Managing severe hypertension in children.

Severe childhood hypertension is uncommon and frequently not recognised and is best defined as a systolic blood pressure (SBP) above the stage 2 threshold of the 95th centile + 12 mmHg. If no signs of end-organ damage are present, this is urgent hypertension which can be managed by the slow introduction of oral or sublingual medication, but if signs are present, the child has emergency hypertension (or hypertensive encephalopathy if they include irritability, visual impairment, fits, coma, or facial palsy), and treatment must be started promptly to prevent progression to permanent neurological damage or death. However, detailed evidence from case series shows that the SBP must be lowered in a controlled manner over about 2 days by infusing short-acting intravenous hypotensive agents, with saline boluses ready in case of overshoot, unless the child had documented normotension within the last day. This is because sustained hypertension may increase pressure thresholds of cerebrovascular autoregulation which take time to reverse. A recent PICU study that suggested otherwise was significantly flawed. The target is to reduce the admission SBP by its excess, to just above the 95th centile, in three equal steps lasting about ≥ 6 h, 12 h, and finally ≥ 24 h, before introducing oral therapy. Few of the current clinical guidelines are comprehensive, and some advise reducing the SBP by a fixed percentage, which may be dangerous and has no evidence base. This review suggests criteria for future guidelines and argues that these should be evaluated by establishing prospective national or international databases.

Posterior reversible leukoencephalopathy syndrome associated with acute postinfectious glomerulonephritis: systematic review.

BACKGROUND: Kidney diseases are a recognized cause of posterior reversible leukoencephalopathy syndrome, usually abbreviated as PRES. The purpose of this review was to systematically address the association between acute postinfectious glomerulonephritis and PRES. METHODS: We performed a systematic review of the literature on acute postinfectious glomerulonephritis associated with PRES. The principles recommended by the Economic and Social Research Council guidance on the conduct of narrative synthesis and on the Preferred Reporting Items for Systematic Reviews and Meta-analyses were used. Databases searched included Excerpta Medica, US National Library of Medicine, and Web of Science. RESULTS: For the final analysis, we evaluated 47 reports describing 52 cases (32 males and 20 females). Fifty patients were ≤ 18 years of age. Blood pressure was classified as follows: normal-elevated (n = 3), stage 1 hypertension (n = 3), stage 2 hypertension (n = 5), and severe hypertension (n = 41). Acute kidney injury was classified as stage 1 in 32, stage 2 in 16, and stage 3 in four cases. Neuroimaging studies disclosed a classic posterior PRES pattern in 28 cases, a diffuse PRES pattern in 23 cases, and a brainstem-cerebellum PRES pattern in the remaining case. Antihypertensive drugs were prescribed in all cases and antiepileptic drugs in cases presenting with seizures. A resolution of clinical findings and neuroimaging lesions was documented in all cases with information about follow-up. CONCLUSIONS: The main factor associated with PRES in acute postinfectious glomerulonephritis is severe hypertension. Prompt clinical suspicion, rapid evaluation, and management of hypertension are crucial. A higher resolution version of the Graphical abstract is available as Supplementary information.

Posterior Reversible Encephalopathy Syndrome.

PURPOSE OF REVIEW: This review provides an updated discussion on the clinical presentation, diagnosis and radiographic features, mechanisms, associations and epidemiology, treatment, and prognosis of posterior reversible encephalopathy syndrome (PRES). Headache is common in PRES, though headache associated with PRES was not identified as a separate entity in the 2018 International Classification of Headache Disorders. Here, we review the relevant literature and suggest criteria for consideration of its inclusion. RECENT FINDINGS: COVID-19 has been identified as a potential risk factor for PRES, with a prevalence of 1-4% in patients with SARS-CoV-2 infection undergoing neuroimaging, thus making a discussion of its identification and treatment particularly timely given the ongoing global pandemic at the time of this writing. PRES is a neuro-clinical syndrome with specific imaging findings. The clinical manifestations of PRES include headache, seizures, encephalopathy, visual disturbances, and focal neurologic deficits. Associations with PRES include renal failure, preeclampsia and eclampsia, autoimmune conditions, and immunosuppression. PRES is theorized to be a syndrome of disordered autoregulation and endothelial dysfunction resulting in preferential hyperperfusion of the posterior circulation. Treatment typically focuses on treating the underlying cause and removal of the offending agents.

Psychiatric Morbidity and Its Prognosis in Posterior Reversible Encephalopathy Syndrome.

Posterior reversible encephalopathy syndrome (PRES) is a clinically and radiologically diagnosed disorder distinguished by subcortical vasogenic cerebral edema. To date, its presentation has been described through summarized neurological categories, such as seizures, headaches, "confusion," and "altered mental function." This retrospective case series identified all cases of clinically confirmed, radiologically diagnosed PRES resulting in treatment in a large teaching hospital from 2010 to 2019. The authors conducted a search for the term "reversible encephalopathy" in the hospital clinical radiology information system, followed by an audit of scan reports and clinical records. The most common reasons for psychiatric referral were addictions, acute psychosis, depression, suicidality, and treatment refusal. Multidisciplinary staff should consider PRES as a rare, organic differential diagnosis for acute mental state changes. Physicians should be aware of elevated rates of post-PRES psychiatric symptoms and consider whether psychiatric consultation may enhance recovery.

Peak blood pressure and prediction of posterior reversible encephalopathy syndrome in children.

BACKGROUND: Hypertension is a risk factor for posterior reversible encephalopathy syndrome (PRES), but the timing and severity of hypertension relative to PRES are unknown. The objective was to identify a clinically meaningful blood pressure (BP) threshold that predicts PRES development in high-risk children. METHODS: We recorded peak systolic BP, diastolic BP, BP z-scores, and mean arterial pressure over the 14 days preceding clinical concern for PRES in 35 subjects who developed PRES, compared to 14 controls who had normal brain magnetic resonance imaging and similar underlying disease, renal function, and medications. We used multivariable logistic regression models adjusted for fluid overload and obesity to estimate the association of peak BP with PRES. We used receiver operating characteristic curves to determine which peak BP thresholds best predicted PRES and calculated the corresponding sensitivity, specificity, and positive and negative predictive values. RESULTS: Peak systolic BP z-score was most strongly associated with PRES (OR 3.97, 95% CI 1.62-9.74), and peak systolic BP z-score ≥ 3.0 predicted PRES (area under the curve 0.95, 95% CI 0.88-1.0) with 91% sensitivity and 85% specificity, indicating 94% positive predictive value and 79% negative predictive value. CONCLUSIONS: We demonstrated that peak systolic BP z-score ≥ 3.0 in the preceding 14 days predicted PRES development in cases compared with controls in children at high risk. Our study suggests that stage 2 hypertension, corresponding to a z-score ≥ 3.0, could help define hypertensive emergency in high-risk children and indicate when more aggressive treatment is warranted to prevent neurologic injury.

Cerebral Hyperperfusion Syndrome and Related Conditions.

Cerebral vasoconstriction is a normal physiological response under determined conditions to preserve a normal cerebral blood flow. However, there are several syndromes, with impaired cerebral autoregulation and cerebral vasoconstriction, not related with infection or inflammation, which share the same radiological and clinical presentation. We review here the cerebral hyperperfusion syndrome and related conditions such as hypertensive encephalopathy, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome. These syndromes might share the same pathophysiological mechanism with endothelial damage, cerebral vasoconstriction, blood-brain barrier disturbance, cerebral edema, and, occasionally, intracerebral hemorrhage, with fatal cases described in all. Despite knowledge of these syndromes, they still remain unknown to us. Why these entities present in some patients and not in others goes further than the actual understanding of these diseases. We have to consider that a genetic susceptibility and molecular disturbances may be involved. Thus, more studies are needed in order to better characterize such syndromes.

Neuropathology of Spontaneous Hypertensive Encephalopathy in Cats.

Pathologic features of 12 cats with naturally acquired systemic hypertension and concomitant hypertensive encephalopathy were analyzed. All cats demonstrated acute onset of signs localized to the forebrain and/or brainstem, including stupor, coma, and seizures. All cats had systemic hypertension, ranging from 160 to 300 mm Hg. Gross lesions were identified in 4 of 12 cases, including caudal herniation of the cerebrum and cerebellum, sometimes with compression of the rostral colliculus and medulla. Histologically, all cases featured bilaterally symmetrical edema of the cerebral white matter. Associated vascular lesions, especially arteriolar hyalinosis, were also observed. Concurrent lesions were chronic tubulointerstitial nephritis (11/12 cases), adenomatous hyperplasia of the thyroid gland (4 cases), hypertensive choroidal arteriopathy (6 cases), and left ventricular hypertrophy (5 cases). This study demonstrates that the typical histologic manifestation of spontaneous hypertensive encephalopathy in cats is bilaterally symmetrical edema of the subcortical cerebral white matter.

HYPERTENSIVE HEART DISEASE AND ENCEPHALOPATHY IN A CENTRAL BEARDED DRAGON (POGONA VITTICEPS) WITH SEVERE ATHEROSCLEROSIS AND FIRST-DEGREE ATRIOVENTRICULAR BLOCK.

A 0.5 kg, 5-yr-old male bearded dragon (Pogona vitticeps) presented with a 2-mo history of lethargy, anorexia, and impaired locomotion. Upon physical examination, bradyarrhythmia (heart rate: 20 beats/min) and balance disorders were noted. Electrocardiography revealed a first-degree atrioventricular block (P-R interval: 360 ms). On echocardiography, all cardiac chambers were slightly above normal ranges. Complete blood count, blood biochemistry, and T4 were unremarkable except for mildly elevated aspartate aminotransferase. Adenovirus testing was negative by polymerase chain reaction. Following euthanasia, necropsy revealed marked thickening of the arterial trunks and histopathology confirmed multifocal atherosclerosis of efferent heart vessels, arteriosclerosis of cerebral arterioles, and multifocal spongiosis of brain tissue, more pronounced in the optic chiasma. Owing to its severity, atherosclerosis may have contributed to chronic arterial hypertension with damages to the heart, brain vessels, and brain tissue-optic chiasma.

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.

Posterior reversible encephalopathy syndrome in eclampsia.

Posterior reversible encephalopathy syndrome is characterized by acute headache, visual impairment, seizures, and altered mental status; neuroimaging may show cerebral edema affecting the parietal and occipital lobes of the brain. The objective of this article is to review the current understanding of posterior reversible encephalopathy syndrome in eclampsia. Literature was searched from PubMed, Scopus, and Google Scholar databases. The search terms included "eclampsia", "eclampsia and posterior reversible encephalopathy syndrome", and "pregnancy and posterior reversible encephalopathy syndrome". We reviewed all published original articles with the search term "posterior reversible encephalopathy syndrome". Up to 100% of eclamptic patients may have reversible posterior leukoencephalopathy syndrome. Two putative mechanisms - "vasogenic" and "vasospasm" - are considered to be responsible. Cerebral edema and petechial cortical hemorrhages are common autopsy findings. Clinical and neuroimaging manifestations are reversible in the majority of patients. Prompt correction of increased blood pressure and treatment of seizures are the cornerstones of treatment. Magnesium sulfate is the drug of choice for seizures. Some survivors may have permanent vision loss and other disabling sequelae. In conclusion, posterior reversible encephalopathy is a devastating complication of eclampsia. Early recognition helps in preventing some of its devastating sequelae.

Predictors of poor outcome in patients with posterior reversible encephalopathy syndrome.

PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome that, although characteristically reversible, can be fatal or result in long-term disability in a subset of patients. Our aim was to identify factors associated with poor discharge outcome in PRES patients. MATERIALS AND METHODS: We retrospectively reviewed the clinical and radiological records of all patients with PRES admitted at our tertiary care medical center from 2007 to 2014. They were divided based their modified Rankin Score at discharge and compared for their baseline variables, clinical, laboratory and imaging features. Poor outcome was defined by a modified Rankin scale 2-6 and was subdivided based on the primary mechanism that led to poor outcome. RESULTS: Out of 100 PRES subjects, 36% had poor discharge outcomes. Factors associated with poor outcomes on univariate analysis were history of diabetes mellitus, coma, high Charlson comorbidity index, post-transplantation, autoimmune condition, lack of systolic or diastolic hypertension, elevated blood urea nitrogen and involvement of the corpus callosum. On multivariate analysis, only prior diabetes mellitus odd ratio (OR) = 6.8 (95% CI 1.1-42.1, p = 0.04), corpus callosum involvement (OR = 11.7; 95% CI 2.4-57.4, p = 0.00) were associated with poor outcome. Poor outcome also correlated with increased length of hospital stay (OR = 7.9; 95% CI 1.3-49.7, p = 0.03). CONCLUSION: Large prospective studies incorporating serial blood glucose values and advanced imaging studies are required to validate these findings.

A Case of Hypertensive Encephalopathy with Enlarged Optic Nerve Sheath Measured by Transorbital Sonography.

This case report describes our experience in using transorbital sonography to evaluate pathological changes in the central nervous system in hypertensive encephalopathy. A 49-year-old man with nausea, headache, and mild confusion was diagnosed with hypertensive encephalopathy by brain magnetic resonance imaging (MRI), which revealed vasogenic edema in the bilateral thalamus and the brain stem. Lumbar puncture showed no severe intracranial hypertension. Transorbital sonography showed an increase in the optic nerve sheath diameter (ONSD). Repeated examination revealed a return of the ONSD to an almost normal range after a reduction in blood pressure and a resolution of symptoms. An improvement in cerebral vasogenic edema was confirmed by brain MRI. ONSD might be related to the severity of cerebral vasogenic edema. Repeated measurement of ONSD by transorbital sonography may be useful to assess the pathological course and the effect of treatment in hypertensive encephalopathy.

Risk of Stroke After the International Classification of Diseases-Ninth Revision Discharge Code Diagnosis of Hypertensive Encephalopathy.

BACKGROUND AND PURPOSE: Although chronic hypertension is a well-established risk factor for stroke, little is known about stroke risk after hypertensive encephalopathy (HE), when neurologic sequelae of hypertension become evident. Therefore, we evaluated the risk of stroke after a diagnosis of HE. METHODS: We identified all patients discharged from California, New York, and Florida emergency departments and acute care hospitals between 2005 and 2012 with a primary International Classification of Diseases, Ninth Edition, Clinical Modification discharge diagnosis of HE (437.2). Patients discharged with a primary diagnosis of seizure (345.x) served as negative controls, whereas patients with a primary diagnosis of transient ischemic attack (435.x) were positive controls. Our primary outcome was the composite of subsequent ischemic stroke or intracerebral hemorrhage. Kaplan-Meier survival statistics were used to calculate cumulative outcome rates, and Cox proportional hazard analysis was used to examine the association between index disease types and outcomes while adjusting for vascular risk factors. RESULTS: We identified 8233 patients with HE, 191 091 with seizure, and 308 680 with transient ischemic attack. The 1-year cumulative rate of ischemic stroke or intracerebral hemorrhage after HE was 4.90% (95% confidence interval [CI], 4.45-5.40) when compared with 0.92% (95% CI, 0.88-0.97) after seizure and 4.49% (95% CI, 4.42-4.57) after transient ischemic attack. The risk of intracerebral hemorrhage was significantly elevated in those with HE (hazard ratio, 2.0; 95% CI, 1.7-2.5) but not in those with transient ischemic attack (hazard ratio, 1.0; 95% CI, 0.9-1.1), when compared with seizure patients. CONCLUSIONS: Patients discharged with a diagnosis of HE face a high risk of future cerebrovascular events, particularly intracerebral hemorrhage.

Predictors of seizures in patients with posterior reversible encephalopathy syndrome.

PURPOSE: Although seizures are common in patients with posterior reversible encephalopathy syndrome (PRES), epilepsy is rare. Our objective was to identify predictors and impact of seizures in patients with PRES. METHODS: A retrospective review of the clinical and radiological parameters of all patients diagnosed with PRES from 2007 to 2014 was performed. Patients were divided into two groups based on the occurrence of PRES-related seizures at presentation or during their hospital course. Univariate and multivariate analyses were performed to determine factors associated with the occurrence of PRES-related seizures. RESULTS: Of 100 patients, 70% experienced at least one seizure from PRES. On univariate analysis, the factors associated with seizures were the following: high Charlson comorbidity index (4.16±2.89 vs. 2.87±2.20, p=0.03), systemic malignancy (41.4% vs. 16.7%, p=0.02), occipital lobe involvement (97.1% vs. 83.3%, p=0.02), more lobes involved (4.6±1.48 vs. 3.9±1.32, p=0.03) but less likely in patients with visual disturbances (15.7% vs. 46.7%, p=0.005), and facial droop (12.9% vs. 16.7%, p=0.002). On multivariate analysis, only occipital lobe involvement was significantly (odds ratio: 9.63, 95% CI: 1.45-64.10, p=0.02) associated with the occurrence of PRES-related seizures. Despite the occurrence of seizures, they were less likely to require a nursing home placement upon hospital discharge (odds ratio: 0.17, 95% CI: 0.03-0.91, p=0.04). CONCLUSION: We conclude that seizures are common in patients with occipital lobe involvement from PRES.

Posterior reversible encephalopathy syndrome (PRES) and hypomagnesemia: A frequent association?

Posterior reversible encephalopathy syndrome (PRES) is a serious neurological condition encountered in various medical fields. Pathophysiological factor(s) common to PRES cases of apparently unrelated etiologies are yet to be found. Based on the hypothesis that hypomagnesemia might participate in the cascade leading to PRES, our study sought to verify whether hypomagnesemia is frequently associated with PRES regardless of etiology. From a retrospective study of a cohort of 57 patients presenting with PRES of different etiologies, presented here are the findings of 19 patients with available serum magnesium levels (SMLs) during PRES. In the acute phase of PRES, hypomagnesemia was present in all 19 patients in spite of differences in etiology (including immunosuppressive drugs, hypertensive encephalopathy, eclampsia, systemic lupus erythematosus, iatrogenic etiology and unknown). SMLs were within normal ranges prior to PRES and below normal ranges during the first 48h of PRES, with a significant decrease in SMLs during the acute phase. In this retrospective study, constant hypomagnesemia was observed during the acute phase of PRES regardless of its etiology. These results now require larger studies to assess the particular importance of acute hypomagnesemia in PRES and especially the possible need to treat PRES with magnesium sulfate.

Long-term risk of seizures and epilepsy in patients with posterior reversible encephalopathy syndrome.

OBJECTIVE: Seizures are common in patients with posterior reversible encephalopathy syndrome (PRES), which is reported in up to 70% of cases, and antiepileptic drugs (AEDs) are commonly prescribed. There is a paucity of data regarding the risk of subsequent seizures following resolution of PRES, and therefore the optimal duration of treatment with AEDs is currently unknown. The objective of this study was to identify the frequency of recurrent seizures and epilepsy following recovery from PRES. METHODS: We performed a retrospective review of consecutive adults diagnosed with PRES between 2000 and 2010. RESULTS: One hundred twenty-seven patients, median age 53 years (interquartile range [IQR] 37-64), were included in the analysis. The most common causes of PRES were hypertension (72%) and immunosuppression (20%). Renal failure was present in 47%. Eighty-four patients (66%) had seizures at presentation (39 focal, 45 generalized), and 13 (15%) of them presented with status epilepticus. Median duration of follow-up was 3.2 years (IQR 4 months to 6.9 years). Patients with seizures were treated with AEDs for a median of 3 months (IQR 2-7). Fifteen patients (12%) had provoked seizures during the follow-up period; in eight (53%) patients seizures were caused by recurrent PRES. Only three patients had subsequent unprovoked seizures, one of whom was considered to have developed epilepsy. SIGNIFICANCE: We conclude that unprovoked seizures and epilepsy are uncommon in patients who have recovered from PRES. Discontinuation of AEDs following resolution of PRES should be considered, provided there is adequate control of risk factors, and absence of factors that could substantially lower the seizure threshold.

Malignant hypertension and retinopathy in a western lowland gorilla (Gorilla gorilla gorilla).

BACKGROUND: A 34-year-old western lowland gorilla presented with peracute blindness. METHODS: Clinical evaluation, diagnostic imaging, laboratory analyses, blood pressure measurements, and necropsy were performed. RESULTS: The clinical and postmortem findings supported malignant hypertension. CONCLUSIONS: We describe a case of naturally occurring hypertensive encephalopathy and retinopathy in a gorilla.

Discharge status and in-hospital mortality in posterior reversible encephalopathy syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome is a serious and increasingly recognized disorder, but data from observational studies on outcome and mortality in posterior reversible encephalopathy syndrome (PRES) are scarce. We aimed to determine the frequency and associations of in-hospital death and discharge status in a large cohort of patients with PRES. METHOD: We retrospectively reviewed the radiological report databases of our university hospitals between January 1999 and March 2011 for patients with PRES. Patients fulfilling the criteria for PRES after detailed investigation of clinical charts and imaging studies were included. Clinical charts, paraclinical and brain imaging data at onset as well as available data on in-hospital mortality and discharge status were analyzed. RESULTS: A total of 103 patients were included. Five (4.8%) patients died during hospital stay, 27 (26.2%) remained hospitalized after discharge. In univariate analyses, significant differences were found between patients discharged home from hospital and patients referred to rehabilitation or who died in hospital for the following variables: severe edema (P = 0.013), etiology of PRES (P = 0.001), altered mental state at onset (P = 0.003), altered coagulation (P = 0.004), and length of hospital stay >30 days (P < 0.001). CONCLUSION: Features of a severe course of PRES such as severe edema and altered mental state are significantly more frequent in patients who were referred to inpatient rehabilitation or died in hospital. Prospective studies are warranted to establish factors that are associated with unfavorable outcome in PRES.