Laser Interstitial Thermal Therapy for Epilepsy.

Laser interstitial thermal therapy is an important new technique with a diverse use in epilepsy. This article gives an up-to-date evaluation of the current use of the technique within epilepsy, as well as provides some guidance to novice users appropriate clinical cases for its use.

Fluorescein-Assisted Microsurgical Resection of Vestibular Schwannoma: A Prospective Feasibility Study.

OBJECTIVE: To evaluate the optimal dose and timing of administration of sodium fluorescein (SF) for selective fluorescence of sporadic vestibular schwannoma (VS) during microsurgery with the YELLOW 560-nm microscope filter (YE560) and to characterize the potential benefit of this fluorescence as determined by intraoperative surgeon assessment. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: Adult patients undergoing VS microsurgery. INTERVENTIONS: Intraoperative intravenous administration of SF and visualization with the YE560. MAIN OUTCOME MEASURES: Time to differential fluorescence, duration of fluorescence, correlation of fluorescence of VS with electrostimulation and white light microscopy visual assessment, and likelihood of surgeons to use SF with the YE560 in future cases. RESULTS: Novel use of SF and YE560 during microsurgery achieved selective fluorescence of VS with capabilities to differentiate nerve fascicles and tumor approximately 30 minutes after administration. Nuances of SF administration and timing are discussed. Seventy-five percent of surgeons observed an excellent correlation of selective fluorescence with white light microscopy. Representative images and cases are presented. CONCLUSIONS: SF and YE560 may be used in VS microsurgery to visually differentiate VS from surrounding nerves. Potential benefits include enhanced visualization of the tumor-nerve interface for tumor dissection and detection of any residual disease, such as in the fundus after hearing preservation microsurgery.

Electrical brain stimulation and continuous behavioral state tracking in ambulatory humans.

Objective.Electrical deep brain stimulation (DBS) is an established treatment for patients with drug-resistant epilepsy. Sleep disorders are common in people with epilepsy, and DBS may actually further disturb normal sleep patterns and sleep quality. Novel implantable devices capable of DBS and streaming of continuous intracranial electroencephalography (iEEG) signals enable detailed assessments of therapy efficacy and tracking of sleep related comorbidities. Here, we investigate the feasibility of automated sleep classification using continuous iEEG data recorded from Papez's circuit in four patients with drug resistant mesial temporal lobe epilepsy using an investigational implantable sensing and stimulation device with electrodes implanted in bilateral hippocampus (HPC) and anterior nucleus of thalamus (ANT).Approach.The iEEG recorded from HPC is used to classify sleep during concurrent DBS targeting ANT. Simultaneous polysomnography (PSG) and sensing from HPC were used to train, validate and test an automated classifier for a range of ANT DBS frequencies: no stimulation, 2 Hz, 7 Hz, and high frequency (>100 Hz).Main results.We show that it is possible to build a patient specific automated sleep staging classifier using power in band features extracted from one HPC iEEG sensing channel. The patient specific classifiers performed well under all thalamic DBS frequencies with an average F1-score 0.894, and provided viable classification into awake and major sleep categories, rapid eye movement (REM) and non-REM. We retrospectively analyzed classification performance with gold-standard PSG annotations, and then prospectively deployed the classifier on chronic continuous iEEG data spanning multiple months to characterize sleep patterns in ambulatory patients living in their home environment.Significance.The ability to continuously track behavioral state and fully characterize sleep should prove useful for optimizing DBS for epilepsy and associated sleep, cognitive and mood comorbidities.

Thalamic deep brain stimulation modulates cycles of seizure risk in epilepsy.

Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (multidien) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months. All subjects had circadian and multiday cycles in the rate of interictal epileptiform spikes (IES). There was seizure phase locking to circadian and multiday IES cycles in five and seven out of eight subjects, respectively. Thalamic DBS modified circadian (all 3 subjects) and multiday (analysis limited to the human participant) IES cycles. DBS modified seizure clustering and circadian phase locking in the human subject. Multiscale cycles in brain excitability and seizure risk are features of human and canine epilepsy and are modifiable by thalamic DBS.

Anterior Nucleus of the Thalamus Deep Brain Stimulation with Concomitant Vagus Nerve Stimulation for Drug-Resistant Epilepsy.

BACKGROUND: The Food and Drug Administration approved the deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) as an adjunctive therapy for drug-resistant epilepsy (DRE) in the United States in 2018. The DBS Therapy for Epilepsy Post-Approval Study is further evaluating the safety and effectiveness of ANT-DBS among different patients' groups. For this study, devices for vagus nerve stimulation (VNS) must be removed prior to enrolment. OBJECTIVE: To investigate the outcomes of concomitant ANT-DBS and VNS treatment for DRE. METHODS: A retrospective analysis was performed for 33 patients who underwent ANT-DBS using previous VNS to define distinct subgroups: standard ANT-DBS (9 subjects), ANT-DBS with functional VNS (12 subjects), and ANT-DBS with the VNS implantable pulse generator explanted or turned off at the time of the DBS (12 subjects). Effectiveness and safety data were analyzed across the whole population and among subgroups. RESULTS: A mean decrease in seizure frequency of 55% was observed after a mean follow-up of 25.5 mo. Approximately 67% of patients experienced ≥50% reduction in seizure frequency. Seizure reduction percentage was not significantly different among groups. Approximately 50% of subjects with no appreciable improvement and 75% of those who showed benefit after VNS (including improvement in seizure frequency, seizure severity, and seizure duration or quality of life) achieved a seizure reduction ≥50% after ANT-DBS surgery. There were no complications related to concomitant VNS and ANT-DBS. CONCLUSION: ANT-DBS for DRE provides excellent results despite previous and ongoing VNS therapy. Removal of VNS does not appear to be necessary before ANT-DBS.

Anterior nucleus of the thalamus seizure detection in ambulatory humans.

There is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device provides constrained brain sensing power within a frequency band (power-in-band [PIB]), recorded in 10-min averaged increments. Here, four patients with temporal lobe epilepsy were implanted with an investigational device providing full bandwidth chronic intracranial electroencephalogram (cEEG) from bilateral ANT and hippocampus (Hc). ANT PIB-based seizure detection was assessed. Detection parameters were cEEG PIB center frequency, bandwidth, and epoch duration. Performance was evaluated against epileptologist-confirmed Hc seizures, and assessed by area under the precision-recall curve (PR-AUC). Data included 99 days of cEEG, and 20, 278, 3, and 18 Hc seizures for Subjects 1-4. The best detector had 7-Hz center frequency, 5-Hz band width, and 10-s epoch duration (group PR-AUC = .90), with 75% sensitivity and .38 false alarms per day for Subject 1, and 100% and .0 for Subjects 3 and 4. Hc seizures in Subject 2 did not propagate to ANT. The relative change of ANT PIB was maximal ipsilateral to seizure onset for all detected seizures. Chronic ANT and Hc recordings provide direct guidance for ANT DBS with brain sensing.

Variability Between Direct and Indirect Targeting of the Anterior Nucleus of the Thalamus.

BACKGROUND: Preoperative thalamic targeting methods have historically relied on indirect targeting techniques that do not fully account for variances in anatomy or for thalamic atrophy in epilepsy. We aimed to address variability noted between traditional indirect targeting and direct targeting methods for the anterior nucleus of the thalamus (ANT). METHODS: Fifteen consecutive patients undergoing ANT deep brain stimulator placement were evaluated (30 thalamic nuclei). Direct ANT targeting was performed using a fast gray matter acquisition T1 inversion recovery sequence and compared with standard stereotactic coordinates. Thalamic volumes were calculated for each patient, and degree of thalamic volume loss was assessed compared with matched control subjects. Vertex analysis was performed to assess shape changes in the thalamus compared with age- and sex-matched subjects. RESULTS: There was significant variation between direct and indirect targets in the y-axis and z-axis on both sides. On the left, the direct target was located at y = 2 ± 1.3 mm and z = 9.3 ± 1.8 mm (both P = 0.02). On the right, the direct target was located at y = 2.9 ± 1.8 mm and z = 9.2 ± 2 mm (both P ≤ 0.0003). There was no significant difference in the x-coordinate on either side (P > 0.5). Additionally, there was a correlation between thalamic volume and difference between direct and indirect targets in the y-axis and the z-axis. CONCLUSIONS: We showed a significant difference in direct and indirect targeting in the y-axis and z-axis when targeting the ANT for deep brain stimulation for epilepsy. This difference is correlated to thalamic volume, with a larger difference noted in patients with thalamic atrophy.

Nuclei-specific thalamic connectivity predicts seizure frequency in drug-resistant medial temporal lobe epilepsy.

BACKGROUND AND OBJECTIVES: We assessed correlations between the resting state functional connectivity (RSFC) of different thalamic nuclei and seizure frequency in patients with drug-resistant medial temporal lobe epilepsy (mTLE). METHODS: Seventeen patients with mTLE and 17 sex-/age-/handedness-matched controls participated. A seed-based correlation method for the resting-state FMRI data was implemented to get RSFC maps of 70 thalamic nuclei seed masks. Group statistics for individual RSFC for subjects and seed masks were performed to obtain within-group characteristics and between-group differences with age covariates. A linear regression was applied to test whether seizure frequency correlated with thalamic nuclear RSFC with the whole brain in mTLE patients. RESULTS: RSFC of thalamic nuclei showed spatially distinguishable connectivity patterns that reflected principal inputs and outputs that were derived from priori anatomical knowledge. We found group differences between normal control and mTLE groups in RSFC for nuclei seeds located in various subdivisions of thalamus. The RSFCs in some of those nuclei were strongly correlated with seizure frequency. CONCLUSIONS: Mediodorsal thalamic nuclei may play important roles in seizure activity or in the regulation of neuronal activity in the limbic system. The RSFC of motor- and sensory-relay nuclei may help elucidate sensory-motor deficits associated with chronic seizure activity. RSFC of the pulvinar nuclei of the thalamus could also be a key reflection of symptom-related functional deficits in mTLE.

Chronic subthreshold cortical stimulation: a therapeutic and potentially restorative therapy for focal epilepsy.

INTRODUCTION: Approximately one third of patients with focal epilepsy continue to have ongoing seizures despite adequate trials of anti-seizure medications. Surgery to remove the epileptogenic zone remains the most efficacious treatment option for focal drug-resistant epilepsy. However, when cortical areas are eloquent or there are multiple epileptogenic zones, surgical resection is not an ideal approach. Cortical stimulation provides an attractive alternative. Area covered: Here, the authors describe Chronic Subthreshold Cortical Stimulation (CSCS), which uses continuous intracranial electrical stimulation applied near the epileptogenic zone to lower seizure probability. The authors review literature related to CSCS. One challenge is finding the most efficacious set of stimulation parameters for each patient. Expert commentary: Data supporting CSCS are limited but promising for the treatment of patients with focal drug resistant epilepsy who are not surgical candidates. Additional electrophysiological biomarkers to estimate cortical excitability are needed.

Spontaneous intraventricular hemorrhage associated with prolonged diosmin therapy.

BACKGROUND: The prevalent use of anticoagulation in a growing elderly population has led to an increasing incidence of intracerebral hemorrhage. Furthermore, the understanding of the interactions and adverse effects of oral anticoagulants when used with non-FDA approved drugs is limited. Diosmin is one such non-FDA approved drug which is a semisynthetic, phlebotropic supplement with multiple microcirculatory effects. We report a case of a patient on oral anticoagulation and diosmin, who presented with spontaneous intraventricular hemorrhage, and discuss the possible etiology behind this rare event. METHODS: A retrospective chart review and a comprehensive search of the literature using the PubMed database were performed. RESULTS: A 77-year old female with a 6 week history of warfarin therapy and a several year history of diosmin use presented with severe bitemporal headache. Computed tomography scan revealed an acute hemorrhage within the right ventricle without associated intraparenchymal hemorrhage. International normalized ratio measured 1.8 and was corrected using fresh frozen plasma and vitamin K. She was discharged without neurological deficits. CONCLUSIONS: Diosmin inhibits platelet aggregation and prolongs the effect of norepinephrine on venous tone, leading to increased venoconstriction. The combined effect of chronic microcirculatory hypertension and inhibition of platelet aggregation due to diosmin may have predisposed to spontaneous hemorrhage in this anticoagulated patient. Individual cases such as this serve as a reminder that over-the-counter dietary supplements may be associated with serious adverse events. The practicing clinician should be aware of this possible adverse event when evaluating patients on oral anticoagulation and chronic diosmin treatment.

Magnetic resonance imaging-graded hypothalamic compression in surgically treated adult craniopharyngiomas determining postoperative obesity.

OBJECT: Obesity as a consequence of management of pediatric craniopharyngioma is a well-described phenomenon related to the degree of hypothalamic involvement. However, weight change and obesity have not been analyzed in adult patients. Therefore, the purpose of this study was 1) to evaluate the pattern of postoperative weight gain related to preoperative body mass index (BMI), 2) determine if postoperative weight gain is an issue in adult patients, and 3) develop an objective MR imaging grading system to predict risk of postoperative weight gain and obesity in adults treated for craniopharyngioma. METHODS: The authors retrospectively screened 296 patients with known craniopharyngioma for the following inclusion criteria: pathologically confirmed craniopharyngioma, index surgery at the authors' institution, and operative weight and height recorded with at least 3 months of follow-up including body weight measurement. Patients aged 18 years or younger were excluded, yielding 28 cases for analysis. Cases of craniopharyngiomas were compared with age- and sex-matched controls (pituitary adenoma patients) to evaluate the pattern and significance of perioperative weight changes. RESULTS: Mean age was 46 +/- 17 years at surgery, and 64% of the patients were male. Complete resection was achieved in 71% of cases. There was no correlation of preoperative BMI and postoperative weight gain testing in a linear model. Sixty-one percent and 46% of patients had postoperative weight gains greater than 4 and 9%, respectively. Comparing craniopharyngioma patients (cases) to age- and sex-matched controls, the preoperative BMIs were similar (p = 0.93) between cases (mean 28.9 [95% CI 30.9-26.9]) and controls (mean 29.3 [95% CI 31.9-26.7]). However, there was a trend to a greater mean postoperative weight change (percentage) in cases (10.1%) than in controls (5.6%) (p = 0.24). Hypothalamic T2 signal change and irregular contrast enhancement correlated and predicted higher-grade hypothalamic involvement. Furthermore, they can be used to objectively grade hypothalamic involvement as the authors propose. Progressive hypothalamic involvement correlated with larger postoperative weight gains (p = 0.022); however, hypothalamic involvement did not correlate with preoperative BMI (p = 0.5). CONCLUSIONS: Postoperative weight gain in adult patients undergoing surgery for craniopharyngioma is a significant problem and correlates with hypothalamic involvement, as it does in pediatric patients. Finally, objective MR imaging criteria can be used to predict risk of postoperative weight gain and aid in grading of hypothalamic involvement.