Electrical stimulation and gene-based neuromodulation for control of medically-refractory epilepsy
The failure of available antiepileptic medications to adequately control seizures in a substantial number of patients underscores the need to develop novel epilepsy therapies. Recent advancements in technology and the success of neuromodulation in treating a variety of neurological disorders have spurred interest in exploring promising therapeutic alternatives, such as electrical stimulation and gene-based synaptic control. A variety of different stimulation approaches to seizure control targeting structures in the central or peripheral nervous system have been investigated. Most studies have been based on uncontrolled observations and empirical stimulation protocols. Today the vagus nerve stimulator is the only FDA approved adjunctive treatment for epilepsy that utilizes electrical stimulation. Other potential strategies including direct stimulation of the epileptogenic cortex and deep brain stimulation of various targets are currently under investigation. Chronically implanted devices for electrical stimulation have a variety of limitations. First, they are susceptible to malfunction and infection. Second, most systems require battery replacement. Finally, electrical stimulation is incapable of manipulating neuronal function in a transmitter specific fashion. Gene delivery to epileptogenic targets or targets implicated in regulating seizure threshold has been investigated as an alternative means of neuromodulation in animal models. In summary, positive preliminary results and the lack of alternative treatment options provide the impetus for further exploration of electrical stimulation and gene-based therapies in pharmacoresistant epilepsy. Various specific targets and approaches to modulating their activity have been investigated in human studies.
KeywordsNeuromodulation gene therapy epilepsy seizures electrical stimulation review
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- 3.Bailey P, Bremer F (1938) A sensory cortical representation of the vagus nerve. J Neurophysiol 1: 405–412Google Scholar
- 5.Benabid AL, Minotti L, Koudsie A, de Saint MA, Hirsch E (2002) Antiepileptic effect of high-frequency stimulation of the subthalamic nucleus (corpus luysi) in a case of medically intractable epilepsy caused by focal dysplasia: a 30-month follow-up: technical case report. Neurosurgery 50: 1385–1391PubMedCrossRefGoogle Scholar
- 7.Bridgers SL (1991) The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects. Electroencephalogr Clin Neurophysiol Suppl 43: 170–179Google Scholar
- 16.Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES, Henry TR, Collins SD, Vaughn BV, Gilmartin RC, Labar DR, Morris GL III, Salinsky MC, Osorio I, Ristanovic RK, Labiner DM, Jones JC, Murphy JV, Ney GC, Wheless JW (1998) Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51: 48–55PubMedCrossRefGoogle Scholar
- 25.Loddenkemper T, Lüders HO (2004) Mechanisms and efficacy of deep brain stimulation in epilepsy. In: Rosenow F, Lüders HO (eds) Presurgical assessment of the epilepsy with clinical neurophysiology and functional imaging, vol. 3. Elsevier, Amsterdam, pp 539–570Google Scholar
- 27.Mattson RH, Cramer JA, Collins JF, Smith DB, Delgado-Escueta AV, Browne TR, Williamson PD, Treiman DM, McNamara JO, McCutchen CB (1985) Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 313: 145–151PubMedCrossRefGoogle Scholar
- 34.Nair DR, Matsumoto R, Lüders HO, Burgess R, Bingaman W (2004) Direct cortical electrical stimulation in the treatment of epilepsy. In: Lüders HO (ed) Deep brain stimulation and epilepsy. Martin Dunitz, London, pp 275–284Google Scholar
- 35.Neme S, Montgomery EB Jr, Rezai A, Wilson K, Lüders HO (2004) Subthalamic nucleus stimulation in patients with intractable epilepsy: the Cleveland experience. In: Lüders HO (ed) Deep brain stimulation and epilepsy. Martin Dunitz, London, pp 349–355Google Scholar
- 39.Richichi C, Lin EJ, Stefanin D, Colella D, Ravizza T, Grignaschi G, Veglianese P, Sperk G, During MJ, Vezzani A (2004) Anticonvulsant and antiepileptogenic effects mediated by adeno-associated virus vector neuropeptide Y expression in the rat hippocampus. J Neurosci 24: 3051–3059PubMedCrossRefGoogle Scholar