Focal treatment for refractory epilepsy: hope for the future?
Despite advances in anti-epileptic drug therapy and epilepsy surgery in recent years, intractable epilepsy remains a large clinical problem. Surgical resection, which can have an excellent outcome, is appropriate for only a minority of patients in whom an identifiable focus in non-eloquent brain can be identified. Systemic drug delivery is inevitably limited by the potential for unwanted side effects, due to actions both outside the CNS and in non-epileptic brain regions. Thus for a substantial number of patients novel treatment approaches are urgently needed. Both focal drug delivery and neuronal stem cell grafting have been evaluated in a variety of experimental epilepsy models in recent years, targeting either the seizure focus or key propagation pathways. The literature in this field is critically reviewed and considered in a clinical context. Studies in both areas are hampered by the limitations of available animal models, and by uncertainties in discerning which changes in the epileptic brain directly promote seizures, and which are compensatory. However, in many cases promising, though short-term, results have been obtained. Before such studies could be considered in humans further investigations that include long-term seizure and behavioural outcomes, in clinically relevant experimental models, are required. However, the current literature does provide proof in principle for a focal treatment approach, which may offer hope for many currently intractable patients for whom drug developments and surgical advances have proved disappointing.
Nilsen
Karen E
KE
Clinical Neurosciences, St. Georges Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
Cock
Hannah R
HR
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D004827:Epilepsy / Q000188:drug therapy* / Q000601:surgery; D006801:Humans
D000927:Anticonvulsants