Congenital, Acquired Pyogenic, and Acquired Viral Infections

Main Text

Preamble

Infectious diseases can be conveniently divided into congenital/neonatal and acquired infections. There are unique infectious agents that affect the developing brain. The stage of fetal development at the time of infection is often more important than the causative organism. The clinical manifestations of fetal and neonatal infection and long-term neurologic consequences compared with infections that affect the more mature or fully developed brain will be emphasized.

We then delineate the first major category of acquired infections, i.e., pyogenic infections. We start with meningitis, the most common of the pyogenic infections. Abscess, together with its earliest manifestations (cerebritis), is discussed next, followed by considerations of ventriculitis (a rare but potentially fatal complication of deep-seated brain abscesses) and intracranial empyemas.

We close the chapter with a discussion of the pathologic and imaging manifestations of acquired viral infections.

Congenital Infections

Preamble

Parenchymal calcifications are the hallmark of most congenital infections (12-1)and have been reported with cytomegalovirus (CMV) (12-1), toxoplasmosis, congenital herpes simplex virus (HSV) infection, rubella, congenital varicella-zoster virus (VZV), Zika virus, and lymphocytic choriomeningitis virus (LCMV).

Infections of the fetal brain result in a spectrum of injury and malformation that depends more on the timing of infection than the infectious agent itself. Infections early in fetal development (e.g., during the first trimester) usually result in miscarriage, severe brain destruction, &/or profound malformations, such as anencephaly, agyria, and lissencephaly.

When infections occur later in pregnancy, encephaloclastic manifestations and myelination disturbance (e.g., demyelination, dysmyelination, and hypomyelination) predominate. Microcephaly with frank brain destruction and widespread encephalomalacia are common.

With few exceptions (toxoplasmosis and syphilis), most congenital/perinatal infections are viral and usually secondary to transplacental passage of the infectious agent. Zika virus is a relative newcomer to the list of viruses recognized as a cause of congenital CNS infection and is capable of causing profound brain destruction and resultant microcephaly. Zika virus infection represents the first reported congenital CNS infection to be mostly transmitted by mosquitoes.

Six members of the herpesvirus family cause neurologic disease in children: HSV-1, HSV-2, VZV, Epstein-Barr virus (EBV), CMV, and human herpesvirus 6 (HHV-6). Aside from CMV, HSV-2, Zika virus, and congenital HIV (vertically transmitted), congenital CNS infections have become less common due to immunization programs, prenatal screening, and global infection surveillance.

We begin the chapter with an overview of TORCH infections and important non-TORCH congenital/perinatal CNS infections. We start with the most globally common of the congenital infections: Congenital CMV infection.

TORCH Infections: Overview

Terminology

Congenital infections include diverse bacteria, viruses, and parasites. They are often grouped together and simply called TORCH infections—the acronym for to xoplasmosis, rubella, CMV, and herpes. The TORCH pneumonic provides a limited description of the expanding list of pathogens that can be associated with congenital infection.

Etiology

The placenta normally restricts vertical transmission but some pathogens access the intraamniotic space and can overcome placental defenses. In addition to the recognized “classic” TORCH(S) infections, a host of new organisms have been identified as causing congenital and perinatal infections. These include Zika virus, LCMV, human parvovirus B19, human parechovirus, hepatitis B, VZV, tuberculosis, HIV, and the parasitic infection toxocariasis.

Sequelae of congenital infections range from asymptomatic infection to severe debilitating disease and still birth.

Imaging

CMV, toxoplasmosis, rubella, Zika virus, VZV, LCMV, and HIV may all cause parenchymal calcifications (12-1A). The location and distribution of the calcifications may strongly suggest the specific infectious agent. CMV—the most common congenital infection in resource-rich countries—causes periventricular calcifications (12-1B), cysts, cortical clefts (12-1C), polymicrogyria (PMG), schizencephaly, and white matter (WM) injury.

Early CNS infection with Zika virus leads to severe microcephaly and calcifications at the gray matter (GM)-WM junction. Rubella and HSV cause lobar destruction, cystic encephalomalacia, and nonpatterned calcifications. Congenital syphilis is relatively rare, causing basilar meningitis, arterial strokes, and scattered dystrophic calcifications. Congenital HIV is associated with basal ganglia calcification, atrophy, and aneurysmal arteriopathy.

TORCH(S), Zika virus, and LCMV infections should be considered in newborns and infants with microcephaly, parenchymal calcifications, chorioretinitis, and intrauterine growth restriction.

The timing of the gestational infection determines the magnitude and appearance of the brain insult. For example, early gestational CMV infection causes germinal zone necrosis with subependymal cysts and dystrophic calcifications. WM volume loss occurs at all gestational ages and can be diffuse or multifocal. Malformations of cortical development are very common, and PMG has the greatest prevalence.

Congenital Cytomegalovirus Infection

Congenital CMV is the leading cause of nonhereditary deafness in children and is the most common cause of congenital brain infection in resource-rich countries.

Terminology

Congenital CMV infection is also called CMV encephalitis. CMV is a ubiquitous DNA virus that belongs to the HHV family. Human CMV is ubiquitous, present in 40-100% of the population worldwide.

Pathology

Timing of the gestational infection determines the magnitude of brain insult. Early gestational CMV infection causes germinal zone necrosis with subependymal cysts and dystrophic calcifications. WM volume loss occurs at all gestational stages and can be diffuse or multifocal. Malformations of cortical development are common, and PMG has the greatest prevalence.

Clinical Issues

Epidemiology

CMV is the most common of congenital infection in the resource-rich world. Between 0.25-1% of newborn infants shed CMV in their urine or saliva at birth. 10-15% of infected newborns develop CNS or systemic symptoms and signs.

Presentation and Natural History

Symptomatic newborns and infants may exhibit microcephaly, jaundice, hepatosplenomegaly, chorioretinitis, and rash. Asymptomatic newborns may show microcephaly but otherwise initially appear developmentally normal. Sensorineural hearing loss, seizures, and developmental delay are the major long-term risks.

Imaging

Advances in fetal MR now permit antenatal detection of PMG, germinolytic cysts, and cerebellar dysgenesis. Postnatal manifestations are protean and include microcephaly, ventriculomegaly, germinolytic cysts, malformations of cortical development, calcifications, cerebellar and hippocampal dysgenesis, and WM abnormalities.

CT Findings

NECT shows intracranial calcifications and ventriculomegaly in the majority of symptomatic infants. Calcifications are predominately periventricular with a predilection for the germinal matrix zones along the caudostriatal interfaces (12-1). Some gross abnormalities, such as cortical clefting and GM anomalies, may be demonstrable on NECT.

MR Findings

Ventriculomegaly is almost universal. Cortical migrational anomalies, such as PMG, are common (12-2). Germinal zone and anterior temporal cysts, parenchymal calcifications, WM abnormalities (dysplastic and demyelinating), hippocampal dysgenesis, and cerebellar malformations are common.

Cortical migrational and organizational abnormalities range from minor dysgenesis with focal cortical clefting, simplified gyral pattern and “open” (i.e., shallow) sylvian fissures to more severe manifestations, including agyria, lissencephaly, and schizencephaly.

T1WIs show microcephaly, enlarged ventricles and germinal zone or anterior temporal cysts. Cerebellar and hippocampal dysgenesis are common. WM hypointensities corresponding to regions of demyelination and dysplasia are common. Brain calcifications are typically best demonstrated on SWI (or to a lesser degree, GRE) (12-3), but may also be evident as hyperintense T1 and hypointense T2 foci.

T2WI and FLAIR show delayed myelination, WM injury, anterior temporal cysts (12-4), and volume loss with focal, patchy or confluent periventricular abnormalities. Malformations of cortical organization and migrational disturbances are common. Coronal FLAIR/T2WIs may show vertically oriented, dysmorphic hippocampi and cerebellar dysgenesis.

Differential Diagnosis

The differential diagnosis of congenital CMV includes other TORCH and non-TORCH infections, including toxoplasmosis, Zika virus, and lymphocytic choriomeningitis (LCMV).

Toxoplasmosis is much less common than CMV and typically causes scattered parenchymal calcifications, not the dominant subependymal pattern observed in CMV. Zika virus infection can also cause multiple peripherally located calcifications. However, Zika generally causes much more severe microcephaly with overlapping sutures and striking craniofacial disproportion. Sulcation-migration disorders with PMG and lissencephaly are also common.

Some genetic disorders called pseudo-TORCH syndromes mimic the imaging abnormalities of congenital infections, such as CMV. Diseases, such as Aicardi-Goutières and Coats plus syndrome, are rare, mostly autosomal recessive degenerative disorders. Basal ganglia and brainstem calcifications are more common than the subependymal pattern characteristic of CMV, Zika, or LCMV infections. Pseudo-TORCH syndromes also typically lack the cortical malformations so common in many of the congenital infections.

Congenital Toxoplasmosis

Etiology

Congenital toxoplasmosis is the second most common of the congenital infections. Intrauterine infection is caused by ingestion of water or food contaminated by Toxoplasma gondii, one of the world’s most common obligate intracellular parasites. The infection is usually acquired by direct contact with the feces of an infected cat.

Pathology

Ependymitis leading to aqueductal obstruction and hydrocephalus with resultant macrocephaly is seen in ~ 50% of congenital toxoplasmosis. Diffuse inflammation of the meninges is typical. Unlike CMV, malformations of cortical development are rare.

Clinical Issues

Congenital toxoplasmosis causes severe chorioretinitis, jaundice, hepatosplenomegaly, growth restriction, and brain damage. Infants with subclinical infection at birth are at risk for seizures and delayed cognitive and motor development. Visual defects from chorioretinitis are common.

Imaging

With some exceptions, imaging features resemble those of CMV, Zika, and LCMV. NECT shows extensive parenchymal calcifications that appear scattered throughout the brain parenchyma (12-5), unlike the germinal zone calcifications of CMV or subcortical calcifications of Zika virus infection.

MR may show multiple subcortical cysts, ventriculomegaly (12-6), and porencephaly. Malformations of cortical development are uncommon.

Differential Diagnosis

The major differential diagnosis is congenital CMV infection. Here, the calcifications are deep in the periventricular zone and cortical dysplasias are common.

Herpes Simplex Virus: Congenital and Neonatal Infections

Terminology

CNS involvement in HSV infection is called congenital or neonatal HSV when it involves neonates. In contradistinction, herpes simplex encephalitis (HSE) (which is also sometimes called HSV encephalitis) describes encephalitis in individuals beyond the first postnatal month. In this section, we discuss neonatal HSV. HSE is discussed subsequently with other acquired viral infections.

Etiology

Approximately 2,000 infants in the USA annually are diagnosed with either HSV-1 or HSV-2 neonatal infection. The vast majority (85%) of cases are acquired at parturition while 10% are contracted postnatally. Only 5% of cases are due to in utero transmission.

Pathology

Neonatal HSV encephalitis is a diffuse disease without the predilection for the temporal lobes and limbic system seen in older children and adults. Early changes include meningoencephalitis with necrosis and hemorrhage. Atrophy with gross cystic encephalomalacia and parenchymal calcifications is typical of late-stage HSV. Near-total loss of brain substance with hydranencephaly is seen in severe cases.

Clinical Issues

Epidemiology

Approximately 2,000 infants in the USA are diagnosed with neonatal HSV-1 or HSV-2 infections each year. HSV-2 is one of the most prevalent sexually transmitted infections worldwide. The majority are asymptomatic and most are completely unaware of the disease.

Neonatal HSV infections are vertically transmitted. The vast majority (85%) are acquired at parturition while 10-15% is acquired postnatally. Only 5% of cases are due to in utero transmission.

Presentation

Neonatal HSV infection causes three clinicopathologic disease patterns: (1) Skin, eye, and mouth disease; (2) encephalitis; and (3) disseminated disease with or without CNS disease. Approximately 50% of all infants with neonatal HSV will have CNS infection.

As most (~ 85%) HSV is transmitted at time of parturition, the onset of symptoms usually occurs ~ 2-4 weeks after delivery. Symptoms include lethargy, poor feeding, jaundice, and seizures. The definitive diagnosis is based on serum or CSF PCR, although up to 25% of neonates with HSV encephalitis have negative PCR studies.

Natural History

Death by one year of age occurs in ~ 50% of untreated neonates with overt CNS disease and 85% with disseminated infection. Surviving infants are at high risk for permanent deafness, vision loss, cerebral palsy, &/or epilepsy. Prompt treatment with antiviral agents significantly reduces morbidity.

Imaging

Unlike childhood or adult HSE, neonatal HSV CNS infection is much more diffuse. Both GM and WM are affected. Radiologists should strongly consider neonatal HSV encephalitis when cranial imaging at 2-4 weeks of neonatal life shows unexplained diffuse cerebral edema with leptomeningeal enhancement, without or with cerebral parenchymal hemorrhage. Early MR with diffusion is advised.

CT Findings

NECT may be normal early in the disease or show diffuse hypoattenuation involving both cortex and subcortical WM, reflecting cerebral edema. Hemorrhages may present as multifocal punctate, patchy, and curvilinear regions of hyperattenuation in the basal ganglia, WM, and cortex.

MR Findings

In the acute and subacute stages of neonatal HSV, multifocal lesions (67%), deep GM involvement (58%), hemorrhage (66%), “watershed” pattern of injury (40%), and the occasional involvement of the brainstem and cerebellum may occur. It is important to note that T1WI and T2WI may be normal in the early stages of disease. DWI is the most sensitive early imaging marker of disease (12-7A). T1WI may show hypointensity in affected areas. T2WIs may be show hyperintensity in the cortex, WM, and basal ganglia. Hemorrhagic foci on T2* or SWI sequences are common. Late-stage disease shows severe volume loss with enlarged ventricles and multicystic encephalomalacia (12-7B).

DWI is key for the initial diagnosis of neonatal HSV encephalitis. DWI is the first sequence to become abnormal and typically is the most accurate sequence in determining the extent of brain involvement. In most patients, DWI demonstrates bilateral or significantly more extensive disease than seen on conventional MR.

FLAIR sequences at under eight months of age underestimate parenchymal pathology, particularly within the hemispheric WM.

Foci of patchy enhancement, typically a meningeal pattern of enhancement, are common on T1 C+. In later stages, T1 shortening and T2 hypointensity with “blooming” on T2* GRE/SWI secondary to hemorrhagic foci may develop.

MRS in early HSV encephalitis shows elevated lactate, lipids, choline, and excitatory neurotransmitters. NAA is reduced.

Differential Diagnosis

The major differential diagnoses for neonatal HSV are other TORCH and non-TORCH infections. Because the initial imaging features of acute and subacute HSV encephalitis are often so nonspecific and may manifest with generalized cerebral edema, metabolic, toxic, and hypoxic-ischemic insults must also be considered in the differential diagnosis.

In some cases, HSV causes watershed distribution ischemic injury in areas remote from the primary herpetic lesions. Findings may be difficult to distinguish from partial protracted or mild to moderate hypoxic-ischemic injury. Hemorrhage with “blooming” on T2* GRE or SWI is uncommon in neonatal hypoxic-ischemic injury.

Congenital (Perinatal) HIV

The imaging presentation of congenital HIV infection is quite different from the findings in acquired HIV/AIDS. The most striking and consistent finding is atrophy, particularly in the frontal lobes. Bilaterally symmetric basal ganglia calcifications are common (12-8). Ectasia and fusiform enlargement of intracranial arteries are found in 3-5% of cases.

Differential Diagnosis

The differential diagnosis of congenital HIV is other TORCH infections. CMV is characterized by periventricular calcifications, microcephaly, and cortical dysplasia. Other than volume loss, the brain in congenital HIV appears normal. Toxoplasmosis is much less common than CMV and causes scattered parenchymal calcifications, not symmetric basal ganglia lesions. Pseudo-TORCH calcifications involve cortex and WM, basal ganglia, brainstem, and cerebellum.

Zika Virus Infection

Etiology

Zika virus is a single-stranded RNA Flavivirus, closely related to dengue fever, yellow fever, West Nile virus, and chikungunya. The virus is mostly transmitted by infected female mosquito bites. It can also be transmitted through blood contamination perinatally and sexually.

Pathology

Zika virus has been directly linked to severe fetal microcephaly in infants born to infected mothers. Like CMV, Zika virus crosses the fetal-placental barrier. Studies have confirmed the tropism of Zika virus for neural progenitor stem cells. Zika virus elicits a deleterious inflammatory response that compromises neurogenesis and brain formation.

Clinical Issues

Presentation

Up to 80% of infected individuals are asymptomatic. Zika virus causes severe fetal brain damage, resulting in extreme microcephaly with overlapping sutures, closed fontanelles, seizures, poor feeding, and lethargy.

Imaging

CT Findings

Microcephaly with craniofacial disproportion can be severe. By comparison to the small brain, the eyes can appear enlarged.

Cerebral parenchymal calcifications—typically at the hemispheric GM-WM junctions—are universally present (12-9A). Calcifications may also occur in the basal ganglia/thalami, brainstem, and cerebellum. Ventriculomegaly and microcephaly are typical. Migrational disorders, such as polymicrogyria (PMG), lissencephaly, and pachygyria, are present in the majority of cases.

MR Findings

MR is the most comprehensive tool to depict parenchymal calcifications (SWI is more sensitive than GRE sequences). Malformations of cortical development, disturbed WM myelination, and ventriculomegaly are almost universal (12-9).

Differential Diagnosis

Congenital CMV can present with microcephaly and PMG. Calcifications along the caudostriatal groove are more common than those at the GM-WM interfaces. Congenital toxoplasmosis presents with macrocephaly, hydrocephalus, scattered calcifications, and lack of cortical malformations.

Lymphocytic Choriomeningitis Virus

Etiology

Congenital lymphocytic choriomeningitis virus (LCMV) is an arenavirus with rodents as its typical vector. Many, but not all, cases are reported from rural environments.

Pathology

LCMV causes a necrotizing ependymitis similar to congenital toxoplasmosis. Microcephaly, periventricular calcifications, hydrocephalus, and cortical migrational anomalies are common.

Clinical Issues

In contrast to other congenital CNS infections, hepatosplenomegaly, jaundice, and skin rashes are absent in congenital LCMV. Definitive diagnosis requires LCMV-specific serologic responses, as they are often not routinely evaluated in TORCH(S) laboratory assessments. Mortality rate is high and survivors often have severe neurologic sequelae.

Imaging

LCMV causes no pathognomonic imaging findings and can mimic CMV or toxoplasmosis (12-10). Hydrocephalus and malformations of cortical development are typical. The diagnosis of LCMV should be considered when imaging findings mimic CMV, Zika, or toxoplasmosis and the clinical and serologic evaluation is reported as “normal.”

Differential Diagnosis

Toxoplasmosis lacks cortical malformations, congenital CMV typically shows caudostriatal groove or periventricular calcification and PMG. Zika virus calcification is most common at the GM-WM junction and pseudo-TORCH calcification involves the brainstem, basal ganglia, WM, and cortex and lacks cortical malformations.

Other Congenital Infections

Congenital rubella infection is rare. With the widespread advent of effective vaccination, the prevalence of congenital rubella syndrome has decreased dramatically. Humans are the only known reservoir for the rubella virus.

Reported imaging findings include microcephaly, parenchymal calcifications (12-11), including cortical calcifications, delayed myelination, periventricular and basal ganglia cysts, frontal-dominant WM lesions (NECT hypoattenuating and MR T2 hyperintense), and atrophy, and, in severe cases, total brain destruction has been described. Imaging findings are nonspecific. Late infection causes generalized brain volume loss, dystrophic calcifications, and regions of demyelination &/or gliosis.

Congenital VZV infection (“chickenpox”) causes microcephaly, parenchymal calcifications (12-12), ventriculomegaly, and PMG with nonpatterned necrosis of WM, lobar cortical and subcortical tissues, and deep gray nuclei.

Congenital/perinatal human parechovirus infection causes bilateral confluent WM abnormalities, often with involvement of the internal/external capsules and thalami (12-13). The symmetric pattern of injury to the WM and thalami is often mistaken for hypoxic-ischemic injury in the neonate. These patients typically present later than perinatal asphyxia, usually with symptom onset and subsequent imaging investigation occurring many days or sometimes even weeks after birth. Chronic appearance is that of deep and periventricular leukomalacia.

Acquired Pyogenic Infections

Meningitis

Meningitis is a worldwide disease that leaves up to 1/2 of all survivors with permanent neurologic sequelae. Despite advances in antimicrobial therapy and vaccine development, bacterial meningitis represents a significant cause of morbidity and mortality. Infants, children, and older adults or immunocompromised patients are at special risk. In this section, we focus on the etiology, pathology, and imaging findings of this potentially devastating disease.

Terminology

Meningitis is an acute or chronic inflammatory infiltrate of meninges and CSF. Pachymeningitis involves the dura-arachnoid;leptomeningitis affects the pia and subarachnoid spaces.

Etiology

Most cases are caused by acute pyogenic (bacterial) infection. Meningitis can also be acute lymphocytic (viral) or chronic (tubercular or granulomatous).

The most common responsible agent varies with age, geography, and immune status. The three most common causes of community-acquired bacterial meningitis worldwide are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Group B β-hemolytic streptococcal meningitis is the leading cause of neonatal meningitis in resource-rich countries.

Vaccination has significantly decreased the incidence of H. influenzae meningitis, so the most common cause of childhood bacterial meningitis is now N. meningitidis. The tetravalent meningococcal vaccine used to vaccinate adolescents in the USA does not contain serotype B, the causative organism of 1/3 of all cases of meningococcal disease in industrialized countries.

Listeria monocytogenes, S. pneumoniae, gram-negative bacilli, such as Escherichia coli, and N. meningitidis, affect pregnant women, older adults, and transplant recipients.

Tuberculous meningitis is common in resource-limited countries and in immunocompromised patients (e.g., HIV/AIDS patients and solid organ transplant recipients).

Pathology

Cloudy CSF initially fills the subarachnoid spaces followed by development of a variably dense purulent exudate that covers the pial surfaces (12-14). The basal cisterns and subarachnoid spaces are the most commonly involved sites by meningitis (12-15)(12-16) followed by the cerebral convexity sulci. Vessels within the exudate may show inflammatory changes and necrosis.

Clinical Issues

Presentation

Presentation depends on patient age. In adults, fever (≥ 38.5 °C) and either headache, nuchal rigidity, or altered mental status are the most common symptoms. Fever, lethargy, poor feeding, and irritability are common among infected infants. Seizures occur in 30% of patients.

Natural History

Despite rapid recognition and effective therapy, meningitis still has significant morbidity and mortality rates. Death rates from 15-25% have been reported in disadvantaged children with poor living conditions.

Complications are both common and numerous. Extraventricular obstructive hydrocephalus is one of the earliest and most common complications. The choroid plexus can become infected, causing choroid plexitis and then ventriculitis. Infection can also extend from the pia along the perivascular spaces into the brain parenchyma itself, causing cerebritis and then abscess.

SDEs and epidural empyemas (EDEs) or sterile effusions may develop. Cerebrovascular complications of meningitis include vasculitis, thrombosis, and occlusion of both arteries and veins.

Imaging

General Features

Remember: Imaging is neither sensitive nor specific for the detection of meningitis! Imaging (CT &/or MR) should be used in conjunction with—and not as a substitute for—appropriate clinical and laboratory evaluation. CSF analysis remains the mainstay of diagnosis.

CT Findings

Initial NECT may be normal or show only mild ventricular enlargement (12-17A). “Blurred” ventricular margins indicate acute obstructive hydrocephalus with accumulation of extracellular fluid in the deep WM. Bone CT should be carefully evaluated for sinusitis and otomastoiditis.

Cellular inflammatory exudate replaces the normally clear CSF. Subtle effacement of surface landmarks may occur as sulcal-cisternal CSF becomes almost isodense with brain on NECT. CECT may show intense enhancement of the inflammatory exudate as it covers the brain surfaces, extending into and filling the sulci (12-17B).

MR Findings

The purulent exudates of acute meningitis are isointense with underlying brain on T1WI, giving the appearance of “dirty” CSF (12-18A). The exudates are isointense with CSF on T2WI and do not suppress on FLAIR (12-18B). Hyperintensity in the subarachnoid cisterns and superficial sulci on FLAIR is a typical but nonspecific finding of meningitis (see box on p. 246).

DWI is especially helpful in meningitis, as the purulent subarachnoid space exudates usually show restriction. pMR may demonstrate multiple regions of increased cerebral blood flow.

Pia-subarachnoid space enhancement occurs in 50% of patients. A curvilinear pattern that follows the gyri and sulci (the pial-cisternal pattern) is typical (12-18C)and more common than dura-arachnoid enhancement. Postcontrast T2-weighted FLAIR and delayed postcontrast T1-weighted sequences may be helpful additions in detecting subtle cases.

Complications of Meningitis

Other than hydrocephalus (12-19), complications from meningitis are relatively uncommon (12-20). Postmeningitis reactive effusions—sterile CSF-like fluid pockets—develop in 5-10% of children treated for acute bacterial meningitis. NECT shows bilateral crescentic extraaxial collections that are iso- to slightly hyperdense compared with normal CSF.

Effusions are iso- to slightly hyperintense to CSF on T1WI and isointense on T2WI. They are often slightly hyperintense relative to CSF on FLAIR. Effusions usually do not enhance on T1 C+ and do not restrict on DWI, differentiating them from subdural empyemas (SDEs).

Less common complications include pyocephalus (ventriculitis), empyema, cerebritis &/or abscess, venous occlusion, and ischemia. All are discussed separately.

Differential Diagnosis

The major differential diagnosis of infectious meningitis is noninfectious meningitis. Other causes of meningitis include noninfectious inflammatory disorders (e.g., rheumatoid or systemic lupus erythematosus-associated meningitis, IgG4-related disease, drug-related aseptic meningitis, and multiple sclerosis) and neoplastic or carcinomatous meningitis. All can appear identical on imaging, so correlation with clinical information and laboratory findings is essential. Remember: Sulcal/cisternal FLAIR hyperintensity is a nonspecific finding and can be seen with a number of different entities.

Abscess

Terminology

A cerebral abscess is a localized infection of the brain parenchyma.

Etiology

Most abscesses are caused by hematogenous spread from an extracranial location (e.g., lung or urinary tract infection and endocarditis). Abscesses may also result from penetrating injury or direct geographic extension from sinonasal and otomastoid infection. These typically begin as extraaxial infections, such as empyema or meningitis, and then spread into the brain itself.

Abscesses are most often bacterial, but they can also be fungal, parasitic, or (rarely) granulomatous. Although myriad organisms can cause abscess formation, the most common agents in immunocompetent adults are Streptococcus species, Staphylococcus aureus, and pneumococci. Enterobacter species like Citrobacter are a common cause of cerebral abscess in neonates. Streptococcus intermedius is emerging as an important cause of cerebral abscess in immunocompetent children and adolescents. In 20-30% of abscesses, cultures are sterile, and no specific organism is identified.

Proinflammatory molecules, such as tumor necrosis factor-α and interleukin-1β, induce various cell adhesion molecules that facilitate extravasation of peripheral immune cells and promote abscess development.

Bacterial abscesses are relatively uncommon in immunocompromised patients. Klebsiella is common in diabetic patients, and fungal infections by Aspergillus and Nocardia are common in transplant recipients. In patients with HIV/AIDS, toxoplasmosis and tuberculosis are the most common opportunistic infections.

In children, predisposing factors for cerebral abscess formation include meningitis, uncorrected cyanotic heart disease, sepsis, suppurative pulmonary infection, paranasal sinus or otomastoid trauma, or suppurative infections, endocarditis, and immunodeficiency or immunosuppression states.

Pathology

Four general stages are recognized in the evolution of a cerebral abscess: (1) Focal suppurative encephalitis/early cerebritis, (2) focal suppurative encephalitis/late cerebritis, (3) early encapsulation, and (4) late encapsulation. Each has its own distinctive pathologic appearance, which, in turn, determines the imaging findings.

Focal Suppurative Encephalitis

Sometimes also called the “early cerebritis”stage of abscess formation, in this earliest stage, suppurative infection is focal but not yet localized (12-21). An unencapsulated, edematous, hyperemic mass of leukocytes and bacteria is present for 1-3 days after the initial infection (12-22).

Focal Suppurative Encephalitis With Confluent Central Necrosis

The next stage of abscess formation is also called “late cerebritis”and begins 2-3 days after the initial infection (12-23). This stage typically lasts between a week and 10 days.

Patchy necrotic foci within the suppurative mass form, enlarge, and then coalesce into a confluent necrotic mass. By days 5-7, a necrotic core is surrounded by a poorly organized, irregular rim of granulation tissue consisting of inflammatory cells, macrophages, and fibroblasts. The surrounding brain is edematous and contains swollen reactive astrocytes.

Early Encapsulation

The “early capsule”stage starts around one week. Proliferating fibroblasts deposit reticulin around the outer rim of the abscess cavity. The abscess wall is now composed of an inner rim of granulation tissue at the edge of the necrotic center (12-26)and an outer rim of multiple concentric layers of fibroblasts and collagen (12-27). The necrotic core liquefies completely by 7-10 days, and newly formed capillaries around the mass become prominent.

Late Capsulation

The “late capsule”stage begins several weeks following infection and may last for several months.

With treatment, the central cavity gradually involutes and shrinks. Collagen deposition further thickens the wall, and the surrounding vasogenic edema disappears. The wall eventually contains densely packed reticulin and is lined by sparse macrophages. Eventually, only a small gliotic nodule of collagen and fibroblasts remains.

Clinical Issues

Demographics

Brain abscesses are rare. Only 2,500 cases are reported annually in the USA. Brain abscesses occur at all ages but are most common in patients between 3rd-4th decades. Almost 25% occur in children under the age of 15 years. The M:F ratio is 2:1 in adults and 3:1 in children.

Presentation and Prognosis

Headache, seizure, and focal neurologic deficits are the typical presenting symptoms. Fever is common but not universal. CSF cultures may be normal early in the infection.

Brain abscesses are potentially fatal but treatable lesions. Rapid diagnosis, stereotactic surgery, and appropriate medical treatment have reduced mortality to 2-4%.

Imaging

General Features

Imaging findings evolve with time and are related to the stage of abscess development. MR is more sensitive than CT and is the procedure of choice.

Early Cerebritis

Very early cerebritis may be invisible on CT. A poorly marginated cortical/subcortical hypodense mass is the most common finding (12-24A). Early cerebritis often shows little or no enhancement on CECT.

Early cerebritis is hypo- to isointense on T1WI and hyperintense on T2/FLAIR. T2* GRE may show punctate “blooming” hemorrhagic foci. Patchy enhancement may or may not be present. DWI shows diffusion restriction (12-24B).

Late Cerebritis

A better-delineated central hypodense mass with surrounding edema is seen on NECT. CECT typically shows irregular rim enhancement (12-25A).

Late cerebritis has a hypointense center and an iso- to mildly hyperintense rim on T1WI. The central core of the cerebritis is hyperintense on T2WI, whereas the rim is relatively hypointense. Intense but somewhat irregular rim enhancement is present on T1 C+ images (12-25B).

Late cerebritis restricts strongly on DWI (12-25A). MRS shows cytosolic amino acids (0.9 ppm), lactate (1.3 ppm), and acetate (1.9 ppm) in the necrotic core (12-29D). The abscess wall demonstrates low rCBV on pMR.

Early Capsule

Abscesses are now well-delineated, round or ovoid masses (12-28)with liquefied, hyperintense cores on T2/FLAIR (12-29A). The rims of abscesses are usually thin, complete, smooth, and hypointense on T2WI. A double rim sign demonstrating two concentric rims, the outer hypointense and the inner hyperintense relative to cavity contents, is seen in 75% of cases (12-29A).

The necrotic core of encapsulated abscesses restricts strongly on DWI (12-29C). T1 C+ sequences show a strongly enhancing rim (12-29B) that is thinnest on its deepest (ventricular) side (12-30B) and “blooms” on T2*.

Late Capsule

With treatment, the abscess cavity gradually collapses while the capsule thickens even as the overall mass diminishes in size. The shrinking abscess often assumes a crenulated appearance, much like a deflated balloon (12-30A).

Contrast enhancement in the resolving abscess may persist for months, long after clinical symptoms have resolved (12-30C).

Differential Diagnosis

The differential diagnosis of abscess varies with its stage of development. Early cerebritis is so poorly defined that it can be difficult to characterize and can mimic many lesions, including cerebral ischemia or neoplasm.

Once a ring develops around the necrotic center, the differential diagnosis is basically that of a generic ring-enhancing mass. Although there are many ring-enhancing lesions in the CNS, the most common differential diagnosis is infection vs. neoplasm (glioblastoma or metastasis).

Tumors have increased rCBV in their “rind,” usually do not restrict (or if they do, not as strongly as an abscess), and do not demonstrate cytosolic amino acids on MRS.

Less common entities that can appear as a ring-enhancing mass include demyelinating disease, in which the ring is usually incomplete and “open” toward the cortex. Resolving hematomas can exhibit a vascular, ring-enhancing pattern.

BRAIN ABSCESS: DIFFERENTIAL DIAGNOSIS

Early Cerebritis

• Encephalitis (may be indistinguishable)

• Stroke

Vascular distribution

 Usually involves both cortex, WM

• Neoplasm (e.g., diffusely infiltrating low-grade astrocytoma)

 Usually does not enhance or restrict

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