Intraventricular gamma-globulin for the management of enterovirus encephalitis


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Abstract

Although bacterial infections predominate in patients with hypogammaglobulinemia, patients who do not produce normal amounts of immunoglobulin also have an increased incidence of viral infections. This is particularly true of infections with enteroviruses. Echovirus encephalitis has been a major problem for patients with hypogammaglobulinemia. Neurologic damage, frequently resulting in death, has been common in such patients. Because there is an obligatory extracellular phase in the cell to cell spread of enteroviruses, therapy with immunoglobulin has been attempted. In certain patients intravenous and intrathecal gammaglobulin has temporarily halted progression of the disease, but, no patients have been cured by this approach. In this report we detail treatment of three children with X-linked hypogammaglobulinemia who had encephalitis caused by echovirus infections. Despite doses of intravenous immunoglobulin that maintained the patient's IgG levels within the normal range, their condition deteriorated in all cases. Treatment with intraventricular immunoglobulin was then tried. In all three cases cerebrospinal fluid protein levels and cell counts returned to normal after this treatment and the echoviruses can no longer be isolated from the cerebrospinal fluid. Follow-up time has ranged from 18 months to 4 years.Ommaya reservoirs were placed into the lateral ventricle of each patient and concentrated (6%) immunoglobulin (Sandoglobulin®) was injected into the reservoir on a daily basis. On Days 1 through 7 of the regimen patients were given 120, 300, 450, 510, 540 and 600 mg of IgG, respectively. Patients then received 300 mg daily for periods ranging from 1 week to 1 month. Cultures of cerebrospinal fluid removed from the reservoir were repeatedly analyzed to determine the need for further treatment. Clinically the patients improved markedly. Seizure activity in one, visual accuity in another and hyperactivity in a third settled rapidly. All children are now free of virus and are attending school. Each of the three patients is being maintained on intravenous immunoglobulin and receives 3 g every week to keep serum IgG level in the range of 600 to 1000 mg/dl. The immunoglobulin used intraventricularly contained antibodies specific for the echovirus infecting these children in a titer of 1:32 or greater. It appears that the previously fatal complication of enterovirus encephalitis in children with sexlinked agammaglobulinemia may be frequently controlled by the use of concentrated gammaglobulin preparations administered intraventricularly. The same preparations administered intravenously do not produce sufficient concentrations of immunoglobulin in the cerebrospinal fluid to produce the neutralizing effect seen with the intraventricular regimen.

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