16 -INFECTIONS OF THE BRAIN and ITS LININGS .

Intrauterine infections can result in developmental brain anomalies, encephaloclastic destructive lesions, or Acute Pyogenic Meningitis Acute Lymphocytic Meningitis Chronic Meningitis Py

Infections of the Brain and Its

tions (see box, p 674 , left)

CNS infections are acquired in the following three ways 2:

1 Through the maternal transplacental route (usual with toxoplasmosis, and most viruses)

hematogenous-2 When the fetus travels through the birth canal (common with herpesviruses)

3 Via ascending infection from the cervix (com mon with bacteria)

Congenital infections often have devastating fects on the developing brain Infectious sequelae re-flect both the specific agent involved and the timing

ef-of the insult relative to fetal development Intrauterine infections can result in developmental brain anomalies, encephaloclastic (destructive) lesions, or

Acute Pyogenic Meningitis

Acute Lymphocytic Meningitis

Chronic Meningitis

Pyogenic Parenchymal Infections

Cerebritis and Abscess

Complications of Cerebral Abscess

Encephalitis

Herpes Simplex Encephalitis

HIV Encephalitis and Other CNS Infections in AIDS

Miscellaneous Viral Encephalitides

674 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Cytomegalovirus

Ubiquituous DNA virus Most common cause of congenital CNS infection Predilection for germinal matrix

Periventricular calcifications May cause abnormal neuronal migration

CMV has a particular affinity for the develop germinal matrix (Fig 16-1, A) Widespread periventricular tissue necrosis with subsequent dystrophic calcification occurs Other frequently affected are the cerebral white matter and cortex,

cerebellum brainstem, and spinal cord

Clinical presentation Infants infected with CMV

are often born prematurely Hepatosplenomegaly, jaundice, thrombocytopenia, and chorioretinits are common manifestations during the newborn period.5 Seizures, mental retardation, optic atrophy, sensorineural hearing loss, and hydrocephalus are later manifestations.2

CMV is diagnosed clinically by positive CMV cultures of body fluids, positive serum titers of MCV- specific immunoglobulin M, and demonstration large intranuclear inclusions with small variable tracytoplasmic inclusions in CMV-infected visceral cells

Natural history CMV may remain latent Reactivation can occur, usually in patients who become immunocompromised.2

Imaging

Plain film radiography The classic plain film

finding of congenital CMV infection is microcephaly with eggshell-like periventricular calcifications

Ultrasound Bilateral periventricular calcificafior4

preceded by hypoechoic periventricular ringlike zones, may be specific for intrauterine CMV.7 CMV may also result in widespread cerebral destruction with severe encephalomalacia

CT NECT scans show atrophy, ventricular

en-largement, and parenchymal calcifications CMV cancause widespread parenchymal calcifications in various locations but the periventricular region t e most common site (Fig 16-1, B) Neuronal migration,

anomalies are also common (see Fig 3-12)

MR MR findings include migrational anomalies

encephalornalacia with nonspecific ventricular enlargement and prominent sulci, delayed myelination and subependymal paraventricular cysts and

Cytomegalovirus

Etiology and pathology

Etiology Human cytomegalovirus (CMV) is a

ubiquitous DNA virus that belongs to the herpesvirus

group Humans are the only reservoir.3 Congenital

CMV results from transplacental virus transmission

(see box, above right)

Gross pathology Patchy spongiosis and

encepha-lomalacia are common.4 Hydranencephaly,

poren-cephaly, and micrencephaly also occur.1 CMV

infec-tion during the first or early second trimester can

cause severe neuronal migration anomalies

Microscopic appearance Intranuclear and

intracy-toplasmic inclusions are present in glial cells and

sometimes in neurons as well Microglial nodules are

common.1

Incidence In the United States, 50% to 85% of

women of childbearing age are seropositive for CMV

and 5% of pregnant women excrete CMV in the

urine Forty percent of the offspring from infected

pregnant women become infected.1

CMV is the most frequent cause of congenital fections and is 2 to 3 times more frequent than toxo-

in-plasmosis, the next most common agent 5 One

per-cent of newborns excrete CMV in their urine; 10% of

these have signs of CNS infection.1

Location Over 60% of infected fetuses have

mul-tiple organ systems involved.6 Intracranial

abnormal-ities are the most common manifestation, seen in

nearly 70% Cardiac anomalies and hepatospleno-

megaly occur in one third of these cases.6

Congenital CNS Infections Agents

TORCH (TOxoplasmosis, Rubella, Cytomegalovirus,

Chapter 16 Infections of the Brain and Its Linings 675

Fig 16-1 A, Axial gross autopsy specimen in an infant born with severe

cytomegalo-virus (CMV) infection shows the striking periventricular lesions (arrows) caused by

the predilection of this virus for the developing germinal matrix B, Axial NECT scan

in another case of a newborn infant demonstrates the typical periventricular

calcifications seen with congenital CMV infection (A, Courtesy archives of the

Armed Forces Institute of Patholoxy.)

Toxoplasmosis

Etiology and pathology

Etiology Toxoplasmosis is caused by Toxoplasma

gondii, a ubiquitous protozoan that is an obligate

in-tracellular parasite (see box) Oocysts in infected meat or

cat feces are the usual sources of infection in humans

Hematogenous spread to the placenta and fetus occurs

during maternal parasitemia Over half of all infected

fetuses develop CNS disease.1

Gross pathology Toxoplasmosis infection is

mul-tifocal and scattered, without the prominent

periven-tricular localization noted with CMV (Fig 16-2, A)

Toxoplasmosis causes necrosis but does not result in

migrational anomalies.1 Nonspecific findings include

atrophy, microcephaly, and hydranencephaly

Microscopic appearance Toxoplasmosis induces a

necrotizing granulomatous reaction with giant cells and

eosinophilic infiltration with or without demonstrable

intracellular organisms.1

Incidence Toxoplasmosis is second only to CMV in

causing congenital CNS infections Toxoplasmosis affects

between 1 in 1000 to 1 in 10,000 pregnancies in the

United States.5 Clinically significant abnormalities occur

when the fetus is infected prior to 26 weeks gestional

age.3

Toxoplasmosis

Intracellular parasite Second most common cause of congenital CNS infec- tion

Multifocal, scattered lesions (basal ganglia/periven- tricular, white matter, cortex)

Chorioretinitis

No migrational anomalies

Location Basal ganglia, periventricular, and

pe-ripheral locations are all common (Fig 16-2).5

Clinical presentation The clinical presentation is

diverse, ranging from mild cases that are initially detected and present later as seizures to severely af-fected infants with microcephaly Very early infections often result in spontaneous abortions

un-Imaging Hydrocephalus, bilateral chorioretinitis,

and intracranial calcifications form the typical triad found in infants with congenital toxoplasmosis encephalitis.3 Although the basal ganglia and cortex arecommon sites, calcifications can occur anywhere and

676 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Fig 16-2 A, Axial gross sutopsy specimen of congenital toxoplasmosis shows the

scat-tered, nonfocal lesions characteristic of this infection Note the subcortical, caudate and

basal ganglia lesions (arrows) (courtesy Rubinstein Collection, University of Virginia)

B, Axial CECT scan in a 27-year-old woman with severe mental retardation and seizures

since birth The brain is microcephalic and there are numerous scattered cortical and

subcortical calcifications (arrows) consistent with residua of congenital toxoplasmosis

are often more diffusely scattered than those

associ-ated with CMV encephalitis (Fig 16-2, B) Hydro

cephalus is due to ependymitis with periaqueductal

necrosis that results in aqueductal stenosis.1

Rubella

Etiology and pathology

Etiology Rubella is transmitted through the

pla-centa to the fetus during maternal viremia Rubella

infection interferes with cellular multiplication,

inhib-iting proliferation of immature undifferentiated

pro-genitor cells located in the germinal matrix.1 The

re-sult is insufficient numbers of neurons and astroglia

Oligodendroglia may also be diminished, resulting in

impaired myelination (see box).9

Gross pathology The results of fetal infection are

both teratogenic and destructive.3 Rubella is

charac-terized by meningoencephalitis, vasculopathy with

ischemia and necrosis, micrencephaly, and delayed

myelination.1 Micrencephalia vera, a rare entity in

which the brain is formed but is markedly diminished

in size, has been reported.9 It is probably related to

inhibition of progenitor cell multiplication with

insuf-ficient generation of neurons and astroglia.1

Microscopic appearance Inflammatory cells in

the meninges and perivascular spaces are present

Rubella

Rare Too few neurons/glia result in small brain, impaired myelination

Prominent ocular abnormalities

Microcephalic brain with cortical, basal ganglia calci-

fications

Leptomeningeal and parenchymal vasculopathy is com- mon Small foci of perivascular necrosis are seen the basal ganglia, periventricular region, and cerebral white matter.1

Incidence Widespread rubella immunization has

markedly diminished the incidence of this devastating neonatal infection Nevertheless, congenital rubella syndrome remains a significant, albeit ran, cause of brain damage in newborn infants.10

Clinical presentation and natural history Maternal

rubella infection results in a spectrum of abnormalities ranging from mild manifestations to spontaneous abortion, stillbirths, and devastating abnormalities.3 Gestational age at the time of infection is

Chapter 16 Infections of the Brain and Its Linings 677

Herpes Simplex

HSV-2 (genital herpes) causes 75% to 90%

CNS manifestations 2 to 4 weeks after birth Brain diffusely affected (no temporal lobe localization)

Cortex appears hyperdense, white matter hypo-

dense; predilection of HSV for vascular endothelial cells may cause thrombosis/hemorrhagic infarction

Fig 16-3 Axial NECT scan in a deaf child with

congenital rubella shows extensive calcifications

in the basal ganglia ,cerebral white matter, and

cortex (Courtesy H Segall.)

have been reported.10 Delayed myelination may occur, perhaps because there are insufficient numbers

of oligodendroglia

Herpes Simplex Etiology and pathology

Etiology Herpes simplex virus (HSV) is a DNA

virus There are two HSV serotypes: type 1 and type

2 Although either type can cause perinatal CNS fections, HSV type 2 (genital herpes) accounts for 75% to 90% of all neonatal herpesvirus infections

in-(see box, above).1,2

Infection is rare during fetal development, possibly because the severe encephaloclastic effects of her-pesvirus infection cause spontaneous abortions Most neonatal infections are parturitional, acquired through direct contact between the infant's skin, eyes or oral cavity, and maternal herpetic lesions in the cervix or vagina.1 Ascending infection can also occur after membranes rupture during delivery

Postnatal infection is uncommon but can be mitted from mothers with oral herpetic lesions, from other adults (such as hospital personnel), or from other infants Defective macrophage function or im-paired production of antiherpes antibody may con-tribute to the devastating effects of postnatal infec-tions with HSV.1

trans-Gross pathology The neuropathology in HSV

in-fection varies with timing and virus dose Early tational infection is rare and produces a spectrum of changes that ranges from minor focal calcifications to severe encephaloclastic lesions.1 Microcephaly, hy-drocephalus, microphthalmia, and chorioretinitis are seen.11

ges-Microscopic appearance All cellular CNS

compo-nents may be infected The particular predilection of HSV for endothelial cells results in vascular throm-bosis and hemorrhagic infarction Microglial nodules with intranuclear inclusions are present.1 Secondary changes of infarction and multicystic encephalornala-cia can be seen in surviving infants

Incidence and age Reported prevalence of

neona-tal HSV infection is between 1 in 200 and 1 in 5000

the most important determinant of outcome.2 Fetal

infection before 8 to 12 weeks gestation causes more

frequent infections with more severe consequences (see

subsequent discussion), whereas infection during the last

trimester is relatively mild with few or no significant

lasting effects.3

Congenital rubella syndrome is usually caused by

first trimester infections A spectrum of abnormalities is

seen Cataracts, glaucoma, chorioretinitis,

mi-crophthalmia, cardiac malformations, and micrencephaly

occur with early, severe infections; deafness is the most

common late manifestation of congenital rubella.2

Meningoencephalitis, thrombocytopenia,

hepatospieno-megaly, and lymphadenopathy are transient

abnormalities in neonates.1

Imaging In general, imaging findings are similar to

other congenital viral infections and are therefore

nonspecific

Ultrasound Subependymal cysts in the caudate

nucleus and striothalamic regions are seen but are not

specific for rubella Echogenic foci in the basal ganglia

may represent mineralizing vasculitis with

calci-fication.10

CT Microcephaly and parenchymal calcifications are

typically present The cortex and basal ganglia are often

affected (Fig 16-3).5

MR Deep and subcortical white matter lesions,

possibly caused by vascular injury and ischemic

678 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Fig 16-4 A 20-day-old infant was born through herpes-infected vaginal canal

Initially healthy at birth, he then developed seizures Axial NECT scans show diffuse, low density changes throughout the cerebral white matter Note

relatively dense-appearing cortex (arrows) Presumed congenital herpes

encephalitis (Courtesy T Miller.)

deliveries.2 Neonates with disseminated HSV usually

present between 9 and 11 days of age, whereas

in-fants with isolated CNS herpesvirus infections

be-come symptomatic

approximately 2 to 4 weeks after birth.2,3

Location Acute neonatal HSV infections cause

diffuse brain involvement The limbic system

local-ization (temporal lobes, cingulate gyrus) that is so

characteristic in older children and adult infections

does not occur

Clinical presentation and natural history

Neonatal herpetic infections are divided into the

following three clinical categories:

1 Skin, eye, and mouth lesions

2 Disseminated disease

3 CNS infections

Cutaneous infections are both the mildest and the

most common manifestation, seen in 40% of cases

Untreated infection progresses to disseminated or

CNS disease in 75% of infected infants.2

Disseminated disease causes signs and symptoms

that suggest severe bacterial sepsis CNS

manifesta-tions are present in approximately half of

dissemi-nated HSV cases The overall mortality rate

ap-proaches 80% in untreated and 50% in treated

in-fants.2

The CNS is affected in approximately 30% of

in-fected infants Clinical onset of isolated CNS herpes-

virus infection occurs 2 to 4 weeks after birth Fever lethargy, and seizures are the most common manifestations; 20% of infected infants have no cutanous lesions. 3

Imaging

CT Acute neonatal HSV encephal4is is seen on

NECT scans as focal or diffuse white matter lucency (Fig 16-4).3 The relative hyperdensity of cortical gray matter appears accentuated Hemorrhagic infarction may occur Diffuse atrophy and multicystic enceph-alomalacia are long-term sequelae (Fig 16-5)

MR Because the neonatal brain is largely

unmy-elinated, diffuse white matter edema is difficult to tect Hemorrhagic changes are occasionally identified Parenchymal or meningeal enhancement following contrast administration is seen in some subacute cases.3

de-HIV Infection Etiology and pathology

Etiology Perinatal transmission is the most

com-mon route of human immunodeficiency virus (HIV) infection in children.12 Nearly 80% of all childhood HIV infections are maternally transmitted, although only one third of HIV positive mothers pass on the infection.5

The HIV virus infects T4 helper cells, allowing

secondary infections such as Pneumocystis carinii

and tumors (lymphoma, Kaposi’s sarcoma) to develop In

Chapter 16 Infections of the Brain and Its Linings 679

Fig 16-5 Axial NECT scan shows residua of

neonatal herpes encephalitis Both hemispheres are

severely encephalomalacic Only a small amount of

residual cerebral tissue is seen around the cerebral

ventricles (Courtesy H Segall.)

Fig 16-6 Axial NECT scan in a 15-month-old infant

with congenital HIV infection Note generalized cerebral atrophy and bilateral basal ganglia

calcifications (curved a rows) (From C Fitz, reprinted from AJNR 13:551-567, 1992.)

incidence is between 5% and 25% of AIDS cases.12Transfusion-acquired HIV is waning.12 Over 70% of seropositive cases in children are now linked to drug abuse in the child's mother or the mother's sexual partner

Clinical presentation and natural history

Pre-senting signs of AIDS in children differ from those usually identified in adults Weight loss, failure to thrive, chronic diarrhea, and chronic fever are seen Minor signs include lymphadenopathy, oral thrush, repeated infections, and dermatitis.12 Definitive diag-nosis may require virologic tests because serologic tests are less reliable in newborn infants

Thirty to fifty percent of HIV-infected infants and children develop a progressive encephalopathy that is characterized by loss of developmental milestones and bilateral pyramidal tract signs with progressive spastic quadriparesis.13 Cognitive and psychomotor abnormalities are common manifestations in children; seizures are rare.1 Infected infants may have cortical atrophy and microcephaly

Most children with AIDS die in the first year of life

In the United States, AIDS is now the ninth ranking cause of death in children between the ages of 1 and 4 years More than 80% of children with AIDS diagnosed before 1 year of age have died.12

highest-Imaging

CT NECT scans show diffuse cerebral atrophy in

nearly 90% of cases.14 Basal ganglia calcifications are seen in one third of all cases (Fig 16-6) but are virtu-

Congenital HIV Infection

Maternally transmitted

CNS symptoms

Due to HIV encephalitis

Opportunistic infection, neoplasm rare

Most infected neonates die in first year

Atrophy, basal ganglia calcifications

children, opportunistic infections and tumors are less

common manifestations of HIV infection CNS signs and

symptoms reflect the primary retroviral encephalitis (see

box).1

Gross pathology Atrophy with diminished brain

weight is characteristic

Microscopic appearance Glial and microglial

nod-ules are present in the basal ganglia, pons, and cerebral

white matter Multinucleated giant cells are seen

Perivascular calcifications are common, particularly in

the putamen and globus pallidus Demyelination and

astrogliosis with relative cortical sparing is typical.1

Incidence In the United States, approximately 2% of

all patients with acquired immune deficiency syndrome

(AIDS) are children The reported worldwide

680 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

ally never identified before 1 year of age.14

Hemor-rhage can occur in children with thrombocytopenia In

contrast to adults, opportunistic infections and tumors

are relatively rare, occurring in only 15% of cases.13,15

MR Nonspecific cerebral atrophy is the most

common finding Foci of increased signal on T2WI are

seen in the peripheral and deep white cerebral matter

Nonhemorrhagic cerebral infarcts have also been

noted.14

Varicella

Varicella-zoster (VZ) infection during the first,

sec-ond, or early third trimester causes a severe necrotizing

encephalomyelitis The anterior horn cells and the

dorsal root ganglia are particularly affected.1

Nonspecific changes include chorioretinitis, cataracts,

microphthalmia, and optic atrophy

VZ infection develops in approximately 25% of

in-fants born to mothers with varicella during the last

month of pregnancy.1 Skin lesions of chicken pox and

shingles are common clinical manifestations of these

late in utero infections, whereas maternal herpes zoster

has not been implicated as a cause of fetal infection or

brain damage.1

Enteroviruses

Enteroviruses include coxsackie A, coxsackie B,

echovirus, and poliovirus These viruses, particularly

the coxsackie B viruses, may produce acute neonatal

infection with myocarditis and encephalitis

Congenital intrauterine enterovirus infections have

not been associated with CNS disease or

mal-formations Infection is typically seasonal and

post-natal, and usually spread from infected parents to

in-fants A diffuse meningoencephalitis occurs with a

high frequency of lesions in the inferior olivary nuclei

and ventral horns of the spinal cord.1

Poliovirus is a picornavirus that affects adults and

immunocompromised children It has a single strand of

RNA, replicates in the host cell cytoplasm, and is

released by cell lysis Most polio cases do not involve

the CNS; only 0.1% to 1% progress to paralysis

Par-alytic poliomyelitis is now uncommon in the United

States with an average of 10 cases per year reported

from 1980 to 1984, mostly vaccine-related.16 poliovirus

involves the CNS by direct infection during viremia or

by retrograde neural spread

Paralytic poliomyelitis may present with spinal cord

symptoms, bulbar (brainstem) symptoms, or both

Between 10% to 15% of paralytic polio cases are

bulbar The brainstem reticular formation and cranial

nerves VII, IX, and X are most commonly involved.16

MR imaging discloses high signal in the midbrain and

medulla on T2WI; the findings are indistinguishable

from other causes of brainstem encephalitis.16

MENINGITIS

Meningitis is the most common form: of CNS in- fection.17 Infectious meningitis is divided into the following three general categories18,19

1 Acute pyogenic meningitis (mostly bacterial in- fections)

2 Lymphocytic meningitis (usually viral)

3 Chronic meningitis (classic examples are tuber

culosis and coccidiodomycosis) Acute Pyogenic Meningitis Etiology and pathology

Etiology Acute pyogenic meningitis is usually caused

by bacteria The specific agents involved vary among

different age groups (see box) The most common cause of

neonatal meningitis is group B streptococcus, followed by

involved in the pathogenesis d neonatal meningitis relate

to delivery (e.g., maternal genitourinary tract infection or prolonged rupture of membranes), immaturity (deficiencies of cellular and humoral immunity), and environment (aerosols, catheters, inhalation therapy equipment).1

In children under 7 years of age, Hemophilus;., enzae

meningitis is common.18 The older the Chi the more adultlike is the infection 5 Neisseria menkitidis is found

in children and young adults, whereas Streptococcus

pneumoniae is the most common infective agent in adults.

Meningitis Agents

Neonates: group B streptococcus, E coli Children under 7: H influenzae

Older children: N meningitidis Adults: S pneumoniae

Pathology

Purulent exudate in basilar cisterns, sulci;

perivascu-lar inflammation, vasospasm common Imaging

Early: may be normal/mild hydrocephalus Effaced cisterns

Enhancing meninges, subarachnoid exudate Complications

Hydrocephalus Ventriculitis/ependymitis Subdural effusion Empyema

Cerebritis/abscess Vasospasm/arterial infarcts

Dural sinus/cortical vein thrombosis, venous infarct

Chapter 16 Infections of the Brain and Its Linings 681

Acute pyogenic meningitis begins in several ways

Hematogenous spread and local extension from

con-tiguous extracerebral infection (e.g., otitis media,

mastoiditis, or sinusitis) are the most common causes

Hematogenous infection probably occurs through the

choroid plexus and CSF pathways.18 Direct implantation

of bacteria into the meninges is less frequent and is

usually seen with penetrating head injury or comminuted

skull fracture

Gross pathology The most striking feature of bacterial

meningitis is a thick, creamy purulent exudate that is

either confined to the basal cisterns or completely fills the

subarachnoid space (Fig 16-7, A) Complications of

meningitis include perivascular inflammation and

vasospasm with secondary venous or arterial infarction,

subdural effusion or empyema, cerebritis, abscess, and

ventriculitis (see subsequent discussion) Subarachnoid

space compromise may cauuse extraventricular

obstructive (communicating)

hydrocephalus, whereas ventriculitis with cerebral

aqueductal ependymitis causes intraventricular

ob-structive hydrocephalus

Microscopic appearance Bacterial and mycobacterial

leptomeningeal inflammations are characterized by polymorphonuclear cell infiltration and extensive fibrinous exudation.20 Vascular endothelial injury with altered blood-brain barrier permeability and vasogenic edema is common.19 Inflammation often extends along the perivascular (Virchow-Robin) spaces into the underlying brain parenchyma.20

Age and incidence Nonepidemic meningitis is most

common in neonates, infants, and children Neonatal sepsis occurs in 1.5 cases per 1000 births; meningitis is seen in 20% of these cases.5 Epidemic meningitis can occur at any age

New antibiotics have markedly diminished the cidence of bacterial meningitis and the once-high mortality rates associated with potentially devastating disease 19

in-Imaging The diagnosis of meningitis is established

by history, physical examination, and laboratory evaluation Neuroimaging studies are typically

Fig 16-7 A, Close-up view of gross pathology

specimen in a patient who died with meningococcal meningitis The typical thick, creamy fibrinopurulent

exudate is seen filling the cerebral sulci (arrows) B and C, A 7-month-old infant had H influenzae

meningitis B, Axial NECT scan shows subtle

effacement of the subarachnoid cisterns over the left

hemisphere (arrows) Compare with the normal

CSF-filled cisterns on the right side C, CECT study

shows striking enhancement of the leptomeninges

and subarachnoid inflammatory exudate (arrows)

682 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

used to monitor the complications of meningeal

in-fection.18

CT A normal scan is the most common finding in

children with acute bacterial meningitis.19 Mild ventricular

dilatation and subarachnoid space enlargement are early

abnormalities on NECT scans Effacement of the basilar

or convexity cisterns by inflammatory exudate can be seen

in some cases (Fig 16-7, B) Less than half of all children

with clinically documented meningitis have abnormally

enhancing meninges on CECT studies (Fig 16-7, C).5

MR MR imaging is superior to CT in the evaluation of

patients with suspected meningitis.21 Precontrast T1WI

may show obliterated cisterns that enhance strongly

following contrast administration Extension of enhancing

subarachnoid exudate deep into the sulci can be seen in

severe cases (Fig 16-8, B and C)

Complications of meningitis CNS complications

develop in 21 50% of adult patients with bacterial

meningitis.21a These include hydrocephalus and

ven-triculitis, subdural effusion, subdural empyema, and

parenchymal lesions such as cerebritis, abscess, edema

with or without cerebral herniation, and cerebral

infarction. 21a

Hydrocephalus and ventriculitis Extensive

fibrin-opurulent exudates can obstruct the subarachnoid

space and result in extraventricular (communicating) hydrocephalus (Fig 16-8, A) Aqueductal or outlet obstruction causes intraventricular (noncommunicating) hydrocephalus Ventriculitis occurs in 30% of all patients and over 90% of neonates with meningitis.17 The ependymal lining of

the ventricles enhance tensely (see box) Choroid

plexitis is sometimes present (Fig, 16-9)

Pineal tumor (germinoma, pineoblastoma) PNET/medulloblastoma

Ependymoma

Uncommon

Collateral venous drainage pathway (Sturge-Weber, dural sinus occlusion, vascular malformation) Primary brain tumor (choroid plexus tumor) Metastatic tumor (extracranial primary)

Fig 16-8 A, Axial CECT scan in a child with H influenzae meningitis shows

mild nonspecific enlargement of the lateral ventricles Subtle meningeal enhancement is present over the frontal lobes and within the anterior

interhemispheric fissure (arrows) Axial (B) and coronal (C) contrast-enhanced

T1-weighted MR scans show thickened, enhancing leptomeninges (small

arrows) Note extension of inflammatory infiltrates deep into the sulci along the

Virchow-Robin spaces with ill-defined contrast-enhancing areas that represent

early cerebritis (large arrows)

Chapter 16 Infections of the Brain and Its Linings 683

Fig 16-10 Axial T2-weighted MR scans (A and B) in a 2-year-old child

with bilateral subdural hygromas complicating meningitis Note the smooth, bilateral high signal extraaxial

fluid collections (small single arrows)

The fluid does not extend into the underlying subarachnoid space, confirming its subdural location Note displaced cortical veins (curved arrows) Also note stretched cortical

veins crossing the frontal subdural space

(double arrows) Axial T1- (C) and

T2-weighted (D) MR scans that demonstrate prominent but normal subarachnoid spaces in a 7-month old infant are shown for comparison The extraaxial fluid extends into the sulci, confirming its subarachnoid location

Fig 16-9 Coronal postcontrast T1-weighted MR

scan demonstrates meningitis (small arrows), cerebritis (large arrow), and choroid plexitis (curved

arrow).

Fig 16-8, cont'd For legend see P 682.

684 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Subdural effusion Subdural effusion (SDE) is a

common feature of some bacterial meningitides (Fig

16-10, A and B) Twenty to fifty percent of meningitis

cases in children less than 1 year old are complicated by

sterile subdural effusions; 2% of these are infected

secondarily and become subdural empyemas 22 SDEs are

probably caused by inflammation of subdural veins with

fluid and albumin seepage into the subdural space.18 SDEs

should be distinguished from the prominent but normal

subarachnoid spaces often seen in infants under 1 year of

age (Fig 16-10, C and D).22a

Imaging findings of SIDE are crescentic extraaxial

fluid collections that are similar to CSF on both CT and MR Most SDEs resolve spontaneously and do not require treatment.18 Cortical vein thrombosis and cerebritis are rare.22

Empyema Sub- and epidural empyemas account

for approximately 20% to 33% of all intracranial infections.2 Nearly half of all cases are caused by sinusitis; the frontal sinus is the most common source.22 Postcraniotomy infection accounts for

an other 30% Between 10% to 15% of empyemas are complications of meningitis Empyema carries an 8%

to 12% mortality rate.22 Imaging studies in cerebral empyemas show cres-centic or lentiform extraaxial fluid collections that are low density on CT (Fig 16-11, A) and mildly hyper-intense compared to CSF on T2-weighted MR studies The cerebral convexities and interhemispheric fissure are common sites A surrounding membrane that enhances intensely and uniformly following contrast

administration is typically identified (Fig 16-11, B and

16-12).24 Cortical vein thrombosis with venous

Fig 16-11 A 29-year-old man with a history of otitis media presented with meningismus A, Axial CECT scan shows a

small left frontal subdural empyema (SDE) (small arrows) with meningitis, seen as an enhancing membrane (large

arrows) underlying the small SDE B, Follow-up CECT scan

9 days later shows the SDE (small arrows) has enlarged and the enhancing meninges (large arrows) appear thicker Note

increased mass effect with subfalcine herniation of the lateral

ventricles C, The SDE was drained but the patient

deteriorated This follow-up scan shows a small residual

SDE (curved arrow) Extensive left frontal lobe edema is seen (large arrows), caused by venous infarction The SDE

caused cortical vein thrombosis

Fig 16-13 A and B, Initial

axial CECT scans in a child with acute tuberculous men-ingitis show extensive basilar and sylvian leptomeningeal

enhancement (arrows) Note

severe extraventricular municating) hydrocephalus, seen as enlargement of the lateral, third, and fourth ven-

(com-tricles C, Follow-up NECT

scan 1 week later shows

bilat-eral cerebral infarcts D, NECT study 2 weeks after (C) shows a

shunt in the right frontal horn Note extensive enceph-alomalacic changes throughout both hemispheres

Fig 16-12 Coronal postcontrast T1-weighted

MR scan in patient with sphenoid sinusitis shows osteomyelitis of e middle cranial fossa floor

(curved arrow) An intensely enhanncing

lentiform-shaped extraaxial mass is present (traight arrows) Epidural empyema was found at surgery

Chapter 16 Infections of the Brain and Its Linings 685

686 PART FOUR Infection, White Matter Abnormalities, and Degenerative

Diseases

Infarction (Fig 16-11, C) and cerebritis or abscess formation

may ensue

Cerebritis and abscess Approximately 10% of patients

with meningitis show parenchymal abnormalities on imaging

studies (see Fig 16-8) Cerebritis is seen in approximately

25% of these cases.18 Cerebritis can evolve to frank abscess

formation (see subsequent discussion)

Cerebrovascular complications CNS infection is one of

the most common causes of acquired cerebrovascular disease

in children Cerebral infarction develops in up to 27% of

children with tubercular or complicated bacterial

meningitis.25 Cerebrovascular lesions are also the most

frequent intracranial complication of bacterial meningitis in

adults, accounting for 37% of all cases Vessel wall

irregularities, focal dilatations, arterial occlusion (Fig

16-13), venous infarcts (Fig 16-14), and dural sinus

thrombosis occur.26 The etiology is probably vasculitis,

coagulopathy, vasospasm, or a combination of these factors.25

Acute Lymphocytic Meningitis

Acute lymphocytic meningitis is usually viral in origin

Most viral meningitides are benign and selflimited

Enteroviruses (echoviruses, coxsackieviruses) are thought to

be responsible for 50% to 80% of viral meningitides Other

agents include mumps virus, Epstein-Barr virus, and

meningismus are similar to those of bacterial meningitis but

are often less severe.18 Imaging findings are usually normal

unless coexisting encephalitis occurs

Chronic Meningitis

Etiology and pathology

Etiology Chronic meningitis is a smoldering, indolent

process that is typified by Mycobacterium tuberculosis (TB)

infection Hematogenous spread from pulmonary tuberculosis

to the meninges is the putative mechanism in the

development of TB meningitis.27 Other organisms that are

less commonly implicated in chronic meningitis include

Gross pathology Chronic meningitis is characterized by a

thick, gray gelatinous exudate that predominately involves

the basilar cisterns.20

Microscopic appearance The exudate consists of

polymorphonuclear cells, fibrin, and hemorrhage In TB

meningitis, pronounced caseous necrosis, chronic

granulomas, endarteritis and perivascular parenchymal

inflammatory changes occur.20

Age and incidence After a decades-long decline, the

incidence of TB is rising in the United States, particularly

among immigrants, the homeless, IV drug abusers,

HIV-infected persons, and residents of priscons

Fig 16-14 Axial CECT scan in a 6-month-old

child with H influenzae meningitis (small

arrows) demonstrates complications of bifrontal

SDEs (arrowheads) and bilateral venous infarcts

(large arrows)

and nursing homes.29 TB remains a significant worldwide public health problem (see subsequent discussion)

Isolated TB meningitis is rare, representing leg than 5% of childhood bacterial meningitis cases 27, and 17.5% of all intracranial TB cases.30 Most children with tuberculous meningitis also have concomitant miliary brain infection27 and 11% of all patients have combined parenchymal/meningeal lesions.30 Diffuse active and chronic meningitis both occur

Location TB and other chronic meningitides have a

predilection for the basilar cisterns, although more generalized disease also occurs.20

Natural history The overall mortality rate in TB

meningitis is 25% to 30% with long-term morbidity ranging from 66% to 88% of survivors.30 Sequelae of chronic meningitis, particularly tuberculosis, include pachymeningitis,31 ischemia and infarction,32 atrophy,30 and calcifications Three quarters of infarctions occur

in the regions supplied by medial lenticulostriate and thalamoperforating arteries; one quarter involve the cerebral cortex Bilateral infarctions occur in 70% of cases.32

Imaging

CT NECT scans in chronic meningitis may dis-

close "en plaque" dural thickening "Popcorn"-like dural calcifications can be seen in some cases, partic-ularly around the basilar cisterns (Fig 16-15, A).33

Chapter 16 bInfections of the Brain and Its Linings 687

Fig 16-15 Classic changes of chronic tuberculous meningitis are illustrated by this case A, Axial

NECT scan demonstrates extensive "popcornlike"

calcifications in the basilar cisterns (arrows) B,

Axial T2-weighted MR scan shows the calcified

nodules (arrows) appear very hypointense compared

to adjacent brain C, Axial postcontrast T1WI shows

the lesions have low signal centers (open arrows) and enhancing rims (large arrows) (Courtesy N Yue.)

CECT may disclose abnormal meningeal enhancement

years after the initial infection has been treated.30

Sequelae of chronic meningitis, including atrophy and

cerebral infarction, may be striking

MR Unenhanced MR images often do not detect

active meningeal inflammation, whereas meningitis is

conspicuous on postcontrast T1Wl.33,34 Contrast

enhanced T1-weighted MR scans in chronic meningitis

show the characteristic basal meningeal inflammatory

pattern seen on CECT studies (Fig 16-16).35

Fig 16-16 MR findings of chronic meningitis are

illus-trated by this sagittal postcontrast T1-weighted scan in

a patient with coccidiodomycosis granulomatous

meningitis Note the extensively thickened, intensely

enhancing basilar meninges (arrows)

688 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Calcific meningeal nodules are markedly hypointense

on all pulse sequences (Fig 16-15, B and Q Peripheral

enhancement often persists (Fig 16-15, C).34

PYOGENIC PARENCHYMAL INFECTIONS

Cerebritis and Abscess

Cerebritis is the earliest stage of purulent brain

in-fection.17 Abscesses evolve from focal cerebritis in

predictable stages (see box) The neuroirnaging features

of cerebral abscesses reflect the underlying

pathophysiology of abscess formation.36

Etiology and pathology

Etiology Infectious agents gain access to the CNS in

several ways The most common cause is hematogenous

spread from an extracranial site Mastoid and sinus

infections spread directly to the CNS through retrograde

thrombophlebitis and may be preceded by empyema,

meningitis, or both (Fig 1617).36 Congenital or acquired

dural dehiscence and dermal sinuses are less common

causes

The specific organisms involved in cerebritis and

abscess are quite variable; in one third of cases, more

than one organism is found Most abscesses are produced

by pyogenic bacteria Overall, the organisms most

frequently isolated from cerebral abscesses are

streptococci (both aerobic and anaerobic) and

staph-ylococci, although gram-negative organisms are an

increasing cause of cerebral abscess.20 In neonates the

most frequently implicated organisms are Citrobacter,

Proteus, Pseudomonas, Serratia, and Staphylococcus

au-reus.1 These abscesses are often large and have poorly

formed capsules.17

Occasionally, organisms other than pyogenic bacteria

cause cerebral abscesses Examples include

My-cobacterium tuberculosis, fungi such as Actinomyces,

and parasites

Pathology The following four stages in abscess

evolution have been described37,38:

1 Early cerebritis

2 Late cerebritis

3 Early capsule formation

4 Late capsule formation

Early cerebritis is the initial phase of abscess

forma-tion During this stage, infection is focal but not yet

localized.1 An unencapsulated mass of congested vessels

with perivascular polymorphonuclear cell in-

Intracranial Abscess Development

Early cerebritis (3 to 5 days)

Late cerebritis (4 to 5 days to 10 to 14 days)

Early capsule (begins at about 2 weeks)

Late capsule (may last for weeks/months)

filtrates and edema is seen Scattered necrotic foci and microscopic petechial hemorrhages without frank tissue destruction are present (Fig 16-18, A).20 The early cerebritis stage typically lasts from 3 to 5 days

The late cerebritis stage then ensues The infection

becomes more focal as small necrotic zones coalesce Vessels proliferate and a central necrotic core is formed that is surrounded by an ill-defined ring of inflammatory cells, macrophages, granulation tissue, and fibroblasts (Fig

16-18, B) The late cerebritis

lasts from 4 to 5 days to 10 to 14 days

The early capsule stage begins around A the second

week following the initial infection Collagen and reticulin form a well-delineated capsule around a core consisting of liquefied necrotic and inflammatory debris The abscess capsule is initially thin and incomplete but becomes thicker

as more collagen is produced (Fig 16-18, C) As the abscess matures, mass effect and surrounding edema begin

to subside Gliosis develops around the abscess periphery During the late capsule stage, the capsule is complete and consists of the following three layers36 :

1 An inner inflammatory layer of granulation tissue and macrophages

2 A middle collagenous layer

3 An outer gliotic layer (Fig 16-18, D) The cavity gradually shrinks as the abscess heals The late capsule stage lasts from several weeks to months,

Fig 16-17 Axial postcontrast T1-weighted MR

scan in patient with frontal sinusitis show

complications of meningitis (small arrows) and abscess (large arrow)

Chapter 16 Infections of the Brain and Its Linings 689

Age and incidence In developed countries,

bac-terial abscesses in children are rare, even in

patients with congenital heart disease and immune

problems.5 Most abscesses in neonates and infants

occur complication of bacterial meningitis.1

Location The corticomedullary (gray-white mat-

ter) junction is the most common location, and the

frontal and parietal lobes are the most frequent

sites Less than 15% of intracranial abscesses occur

in the posterior fossa Multiple abscesses are

uncommon except in immunocompromised

patients.36

Natural history Improved diagnostic imaging

techniques and new antibiotic treatments have matically improved the prognosis of cerebral abscess Mortality has decreased from 40% to 50% to under 5%.36

dra-Imaging

Nuclear medicine Although CT or MR are the

most common imaging modalities used to evaluate patients with possible abscess, it is occasionally diffi-cult to distinguish between brain abscess and neo-plasm or between postoperative changes and infec-

Fig 16-18 Stages in abscess development are illustrated by these gross autopsy

speci-mens A, Meningitis (small arrows) is complicated by early cerebritis (large arrow)

Vascular congestion with an unencapsulated mass that consists of edema, inflammatory

infiltrate, and petechial hemorrhage is present B, Late cerebritis stage is illustrated by

this case Several necrotic zones have coalesced and formed a central liquefied core An

ill-defined rim of inflammatory cells and granulation tissue is present (arrows) C, Late

cerebritis/early capsule stage of abscess formation is shown D, Late capsule stage has a

welldelineated collagenous wall (small arrows) that surrounds the necrotic core Note

"daughter" or satellite lesion (open arrow) (D, Courtesy Royal College of Surgeons of

England, Slide Atlas of Pathology, Gower Medical Publishing.)

690 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

tion 99mTc HMPAO, a new radionuclide imaging label

for leukocytes, and radiolabeled polyclonal

immu-noglobulin (IgG) antibodies may be helpful in selected

cases.39,40

CT The neuroirnaging features of brain abscesses

vary with lesion stage During the early cerebritis

stage, NECT scans may be normal or show only a

poorly marginated subcortical hypodense area.36 In

some cases CECT studies disclose an ill-defined

contrast-enhancing area within the edematous region

(Fig 16-19, A)

As the lesion coalesces during the late cerebritis stage, a somewhat irregular enhancing rim that sur-rounds a central low density area is typical Delayed scans may show contrast "fills in" the central low density region.37,38 Peripheral edema is usually marked, and mass effect with sulcal obliteration is apparent The early capsule stage is characterized by formation

of a distinct collagenous capsule (see previous discussion) A relatively thin, well-delineated capsule that enhances strongly, uniformly, and continuosly

Fig 16-19 This 57-year-old woman was found unresponsive Axial CECT scan (A) was read

as normal (in retrospect, a tiny ill-defined enhancing focus is present in the left frontal lobe

[arrow] This is very early cerebritis) Pre- (B) and postcontrast (C) axial T1-weighted MR scans performed 9 days later show a predominately low signal left frontal mass (B, small

arrows) with focal hemorrhage (large arrow) and an irregularly enhancing rim (C, arrows)

The rim is slightly hyperintense on the unenhanced T1WI (B, small arrows) This is the late

cerebritis stage of abscess formation Axial CECT scans (D and E) obtained 5 weeks after

stereotactic drainage and antibiotic therapy show a small, ring-enhancing residual left frontal

lobe mass (D, arrows) Some edema persists but is diminished This is the late capsule stage

of abscess formation Note enlarged lateral ventricles and persistent choroid plexitis (E,

arrows).

is typical (Fig 16-20) Moderate vasogenic edema is

present.36 At this stage, the "ring-enhancing" mass N a

nonspecific imaging finding that can be seen in various

noninflammatory benign and neoplastic processes (see

box) In contrast to other lesions such as tumor, an

abscess rim typically is thickest near the cortex and

thinnest near the ependyma

Late capsule stage abscesses gradually shrink and the

peripheral edema diminishes and then disappears (Fig

16-19, D) Rim enhancement may persist for months,

long after clinical resolution occurs

MR MR findings in brain abscess also vary with

time During the initial, early cerebritis stage an

ill-defined subcortical hyperintense zone can be noted on

T2WI Postcontrast T1-weighted studies may disclose

poorly delineated enhancing areas within the iso- to

mildly hypointense edematous region (see Figs 16-8, B

and C, and 16-9)

During the late cerebritis stage, the central necrotic

area is typically hyperintense to brain on protondensity

and T2-weighted sequences The thick, somewhat

irregularly marginated rim appears iso- to mildly

hyperintense on T1WI (Fig 16-18, B) and iso- to

relatively hypointense on proton density- and

T2 weighted scans Peripheral edema is nearly always

present The rim enhances intensely following contrast

administration (Fig 16-18, C) Satellite lesions are

commonly present.41

During the early and late capsule stages, the

col-lagenous abscess capsule is visible on unenhanced scans

as a comparatively thin-walled, well-delineated iso- to

slightly hyperintense ring that becomes hypointense on

T2-weighted sequences (Fig 16-21)

Abscesses in immunocompromised patients

Im-paired host response can alter the imaging appearance of

cerebral abscesses Steroid treatment reduces edema and

mass effect; the capsule is thinner and enhances less

intensely.36 Patients with systemic diseases such as

lymphoma or leukemia frequently develop multiple

abscesses, often with unusual opportunistic organisms.36

Abscess morphology also varies in these patients

Lesions may have thick and irregular walls,

indistinguishable from primary or metastatic neoplasm

(Fig 16-22)

Patients with acquired immunodeficiency syndrom

(AIDS) rarely develop pyogenic abscesses, although

infections with opportunistic organisms are common

(see subsequent discussion)

Complications of Cerebral Abscesses

Abscess complications include the following20

1 Formation of satellite or "daughter abscesses"

rupture of poorly developed capsules and extension of the inflammatory process into the adjacent parenchyma.20 Satellite abscesses can also be formed when adjacent areas

of cerebritis coalesce

Ventriculitis Ventriculitis most often follows shunting

procedures, intraventricular surgery, placement of indwelling prosthetic devices, intrathecal

Infarct Less common

Thrombosed vascular malformation

Demyelinating disease (e.g., multiple sclerosis) Uncommon

Thrombosed aneurysm Other primary brain tumors (e.g., primary CNS lymphoma in AIDS)

Fig 16-20 Axial CECT scan in a patient with two

occipital lobe abscesses The well-delineated lesions with thin, ringlike enhancement patterns are typical of-but not pathognomonic for-abscess

Fig 16-21 Axial precontrast T1- (A) and T2-weighted (B) MR scans show the thin, well-delineated wall

(arrows) that characterizes the early capsule stage of

abscess formation The collagenous capsule is isointense

on T1- and hypointense on T2WI Postcontrast T1WI (C)

shows the typical in tensely enhancing capsule (arrows).

Fig 16-22 Axial pre- (A) and postcontrast (B) CT scans in this elderly patient

with poor nutritional status show an irregularly enhancing right frontal lobe mass with focal nodular thickening Preoperative diagnosis was glioblastoma multiforme Poorly loculated abscess was found at surgery

692 PART FOUR Infection, White Matter Abnormalities, and Degenerative Diseases

Chapter 16 Infections of the Brain and Its Linings 693

Fig 16-23 Axial gross pathology specimen (A) shows an abscess (large arrow) that has ruptured into the atrium, causing ependymitis (small arrows) Axial (B)

and coronal (C) postcontrast T1-weighted MR scans in another case, a

12-year-old boy with acute leukemia, show multiple parenchymal brain

abscesses (large arrows) An abscess in the deep cerebral white matter ruptured into the left atrium, causing intense ventriculitis (small arrows)

chemotherapy, or meningitis.42Purulent ependymitis

is occasionally caused by intraventricular abscess

rupture The medial side of an abscess cavity is

thin-ner than the well-vascularized cortical surface in

50% of cases Abscesses expand centrally toward

the white matter and may rupture through the

adjacent ependyma, inciting a pyogenic ventriculitis

Diffusely thickened, intensely enhancing ependyma

is seen on contrast-enhanced MR scans (Fig

16-23).42

Choroid plexitis The choroid plexus may serve as

a primary portal through which infectious agents gain entry to the CNS It can also be affected secondarily

when there is associated meningitis (see Fig 169),

encephalitis, or abscess rupture with ependymitis (Fig 16-19, E).43 The choroid plexus appears enlarged and enhances prominently on postcontrast T1-weighted MR scans