Spinal Nerve Root Stimulation for Chronic Pain: A Systematic Review.

OBJECTIVE: Spinal cord stimulation (SCS) has been used as a minimally invasive and effective treatment modality for various chronic pain disorders, with the main target being stimulation of the dorsal columns; however, certain neuropathic pain areas involve dermatomes that are suboptimally covered by SCS. Stimulation of the spinal nerve roots has the advantage of targeting one or several dermatomes at the same time. The aim of this systematic review is to investigate the efficacy of spinal nerve root stimulation (SNRS) for chronic pain disorders. MATERIALS AND METHODS: A detailed literature review was performed through the Ovid Embase and MEDLINE data bases in addition to reference searching. Gray literature was included by searching through common search engines using a simplified search strategy. Studies included were focused on adult patients (aged >18 years), diagnosis of chronic pain syndrome (including but not limited to complex regional pain syndrome, persistent spinal pain syndrome, neuropathic pain secondary to trauma or infection, postherpetic pain, and cancer pain). Patients must have undergone SNRS insertion, with ≥six months of documented pain intensity scores on follow-up. RESULTS: A total of 40 studies underwent full text review, and 13 articles were included in final analysis. Mean preoperative pain intensity was 8.14 ± 0.74 on the visual analog scale, whereas mean postoperative pain intensity at one year was 3.18 ± 1.44. Of 119 patients, 83 (70%) achieved ≥50% reduction in pain intensity after SNRS, whereas 36 (30%) achieved <50% reduction in pain intensity. Only three studies assessed changes in analgesia medication dose and reported morphine equivalent doses varied by case series. Overall, there was a trend toward a reduction in analgesia medications in the postoperative period. CONCLUSIONS: SNRS led to a mean 44% reduction in pain intensity, with a low level of certainty. In addition, there is some evidence to suggest that using SNRS is associated with reduced use of analgesics, including morphine and gabapentin.

Surgical Interventions Targeting the Nucleus Caudalis for Craniofacial Pain: A Systematic and Historical Review.

INTRODUCTION: Craniofacial pain is a prevalent group of conditions, and when refractory to conventional treatments, it poses a significant burden. The last decade has seen a renewed interest in the multimodal management of pain. Interventions targeting the nucleus caudalis (NC) of the trigeminocervical complex have been available as a treatment option since the 1930s, yet evidence for efficacy remains limited. MATERIALS AND METHODS: We present a systematic review of the literature providing a historical perspective on interventions targeting the NC leading up to the present. We examine the various intervention techniques, clinical indications, and procedural efficacy. A novel outcome-reporting scheme was devised to enable comparison among studies owing to historically variable reporting methods. RESULTS: A review of the literature revealed 33 retrospective studies published over the last 80 years, reporting on 827 patients. The most common technique was the open NC dorsal root entry zone nucleotomy/tractotomy; however, there has been an emergence of novel approaches such as endoscopic and spinal cord stimulation in the last ten years. Regardless of intervention technique or preoperative diagnosis, 87% of patients showed improvement with treatment. CONCLUSIONS: The literature surrounding NC intervention techniques is reviewed. Recent advancements and the wide range of craniofacial pain syndromes for which these interventions show potential efficacy are discussed. New and less invasive techniques continue to emerge as putative therapeutic options. However, prospective studies are lacking. Furthermore, the evidence supporting even well-established techniques remains of poor quality. Future work should be prospective, use standard outcome reporting, and address efficacy comparisons between intervention type and preoperative diagnosis.

Mapping the subcortical connectome using in vivo diffusion MRI: Feasibility and reliability.

Tractography combined with regions of interest (ROIs) has been used to non-invasively study the structural connectivity of the cortex as well as to assess the reliability of these connections. However, the subcortical connectome (subcortex to subcortex) has not been comprehensively examined, in part due to the difficulty of performing tractography in this complex and compact region. In this study, we performed an in vivo investigation using tractography to assess the feasibility and reliability of mapping known connections between structures of the subcortex using the test-retest dataset from the Human Connectome Project (HCP). We further validated our observations using a separate unrelated subjects dataset from the HCP. Quantitative assessment was performed by computing tract densities and spatial overlap of identified connections between subcortical ROIs. Further, known connections between structures of the basal ganglia and thalamus were identified and visually inspected, comparing tractography reconstructed trajectories with descriptions from tract-tracing studies. Our observations demonstrate both the feasibility and reliability of using a data-driven tractography-based approach to map the subcortical connectome in vivo.

Effects of MP2RAGE B1+ sensitivity on inter-site T1 reproducibility and hippocampal morphometry at 7T.

Most neuroanatomical studies are based on T1-weighted MR images, whose intensity profiles are not solely determined by the tissue's longitudinal relaxation times (T1), but also affected by varying non-T1 contributions, hampering data reproducibility. In contrast, quantitative imaging using the MP2RAGE sequence, for example, allows direct characterization of the brain based on the tissue property of interest. Combined with 7 Tesla (7T) MRI, this offers unique opportunities to obtain robust high-resolution brain data characterized by a high reproducibility, sensitivity and specificity. However, specific MP2RAGE parameter choices - e.g., to emphasize intracortical myelin-dependent contrast variations - can substantially impact image quality and cortical analyses through remnants of B1+-related intensity variations, as illustrated in our previous work. To follow up on this: we (1) validate this protocol effect using a dataset acquired with a particularly B1+ insensitive set of MP2RAGE parameters combined with parallel transmission excitation; and (2) extend our analyses to evaluate the effects on hippocampal morphometry. The latter remained unexplored initially, but can provide important insights related to generalizability and reproducibility of neurodegenerative research using 7T MRI. We confirm that B1+ inhomogeneities have a considerably variable effect on cortical T1 estimates, as well as on hippocampal morphometry depending on the MP2RAGE setup. While T1 differed substantially across datasets initially, we show the inter-site T1 comparability improves after correcting for the spatially varying B1+ field using a separately acquired Sa2RAGE B1+ map. Finally, removal of B1+ residuals affects hippocampal volumetry and boundary definitions, particularly near structures characterized by strong intensity changes (e.g. cerebral spinal fluid). Taken together, we show that the choice of MP2RAGE parameters can impact T1 comparability across sites and present evidence that hippocampal segmentation results are modulated by B1+ inhomogeneities. This calls for careful (1) consideration of sequence parameters when setting acquisition protocols, as well as (2) acquisition of a B1+ map to correct MP2RAGE data for potential B1+ variations to allow comparison across datasets.

Direct visualization and characterization of the human zona incerta and surrounding structures.

The zona incerta (ZI) is a small gray matter region of the deep brain first identified in the 19th century, yet direct in vivo visualization and characterization has remained elusive. Noninvasive detection of the ZI and surrounding region could be critical to further our understanding of this widely connected but poorly understood deep brain region and could contribute to the development and optimization of neuromodulatory therapies. We demonstrate that high resolution (submillimetric) longitudinal (T1) relaxometry measurements at high magnetic field strength (7 T) can be used to delineate the ZI from surrounding white matter structures, specifically the fasciculus cerebellothalamicus, fields of Forel (fasciculus lenticularis, fasciculus thalamicus, and field H), and medial lemniscus. Using this approach, we successfully derived in vivo estimates of the size, shape, location, and tissue characteristics of substructures in the ZI region, confirming observations only previously possible through histological evaluation that this region is not just a space between structures but contains distinct morphological entities that should be considered separately. Our findings pave the way for increasingly detailed in vivo study and provide a structural foundation for precise functional and neuromodulatory investigation.

A framework for evaluating correspondence between brain images using anatomical fiducials.

Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, we found that commonly used voxel overlap metrics were relatively insensitive to focal misregistrations compared to AFID point-based measures. Our entire protocol and study framework leverages open resources and tools, and has been developed with full transparency in mind so that others may freely use, adopt, and modify. This protocol holds value for a broad number of applications including alignment of brain images and teaching neuroanatomy.

Position Statement on the Use of Medical Cannabis for the Treatment of Epilepsy in Canada.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Énoncé de position quant à l'utilisation du cannabis médical dans le traitement de l'épilepsie. L'utilisation du cannabis à des fins récréatives a été légalisée au Canada en octobre 2018. Parallèlement à ce changement de politique, de récentes publication visant à évaluer l'efficacité du cannabis dans le traitement de l'épilepsie, de même qu'une sensibilisation médiatique accrue en ce qui concerne son utilisation, ont eu pour effet d'augmenter l'intérêt du grand public à son égard. Le Comité médical thérapeutique de la Ligue canadienne contre l'épilepsie (LCCE), de concert avec un groupe multidisciplinaire d'experts et des représentants de l'Alliance canadienne de l'épilepsie, a ainsi élaboré un énoncé de position en ce qui regarde l'utilisation du cannabis médical dans le traitement de l'épilepsie. Cet article entend donc aborder le cadre légal qui prévaut actuellement au Canada et examiner de récentes publications s'étant penchées sur le profil sécuritaire et sur l'efficacité du cannabis. De plus, nous voulons apporter un éclairage au sujet des aspects cliniques dont il faudrait tenir compte au moment d'envisager l'utilisation du cannabis à des fins médicales.

Radiology reporting of low-grade glioma growth underestimates tumor expansion.

BACKGROUND: An important aspect in the management of patients with diffuse low-grade gliomas (LGGs) involves monitoring the lesions via serial magnetic resonance imaging (MRI). However, radiological interpretations of LGG interval scans are often qualitative and thus difficult to use clinically. METHODS: To contextualize these assessments, we retrospectively compared radiological interpretations of LGG growth or stability to volume change measured by manual segmentation. Tumor diameter was also measured in one, two, and three dimensions to evaluate reported methods for assessment of glioma progression, including RECIST criteria, Macdonald/RANO criteria, and mean tumor diameter/ellipsoid method. RESULTS: Tumors evaluated as stable by radiologists grew a median volume of 5.1 mL (11.1%) relative to the comparison scan, and those evaluated as having grown had a median volume increase of 13.3 mL (23.7%). Diameter-based measurements corresponded well but tended to overestimate gold standard segmented volumes. In addition, agreement with segmented volume measurements improved from 17.6 ± 8.0 to 4.5 ± 5.8 to 3.9 ± 3.6 mm for diameter and from 104.0 ± 96.6 to 25.3 ± 36.8 to 15.9 ± 21.3 mL for volume with radiological measurements in one, two, and three dimensions, respectively. Measurement overestimation increased with tumor size. CONCLUSIONS: Given accumulating evidence that LGG volume and growth are prognostic factors, there is a need for objective lesion measurement. Current radiological reporting workflows fail to appreciate and communicate the true expansion of LGGs. While volumetric analysis remains the gold standard for assessment of growth, careful diametric measurements in three dimensions may be an acceptable alternative.

Unfolding the hippocampus: An intrinsic coordinate system for subfield segmentations and quantitative mapping.

The hippocampus, like the neocortex, has a morphological structure that is complex and variable in its folding pattern, especially in the hippocampal head. The current study presents a computational method to unfold hippocampal grey matter, with a particular focus on the hippocampal head where complexity is highest due to medial curving of the structure and the variable presence of digitations. This unfolding was performed on segmentations from high-resolution, T2-weighted 7T MRI data from 12 healthy participants and one surgical patient with epilepsy whose resected hippocampal tissue was used for histological validation. We traced a critical image feature composed of the hippocampal sulcus and stratum radiatum lacunosum-moleculare, (SRLM) in these images, then employed user-guided semi-automated techniques to detect and subsequently unfold the surrounding hippocampal grey matter. This unfolding was performed by solving Laplace's equation in three dimensions of interest (long-axis, proximal-distal, and laminar). The resulting 'unfolded coordinate space' provides an intuitive way of mapping the hippocampal subfields in 2D space (long-axis and proximal-distal), such that similar borders can be applied in the head, body, and tail of the hippocampus independently of variability in folding. This unfolded coordinate space was employed to map intracortical myelin and thickness in relation to subfield borders, which revealed intracortical myelin differences that closely follow the subfield borders used here. Examination of a histological resected tissue sample from a patient with epilepsy reveals that our unfolded coordinate system has biological validity, and that subfield segmentations applied in this space are able to capture features not seen in manual tracing protocols.

Quantification of local geometric distortion in structural magnetic resonance images: Application to ultra-high fields.

Ultra-high field magnetic resonance imaging (MRI) provides superior visualization of brain structures compared to lower fields, but images may be prone to severe geometric inhomogeneity. We propose to quantify local geometric distortion at ultra-high fields in in vivo datasets of human subjects scanned at both ultra-high field and lower fields. By using the displacement field derived from nonlinear image registration between images of the same subject, focal areas of spatial uncertainty are quantified. Through group and subject-specific analysis, we were able to identify regions systematically affected by geometric distortion at air-tissue interfaces prone to magnetic susceptibility, where the gradient coil non-linearity occurs in the occipital and suboccipital regions, as well as with distance from image isocenter. The derived displacement maps, quantified in millimeters, can be used to prospectively evaluate subject-specific local spatial uncertainty that should be taken into account in neuroimaging studies, and also for clinical applications like stereotactic neurosurgery where accuracy is critical. Validation with manual fiducial displacement demonstrated excellent correlation and agreement. Our results point to the need for site-specific calibration of geometric inhomogeneity. Our methodology provides a framework to permit prospective evaluation of the effect of MRI sequences, distortion correction techniques, and scanner hardware/software upgrades on geometric distortion.

Novel connectivity map normalization procedure for improved quantitative investigation of structural thalamic connectivity in temporal lobe epilepsy patients.

BACKGROUND: Connectivity studies targeting the thalamus have revealed patterns of atrophy and deafferentiation in temporal lobe epilepsy (TLE). The thalamus can be parcellated using probabilistic tractography to demonstrate regions of cortical connectivity; however, sensitivity to smaller or less connected regions is low. PURPOSE/HYPOTHESIS: To investigate thalamic structural connectivity in a wider range of cortical and limbic structures in TLE patients using a novel connectivity map normalization procedure. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: Patients (N = 23) with medication-resistant TLE and 34 healthy age-matched controls. FIELD STRENGTH/SEQUENCE: For T1 and diffusion weighting a spoiled gradient sequence was used (41 gradient directions [b = 1000]). For T2 mapping balanced steady-state free precession was used. Images were acquired at 3T. ASSESSMENT: Probabilistic tractography and a novel normalization procedure allowed comparison of groups with respect to thalamic connected volume, quantitative MRI, and diffusion tensor imaging (DTI) metrics. STATISTICAL TESTS: Independent samples t-test, Cohen's d, and Mann-Whitney tests. RESULTS: Following normalization, significant differences in thalamic connected volumes were found in left TLE vs. controls bilaterally within the posterior parahippocampal gyrus (L: P = 0.007, confidence interval [CI]: [173.306,1044.41], effect size [ES] = 1.072; R: P = 0.017, CI: [98.677,947.653], ES = 0.945), and contralaterally in the anterior temporal neocortex (P = 0.01, CI: (-2348.09, -333.719), ES = -1.021). This procedure revealed differences in thalamic connected volumes, where previously published procedures could not, and provided a basis for exploratory analysis of quantitative MRI and DTI metrics. DATA CONCLUSION: The novel connectivity map normalization scheme proposed here successfully allowed comparison between a wider range of cortical and limbic structures. Multiple volumetric and quantitative MRI and DTI-related differences between TLE patients and controls were revealed following normalization. With validation from a larger cohort, thalamo-temporal connection aberrancies may become useful biomarkers of disease states and probabilistic tractography as a procedure for identification of thalamic targets in modulatory therapies for TLE. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1529-1539.

Tumor growth dynamics in serially-imaged low-grade glioma patients.

BACKGROUND: Diffuse low-grade gliomas (LGGs) are infiltrative, slow-growing primary brain tumors that remain relatively asymptomatic for long periods of time before progressing into aggressive and fatal high-grade gliomas. METHODS: We retrospectively identified LGG patients with numerous (≥ 8) serial magnetic resonance imaging (MRI) studies. Tumor volumes were measured by manual segmentation on serial imaging to study the natural history and growth of the lesion. Patient demographic information, tumor characteristics, and histological data were collected from electronic medical records and paper charts. RESULTS: Out of 74 LGG patients, 10 patients (13.5%) were identified to meet the study criteria with number of MRIs acquired ranging from 8 to 18 (median, 11.5) over a median of 79.7 months (range 39.8-113.8 months). Tumor diameter increased at a median of 2.17 mm/year in a linear trajectory. Cox regression analysis revealed that initial tumor volume was an independent predictor of time to clinical intervention, and Mann-Whitney U test found that patients younger than 50 years old had significantly slower-growing tumors. Clinical intervention was more likely for tumors above a volume threshold of 73.6 mL. CONCLUSION: We retrospectively analyzed the natural history of LGGs of patients managed at a single institution with numerous serial MRI scans. Comparisons of our cohort to the literature suggest that this is a subset of particularly slow-growing and low-risk tumors.

Image-guided Ommaya reservoir insertion for intraventricular chemotherapy: a retrospective series.

BACKGROUND: Ayub Ommaya proposed a surgical technique for subcutaneous reservoir and pump placement in 1963 to allow access to intraventricular cerebrospinal fluid (CSF). Currently, the most common indication for Ommaya reservoir insertion (ORI) in adults is for patients with hematologic or leptomeningeal disorders requiring repeated injection of chemotherapy into the CSF space. Historically, the intraventricular catheter has been inserted blindly based on anatomical landmarks. The purpose of this study was to examine short-term complication rates with ORI with image guidance (IG) and without image guidance (non-IG). METHODS: We retrospectively evaluated all operative cases of ORI from 2000 to 2014 by the senior author. Patient demographic data, surgical outcomes, and peri-operative complications were collected. Accurate placement and early (30-day) morbidity or mortality were considered primary outcomes. RESULTS: Fifty-five consecutive patients underwent ORI by the senior author over the study period (43.5 ± 16.6 years; 40.0% female). Indications for placement included acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and leptomeningeal carcinomatosis. There were seven (12.7%) total complications: three (37.5%) with no-IG versus four (8.5%) with IG. Catheter malpositions were significantly higher in the non-IG group at 37.5% compared to 2.1%. Catheters were also more likely to require multiple passes with non-IG at 25% compare to 0% with IG. There were no early infections in either group. CONCLUSIONS: We demonstrate improved accuracy and decreased complications using an image-guided approach compared with a traditional approach. Our results support routine use of intra-operative image guidance for proximal catheter insertion in elective ORI for intraventricular chemotherapy.

Investigation of hippocampal substructures in focal temporal lobe epilepsy with and without hippocampal sclerosis at 7T.

PURPOSE: To provide a more detailed investigation of hippocampal subfields using 7T magnetic resonance imaging (MRI) for the identification of hippocampal sclerosis in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Patients (n = 13) with drug-resistant TLE previously identified by conventional imaging as having hippocampal sclerosis (HS) or not (nine without HS, four HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( R2*) were studied between the two groups. In addition, qualitative assessment at 7T and clinical outcomes were correlated with measured subfield changes. RESULTS: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 (P = 0.001) and CA4+DG (P < 0.001). Volumetry also uncovered subfield atrophy in 33% of patients without HS, which had not been detected using conventional imaging. R2* was significantly lower in the CA4+DG subfields (P = 0.001) and the whole hippocampus (P = 0.029) of HS patients compared to controls but not significantly lower than the group without HS (P = 0.077, P = 0.109). No correlation was found between quantitative volumetry and qualitative assessment as well as surgical outcomes (Sub, P = 0.495, P = 0.567, P = 0.528; CA1, P = 0.104 ± 0.171, P = 0.273, P = 0.554; CA2+CA3, P = 0.517, P = 0.952, P = 0.130 ± 0.256; CA4+DG, P = 0.052 ± 0.173, P = 0.212, P = 0.124 ± 0.204; WholeHipp, P = 0.187, P = 0.132 ± 0.197, P = 0.628). CONCLUSION: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T is capable of identifying characteristic patterns of hippocampal atrophy in HS patients; however, difficulty remains in using imaging to identify hippocampal pathologies in cases without HS. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1359-1370.

Functional Magnetic Resonance Imaging for Preoperative Planning in Brain Tumour Surgery.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is being increasingly used for the preoperative evaluation of patients with brain tumours. METHODS: The study is a retrospective chart review investigating the use of clinical fMRI from 2002 through 2013 in the preoperative evaluation of brain tumour patients. Baseline demographic and clinical data were collected. The specific fMRI protocols used for each patient were recorded. RESULTS: Sixty patients were identified over the 12-year period. The tumour types most commonly investigated were high-grade glioma (World Health Organization grade III or IV), low-grade glioma (World Health Organization grade II), and meningioma. Most common presenting symptoms were seizures (69.6%), language deficits (23.2%), and headache (19.6%). There was a predominance of left hemispheric lesions investigated with fMRI (76.8% vs 23.2% for right). The most commonly involved lobes were frontal (64.3%), temporal (33.9%), parietal (21.4%), and insular (7.1%). The most common fMRI paradigms were language (83.9%), motor (75.0%), sensory (16.1%), and memory (10.7%). The majority of patients ultimately underwent a craniotomy (75.0%), whereas smaller groups underwent stereotactic biopsy (8.9%) and nonsurgical management (16.1%). Time from request for fMRI to actual fMRI acquisition was 3.1±2.3 weeks. Time from fMRI acquisition to intervention was 4.9±5.5 weeks. CONCLUSIONS: We have characterized patient demographics in a retrospective single-surgeon cohort undergoing preoperative clinical fMRI at a Canadian centre. Our experience suggests an acceptable wait time from scan request to scan completion/analysis and from scan to intervention.

In vivo MRI signatures of hippocampal subfield pathology in intractable epilepsy.

OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo. EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG. PRINCIPAL OBSERVATIONS: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy. CONCLUSION: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology.

Latent infection of myeloid progenitors by human cytomegalovirus protects cells from FAS-mediated apoptosis through the cellular IL-10/PEA-15 pathway.

Latent infection of primary CD34(+) progenitor cells by human cytomegalovirus (HCMV) results in their increased survival in the face of pro-apoptotic signals. For instance, we have shown previously that primary myeloid cells are refractory to FAS-mediated killing and that cellular IL-10 (cIL-10) is an important survival factor for this effect. However, how cIL-10 mediates this protection is unclear. Here, we have shown that cIL-10 signalling leading to upregulation of the cellular factor PEA-15 mediates latency-associated protection of CD34(+) progenitor cells from the extrinsic death pathway.

Optimal hippocampal targeting in responsive neurostimulation for mesial temporal lobe epilepsy.

OBJECTIVE: The aim of this study was to identify features of responsive neurostimulation (RNS) lead configuration and contact placement associated with greater seizure reduction in mesial temporal lobe epilepsy (MTLE). METHODS: A single-center series of patients with MTLE treated with RNS were retrospectively analyzed to assess the relationship between anatomical targeting and seizure reduction. Targeting was determined according to both the preoperatively conceived lead configuration and the actual placement of RNS contacts. Three lead configurations were used: 1) single bilateral, with 1 depth lead in each hippocampus; 2) single unilateral, with 1 hippocampal depth lead and another implant outside the mesial temporal lobe; and 3) dual unilateral, with 2 leads in 1 hippocampus. Contact placement on postoperative imaging was measured according to the number of hippocampal contacts per targeted hippocampus (contact density) and per patient (contact count), distribution throughout the hippocampus, and proximity to the anteromedial hippocampus. RESULTS: Dual unilateral lead placement resulted in significantly higher hippocampal contact density compared with the single hippocampal approaches, but only showed a nonsignificant trend toward a higher rate of response. However, those patients with more than 4 contacts in a single hippocampus, achievable only with dual unilateral leads, had a significantly higher rate of response. The higher likelihood of response was poorly explained by more widespread hippocampal coverage, but well correlated with proximity to the anteromedial hippocampus. CONCLUSIONS: Dual unilateral hippocampal implantation increased RNS contact density in patients with unilateral MTLE, which contributed to improved outcomes, not by stimulating more of the hippocampus, but instead by being more likely to stimulate a latent subtarget in the anterior hippocampus. It remains to be explored whether a single electrode targeted selectively to this region would also result in improved outcomes.

Teaching NeuroImage: Unilateral Primary Angiitis of the CNS.

A 48-year-old woman was referred with an 18-year history of focal-onset seizures. She also reported years-long slowly progressive right-sided weakness that was corroborated on examination. Repeated brain MRIs over 15 years showed multifocal left hemispheric T2 fluid-attenuated inversion recovery-hyperintense lesions with patchy enhancement and microhemorrhages, no diffusion restriction, and a left cerebellar infarct (Figure 1, A-F). Only 2 nonspecific white matter lesions were seen contralaterally, indicating largely unihemispheric disease. Differential diagnosis included unilateral primary angiitis of the CNS (PACNS), Rasmussen encephalitis, and myelin oligodendrocyte glycoprotein antibody-associated disease.1 Serum and CSF testing for autoimmune, infectious, and malignant etiologies and whole-body fluorodeoxyglucose-PET, whole-exome genetic sequencing, and MR vessel-wall imaging were nondiagnostic. Brain biopsy revealed vasculitis (Figure 2, A-F), and the patient was diagnosed with unilateral PACNS. Treatment with mycophenolate mofetil has been initiated. Unilateral PACNS is a rare unihemispheric disease characterized by an indolent course and seizures, recognition of which is critical to accurate diagnosis.1,2.

A population-averaged structural connectomic brain atlas dataset from 422 HCP-aging subjects.

Population-averaged brain atlases, that are represented in a standard space with anatomical labels, are instrumental tools in neurosurgical planning and the study of neurodegenerative conditions. Traditional brain atlases are primarily derived from anatomical scans and contain limited information regarding the axonal organization of the white matter. With the advance of diffusion MRI that allows the modeling of fiber orientation distribution (FOD) in the brain tissue, there is an increasing interest for a population-averaged FOD template, especially based on a large healthy aging cohort, to offer structural connectivity information for connectomic surgery and analysis of neurodegeneration. The dataset described in this article contains a set of multi-contrast structural connectomic MRI atlases, including T1w, T2w, and FOD templates, along with the associated whole brain tractograms. The templates were made using multi-contrast group-wise registration based on 3T MRIs of 422 Human Connectome Project in Aging (HCP-A) subjects. To enhance the usability, probabilistic tissue maps and segmentation of 22 subcortical structures are provided. Finally, the subthalamic nucleus shown in the atlas is parcellated into sensorimotor, limbic, and associative sub-regions based on their structural connectivity to facilitate the analysis and planning of deep brain stimulation procedures. The dataset is available on the OSF Repository: https://osf.io/p7syt.