Deep brain stimulation for medically refractory epilepsy.
ABSTRACT Epilepsy is a chronic neurological disorder that affects 0.5-1% of the population. Up to one-third of patients will have incompletely controlled seizures or debilitating side effects of anticonvulsant medications. Although some of these patients may be candidates for resection, many are not. The desire to find alternative treatments for epilepsy has led to a resurgence of interest in the use of deep brain stimulation (DBS), which has been used quite successfully in movement disorders. Small pilot studies and open-label trials have yielded results that may support the use of DBS in selected patients with refractory seizures. Because of the diversity of regions involved with seizure initiation and propagation, a variety of targets for stimulation have been examined. Moreover, stimulation parameters such as amplitude, frequency, pulse duration, and continuous versus intermittent on vary from one study to the next. More studies are necessary to determine if there is an appropriate population of seizure patients for DBS, the optimal target, and the most efficacious stimulation parameters.
- SourceAvailable from: Joost H Heeroma[Show abstract] [Hide abstract]
ABSTRACT: Motivated by its success as a therapeutic treatment in other neurological disorders, most notably Parkinson's disease, Deep Brain Stimulation (DBS) is currently being trialled in a number of patients with drug unresponsive epilepsies. However, the mechanisms by which DBS interferes with neuronal activity linked to the disorder are not well understood. Furthermore, there is a need to identify optimized values of parameters (for example in amplitude/frequency space) of the stimulation protocol with which one aims to achieve the desired outcome. In this paper we characterise the system response to stimulation, to gain an understanding of the role different brain regions play in generating the output observed in EEG. We perform a number of experiments in healthy rats, where the ventral-lateral thalamic nucleus is stimulated using a train of square-waves with different frequency and amplitudes. The response to stimulation in the motor cortex is recorded and the drive-response relationship over frequency/amplitude space is considered. Subsequently, we compare the experimental data with simulations of a mean-field model, finding good agreement between the output of the model and the experimental data--both in the time and frequency domains--when considering a transition to oscillatory activity in the cortex as the frequency of stimulation is increased. Overall, our study suggests that mean-field models can appropriately characterise the stimulus-response relationship of DBS in healthy animals. In this way, it constitutes a first step towards the goal of developing a closed-loop feedback control protocol for suppressing epileptic activity, by adaptively adjusting the stimulation protocol in response to EEG activity.Journal of neuroscience methods 08/2009; 183(1):77-85. · 2.30 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background Deep brain stimulation, specifically high-frequency stimulation (HFS), is an alternative and promising treatment for intractable epilepsies; however, the optimal targets are still unknown. The thalamic reticular nucleus (TRN) occupies a key position in the modulation of the cortico-thalamic and thalamo-cortical pathways. Objective We determined the efficacy of HFS in the TRN against tonic-clonic generalized seizures (TCGS) and status epilepticus (SE), which were induced by scheduled pentylenetetrazole (PTZ) injections. Methods Male Wistar rats were stereotactically implanted and assigned to three experimental groups: Control group, which received only PTZ injections; HFS-TRN group, which received HFS in the left TRN prior to PTZ injections; and HFS-Adj group, which received HFS in the left adjacent nuclei prior to PTZ injections. Results The HFS-TRN group reported a significant increase in the latency for development of TCGS and SE compared with the HFS-Adj and Control groups (p < 0.009). The number of PTZ-doses required for SE was also significantly increased (p < 0.001). Spectral analysis revealed a significant decrease in the frequency band from 0.5 Hz to 4.5 Hz of the left motor cortex in the HFS-TRN and HFS-Adj groups, compared to the Control group. Conversely, HFS-TRN provoked a significant increase in all frequency bands in the TRN. EEG asynchrony was observed during spike-wave discharges by HFS-TRN. Conclusion These data indicate that HFS-TRN has an anti-epileptogenic effect and is able to modify seizure synchrony and interrupt abnormal EEG recruitment of thalamo-cortical and, indirectly, cortico-thalamic pathways.Brain Stimulation 01/2014; · 4.54 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Preliminary results from animal and clinical studies demonstrate that electrical stimulation of brain structures can reduce seizure frequency in patients with refractory epilepsy. Since most researchers derive stimulation parameters by trial and error, it is unclear what stimulation frequency, amplitude and duration constitutes a set of optimal stimulation parameters for aborting seizure activity in a given patient. In this investigation, we begin to quantify the independent effects of stimulation parameters on electrographic seizures, such that they could be used to develop an efficient closed-loop prosthesis that intervenes before the clinical onset of a seizure and seizure generalization. Biphasic stimulation is manually delivered to the hippocampus in response to a visually detected electrographic seizure. Such focal, responsive stimulation allows for anti-seizure treatment delivery with improved temporal and spatial specificity over conventional open-loop stimulation paradigms, with the possibility of avoiding tissue damage stemming from excessive exposure to electrical stimulation. We retrospectively examine the effects of stimulation frequency (low, medium and high), pulse-width (low and high) and amplitude (low and high) in seizures recorded from 23 kainic acid treated rats. We also consider the effects of total charge delivered and the rate of charge delivery, and identify stimulation parameter sets that induce after-discharges or more seizures. Among the stimulation parameters evaluated, we note 2 major findings. First, stimulation frequency is a key parameter for inhibiting seizure activity; the anti-seizure effect cannot be attributed to only the charge delivered per phase. Second, an after-discharge curve shows that as the frequency and pulse-width of stimulation increases, smaller pulse amplitudes are capable of eliciting an after-discharge. It is expected that stimulation parameter optimization will lead to devices with enhanced treatment efficacies and reduced side-effect profiles, especially when used in conjunction with seizure prediction or detection algorithms in a closed-loop control application.International Journal of Neural Systems 04/2011; 21(2):151-62. · 5.05 Impact Factor