Encephalitis

Encephalitis is defined as a brain inflammatory process associated with neurologic dysfunction. CNS dysfunction includes seizures, focal neurologic findings, and alteration in mental status. The inflammation can result from different processes: immune disorders, cancer, toxic or metabolic encephalopathies, vascular disorders, or infectious diseases. Infectious encephalitis is mainly caused by viruses, with herpes simplex virus (HSV) being the most frequently isolated. However, recent studies have emphasized the role of bacteria, especially mycoplasma pneumoniae, fungi, and parasites.

Pathogenesis

There are at least two forms of infection-related encephalitis: primary and post- or parainfectious. Primary encephalitis results from direct CNS invasion by the offending agent, and the gray matter often is targeted. A post-infectious or parainfectious encephalitis presents much like primary encephalitis, but the illness is not caused by direct CNS infection. In post/parainfectious encephalitis, neurologic effects are the consequence of the host’s immune response, which often affects the white matter.

Causes

Viruses, bacteria, fungi, and parasites all can cause encephalitis. Herpesviruses, varicella, and arboviruses were the viral causes reported most frequently. From a practical standpoint, there are too many possible causes of encephalitis for every patient to receive an exhaustive evaluation. Focused historical questions may establish the risk of specific causes and guide the prioritization of testing.

Fig.1 Pathogens of Encephalitis. (Lewis, 2005)

Immunologic Features

In the autoimmune encephalitides, the antibodies bind to extracellular epitopes of cell-surface proteins and cause reversible neuronal dysfunction. These features may explain the better outcomes for patients with autoimmune encephalitides, as compared with the outcomes for patients with neurologic syndromes related to antibodies against intracellular proteins, in which neuronal loss is frequent and cytotoxic T-cell mechanisms predominate.

Herpes simplex encephalitis, and possibly other viral encephalitides, can trigger antibodies against the NMDAR and other neuronal cell-surface proteins; such antibodies might explain relapsing neurologic symptoms that arise weeks after the onset of herpes simplex encephalitis.

Fig.2 Antibody reactivity and pathological features of encephalitis associated with antibodies against neuronal cell-surface antigens as compared with encephalitis associated with antibodies against intracellular antigens. (Dalmau, 2018)

Imaging and Ancillary Studies

Magnetic resonance imaging (MRI) is much more sensitive than CT scans for acute changes associated with encephalitis. Electroencephalography (EEG) can be a helpful adjunct in the early assessment of encephalitis. EEG may be needed to assess seizure activity and may help localize the region of encephalitic involvement. Compared with CT scans, EEG is considerably more sensitive in detecting focal encephalitis at the time of presentation.

Treatment

The composition and duration of treatment for encephalitis depend on the underlying cause. Of the viral causes, only HSV and varicella have well-established therapy. In contrast, most bacterial, fungal, and parasitic causes have accepted treatments for systemic infection. Patients whose diagnosis is infectious encephalitis should receive empiric acyclovir for HSV and antibacterial agents for meningitis until bacterial and viral study results are available. In cases of suspected postinfectious encephalitis or encephalitis of unknown cause, a neurologist and an infectious disease specialist should be consulted regarding the use of intravenous immune globulin (IVIG), corticosteroids, or other immune system modulators.

Products We Can Provide for Encephalitis Research

Studies of how autoantibodies alter the structure and function of synaptic proteins and cause symptoms are critical for an understanding of the underlying pathogenic mechanisms, which in turn could lead to the development of new treatment strategies. Creative Biolabs is a leading international biotechnology company. We are flexible to meet the unique needs of client projects, please feel free to contact us.

References

1. Lewis, P.; Glaser, C.A. Encephalitis. Pediatrics in review. 2005, 26(10): 347.
2. Dalmau, J.; Graus, F. Antibody-Mediated Encephalitis. N Engl J Med. 2018 Mar 1; 378(9): 840-851.