CARLA: Adjusted common average referencing for cortico-cortical evoked potential data.

Human brain connectivity can be mapped by single pulse electrical stimulation during intracranial EEG measurements. The raw cortico-cortical evoked potentials (CCEP) are often contaminated by noise. Common average referencing (CAR) removes common noise and preserves response shapes but can introduce bias from responsive channels. We address this issue with an adjusted, adaptive CAR algorithm termed "CAR by Least Anticorrelation (CARLA)". CARLA was tested on simulated CCEP data and real CCEP data collected from four human participants. In CARLA, the channels are ordered by increasing mean cross-trial covariance, and iteratively added to the common average until anticorrelation between any single channel and all re-referenced channels reaches a minimum, as a measure of shared noise. We simulated CCEP data with true responses in 0-45 of 50 total channels. We quantified CARLA's error and found that it erroneously included 0 (median) truly responsive channels in the common average with ≤42 responsive channels, and erroneously excluded ≤2.5 (median) unresponsive channels at all responsiveness levels. On real CCEP data, signal quality was quantified with the mean R2 between all pairs of channels, which represents inter-channel dependency and is low for well-referenced data. CARLA re-referencing produced significantly lower mean R2 than standard CAR, CAR using a fixed bottom quartile of channels by covariance, and no re-referencing. CARLA minimizes bias in re-referenced CCEP data by adaptively selecting the optimal subset of non-responsive channels. It showed high specificity and sensitivity on simulated CCEP data and lowered inter-channel dependency compared to CAR on real CCEP data.

Clinical evaluation of a stereotactic system for single-stage deep brain stimulation surgery under general anesthesia: technical note.

OBJECTIVE: Conventional frame-based stereotactic systems have circumferential base frames, often necessitating deep brain stimulation (DBS) surgery in two stages: intracranial electrode insertion followed by surgical re-preparation and pulse generator implantation. Some patients do not tolerate awake surgery, underscoring the need for a safe alternative for asleep DBS surgery. A frame-based stereotactic system with a skull-mounted "key" in lieu of a circumferential base frame received US FDA clearance. The authors describe the system's application for single-stage, asleep DBS surgery in 8 patients at their institution and review its workflow and technical considerations. METHODS: Eight patients underwent DBS lead insertion and IPG implantation in a single surgical preparation under general anesthesia using the system. Postoperative CT imaging confirmed lead placement. RESULTS: Eight patients underwent implantation of 15 total leads targeting the ventral intermediate nucleus (4 patients), globus pallidus internus (GPi; 3 patients), and subthalamic nucleus (STN; 1 patient). Intraoperative microelectrode recording was conducted for GPi and STN targets. Postoperative CT imaging revealed a mean ± SD radial error of 1.24 ± 0.45 mm (n = 15 leads), without surgical complications. CONCLUSIONS: The stereotactic system facilitated safe and effective asleep, single-stage DBS surgery, maintaining traditional lead accuracy standards.

Status Epilepticus in Older Adults: Diagnostic and Treatment Considerations.

Status epilepticus (SE) is one of the leading life-threatening neurological emergencies in the elderly population, with significant morbidity and mortality. SE presents unique diagnostic and therapeutic challenges in the older population given overlap with other causes of encephalopathy, complicating diagnosis, and the common occurrence of multiple comorbid diseases complicates treatment. First-line therapy involves the use of rescue benzodiazepine in the form of intravenous lorazepam or diazepam, intramuscular or intranasal midazolam and rectal diazepam. Second-line therapies include parenteral levetiracetam, fosphenytoin, valproate and lacosamide, and underlying comorbidities guide the choice of appropriate medication, while third-line therapies may be influenced by the patient's code status as well as the cause and type of SE. The standard of care for convulsive SE is treatment with an intravenous anesthetic, including midazolam, propofol, ketamine and pentobarbital. There is currently limited evidence guiding appropriate therapy in patients failing third-line therapies. Adjunctive strategies may include immunomodulatory treatments, non-pharmacological strategies such as ketogenic diet, neuromodulation therapies and surgery in select cases. Surrogate decision makers should be updated early and often in refractory episodes of SE and informed of the high morbidity and mortality associated with the disease as well as the high probability of subsequent epilepsy among survivors.

Emerging approaches in neurostimulation for epilepsy.

PURPOSE OF REVIEW: Neurostimulation is a quickly growing treatment approach for epilepsy patients. We summarize recent approaches to provide a perspective on the future of neurostimulation. RECENT FINDINGS: Invasive stimulation for treatment of focal epilepsy includes vagus nerve stimulation, responsive neurostimulation of the cortex and deep brain stimulation of the anterior nucleus of the thalamus. A wide range of other targets have been considered, including centromedian, central lateral and pulvinar thalamic nuclei; medial septum, nucleus accumbens, subthalamic nucleus, cerebellum, fornicodorsocommissure and piriform cortex. Stimulation for generalized onset seizures and mixed epilepsies as well as increased efforts focusing on paediatric populations have emerged. Hardware with more permanently implanted lead options and sensing capabilities is emerging. A wider variety of programming approaches than typically used may improve patient outcomes. Finally, noninvasive brain stimulation with its favourable risk profile offers the potential to treat increasingly diverse epilepsy patients. SUMMARY: Neurostimulation for the treatment of epilepsy is surprisingly varied. Flexibility and reversibility of neurostimulation allows for rapid innovation. There remains a continued need for excitability biomarkers to guide treatment and innovation. Neurostimulation, a part of bioelectronic medicine, offers distinctive benefits as well as unique challenges.

Ictal Interictal Continuum Patterns.

PURPOSE OF REVIEW: To present data available on the epidemiology and significance of rhythmic and periodic patterns that lie on the ictal interictal continuum and propose an algorithm for the clinical approach to patients exhibiting these patterns. RECENT FINDINGS: There is accumulating evidence on the prognostic implications of various rhythmic and periodic patterns in the critically ill population. These patterns are not only associated with increased seizure risk but have also been associated with worse outcome and increased long-term risk of epilepsy in recent studies. There is emerging evidence suggesting that certain EEG features as well as ancillary studies including serum, neuroimaging, and invasive multimodality monitory can assist in the risk stratification of neuronal injury associated with these patterns, allowing for a targeted approach to these patterns. We present a case illustrating the clinical nuances of these patterns. We propose an algorithm for a personalized and targeted approach to ictal interictal patterns based on risk stratification according to clinical, EEG, imaging, and invasive monitoring markers.