Investigation of the intraoperative cortical responses to spinal motor mapping in a patient with chronic pain.

Intraoperative neurophysiological monitoring (IONM) in spinal cord stimulation (SCS) surgery for chronic pain is shown to provide effective guidance during device placement. Electromyography (EMG) is used to determine the laterality of the paddle. In some SCS cases, laterality cannot be obtained via EMG due to patient physiology. Electroencephalography (EEG) is already used in IONM to monitor cortical responses. Here, we show proof-of-concept of assessing the responses of epidurally evoked EMGs simultaneously with EEGs to determine laterality during IONM using a high-resolution (HR) SCS paddle. An 8-column HR-SCS paddle was acutely placed at T9-T10 interspace in patients with failed back surgery syndrome. EMG signals from 18 muscle groups were recorded simultaneously with 60-channel EEG signals at various stimulation amplitudes (0-10 mA). Particular attention was paid to regions associated with pain including the somatosensory cortex (S1), prefrontal cortex (PFC), and motor cortex (M1). When left and right lateral contacts were stimulated at low amplitudes (1-2 mA), significant changes were seen in θ, α, and ß powers in the contralateral PFC but not in M1 or S1. There was a significant correlation between M1 and contralateral contacts in α power. At higher currents (7-8 mA), right-sided contacts resulted in α power change. We found significant differences in α, θ, and ß powers in PFC for contralateral stimulation of the lateral SCS contacts at low amplitudes and in α power at higher amplitudes. The changes in PFC suggest the potential of EEG for understanding a cortical mechanism of action of SCS and provide insight into the pathophysiology of chronic pain.NEW & NOTEWORTHY Here, we present proof of concept of assessing the responses of epidurally evoked electromyography simultaneously with scalp electroencephalography to determine whether both laterality and insights into pain mechanisms can be elucidated. With stimulation, significant changes were seen in θ, α, and ß band power in the contralateral prefrontal cortex and in α power in the motor cortex. We provide insight into the mechanism of action of SCS in preventing pain in this patient.

Identification of the Somatomotor Network from Language Task-based fMRI Compared with Resting-State fMRI in Patients with Brain Lesions.

Background Resting-state functional MRI (rs-fMRI) is a potential alternative to task-based functional MRI (tb-fMRI) for somatomotor network (SMN) identification. Brain networks can also be generated from tb-fMRI by using independent component analysis (ICA). Purpose To investigate whether the SMN can be identified by using ICA from a language task without a motor component, the sentence completion functional MRI (sc-fMRI) task, compared with rs-fMRI. Materials and Methods The sc-fMRI and rs-fMRI scans in patients who underwent presurgical brain mapping between 2012 and 2016 were analyzed, using the same imaging parameters (other than scanning time) on a 3.0-T MRI scanner. ICA was performed on rs-fMRI and sc-fMRI scans with use of a tool to separate data sets into their spatial and temporal components. Two neuroradiologists independently determined the presence of the dorsal SMN (dSMN) and ventral SMN (vSMN) on each study. Groups were compared by using t tests, and logistic regression was performed to identify predictors of the presence of SMNs. Results One hundred patients (mean age, 40.9 years ± 14.8 [standard deviation]; 61 men) were evaluated. The dSMN and vSMN were identified in 86% (86 of 100) and 76% (76 of 100) of rs-fMRI scans and 85% (85 of 100) and 69% (69 of 100) of sc-fMRI scans, respectively. The concordance between rs-fMRI and sc-fMRI for presence of dSMN and vSMN was 75% (75 of 100 patients) and 53% (53 of 100 patients), respectively. In 10 of 14 patients (71%) where rs-fMRI did not show the dSMN, sc-fMRI demonstrated it. This rate was 67% for the vSMN (16 of 24 patients). Conclusion In the majority of patients, independent component analysis of sentence completion task functional MRI scans reliably demonstrated the somatomotor network compared with resting-state functional MRI scans. Identifying target networks with a single sentence completion scan could reduce overall functional MRI scanning times by eliminating the need for separate motor tasks. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Field and Birn in this issue.

Perceptual and computational detection of face morphing.

A relatively new type of identity theft uses morphed facial images in identification documents in which images of two individuals are digitally blended to create an image that maintains a likeness to each of the original identities. We created a set of high-quality digital morphs from passport-style photos for a diverse set of people across gender, race, and age. We then examine people's ability to detect facial morphing both in terms of determining if two side-by-side faces are of the same individual or not and in terms of identifying if a face is the result of digital morphing. We show that human participants struggle at both tasks. Even modern machine-learning-based facial recognition struggles to distinguish between an individual and their morphed version. We conclude with a hopeful note, describing a computational technique that holds some promise in recognizing that one facial image is a morphed version of another.

Repeatability of language fMRI lateralization and localization metrics in brain tumor patients.

To assess the within-subject intra-scan session repeatability of language functional MRI (fMRI) activation maps in patients with brain tumors who were undergoing presurgical fMRI as part of their preoperative clinical workup. Sentence completion (SC) and silent word generation (SWG) tasks were used for language localization and hemispheric lateralization for identifying the primary language cortex. Within-subject repeatability for each of these paradigms was assessed in right-handed patients-37 for SC and 78 for SWG. Repeatability of activation maps between consecutive runs of the same task within the same scan session was evaluated by comparing lateralization indexes in holohemispheric and regional language areas. Displacement of center of activation between consecutive runs was also used to assess the repeatability of activation maps. Holohemispheric and regional language lateralization results demonstrated high intra-subject intra-scan repeatability when lateralization indices were calculated using threshold-dependent and threshold-independent approaches. The high repeatability is demonstrated both when centers of mass of activation are considered within key eloquent regions of the brain, such as Broca's area and Wernicke's area, as well as in larger more inclusive expressive and receptive language regions. We examined two well-known and widely accepted language tasks that are known to activate eloquent language cortex. We have demonstrated very high degree of repeatability at a single-subject level within single scan sessions of language mapping in a large cohort of brain tumor patients undergoing presurgical fMRI across several years at our institution.

Multimodality neuromonitoring in severe pediatric traumatic brain injury.

Each year, the annual hospitalization rates of traumatic brain injury (TBI) in children in the United States are 57.7 per 100K in the <5 years of age and 23.1 per 100K in the 5-14 years age group. Despite this, little is known about the pathophysiology of TBI in children and how to manage it most effectively. Historically, TBI management has been guided by clinical examination. This has been assisted progressively by clinical imaging, intracranial pressure (ICP) monitoring, and finally a software that can calculate optimal brain physiology. Multimodality monitoring affords clinicians an early indication of secondary insults to the recovering brain including raised ICP and decreased cerebral perfusion pressure. From variables such as ICP and arterial blood pressure, correlations can be drawn to determine parameters of cerebral autoregulation (pressure reactivity index) and "optimal cerebral perfusion pressure" at which the vasculature is most reactive. More recently, significant advances using both direct and near-infrared spectroscopy-derived brain oxygenation plus cerebral microdialysis to drive management have been described. Here in, we provide a perspective on the state-of-the-art techniques recently implemented in clinical practice for pediatric TBI.

Src-like-adaptor protein (SLAP) differentially regulates normal and oncogenic c-Kit signaling.

The Src-like-adaptor protein (SLAP) is an adaptor protein sharing considerable structural homology with Src. SLAP is expressed in a variety of cells and regulates receptor tyrosine kinase signaling by direct association. In this report, we show that SLAP associates with both wild-type and oncogenic c-Kit (c-Kit-D816V). The association involves the SLAP SH2 domain and receptor phosphotyrosine residues different from those mediating Src interaction. Association of SLAP triggers c-Kit ubiquitylation which, in turn, is followed by receptor degradation. Although SLAP depletion potentiates c-Kit downstream signaling by stabilizing the receptor, it remains non-functional in c-Kit-D816V signaling. Ligand-stimulated c-Kit or c-Kit-D816V did not alter membrane localization of SLAP. Interestingly oncogenic c-Kit-D816V, but not wild-type c-Kit, phosphorylates SLAP on residues Y120, Y258 and Y273. Physical interaction between c-Kit-D816V and SLAP is mandatory for the phosphorylation to take place. Although tyrosine-phosphorylated SLAP does not affect c-Kit-D816V signaling, mutation of these tyrosine sites to phenylalanine can restore SLAP activity. Taken together the data demonstrate that SLAP negatively regulates wild-type c-Kit signaling, but not its oncogenic counterpart, indicating a possible mechanism by which the oncogenic c-Kit bypasses the normal cellular negative feedback control.

Presurgical brain mapping of the language network in patients with brain tumors using resting-state fMRI: Comparison with task fMRI.

PURPOSE: To compare language networks derived from resting-state fMRI (rs-fMRI) with task-fMRI in patients with brain tumors and investigate variables that affect rs-fMRI vs task-fMRI concordance. MATERIALS AND METHODS: Independent component analysis (ICA) of rs-fMRI was performed with 20, 30, 40, and 50 target components (ICA20 to ICA50) and language networks identified for patients presenting for presurgical fMRI mapping between 1/1/2009 and 7/1/2015. 49 patients were analyzed fulfilling criteria for presence of brain tumors, no prior brain surgery, and adequate task-fMRI performance. Rs-vs-task-fMRI concordance was measured using Dice coefficients across varying fMRI thresholds before and after noise removal. Multi-thresholded Dice coefficient volume under the surface (DiceVUS) and maximum Dice coefficient (MaxDice) were calculated. One-way Analysis of Variance (ANOVA) was performed to determine significance of DiceVUS and MaxDice between the four ICA order groups. Age, Sex, Handedness, Tumor Side, Tumor Size, WHO Grade, number of scrubbed volumes, image intensity root mean square (iRMS), and mean framewise displacement (FD) were used as predictors for VUS in a linear regression. RESULTS: Artificial elevation of rs-fMRI vs task-fMRI concordance is seen at low thresholds due to noise. Noise-removed group-mean DiceVUS and MaxDice improved as ICA order increased, however ANOVA demonstrated no statistically significant difference between the four groups. Linear regression demonstrated an association between iRMS and DiceVUS for ICA30-50, and iRMS and MaxDice for ICA50. CONCLUSION: Overall there is moderate group level rs-vs-task fMRI language network concordance, however substantial subject-level variability exists; iRMS may be used to determine reliability of rs-fMRI derived language networks.

Neurovascular uncoupling in resting state fMRI demonstrated in patients with primary brain gliomas.

BACKGROUND: To demonstrate that the problem of brain tumor-related neurovascular uncoupling (NVU) is a significant issue with respect to resting state blood oxygen level dependent (BOLD) functional MRI (rsfMRI) similar to task-based BOLD fMRI, in which signal detectability can be compromised by breakdown of normal neurovascular coupling. METHODS: We evaluated seven de novo brain tumor patients who underwent resting state fMRI as part of comprehensive clinical fMRI exams at 3 Tesla. For each of the seven patients who demonstrated evidence of NVU on task-based motor fMRI, we performed both an independent component analysis (ICA) and an atlas-based parcellation-based seed correlation analysis (SCA) of the resting state fMRI data. For each patient, ipsilesional (IL) and contralesional (CL) regions of interest (ROIs) comprising primary motor and somatosensory cortices were used to evaluate BOLD signal changes on Z score maps derived from both ICA and SCA analysis for evidence of NVU. A subsequent two-tailed t-test was performed to determine whether statistically significant differences between the two sides were present that were consistent with NVU. RESULTS: In seven patients, overall decreased BOLD signal (based on suprathreshold voxels in ICA and SCA-derived Z-score maps) was noted in IL compared with CL ROIs (P < 0.01), consistent with NVU. CONCLUSION: We have demonstrated that NVU can result in false negative BOLD signal changes on rsfMRI comparable to previously published findings on standard motor task-based fMRI.

Measurement of arteriolar blood volume in brain tumors using MRI without exogenous contrast agent administration at 7T.

PURPOSE: Arteriolar cerebral-blood-volume (CBVa) is an important perfusion parameter that can be measured using inflow-based vascular-space-occupancy (iVASO) MRI without exogenous contrast agent administration. The purpose of this study is to assess the potential diagnostic value of CBVa in brain tumor patients by comparing it with total-CBV (including arterial, capillary and venous vessels) measured by dynamic-susceptibility-contrast (DSC) MRI. MATERIALS AND METHODS: Twelve brain tumor patients were scanned using iVASO (on 7T as part of a research project) and DSC (on 3T as part of routine clinical protocols) MRI. Region-of-interest analysis was performed to compare the resulting perfusion measures between tumoral and contralateral regions, and to evaluate their associations with tumor grades. RESULTS: CBVa measured by iVASO MRI significantly correlated with WHO grade (ρ = 0.37, P = 0.04). Total-CBV measured by DSC MRI showed a trend of correlation with WHO grade (ρ = 0.28, P = 0.5). The signal-to-noise ratio was comparable (P > 0.1) between the two methods, while the contrast-to-noise ratio between tumoral and contralateral regions was higher in iVASO-CBVa than DSC-CBV in WHO II/III patients (P < 0.05) but comparable in WHO IV patients (P > 0.1). A trend of positive correlation between DSC-CBV and iVASO-CBVa was observed (R2 = 0.28, P = 0.07). CONCLUSION: In this initial patient study, CBVa demonstrated a stronger correlation with WHO grade than total-CBV. Further investigation with a larger cohort is warranted to validate whether CBVa can be a better classifier than total-CBV for the stratification of brain tumors, and whether iVASO MRI can be a useful alternative method for the assessment of tumor perfusion, especially when exogenous contrast agent administration is difficult in certain patient populations. J. Magn. Reson. Imaging 2016;44:1244-1255.

Whole-brain amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging in glioma patients using low-power steady-state pulsed chemical exchange saturation transfer (CEST) imaging at 7T.

PURPOSE: To explore the relationship of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signal intensities with respect to different World Health Organization (WHO) brain tumor grades (II to IV) at 7T. MATERIALS AND METHODS: APT-based and NOE-based signals at 7T using low-power steady-state chemical exchange saturation transfer (CEST) were compared among de novo primary gliomas of different WHO grades (II to IV). The quantitative APT and NOE signals, calculated by fitting approach using extrapolated semisolid MT reference (EMR) signals, were compared with the magnetization transfer ratio asymmetry (MTRasym ) analysis, commonly used in APT-weighted MRI. RESULTS: The observed NOE signals of all glioma grades were significantly lower than normal brain tissue (P < 0.01). NOE signals significantly differed between low-grade (II) gliomas and high-grade (III, IV) gliomas (P < 0.05). APT signals showed no difference between the tumor regions for any glioma grades (M = 3.08%, 2.64%, and 3.10%, 95% confidence interval [CI] = 2.81% ∼ 3.33%, 2.36% ∼ 2.91%, and 2.85% ∼ 3.36% for grade II, III, and IV, respectively), and between normal brain tissue and all glioma grades (P = 0.08, M = 4.29% and 2.94%, 95% CI = 3.57% ∼ 4.99% and 2.47% ∼ 3.41% for normal and average grade II, III, and IV), while MTRasym differed significantly between normal tissue and all glioma grades (P < 0.05). CONCLUSION: NOE contributes substantially to APT-weighted MRI at 7T at low RF saturation power and provides a promising biomarker for glioma grading.J. Magn. Reson. Imaging 2016;44:41-50.

Phosphorylation of the activation loop tyrosine 823 in c-Kit is crucial for cell survival and proliferation.

The receptor tyrosine kinase c-Kit, also known as the stem cell factor receptor, plays a key role in several developmental processes. Activating mutations in c-Kit lead to alteration of these cellular processes and have been implicated in many human cancers such as gastrointestinal stromal tumors, acute myeloid leukemia, testicular seminomas and mastocytosis. Regulation of the catalytic activity of several kinases is known to be governed by phosphorylation of tyrosine residues in the activation loop of the kinase domain. However, in the case of c-Kit phosphorylation of Tyr-823 has been demonstrated to be a late event that is not required for kinase activation. However, because phosphorylation of Tyr-823 is a ligand-activated event, we sought to investigate the functional consequences of Tyr-823 phosphorylation. By using a tyrosine-to-phenylalanine mutant of tyrosine 823, we investigated the impact of Tyr-823 on c-Kit signaling. We demonstrate here that Tyr-823 is crucial for cell survival and proliferation and that mutation of Tyr-823 to phenylalanine leads to decreased sustained phosphorylation and ubiquitination of c-Kit as compared with the wild-type receptor. Furthermore, the mutated receptor was, upon ligand-stimulation, quickly internalized and degraded. Phosphorylation of the E3 ubiquitin ligase Cbl was transient, followed by a substantial reduction in phosphorylation of downstream signaling molecules such as Akt, Erk, p38, Shc, and Gab2. Thus, we propose that activation loop tyrosine 823 is crucial for activation of both the MAPK and PI3K pathways and that its disruption leads to a destabilization of the c-Kit receptor and decreased survival of cells.

Clathrin-mediated hemoglobin endocytosis is essential for survival of Leishmania.

Leishmania is auxotroph for heme. Previously, we have shown that Leishmania acquire heme from the degradation of endocytosed hemoglobin via a specific receptor located in the flagellar pocket. Here, we report the cloning and expression of clathrin heavy chain from Leishmania (Ld-CHC) and provide evidences that Ld-CHC is localized in flagellar pocket and regulates Hb-endocytosis in Leishmania. Kinetic analysis of Hb trafficking in GFP-Ld-CHC overexpressed Leishmania reveals that Hb is internalized through Ld-CHC coated region and remains associated with Ld-CHC containing vesicles at early time points of internalization and subsequently starts dissociating from Hb-containing vesicles at later time points indicating that clathrin-coating and uncoating regulate Hb trafficking in Leishmania. Interestingly, overexpression of dominant negative mutant of clathrin heavy chain of Leishmania (GFP-Ld-CHC-Hub) blocks the Hb internalization and causes severe growth defect in parasite. Moreover, we have shown that chlorpromazine, a pharmacological agent, blocks Hb internalization in Leishmania by depolymerizing Ld-CHC and thereby inhibits the growth of the parasites. Taken together, our results have shown that Hb endocytosis in Leishmania is a clathrin dependent process and is essential for the survival of the parasites.

Longitudinal strain from velocity encoded cardiovascular magnetic resonance: a validation study.

BACKGROUND: Regional myocardial function is typically evaluated by visual assessment by experienced users, or by methods requiring substantial post processing time. Visual assessment is subjective and not quantitative. Therefore, the purpose of this study is to develop and validate a simple method to derive quantitative measures of regional wall function from velocity encoded cardiovascular magnetic resonance (CMR), and provide associated normal values for longitudinal strain. METHOD: Both fast field echo (FFE) and turbo field echo (TFE) velocity encoded CMR images were acquired in three long axis planes in 36 healthy volunteers (13 women, 23 men), age 35±12 years. Strain was also quantified in 10 patients within one week after myocardial infarction. The user manually delineated myocardium in one time frame and strain was calculated as the myocardium was tracked throughout the cardiac cycle using an optimization formulation and mechanical a priori assumptions. A phantom experiment was performed to validate the method with optical tracking of deformation as an independent gold standard. RESULTS: There was an excellent agreement between longitudinal strain measured by optical tracking and longitudinal strain measured with TFE velocity encoding. Difference between the two methods was 0.0025 ± 0.085 (ns). Mean global longitudinal strain in the 36 healthy volunteers was -0.18 ± 0.10 (TFE imaging). Intra-observer variability for all segments was 0.00 ± 0.06. Inter-observer variability was -0.02 ± 0.07 (TFE imaging). The intra-observer variability for radial strain was high limiting the applicability of radial strain. Mean longitudinal strain in patients was significantly lower (-0.15± 0.12) compared to healthy volunteers (p<0.05). Strain (expressed as percentage of normal strain) in infarcted regions was lower compared to remote areas (p<0.01). CONCLUSION: In conclusion, we have developed and validated a robust and clinically applicable technique that can quantify longitudinal strain and regional myocardial wall function and present the associated normal values for longitudinal strain.

Extracorporeal irradiation in malignant bone tumors: Single institution experience and review of literature.

In the last couple of decades, the management of malignant bone tumor (MBT) has seen a sea change. With the advent in surgical technics, radiation therapy, and chemotherapy, it has moved from disabling amputation to limb salvage surgery. Extracorporeal irradiation (ECI) and re-implantation of resected bone is a useful method of limb salvage of MBTs. In our study, we analyzed and presented the results of 8 cases of MBTs treated with this modality. Between 2014 and 2017, 8 patients with primary MBT were enrolled for ECI technique who are meeting the eligibility criteria. Before taking the patient for ECI treatment, a multispecialty tumor board discussion was done for each patient. All of them received neo-adjuvant and adjuvant chemotherapy except the patients with histology of giant cell tumor. Following neoadjuvant chemotherapy bone excision surgery was performed, and the resected bone was taken for ECI with the dose of 50 Gray in a single fraction. After ECI, bone segment was re-implanted at osteotomy site in the same setting. After completion of adjuvant chemotherapy, the patients were then followed up for any sequelae, local and systemic control, ambulation, and functional outcome. Out of 8 patients, there were 5 males and 3 females with mean age of 22 (range 13-36). The involved bone was the tibia in 6 patients, ischium in 1 patient, and femur in 1 patient. Histopathologically, the malignancies included 3 osteosarcoma, 3 Giant cell tumor, 1 Ewing's sarcoma and 1 chondrosarcoma. At median follow-up of 12 months (range 6-26 months), local control rate was 87.5% and systemic control rate was 75%. Perioperative ECI and re-implantation is a useful, convenient, and inexpensive technique. The overall treatment time is reduced. The patient's own bone fits perfectly to the resection site with reduced risk of graft site infection. The risk of local recurrence due to tumor re-implantation is negligible with tumoricidal radiation doses of ECI, and it is usually associated with manageable sequelae. Recurrence rates are acceptable and salvageable with surgery.

Epidemiological characteristics of endometrial cancer patients treated at a tertiary health center in National Capital Territory of India.

Settings and Design: A retrospective study which analyzed the data of female patients attending a tertiary care center in National Capital Territory for the treatment of endometrial cancer. Materials and Methods: Eighty-six histopathologically confirmed cases of carcinoma endometrium were taken from January 2016 to December 2019. Detailed information was collected regarding patient's case history, sociodemographic data (age of presentation, occupation, religion, residence, and substance addiction), clinical presentation, diagnostic and therapeutic procedures, and known risk factors (age at menarche and menopause, parity, obesity, use of oral contraceptive pills, hormone replacement therapy, and comorbidities such as hypertension and diabetes). Statistical Analysis Used: After analysis, results were presented as mean ± standard deviation and frequency. Results: Eighty-six percent of the patients (n = 73) were in the age group of 40-70 years; the mean age of the patients at diagnosis of endometrial cancer was 54 years. Eighty-one percent (n = 70) of the patients were from urban areas. Sixty-seven percent of the females (n = 54) were Hindu. All the patients were housewives with nonsedentary lifestyles. Most patients (88%; n = 76) presented with bleeding per vaginum. Fifty-nine percent (n = 51) had stage I disease, followed by 15% (n = 13) with stage II, 14% (n = 12) with stage III, and 12% (n = 10) with stage IV disease. Eighty-two percent (n = 72) of the patients had endometrioid carcinoma. Other less common variants were mixed Mullerian malignant tumor, squamous, adenosquamous, serous, and endometrioid stromal. Forty-four percent (n = 38), 39% (n = 34), and 16% (n = 14) of the patients had grade I, grade II, and grade III tumor, respectively. 53.5% of the cases (n = 46) had >50% myometrial invasion at the time of presentation. Eighty-two percent (n = 71) of the patients were postmenopausal. The mean age at menarche and menopause was 13 years and 47 years, respectively. Fifteen percent (n = 13) of the females were nulliparous. Forty-six percent (n = 40) of the patients were overweight. Most patients (82%) had no history of addiction. Twenty-five percent (n = 22) of the patients had hypertension, and 27% (n = 23) has diabetes as comorbidity. Conclusions: The incidence of endometrium cancer is showing a steady rise in the recent past. Early age of menarche, late age of menopause, nulliparity, obesity, and diabetes mellitus are well-documented risk factors for uterine cancer. Better outcome and control of disease is possible by understanding of endometrial cancer etiology, risk factors, and its preventive measures. Thus, a robust screening program is warranted to detect the disease in early stage and for increased survival.

A Rare Case of Mosaic 3pter and 5pter Deletion-Duplication with Autism Spectrum Disorder and Dyskinesia.

Introduction: There is evidence that neurodevelopmental disorders are associated with chromosomal abnormalities. Current genetic testing can clinch an exact diagnosis in 20-25% of such cases. Case Description. A 3 years and 11 months old boy with global developmental delay had repetitive behaviors and hyperkinetic movements. He was stunted and underweight. He had ataxia, limb dyskinesia, triangular face, microcephaly, upward slanting palpebral fissure, hypertelorism, retrognathia, posteriorly rotated ears, long philtrum, thin lips, broad nasal tip, polydactyly, tappering fingers, and decreased tone in the upper and lower limbs with normal deep tendon reflexes. Magnetic resonance imaging of the brain, ultrasound of the abdomen, and ophthalmological evaluation were normal. Brain evoked response auditory revealed bilateral moderate hearing loss. He fulfilled the Diagnostic Statistical Manual 5 criteria for autism. In the Vineland Social Maturity Scale, his score indicated a severe delay in social functioning. His genetic evaluation included karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA). The karyotype report from high-resolution lymphocyte cultures was mos 46, XY, der(3)t(3; 5)(p26; p15.3)[50]/46, XY,der(5) t(3;5) (p26;p15.3)[50].ish. His karyotype report showed a very rare and abnormal mosaic pattern with two cell lines (50% each). Cell-line#1: 3pter deletion with 5pter duplication (3pter-/5pter+) and cell-line#2: 3pter duplication with 5pter deletion (3pter+/5pter-) derived from a de novo reciprocal translocation t(3; 5)(p26; p15.3) which was confirmed by FISH. The chromosomal microarray analysis report was normal. The two cell lines (50% each) seem to have balanced out at the whole genome level. Occupational, sensory integration, and behavior modification therapy were initiated for his autistic features, and anticholinergic trihexiphenidyl was prescribed for hyperkinetic movements. Conclusion: This case highlights a rare genetic finding and the need for timely genetic testing in a child with dysmorphism and autism with movement disorder to enable appropriate management and genetic counselling.

Detection and Mitigation of Neurovascular Uncoupling in Brain Gliomas.

Functional magnetic resonance imaging (fMRI) with blood oxygen level-dependent (BOLD) technique is useful for preoperative mapping of brain functional networks in tumor patients, providing reliable in vivo detection of eloquent cortex to help reduce the risk of postsurgical morbidity. BOLD task-based fMRI (tb-fMRI) is the most often used noninvasive method that can reliably map cortical networks, including those associated with sensorimotor, language, and visual functions. BOLD resting-state fMRI (rs-fMRI) is emerging as a promising ancillary tool for visualization of diverse functional networks. Although fMRI is a powerful tool that can be used as an adjunct for brain tumor surgery planning, it has some constraints that should be taken into consideration for proper clinical interpretation. BOLD fMRI interpretation may be limited by neurovascular uncoupling (NVU) induced by brain tumors. Cerebrovascular reactivity (CVR) mapping obtained using breath-hold methods is an effective method for evaluating NVU potential.

Can we accurately diagnose endometriosis without a diagnostic laparoscopy?

Endometriosis is a progressive, estrogen-dependent, chronic inflammatory disease that affects approximately 6-10% of reproductive age women. Patients usually presents with symptoms, such as non-menstrual pelvic and abdominal pain, ovulatory pain, dyspareunia, dysmenorrhea, dyschezia, and/or changes to bowel or bladder function, which can be exacerbated during ovulation or menses. Endometriosis is a leading cause of unexplained infertility, accounting for up to 50-80% of cases. Currently, altered endometrial receptivity and progesterone resistance are some of the leading theories that could explain endometriosis-related implantation failure. In the endometrium, the B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL-6) protein forms a complex that binds to and inactivates regulators of the progesterone pathway, leading to progesterone resistance, aberrant decidualization, implantation failure, and recurrent miscarriages in women diagnosed with endometriosis. Surgical diagnosis consisting of laparoscopy, with or without histologic confirmation, is still considered the gold standard for diagnosis of endometriosis. Development of noninvasive screening and diagnostic tests to accurately identify patients with endometriosis has become increasing popular. A screening test for endometriosis has been developed to detect endometrial BCL-6 overexpression in asymptomatic women with unexplained infertility or recurrent pregnancy loss. Positive endometrial BCL-6 testing has been associated with recurrent miscarriages and poor in vitro fertilization outcomes. When the underlying cause of endometrial inflammation secondary to endometriosis was treated, an improvement in subsequent live birth rates was seen. Endometrial BCL-6 testing has a high positive predictive value that could help physicians and patients undergoing infertility treatment to seek surgical evaluation for endometriosis, to improve their reproductive outcomes.