Immune checkpoint inhibitor treatment of brain metastasis associated with a less invasive growth pattern, higher T-cell infiltration and raised tumor ADC on diffusion weighted MRI.

BACKGROUND: Brain metastases are the most common intracranial tumors with an increasing incidence. They are an important cause of morbidity and mortality in patients with solid organ cancer and a focus of recent clinical research and experimental interest. Immune checkpoint inhibitors are being increasingly used to treat solid organ cancers. METHODS: To determine whether immune checkpoint inhibitors were biologically effective in the brain, we compared melanoma brain metastasis samples where treatment with ipilimumab had occurred preoperatively to those who had not received any immune modulating therapy and looked for histopathological (invasion, vascularity, metastasis inducing proteins, matrix metalloproteinases, immune cell infiltration, tissue architecture) and advanced MRI differences (diffusion weighted imaging). RESULTS: Co-localized tissue samples from the same regions as MRI regions of interest showed significantly lower vascularity (density of CD34 + vessels) in the core and higher T-cell infiltration (CD3 + cells) in the leading edge for ipilimumab-treated brain metastasis samples than for untreated cases and this correlated with a higher tumor ADC signal at post-treatment/preoperative MRI brain. CONCLUSIONS: Treatment of a melanoma brain metastasis with ipilimumab appears to cause measurable biological changes in the tumor that can be correlated with post-treatment diffusion weighted MRI imaging, suggesting both a mechanism of action and a possible surrogate marker of efficacy.

Midbrain structure volume, estimated myelin and functional connectivity in idiopathic generalised epilepsy.

BACKGROUND: Structural and functional neuroimaging studies often overlook lower basal ganglia structures located in and adjacent to the midbrain due to poor contrast on clinically acquired T1-weighted scans. Here, we acquired T1-weighted, T2-weighted, and resting-state fMRI scans to investigate differences in volume, estimated myelin content and functional connectivity of the substantia nigra (SN), subthalamic nuclei (SubTN) and red nuclei (RN) of the midbrain in IGE. METHODS: Thirty-three patients with IGE (23 refractory, 10 non-refractory) and 39 age and sex-matched healthy controls underwent MR imaging. Midbrain structures were automatically segmented from T2-weighted images and structural volumes were calculated. The estimated myelin content for each structure was determined using a T1-weighted/T2-weighted ratio method. Resting-state functional connectivity analysis of midbrain structures (seed-based) was performed using the CONN toolbox. RESULTS: An increased volume of the right RN was found in IGE and structural volumes of the right SubTN differed between patients with non-refractory and refractory IGE. However, no volume findings survived corrections for multiple comparisons. No myelin alterations of midbrain structures were found for any subject groups. We found functional connectivity alterations including significantly decreased connectivity between the left SN and the thalamus and significantly increased connectivity between the right SubTN and the superior frontal gyrus in IGE. CONCLUSIONS: We report volumetric and functional connectivity alterations of the midbrain in patients with IGE. We postulate that potential increases in structural volumes are due to increased iron deposition that impacts T2-weighted contrast. These findings are consistent with previous studies demonstrating pathophysiological abnormalities of the lower basal ganglia in animal models of generalised epilepsy.

Increased volume of cerebral oedema is associated with risk of acute seizure activity and adverse neurological outcomes in encephalitis - regional and volumetric analysis in a multi-centre cohort.

BACKGROUND: Seizures can occur unpredictably in patients with acute encephalitis syndrome (AES), and many suffer from poor long-term neurological sequelae. Establishing factors associated with acute seizures risk and poor outcomes could support clinical care. We aimed to conduct regional and volumetric analysis of cerebral oedema on magnetic resonance imaging (MRI) in patients with AES. We assessed the relationship of brain oedema with acute seizure activity and long-term neurological outcome. METHODS: In a multi-centre cohort study, adults and children presenting with an AES were recruited in the UK. The clinical and brain MRI data were retrospectively reviewed. The outcomes variables were inpatient acute seizure activity and neurological disability at six-months post-discharge. A poor outcome was defined as a Glasgow outcome score (GOS) of 1-3. We quantified regional brain oedema on MRI through stereological examination of T2-weighted images using established methodology by independent and blinded assessors. Clinical and neuroimaging variables were analysed by multivariate logistic regression to assess for correlation with acute seizure activity and outcome. RESULTS: The study cohort comprised 69 patients (mean age 31.8 years; 53.6% female), of whom 41 (59.4%) had acute seizures as inpatients. A higher Glasgow coma scale (GCS) score on admission was a negative predictor of seizures (OR 0.61 [0.46-0.83], p = 0.001). Even correcting for GCS on admission, the presence of cortical oedema was a significant risk factor for acute seizure activity (OR 5.48 [1.62-18.51], p = 0.006) and greater volume of cerebral oedema in these cortical structures increased the risk of acute seizures (OR 1.90 [1.12-3.21], p = 0.017). At six-month post-discharge, 21 (30.4%) had a poor neurological outcome. Herpes simplex virus encephalitis was associated with higher risk of poor outcomes in univariate analysis (OR 3.92 [1.08-14.20], p = 0.038). When controlling for aetiology, increased volume of cerebral oedema was an independent risk factor for adverse neurological outcome at 6 months (OR 1.73 [1.06-2.83], p = 0.027). CONCLUSIONS: Both the presence and degree of cerebral oedema on MRIs of patients with AES may help identify patients at risk of acute seizure activity and subsequent long-term morbidity.

Automated subcortical volume estimation from 2D MRI in epilepsy and implications for clinical trials.

PURPOSE: Most techniques used for automatic segmentation of subcortical brain regions are developed for three-dimensional (3D) MR images. MRIs obtained in non-specialist hospitals may be non-isotropic and two-dimensional (2D). Automatic segmentation of 2D images may be challenging and represents a lost opportunity to perform quantitative image analysis. We determine the performance of a modified subcortical segmentation technique applied to 2D images in patients with idiopathic generalised epilepsy (IGE). METHODS: Volume estimates were derived from 2D (0.4 × 0.4 × 3 mm) and 3D (1 × 1x1mm) T1-weighted acquisitions in 31 patients with IGE and 39 healthy controls. 2D image segmentation was performed using a modified FSL FIRST (FMRIB Integrated Registration and Segmentation Tool) pipeline requiring additional image reorientation, cropping, interpolation and brain extraction prior to conventional FIRST segmentation. Consistency between segmentations was assessed using Dice coefficients and volumes across both approaches were compared between patients and controls. The influence of slice thickness on consistency was further assessed using 2D images with slice thickness increased to 6 mm. RESULTS: All average Dice coefficients showed excellent agreement between 2 and 3D images across subcortical structures (0.86-0.96). Most 2D volumes were consistently slightly lower compared to 3D volumes. 2D images with increased slice thickness showed lower agreement with 3D images with lower Dice coefficients (0.55-0.83). Significant volume reduction of the left and right thalamus and putamen was observed in patients relative to controls across 2D and 3D images. CONCLUSION: Automated subcortical volume estimation of 2D images with a resolution of 0.4 × 0.4x3mm using a modified FIRST pipeline is consistent with volumes derived from 3D images, although this consistency decreases with an increased slice thickness. Thalamic and putamen atrophy has previously been reported in patients with IGE. Automated subcortical volume estimation from 2D images is feasible and most reliable at using in-plane acquisitions greater than 1 mm x 1 mm and provides an opportunity to perform quantitative image analysis studies in clinical trials.

Resilience level, its determinants and its effect on psychological well-being: A cross-sectional evaluation among school-going adolescents of Patna, Bihar, India.

BACKGROUND: Adolescents with higher resilience levels are reported to be less vulnerable to psychological illnesses. The study examined resilience level, its determinants and its effect on psychological well-being among school-going adolescents of Patna, Bihar, India. METHODS: Adopting cross-sectional design we examined resilience levels among the study participants reading in the sixth, seventh and eighth standards of selected schools of Patna district using the Child Youth Resilience Measure-Revised questionnaire during March 2021. Psychological well-being was assessed using Patient Health Questionnaire-4. Data of in total 468 enrolled participants were analysed using SPSS 22.0. RESULTS: The mean resilience score was observed to be 62.4 ± 8.8. In multiple linear regression analysis using backward method; increasing age (unstandardised beta [ß]: 0.564, standard error [SE]: 0.271, P: 0.038), male gender (ß: 2.753, SE: 0.775, P < 0.001), high per capita monthly family income (≥18 USD [median]) (ß: 1.829, SE: 0.743, P: 0.014), academic satisfaction (ß: 2.003, SE: 0.962, P: 0.038), no history of abuse (physical or mental) in the past 30 days (ß: 2.752, SE: 1.220, P: 0.025) and increasing self-esteem score (measured by Rosenberg Self-Esteem Scale) (ß: 0.808, SE: 0.098, P: < 0.001) were found to be positive determinants of the total resilience level. Resilience was found to be positively correlated with psychological well-being (spearman rho correlation co-efficient [ρ]: 0.363, P < 0.001). CONCLUSIONS: Abuse, academic satisfaction and self-esteem were the modifiable determinates of resilience that could be elucidated in this investigation. Resilience level positively influenced psychological well-being.

Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy.

It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is currently unknown which thalamic nuclei and how nuclear-specific thalamocortical functional connectivity are differentially impacted in patients with medically refractory and non-refractory idiopathic generalised epilepsy (IGE). In the present study, we performed structural and resting-state functional magnetic resonance imaging (MRI) in patients with refractory and non-refractory IGE, segmented the thalamus into constituent nuclear regions using a probabilistic MRI segmentation method and determined thalamocortical functional connectivity using seed-to-voxel connectivity analyses. We report significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory IGE. Compared to healthy controls, patients with refractory and non-refractory IGE had significant alterations of functional connectivity between the centromedian nucleus and cortex, but only patients with refractory IGE had altered cortical connectivity with the ventral lateral nuclear group. Patients with refractory IGE had significantly increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to patients with non-refractory IGE. Cortical effects were predominantly located in the frontal lobe. Atrophy of the anterior thalamic nuclei and resting-state functional hyperconnectivity between ventral lateral nuclei and cerebral cortex may be imaging markers of pharmacoresistance in patients with IGE. These structural and functional abnormalities fit well with the known importance of thalamocortical systems in the generation and maintenance of primary generalised seizures, and the increasing recognition of the importance of limbic pathways in IGE.

Independent Geometrical Control of Spin and Charge Resistances in Curved Spintronics.

Spintronic devices operating with pure spin currents represent a new paradigm in nanoelectronics, with a higher energy efficiency and lower dissipation as compared to charge currents. This technology, however, will be viable only if the amount of spin current diffusing in a nanochannel can be tuned on demand while guaranteeing electrical compatibility with other device elements, to which it should be integrated in high-density three-dimensional architectures. Here, we address these two crucial milestones and demonstrate that pure spin currents can effectively propagate in metallic nanochannels with a three-dimensional curved geometry. Remarkably, the geometric design of the nanochannels can be used to reach an independent tuning of spin transport and charge transport characteristics. These results laid the foundation for the design of efficient pure spin current-based electronics, which can be integrated in complex three-dimensional architectures.

Motor cortex relocation after complete anatomical hemispherectomy for intractable epilepsy secondary to Rasmussen's encephalitis.

BACKGROUND: The authors report a case with interesting clinical and radiological outcomes following complete anatomical hemispherectomy. METHODS: A seven-year-old female with medically refractory epilepsy secondary to Rasmussen's encephalitis was treated with a complete right-sided anatomical hemispherectomy. RESULTS: Surgical intervention provided seizure relief, and at eleven-years post-operatively she was independently mobile, with spasticity of the upper limb. She had normal intellect and was pursuing higher education. Functional MRI found re-location of left-sided motor control to the remaining left hemisphere, alongside the existing motor cortex. CONCLUSION: This interesting case is a good example of effective neuroplasticity; motor functionality relocated an area in the contralateral hemisphere that already contained the prerequisite cellular architecture and white matter connectivity required to control movement.

Efficient Injection and Detection of Out-of-Plane Spins via the Anomalous Spin Hall Effect in Permalloy Nanowires.

We report a novel mechanism for the electrical injection and detection of out-of-plane spin accumulation via the anomalous spin Hall effect (ASHE), where the direction of the spin accumulation can be controlled by manipulating the magnetization of the ferromagnet. This mechanism is distinct from the spin Hall effect (SHE), where the spin accumulation is created along a fixed direction parallel to an interface. We demonstrate this unique property of the ASHE in nanowires made of permalloy (Py) to inject and detect out-of-plane spin accumulation in a magnetic insulator, yttrium iron garnet (YIG). We show that the efficiency for the injection/detection of out-of-plane spins can be up to 50% of that of in-plane spins. We further report the possibility to detect spin currents parallel to the Py/YIG interface for spins fully oriented in the out-of-plane direction, resulting in a sign reversal of the nonlocal magnon spin signal. The new mechanisms that we have demonstrated are highly relevant for spin torque devices and applications.

Effectiveness of Integrated Simulation and Clinical Experiences Compared to Traditional Clinical Experiences for Nursing Students.

AIM: The focus of this research study was the evaluation of the effectiveness of using high-fidelity simulations to replace 50 percent of traditional clinical experiences in obstetrics, pediatrics, critical care, and mental health nursing. BACKGROUND: Increasing student admissions to nursing programs require additional clinical learning opportunities to accommodate extra students. METHOD: Three schools with associate degree nursing programs partnered to identify, implement, and evaluate a creative solution to this dilemma. The resulting quasi-experimental study investigated if substituting half of the conventional clinical experiences with simulations was as effective as traditional clinical activities in obstetrics, pediatrics, mental health, and critical care. One hour of simulation counted for two hours of clinical time. RESULTS Findings indicated combining simulations with conventional clinical experiences resulted in significantly higher scores on the pre-graduation exit exam than traditional clinical experiences alone. CONCLUSIONS: Findings have implications for articulation and basic students in associate degree nursing programs.

Cerebral CT Venography Using a 320-MDCT Scanner With a Time-Density Curve Technique and Low Volume of Contrast Agent: Comparison With Fixed Time-Delay Technique.

OBJECTIVE: The purpose of this study was to compare a cerebral CT venography (CTV) technique performed on a 320-MDCT scanner with the use of a time-density curve (TDC) and a small volume of IV contrast medium (35 mL, with 15 mL used for the test bolus) with CTV performed using an established reference technique in which scanning is performed at a fixed time delay of 30 seconds with the use of a larger volume of contrast medium (100 mL). MATERIALS AND METHODS: The time of peak enhancement was determined from the TDC generated from a scan in which a test bolus dose was used. CTV was performed at the time of peak enhancement. The diagnostic quality of 31 CTV venograms acquired using this technique was compared retrospectively with the diagnostic quality of 29 CTV venograms obtained at a fixed time delay of 30 seconds. The densities in the major venous sinuses and the degree of arterial contamination on the scans acquired using the two techniques were compared using objective and semiobjective methods. The semiobjective assessments were made independently by two neuroradiologists. RESULTS: Attenuation was higher in the venous structures seen on CTV images acquired using the TDC technique. Of the scans obtained using the TDC technique, the proportion deemed to be of good quality, on the basis of a grading scale, was statistically significantly higher (p < 0.05). Also, the degree of arterial contamination was statistically significantly lower (p < 0.05). The interrater agreement for semiobjective assessments ranged from good to very good. CONCLUSION: We describe a CTV technique performed using a low volume of IV contrast medium and a TDC on a 320-MDCT scanner. This technique provides better venous opacification and lower arterial contamination compared with use of the fixed time-delay technique.

Diagnostic challenges, management and outcomes of midline low-grade gliomas.

INTRODUCTION: Low-grade gliomas (LGGs) are slow-growing and diffusely infiltrating tumours constituting 25-30 % of adult gliomas. Rarely, these tumours may arise in the cerebral midline, including the thalamus, hypothalamus, tectum and brainstem. Here we present a contemporary experience with midline LGGs. METHODS: Midline LGGs were identified from a retrospective database of adult patients who received a histological diagnosis of WHO grade II glioma between 2006 and 2012 at a single institution. Location, radiological data and clinical outcomes were collected. IDH1 status was assessed by immunohistochemistry. RESULTS: Eighteen patients with midline LGGs were identified, with a median age of 45. Most received biopsy upon diagnosis, though asymptomatic patients with tectal tumours underwent active surveillance. Oligodendroglial tumours were much less common than in a comparable group of lobar tumours (6 vs. 38 %, Fisher's exact test, p = 0.007). Only one tumour was immunopositive for IDH1 (1/17). Radiological diagnosis correlated with histology in only 71 % of patients. Median survival of midline LGGs was 48 months (3-90 months) and radiological features such as contrast enhancement, size and radiological diagnosis did not predict survival in this cohort. Median overall survival of midline LGGs was less than lobar LGGs (log-rank, p = 0.006), though differences became insignificant when considering only biopsied astrocytomas in both locations (log-rank, p = 0.491). CONCLUSIONS: Diagnosis of midline LGGs is complicated by both limitations of biopsy and imaging. Midline tumours have a poorer prognosis compared to lobar equivalents and survival differences are probably due to the absence of significant surgical intervention in midline locations.

Diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predicts patient outcomes.

BACKGROUND: Diffusion-weighted MRI (DWI) has been used in neurosurgical practice mainly to distinguish cerebral metastases from abscess and glioma. There is evidence from other solid organ cancers and metastases that DWI may be used as a biomarker of prognosis and treatment response. We therefore investigated DWI characteristics of cerebral metastases and their peritumoral region recorded pre-operatively and related these to patient outcomes. METHODS: Retrospective analysis of 76 cases operated upon at a single institution with DWI performed pre-operatively at 1.5T. Maps of apparent diffusion coefficient (ADC) were generated using standard protocols. Readings were taken from the tumor, peritumoral region and across the brain-tumor interface. Patient outcomes were overall survival and time to local recurrence. RESULTS: A minimum ADC greater than 919.4 × 10(-6) mm(2)/s within a metastasis predicted longer overall survival regardless of adjuvant therapies. This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer. The change in diffusion across the tumor border and into peritumoral brain was measured by the "ADC transition coefficient" or ATC and this was more strongly predictive than ADC readings alone. Metastases with a sharp change in diffusion across their border (ATC >0.279) showed shorter overall survival compared to those with a more diffuse edge. The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 - 0.97, p = 0.04). CONCLUSIONS: DWI demonstrates changes in the tumor, across the tumor edge and in the peritumoral region which may not be visible on conventional MRI and this may be useful in predicting patient outcomes for operated cerebral metastases.

Atypical benign melanotic thoracic intradural schwannoma.

We discuss the 8th known case of a patient who presented with an intradural intramedullary spinal melanocytic schwannoma. In this report we will discuss the hypothesis regarding the pathogenesis of the development of intradural schwannomas, the imaging modality of choice and treatment options.

Somatosensory change and pain relief induced by repetitive transcranial magnetic stimulation in patients with central poststroke pain.

OBJECTIVE: To quantify changes in pain and somatosensory function in patients with central poststroke pain (CPSP) syndrome following five sessions of repetitive transcranial magnetic stimulation (rTMS). METHODS: Fourteen CPSP patients underwent MRI-guided TMS mapping to identify the motor hotspot for evoked responses from a muscle corresponding to a painful region (hand, N = 11, or distal leg, N = 3). Targeted rTMS consisting of 2000 stimuli/10 Hz each session was delivered over five sessions. Quantitative somatosensory testing (QST) was performed within the painful area and at the contralateral mirror-image site at baseline and after the rTMS. RESULTS: At baseline there were significant sensory deficits of the affected body side for warm and cold detection and heat/cold pain thresholds. Following rTMS, sensory thresholds showed significant improvements for cold detection threshold (repeated-measures ANOVA, p = 0.04). Subjects' pain reports (numerical rating scale 0-10) showed modest but significant improvements in the first week after rTMS (baseline 7.0 ± 1.5; post-TMS 6.3 ± 1.5; Wilcoxon signed-rank test, p = 0.018), and these were largely maintained for up to four weeks post-rTMS. Improvements in warm detection threshold showed a significant correlation with decrease in pain score (Spearman's rank-order correlation, p = 0.007). CONCLUSIONS: Five sessions of open-label rTMS provided analgesia and improved thermal sensibility. The correlation of reduction of detection threshold for warmth and pain relief suggest that the effect of rTMS may be mediated via circuitries that share the processing of noxious and thermal signals, such as the insula and the somatosensory and anterior cingulate cortices. QST may have a role in the assessment of patients with neuropathic pain for suitability for rTMS treatment and is likely to add to our understanding of how rTMS induces pain relief.

Neuropathic pruritus (itch) in neuromyelitis optica.

BACKGROUND: Neuropathic pruritus (itch) is an uncommon, but well described, symptom in neurology. There are itch-specific neurons in the dorsal horn of the spinal cord. We noted excessive pruritus in patients with neuromyelitis optica (NMO). OBJECTIVE: We aimed to explore the characteristics of pruritus in NMO patients. METHODS: We reviewed case records of a well-defined cohort of 45 serial aquaporin-4 antibody-positive patients visiting the national NMO service. All patients were interviewed. RESULTS: Of the 45 antibody-positive NMO patients, 44 had myelitis and 12 of those 44 (27.3%) patients reported pruritus within a week of other symptoms of transverse myelitis with central cord involvement. In three patients, pruritus was the first symptom of a relapse, while in one case, pruritus was the very first symptom of the index episode of NMO. CONCLUSION: Neuropathic pruritus seems to be a common, but under-recognised symptom of myelitis associated with NMO.

Clinical predictors of encephalitis in UK adults-A multi-centre prospective observational cohort study.

OBJECTIVES: Encephalitis, brain inflammation and swelling, most often caused by an infection or the body's immune defences, can have devastating consequences, especially if diagnosed late. We looked for clinical predictors of different types of encephalitis to help clinicians consider earlier treatment. METHODS: We conducted a multicentre prospective observational cohort study (ENCEPH-UK) of adults (> 16 years) with suspected encephalitis at 31 UK hospitals. We evaluated clinical features and investigated for infectious and autoimmune causes. RESULTS: 341 patients were enrolled between December 2012 and December 2015 and followed up for 12 months. 233 had encephalitis, of whom 65 (28%) had HSV, 38 (16%) had confirmed or probable autoimmune encephalitis, and 87 (37%) had no cause found. The median time from admission to 1st dose of aciclovir for those with HSV was 14 hours (IQR 5-50); time to 1st dose of immunosuppressant for the autoimmune group was 125 hours (IQR 45-250). Compared to non-HSV encephalitis, patients with HSV more often had fever, lower serum sodium and lacked a rash. Those with probable or confirmed autoimmune encephalitis were more likely to be female, have abnormal movements, normal serum sodium levels and a cerebrospinal fluid white cell count < 20 cells x106/L, but they were less likely to have a febrile illness. CONCLUSIONS: Initiation of treatment for autoimmune encephalitis is delayed considerably compared with HSV encephalitis. Clinical features can help identify patients with autoimmune disease and could be used to initiate earlier presumptive therapy.

Altered Structural Brain Networks in Refractory and Nonrefractory Idiopathic Generalized Epilepsy.

Introduction: Idiopathic generalized epilepsy (IGE) is a collection of generalized nonlesional epileptic network disorders. Around 20-40% of patients with IGE are refractory to antiseizure medication, and mechanisms underlying refractoriness are poorly understood. Here, we characterize structural brain network alterations and determine whether network alterations differ between patients with refractory and nonrefractory IGE. Methods: Thirty-three patients with IGE (10 nonrefractory and 23 refractory) and 39 age- and sex-matched healthy controls were studied. Network nodes were segmented from T1-weighted images, while connections between these nodes (edges) were reconstructed from diffusion magnetic resonance imaging (MRI). Diffusion networks of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and streamline count (Count) were studied. Differences between all patients, refractory, nonrefractory, and control groups were computed using network-based statistics. Nodal volume differences between groups were computed using Cohen's d effect size calculation. Results: Patients had significantly decreased bihemispheric FA and Count networks and increased MD and RD networks compared with controls. Alterations in network architecture, with respect to controls, differed depending on treatment outcome, including predominant FA network alterations in refractory IGE and increased nodal volume in nonrefractory IGE. Diffusion MRI networks were not influenced by nodal volume. Discussion: Although a nonlesional disorder, patients with IGE have bihemispheric structural network alterations that may differ between patients with refractory and nonrefractory IGE. Given that distinct nodal volume and FA network alterations were observed between treatment outcome groups, a multifaceted network analysis may be useful for identifying imaging biomarkers of refractory IGE.