Pathogenesis

With the exception of the optic and olfactory nerves, the HSV-1 genome has been detected in all sensory cranial ganglia (Fig. 2) and from cervical ganglia 2 and 3. When HSV-1 is injected into the cornea of experimental animals, the virus proceeds to the otic ganglion, then to the trigeminal ganglion, the glossopharyngeal and vagal ganglia, and finally down to the level of the second and third cervical ganglia. The virus also crosses the midline to infect contralateral ganglia.

HSV-1 infection occurs in three stages: the primary disease stage, the dormant (latent) stage, and the recurrent disease stage.

In the primary disease stage, infection is initiated by contact with infected oral secretions or lesions. The virus enters through mucocutaneous membranes or through a break in the skin. In the latent stage, the virus travels up the sensory nerves that reside in the nucleus of the cranial and spinal ganglia, where the virus is protected from circulating

FIGURE 2 Schematic drawing of the cranial and cervical 2-3 nerves shows multiple areas of potential signs and symptoms of HSV-1 reactivation. Abbreviation: HSV-1, herpes simplex virus type 1.

antibodies but can be reactivated. Disease recurrence is triggered by multiple factors, including fever, trauma, emotional stress, sunlight, menstruation, and ovulation (5).

Because every replication begins in ganglion cells, every case of recurrent HSV infection starts as ganglionitis (8). When the virus is episodically reactivated in multiple ganglia, it does so as polyganglionitis episodica (PGE). The virus only then passes down the axons to induce radiculitis and finally mucocutaneous disease. The virus also travels up the axon to the brain stem to form a localized arachnoiditis, but usually does not cause generalized encephalitis.

When the virus genome leaves the nucleus, it acquires a nuclear protein coat from the nucleus and thus forms a nucleocapsid. This nucleocapsid acquires an envelope of lipoprotein from the plasma membrane of the infected cell (Fig. 3). This alteration in the host cell membrane and deposition of neural protein in perineural areas leads to processes— T lymphocyte sensitization and virally induced immune response—that cause demyeliniza-tion. The mucocutaneous vesicles caused by the virus invading epithelial cells merely represent the visible perimeter of the infected area. These virally mediated cranial neurologic syndromes include many sensory symptoms as well as motor paralysis (9).

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