ rmation of the diagnosis in patients under treatment (Fig. 27.11f).

In patients who are not improving with antibiotics, the diagnosis of toxoplasmosis must be reconsidered, with the primary goal of differentiating toxoplasmosis from lymphoma. Although it is rare, lymphoma is the second most common causes of mass lesions in patients with AIDS (Ramsey and Dean 1997).

Lymphoma lesions are usually single and located in the deep gray and white matter (basal ganglia and corpus callosum). Lymphoma is often hypointense on T2-weighted images. There is mild, adjacent edema, with a mass effect lower than expected. Enhancement is usually diffuse but may be of a ring appearance, especially when the lesion is superior to 3.5 cm. Single photon emission CT (SPECT) with radioactive thallium can be used to conﬁ rm the diagnosis of lymphoma prior to therapy. Inﬂ ammatory lesions, including toxoplasmosis, are negative on SPECT, while lymphoma uptakes the radioactive thallium. When the diagnosis cannot be established non-invasively, biopsy is necessary. Non-Hodgkin lymphoma type B is the most common. Its outcome is, unfortunately, fatal.

27.5.5

Toxocara canis and Toxocara cati Infections These are dog and cat nematodes. Human infection occurs by accidental ingestion of their eggs passed from pet animals. The liver, lung and peritoneum are most frequently involved. They produce focal lesions in the white matter, which spontaneously resolve.

Vasculitis or granulomas around the larvae may form in the parenchyma (Fig. 27.12a, b) (Dousset et al. 2003). The death of the parasite in the brain is followed by a non-encapsulated granulomatous reaction (Gray et al. 2004).

27.6

Mycotic Infections

CNS fungal infections are possible in exposed popu- lations such as immunocompromised patients with AIDS, leukemia, diabetes mellitus, renal diseases, those under aggressive chemotherapy and in intravenous drug abusers with unsterilized materials (Harris and Enterline 1997).

The most frequent fungal infections are: crypto- coccosis due to Cryptococcus neoformans, aspergil- losis, mucormycosis, candidiasis and histoplasmosis.

They are responsible for meningitis in infections

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Fig. 27.11a–f.

Toxoplasmosis.a Gadolinium-enhanced MR imaging. Focal slight enhancement of the left basal ganglia in toxo- plasmic encephalitis. b Gadolinium-enhanced MR imaging. Focal enhancing cortical lesion of the left parietal cortex. c Gadolinium-enhanced MR imaging. Two ring-enhancing toxoplasmic lesions.

d Gadolinium-enhanced MR imaging. Enhancing lesion of the right cerebel- lar hemisphere. e Diffusion (b=1,000 mm²/s, trace image) MR imaging. Low signal intensity in the toxoplasmic lesion indicating an increase in water diffusion. This is different from bacteria abscesses, which usually show a decrease in water diffusion. f Sagittal T1 MR imaging. Treated toxoplasmic lesion of the cerebellar hemisphere that appears with a spontaneous high signal intensity due to the presence of methemoglobin in subacute hemorrhage

a b

c d

e f

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Fig. 27.12a, b. Toxocariasis.

Flair MR imaging. Several lesions of the subcortical white matter (a) and of the cortex (b). The imaging ﬁ ndings are not sufﬁ cient to make the diagnosis, which requires blood se- rology for Toxocara canis or Toxocara cati

by the smallest fungi like Cryptococcus neoformans or small to extensive infarcts following occlusion of the vessels by bigger fungi such as Aspergillus and Candida.

27.6.1

Cryptococcosis

The patient usually presents with a meningoencephalitis (Harris and Enterline 1997). The infection is fatal without appropriate treatment using ampho- tericin B. Lumbar puncture is the single most use- ful test. After reaching the CSF, the organisms may extend along the perforating arteries in the perivascular Virchow-Robin spaces. The signal intensity is similar to the cerebrospinal ﬂ uid. Cerebral edema rarely occurs.

27.6.2 Aspergillosis

It is relatively rare in the AIDS population, but is more common in patients under corticosteroids. The organisms invade the lung parenchyma and spread hematogenously. Aspergillus may reach the CNS via direct spread from the paranasal sinuses or orbits.

Aspergillus abscesses have a nonspeciﬁ c appearance.

27.6.3

Mucormycosis

Most CNS mucormycosis-infected patients are dia- betic, drug abusers, or patients receiving long-term antibiotics and corticosteroids. It has a secondary focus in skin, nasal mucosa and lungs. Rhinocerebral mucormycosis is a common feature. It provokes necrosis and vasculitis with hemorrhage.

27.7

Granulomatous Infections and Immunoreactive Diseases

27.7.1

Granulomatous Infections

Granulomas correspond to cellular mass with T-cells, macrophages and histiocytes without liqueﬁ ed necrotic debris. Caseous (“cheesy”) necrosis is typical of tuberculous granulomas.

Granulomatous infections can result from di- verse pathogens, including bacteria (Mycobacterium, Nocardia, Actinomyces, spirochetes), fungi (aspergil- losis or mucormycosis), and parasites. Sarcoidosis is an idiopathic granulomatous disease that most commonly affects young, otherwise healthy adult patients (Ulmer and Ester 1991). Most granulomatous infections affect the meninges. The brain parenchyma

a b

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might be involved, usually by the spread of the granuloma along the perivascular Virchow-Robin spaces.

Inﬂ ammatory pseudotumors may also affect the cavernous sinuses, the orbits and, rarely, the hypophysis sellae.

CT or MRI features of granulomatous meningitis are cisternal enhancement, usually following the vessel routes. Thus, contrast-enhanced images are critical in establishing the diagnosis of granulomatous meningitis. Basal meningitis often leads to hydrocephalus. There is often compromise of the vascular system, with secondary infarction or hemorrhage. The combination of hydrocephalus and deep infarction in a young adult should, therefore, always raise the suspicion of granulomatous meningitis (Zimmerman 2000).

The differential diagnosis of granulomatous infectious meningitis is neoplastic carcinomatous meningitis (Aparicio and Chamberlain 2002). It has a predilection for the retro-cerebellar cisterns.

Sarcoidosis has a predilection for the suprasellar cistern, often producing thickening of the pituitary stalk (Ulmer and Ester 1991). Enhancement along the course of the cranial nerves is characteristic of sarcoidosis but can also be seen in lymphoma.

27.7.2 Vasculitis

Vasculitis may be the result of direct spread from the leptomeninges along the perivascular spaces or direct invasion and growth within the lumen of the vessel.

It also can be the result of an immune reaction at the endothelial level, without infectious agents. Infarcts occur in the deep gray matter or in the cortex.

27.7.3

Acute Disseminated Encephalomyelitis

Acute disseminated encephalomyelitis is an autoim- mune disorder that is similar to multiple sclerosis, except that it is monophasic (Talbot et al. 2001).

Acute disseminated encephalomyelitis occurs with a latency of 1 week to several weeks after viral ex- posure or vaccination. In most of the cases, multiple lesions are present at the same time in the white matter, affecting the gray matter in at least one-third of cases. The disease may produce multifocal demyelination similar to viral encephalitis or multiple sclerosis. Enhancement is inconstant, although frequent. In most cases, improvement is

good under steroids. Death is possible in the most severe cases.

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