Nealen G. Laxpati

Real-time magnetic resonance-guided stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy.

BACKGROUND Open surgery effectively treats mesial temporal lobe epilepsy, but carries the risk of neurocognitive deficits, which may be reduced with minimally invasive alternatives. OBJECTIVE To describe technical and clinical outcomes of stereotactic laser amygdalohippocampotomy with real-time magnetic resonance thermal imaging guidance. METHODS With patients under general anesthesia and using standard stereotactic methods, 13 adult patients with intractable mesial temporal lobe epilepsy (with and without mesial temporal sclerosis [MTS]) prospectively underwent insertion of a saline-cooled fiberoptic laser applicator in amygdalohippocampal structures from an occipital trajectory. Computer-controlled laser ablation was performed during continuous magnetic resonance thermal imaging followed by confirmatory contrast-enhanced anatomic imaging and volumetric reconstruction. Clinical outcomes were determined from seizure diaries. RESULTS A mean 60% volume of the amygdalohippocampal complex was ablated in 13 patients (9 with MTS) undergoing 15 procedures. Median hospitalization was 1 day. With follow-up ranging from 5 to 26 months (median, 14 months), 77% (10/13) of patients achieved meaningful seizure reduction, of whom 54% (7/13) were free of disabling seizures. Of patients with preoperative MTS, 67% (6/9) achieved seizure freedom. All recurrences were observed before 6 months. Variances in ablation volume and length did not account for individual clinical outcomes. Although no complications of laser therapy itself were observed, 1 significant complication, a visual field defect, resulted from deviated insertion of a stereotactic aligning rod, which was corrected before ablation. CONCLUSION Real-time magnetic resonance-guided stereotactic laser amygdalohippocampotomy is a technically novel, safe, and effective alternative to open surgery. Further evaluation with larger cohorts over time is warranted.

Deep Brain Stimulation for the Treatment of Epilepsy: Circuits, Targets, and Trials

Deep brain stimulation (DBS) has proven remarkably safe and effective in the treatment of movement disorders. As a result, it is being increasingly applied to a range of neurologic and psychiatric disorders, including medically refractory epilepsy. This review will examine the use of DBS in epilepsy, including known targets, mechanisms of neuromodulation and seizure control, published clinical evidence, and novel technologies. Cortical and deep neuromodulation for epilepsy has a long experimental history, but only recently have better understanding of epileptogenic networks, precise stereotactic techniques, and rigorous trial design combined to improve the quality of available evidence and make DBS a viable treatment option. Nonetheless, underlying mechanisms, anatomical targets, and stimulation parameters remain areas of active investigation.

Electrical Stimulation for Epilepsy: Experimental Approaches

Direct electrical stimulation of the brain is an increasingly popular means of treating refractory epilepsy. Although there has been moderate success in human trials, the rate of seizure freedom does not yet compare favorably to resective surgery. It therefore remains critical to advance experimental investigations aimed toward understanding brain stimulation and its utility. This article introduces the concepts necessary for understanding these experimental studies, describing recording and stimulation technology, animal models of epilepsy, and various subcortical targets of stimulation. Bidirectional and closed-loop device technologies are also highlighted, along with the challenges presented by their experimental use.

Spontaneous and Evoked High Frequency Oscillations in the Tetanus Toxin Model of Epilepsy

Purpose:  High‐frequency oscillations (HFOs) are an emerging biomarker for epileptic tissue. Yet the mechanism by which HFOs are produced is unknown, and their rarity makes them difficult to study. Our objective was to examine the occurrence of HFOs in relation to action potentials (APs) and the effect of microstimulation in the tetanus toxin (TT) model of epilepsy, a nonlesional model with a short latency to spontaneous seizures.

Real-time in vivo optogenetic neuromodulation and multielectrode electrophysiologic recording with NeuroRighter.

Optogenetic channels have greatly expanded neuroscience’s experimental capabilities, enabling precise genetic targeting and manipulation of neuron subpopulations in awake and behaving animals. However, many barriers to entry remain for this technology – including low-cost and effective hardware for combined optical stimulation and electrophysiologic recording. To address this, we adapted the open-source NeuroRighter multichannel electrophysiology platform for use in awake and behaving rodents in both open and closed-loop stimulation experiments. Here, we present these cost-effective adaptations, including commercially available LED light sources; custom-made optical ferrules; 3D printed ferrule hardware and software to calibrate and standardize output intensity; and modifications to commercially available electrode arrays enabling stimulation proximally and distally to the recording target. We then demonstrate the capabilities and versatility of these adaptations in several open and closed-loop experiments, demonstrate spectrographic methods of analyzing the results, as well as discuss artifacts of stimulation.

Extraventricular Long-Axis Cannulation of the Hippocampus: Technical Considerations

BACKGROUND: Patients with hippocampal epileptogenic foci may benefit from targeted intracranial monitoring of seizures and treatments such as hippocampal electrical stimulation, closed-loop stimulation, and stereotactic laser ablation. Each may benefit from a greater volume of hippocampal coverage with long-axis cannulation. Furthermore, an extraventricular trajectory avoids brain shift and reduces the risk of hemorrhage from ependymal breach. Unfortunately, detailed descriptions of the technical aspects of longitudinal cannulation of the hippocampus remain sparse. OBJECTIVE: To develop a standard protocol for extraventricular longitudinal hippocampal cannulation. METHODS: Images from 25 patients stereotactically implanted with 27 longitudinal hippocampal devices were retrospectively reviewed to determine the location of the burr hole or twist drill craniostomy. Simulated planning for bilateral occipital trajectories was then performed on a second cohort of 25 patients (50 trajectories) with mesial temporal sclerosis. An entry point derived from these 77 trajectories was subsequently validated on a third cohort of 25 patients (50 trajectories). RESULTS: Extraventricular long-axis hippocampal implantation necessitates a lateral-to-medial and cephalad-to-caudal trajectory that skirts the inferomedial border of the temporal horn. Measurements from 64 trajectories suggested a consensus entry point that successfully facilitated 50 test trajectories as well as frame placement on 4 patients requiring long-axis hippocampal cannulation. CONCLUSION: Although trajectories must be individually tailored for each patient, we recommend a starting entry point approximately 5.5 cm superior to the external occipital protuberance and 5.5 cm lateral to midline for extraventricular long-axis hippocampal cannulation in adult patients. Identification of this point is particularly important when positioning the stereotactic frame. ABBREVIATIONS: AC-PC, anterior commissure-posterior commissure CRW, Cosman-Roberts-Wells EEG, electroencephalographic EOP, external occipital protuberance SLA, stereotactic laser ablation

Adapting NeuroRighter for in vivo optogenetic stimulation

The temporal and cell-type specific precision of optogenetics provides effective functional dissection of the intact nervous system. Integrating these techniques with existing multielectrode electrophysiological recording methods is essential in realizing this goal. This work describes the adaptation of the low-cost, closed-loop, open-source electrophysiology system - NeuroRighter - for use with high-intensity LED optical stimulation. We apply this system in vivo to ChR2-based activation of medial septal neurons alongside simultaneous dorsal hippocampal recordings in both anesthetized and awake rats. We demonstrate the effectiveness of this system in modulating local field potential and single unit activity in the septohippocampal circuitry. The adapted NeuroRighter system can be readily applied to a number of in vivo experimental tasks requiring multielectrode recording and optogenetic stimulation.