Most patients with N-methyl D-aspartate-receptor antibody encephalitis develop seizures but the epileptogenicity of the antibodies has not been investigated in vivo. Wireless electroencephalogram transmitters were implanted into 23 C57BL/6 mice before left lateral ventricle injection of antibody-positive (test) or healthy (control) immunoglobulin G. Mice were challenged 48 h later with a subthreshold dose (40 mg/kg) of the chemo-convulsant pentylenetetrazol and events recorded over 1 h. Seizures were assessed by video observation of each animal and the electroencephalogram by an automated seizure detection programme. No spontaneous seizures were seen with the antibody injections. However, after the pro-convulsant, the test mice (n = 9) had increased numbers of observed convulsive seizures (P = 0.004), a higher total seizure score (P = 0.003), and a higher number of epileptic 'spike' events (P = 0.023) than the control mice (n = 6). At post-mortem, surprisingly, the total number of N-methyl D-aspartate receptors did not differ between test and control mice, but in test mice the levels of immunoglobulin G bound to the left hippocampus were higher (P < 0.0001) and the level of bound immunoglobulin G correlated with the seizure scores (R(2) = 0.8, P = 0.04, n = 5). Our findings demonstrate the epileptogenicity of N-methyl D-aspartate receptor antibodies in vivo, and suggest that binding of immunoglobulin G either reduced synaptic localization of N-methyl D-aspartate receptors, or had a direct effect on receptor function, which could be responsible for seizure susceptibility in this acute short-term model.
Various aspects of calcium and bone metabolism were studied in 50 cases of chronic renal failure. It was found that elevation of plasma alkaline phosphatase was generally associated with reduced metacarpal cortical thickness and in a small number of biopsies reflected the osteomalacic rather than the resorptive component of renal bone disease. Patients with an elevated plasma alkaline phosphatase tended to have a lower plasma calcium, lower plasma bicarbonate and lower radiocalcium absorption than patients with a normal alkaline phosphatase. Hypocalcaemia was frequently associated with, and attributed by the authors to reduced tubular reabsorption of calcium, which in turn appeared to be related to the degree of metabolic acidosis. The authors conclude that metabolic acidosis predisposes to hypocalcaemia and, therefore, to renal osteomalacia.
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