24 - 145 Brain Abscess and Empyema

145 Brain Abscess and Empyema

tomography with fluorodeoxyglucose may be useful in identifying a systemic site for biopsy in patients with suspected carcinomatous meningitis or sarcoidosis when other tests are unrevealing. Genetic testing can identify mutations that cause rare monogenic autoin­ flammatory disorders or underlying immunocompromised states. MENINGEAL BIOPSY If CSF is not diagnostic, then a meningeal biopsy should be strongly considered in patients who are severely disabled, who need chronic ventricular decompression, or whose illness is progressing rap­ idly. The activities of the surgeon, pathologist, microbiologist, and cytologist should be coordinated so that a large enough sample is obtained and the appropriate cultures and histologic and molecular studies, including electron-microscopic and PCR studies, are per­ formed. The diagnostic yield of meningeal biopsy can be increased by targeting regions that enhance with contrast on MRI or CT. With current microsurgical techniques, most areas of the basal meninges can be accessed for biopsy via a limited craniotomy. In one series, MRI demonstrated meningeal enhancement in 47% of patients undergo­ ing meningeal biopsy; biopsy of an enhancing region was diagnostic in 80% of cases, biopsy of nonenhancing regions was diagnostic in only 9%, and sarcoidosis (31%) and metastatic adenocarcinoma (25%) were the most common conditions identified. Tuberculosis is the most common condition identified in many reports from outside the United States. APPROACH TO THE ENIGMATIC CASE In approximately one-third of cases, the diagnosis is not known despite careful evaluation of CSF and potential extraneural sites of disease. A number of the organisms that cause chronic meningitis may take weeks to be identified by cultures. In enigmatic cases, several options are available, determined by the extent of the clinical deficits and rate of progression. It is prudent to wait until cultures are finalized if the patient is asymptomatic or symptoms are mild and not progressive. Unfortunately, in many cases, progressive neurologic deterioration occurs, and rapid treatment is required. Ventricular-peritoneal shunts may be placed to relieve hydrocepha­ lus, but the risk of disseminating the undiagnosed inflammatory process into the abdomen must be considered. Empirical Treatment  Diagnosis of the causative agent is essential because effective therapies exist for many etiologies of chronic men­ ingitis, but if the condition is left untreated, progressive damage to the CNS and cranial nerves and roots is likely to occur. Occasion­ ally, empirical therapy must be initiated when all attempts at diag­ nosis fail. In general, empirical therapy in the United States consists of antimycobacterial agents, amphotericin B (often combined with flucytosine) for fungal infection, and/or glucocorticoids for non­ infectious inflammatory causes. It is important to direct empirical therapy of lymphocytic meningitis at tuberculosis, particularly if the condition is associated with low CSF glucose, since untreated disease can be devastating within weeks. Prolonged anti-TNF ther­ apy and anti–programmed cell death 1 (PD-1) inhibitors can cause reactivation of TB, and such patients who develop chronic menin­ gitis should be treated empirically with antituberculous therapy if the etiology is uncertain. Even with treatment, TB meningitis can carry high rates of morbidity. In the Mayo Clinic series, the most useful empirical therapy was administration of glucocorticoids rather than antituberculous therapy. When proceeding with empiric glucocorticoids, caution should be maintained whenever a transient response to treatment is noted, as some infectious (e.g., tuberculosis and cysticercosis) and noninfectious (e.g., lymphoma) etiologies may temporarily respond to glucocorticoid monotherapy. Carcino­ matous or lymphomatous meningitis may be difficult to diagnose initially, but the diagnosis becomes evident with time. ■ ■THE IMMUNOSUPPRESSED PATIENT Chronic meningitis is not uncommon in the course of HIV infec­ tion. Pleocytosis and mild meningeal signs often occur at the onset

of HIV infection, and occasionally, low-grade meningitis persists. In worldwide populations, M. tuberculosis is the most common cause of chronic meningitis, followed by C. neoformans. Toxoplasmosis com­ monly presents as intracranial abscesses and also may be associated with meningitis. Other important causes of chronic meningitis in AIDS include infection with Nocardia, Candida, or other fungi; syphilis; and lymphoma (Fig. 144-2). With HIV infection, primary CNS lymphomas may arise, which are typically positive for EBV infection. Toxoplasmo­ sis, nocardiosis, cryptococcosis and other fungal infections are impor­ tant etiologic considerations in individuals with immunodeficiency states other than AIDS, including those due to immunosuppressive medications. Because of the increased risk of chronic meningitis and the attenuation of clinical signs of meningeal irritation in immunosup­ pressed individuals, CSF examination should be performed for any persistent headache or unexplained change in mental state.

■ ■FURTHER READING Aksamit AJ: Chronic meningitis. N Engl J Med 385:930, 2021. Baldwin K, Avila JD: Diagnostic approach to chronic meningitis. Neurol Clin 36:831, 2018. Chang CC et al: Global guideline for the diagnosis and management of cryptococcosis: An initiative of the ECMM and ISHAM in coopera­ tion with the ASM. Lancet Infect Dis 24:e495, 2024. Johnson TP, Nath A: Biotypes of HIV associated neurocognitive dis­ orders. Curr Opin Inf Dis 335:223, 2022. Kacar M et al: Hereditary systemic autoinflammatory diseases and Schnitzler’s syndrome. Rheumatology 58:vi31, 2019. Lu LX et al: IgG4-related hypertrophic pachymeningitis: Clinical fea­ CHAPTER 145 tures, diagnostic criteria and treatment. JAMA Neurol 71:785, 2014. Saifon W et al: Distinguishing clinical characteristics of central ner­ vous system tuberculosis in immunodeficient and non-immunodefi­ cient individuals: A 12-year retrospective study. Ann Clin Microbiol Antimicrob 22:69, 2023. Wilson MR et al: Chronic meningitis investigated via metagenomic Brain Abscess and Empyema next-generation sequencing. JAMA Neurol 75:947, 2018. Karen L. Roos, Kenneth L. Tyler

Brain Abscess and

Empyema BRAIN ABSCESS ■ ■DEFINITION A brain abscess is a focal, suppurative infection within the brain parenchyma, typically surrounded by a vascularized capsule. The term cerebritis is often employed to describe a nonencapsulated brain abscess. ■ ■EPIDEMIOLOGY A bacterial brain abscess is a relatively uncommon intracranial infec­ tion, with an incidence of ~0.3–1.3:100,000 persons per year. Pre­ disposing conditions include otitis media and mastoiditis, paranasal sinusitis, pyogenic infections in the chest or other body sites, penetrat­ ing head trauma or neurosurgical procedures, and dental infections. In immunocompetent individuals, the most important pathogens are Streptococcus spp. (anaerobic, aerobic, and viridans [40%]), Entero­ bacteriaceae (Proteus spp., Escherichia coli sp., Klebsiella spp. [25%]), anaerobes (e.g., Bacteroides spp., Fusobacterium spp. [30%]), and staphylococci (10%). In immunocompromised hosts with underlying HIV infection, organ transplantation, cancer, or immunosuppressive therapy, most brain abscesses are caused by Nocardia spp., Toxoplasma

gondii, Aspergillus spp., Candida spp., and Cryptococcus neoformans. In Latin America and in immigrants from Latin America, the most common cause of brain abscess is Taenia solium (neurocysticercosis). In India and East Asia, mycobacterial infection (tuberculoma) remains a major cause of focal CNS mass lesions.

■ ■ETIOLOGY A brain abscess may develop (1) by direct spread from a contiguous cranial site of infection, such as paranasal sinusitis, otitis media, mas­ toiditis, or dental infection; (2) following head trauma or a neurosurgi­ cal procedure; or (3) as a result of hematogenous spread from a remote site of infection. In up to 25% of cases, no obvious primary source of infection is apparent (cryptogenic brain abscess). Approximately one-third of brain abscesses are associated with otitis media and mastoiditis, often with an associated cholestea­ toma. Otogenic abscesses occur predominantly in the temporal lobe (55–75%) and cerebellum (20–30%). In some series, up to 90% of cere­ bellar abscesses are otogenic. Common organisms include streptococci, Bacteroides spp., Pseudomonas spp., Haemophilus spp., and Enterobac­ teriaceae. Abscesses that develop as a result of direct spread of infec­ tion from the frontal, ethmoidal, or sphenoidal sinuses and those that occur due to dental infections are usually located in the frontal lobes. Approximately 10% of brain abscesses are associated with paranasal sinusitis, and this association is particularly strong in young males in their second and third decades of life. The most common pathogens in brain abscesses associated with paranasal sinusitis are streptococci (especially Streptococcus milleri), Haemophilus spp., Bacteroides spp., Pseudomonas spp., and Staphylococcus aureus. Dental infections are associated with ~2% of brain abscesses, although it is often suggested that many “cryptogenic” abscesses are in fact due to dental infections. The most common pathogens in this setting are streptococci, staphylo­ cocci, Bacteroides spp., and Fusobacterium spp. PART 5 Infectious Diseases Hematogenous abscesses account for ~25% of brain abscesses. Hematogenous abscesses are often multiple, and multiple abscesses often (50%) have a hematogenous origin. These abscesses show a pre­ dilection for the territory of the middle cerebral artery (i.e., posterior frontal or parietal lobes). Hematogenous abscesses are often located at the junction of the gray and white matter and are often poorly encap­ sulated. The microbiology of hematogenous abscesses is dependent on the primary source of infection. For example, brain abscesses that develop as a complication of infective endocarditis are often due to viridans streptococci or S. aureus. Abscesses associated with pyogenic lung infections such as lung abscess or bronchiectasis are often due to streptococci, staphylococci, Bacteroides spp., Fusobacterium spp., or Enterobacteriaceae. Enterobacteriaceae and Pseudomonas aerugi­ nosa are important causes of abscesses associated with urinary sepsis. Congenital cardiac malformations that produce a right-to-left shunt allow bloodborne bacteria to bypass the pulmonary capillary bed and reach the brain. Similar phenomena can occur with pulmonary arteriovenous malformations. The decreased arterial oxygenation and saturation from the right-to-left shunt and polycythemia may cause focal areas of cerebral ischemia, thus providing a nidus for microorgan­ isms that bypassed the pulmonary circulation to multiply and form an abscess. Streptococci are the most common pathogens in this setting. Abscesses that follow penetrating head trauma or neurosurgical procedures are frequently due to methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, Enterobacteriaceae, Pseudomonas spp., and Clostridium spp. ■ ■PATHOGENESIS AND HISTOPATHOLOGY Results of experimental models of brain abscess formation suggest that for bacterial invasion of brain parenchyma to occur, there must be preexisting or concomitant areas of ischemia, necrosis, or hypoxemia in brain tissue. The intact brain parenchyma is relatively resistant to infection. Once bacteria have established infection, brain abscess frequently evolves through a series of stages, influenced by the nature of the infecting organism and by the immunocompetence of the host. The early cerebritis stage (days 1–3) is characterized by a perivascu­ lar infiltration of inflammatory cells, which surround a central core

of coagulative necrosis. Marked edema surrounds the lesion at this stage. In the late cerebritis stage (days 4–9), pus formation leads to enlargement of the necrotic center, which is surrounded at its border by an inflammatory infiltrate of macrophages and fibroblasts. A thin capsule of fibroblasts and reticular fibers gradually develops, and the surrounding area of cerebral edema becomes more distinct than in the previous stage. The third stage, early capsule formation (days 10–13), is characterized by the formation of a capsule that is better developed on the cortical than on the ventricular side of the lesion. This stage correlates with the appearance of a ring-enhancing capsule on neu­ roimaging studies. The final stage, late capsule formation (day 14 and beyond), is defined by a well-formed necrotic center surrounded by a dense collagenous capsule. The surrounding area of cerebral edema has regressed, but marked gliosis with large numbers of reactive astrocytes has developed outside the capsule. This gliotic process may contribute to the development of seizures as a sequela of brain abscess. ■ ■CLINICAL PRESENTATION A brain abscess typically presents as an expanding intracranial mass lesion rather than as an infectious process. Although the evolution of signs and symptoms is extremely variable, ranging from hours to weeks or even months, most patients present to the hospital 11–12 days following onset of symptoms. The classic clinical triad of headache, fever, and a focal neurologic deficit is present in <50% of cases. The most common symptom in patients with a brain abscess is headache, occurring in >75% of patients. The headache is often characterized as a constant, dull, aching sensation, either hemicranial or generalized, and it becomes progressively more severe and refractory to therapy. Fever is present in only 50% of patients at the time of diagnosis, and its absence should not exclude the diagnosis. The new onset of focal or generalized seizure activity is a presenting sign in 15–35% of patients. Focal neurologic deficits including hemiparesis, aphasia, or visual field defects are part of the initial presentation in >60% of patients. The clinical presentation of a brain abscess depends on its location, the nature of the primary infection if present, and the level of the intra­ cranial pressure (ICP). Hemiparesis is the most common localizing sign of a frontal lobe abscess. A temporal lobe abscess may present with a disturbance of language (dysphasia) or an upper homony­ mous quadrantanopia. Nystagmus and ataxia are signs of a cerebellar abscess. Signs of raised ICP—papilledema, nausea and vomiting, and drowsiness or confusion—can be the dominant presentation of some abscesses, particularly those in the cerebellum. Meningismus is not present unless the abscess has ruptured into the ventricle or the infec­ tion has spread to the subarachnoid space. ■ ■DIAGNOSIS Diagnosis is made by neuroimaging studies. Magnetic resonance imag­ ing (MRI) (Fig. 145-1) is better than computed tomography (CT) for demonstrating abscesses in the early (cerebritis) stages and is supe­ rior to CT for identifying abscesses in the posterior fossa. Cerebritis appears on MRI as an area of low signal intensity on T1-weighted images with irregular postgadolinium enhancement and as an area of increased signal intensity on T2-weighted images. Cerebritis is often not visualized by CT scan, but when present, appears as an area of hypodensity. On a contrast-enhanced CT scan, a mature brain abscess appears as a focal area of hypodensity surrounded by ring enhance­ ment with surrounding edema (hypodensity). On contrast-enhanced T1-weighted MRI, a mature brain abscess has a capsule that enhances surrounding a hypodense center and surrounded by a hypodense area of edema. On T2-weighted MRI, there is a hyperintense central area of pus surrounded by a well-defined hypointense capsule and a hyperintense surrounding area of edema. It is important to recognize that the CT and MRI appearance, particularly of the capsule, may be altered by treatment with glucocorticoids. The distinction between a brain abscess and other focal CNS lesions such as primary or metastatic tumors may be facilitated by the use of diffusion-weighted imaging sequences on which a brain abscess typically shows increased signal due to restricted diffusion of the abscess cavity with corresponding low signal on apparent diffusion coefficient images.

A B C FIGURE 145-1  Pyogenic brain abscess. Note that the abscess wall enhances prominently after gadolinium administration on the magnetic resonance axial T1-weighted image (A). The abscess is hyperintense on the diffusion-weighted image (B) and dark on the apparent diffusion coefficient (ADC) image (C). (Courtesy of Aaron Kamer, MD; with permission.) Microbiologic diagnosis of the etiologic agent is most accurately determined by Gram’s stain and culture of abscess material obtained by CT-guided stereotactic needle aspiration. Aerobic and anaerobic bacte­ rial cultures and mycobacterial and fungal cultures should be obtained. Blood cultures are positive in ~10% of cases overall but may be posi­ tive in >85% of patients with abscesses due to Listeria. About 50% of patients have a peripheral leukocytosis, 60% an elevated erythrocyte sedimentation rate, and 80% an elevated C-reactive protein. Lumbar puncture (LP) should not be performed in patients with known or suspected focal intracranial infections such as abscess or empyema; cerebrospinal fluid (CSF) analysis contributes nothing to diagnosis or therapy, and LP increases the risk of herniation. ■ ■DIFFERENTIAL DIAGNOSIS Conditions that can cause headache, fever, focal neurologic signs, and seizure activity include brain abscess, subdural empyema, bacte­ rial meningitis (Chap. 143), viral meningoencephalitis (Chap. 142), superior sagittal sinus thrombosis (Chap. 438), and acute disseminated encephalomyelitis (Chap. 456). When fever is absent, primary and metastatic brain tumors become the major differential diagnosis. Less commonly, cerebral infarction or hematoma can have an MRI or CT appearance resembling brain abscess. TREATMENT Brain Abscess Optimal therapy of brain abscesses involves a combination of high-dose parenteral antibiotics and neurosurgical drainage. Empirical therapy of community-acquired brain abscess in an immunocompetent patient typically includes a third- or fourthgeneration cephalosporin (e.g., cefotaxime, ceftriaxone, or cefepime) and metronidazole (see Table 143-1 for antibiotic dosages). In patients with penetrating head trauma or recent neurosurgical procedures, treatment should include ceftazidime as the thirdgeneration cephalosporin to enhance coverage of Pseudomonas spp. and vancomycin for coverage of staphylococci. Meropenem plus vancomycin also provides good coverage in this setting. Aspiration and drainage of the abscess under stereotactic guidance are beneficial for both diagnosis and therapy. Empiri­ cal antibiotic coverage should be modified based on the results of Gram’s stain and culture of the abscess contents. Complete excision

of a bacterial abscess via craniotomy or craniectomy is generally reserved for multiloculated abscesses or those in which stereotactic aspiration is unsuccessful. CHAPTER 145 Medical therapy alone is not optimal for treatment of brain abscess and should be reserved for patients whose abscesses are neurosurgically inaccessible, for patients with small (<2–3 cm) or nonencapsulated abscesses (cerebritis), and for patients whose condition is too tenuous to allow performance of a neurosurgical procedure. All patients should receive a minimum of 6–8 weeks of parenteral antibiotic therapy. The role, if any, of supplemental oral antibiotic therapy following completion of a standard course of parenteral therapy has never been adequately studied. Brain Abscess and Empyema In addition to surgical drainage and antibiotic therapy, patients should receive prophylactic anticonvulsant therapy because of the high risk (~35%) of focal or generalized seizures. Anticonvulsant therapy is continued for at least 3 months after resolution of the abscess, and decisions regarding withdrawal are then based on the electroencephalogram (EEG). If the EEG is abnormal, anticonvulsant therapy should be continued. If the EEG is normal, anticonvulsant therapy can be slowly withdrawn, with close follow-up and repeat EEG after the medication has been discontinued. Glucocorticoids should not be given routinely to patients with brain abscesses. Intravenous dexamethasone therapy (10 mg every 6 h) is usually reserved for patients with substantial periabscess edema and associated mass effect and increased ICP. Dexametha­ sone should be tapered as rapidly as possible to avoid delaying the natural process of encapsulation of the abscess. Serial MRI or CT scans should be obtained on a monthly or twice-monthly basis to document resolution of the abscess. More frequent studies (e.g., weekly) are probably warranted in the sub­ set of patients who are receiving antibiotic therapy alone. A small amount of enhancement may remain for months after the abscess has been successfully treated. ■ ■PROGNOSIS The mortality rate of brain abscess has declined in parallel with the development of enhanced neuroimaging techniques, improved neuro­ surgical procedures for stereotactic aspiration, and improved antibiot­ ics. In modern series, the mortality rate is typically <15%. Significant sequelae, including seizures, persisting weakness, aphasia, or mental impairment, occur in ≥20% of survivors.

NONBACTERIAL CAUSES OF INFECTIOUS FOCAL CNS LESIONS

■ ■ETIOLOGY Neurocysticercosis is the most common parasitic disease of the CNS worldwide. Humans acquire cysticercosis by the ingestion of food contaminated with the eggs of the parasite Taenia solium (Chap. 242). Toxoplasmosis (Chap. 235) is a parasitic disease caused by T. gondii and acquired from the ingestion of undercooked meat and from handling cat feces. ■ ■CLINICAL PRESENTATION The most common manifestation of neurocysticercosis is new-onset partial seizures with or without secondary generalization. Cysticerci may develop in the brain parenchyma and cause seizures or focal neurologic deficits. When present in the subarachnoid or ventricular spaces, cysticerci can produce increased ICP by interference with CSF flow. Spinal cysticerci can mimic the presentation of intraspinal tumors. When the cysticerci first lodge in the brain, they frequently cause little in the way of an inflammatory response. As the cysticercal cyst degenerates, it elicits an inflammatory response that may present clinically as a seizure. Eventually the cyst dies, a process that may take several years and is typically associated with resolution of the inflam­ matory response and, often, abatement of seizures. Primary Toxoplasma infection is often asymptomatic. However, dur­ ing this phase, parasites may spread to the CNS, where they become latent. Reactivation of CNS infection is almost exclusively associated with immunocompromised hosts, particularly those with HIV infec­ tion. During this phase, patients present with headache, fever, seizures, and focal neurologic deficits. PART 5 Infectious Diseases ■ ■DIAGNOSIS The lesions of neurocysticercosis are readily visualized by MRI or CT scans depending on the stage of the lesion. There are four stages of neurocysticercosis: (1) the vesicular stage, (2) the colloidal stage, (3) the granulonodular stage, and (4) the nodular-calcified stage. Lesions with viable parasites appear as cystic lesions, and the scolex can often be visualized on MRI. Cystic lesions with small nodules (scolex) within the cyst are in the vesicular stage of neurocysticercosis (Fig. 145-2A and B). There is no significant edema surrounding a lesion in the vesicular stage. Lesions in the colloidal stage demonstrate peripheral enhancement on postcontrast imaging (Fig. 145-2C) with substantial surrounding edema on T2 images (Fig. 145-2D). In the granulonodu­ lar stage, on postcontrast imaging, the lesion enhances in a homog­ enous fashion (Fig. 145-2E). On fluid-attenuated inversion recovery (FLAIR) images, there is no surrounding edema (Fig. 145-2F). Paren­ chymal brain calcifications are the most common finding and evidence that the parasite is no longer viable. These chronic lesions are best seen on CT (Fig. 145-2G) and can be difficult to detect on MRI. The most sensitive technique for the detection of these small calcific foci on MRI is susceptibility-weighted imaging (SWI). If a confirmatory test for neurocysticercosis is needed, the enzyme-linked immunotransfer blot is recommended. A funduscopic exam is also recommended for all patients with suspected neurocysticercosis. MRI findings of toxoplasmosis consist of multiple lesions in the deep white matter, the thalamus, and basal ganglia and at the graywhite junction in the cerebral hemispheres. With contrast adminis­ tration, the majority of the lesions enhance in a ringed, nodular, or homogeneous pattern and are surrounded by edema. In the presence of the characteristic neuroimaging abnormalities of T. gondii infection, serum IgG antibody to T. gondii should be obtained and, when positive, the patient should be treated. TREATMENT Infectious Focal CNS Lesions Anticonvulsant therapy is initiated when the patient with neuro­ cysticercosis presents with a seizure. Anthelmintic therapy is given to patients based on the stage of the lesion(s). Cysticerci appearing

as cystic lesions in the brain parenchyma with or without pericystic edema or in the subarachnoid space at the convexity of the cerebral hemispheres should be treated with anticysticidal therapy. Cys­ ticidal drugs accelerate the destruction of the parasites, resulting in a faster resolution of the infection. Albendazole monotherapy is recommended for patients with one to two parenchymal cysts. The dose of albendazole is 15 mg/kg per day in two daily doses for 10–14 days. A combination of albendazole plus praziquantel is recommended for patients with more than two viable cysts. Viable cysts are defined as those in the vesicular or colloidal stages (see above). The recommended dose of praziquantel is 50 mg/kg per day for 10–14 days. Prednisone or dexamethasone is begun prior to anticysticidal therapy to reduce the host inflammatory response to degenerating parasites. Only cysts in the vesicular stage, where the cyst contains living larva (scolex seen on CT or MRI), and cysts in the colloidal stage, as the larva degenerates (edema surrounds the lesion), are treated with anticysticidal therapy. Some, but not all, experts recommend anticysticidal therapy for lesions that are in the granulonodular stage (surrounded by a contrast-enhancing ring). There is universal agreement that calcified lesions do not need to be treated with anticysticidal therapy. Antiepileptic therapy can be stopped once a follow-up CT or MRI scan shows resolution of the lesion and the patient has had no seizures for 24 consecutive months. Long-term antiepileptic therapy is recommended when seizures occur after resolution of edema and resorption or calcifica­ tion of the degenerating cyst. CNS toxoplasmosis is treated with a combination of sulfadiazine, 1.5–2.0 g orally qid, plus pyrimethamine, 100 mg orally to load, then 75–100 mg orally qd, plus folinic acid, 10–15 mg orally qd. Folinic acid is added to the regimen to prevent megaloblastic anemia. Therapy is continued until there is no evidence of active disease on neuroimaging studies, which typically takes at least 6 weeks, and then the dose of sulfadiazine is reduced to 2–4 g/d and pyrimethamine to 50 mg/d. Clindamycin plus pyrimethamine is an alternative therapy for patients who cannot tolerate sulfadiazine, but the combination of pyrimethamine and sulfadiazine is more effective. SUBDURAL EMPYEMA A subdural empyema (SDE) is a collection of pus between the dura and arachnoid membranes (Fig. 145-3). ■ ■EPIDEMIOLOGY SDE is a rare disorder that accounts for 15–25% of focal suppurative CNS infections. Sinusitis is the most common predisposing condition and typically involves the frontal sinuses, either alone or in combi­ nation with the ethmoid and maxillary sinuses. Sinusitis-associated empyema has a striking predilection for young males, possibly reflect­ ing sex-related differences in sinus anatomy and development. It has been suggested that SDE may complicate 1–2% of cases of frontal sinusitis severe enough to require hospitalization. As a consequence of this epidemiology, SDE shows an ~3:1 male/female predominance, with 70% of cases occurring in the second and third decades of life. SDE may also develop as a complication of head trauma or neuro­ surgery. Secondary infection of a subdural effusion may also result in empyema, although secondary infection of hematomas, in the absence of a prior neurosurgical procedure, is rare. ■ ■ETIOLOGY Aerobic and anaerobic streptococci, staphylococci, Enterobacteriaceae, and anaerobic bacteria are the most common causative organisms of sinusitis-associated SDE. Staphylococci and gram-negative bacilli are often the etiologic organisms when SDE follows neurosurgical proce­ dures or head trauma. Up to one-third of cases are culture-negative, possibly reflecting difficulty in obtaining adequate anaerobic cultures. ■ ■PATHOPHYSIOLOGY Sinusitis-associated SDE develops as a result of either retrograde spread of infection from septic thrombophlebitis of the mucosal veins

A B C D E F G FIGURE 145-2  The four stages of neurocysticercosis. A, B. The vesicular stage. A. Postcontrast T1 magnetic resonance image (MRI). Note lesion in right parietal area. Small hypointense nodules within the cyst likely represent scolex. B. T2 MRI. The cyst is now visualized as a uniform hyperintense lesion with the small hypointense nodules likely representing scolex. No significant edema is present around the lesion on T2, typical for this stage of the disease. C, D. The colloidal stage. C. A medial left occipital lesion demonstrates peripheral enhancement on postcontrast imaging. D. On fluid-attenuated inversion recovery (FLAIR) MRI, the lesion has substantial surrounding hyperintense edema. E, F. The granulonodular stage. E. Postcontrast T1-weighted imaging demonstrates enhancing lesions in the left putamen and in the genu of the internal capsule near the foramen of Monro. F. These lesions demonstrate no surrounding edema on FLAIR imaging, typical for this stage of the disease. G. The nodular-calcified stage. Computed tomography scan demonstrates typical parenchymal brain calcifications. (Courtesy of Aaron Kamer, MD; with permission.) draining the sinuses or contiguous spread of infection to the brain from osteomyelitis in the posterior wall of the frontal or other sinuses. SDE may also develop from direct introduction of bacteria into the subdural space as a complication of a neurosurgical procedure. The evolution of SDE can be extremely rapid because the subdural space is a large compartment that offers few mechanical barriers to the spread of infection. In patients with sinusitis-associated SDE, suppuration typi­ cally begins in the upper and anterior portions of one cerebral hemi­ sphere and then extends posteriorly. SDE is often associated with other

CHAPTER 145 Brain Abscess and Empyema intracranial infections, including epidural empyema (40%), cortical thrombophlebitis (35%), and intracranial abscess or cerebritis (>25%). Cortical venous infarction produces necrosis of underlying cerebral cortex and subcortical white matter, with focal neurologic deficits and seizures (see below). ■ ■CLINICAL PRESENTATION A patient with SDE typically presents with fever and a progressively worsening headache. The diagnosis of SDE should always be suspected

Subdural empyema Thrombosed veins Dura mater Arachnoid FIGURE 145-3  Subdural empyema. in a patient with known sinusitis who presents with new CNS signs or symptoms. Patients with underlying sinusitis frequently have symptoms related to this infection. As the infection progresses, focal neurologic deficits, seizures, nuchal rigidity, and signs of increased ICP commonly occur. Headache is the most common complaint at the time of presentation; initially it is localized to the side of the subdural infection, but then it becomes more severe and generalized. Contralat­ eral hemiparesis or hemiplegia is the most common focal neurologic deficit and can occur from the direct effects of the SDE on the cortex or as a consequence of venous infarction. Seizures begin as partial motor seizures that then become secondarily generalized. Seizures may be due to the direct irritative effect of the SDE on the underlying cortex or result from cortical venous infarction. In untreated SDE, the increas­ ing mass effect and increase in ICP cause progressive deterioration in consciousness, leading ultimately to coma. PART 5 Infectious Diseases ■ ■DIAGNOSIS MRI (Fig. 145-4) is superior to CT in identifying SDE and any associ­ ated intracranial infections. The administration of gadolinium greatly improves diagnosis by enhancing the rim of the empyema and allowing A B C FIGURE 145-4  Subdural empyema. The purulent fluid collection along the left falx and left frontal convexity is hypointense on T1-weighted images (A) but markedly hyperintense on the diffusion-weighted (B) and the T2 fat-saturation (C) magnetic resonance images.

the empyema to be clearly delineated from the underlying brain paren­ chyma. Cranial MRI is also extremely valuable in identifying sinusitis, other focal CNS infections, cortical venous infarction, cerebral edema, and cerebritis. CT may show a crescent-shaped hypodense lesion over one or both hemispheres or in the interhemispheric fissure. Frequently the degree of mass effect, exemplified by midline shift, ventricular compression, and sulcal effacement, is far out of proportion to the mass of the SDE. CSF examination should be avoided in patients with known or suspected SDE because it adds no useful information and is associated with the risk of cerebral herniation. ■ ■DIFFERENTIAL DIAGNOSIS The differential diagnosis of the combination of headache, fever, focal neurologic signs, and seizure activity that progresses rapidly to an altered level of consciousness includes subdural hematoma, bacterial meningitis, viral encephalitis, brain abscess, superior sagittal sinus thrombosis, and acute disseminated encephalomyelitis. The presence of nuchal rigidity is unusual with brain abscess or epidural empyema and should suggest the possibility of SDE when associated with signifi­ cant focal neurologic signs and fever. Patients with bacterial meningitis also have nuchal rigidity but do not typically have focal deficits of the severity seen with SDE. TREATMENT Subdural Empyema SDE is a medical emergency. Emergent neurosurgical evacuation of the empyema, either through craniotomy, craniectomy, or burr-hole drainage, is the definitive step in the management of this infec­ tion. Empirical antimicrobial therapy for community-acquired SDE should include a combination of a third-generation cephalosporin (e.g., cefotaxime or ceftriaxone), vancomycin, and metronidazole (see Table 143-1 for dosages). Patients with hospital-acquired SDE may have infections due to Pseudomonas spp. or MRSA and should receive coverage with a carbapenem (e.g., meropenem) and vancomycin. Metronidazole is not necessary for antianaero­ bic therapy when meropenem is being used. Parenteral antibiotic therapy should be continued for a minimum of 3–4 weeks after SDE drainage. Patients with associated cranial osteomyelitis may require longer therapy. Specific diagnosis of the etiologic organisms is made based on Gram’s stain and culture of fluid obtained via either burr holes or craniotomy; the initial empirical antibiotic coverage can be modified accordingly.

■ ■PROGNOSIS Prognosis is influenced by the level of consciousness of the patient at the time of hospital presentation, the size of the empyema, and the speed with which therapy is instituted. Long-term neurologic sequelae, which include seizures and hemiparesis, occur in up to 50% of cases. CRANIAL EPIDURAL ABSCESS Cranial epidural abscess is a suppurative infection occurring in the potential space between the inner skull table and dura (Fig. 145-5). ■ ■ETIOLOGY AND PATHOPHYSIOLOGY Cranial epidural abscess is less common than either brain abscess or SDE and accounts for <2% of focal suppurative CNS infections. A cranial epidural abscess develops as a complication of a craniotomy or compound skull fracture or as a result of spread of infection from the frontal sinuses, middle ear, mastoid, or orbit. An epidural abscess may develop contiguous to an area of osteomyelitis, when craniotomy is complicated by infection of the wound or bone flap, or as a result of direct infection of the epidural space. Infection in the frontal sinus, middle ear, mastoid, or orbit can reach the epidural space through retrograde spread of infection from septic thrombophlebitis in the emissary veins that drain these areas or by way of direct spread of infection through areas of osteomyelitis. Unlike the subdural space, the epidural space is really a potential rather than an actual compart­ ment. The dura is normally tightly adherent to the inner skull table, and infection must dissect the dura away from the skull table as it spreads. As a result, epidural abscesses are often smaller than SDEs. Cranial epidural abscesses, unlike brain abscesses, only rarely result from hematogenous spread of infection from extracranial primary sites. The bacteriology of a cranial epidural abscess is similar to that of SDE (see above). The etiologic organisms of an epidural abscess that arises from frontal sinusitis, middle-ear infections, or mastoiditis are usually streptococci or anaerobic organisms. Staphylococci or gram-negative organisms are the usual cause of an epidural abscess that develops as a complication of craniotomy or compound skull fracture. ■ ■CLINICAL PRESENTATION Patients present with fever (60%), headache (40%), nuchal rigidity (35%), seizures (10%), and focal deficits (5%). Development of symp­ toms may be insidious, as the empyema usually enlarges slowly in the confined anatomic space between the dura and the inner table of the skull. Periorbital edema and Pott’s puffy tumor, reflecting underlying associated frontal bone osteomyelitis, are present in ~40%. In patients with a recent neurosurgical procedure, wound infection is invariably present, but other symptoms may be subtle and can include altered mental status (45%), fever (35%), and headache (20%). The diagnosis should be considered when fever and headache follow recent head trauma or occur in the setting of frontal sinusitis, mastoiditis, or otitis media. Epidural abscess FIGURE 145-5  Cranial epidural abscess is a collection of pus between the dura and the inner table of the skull.

■ ■DIAGNOSIS Cranial MRI with gadolinium enhancement is the procedure of choice to demonstrate a cranial epidural abscess. The sensitivity of CT is limited by the presence of signal artifacts arising from the bone of the inner skull table. The CT appearance of an epidural empyema is that of a lens or crescent-shaped hypodense extraaxial lesion. On MRI, an epidural empyema appears as a lentiform or crescent-shaped fluid col­ lection that is hyperintense compared to CSF on T2-weighted images. On T1-weighted images, the fluid collection may be either isointense or hypointense compared to brain. Following the administration of gadolinium, there is linear enhancement of the dura on T1-weighted images. In distinction to subdural empyema, signs of mass effect or other parenchymal abnormalities are uncommon.

TREATMENT Epidural Abscess Immediate neurosurgical drainage is indicated. Empirical anti­ microbial therapy, pending the results of Gram’s stain and cul­ ture of the purulent material obtained at surgery, should include a combination of a third-generation cephalosporin, vancomycin, and metronidazole (see Table 143-1). Ceftazidime or meropenem should be substituted for ceftriaxone or cefotaxime in neurosur­ gical patients. Metronidazole is not necessary for antianaerobic coverage in patients receiving meropenem. When the organism has been identified, antimicrobial therapy can be modified accordingly. Antibiotics should be continued for 3–6 weeks after surgical drain­ age. Patients with associated osteomyelitis may require additional therapy. CHAPTER 145 ■ ■PROGNOSIS The mortality rate is <5% in modern series, and full recovery is the rule in most survivors. Brain Abscess and Empyema SUPPURATIVE THROMBOPHLEBITIS ■ ■DEFINITION Suppurative intracranial thrombophlebitis is septic venous thrombosis of cortical veins and sinuses. This may occur as a complication of bac­ terial meningitis; SDE; epidural abscess; or infection in the skin of the face, paranasal sinuses, middle ear, or mastoid. ■ ■ANATOMY AND PATHOPHYSIOLOGY The cerebral veins and venous sinuses have no valves; therefore, blood within them can flow in either direction. The superior sagittal sinus is the largest of the venous sinuses (Fig. 145-6). It receives blood from the Superior sagittal sinus Transverse sinus Straight sinus Superior ophthalmic vein Inferior ophthalmic vein Sigmoid sinus Internal jugular vein Cavernous sinus FIGURE 145-6  Anatomy of the cerebral venous sinuses.