Disrupting abnormal electrical activity with deep brain stimulation: is epilepsy the next frontier?

Abstract

<jats:p>Given the tremendous success of deep brain stimulation (DBS) for the treatment of movement and neuropsychiatric disorders, clinicians have begun to open up to the possible use of electrical stimulation for the treatment of patients with uncontrolled seizures. This process has resulted in the discovery of a wide array of DBS targets, including the cerebellum, hypothalamus, hippocampus, basal ganglia, and various thalamic nuclei. Despite the ambiguity of the mechanism of action and the unknowns surrounding potentially ideal stimulation settings, several recent trials have empirically demonstrated reasonable efficacy in selected cases of medication-refractory seizures. These exciting results have fueled a number of studies aimed at firmly establishing DBS as an effective treatment for selected cases of intractable epilepsy, and many companies are aiming at Food and Drug Administration approval. We endeavor to review the studies in the context of the various DBS targets and their relevant circuitry for epilepsy. Based on the unfolding research, DBS has the potential to play an important role in treating refractory epilepsy. The challenge, as in movement disorders, is to assemble interdisciplinary teams to screen, implant, and follow patients, and to clarify patient selection. The future will undoubtedly be filled with optimization of targets and stimulation parameters and the development of best practices. With tailored therapeutic approaches, epilepsy patients have the potential to improve with DBS.</jats:p>

Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy

“…A recent Cochrane review of three trials of cerebellar stimulation ( Van Buren et al, 1978 ; Wright et al, 1984 ; Velasco et al, 2005 ) found that there was simply insufficient evidence to make conclusive statements on the efficacy of cerebellar stimulation ( Sprengers et al, 2014 ). The mixed results in human studies has also contributed to the weakened enthusiasm for the potential of cerebellar-directed intervention, and despite the continued listing of the cerebellum as a potential target in reviews of electrical stimulation for epilepsy ( Theodore and Fisher, 2004 ; Morrell, 2006 ; Boon et al, 2007 ; Karceski, 2007 ; Krauss and Koubeissi, 2007 ; Ellis and Stevens, 2008 ; Hamani et al, 2009 ; Lockman and Fisher, 2009 ; Saillet et al, 2009 ; Wyckhuys et al, 2009 ; Kahane and Depaulis, 2010 ; Lega et al, 2010 ; Rahman et al, 2010 ; Zhong et al, 2011 ; Tykocki et al, 2012 ; Fisher, 2013 ; Ge et al, 2013 ; Fisher and Velasco, 2014 ; Laxpati et al, 2014 ), relatively little recent experimental work has actually examined this topic. While our results clearly support renewed interest in the cerebellum as a potential intervention target, future translational success will require identifying the appropriate population for this intervention (e.g., perhaps patients with temporal lobe epilepsy), the appropriate location for intervention (e.g., the midline), the appropriate stimulation parameters (e.g., to activate, rather than inhibit, the midline), an appropriate sample same size, improvements in surgical procedures including device implantation (to avoid electrode migration), and possibly the implementation of an on-demand, responsive system to control the timing of intervention ( Fountas et al, 2010 ; Rahman et al, 2010 ; Armstrong et al, 2013 ; Heck et al, 2014 ; Sprengers et al, 2014 ).…”

Seizure frequency reduction after posteromedial hypothalamus deep brain stimulation in drug‐resistant epilepsy associated with intractable aggressive behavior

“…The stimulation of the pHyp also modulates the electrical activity on the mammillary bodies (MB), which have connections with the anterior nucleus of the thalamus via the mamillothalamic fascicle of Vicq d'Azir (MMT) (Fig. ).…”

Neues aus der Epileptologie

“…In kleineren Fallserien wurden verschiedene Targets beschrieben wie der Hypothalamus, der Hippokampus, das Zere-bellum, der Nucleus subthalamicus, der Nucleus centromedianus thalami, der anteriore Thalamuskern sowie der Nucleus caudatus. Alle Studien zeigten einen mehr oder minder begrenzten Erfolg [49]. Der eigentliche Wirkmechanismus der DBS ist nur bedingt geklärt, es werden aber Veränderungen der Neurotransmitterausschüttung und Modifikationen im neuronalen Netzwerk beschrieben z.…”