Cerebral infections. Introduction NEURO. Spyros Karampekios John Hesselink

Transcription

1 Eur Radiol (2005) 15: DOI /s NEURO Spyros Karampekios John Hesselink Cerebral infections Received: 5 July 2004 Revised: 18 October 2004 Accepted: 19 October 2004 Published online: 31 December 2004 # Springer-Verlag 2004 S. Karampekios (*) Department of Radiology, University of Crete, Stavrakia, Heraklion, Crete, Greece karampek@med.uoc.gr J. Hesselink Department of Radiology, UCSD, San Diego, CA, USA Abstract Despite the development of many effective antibiotic therapies and the general improvement in hygiene and health care systems all over the world, the incidence of central nervous system (CNS) infection has increased significantly in the past 15 years. This can be attributed primarily to the acquired immunodeficiency syndrome (AIDS) epidemic and its devastating effect on the immune system and secondarily to various immunosuppressive agents that are being used in aggressive cancer treatment and in organ transplantations. The brain particularly is protected from infection by the calvarium, meninges and blood brain barrier. However, different types of pathogens, including bacteria, viruses, fungi and parasites, can reach the brain hematogenously or, less likely, by direct extension from an adjacent infected focus. The early detection and specific diagnosis of infection are of great importance, since brain infections are potentially treatable diseases. Imaging studies play a crucial role in the diagnostic process, along with the history (exposure to infectious agents), host factors (open head trauma, CSF leak, sinusitis, otitis, immune status), physical examination and laboratory analysis of CSF. Keywords Immunosuppression. Infections. Imaging Introduction CNS infections constitute a group of life-threatening diseases that present with various clinical and imaging manifestations that form an interesting and challenging pattern for diagnosticians. Once an intracranial infection is established, even weak pathogens may produce a severe inflammatory response that is mainly due to some unique features of the brain, such as the absence of lymphatics, the lack of capillaries in the subarachnoid space and the existence of CSF, which acts as an excellent culture medium for dissemination of an infectious process. In a practical approach to differentiate CNS infections, we use some broad categories to localize them by the anatomic compartment involved. Some pathogens can involve the brain parenchyma, producing focal (abscess, cyst) or diffuse (encephalitis) lesions, the meninges (meningitis, ependymitis) and the extra-axial spaces (subdural, epidural empyema). We also include a special section dedicated to AIDS-related infections, since AIDS has become the leading cause of infections of the CNS today, causing multiple opportunistic infections. Magnetic resonance imaging (MRI) is the most sensitive imaging modality in detecting focal or diffuse parenchymal infectious lesions, and today it has clearly replaced computed tomography (CT). MRI s optimal contrast resolution, its multiplanar capability and the absence of signal intensity from the surrounding bone allow an earlier and more precise localization of brain infection. Recently, by using advanced MRI techniques, such as proton MR spectroscopy ( 1 H-MRS), diffusion-weighted (DW) imaging, perfusion-weighted (PW) imaging and magnetization transfer (MT) sequences, further improvement in the detection and characterization of infectious brain lesions is possible.

2 486 Brain abscess Brain abscess is the most common focal infectious lesion and can be caused by many different types of pathogens, usually bacteria. Brain abscesses frequently arise secondary to hematogenous dissemination of an extracranial site, by direct extension from a contiguous suppurative focus (paranasal sinuses, middle ear, mastoids), or secondary to a meningitis. Regardless of the pathogen, the brain tissue reacts in a predictable way, initially developing an area of local cerebritis, which consists of vascular congestion, petechial hemorrhage and brain edema. With time, the infectious process progresses and a true encapsulated brain abscess with a central area of liquefied-necrotic material is formed. Thus, cerebritis and abscess formation constitute a spectrum of the same process. Although the rapidity of this infectious process depends on the type of the invading pathogen, the origin of the infection, and the patient s immunocompetence, typically the whole process requires days. Patients usually present in the late cerebritis or early abscess stage with clinical manifestations of a rapidly expanding spaceoccupying lesion rather than symptoms specific for an infection [1]. The MRI features of cerebritis and brain abscess depend on the stage of the infectious process at the time of imaging. In the early cerebritis stage, MRI depicts the ill-defined infectious focus, as an area mildly hypointense on T1- and hyperintense on T2-weighted images. As the infection matures, it increases in size and necrotic debris accumulates centrally, while the body attempts to isolate the infection by forming a collagenous capsule. The proteinaceous, necrotic fluid of the abscess cavity has signal intensity higher than CSF on T1-weighted and fluid-attenuated inversion recovery (FLAIR) images. Peripherally, there is a moderate degree of vasogenic edema. On T1-weighted images, the abscess capsule stands out as an isointense or slightly hyperintense ring against the hypointense background of the necrotic center and the surrounding edema. On T2-weighted images, the ring is markedly hypointense (Fig. 1a). There is still discussion about the causes of capsular intensity. Some authors attribute the hyperintensity of the abscess capsule on T1-weighted images to capsular hemorrhage, reflecting paramagnetic effects of methemoglobin. More recently, the signal properties of the abscess capsule have been ascribed to paramagnetic hemoglobin degradation products or to free radicals within macrophages. Another characteristic feature of cerebral abscess is its tendency to grow into the white matter away from the well-vascularized cortex, resulting in an oblong configuration and thickening of the cortical surface of the abscess capsule. The thinner portion of the capsule toward the white matter accounts for the predilection of abscesses to rupture centrally into the ventricles, producing ventriculitis (ependymitis), and less commonly into the subarachnoid space. Contrast administration is very helpful in the evaluation of brain abscesses. Gadolinium produces mottled, heterogeneous areas of enhancement during the cerebritis stage, with an enhancing thin walled rim, developing as the abscess matures (Fig. 1b). If an abscess ruptures into a ventricle and secondary ependymitis develops, the ventricular wall enhances, suggesting a poor prognosis. Ring enhancement persists for up to 8 months, and its presence should not be considered as a treatment failure. More reliable signs of healing are shrinkage of the necrotic center and a decrease in capsular hypointensity on T2-weighted images [2]. Frequently, imaging characteristics alone may not clearly distinguish a cerebral abscess from other ring-enhancing lesions, such as cystic or necrotic tumor, a resolving hematoma, a deep subacute infarct or postoperative change. Advanced Fig. 1 Streptococcus brain abscesses. a T2-weighted, axial image displays multiple hyperintense foci within the right parietal lobe, with surrounding vasogenic edema. Note that the abscess capsule exhibits low signal (arrows). b Axial, postcontrast image at the same level, shows the ring-like enhancing lesions. c Diffusion-weighted image shows marked hyperintensity of the lesions. d On the ADC map they are distinctly hypointense

3 487 neuroimaging techniques, such as 1 H-MRS and diffusionweighted imaging, have been proposed to establish the correct diagnosis non-invasively [3]. The main finding of 1 H-MRS in brain abscesses is elevation of metabolites of bacterial origin, including acetate, lactate, succinate and amino acids. The spectral pattern of necrotic brain tumors is quite different and normally contains elevated choline and decreased N-acetylaspartate (NAA). The 1 H-MRS pattern may also confirm the effectiveness of medical treatment of a brain abscess, showing a decline of the metabolites after a positive response to therapy [4]. DW imaging, along with apparent diffusion coefficient (ADC) maps, can be decisive in characterizing brain abscesses. The presence of pus within the abscess cavity, which consists of numerous leukocytes and proteinaceous fluid with high viscosity, accounts for the restricted diffusion and high signal intensity on DW imaging and low ADC values (Fig. 1c, d). In contrast, the cystic or necrotic portions of brain tumors typically are less cellular and have less viscous fluid consistency. As a result, tumors show low signal intensity on DW imaging and higher ADC values [5]. Meningitis Meningitis is an acute or chronic inflammation of the piaarachnoid (leptomeninges) and the adjacent CSF. The two main diagnostic groups are bacterial (purulent) and viral (aseptic) meningitis. They may have an acute, subacute or chronic presentation and course. The clinical signs and symptoms of meningitis are usually characteristic. Patients present with fever, headache, neck stiffness, vomiting, photophobia and altered consciousness. Almost all patients with viral and the majority of patients with bacterial meningitis have a subacute onset of symptoms (1 7-day duration). Patients with an acute presentation (less than 24 h) constitute a medical emergency that requires immediate institution of antimicrobial therapy. The outcome of patients with acute purulent meningitis depends on many factors, such as age, underlying health condition, the specific invading organism and the delay in treatment. So in patients with acute presentation of meningitis, the first consideration is therapy and not specific diagnosis, whereas in cases with subacute or chronic presentation, attention should be focused on identification of the specific organism. The diagnosis of chronic meningitis is made when clinical symptoms persist and the CSF examination remains abnormal for at least 4 weeks. A large number of infectious and noninfectious agents can cause chronic meningitis, with Mycobacterium tuberculosis being the most common. Tuberculous meningitis presents as a long-standing, insidious process, in which vasculitis of the circle of Willis and cerebral infarctions from basal meningeal inflammation predominate. Neuroimaging plays a limited role in the diagnosis of meningitis, which is usually made on a clinical basis by history, physical examination and laboratory CSF findings. Imaging studies (CT and MRI) are employed in patients in whom complications are suspected, such as vascular thrombosis, brain infarctions, brain abscess, ventriculitis, hydrocephalus, empyemas of epidural or subdural spaces and subdural effusions. Imaging is also undertaken to confirm the diagnosis of meningitis, to identify possible sources and to exclude other intracranial diseases. Patients with meningitis, either acute or chronic, usually have a normal nonenhanced MRI study. Contrast administration is very helpful in the evaluation of suspected meningeal infection, because the involved meninges enhance diffusely and intensely. In the majority of cases of acute bacterial or viral meningitis, the abnormal meningeal enhancement occurs predominantly over the cerebrum and the interhemispheric and sylvian fissures. In cases of chronic meningitis of tuberculous, fungal or sarcoid origin, the enhancement is most prominent in the basal cisterns, where the inflammation is intense and profound (Fig. 2). Contrast-enhanced MRI is much more sensitive than postcontrast CT in the detection of meningeal enhancement, particularly when it occurs near the skull vault. Although more sensitive, postcontrast MRI is no more specific. Any condition that is likely to produce meningeal irritation, such as craniotomy, ventriculoperitoneal shunting, subarachnoid hemorrhage or meningitis of carcinomatous or chemical origin, may cause meningeal enhancement. Also, abnormal meningeal enhancement is not seen in every case of meningitis, and, therefore, an unremarkable MRI study does not exclude this diagnosis [6]. The fluid-attenuated inversion recovery (FLAIR) sequence has been proposed as very sensitive for the detection of meningeal and subarachnoid space disease, even more sensitive than postcontrast T1-weighted images [7]. Furthermore, FLAIR has proved to be very sensitive for conditions that increase CSF protein concentration, such as infectious meningitis. The additional of gadolinium increases the sensitivity of the FLAIR sequence even further, by summing the signal from the subarachnoid protein and the enhancing leptomeninges. Fig. 2 Coccidiomycosis meningitis. Contrast-enhanced, axial image reveals diffuse, intense meningeal enhancement in the suprasellar and perimesencephalic cisterns

4 488 Encephalitis Encephalitis refers to a diffuse parenchymal inflammation of the brain caused primarily by viruses. Viruses usually gain access to the CNS through hematogenous dissemination, although in certain viral infections entry into the CNS occurs by the peripheral nerves. Viral encephalitis is usually acute, although it can occur from reactivation of a latent virus. The most common invading viruses are herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), herpes zoster, arboviruses and enteroviruses, which produce almost the same inflammatory reaction in brain tissue and appear similar on CT and MRI [2, 8]. Viral encephalitis in immunosuppressed patients includes infection caused by human immunodeficiency virus (HIV), CMV and the papovavirus (progressive multifocal leukoencephalopathy) and is discussed separately in the section on AIDS-related infections. Clinically acute encephalitis should be suspected if the patients present with convulsions, altered consciousness, delirium, aphasia or ataxia. Particularly in cases of herpetic encephalitis, there are some added, bizarre clinical signs, such as hallucinations, seizures and personality changes, reflecting the propensity to involve the subfrontal and temporal lobes. HSV-1 accounts for 95% of herpetic encephalitis in adults. The virus usually invades the brain after reactivation of a latent form, which is frequently located in the trigeminal (gasserian) ganglion. The marked predilection for temporal lobe involvement supports the proposed theory that the infection spreads intracranially from the trigeminal ganglion along the meningeal branches of the trigeminal nerve [9]. The resulting necrotizing encephalitis rapidly disseminates in the brain, sparing the basal ganglia and producing edema and petechial hemorrhages. Early diagnosis is crucial, owing to the significant mortality rate (approaching 70%), the high incidence of sequelae and the availability of effective antiviral drugs. Definitive diagnosis of HSV-1 encephalitis is made after isolation of the virus from brain biopsy. However, given the appropriate clinical presentation, with or without MRI or other laboratory diagnostic confirmation, medical treatment should be instituted immediately to avoid the devastating and irreversible brain damage. In the early phase of the infection, HSV-1 encephalitis has a characteristic distribution in the medial temporal and inferior frontal lobes. On MR images the early edematous changes appear as ill-defined areas of low signal intensity on T1-weighted images and high signal intensity on T2- weighted and FLAIR images, usually beginning unilaterally, but rapidly progressing to both hemispheres [10]. Variable mass effect and gyral enhancement may occur. Occasionally, foci of hemorrhage are visualized as areas of high signal intensity on both T1- and T2-weighted images. Extra-axial spaces Subdural and epidural empyemas are uncommon purulent collections that develop in the subdural or, less frequently, in the epidural space, and they may occur alone or in combination. The main predisposing conditions are sinusitis, mastoiditis, infection secondary to previous craniotomy and post-traumatic infection [8, 11]. Rarely, empyemas are secondary to meningitis or to hematogenous spread from a distant infectious focus. Particularly in infants, both sterile subdural effusions and infected subdural empyemas are often seen as a complication of purulent meningitis. Subdural empyema In the majority of patients who develop subdural empyemas, the source of infection is sinusitis or otitis, with frontal sinusitis accounting for 50 80% of the cases. The pathogens that are commonly isolated are similar to those from sinusitis or brain abscesses. Patients present with fever, headache, alteration in mental status, seizures and focal neurologic deficits. Subdural empyemas secondary to an infected post-traumatic subdural hematoma or to previous craniotomy follow a more prolonged and indolent course, occurring months to years after the original insult. If the subdural empyema remains untreated, rapid clinical deterioration occurs and the mortality is quite high. Even small subdural empyemas may cause severe complications such as vein thrombosis, infarcts and parenhymal abscesses. In most cases, antibiotic therapy alone is not sufficient for satisfactory recovery, and neurosurgical intervention is required for drainage and brain decompression. Subdural empyema should be considered as a medical emergency, particularly when related to a preceding sinusitis or osteomyelitis. Thus, neuroimaging (CT and MRI) plays a significant role in early diagnosis and successful outcome. Several authors have emphasized the failure of CT to visualize small, crescentic extra-axial collections of fluid, especially when they are located superficially near the inner table of the skull [12]. MRI has become the imaging modality of choice for detecting and defining the extent of subdural empyemas with the greatest accuracy. On T1-weighted and FLAIR images, the purulent collections depict signal intensity higher than pure CSF, owing to the increased content of proteins and inflammatory debris, whereas on T2-weighted images the signal intensity approaches that of CSF. MRI can also evaluate the presence of mass effect on the adjacent brain or CSF spaces, as well as the underlying parenchymal abnormalities such as cerebral edema, brain abscess or cortical vein and dural sinus thrombosis. After contrast administration, subtle enhancement occurs at the margins of the empyema, which becomes more prominent after time and is due to formation of a vascular membrane of granulation tissue (Fig. 3). On the basis of signal differences, MRI easily differentiates between subdural empyemas and sterile subdural effusions or subdural hematomas. Recently, diffusion-weighted imaging has been proposed for the detection and characterization of extra-axial empyemas. Subdural empyemas may appear as areas of high signal on DW imaging and low ADC values, similar to that produced by most brain abscesses. This is attributed to the

5 489 Cystic lesions Cystic infections are typically caused by parasitic diseases, which are still an important and not uncommon clinical issue in underdeveloped countries and in patients with defective or suppressed immune status. Cysticercosis Fig. 3 Subdural empyema. Post-contrast, coronal image demonstrates an extra-axial, lentiform fluid collection in the right frontal region. Note that the purulent fluid exhibits higher signal intensity than pure CSF and there is abnormal enchancement at the margins of the empyema high viscosity of the infected, subdural fluid which restricts the free proton movement [13]. Epidural empyema In cases of epidural empyemas, the purulent collection tends to localize outside the inelastic and firm dura, which protects the underlying brain parenchyma from undesirable concomitant abnormalities. Thus, patients with epidural empyemas have a more insidious and benign clinical course than those with subdural empyemas, with headache and fever often the only clinical clues. Frontal sinusitis is the primary preceding condition, although mastoiditis, previous surgery and trauma are other causes. As with subdural empyemas, MRI is the most sensitive imaging modality for the detection of epidural empyemas. The signal characteristics of these lentiform extra-axial collections are similar to those of subdural empyemas on both T1- and T2-weighted images. On post-contrast scans, there is profound enhancement of the inflamed dura, often thicker than that observed in subdurals. An important imaging feature of epidural empyemas is the normal appearance of the adjacent brain parenchyma, in contrast to subdural empyemas. Other diagnostic clues for an epidural empyema are the presence of a thick hypointense dura on the medial side of the collection and also the presence of osteomyelitis or subgaleal abscess, which makes an epidural empyema more likely. DW imaging may also be used as an adjunct to conventional MRI, for the detection and differentiation of an epidural fluid collection. However, in cases of epidural empyemas, the signal characteristics on DW imaging are not as straightforward as in subdural empyemas. Epidural empyemas typically have a prolonged and insidious clinical course, allowing time for resolution of the pus, which becomes less viscous and exhibits low or mixed signal on DW imaging [14]. Cysticercosis is the most common parasitic infection of the CNS in immunocompetent individuals and is caused by the larval pork tapeworm, Taenia solium. CNS infection is reported in 70 90% of cases and constitutes the most common cause of seizures in young patients in developing countries with poor hygiene. Neurocystisercosis may involve the brain parenchyma, the ventricles or the subarachnoid space [15]. In the parenchymal form there are four different phases of evolution, and imaging findings depend on the stage of the infectious process. The initial phase of invasion is typically undetectable; the next stage is that of cyst formation with a small invagination developing along one cystic wall (scolex); during the third stage the parasite degenerates and dies, inducing an inflammatory reaction of the surrounding neural tissue with edema and ring-like enhancement. Finally at the end stage of evolution the cysts are shrunken and mineralized and only punctuate foci of calcifications may be seen [16]. Intraventricular cysticercosis occurs in 20% of the cases, and the cysts are more often located in the aqueduct of Sylvius, or the fourth ventricle. The cysts can migrate within or between ventricles and can produce acute, obstructive hydrocephalus. The cystic content exhibits signal similar to CSF and sometimes the only clue to the diagnosis is the identification of the scolex. Cysticercosis may occur in the subarachnoid space, particularly in the CP angle or the suprasellar region, where the cysts have a racemose form and are larger, sterile and usually without scolices. AIDS-related infections With the increasing number of patients seropositive for HIV, AIDS has become the leading cause of CNS infections and one of the most common reasons for neuroimaging. At least 10% of all patients with AIDS present initially with neurological complaints, and more than one third will manifest a clinically apparent neurological disorder sometime during the course of their disease [17]. On autopsy series, evidence of significant neuropathologic abnormalities has been shown in 75 90% of patients with AIDS, and usually more than one disease process was present [18]. The CNS infections in the AIDS population share some atypical clinical and imaging characteristics, different from the corresponding picture in individuals with normal immune status. The defective immune system makes the nervous

6 490 system incapable of fighting common pathogens. Therefore, the number of pathogens is large, multiple concurrent microbial agents may be responsible for the infection, and there is minimal inflammatory response of the adjacent neural tissue. Neuroimaging features in pantients with AIDS are based primarily on four different patterns of brain involvement, which include cerebral atrophy, mass lesions, white matter changes and chronic meningitis [19]. Toxoplasmosis Fig. 4 Toxoplasmosis. Post-contrast, coronal image demonstrates a ring-like enhancing lesion in the right cerebral peduncle, surrounded by vasogenic edema. Note also the small, eccentric enhancing nodule along the wall of the lesion (arrow), which represents the asymmetric target sign Toxoplasmosis is the most frequent opportunistic brain infection in AIDS patients. It is caused by the parasite Toxoplasma gondii, an obligate intracellular protozoan, which invades subclinically (latent form) a large portion of the adult population (up to 70% in some areas). In patients with AIDS seropositive for Toxoplasma, the risk for cerebral toxoplasmosis approaches 30%, and the infection is secondary to reactivation of a latent parasite encysted in the brain. Infection with Toxoplasma produces multiple, scattered necrotic and inflammatory brain abscesses, which have a predilection for the corticomedullary junction and the basal ganglia. Patients may present with clinical symptoms of focal mass effect, such as seizures, focal neurological deficits or cranial nerve palsies. MRI has proved to be the most sensitive imaging modality for the detection of cerebral toxoplasmosis, by demonstrating lesions in patients with normal CT scans and by delineating the true extent of the disease. Postcontrast MR images demonstrate multiple, nodular or ring-like enhancing lesions, involving both white matter and deep gray matter and surrounded by vasogenic edema. An imaging finding highly suggestive for toxoplasmosis is the asymmetric target sign, which is a small eccentric nodule along the wall of the enhancing ring. This appearance probably represents an infolding of the cyst wall on itself and offers a very useful key for differential diagnosis [20] (Fig. 4). The neuroimaging findings with both CT and MRI are not pathognomonic for toxoplasmosis because they can be seen in various infectious or noninfectious diseases, such as brain metastases, intracerebral lymphoma or Kaposi s sarcoma, or in brain abscesses of nonpyogenic origin (tuberculomas, cryptococcomas). Once toxoplasmosis is suspected by imaging criteria and positive Toxoplasma serologic test results, empiric antitoxoplasma medication is begun and the response of treatment can be monitored with clinical examination and follow-up CT or MRI. Clinical and radiographic improvement is a reliable indicator of toxoplasmosis and should be evident within 2 3 weeks of therapy, manifested by resolution of neurologic abnormalities and a decrease in the size and number of lesions. Cerebral toxoplasmosis and primary brain lymphoma are the two most common focal lesions in AIDS patients, and their discrimination is frequently impossible based on clinical and radiologic findings, which overlap significantly. Noninvasive techniques have been introduced for their differentiation, including nuclear medicine techniques, such as single-photon emission CT (SPECT) and positron emission tomography (PET), as well as non-conventional MR techniques, such as proton MR spectroscopy 1 H-MRS and diffusion-weighted or perfusion-weighted imaging (DW PW) [21]. The 1 H-MRS findings in cases of toxoplasmosis confirm the infectious origin of the lesions, which are essentially abscesses with a central cavity. In contrast, MR spectroscopy in lymphoma shows marked elevation of choline and moderate elevation of lactate and lipid, due to the increased cellularity and membrane turnover in the neoplasm. Diffusion- and perfusion-weighted (DW-PW) MRI have been proposed as valuable tools for the efficient, noninvasive differentiation between brain lymphoma and toxoplasmosis. Perfusion MRI seems to be a very practical and rapid way to differentiate cerebral toxoplasmosis and lymphoma. The same dose of gadolinium given for the conventional MR examination can be used for the perfusion sequence, adding less than 2 min to the total scan time. It is well known that metabolism and perfusion are strongly correlated. Lymphoma, which is a neoplastic hypervascular process, will have increased rcbv, whereas toxoplasmosis lesions consistently demonstrate decreased rcbv (hypoperfusion) [22]. Cryptococcosis Cryptococcus neoformans causes the most common CNS fungal infection in patients with AIDS, which in terms of relative frequency ranks third after HIV encephalitis and toxoplasmosis. Intracranial cryptococcosis typically produces a chronic basilar meningitis or meningoencephalitis with minimal inflammatory reaction. Fungal invasion can also occur in the distribution of the perforating brain ar-

7 491 teries, along the perivascular Virchow-Robin spaces, producing small cystic areas in the brain parenchyma (Fig. 5). Another common location for cryptococcal infection is the choroid plexus, where it can cause the formation of masslike lesions. Rarely, Cryptococcus may produce focal parenchymal lesions (cryptococcomas) [23]. Other brain abscesses In immunosuppressed patients, brain abscesses are most frequently caused by nonpyogenic organisms (parasites, mycobacteria, fungi) and share almost the same imaging characteristics as the bacterial ones. Mycobacterial infection, which has experienced a marked decline in developed countries over the past decades, is now back again in epidemic proportions, mostly due to the onset of AIDS. Extrapulmonary dissemination of tuberculosis is more common in patients with AIDS, and CNS involvement may manifest as meningitis, tuberculoma or brain abscess. Tuberculous brain abscesses contain encapsulated pus with viable tubercle bacilli and differ from the more common tuberculomas (granulomas), which are smaller and contain caseous debris. Occasionally, tuberculomas with central caseating necrosis appear hypointense to brain parenchyma on T2-weighted images, with ring enhancement postcontrast [24]. A helpful clue to the diagnosis of tuberculosis is the presence of other associated lesions, such as basal meningitis, multiple granulomas and deep cerebral infarctions [25]. Another cause of nonpyogenic brain abscesses in the population with AIDS is fungal infection. The most frequently encountered fungi are Aspergillus, Mucormycosis and Candida [26]. Because they have large hyphal forms allowing only limited access to the leptomeninges, meningitis is relatively uncommon, and focal parenchymal lesions are more likely to occur. Human immunodeficiency virus encephalitis HIV can cause damage to the nervous system directly, resulting in a subacute encephalomyelitis with a subtle and gradual clinical course. HIV encephalitis, also known as AIDS encephalopathy or AIDS dementia complex, is the most common CNS complication in AIDS. It has been described in nearly two thirds of all patients with neurological symptoms and results in a progressive, subacute encephalitis with associated mental impairment, as well as motor and behavioral abnormalities. Patients present with progressive cognitive impairment, memory loss, language difficulties, somnolence, bradykinesia and diminished concentration. Despite the presence of diffuse and extensive parenchymal changes seen in brain autopsy specimens in patients with HIV encephalitis, both CT and conventional MRI usually fail to identify the brain abnormalities or grossly underestimate them. Most frequently, the only imaging finding is a progressive, diffuse, nonspecific brain atrophy inappropriate for the patient s age with a central predominance. In more advanced cases there is variable involvement of white matter, particularly in the periventricular areas and the centrum semiovale. MRI is the most sensitive imaging modality for detecting the demyelinating lesions, which are depicted best on T2-weighted and FLAIR images as large, nearly symmetric, patchy or confluent areas of high signal intensity, without any evidence of mass effect or contrast enhancement. Due to the inability of conventional MRI sequences to detect abnormalities of HIV encephalitis until advanced stages of the disease, new advanced neuroimaging techniques have been proposed for better assessment of HIV seropositive subjects. 1 H- MRS demonstrates biochemical abnormalities early in the course of HIV infection. The main findings are a significant drop in NAA and an elevation of choline and myoinositol, reflecting early neuronal damage before any structural abnormality becomes evident on conventional MR. Furthermore, initiation of treatment at this early stage may reverse the metabolite abnormalities, particularly the glial marker (myoinositol), indicating that the cellular injury is, to some extent, reversible [27]. Cytomegalovirus encephalitis Fig. 5 a Cryptococcosis with fungal extension into the basal ganglia- VR spaces. Axial, FLAIR image demonstrates multiple hyperintense foci within the basal ganglia bilaterally, but predominantly on the right side. b Cryptococcosis with fungal extension into the basal ganglia-vr spaces. Post-contrast image at the same level shows only punctuate areas of minimum contrast enhancement (arrow), probably due to decreased inflammatory reaction CMV is a herpes virus that can reactivate in the immunosuppressed host and produce a necrotizing encephalitis and ependymitis. The pathologic abnormalities of CMV infection involve the gray matter and the ventricular ependyma more than the white matter, differentiating CMV encephalitis from the other viral encephalitides in patients with AIDS, such as HIVencephalitis or PML, which show a

8 492 marked predilection for white matter involvement. Despite the high incidence of CMV encephalitis in autopsy series, the clinical correlation is poor, owing to the insidious and nonspecific clinical course, the insensitive and atypical CSF cultures, and the absence of pathognomonic neuroimaging findings. On FLAIR and T2-weighted images, MRI depicts a thick or nodular periventricular hyperintensity, often involving the splenium and the genu of the corpus callosum. After contrast administration, irregular subependymal enhancement can be seen, representing the changes of ependymitis [28]. CMV infection usually has a centrifugal spread from the ventricular system, involving diffusely the gray matter and, less frequently, the white matter. From the onset of the AIDS epidemic, a close and complex relationship of CMV and HIV has been observed. Synergism between the two viruses could result in co-infection of the same cells with molecular trans-activation. Therefore, an interaction between CMV and HIV may play a significant role in the pathogenesis of encephalitis in individuals with AIDS. Fig. 6 Progressive multifocal leukoencephalopathy. Axial, FLAIR image demonstrates bitateral areas of high signal intensity in the peripheral, subcortical white matter, with scalloped outer margins Progressive multifocal leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) is a progressive neurologic disorder associated with reactivation of a latent papovavirus infection that occurs when cellmediated immunity is impaired. The main target of PML is the oligodendrocyte, the myelin-producing cell. The resulting demyelination involves the subcortical and deep white matter and produces a rapidly deteriorating neurologic syndrome with altered mental status, limb weakness, visual field deficits, headache and ataxia. Dementia is not a main feature of this disorder, an important point for differentiating PML from HIV encephalitis. PML has typically a rapidly progressive and fatal clinical course; however, advances in antiretroviral therapy have resulted in a better prognosis, with clinical and imaging remission of PML in some cases [29]. Due to its increased sensitivity, MRI can detect white matter abnormalities that are either missed or underestimated by CT, and it can also identify lesions of PML, even when they are clinically silent. T2- weighted and FLAIR sequences reveal bilateral, asymmetric focal areas of high signal intensity, which become larger and confluent with time and lack any significant associated edema or mass effect. The disorder tends to involve the peripheral white matter, giving the lesions a scalloped outer margin (Fig. 6). The lesions are predominantly located in the white matter of the parieto-occipital regions. After contrast medium administration, enhancement has been the exception in imaging of PML, although the presence of faint enhancement at the periphery of the lesion is not uncommon. An interesting observation is that patients with contrast-enhancing lesions of PML may develop a relatively favorable outcome, probably because abnormal enhancement results from improved immune status [30]. Since PML is essentially a demyelinating process, magnetization transfer (MT) has been introduced, and the progressive decrease in MT contrast values correlate with areas with a greater degree of myelin destruction [31]. References 1. Mathisen GE, Johnson JP (1997) Brain abscess. Clin Infect Dis 25(4): Falcone S, Post MJ (2000) Encephalitis, cerebritis and brain abscess: pathophysiology and imaging findings. Neuroimaging Clin N Am 10(2): Lai PH, Ho JT, Chen WL et al (2002) Brain abscess and necrotic brain tumor: discrimination with proton MR. Spectroscopy and diffusion-weighted imaging. Am J Neuroradiol 23: Burtscher IM, Holtas S (1999) In vivo proton MR spectroscopy of untreated and treated brain abscesses. Am J Neuroradiol 20: Guzman R, Barth A, Lovblad KO et al (2002) Use of diffusion-weighted MRI in differentiating purulent brain processes from cystic brain tumors. J Neurosurg 97(5):

9 Phillips ME, Ryals TJ, Kambhu SA, Vuh WTC (1990) Neoplastic vs. inflammatory meningeal enhancement with Gd-DTPA. J Comput Assist Tomogr 14: Singer MB, Atlas SW, Drayer BP (1998) Subarachnoid space disease: diagnosis with FLAIR MR imaging and comparison with gadolonium-enhanced spin echo MRI blinded reader study. Radiology 208: Anslow P (2004) Cranial bacterial infection. Eur Radiol [Suppl 3] 14: E145 E Tien RD, Felsberg GJ, Osumi AK (1993) Herpesvirus infections of the CNS: MR findings. Am J Roentgenol 161: White ML, Edwards-Brown MK (1995) Fluid attenuated inversion recovery (FLAIR) MRI of herpes encephalitis. J Comput Assist Tomogr 19: Tsai YD, Chang WN, Shen CC et al (2003) Intracranial suppuration: a clinical comparison of subdural and epidural abscesses. Surg Neurol 59 (3): Nathoo N, Nadvi SS, van Deller JR, Gouws E (1999) Intracranial subdural empyemas in the era of computed tomography: a review of 699 cases. Neurosurgery 44(3): Ramsey DW, Mohammad A, Cherryman GR (2000) Diffusionweighted imaging of cerebral abscess and subdural empyema. Am J Neuroradiol 21: Tsuchiya K, Osawa A, Katase S et al (2003) Diffusion-weighted MRI of subdural and epidural empyemas. Neuroradiology 45: Del Brutto OH, Sotelo J (1998) Neurocysticercosis: an update. Rev Infect Dis 10: Chang KH, Cho SY, Hesselink JR et al (1991) Parasitic diseases of the central nervous system. Neuroimaging Clin N Am 1: Gray F, Chretien F, Vallat-Decouvelaere AV, Scaravilli F (2003) The changing pattern of HIV neuropathology in the HAART era. Neuropathol Exp Neurol 62(5): Lantos PL, Mclaughlin JE, Scholtz CL et al (1989) Neuropathology of the brain in HIV infection. Lancet 1: Federle MP (1988) A radiologist looks at AIDS: imaging evaluation based on symptom complexes. Radiology 166: Ramsey RG, Geremia GK (1988) CNS complications of AIDS: CT and MR findings. Am J Roentgenol 151: Chang L, Ernst T (1997) MR spectroscopy and diffusion-weighted MRI in focal brain lesions in AIDS. Neuroimaging Clin N Am 7(3): Ernst TM, Chang L, Witt MD et al (1998) Cerebral toxoplasmosis and lymphoma in AIDS: perfusion MRI experience in 13 patients. Radiology 208: Andreula CF, Burdi N, Carella A (1993) CNS cryptococcosis in AIDS: spectrum of MR findings. J Comput Assist Tomogr 17: Shah GV (2000) Central nervous system tuberculosis. Neuroimaging Clin N Am 10(2): Bernaerts A, Vanhoenacker FM, Parizel PM (2003) Tuberculosis of the central nervous system: overview of neuroradiological findings. Eur Radiol 13: Guermazi A, Gluckman E, Tabt B, Miaux Y (2003) Invasive central nervous system aspergillosis in bone marrow transplantation recipients.: an overview. Eur Radiol 13(2): Moller HE, Vermathen P, Lentsching et al (1999) Metabolic characterization of AIDS dementia complex by spectroscopic imaging. J Magn Reson Imaging 9(1): Kalayjian RC, Cohen ML, Bonomo RA, Flanigan TP (1993) CMV ventriculoencephalitis in AIDS: a syndrome with distinct clinical and pathologic features. Medicine 72: Domingo P, Guadiola JM, Iranzo A, Margall N (1997) Remission of prograssive multifocal leukoencephalopathy and antiviral therapy. Lancet 349: Kotecha N, George MJ, Smith TW et al (1998) Enhancing progressive multi focal leukoencephalopathy: an indicator of improved immune status. Am J Med 105: Dousset V, Armand JP, Lacoste D et al (1997) Magnetization transfer study of HIV-encephalitis and progressive multifocal leukoencephalopathy. Am J Neuroradiol 18: