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Signs of systemic involvement may (e.g. certain viral diseases or mycotic disorders) or may not (e.g. cerebral abscess, neurotropic infections, immune-mediated encephalitis) be present. Ophthalmologic examination may reveal fundic changes or uveitis.

Neurological signs in animals with inflammatory CNS disease often have an acute to subacute onset, are progressive and reflect multifocal or diffuse involvement of the CNS. However, focal neurological deficits can also occur (e.g. cerebral abscess, fungal granuloma). Seizures commonly occur in animals with forebrain involvement.