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Maintaining Concentration of Ribavirin in Cerebrospinal Fluid by a New Dosage Method; 3 Cases of Subacute Sclerosing Panencephalitis Treated Using a Subcutaneous Continuous Infusion Pump

Miyazaki, Kyohei, MD, PhD; Hashimoto, Koichi, MD, PhD; Suyama, Kazuhide, MD, PhD; Sato, Masatoki, MD, PhD; Abe, Yusaku, MD, PhD; Watanabe, Masahiro, MD, PhD; Kanno, Syuto, MD, PhD; Maeda, Hajime, MD; Kawasaki, Yukihiko, MD, PhD; Hosoya, Mitsuaki, MD, PhD

The Pediatric Infectious Disease Journal: May 2019 - Volume 38 - Issue 5 - p 496–499
doi: 10.1097/INF.0000000000002181
Antimicrobial Reports

Background: Subacute sclerosing panencephalitis (SSPE) is a slow virus infectious disease resulting from persistent infection with mutant measles virus. At present, there is no effective treatment for SSPE. Interferon-α and inosine pranobex have both been used for the treatment of SSPE, and partial success has been reported for the antiviral drug, ribavirin (RBV). The standardization of dosage method is necessary to carry out treatment with RBV more safely and effectively. In this study, RBV concentrations in cerebrospinal fluid (CSF) were monitored during the intraventricular administration using a subcutaneous continuous infusion pump.

Methods: Three patients with new-onset SSPE were treated with RBV using a subcutaneous continuous infusion pump. On days 3–10 after the start of RBV infusion, CSFs were obtained by lumbar tap, and the concentration of RBV in the CSF was measured using high-performance liquid chromatography.

Results: RBV concentration increased in a dose-dependent manner in all 3 patients, and the target concentration could be generally maintained without any severe side effects. We observed that the clinical symptoms were temporarily relieved in each case. In the 2 cases for whom treatment is continuing, the patients remain in stage III, while the patient who discontinued the therapy progressed to stage IV.

Conclusion: The target RBV concentration in the CSF could be maintained continuously by intraventricular administration using a subcutaneous continuous infusion pump. The accumulation of further cases is necessary to confirm the safety and efficacy of this medical treatment.

From the Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.

Accepted for publication August 6, 2018.

This research is supported by the Research Committee of Molecular Pathogenesis and Therapies for Prion Disease and Slow Virus Infection of The Practical Research Project for Rare / Intractable Disease from Japan Agency for Medical Research and Development, AMED. Grant Number: 16ek0109044h0003.

The authors have no conflicts of interest to disclose.

Address for correspondence: Kyohei Miyazaki, MD, PhD, Department of Pediatrics, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960–1295, Japan. E-mail:

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