Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
-
Despite the advent of new pharmacological treatments and the high success rate of many surgical treatments for epilepsy, a substantial number of patients either do not become seizure-free or they experience major adverse events (or both). Neurostimulation-based treatments have gained considerable interest in the last decade. Vagus nerve stimulation (VNS) is an alternative treatment for patients with medically refractory epilepsy, who are unsuitable candidates for conventional epilepsy surgery, or who have had such surgery without optimal outcome. ⋯ Data from pilot studies suggest that chronic DBS for epilepsy may be a feasible, effective, and safe procedure. Further trials with larger patient populations and with controlled, randomized, and closed-loop designs should now be initiated. Further progress in understanding the mechanism of action of DBS for epilepsy is a necessary step to making this therapy more efficacious and established.
-
Epilepsy is a common chronic neurological disorder effecting 1 to 2% of the population. Despite advances in anti-epileptic drug therapy, epilepsy surgery, and vagus nerve stimulation, approximately 30% of patients continue to have seizures. Intracranial stimulation is currently under investigation as an adjunctive treatment to anti-epileptic medications in adults with medically intractable epilepsy. ⋯ In contrast, a number of recent investigations have demonstrated the feasibility of closed-loop or responsive stimulation, which is stimulation that is contingent upon the detection of epileptiform activity. This chapter will review the acute and long-term clinical studies of intracranial stimulation, including focal, and nonfocal, and open-loop and responsive stimulation. We will also discuss the optimization and safety of therapeutic parameters used in neurostimulation for epilepsy.
-
Retrospective studies suggest that precipitating events such as prolonged seizures, stroke, or head trauma increase the risk of developing epilepsy later in life. The process of epilepsy development, known as epileptogenesis, is associated with changes in the expression of a myriad of genes. One of the major challenges for the epilepsy research community has been to determine which of these changes contributes to epileptogenesis, which may be compensatory, and which may be noncontributory. ⋯ Prevention of GABA(A) receptor subunit changes after SE using viral gene transfer inhibits development of epilepsy in an animal model, suggesting that these changes directly contribute to epileptogenesis. The mechanisms that regulate differential expression of GABA(A) receptor subunits in hippocampus after SE have recently been identified, and include the CREB-ICER, JAK-STAT, BDNF, and Egr3 signaling pathways. Targeting signaling pathways that alter the expression of genes involved in epileptogenesis may provide novel therapeutic approaches for preventing or inhibiting the development of epilepsy after a precipitating insult.
-
Tourette's Syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics, often associated with behavioral disorders. Symptoms often disappear before or during adulthood. The pathophysiology of TS is still a matter of considerable debate. ⋯ In 1999, thalamic DBS was introduced for intractable TS. Since then, multiple targets have been used in a small number of patients, including the globus pallidus pars interna and the nucleus accumbens. Inclusion and exclusion criteria have been formulated to identify good candidates for DBS.
-
The surgical treatment of Parkinson's disease has been through a revival phase over the last 20 years with the development of deep brain stimulation (DBS). Thalamic DBS was developed first and has proven to be a very effective treatment for tremor. The limitation is the lack of effect on other symptoms. ⋯ When STN DBS is not advised, thalamic DBS remains an option for patients with severe tremor, and GPi stimulation for those with severe dyskinesias. DBS remains a symptomatic treatment for a limited number of patients; it does not seem to alter the disease progression, and many patients are not suitable. There is, therefore, the need for further research into other targets and other approaches.