Epidural Abscess

Epidural abscess is most often the result of infection extending from an operative bed, the mastoids, paranasal sinuses, or calvarium into the epidural space. The imaging findings of epidural abscess are those of a focal epidural mass of low density on computed tomography (CT), low intensity or isointense on T1-weighted images (T1WI), and high signal on T2-weighted images (T2WI/fluid-attenuated inversion recovery [FLAIR] imaging). Enhancement, particularly on a thickened dural surface or in a ring configuration, and restricted diffusion (bright on DWI scans) may be observed. An epidural abscess can extend into the subgaleal space through emissary veins or intervening osteomyelitis, a finding more frequent when the abscess occurs as a postoperative complication. These same veins can lead to thrombophlebitis of draining veins and sinuses.

Epidural abscesses can cross the midline, distinguishing them from a subdural empyema, which is usually confined by the midline falx. Epidural abscess, like other epidural lesions such as hematoma, can be confined by sutures. A specific site of origin for the infection and its contiguous spread into the extracerebral space also helps establish the diagnosis of epidural abscess (Fig. 6-2).

Figure 6-2 Epidural abscess resulting from mastoiditis (M) on enhanced T1-weighted image. Arrows demonstrate medial extent of epidural collection. Enhancement is identified along the tentorium.

Subdural Empyema

Disruption of the arachnoid meningeal barrier by infection leads to the formation of CSF collections within the potential compartment of the subdural space. These may present acutely or chronically, and can be sterile or infected at time of presentation. Empyema rather than abscess is the appropriate term for a purulent infection in this potential space. Box 6-1 lists the causes of subdural empyema. Among the several possible mechanisms by which a subdural empyema is thought to form are (1) a distended arachnoid villus could rupture into the subdural space and infect it; (2) phlebitic bridging veins (secondary to meningitis) may infect the subdural space; (3) the subdural space may be infected by direct hematogenous dissemination; and (4) direct extension may occur through a necrotic arachnoid membrane from the subarachnoid space or from extracranial infections.

Clinical signs and symptoms in this group of patients include fever, vomiting, meningismus, seizures, and hemiparesis. The duration of symptoms before presentation ranges from 1 to 8 weeks. Venous thrombosis or brain abscess develops in more than 10% of patients with subdural empyema. The mortality rate from subdural empyema has been reported to range approximately from 12% to 40%. Prompt treatment with appropriate antibiotics and drainage through an extensive craniotomy can result in a favorable outcome.

Features of subdural empyema are those of extracerebral collections over the convexities and within the interhemispheric fissure, which on magnetic resonance (MR) display isointensity on T1WI and high signal on T2WI/FLAIR, and on CT show an isodense to low density extra-axial mass (Fig. 6-3). Empyema may be distinguished from subdural effusion on DWI if restricted diffusion is identified in the former; that is, empyemas are hyperintense on DWI (low apparent diffusion coefficient [ADC] value), whereas sterile effusions are low intensity on DWI and have ADCs similar to those of CSF. There may be effacement of the cortical sulci and compression of the ventricular system. A rim of enhancement may be observed. This enhancement occurs from granulation tissue that has formed over time in reaction to the adjacent infection. Coronal MR is a useful aid in confirming the exact location of the collection.

Figure 6-3 Subdural empyema on enhanced T1-weighted image. Open arrows point to thickened subdural collection. Enhancement is also noted along the tentorium. Note the second subdural empyema (asterisks) at the edge of the film.

Unfortunately, a chronic subdural hematoma can at times mimic the MR characteristics of a subdural empyema. On CT, chronic subdural hematomas might be low density or isodense and show thick membrane enhancement. On MR, chronic subdural hematomas can be isointense on T1WI and high intensity on T2WI/FLAIR. This occurs because methemoglobin from the old hematoma is absorbed and degraded. The hematoma consists of fluid and protein, including methemoglobin, so that the sum of these components is isointensity to brain on T1WI, whereas the increased water content produces high intensity on T2WI/FLAIR. MR enhancement is similar to that of CT. Subdural empyema can produce inflammatory changes in the subjacent part of the brain, whereas this does not occur in chronic hematoma. History and symptoms are also useful in distinguishing these different processes. Pick up the telephone before you pick up the Dictaphone. DWI may be helpful; if unrestricted ADC, suggest chronic hematoma.

Leptomeningitis

The pathologic process of meningitis (leptomeningitis) involves inflammatory infiltration of the pia mater and arachnoid mater (Fig. 6-4). Leptomeningeal inflammation most often occurs after direct hematogenous dissemination from a distant infectious focus. Pathogens also gain access by passing through regions that may not have a normal blood-brain barrier, such as the choroid plexus or circumventricular organs. Direct extension from sinusitis, orbital cellulitis, mastoiditis, or otitis media is also possible, as is infection after brain surgery. After septicemia, bacteria may lodge in venous sinuses and precipitate inflammatory changes, which in turn can interfere with CSF drainage, leading to hydrocephalus. With stagnation of CSF flow, bacteria are offered the opportunity to invade the meninges and indulge themselves. Early in the course of infection, congestion and hyperemia of the pia and arachnoid mater are present. Later, an exudate covers the brain, especially in the dependent sulci and basal cisterns. The leptomeninges become thickened. Clinical features are related to patient age (Box 6-2). Infants and particularly neonates may have a perplexing clinical picture, lacking physical signs that directly demonstrate meningeal irritation.

Figure 6-4 Leptomeningitis. A, FLAIR scan with normal cerebrospinal fluid (CSF) intensity (seen in ventricles) has bright CSF in subarachnoid space over convexities. B, Note the enhancement on this T1-weighted image deep within the sulci (arrowheads). Although some of the enhancement may be attributable to veins, especially with edematous meninges, the thickness and smeared margins argue for pial inflammation.

Imaging findings in early and successfully treated cases of meningitis are reported to be normal. Exceptions to this in acute meningitis are (1) visualization of distended subarachnoid space, particularly noted in the basal cisterns and along the interhemispheric fissure (most easily recognized in children as abnormal, especially on sequential studies leading to recovery); (2) high intensity of the subarachnoid fluid on FLAIR; (3) acute cerebral swelling (often leading to herniation and death); and (4) communicating hydrocephalus, with enlargement of the temporal horns and effacement of the basal cisterns.

Shortly after the onset of meningitis, it is not uncommon to visualize marked enhancement of the leptomeninges, better visualized on MR than on CT (much more common with bacterial lesions). Postgadolinium FLAIR images appear to be very sensitive for subarachnoid disease. Parenchymal abnormalities (uncommon) are primarily those of high signal on T2WI/FLAIR or of low density on CT. DWI is usually normal unless adjacent encephalitis develops. Vasculitis may ensue and involve either arteries or veins; hence, patterns of infarction associated with meningitis differ depending on the location, number, and type of vessels involved. It is more demarcated than cerebritis. Box 6-3 summarizes the spectrum of imaging abnormalities in purulent meningitis.

Many additional complications occur as a result of inflammation involving the meninges. These sequelae are better imaged and characterized than are the manifestations of the meningitis itself. Communicating hydrocephalus can occur as both an early and a late manifestation of leptomeningitis, often becoming symptomatic to the point of requiring ventricular shunting. The subacute imaging findings of complicated leptomeningeal infection are those of atrophy, encephalomalacia (infarction), focal abscess, subdural empyema formation, and basilar loculations of CSF (Box 6-4).

Sinusitis can serve as a nidus for leptomeningeal infection and can produce septic thrombosis of adjacent venous sinuses and pseudoaneurysm formation if the cavernous sinus is affected (Fig. 6-5). Labyrinthitis ossificans (see Chapter 12) may occur as a late finding secondary to infiltration of the cochlear channels by infected CSF.

Figure 6-5 A, Septic thrombosis of the sagittal sinus (arrow) from meningitis (note enhancing leptomeninges—arrowheads) caused an infarct in the left high frontal lobe (low intensity area—open arrow). B, Meningitis as a complication of sphenoid sinusitis (s) produced this cavernous sinus thrombosis with swelling of the sinus (arrowheads). Observe the soft tissue in the cavernous sinus and the unusual pattern of flow voids. Long arrow is on the mycotic aneurysm that has developed. C, Common carotid angiogram reveals this mycotic aneurysm.

Neonates represent a special case with respect to the cerebral sequelae of bacterial leptomeningitis. The most commonly encountered organism is gram-negative bacilli, followed by group B Streptococcus, Listeria monocytogenes, and others. The neonatal meningitides are believed to be acquired as a result of the delivery process, chorioamnionitis, immaturity, or iatrogenic problems (e.g., catheters, inhalation therapy equipment). The lack of a developed immune system at birth makes neonates susceptible to organisms that are normally not very virulent. These children frequently have severe parenchymal brain damage as a result of the infection that ultimately produces a multicystic-appearing brain, often with hydrocephalus. The late imaging findings are those of multifocal encephalomalacia leading to multiple distended intraventricular and paraventricular cysts (Fig. 6-6). In children (age 1 month to 15 years), Haemophilus influenzae is a common pathogen associated with upper respiratory infections and can produce a virulent meningitis with vascular infarction. Other bacteria in this group are Neisseria meningitidis and Streptococcus pneumoniae. In adults, S. pneumoniae and N. meningitidis are the most common bacterial organisms producing meningitis. H. influenzae characteristically produces a high rate of subdural effusions.

Figure 6-6 Computed tomography of a child demonstrates paraventricular cysts (c), porencephaly, central atrophy, and a left subdural empyema (arrows).

The radiologist should appreciate that the diagnosis of bacterial meningitis is a clinical one based on history and physical examination and confirmed by CSF studies. The radiologist does not identify the organism with imaging (without cheating and looking at the microbiology report). Imaging is important, however, to rule out a mass lesion or other diagnostic possibilities before lumbar puncture (LP) and to delineate the complications of meningitis. The most common presentation is headache and stiff neck, and the differential is migraine versus subarachnoid hemorrhage versus leptomeningitis. Subarachnoid hemorrhage is first excluded by CT before LP.

What should you look for before clearing a patient for LP? Be sure that you do not see cerebellar tonsils impacted in the foramen magnum, cerebellar herniation syndromes, obliterated or trapped fourth ventricles (see Chapter 8), cerebellar masses or strokes, transtentorial downward herniation, completely effaced basal cisterns/sulci, or significant subfalcine herniation. Obliteration of the superior cerebellar and quadrigeminal plate cisterns with sparing of the ambient cisterns is concerning. Better to err on suggesting use of clinical acumen in diagnosing meningitis than clearing a patient for LP and having them herniated and die from the “approved tap.”

Leptomeningitis versus Pachymeningitis (Fig. 6-7)

These entities may be legitimately separated by their enhancement pattern on MR. Leptomeningeal enhancement follows the gyri/sulci or involves the meninges around the basal cisterns (because the dura-arachnoid is widely separated from the pia-arachnoid here) (see Figs. 6-4 and 6-5A). Pachymeningeal enhancement is thick and linear/nodular, following the inner surface of the calvarium, falx, and tentorium and without extension into the sulci or involvement of the basal cisterns (see Fig. 6-7). An inflammatory process involving endothelial cells opens the tight junctions, allowing the pathogens to reach the leptomeninges and producing leptomeningitis. In carcinomatous meningitis, the tumor cells lack the properties that bacterial cell walls possess. They do not produce the same inflammatory process and the blood-brain barrier remains intact. The tumor cells can pass through the capillaries (no tight junctions) of the dura, resulting in dural inflammation. CSF cytology in these cases may be negative. As everyone is aware, the leptomeninges can be involved by tumor. In such cases, the CSF is positive and the tumor cells probably get there via the choroid plexus (no blood-brain barrier) or from extension of superficial parenchymal lesions. Box 6-5 provides a list of conditions that can produce pachymeningeal versus leptomeningeal enhancement.

Figure 6-7 Pachymeningitis. Note that the very thick enhancement of the dura mater of the tentorium (arrows) and middle cranial fossa does not extend to the depths of the sulci. This is characteristic of pachymeningitis and distinguishes it from leptomeningitis.

Box 6-5 Conditions That Produce Pachymeningeal and Leptomeningeal Enhancement

PACHYMENINGEAL

CSF leak

Idiopathic hypertrophic

Metastases, including those involving the skull

Pachymeningitis

Shunting

Spontaneous intracranial hypotension

LEPTOMENINGEAL

Infection

Subarachnoid hemorrhage

Metastases

Sarcoidosis

Stroke

Pyogenic Brain Abscess

Cerebral abscess is most often the result of hematogenous dissemination from a primary infectious site. The various causes of cerebral abscess are listed in Box 6-6. The most frequent locations are the frontal and parietal lobes in the distribution of the middle cerebral artery. Intracranial abscess affects predominantly preadolescent and middle-age groups. In part, this is related to the incidence of congenital heart disease, IV drug abuse, acquired immune deficiency syndrome (AIDS), and tympanomastoid and paranasal sinus infections. In all series there is a preponderance of male patients over female. Abscesses may be unilocular or multilocular, solitary or multiple. A variety of bacterial organisms are commonly cultured from brain abscesses (Box 6-7). In addition, numerous other pathogens can infect the brain when the immune system is compromised.

Abscess formation appears to depend on stasis of bacteria and a focus of ischemic or necrotic brain. Abscess formation has been divided into four stages based on animal work performed with CT: (1) early cerebritis (1 to 3 days), (2) late cerebritis (4 to 9 days), (3) early capsule formation (10 to 13 days), and (4) late capsule formation (14 days and later). The cerebritis phase of abscess formation consists of an inflammatory infiltrate of polymorphonuclear cells, lymphocytes, and plasma cells. By the third day a necrotic center is formed. This deliquescent region is surrounded by inflammatory cells, new blood vessels, and hyperplastic fibroblasts. In the late cerebritis phase, extracellular edema and hyperplastic astrocytes are seen. Thus, the cerebritis phase of abscess formation starts as a suppurative focus that breaks down and begins to become encapsulated by collagen at 10 to 13 days. This process continues with increasing capsule thickness.

The deposition of collagen is particularly important because it directly limits the spread of the infection. Factors that affect collagen deposition include host resistance, duration of infection, characteristics of the organism, and drug therapy. Steroids may decrease the formation of a fibrous capsule and the effectiveness of antibiotic therapy in the cerebritis phase and may reduce antibiotic penetration into the brain abscess. Brain abscesses that are spread hematogenously usually occur at the junction of the gray and white matter. Collagen deposition is asymmetric, with the side toward the white matter and ventricle having a thinner wall, resulting in a propensity for intraventricular rupture or daughter abscess formation, which is sometimes useful to neophytes in distinguishing abscess from tumor (neoplastic walls are uniformly thick). Death from cerebral abscess is due to its mass effect with herniation or the development of a ventricular empyema. In the late capsule phase, there is continued encapsulation and decreasing diameter of the necrotic center. Conservative therapy with antibiotics alone has been advocated in conjunction with close monitoring of the clinical and imaging findings in patients with multiple abscesses, in eloquent locations, and in poor surgical candidates.

The characteristics of cerebral abscess depend on the pathologic phase during which the abscess is being examined. In the cerebritis phase, CT demonstrates low-density abnormalities with mass effect. Patchy or gyriform enhancement is present. On MR, one may see low intensity on T1WI and high signal intensity on T2WI/FLAIR (Fig. 6-8), with a typical epicenter at the corticomedullary junction and patchy enhancement. In the late cerebritis phase, ring enhancement may be present. The presence of ring enhancement should not unequivocally imply capsular formation. It is important for the surgeon contemplating drainage to appreciate that a firm, discrete abscess may not be present despite ring enhancement.

Figure 6-8 Early cerebritis. A, T2-weighted image (T2WI)/FLAIR with high intensity in right parietal region of a drug addict, 3 days after becoming symptomatic. Note absence of defined margins. B and C, Late cerebritis (10 days after onset of symptoms). T1WI (B) and T2WI/FLAIR (C) demonstrate more definition in the forming abscess.

A thin rim of low signal on T2WI and possibly high signal on T1WI characterize the wall of an abscess and would be more unusual for necrotic tumors. This may be related to free radical formation (secondary to oxidative effect of the respiratory burst of the bacteria), hemorrhage, or other factors. At this point the DWI scan may be bright; however, some cases of cerebritis may also show cytotoxic edema. The low ADC is probably related to high protein, high viscosity, and cellularity (pus) within the abscess cavity.

After 2 to 3 weeks a mature abscess appears on T1WI as a round, well-demarcated low-intensity region with mass effect and peripheral low intensity (edema) beyond the margin of the lesion. On T2WI/FLAIR, high intensity is noted in the cavity and in the parenchyma surrounding the lesion (Fig. 6-9). Concentric bands of varying thickness on T2WI/FLAIR have been seen in abscesses. DWI is usually positive (Fig. 6-10).

Figure 6-9 Abscess. A, Unenhanced sagittal T1-weighted image (T1WI) demonstrating frontal high-intensity ring with low intensity surrounding the abscess. B, Abscess is well defined on this T2WI/FLAIR together with the surrounding high-intensity vasogenic edema. C, Ring enhancement on T1WI. Ring is smoother on outside than inside, which is considered a sign of abscess (arrows). This was a streptococcal abscess. D, Note the ring enhancement with leptomeningeal/venous engorgement in this patient with multiple abscesses.

Figure 6-10 Diffusion-positive (low apparent diffusion coefficient [ADC]) brain abscess. A, Diffusion-weighted imaging (DWI) typifies the very bright abnormality in brain abscess caused by high protein, high viscosity, and cellularity (pus) resulting in restricted diffusion (low ADC; very bright DWI). B, FLAIR image at a slightly different level with a complete ring surrounded by vasogenic edema (increased intensity). C, Postcontrast T1-weighted image with complete ring enhancement.

The vast majority of pyogenic abscesses evoke considerable edema. Remember that the vasogenic edema surrounding the pyogenic abscess will be bright on ADC maps, indicating NO restricted diffusion unlike the abscess itself, which is dark on ADC with restriction of diffusion. A ring-enhancing lesion that does not evoke much edema should steer you away from a diagnosis of abscess. A differential diagnosis, including granuloma, primary or metastatic tumor, and demyelinating disease, is more appropriately proffered in such ambiguous cases. Most pyogenic lesions enhance with a thin rim surrounding the necrotic center. Tiny abscesses may appear to have nodular enhancement. Ventricular or subarachnoid spread has been described on FLAIR as having higher intensity than CSF.

On CT, the encapsulated intracerebral abscess shows a low-density center and low density surrounding the lesion (edema). Ring enhancement is virtually always present in pyogenic brain abscess. Thickness, irregularity, and nodularity of the enhancing ring should raise the suspicion that one is dealing with a tumor (most of them) or an unusual infection (e.g., fungus). However, many exceptions to this rule occur and nodular, irregular pyogenic abscesses are not that infrequent. Some of these represent subacute and chronic abscesses, whereas others are the result of adjacent daughter abscess formation. Multiple ring-enhancing lesions are more consistent with hematogenous dissemination of an infectious focus. Multiple rings in a single location can be seen with daughter abscesses but have also been noted with glioma (and other lesions). Box 6-8 is a partial differential diagnosis of the ring-enhancing lesion.

An uncommon observation on noncontrast CT is the presence of a complete ring (Fig. 6-11). The noncontrast ring is most often identified in metastases, less often in abscess or glioma, and hardly ever in hematoma or infarct. This finding could help in unknown cases of ring enhancement by narrowing the differential diagnosis.

Figure 6-11 Brain abscess with rings on computed tomography and magnetic resonance imaging. A, Noncontrast CT illustrates the complete ring in the right thalamus, indicating a structural abnormality—in this case an abscess. Note the ring is surrounded by low density representing vasogenic edema. B, T1-weighted image (T1WI) also shows a complete ring, which may be slightly hyperintense (from hemorrhage versus free radicals). C, T2WI with hypointensity in the ring. Surrounding vasogenic edema is high intensity. D, Postcontrast T1WI demonstrates the thin ring enhancement consistent with pyogenic brain abscess. E, Diffusion-weighted imaging with very bright central region.

Occasionally, the abscess may spread into the ventricles because of lower collagen content in the medial wall, producing periventricular enhancement or high density within the ventricles. Hemorrhage is rare in acute abscesses. Toxoplasmosis after treatment may show hemorrhagic byproducts.

The treated brain abscess may enhance and show high signal on T2WI/FLAIR or low density on CT for long periods of time (>8 months) in an otherwise asymptomatic patient.

Several reports in the literature discuss proton MRS (1HMRS) in pyogenic abscess. These include resonances from cytosolic amino acids (0.9 ppm), acetate (1.92 ppm), lactate (1.3 ppm), and alanine (1.5 ppm). It is believed that the presence of amino acid resonances may distinguish pyogenic abscess from necrotic brain tumors. See Box 6-9 for MRS helpful hints.

Ventriculitis (Ependymitis)

Ventriculitis can be seen as part of the spectrum of infection, including meningitis as a postoperative complication (particularly related to ventricular shunting) or as an isolated finding. Ventriculitis is more commonly seen in neonates with meningitis and is a feature of cytomegalovirus (CMV) infection as well as some peripartal anaerobic infections. Organisms are introduced into the ventricle as a result of bacteremia, from abscess, trauma, or instrumentation of the ventricle. The ventricles can be enlarged, and on T2WI/FLAIR high intensity can be observed surrounding the ventricles or even within the CSF on FLAIR. The key to the diagnosis is subependymal enhancement (Fig. 6-12). Choroid plexus enhancement has been reported. Periventricular calcification can be seen on CT after neonatal ventriculitis. Purulent ependymitis can be bright on DWI.

Figure 6-12 Ependymitis. Enhancement of the ependyma (arrows) on T1-weighted image.

Enhancement of the ependyma is also observed in lymphoma (the most likely diagnosis in patients infected with human immunodeficiency virus [HIV] with subependymal enhancement) and other malignant lesions with subependymal spread. This finding would be unusual in toxoplasmosis.

Choroid Plexitis

Capillaries of the choroid plexus, because of their fenestrated epithelium, serve as a conduit through which infections may gain access to the brain. A second barrier between blood and CSF, the choroidal epithelium, possesses tight junctions and prevents passive exchange of proteins and other solutes. Usually, choroid plexitis is seen in association with encephalitis, meningitis, or ventriculitis. It is rarely seen as an isolated infection. Pathogens with a propensity for producing choroid plexitis include Nocardia and Cryptococcus.

The normal choroid plexus is isodense on CT or isointense to brain on MR and enhances. Calcifications of the choroid plexus produce hypointensity on MR and high density on CT. Xanthogranulomatous change to the choroid plexus is bright on DWI and sometimes FLAIR but does not enhance much. Asymmetry of the lateral ventricle choroid plexus or bilateral symmetric enlargement of the choroid plexus should alert one to possible choroid plexitis. The differential diagnosis of choroid plexus disease is provided in Box 6-10.

Septic Embolus

The most frequent manifestation of infective endocarditis is stroke, with Staphylococcus aureus by far the most common organism. However, sepsis from any cause, including pulmonary arteriovenous malformations, pulmonary infection, intravenous drug abuse, infected catheters with cardiac septal defects, and occult infection may produce septic emboli to the brain. Septic emboli are associated with persistent mass effect, edema, and enhancement beyond a 6-week period. This should alert the radiologist to consider septic infarction with development of abscess formation in association with cerebral infarction. Rarely, bland infarction may serve as a nidus for subsequent bacterial colonization from bacteremia and abscess formation. Another diagnostic possibility would be tumor emboli mimicking a stroke. This usually results in hemorrhage or tumoral edema. Cardiac myxoma can embolize and produce acute stroke, and later the tumor grows into the vessel wall to produce aneurysmal dilatation. The vast majority of septic emboli are self-induced by drug users. Septic emboli result in brain abscess, mycotic aneurysm (these occur in distal vessels, usually the middle cerebral artery, and are less likely to hemorrhage), or obliterative vasculitis (Fig. 6-13). Mycotic aneurysm presents with intraparenchymal-dominating subarachnoid hemorrhage. DWI scans may be positive for both the stroke and the infection, but the size is smaller than typical strokes.

Figure 6-13 Subacute bacterial endocarditis. A, Enhanced T1-weighted image in a patient with subacute bacterial endocarditis. Note the multiple enhancing abscesses at the corticomedullary junction (arrows). B, Lateral angiogram in a patient with subacute bacterial endocarditis. Two mycotic aneurysms (arrows) on branches of middle cerebral artery are identified.

Thus far, we have covered generic CNS infections with respect to their location and particular imaging appearances. We now consider specific pathogens in normal patients, in patients with AIDS, and in immunosuppressed patients without AIDS. Making the winning diagnosis in immunosuppressed patients is challenging because of their clinical state and the propensity for multiple pathologic processes to occur in tandem. The bottom line is that many infections today occur in a complex environment. The radiologist must attempt to unravel the vagaries of the imaging findings in the context of the clinical findings.

This section is not intended to be comprehensive but provides a sample of what you might encounter.

Herpes Simplex

Herpes simplex virus (HSV) is the most common cause of fatal endemic encephalitis in the United States. The survivors of infections with this virus have severe memory and personality problems. Early diagnosis and therapy with antiviral agents can favorably affect the outcome. Both the oral strain (type 1) and the genital strain (type 2) may produce encephalitis in human beings. Type 2 is responsible for infection in the neonatal period, presumably acquired either transplacentally or during birth from mothers with genital herpes. This strain may cause a variety of teratogenic problems, including intracranial calcifications, microcephaly, microphthalmia, and retinal dysplasia. It carries a high morbidity and mortality rate, with CNS infection either primary or part of a disseminated infection. Sequelae from neonatal herpes also include multicystic encephalomalacia, seizures, motor deficits, mental and motor retardation, and porencephaly. The features of intracranial neonatal herpes are different from those in adults and are summarized in Box 6-11. The early findings in neonatal herpes are subtle regions of low density on CT in various regions in the brain parenchyma, including gray matter and cerebellum. These regions enlarge rapidly, with meningeal and gyriform enhancement. Later gyri may demonstrate strikingly high density on noncontrast CT. Calcification can appear between 17 and 21 days after disease onset and can be variable in location. Thalamic hemorrhage has been observed. Atrophy is also seen early in this disease. The normal low intensity on T1WI of neonatal white matter and high intensity on T2WI/FLAIR limit the sensitivity of MR in this disease. Loss of gray-white contrast is an early abnormality that can be incorrectly interpreted as poor quality images. DWI may show gyriform high signal. The MR correlate of the high density in the cortex on CT is hypointensity on T2WI/FLAIR. The cause of these characteristic cortical changes is not understood, but increased cortical blood volume (with deoxyhemoglobin), calcification, laminar necrosis, and other associated paramagnetic ions may be possible causes. Cystic encephalomalacia is often the end game of neonatal herpes.

Table 6-1 Characteristic Targets of Viral Encephalitides

The HSV type 1 virus is responsible for the fulminant necrotizing encephalitis seen in children and adults. It has an incidence of one to three cases per million. The clinical picture (just like board examination encephalopathy) is one of acute confusion and disorientation followed rapidly by stupor and coma. Seizures, viral prodrome, fever (in more than 95% of cases), and headache are common presentations. Focal neurologic deficits such as cranial nerve palsies are found in less than 30% of cases. Those patients with left temporal lobe disease become symptomatic earlier because of their language impairment and thus may have more subtle imaging findings at the time of presentation.

The pathologic findings are stereotypic. The virus asymmetrically attacks the temporal lobes, insula, orbitofrontal region, and cingulate gyrus. Approximately one third of CNS herpes infections are due to primary infection (usually in persons younger than age 18 years), whereas two thirds are the result of reactivation confirmed by the presence of preexisting antibodies. One proposed route of entry has been through the nasal airway to the olfactory tracts. A possible explanation for the focality and latency of HSV type 1 may depend on its known residence in the trigeminal ganglia. This latent virus under certain circumstances becomes reactivated and spreads along the trigeminal nerve fibers, which innervate the meninges of the anterior and middle cranial fossae. A diffuse meningoencephalitis with a predominant lymphocytic infiltration is seen. There is marked necrosis and hemorrhage, with loss of all neural and glial elements. The result in untreated cases, if the patient survives, is an atrophic cystic parenchyma. Laboratory diagnosis is dependent on polymerase chain reaction (PCR) on CSF for herpes.

In type 1 herpes encephalitis, MR findings within the first 5 days of the disease show high intensity on T2WI/FLAIR and either positive or negative DWI in the temporal and inferior frontal lobes and progressive mass effect, including the cingulate region, whereas CT findings at this time may be subtle to nonexistent (Fig. 6-14). Negative diffusion images may indicate some possibility for reversibility. The earliest CT abnormalities are low-density areas in the temporal lobe and insular cortex. Hemorrhage may be identified. The areas of abnormality in the temporal lobe and insula abruptly end at the lateral putamen, which is characteristically spared. MR is frequently able to detect asymmetric bilateral temporal lobe involvement. This picture is virtually pathognomonic of HSV infection. Unlike other viral encephalitides (see later discussion), HSV type 2 rarely involves the basal ganglia. The full extent of parenchymal damage is difficult to assess during the first 10 days of the disease.

Figure 6-14 Herpes simplex virus type 1 gallery. Case 1: A, Subtle swelling of the left temporal lobe without enhancement is seen on the postcontrast T1-weighted image (T1WI). B, Coronal T2WI shows sparing of the basal ganglia but involvement of the hippocampus and perinsular region. Case 2: C, Computed tomography demonstrates bilateral swelling of the medial frontal and insular cortex. D, Bilateral disease is clearly evident on the T2WI. Case 3: E, This case shows involvement superiorly of biparietal regions. F, The gradient echo scan shows punctate hemorrhages (arrowheads) in the cortex.