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  • Autoimmune diseases of the central nervous system (CNS) can cause profound neurologic dysfunction, but if treated promptly many have a favorable prognosis.

  • Patients may manifest a classic clinical syndrome such as limbic or brainstem encephalitis but commonly present with a nonspecific decline in functional status and level of arousal.

  • Clinical features suggesting noninfectious encephalitis include subacute onset, younger age, seizure, personality change, history of cancer, and mild/moderate cerebrospinal fluid (CSF) pleocytosis.

  • Diagnostic workup includes MRI, lumbar puncture, antibody studies, EEG, and, in certain indications, advanced imaging studies including FDG-PET.

  • Definitive diagnosis often takes weeks during which irreversible parenchymal injury may occur. To optimize long-term neurologic outcome, empiric treatment should be initiated as soon as alternative diagnoses have been reasonably excluded.

  • Empiric treatment with immunomodulatory therapy should be directed at the presumed mechanism of immune dysfunction and can be tailored as specific diagnostic studies are resulted.


Noninfectious inflammatory disorders of the central nervous system (CNS) are among the most challenging encountered in the intensive care unit (ICU). Though there exist several well-defined clinical syndromes, most patients with noninfectious encephalitis present with a nonspecific syndrome of subacute to rapid functional decline with laboratory and radiographic evidence of CNS inflammation in the absence of an identifiable infectious etiology. In most cases, the urgency to intervene to prevent permanent neurologic injury conflicts with substantial diagnostic uncertainty. Moreover, treatment options are limited, and although associated with significant risks, prompt intervention can result in dramatic clinical improvement. It is thus imperative that intensivists be comfortable with the basic pathophysiologic principles underlying these disorders, so that treatment decisions may be approached in a rational, mechanism-based fashion. In this chapter, we outline the basic diagnostic and therapeutic principles in the management of noninfectious encephalitis in the ICU.

In many traditional texts, these disorders are presented as a laundry list of named disease entities, with common presenting signs and symptoms associated with each autoantibody.1–5 However, a compendium of this sort is of little utility to the practicing intensivist managing an acutely decompensating patient, as these conditions commonly present in forme fruste and specific diagnostic tests take days to weeks to result. Moreover, in a substantial proportion of cases, all serologic studies may be negative despite clear evidence of disease pathology.3,6,7 This point is underscored by the ever-growing list of pathologic antibodies available for testing and further emphasizes the importance of initiating treatment prior to reaching a conclusive diagnosis.4,5,7–9

To this end, we consider these disorders not as a list of distinct molecular targets of autoimmunity, but rather as clusters of syndromes based on common underlying modes of immune dysfunction. This approach emphasizes early intervention over precise diagnosis and establishes a framework upon which ongoing research can be integrated into a sophisticated approach to the management of these often devastating but frequently reversible neurologic illnesses.

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