Elsevier

Neurologic Clinics

Volume 26, Issue 2, May 2008, Pages 427-468
Neurologic Clinics

Update in the Diagnosis and Management of Central Nervous System Infections

https://doi.org/10.1016/j.ncl.2008.03.013Get rights and content

Central nervous system (CNS) infections presenting to the emergency room include meningitis, encephalitis, brain and spinal epidural abscess, subdural empyema, and ventriculitis. These conditions often require admission to an intensive care unit (ICU) and are complications of ICU patients with neurologic injury, contributing significantly to morbidity and mortality. Reducing morbidity and mortality is critically dependent on rapid diagnosis and, perhaps more importantly, on the timely initiation of appropriate antimicrobial therapy. New insights into the role of inflammation and the immune response in CNS infections have contributed to development of new diagnostic strategies using markers of inflammation, and to the study of agents with focused immunomodulatory activity, which may lead to further adjunctive therapy in human disease.

Section snippets

Anatomy and inflammation of the central nervous system

Invasive infections of the CNS begin with entry of bacteria between the pia (internal layer in direct contact with brain parenchyma) and arachnoid (middle layer) membranes delimiting the subarachnoid space, a multistep process requiring evasion of host defenses (Fig. 1). Bacteria responsible for meningitis attach to the nasopharyngeal epithelium, and are nearly all capable of secreting IgA proteases that prevent their destruction and allow them to traverse the epithelium and invade the

Evaluating the patient with suspected central nervous system infection

The approach to a patient suspected to have a CNS infection begins with an evaluation of clinical features, which provides critical information leading to etiologic diagnosis [29]. The identification of infectious agents in CNS infection remains highly dependent on the CSF analysis, and occasionally serum or biopsy data. Neuroimaging also plays a crucial role in diagnosis and therapeutic decision-making.

Cerebrospinal fluid analysis

CSF analysis is the cornerstone of diagnosis and management of CNS infection. The two major issues that may interfere with appropriate and timely CSF analysis (either by lumbar puncture or shunt tap) are concerns about uncal or cerebellar tonsillar herniation and the need to initiate empiric antibiotics emergently. The availability of CT frequently delays starting antimicrobial therapy [75]. In van de Beek and colleague's study [32], CT was performed before lumbar puncture (LP) in 48% of

Neuroimaging of central nervous system infections

In uncomplicated bacterial meningitis, CT scans are usually sufficient for clinical management to exclude cerebral edema, hydrocephalus, and base of skull pathology (eg, fractures, inner ear infection, or mastoiditis). Other findings include subdural effusions, brain stem encephalitis (rhombencephalitis) with Listeria infection, and cortical infarcts secondary to vasculitis in up to 20% of cases [112]. CT or MR venography should be considered to diagnose complicating cerebral venous sinus

Distribution of drug into the central nervous system

Antimicrobial distribution into the CNS is influenced by both physical barriers, as well as inherent physiochemical properties of the antimicrobial itself. The major physiochemical factors governing antimicrobial penetration of the CNS are listed in Table 2. Because only the unbound concentration of drug is available for diffusion across the BBB and blood-CSF barrier, highly protein-bound agents have limited ability to penetrate the CNS [115]. The tight junctions within the BBB and blood-CSF

Glucocorticoids for bacterial meningitis

Although it is accepted that inflammatory mechanisms contribute to the morbidity associated with bacterial meningitis, debate continues regarding the appropriate use of anti-inflammatory drugs in particular glucocorticoids. The rationale for use of steroids is based on experimental data that show that the inflammatory response in the subarachnoid space contributes significantly to the morbidity and mortality of bacterial meningitis [30]. De Gans and colleagues [170] demonstrated in a large

Summary

The management of patients who have CNS infections is challenging. Therapy for CNS infections is evolving in light of changing microbial resistance patterns and with the introduction of new antimicrobial agents. Knowledge of cerebral inflammation, molecular diagnostics, and the evolving microbial epidemiology are important to optimizing therapy in patients with meningitis. Future investigations into the role of selective immunomodulation and other neuroprotective strategies may lead to

Acknowledgments

The authors would like to gratefully acknowledge the contribution of Brian Cole for his drawing of Fig. 1.

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