Elevated Venous Pressure Research Articles

Elevated Arterial-Central Venous Carbon Dioxide Partial Pressure Difference Indicates Poor Prognosis in the Early Postoperative Period of Open Heart Surgery in Infants with Congenital Heart Disease.

Elevated arterial-central venous carbon dioxide partial pressure difference (AVCO2) may be an important marker to predict tissue and organ hypoperfusion in adults. We analyzed the hemodynamic data of infants with congenital heart disease who underwent corrective repair with cardiopulmonary bypass (CPB) to identify whether AVCO2 has clinical significance in early postoperative tissue hypoperfusion, occurrence of complications, and clinical outcomes. Infants with clinical conditions of hypoperfusion, without volume responsiveness and with ineffective initial treatment, within 3h of cardiac surgery were enrolled in this study. A pulse contour cardiac output catheter was used to monitor the cardiac index (CI). Eight measurements of arterial blood gas and central venous blood gas were taken within 42h after surgery. Clinical data of all patients were recorded. A total of 69 children were enrolled in this study. Arteriovenous oxygen difference, AVCO2, lactic acid level, and vasoactive inotropic score in the hypoperfusion group (oxygen supply/oxygen consumption ratio [DO2/VO2] of ≤ 2) were significantly higher than those in the non-hypoperfusion group (DO2/VO2 > 2), while the CI in the hypoperfusion group was significantly lower than that in the non-hypoperfusion group. The cutoff value of AVCO2 to predict DO2/VO2 ≤ 2 was 12.3 within 42h of surgery with area under the curve of 0.84. High AVCO2 is more likely to be associated with some complications and prolonged mechanical ventilation and length of stay in the intensive care unit. Elevated AVCO2 within 42h of CPB in infants is associated with tissue and organ hypoperfusion and incidence of complications. Persistent or repeated increase in AVCO2 indicates poor prognosis.

Nodular regenerative hyperplasia in X-linked agammaglobulinemia: An underestimated and severe complication

Late-onset complications in X-linked agammaglobulinemia (XLA) are increasingly recognized. Nodular regenerative hyperplasia (NRH) has been reported in primary immunodeficiency but data in XLA are limited. This study sought to describe NRH prevalence, associated features, and impact in patients with XLA. Medical records of all patients with XLA referred to the National Institutes of Health between October 1994 and June 2019 were reviewed. Liver biopsies were performed when clinically indicated. Patients were stratified into NRH+ or NRH- groups, according to their NRH biopsy status. Fisher exact test and Mann-Whitney test were used for statistical comparisons. Records of 21 patients with XLA were reviewed, with a cumulative follow-up of 129 patient-years. Eight patients underwent ≥1 liver biopsy of whom 6 (29% of the National Institutes of Health XLA cohort) were NRH+. The median age at NRH diagnosis was 20 years (range, 17-31). Among patients who had liver biopsies, alkaline phosphatase levels were only increased in patients who were NRH+ (P= .04). Persistently low platelet count (<100,000 per μL for >6 months), mildly to highly elevated hepatic venous pressure gradient and either hepatomegaly and/or splenomegaly were present in all patients who were NRH+. In opposition, persistently low platelet counts were not seen in patients who were NRH-, and hepatosplenomegaly was observed in only 1 patient who was NRH-. Hepatic venous pressure gradient was normal in the only patient tested who was NRH-. All-cause mortality was higher among patients who were NRH+ (5 of 6, 83%) than in the rest of the cohort (1 of 15, 7% among patients who were NRH- and who were classified as unknown; P= .002). NRH is an underreported, frequent, and severe complication in XLA, which is associated with increased morbidity and mortality.

Abdominal Imaging of Children and Young Adults With Fontan Circulation: Pathophysiology and Surveillance.

OBJECTIVE. The Fontan procedure has significantly improved the survival in children with a functional single ventricle, but it is associated with chronically elevated systemic venous pressure that leads to multisystemic complications. Imaging plays an important role in assessing these complications and guiding management. The pathophysiology, imaging modalities, and current surveillance recommendations are discussed and illustrated. CONCLUSION. Significant improvement in survival of patients with Fontan circulation is associated with ongoing cardiac and extracardiac comorbidities and multisystemic complications. The liver and intestines are particularly vulnerable to damage. In addition, this patient population has been shown to be at increased risk of certain malignancies such as hepatocellular carcinoma and neuroendocrine tumors. Familiarity with imaging findings of Fontan-associated liver disease and other abdominal complications of the Fontan circulation is essential for radiologists because we are likely to encounter these patients in our general practice.

Radius maumenee syndrome - Idiopathic elevated episcleral venous pressure

A 42-year-old female patient has been referred for high intraocular pressure (IOP) in both eyes (BE). Examination revealed dilated, tortuous conjunctival, and episcleral vessels in BE with no apparent cause, also the patient had advanced glaucomatous damage in the left eye (LE). A diagnosis of bilateral idiopathic elevated episcleral venous pressure with secondary open-angle glaucoma (Radius Maumenee syndrome) was made. She was treated with aqueous suppressants in BE and underwent Partial diode cyclophotocoagulation in LE for control of high IOP. Nearly 50–55 cases have been reported till now. We publish here as this is a rare entity; also we discuss certain management controversies and provide literature review about this entity.

B-type natriuretic peptide/ferritin ratio as a predictor of the risk of developing acute renal injury in acute decompensated heart failure.

OBJECTIVES:Acute decompensated heart failure (ADHF) is a clinical condition that requires urgent diagnosis and treatment. Patients present with pulmonary capillary wedge pressure, pulmonary arterial pressure, and venous pressure elevation. Along with the progressive deterioration observed in the clinical picture, impairment or deterioration of kidney function may also occur. In this study, we evaluated the B-type natriuretic peptide (BNP)/ferritin ratio as a predictor of the risk of developing acute renal injury (ARI) in ADHF.METHODS:A total of 157 patients with a diagnosis of ischemic dilated cardiomyopathy for more than 6 months that presented to our clinic with ADHF were included in this cohort study. After the treatment protocol was applied, the sample was divided into two groups as patients with and without ARI. The BNP and ferritin levels were examined along with the routine blood parameters (BNP), and the BNP, ferritin, and BNP/ferritin values were compared between the groups.RESULTS:ARI was present in 34.3% (n = 54) of the patients, who were also found to have higher BNP (892.76 vs. 817.54), lower ferritin (86.78 ± 57.2 vs. 105.46 ± 38.3), and higher BNP/ferritin (10.48 ± 2.14 vs. 7.89 ± 1.89). The multivariate logistic regression analysis revealed the BNP/ferritin ratio as an independent risk factor for ARI (odds ratio = 3.19; 95% CI, 1.92-6.54; P = 0.001). Using the receiver operating characteristic curve, a cutoff value of 9.32 for BNP/ferritin ratio had a sensitivity of 81.8% and a specificity of 93.5% (area under the curve 0.842, P < 0.001) for the prediction of ARI.CONCLUSION:The BNP/ferritin ratio is a new parameter that can be used to draw attention to the severity of the treatment and renal function in ADHF cases in emergency situations.

Bilateral facial palsy in cerebral venous sinus thrombosis – An uncommon association

Background: Cranial nerve palsy in cerebral venous sinus thrombosis (CVST) is not a very common presentation, its pathophysiology is not well understood. Case Description: We report a 27 year old young man with CVST having protein-S deficiency & hyperhomocystinemia, who during his initial days of hospitalization developed bilateral facial palsy. With conservative treatment of CVST, complete recovery of facial palsy occurred with recanalization of transverse sinus. Conclusions: Facial palsy in this patient was probably caused by transient neurapraxia in the intracranial segment of the nerve. It may be hypothesised that elevated venous transmural pressure in the nerve’s satellite vein, which belongs to the affected drainage territory of the transverse sinus, might have caused venous blood-brain barrier dysfunction in the intrinsic vascular system of the nerve, with leakage of fluids and ions into the endoneurial space and thus an increase in interstitial resistance causing conduction defects.

Transcriptomic Bioinformatic Analyses of Atria Uncover Involvement of Pathways Related to Strain and Post-translational Modification of Collagen in Increased Atrial Fibrillation Vulnerability in Intensely Exercised Mice.

Atrial Fibrillation (AF) is the most common supraventricular tachyarrhythmia that is typically associated with cardiovascular disease (CVD) and poor cardiovascular health. Paradoxically, endurance athletes are also at risk for AF. While it is well-established that persistent AF is associated with atrial fibrosis, hypertrophy and inflammation, intensely exercised mice showed similar adverse atrial changes and increased AF vulnerability, which required tumor necrosis factor (TNF) signaling, even though ventricular structure and function improved. To identify some of the molecular factors underlying the chamber-specific and TNF-dependent atrial changes induced by exercise, we performed transcriptome analyses of hearts from wild-type and TNF-knockout mice following exercise for 2 days, 2 or 6 weeks of exercise. Consistent with the central role of atrial stretch arising from elevated venous pressure in AF promotion, all 3 time points were associated with differential regulation of genes in atria linked to mechanosensing (focal adhesion kinase, integrins and cell-cell communications), extracellular matrix (ECM) and TNF pathways, with TNF appearing to play a permissive, rather than causal, role in gene changes. Importantly, mechanosensing/ECM genes were only enriched, along with tubulin- and hypertrophy-related genes after 2 days of exercise while being downregulated at 2 and 6 weeks, suggesting that early reactive strain-dependent remodeling with exercise yields to compensatory adjustments. Moreover, at the later time points, there was also downregulation of both collagen genes and genes involved in collagen turnover, a pattern mirroring aging-related fibrosis. By comparison, twofold fewer genes were differentially regulated in ventricles vs. atria, independently of TNF. Our findings reveal that exercise promotes TNF-dependent atrial transcriptome remodeling of ECM/mechanosensing pathways, consistent with increased preload and atrial stretch seen with exercise. We propose that similar preload-dependent mechanisms are responsible for atrial changes and AF in both CVD patients and athletes.

Hepatocellular carcinoma after Fontan surgery: A systematic review

Fontan surgery is often the procedure of choice for patients with congenital single effective ventricle. In the long term, elevated systemic venous pressure and chronic ischemia following this procedure could lead to advanced chronic liver disease and there is also a risk of hepatocellular carcinoma (HCC). This review systematically summarizes the characteristics and outcomes of this rare condition. PubMed and Embase databases were searched from inception to January 2020 for studies reporting on HCC after Fontan surgery. The factors analyzed were clinical presentation, histology, imaging findings, treatments, and survival. Our primary analysis was based on biopsy-proven HCC. The records selected were 26 observational studies (19 case reports/case series and seven cohort studies) including 65 biopsy-proven HCC. Age at the time of HCC diagnosis ranged from 12 to 52years, and 62% of the patients were female. Only one case occurred earlier than 10 years after Fontan surgery. Twenty patients had no imaging or histological evidence of liver cirrhosis and 78.3% had elevated α-fetoprotein levels. Advanced stage was the most common at diagnosis. The most frequent treatments were transarterial chemoembolization (n = 18) and surgery (n = 12). One-year survival was 50% and only four patients (6.2%) were under liver imaging surveillance. We also analyzed 17 patients with non-biopsy-proven HCC. After Fontan surgery, HCC usually occurs at least 10 years later and can develop in the absence of cirrhosis. Biopsy is mandatory to confirm the diagnosis. Patients were diagnosed at a late stage and survival outcomes were poor, highlighting a need for liver surveillance.

Valsalva Choroidopathy: A Rare Manifestation of Acutely Elevated Venous Pressure

Valsalva Choroidopathy: A Rare Manifestation of Acutely Elevated Venous Pressure

Reversal of blood flow in deep cerebral vein in preterm intraventricular hemorrhage: two case reports

BackgroundIntraventricular hemorrhage during the early stage is a major complication in very low birth weight infants. Elevation of venous pressure is one of the contributing factors. The internal cerebral vein receives most of the venous flow from the subependymal germinal matrix, the most common site of origin of intraventricular hemorrhage. Recently, it has been reported that pulsatile or partially interrupted internal cerebral vein waveforms might also be risk factors for intraventricular hemorrhage in extremely low birth weight infants. Here, we report two cases of partially reversed internal cerebral vein flow with intraventricular hemorrhage. There are no published reports documenting this unique flow pattern.Case presentationBetween 2013 and 2020, we had in our neonatal intensive care unit two cases of very low birth weight infants (27 and 25 weeks of gestational age) who showed a partially reversed internal cerebral vein waveform pattern, which was recognized as a new blood flow pattern. Their internal cerebral vein flow patterns were continuously flat early after birth. They showed an intraventricular hemorrhage on the unilateral side with partially interrupted internal cerebral vein flow at 31 and 41 hours after birth (27- and 25-week-old neonates, respectively). Consecutively, their internal cerebral vein flow changed to a partially reversed pattern with intraventricular hemorrhage on the contralateral side at 43 and 87 hours after birth (27- and 25-week-old neonates, respectively). Their flow patterns improved by day 7. These partially reversed patterns were equivalent to triphasic venous flow, and the reverse flow corresponded to A- and V-waves.ConclusionIn the two cases, the internal cerebral vein flow patterns were normal and flat before intraventricular hemorrhage and changed to a severe flow pattern (partially interrupted or reversed flow) at the same time as the detection of intraventricular hemorrhage. After the development of intraventricular hemorrhage, they improved. These cases indicate that a partially reversed or interrupted internal cerebral vein flow pattern may be derived from central venous pressure elevation and related to intraventricular hemorrhage in very low birth weight infants, however, it is difficult to determine when this flow pattern occurs in relation to intraventricular hemorrhage.

TRANSUDATIVE CHYLOTHORAX IN LIVER CIRRHOSIS: A RARE MANIFESTATION OF PORTAL HYPERTENSION

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Hepatic hydrothorax is a well-recognized pulmonary complication of decompensated liver cirrhosis that can be found in 5-11% of cases. It typically presents as exertional dyspnea in patients with Child-Pugh Class (CPC) B or C cirrhosis and abdominal ascites. The pleural effusion involves the right lung approximately 80% of the time, and pleural fluid analysis is consistent with a transudative effusion. Underlying infection or malignancy should be ruled out. Transudative chylothorax is an exceedingly rare manifestation of portal hypertension in this patient population. CASE PRESENTATION: A 46-year-old man with CPC B, MELD 19 alcoholic liver cirrhosis who recently underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure with revisions for refractory ascites, presented with progressive cough and dyspnea on exertion for 2 weeks. He reported needing a therapeutic paracentesis approximately every 10 days prior to TIPS; however, since his most recent TIPS revision 4 weeks prior to presentation, he did not have recurrence of his ascites. Exam was notable for diminished breath sounds throughout the right lung fields and trace ascites. Chest radiograph revealed a moderate pleural effusion at the right lower lobe. A thoracentesis yielded 1.5 liters of milky yellow fluid with initial labs suggesting a transudative effusion. A chest tube was placed. Given the milky appearance, further studies were sent, revealing triglycerides at 335 mg/dL and cholesterol at 11 mg/dL, consistent with chylothorax. To evaluate for other etiologies of chylothorax, lymphoscintigraphy was performed, which did not reveal any lymphatic leak or thoracic duct injury. A CT scan of the chest did not demonstrate any lesions concerning for infection or malignancy, and pleural fluid cultures and cytology confirmed the absence of either. The patient underwent TIPS revision with angioplasty, with improvement of the transhepatic pressure gradient. The patient was discharged after increasing his home dose of diuretics and remained asymptomatic at his follow-up appointment 1 week later. DISCUSSION: Liver cirrhosis is an underappreciated cause of chylothorax, with only about 20 cases described in the literature. The pathophysiologic mechanism is thought to be mediated by elevated venous pressures caused by portal hypertension. Diagnostic thoracentesis is required in these patients to rule out malignancy or infection, which are also known etiologies of chylothorax. When the effusion is transudative, interventions aimed at decreasing portal hypertension, such as TIPS, should be considered to prevent recurrence of the chylothorax. CONCLUSIONS: Chylothorax is a rare complication of liver cirrhosis that can be successfully treated by medically managing ascites and/or by TIPS. Reference #1: Chaaban T, Kanj N, Aki IB. Hepatic hydrothorax: an updated review on a challenging disease. Lung. 2019; 197:399-405. Reference #2: Mukherjee A, Sehgal IS, Mittal BR, Dhooria S. Transudative chylothorax: an uncommon illness due to a common cause. BMJ Case Rep. 2018; Feb 7. pii: bcr-2017-223158. Reference #3: Tsauo J, Hoon Shin J, Han K, Yoon HK, Ko GY, Ko HK, Gwon DI. Transjugular intrahepatic portosystemic shunt for the treatment of chylothorax and chylous ascites in cirrhosis: a case report and systematic review of the literature. J Vasc Interv Radiol. 2016; 27: 112-116. DISCLOSURES: No relevant relationships by Argin Baghramian, source=Web Response No relevant relationships by Stefano Iantorno, source=Web Response No relevant relationships by Sonia Lin, source=Web Response No relevant relationships by Alex Rosenberg, source=Web Response

Multisensor Remote Monitoring for Heart Failure Exacerbations in Patients with Left Ventricular Assist Devices

Background Continuous flow left ventricular assist devices (cfLVADs) have improved outcomes for advanced Heart Failure (HF) patients. Recurrent HF continues to be a complication and clinical examination is limited by the nature of the LVAD therapy requiring better diagnostics to improve patient outcomes. Methods We describe a multisensory diagnostic in two LVAD patients. Results Two patients with end-stage HF supported with a HeartMate II and HeartMate III containing a multisensor diagnostic for HF (HeartLogic) presented to clinic with exercise intolerance. In both, exam revealed no elevation of venous pressure, lungs were clear and no heart sounds were appreciated above the normal LVAD hum. On right heart catheterization of patient A, RA pressure was 14 mmHg, PCWP 18 mmHg and CI 1.9 L/min/m2. LVAD speed was increased from 10,000 to 10,400 rpm. Similarly, elevated filling pressures were seen with patient B, who had LVAD speed increased as well. In both cases, S3 magnitude decreased following LVAD speed increase. Both patients later had outpatient alerts detected and diuretics were doubled until alert resolution. In each instance, the clinical events were associated with a HeartLogic alert, and remarkably, the S3 changed in manner consistent with the interventions that occurred although clinicians could not appreciate an S3. Conclusion These cases demonstrate that a multisensory HF diagnostic changes and alerts during clinically meaningful events that is useful in the management of LVAD patients.

CT angiography identifies collaterals in dogs with splenic vein obstruction and presumed regional splenic vein hypertension

Occlusion of the splenic vein, without occlusion of the portal vein, can lead to a localized, regional splenic hypertension, referred as sinistral or left-sided portal hypertension in the human radiology literature. In people, may cause gastrointestinal hemorrhages from the esophageal and gastric varices and the primary pathology usually includes pancreatitis and pancreatic neoplasms. The final diagnosis of localized splenic hypertension necessitates accompanying normal liver functions and a patent extrahepatic portal vein. Following obstruction, the resultant elevated splenic bed venous pressure causes formation of collateral routes, the extent of which depends upon the level and degree of obstruction. In this retrospective descriptive study, authors assessed the collateral pathways in dogs with isolated splenic vein occlusion and possible regional splenic vein hypertension. Out of the 46 patients initially recruited, 25 were excluded due to the presence of concomitant portal thrombosis and direct/indirect CT signs of portal hypertension. The remaining 21 dogs had clinicopathological tests suggesting normal liver function. The causes of obstruction identified included splenic pedicle torsion, tumoral splenic vein invasion, and splenic vein thrombosis. Four of 21 dogs with isolated splenic vein obstruction showed collateral pathways through the left gastroepiploic vein (4/4), left gastric vein (2/4), and splenogonadal vein (1/4). The diagnosis of isolated, regional splenic hypertension should be based on clinical, biochemical, and radiological evaluation. Computed tomography is an excellent tool to assess the collateral patterns and to determine the underlying cause.

The incidence of obesity, venous sinus stenosis and cerebral hyperaemia in children referred for MRI to rule out idiopathic intracranial hypertension at a tertiary referral hospital: a 10\xa0year review

BackgroundChildren referred to a tertiary hospital for the indication, “rule out idiopathic intracranial hypertension (IIH)” may have an increased risk of raised venous sinus pressure. An increase in sinus pressure could be due to obesity, venous outflow stenosis or cerebral hyperemia. The purpose of this paper is to define the incidence of each of these variables in these children.MethodsFollowing a data base review, 42 children between the ages of 3 and 15 years were found to have been referred over a 10 year period. The body mass index was assessed. The cross sectional areas and circumferences of the venous sinuses were measured at 4 levels to calculate the hydraulic and effective diameters. The arterial inflow, sagittal and straight sinus outflows were measured. Automatic cerebral volumetry allowed the brain volume and cerebral blood flow (CBF) to be calculated. The optic nerve sheath diameter was used as a surrogate marker of raised intracranial pressure (ICP). The sagittal sinus percentage venous return was used as a surrogate marker of elevated venous pressure. Age and sex matched control groups were used for comparison.ResultsCompared to controls, the obesity rates were not significantly different in this cohort. Compared to controls, those at risk for IIH had a 17% reduction in transverse sinus and 14% reduction in sigmoid sinus effective cross sectional area (p = 0.005 and 0.0009). Compared to controls, the patients at risk for IIH had an arterial inflow increased by 34% (p < 0.0001) with a 9% larger brain volume (p = 0.02) giving an increase in CBF of 22% (p = 0.005). The sagittal and straight sinus venous return were reduced by 11% and 4% respectively (p < 0.0001 and 0.0009) suggesting raised venous sinus pressure. Forty five percent of the patients were classified as hyperemic and these had optic nerve sheath diameters 17% larger than controls (p < 0.0002) suggesting raised ICP.ConclusionIn children with the chronic headache/ IIH spectrum, the highest associations were with cerebral hyperemia and mild venous sinus stenosis. Obesity was not significantly different in this cohort. There is evidence to suggest hyperemia increases the venous sinus pressure and ICP.

Syndrome de Radius-Maumenee : une cause rare de glaucome

Radius-Maumenee syndrome is a rare cause of severe secondary open-angle glaucoma. The ocular hypertension is due to episcleral venous hypertension. This syndrome consists of open angle glaucoma and episcleral venous dilatation without orbital or systemic abnormalities. It is diagnosis of exclusion after ruling out carotid-cavernous fistula, thyroid orbitopathy and an invasive orbital process that might explain the elevated episcleral venous pressure. Treatment begins with glaucoma eyedrops and, in case of failure, filtering surgery. Uveal effusion syndrome and postoperative choroidal detachment are frequent complications of filtering surgery in patients with this syndrome. We present the case report of a 59-year-old woman with Radius-Maumenee syndrome.

Retinal and Optic Nerve Deformations Due to Orbital Versus Intracranial Venous Hypertension.

Abnormal forces around the optic nerve head (ONH) due to orbital diseases, intracranial hypertension (IH), glaucoma, and space travel, are associated with alterations of the ONH shape. Elevated cerebral and ophthalmic venous pressure can contribute to stress and strain on the ONH and peripapillary retina. We hypothesize that IH and elevated ophthalmic venous pressure without IH cause different ONH and retinal changes. We compared MRI and spectral domain optical coherence tomography (SDOCT) findings in patients with cavernous sinus arteriovenous shunts (CSAVSs), where orbital venous pressure is known to be elevated, with patients with intracranial dural venous sinus thrombosis and secondary IH. We also compared the results to those obtained in the Idiopathic IH (IIH) Treatment Trial. Among 18 patients with dural venous sinus thrombosis, the MRI/magnetic resonance venography displayed partial empty sella (61%) and optic nerve sheath distension (67%). None exhibited ophthalmic vein dilation or signs of orbital congestion. SDOCT of these eyes and IIH eyes showed a similar frequency of abnormal thickening of the mean retinal nerve fiber layer, anterior displacement of the basement membrane opening, peripapillary wrinkles, retinal folds (RF), and choroidal folds (CF). Among 21 patients with CSAVSs, MRI showed ipsilateral dilated superior ophthalmic vein (76%) and orbital congestion (52%) without distension of the optic nerve sheath or globe distortion. SDOCT showed CF (19%), one with overlying RF, and no ONH deformations. SDOCT findings for dural venous sinus thrombosis are similar to those seen with IIH but distinct from changes due to local ophthalmic venous hypertension. These data support the concept that IH even if due to a vascular cause and local orbital venous hypertension cause different stresses and strains on the ONH.

Integral role for lysyl oxidase-like-1 in conventional outflow tissue function and behavior.

Lysyl oxidase-like-1 (LOXL1), a vital crosslinking enzyme in elastin fiber maintenance, is essential for the stability and strength of elastic vessels and tissues. Variants in the LOXL1 locus associate with a dramatic increase in risk of exfoliation syndrome (XFS), a systemic fibrillopathy, which often presents with ocular hypertension and exfoliation glaucoma (XFG). We examined the role of LOXL1 in conventional outflow function, the prime regulator of intraocular pressure (IOP). Using Loxl1-/- , Loxl1+/- , and Loxl1+/+ mice, we observed an inverse relationship between LOXL1 expression and IOP, which worsened with age. Elevated IOP in Loxl1-/- mice was associated with a larger globe, decreased ocular compliance, increased outflow facility, extracellular matrix (ECM) abnormalities, and dilated intrascleral veins, yet, no dilation of arteries or capillaries. Interestingly, in living Loxl1-/- mouse eyes, Schlemm's canal (SC) was less susceptible to collapse when challenged with acute elevations in IOP, suggesting elevated episcleral venous pressure (EVP). Thus, LOXL1 expression is required for normal IOP control, while ablation results in altered ECM repair/homeostasis and conventional outflow physiology. Dilation of SC and distal veins, but not arteries, is consistent with key structural and functional roles for elastin in low-pressure vessels subjected to cyclical mechanical stress.

Recombinant Tissue Plasminogen Activator Use in an Acute Stroke Patient With Tuberous Sclerosis

Tuberous sclerosis (TS) is an autosomal dominant disease known for over a century and recognized by characteristic hamartomatous lesions involving any organ. In this report, we are presenting a patient with TS who presented with acute embolic stroke and received tissue plasminogen activator (tPA) and had a mechanical thrombectomy (MT). She had a dramatic response without any hemorrhagic complications. She is a 68-year-old Caucasian woman with the past medical history of TS since childhood who presented to the hospital with symptoms of left middle cerebral artery (MCA) syndrome (right-sided weakness, sensory loss, right facial droop, aphasia, hemianopia, and dysarthria). National Institute of Health Stroke Scale (NIHSS) score was 19. Head computed tomography (CT) was negative for any acute abnormality except cortical tubers, subependymal ventricular calcification. CT angiography of the head and neck showed proximal occlusion of the left internal carotid artery. After ruling out all exclusion criteria, the patient received tPA and had an MT with complete reperfusion (thrombolysis in cerebral infarction (TICI) 3). Brain magnetic resonance imaging (MRI) showed an acute stroke in the multivessel territories (bilateral parietal cortices, the left lentiform nucleus, medial left temporal lobe, left thalamus, and right occipital lobe) suggestive of an embolic phenomenon and did not show any hemorrhagic complication. TS patients are at increased risk of intracerebral hemorrhage either in the setting of vascular malformation or due to hemorrhage into the subependymal giant cell astrocytoma. The best explanation for the latter could be secondary to elevated venous pressure from increased intracranial pressure. Fortunately, our TS patient who presented with acute ischemic stroke was within the window and received tPA and MT. The patient not only did not have any hemorrhagic side effects afterward but also had a significant improvement in her neurologic symptoms. To our best knowledge, this is the only case report of tPA administration in a TS patient. Moreover, we need more case reports to evaluate the safety of tPA in these patients. J Neurol Res. 2020;10(4):140-143 doi: https://doi.org/10.14740/jnr595

52-Year-Old Woman With Fever, Diaphoresis, and Abdominal Pain

52-Year-Old Woman With Fever, Diaphoresis, and Abdominal Pain

Nonalcoholic fatty liver disease and portal hypertension.

Nonalcoholic fatty liver disease (NAFLD) is a substantial and growing problem worldwide and has become the second most common indication for liver transplantation as it may progress to cirrhosis and develop complications from portal hypertension primarily caused by advanced fibrosis and erratic tissue remodeling. However, elevated portal venous pressure has also been detected in experimental models of fatty liver and in human NAFLD when fibrosis is far less advanced and cirrhosis is absent. Early increases in intrahepatic vascular resistance may contribute to the progression of liver disease. Specific pathophenotypes linked to the development of portal hypertension in NAFLD include hepatocellular lipid accumulation and ballooning injury, capillarization of liver sinusoidal endothelial cells, enhanced contractility of hepatic stellate cells, activation of Kupffer cells and pro-inflammatory pathways, adhesion and entrapment of recruited leukocytes, microthrombosis, angiogenesis and perisinusoidal fibrosis. These pathological events are amplified in NAFLD by concomitant visceral obesity, insulin resistance, type 2 diabetes and dysbiosis, promoting aberrant interactions with adipose tissue, skeletal muscle and gut microbiota. Measurement of the hepatic venous pressure gradient by retrograde insertion of a balloon-tipped central vein catheter is the current reference method for predicting outcomes of cirrhosis associated with clinically significant portal hypertension and guiding interventions. This invasive technique is rarely considered in the absence of cirrhosis where currently available clinical, imaging and laboratory correlates of portal hypertension may not reflect early changes in liver hemodynamics. Availability of less invasive but sufficiently sensitive methods for the assessment of portal venous pressure in NAFLD remains therefore an unmet need. Recent efforts to develop new biomarkers and endoscopy-based approaches such as endoscopic ultrasound-guided measurement of portal pressure gradient may help achieve this goal. In addition, cellular and molecular targets are being identified to guide emerging therapies in the prevention and management of portal hypertension.