Transfemoral Approach to Induce Transient Middle Cerebral Artery Occlusion in Rats: The Use of Commercially Available Endovascular Wires.

BACKGROUND: Animal models of stroke play a crucial role in determining the pathophysiology of stroke progression and assessment of any new therapeutic approaches. Transient middle cerebral artery occlusion (tMCAo) in rodent models are the most common site-specific type of ischemia because of their relevance to the clinical setting. Compared with the intraluminal filament technique for inducing tMCAo, the transfemoral approach using endovascular wires is relatively a new technique METHODS: Here we present the use of commercially available wires used for neuro-endovascular surgical procedures to induce tMCAo in rats via a transfemoral approach. We used male Wistar rats in four groups to assess the effect of occlusion time (1 vs. 2 hours) and the wire type (PT2 TM 0.014″ vs. TransendTM EX, 0.014″, Boston Scientific, MA, USA). Infarct volume, edema, neurological deficits, and pro-inflammatory/anti-inflammatory blood biomarkers were used as outcome measures. RESULTS: We observed a significant effect of the wire type on the infarct volume (p value = 0.0096) where infarcts were slightly larger in the PT2 wiregroups. However, the occlusion time had no significant effect on infarct volume, even though the interaction between wire-type * occlusion-time was significant (p value = 0.024). Also, the amount of edema and blood pro-inflammatory/anti-inflammatory biomarkers were not statistically different among the wire-type and occlusion-time groups. CONCLUSIONS: The choice of appropriate endovascular wire should probably be the focus of the study design instead of the occlusion time when planning an experiment. The transfemoral approach using endovascular wires for inducing tMCAo in rats provides a more consistent outcome with fewer complications compared with suture filament models.

A Congenital Case of Ependymoblastoma: A Rare and Aggressive Brain Tumor.

Congenital brain tumors are rare, representing <2% of all childhood brain tumors. Of these, ependymoblastoma is a profoundly aggressive embryonal brain tumor that is included in the diagnostic entity known as an embryonal tumor with multilayered rosettes. This report of a congenital ependymoblastoma diagnosed at birth aims to highlight how much remains unknown about embryonal tumor with multilayered rosettes and the devastating prognosis of this condition. Despite recent advancements made in identifying molecular targets for therapy, this tumor continues to have a high rate of recurrence with few successful treatment options, especially when diagnosed in the newborn period.

Inducing Different Brain Injury Levels Using Shock Wave Lithotripsy.

OBJECTIVES: To assess the feasibility of inducing different severities of shock wave (SW)-induced traumatic brain injury (TBI) using lithotripsy. METHODS: Wistar rats (n = 36) were divided into 2 groups: group 1 (n = 20) received 5 SW pulses, and group 2 (n = 16) received 15 SWs pulses. The SW pulses were delivered to the right side of the frontal cortex. Neurologic and behavioral assessments (Garcia test, beam walking, rotarod, and elevated plus maze) were performed at the baseline and at 3, 6, 24, 72, and 168 hours after injury. At day 7 after injury (168 hours), we performed cerebral angiography to assess the presence of cerebral vasospasm and vascular damage due to SW-induced TBI. At the conclusion of the study, the animals were euthanized to assess damage to brain tissue using an overall histologic severity score. RESULTS: The Garcia score was significantly higher, and the anxiety index (based on the elevated plus maze) was significantly lower in group 1 compared to group 2 (P < .05). The anxiety index for group 1 returned to the baseline level in a fast nonlinear fashion, whereas the anxiety index for group 2 followed a distinct slow linear reduction. Cerebral angiograms revealed a more severe vasospasm for the animals in group 2 compared to group 1 (P = .027). We observed a statistically significant difference in the overall histologic severity scores between the groups. The median (interquartile range) overall histologic severity scores for groups 1 and 2 were 3.0 (2.75) and 6.5 (6.0), respectively (P = .023). CONCLUSIONS: We have successfully established different SW-induced TBI severities in our SW-induced TBI model by delivering different numbers of SW pulses to brain tissue.

Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy.

Noonan syndrome (NS) is an autosomal dominant developmental disorder caused by mutations in the RAS-MAPK signaling pathway that is well known for its relationship with oncogenesis. An 8.1-fold increased risk of cancer in Noonan syndrome has been reported, including childhood leukemia and solid tumors. The same study found a patient with a dysembryoplastic neuroepithelial tumor (DNET) and suggested that DNET tumors are associated with NS. Herein we report an 8-year-old boy with genetically confirmed NS and a DNET. Literature review identified eight other reports, supporting the association between NS and DNETs. The review also ascertained 13 non-DNET brain tumors in individuals with NS, bringing to 22 the total number of NS patients with brain tumors. Tumor growth while receiving growth hormone (GH) occurred in our patient and one other patient. It is unknown whether the development or progression of tumors is augmented by GH therapy, however there is concern based on epidemiological, animal and in vitro studies. This issue was addressed in a 2015 Pediatric Endocrine Society report noting there is not enough data available to assess the safety of GH therapy in children with neoplasia-predisposition syndromes. The authors recommend that GH use in children with such disorders, including NS, be undertaken with appropriate surveillance for malignancies. Our case report and literature review underscore the association of NS with CNS tumors, particularly DNET, and call attention to the recommendation that clinicians treating NS patients with GH do so with awareness of the possibility of increased neoplasia risk.

Progressive Disruption of Sphingosine-1-Phosphate Receptor 1 Correlates with Blood-Brain Barrier Leakage in A Rat Model of Chronic Hypoxic Hypoperfusion.

Endothelial dysfunction and blood-brain barrier (BBB) leakage have been suggested as a fundamental role in the development of cerebral small vessel disease (SVD) pathology. However, the molecular and cellular mechanisms that link cerebral hypoxic hypoperfusion and BBB disruption remain elusive. Sphingosine-1-phosphate (S1P) regulates the BBB integrity by binding to its receptor isoform 1 (S1PR1) on endothelial cells. This study tested the hypothesis that hypoxic hypoperfusion triggers capillary endothelial S1PR1 disruption, which compromises BBB integrity and leads to SVD-related neuropathological changes, using a chronic hypoxic hypoperfusion model with BBB dysfunction. Spontaneously hypertensive rat stroke-prone underwent unilateral carotid artery occlusion (UCAO) followed by a Japanese permissive diet (JPD) for up to 9 weeks. Selective S1PR1 agonist SEW2871 was used to activate S1PR1. Significant progressive reduction of S1PR1 was detected in rat brains from 4 to 9 weeks following UCAO/JPD onset, which was also detected in cerebral vasculature in human SVD. S1PR1 activation by SEW2871 significantly reduced lesions in both white and grey matter and ameliorated cerebral blood flow. SEW2871 reversed the loss of endothelial S1PR1 and tight junction proteins, and significantly attenuated UCAO/JPD induced accumulation of neuronal phosphorylated tau. This protective role of SEW2871 is associated with promotion of Akt phosphorylation and inhibition of S1PR2/Erk1/2 activation. Our data suggest S1PR1 signalling as a potential molecular mechanistic basis that links hypoxic hypoperfusion with BBB damage in the neuropathological cascades in SVD. The reversal of BBB disruption through pharmacological intervention of S1PR1 signalling likely reveals a novel therapeutic target for SVD.

Non-Invasive Vagus Nerve Stimulation Improves Brain Lesion Volume and Neurobehavioral Outcomes in a Rat Model of Traumatic Brain Injury.

Abstract Traumatic brain injury (TBI) continues to be a major cause of death and disability worldwide. This study assessed the effectiveness of non-invasive vagus nerve stimulation (nVNS) in reducing brain lesion volume and improving neurobehavioral performance in a rat model of TBI. Animals were randomized into three experimental groups: (1) TBI with sham stimulation treatment (Control), (2) TBI treated with five lower doses (2-min) nVNS, and (3) TBI treated with five higher doses (2 × 2-min) nVNS. We used the gammaCore nVNS device to deliver stimulations. Magnetic resonance imaging studies were performed 1 and 7 days post-injury to confirm lesion volume. We observed smaller brain lesion volume in the lower dose nVNS group compared with the control group on days 1 and 7. The lesion volume for the higher dose nVNS group was significantly smaller than either the lower dose nVNS or the control groups on days 1 and 7 post-injury. The apparent diffusion coefficient differences between the ipsilateral and contralateral hemispheres on day 1 were significantly smaller for the higher dose (2 × 2 min) nVNS group than for the control group. Voxel-based morphometry analysis revealed an increase in the ipsilateral cortical volume in the control group caused by tissue deformation and swelling. On day 1, these abnormal volume changes were 13% and 55% smaller in the lower dose and higher dose nVNS groups, respectively, compared with the control group. By day 7, nVNS dampened cortical volume loss by 35% and 89% in the lower dose and higher dose nVNS groups, respectively, compared with the control group. Rotarod, beam walking, and anxiety performances were significantly improved in the higher-dose nVNS group on day 1 compared with the control group. The anxiety indices were also improved on day 7 post-injury compared with the control and the lower-dose nVNS groups. In conclusion, the higher dose nVNS (five 2 × 2-min stimulations) reduced brain lesion volume to a level that further refined the role of nVNS therapy for the acute treatment of TBI. Should nVNS prove effective in additional pre-clinical TBI models and later in clinical settings, it would have an enormous impact on the clinical practice of TBI in both civilian and military settings, as it can easily be adopted into routine clinical practice.

Hippocampal sclerosis in advanced age: clinical and pathological features.

Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR DNA protein 43. To help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically, the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age, gender, education level and apolipoprotein E genotype. These individuals were followed from intake assessment, with 8.2 (average) longitudinal cognitive assessments. A neuropsychological profile with relatively high-verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake (P<0.015) and also 5.5-6.5 years before death (P<0.005). This may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure Alzheimer's disease in their earliest stages. In summary, in the largest series of autopsy-verified patients with hippocampal sclerosis to date, we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing.

Cognitive Reserve and Mild Cognitive Impairment: Predictors and Rates of Reversion to Intact Cognition vs Progression to Dementia.

BACKGROUND AND OBJECTIVES: Little is known about the effect of education or other indicators of cognitive reserve on the rate of reversion from mild cognitive impairment (MCI) to normal cognition (NC) or the relative rate (RR) of reversion from MCI to NC vs progression from MCI to dementia. Our objectives were to (1) estimate transition rates from MCI to NC and dementia and (2) determine the effect of age, APOE, and indicators of cognitive reserve on the RR of reversion vs progression using multistate Markov modeling. METHODS: We estimated instantaneous transition rates between NC, MCI, and dementia after accounting for transition to death across up to 12 assessments in the Nun Study, a cohort study of religious sisters aged 75+ years. We estimated RRs of reversion vs progression for age, APOE, and potential cognitive reserve indicators: education, academic performance (high school grades), and written language skills (idea density, grammatical complexity). RESULTS: Of the 619 participants, 472 were assessed with MCI during the study period. Of these 472, 143 (30.3%) experienced at least one reverse transition to NC, and 120 of the 143 (83.9%) never developed dementia (mean follow-up = 8.6 years). In models adjusted for age group and APOE, higher levels of education more than doubled the RR ratio of reversion vs progression. Novel cognitive reserve indicators were significantly associated with a higher adjusted RR of reversion vs progression (higher vs lower levels for English grades: RR ratio = 1.83; idea density: RR ratio = 3.93; and grammatical complexity: RR ratio = 5.78). DISCUSSION: Knowledge of frequent reversion from MCI to NC may alleviate concerns of inevitable cognitive decline in those with MCI. Identification of characteristics predicting the rate of reversion from MCI to NC vs progression from MCI to dementia may guide population-level interventions targeting these characteristics to prevent or postpone MCI and dementia. Research on cognitive trajectories would benefit from incorporating predictors of reverse transitions and competing events, such as death, into statistical modeling. These results may inform the design and interpretation of MCI clinical trials, given that a substantial proportion of participants may experience improvement without intervention.

Advanced frailty assessment tool predicts successful awake craniotomy in a 92-year-old patient: A case report.

Background: The awake craniotomy (AC) procedure allows for safe and maximal resection of brain tumors from highly eloquent regions. However, geriatric patients are often viewed as poor candidates for AC due to age and medical comorbidities. Frailty assessments gauge physiological reserve for surgery and are valuable tools for preoperative decision-making. Here, we present a novel case illustrating how frailty scoring enabled an elderly but otherwise healthy female to undergo successful AC for tumor resection. Case Description: A 92-year-old right-handed female with history of hypertension and basal cell skin cancer presented with a 1-month history of progressive aphasia and was found to have a ring-enhancing left frontoparietal mass abutting the rolandic cortex concerning for malignant neoplasm. Frailty scoring with the recalibrated risk analysis index (RAI-C) tool revealed a score of 30 (of 81) indicating low surgical risk. The patient and family were counseled appropriately that, despite advanced chronological age, a low frailty score predicts favorable surgical outcomes. The patient underwent left-sided AC for resection of tumor and experienced immediate improvement of speech intraoperatively. After surgery, the patient was neurologically intact and had an unremarkable postoperative course with significant improvements from preoperatively baseline at follow-up. Conclusion: To the best of our knowledge, this case represents the oldest patient to undergo successful AC for brain tumor resection. Nonfrail patients over 90 years of age with the proper indications may tolerate cranial surgery. Frailty scoring is a powerful tool for preoperative risk assessment in the geriatric neurosurgery population.

Fenestration of intracranial neurenteric cyst: A case report.

BACKGROUND: Neurenteric cysts are rare congenital lesions of endodermal origin which result from the failure of the neurenteric canal to close during embryogenesis. The majority of neurenteric cysts occur in the spinal cord, though in rare instances can occur intracranially, typically in the posterior fossa anterior to the pontomedullary junction (80%) or in the supratentorial region adjacent to the frontal lobes (20%). CASE DESCRIPTION: We present the case of a 75-year-old woman with an extra-axial cystic lesion centered in the premedullary cistern causing brainstem compression. The lesion was later histopathologically confirmed to be a neurenteric cyst. She presented initially with a 4-month history of worsening headache, dizziness, and unsteady gait. We performed a left retrosigmoid craniotomy for cyst fenestration/biopsy with the aid of operating microscope and stealth neuronavigation. Following the procedure, the patient recovered without complications or residual deficits. CONCLUSION: This case illustrates the successful fenestration of an intracranial neurenteric cyst with good clinical outcome. We present the pre- and post-operative imaging findings, a technical video of the procedure, histopathological confirmation, and a brief review of the relevant clinical literature on the topic.

MicroRNA Analysis of Human Stroke Brain Tissue Resected during Decompressive Craniectomy/Stroke-Ectomy Surgery.

BACKGROUND: Signaling pathways mediated by microRNAs (miRNAs) have been identified as one of the mechanisms that regulate stroke progression and recovery. Recent investigations using stroke patient blood and cerebrospinal fluid (CSF) demonstrated disease-specific alterations in miRNA expression. In this study, for the first time, we investigated miRNA expression signatures in freshly removed human stroke brain tissue. METHODS: Human brain samples were obtained during craniectomy and brain tissue resection in severe stroke patients with life-threatening brain swelling. The tissue samples were subjected to histopathological and immunofluorescence microscopy evaluation, next generation miRNA sequencing (NGS), and bioinformatic analysis. RESULTS: miRNA NGS analysis detected 34 miRNAs with significantly aberrant expression in stroke tissue, as compared to non-stroke samples. Of these miRNAs, 19 were previously identified in stroke patient blood and CSF, while dysregulation of 15 miRNAs was newly detected in this study. miRNA direct target gene analysis and bioinformatics approach demonstrated a strong association of the identified miRNAs with stroke-related biological processes and signaling pathways. CONCLUSIONS: Dysregulated miRNAs detected in our study could be regarded as potential candidates for biomarkers and/or targets for therapeutic intervention. The results described herein further our understanding of the molecular basis of stroke and provide valuable information for the future functional studies in the experimental models of stroke.

Clinical and imaging features of fludarabine neurotoxicity.

Neurotoxicity from intravenous fludarabine is a rare but recognized clinical entity. Its brain imaging features have not been extensively described. Three patients received 38.5 mg or 40 mg/m per day fludarabine in a 5-day intravenous infusion before bone marrow transplantation in treatment of hematopoietic malignancies. Several weeks later, each patient developed progressive neurologic decline, including retrogeniculate blindness, leading to coma and death. Brain MRI showed progressively enlarging but mild T2/FLAIR hyperintensities in the periventricular white matter. The lesions demonstrated restricted diffusion but did not enhance. Because the neurotoxicity of fludarabine appears long after exposure, neurologic decline in this setting is likely to be attributed to opportunistic disease. However, the imaging features are distinctive in their latency and in being mild relative to the profound clinical features. The safe dose of fludarabine in this context remains controversial.

Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease.

Brains that have many neurofibrillary tangles (NFTs) in medial temporal lobe structures (Braak stage III or IV) but no cortical neuritic plaques (NPs) may be a diagnostic dilemma; they also raise questions about the amyloid cascade hypothesis of Alzheimer disease (AD) in which NFT development is thought to occur downstream of the development of amyloid plaques. To determine the clinical, demographic, and biological factors related to NFT+/NP- cases, we analyzed 26 NFT+/NP- patient brains identified from the University of Kentucky AD Center autopsy cohort (n=502); most of these patients were at least 85 years old and lacked profound antemortem cognitive impairment. A subset of the cases had NFTs in the medulla oblongata. Aberrant trans-activator regulatory DNA-binding protein 43 immunohistochemical staining was seen in 5 of the 26 cases with the clinical diagnoses of AD or mild cognitive impairment. We also queried cases in the National Alzheimer's Coordinating Center Registry (n=5,108) and found 219 NFT+/NP- cases. Those patients had a relatively high likelihood of belonging to a birth cohort with the highest incidence of influenza infection during the 1918 to 1919 pandemic. This observation may link the pathogenesis in NFT+/NP- cases to encephalitis during childhood. We conclude that NFT+/NP- cases comprise approximately 5% of aged individuals in multiple data sets; these cases are not necessarily within the spectrum of AD.

Acute toxic leukoencephalopathy: potential for reversibility clinically and on MRI with diffusion-weighted and FLAIR imaging.

OBJECTIVE: Toxic leukoencephalopathy may present acutely or subacutely with symmetrically reduced diffusion in the periventricular and supraventricular white matter, hereafter referred to as periventricular white matter. This entity may reverse both on imaging and clinically. However, a gathering together of the heterogeneous causes of this disorder as seen on MRI with diffusion-weighted imaging (DWI) and an analysis of their likelihood to reverse has not yet been performed. Our goals were to gather causes of acute or subacute toxic leukoencephalopathy that can present with reduced diffusion of periventricular white matter in order to promote recognition of this entity, to evaluate whether DWI with apparent diffusion coefficient (ADC) values can predict the extent of chronic FLAIR abnormality (imaging reversibility), and to evaluate whether DWI can predict the clinical outcome (clinical reversibility). MATERIALS AND METHODS: Two neuroradiologists retrospectively reviewed the MRI examinations of 39 patients with acute symptoms and reduced diffusion of periventricular white matter. The reviewers then scored the extent of abnormality on DWI and FLAIR. ADC ratios of affected white matter versus the unaffected periventricular white matter were obtained. Each patient's clinical records were reviewed to determine the cause and clinical outcome. Histology findings were available in three patients. Correlations were calculated between the initial MRI markers and both the clinical course and the follow-up extent on FLAIR using Spearman's correlation coefficient. RESULTS: Of the initial 39 patients, seven were excluded because of a nontoxic cause (hypoxic-ischemic encephalopathy [HIE] or congenital genetic disorders) or because of technical errors. In the remaining 32 patients, no correlation was noted between any of the initial MRI markers (percentage of ADC reduction, DWI extent, or FLAIR extent) with the clinical outcome. Three patients had histologic correlation. However, moderate correlation was seen between the extent of abnormality on initial FLAIR and the extent on follow-up FLAIR (r = 0.441, p = 0.047). Of the 13 patients who underwent repeat MRI at 21 days or longer, the reduced diffusion resolved in all but one. Significant differences were noted between ADC values in affected white matter versus unaffected periventricular white matter on initial (p < 0.0001) but not on follow-up MRI (p = 0.13), and in affected white matter on initial versus follow-up (p = 0.0014) in those individuals who underwent repeat imaging on the same magnet (n = 9), confirming resolution of the DWI abnormalities. CONCLUSION: Acute toxic leukoencephalopathy with reduced diffusion may be clinically reversible and radiologically reversible on DWI, and may also be reversible, but to a lesser degree, on FLAIR MRI. None of the imaging markers measured in this study appears to correlate with clinical outcome, which underscores the necessity for prompt recognition of this entity. Alerting the clinician to this potentially reversible syndrome can facilitate treatment and removal of the offending agent in the early stages.

Apolipoprotein e deficiency leads to altered brain uptake of alpha tocopherol injected into lateral cerebral ventricles.

The incorporation of radioactive alpha tocopherol by various brain regions of wild type and apolipoprotein E (apoE)-deficient mice was investigated. Labeled tocopherol was injected into the lateral cerebral ventricles of 11 weeks old, male mice. Radioactive cholesterol injected simultaneously was used as an internal standard to account for experimental variability. Most areas of the brain of apoE-deficient mice took up less of alpha tocopherol per mg of protein than wild type animals. However, specific activity of alpha tocopherol was higher in cerebellum, pons, hypothalamus, midbrain and cerebral cortex in apoE-deficient brains than the wild type. This could be due to (a) the lower levels of alpha tocopherol in apoE-deficient brain and (b) reductions in the clearance and transport of tocopherol (possibly mediated by apoE). Tocopherol uptake by hippocampus was unusual since it was lower in apoE deficiency whether the data were expressed as specific activity or per mg of protein. Nearly all of the injected alpha tocopherol remained unchanged in the brains of both apoE-deficient and wild type animals suggesting low turnover. Overall, the current data reinforce the hypothesis that apoE is a key protein involved with the transport and/or retention of alpha tocopherol in brain.

Schimke immuno-osseous dysplasia: a clinicopathological correlation.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a fatal autosomal recessive disorder caused by loss-of-function mutations in swi/snf-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1). METHODS: Analysis of detailed autopsies to correlate clinical and pathological findings in two men severely affected with SIOD. RESULTS: As predicted by the clinical course, T cell deficiency in peripheral lymphoid organs, defective chondrogenesis, focal segmental glomerulosclerosis, cerebral ischaemic lesions and premature atherosclerosis were identified. Clinically unexpected findings included a paucity of B cells in the peripheral lymphoid organs, emperipolesis-like (penetration of one cell by another) abnormalities in the adenohypophysis, fatty infiltration of the cardiac right ventricular wall, pulmonary emphysema, testicular hypoplasia with atrophy and azospermia, and clustering of small cerebral vessels. CONCLUSIONS: A regulatory role for the SMARCAL1 protein in the proliferation of chondrocytes, lymphocytes and spermatozoa, as well as in the development or maintenance of cardiomyocytes and in vascular homoeostasis, is suggested. Additional clinical management guidelines are recommended as this study has shown that patients with SIOD may be at risk of pulmonary hypertension, combined immunodeficiency, subcortical ischaemic dementia and cardiac dysfunction.

Changes in [18F]Fluorodeoxyglucose Activities in a Shockwave-Induced Traumatic Brain Injury Model Using Lithotripsy.

We present a longitudinal study of cerebral metabolism using [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a rat model of shockwave-induced traumatic brain injury (SW-TBI). Anesthetized rats received 5 or 10 SW pulses to the right anterior lateral or dorsal frontal regions using SW lithotripsy. Animals were scanned for FDG uptake at baseline, 3 h post-injury, and 3 days post-injury, using a small animal PET/computed tomography (CT) scanner. FDG uptake at all time-points was quantified as the ratio of brain activity relative to peripheral activity in the left ventricle (LV) in the heart (Abrain/ALV) for the entire brain, each hemisphere, and four cortices (motor, cingulate, somatosensory, and retrosplenial). The mixed-designed models analysis of variance (ANOVA) for the hemispheric and global FDG uptake ratio showed a significant effect of the time-of-scan (p = 0.038) and measured region (p = 6.12e-09). We also observed a significant effect of the time-of-scan (p = 0.046) and measured region (p = 2.28e-09) for the FDG uptake ratio in four cortical regions. None of the measurements (global or local) showed a significant effect for the number of SW pulses (5 or 10) or SW location (lateral or dorsal frontal regions). Our data suggest that SW-TBI causes hypermetabolism on the impact side of the rat brain at 3 h post-injury compared with the baseline measurements. However, the increase in FDG uptake by day 3 post-injury was not significant. Further studies on post-TBI metabolic changes are needed to understand better the pathophysiology of the injury.

Sellar Region Atypical Teratoid/Rhabdoid Tumors in Adults: Clinicopathological Characterization of Five Cases and Review of the Literature.

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant CNS neoplasms that typically occur in children <2 years of age. These are characterized by high-grade histologic features and mutations of the INI1/SMARCB1 gene readily detected by loss of expression by immunohistochemistry. Among adults, the majority of AT/RTs occurs in the cerebral hemispheres. A small number of adult AT/RTs involving the sellar and suprasellar region reported in the literature suggest a distinct clinical course for this group. Here, we describe detailed clinical and genetic characterization of 5 adult patients with AT/RTs involving the sellar and suprasellar region, and provide a review of the available clinical and genetic features of 22 previously reported cases in order to help increase our understanding of this unusual entity.