Links between brain neuroimaging and blood inflammatory markers in urological chronic pelvic pain syndrome.

Urological chronic pelvic pain syndrome (UCPPS) is a debilitating painful condition with unclear etiology. Prior researchers have indicated that compared to healthy controls, patients with UCPPS demonstrated altered brain activity. Researchers have also shown that in UCPPS, several blood inflammatory markers relate to clinical variables of pain, fatigue, and pain widespreadness. However, how altered brain function in patients with UCPPS relates to blood inflammation remains unknown. To extend and connect prior findings of altered brain function and inflammatory factors in UCPPS, we conducted a secondary analysis of data from a cohort of UCPPS patients (N = 29) and healthy controls (N = 31) who provided both neuroimaging and blood data (National Institute of Health MAPP Research Network publicly available dataset). In our present study, we aimed to evaluate relationships between a priori-defined brain neuroimaging markers and inflammatory factors of interest and their relationships to pain-psychological variables. We hypothesized that two brain alterations of interest (i.e., PCC - left hippocampus functional connectivity and PCC - bilateral amygdala functional connectivity) would be correlated with four cytokine markers of interest: interleukin (IL) - 6, tumor necrosis factor-alpha (TNF-a), IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the UCPPS cohort, we identified a significant PCC - left hippocampus functional connectivity relationship with IL-6 (p = 0.0044). Additionally, in the UCPPS cohort, we identified a PCC - amygdala functional connectivity relationship with GM-CSF which did not meet our model's threshold for statistical significance (p = 0.0665). While these data are preliminary and cross-sectional, our findings suggest connections between brain function and levels of low-grade systemic inflammation in UCPPS. Thus, while further study is needed, our data indicate the potential for advancing the understanding of how brain functional circuits may relate to clinical symptoms and systemic inflammation.

Diagnostic accuracy of neuroimaging in emergency department patients with acute vertigo or dizziness: A systematic review and meta-analysis for the guidelines for reasonable and appropriate care in the emergency department.

BACKGROUND: Patients presenting to the emergency department (ED) with acute vertigo or dizziness represent a diagnostic challenge. Neuroimaging has variable indications and yield. We aimed to conduct a systematic review and meta-analysis of the diagnostic test accuracy of neuroimaging for patients presenting with acute vertigo or dizziness. METHODS: An electronic search was designed following patient-intervention-control-outcome (PICO) question-(P) adult patients with acute vertigo or dizziness presenting to the ED; (I) neuroimaging including computed tomography (CT), CT angiography (CTA), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and ultrasound (US); (C) MRI/clinical criterion standard; and (O) central causes (stroke, hemorrhage, tumor, others) versus peripheral causes of symptoms. Articles were assessed in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to assess certainty of evidence in pooled estimates. RESULTS: We included studies that reported diagnostic test accuracy. From 6309 titles, 460 articles were retrieved, and 12 were included: noncontrast CT scan-six studies, 771 patients, pooled sensitivity 28.5% (95% confidence interval [CI] 14.4%-48.5%, moderate certainty) and specificity 98.9% (95% CI 93.4%-99.8%, moderate certainty); MRI-five studies, 943 patients, sensitivity 79.8% (95% CI 71.4%-86.2%, high certainty) and specificity 98.8% (95% CI 96.2%-100%, high certainty); CTA-one study, 153 patients, sensitivity 14.3% (95% CI 1.8%-42.8%) and specificity 97.7% (95% CI 93.8%-99.6%), CT had higher sensitivity than CTA (21.4% and 14.3%) for central etiology; MRA-one study, 24 patients, sensitivity 60.0% (95% CI 26.2%-87.8%) and specificity 92.9% (95% CI 66.1%-99.8%); US-three studies, 258 patients, sensitivity ranged from 30% to 53.6%, specificity from 94.9% to 100%. CONCLUSIONS: Noncontrast CT has very low sensitivity and MRI will miss approximately one in five patients with stroke if imaging is obtained early after symptom onset. The evidence does not support neuroimaging as the only tool for ruling out stroke and other central causes in patients with acute dizziness or vertigo presenting to the ED.

[CASE SERIES OF EARLY NEUROIMAGING IN PATIENTS WITH VASCULAR RISK FACTORS AND ISOLATED SIX CRANIAL NERVE PALSY, DEMONSTRATING THE DILEMMA OF EARLY IMAGING].

INTRODUCTION: There are various etiologies for isolated third, fourth and sixth cranial nerve palsies. The most common etiology in adults aged 50 years and older with vascular risk factors such as diabetes, hyperlipidemia, and hyperlipidemia, is microvascular ischemia. The role of early neuroimaging in older patients with vascular risk factors presenting with acute isolated ocular motor nerve palsy is controversial. AIMS: We present six cases of patients aged 50 years and older, with vascular risk factors, who suffered from acute isolated paralysis of the sixth nerve. All cases were diagnosed with a non-microvascular ischemia etiology. RESULTS: The identified etiologies included petroclival meningioma with involvement of the cavernous sinus, metastatic hepatoma, plasmacytoma, venous thrombosis, arterial-venous malformation and aneurysm. CONCLUSIONS: Despite the high cost and presumed low yield, early neuroimaging can change the clinical management in certain cases. DISCUSSION: Previous studies have found the yield of early neuroimaging in older vasculopathic patients with acute 4th or 6th cranial nerve palsies to be 1-15%. In spite of these reports, our cases demonstrate the need for early onset imaging in these cases.

Single-center experience on progressive multifocal leukoencephalopathy (PML) cases, neuroimaging relevance, and management at West Virginia University (WVU).

Progressive multifocal leukoencephalopathy (PML) is an increasingly common and rapidly fatal demyelinating infection of central nervous system caused by the highly prevalent John Cunningham (JC) virus in immunocompromised individuals belonging to all age groups and genders. Human immunodeficiency virus (HIV) is the most common predisposing factor among other immunodeficient conditions leading to reactivation and multiple neurological symptoms. It has varied findings on magnetic resonance imaging (MRI) and diagnosis is confirmed by positive JC virus in cerebrospinal fluid (CSF). We report 12 confirmed cases of PML from a single academic center. We comprehensively described clinical presentations, risk factors, CSF and neuroimaging findings, treatment and outcome for these cases of PML, a rare disease. The cases were almost equivalently distributed among young and old age groups and both genders. Positive JC virus on CSF was present in the majority of cases along with mild to severe reduction in lymphocyte counts. Significant MRI changes were present in all cases ranging from T2 hypertense signals to white matter lesions in various regions. Treatment with the reversion of immune-modulators, optimization of antiviral therapy (ART), plasmapheresis (PLEX), IVIG, Mirtazapine, oral steroids, and others was started as soon as the diagnosis was made in the majority of the cases. However, PML is a rapidly fatal illness and hence, survival was only seen in 4 cases in our study. The objective of this article is to highlight the importance of early diagnosis of PML with CSF findings and neuroimaging, early reversion of immunosuppressive medications, and careful monitoring and treatment of HIV cases with goals to reduce mortality, long-term morbidity, and deficits.

Magnetic resonance neuroimaging after laser for twin-twin transfusion syndrome with single fetal demise.

BACKGROUND: Neurologic injury in the surviving twin is a risk after single fetal demise in a monochorionic pregnancy. OBJECTIVE: This study aimed to describe fetal magnetic resonance neuroimaging findings in pregnancies complicated by single fetal demise after laser photocoagulation for twin-twin transfusion syndrome. STUDY DESIGN: This was a single-center retrospective analysis of a cohort of prospectively collected patients in a monochorionic twin registry who had fetoscopic laser photocoagulation for twin-twin transfusion syndrome with single fetal demise at follow-up. Magnetic resonance neuroimaging was offered 3 to 4 weeks after the demise to assess for potential neurologic sequelae. Magnetic resonance images were interpreted by 2 board-certified neuroradiologists and classified as normal, mildly abnormal, or severely abnormal. The groups were compared on the basis of recipient vs donor demise using the Fisher exact test and Mann-Whitney U test. Multivariate logistic regression was performed to determine risk factors for abnormal magnetic resonance neuroimaging. RESULTS: In 378 laser photocoagulation procedures, 64 cases (16.9%) of single demise were identified (36 in the donor group and 28 in the recipient group). Of note, 6 patients had rupture of membranes with nonviable delivery (3 from each group). Moreover, 40 patients (69%) underwent magnetic resonance imaging. Of those patients, 12 (30%) had abnormal findings: 10 (83%) were associated with mild changes, and 2 (17%) were associated with severe findings. Abnormal magnetic resonance neuroimaging was seen in 3 of 22 patients (14%) after donor demise and 9 of 18 patients (50%) after recipient demise (P=.02). Logistic regression revealed that recipient vs donor demise was an independent risk factor for abnormal magnetic resonance imaging. In addition, 2 pregnancies with severe magnetic resonance imaging findings had complicated courses. CONCLUSION: Mildly abnormal magnetic resonance neuroimaging findings were common after laser photocoagulation for twin-twin transfusion syndrome complicated by single fetal demise and were more common in cases of recipient demise than donor demise. Severe magnetic resonance neuroimaging findings in this series were limited to patients with complicated peri- or postoperative courses.

[Posterior reversible encephalopathy syndrome (PRES) as a presentation of AL amyloidosis]. / Síndrome de encefalopatía posterior reversible (PRES) como forma de presentación de una amiloidosis AL.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity linked to multiple aetiologies with similar neuroimaging findings. Its incidence is unknown, and its pathogenesis is multifactorial, encompassing phenomena of endothelial dysfunction and cerebral flow autoregulation, inter alia. There is a wide variety of associated conditions, the most frequent being hypertension, eclampsia, and immunosuppressive therapy, along with other drugs, autoimmune diseases, and even uraemia. We present the case of a reversible posterior encephalopathy syndrome secondary to renal involvement as a debut form of AL amyloidosis.

Radiation exposure during computerized tomography-based neuroimaging for acute ischemic stroke: a case-control study.

Patients and clinicians often raise concerns about radiation exposure to various organs during computerized tomography-based imaging. We evaluated radiation exposure during standard and low-dose imaging protocols for non-contrast computerized tomography, computerized tomography angiography and computerized tomography perfusion of the head. Whether reducing the radiation dose affected the image quality was also evaluated. Radiation data were retrieved for computerized tomography-based imaging studies performed for acute ischemic stroke patients during 2015. The volume-weighted computerized tomography dose index, dose-length product, scan length, effective dose and whole-body integral dose for brain, skin, eye, thyroid and red bone marrow were extracted from dose-tracking software. Dose metrics for low-dose protocols data were compared with standard protocols. The calculated effective doses for non-contrast computerized tomography, computerized tomography angiography and computerized tomography perfusion were 2.56 ± 0.67 mSv, 4.45 ± 2.5 mSv, and 4.47 ± 0.85 mSv, respectively for 391 acute ischemic stroke patients. Corresponding radiation exposures for low-dose protocol (n = 31) were non-contrast computerized tomography (2.36 ± 0.65 mSv), computerized tomography angiography (1.57 ± 0.74 mSv) and computerized tomography perfusion (2.20 ± 0.55 mSv). Overall, the effective dose for one complete stroke imaging protocol (non-contrast computerized tomography + computerized tomography angiography + computerized tomography perfusion) for the standard-dose protocol was 11.48 mSv, which was reduced to 6.13 mSv (46.6% reduction) using a low-dose protocol (p < 0.001). Reduced radiation exposure was noted for other radiosensitive organs. Radiation exposures of sensitive organs are within acceptable limits with standard neuroimaging protocols for acute ischemic stroke. Lower-dose computerized tomography imaging protocols reduced the radiation doses without appreciable deterioration in image quality.

Isolated acute pseudobulbar palsy with infarction of artery of percheron: case report and literature review.

INTRODUCTION: Pseudobulbar palsy (PBP) is characterized by supranuclear lesions in the corticobulbar pathway. Neoplasia, inflammatory, demyelinating, and stroke are possible etiologies of this disorder. CASE REPORT: We report an elderly female who presented with dysarthria. She was dysarthric with a hypernasal voice, no apraxia or aphasia was observed. Tongue movements were slow with limited amplitude. Her soft palate dropped bilaterally; gag reflex was present. Also, she reported swallowing difficulty and choking with her saliva. Bilateral vertical and horizontal gaze were intact to either voluntary or oculocephalic movements. A cranial CT scan was suggestive of artery of Percheron (AOP) infarction. Brain magnetic resonance imaging showed hypersignal on diffusion-weighted and T2-weighted images and hyposignal on apparent diffusion coefficient in both thalami. CT angiography scan revealed an AOP originating from the left posterior cerebral artery. The swallowing study with a videofluoroscopic demonstrated oral and pharyngeal phases with severe dysfunction. CONCLUSION: To the authors' knowledge, there are two cases of individuals with artery of Percheron infarction who developed PBP associated with other clinical syndromes. Still, isolated PBP following infarction of Percheron's artery was not reported. We hypothesized that the PBP may have occurred because of the existence of vascular territory variations in the perforating arteries that arise from the AOP.

Neurological manifestations following cured malaria: don't forget post-malaria neurological syndrome.

INTRODUCTION: Cerebral malaria which occurs during the active infection is the most common neurological complication of malaria. Other complications including post-malaria neurological syndrome (PMNS) can rarely occur following complete recovery from the disease. We report a case of post-malaria neurological syndrome in a Tunisian patient. CASE PRESENTATION: A 26-year-old Tunisian man with no past medical history was admitted in 2016 for a muscle weakness of the 4 limbs, seizures, tetraparesis and myoclonus which appeared after he returned from Côte d'Ivoire where he had been treated three weeks ago for Plasmodium falciparum malaria with favorable outcome. Blood smears for malaria were negative. Brain MRI showed multiple hypersignal cerebral lesions. Investigations didn't show any infectious, metabolic, toxic, vascular or tumoral etiology. Thus, the diagnosis of PMNS was considered. The patient was treated with methylprednisolone with favorable outcome. Two years later, he was completely asymptomatic. CONCLUSION: PMNS should be considered in patients with neurological symptoms occurring within two months of cured acute disease in which blood smears for malaria are negative and other etiologies have been ruled out. In most cases, the disease is self-limited while in severe cases corticosteroid therapy should be prescribed with favorable outcome.

Pseudohypoxic Brain Swelling after Drilling and Drainage for Chronic Subdural Hematoma.

Pseudohypoxic brain swelling (PHBS) is a rare and potentially fatal complication that may occur in patients following uneventful brain surgery. We present a case of PHBS that developed after drilling and drainage of a chronic subdural hematoma. Neuroimaging findings, pathogenic factors, and therapy are also discussed.

Neuroimaging in infants and children in select neurocutaneous disorders.

The role of neuroimaging in neurocutaneous disorders is an evolving field. Research can be inconsistent and inconclusive, leading to divergent practice for some disorders. This study provides an overview of the current role of magnetic resonance imaging (MRI) of the brain in select neurocutaneous disorders, namely Sturge-Weber syndrome, congenital melanocytic naevus syndrome, neurofibromatosis type 1, tuberous sclerosis complex, incontinentia pigmenti and basal cell naevus syndrome. Future research assessing new targeted treatments and novel MRI techniques may change current practice.

Contrast-induced neurotoxicity related to neurological endovascular procedures: a systematic review.

Contrast-induced neurotoxicity (CIN) is an adverse reaction to contrast agents which can occur in the context of diagnostic and therapeutic neurological endovascular procedures. Our goal was to conduct a systematic review of patients reported in the literature diagnosed with CIN after neurological endovascular procedures. A systematic search of EMBASE and MEDLINE databases was conducted. Inclusion criteria were age ≥ 18 years; neurological endovascular procedure performed ≤ 24 h before ictus; new manifestations compatible with encephalic dysfunction; imaging performed < 7 days after ictus; exclusion of other causes and manifestations attributed to pre-existing conditions. Forty-eight patients were included, of which 60.4% were female and 60.4% had arterial hypertension; median age was 63 years. The most frequent procedure was diagnostic cerebral angiography (n = 24, 50.0%) and non-ionic contrast agents were more frequently used (n = 40, 83.3%). Twenty-six patients (54.2%) developed clinical manifestations compatible with CIN during or immediately after the procedure, and the most frequent manifestations were encephalopathy, cortical blindness and motor deficit. The most frequent imaging findings were cortical contrast enhancement on CT (n = 23/42), and cortical sulci effacement (n = 18/48). Most patients presented complete clinical recovery (89.6%) at a median time of 3 days. Among patients with neuroimaging changes who underwent follow-up, complete regression of the abnormalities was shown in 81.5% at a median time of 5 days. CIN is a rare adverse reaction in the context of neurological endovascular procedures. Recognition of clinical manifestations and typical imaging abnormalities, while excluding other causes, is essential for diagnosis.

Patient Safety Analysis in Radiation Burden of Head Computed Tomography Imaging in 1185 Neurosurgical Inpatients.

OBJECTIVE: We performed a retrospective analysis in a cohort of 1185 patients at our institution who were identified as undergoing ≥1 head computed tomography (CT) examinations during their inpatient stay on the neurosurgery service, to quantify the number, type, and associated radiation burden of head CT procedures performed by the neurosurgery service. METHODS: CT procedure records and radiology reports were obtained via database search and directly validated against records retrieved from manual chart review. Next, dosimetry data from the head CT procedures were extracted via automated text mining of electronic radiology reports. RESULTS: Among 4510 identified adult head CT procedures, 88% were standard head CT examinations. A total of 3.65 ± 3.60 head CT scans were performed during an average adult admission. The most common primary diagnoses were neoplasms, trauma, and other hemorrhage. The median cumulative effective dose per admission was 5.66 mSv (range, 1.06-84.5 mSv; mean, 8.56 ± 8.95 mSv). The median cumulative effective dose per patient was 6.4 mSv (range, 1.1-127 mSv; mean, 9.26 ± 10.0 mSv). CONCLUSIONS: The median cumulative radiation burden from head CT imaging in our cohort equates approximately to a single chest CT scan, well within accepted limits for safe CT imaging in adults. Refined methods are needed to characterize the safety profile of the few pediatric patients identified in our study.

Brain Iron Distribution after Multiple Doses of Ultra-small Superparamagnetic Iron Oxide Particles in Rats.

The purpose of this study is to determine the effects of high cumulative doses of ultra-small paramagnetic iron oxide (USPIO) used in neuroimaging studies. We intravenously administered 8 mg/kg of 2 USPIO compounds daily for 4 wk to male Sprague-Dawley rats (Crl:SD). Multiecho gradient-echo MRI, serum iron levels, and histology were performed at the end of dosing and after a 7-d washout period. R2* maps and quantitative susceptibility maps (QSM) were generated from multiecho gradient-echo data. R2* maps and QSM showed iron accumulation in brain ventricles on MR images acquired at the 4- and 5-wk time points. Estimates from QSM data showed ventricular iron concentration was equal to or higher than serum iron concentration. Histologic analysis revealed choroid plexus hemosiderosis and midbrain vacuolation, without iron deposition in brain parenchyma. Serum iron levels increased with administration of both compounds, and a 7-d washout period effectively reduced serum iron levels of one but not both of the compounds. High cumulative doses from multiple, frequent administrations of USPIO can lead to iron deposition in brain ventricles, resulting in persistent signal loss on T2*-weighted images. Techniques such as QSM are helpful in quantifying iron biodistribution in this situation.

Frequency and Risk Factors for Cerebral Arterial Disease in a HIV/AIDS Neuroimaging Cohort.

BACKGROUND: Infection with HIV predisposes patients to a myriad of neurologic disorders, including cerebrovascular disease. The pathophysiology is likely multifactorial, with proposed mechanisms including infectious vasculitis, HIV-induced endothelial dysfunction and adverse effects of combination antiretroviral therapy (cART). Epidemiologic data on clinically evident cerebral vasculopathy in HIV-infected adults is scarce, even though stroke hospitalizations are rising in this patient population. METHODS: A total of 6,298 HIV-infected adults (San Francisco General Hospital, 2000-2013) were screened to generate a cohort of patients with dedicated neuroimaging of the intra- and extracranial cerebral vasculature. We extracted information regarding the extent of HIV disease (including serial viral load and CD4 counts), cardiovascular disease risk factors and exposure to cART (cross-referenced with pharmacy records) and performed multivariate logistic regression analysis to identify predictors of vasculopathy. RESULTS: Of 144 patients, 55 patients (38.2%) had radiographic evidence of cerebral vasculopathy. Twenty (13.9%) had a vasculopathy characterized by vessel dolichoectasia and intracranial aneurysm formation. Thirty-five patients (24.3%) had intra- and or extracranial stenosis/occlusion. cART use (OR 2.27, 95% CI 1.03-5) and tobacco abuse (OR 2.35, 95% CI 1.04-5.25) were independently associated with the development of any vasculopathy, whereas cART use was also an independent risk factor for the stenosis/occlusion subtype specifically (OR 2.87, 95% CI 1.11-7.45). CONCLUSIONS: There was a high frequency of cerebral arterial disease in this neuroimaging cohort of HIV/AIDS patients. A history of cART use and a history of tobacco abuse were independent risk factors for vasculopathy, though these findings should be confirmed with large-scale prospective studies.

Strategies for Computed Tomography Radiation Dose Reduction in Pediatric Neuroimaging.

BACKGROUND: Radiation exposure from diagnostic imaging is a significant concern, particularly in the care of pediatric patients. Computed tomography (CT) scanning is a significant source of radiation. OBJECTIVE: To demonstrate that diagnostic quality CT images can be obtained while minimizing the effective radiation dose to the patient. METHODS: In this retrospective cross-sectional study, noncontrast head CT scan data were reviewed, and indications for scans and estimated radiation dose delivered were recorded. The estimated effective radiation dose (EERD) for each CT protocol was reviewed. RESULTS: We identified 251 head CT scans in a single month. Of these, 96 scans were using a low-dose shunt protocol with a mean EERD of 0.82 mSv. The remaining 155 scans were performed using the standard protocol, and the mean EERD was 1.65 mSv. Overall, the EERD was minimized while maintaining diagnostic scan quality. CONCLUSION: Although replacing a CT with magnetic resonance imaging is ideal to completely avoid ionizing radiation, this is not always practical or preferred. Therefore, it is important to have CT protocols in place that minimize radiation dose without sacrificing diagnostic quality. The protocols in place at our institution could be replicated at other academic and community hospitals and imaging centers.

Comparative effectiveness of frame-based, frameless, and intraoperative magnetic resonance imaging-guided brain biopsy techniques.

OBJECTIVE: To compare the diagnostic yield and safety profiles of intraoperative magnetic resonance imaging (MRI)-guided needle brain biopsy with 2 traditional brain biopsy methods: frame-based and frameless stereotactic brain biopsy. METHODS: A retrospective analysis was performed of 288 consecutive needle brain biopsies in 277 patients undergoing stereotactic brain biopsy with any of the 3 biopsy methods at Brigham and Women's Hospital from 2000-2008. Variables including age, sex, history of radiation and previous surgery, pathology results, complications, and postoperative length of hospital stay were analyzed. RESULTS: Over the course of 8 years, 288 brain biopsies were performed. Of these, 253 (87.8%) biopsies yielded positive diagnostic tissue. Young age (<40 years old) and history of brain radiation or surgery were significant negative predictors for a positive biopsy diagnostic yield. Excluding patients with prior radiation or surgeries, no significant difference in diagnostic yield was detected among the 3 groups, with frame-based biopsies yielding 96.9%, frameless biopsies yielding 91.8%, and intraoperative MRI-guided needle biopsies yielding 89.9% positive diagnostic yield. Serious adverse events occurred 19 biopsies (6.6%). Intraoperative MRI-guided brain biopsies were associated with less serious adverse events and the shortest postoperative hospital stay. CONCLUSIONS: Frame-based, frameless stereotactic, and intraoperative MRI-guided brain needle biopsy techniques have comparable diagnostic yield for patients with no prior treatments (either radiation or surgery). Intraoperative MRI-guided brain biopsy is associated with fewer serious adverse events and shorter hospital stay.

Neuroimaging during pregnancy.

Pregnancy can be associated with a wide variety of neurologic problems, resulting from alterations in physiology of the pregnant state. The pregnant patient presenting with neurologic symptoms poses both diagnostic and therapeutic challenges. The physician will often require some form of neuroimaging as part of their ongoing evaluation. This review discusses potential risks to the embryo and fetus that can be caused by undergoing computed tomography (CT) and magnetic resonance imaging (MRI), including those associated with the administration of intravenous contrast. Neurologic diseases or syndromes specifically associated with pregnancy are also discussed.