Herpes Simplex Encephalitis

Herpes Simplex Encephalitis SIR-Doctors Brown and Bower have described a case of neonatal herpes simplex infection with encephalitis which they treated with cytosine arabinoside (Ara-C) (DMCN, 17, 493). During the remaining seven months or so of the child’s life it required almost constant tube-feeding and the neurological and developmental status remained poor. At death there was microcephaly and other severe neuropathology. Decision to treat with this inhibitor of DNA synthesis must have been extremely difficult. The poor prognosis anyway will have weighed heavily, as did also “the report of its effcacy in several adult patients” and an apparently normal outcome in half the neonatal cases so far reported as receiving Ara-C. However, as the authors say, only four such cases have been reported, and the ‘successful’ two did not have encephalitis. Without being in any way qualified to comment on this particular case, I feel that the nature of the drug and its known effects on developing brain should be brought to the notice of the general reader more fully than was possible in a brief case report. Ara-C is an antimetabolite which acts primarily as an inhibitor of DNA polymerase. This basis of its action against DNA viruses also makes it an antimitotic agent. Thus its efficacy or safety in adult brain, where there are virtually no mitoses, is theoretically not a good analogy for its use in the neonatal brain. We have recently discussed the effects of Ara-C on developing brains at several stages of development, including those thought to be comparable with the human neonate’. We have also recognised the difficulties in this context of interpreting experimental results in human-equivalent terms. The effects of Ara-C on normal developing brains are very severe, although we would not have predicted that the particular neuropathological findings in Brown and Bower’s case would all have resulted from use of the drug. Presumably most of them were primarily of viral origin. Adenine arabinoside (Ara-A) may be a more suitable antiviral agent in these extreme cases, again bearing in mind the very poor alternative prognosis, since we found it to have a negligible detectable effect on normal brain development. We have been very interested in, and grateful for, Dr. Brown’s and Dr. Bower’s report, and would only add that if arabinosides are to be used again, and if autopsy material comes to hand, we would be especially interested in the condition of the cerebellum for reasons set out in our paper.