Noncongenital central nervous system infections in children: radiology review.

ORIGINAL ARTICLE

Noncongenital Central Nervous System Infections in Children Radiology Review Jorge Humberto Davila Acosta, MD,* Claudia Isabel Lazarte Rantes, MD,* Andres Arbelaez, MD,†‡ Feliza Restrepo, MD,†‡ and Mauricio Castillo, MD§∥ Abstract: Infections of the central nervous system (CNS) are a very common worldwide health problem in childhood with significant morbidity and mortality. In children, viruses are the most common cause of CNS infections, followed by bacterial etiology, and less frequent due to mycosis and other causes. Noncomplicated meningitis is easier to recognize clinically; however, complications of meningitis such as abscesses, infarcts, venous thrombosis, or extra-axial empyemas are difficult to recognize clinically, and imaging plays a very important role on this setting. In addition, it is important to keep in mind that infectious process adjacent to the CNS such as mastoiditis can develop by contiguity in an infectious process within the CNS. We display the most common causes of meningitis and their complications. Key Words: pediatric CNS infections, complications of CNS infections, complicated meningitis, pediatric neuroimaging (Top Magn Reson Imaging 2014;23: 153–164)

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nfections of the central nervous system (CNS) are a very common worldwide health problem in childhood with significant morbidity and mortality.1 These CNS infections account for 1% of primary hospital admissions and 2% of nosocomial infections.2 The number of CNS infections that occur as a result of viral agents far exceeds those caused by bacteria, yeast, molds, and protozoa combined. Enteroviruses (EVs) account for 85% to 95% of viral meningitis in the developed world; however, the most common form of viral encephalitis in the underdeveloped world is herpes simplex encephalitis. Other viruses that occasionally cause encephalitis with marked focal features include arboviruses and Epstein-Barr virus. The number of cases of meningitis caused by Haemophilus influenzae type B (HIb) decreased by 94% after 1988 when the vaccine was introduced.3 The HIb was one of the leading causes of invasive bacterial disease and pneumonia in children in 2000, killing more than 370,000 children globally, with the highest burden of disease in low- and middle-income countries.4 Meningitis caused by Streptococcus pneumoniae has also decreased by 30%, from 1.1 cases per 100,000 in the late 1990s to 0.79 per 100,000 in the period of 2004 to 2005.5 Recent data suggest that, in very low birth weight population, gram-negative bacilli are important causes of neonatal hospital-acquired infections.6 The most commonly isolated gramnegative rod organisms, in approximately equal distribution, are Escherichia (E.) coli, Klebsiella, Enterobacter, Serratia, and From the *Diagnostic Imaging Department, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada; †Neuroradiology Section, Radiological Department, Hospital Pablo Tobon Uribe, Medellin, Colombia; ‡Neuroradiology Unit, Link Diagnostico Digital, Medellín, Colombia; §University of North Carolina at Chapel Hill, Chapel Hill, NC. Reprints: Jorge Humberto Davila Acosta, MD, Diagnostic Imaging Department, Children’s Hospital of Eastern Ontario, (CHEO) 401 Smyth Road, Ottawa, Ontario, Canada K1H 8L1 (e‐mail: [email protected]). The authors declare no conflict of interest. Copyright © 2014 by Lippincott Williams & Wilkins

Pseudomonas.7 Neonatal sepsis is divided into early-onset and late-onset sepsis, based on the timing of infection and presumed mode of transmission. Early-onset sepsis is defined by an onset in the first week of life, with some studies limiting early-onset sepsis to infections occurring in the first 72 hours and that are caused by maternal intrapartum transmission of invasive organisms. Lateonset sepsis is usually defined as infection occurring after 1 week of life and is attributed to pathogens acquired postnatal.8 In earlyonset sepsis, the most common organisms described are Group B Streptococcus (GBS), E. coli, Listeria monocytogenes, Enterococci, and HI. In late-onset sepsis, there are coagulase-negative Staphylococcus, Staphylococcus aureus, Enterococci, multidrugresistant gram-negative rods (E. coli, Klebsiella, Pseudomonas, Enterobacter, Citrobacter, Serratia), and Candida.9 Accurate early recognition and treatment are paramount to avoid long-term complications of brain injury, especially in very young patients. Imaging features of the CNS infections in children share similar characteristics to those of adults; however, the complications are different. Recognizing this complication is crucial for radiologists to be able to provide a diagnosis. The CNS infections can be classified as congenital and noncongenital infections. Noncongenital, non-TORCH source of infections due to viral, bacterial, and fungal diseases with their complications will be discussed here.10

IMAGING MODALITIES Ultrasound Ultrasound (US) is the primary imaging modality to assess for cerebral pathologies such as hemorrhages or extra-axial collections in neonates up to the first 4 to 5 months (Fig. 1). Brain US is a broadly and easily available and a sensitive imaging modality that can be performed with minimal or no disturbance in neonates, especially in the sick and unstable ones.11 However, cranial US has a low sensitivity in term babies with hypoxic-ischemic injury.12 Differentiating ischemic stroke from hemorrhagic infarction is sometimes difficult by US in the early stages because of their similar echogenicity.13 Despite its low sensitivity in hypoxic ischemic injury, US remains the primary imaging modality because it allows detection of periventricular/intraventricular hemorrhage and hydrocephalus.11

Cranial Computed Tomography The ionizing radiation dose is the main consideration in pediatric imaging because younger patients have higher risk of developing radiation-associated diseases.14 However, CT is more accessible than magnetic resonance imaging (MRI) and does not require sedation as frequently as MRI contributing positively to a prompt diagnosis.

Brain MRI It is a highly sensitive technique in the assessment of the brain and is preferred over CT for most diseases outside acute head trauma; however, it may be difficult to obtain especially if sedation is required.

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FIGURE 1. Four-month-old female infant with GBS meningitis and new onset of seizures. A, Head US shows a right-sided subdural collection containing multiple debris (arrows). B, DWI shows decreased diffusivity involving the cortex and subcortical white matter of the right frontal lobe (arrow) representing ischemia related to meningitis. C and D, Axial T1 WI and axial T2 WI show cortical laminar necrosis (arrowhead) and a multiseptated subdural collection (arrow).

Sagittal sequences allow for the assessment of midline structures and are optimal for evaluating the corpus callosum, pituitary gland, hypothalamus, and cerebellum.10 T1- and T2-weighted images in at least 2 planes should be obtained in all patients younger than 18 months old. Single-shot T2 weighted images (WI) (ie, SSFSE, HASTE) is not efficient enough in evaluating the neonatal or pediatric brain. Although these sequences can give anatomic information, brain maturation and brain damage are not well evaluated.11 FLAIR images are not useful in neonates and infants because, in the early stages of the brain maturation process, the white matter has a higher water content; however, it

may be useful in older children in whom maturation is more advanced (>2 years).15 Gadolinium injection is not often performed in neonates except in cases of meningitis to look for complications.11 The MR spectroscopy (MRS) and diffusion-weighted images (DWIs) are effective in detecting and characterizing abnormal areas in the brain.11 The MR angiography (MRA) and MR venography (MRV) are useful to rule out venous thrombosis or lack of signal in brain arteries in case of infarcts. Susceptibility-weighted MR sequences and/or echo-gradient sequences are useful in the assessment of hemorrhage or calcification. The DWI is sensitive in the detection of brain lesions

FIGURE 2. Three-year-old boy with postsurgical endocarditis and multiple brain septic embolic abscesses. A, Sagittal T1 WI postcontrast demonstrates a rounded peripheral ring enhancing lesion at the right frontal lobe. B, Axial DWI shows restricted diffusion within the pons.

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Noncongenital CNS Infections in Children

FIGURE 3. Three-year-old boy with infected midline posterior fossa scalp dermoid cyst. Sagittal (A) T1 WI postgadolinium and (B) T2 WI show intracranial extension (arrow) and cerebellitis with postgadolinium enhancement (arrow head).

related to hypoxic-ischemic injury in very early stages.16,17 It also plays an important role in detecting intracranial empyemas and pyogenic abscesses. Pyogenic abscess and empyema classically can show restricted diffusion; however, restricted diffusion is not specific to pyogenic abscess, and it may be present in other ring-enhancing lesions, such as hypercellular tumors, subacute hematomas, and nonpyogenic infections.18

NONCONGENITAL INFECTIONS There are 4 common routes of entry of infectious agents into the CNS2: 1. Hematogenous dissemination from a distant infectious focus is the most common; an example for this is embolization of infected vegetation in a patient with myocarditis (Fig. 2). 2. Direct implantation is usually traumatic and rarely iatrogenic when microorganisms are introduced through a lumbar puncture needle or during surgery. 3. Local extension from infected dermal sinus (Fig. 3), infected open encephaloceles, infected opened dysraphism, sinusitis, orbital cellulitis, mastoiditis, otitis media (Fig. 4), osteomyelitis (Fig. 5), or an infected tooth is less common. 4. Spread of infection along the peripheral nervous system has also been described for certain viruses such as rabies and herpes simplex.

playing a limited role. The clinical presentation is often characteristic, with fever, headache, neck stiffness, vomiting, and photophobia being most common.23 Typical signs of infective meningitis, including neck stiffness and Kerning sign, are typically subtle or may be even absent in very young children. Seizures are seen in up to 40% of patients.24 Most cases of bacterial meningitis in immunologically normal infants older than 1 month are caused by HIb, Streptococcus pneumonia, or Neisseria meningitis; E. coli is also an important organism in older infants.25,26 Because of the lack of ionizing radiation, its higher sensitivity for ischemic lesions and infarctions, and its ability to easily detect purulent collections, MRI is preferred over CT, even in emergency situations.27,28 Usually, CT and MRI do not show any significant changes in the early stage of acute bacterial meningitis.2 When abnormal, the extracerebral spaces and ventricular system may be normal or enlarged or show evidence of protein or pus accumulation27 (Fig. 1). As the infection progresses, unenhanced CT shows mild dilatation of the ventricular system and subarachnoid spaces with diffuse cerebral swelling. On MRI, the cerebral parenchyma in

BACTERIAL MENINGITIS Bacterial meningitis is a serious infection of the CNS that affects approximately 1 per 100,000 children each year. It is mainly caused by Neisseria meningitidis (Fig. 6) and Streptococcus pneumonia19(Fig. 1). Bacterial meningitis can lead to severe damage of cerebral tissues, which is mediated by a complex system of inflammatory pathways such as proinflammatory and anti-inflammatory cytokines and reactive oxygen intermediates and by ischemia, which is caused by vasculitis and cerebral edema20,21 Bacterial meningitis occurs when pathogenic virulence factors overcome host defense mechanisms. Related to this, the neurotropic potential of the most common bacterial causes of meningitis (S. pneumonia, HI, Neisseria meningitides, and E. coli) relates to their ability to evade host defenses. Specifically, a meningeal pathogen must sequentially colonize host mucosal epithelium, invade and survive in the intravascular space, cross the blood-brain barrier, and survive in the cerebrospinal fluid.22 The diagnosis is usually based on clinical history, physical examination, and cerebrospinal fluid (CSF) analysis, with imaging © 2014 Lippincott Williams & Wilkins

FIGURE 4. Six-year-old girl with right-sided otitis media (arrow) and meningeal enhancement around the right-sided VII/VIII cranial nerves (arrowhead) representing meningitis. www.topicsinmri.com


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FIGURE 5. Three-year-old boy with osteomyelitis of the clivus (arrow head) and a small epidural collection (arrow) at the perimedullary cistern, which shows peripheral enhancement (A, B) and diffusion restriction (C).

early stages may show normal signal intensity, edema, ischemia, infarction (Figs. 7, 8), hemorrhage, inflammatory changes, or necrosis with abscess. Periventricular edema may be related to bacteria-induced periventricular white matter necrosis or to unbalanced CSF circulation with development of hydrocephalus.27 Previous skull base trauma and dysraphism (mostly dermal tracts and neuroenteric fistulae) are common in children, often

resulting in recurrent meningitis (Fig. 9). Once the infection is lodged into the meninges, it can spread via the leptomeningeal sheaths of the penetrating cortical vessels in the perivascular spaces, resulting in cerebritis and brain abscess formation.29 Spread of infection to the ependymal surfaces can lead into subsequent ventriculitis and aqueductal ependymitis, resulting in obstructive hydrocephalus. Ventriculitis is seen in almost

FIGURE 6. Two-week-old newborn with Neisseria meningitides meningitis. A, T2 WI shows cortical edema (long arrow), enlarged subarachnoid spaces, and high signal intensity within the cortical veins, suggesting cortical venous thrombosis (short arrow). B, DWI shows restriction diffusion in the cortex (arrowhead). C, Postcontrast T1 WI shows avid meningeal enhancement (arrowheads). D, 3 weeks later, axial T2 WI shows multiple areas of cystic encephalomalacia (arrowheads).

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FIGURE 7. Fifteen-month-old female infant with GBS meningitis. A, Axial DWI shows focal area of infarct at the deep white matter of the left frontal lobe. B, 6 days later, there were multiple new areas of restricted diffusion in the bilateral basal ganglia, related to new infarcts related to encephalitis.

30% of patients with bacterial meningitis, and this number can be as high as 92% of neonates, compromising the secretion of CSF and its washout of the ventricles.10

VIRAL INFECTION The EVs are the most common cause of viral meningitis in the United States in children aged 5 to 10 years30 (Fig. 10). Nonsimplex herpes viruses such as Herpes zoster are infrequent causes of meningitis and encephalitis in healthy children.31 The onset of EV meningitis is abrupt and associated with fever.

FIGURE 8. Five-month-old female infant with bacterial meningitis. Axial DWI shows focal areas of restricted diffusion in the cortex and subcortical right white matter in the right frontal and right occipital lobes. © 2014 Lippincott Williams & Wilkins

Neonates and infants commonly present nonspecific clinical findings such as poor feeding, vomiting, exanthema, and respiratory tract findings. In older children and adolescents, the constitutional symptoms may be more frequent and include anorexia, vomiting, headaches, respiratory tract symptoms, and abdominal pain. The CNS viral infections often also can cause encephalitis, which happens when there is infection of the brain parenchyma with associated inflammation. This is accompanied by changes in mental status and behavior and, sometimes, reduced level of consciousness.1 In the setting of meningitis, CT or MRI is usually acquired before lumbar puncture to exclude increased intracranial pressure. The MRI is the best tool for early diagnosis of meningitis,

FIGURE 9. Two-year-old boy with frontal dermal sinus. Coronal T1 WI postcontrast demonstrates multiple abscess formations, which communicate with a congenital dermal sinus (arrowhead). www.topicsinmri.com


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FIGURE 10. Five-year-old boy with EV encephalitis. Axial FLAIR WI shows multiple foci of abnormal signal intensity involving the bilateral centrum semiovale. There was no associated restricted diffusion or susceptibility artifact.

and FLAIR seems to be the most sensitive sequence for detecting meningeal disease by showing increased signal intensity in the subarachnoid spaces.32 T2-weighted images can show hyperintense areas in the brain due to edema caused by the inflammatory process (Fig. 11). T1-weighted images with contrast show meningeal or leptomeningeal enhancement. The MRI is important to detect complications of the viral meningitis such as hydrocephalus, ventriculitis, empyema, venous sinus thrombosis, and arterial or venous infarcts. Herpes encephalitis usually involves the medial temporal lobes, inferolateral frontal lobes, and insular cortex in immunocompetent patients with sparing of the basal ganglia (Fig. 12). In immunosuppressed children, the involvement is diffuse, and in neonates, it tends to be extralimbic with sparing of the basal ganglia. Measles may also involve the CNS in 3 different fashions: acute postinfectious encephalitis, acute progressive encephalitis, and subacute sclerosing encephalitis.33 Acute postinfectious encephalitis complicates approximately 0.1% of measles cases and is associated with a high mortality. Neurologic symptoms begin

FIGURE 12. Axial T2 WI demonstrates increased signal intensity involving the cortex of the right insula and right parietal-occipital lobe—characteristic findings for virus herpes simple encephalitis in a 12-year-old boy.

4 to 14 days after the cutaneous rash. The thalami, corpus striatum, and cerebral cortex can be involved and are well seen by MRI.34 In progressive encephalitis, the symptoms begin 3 to 6 months after the disease. Subacute sclerosing encephalitis predominantly affects children and has a gradually progressive course leading to death within 1 to 2 years. It seems to be an infection caused by the measles virus that reactivates many years after the initial illness.35 The MRI is very sensitive in detecting changes in the CNS, whereas CT findings are nonspecific. The MRI may be normal in the first 3 to 4 months after 1 set of clinical signs. Later, increased T2 signal intensity can be seen in the cerebral cortex and subcortical white matter most commonly in the parietal and temporal lobes, which is bilateral but asymmetrical.36 Mass effect and contrast enhancement can be found in the early stages. When the disease progresses, increased T2 signal intensity is seen in the periventricular white matter and corpus callosum. Finally, diffuse cerebral atrophy develops.37 Rasmussen encephalitis is one of the intractable epilepsies of childhood. It is a disorder characterized by seizures,

FIGURE 11. Three-year-old girl with viral cerebellitis. A, Axial T2 WI displays high signal intensity in the left cerebellar hemisphere. B, Sagittal postgadolinium T1 WI shows enhancement of the left cerebellar hemisphere.

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FIGURE 13. Ten-year-old boy with varicella. A, Axial T2 WI shows focal areas of gliosis in the left caudate nucleus from previous focal infarcts. B, MRA demonstrates irregularity and severe narrowing in the M1 segment of the left MCA representing vasculitis.

progressive hemiplegia, and progressive psychomotor deterioration. Different patterns of epilepsy have been described, the most common being partial motor epilepsy, which is characterized by clonic movements, frequently in the face and upper extremities.38 Viruses have been described in neurons, astrocytes, oligodendrocytes, and perivascular cells in affected brains, suggesting a viral etiology.10 Usually, first imaging studies in Rasmussen encephalitis are normal. Thereafter, high T2 signal intensity develops in the cerebral cortex and subcortical white matter, and later on, atrophy develops. The frontal and temporal lobes are most commonly affected.39 In the terminal stages, MRI demonstrates destruction of the involved areas and unilateral ventricular enlargement. The MRS can show low N-acetylaspartate in the white matter throughout the affected hemisphere.32 The MRS, using short echo time, can demonstrate elevated glutamate/glutamine, possibly secondary to the nearly continuous seizure activity.40 Varicella-Zoster encephalitis is not a common overall cause of encephalitis. Usually, children present acute cerebellar ataxia, dysarthria, nystagmus, and vomiting in clinical onset. The CT is usually negative. The MRI shows increased signal intensities in

the T2 and FLAIR sequences in the cerebellum, and small lesions may be seen at the cortical-white matter junction in the cerebral cortex and in the basal nuclei.41 The lesions in the basal ganglia, especially in the lentiform nuclei, represent infarctions. Varicella has an affinity for the M1 segment of the middle cerebral artery resulting in a focal vasculitis (Fig. 13). Involvement of other large intracranial arteries with subsequent infarctions has also been described.

FUNGAL INFECTIONS Systemic fungal infections affect predominantly either extremely preterm neonates, because of the immaturity of their immune systems, their poor skin barrier to fungal invasion, and the use of corticosteroids to treat chronic lung disease, or neonates with congenital or acquired immunodeficiencies.42 Parenchymal involvement by CNS fungal disease may result in granuloma formation, cerebritis, and abscess formation (Fig. 14). Fungal infections are uncommon but are important sources for meningitis in the immunosuppressed population.

FIGURE 14. Fifteen-year-old boy with relapsed acute lymphoblastic leukemia and fungal infection (Mucormicosis). A, Coronal T1 WI with gadolinium demonstrates a peripheral ring enhancing formation involving the intraconal and extraconal portions of the left orbit in its medial aspect (small arrowhead) with intracranial extension into the left frontal region (large arrowhead). B, Axial DWI shows decreased diffusivity of the intracranial lesion in the left frontal region (small arrow), representing abscess formation. © 2014 Lippincott Williams & Wilkins

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FIGURE 15. Fourteen-year-old teenager with disseminated histoplasmosis. A, Sagittal T1 WI postgadolinium shows an oval-shaped abscess within the cervical cord with peripheral ring enhancement. B, Axial DWI evidences multiple focal areas of restricted diffusion in both cerebral hemispheres, in keeping with multiple abscesses secondary to histoplasmosis.

Candida Infections with Candida species are usually in the form of skin and mucous membrane involvement. Candida occurs frequently in immunodeficiency illnesses characterized by depressed T-cell function. Risk factors contributing to the development of candidemia include treatment with broad-spectrum antibiotics and intravenous catheterization. Candida meningitis usually develops via hematogenous seeding of the meninges from the oropharyngeal.43 Clinical features of neonatal candidiasis consist of meningitis or meningoencephalitis with prominent fontanelles, seizures, lethargy, and/or coma. When Candida invades the CNS, it usually progresses to gross abscess formation, and this is commonly seen in patients who develop candidiasis as a complication of antibiotic therapy where a diffuse cerebritis with widespread microabscesses may also develop.10 Unenhanced MRI may show hypointense T2 lesions secondary to hemorrhage or nonspecific hyperintense white matter lesions.44 Small enhancing lesions are seen, which may have restricted diffusion. Meningitis has also been described. Like other fungal disease, Candida vascular involvement may

lead to infarctions, particularly in the basal ganglia, and mycotic aneurysms leading to subarachnoid hemorrhage.45

Cryptococcosis It is a very common fungal infection of the CNS in immunosuppressed adults, although it is unusual in children. Children infected by this fungus most commonly show hydrocephalus, cortical atrophy, gelatinous pseudocysts, choroid plexitis, and ischemic changes.10

Aspergillosis This occurs more commonly in premature infants, in children with malignancies such leukemia, and/or those undergoing immunosuppressive therapies.10 Although imaging findings of aspergillosis are nonspecific, certain imaging characteristics may help in narrowing the differential diagnosis. Invasive aspergillosis can result in granuloma formation and/or encephalitis, with or without abscess formation.42 Because aspergillus grows branching hyphae at physiologic body temperatures, brain parenchymal involvement is more commonly found than meningeal infection,

FIGURE 16. Four-year-old girl with left otitis media. A, coronal CT with contrast shows an epidural collection on the left temporal fossa (black arrow) displacing the left transverse sinus medially; no thrombosis is visualized. B, Axial DWI displays restricted diffusion (arrow head) of the epidural collection representing empyema.

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FIGURE 17. Five-year-old girl with otomastoiditis. Axial T1 WI with gadolinium shows hyperenhancing soft tissue within the left-sided mastoid cells, in keeping with otitis media (arrow). There is a filling defect within the left transverse sinus consistent with venous sinus thrombosis.

which is typically associated with unicellular yeast organisms. Aspergillus abscesses may be surrounded by low signal intensity on T2-weighted and gradient-echo images. The hypointense T2 signal rim has been attributed to small amount of hemorrhage with hemosiderin-laden macrophages.46 Aspergillus has a tendency to invade blood vessels.47 There is evidence of intracranial vascular invasion with secondary thrombosis and infarction as a complication.

Histoplasmosis It is an infection that occurs from breathing in the spores of the fungus Histoplasma capsulatum. The CNS involvement is recognized in 10% of disseminated histoplasmosis and includes parenchymal lesions and lymphocytic meningitis48 (Fig. 15).

Uncomplicated Meningitis The CT and MRI studies in uncomplicated meningitis are usually unremarkable; however, some enhancement of the meninges


FIGURE 19. Newborn with sepsis born from mother with chorioamnionitis. Coronal DWI shows restricted diffusion of the corpus callosum and deep periventricular white matter, likely representing areas of infarction secondary to vasculitis.

after contrast can be found. Usually, in bacterial meningitis, the contrast enhancement occurs in the convexities, whereas in granulomatous meningitis, the enhancement is usually in the basal meninges. The diagnosis of early meningitis is based on clinical signs and symptoms and the results of lumbar puncture; imaging is best reserved to look for complications in infants.10

Complications of Meningitis Empyemas Subdural effusions are simple fluid collections that show CSF-like signal in all MRI sequences and do not enhance (Fig. 16). Sterile subdural collections without significant mass effect do not need treatment and usually regress with treatment of meningitis. They can become infected, resulting in subdural empyemas (SDEs). These SDEs are seen along the cerebral convexities in nearly 50% of cases and along the falx in another 20% of cases.49 They appear as extra-axial fluid collections on CT that are isodense to slightly hyperdense to CSF. They can be large and/or bilateral. On MRI, SDEs typically appear

FIGURE 18. Six-year-old girl with myocarditis presented with focal seizure. Axial T2 WI (A) displays increased signal intensity in the white matter/cortex of the right frontal-parietal lobes and right insula. MRA (B) shows complete obliteration of the major branches (M2 and M3) of the right middle cerebral artery in keeping with septic embolus. © 2014 Lippincott Williams & Wilkins

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FIGURE 20. Preterm baby of 34-week corrected gestational age with gram-negative sepsis and ventriculitis. Sagittal T2 (A) and axial DWI (B) demonstrate severe hydrocephalus. There is a focus of restricted diffusion adjacent to the lateral wall of the posterior horn of the right lateral ventricle (small arrow), likely representing a small abscess.

as crescentic extra-axial fluid collections, often bilateral. They show mildly hyperintense signal intensity compared with CSF on T1-weighted images and show isointensity or hyperintensity compared with CSF on T2-weighted images. Because SDEs contain pus, they have restricted diffusion on apparent diffusion coefficient maps. After contrast administration, they show enhancement of their limiting membranes, which is caused by inflammatory changes with fibrosis and hypervascularity.

Venous Thrombosis Venous sinus thrombosis may arise as a direct consequence of meningitis or be secondary to adjacent mastoiditis, which itself may be a cause of meningitis50,51 (Fig. 17). This thrombosis may involve the cortical venous sinuses or cortical veins. Thrombosis of the subependymal veins results in periventricular necrosis. Focal necrosis within the arterial and venous walls may result in

arterial or venous thrombosis.29 Overall, cerebral infarctions can be seen in up to 30% of neonates with bacterial meningitis.10,25 Venous thrombosis can be visualized in acute phase in noncontrast CTas a hyperdensity in the sinuses or cortical veins (“cord” sign). Subacute sinus thrombosis can also be seen by CT with contrast as the “empty delta sign,” which is a triangle of decreased density in the posterior region of the affected sinus surrounded by either enhancing sinus walls and/or peripherally enhanced flowing blood.52,53 On MRI, subacute sinus thrombosis is hyperintense on T1weighted images. In the acute or chronic phase, the diagnosis of sinus thrombosis by MR may be difficult.3 Nowadays, MRV facilitates the diagnosis of venous sinus thrombosis, despite that moving blood and subacute clot are hyperintense and of timeof-flight venograms. This is why, in a patient with a subacute thrombus in the T1-weighted images, an MRV with contrast should be performed.3

FIGURE 21. Five-year-old girl with meningoencephalitis. A, axial T2 WI demonstrates increased signal of the cortex of the right frontal lobe (arrows). B, Axial DWI shows decreased diffusivity at the same region related to infarct postvasculitis secondary to meningitis. C, Follow-up axial T2 WI 1 year later shows enlargement of the pericerebral CSF spaces in the right frontal and insular region representing atrophy with associated gliosis secondary to previous meningoencephalitis.

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Venous Infarctions Venous infarcts from thrombosis of the cortical veins (Fig. 4) are easily documented, and imaging findings are as per the site of involvement. Compared with arterial infarcts, venous infarcts do not always show restricted diffusion, are often hemorrhagic, and occur in nonarterial territories.29

Arterial Infarcts Arterial infarctions in the setting of meningitis are usually caused by arteritis from involvement of the perivascular spaces and arterial walls.29 The DWI is the best tool to study early infarcts. The classic location of arterial infarcts related to meningitis is along the perforator vessels of anterior and middle cerebral arteries (Fig. 18). Allergic fungal sinusitis can also produce infarcts and/or intracranial invasion.54 Another frequent complication is postviral vasculitis.

Cerebritis and Abscess Most bacterial abscesses in children are caused by complications of bacterial meningitis. Four different stages of evolution from cerebritis to abscess are classically known, and these are early cerebritis, late cerebritis, early capsule formation, and late capsule formation. Cerebritis means inflammation of the brain parenchyma. It usually shows decreased diffusivity, hypointense signal intensity on T1 WI and hyperintense signal on T2 WI. After contrast administration, it could demonstrate inhomogeneous enhancement (Fig. 19). In the late stage of cerebritis, an abscess begins to form with a well-defined walled-off capsule. On T2 images, the capsule is hypointense, and its contents are hyperintense. On FLAIR sequences, the lesion is hyperintense. On T1-weighted images after contrast administration, the well-defined wall shows enhancement, which implies a mature abscess. Some neoplasms can have a cystic appearance and may simulate an abscess. On DWI, abscesses show central restricted diffusion. Perfusion MRI helps to differentiate brain abscess from neoplasm, because the former has decreased cerebral blood volume and flow in the enhancing capsule.

Hydrocephalus Hydrocephalus is the most common complication of meningitis. It can be communicating or noncommunicating, depending on whether the site of obstruction is intraventricular or extraventricular. The CT and MRI both show the presence of hydrocephalus with subependymal edema acutely secondary to fluid reabsorption (Fig. 20).

Gliosis and Cystic Encephalomalacia Depending on the patient’s age at the time of the occurrence of the intracranial infection, the result of the injury may result in the loss of white matter with resultant changes of cystic encephalomalacia in perinatal age and gliosis in older children (Figs. 6, 21). REFERENCES 1. Riddell JT, Shuman EK. Epidemiology of central nervous system infection. Neuroimaging Clin N Am. 2012;22:543–556.


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Central nervous system infections in travelers.

Role of radiology in central nervous system stimulation.

Bacterial Infections of the Central Nervous System.

Bacterial infections of the central nervous system.

Emerging infections of the central nervous system.

Sequelae of central-nervous-system enterovirus infections.

Rickettsial infections of the central nervous system.

Fungal infections of the central nervous system.

Aetiology and Outcomes of Suspected Infections of the Central Nervous System in Children in Mbarara, Uganda.

Neuroinvasion and Inflammation in Viral Central Nervous System Infections.

Neurotropic Enterovirus Infections in the Central Nervous System.

Overview of the effect and epidemiology of parasitic central nervous system infections in African children.

Isotonic intravenous maintenance fluid reduces hospital acquired hyponatremia in young children with central nervous system infections.

Central nervous system germinomas. A review.

Neuroimaging of viral infections of the central nervous system.

Letter: Warning about using cephalothin with central nervous system infections.

Treatment strategies for central nervous system infections: an update.

Fungal central nervous system infections: prevalence and diagnosis.

Nonanthrax Bacillus infections of the central nervous system.

Central nervous system infections due to vancomycin-resistant enterococci: case series and review of the literature.

Central nervous system infections masquerading as cerebrovascular accidents: Case series and review of literature.

Histoplasma capsulatum infections of the central nervous system. A clinical review.

Cavernous angiomas of the central nervous system in children.

Trauma of the central nervous system in children.