Cortical Sparing Research Articles

Dissociable spatial topography of neurodegeneration in Early‐onset and Late‐onset Alzheimer’s Disease: A head‐to‐head comparison of MRI‐derived atrophy measures between the LEADS and ADNI cohorts

AbstractBackgroundUnderstanding how early‐onset Alzheimer’s disease (EOAD) differs from typical late‐onset AD (LOAD) is an important goal of AD research that may help increase the sensitivity of unique biomarkers for each phenotype. Building upon prior work based on small samples, here we leveraged two large, well‐characterized natural history study cohorts of AD patients (LEADS and ADNI3) to test the hypothesis that EOAD patients would show more prominent lateral and medial parietal and lateral temporal cortical atrophy sparing the medial temporal lobe (MTL), whereas LOAD patients would show prominent MTL atrophy.MethodWe investigated differences in the spatial topography of cortical atrophy between EOAD and LOAD patients by analyzing structural MRI data collected from 211 patients with sporadic EOAD and 88 cognitively unimpaired (CU) participants from the LEADS cohort as well as 144 patients with LOAD and 365 CU participants from the ADNI3 cohort. MRI data were processed via FreeSurfer v6.0 to estimate cortical thickness for each participant. A direct comparison of cortical thickness was performed between EOAD and LOAD patients based on W‐scores (i.e., Z‐scores adjusted for age and sex relative to CU participants within each cohort) while controlling for MMSE total scores. All patients underwent amyloid PET with 18F‐Florbetaben or 18F‐Florbetapir and amyloid positivity was centrally determined by quantification‐supported visual read.ResultAs expected, a direct comparison of cortical thickness between patients with EOAD and LOAD revealed a double dissociation between AD clinical phenotype and localization of cortical atrophy: EOAD patients showed greater atrophy in widespread cortical areas including the inferior parietal lobule (EOAD marginal mean W‐score ± SEM = ‐1.33±0.08 vs. LOAD = ‐0.52±0.09, p<.001, η2=.097), precuneus (‐1.66±0.09 vs. ‐0.59±0.10, p<.001, η2=.13), and caudal middle frontal gyrus (‐1.65±0.08 vs. ‐0.90±0.10, p<.001, η2=.074), whereas LOAD patients showed greater atrophy in the entorhinal/perirhinal cortex and temporal pole (‐1.00±0.09 vs. ‐1.41±0.11, p<.008, η2=.019).ConclusionThese findings demonstrate a clearly dissociable spatial pattern of neurodegeneration between EOAD and LOAD, supporting our previously developed LOAD and EOAD signatures of cortical atrophy, which underlies the distinct episodic memory and other cognitive characteristics of these AD clinical phenotypes.

Impact of indocyanine green on decision making for performing laparoscopic cortical sparing adrenalectomy.

Indocyanine green imaging (ICG) is an expansion technology that can contribute to the development of demanding techniques such as cortical-sparing adrenalectomy (CSA). The aim of this study was to determine in which cases CSA should be performed and when total adrenalectomy should be performed instead based on ICG fluorescence. Here, we present our experience through a series of cases and videos. Prospective and descriptive study on patients with surgical adrenal lesions who were proposed for CSA using ICG with near-infrared fluorescence imaging in our center. A first bolus of 6,25mg ICG was administered intravenously upon exposure of the retroperitoneal plane. Fluorescence was visualized using a Storz® NIR/ICG endoscopic system. Seven patients were proposed for CSA. After the application of ICG, a change in attitude was carried out in 71.4% of the cases (five of seven). In the two patients in whom CSA could be performed, the adrenal remnants were functional, and the resection margins of the surgical specimens were free of disease. The reasons why partial adrenalectomy could not be completed, and a total adrenalectomy was decided instead were the presence of a tumor located very close to the adrenal vein that prevented a correct remnant volume (n = 4) and one case of isofluorescent tumor with the adrenal parenchyma. ICG fluorescence guidance could help in the decision making to select patients intraoperatively for successful cortical preservation.

Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns.

We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p=1.15×10-10 ). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. MRI findings differ across cognitively defined AD subgroups.

Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) is caused by an impact or penetrating injury to the head resulting in abnormal brain function. Mitochondrial dysfunction is an important hallmark of TBI and has been thoroughly studied in male rodent models of brain injury, but relatively little is known about these outcomes in females. These studies were designed to examine sex as a biological variable for mitochondria-related outcomes after the severe controlled cortical impact (CCI) mouse model of TBI. Synaptic and non-synaptic mitochondria were isolated from the sham- or CCI-injured cortex as well as the hippocampus ipsilateral to the craniotomy 3, 12, 24, or 48 h post-surgery, and then bioenergetics were measured. Subtle variations were observed in the timeline of mitochondrial dysfunction between sexes. Non-synaptic cortical mitochondria from injured females showed early impairment at 12 h post-CCI compared to mitochondria from injured males at 24 h post-CCI. Contrastingly, in the synaptic fraction, mitochondria from injured males showed early impairment at 12 h post-CCI, whereas mitochondria from injured females showed impairment at 24 h post-CCI. Based on bioenergetic impairments at 24 h post-CCI, synaptic and non-synaptic mitochondrial calcium loading was also measured at this time point. Consistent with bioenergetic data at 24 h, non-synaptic mitochondria from injured males had increased calcium loading compared to uninjured control, but this effect was not observed in females. Finally, histological assessment of cortical tissue sparing in each sex was measured at 7 days post-injury. There was a lack of sex-based differences in cortical tissue sparing after severe CCI. Overall, there were some subtle sex differences in mitochondrial outcomes after CCI, but these findings were not statistically significant. This study highlights the importance of utilizing both sexes when measuring mitochondrial function after severe CCI.

Pioglitazone restores mitochondrial function but does not spare cortical tissue following mild brain contusion.

Pioglitazone interacts through the mitochondrial protein mitoNEET to improve brain bioenergetics following traumatic brain injury. To provide broader evidence regarding the therapeutic effects of pioglitazone after traumatic brain injury, the current study is focused on immediate and delayed therapy in a model of mild brain contusion. To assess pioglitazone therapy on mitochondrial bioenergetics in cortex and hippocampus, we use a technique to isolate subpopulations of total, glia-enriched and synaptic mitochondria. Pioglitazone treatment was initially administered at either 0.25, 3, 12 or 24 h following mild controlled cortical impact. At 48 h post-injury, ipsilateral cortex and hippocampus were dissected and mitochondrial fractions were isolated. Maximal mitochondrial respiration injury-induced deficits were observed in total and synaptic fractions, and 0.25 h pioglitazone treatment following mild controlled cortical impact was able to restore respiration to sham levels. While there are no injury-induced deficits in hippocampal fractions, we do find that 3 h pioglitazone treatment after mild controlled cortical impact can significantly increase maximal mitochondrial bioenergetics compared to vehicle-treated mild controlled cortical impact group. However, delayed pioglitazone treatment initiated at either 3 or 24 h after mild brain contusion does not improve spared cortical tissue. We demonstrate that synaptic mitochondrial deficits following mild focal brain contusion can be restored with early initiation of pioglitazone treatment. Further investigation is needed to determine functional improvements with pioglitazone beyond that of overt cortical tissue sparing following mild contusion traumatic brain injury.

Epilepsy with anterior temporal encephaloceles: Baseline characteristics, post-surgical outcomes, and comparison to mesial temporal sclerosis

ObjectiveTo review clinical and neuropsychological characteristics and natural history of a series of patients with temporal lobe epilepsy (TLE) and anterior temporal encephaloceles (ATE) and compare them to a similar series of TLE patients with mesial temporal sclerosis (MTS) to identify characteristics suggestive of ATE-related epilepsy. MethodsPatients with epilepsy and ATE were identified via clinic encounters and consensus epilepsy surgery conference at a Level 4 epilepsy center. The drug-resistant subset of these patients who underwent epilepsy surgery (twenty-two of thirty-five) were compared to age- and laterality-matched patients with MTS. Clinical, neuropsychological, electrophysiologic, and surgical data were abstracted through chart review. ResultsIn comparison with MTS, ATE patients were more often female, had significantly later onset of epilepsy, and did not have prior febrile seizures. In addition, ATE patients were more likely to have chronic headaches and other historical features consistent with idiopathic intracranial hypertension (IIH). Failure to identify ATE on initial imaging was common. Most patients had limited temporal cortical resections sparing mesial structures. Of the twenty ATE patients who had a long-term postsurgical follow-up, seventeen (85%) had International League Against Epilepsy (ILAE) Class 1 or 2 outcomes. SignificanceA shorter duration of epilepsy, female gender, and lack of history of febrile seizures may suggest ATE as an etiology of refractory TLE in adults. Targeted encephalocele resections can result in seizure freedom, underscoring the importance of encephalocele identification.

Neurocognitive considerations in the treatment of meningioma with radiation therapy: applications for quantitative neuroimaging and precision radiation medicine.

This article focuses on the role of radiotherapy in the management of meningioma, in the definitive and adjuvant setting and across the spectrum of meningioma grade. Treatment paradigms, informed by clinical evidence, are discussed. Notably, we focus on the impact of radiotherapy on normal brain tissues and neurocognitive function, particularly the dose-dependent changes in white matter and cerebral cortex thickness. Novel imaging techniques have allowed the identification of microstructural changes to eloquent white matter, cortex, and subcortical regions as biomarkers for understanding RT-induced changes in cognitive functioning. Deficits in multiple domains including attention, memory, language and executive function can become more pronounced following radiation. Longitudinal assessment with imaging and neurocognitive testing pre- and post-radiation have allowed correlation between dose to specific regions of the brain and decline in associated domains of neurocognitive function. These findings suggest incorporation of areas at higher risk for neurocognitive sequelae into precision radiation planning. Volumetric arc therapy, advanced planning with cortical sparing, proton therapy and stereotactic radiosurgery are reviewed as options for delivering therapeutic dose to target volumes while minimizing risk to adjacent sensitive regions. The treatment of meningioma is an evolving area, with improving outcomes for higher grade disease in modern trials, where care must be taken to maximize both disease control as well as quality of life for patients.

Clinical and magnetic resonance imaging features, and pathological findings of spinal lymphoma in 27 cats.

This multicentric retrospective study describes the clinical and MRI features and pathological studies of spinal lymphoma in 27 cats. MRI characteristics and their possible correlations with histopathological findings were studied. The most frequent neurological signs were rapidly progressive paraparesis (62.9%) or paraplegia (22.2%). Bimodal age distribution was found with 40.7% of cats aged ≤2.5 years (63.6% of them FeLV positive), and 44.4% of cats aged ≥8 years (16.7% of them FeLV positive). Spinal lymphoma was generally presented on MRI as an ill-defined epidural focal lesion with moderate to severe spinal cord compression, expanding more than one vertebral body. MRI lesions were typically localized in the lumbar vertebral segment (p = 0.01), circumferential to the spinal cord (p = 0.04), hyperintense on T2-weighted sequences (p = 4.3e-06), and isointense on T1-weighted sequences (p = 8.9e-07). The degree and pattern of contrast enhancement were variable. Other morphological patterns included paravertebral masses with extension into the vertebral canal and lesions centered in the spinal nerve roots. Involvement of vertebrae and adjacent spinal soft tissues was present in 74% of cases when present vertebral involvement was characterized by cortical sparing. When follow-up MRI studies (n = 4) were performed after treatment new lesions of similar nature but different localizations and extension were observed. Confirmation of spinal lymphoma was performed by CSF analysis in 4/27 (14.8%) of cases, by FNA in 6/27 (22.2%) of cases, by surgical biopsy in 10/27 (37%) of cases, by FNA and surgical biopsy in 1/27 (3.7%) of cases, by CSF, FNA, surgical biopsy and postmorten examination in 1/27 (3.7%) of cases, and postmorten studies in 5/27 (18.5%) of cases. Antemortem diagnosis was achieved in 22/27 (81.5%) cats. The presence of necrosis in histopathological studies as an unfavorable prognostic indicator of survival was significantly more probable when lesions were not hyperintense on T2-weighted sequences (p = 0.017). Spinal lymphoma in cats is a complex entity with heterogeneous imaging and histopathological appearance. However, certain MRI features may support a tentative diagnosis, which in a group of cases can be confirmed when combined with the CSF findings. For the rest of the cases, tissue sampling assisted by imaging findings remains necessary for definitive diagnosis.

PARTIAL ADRENALECTOMY - HOW FAR CAN WE GO?

Organ preservation and functional resections are the mainstays of most surgical sub-specialties at the present time. This is even more evident in endocrine surgery, where the product of secretion of these petit organs is of paramount importance. Partial adrenalectomy and cortical sparing techniques have evolved to actually compete with total adrenalectomy, the historical gold standard treatment. Much refined imaging techniques can readily identify smaller adrenal lesions that can be addressed surgically or percutaneously given the indication. The trend towards partial adrenalectomy is straightforward in bilateral disease where steroid replacement can be avoided while for unilateral disease, normal hormonal levels can be obtained. The reviewed publications offer deep insight into the advancement of partial or cortical sparing adrenal procedures from pioneering work to large cohort studies.

Initial experience with laparoscopic posterior retroperitoneal adrenalectomy in single tertiary center.

Laparoscopic posterior retroperitoneal adrenalectomy (LPRA) is a surgical method that accesses the adrenal gland through the back. The aim of this study was to report initial experience of LPRA and evaluate possibilities for surgical application. From March 2018 to December 2019, a total of 30 consecutive patients diagnosed with adrenal tumor underwent surgical treatment at Pusan National University Hospital were enrolled. Clinicopathologic features and various peri- and postoperative parameters were analyzed by retrospective medical record review. The mean age of the patients was 48.20±13.66 years. The mean body mass index (BMI) was 25.50±4.30 kg/m2. Primary hyperaldosteronism was the most frequently preoperative diagnosed disease (n=13, 43.4%), followed by adrenal incidentaloma (n=8, 26.6%), Cushing syndrome (n=5, 16.6%) and pheochromocytoma (n=4, 13.3%). The mean size of postoperative adrenal tumor was 2.72±1.76 cm. The mean operating time was 162±58.14 minutes. Among the 30 patients, 28 patients underwent total adrenalectomy (93.3%) and two patients underwent cortical sparing adrenalectomy (6.7%). When LPRA was performed for patients with BMI >23.16 kg/m2, the operating time was longer than the average (P=0.016). LPRA was suitable and safe for patients with benign adrenal tumors. BMI, retroperitoneal fat density and postoperative adrenal weight may be related to the operating time, so they should be considered when deciding on a surgical method for adrenalectomy.

Outcomes of nephron sparing surgery and cortical sparing adrenalectomy in the management of Von Hippel\u2013Lindau syndrome

BackgroundThe management of Von Hippel–Lindau syndrome (VHLS) is multidisciplinary. The urologist is involved in treating the renal, epididymal tumors and often adrenal pheochromocytoma. Preservation of renal and adrenal function is a challenge. We present 17 cases of VHLS in a tertiary care center in South India.MethodsA retrospective review of the patients who underwent surgical treatment under urology for VHLS from January 2009 to November 2018 was conducted. The demographic data, the spectrum of manifestation, treatment, change in glomerular filtration rate, adrenal insufficiency, and recurrence-free survival were analyzed.ResultsThere were 17 patients diagnosed with VHLS. The median age of diagnosis was 39 years (range 23–41). The spectrum of clinical manifestation was: multifocal RCC (88%), pancreatic cysts/tumors (70%), cerebellar hemangioblastoma (59%), retinal angiomas (47%), epididymal cysts/tumors (47%), pheochromocytomas (41%), and spinal hemangiomas (30%). There were seven patients with ten pheochromocytoma lesions. Three underwent cortical sparing and seven total adrenalectomies; 13 patients underwent nephron sparing surgery (NSS), of which seven patients had bilateral tumors. The median duration of follow-up was 6.5 years (range 2–12 years). Following NSS, seven patients had a local recurrence, and one developed pancreatic metastasis. Two patients (11%) were lost to follow-up. Renal function was preserved in all patients at the last follow-up, and there was no postoperative adrenal crisis or mortality.ConclusionNephron sparing surgery and cortical sparing adrenalectomy are the treatment of choice for multifocal RCC and pheochromocytomas in patients with VHLS providing good oncological outcomes and preservation of renal and adrenal function.

Osteolytic Bone Lesions in Patients with Primary Myelofibrosis: A Systematic Review

▪Background:Philadelphia negative Myeloproliferative neoplasms classically characterized by excess production of terminal myeloid cells in the peripheral blood. Among this group, primary myelofibrosis is the least common and usually carries the worst prognosis. Bone involvement in primary myelofibrosis has many forms and tend to manifest as osteosclerotic lesions in vast majority of cases, however osteolytic lesions are reported in exceptional occasions. In this review, we tried to shed the light on this rare association.Methods:We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the English literature (Google scholar, PubMed, and SCOPUS) for studies, reviews, case series, and case reports about patient with myelofibrosis who develop lytic bone lesion. We used the terms in combination: “Myelofibrosis'” or “Primary myelofibrosis” OR “chronic idiopathic myelofibrosis” OR “agnogenic myeloid metaplasia” and “Osteolytic bone lesion”, “Osteolytic lesion”, “lytic bone lesion”. The review included patients with primary myelofibrosis confirmed by biopsy. The reference lists of the included studies were scanned for any additional articles. The search included all articles published up to 10th April 2021. Two independent reviewers screened the titles and abstracts of the records independently and papers unrelated to our inclusion criteria were excluded. A total of 13 articles were included in the review.Results :Total of 13 patients were included in the review. 7 patients were males, male to female ratio almost of 1:1. The mean age at time of diagnosis was 57.69 year, only two cases were diagnosed at young age, however the majority have osteolytic bone lesion at age above 50 years (12/13) of cases.The mean time between the diagnosis of primary myelofibrosis until the osteolytic bone lesion capturing was approximately 8.8 years. 9 out of 13 patients have painful bone lesion, others were incidental finding during a scan for other reasons. All patients have significant splenomegaly. All patients had the lytic lesion detected on x ray, and 2 patients had confirmed findings on magnetic resonance imaging (MRI). The most common affected bones were the vertebrae, pelvis, ribs, humerus then the scapula, femur and skull and less frequently wrist bones and calcaneus. Only one case has reported involvement of the tibia and fibula. The shape, the extension and the numbers of lesion were variable, some showed cortical sparing and others come with cortical destruction. 10 out of 13 cases have confirmed the nature of the osteolytic lesion containing hematopoietic stem cells with or without fibrosis, 2 cases were positive for JAK2 mutation. 2 patients have received ruxolitinib, one of them preceded with bone marrow transplant, others received nonspecific therapies.Discussion:The hyperdynamic ineffective bone marrow can have a negative impact on the bone structure resulting in different types of bone pathology including lytic and sclerotic lesions.The exact mechanism beyond developing lytic lesions is not fully studied, observations revealed two possible causes: systemic inflammation and direct mechanical compression from para-osseus lymph nodes.Lesions prevalence was equal in both genders which can be attributable to a small sample size, in addition, most of the patients were in advanced stages when the lytic lesions discovered and this observation can be explained by the needed time to generate extramedullary hematopoiesis and its subsequent effect on bone structure.The variation in time between the diagnosis of PMF and development of osteolytic bone lesions could be due to the indolent phase of the disease, in which patients can survive for decades without symptoms.Until recently the treatment of myelofibrosis was supportive, but after establishing the JAK2-stat pathway role in myeloproliferative disorders the FDA approved ruxolitinib a JAK2 inhibitor which shows not only survival benefit but also has a significant impact on the resolution of the lytic bone lesions as well.conclusionOsteolytic bone lesions in patients with primary myelofibrosis is extremely rare finding, and noticed shortly after diagnosis in elderly and after longer duration in young patients. The lytic lesion seems to have a bad prognostic value as we can notice 11 out of 13 patients died within one year of detection. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Acute Brain Activation Patterns of High- Versus Low-Frequency Stimulation of the Anterior Nucleus of the Thalamus During Deep Brain Stimulation for Epilepsy.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an increasingly utilized treatment of drug-resistant epilepsy. To date, the effect of high-frequency stimulation (HFS) vs low-frequency stimulation (LFS) in ANT DBS is poorly understood. To assess differences in the acute effect of LFS vs HFS in ANT DBS utilizing blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI). In this prospective study of 5 patients with ANT DBS for epilepsy, BOLD activation and deactivation were modeled for 145-Hz and 30-Hz ANT stimulation using an fMRI block design. Data were analyzed with a general linear model and combined via 2-stage mixed-effects analysis. Z-score difference maps were nonparametrically thresholded using cluster threshold of z >3.1 and a (corrected) cluster significance threshold of P=.05. HFS produced significantly greater activation within multiple regions, in particular the limbic and default mode network (DMN). LFS produced minimal activation and failed to produce significant activation within these same networks. HFS produced widespread cortical and subcortical deactivation sparing most of the limbic and DMN regions. Meanwhile, LFS produced deactivation in most DMN and limbic structures. Our results show that HFS and LFS produce substantial variability in both local and downstream network effects. In particular, largely opposing effects were identified within the limbic network and DMN. These findings may serve as a mechanistic basis for understanding the potential of HFS vs LFS in various epilepsy syndromes.

Bilateral Posterior Retroperitoneoscopic Adrenalectomy with Cortical Sparing on Right Side

Cortical sparing adrenalectomy allows for resection of adrenal tumor(s) while preserving unaffected adrenal tissue to prevent adrenal insufficiency. This is especially important in patients affected with bilateral adrenal tumors, typically pheochromocytomas. Posterior retroperitoneoscopic adrenalectomy (PRA) allows for a minimally invasive approach to adrenal gland resection compared to the more traditional laparoscopic transabdominal adrenalectomy and open approaches. The PRA technique is increasingly used by high-volume endocrine surgeons throughout the world. This approach is ideal to address patients with bilateral disease and was utilized in this case of a patient presenting with bilateral pheochromocytomas in the setting of multiple endocrine neoplasia 2A syndrome.

Genetic Approach to Elucidate the Role of Cyclophilin D in Traumatic Brain Injury Pathology.

Cyclophilin D (CypD) has been shown to play a critical role in mitochondrial permeability transition pore (mPTP) opening and the subsequent cell death cascade. Studies consistently demonstrate that mitochondrial dysfunction, including mitochondrial calcium overload and mPTP opening, is essential to the pathobiology of cell death after a traumatic brain injury (TBI). CypD inhibitors, such as cyclosporin A (CsA) or NIM811, administered following TBI, are neuroprotective and quell neurological deficits. However, some pharmacological inhibitors of CypD have multiple biological targets and, as such, do not directly implicate a role for CypD in arbitrating cell death after TBI. Here, we reviewed the current understanding of the role CypD plays in TBI pathobiology. Further, we directly assessed the role of CypD in mediating cell death following TBI by utilizing mice lacking the CypD encoding gene Ppif. Following controlled cortical impact (CCI), the genetic knockout of CypD protected acute mitochondrial bioenergetics at 6 h post-injury and reduced subacute cortical tissue and hippocampal cell loss at 18 d post-injury. The administration of CsA following experimental TBI in Ppif-/- mice improved cortical tissue sparing, highlighting the multiple cellular targets of CsA in the mitigation of TBI pathology. The loss of CypD appeared to desensitize the mitochondrial response to calcium burden induced by TBI; this maintenance of mitochondrial function underlies the observed neuroprotective effect of the CypD knockout. These studies highlight the importance of maintaining mitochondrial homeostasis after injury and validate CypD as a therapeutic target for TBI. Further, these results solidify the beneficial effects of CsA treatment following TBI.

Magnetic Resonance Imaging Features of Extradural Spinal Neoplasia in 60 Dogs and Seven Cats.

This retrospective study describes the MRI features of extradural spinal neoplasia in 60 dogs and seven cats to identify potential distinguishing features between tumor classes and individual tumor types within each class. In dogs, mesenchymal tumors were most common (48%), with undifferentiated sarcomas being the predominant tumor type. Round cell neoplasms were second most common (35%), with lymphoma and multiple myeloma/plasma cell tumor comprising the majority of cases. Only two benign tumors were identified. In cats, lymphoma was most common (5/7), with one case of mesenchymal neoplasia and one case of metastatic carcinoma. Despite some overlap, certain imaging features were able to help prioritize differential diagnoses. The combined features that predicted round cell neoplasia (84%) included the preservation of vertebral shape, homogeneous contrast enhancement, and lesion centering on bone. The combined features that predicted mesenchymal neoplasia (73%) included altered vertebral shape, heterogeneous contrast enhancement, and lesion centering on paraspinal soft tissues. Round cell neoplasms were more likely to have cortical sparing, preservation of overall shape, lesion centering on bone, small soft tissue tumor size, and homogeneous contrast enhancement. Both epithelial and mesenchymal neoplasms were more likely to have cortical lysis, a cavitary component to the soft tissue mass and medium to large soft tissue mass size. The findings of this study can aid in prioritizing differential diagnoses in cases of extradural spinal neoplasia in cats and dogs, which can impact case management, but tissue sampling remains the gold standard for definitive diagnosis.

Laparoscopic cortical-sparing adrenal surgery in pheochromocytomas associated with hereditary neoplasia syndromes.

Pheochromocytomas in hereditary syndromes tend to grow multifocal with adrenal involvement on both sides. Surgical treatment with bilateral adrenalectomy inevitably leads to life-long hormonal dependence, which significantly affects quality of life. The development of minimally invasive adrenal surgery has created a chance to preserve adrenal cortex function in these patients. The aim of the present study was to evaluate the safety of laparoscopic cortical-sparing adrenal surgeries and their efficacy in the prevention of postoperative adrenal insufficiency in patients with hereditary pheochromocytomas. We retrospectively analysed the medical histories of 10 patients, who underwent 10 laparoscopic cortical sparing adrenal surgeries from January 2015 to January 2019 in our centre. The decision to perform sparing surgery was based on preoperative diagnosis of hereditary syndrome in line with the result of DNA analysis or its diagnosis based on the clinical appearance. All surgeries were performed laparoscopically from transperitoneal access in the lateral decubitus position, with preserving 1/3-1/4 adrenal tissue. The sufficiency of remnant adrenal tissue was assessed in all patients. The median time of follow-up was three years (ranged 0.5-4 years). No intraoperative complications were observed. One case of acute heart failure was the only early postoperative adverse event. There were no late postoperative complications and no local recurrences observed. In one out of three patients undergoing sparing surgery as a second procedure after former total adrenalectomy, adrenal cortex failure occurred. In all patients after unilateral surgery or after bilateral surgery performed simultaneously (total adrenalectomy at one side and sparing surgery contralaterally), function of remnant adrenal tissue was preserved. In hereditary pheochromocytomas, with minimal risk of malignant process, laparoscopic cortical sparing adrenal surgeries are the safe approach and provide the chance to preserve adrenal cortex function.

SAT-229 Bilateral Pheochromocytoma as Incidental Finding in a Patient with Neurofibromatosis Type 1

Background.In contrast to other genetic syndromes associated with Pheochromocytoma and Paraganglioma (PPGL) in which yearly biochemical screening is recommended, in neurofibromatosis due to the low penetrance of these tumors, screening is only recommended when there is clinical suspicion1. Given that signs and symptoms of catecholamine excess are vague and non-specific, clinicians should keep a low threshold for biochemical testing in these patients.Clinical Case.70 year old female with Neurofibromatosis type 1 (NF-1) diagnosed at age 24, hypertension and atrial fibrillation, was referred to our institution after being found incidentally with bilateral adrenal nodules. She had a 2 year history of poorly controlled, labile hypertension. Treatment at the time of presentation included doxazosin, metoprolol, valsartan and hydralazine. She denied other symptoms of catecholamine excess.Further workup revealed elevated 24 hour urine normetanephrine at 2,530 mcg (ULN 500 mcg) and metanephrine at 1,325 mcg (ULN 290 mcg). Serum metanephrines were also elevated with free metanephrine of 1.6 nmol/L (ULN 0.5 nmol/L) and free normetanephrine of 4.1 nmol/L (ULN 0.9 nmol/L). Her biochemical metanephrine profile was consistent with pheochromocytomas in NF-1. MIBG uptake confirmed the presence of bilateral pheochromocytomas. She underwent a complete right adrenalectomy and a left cortical sparing adrenalectomy. Her adrenocortical function remains adequate. Post operatively while her blood pressures were no longer labile, she continued to require anti-hypertensive therapy.Conclusion.Patients who are at risk of developing pheochromocytomas and paragangliomas due to genetic syndromes or known germline mutations need ongoing clinical follow and biochemical testing for timely case detection. While in NF-1 pheochromocytomas are usually unilateral and present during early adulthood, they can present with bilateral disease and later in life2. During surgical treatment, even with unilateral disease, adrenocortical function should be preserved when possible3. Hypertension may persist despite complete surgical resection.

The "salt and pepper" pattern on renal ultrasound in a group of children with molecular-proven diagnosis of ciliopathy-related renal diseases.

While typical ultrasound patterns of ciliopathy-related cystic kidney diseases have been described in children, ultrasound findings can overlap between different diseases and atypical patterns exist. In this study, we assessed the presence of the "salt and pepper" pattern in different renal ciliopathies and looked for additional ultrasound features. This single-center, retrospective study included all patients with a molecular-proven diagnosis of renal ciliopathy, referred to our center between 2007 and 2017. Images from the first and follow-up ultrasound exams were reviewed. Basic ultrasound features were grouped into patterns and compared to genetic diagnoses. The "salt and pepper" aspect was described as enlarged kidneys with heterogeneous, increased parenchymal echogenicity. A total of 41 children with 5 different renal ciliopathies were included (61% male; median age, 6years [range, 3days to 17years]). The "salt and pepper" pattern was present in 14/15 patients with an autosomal recessive polycystic kidney disease (ARPKD). A similar pattern was found in 1/4 patients with an autosomal dominant polycystic kidney disease and in 1/11 patients with HNF1B mutation. Additional signs found were areas of cortical sparing, comet-tail artifacts, and color comet-tail artifacts. Although the "salt and pepper" ultrasound pattern is predominantly found in ARPKD, it may be detected in other ciliopathies. The color comet-tail artifact is an interesting sign when suspecting a renal ciliopathy in case of enlarged hyperechoic kidneys with no detectable microcysts on B-mode grayscale ultrasound.

Biomarker evidence for distal tubular damage but cortical sparing in hospitalized diabetic patients with acute kidney injury (AKI) while on SGLT2 inhibitors

Background Inhibitors of sodium-glucose co-transporter-2 (SGLT2i) were found to improve renal outcome in diabetic patients in large prospective randomized trials. Yet, SGLT2i may acutely reduce kidney function through volume depletion, altered glomerular hemodynamics or intensified medullary hypoxia leading to acute tubular injury (ATI). The aim or this study was to prospectively assess the pathophysiology of acute kidney injury (AKI) in patients hospitalized while on SGLT2i, differing ATI from pre-renal causes using renal biomarkers. Methods Serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Ischemia Molecule (KIM)-1, markers of distal and proximal tubular injury, respectively, were determined in 46 diabetic patients who were on SGLT2i upon hospitalization with an acute illness. Results Serum and urine NGAL, but not KIM-1, were significantly increased in 21 of the patients who presented with AKI upon admission, as compared with 25 patients that maintained kidney function. Both serum and urinary NGAL correlated with the degree of impaired renal function, which in many cases was likely the result of additional acute renal perturbations, such as sepsis. Conclusions Increased urinary and serum NGAL indicates that ATI, principally affecting distal tubular segments, may develop in some of the patients hospitalized with an acute illness and AKI while on SGLT2i. It is suggested that intensified medullary hypoxia by SGLT2i might be detrimental in this injury. By contrast, concomitantly unaltered KIM-1 might reflect improved cortical oxygenation by SGLT2i, and may explain an overall reduced risk of AKI with SGLT1i in large series. The independent potential of SGLT2i to inflict medullary hypoxic damage should be explored further.