Acute blood pressure elevation associated with biological therapies for cancer: a focus on VEGF signaling pathway inhibitors.

INTRODUCTION: Treatment with biological agents interfering with mechanisms of angiogenesis, such as vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors, was associated with an enhanced risk of acute and severe blood pressure (BP) increase and development of hypertensive emergencies. Areas covered: The present article will review the scientific literature reporting hypertensive emergencies as a complication of biological treatment with VSP inhibitors. Hypertensive emergency is a life-threatening condition characterized by very high BP values (>180/110 mmHg) associated with acute organ damage. The exact mechanism of action is still incompletely clarified. Endothelial dysfunction following reduced bioavailability of nitric oxide has been hypothesized to play an important role in promoting hypertension and the occurrence of acute organ damage. Expert opinion: Prevention, prompt recognition and treatment of hypertensive emergencies associated with treatment with VSP-inhibitors are essential to reduce the risk of adverse events. Not infrequently, the occurrence of hypertensive emergency led to VSP treatment discontinuation, with potential negative consequences on patient overall survival. The present review aims at providing detailed knowledge for the clinician regarding this specific issue, which could be of high impact in usual clinical practice, given the increasing burden of indications to treatment with biological agents targeted to the VEGF pathway.

Encefalopatía posterior reversible en el curso de una emergencia hipertensiva, serie de cuatro niños hospitalizados en el Centro Hospitalario Pereira Rossell / Posterior reversible encephalopathy during a hypertensive emergency in 4 children hospitalized at the Pereira Rossell Pediatric Hospital / Encefalopatia reversível durante uma emergência hipertensiva em 4 crianças hospitalizadas no Centro Hospitalar Pereira Rossell

Introducción: la encefalopatía posterior reversible (PRES) es un complejo sindromático caracterizado por cefaleas, crisis epilépticas, trastornos visuales y alteración del sensorio asociado a cambios en la sustancia blanca de lóbulos occipitales y parietales en la resonancia nuclear magnética. Se relaciona con diversas causas que provocan edema cerebral, entre las que se destaca la hipertensión arterial (HTA) y los tratamientos inmunosupresores. Descripción de casos: se incluyeron cuatro niños hospitalizados entre el 1 de enero de 2005 y el 31 de diciembre de 2015 en el Centro Hospitalario Pereira Rossell. La mediana de edad fue 11,5 años. La manifestación clínica inicial en tres de los cuatro pacientes fue disnea y edemas generalizados. Todos presentaron hipertensión endocraneana y convulsiones generalizadas. La tomografía computada fue la primera imagen solicitada en todos los pacientes, evidenciado lesiones hipodensas córtico-subcorticales occipitales, parietales y frontales. Se realizó resonancia magnética en tres casos con hallazgos característicos. Todos presentaron síndrome nefrítico con cifras de tensión arterial mayores al P99, insuficiencia renal reversible, disminución de C3 y aumento del antiestreptolisina O (AELO). El control de HTA requirió politerapia en unidad de cuidado crítico. Ninguno presentó secuelas neurológicas. Conclusiones: la PRES es una asociación o manifestación poco habitual de la emergencia hipertensiva. Es necesaria la sospecha e identificación por parte del pediatra con el fin de realizar un abordaje terapéutico adecuado y precoz.

Introduction: posterior reversible encephalopathy (PRES) is a complex syndrome characterized by headaches, epileptic seizures, visual disturbances and sensorial alterations associated to changes of white matter in parieto-occipital regions shown in magnetic nuclear resonance. It is linked to various causes that provoke cerebral edema including arterial hypertension (AH) and immunosuppressive treatments. Clinical cases: 4 children admitted between January 1st, 2005 and December 31st, 2015 at the Pereira Rossell Pediatric Hospital. Median age: 11.5 years. The initial clinical manifestation in 3 of 4 patients was dyspnea and generalized edema. All of them presented endocranial hypertension and generalized convulsions. CT was the first requested image to all patients, and it was clear that all of them had experienced occipital cortical-subcortical, parietal and frontal hypodense lesions. In three of the cases we performed a Magnetic Resonance that showed typical findings. All of them presented nephritic syndrome with arterial hypertension over P99, reversible renal failure, a decrease of C3 and an increase of Antistreptolysin O (AELO). HTA control required polytherapy at the critical care unit. None of them presented neurological sequelae. Conclusions: PRES is an association or unusual manifestation of hypertensive emergency. Early detection by pediatricians seems essential to provide an appropriate therapeutic approach.

Introdução: a encefalopatia posterior reversível (PRES) é uma síndrome complexa caracterizada por dores de cabeça, convulsões epilépticas, distúrbios visuais e alterações sensoriais associadas à mudança da substância branca nas regiões parieto-occipitais observadas na ressonância magnética nuclear. Está ligada a várias causas que provocam o edema cerebral, incluindo hipertensão arterial (HA) e tratamentos imunossupressores. Casos clínicos: 4 crianças internadas entre 1º de janeiro de 2005 e 31 de dezembro de 2015 no Hospital Pediátrico Pereira Rossell. Idade mediana: 11,5 anos. A manifestação clínica inicial em 3 dos 4 pacientes foi dispneia e edema generalizado. Todos apresentaram hipertensão endocraniana e convulsões generalizadas. A TC foi a primeira imagem solicitada e todos os pacientes mostraram lesões occipitais corticais-subcorticais, parietais e hipodensas frontais evidentes. Em três dos casos, a Ressonância Magnética mostrou achados típicos. Todos apresentaram síndrome nefrítica com hipertensão arterial acima de P99, insuficiência renal reversível, diminuição de C3 e aumento de antiestreptolisina O (AELO). O controle de HTA requereu politerapia na unidade de terapia intensiva. Nenhum dos pacientes apresentou sequelas neurológicas. Conclusões: A PRES é uma associação ou manifestação de emergência hipertensiva pouco comum. A detecção precoce do pediatra é essencial para fornecer uma abordagem terapêutica adequada.

New Developments in Hypertensive Encephalopathy.

PURPOSE OF REVIEW: This review summarizes the latest science on hypertensive encephalopathy and posterior reversible encephalopathy syndrome (PRES). We review the epidemiology and pathophysiology of these overlapping syndromes and discuss best practices for diagnosis and management. RECENT FINDINGS: Diagnosis of hypertensive encephalopathy largely relies on exclusion of other neurological emergencies. We review the extensive causes of PRES and its imaging characteristics. Management strategies have not changed substantially in the past decade, though newer calcium channel blockers simplify the approach to blood pressure reduction. While this alone may be sufficient for treatment of hypertensive encephalopathy in most cases, management of PRES also depends on modification of other precipitating factors. Hypertensive encephalopathy and PRES are overlapping disorders for which intensive blood pressure lowering is critical. Further research is indicated to both in diagnosis and additional management strategies for these critical conditions.

Venous hypertensive encephalopathy secondary to venous sinus thrombosis and dural arteriovenous fistula.

A 52-year-old man with a history of factor V Leiden thrombophilia, persistent headaches and papilloedema presented with worsening vision and confusion. MRI and MR angiography of the brain at the time of this presentation showed findings concerning for transverse sinus thrombosis and an associated dural arteriovenous fistula. Dural venous sinus thrombosis can lead to the formation of a dural arteriovenous fistula, which must be considered in the differential diagnosis for intracranial hypertension in patients with thrombophilia.

Multidisciplinary Approach to Complicated Pregnancy.

A nulliparous pregnant woman in her mid-20s and in the 32nd week of gestation presented to the emergency department with severe headache and vomiting. She had an uneventful medical history; however, the physical examination upon hospital admission revealed a hypertensive emergency, papilledema, and 2+ dipstick proteinuria. Upon establishing the diagnosis of preeclampsia, aggressive therapy with corticosteroids, antihypertensive medication, and seizure prophylaxis was initiated. Hemodynamic stability was achieved within 24 hours and the patient remained in the observation unit located within the gynecology clinic. On the ninth day postadmission, however, her condition abruptly deteriorated and advanced to imminent eclampsia, accompanied by transient vision loss, altered mental status, and acute hypertensive crisis. After the patient underwent successful emergent delivery via caesarean section, a laboratory workup revealed hemolysis, elevated liver enzymes, and low platelet count, suggesting HELLP syndrome, a serious complication of eclampsia. This patient concurrently developed posterior reversible encephalopathy syndrome, which was confirmed by magnetic resonance imaging and acute respiratory distress syndrome (the latter presented with diffuse bilateral infiltrates on x-ray and developing pulmonary edema in the absence of cardiac etiology). Because of these life-threatening dynamics, the patient was transferred to the intensive care unit for further treatment. This case is a rare cascade of life-threatening complications that developed in a patient and required skillful multidisciplinary decision making and experienced management within an acute critical care setting. The final outcome of the treatment and intensive care was successful because both the patient and child survived and had no chronic or debilitating sequelae.

[Hypertensive urgencies and emergencies]. / Urgencias y emergencias hipertensivas.

Hypertensive urgencies and emergencies are common situations in clinical practice. Hypertensive urgencies are characterized by acute elevation of blood pressure without target organ damage. Hypertensive emergencies are life-threatening situations characterized by acute elevation of blood pressure and target organ damage. The aims of blood pressure control, antihypertensive drugs to use and route of administration will depend on the presence or absence of target organ damage and individual patient characteristics. The correct diagnosis and treatment of these situations are essential for patient prognosis. © 2017 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

A new improved method for assessing brain deformation after decompressive craniectomy.

BACKGROUND: Decompressive craniectomy (DC) is a surgical intervention used following traumatic brain injury to prevent or alleviate raised intracranial pressure. However the clinical effectiveness of the intervention remains in doubt. The location of the craniectomy (unilateral or bifrontal) might be expected to change the brain deformation associated with the operation and hence the clinical outcome. As existing methods for assessing brain deformation have several limitations, we sought to develop and validate a new improved method. METHODS: Computed tomography (CT) scans were taken from 27 patients who underwent DC (17 bifrontal patients and 10 unilateral patients). Pre-operative and post-operative images were processed and registered to determine the change in brain position associated with the operation. The maximum deformation in the herniated brain, the change in volume and estimates of the craniectomy area were determined from the images. Statistical comparison was made using the Pearson's correlation coefficient r and a Welch's two-tailed T-test, with statistical significance reported at the 5% level. RESULTS: There was a reasonable correlation between the volume increase and the maximum brain displacement (r = 0.64), a low correlation between the volume increase and the craniectomy area (r = 0.30) and no correlation between the maximum displacement and the craniectomy area (r = -0.01). The maximum deformation was significantly lower (P  = 0.023) in the bifrontal patients (mean = 22.5 mm) compared with the unilateral patients (mean = 29.8 mm). Herniation volume was significantly lower (P = 0.023) in bifrontal (mean = 50.0 ml) than unilateral patients (mean = 107.3 ml). Craniectomy area was not significantly different for the two craniectomy locations (P = 0.29). CONCLUSIONS: A method has been developed to quantify changes in brain deformation due to decompressive craniectomy from CT images and allow comparison between different craniectomy locations. Measured displacement is a reasonable way to characterise volume changes.

Post-streptococcal glomerulonephritis leading to posterior reversible encephalopathy syndrome: a case report.

BACKGROUND: Posterior reversible encephalopathy syndrome is a clinical radiographic syndrome of heterogeneous etiologies. Developing hypertensive encephalopathy following post-streptococcal glomerulonephritis is a known but uncommon manifestation and developing posterior reversible encephalopathy syndrome in such a situation is very rare. We report a case with contrast-enhanced computed tomography and magnetic resonance imaging findings of posterior reversible encephalopathy syndrome in the background of acute post-streptococcal glomerulonephritis. CASE PRESENTATION: A thirteen-year-old Sri Lankan boy presented with a focal fit by way of secondary generalization with duration of 10 minutes, and developed 2 similar fits subsequently following admission. He later developed severe hypertension with evidence of glomerulonephritis, which was diagnosed as acute post-streptococcal glomerulonephritis. A contrast-enhanced computed tomography imaging of brain done on day-3 revealed non-enhancing low-attenuating areas in fronto-parietal regions. A T2 weighted film of magnetic resonance imaging was done on day-10 of the admission and found to have linier sub-cortical hyper intensities in both parietal regions which were compatible with the radiological diagnosis of posterior reversible encephalopathy syndrome. CONCLUSION: Post-streptococcal glomerulonephritis is an important cause of acute nephritic syndrome especially in children. This case report illustrates a rare association of posterior reversible encephalopathy syndrome in a patient with post-streptococcal glomerulonephritis.

A case of Liddle's syndrome; unusual presentation with hypertensive encephalopathy.

Liddle's syndrome is a rare cause of secondary hypertension. Identification of this disorder is important because treatment differs from other forms of hypertension. We report an interesting case of a 35-year-old lady, a known diabetic and hypertensive patient, who presented with features of hypertensive encephalopathy. The family history was unremarkable. Past treatment with various combinations of antihypertensive medications including spironolactone, all at high doses, failed to control her blood pressure. Upon evaluation, the patient had hypokalemic alkalosis, low 24-h urine potassium and suppressed plasma renin activity. Although these findings were similar to hyperaldosteronism, plasma aldosterone was lower than the normal range. Blood pressure decreased markedly after administration of amiloride. Along with hyporeninemic hypo-aldosteronism, the non-responsiveness to spironolactone and good response to amiloride established the diagnosis of Liddle's syndrome.

Hypertensive encephalopathy as a late complication of autonomic dysreflexia in a 12-year-old boy with a previous spinal cord injury.

UNLABELLED: The scope of paediatric autonomic disorders is not well recognised, and paediatricians seem to be generally unaware of the complexity and diversity of their clinical manifestations. We report a 12-year-old boy presenting with hypertensive encephalopathy caused by autonomic dysreflexia. CONCLUSION: This observation emphasises the importance of the recognition of this rare autonomic disorder, which can have potentially life-threatening neurological complications.

[Neyromidin in the treatment of stage I hypertensive dyscirculatory encephalopathy].

AIM: To evaluate the efficacy and safety of neyromidin in the treatment of Stage I hypertensive dyscirculatory encephalopathy (HDE) and to analyze long-term treatment results. SUBJECTS AND METHODS: Fifty-seven with Stage I dyscirculatory encephalopathy in the presence of grades 1-2 arterial hypertension were examined. Clinical, psychological, and electrophysiological studies were performed and the efficacy of neyromidin was evaluated using the SANDOS geriatric scale. Neyromidin as monotherapy was used as one tablet (20 mg) b.i.d. during a meal. The duration of course treatment was 3 months. RESULTS: Positive changes in the early manifestations of HDE were observed just on day 45 of therapy. The therapeutic effect of the drug manifested as a reduction in the degree of clinical symptoms. There were positive changes in attention, memory, kinetics, verbal associations, counting. The most noticeable improvement was seen in the values of memory and intellectual processes, suggesting higher working capacity, reduced fatigability, and eliminated sluggishness of intellectual processes. EEG displayed a higher amplitude level, a better response to rhythmic photostimulation, and a total power rise in a- and 8-ranges, which was indicative of the activated effect of neyromidin on the functional state of brain structures. CONCLUSION: Neyromidin (20 mg b.i.d. for 3 months) was shown to be effective and well tolerated. The drug reduced the magnitude of clinical manifestations and improved psychological functions and electrophysiological parameters.

Severe posterior reversible encephalopathy in pheochromocytoma: importance of susceptibility-weighted MRI.

Pheochromocytoma is a rare cause of hypertension in children. Hypertension is one of the common reasons of posterior reversible encephalopathy. Intracerebral hemorrhage is a serious and unexpected complication of hypertensive encephalopathy due to pheochromocytoma, and very rarely seen in the childhood. Intracerebral hemorrhages should be searched if there are hypertensive reversible signal changes on the brain. Susceptibility weighted imaging (SWI) is a more sensitive method than conventional MRI when demonstrating cerebral microhemorrhagic foci. This is the first report of SWI findings on intracerebral hemorrhages in basal ganglia, brain stem and periventricular white matter due to hypertensive encephalopathy in a child with pheochromocytoma.

[Hypertensive crisis: pathogenesis, clinic, treatment].

Contemporary data on mechanisms of development, types, and clinical picture of hypertensive crisis (HC) are presented. Algorithms of rational therapy of uncomplicated and complicated HC are considered. Appropriateness of the use in HC of antihypertensive drugs with multifactorial action is stressed. These drugs include urapidil - an antihypertensive agent with complex mechanism of action. Blocking mainly the postsynaptic 1-adrenoreceptors urapidil attenuates vasoconstrictor effect of catecholamines and decreases total peripheral resistance. Stimulation of 5HT1-receptors of medullary vasculomotor center promotes lowering of elevated vascular tone and prevents development of reflex tachycardia.

Reninoma: a rare cause of curable hypertension.

A 25-year-old lady presented with hypertensive encephalopathy. She also had chronic refractory hypertension for the past 7 years. Workup revealed persistent hypokalaemia with metabolic alkalosis suggesting hyperaldosteronism. Hyperaldosteronic states such as renal artery stenosis, Conn's syndrome and Liddle's syndrome were ruled out. Her plasma renin activity was high. Contrast-enhanced CT of the abdomen showed a 1.9×2 cm heterogeneously enhancing lesion in the anterior aspect of the right kidney suggesting a possibility of reninoma. The benign tumour was resected by a nephron-sparing surgery. Histopathology suggested a juxtaglomerular cell tumour. Anti-hypertensive drugs were completely withdrawn postoperatively.

Concealed primary aortic sarcoma induced hypertensive encephalopathy resulting from a thoracic aortic occlusion: a case report.

Primary aortic sarcoma is a rare condition that is frequently associated with distal embolization. In addition, growth characteristics of primary aortic sarcoma lead to the narrowing of the involved aortic lumen. A 72-year-old Korean male with primary aortic sarcoma showed progressive unexplained blood pressure elevation that didn't improve with additional antihypertensive drug therapy. Because follow-up measures were not taken, the patient ultimately developed hypertensive encephalopathy with concurrent embolic dissemination. Although we successfully performed open transcatheter embolectomy in both legs, the patient died because of multiple organ failure 3 days after surgery. Given the ominous prognosis for this condition, this case report highlights the fact that the value of early detection and prompt evaluation of altered vital signs should not be overemphasized. We describe a rare case of primary aortic sarcoma that showed hypertensive encephalopathy caused by thoracic aortic occlusion and also had embolic metastases to the lower extremities.