General Features of Viral Encephalitis

Overview Inflammatory cells Inclusion bodies Necrosis Microglial cells Demyelination Differential diagnosis

· A thorough clinical investigation for including PCR of the spinal fluid must be performed before a brain biopsy is performed to rule out viral encephalitis.

· Biopsy: Viral encephalitis often, but not always, present as meningoencephalitis. An adequate brain biopsy that is performed to rule out brain viral encephalitis should include brain cortex, subcortical white matter, leptomeninges and the dura. The location for biopsy should be taken from area that shows abnormal changes on MRI, if possible.

· The absence of features indicating viral encephalitis does not rule out viral encephalitis since the lesional tissue may not have been biopsied.

· Five common features in viral meningoencephalitis include: inflammation, inclusion bodies, necrosis, microglial formation, and demyelination. The histopathology is rarely specific for a certain virus but the morphology of inclusion may be helpful in some cases.

· Location: Some virus have predilection on certain anatomical locations. For example, herpes simplex encephalitis usually causes necrotic inflammatory changes in the temporal lobes. Other viruses may produce a diffuse meningoencephalitis.

Inflammatory cells: Head

· Inflammatory infiltration in viral encephalitis may have PMN at the very early stage but a lot of the time the infiltration is composed exclusively of lymphocytes and plasma cells.

· They may range from a thick perivascular cuffing to a single layer of mononuclear cells in the Vichow-Rubin space. Unless necrosis occurs in the surrounding tissue, the inflammatory infiltrates are usually limited to the perivascular spaces. A single layer of mononuclear cells in the Vichow-Robin spaces of small venules and thicker cuffs of lymphocytes around the larger blood vessels are particularly characteristic features.

· B-cells tend to be confined to the perivascular space while T-cells and NK cells may distribute widely.

Inclusion bodies: Head

· Inclusion bodies and glassy nuclei may be seen in astrocytes, neurons, and oligodendroglial cells. Most of them are intranuclear with a few of them are intracytoplasmic (e.g. Negri body of rabies). The absence of inclusion bodies does not rule out viral encephalitis.

Necrosis: Head

· Necrosis is an important feature in acute viral encephalitis. When tissue necrosis has occurred as a direct result of viral infection per se, histological examination will reveal inflammatory cell infiltration admixed with necrotic parenchyma similar to infarcted brain tissue.

· However, histologic pictures resembling pure infarction may also be seen. The anatomic distribution of the necrotic tissue is very important in evaluating viral encephalitis. Although the histologic picture reveals infarction, the location may not conform to that of a vascular territory. On the other hand, some viral encephalitis such as herpes simplex encephalitis is usually associated with necrosis in the temporal lobe.

· The timing of the biopsy is also important. Viral encephalitis of a duration of less than one week may not reveal any necrosis. Also, necrosis may be a secondary or terminal event. For example, individual neuronal necrosis may be resulted from hypoxia secondary to the viral encephalitis.

Microglial cells: Head

· Hypertrophy and proliferation of microglial cells

· Hypertrophic microglial "rod cells" can be seen in the cerebrum, cerebellum and brain stem.

· Microglial proliferation and hypertrophy are also frequently seen in areas of tissue destruction admixed with lipid laden macrophages.

· Microglial nodules are usually seen in white matter and neuronophagia is usually seen in gray matter. In HIV encephalopathy, they may form giant cells.

· Microglial nodules and neuornphagia may also be seen in other lesions such as hypoxic injury, trauma, and neurodegenerative diseases such as ALS.

Demyelination: Head

· They can be perivascular and associated with perivascular inflammatory cell cuffing.

· In PML and HIV infection, demyelination may result from lytic viral infection of oligodendrocytes appear as focal demyelination not confined to the perivenous zone.

· Demyelination may be associated with more axonal destruction than expected in demyelinating disorders.

· Gliosis may be seen in long standing cases. Astrocytic proliferation and hypertrophic astrocytes are seen in SSPE and PML. Neuronal changes are usually non-specific.

Differential diagnosis: Head

Lymphoma:

· Lymphoma are more frequently seen in patients older than 55 years of age. Lymphoma associated with immunosuppression are frequetly seen in younger patients. They may be associated with Epstein-Barr virus.

· Lymphoma may present as solitary mass or as multifocal lesion, sometimes as diffuse meningeal infiltration or periventricular infiltration, and rarely as uveitis/vitreitis.

Vasculitis: It is necessary to demonstration destruction of vessel wall.