Central Nervous System Infections

Central Nervous System Infections Zoran Rumboldt,* Majda M. Thurnher,† and Rakesh K. Gupta‡

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he incidence of central nervous system (CNS) infection has been increasing over the past decades despite the general improvement in hygiene and health care as well as continuous development of effective therapies. This is primarily attributed to the acquired immunodeficiency syndrome (AIDS) epidemic, followed by widespread use of various immunosuppressive agents, as for aggressive cancer treatment and in organ transplantations.1 Different types of pathogens can reach the brain and spinal cord hematogenously or, less frequently, by direct extension from another focus. The early detection and specific diagnosis are of great importance, as these are potentially treatable diseases. In many cases neuroimaging constitutes an important component in the diagnostic process, along with the history, physical examination, and cerebrospinal fluid (CSF) analysis. Diffusion magnetic resonance imaging (MRI) has been found particularly helpful both for early detection of infectious processes and for their differentiation from other diseases. Magnetic resonance spectroscopy (MRS) and perfusion MRI may provide additional information in selected cases.1,2

Viral Infections Over 100 of different viruses have been identified as causative agents of encephalitis. Many viruses have a predilection for the gray matter, whether it is cortical, deep, or intramedullary (Fig. 1). Acute viral infection produces parenchymal infiltration with inflammatory cells, leading to neuronal injury and at times to extensive necrosis.

Herpes Encephalitis Herpes simplex virus (HSV) is the most common cause of viral encephalitis in adults. Clinical presentation of herpes simplex encephalitis (HSE) is typically acute onset of severe neurological symptoms, primarily confusion and seizures, *Department of Radiology, Medical University of South Carolina, Charleston, South Carolina, USA. †Department of Radiology, University of Vienna, Vienna, Austria. ‡Department of Radiology, Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India. Address reprint requests to Zoran Rumboldt, MD, Associate Professor, Department of Radiology, Medical University of South Carolina, 169 Ashley Avenue, PO Box 250322, Charleston, SC 29425, USA. E-mail: [email protected]

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usually with signs of systemic infectious process. Untreated HSE has an extremely high mortality rate and early diagnosis is essential, as the prognosis is dependent on early recognition. The HSV gains entry into the brain through the sensory cranial nerves, most commonly the trigeminal nerve branches. Polymerase chain reaction for the detection of the viral DNA is the definite diagnostic test with sensitivity over 95% and specificity approaching 100%. While computed tomographic (CT) studies are frequently negative in the early HSE, areas of low attenuation may be detected in the temporal lobes bilaterally (Fig. 2). MR imaging is much more sensitive, demonstrating lesions that are hyperintense on T2- and hypointense on T1-weighted images predominantly involving the cortical gray matter of bilateral anterior and medial temporal lobes (Fig. 3).3 The hyperintense abnormalities are seen on fluid-attenuated inversion-recovery (FLAIR) images within 48 hours from the onset of symptoms, while diffusionweighted imaging (DWI) appears to be the most sensitive imaging technique for early detection of HSE encephalitis (Fig. 4).4-7 Hyperintense lesions involving the cortex and adjacent white matter on DWI, especially in the anterior and medial temporal lobes, in the appropriate clinical setting should be considered HSE until proven otherwise (Fig. 5). Unilateral temporal lobe involvement is not unusual, while the insula, amygdala, cingulate gyrus, and orbitofrontal region are commonly involved. Contrast enhancement is usually not present early on, while gyriform enhancement may be observed with disease progression.3 Areas of hemorrhage may or may not be detected. Changes in diffusion abnormalities on MRI in patients with HSE also appear to correlate better than conventional MRI with disease activity and response to treatment.8 It seems that apparent diffusion coefficient (ADC) values of the lesions correspond to clinical presentation and outcome, with high ADC values found with a more benign clinical course.7 In some cases HSV may involve other parts of the brain, so absence of bilateral temporal lobe lesions does not exclude HSE. This atypical imaging appearance seems to be particularly common in infants.9 A few other rare conditions may also involve both temporal lobes in a similar fashion on imaging studies, most notably paraneoplastic limbic encephalitis, but also Japanese encephalitis and neurosyphilis.

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Figure 1 Encephalitis, unidentified causative agent. (A) Axial fast spin-echo (FSE) T2-weighted (T2w) image shows bilateral basal ganglia, thalamic and cortical hyperintense abnormalities without significant mass effect (arrowheads). Diagnosis of viral encephalitis was based on clinical course, CSF analysis, and MRI appearance. Imaging findings may be indistinguishable from metabolic and toxic etiologies. (B) Corresponding axial fluid-attenuated inversion recovery (FLAIR) image demonstrates increased conspicuity of the lesions.

Arbovirus Infections Arboviruses (arthropod-borne viruses) include three different groups of viruses that are transmitted by insects, most commonly mosquitoes. Flaviviridae are a prominent group of arboviruses that includes agents causing Japanese, West Nile, St. Louis, and Murray Valley encephalitides, which all belong to the Japanese encephalitis antigenic complex, as well as tick-borne encephalitides. Japanese encephalitis (JE) is a mosquito-borne flaviviral infection that remains a major health problem in Asia with case fatality ranging from 10 to 60% and frequent disabling neurologic deficits in the survivors.10 The characteristic imaging findings of JE include bilateral thalamic and brainstem, especially substantia nigra, lesions that are of low attenuation on CT and of high T2 signal on MR imaging (Fig. 6). Cerebellum, cerebral cortex, and basal ganglia may also be affected. The abnormalities are frequently hemorrhagic, and bilateral thalamic hemorrhages are considered highly specific for JE.10,11 Medial temporal lobe involvement may also be encountered, characteristically in the posterior part of the hippocampus. Unlike HSE, the anterior temporal lobe is usually spared and insular involvement is rare. DWI enables early diagnosis of JE by showing characteristic involvement of bilateral thalami.11 The imaging findings of encephalitides caused by other flaviviridae are similar to JE. West Nile Virus encephalitis may show some additional findings or present with normal imag-

Figure 2 Herpes encephalitis (HSE). Axial CT image at the level of the pineal gland shows bilateral hypodense areas (*) located primarily in temporal lobes.

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Figure 3 HSE. Axial single shot (SSE) T2w image reveals bilateral almost symmetric hyperintense abnormalities of the entire temporal lobes.

Figure 5 HSE. Axial DWI demonstrates hyperintensity of the entire left temporal lobe as well as of the antero-mesial part of the right temporal lobe. This imaging finding is virtually pathognomonic for HSE.

ing studies. Isolated abnormalities on DWI can be detected in the cerebral white matter in milder cases. In patients with flaccid paralysis abnormal high T2 signal in the ventral gray matter horns and/or enhancement around the conus medullaris and cauda equina is found on MR imaging.12,13

Enteroviruses The enteroviruses include Coxsackie viruses A and B, poliovirus, echoviruses, and enteroviruses 68 to 71 and they may cause a number of disease processes, including poliomyelitis, meningitis, and encephalitis. The pathologic CNS involvement by enteroviruses is characteristically located in the posterior portion of the medulla oblongata, posterior portion of the pons, central portion of the midbrain, bilateral dentate nuclei of the cerebellum, and ventral horns of cervical spinal cord.14 MRI studies accordingly show T2 hyperintensity of the involved areas with symmetric bilateral lesions in the dorsal brain stem and ventral horns of cervical spinal cord (Fig. 7) considered characteristic findings of enteroviral encephalomyelitis.14

Human Immunodeficiency Virus (HIV) and Associated Opportunistic Viral Infections Figure 4 HSE. Axial FLAIR image shows mild hyperintensity in the left mesial and anterior temporal lobe (arrows).

The CNS is the second most commonly affected organ in patients with AIDS, following the lung. Neurologic symp-

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Figure 6 Japanese encephalitis (JE). (A) Axial FSE T2w image shows hyperintense signal in bilateral thalami, right putamen, and adjacent cortical gray matter (arrows). The abnormality is very prominent in the right thalamus, which is also enlarged. (B) Corresponding DWI shows the hyperintense lesions to be more pronounced in the right insula and left thalamus. (C) Corresponding apparent diffusion coefficient (ADC) map calculated from DWI data reveals low signal intensity in the left thalamus, as well as in the right insula, temporal lobe and putamen (arrowheads), consistent with decreased diffusion of water molecules, indicative of shorter duration of the disease in these regions.

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Figure 7 Enterovirus encephalitis. (A) Axial SSE T2w image shows bilateral hyperintense abnormalities in dorsal pons (arrowheads). (B) Axial FSE T2w image at level of cervico-thoracic junction shows bilateral hyperintense intramedullary lesions located in anterior portion of the spinal cord (arrows), also referred to as “owl’s eyes.” The combination of the brainstem and spinal cord lesions is highly suggestive of enteroviral infection.

toms are the presenting complaint in about 10% of these patients; CNS symptoms eventually develop in up to 40%, and brain is involved in the majority of autopsies. CNS lesions in patients with AIDS may be due to primary HIV infection or to the opportunistic infections and neoplasms.15 Primary HIV infection is the most common CNS abnormality in HIV-positive patients, clinically manifested with progressive dementia with cognitive, motor, and behavioral abnormalities. This subacute encephalitis is called AIDS dementia complex and is also known as HIV or AIDS encephalopathy. While the incidence of HIV dementia has decreased with the advent of highly active anti-retroviral therapy (HAART), the prevalence of milder neuropsychological impairments rise as individuals infected with HIV live longer. In contrast to most other viral pathogens, HIV and associated opportunistic viruses have predilection for the white matter of CNS. The most common reported imaging finding in HIV encephalopathy is cerebral atrophy, followed by white-matter abnormalities (Fig. 8).16 The white-matter lesions are of high T2 signal intensity and are usually isointense or minimally hypointense on T1-weighted MR images, without contrast enhancement or mass effect.17 When these abnormalities are prominent, they show decreased attenuation on CT images (Fig. 8A). Diffuse, bilateral, and symmetric white-matter hyperintensity with relative sparing of the subcortical U-fibers is typical for HIV encephalopathy and best seen on FLAIR

images (Fig. 8D). These abnormalities increase in size with disease progression.18 MRI is not sensitive enough to show early pathologic involvement and it underestimates the lesion load compared with histopathological studies. Proton MRS may be more sensitive in detecting early CNS involvement, demonstrating moderately decreased levels of n-acetyl aspartate (NAA) and elevated cholin.19,20 HAART may result in stabilization or even regression of white matter and metabolite abnormalities observed on MRI and MRS.20-22 The progression of whitematter lesions on initial follow-up studies is probably the result of postinflammatory reactions due to immune reconstitutive effects after the initiation of HAART.22 Vacuolar myelopathy (VM), also known as AIDS-associated myelopathy, is the most severe in the lateral and posterior columns of the thoracic spinal cord.23 Twenty to 55% of patients with AIDS have evidence of this disease. A clinical picture of VM includes paraparesis, spasticity, and/or ataxia as well as sensory abnormalities in the lower extremities, impotence, and urinary disturbances. The pathogenesis VM appears to be related to metabolic abnormalities rather than to direct HIV infection. The striking pathologic similarity between VM and the myelopathy associated with vitamin B12 deficiency appears to be due to abnormal B12 metabolism in the patients with VM.24 The characteristic MRI finding is bilateral symmetric high T2 signal intensity in the dorsal

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Figure 8 HIV encephalitis. (A) Axial contrast-enhanced CT image shows diffuse decreased attenuation of cerebral white matter (arrowheads) without enhancing lesions. (B) Axial nonenhanced T1-weighted (T1w) image at a similar level as (A) reveals no clear abnormality. (C) Corresponding axial T2w image shows diffuse white matter hyperintensity comparable to hypodensity on CT. Note preserved subcortical U-fibers (arrowheads). (D) Corresponding FLAIR image depicts diffuse white-matter abnormality clearly.

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Figure 9 Abnormal B12 metabolism. (A) Axial FSE T2w image through thoracic spine in a patient with AIDS shows dorsal paramedial intramedullary hyperintensity (arrows), primarily involving dorsal columns. The imaging appearance is consistent with vacuolar myelopathy (VM) seen with HIV (image courtesy of Mauricio Castillo). (B) Axial gradient echo (GRE) T2w image through cervical spine in different patient with copper deficiency myelopathy shows hyperintensity in the dorsal columns of the spinal cord, indistinguishable from findings in (A) (image courtesy of Neeraj Kumar). Identical imaging appearance is encountered with vitamin B12 deficiency.

columns of the spinal cord that extends over multiple segments (Fig. 9A).25,26 As expected, subacute combined degeneration due to vitamin B12 deficiency shows identical imaging appearance, which may also be seen with copper deficiency (Fig. 9B).27

lobes with surrounding edema due to CMV have been described.31 CMV infection can also present as choroid plexitis with marked enhancement of a slightly enlarged choroid plexus.32 CMV appears to be the most common opportunistic infection involving the spine in patients with AIDS. The most

Cytomegalovirus Cytomegalovirus (CMV) encephalitis in adults is a result of reactivated latent infection that affects the immunocompromised population, especially patients with advanced HIV infection and transplant recipients. In HIV-seropositive individuals CMV may produce progressive dementia without specific findings on imaging studies. Five distinct neurological syndromes due to the CMV infection have been described, including retinitis. The fact that CMV retinitis is present in the majority of patients with CMV brain infection is frequently helpful, and the most specific diagnostic tool is the polymerase chain reaction detection of CMV DNA in the CSF.28,29 The most common imaging findings in patients with CMV encephalitis are cortical atrophy, diffuse white-matter abnormalities, and periventricular contrast enhancement.30 Generalized atrophy and white-matter T2 hyperintensity are indistinguishable from HIV encephalopathy. Characteristic findings of ependymal and subependymal linear periventricular hyperintensities on FLAIR images and a thin, linear postcontrast enhancement along the ventricular margin are suggestive, but not specific of CMV infection. A few cases of large contrast-enhancing masses in frontal

Figure 10 Progressive multifocal leukoencephalopathy (PML). Coronal FSE T2w image shows asymmetric hyperintense lesions involving the white matter of both temporal lobes, as well as the right thalamus and brainstem (arrowheads).

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Figure 11 PML. (A) Axial CT image in patient with AIDS shows prominent hypodensity in right frontal white matter (*). (B) Axial FSE T2w at similar level demonstrates corresponding diffuse hyperintensity with associated mild mass effect. The subcortical U-fibers are involved and only thin strip of cortical gray matter (arrowheads) is visualized. (C) Axial contrast-enhanced T1w image shows hypointensity of lesion without enhancement, in contrast to isointense appearance of HIV encephalitis. (D) Proton MR spectroscopy (MRS) of lesion with echo time of 270 ms shows prominent decrease in n-acetyl aspartate (NAA) level with elevated choline (Cho) peak and presence of characteristic lactate doublet at 1.33 ppm. Normal MRS would show similar levels of choline and creatine (Cre), approximately twice as high NAA peak and no evidence of lactate.

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Figure 12 Pyogenic abscesses. (A) Axial FSE T2w image at level of lateral ventricles shows two oval predominantly hyperintense lesions with peripheral ring-like hypointensity (arrowheads), corresponding to capsule, and surrounding edema. (B) Nonenhanced T1w image shows low signal in center of lesions with iso- to hyperintense rim and perifocal edema. (C) Contrast-enhanced T1w demonstrates dense and smooth ring-like enhancement of the capsule. (D) Corresponding DWI shows pronounced hyperintensity of the central nonenhancing portion of lesions. (E) Corresponding ADC map reveals core of lesions is very dark, from restricted diffusion due to dense pus within the cavity.

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Figure 13 Pyogenic abscesses. (A) Axial nonenhanced CT image at the level of the third ventricle shows right frontal round lesion with hypodense core and iso- to hyperintense periphery (arrowheads). The lesion is surrounded by vasogenic edema with its typical appearance of white-matter hypodensity with finger-like extension into the subcortical regions (arrows). (B) Corresponding contrast-enhanced CT image shows smooth and thin enhancement of the capsule.

common imaging finding is nonspecific diffuse leptomeningeal enhancement on MR imaging.25

Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by JC Polyomavirus (JCV), which has a predilection for oligodendrocytes and may affect any subset of immunocompromised patients. The incidence of PML has greatly increased due to the AIDS epidemic; it develops in up to11% of HIV patients. The clinical presentation includes altered mental status, visual symptoms, and focal motor and sensory deficits, without prominent dementia. Histopathological hallmark of PML is demyelination with enlarged oligodendroglial nuclei and bizarre astrocytes.33,34 PML was recently reported in patients treated with natalizumab and a review study estimated the risk of PML to be roughly 1 in 1000 for the average treatment over 18 months.35 On MRI, PML lesions present as patchy areas of high T2 signal in the white matter; they are usually multifocal, commonly in the parieto-occipital region, corpus callosum, and cerebellum. Lesions can be solitary and occur in any location, including basal ganglia, thalami, and cortex. Enhancement is usually absent and hemorrhage is unusual; however, pres-

ence of these findings does not exclude PML. In contrast to HIV encephalopathy, the lesions are asymmetrical, with mild mass effect and common involvement of subcortical U-fibers (Figs. 10 and 11). On T1-weighted images, the PML lesions are of clearly low signal intensity, in contrast to generally isointense HIV-associated changes (Figs. 8 and 11).34,36 MRI with magnetization transfer (MT) can help in differentiation, since the MT ratio of PML lesions is lower than in HIV abnormalities.37 MRS may also play a role, since spectra of PML lesions demonstrate more severe reduction in NAA and increase in choline levels, as well as prominent resonances of lactate38 (Fig. 11D). Without treatment the prognosis of PML is very poor with overall survival of 6 to 12 months. Follow-up imaging shows rapid progression in both size and number of the lesions with central necrosis. Recent studies have shown clinical and radiological improvement in approximately half of the patients with PML who undergo HAART.39,40 Initial worsening of the MRI findings with development of temporary contrast enhancement, mass effect, and edema is observed in long-term survivors.40 Acute lesions of PML survivors also show twofold higher ratio of myoinositol to creatine on MRS compared with lesions in patients with progressive disease.41 These findings are probably caused by a posttreatment inflammatory reaction due to the immune reconstitutive effect.

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Figure 14 Pyogenic abscesses. Axial nonenhanced CT image shows a round left posterior temporal lobe mass with central low attenuation and an iso- to hyperintense rim. The lesion is centered at the gray– white-matter junction and its rim is thicker on its deeper, whitematter side (arrowhead), which is unusual for brain abscesses. Surrounding edema and mass effect with effacement of the adjacent cortical sulci are present.

Bacterial Infections Bacterial infections of the CNS lead to meningitis, abscesses, subdural and epidural empyemas, and ventriculitis. Although most commonly associated with bacteria, these pathologic processes may be also caused by other infective agents, especially fungi. A few bacterial pathogens may show other, characteristic imaging findings.

Abscess Brain abscess is the most common focal infectious CNS lesion, most commonly caused by bacteria. Abscesses arise by hematogenous dissemination, direct extension (from paranasal sinuses or mastoids), or secondary to a meningitis. Intracerebral abscess accounts for up to 5% of all intracranial mass lesions and carries a very high mortality rate.42 Patients usually present with neurological abnormalities related to rapidly expanding mass and the systemic signs of infection are often missing. Imaging depends on the stage of the lesions; the whole process typically spreads over 10 to 14 days. The brain reacts by initially developing an area of local cerebritis, which consists of vascular congestion, petechial hemorrhage, and edema. Early cerebritis stage is characterized by a nonspecific poorly demarcated area of high signal intensity on T2-weighted MR images at times with heterogenous patchy

Z. Rumboldt, M.M. Thurnher, and R.K. Gupta enhancement and corresponding low attenuation on CT. During the late cerebritis and abscess stages, a collagenous capsule is forming, visualized as a thin-walled markedly hypointense ring on T2-weighted MRI with prominent surrounding vasogenic edema (Fig. 12A). The wall is of isointense to hyperintense T1 signal and a well-defined complete ring of enhancement indicates a mature abscess.43 The proteinaceous, necrotic fluid within the abscess cavity is hyperintense to CSF on T1-weighted and FLAIR images. On precontrast CT images, formed abscesses frequently exhibit a smooth complete capsular ring, which enhances with contrast (Fig. 13). A possibly distinguishing feature is the tendency of growth into the white matter, so that the abscess wall is usually thinner on the side that is closer to the ventricular system (Fig. 14).1 The capsule is also generally smoother on the outside than inside. If an abscess ruptures, the prognosis is poor; intraventricular extension leads to development of pyogenic ventriculitis, which is characteristically visualized as irregular ventricular debris, while ependymal enhancement, periventricular hyperintense signal on FLAIR images, and hydrocephalus are not always present (Fig. 15).44 Ring-enhancing brain lesions are nonspecific and need to be distinguished from other cystic lesions, primarily necrotic neoplasms. DWI has proven to be quite reliable for this task. The presence of pus, which consists of numerous white blood cells and highly viscous proteinaceous fluid, accounts for restricted diffusion of water molecules, seen as strong hyperintensity on DWI and reduced ADC values in brain abscesses (Fig. 12D and E), whereas necrotic or cystic parts of tumors have low to intermediate DWI signal and elevated ADC values.45-48 This distinction is quite reliable in clinical practice, although it is not pathognomonic as cases of metastatic brain tumors with DWI hyperintensity and low ADC values have been described.49,50 This is probably due to early tumor necrosis,49 similar to acute ischemic brain infarcts. Perfusion MRI may also distinguish brain abscesses that show relative decrease in cerebral blood volume (CBV) from neoplasms, which demonstrate significantly elevated CBV.51 On MRS, the main brain metabolites—NAA, creatine, and choline—are usually not detectable in abscesses, while the spectra reveal peaks of acetate (1.92 ppm), succinate (2.4 ppm), other amino acids (0.9 ppm), as well as lactate (1.3 ppm).52 Aerobic organisms show spectra with resonances of amino acids and lactate, while only anaerobic bacteria demonstrate the presence of additional acetate and succinate peaks (Fig. 16).53 Ring enhancement in treated abscesses may persist for up to 8 months, while shrinkage of the necrotic center and decreasing hypointensity of the capsule on T2-weighted images occur earlier and are more reliable signs of healing.43 Decreasing signal intensity on DWI and increasing ADC values in the abscess cavity correlate with a successful treatment. Conversely, persistent or re-appearing DWI hyperintensity and low ADC values of restricted diffusion correlate with pus re-accumulation and are indicative of treatment failure.54 Loss of acetate and succinate peaks on MRS that occurs with treatment seems to confirm positive response to medical therapy.53,55

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Figure 15 Pyogenic abscesses with intraventricular extension. (A) Axial FLAIR image at level of third ventricle shows slightly hyperintense oval mass in right occipital lobe with surrounding vasogenic edema. The abnormal signal of lesion extends into right lateral ventricle (arrow). (B) Axial contrast-enhanced T1w image shows rim enhancement of the lesion that extends into right lateral ventricle (arrowheads).

Figure 16 MRS of pyogenic abscesses. (A) MRS of abscess with echo time of 144 ms shows presence of glycine at 3.56 ppm, different from other amino acids (AA) at 0.9 ppm, lactate at 1.33 ppm, and, most prominent, acetate at 1.92 ppm succinate (Succ) at 2.4 ppm. The lactate doublet is characteristically inverted with this echo time. The spectral pattern is consistent with anaerobic abscess. Culture revealed anaerobic streptococci and Bacteroides species. (B) MRS of an abscess in a different patient with echo time of 144 ms clearly shows only combined lipid and lactate peaks at 1.33 ppm. Note absence of acetate and succinate peaks in contrast to (A). This spectral pattern is consistent with aerobic abscess. Culture showed Pseudomonas aeruginosa.

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Figure 17 Meningitis. (A) Axial FLAIR image shows diffuse hyperintensity within cortical sulci (arrowheads), consistent with increased protein content within the subarachnoid space. Symmetric linear hyperintensities (arrows) represent wrap-around artifact. (B) Axial contrast-enhanced T1w image at a slightly higher level reveals enhancement within cortical sulci (arrowheads) on left.

Figure 18 Subdural empyema. (A) Coronal contrast-enhanced T1w image with fat saturation (FS) demonstrates pachymeningeal (arrowheads) and leptomeningeal (arrows) thickening and enhancement, along the convexity of left cerebral hemisphere. (B) Corresponding DWI reveals hyperintensity of subarachnoid spaces (arrowheads) surrounded by enhancing meninges, consistent with restricted diffusion of pus.

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Figure 19 Tuberculous meningitis with tuberculomas. (A) Axial FSE T2w image shows thickening of the optic chiasm and loss of CSF signal in basilar cisterns (arrowheads). There are small hyperintense lesions with hypointense rim (arrows) in adjacent left temporal lobe with surrounding edema. (B) Corresponding T1w image also shows thickening of the optic chiasm and loss of CSF signal in the basilar cisterns. Left temporal lesions appear hypointense on T1 with mild hyperintensity of the wall. (C) Contrast-enhanced T1w image shows dense enhancement in optic chiasm and basal cisterns along with rim enhancement of tuberculomas in left temporal lobe.

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Figure 20 Tuberculoma. (A) Axial FSE T2-weighted image shows hypointense mass in right frontal lobe with perifocal edema. (B) Contrast-enhanced T1w shows thick enhancement of lesion wall. (C) Corresponding DWI reveals hypointensity in center of mass. (D) MRS with echo time of 135 ms shows prominent lipid peak without significant other resonances.

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Figure 21 Neuroborreliosis (Lyme disease). (A) Contrast-enhanced midsagittal FS T1w image of the cervical spine shows thin linear enhancement along the surface of the spinal cord and brainstem (arrows). (B) Contrast-enhanced axial T1w image through the cervical spine demonstrates diffuse linear enhancement along the cord surface (arrows). (C) Contrast-enhanced axial T1w image at suprasellar level shows enhancement of the oculomotor nerves (arrows). This imaging appearance is not specific and may be seen with CMV infection, Guillain–Barre syndrome, chronic inflammatory demyelinating polyradiculopathy (CIDP), and other disorders.

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Figure 22 Cryptococcal meningitis. (A) T1w is normal without hyperintensities in the subarachnoid spaces. (B) Contrast-enhanced T1w image shows only mild leptomeningeal enhancement, most pronounced in right occipital region (arrowheads).

Meningitis and Complications Meningitis is an infectious inflammatory infiltration of the leptomeninges (pia mater and arachnoid mater), which can be bacterial (purulent) or viral (aseptic), and the diagnosis is based on clinical presentation, typically headache, fever, neck stiffness, photophobia, vomiting, and altered consciousness, in combination with appropriate CSF findings. Leptomeningeal contrast enhancement and CSF hyperintensity on FLAIR images, presumably corresponding to increased protein content, are frequently seen on MRI56 (Fig. 17). CT is clearly inferior to MRI in detection and characterization of meningeal conditions. In acute meningitis, the pathologic enhancement is preferentially located over the cerebral convexity, whereas in chronic meningitis as seen with tuberculosis or fungal organisms, the enhancement is most prominent in the basal cisterns.1,57 Metastatic neoplasms may cause carcinomatous meningitis, which typically presents with dural enhancement and thus may usually be differentiated from infectious etiology.58 Imaging studies should be performed in patients with suspected complications, most commonly hydrocephalus, followed by sterile subdural effusions. Only approximately 2% of subdural collections become infected and form subdural empyemas.57 Most subdural empyemas in children occur in the setting of meningitis, while in adults they are most commonly due to spread of infection from paranasal sinuses and

are thus epidural. Despite antibiotic and surgical treatment, extra-axial empyemas still carry a high mortality rate. Compared with sterile collections, empyemas may show slightly higher signal intensity on T1-weighted and especially FLAIR images. Similar to abscesses, empyemas are typically very bright on DWI, consistent with restricted diffusion of pus, while sterile collections are similar to CSF59 (Fig. 18).

Tuberculosis The incidence of tuberculosis (TB) has been increasing over past two decades primarily due to incomplete therapy giving rise to multi-drug-resistant strains and to an increase in AIDS and other immunodeficiency states. CNS involvement occurs in 2 to 5% of all TB patients and in 10 to 15% of AIDS patients. At the present time, about 30% of patients with tuberculosis are HIV-positive; conversely, 5 to 9% of patients with AIDS develop tuberculosis.60,61 CNS infection with Mycobacterium tuberculosis occurs either in a diffuse form as leptomeningitis or in a localized parenchymal form as tuberculoma, abscess, and focal cerebritis. Tuberculous meningitis is the most common presentation of neurotuberculosis, with a predilection for the meninges covering the base of the brain. Cell-mediated immune response leads to the development of a thick exudate, most notably in the interpeduncular fossa, suprasellar, and ambient cisterns. Meningeal enhancement on CT and MRI in the

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79 All caseating granulomas show rim enhancement with contrast.61,64 In around one-third of patients, the target sign, which appears to be pathognomonic of tuberculoma, is present on CT scans: a central calcification or punctate enhancement within a region of low attenuation with surrounding rim enhancement.66 Healed tuberculomas no longer enhance and may calcify, while many lesions completely disappear with successful treatment.61 Tuberculous abscesses are rare and, in contrast to tuberculomas, in which only a few bacilli are found, the pus contains numerous microorganisms. They show imaging appearance of pyogenic abscesses, are frequently multiloculated and larger and have a more rapid course than tuberculomas.67,68 Differentiation of TB from pyogenic abscesses may be very difficult on imaging studies. A combination of MRS and MT MRI may allow for distinction of these two entities.68 TB abscesses show only elevated levels of lipids and lactate, without presence of amino acids, which are a hallmark of the pyogenic abscess. The meninges in the basal and supratentorial cisterns are also hyperintense on MT images in patients with TB meningitis (Fig. 19).69 The MT ratio from the thickened meninges of tuberculous meningitis is lower compared with cryptococcal and pyogenic disease.

Spirochetal Infections Figure 23 Cerebral cryptococcosis with dilated perivascular spaces. Axial FSE T2w image demonstrates multiple small confluent areas of increased signal throughout bilateral basal ganglia and thalami (arrows), slightly more prominent on left side.

basal cisterns and over the convexity of the brain is seen in 36 to 61% of the cases61-64 (Fig. 19). A frequent complication is involvement of the vessels coursing through the affected cisterns, resulting in panarteritis with vessel narrowing and occlusions leading to subsequent infarctions. Involvement of the small perforating arteries supplying the basal ganglia and internal capsule usually leads to infarcts in these locations.61,64,65 Communicating hydrocephalus is considered the single most common complication in meningeal TB and is more prominent in children. The common triad of imaging findings in TB meningitis consists of thick enhancement in the basal cisterns, hydrocephalus, and infarctions.61 Parenchymal TB is more common in HIV-infected patients and tuberculoma (tuberculous granuloma) is the most frequent lesion.61,64 Tuberculomas occur predominantly in the supratentorial compartment in adults and infratentorially in children, typically at the cortico-medullary junction, indicating hematogenous spread. The noncaseating granuloma is usually of relatively low T1 and high T2 signal and with homogeneous enhancement. The caseating granuloma with solid caseation appears relatively hypointense on T2weighted images (Fig. 20), similar to other granulomatous diseases, most notably fungal infections and sarcoidosis. The wall of a caseating tuberculoma often shows a striking hypointense rim on T2-weighted images. The central T2 signal increases and becomes bright once central liquefaction develops, with remaining peripheral hypointense rim (Fig. 19A).

Lyme Disease Lyme disease is a multisystem illness caused by Borrelia burgdorferi and transmitted by tick bite, and it is the most com-

Figure 24 Spinal cryptococcosis. Axial contrast-enhanced T1w image of lumbar spine at L1 level reveals posterior epidural mass with rim-enhancement (arrowheads). There is also an enhancing mass involving posterior spinal elements and adjacent muscles (black arrows), as well as destructive vertebral body lesions (white arrows).

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Figure 25 Invasive fungal sinusitis, early signs. (A) Axial nonenhanced CT image at sphenoid sinus level shows opacification of paranasal sinuses along with increased attenuation in left pterygopalatine fossa (black arrows) compared with normal fat on opposite side (white arrow). (B) Axial nonenhanced T1w image at a similar level shows loss of normal fat signal in left pterygopalatine fossa and pterygomaxillary fissure (arrowheads).

mon vector-borne disease in the United States and in some temperate regions of Europe and Asia. Neuroborreliosis may occur during early disseminated or late persistent disease in up to 10% of untreated individuals. MRI detects abnormalities in less than half of the patients. Foci of high T2 signal, which simulate multiple sclerosis, may be visualized in the cerebral white matter and brain stem.70 Focal or diffuse leptomeningeal enhancement involving cranial nerves, surface of the spinal cord, cauda equina, and spinal nerve roots is a nonspecific MRI finding that is commonly present in patients with Lyme disease71,72 (Fig. 21).

Neurosyphilis Over the last few decades there has been a significant rise in the number of syphilis cases with concomitant increase in the incidence of neurosyphilis. Making the diagnosis is often difficult, because most patients are either asymptomatic or present with nonspecific symptoms, and there is a wide range of neuroimaging findings.73-75 Neurosyphilis most commonly takes the meningeal or vascular form, which often occur together. The vascular form presents with cortical and subcortical infarcts and varying degrees of narrowing and ectasia of the supraclinoid carotid, basilar, proximal anterior,

Figure 26 Invasive fungal sinusitis, intracranial extension. (A) Sagittal nonenhanced T1w shows loss of normal bone marrow signal in clivus (*). (B) Coronal FS contrast-enhanced T1w reveals intracranial extension from sphenoid sinus along left Sylvian fissure (arrowheads). There is left temporal abscess (arrow).

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Figure 27 Aspergilloma. (A) Coronal FSE T2w image shows small hypointense lesion (arrow) in right basal ganglia with perifocal edema. (B) Contrast-enhanced axial T1w image shows predominantly peripheral contrast enhancement (arrow). The imaging appearance is indicative of granuloma. Compare with tuberculoma (Fig. 20).

and middle cerebral arteries.75 The manifestations of meningeal form include leptomeningeal granulomas, known as gummata, which may also occur intra-axially and be indistinguishable from primary brain tumors, meningiomas, or sarcoidosis.74-76 Bilateral mesiotemporal T2 hyperintensity has been recently reported in neurosyphilis and represents an important although rare differential diagnostic consideration for characteristic HSE MRI findings.73

Fungal Infections Fungal CNS infections most commonly occur in diabetic and immunocompromised patients. A few fungal microorganisms lead to processes with characteristic clinical and imaging presentations and will be further discussed. Although fungal cerebral abscesses are not purulent, they show restricted diffusion similar to bacterial abscesses on MRI, presumably due to dense cellular infiltration and necrosis.77

Cryptococcosis Cryptococcus neoformans infection may occur in immunocompetent individuals but is much more common in immunocompromised patients and represents the most common fungal CNS infection in AIDS, occurring in approximately 5 to 10% of patients. The disease is a result of a newly acquired infection with hematogenous dissemination from the lung to the CNS. Meningitis is the most common manifestation with the subarachnoid spaces filled with multiple organisms and capsular material. There is usually minimal inflammatory reaction so that imaging studies rarely show meningeal en-

hancement and are frequently normal; however, dense enhancement in the basal cisterns is occasionally present (Fig. 22).78-80 On the other hand, cryptococcosis may be easily diagnosed by CSF stains and detection of the capsular antigen in the blood and CSF. Cryptococcal meningitis also involves the ependymal surfaces with resultant hydrocephalus in approximately half of the cases. Thus, communicating hydrocephalus in an HIV-infected patient raises consideration of cryptococcosis.78 CNS cryptococcosis may manifest with two other pathologic changes: gelatinous pseudocysts and cryptococcomas. From the subarachnoid space cryptococcus extends along the perivascular (Virchow–Robin) spaces, which become dilated, without involvement of the brain parenchyma. These widened perivascular spaces are visualized as hypodensities on CT and punctate confluent hyperintensities on T2weighted and FLAIR images, typically located in the basal ganglia, usually bilaterally (Fig. 23). Dentate nuclei in the cerebellum, thalami, and midbrain are also frequently involved, which is rarely visualized on CT.81 Inflammatory response is absent and contrast enhancement is therefore usually not present. With disease progression the dilated perivascular spaces become confluent cystic lesions that develop into gelatinous pseudocysts. Mild mass effect and enhancement occur in some cases. Cryptococcoma is the only parenchymal form of CNS infection and it may develop in immunocompetent individuals. The lesions result from the direct invasion of the brain with development of a granulomatous reaction. Cryptococcomas are frequently of relatively low T2 signal with a ring-like or

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Figure 28 Toxoplasmosis. (A) FSE T2w image demonstrates heterogenous appearance of left basal ganglia lesion. (B) The lesion is dark on corresponding DWI, in contrast to pyogenic abscesses. (C) ADC map reveals hyperintensity (arrow) due to high diffusion within center of lesion. Lymphoma would typically present with very low diffusion. (D) Corresponding dynamic susceptibility perfusion MRI shows decreased cerebral blood volume in left basal ganglia region. Malignant neoplasms would exhibit increased perfusion.

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83 or abnormal signal on MRI in the retroantral perisinus fat and signal changes in the bone marrow (Fig. 25), most notably decreased T1 signal in the clivus85,86 (Fig. 26). These early findings are crucial since patients rarely survive the disease at later stages. Aspergillus granulomas usually have low T2 signal centrally or peripherally that is due to accumulation of fungi containing iron, magnesium, and manganese, as well as blood breakdown products (Fig. 27).87 This finding is not specific as it may be seen in tuberculomas, other fungal granulomas, and cysticercosis. Contrast enhancement is frequently absent, depending on the patient’s immunocompetence.

Parasitic Infections The two most common parasitic CNS infections are by far toxoplasmosis in immunocompromised, primarily AIDS, patients and cysticercosis in immunocompetent individuals. Other protozoan diseases, such as cerebral malaria, and helmintic infections, such as hydatid disease and schistosomiasis, are beyond the scope of this review and will not be discussed. Figure 29 Toxoplasmosis— eccentric target sign. Axial contrast-enhanced T1w image shows rim enhancing mass with eccentric internal enhancement (arrow) in right basal ganglia with perifocal edema.

nodular enhancement on MRI and cannot be distinguished from granulomas of other origin. However, granulomas of the choroids plexus are characteristic and relatively specific for cryptococcosis.78 Similar to other fungal pathogens, cryptococcal abscesses and inflammatory masses show hyperintensity on DWI77,82 (Fig. 24).

Aspergillosis and Mucormycosis Aspergillus species accounts for a large proportion of fungal brain abscesses, and aspergillosis is the most common CNS complication following bone marrow transplantation.77,83,84 Because of the high mortality rate of 85 to 100% and treatment difficulties, early diagnosis is crucial. Cerebral aspergillosis occurs after hematogenous dissemination from an extracerebral focus or as invasive fungal sinusitis, which usually affects immunocompromised or diabetic patients, frequently with a fatal outcome. Mucormycosis is caused by saprophytic fungi frequently found in the upper respiratory tract and is nonpathogenic in normal hosts. Classically, rhinocerebral mucormycosis presents as an acute, fulminant, and often deadly invasive fungal sinusitis, similar to aspergillosis.85 Both Mucor and Aspergillus have a prominent affinity for blood vessels leading to thrombosis and cerebral infarcts. Spread of the infection from the paranasal sinuses is usually without destruction of sinus walls since the organisms grow through the vascular channels. Subtle early signs of invasive fungal infection are the presence of soft-tissue density on CT

Toxoplasmosis Cerebral toxoplasmosis is caused by an obligate intracellular protozoan, Toxoplasma gondii, which subclinically invades 20 to 90% of healthy adults. The risk for encephalitis caused by reactivation of parasite encysted in the brain is up to 30% in HIV-infected patients, explaining why toxoplasmosis is the most frequent opportunistic CNS infection in AIDS.1,88 The presenting symptoms include headache, fever, and confusion, as well as focal neurological signs and seizures. On nonenhanced CT scans, toxoplasma lesions are hypodense masses with surrounding vasogenic edema. Solid, or, more commonly, peripheral ring enhancement is typically observed (Fig. 28). The hypodense center correlates with avascular necrosis; the enhancing portion corresponds to the inflammatory zone, and edema corresponds to the peripheral zone with encysted parasites.88,89 The most common locations are the basal ganglia and the corticomedullary junction. The necrotic center is isointense to hypointense on T1weighted MRI with ring or nodular postcontrast enhancement. Signal intensity on T2-weighted images varies, depending on the stage of the lesion.89 In around 30% of lesions an enhancing nodule is found within and adjacent to the enhancing rim on imaging studies (Figs. 28 and 29), probably representing an infolding of the cyst wall that has been termed eccentric target sign and is considered very specific for toxoplasmosis.88 After approximately 10 days of treatment, a decrease in the number and size of lesions with reduction in edema should be observed on MRI. Full resolution may take up to 6 months, and healed foci may calcify or show encephalomalacia. Lifelong maintenance therapy is needed since encysted parasites cannot be cured and discontinuation of treatment results in recurrence.88 The two most common focal brain masses in patients with

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Figure 30 Neurocysticercosis (NCC), vesicular stage. (A) Axial nonenhanced CT image at the level of centrum semiovale shows a round left frontal cortico-subcortical hypodense lesion with a small eccentrically placed scolex (arrow). (B) Corresponding contrastenhanced CT image shows mild enhancement of the cyst wall. There is very mild perifocal edema (arrowhead). (C) Corresponding FLAIR image allows for better visualization of mild surrounding edema (arrowheads) and scolex (arrow).

AIDS are toxoplasmosis and primary CNS lymphoma (PCNSL), which frequently have similar imaging characteristics. These patients used to be presumptively treated for toxoplasmosis, which has changed since any delay in the appropriate PCNSL treatment may diminish the benefit and

the patient’s neurologic status may deteriorate. PCNSL may also favorably respond to the steroids included in antitoxoplasmosis therapy trial, falsely suggesting Toxoplasma as the causative agent. This is further complicated by the possibility of coexistent pathologies.

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Figure 31 NCC, colloidal/granular stage. (A) Axial FSE T2w image shows slightly hypointense small lesion (arrow) at gray–white-matter junction in medial left frontal lobe with surrounding edema (arrowheads). (B) Corresponding contrast-enhanced T1w image demonstrates enhancement of lesion.

Toxoplasmosis is frequently multifocal, has predilection for basal ganglia, does not show periventricular spread, and may occasionally hemorrhage, and enhancement is usually peripheral. The eccentric target sign is highly suggestive of toxoplasmosis. PCNSL is more frequently a single, typically periventricular mass, shows no hemorrhage, and enhances in a diffuse fashion. Ependymal or subarachnoid spread, seen as linear enhancement and subtle signal abnormality, highly favors lymphoma. PCNSL is characteristically hyperdense on CT, which is not always the case in AIDS patients.90 In many cases none of these differentiating features are present. Early studies advocated the use of thallium-201 single-photon emission CT (SPECT), with toxoplasmosis demonstrating relatively low uptake in contradistinction to high uptake in lymphoma. This was then followed by discouraging results, while lesion size has been recently reported as crucial, yielding very high accuracy of SPECT for masses over 2 cm.91,92 It seems that positron emission tomography may distinguish hypometabolic toxoplasmosis from hypermetabolic PCNSL with very high sensitivity and specificity.93 Increased cerebral blood volume is found in PCNSL on perfusion MRI, while toxoplasmosis, similar to other infections, exhibits very low perfusion due to lack of vasculature (Fig. 28F).94 On MRS, toxoplasmosis shows elevated myoinositol, while lymphoma typically has low myoinositol and markedly elevated lipids; however, there is a significant overlap.95,96 The ratio of ADC values within the center of the lesion compared with normal-appearing white matter is

higher in toxoplasmosis compared with PCNSL.97 In other words, the lesion core is dark in lymphoma and bright in toxoplasmosis on ADC maps (Fig. 28E). Although a recent study demonstrated that this differentiation may not be reliable,98 ADC maps combined with other MR sequences, including perfusion and MRS, should be sufficient for adequate lesion characterization. Unlike pyogenic and fungal abscesses that are characteristically very bright on DWI, the Toxoplasma lesion core is dark to isointense, reflecting low viscosity and absence of purulent fluid, likely due to impaired immune response in immunocompromised patients.99 Disseminated toxoplasmosis following allogenic bone marrow transplant has been reported in around 5% of recipients. In addition to typical appearance of cerebral toxoplasmosis, the lesions may present without any edema or enhancement.100

Cysticercosis Parasitic CNS diseases frequently present as cystic lesions on imaging studies and cysticercosis is a typical example. This most common parasitic disease of the immunocompetent population is caused by the pork worm (Taenia solium). Humans become definitive host when ingesting larvae, which then grow in the small bowel and cause intestinal disease. However, if the eggs are ingested, humans become the intermediate host, and when the eggs mature, larvae are released into the bloodstream. Once this occurs, the incidence of CNS

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Figure 32 NCC, multiple cysticerci in different stages of evolution. (A) Axial FSE T2w image shows numerous cysts in both cerebral hemispheres. Some of cysts contain scolices and a few are surrounded by vasogenic edema (arrowheads). A single left occipital lesion is hypointense (arrow), simulating granuloma. (B) Corresponding nonenhanced T1w image shows scolices to better advantage. (C) Contrast-enhanced T1w shows rim enhancement of some neurocysticerci (arrowheads). (D) Axial DWI image shows low signal intensity of the lesions.

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Figure 33 Racemose NCC with vasculitis and infarcts. (A) Axial heavily T2w image with high spatial resolution and 3D acquisition shows extra-axial multilobulated cystic mass (arrowheads) without internal scolices located within interhemispheric fissure. Anterior cerebral arteries, seen as very dark flow-voids (arrows), are surrounded by the abnormality. (B) Axial contrast-enhanced T1w image at a slightly lower level shows lack of enhancement of the interhemispheric cystic mass. Some internal septa are visualized. (C) Maximum intensity projection image from 3D time-of-flight MR angiogram reveals areas of narrowing involving both anterior cerebral arteries (ACAs) (arrowheads), indicative of vasculitis. (D) Axial DWI at the level of centrum semiovale shows subcortical and cortical areas of high signal (arrows), corresponding to acute infarcts in ACA territories.

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Figure 34 Sporadic Creutzfeldt–Jakob Disease (sCJD). (A-C) Axial DWI images show multiple areas of hyperintensity in cerebral cortices (arrowheads) and basal ganglia (arrows). These findings are virtually pathognomonic of CJD in patients with rapidly progressive dementia. (D) Axial FLAIR image demonstrates corresponding increased signal of the involved gray matter (arrowheads).

CNS infections involvement is nearly 100%. Neurocysticercosis is a major cause of acquired epilepsy in most low-income countries and it is becoming more common in high-income countries because of increased migration and travel. The most common clinical presentation is headache and seizures.101,102 Intra-axial lesions are most commonly encountered on imaging studies, presenting as cysts that typically contain a scolex, generally without surrounding edema and with possible minimal peripheral enhancement in the early (vesicular) infection stage (Fig. 30). The lesions are commonly located at the junction of gray and white matter, reflecting hematogenous disease spread. The edema and enhancement are indicative of inflammatory reaction due to antigen leakage (Fig. 31), which is responsible for seizures and most commonly occurs when the parasites die. This usually occurs after 5 to 10 years, in the colloidal and granular stages of the infection, when the lesions may resemble granulomas of other etiology. In the last, nodular stage, the lesions become calcified but may still continue to function as an epileptogenic focus. Most patients harbor parasites in all phases of their evolution, leading to frequent heterogenous imaging appearance (Fig. 32).102 In around 10 to 15% of the affected individuals, the parasites are extra-axial, located in the subarachnoid spaces. The vesicles in this racemose type of neurocysticercosis do not contain a scolex and are seen as single or, more commonly, multilobulated cystic masses (Fig. 33). Intraventricular cysticerci, which are frequently not seen on standard imaging studies, can cause rapidly progressive and potentially fatal noncommunicating hydrocephalus. Visualization of the racemose cysticercosis can be improved with acquisition of heavily T2-weighted 3D MRI. FLAIR images obtained following continuous inhalation of 100% oxygen show increased signal intensity of the CSF, leading to much better conspicuity of cyst walls.103 The subarachnoid cysts may also lead to vasculitis of the adjacent arteries and associated infarcts104 (Fig. 33). Neurocysticercosis may be coexistent with other CNS infections, such as TB or JE. MRS appears to differentiate lesions caused by cysticercosis from TB, based on increased choline and lactate in TB.105 The MT ratio of cysticercus granuloma is also significantly higher than that of tuberculoma.69

Prion Infections Subacute Spongiform Encephalopathies Subacute spongiform encephalopathies (SSE) are rare fatal diseases affecting the CNS that are thought to be caused by prions. SSEs are clinically characterized by a rapidly progressive dementia and generalized myoclonus. The prototype of these conditions is Creutzfeldt–Jakob Disease (CJD) with the most common sporadic form, inherited familial form, and the variant form (vCJD), which is considered transmissible and has been associated with bovine spongiform encephalopathy (“mad cow disease”).106 The single best diagnostic modality for CJD is brain MRI with DWI and FLAIR images, having a reported accuracy of around 95%.107,108 The most typical and specific patterns are

89 hyperintensities confined to the gray matter in the cortex, striatum, and medial or posterior thalamus (Fig. 34). Any area of cerebral cortex may be involved, with the exception of primary sensorimotor and visual cortices. During the early phase, DWI reveals abnormal high signal in the cortex and basal ganglia, which is sometimes also present on FLAIR images. This is followed by progressive expansion of abnormalities and cerebral atrophy. During the terminal phase, the DWI hyperintensities eventually disappear.109 Posterior and medial thalamus are very frequently involved in vCJD and the pulvinar sign, the T2 hyperintensity of the posterior thalamus, is the most sensitive, although not quite specific, radiologic marker for vCJD.107-109

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