Lilit Mnatsakanyan

Intravenous Lacosamide in refractory nonconvulsive status epilepticus

BACKGROUND Many patients present with refractory Status epilepticus (SE) despite multiple anti-epileptic drugs (AEDs). Lacosamide (LCM) was recently approved as an adjunct AED for partial-onset seizures. It has unique mechanism of modulating voltage-gated sodium channels by enhancing their slow inactivation. LCM has demonstrated efficacy in animal models of pharmacoresistant seizures. To date, there are isolated anecdotal reports of LCM use in SE. OBJECTIVE To report a single center experience with IV Lacosamide in patients with NCSE. METHODS Pharmacy records were reviewed to identify patients with SE who received IV LCM in our institution. Data on demographics, response to therapy and adverse effects/outcomes were analyzed. All patients had continuous EEG monitoring. RESULTS 10 patients (4 men, 6 women), age 16-90 years with refractory SE were given LCM. Eight patients were in focal non-convulsive SE (NCSE), 2 were in generalized non-convulsive SE. The etiologies included anoxic brain injury, idiopathic, encephalitis, tumor, posterior reversible encephalopathy syndrome (PRES), stroke, and AVM. IV LCM was added after traditional AEDs, including drug-induced coma in some, failed to control the SE. NCSE resolved in 7/10 patients whereas 1/10 patient showed partial response with cessation of NCSE but still frequent electrographic seizures and 2/10 patients were resistant to therapy. CONCLUSIONS LCM is a useful adjunct in refractory NCSE. The IV formulation allows prompt administration in the intensive care unit setting. Response was seen especially in focal SE. Similar to other AEDs, response was poor in patients with postanoxic injury. Our data is limited by the small number of patients. Larger controlled studies are necessary to assess accurately the efficacy of IV LCM as an early treatment of SE.

Association of MBP peptides with Hsp70 in normal appearing human white matter.

Multiple Sclerosis is an autoimmune disease directed against myelin proteins. The etiology of MS is poorly defined though, with no definitive causative agent yet identified. It has been hypothesized that MS may be a multifactorial disease resulting in the same end product: the destruction of myelin by the immune system. In this report we describe a potential role for heat shock proteins in the pathogenesis of MS. We isolated Hsp70 from the normal appearing white matter of both MS and normal human brain and found this was actively associated with, among other things, immunodominant MBP peptides. Hsp70-MBP peptide complexes prepared in vitro were shown to be highly immunogenic, with adjuvant-like effects stimulating MBP peptide-specific T cell lines to respond to normally sub-optimal concentrations of peptide. This demonstration of a specific interaction between Hsp70 and different MBP peptides, coupled with the adjuvanticity of this association is suggestive of a possible role for Hsp70 in the immunopathology associated with MS.

Amygdala-hippocampal dynamics during salient information processing

Recognizing motivationally salient information is critical to guiding behaviour. The amygdala and hippocampus are thought to support this operation, but the circuit-level mechanism of this interaction is unclear. We used direct recordings in the amygdala and hippocampus from human epilepsy patients to examine oscillatory activity during processing of fearful faces compared with neutral landscapes. We report high gamma (70–180 Hz) activation for fearful faces with earlier stimulus evoked onset in the amygdala compared with the hippocampus. Attending to fearful faces compared with neutral landscape stimuli enhances low-frequency coupling between the amygdala and the hippocampus. The interaction between the amygdala and hippocampus is largely unidirectional, with theta/alpha oscillations in the amygdala modulating hippocampal gamma activity. Granger prediction, phase slope index and phase lag analysis corroborate this directional coupling. These results demonstrate that processing emotionally salient events in humans engages an amygdala-hippocampal network, with the amygdala influencing hippocampal dynamics during fear processing.

Using electrocorticogram baseline seizure frequency to assess the efficacy of responsive neurostimulation

BACKGROUND The effect of direct brain responsive neurostimulation on the frequency of electrographic seizures in patients with medically refractory focal epilepsy has not been evaluated by chronic ambulatory electrocorticographic monitoring. METHODS This was a retrospective study of 9 patients who underwent implantation of the responsive neurostimulator (RNS) system from 2015 to 2017 at the University of California, Irvine. Leads were placed at the ictal onset zone as determined by intracranial electroencephalography (EEG). The neurostimulator was programmed to detect and deliver stimulation following identification of the individuals epileptiform patterns. Electrographic seizures were determined by review of all detections. The electrocorticography (ECoG) seizure frequency baseline was the average of the first 2 months postimplantation. The patient-reported seizure frequency baseline was the average of the 2 most recent months prior to RNS implantation. Seizure control was assessed at 3 months, 6 months, and 12 months. RESULTS Nine patients were included in the study. All 9 patients have been treated with responsive stimulation for at least 3 months, 7/9 for 6 months, and 4/9 for 12 months. The mean change in seizure frequency was -10%, -19%, and -56% at 3, 6, and 12 months, respectively, using a self-reported seizure frequency baseline compared with -85%, -71%, and -56% at 3, 6, and 12 months, respectively, using the ECoG seizure frequency baseline. CONCLUSION Chronic ECoG may provide a more accurate estimate of seizure frequency and provide additional insight into the true efficacy of the RNS system.

Language recovery after epilepsy surgery of the Broca's area

Epilepsy surgery is indicated in select patients with drug-resistant focal epilepsy. Seizure freedom or significant reduction of seizure burden without risking new neurological deficits is the expected goal of epilepsy surgery. Typically, when the seizure onset zone overlaps with eloquent cortex, patients are excluded from surgery. We present a patient with drug-resistant frontal lobe epilepsy who underwent successful surgery with resection of Brocas area, primarily involving the pars triangularis (BA 45). We report transient expressive aphasia followed by recovery of speech. This case provides new insights into adult neuroplasticity of the language network.

Hippocampal CA1 gamma power predicts the precision of spatial memory judgments

Significance Spatial memory is critical to every facet of our lives. The hippocampus is known to play a prominent role in the formation and retrieval of spatial memories; however, the exact mechanisms remain elusive. Using electrophysiology recordings from presurgical epilepsy patients implanted with depth electrodes, we measured high-frequency neural activity from the CA1 region of the hippocampus and the dorsolateral prefrontal cortex. We found associations between increased high-frequency activity and the precision of spatial memory retrieval. These data suggest that local processing within the CA1 subfield and the dorsolateral prefrontal cortex underlie the quality of retrieved spatial memories. The hippocampus plays a critical role in spatial memory. However, the exact neural mechanisms underlying high-fidelity spatial memory representations are unknown. We report findings from presurgical epilepsy patients with bilateral hippocampal depth electrodes performing an object-location memory task that provided a broad range of spatial memory precision. During encoding, patients were shown a series of objects along the circumference of an invisible circle. At test, the same objects were shown at the top of the circle (0°), and patients used a dial to move the object to its location shown during encoding. Angular error between the correct location and the indicated location was recorded as a continuous measure of performance. By registering pre- and postimplantation MRI scans, we were able to localize the electrodes to specific hippocampal subfields. We found a correlation between increased gamma power, thought to reflect local excitatory activity, and the precision of spatial memory retrieval in hippocampal CA1 electrodes. Additionally, we found a similar relationship between gamma power and memory precision in the dorsolateral prefrontal cortex and a directional relationship between activity in this region and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in postretrieval processing. These results indicate that local processing in hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial memory representations.

Accuracy and Efficacy for Robotic Assistance in Implanting Responsive Neurostimulation Device Electrodes in Bilateral Mesial Temporal Lobe Epilepsy

BACKGROUND Responsive neurostimulation (RNS) is a relatively new treatment option that has been shown to be effective for patients with medically refractory focal epilepsy when resection is not possible, especially in bilateral mesial temporal onset. Robotic devices are becoming increasingly popular for use in stereotactic procedures such as stereoelectroencephalography, but have yet to be used when implanting RNS devices. OBJECTIVE To show that these 2 forms of advanced technology were compatible and could be used effectively in patient care. METHODS We implanted RNS devices in 3 patients with bilateral mesial temporal lobe epilepsy. Each patient was placed in the prone position, and electrode trajectories were planned via the robotic navigation system via a transoccipital approach. One lead was placed along each amygdalohippocampal complex. A small craniectomy was then created in the parietal region for RNS generator implantation. Actual and expected target locations and distance were calculated for each depth. There were no complications in this group. RESULTS RNS devices with bilateral leads were successfully implanted in all 3 patients, with bilateral mesial temporal lobe onset. Follow-up ranged from 3 to 6 mo, and there were no complications in this group. The median distance between the estimate and actual targets was 2.18 (range = 1.11-3.27) mm. CONCLUSION We show that implanting RNS devices with robotic assistance is feasible with excellent precision and accuracy. The advantages of using robotic assistance include higher flexibility, accuracy, precision, and consistency.

Length of stay for patients undergoing invasive electrode monitoring with stereoelectroencephalography and subdural grids correlates positively with increased institutional profitability

Lowering the length of stay (LOS) is thought to potentially decrease hospital costs and is a metric commonly used to manage capacity. Patients with epilepsy undergoing intracranial electrode monitoring may have longer LOS because the time to seizure is difficult to predict or control. This study investigates the effect of economic implications of increased LOS in patients undergoing invasive electrode monitoring for epilepsy.

New Onset Seizures During Pregnancy

A 24-year-old pregnant woman (G1P0) presents with new onset epilepsy. She found out about her pregnancy after her first witnessed generalized tonic-clonic seizure when she ended up in the emergency room and beta HCG was sent for by the emergency room physician. The week before her visit to your office, she experienced a second unprovoked generalized tonic-clonic seizure out of sleep which was accompanied with tongue laceration. Both seizures were witnessed by her husband who accompanies her to this consultation visit. She is at her 5th week of gestation and has no known risk factors for epilepsy. Her MRI of brain is within normal limits. Her EEG shows left temporal sharp waves potentiated during sleep. What is the treatment you suggest? How do you counsel the patient if she is hesitant or decides not to take seizure medications during her pregnancy?

Saphenous Nerve Somatosensory Evoked Potentials Monitoring During Lateral Interbody Fusion

IntroductionLateral transpsoas interbody fusion (LIF) is a novel minimally invasive technique reducing risks related to traditional anterior approaches. Despite advantages, transpsoas exposure carr...