Stephen J. Gluckman

Epidemiology and Etiology

Pathogenesis

Acute meningitis and encephalitis are primarily caused by relatively few pathogens with unique abilities to invade the cerebrospinal fluid (CSF). As a rule, viral and bacterial CNS pathogens gain entry into the CSF via a hematogenous route. However, some viruses may also gain access by retrograde spread along nerves, and some bacteria occasionally invade the CNS from a contiguous focus or by direct inoculation during or after trauma or neurosurgery.

In bacterial meningitis, once these agents gain access to the CSF fluid, few host defenses are available to control their rapid multiplication. CSF is devoid of phagocytic cells or effective humoral immunity via immunoglobulins or complement. The pathogens induce an inflammatory response that is mediated by a number of cytokines within the CSF, particularly interleukins 1 and 6 and tumor necrosis factor. These cytokines induce phagocytes to adhere to endothelium and enter the CSF. The resultant inflammation and microvascular injury produces brain edema, increased intracerebral pressure, decreased tissue perfusion, and direct tissue injury. Improved understanding of this pathogenesis has led to considerations for therapeutic intervention with drugs that can modulate the inflammatory response.

Viral encephalitis can be either primary or postinfectious. Primary infection is characterized by direct viral invasion of the CNS, which can be demonstrated by light or electron microscopy. The virus can often be cultured from brain tissue or identified by immunofluorescent staining. In postinfectious encephalitis, the virus cannot be detected in tissue or recovered in culture. Although the neurons are not involved, perivascular inflammation and demyelination are prominent.

Clinical Presentation and Complications

Most patients with acute viral meningitis present with fever, headache, and nuchal rigidity. The headache is typically severe and either frontal or diffuse. Photophobia is also common. Meningismus limits head flexion but not rotation. In contrast, both flexion and rotation are limited in patients with cervical arthritis, Parkinson disease, and neuroleptic malignant syndrome. Additional symptoms might include nausea, vomiting, diarrhea, and myalgias. Patients with viral meningitis are usually uncomfortable but do not appear toxemic. Although most patients have a nonspecific presentation, associated clinical clues to the cause might include an enteroviral exanthem, mumps parotitis, or herpes genitalis. The duration of viral meningitis is generally less than a week, and it usually resolves without sequelae.

Acute bacterial meningitis also presents with fever, headache, and findings of meningeal irritation. In addition, an altered sensorium with a nonfocal neurologic examination can rapidly develop. Mental status derangement can vary from mild confusion to complete unresponsiveness. If these symptoms occur, focal neurologic findings include cranial nerve palsies, hemiparesis, and aphasia. They are often associated with complications such as subdural empyema, cortical vein thrombosis, sagittal or cavernous sinus thrombosis, or hydrocephalus. Focal or generalized seizures may also occur. Because papilledema is not a feature of uncomplicated meningitis, this finding suggests the presence of a complication or an alternative diagnosis.

In certain groups of patients, the presentation of bacterial meningitis is more likely to be atypical. Meningitis in the elderly may be subtle with only a change in mental status. In patients who have sustained head trauma, the findings of an associated meningitis may be attributed to the injury. In neutropenic patients, the inflammatory response in the CSF may be attenuated. For these reasons, bacterial meningitis must be considered in any patient with an altered mental status, especially if febrile.

The general physical examination may occasionally give clues to the cause of the bacterial meningitis. A localized source of infection, such as pneumonia or sinusitis, may be found. Characteristic cutaneous findings of meningococcemia—that is, petechiae or purpura—suggest that organism, but these findings can also be seen with other pathogens. Other possible clues include the presence of a CSF shunt, sinusitis, or CSF rhinorrhea.

The primary initial distinction between viral and bacterial CNS infections is based on the cerebrospinal fluid analysis. The clinical distinction between viral meningitis and encephalitis is based on the state of brain function. Patients with viral meningitis may be uncomfortable, lethargic, or distracted by headache, but their cerebral function remains normal. Abnormalities in brain function in encephalitis, however, are expected and include altered mental status, motor or sensory deficits, and speech or movement disorders. Seizures and postictal states can be seen with meningitis alone and should not be construed as definitive evidence of encephalitis. Encephalitis with herpes simplex virus type 1 (HSV-1) has a particular affinity for the medial temporal and inferior frontal lobes of the brain. For this reason, symptoms such as bizarre behavior, speech disorders, and gustatory or olfactory hallucinations are characteristic of infection with this organism. Accompanying herpes labialis is seen in less than 10% of cases. Furthermore, the appearance of herpetic skin lesions can be a nonspecific complication of many febrile illnesses. Therefore, the presence or absence of mucocutaneous herpes infection is not of diagnostic importance in evaluating patients for HSV-1 encephalitis.

General Diagnostic Approach

Examination of the CSF obtained by lumbar puncture is the key initial test in the evaluation of a patient for CNS infection. The CSF should routinely be sent for cell count and differential, glucose and protein determinations, Gram stain, and bacterial culture. These CSF findings will confirm or rule out the presence of CNS inflammation. Although the specific pattern of results will also generally allow the clinician to distinguish a bacterial from a nonbacterial process, the routine CSF findings in viral meningitis, other causes of aseptic meningitis, and viral encephalitis are indistinguishable.

In most patients, the presentation of an acute meningitis is sufficiently distinct from the presentation of a CNS mass lesion that imaging before a lumbar puncture is unnecessary and might potentially delay therapy (Figure 64.1). A number of historical and physical examination findings have been shown to increase the likelihood of a CNS mass lesion and should prompt either computed tomography or magnetic resonance imaging of the brain before lumbar puncture. These include age > 60, immunosuppressed state, recent seizure, altered mental status, papilledema, focal neurologic findings, or evidence of head trauma. If meningitis is a consideration but the presence of any of these findings suggest the possibility of a focal CNS problem, antibiotic therapy should not be delayed while obtaining CNS imaging studies before lumbar puncture. In addition to the initial tests mentioned earlier, several milliliters of CSF should be saved in a refrigerator pending the results of these initial tests in case further testing is needed. Generally the results of the initial tests reflect whether or not the process is bacterial (Figure 64.2). If bacterial meningitis is not diagnosed, this reserved fluid can be tested for other pathogens.