Continuous Intrathecal Interferon Alpha Application in Subacute Sclerosing Panencephalitis

To the Editors: Subacute sclerosing panencephlitis (SSPE) is a slow virus disease of the central nervous system caused by a defective measles virus and has a very poor prognosis. Treatment includes oral isoprinosine, oral lamivudine, and subcutaneous, intraventricular or intrathecal interferon alpha (IFN-α) administration. The latter aims at promoting a TH1-type antiviral immune response. Whereas improvement rates of 35% for subcutaneous1 and 35%–50% for intraventricular IFN-α treatment have been reported,2,3 complete and sustained clinical recovery is rare. A 15-year-old boy of Turkish descent developed progressive myoclonic jerks initially considered to be epileptic seizures, which did not respond to antiepileptic treatment. On first admission to our hospital he was able to walk with aid and responded adequately to simple questions. SSPE was confirmed by a marked intrathecal synthesis of antimeasles antibodies, Radermecker complexes on electroencephalography and bilateral high signal intense white matter changes on T2-weighted brain magnetic resonance imaging (MRI, Fig. 1, [online only]—MR spectroscopical (A, B, C) and T2-weighted MR images (D, E, F) performed after primary admission (A, D), five months later (B, E) and after one year of continuous lumbar IFN-α application (C, F). Progressive white matter disease (D, E) with a decrease of N-acetylaspartate (NAA) and an increase of the choline/creatine ratio (A, B) was observed during the five months before initiating continuous intrathecal IFN-α application. Treatment resulted in a regression of the white matter changes and an amelioration of the MR-spectroscopical findings). MR-spectroscopy revealed a decrease of the N-acetylaspartate/creatine ratio (1.6) with a slight increase of the choline/creatine ratio (1.4). Treatment was initiated with oral isoprinosine (50 mg/kg daily) and subcutaneous IFN-α three times weekly (10,000,000 U/m2 body surface maximum), resulting in no clinical improvement, but in treatment-related side effects, including fever and myalgia. He lost the ability to walk or to answer simple questions, developed echolalia, perseverations, and continuous sleepiness. The myoclonia increased and epileptic seizures occurred. A second MRI performed four months after diagnosis showed progressive white matter lesions. A further decrease of the N-acetylaspartate/creatine ratio (0.8) and increase of the choline/creatine ratio (2.0) on MR spectroscopy indicated progressive neuronal loss and demyelination. At this stage a lumbar infusion device (Medtronic Synchromed® II) was implanted.4 Continuous lumbar infusion of 300,000 U IFN-α daily resulted in a gradual stabilization. He became more alert, could perform more complex tasks, and spoke complete sentences again. His perseverations, echolalia, and myoclonic jerks improved. A repeat MRI performed 12 months after the initiation of continuous IFN-α application showed regression of the white matter lesions and improved MR spectroscopical findings (N-acetylaspartate/creatine ratio: 1.1; choline/creatine ratio: 1.7). After an additional 3 months of therapy he became able to walk again without aid. Our findings suggest that continuous lumbar IFN-α application is a valuable treatment option for SSPE. It was well tolerated and greatly improved the patient's clinical and radiologic findings. Since only three patients with continuous IFN-α application have been reported so far,4,5 it remains speculative whether this treatment regimen increases the chance for a sustained stabilization. However, two advantages can be hypothesized: First, continuous infusion of moderate IFN-α doses might be more physiologic than intermittent intraventricular application of high dose therapy, and second, the pump system only has to be refilled once every three weeks, resulting in a better quality of life and probably in a lower rate of infective complications. This new mode of IFN-α application should be further evaluated. Bernhard Thurner, MD Department of Pediatrics University Hospital RWTH Aachen Germany [email protected] Peter Spangenberg, MD Department of Neurosurgery University Hospital RWTH Aachen Germany Michael Kleines, PhD Institute of Medical Microbiology/Virology Division University Hospital RWTH Aachen Germany Marcus Blaum, MD Department of Neuroradiology University Hospital RWTH Aachen Germany Simone Scheithauer, MD Institute of Medical Microbiology/Virology Division University Hospital RWTH Aachen Germany Martin Häusler, MD Department of Pediatrics University Hospital RWTH Aachen Germany