18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease.

Intravenous immunoglobulin (IVIg) has been proposed as a potential agent for Alzheimer's disease (AD) immunotherapy because it contains antibodies against beta-amyloid (Abeta). We carried out an open label dose-ranging study in 8 mild AD patients in which IVIg was added to approved AD therapies for 6 months, discontinued, and then resumed for another 9 months. Infusions were generally well-tolerated. Anti-Abeta antibodies in the serum from AD patients increased in proportion to IVIg dose and had a shorter half-life than anti-hepatitis antibodies and total IgG. Plasma Abeta levels increased transiently after each infusion. Cerebrospinal fluid Abeta decreased significantly at 6 months, returned to baseline after washout and decreased again after IVIg was re-administered for an additional 9 months. Mini-mental state scores increased an average of 2.5 points after 6 months, returned to baseline during washout and remained stable during subsequent IVIg treatment. Our findings confirm and extend those obtained by Dodel et al. [Dodel, R.C., Du, Y., Depboylu, C., Hampel, H., Frolich, L., Haag, A., Hemmeter, U., Paulsen, S., Teipel, S.J., Brettschneider, S., Spottke, A., Nolker, C., Moller, H.J., Wei, X., Farlow, M., Sommer, N., Oertel, W.H., 2004. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 75, 1472-1474] from a 6-month trial of IVIg in 5 AD patients and justify further studies of IVIg for treatment of AD.

Gadodiamide administration causes spurious hypocalcemia.

PURPOSE: To evaluate the prevalence of spurious hypocalcemia after gadodiamide-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: Eight hundred ninety-six inpatients with available serum calcium data obtained before and after gadodiamide-enhanced MR imaging were identified. Changes in serum calcium measurements following gadodiamide administration in 1,049 MR imaging examinations performed in these patients were correlated with gadodiamide dose, renal function, and time between gadodiamide administration and phlebotomy. RESULTS: Following 42 gadodiamide-enhanced examinations, serum calcium measurements spuriously decreased by more than 2 mg/dL (0.5 mmol/L), resulting in laboratory reports of "critical" hypocalcemia (ie, calcium level < 6 mg/dL [1.5 mmol/L]) in 25 examinations. These reduced calcium measurements were correlated with serum creatinine level (r = 0.39, P <.001), gadodiamide dose (r = 0.37, P <.001), and time between gadodiamide injection and phlebotomy (r = -0.28, P <.001). Spurious reductions in calcium measurements after administration of 0.1 mmol of gadodiamide per kilogram of body weight were greater in patients with renal insufficiency (0.6 mg/dL [0.15 mmol/L] +/- 0.5 [0.125, SD]) than in those with normal renal function (0.14 mg/dL [0.035 mmol/L] +/- 0.4 [0.1]) (P <.001). After administration of more than 0.2 mmol/kg of gadodiamide, spurious calcium measurement decreases were greater in patients with renal insufficiency (2.4 mg/dL [0.6 mmol/L] +/- 3.6 [0.9]) than in those with normal renal function (0.4 mg/dL [0.1 mmol/L] +/- 0.7 [0.175]) (P <.001). Patients with renal insufficiency had spuriously low calcium measurements up to 4(1/2) days after gadodiamide administration. Seven patients were inappropriately treated with intravenous calcium and eleven with oral calcium in response to false-positive laboratory reports of critical hypocalcemia. No patient had characteristic symptoms of hypocalcemia or injuries attributed to the inappropriate medical treatment. CONCLUSION: Gadodiamide administration causes spurious hypocalcemia, particularly at doses of 0.2 mmol/kg or higher and in patients with renal insufficiency.