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Helldén, A. et al.

Helldén, Lycke, Vander, Svensson, Odar-Cederlöf, Ståhle,

The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment.

OBJECTIVES: Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy. METHODS: We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis. RESULTS: CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 mumol/L, range 0.6-7.0). The concentration of CMMG was below the limit of quantification (<0.5 mumol/L) in asymptomatic subjects (P < 0.001). All patients with neuropsychiatric signs and symptoms, except one, had acute renal function impairment or chronic renal failure. CONCLUSIONS: These results are consistent with the hypothesis that CMMG is involved in the development of neuropsychiatric side effects in aciclovir- or valaciclovir-treated patients. Measurement of CMMG in CSF and/or serum is a promising tool in the diagnostic procedure for aciclovir- or valaciclovir-treated patients with neuropsychiatric symptoms and may help to differentiate between side effects and herpes encephalitis.[1]

References

The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment. Helldén, A., Lycke, J., Vander, T., Svensson, J.O., Odar-Cederlöf, I., Ståhle, L. J. Antimicrob. Chemother. (2006) [Pubmed]

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