Intraventricular α-interferon in subacute sclerosing panencephalitis

To the Editor: Anlar et al.¹ reported the favorable effect of intraventricular (IVC) human α-interferon (IFN) plus isoprinosine in subacute sclerosing panencephalitis (SSPE). Theirα-IFN treatment regimen consisted of a 6-week course, 5-day/week administration, with a total of 30 × 10⁶ U/m² (5× 10⁶ U/m² each week); in some cases (not specified how many), the course was repeated at 2- to 6-month intervals, up to 6 times.

We wonder whether better results could be obtained by a more prolonged administration at slightly lower doses, as done by others^2,3 and ourselves⁴

In the eight patients we have treated since 1986, recombinant α-2a IFN (Roferon A, Roche Laboratories, Nutley, NJ) was given in 1 or 2 IVC administrations/week for at least 6 months, or more if no adverse effect occurred. IVC doses ranged from an initial 0.5 × 10⁶ to a maximum of 2.2 × 10⁶ U/m² twice a week, reduced to once a week after improvement had occurred. Biological activity of α-2a IFN in CSF of our first three patients was found to be present a week after IVC administration (A. Dolei, Inst. Virology, University of Sassari). In all cases, we added oral isoprinosine (Inosiplex, Newport Pharmaceuticals, Newport Beach, CA) 100 mg/kg/day and, on the basis of the report of measles virus RNA in peripheral blood lymphocytes,⁵ subcutaneousα2-a IFN 1 to 2 × 10⁶ U/m² twice a week (in the first two patients treated, we performed a dot-blot hybridization of measles virus RNA in peripheral lymphocytes and found its reduction parallel to clinical improvement).⁴

Our patients began treatment in an early phase of the disease, i.e., stage 1 or 2a or 2b according to Risk and Haddad.⁶ In the first months, an improvement, sometimes substantial, of the clinical conditions was observed in all the patients. Consistently, measles antibody titers in CSF and blood and oligoclonal bands in CSF were slightly reduced in most cases.

Early interruption of treatment in two patients was followed by a quick clinical deterioration; in one of these patients, reassumption of IVCα-2a IFN led to adverse effects, which again continued to improve after interruption of treatment. Moreover, after 13 months' administration, we observed in two patients a motor deficit at the lower limbs with an electrophysiologic pattern consistent with spinal motor neuron damage.⁷

On the complex, our eight treated patients have a mean survival of 41 months (range, 12 to 105), underestimated since four are still alive; they maintained satisfactory clinical conditions (autonomously walking and communicating-that is, not beyond stage 2b) for a mean of 30 months (range, 5 to 105), again underestimated values since three patients are still autonomously walking and communicating. Our preceding population of 11 patients (all deceased) treated with only isoprinosine since early stages (1, 2a, 2b) maintained a clinical condition not beyond stage 2b for a mean of 14 months (range, 4 to 36) and had a mean survival of 25 months (range, 4 to 72).

To evaluate the efficacy of a treatment of SSPE, the duration of a somewhat satisfactory quality of life should be considered more relevant than the total survival time: it is well-known that when patients reach a vegetative state they may naturally survive in this condition for many years, probably irrespective of treatment.

Although it is difficult to compare different case series, we did not evidentiate relevant differences between our results and those obtained by Anlar et al.¹ in the 10 of 22 patients treated when still in stage 1 to 2b. However, our experience of deterioration in a few patients after IVC α-IFN withdrawal as well as the improvement with its reassumption suggest the usefulness of a prolonged treatment regimen. This is also suggested by the experience of α-IFN treatment for hepatitis B and C. Speculatively, since α-IFN appears to slow, or temporarily block, proliferation and diffusion of SSPE virus in the central nervous system without eradicating the infection, it seems more appropriate to continue it for as long as possible.