Towards optimizing single pulse electrical stimulation: High current intensity, short pulse width stimulation most effectively elicits evoked potentials.

BACKGROUND: While single pulse electrical stimulation (SPES) is increasingly used to study effective connectivity, the effects of varying stimulation parameters on the resulting cortico-cortical evoked potentials (CCEPs) have not been systematically explored. OBJECTIVE: We sought to understand the interacting effects of stimulation pulse width, current intensity, and charge on CCEPs through an extensive testing of this parameter space and analysis of several response metrics. METHODS: We conducted SPES in 11 patients undergoing intracranial EEG monitoring using five combinations of current intensity (1.5, 2.0, 3.0, 5.0, and 7.5 mA) and pulse width at each of three charges (0.750, 1.125, and 1.500 µC/phase) to study how CCEP amplitude, distribution, latency, morphology, and stimulus artifact amplitude vary with each parameter. RESULTS: Stimulations with a greater charge or a greater current intensity and shorter pulse width at a given charge generally resulted in greater CCEP amplitudes and spatial distributions, shorter latencies, and increased waveform correlation. These effects interacted such that stimulations with the lowest charge and highest current intensities resulted in greater response amplitudes and spatial distributions than stimulations with the highest charge and lowest current intensities. Stimulus artifact amplitude increased with charge, but this could be mitigated by using shorter pulse widths. CONCLUSIONS: Our results indicate that individual combinations of current intensity and pulse width, in addition to charge, are important determinants of CCEP magnitude, morphology, and spatial extent. Together, these findings suggest that high current intensity, short pulse width stimulations are optimal SPES settings for eliciting strong and consistent responses while minimizing charge.

Ablation of apparent diffusion coefficient hyperintensity clusters in mesial temporal lobe epilepsy improves seizure outcomes after laser interstitial thermal therapy.

OBJECTIVE: Laser interstitial thermal therapy (LiTT) is a minimally invasive surgical procedure for intractable mesial temporal epilepsy (mTLE). LiTT is safe and effective, but seizure outcomes are highly variable due to patient variability, suboptimal targeting, and incomplete ablation of the epileptogenic zone. Apparent diffusion coefficient (ADC) is a magnetic resonance imaging (MRI) sequence that can identify potential epileptogenic foci in the mesial temporal lobe to improve ablation and seizure outcomes. The objective of this study was to investigate whether ablation of tissue clusters with high ADC values in the mesial temporal structures is associated with seizure outcome in mTLE after LiTT. METHODS: Twenty-seven patients with mTLE who underwent LiTT at our institution were analyzed. One-year seizure outcome was categorized as complete seizure freedom (International League Against Epilepsy [ILAE] Class I) and residual seizures (ILAE Class II-VI). Volumes of hippocampus and amygdala were segmented from the preoperative T1 MRI sequence. Spatially distinct hyperintensity clusters were identified in the preoperative ADC map. Proportion of cluster volume and number ablated were associated with seizure outcomes. RESULTS: The mean age at surgery was 37.5 years and the mean follow-up duration was 1.9 years. Proportions of hippocampal cluster volume (p = .013) and number (p = .03) ablated were significantly higher in patients with seizure freedom. For amygdala clusters, the proportion of cluster number ablated was significantly associated with seizure outcome (p = .026). In the combined amygdalohippocampal complex, ablation of amygdalohippocampal clusters reliably predicted seizure outcome by their volume ablated (area under the curve [AUC] = 0.7670, p = .02). SIGNIFICANCE: Seizure outcome after LiTT in patients with mTLE was associated significantly with the extent of cluster ablation in the amygdalohippocampal complex. The results suggest that preoperative ADC analysis may help identify high-yield pathological tissue clusters that represent epileptogenic foci. ADC-based cluster analysis can potentially assist ablation targeting and improve seizure outcome after LiTT in mTLE.

Cortico-cortical evoked potentials in response to varying stimulation intensity improves seizure localization.

OBJECTIVE: As single pulse electrical stimulation (SPES) is increasingly utilized to help localize the seizure onset zone (SOZ), it is important to understand how stimulation intensity can affect the ability to use cortico-cortical evoked potentials (CCEPs) to delineate epileptogenic regions. METHODS: We studied 15 drug-resistant epilepsy patients undergoing intracranial EEG monitoring and SPES with titrations of stimulation intensity. The N1 amplitude and distribution of CCEPs elicited in the SOZ and non-seizure onset zone (nSOZ) were quantified at each intensity. The separability of the SOZ and nSOZ using N1 amplitudes was compared between models using responses to titrations, responses to one maximal intensity, or both. RESULTS: At 2 mA and above, the increase in N1 amplitude with current intensity was greater for responses within the SOZ, and SOZ response distribution was maximized by 4-6 mA. Models incorporating titrations achieved better separability of SOZ and nSOZ compared to those using one maximal intensity. CONCLUSIONS: We demonstrated that differences in CCEP amplitude over a range of current intensities can improve discriminability of SOZ regions. SIGNIFICANCE: This study provides insight into the underlying excitability of the SOZ and how differences in current-dependent amplitudes of CCEPs may be used to help localize epileptogenic sites.

Sudden Unexpected Death in Epilepsy: Pathogenesis, Risk Factors, and Prevention.

Sudden unexpected death in epilepsy (SUDEP) is a tragic and unexpected cause of death in patients with a known diagnosis of epilepsy. It occurs in up to 6.3 to 9.3/1,000 patients with drug-resistant epilepsy. The main three risk factors associated with SUDEP are the presence of generalized tonic-clonic seizures, the presence of a seizure in the past year, and an intellectual disability. There are several mechanisms that can result in SUDEP. The most likely sequence of events appears to be a convulsive seizure, overactivation of the autonomic nervous system, cardiorespiratory dysfunction, and death. While the risk of SUDEP is relatively high in patients with drug-resistant epilepsy, studies indicate that more than 50% of patients and caregivers are unaware of the diagnosis. Counseling about the diagnosis and preventative measures at the time of diagnosis is important. There are numerous interventions that may reduce the risk of SUDEP, including conservative measures such as nocturnal surveillance with a bed partner (where applicable) and automated devices. Optimizing seizure control with antiseizure medications and surgical interventions can result in a reduced risk of SUDEP.

Stimulating native seizures with neural resonance: a new approach to localize the seizure onset zone.

Successful outcomes in epilepsy surgery rely on the accurate localization of the seizure onset zone. Localizing the seizure onset zone is often a costly and time-consuming process wherein a patient undergoes intracranial EEG monitoring, and a team of clinicians wait for seizures to occur. Clinicians then analyse the intracranial EEG before each seizure onset to identify the seizure onset zone and localization accuracy increases when more seizures are captured. In this study, we develop a new approach to guide clinicians to actively elicit seizures with electrical stimulation. We propose that a brain region belongs to the seizure onset zone if a periodic stimulation at a particular frequency produces large amplitude oscillations in the intracranial EEG network that propagate seizure activity. Such responses occur when there is 'resonance' in the intracranial EEG network, and the resonant frequency can be detected by observing a sharp peak in the magnitude versus frequency response curve, called a Bode plot. To test our hypothesis, we analysed single-pulse electrical stimulation response data in 32 epilepsy patients undergoing intracranial EEG monitoring. For each patient and each stimulated brain region, we constructed a Bode plot by estimating a transfer function model from the intracranial EEG 'impulse' or single-pulse electrical stimulation response. The Bode plots were then analysed for evidence of resonance. First, we showed that when Bode plot features were used as a marker of the seizure onset zone, it distinguished successful from failed surgical outcomes with an area under the curve of 0.83, an accuracy that surpassed current methods of analysis with cortico-cortical evoked potential amplitude and cortico-cortical spectral responses. Then, we retrospectively showed that three out of five native seizures accidentally triggered in four patients during routine periodic stimulation at a given frequency corresponded to a resonant peak in the Bode plot. Last, we prospectively stimulated peak resonant frequencies gleaned from the Bode plots to elicit seizures in six patients, and this resulted in an induction of three seizures and three auras in these patients. These findings suggest neural resonance as a new biomarker of the seizure onset zone that can guide clinicians in eliciting native seizures to more quickly and accurately localize the seizure onset zone.

Apparent diffusion coefficient of piriform cortex and seizure outcome in mesial temporal lobe epilepsy after MR-guided laser interstitial thermal therapy: a single-institution experience.

OBJECTIVE: Piriform cortex (PC) is one of the critical structures in the epileptogenesis of mesial temporal lobe epilepsy (mTLE), but its role is poorly understood. The authors examined the utility of apparent diffusion coefficient (ADC; an MR-based marker of tissue pathology) of the PC as a predictor of seizure outcome in patients with mTLE undergoing MR-guided laser interstitial thermal therapy (MRgLITT). METHODS: A total of 33 patients diagnosed with mTLE who underwent MRgLITT at the authors' institution were included in the study. The 6-month postoperative seizure outcomes were classified using the International League Against Epilepsy (ILAE) system as good (complete seizure freedom, ILAE class I) and poor (seizure present, ILAE classes II-VI). The PC and ablation volumes were manually segmented from both the preoperative and intraoperative MRI sequences, respectively. The mean ADC intensities of 1) preablation PC; 2) total ablation volume; 3) ablated portion of PC; and 4) postablation residual PC were calculated and compared between good and poor outcome groups. Additionally, the preoperative PC volumes and proportion of PC volume ablated were examined and compared between the subjects in the two outcome groups. RESULTS: The mean age at surgery was 36.5 ± 3.0 years, and the mean follow-up duration was 1.9 ± 0.2 years. Thirteen patients (39.4%) had a good outcome. The proportion of PC ablated was significantly associated with seizure outcome (10.16 vs 3.30, p < 0.05). After accounting for the variability in diffusion tensor imaging acquisition parameters, patients with good outcome had a significantly higher mean ADC of the preablation PC (0.3770 vs -0.0108, p < 0.05) and the postoperative residual PC (0.4197 vs 0.0309, p < 0.05) regions compared to those with poor outcomes. No significant differences in ADC of the ablated portion of PC were observed (0.2758 vs -0.4628, p = 0.12) after performing multivariate analysis. CONCLUSIONS: A higher proportion of PC ablated was associated with complete seizure freedom. Preoperative and postoperative residual ADC measures of PC were significantly higher in the good seizure outcome group in patients with mTLE who underwent MRgLITT, suggesting that ADC analysis can assist with postablation outcome prediction and patient stratification.

Piriform Cortex Ablation Volume Is Associated With Seizure Outcome in Mesial Temporal Lobe Epilepsy.

BACKGROUND: Growing evidence suggests that piriform cortex resection during anterior temporal lobectomy is important for achieving good seizure outcome in mesial temporal lobe epilepsy (mTLE). However, the relationship between seizure outcome and piriform cortex ablation during MR-guided laser interstitial thermal therapy (MRgLITT) remains unclear. OBJECTIVE: To determine whether ablation of piriform cortex was associated with seizure outcome in patients with mTLE undergoing MRgLITT. METHODS: We performed preablation and postablation volumetric analyses of hippocampus, amygdala, piriform cortex, and ablation volumes in patients with mTLE who underwent MRgLITT at our institution from 2014 to 2019. RESULTS: Thirty nine patients with mTLE were analyzed. In univariate logistic regression, percent piriform cortex ablation was associated with International League Against Epilepsy (ILAE) class 1 at 6 months (odds ratio [OR] 1.051, 95% CI [1.001-1.117], P = .045), whereas ablation volume, percent amygdala ablation, and percent hippocampus ablation were not ( P > .05). At 1 year, ablation volume was associated with ILAE class 1 (OR 1.608, 95% CI [1.071-2.571], P = .021) while percent piriform cortex ablation became a trend (OR 1.050, 95% CI [0.994-1.109], P = .054), and both percent hippocampus ablation and percent amygdala ablation were not significantly associated with ILAE class 1 ( P > .05). In multivariable logistic regression, only percent piriform cortex ablation was a significant predictor of seizure freedom at 6 months (OR 1.085, 95% CI [1.012-1.193], P = .019) and at 1 year (OR 1.074, 95% CI [1.003-1.178], P = .041). CONCLUSION: Piriform cortex ablation volume is associated with seizure outcome in patients with mTLE undergoing MRgLITT. The piriform cortex should be considered a high yield ablation target to achieve good seizure outcome.

Association of intraoperative end-tidal carbon dioxide level with ablation volume during magnetic resonance-guided laser interstitial thermal therapy for mesial temporal lobe epilepsy.

OBJECTIVE: Maximal safe ablation of target structures during magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) is critical to achieving good seizure outcome in patients with mesial temporal lobe epilepsy (mTLE). The authors sought to determine whether intraoperative physiological variables are associated with ablation volume during MRgLiTT. METHODS: Patients with mTLE who underwent MRgLiTT at our institution from 2014 to 2019 were retrospectively analyzed. Ablation volume was determined with volumetric analysis of intraoperative postablation MR images. Physiological parameters (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP], end-tidal carbon dioxide [ETCO2]) measured 40 minutes prior to ablation were analyzed. Univariate and multivariate regression analyses were performed to determine independent predictors of ablation volume. RESULTS: Forty-four patients met the inclusion criteria. The median (interquartile range) ablation volume was 4.27 (2.92-5.89) cm3, and median ablation energy was 7216 (6402-8784) J. The median MAP, SBP, DBP, and ETCO2 values measured during the 40-minute period leading up to ablation were 72.8 (66.2-81.5) mm Hg, 104.4 (96.4-114.4) mm Hg, 62.4 (54.1-69.8) mm Hg, and 34.1 (32.0-36.2) mm Hg, respectively. In univariate analysis, only total laser energy (r = 0.464, p = 0.003) and 40-minute average ETCO2 (r = -0.388, p = 0.012) were significantly associated with ablation volume. In multivariate analysis, only ETCO2 ≤ 33 mm Hg (p = 0.001) was significantly associated with ablation volume. CONCLUSIONS: Total ablation energy and ETCO2, but not blood pressure, may significantly affect ablation volume in mTLE patients undergoing MRgLiTT. Mild hypocapnia was associated with increased extent of ablation. Intraoperative monitoring and modulation of ETCO2 may help improve extent of ablation, prediction of ablation volume, and potentially seizure outcome.

Effects of stimulation intensity on intracranial cortico-cortical evoked potentials: A titration study.

OBJECTIVE: The aim of the present study was to investigate the optimal stimulation parameters for eliciting cortico-cortical evoked potentials (CCEPs) for mapping functional and epileptogenic networks. METHODS: We studied 13 patients with refractory epilepsy undergoing intracranial EEG monitoring. We systematically titrated the intensity of single-pulse electrical stimulation at multiple sites to assess the effect of increasing current on salient features of CCEPs such as N1 potential magnitude, signal to noise ratio, waveform similarity, and spatial distribution of responses. Responses at each incremental stimulation setting were compared to each other and to a final set of responses at the maximum intensity used in each patient (3.5-10 mA, median 6 mA). RESULTS: We found that with a biphasic 0.15 ms/phase pulse at least 2-4 mA is needed to differentiate between non-responsive and responsive sites, and that stimulation currents of 6-7 mA are needed to maximize amplitude and spatial distribution of N1 responses and stabilize waveform morphology. CONCLUSIONS: We determined a minimum stimulation threshold necessary for eliciting CCEPs, as well as a point at which the current-dependent relationship of several response metrics all saturate. SIGNIFICANCE: This titration study provides practical, immediate guidance on optimal stimulation parameters to study specific features of CCEPs, which have been increasingly used to map both functional and epileptic brain networks in humans.

Apparent diffusion coefficient is associated with seizure outcome after magnetic resonance-guided laser interstitial thermal therapy for mesial temporal lobe epilepsy.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) is becoming a first-line surgical therapy for mesial temporal lobe epilepsy (mTLE) due to good seizure control and low complication risk. However, seizure outcomes after MRgLiTT remain highly variable and there is a need to improve patient selection and post-operative prognostication. In this retrospective study, we investigated whether the pre-operative MRI-derived apparent diffusion coefficient (ADC), used as a marker of tissue pathology in the mesial temporal structures could help predict seizure outcome. METHODS: Thirty-five patients who underwent MRgLiTT at our institution between 2014 and 2019 were included in the study. Demographic and clinical data were retrospectively collected. Seizure outcome was defined as good (ILAE Class I-II) and poor (ILAE Class III-VI). Volumetrics were performed on pre-ablation hippocampus and amygdala. Ablation volumes, and the proportion of ablated hippocampus and amygdala calculated via their respective mean voxel-wise ADC intensities were quantified from pre-operative and intra-operative post-ablation MRIs and statistically compared between the two outcome cohorts. Univarate and multivariate regression analysis was performed to identify demographic, clinical, and radiographic predictors of seizure outcome. RESULTS: Mean age at LiTT was 36 years and 14 (40 %) were female. Mean follow-up duration was 1.90 ± 0.17 years. Twenty-seven (77 %) patients had mesial temporal sclerosis. There was no significant difference in the ablation volumes and proportion of ablated volume of hippocampus and amygdala between the two outcome groups. Patients with good seizure outcome had significantly higher normalized ADC intensities in the ablated mesial temporal structures compared to those with poor outcome (0.01 ± 0.08 vs.-0.29 ± 0.06; p = 0.015). CONCLUSIONS: mTLE patients with higher ADC intensities in the ablated regions of the hippocampus and the amygdala are more likely to have good seizure outcome following MRgLiTT. Our results suggest that pre-operative ADC analysis may improve both patient selection and epileptogenic zone targeting during MRgLiTT. Further investigation with large, prospective cohorts is needed to validate the clinical utility of ADC in improving seizure outcome following MRgLiTT.

Graph theoretical analysis of evoked potentials shows network influence of epileptogenic mesial temporal region.

It is now widely accepted that seizures arise from the coordinated activity of epileptic networks, and as a result, traditional methods of analyzing seizures have been augmented by techniques like single-pulse electrical stimulation (SPES) that estimate effective connectivity in brain networks. We used SPES and graph analytics in 18 patients undergoing intracranial EEG monitoring to investigate effective connectivity between recording sites within and outside mesial temporal structures. We compared evoked potential amplitude, network density, and centrality measures inside and outside the mesial temporal region (MTR) across three patient groups: focal epileptogenic MTR, multifocal epileptogenic MTR, and non-epileptogenic MTR. Effective connectivity within the MTR had significantly greater magnitude (evoked potential amplitude) and network density, regardless of epileptogenicity. However, effective connectivity between MTR and surrounding non-epileptogenic regions was of greater magnitude and density in patients with focal epileptogenic MTR compared to patients with multifocal epileptogenic MTR and those with non-epileptogenic MTR. Moreover, electrodes within focal epileptogenic MTR had significantly greater outward network centrality compared to electrodes outside non-epileptogenic regions and to multifocal and non-epileptogenic MTR. Our results indicate that the MTR is a robustly connected subnetwork that can exert an overall elevated propagative influence over other brain regions when it is epileptogenic. Understanding the underlying effective connectivity and roles of epileptogenic regions within the larger network may provide insights that eventually lead to improved surgical outcomes.

Spatial-Temporal Functional Mapping Combined With Cortico-Cortical Evoked Potentials in Predicting Cortical Stimulation Results.

Functional human brain mapping is commonly performed during invasive monitoring with intracranial electroencephalographic (iEEG) electrodes prior to resective surgery for drug- resistant epilepsy. The current gold standard, electrocortical stimulation mapping (ESM), is time -consuming, sometimes elicits pain, and often induces after discharges or seizures. Moreover, there is a risk of overestimating eloquent areas due to propagation of the effects of stimulation to a broader network of language cortex. Passive iEEG spatial-temporal functional mapping (STFM) has recently emerged as a potential alternative to ESM. However, investigators have observed less correspondence between STFM and ESM maps of language than between their maps of motor function. We hypothesized that incongruities between ESM and STFM of language function may arise due to propagation of the effects of ESM to cortical areas having strong effective connectivity with the site of stimulation. We evaluated five patients who underwent invasive monitoring for seizure localization, whose language areas were identified using ESM. All patients performed a battery of language tasks during passive iEEG recordings. To estimate the effective connectivity of stimulation sites with a broader network of task-activated cortical sites, we measured cortico-cortical evoked potentials (CCEPs) elicited across all recording sites by single-pulse electrical stimulation at sites where ESM was performed at other times. With the combination of high gamma power as well as CCEPs results, we trained a logistic regression model to predict ESM results at individual electrode pairs. The average accuracy of the classifier using both STFM and CCEPs results combined was 87.7%, significantly higher than the one using STFM alone (71.8%), indicating that the correspondence between STFM and ESM results is greater when effective connectivity between ESM stimulation sites and task-activated sites is taken into consideration. These findings, though based on a small number of subjects to date, provide preliminary support for the hypothesis that incongruities between ESM and STFM may arise in part from propagation of stimulation effects to a broader network of cortical language sites activated by language tasks, and suggest that more studies, with larger numbers of patients, are needed to understand the utility of both mapping techniques in clinical practice.

Magnetic resonance-guided laser interstitial thermal therapy: Correlations with seizure outcome.

OBJECTIVE: This study was undertaken to identify clinical factors associated with seizure freedom after magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) in temporal lobe epilepsy patients with unilateral mesial temporal sclerosis (MTS). METHODS: We identified 56 patients with magnetic resonance imaging-defined MTS who underwent MRgLiTT with at least 1 year of follow-up. Primary outcome was seizure freedom at 1 year. We examined the association of seizure freedom and the following clinical factors: age at surgery, gender, history of febrile seizures, history of focal to bilateral tonic-clonic seizures, duration of epilepsy at the time of surgery, frequency of interictal epileptiform discharges (IEDs), seizure frequency, and presence of bilateral IEDs. RESULTS: Thirty-five (62.5%) patients were seizure-free at 1 year. The presence of bilateral IEDs and age at surgery were associated with 1-year seizure freedom after MRgLiTT. The presence of bilateral IEDS was associated with lower odds of seizure freedom (odds ratio [OR] = .05, 95% confidence interval [CI] = .01-.46, p = .008), whereas increasing age at surgery was associated with increased odds of seizure freedom (OR = 1.10, 95% CI = 1.03-1.19, p = .009). SIGNIFICANCE: This study demonstrates associations between presence of bilateral IEDs and age at surgery and seizure freedom at 1 year after MRgLiTT.

Transfer Function Models for the Localization of Seizure Onset Zone From Cortico-Cortical Evoked Potentials.

Surgical resection of the seizure onset zone (SOZ) could potentially lead to seizure-freedom in medically refractory epilepsy patients. However, localizing the SOZ can be a time consuming and tedious process involving visual inspection of intracranial electroencephalographic (iEEG) recordings captured during passive patient monitoring. Cortical stimulation is currently performed on patients undergoing invasive EEG monitoring for the main purpose of mapping functional brain networks such as language and motor networks. We hypothesized that evoked responses from single pulse electrical stimulation (SPES) can also be used to localize the SOZ as they may express the natural frequencies and connectivity of the iEEG network. To test our hypothesis, we constructed patient specific transfer function models from the evoked responses recorded from 22 epilepsy patients that underwent SPES evaluation and iEEG monitoring. We then computed the frequency and connectivity dependent "peak gain" of the system as measured by the H ∞    norm from systems theory. We found that in cases for which clinicians had high confidence in localizing the SOZ, the highest peak gain transfer functions with the smallest "floor gain" (gain at which the dipped H ∞    3dB below DC gain) corresponded to when the clinically annotated SOZ and early spread regions were stimulated. In more complex cases, there was a large spread of the peak-to-floor (PF) ratios when the clinically annotated SOZ was stimulated. Interestingly for patients who had successful surgeries, our ratio of gains, agreed with clinical localization, no matter the complexity of the case. For patients with failed surgeries, the PF ratio did not match clinical annotations. Our findings suggest that transfer function gains and their corresponding frequency responses computed from SPES evoked responses may improve SOZ localization and thus surgical outcomes.

State-space models of evoked potentials to localize the seizure onset zone.

Surgical removal of the seizure onset zone (SOZ) in epilepsy patients is a potentially curative treatment, but the process heavily relies on accurate localization of the SOZ via visual inspection. SPES (Single-pulse electrical stimulation) is a method recently used to explore inter-areal connectivity in vivo to probe functional brain networks such as language and motor networks, and to a much lesser degree, seizure networks. We hypothesized that a dynamical quantification of the connectivity networks derived from the evoked responses induced by SPES could also be used to localize the SOZ. To test our hypothesis, we used an intracranial EEG (iEEG) data set in which five epilepsy patients underwent extensive SPES evaluation. For each patient, and for each dataset that stimulated a different pair of electrodes, we constructed a state-space model from the patient's data. Specifically, we simultaneously estimated model parameters under an exogenous pulse input to a dynamical system whose state vector consisted of the response iEEG signals. Then, the size of the reachable state space, as quantified by the maximum singular value of the reachability matrix, σmax(R), was computed and denoted as the "largest" network response possible when stimulating the given pair. Our results suggest high agreement between σmax(R) and clinically annotated SOZ for patients with localizable SOZs.Clinical Relevance- Our study applies dynamical systems theory to identify epileptogenic brain regions, creating a novel tool that clinicians may use in surgical planning for medically-refractory epilepsy patients.

Localizing the seizure onset zone from single pulse electrical stimulation responses using transfer function models.

Surgical resection of the seizure onset zone (SOZ) could potentially lead to seizure-freedom in medically refractory epilepsy patients. However, localizing the SOZ can be a time consuming and tedious process involving visual inspection of intracranial electroencephalographic (iEEG) recordings captured during passive patient monitoring. Single pulse electrical stimulation (SPES) is currently performed on patients undergoing invasive EEG monitoring for the main purposes of mapping functional brain networks such as language and motor networks. We hypothesize that evoked responses from SPES can also be used to localize the SOZ as they may express the natural frequencies and connectivity of the iEEG network. To test our hypothesis, we construct patient specific single-input multi-output transfer function models from the evoked responses recorded from five epilepsy patients that underwent SPES evaluation and iEEG monitoring. Our preliminary results suggest that the stimulation electrodes that produced the highest gain transfer functions, as measured by the ${\mathcal{H}_\infty }$ norm, correspond to those electrodes clinically defined in the SOZ in successfully treated patients.Clinical Relevance- This study creates an innovative tool that allows clinicians to identify the seizure onset zone in medically refractory epilepsy patients using quantitative metrics thereby increasing surgical success outcomes, mitigating patient risks, and decreasing costs.

Odor identification predicts postoperative seizure control following magnetic resonance-guided laser interstitial thermal therapy.

OBJECTIVE: Olfactory dysfunction has been well documented in individuals with temporal lobe epilepsy, but its use in presurgical planning has yet to be examined. We assessed the role of preoperative odor identification in mesial onset seizure localization utilizing stereoelectroencephalography (S-EEG) and magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) outcome. METHODS: We identified 30 patients who had typical seizures captured during S-EEG monitoring or MRgLiTT of mesial temporal structures (n = 17 S-EEG, n = 13 MRgLiTT); seizure onset zone was classified as unilateral mesial seizure onset, or multifocal with unilateral mesial onset and nonmesial onset. Odor identification ability was assessed using the Sniffin' Sticks Odor Identification Test (SSOIT). Patients also completed measures of confrontation naming and auditory-verbal learning/memory using the Boston Naming Test and Hopkins Verbal Learning Test-Revised, respectively. RESULTS: Overall, patients with intractable focal epilepsy exhibited poor olfactory performance (median [M] = 10.4, interquartile range [IQR] = 9.4-11.8). Of 19 patients who underwent MRgLiTT, 10 patients (52.6%) were seizure-free at last follow-up (M = 13 months, IQR =10-18). Patients who were seizure-free after MRgLiTT (n = 10) had poorer odor identification scores (M = 9, IQR = 7-13) compared to patients with seizure reoccurrence (M = 13, IQR = 12.5-15). Odor identification score was inversely associated with seizure freedom, with odds ratio = 0.60 (95% confidence interval [CI] = 0.38-0.95, P = .03). Receiver operating characteristic analysis revealed that an SSOIT score of 12 was the ideal cutoff for predicting favorable seizure outcome (area under the curve = 0.84, 95% CI = 0.64-1.0). Sensitivity was 88.9% and specificity was 78.9%, with a likelihood ratio of 2.9 of seizure failure in patients who had an odor identification score ≥ 12. SIGNIFICANCE: Interictal olfactory dysfunction is commonly seen in patients with intractable focal epilepsy. Odor identification is a novel, noninvasive presurgical biomarker to distinguish who may or may not benefit from MRgLiTT of mesial temporal structures.

Laser interstitial thermal therapy after failed anterior temporal lobectomy and amygdalohippocampectomy can improve seizure outcome.

Anterior temporal lobectomy and amygdalohippocampectomy (ATL) is the gold standard surgical treatment for drug resistant mesial temporal lobe epilepsy (mTLE). Nevertheless, seizure recurrence after ATL is not uncommon. Insufficient resection of the mesial temporal structures remains one of the most common reasons for ATL failure. Extending the resection leads to improved seizure outcome in a majority of patients. However, repeat craniotomy can be higher risk for the patient and also can be technically challenging due to scarring and altered anatomy. Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to ATL, and it has been shown to be safe and effective. However, it is unclear if LITT has a role in managing post-ATL mTLE patients with recurrent seizures and residual epileptogenic structures. LITT is an attractive option for post-ATL patients with residual mesial structures because the surgery is minimally invasive, and it allows precise targeting and real time confirmation of tissue ablation under MRI guidance. We present a case of an mTLE patient with recurrent seizures after ATL who achieved long-term seizure-freedom after successfully undergoing LITT to ablate the residual hippocampus. This approach, if demonstrated to be safe, effective and durable, can benefit select post-ATL mTLE patients.

Postictal stertor: Associations with focal and bilateral seizure types.

OBJECTIVE: The objective of the present study was to determine the association between respiratory stertor and focal and bilateral seizure types. METHODS: We characterized ictal and postictal behaviors during symmetric bilateral tonic-clonic (TC) and asymmetric TC seizures in the Johns Hopkins University (JHU) epilepsy monitoring unit, comparing these to focal unaware seizures. We measured the presence and duration of postictal stertorous respirations, postictal generalized electroencephalographic suppression (PGES), immobility/motor dysfunction, and encephalopathy and determined their associations and relationship to seizure types. RESULTS: In initial seizures recorded in 80 consecutive patients, bilateral symmetric TC seizures (N = 35) were strongly associated with PGES (97%, p < 0.001) and postictal stertorous respirations (89%, p < 0.001). Only 10% of the 20 patients with asymmetric TC seizures had brief PGES; focal unaware seizures (N = 25) were not associated with PGES or stertorous breathing. Some patients (24%) with asymmetric or bilateral symmetric TC seizures had severe postictal encephalopathy with stertor that was separate or extended beyond periods of PGES. CONCLUSION: Bilateral symmetric TC seizures, but not focal unaware seizures, have postictal stertor during PGES. Severe postictal encephalopathy, however, is also associated with motor dysfunction and stertor. Stertor appears to be a compensatory postictal respiratory pattern for ictal/postictal hypoxemia and occurs with PGES or postictal encephalopathy.