Intracranial Infections: Key Neuroimaging Findings Jitender Saini, MD, DM,* Rakesh K. Gupta, MD,† and Krishan K. Jain, MD†

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entral nervous system (CNS) infections are treatable lifethreatening conditions; however, clinical outcome largely depends on early diagnosis and treatment. Diagnosis of infectious diseases relies on the demonstration of an offending organism using laboratory investigations. Neuroimaging studies play an important role in early diagnosis, as laboratory confirmation may take days to reach a definitive diagnosis. Magnetic resonance imaging (MRI) is considered the modality of choice as it is more sensitive and specific for detection of both parenchymal and meningeal abnormalities. In addition, the use of advanced MRI tools may help in improving the specificity of a diagnosis. In this review, we briefly discuss the key neuroimaging features of the commonly encountered CNS infections.

Viral Infections Viral infections commonly occur in the form of viral meningitis, viral encephalitis, or a combination of both. Pathologically, these are characterized by neuronophagia-parenchymal infiltration by inflammatory cells, edema, and vascular inflammation involving cortical vessels. Patients with acute viral encephalitis present with a triad of fever, headache, and altered level of consciousness. Other common clinical findings include disorientation, behavioral disturbances, and focal neurologic signs.1-3

Herpes Simplex Encephalitis (HSE) HSE in adults is usually caused by herpes simplex virus (HSV) 1. It is results from either primary infection or viral reactivation, however most adult cases result from viral reactivation.3,4 HSE presents clinically with altered sensorium, seizures, and focal neurologic deficits. Delayed clinical features include *Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India. †Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, Haryana, India. *Address reprint requests to Rakesh K. Gupta, MD, Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, Haryana 122002, India. E-mail: [email protected]

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depression, somnambulism, and memory disturbances.5 Diagnosis is confirmed by identifying HSV DNA in cerebrospinal fluid (CSF) using a polymerase chain reaction assay; however, neuroimaging plays an important role as laboratory tests may initially show negative results.2,3 Initial infection typically results in asymmetric lesions involving the temporal lobes, insula, cingulate gyrus, posterior part of the orbitofrontal cortex, and the underlying white matter (WM). During the early phase, computed tomography (CT) is usually normal or shows subtle low-density areas. Later in the course of disease, hemorrhage and contrast enhancement may appear.4 In the acute phase, MRI shows focal abnormalities that appear isointense to hypointense on T1weighted images (T1WI) and hyperintense on T2/fluidattenuated inversion recovery (FLAIR) images.4,6,7 In the subacute phase, gadolinium-enhanced T1WI show gyriform enhancement and susceptibility-weighted images frequently detect hemorrhage. Less common features of HSE include isolated abnormalities outside of the limbic system, cranial nerve enhancement, and focal myelitis.4,7,8 Diffusion-weighted imaging (DWI) enables early diagnosis of HSE and lesions may show increased or decreased diffusivity during the acute phase.4,9 In immune-compromised patients, HSE may present with atypical clinical features, lack of CSF pleocytosis, and more extensive CNS involvement on MRI.7 In the subacute phase, gadolinium-enhanced T1WI show gyriform enhancement and susceptibility-weighted images frequently detect hemorrhage. HSV 2 infection is usually seen in neonates but may also rarely affect adults. Imaging features in adults are similar to those of HSV 1 infection with predilection for the frontotemporal regions; however, MRI may be normal or may show atypical patterns such as more widespread signal changes or isolated brainstem encephalitis.10

Varicella Zoster Infection (VZV) VZV causes exanthematous cutaneous lesions of chickenpox in pediatric patients and focal dermatomal shingles in adult patients. Primary CNS infection is acquired by inhalation or mucosal contact with infected secretions, following which the virus establishes latency in the dorsal root and cranial nerve

Intracranial infections ganglia.2,3 Reactivation of the virus and its centripetal spread toward the CNS leads to neurologic deficits. The trigeminal nerve is the most commonly involved cranial nerve, but other cranial nerves may also be infected.11 On MRI, gadoliniumenhanced T1WI show smooth enhancement of the affected cranial nerves and there may be associated patchy intraparenchymal signal abnormalities.4,11 In immunocompromised patients, varicella infection may present as multifocal leukoencephalitis, ventriculitis, and acute meningomyeloradiculitis.12 VZV encephalitis may be seen as an area of parenchymal FLAIR-T2 hyperintense signal abnormality involving both the cortex and the underlying WM (Fig. 1). The deep gray nuclei and the deep WM may also be involved. On gadoliniumenhanced T1WI, parenchymal lesions show patchy enhancement with concomitant meningeal enhancement.13 Other less common forms of varicella infection include chronic encephalitis in immunocompromised patients and immune-mediated focal brainstem encephalitis called Bickerstaff encephalitis.4 Varicella vasculopathy results from direct infection of the cerebral arteries. It typically has a large vessel unifocal or small vessel multifocal pattern, resulting in ischemic infarction of the brain, subarachnoid and intraparenchymal hemorrhage, aneurysm formation, and carotid dissection.14 In the case of multifocal vasculopathy, multiple areas of vessel narrowing are seen on angiography. Infarctions characterized by FLAIR-T2 hyperintensity and restricted diffusion are identified in the cortex, deep gray nuclei, and WM, and at gray matter-WM junctions.10,14

Japanese Encephalitis (JE) JE is transmitted to humans by the Culicine mosquitos. The virus spreads hematogenously to the CNS. JE is commonly seen in children and young adults.15 Imaging studies show focal abnormalities in the thalami, substantia nigra, basal ganglia, and hippocampi. Brainstem, cerebellum, and cerebral cortex involvement is less common. Asymmetric thalamic lesions with surrounding edema are the

87 key neuroimaging features. On MRI, lesions appear hypointense on T1WI and hyperintense on T2WI with variable enhancement.16-18 Lesions may also show hemorrhage. In a study, DWI was useful in the diagnosis of JE as it showed additional lesions.17 However, other studies have reported poor conspicuity of JE lesions on DWI and restricted diffusion is also less common in acute JE lesions compared with HSV lesions. Chronic lesions may show facilitated diffusion.16,18

West Nile Encephalitis West Nile virus is an arbovirus that is transmitted to humans by the Culex mosquito. It usually causes mild fever, headache, and generalized aches. However, a small number of patients develop meningoencephalitis that manifests as severe headache, fever, stupor, disorientation, coma, tremors, convulsions, and abnormal movements. Some patients present with acute flaccid paralysis.19 MRI typically shows patchy nonspecific discrete signal abnormalities in the cerebral WM and basal ganglia, and lesions may simulate the demyelinating lesions of multiple sclerosis. Lesions usually do not show hemorrhage, enhancement, or mass effect. Brainstem and cerebellar signal abnormalities may also be present. There may be thickening and enhancement of the meninges. In cases of acute flaccid paralysis, spinal cord signal changes may be seen along with enhancement of the cauda equina roots. The lesions show regression on follow-up studies following treatment; however, in immunocompromised patients, the appearance of new lesions can be seen.20,21 DWI is the most sensitive MR sequence for detection of signal changes secondary to West Nile virus infection.21

Chikungunya Encephalitis Chikungunya virus is an arbovirus belonging to the Togaviridae family. The disease is transmitted to humans by the mosquito of the Aedes genus. Chikungunya virus infection clinically presents with myalgia, maculopapular rash, fever,

Figure 1 Imaging findings in a 56-year-old man with varicella zoster encephalitis. Axial FLAIR (A and B) and coronal T2W (C) images show extensive, symmetric hyperintense signal changes in the brainstem, thalami, striatum, and cerebral white matter, with some involvement of adjacent cortex.

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88 articular pain, headache, and gastrointestinal complaints. Neurologic features include seizures, meningitis, and encephalitis.22,23 MRI shows FLAIR and T2 hyperintense signal changes in the periventricular WM and limbic region (Fig. 2). Lesions can be hemorrhagic and restricted diffusion can be seen on DWI. Gadolinium-enhanced images show patchy enhancement of parenchymal lesions. In addition, spinal nerve root enhancement may also occur.23

Dengue Encephalitis Dengue virus infection is an arbovirus infection that is transmitted to humans by the Aedes aegypti mosquito.

Clinically, the disease manifests in 2 forms: dengue fever and dengue hemorrhagic fever or dengue shock syndrome. Neurologic manifestations of dengue infection include encephalitis, encephalopathy, myelitis, GuillainBarré syndrome, and cranial nerve palsies.24 Neuroimaging abnormalities in cases of dengue infection include focal or diffuse cerebral FLAIR hyperintense changes with variable enhancement and intracranial hemorrhage (Fig. 3). Topographic distribution of signal changes includes abnormalities in the hippocampi, thalamus, brainstem, and spinal cord. No distinctive tropism for selective brain regions has been reported, and the imaging findings are nonspecific.25,26

Figure 2 Imaging findings in a patient with Chikungunya viral infection. Axial FLAIR images (A and B) show focal hyperintense lesions involving the medulla, left middle cerebellar peduncle, and predominantly deep cerebral white matter. Sagittal T2W images (C and D) show extensive hyperintense signal changes involving the whole spinal cord with no enhancement on the postcontrast T1W image (E).

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Figure 3 Imaging findings in dengue encephalitis. Axial T2W image (A) shows increased signal intensity in bilateral thalami with focal areas of diffusion restriction on DWI (B) and susceptibility on gradient echo image (C). Postcontrast T1W image (D) shows mild heterogeneous enhancement surrounding focal areas of necrosis.

Rabies Encephalitis Rabies is an acute CNS infection caused by the rhabdovirus family. Disease is usually transmitted to humans by dog and wild animals bites, and rarely after corneal transplants. Clinically, the disease manifests in 2 forms: paralysis and encephalitis. The virus is transmitted to the CNS by retrograde axoplasmic flow. Patients typically present with fever, pain, or paresthesias at the bite site, hydrophobia, aerophobia, hypersalivation, hyperirritability, and altered sensorium. In the paralytic type, presentation is in the form of flaccid paralysis resembling Guillain-Barré syndrome.27 The diagnosis of rabies is often clinical, and as the condition is rapidly fatal, imaging is rarely performed. The imaging pattern is similar in both clinical forms of rabies. MRI shows FLAIR-T2 hyperintense signal abnormalities in the basal ganglia, hippocampi, dorsal brainstem, and spinal cord gray matter. In addition to involvement of these characteristic areas, signal abnormalities of cerebral WM and cortical gray matter have been reported. Hemorrhage can be seen in the areas of signal alteration.28-31

Measles Encephalitis Neurologic presentations of measles include acute measles encephalitis, subacute measles encephalopathy, and subacute sclerosing panencephalitis. On MRI, 3 distinct imaging patterns have been identified in acute measles encephalitis. The patterns can be normal, show only WM signal changes, or show predominant gray matter abnormalities involving both cortical and deep gray matter structures.32 Subacute measles encephalopathy occurs in immunocompromised children, and the onset is usually within a year of primary infection. Patients present with altered sensorium and refractory seizures. Neuroimaging studies are often normal. However, in rare cases, MRI shows focal abnormalities of cerebral WM and cortical gray matter.33 Subacute sclerosing panencephalitis is a progressive neurologic disorder caused by persistent defective measles virus. Clinical features include behavioral changes, myoclonus,

dementia, visual disturbances, and pyramidal and extrapyramidal signs. The disease has a slowly progressive course leading to death within 1-3 years.34 The diagnosis is usually based on clinical manifestations, periodic electroencephalogram discharges, and demonstration of a raised antibody titer against measles in the plasma and CSF.39 MRI abnormalities include asymmetric, focal FLAIR-T2 hyperintense lesions involving the cerebral cortex, periventricular WM, basal ganglia, thalami, and corpus callosum with variable enhancement and tissue loss. The cerebellum and brainstem are also rarely involved.35-37 MR spectroscopy (MRS) may show decreased N-acetyl aspartate (NAA) and increased myoinositol in the normal-appearing WM.38

Bacterial Infections Common bacterial infections of the CNS include cerebritis, cerebral abscess, ventriculitis, meningitis, and subdural empyema. A pyogenic abscess is a focal parenchymal infection that contains a central collection of pus surrounded by a vascularized collagenous capsule.39,40 Clinical features include headache, fever, focal neurologic deficit, nausea, vomiting, and seizures. A cerebral abscess evolves in 4 stages starting as early cerebritis followed by late cerebritis, early capsule formation, and late capsule formation stages.41 On MRI, cerebritis appears as a poorly defined area of T2 hyperintense signal change. The necrotic core of a well-defined abscess has low signal on T1WI and high signal on T2WI. The smooth capsule appears hyperintense on T1WI and hypointense on T2WI and densely enhances following gadolinium injection. Abscesses are typically surrounded by abundant T2 hyperintense perilesional edema.42 On DWI, the central necrotic portion of bacterial abscesses demonstrates homogenous hyperintensity due to restricted diffusion, and this finding is useful in differentiating abscess from other ring-enhancing lesions. The low apparent diffusion coefficient (ADC) values have been attributed to the presence of intact inflammatory cells and bacteria that collectively impede the microscopic motion of water molecules.43,44

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90 On proton MRS, pyogenic abscesses may show lipid or lactate, amino acid, acetate, and succinate peaks (Fig. 4). The presence of amino acid peaks is the hallmark of pyogenic abscesses although they may not be seen in all cases. Staphylococcus infections may show lack of amino acid peaks because of their inability to produce proteolytic enzymes. The presence of an acetate peak with or without a succinate peak may be useful in discriminating aerobic and anaerobic abscesses as abscesses caused by aerobic organisms do not show acetate and succinate peaks. The presence of a lipid peak with absence of other metabolites is a typical pattern seen in tubercular abscesses. Fungal abscess spectra may appear similar to those of pyogenic abscesses showing amino acid and lipid or lactate peaks. The presence of a trehalose sugar peak at 3.6-3.8 ppm may differentiate fungal from nonfungal abscesses.44,45 Acute pyogenic meningitis is a diffuse inflammation of the leptomeninges most commonly seen in children. Diagnosis of acute meningitis relies on clinical findings and CSF examination. Clinical features include headache, fever, neck stiffness, photophobia, vomiting, and altered consciousness. Causative agents vary with the patient's age.46,47 Imaging findings include a normal scan, enlargement of CSF spaces, poor visualization of basal cisterns, generalized cerebral swelling, diffuse

meningeal enhancement, communicating hydrocephalus, subdural effusion, subdural or epidural empyema, and venous or arterial cerebral infarction or both. FLAIR images may show sulcal hyperintensity owing to increased protein content.48 Diffusion tensor imaging (DTI) studies have revealed increased fractional anisotropy (FA) in the cerebral cortex of neonatal and adult brains associated with acute meningitis. Similarly, DTI has been found to be useful for detecting abnormalities of cerebral WM in neonatal meningitis.49,50 Ventriculitis refers to inflammation of the ependyma lining the ventricles and is commonly associated with staphylococcus and enterobacter infection.48,51 Imaging findings include ventricular enlargement, ventricular debris, and ependymal thickening, and T2 hyperintensity and enhancement. DWI may show restricted diffusion within the debris.52 Subdural empyema is the collection of pus between the dura and leptomeninges. It commonly occurs secondary to retrograde thrombophlebitis via emissary veins. CT shows a crescentic collection that is denser than CSF. On MRI, the collection appears mildly hyperintense on T1WI and FLAIR images and hyperintense on T2WI. Following the injection of gadolinium, there is smooth marginal enhancement. DWI shows restricted diffusion in a subdural empyema and this feature is helpful in differentiating it from a sterile subdural

Figure 4 Pyogenic abscess in right frontal lobe. Axial T2W image (A) shows a focal hyperintense lesion with hypointense rim and abundant perilesional edema. There is peripheral rim enhancement on the postcontrast T1W image (B) and restricted diffusion on DWI (C). MRS (D) taken from the central necrotic part of the lesion shows presence of amino acids (AA) at 0.9 ppm, lactate (Lac) at 1.3 ppm, and acetate (Ac) at 1.9 ppm.

Intracranial infections effusion. Subdural empyema may be associated with adjacent cerebritis and meningitis as well as cortical venous thrombosis, venous infarcts, and abscess formation. Epidural empyema is the collection of pus between the dura and calvarium. Imaging features are similar to those of subdural empyema.48

Neurosyphilis Syphilis is a sexually transmitted disease caused by a spirochete Treponema pallidum. Neurosyphilis is a potentially treatable condition with antibiotics; however, the clinical features are not pathognomic.53 Patients may present with neuropsychiatric symptoms, cerebrovascular accidents, seizures, cranial nerve palsies, myelopathy, and ocular symptoms.54 Meningitis and meningovascular disease are usually seen in the early course of disease whereas encephalitis and tabes dorsalis are late manifestations. The imaging features of neurosyphilis are variable, and imaging studies may have normal findings in a large number of patients. Meningeal disease presents with meningeal signs and cranial nerve palsies. MRI shows meningeal thickening and enhancement. Gummas, or focal dural-based enhancing mass lesions that can invade cortex, may form. Involved cranial nerves typically enhance and hydrocephalus may be present.53,55 Vascular manifestations of neurosyphilis appear after 5-10 years of primary infection. Patients present with focal neurologic deficits related to vascular events. Heubner endarteritis, a medium and large vessel endarteritis obliterans, and NisslAlzheimer endarteritis, a small vessel vasculitis, are the 2 forms of vascular pathology seen in patients with neurosyphilis. Angiographic abnormalities include vascular irregularity, narrowing, or complete occlusion and are most commonly seen in the middle cerebral artery and basilar artery.53,54

91 General paresis of the insane is a chronic parenchymal disease usually seen after 10 years of primary infection, and the patients show cognitive decline and psychiatric symptoms.54,56 Radiological abnormalities include atrophy, mesiotemporal signal changes, and hydrocephalus. Imaging findings may mimic limbic encephalitis or herpes encephalitis because of the characteristic distribution of signal changes.57 Ventricular prominence with periventricular WM changes can mimic imaging features of normal pressure hydrocephalus (Fig. 5).58 Tabes dorsalis is a slowly progressing degenerative disease involving the posterior columns and roots of the spinal cord, which typically presents 20-30 years after initial infection with loss of pain sensation, peripheral reflexes, and vibration and position senses, and progressive ataxia. MRI demonstrates diffuse T2 hyperintensity in the dorsal columns.

Neurobrucellosis Neurobrucellosis is a rare CNS infection that is transmitted to humans by consumption of uncooked meat or unpasteurized dairy products. Bacterial spread to the CNS is possibly hematogenous and can involve both the meninges and cerebral parenchyma.59 On imaging, inflammation results in enhancing meninges, cranial nerves, intraparenchymal granulomas, and spinal nerve roots. Nonenhancing WM lesions can also be seen in both the supratentorial and infratentorial compartments. Vascular abnormalities, such as mycotic aneurysms, arterial narrowing, and chronic venous thrombosis with associated arterial and venous infarcts, and intraparenchymal and subarachnoid hemorrhages have also been described.60-62

Tuberculosis CNS tuberculosis is a granulomatous infection caused by the organism Mycobacterium tuberculosis. The organism may involve the skull bones, meninges, brain parenchyma, and

Figure 5 Imaging findings in a patient with neurosyphilis. Axial (A) and coronal T2W (B) images show prominent ventricles, cerebral atrophy, and increased signal intensity in the bilateral temporal lobe white matter.

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92 spine. Infection commonly spreads to the CNS hematogenously from the lungs. Imaging plays an important role in the diagnosis of CNS tuberculosis. In cases of tubercular meningitis, imaging abnormalities include sulcal effacement, sulcal FLAIR hyperintensity, and profuse meningeal enhancement, especially in the region of the basal cisterns.63,64 In addition, the meninges appear hyperintense on noncontrast magnetization transfer (MT) T1WI, which is unusual in nontubercular meningitis (Fig. 6).60 Communicating hydrocephalus may result from the inflammatory exudates, preventing normal resorption of CSF through the arachnoid granulations. Obstructive hydrocephalus may occur because of the formation of adhesions resulting from ependymitis.65 Infection of the basilar meninges frequently results in arteritis involving the proximal middle, anterior, and posterior cerebral arteries and the small penetrating arteries. Infarcts are commonly seen in the distribution of the middle cerebral artery and the lenticulostriate arteries affecting the basal ganglia and the internal capsule. MR angiography shows narrowing of the major arteries of the circle of Willis. DWI is the gold standard for identifying acute infarctions.63,66 A rare manifestation of tuberculosis is isolated dural infection, which may be diffuse or focal. The dura is thickened and appears isointense on T1WI, isointense to hypointense on T2WI, and densely enhances on postcontrast T1WI.63 CNS tuberculosis causes 2 common forms of intraparenchymal lesions: tuberculomas and tubercular abscesses. Tuberculomas are focal granulomas that are commonly seen near the corticomedullary junction or in a periventricular location. They usually present with seizures, focal neurologic deficits, and raised intracranial pressure.63,66,67 Pathologically, granulomas may be noncaseating, caseating with a solid center, or caseating with central liquefaction. Noncaseating granulomas appear hyperintense on T2WI, hypointense on T1WI, and show homogenous enhancement on postcontrast T1WI. Solid

caseating granulomas appear isointense or hypointense on both T1WI and T2WI with surrounding edema and show rim enhancement. Caseating granulomas with central liquefaction appear as hyperintense lesions with a peripheral hypointense rim and surrounding edema on T2WI and show rim enhancement on postcontrast T1WI.63,67 The cellular components of tuberculomas show increased signal on MT T1WI, and quantitative MT ratio values are useful in distinguishing tubercular granulomas from other infective granulomas. MT T1WI can also detect more parenchymal lesions than conventional spin echo sequences.63 DWI may show restricted diffusion in caseating granulomas with liquefaction. In vivo MRS of tuberculomas shows lipid resonances at 0.9, 1.3, 2.0, 2.8, and 3.7 ppm and a choline (Cho) resonance at 3.22 ppm in more cellular lesions. Dynamic contrast-enhanced MRI– derived ktrans is useful for assessment of therapeutic response in brain tuberculomas.68 Tubercular abscesses are rare lesions that appear as large, solitary, ring-enhancing lesions with surrounding edema and mass effect on MRI, which may be difficult to differentiate from an abscess of nontubercular origin or a cystic neoplasm. Tubercular abscesses show lower Magnetization transfer ratio (MTR) values as compared with pyogenic abscesses.69 DWI may show decreased ADC and increased FA in the center of an abscess which would be unusual for a cystic neoplasm.70

Parasitic Infections Neurocysticercosis Neurocysticercosis is caused by the larvae of the tapeworm Taenia solium. Humans are usually definitive hosts where pigs are intermediate hosts. Humans acquire neurocysticercosis infection either by ingestion of pork meat contaminated with larva or through T. solium eggs by the fecal-oral route in individuals harboring the intestinal cestode.2,67

Figure 6 Tubercular meningitis and multiple tuberculomas with hydrocephalus and vasculitis in a 16-year-old boy who presented with seizures, memory loss, and fever. An axial T2WI (A) demonstrates dilatation of the temporal horns of the lateral ventricles, obliteration of the basal cisterns, and multiple small hypointense tuberculomas in the left cerebellar hemisphere and along the basal cisterns. Increased signal intensity is present along the basal cisterns and periphery of tuberculomas on an MT T1W image (B). An axial gadolinium-enhanced T1WI (C) shows enhancement of the basal exudates and peripheral enhancement of the tuberculomas. On MR angiogram (D), there is nonvisualization of the proximal left MCA. MCA, middle cerebral artery.

Intracranial infections After entering the CNS, cysticercal cysts tend to lie in the cerebral cortex, basal ganglia, or subarachnoid spaces. In the initial vesicular stage, cysts are viable and induce very little inflammatory changes in the surrounding brain parenchyma. On CT, vesicular stage lesions are small and hypodense with

93 normal surrounding parenchyma. The tapeworm scolex can be seen in some lesions. On MRI, vesicular lesions appear as nonenhancing cystic lesions with CSF intensity fluid on all sequences and an eccentric, T1 hyperintense, and T2 hypointense scolex. In the colloid vesicular stage, the cyst

Figure 7 Spectrum of neurocysticercosis (NCC). Small vesicular NCC in right caudate nucleus is hyperintense on T2WI (A) with eccentric hypointense scolex visualized on balanced turbo field echo image (BTFE) image (B). Colloid vesicular stage left parietal lobe lesion is centrally hyperintense with hypointense rim and mild perilesional edema on T2WI (C), an eccentric hypointense scolex on SWI (D), and peripheral enhancement on gadolinium-enhanced T1WI (E). Granular nodular stage with moderate perilesional edema, irregular hyperintense lesion with eccentric hypointense scolex and hypointense peripheral rim on T2WI (F) and peripheral enhancement on gadolinium-enhanced T1WI (G). Calcified nodular lesion in left temporal lobe showing hypointense signal on T2WI (H) with eccentric scolex on SWI (I) and minimal peripheral enhancement on gadolinium-enhanced T1WI (J). Intraventricular fourth ventricle hyperintense NCC with eccentric hypointense scolex on BTFE (K) with prominent succinate peak at 2.3 ppm on single-voxel MRS (L) at 144 TE. Multiple well-defined hyperintense NCC with eccentric scolex in both cerebral hemispheres on T2WI (M). Subarachnoid NCC, with multiple well-defined hyperintense lesions in the right parasellar and left basifrontal regions and basal cisterns on T2WI (N) with facilitated diffusion on DWI (O) and prominent succinate peak on single-voxel MRS (P) at 144 TE. TE, echo time.

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94 degenerates and the clear fluid present in the vesicular stage converts to a viscous and turbid fluid. Cysts may appear hyperintense on both T1WI and T2WI with perilesional edema and rim enhancement on postcontrast T1WI. In the next granular nodular stage, the cyst wall thickens and the scolex may mineralize. The lesion shrinks and appears as an enhancing nodule or a small rim-enhancing lesion. At this stage, the perilesional edema has increased, the enhancing rim is thicker, and the scolex appears calcified. Finally, in the calcified stage, the parasite remnants turn in to a calcified nodule with no surrounding edema or enhancement.67,70 Susceptibility-weighted imaging (SWI) can demonstrate the scolex in fully calcified lesions, a finding that has been linked to the presence of perilesional edema and risk of seizures.71 Volumetric T2WI are also useful in demonstrating the scolex (Fig. 7). Calcified lesions without perilesional edema may also show disruption of the blood-brain barrier, which may be quantified using dynamic contrast-enhanced MRI and may be the cause of seizures in these patients.72 DTI shows successive decrease in Mean diffusivity (MD) values on moving from the vesicular to the granular nodular stage. There is a significant increase in FA values in the calcified stage as compared with the other stages.73 MRS in large parenchymal and subarachnoid cysticercal cysts shows the presence of succinate, acetate, and lactate along with amino acids; these findings may help in diagnosis when the scolex is not demonstrable on MRI (Fig. 7).74

Toxoplasmosis Toxoplasmosis is commonly seen in patients with underlying immune deficiency and is caused by Toxoplasmosis gondii, an intracellular protozoan. Clinical features include focal neurologic deficits, seizures, and symptoms secondary to mass effect. Pathology shows necrotizing encephalitis with intracellular and extracellular tachyzoites and cysts containing bradyzoites at the margins of necrotic lesions.75 Lesions are commonly seen in the basal ganglia, in the thalami, and at the corticomedullary junctions. Neuroimaging usually shows multiple lesions with central necrosis. The central portion tends to be hypoattenuating on

CT, hypointense on T1W MR images, and hyperintense on T2W MR images. The rim is relatively hyperdense on CT, hyperintense on T1WI, and hypointense on T2WI.75 Lesions typically have extensive surrounding edema and may show areas of susceptibility on gradient recalled echo images because of the presence of hemorrhage.76 On postcontrast images, lesions typically demonstrate irregular rim enhancement. Some lesions also demonstrate an enhancing eccentric nodule; the resulting “target” appearance is considered a specific sign for the diagnosis of toxoplasmosis. Toxoplasma lesions rarely calcify following treatment. On DWI, the rim commonly shows low ADC values, and the center typically shows elevated ADC values, although restricted diffusion in the center can also be seen.75,77 On MRS, lesions show a prominent lipid resonance, decreased NAA-creatine (Cr), and increased ChoCr ratios (Fig. 8).78,79 In patients with bone marrow transplant, enhancement is usually absent.79

Echinococcosis Echinococcosis is caused by 2 organisms: Echinococcus granulosus and E. multilocularis. Humans are infected by ingestion of food or water contaminated with parasite eggs. Clinical features include headache, seizure, and focal neurologic deficits.80 On imaging studies, lesions appear as large, well-defined, smooth, thin-walled, cystic lesions that are spherical or oval in shape with little to no surrounding edema. The cyst contents typically have CSF-like density on CT and CSF-like signal characteristics on all MR sequences. On postcontrast images, a thin rim of enhancement may be seen. The presence of a daughter cyst within a cystic lesion is considered pathognomonic of an echinococcus cyst. Floating membranes can also be seen within a cyst. MRS reveals succinate, alanine, acetate, and lactate peaks.80-82

Fungal Infections Intracranial fungal infections may lead to meningitis, meningoencephalitis, inflammatory granulomas, stroke due to

Figure 8 Right basal ganglia toxoplasmosis in a 26-year-old immune-competent patient who presented with left-sided weakness and intermittent fever. Axial T2WI (A) shows a mixed–signal intensity, well-defined lesion with fluid-debris (hyperintense-hypointense) level in the right basal ganglia with moderate perilesional edema and mild mass effect. DWI and ADC map (B and C) show restricted diffusion in the posterior part of lesion. MRS (D) taken from the central part of the lesion shows prominent lipid and Cho peaks at 1.3 and 3.2 ppm, respectively.

Intracranial infections vasculitis, and intracerebral and subarachnoid hemorrhage due to rupture of a mycotic aneurysm.87

Mucormycosis Mucormycosis is caused by filamentous fungi of the mucoraceal family, including Absidia, Mucor, and Rhizopus. Infection usually spreads to the brain directly from the paranasal sinuses. Mucormycosis infection is angioinvasive with hematogenous dissemination, vascular thrombosis, and necrosis.83,84 CT shows dense opacification of the paranasal sinuses with bone destruction. On MRI, affected sinuses are typically hypointense on T2WI but may show variable signal intensity. Intracranial imaging findings include an infiltrative mass involving the sinuses or orbits or both and intracranial compartment, meningeal thickening, meningeal enhancement, cavernous sinus enlargement, cavernous sinus thrombosis, large vessel occlusions, parenchymal abscesses, and infarctions. Common sites of parenchymal involvement are the frontal and temporal lobes and basal ganglia region.84,85 Fungal cerebritis and cerebral abscess can both show diffusion

95 restriction. DWI can occasionally characterize fungal abscesses by demonstrating restricted diffusion in the wall and peripheral intracavitary projections and facilitated diffusion in the central necrotic part of the abscess (Fig. 9).86 Acute infarcts secondary to vascular invasion and thrombosis also show diffusion restriction.84 Mucormycosis infection of brain can also rarely lead to mycotic aneurysm formation and hemorrhage.87,88

Aspergillosis CNS infection either occurs directly from the paranasal sinuses or spreads hematogenously from distant sites such as the lungs and gastrointestinal tract. Aspergillus infection may result in aneurysm formation, hemorrhage, infarction, abscess formation, granulomas, meningitis, and cerebritis.83,84,89 Fungus can directly invade the adjacent brain parenchyma, thus converting hemorrhagic infarcts into septic infarcts and focal cerebritis. Tissue breakdown can also lead to the formation of cerebral abscess.89,92 CT may show hyperdense, hypodense, or mixed parenchymal lesions.90 On MRI, aspergillomas show hypointense signal on T1WI, mixed signal on T2WI, and variable

Figure 9 Mucormycosis abscess in a 30-year-old woman. Axial T2W image (A) shows a large ill-defined focal lesion in the right cerebellar hemisphere and right temporal lobe with a peripheral hypointense rim and perilesional edema. Axial gadolinium-enhanced T1WI (B) shows peripheral rim enhancement and continuity between the 2 components of the lesion. Axial GRE image (C) shows a few small foci of susceptibility in the periphery of the lesion. DWI (D) shows a peripheral rim of restricted diffusion with facilitated diffusion in the center of the lesion. In vivo MRS at 144 TE (E) reveals a large lipid resonance at 1.2 ppm in the necrotic part of the lesion. GRE, gradient recalled echo; TE, echo time.

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Figure 10 Imaging findings in a focal cryptococcal cryptococcoma of the cerebellum. Axial T2W image (A) shows a large hyperintense lesion in the right cerebellar hemisphere with surrounding edema. Gadolinium-enhanced T1W image (B) shows peripheral rim enhancement. There is facilitated diffusion on DWI (C). In vivo MRS at 144 TE (D) acquired from the central part of the lesion shows presence of lipid resonance at 1.3 ppm. TE, echo time.

enhancement following the administration of intravenous contrast. Low–signal intensity areas on T2WI may be due to hemorrhage, free radicals produced by macrophages, or metal ion accumulation by the organisms.90-92 Aspergillomas may show diffusion restriction that may be secondary to cellular infiltrate or possibly due to the presence of hemorrhage.91 MRS of aspergillomas may show high levels of Cho, low levels of Cr, and lactate with absence of NAA. Aspergillus abscesses, similar to bacterial abscesses, may have rim enhancement with central restricted diffusion.90 Multifocal infarctions demonstrate diffusion restriction because of acute ischemia. Intraparenchymal hemorrhages show hypointensity on SWI sequences because of the susceptibility effects associated with deoxyhemoglobin, intracellular methemoglobin, and hemosiderin. Edema is best depicted as hyperintensity on FLAIR sequences.

Cryptococcal Infection Cryptococcal infection is an opportunistic infection usually seen in immunocompromised patients but may occasionally be seen in immune-competent individuals. Cryptococcus typically spreads hematogenously from the lungs to the meninges. Meningeal infection spreads along the base of the skull and may involve the adjacent brain parenchyma, giving rise to cryptococcomas, or may extend along the VirchowRobin spaces to form pseudocysts.93-95 Neuroimaging may show a parenchymal mass, dilated Virchow-Robin spaces (pseudocysts), and multiple enhancing parenchymal and leptomeningeal nodules or mixed nodules. Typical sites for these lesions are the basal ganglia and midbrain. Cryptococcomas usually appear as a solid nodule with or without associated edema. They show hypointense signal on T1WI and hyperintense signal on T2WI. Following contrast administration, they may not enhance or may show rim enhancement (Fig. 10).93-95

Summary Neuroimaging using advanced techniques like DWI, SWI, and MRS can assist in establishing an early diagnosis and

identifying the potential complications of CNS infections. Key imaging features may help in timely identification of these infections and provide support in therapeutic decision making, thus reducing morbidity and mortality.

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