Oblique anterior column realignment with a mini-open posterior column osteotomy for minimally invasive adult spinal deformity correction: illustrative case.

BACKGROUND: Adult spinal deformity (ASD) occurs from progressive anterior column collapse due to disc space desiccation, compression fractures, and autofusion across disc spaces. Anterior column realignment (ACR) is increasingly recognized as a powerful tool to address ASD by progressively lengthening the anterior column through the release of the anterior longitudinal ligament during lateral interbody approaches. Here, we describe the application of minimally invasive ACR through an oblique antepsoas corridor for deformity correction in a patient with adult degenerative scoliosis and significant sagittal imbalance. OBSERVATIONS: A 65-year-old female with a prior history of L4-5 transforaminal lumbar interbody fusion and morbid obesity presented with refractory, severe low-back and lower-extremity pain. Preoperative radiographs showed significant sagittal imbalance. Computed tomography showed a healed L4-5 fusion and a vacuum disc at L3-4 and L5-S1, whereas magnetic resonance imaging was notable for central canal stenosis at L3-4. The patient was treated with a first-stage L5-S1 lateral anterior lumbar interbody fusion with oblique L2-4 ACR. The second-stage posterior approach consisted of a robot-guided minimally invasive T10-ilium posterior instrumented fusion with a mini-open L2-4 posterior column osteotomy (PCO). Postoperative radiographs showed the restoration of her sagittal balance. There were no complications. LESSONS: Oblique ACR is a powerful minimally invasive tool for sagittal plane correction. When combined with a mini-open PCO, substantial segmental lordosis can be achieved while eliminating the need for multilevel PCO or invasive three-column osteotomies.

Intraoperative physiology augments atlas-based data in awake deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) is commonly performed with patients awake to perform intraoperative microelectrode recordings and/or macrostimulation testing to guide final electrode placement. Supplemental information from atlas-based databases derived from prior patient data and visualised as efficacy heat maps transformed and overlaid onto preoperative MRIs can be used to guide preoperative target planning and intraoperative final positioning. Our quantitative analysis of intraoperative testing and corresponding changes made to final electrode positioning aims to highlight the value of intraoperative neurophysiological testing paired with image-based data to optimise final electrode positioning in a large patient cohort. METHODS: Data from 451 patients with movement disorders treated with 822 individual DBS leads at a single institution from 2011 to 2021 were included. Atlas-based data was used to guide surgical targeting. Intraoperative testing data and coordinate data were retrospectively obtained from a large patient database. Medical records were reviewed to obtain active contact usage and neurologist-defined outcomes at 1 year. RESULTS: Microelectrode recording firing profiles differ per track, per target and inform the locations where macrostimulation testing is performed. Macrostimulation performance correlates with the final electrode track chosen. Centroids of atlas-based efficacy heat maps per target were close in proximity to and may predict active contact usage at 1 year. Overall, patient outcomes at 1 year were improved for patients with better macrostimulation response. CONCLUSIONS: Atlas-based imaging data is beneficial for target planning and intraoperative guidance, and in conjunction with intraoperative neurophysiological testing during awake DBS can be used to individualize and optimise final electrode positioning, resulting in favourable outcomes.

Enlarging symptomatic arachnoid cyst in an elderly patient: illustrative case.

BACKGROUND: Arachnoid cysts are congenital or acquired structures found within the brain and are rarely symptomatic for adults. The literature documenting enlarging arachnoid cysts in adults is also discussed. OBSERVATIONS: An elderly woman presented with acutely worsening headaches, photophobia, cognitive function, and a seizure-like episode. The patient had a known arachnoid cyst with a decade of radiographic stability, which was now idiopathically enlarging. The patient had a previous history of traumatic brain injuries but no reported trauma around the time of presentation. Due to the severity of midline shift and symptomatology, the decision was made to treat the patient surgically with fenestration and shunting. She recovered well postoperatively. LESSONS: During the workup for a symptomatic elderly patient, enlargement of a previously asymptomatic arachnoid cyst should remain on the differential until specifically ruled out, even in the absence of recent trauma. While rare, enlarging arachnoid cysts result in neurological findings and impact the quality of life for patients.

Abnormal functional connectivity of the posterior hypothalamus and other arousal regions in surgical temporal lobe epilepsy.

OBJECTIVE: This study sought to characterize resting-state functional MRI (fMRI) connectivity patterns of the posterior hypothalamus (pHTH) and the nucleus basalis of Meynert (NBM) in surgical patients with mesial temporal lobe epilepsy (mTLE), and to investigate potential correlations between functional connectivity of these arousal regions and neurocognitive performance. METHODS: The study evaluated resting-state fMRI in 60 patients with preoperative mTLE and in 95 healthy controls. The authors first conducted voxel-wise connectivity analyses seeded from the pHTH, combined anterior and tuberal hypothalamus (atHTH; i.e., the rest of the hypothalamus), and the NBM ipsilateral (ipsiNBM) and contralateral (contraNBM) to the epileptogenic zone. Based on these results, the authors included the pHTH, ipsiNBM, and frontoparietal neocortex in a network-based statistic (NBS) analysis to elucidate a network that best distinguishes patients from controls. The connections involving the pHTH and ipsiNBM from this network were included in age-corrected pairwise region of interest (ROI) analysis, along with connections between arousal structures, including the pHTH, ipsiNBM, and brainstem arousal regions. Finally, patient functional connectivity was correlated with clinical neurocognitive testing scores for IQ as well as attention and concentration tests. RESULTS: The voxel-wise analysis demonstrated that the pHTH, when compared with the atHTH, showed more widespread functional connectivity decreases in surgical mTLE patients when compared with controls. It was also observed that the ipsiNBM, but not the contraNBM, showed decreased functional connectivity in mTLE. The NBS analysis uncovered a perturbed network of frontoparietal regions, the pHTH, and ipsiNBM that distinguishes patients from controls. Age-corrected ROI analysis revealed functional connectivity decreases between the pHTH and bilateral superior frontal gyri, medial orbitofrontal cortices, rostral anterior cingulate cortices, and inferior parietal cortices in mTLE when compared with controls. For the ipsiNBM, there was reduced connectivity with bilateral medial orbitofrontal and rostral anterior cingulate cortices. Age-corrected ROI analysis also demonstrated upstream connectivity decreases from controls between the pHTH and the brainstem arousal regions, cuneiform/subcuneiform (CSC) nuclei, and ventral tegmental area, as well as the ipsiNBM and CSC nuclei. Reduced functional connectivity was also detected between the pHTH and ipsiNBM. Lastly, neurocognitive test scores for attention and concentration were found to be positively correlated with the functional connectivity between the pHTH and ipsiNBM, suggesting worse performance associated with connectivity perturbations. CONCLUSIONS: This study demonstrated perturbed resting-state functional connectivity of arousal regions in surgical mTLE and is one of the first investigations to demonstrate decreased functional connectivity of the pHTH with frontoparietal regions and other arousal regions. Connectivity disturbances in arousal regions may contribute to neurocognitive deficits in surgical mTLE patients.

Localizing seizure onset zones in surgical epilepsy with neurostimulation deep learning.

OBJECTIVE: In drug-resistant temporal lobe epilepsy, automated tools for seizure onset zone (SOZ) localization that use brief interictal recordings could supplement presurgical evaluations and improve care. Thus, the authors sought to localize SOZs by training a multichannel convolutional neural network on stereoelectroencephalography (SEEG) cortico-cortical evoked potentials. METHODS: The authors performed single-pulse electrical stimulation in 10 drug-resistant temporal lobe epilepsy patients implanted with SEEG. Using 500,000 unique poststimulation SEEG epochs, the authors trained a multichannel 1-dimensional convolutional neural network to determine whether an SOZ had been stimulated. RESULTS: SOZs were classified with mean sensitivity of 78.1% and specificity of 74.6% according to leave-one-patient-out testing. To achieve maximum accuracy, the model required a 0- to 350-msec poststimulation time period. Post hoc analysis revealed that the model accurately classified unilateral versus bilateral mesial temporal lobe seizure onset, as well as neocortical SOZs. CONCLUSIONS: This was the first demonstration, to the authors' knowledge, that a deep learning framework can be used to accurately classify SOZs with single-pulse electrical stimulation-evoked responses. These findings suggest that accurate classification of SOZs relies on a complex temporal evolution of evoked responses within 350 msec of stimulation. Validation in a larger data set could provide a practical clinical tool for the presurgical evaluation of drug-resistant epilepsy.

Arousal and salience network connectivity alterations in surgical temporal lobe epilepsy.

OBJECTIVE: It is poorly understood why patients with mesial temporal lobe epilepsy (TLE) have cognitive deficits and brain network changes that extend beyond the temporal lobe, including altered extratemporal intrinsic connectivity networks (ICNs). However, subcortical arousal structures project broadly to the neocortex, are affected by TLE, and thus may contribute to these widespread network effects. The authors' objective was to examine functional connectivity (FC) patterns between subcortical arousal structures and neocortical ICNs, possible neurocognitive relationships, and FC changes after epilepsy surgery. METHODS: The authors obtained resting-state functional magnetic resonance imaging (fMRI) in 50 adults with TLE and 50 controls. They compared nondirected FC (correlation) and directed FC (Granger causality laterality index) within the salience network, default mode network, and central executive network, as well as between subcortical arousal structures; these 3 ICNs were also compared between patients and controls. They also used an fMRI-based vigilance index to relate alertness to arousal center FC. Finally, fMRI was repeated in 29 patients > 12 months after temporal lobe resection. RESULTS: Nondirected FC within the salience (p = 0.042) and default mode (p = 0.0008) networks, but not the central executive network (p = 0.79), was decreased in patients in comparison with controls (t-tests, corrected). Nondirected FC between the salience network and subcortical arousal structures (nucleus basalis of Meynert, thalamic centromedian nucleus, and brainstem pedunculopontine nucleus) was reduced in patients in comparison with controls (p = 0.0028-0.015, t-tests, corrected), and some of these connectivity abnormalities were associated with lower processing speed index, verbal comprehension, and full-scale IQ. Interestingly, directed connectivity measures suggested a loss of top-down influence from the salience network to the arousal nuclei in patients. After resection, certain FC patterns between the arousal nuclei and salience network moved toward control values in the patients, suggesting that some postoperative recovery may be possible. Although an fMRI-based vigilance measure suggested that patients exhibited reduced alertness over time, FC abnormalities between the salience network and arousal structures were not influenced by the alertness levels during the scans. CONCLUSIONS: FC abnormalities between subcortical arousal structures and ICNs, such as the salience network, may be related to certain neurocognitive deficits in TLE patients. Although TLE patients demonstrated vigilance abnormalities, baseline FC perturbations between the arousal and salience networks are unlikely to be driven solely by alertness level, and some may improve after surgery. Examination of the arousal network and ICN disturbances may improve our understanding of the downstream clinical effects of TLE.

Functional connectivity between mesial temporal and default mode structures may help lateralize surgical temporal lobe epilepsy.

OBJECTIVE: The most common surgically treatable epilepsy syndrome is mesial temporal lobe epilepsy (mTLE). Preoperative noninvasive lateralization of mTLE is challenging in part due to rapid contralateral seizure spread. Abnormal connections in both the mesial temporal lobe and resting-state networks have been described in mTLE, but it is unclear if connectivity between these networks may aid in lateralization. METHODS: In 52 patients with left mTLE (LmTLE) or right mTLE (RmTLE) and 52 matched control subjects, the authors acquired 20 minutes of resting-state functional MRI (fMRI) and evaluated functional connectivity of bilateral hippocampi and amygdalae with selected resting-state networks. They used Pearson correlation, network-based statistic, and dynamic causal modeling. Also, to evaluate the clinical utility of a resting-state connectivity model in lateralizing unilateral presurgical mTLE patients, they used receiver operating characteristic curve analysis. RESULTS: RmTLE patients demonstrated decreased nondirected connectivity between the right hippocampus and default mode network compared with LmTLE patients and control subjects. Network-based statistic analysis revealed that the network with most decreased connectivity that distinguished LmTLE from RmTLE patients included the right hippocampus and amygdala, right lateral orbitofrontal cortices, and bilateral inferior parietal lobules, precuneus, and medial orbitofrontal cortices. Dynamic causal modeling analysis revealed that cross-hemispheric connectivity between hippocampi and amygdalae was predominantly inward toward the epileptogenic side. A regression model incorporating these connectivity patterns was used to accurately lateralize mTLE patients with an area under the receiver operating characteristic curve of 0.87. CONCLUSIONS: Evaluating fMRI connectivity between mesial temporal structures and default mode network may aid in mTLE lateralization, reduce need for intracranial monitoring, and guide surgical planning.

Temporal lobe epilepsy lateralisation and surgical outcome prediction using diffusion imaging.

OBJECTIVE: We sought to augment the presurgical workup of medically refractory temporal lobe epilepsy by creating a supervised machine learning technique that uses diffusion-weighted imaging to classify patient-specific seizure onset laterality and surgical outcome. METHODS: 151 subjects were included in this analysis: 62 patients (aged 18-68 years, 36 women) and 89 healthy controls (aged 18-71 years, 47 women). We created a supervised machine learning technique that uses diffusion-weighted metrics to classify subject groups. Specifically, we sought to classify patients versus healthy controls, unilateral versus bilateral temporal lobe epilepsy, left versus right temporal lobe epilepsy and seizure-free versus not seizure-free surgical outcome. We then reduced the dimensionality of derived features with community detection for ease of interpretation. RESULTS: We classified the subject groups in withheld testing data sets with a cross-fold average testing areas under the receiver operating characteristic curve of 0.745 for patients versus healthy controls, 1.000 for unilateral versus bilateral seizure onset, 0.662 for left versus right seizure onset, 0.800 for left-sided seizure-free vsersu not seizure-free surgical outcome and 0.775 for right-sided seizure-free versus not seizure-free surgical outcome. CONCLUSIONS: This technique classifies important clinical decisions in the presurgical workup of temporal lobe epilepsy by generating discerning white-matter features. We believe that this work augments existing network connectivity findings in the field by further elucidating important white-matter pathology in temporal lobe epilepsy. We hope that this work contributes to recent efforts aimed at using diffusion imaging as an augmentation to the presurgical workup of this devastating neurological disorder.

Concurrent brain-responsive and vagus nerve stimulation for treatment of drug-resistant focal epilepsy.

OBJECTIVE: Clinical trials of a brain-responsive neurostimulator, RNS® System (RNS), excluded patients with a vagus nerve stimulator, VNS® System (VNS). The goal of this study was to evaluate seizure outcomes and safety of concurrent RNS and VNS stimulation in adults with drug-resistant focal-onset seizures. METHODS: A retrospective multicenter chart review was performed on all patients with an active VNS and RNS who were treated for a minimum of 6 months with both systems concurrently. Frequency of disabling seizures at baseline before RNS, at 1 year after RNS placement, and at last follow-up were used to calculate the change in seizure frequency after treatment. Data on adverse events and complications related to each device were collected. RESULTS: Sixty-four patients from 10 epilepsy centers met inclusion criteria. All but one patient received RNS after VNS. The median follow-up time after RNS implantation was 28 months. Analysis of the entire population of patients with active VNS and RNS systems revealed a median reduction in seizure frequency at 1 year post-RNS placement of 43% with a responder rate of 49%, and at last follow-up a 64% median reduction with a 67% responder rate. No negative interactions were reported from the concurrent use of VNS and RNS. Stimulation-related side-effects were reported more frequently in association with VNS (30%) than with RNS (2%). SIGNIFICANCE: Our findings suggest that concurrent treatment with VNS and RNS is safe and that the addition of RNS to VNS can further reduce seizure frequency.

SEEG Functional Connectivity Measures to Identify Epileptogenic Zones: Stability, Medication Influence, and Recording Condition.

BACKGROUND AND OBJECTIVES: Functional connectivity (FC) measures can be used to differentiate epileptogenic zones (EZs) from non-EZs in patients with medically refractory epilepsy. Little work has been done to evaluate the stability of stereo-EEG (SEEG) FC measures over time and their relationship with antiseizure medication (ASM) use, a critical confounder in epilepsy FC studies. We aimed to answer the following questions: Are SEEG FC measures stable over time? Are they influenced by ASMs? Are they affected by patient data collection state? METHODS: In 32 patients with medically refractory focal epilepsy, we collected a single 2-minute prospective SEEG resting-state (awake, eyes closed) data set and consecutive 2-minute retrospective pseudo-rest (awake, eyes open) data sets for days 1-7 postimplantation. ASM dosages were recorded for days 1-7 postimplantation and drug load score (DLS) per day was calculated to standardize and compare across patients. FC was evaluated using directed and nondirected measures. Standard clinical interpretation of ictal SEEG was used to classify brain regions as EZs and non-EZs. RESULTS: Over 7 days, presumed EZs consistently had higher FC than non-EZs when using between imaginary coherence (ImCoh) and partial directed coherence (PDC) inward strength, without accounting for DLS. These measures were demonstrated to be stable over a short-term period of 3 consecutive days with the same DLS. Between ImCoh FC differences between EZs and non-EZs were reduced with DLS decreases, whereas other measures were not affected by DLS. FC differences between EZs and non-EZs were seen during both resting-state and pseudo-rest conditions; ImCoh values were strongly correlated between the 2 conditions, whereas PDC values were not. DISCUSSION: Inward and nondirected SEEG FC is higher in presumed EZs vs non-EZs and measures are stable over time. However, certain measures may be affected by ASM dose, as between ImCoh differences between EZs and non-EZs are less pronounced with lower doses, and other measures such as PDC are poorly correlated across recording conditions. These findings allow novel insight into how SEEG FC measures may aid surgical localization and how they are influenced by ASMs and other factors.

Characterization of resting functional MRI activity alterations across epileptic foci and networks.

Brain network alterations have been studied extensively in patients with mesial temporal lobe epilepsy (mTLE) and other focal epilepsies using resting-state functional magnetic resonance imaging (fMRI). However, little has been done to characterize the basic fMRI signal alterations caused by focal epilepsy. Here, we characterize how mTLE affects the fMRI signal in epileptic foci and networks. Resting-state fMRI and diffusion MRI were collected from 47 unilateral mTLE patients and 96 healthy controls. FMRI activity, quantified by amplitude of low-frequency fluctuations, was increased in the epileptic focus and connected regions in mTLE. Evidence for spread of this epileptic fMRI activity was found through linear relationships of regional activity across subjects, the association of these relationships with functional connectivity, and increased activity along white matter tracts. These fMRI activity increases were found to be dependent on the epileptic focus, where the activity was related to disease severity, suggesting the focus to be the origin of these pathological alterations. Furthermore, we found fMRI activity decreases in the default mode network of right mTLE patients with different properties than the activity increases found in the epileptic focus. This work provides insights into basic fMRI signal alterations and their potential spread across networks in focal epilepsy.

Resting-state hippocampal networks related to language processing reveal unique patterns in temporal lobe epilepsy.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) commonly experience a broad range of language impairments. These deficits are thought to arise from repeated seizure activity that damages language regions. However, connectivity between the seizure onset region in the hippocampus and regions related to language processing has rarely been studied, and could also have a strong impact on language function. The purpose of this study was to use resting-state functional connectivity (FC) measures to assess hippocampal network patterns and their relation to language abilities in patients with right TLE (RLTE), left TLE (LTLE), and healthy controls. METHODS: Presurgical resting-state 3T functional MRI data were acquired from 40 patients with mesial TLE (27 RTLE, 13 LTLE) and 54 controls. The regions of interest were the anterior and posterior bilateral hippocampi and eleven regions grouped by frontal or temporo-parietal locations, including large areas of language-related cortex. FC values were computed with the right/left anterior and posterior hippocampi as the seeds and frontal and temporo-parietal regions as targets. Resting-state lateralization indices were also calculated (LI-Rest), and all FC measures were correlated to neuropsychological language scores and measures related to manifestation of epilepsy including age of onset, duration of disease, monthly seizure frequency, and hippocampal volume. RESULTS: We found significant group differences between the anterior hippocampi and temporo-parietal regions closest to the seizure focus, in which RTLE and LTLE showed stronger connectivity to their contralateral hippocampus, while controls showed similar connectivity to both hippocampi. In addition, LI-Rest demonstrated significantly more right lateralization in LTLE compared to RTLE for temporo-parietal regions only. In LTLE, we found significant associations between stronger hippocampal network resting-state FC and later age of onset and decreased left anterior hippocampal volume. SIGNIFICANCE: The results of our study indicate that the presence of TLE impacts hippocampal-temporo-parietal networks relevant to language processing.

Role of the Nucleus Basalis as a Key Network Node in Temporal Lobe Epilepsy.

OBJECTIVE: To determine whether the nucleus basalis of Meynert (NBM) may be a key network structure of altered functional connectivity in temporal lobe epilepsy (TLE), we examined fMRI with network-based analyses. METHODS: We acquired resting-state fMRI in 40 adults with TLE and 40 matched healthy control participants. We calculated functional connectivity of NBM and used multiple complementary network-based analyses to explore the importance of NBM in TLE networks without biasing our results by our approach. We compared patients to controls and examined associations of network properties with disease metrics and neurocognitive testing. RESULTS: We observed marked decreases in connectivity between NBM and the rest of the brain in patients with TLE (0.91 ± 0.88, mean ± SD) vs controls (1.96 ± 1.13, p < 0.001, t test). Larger decreases in connectivity between NBM and fronto-parietal-insular regions were associated with higher frequency of consciousness-impairing seizures (r = -0.41, p = 0.008, Pearson). A core network of altered nodes in TLE included NBM ipsilateral to the epileptogenic side and bilateral limbic structures. Furthermore, normal community affiliation of ipsilateral NBM was lost in patients, and this structure displayed the most altered clustering coefficient of any node examined (3.46 ± 1.17 in controls vs 2.23 ± 0.93 in patients). Abnormal connectivity between NBM and subcortical arousal community was associated with modest neurocognitive deficits. Finally, a logistic regression model incorporating connectivity properties of ipsilateral NBM successfully distinguished patients from control datasets with moderately high accuracy (78%). CONCLUSIONS: These results suggest that while NBM is rarely studied in epilepsy, it may be one of the most perturbed network nodes in TLE, contributing to widespread neural effects in this disabling disorder.

Contralateral sialadenitis after resection of a right cerebellar metastasis: illustrative case.

BACKGROUND: Acute postoperative sialadenitis is a rare and potentially morbid complication of cranial neurosurgery. This rapidly progressive, unilateral neck swelling often presents within hours of extubation. Diagnosis is made by imaging and exclusion of other causes of etiologies, such as neck hematoma, sialolithiasis, and dependent soft tissue edema. OBSERVATIONS: The authors presented a case of acute postoperative sialadenitis after suboccipital resection of a right cerebellar metastasis. Shortly after extubation, extensive left-sided neck swelling was apparent in the postanesthesia care unit. No central lines were placed during the procedure. Imaging revealed submandibular gland edema and fluid accumulation in the surrounding tissue. The patient was managed conservatively with steroids, antibiotics, and warm compresses, with complete resolution of symptoms 2 weeks after the procedure. LESSONS: This case emphasizes the broad differential of acute neck swelling after cranial surgery. Physical examination of the neck and airway protection should guide initial treatment. If a patient is stable, bedside ultrasound and computed tomography can be helpful with the differential diagnosis. Here the authors proposed an algorithm for diagnosis and treatment of acute neck swelling after cranial surgery.

People with mesial temporal lobe epilepsy have altered thalamo-occipital brain networks.

While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention and learning in TLE may be related to thalamic arousal nuclei connectivity. Our prior preliminary work in a smaller patient cohort suggests that patients with TLE demonstrate abnormal functional connectivity between central lateral (CL) thalamic nucleus and medial occipital lobe. Others have shown pulvinar connectivity disturbances in TLE, but it is incompletely understood how TLE affects pulvinar subnuclei. Also, the effects of epilepsy surgery on thalamic functional connectivity remains poorly understood. In this study, we examine the effects of TLE on functional connectivity of two key thalamic arousal-nuclei: lateral pulvinar (PuL) and CL. We evaluate resting-state functional connectivity of the PuL and CL in 40 patients with TLE and 40 controls using fMRI. In 25 patients, postoperative images (>1 year) were also compared with preoperative images. Compared to controls, patients with TLE exhibit loss of normal positive connectivity between PuL and lateral occipital lobe (p < 0.05), and a loss of normal negative connectivity between CL and medial occipital lobe (p < 0.01, paired t-tests). FMRI amplitude of low-frequency fluctuation (ALFF) in TLE trended higher in ipsilateral PuL (p = 0.06), but was lower in the lateral occipital (p < 0.01) and medial occipital lobe in patients versus controls (p < 0.05, paired t-tests). More abnormal ALFF in the ipsilateral lateral occipital lobe is associated with worse preoperative performance on Rey Complex Figure Test Immediate (p < 0.05, r = 0.381) and Delayed scores (p < 0.05, r = 0.413, Pearson's Correlations). After surgery, connectivity between PuL and lateral occipital lobe remains abnormal in patients (p < 0.01), but connectivity between CL and medial occipital lobe improves and is no longer different from control values (p > 0.05, ANOVA, post hoc Fischer's LSD). In conclusion, thalamic arousal nuclei exhibit abnormal connectivity with occipital lobe in TLE, and some connections may improve after surgery. Studying thalamic arousal centers may help explain distal network disturbances in TLE.

Seizure-onset regions demonstrate high inward directed connectivity during resting-state: An SEEG study in focal epilepsy.

OBJECTIVE: In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. METHODS: In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity. RESULTS: Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes. SIGNIFICANCE: Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.

Brainstem Functional Connectivity Disturbances in Epilepsy may Recover After Successful Surgery.

BACKGROUND: Focal seizures in temporal lobe epilepsy (TLE) are associated with widespread brain network perturbations and neurocognitive problems. OBJECTIVE: To determine whether brainstem connectivity disturbances improve with successful epilepsy surgery, as recent work has demonstrated decreased brainstem connectivity in TLE that is related to disease severity and neurocognitive profile. METHODS: We evaluated 15 adult TLE patients before and after (>1 yr; mean, 3.4 yr) surgery, and 15 matched control subjects using magnetic resonance imaging to measure functional and structural connectivity of ascending reticular activating system (ARAS) structures, including cuneiform/subcuneiform nuclei (CSC), pedunculopontine nucleus (PPN), and ventral tegmental area (VTA). RESULTS: TLE patients who achieved long-term postoperative seizure freedom (10 of 15) demonstrated increases in functional connectivity between ARAS structures and fronto-parietal-insular neocortex compared to preoperative baseline (P = .01, Kruskal-Wallis), with postoperative connectivity patterns resembling controls' connectivity. No functional connectivity changes were detected in 5 patients with persistent seizures after surgery (P = .9, Kruskal-Wallis). Among seizure-free postoperative patients, larger increases in CSC, PPN, and VTA functional connectivity were observed in individuals with more frequent seizures before surgery (P < .05 for each, Spearman's rho). Larger postoperative increases in PPN functional connectivity were seen in patients with lower baseline verbal IQ (P = .03, Spearman's rho) or verbal memory (P = .04, Mann-Whitney U). No changes in ARAS structural connectivity were detected after successful surgery. CONCLUSION: ARAS functional connectivity disturbances are present in TLE but may recover after successful epilepsy surgery. Larger increases in postoperative connectivity may be seen in individuals with more severe disease at baseline.

Resting-State SEEG May Help Localize Epileptogenic Brain Regions.

BACKGROUND: Stereotactic electroencephalography (SEEG) is a minimally invasive neurosurgical method to localize epileptogenic brain regions in epilepsy but requires days in the hospital with interventions to trigger several seizures. OBJECTIVE: To make initial progress in the development of network analysis methods to identify epileptogenic brain regions using brief, resting-state SEEG data segments, without requiring seizure recordings. METHODS: In a cohort of 15 adult focal epilepsy patients undergoing SEEG, we evaluated functional connectivity (alpha-band imaginary coherence) across sampled regions using brief (2 min) resting-state data segments. Bootstrapped logistic regression was used to generate a model to predict epileptogenicity of individual regions. RESULTS: Compared to nonepileptogenic structures, we found increased functional connectivity within epileptogenic regions (P < .05) and between epileptogenic areas and other structures (P < .01, paired t-tests, corrected). Epileptogenic areas also demonstrated higher clustering coefficient (P < .01) and betweenness centrality (P < .01), and greater decay of functional connectivity with distance (P < .05, paired t-tests, corrected). Our functional connectivity model to predict epileptogenicity of individual regions demonstrated an area under the curve of 0.78 and accuracy of 80.4%. CONCLUSION: Our study represents a preliminary step towards defining resting-state SEEG functional connectivity patterns to help localize epileptogenic brain regions ahead of neurosurgical treatment without requiring seizure recordings.

Characterization of postsurgical functional connectivity changes in temporal lobe epilepsy.

OBJECTIVE: Seizure outcome after mesial temporal lobe epilepsy (mTLE) surgery is complex and diverse, even across patients with homogeneous presurgical clinical profiles. The authors hypothesized that this is due in part to variations in network connectivity across the brain before and after surgery. Although presurgical network connectivity has been previously characterized in these patients, the objective of this study was to characterize presurgical to postsurgical functional network connectivity changes across the brain after mTLE surgery. METHODS: Twenty patients with drug-refractory unilateral mTLE (5 left side, 10 female, age 39.3 ± 13.5 years) who underwent either selective amygdalohippocampectomy (n = 13) or temporal lobectomy (n = 7) were included in the study. Presurgical and postsurgical (36.6 ± 14.3 months after surgery) functional connectivity (FC) was measured with 3-T MRI and compared with findings in age-matched healthy controls (n = 44, 21 female, age 39.3 ± 14.3 years). Postsurgical connectivity changes were then related to seizure outcome, type of surgery, and presurgical disease parameters. RESULTS: The results demonstrated significant decreases of FC from control group values across the brain after surgery that were not present before surgery, including many contralateral hippocampal connections distal to the surgical site. Postsurgical impairment of contralateral precuneus to ipsilateral occipital connectivity was associated with seizure recurrence. Presurgical impairment of the contralateral precuneus to contralateral temporal lobe connectivity was associated with those who underwent selective amygdalohippocampectomy compared to those who had temporal lobectomy. Finally, changes in thalamic connectivity after surgery were linearly related to duration of epilepsy and frequency of consciousness-impairing seizures prior to surgery. CONCLUSIONS: The widespread contralateral hippocampal FC changes after surgery may be a reflection of an ongoing epileptogenic progression that has been altered by the surgery, rather than a direct result of the surgery itself. This network evolution may contribute to long-term seizure outcome. Therefore, the combination of presurgical network mapping with the understanding of the dynamic effects of surgery on the networks may ultimately be used to create predictors of the likelihood of long-term seizure recurrence in individual patients after mTLE surgery.

Thalamic arousal network disturbances in temporal lobe epilepsy and improvement after surgery.

OBJECTIVE: The effects of temporal lobe epilepsy (TLE) on subcortical arousal structures remain incompletely understood. Here, we evaluate thalamic arousal network functional connectivity in TLE and examine changes after epilepsy surgery. METHODS: We examined 26 adult patients with TLE and 26 matched control participants and used resting-state functional MRI (fMRI) to measure functional connectivity between the thalamus (entire thalamus and 19 bilateral thalamic nuclei) and both neocortex and brainstem ascending reticular activating system (ARAS) nuclei. Postoperative imaging was completed for 19 patients >1 year after surgery and compared with preoperative baseline. RESULTS: Before surgery, patients with TLE demonstrated abnormal thalamo-occipital functional connectivity, losing the normal negative fMRI correlation between the intralaminar central lateral (CL) nucleus and medial occipital lobe seen in controls (p < 0.001, paired t-test). Patients also had abnormal connectivity between ARAS and CL, lower ipsilateral intrathalamic connectivity, and smaller ipsilateral thalamic volume compared with controls (p < 0.05 for each, paired t-tests). Abnormal brainstem-thalamic connectivity was associated with impaired visuospatial attention (ρ = -0.50, p = 0.02, Spearman's rho) while lower intrathalamic connectivity and volume were related to higher frequency of consciousness-sparing seizures (p < 0.02, Spearman's rho). After epilepsy surgery, patients with improved seizures showed partial recovery of thalamo-occipital and brainstem-thalamic connectivity, with values more closely resembling controls (p < 0.01 for each, analysis of variance). CONCLUSIONS: Overall, patients with TLE demonstrate impaired connectivity in thalamic arousal networks that may be involved in visuospatial attention, but these disturbances may partially recover after successful epilepsy surgery. Thalamic arousal network dysfunction may contribute to morbidity in TLE.