The matter of relapse after treatment with acyclovir has been recognized, particularly in children. Several potential mechanisms have been suggested by Tiége and colleagues, including an immune-mediated inflammatory response, but treatment with too low a dose or for too brief a period is undoubtedly the main cause of the rare relapses that occur in adults. In children, a second course of acyclovir is usually successful. A curious finding in approximately 20 percent of patients has been the subsequent appearance of anti-NMDA antibodies, a finding more typical of antibody mediated limbic encephalitis; there may be movement disorders or seizures in children and delirium in adults, usually more than a month removed from the onset of the infection. Ostensible relapses of encephalitis have been attributed to the antibodies but they may also be asymptomatic as noted by Armangue and coauthors.
Prognosis The outcome of this disease, both mortality and morbidity, is governed to a large extent by the patient’s age and state of consciousness, particularly at the time of institution of acyclovir therapy. If the patient is unconscious (except immediately after a convulsion), the outcome is usually poor. However, if treatment is begun within 4 days of onset of the illness in an awake patient, survival is greater than 90 percent (Whitley 1990). Evaluation of patients 2 years after treatment showed 38 percent to be normal or nearly normal, whereas 53 percent were dead or severely impaired. The neurologic sequelae are often of the most serious type, consisting of a Korsakoff amnesic defect or a global dementia, seizures, and aphasia as described by Drachman and Adams in the era before treatment became available. If there were seizures during the acute illness, it may be advisable to continue antiepileptic medications for a year or more and then judge the risk of discontinuing them on the basis of further seizures, the EEG, and the patient’s exposure to situations that pose a danger, such as driving. With the exception of the rare relapsing cases mentioned earlier, the infection does not recur.
This agent, the cause of roseola (exanthema subitum), has had a controversial role in a number of acute febrile neurologic illnesses, including febrile seizures in infants and young children, subsequent temporal lobe epilepsy, cranial-nerve palsies, and other conditions. However, it is fairly firmly established as the cause of a medial temporal lobe (limbic) encephalitis in adult patients following allogenic hematopoietic stem cell bone marrow transplantation, as summarized by Seeley and colleagues. All of their patients also developed a graft-versus-host reaction. The clinical and imaging features closely resemble a mild case of herpes encephalitis but more so, the paraneoplastic and anti–voltage-gated potassium channel limbic encephalitis that is discussed in Chap. 30. The prognosis is far better than in herpetic encephalitis. It is mentioned here that mundane adenoviruses can also produce a severe medial temporal lobe encephalitis in bone marrow transplant cases, in one of our patients associated with gray matter damage in the spinal cord.
The other viral agents that appear as causes of encephalitis with some regularity in stem-cell and organ transplant patients include parvovirus, CMV, EBV, adenovirus, HSV, and varicella zoster virus. Quite often, these infections are but one component of multiorgan viral infection. Some of these agents also cause manifestations of infection in peripheral and cranial nerves.