Approach to Infection, Inflammation, and Demyelination
Main Text
Preamble
Although any part of the human body can become inflamed or infected, the brain has long been considered an “immunologically protected” site because of the blood-brain barrier. While CNS infections are considerably less common than their systemic counterparts, the brain is by no means invulnerable to onslaught from pathogenic organisms.
The role of medical imaging in the emergent evaluation of intracranial infection ideally should be supportive, not primary. But in many health care facilities worldwide, triage of acute CNS disease frequently uses brain imaging as an initial noninvasive “screening procedure.” Therefore, the radiologist may be the first—not the last—to recognize the presence of possible CNS infection.
In this part, we devote Chapters 12 and 13 to CNS infections. HIV/AIDS is covered in Chapter 14. The last chapter, Chapter 15, considers the surprisingly broad spectrum of noninfectious idiopathic inflammatory and demyelinating disorders that affect the CNS.
CNS Infections
Preamble
The concept that the brain was an “immune-privileged” organ in which the blood-brain barrier (BBB) was a relative fortress that restricted pathogen entry and limited inflammation has recently undergone significant revision. Lymphocytes circulate through the normal healthy brain, immune responses can occur without lasting consequence, and cross-talk between the brain and extra-CNS organs is both extensive and robust.
Evidence has also recently emerged that there is extensive CSF and interstitial fluid (ISF) exchange throughout the brain, a process now termed “glymphatics.”
A pathway of waste removal from the CNS does exist and is facilitated by CSF entering the brain parenchyma and spinal cord via aquaporin-4 water channels on astrocytes that surround the brain vasculature. This wave of CSF entry drives ISF toward the perivenous space where it collects and drains through lymphatic channels in the dural sinuses through foramina at the skull base to the deep cervical lymph nodes. The process flushes extracellular debris (including β-amyloid) from the parenchyma.
The presence of these drainage systems within the CNS is evidence that there is a constant flow and exchange of proteins within the brain and the blood. CD4(+) central and effector memory T cells are found in healthy CSF. The brain is therefore not a “privileged organ” that is immunologically isolated from the rest of the body but rather is actively monitored by—and accessible to—blood-borne lymphocytes and their mediators.
A surprisingly large number of pathogens, including many neurotropic viruses, can infect the CNS. Well over 200 different organisms have been described as causing CNS infections of one type or another. Most recently, the importance of recognizing brain disorders in patients infected with SARS-CoV-2 virus has become paramount. Patients with COVID-19 infections may experience an array of neurologic manifestations ranging in severity from headaches to life-threatening strokes and brain bleeds. Awareness of neurologic involvement in SARS-CoV-2 infection and the broad spectrum of its potential imaging manifestations is essential for clinical neuroimaging.
In this text, we divide infections into congenital and acquired disorders. Congenital infections are briefly covered in Chapter 12. Because this is a relatively short discussion, we combine these with acquired pyogenic and viral infections.
Our discussion of pyogenic infections begins with meningitis followed by a consideration of focal brain infections (cerebritis, abscess), ventriculitis (11-1), and pus collections in the extraaxial spaces (subdural/epidural empyemas) (11-2). We close the chapter with CNS manifestations of acquired viral infections.
The pathogenesis and imaging of tuberculosis (TB), fungal infections, and parasitic and protozoal infestations are considered in Chapter 13.
HIV/AIDS
Preamble
In the more than four decades since AIDS was first identified, the disease has become a worldwide epidemic. With the development of effective combination antiretroviral therapies, HIV/AIDS has evolved from a virtual death sentence to a chronic but manageable disease if the treatment is (1) available and (2) affordable. As treated patients with HIV/AIDS now often survive for a decade or longer, the imaging spectrum of HIV/AIDS has also evolved.
Treated HIV/AIDS as a chronic disease looks very different from HIV/AIDS in so-called high-burden regions of the world. In such places, HIV in socioeconomically disadvantaged patients often behaves as an acute, fulminant infection. Comorbid diseases, such as TB, malaria, or overwhelming bacterial sepsis, are common complications and may dominate the imaging presentation.
Complications of HAART treatment have created their own set of recognized disorders, such as immune reconstitution inflammatory syndrome (IRIS). In Chapter 14, we consider the effect of HIV itself on the CNS (HIV encephalitis) as well as opportunistic infections, IRIS, miscellaneous manifestations of HIV/AIDS, and HIV-associated neoplasms.
Demyelinating and Inflammatory Diseases
Preamble
The final chapter in this section is devoted to demyelinating and noninfectious inflammatory diseases of the CNS (11-5).
Inflammation is not synonymous with infection. Inflammation (from Latin, meaning “to ignite” or “set alight”) is the response of tissues to a variety of pathogens (which may or may not be infectious microorganisms). The inflammatory “cascade” is complex and multifactorial. It involves the vascular system, immune system, and cellular responses, such as microglial activation, the primary component of the brain’s innate immune response.
The CNS functions as a unique microenvironment that responds differently than the body’s other systems to infiltrating immune cells. The brain white matter is especially susceptible to inflammatory disease. Inflammation can be acute or chronic, manageable or life threatening. Therefore, imaging plays a central role in the identification and follow-up of neuroinflammatory disorders.
The bulk of Chapter 15 is devoted to multiple sclerosis (MS) (11-6). Also included is a discussion of MS variants and the surprisingly broad spectrum of idiopathic (noninfectious) inflammatory demyelinating diseases (IIDDs), such as neuromyelitis optica. Susac syndrome is a retinocochleocerebral vasculopathy that is often mistaken for MS on imaging studies, so it is also discussed in the context of IIDDs.
Postinfection, postvaccination, autoimmune-mediated demyelinating disorders are considered next. Acute disseminated encephalomyelitis (ADEM) and its most fulminant variant, acute hemorrhagic leukoencephalitis (AHLE), are delineated in detail.
We close the chapter with a discussion of neurosarcoid and inflammatory pseudotumors, including the rapidly expanding category of IgG4-related disorders.
Selected References: The complete reference list is available on the eBooks+ version included with purchase.
