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Immune and anti-inflammatory therapies

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If immune mechanisms and inflammation do indeed have a role in the generation of seizures, immune-modulating and anti-inflammatory therapies might be effective treatments for some or all forms of epilepsy. Therapies such as ACTH, corticosteroids, plasmapheresis and intravenous immunoglobulin (IVIg) have been employed to treat seizures and/or epilepsy, with varying success. These therapies have all been employed in human patients with presumed autoimmune limbic encephalitis, where early and aggressive treatment often seems to be useful (Vincent et al., 2010).

The presumed mechanism of action of the therapeutic agents listed above is suppression of inflammation; however, other modes of action might also be involved, including direct effects on brain excitability, and suppression of endogenous proconvulsant brain agents (Baram and Hatalski, 1998; Joels and Baram, 2009).

The use of steroids in various forms is common for more severe, treatment-resistant forms of childhood epilepsy. ACTH, steroids and IVIg have all been employed to treat AEM-unresponsive paediatric epilepsies, difficult focal (partial) epilepsies and myoclonic epilepsies (You et al., 2008). Unfortunately, determination of whether patients received benefit from these treatments is problematic, since most of these epilepsies are extremely heterogeneous in aetiology and severity, and exhibit notoriously variable courses. In addition, most of the clinical studies are retrospective case series, with occasional prospective case series that lack controls (Mikati et al., 2002; Verhelst et al., 2005).

Follow-up duration in these case series was also often variable. A recent review of investigations of IVIg in intractable childhood epilepsy found no randomized or controlled studies and, in fact, only two case series employed statistics in assessing outcome (Mikati et al., 2010). One series showed a statistically significant reduction in seizures with IVIg treatments, while the other revealed an insignificant trend with such therapy (Mikati et al., 2010). However, a Cochrane Collaboration review on the use of ACTH for other childhood epilepsies, published in 2007, found only a single randomized controlled trial, which only included five patients (Gayatri et al., 2007). The authors of this review concluded that, at present, no evidence exists to support either the safety or the efficacy of ACTH for general paediatric epilepsies (Gayatri et al., 2007).

Canine and Feline Epilepsy

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