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May 2019

Updated to reflect new data and a new reference on the potential benefits of the PD-1 inhibitor pembrolizumab in the management of patients with PML encephalitis.


Encephalitis is defined as an inflammation of the brain caused either by infection, usually with a virus, or from a primary autoimmune process. This chapter will focus on infectious causes of encephalitis; non-infectious etiologies are considered elsewhere (Chaps. 90, 436, and 437). In contrast to meningitis (Chaps. 133 and 134), in which the infectious process and associated inflammatory response are limited largely to the meninges, in encephalitis the brain parenchyma is also involved. Many patients with encephalitis also have evidence of associated meningitis (meningoencephalitis) and, in some cases, involvement of the spinal cord or nerve roots (encephalomyelitis, encephalomyeloradiculitis).


In addition to the acute febrile illness with evidence of meningeal involvement characteristic of meningitis, the patient with encephalitis commonly has an altered level of consciousness (confusion, behavioral abnormalities), or a depressed level of consciousness ranging from mild lethargy to coma, and evidence of either focal or diffuse neurologic signs and symptoms. Patients with encephalitis may have hallucinations, agitation, personality change, behavioral disorders, and, at times, a frankly psychotic state. Focal or generalized seizures occur in many patients with encephalitis. Virtually every possible type of focal neurologic disturbance has been reported in viral encephalitis; the signs and symptoms reflect the sites of infection and inflammation. The most commonly encountered focal findings are aphasia, ataxia, upper or lower motor neuron patterns of weakness, involuntary movements (e.g., myoclonic jerks, tremor), and cranial nerve deficits (e.g., ocular palsies, facial weakness). Involvement of the hypothalamic-pituitary axis may result in temperature dysregulation, diabetes insipidus, or the development of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Even though neurotropic viruses typically cause pathologic injury in distinct regions of the central nervous system (CNS), variations in clinical presentations make it impossible to reliably establish the etiology of a specific case of encephalitis on clinical grounds alone (see “Differential Diagnosis,” below).


In the United States, there are an estimated ~20,000 cases of encephalitis per year, although the actual number of cases is likely to be significantly larger. Despite comprehensive diagnostic efforts, the majority of cases of acute encephalitis of suspected viral etiology remain of unknown cause. Hundreds of viruses are capable of causing encephalitis, although only a limited subset is responsible for most cases in which a specific cause is identified (Table 132-1). The most commonly identified viruses causing sporadic cases of acute encephalitis in immunocompetent adults are herpesviruses (herpes simplex virus [HSV], varicella-zoster virus [VZV], Epstein-Barr virus [EBV]). Epidemics of encephalitis are caused by arboviruses, which belong to several different viral taxonomic groups including Alphaviruses (e.g., eastern equine encephalitis [EEE] virus), Flaviviruses (e.g., West Nile virus ...

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