Sorting Out and Treating Encephalitis

FIGURE 5.1 Brain imaging in our patient with acute HSV-1 encephalitis. CT scan (A and B) showing low attenuation changes in the right temporal lobe and right insular region. Notice also the slightly hyperdense appearance in the Sylvian fissure, which may be confused for a fresh thrombus in the middle cerebral artery (A). The areas of brain swelling are much better visualized on the FLAIR sequence of the MRI (C and D), which also reveals the characteristic asymmetric bilaterality of the inflammation.

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The diagnosis of encephalitis as a syndrome is relatively straightforward. Patients present with headache, fever, confusion, and, when more advanced, abnormal consciousness. Seizures (focal or more generalized) are a common manifestation. Examination may show neck stiffness or focal deficits, but there may be no localizing signs. In fact the diagnosis may not even be considered if the patient is seen early in the course and is just “confused”. While the CT scan can be highly suggestive of certain forms of encephalitis (as illustrated by the temporal and insular areas of swelling in our patient with herpes simplex virus type 1 [HSV-1] encephalitis) (Figure 5.1), radiological changes are generally not characteristic of specific encephalitis etiologies. A brain MRI is far more helpful (Table 5.1). Cerebrospinal fluid (CSF) showing increased white blood cell count, and an increased protein concentration confirms the presence of encephalitis. A normal CSF strongly points towards alternative diagnoses (such as noninfectious limbic encephalitis).

TABLE 5.1 Causes of Acute Encephalitis with Characteristic Radiological Features

Cause	Characteristic radiological features
Herpes simplex virus type 1	Inflammatory lesions in temporal lobes, insula, and operculum
Varicella herpes zoster	Multifocal infarctions and irregularities of arterial lumen
	Cerebellitis in children
Cytomegalovirus	Ventriculitis (subependymal enhancement). Brainstem inflammation
West Nile virus	Myelitis^*
Tuberculosis	Basilar meningitis^†
Fungal infections	Abscess formation^**
Autoimmune limbic encephalitis	Inflammatory lesions in mesial temporal lobes
Acute disseminated encephalomyelitis	Bilateral white matter T2-hyperintense lesions. Corpus callosum involvement
Progressive multifocal leukoencephalopathy (JC virus)	Bilateral, confluent T2-hyperintense lesions in temporo-occipital white matter with involvement of U fibers and cortical sparing

^* Presentation with acute flaccid paralysis may occur with or without radiological signs of myelitis.

† Also with fungal meningoencephalitis caused by Blastomycosis

^** Aspergillus species is characterized by infarctions and hemorrhages

Recognizing a clinical presentation consistent with the diagnosis of acute encephalitis is just the first step. Encephalitis can be infectious, postinfectious, and noninfectious (Table 5.2). Autoimmune (paraneoplastic or not) and radiation-induced encephalitis are noninfectious examples. Defining the precise cause of the acute encephalitis is a much more difficult task that requires almost encyclopedic knowledge of neurological and infectious diseases, and working with a knowledgeable infectious disease consultant can be very helpful in these cases. Equally important is to narrow the differential diagnosis depending on the season, geographic area, specific exposures (including recent travel history) and risk factors.

Viral infection is the most common cause of acute encephalitis in adults. Epidemic outbreaks can be produced by the seasonal spread of arboviruses (i.e., viruses transmitted by arthropod vectors, such as mosquitoes). Most of these agents are constrained to specific geographical locations, but there are exceptions such as the West Nile virus or H1N1, which has been identified as a cause of outbreaks of encephalitis in all continents. Viral encephalitis can also be sporadic. Sporadic cases can occur in the immunocompetent and the immunodepressed patient.

HSV-1 is the most frequent cause of sporadic viral encephalitis in immunocompetent patients. HSV-1 encephalitis has a predilection for the temporal lobes, insula, and operculum. Consequently, it should be suspected when a febrile patient develops confusion or drowsiness associated with seizures or focal deficits referable to those locations. Aphasia, amnesia, hallucinations, agitation, visual field deficits and oral apraxia can be seen. When present, the typical distribution of swelling on brain MRI (Figure 5.1 C and D) strongly supports the diagnosis. Yet, the diagnosis should be established by confirming the presence of the virus in the CSF. Polymerase chain reaction (PCR) can detect HSV-1 DNA in the CSF with great sensitivity and specificity. If PCR is negative but the clinical-radiological presentation is suspicious for HSV-1 infection, the test should be repeated on a new CSF sample after 3–5 days.

TABLE 5.2 Main Causes of Acute Encephalitis, Diagnostic Test, and Principal Aspects of Management