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The purpose of this study is to ascertain possible efficacy and to understand possible mechanisms of action of intramuscular or intravenous immunoglobulin (IVIg) in the treatment of intractable epilepsy, through a review of all identifiable articles on this topic. In 24 studies, none with a placebo controlled design, 368 patients with epilepsy receiving IVIg were identified. Patients' ages ranged from < 1 to 35 years, mean 7.3 years. Female/male ratio was 0.6. All patients were reported to suffer from intractable epilepsy. The average percentage of patients with an IgG2 deficiency was 25%. The total dose of IVIg varied between 0.3 and 6.8 g/kg for a period of 0.15 to 12 months. Whenever reported, adverse effects of IVIg were minimal. None of the studies reported the need of cessation of IVIg administration due to adverse effects. On the average, the mean clinical seizure reduction and the mean EEG improvement were 52% and 45%, respectively. On the average the percentage of patients with complete seizure remission and the percentage of patients with behavioral improvement were 23% and 63%, respectively. Cumulative meta-analysis of the identified articles is not possible due to the lack of controlled studies, the heterogeneity of the available studies, and the possible publication bias of unpublished negative data. Given these pitfalls, this literature study nevertheless allows some conclusions: (i) There is no formal proof of efficacy of IVIg treatment in epilepsy, and the present review underscores the need of controlled clinical trials before firm conclusions concerning efficacy can be drawn. The uncontrolled clinical observations discussed in this 'state-of-the-art' review generate suggestive evidence at best. They suggest that IVIg might be effective in some patients with intractable epilepsy, and may be considered as a safe add-on medication in various types of idiopathic and symptomatic intractable epilepsy. (ii) Review of the literature did not help in explaining intractable epilepsy or the mechanism of action of IVIg, but did permit some inferences that could serve to design future clinical and experimental approaches to IVIg administration in epilepsy.

Before and after administration of intravenous immunoglobulin (IVIg), cerebrospinal fluid (CSF) was examined in a homogeneous group of 15 patients with cryptogenic types of West syndrome (WS) and Lennox-Gastaut syndrome (LGS). The purpose of the present CSF study was: (i) to elucidate possible etiological factors and consequences of these severe forms of epilepsy, and (ii) to elucidate mechanisms of action and adverse effects of IVIg. Hypotheses concerning etiological factors like central nervous system infections, neuroimmunological disorders, or disturbances in neurotransmitter metabolites could not be confirmed. These normal CSF findings are in accordance with the concept of a cryptogenic etiology of the epilepsies in the reported patients. Nor could we confirm hypotheses concerning seizure consequences, such as increased blood-CSF permeability, increased markers of brain cell destruction, or increased metabolic components. Following IVIg administration in these patients, all with an on the whole undisturbed blood-CSF barrier permeability as measured by Q albumin, the CSF IgG concentrations increased significantly and proportionally to the Q albumin level. No signs of adverse effects of IVIg such as aseptic meningoencephalitis were found in 165 infusions of IVIg performed in the 15 children.

Serum immunoglobulin G, A and M concentrations and their respective kappa/lambda (kappa/lambda) light chain ratios were studied in 26 children with epilepsy. Fifteen had cryptogenic West syndrome or Lennox-Gastaut syndrome and 11 had other forms of childhood epilepsy. The results were compared to the data of a reference group of healthy children. The mean serum IgG and IgM concentrations were respectively 2.2 g/l (P = 0.007) and 0.4 g/l (P = 0.016) higher in the 26 children with epilepsy compared to the reference group. The kappa/lambda ratios of total serum immunoglobulins, IgG and IgM were respectively 0.10 (P = 0.057), 0.20 (P = 0.001) and 0.14 (P = 0.005) lower in the children with epilepsy than in the reference group. IgA concentration and IgA kappa/lambda ratio were not affected. There were no significant differences between the kappa/lambda ratios of the West and Lennox-Gastaut epilepsy and the other types of childhood epilepsies. The results are further evidence of reciprocal interaction between the nervous system and the immune system in childhood epilepsy.