Secondary Hypertension Research Articles

Significance of screening and confirmatory tests in identifying primary hyperaldosteronism among patients investigated for secondary endocrine hypertension

Significance of screening and confirmatory tests in identifying primary hyperaldosteronism among patients investigated for secondary endocrine hypertension

Diagnostic challenges in patients with reninomas and extrarenal renin-producing tumours.

Renin-secreting tumours are rare causes of secondary hypertension and hypokalaemia. They are usually surgically curable, hence proper diagnostic work-up and tumour localisation is essential. In this paper, we present three Swedish patients recently diagnosed with renin secreting tumours, two with reninomas and one with an extrarenal renin-producing tumour, to illustrate diagnostic challenges. We also discuss the biochemical work-up, the pros and cons of different imaging techniques (computer tomography [CT], magnetic resonance imaging and [18F]fluorodeoxyglucose-positron emission tomography-CT), as well as how renal vein sampling (RVC) may contribute to localisation of the tumour.

Comparative Efficacy of Monotherapy of Angiotensin-converting Enzyme Inhibitors Versus Angiotensin Receptor Blockers in Treating Essential Hypertension – A Meta-analysis

Background: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely used medications for treating essential hypertension, but there is limited research comparing their effectiveness. To address this gap, a recent meta-analysis was conducted to evaluate and compare the efficacy of these two drug classes in decreasing blood pressure (BP) among patients with essential hypertension. Objective: Evaluating of comparative efficacy of ACEIs versus ARBs in reducing BP in essential hypertension. Methods: An extensive literature search for randomized controlled trials (RCTs) following PRISMA guidelines (2020), with inclusion criteria of age ≥18 years, with either gender and diagnosed of essential hypertension and receiving ACEIs or ARBs for at least 4 weeks. Patients with secondary hypertension, malignancy, symptomatic cardiovascular system (CVS) disease, hepatic involvement, and studies with Fimasartan and Allisartan were excluded. For this study, all RCTs that reported changes in mean systolic BP (SBP) and diastolic BP (DBP) before and after administration of the drugs were gathered. Standardized mean difference (SMD) was calculated using RevMan 5.4.1 software. The significance level was set at a P < 0.05. Results: A total of 28 RCTs ( n = 9778) were included in our study. Both groups reduce SBP and DBP from the baseline values. Pooled analyses of studies showed that ARBs were superior to ACEIs with SMD = 0.179 in the random-effect model, 95% confidence interval (CI) (0.0975–0.260), P < 0.001, and in the fixed-effect model, SMD = 0.207, 95% CI (0.167–0.248), P < 0.001 in the mean reduction of SBP. Furthermore, for a mean reduction in DBP, ARBs were superior to ACEIs with SMD = 0.329 in the random-effect model, 95% CI (0.161–0.496), P < 0.001, and in the fixed-effect model, SMD = 0.317, 95% CI (0.276–0.357), P < 0.001. Our study included 28 RCTs with a combined sample size of 9778 participants. Both ACEIs and ARBs were found to effectively reduce SBP and DBP from their baseline values. However, our pooled analysis of the studies revealed that ARBs were more effective than ACEIs in reducing mean SBP, with an SMD of 0.179 in the random-effect model and 0.207 in the fixed-effect model. The 95% CIs for these estimates were (0.0975–0.260) and (0.167–0.248), respectively, with P < 0.001. Similarly, for a mean reduction in DBP, ARBs were found to be superior to ACEIs with a SMD of 0.329 in the random-effect model and 0.317 in the fixed-effect model, with 95% CIs of (0.161–0.496) and (0.276–0.357), respectively, and a P < 0.001. Conclusion: ARBs are more efficacious as compared to ACEIs in essential hypertension.

Systemic Hormonal Unloading (SHU) in Secondary Hypertension: Addressing the Long-Term Adverse Cardiovascular Outcomes

Excess hormone production from adrenal tumors caused by primary hyperaldosteronism or pheochromocytoma are common etiologies for secondary hypertension. Studies have shown that sustained long-term circulating hormones in excess affect the blood vessels and cardiac structures. Inflammation of cardiomyocytes leads to fibrosis and eventual cardiomyopathy and is clinically presented as arrhythmia, nonfatal myocardial infarction, heart failure, or even death. The tissue changes and/or impaired cardiac function are reversible if early diagnosis and removal of the adrenal tumor by unilateral adrenalectomy is done. However, the condition becomes challenging if the adrenal lesions are bilateral. This article introduces the concept of systemic hormonal unloading and will discuss the philosophy of quality of life in managing bilateral adrenal disease. Keywords: systemic hormonal unloading, secondary hypertension, primary hyperaldosteronism, pheochromocytoma, bilateral adrenal venous sampling, cardiovascular adverse outcomes, quality of life

Control of blood pressure in hypertensive children and adolescents assessed by ambulatory blood pressure monitoring

BackgroundThere have been few studies evaluating the control of hypertension (HT) in children. This study aimed to assess the control of HT using ambulatory blood pressure monitoring (ABPM) and to compare the parameters between the uncontrolled HT and controlled HT groups.MethodsHypertensive patients aged ≥ 5 years who underwent ABPM to assess the control of HT were enrolled. Demographics, office blood pressure (BP), ABPM, and echocardiographic data were collected. Controlled HT was defined using a BP goal recommended by the 2016 European Society of Hypertension guidelines.ResultsThere were 108 patients (64.8% males) with a mean age of 14.3 years and 51.9% had primary HT. Controlled HT was detected in 41.1% and 33.3% by office BP and ABPM, respectively. Based on ABPM, there was a greater prevalence of controlled HT in the primary HT than the secondary HT group (44.6% vs. 21.2%, P = 0.01). In the primary HT group, BMI z-score at the last follow-up had a significant decrease in the controlled HT than the uncontrolled HT group (-0.39 vs. 0.01, P = 0.032). Primary HT was negatively associated with uncontrolled HT by ABPM. In addition, ABPM showed greater sensitivity (77.8% vs. 55.8%) and negative predictive value (80.9% vs. 70.8%) to predict LVH than those of office BP measurement.ConclusionOnly one-third of patients achieved the BP goal by ABPM and most were in the primary HT group. Weight reduction is an important measure of BP control in patients with primary HT to attenuate the risk of LVH.

Emerging approaches in secondary hypertension due to renal artery stenosis: evaluation and treatment - systematic review

Hypertension, a global health concern, affects a staggering 1.28 billion people worldwide, as stated by the World Health Organization (WHO) however renal artery stenosis (RAS), a common cause of secondary hypertension, is characterized by the narrowing of renal arteries, leading to physiological changes such as arterial stiffening and elevated blood pressure. The major causes of RAS include atherosclerosis and fibromuscular dysplasia. Diagnosis involves clinical suspicion and imaging studies such as Doppler ultrasonography and angiography. Treatment strategies encompass lifestyle modifications, pharmacotherapy, interventional procedures like angioplasty with stenting, and emerging options such as renal denervation and gene therapy. Our aim is to provide a comprehensive examination of the pathophysiology, prevalence, risk factors, causes, diagnosis, and treatment modalities through a systematic search gathering qualitative and quantitative data. We address the challenges in diagnosis and treatment, emphasizing the need for tailored approaches considering patient-specific factors. We will review emerging approaches in evaluating and treating secondary hypertension due to RAS.

Advantages of UltrafastTM ultrasound in the screening for renal artery disease

Aim: Renal artery disease is the most common cause of secondary hypertension worldwide. B-mode and Doppler ultrasound are considered the modalities of choice for the imaging of the renal arteries. However, an adequate examination can be plagued by difficulties in patients with unfavorable anatomy. UltraFastTM ultrasound is faster, performed with higher frame rates, and enables prospective and ret- rospective data analysis with quantification of flow data in the obtained image, so it may be able to resolve some of the difficulties encountered during conventional ultrasound examinations in patients with suspected renal artery disease. Material and methods: Comparison of the duration of conven- tional and UltraFastTM Doppler examinations of segmental renal arteries was performed on 52 young, healthy volunteers. Duration times were summarized using the median and interquartile range, and comparisons between the two methods were performed using the Wilcoxon test for paired samples. Results: The duration of UltraFastTM ultrasound examinations was significantly shorter in comparison to conventional ultrasound for both kidneys and in total (p <0.001, median difference in duration 65 s, median 64% shorter duration of analysis), while both conventional and UltraFastTM ultrasound examina- tions demonstrated consistent velocity measurements with very high correlation (Rho = 0.94, p <0.001). Conclusions: The study provides evidence that UltraFastTM ultrasound is faster than conventional Dop- pler ultrasonography for the assessment of renal artery disease in healthy adults without a history of renal disease. The findings have important implications for clinical practice, as they suggest that Ultra- FastTM imaging could offer a more efficient and time-saving approach to vascular imaging in patients with suspected renal artery disease.

Juxtaglomerular Cell Tumor Mimicking Renal Cell Carcinoma on 99mTc-MIBI SPECT/CT.

Juxtaglomerular cell tumor or reninoma is an extremely rare, typically benign, renin-secreting tumor of the kidney that causes secondary hypertension. We describe 99mTc-MIBI SPECT/CT findings in a case of juxtaglomerular cell tumor. The renal tumor showed isodensity and photopenia on 99mTc-MIBI SPECT/CT. This case indicates that juxtaglomerular cell tumor can appear cold on 99mTc-MIBI SPECT/CT, mimicking renal cell carcinoma.

IJCM_139A: Prevalence of Hypertension among the Urban Adolescents: A Prospective Robust Survey

Background: Childhood Blood pressure (BP) is a strong indicator of adult blood pressure (BP), hence, early detection and intervention is important in adolescents. Studies from China and United States have shown BP in adolescents to be variable and has indeed outlined the need to obtain three separate readings before diagnosing hypertension. There is a dearth of this documentation of blood pressure readings at different occasions in adolescents from the Indian settings. Objective: To determine the prevalence of elevated blood pressure and hypertension among 10-18 years school going adolescents. Methodology: This was a prospective longitudinal study conducted across the five urban schools of Bhopal amongst 10-18 years adolescents. Multistage cluster sampling was adopted to cover an estimated sample size of 780 over a one-year period. Those adolescents who were present during the time of survey following their parent’s consent were included. Those who were absent at two occasions during the follow up visit and those who were diagnosed with secondary hypertension were excluded. Those who satisfied the study criteria were given a self-administered WHO STEPS questionnaire initially. The height and weight were obtained followed by measurement of three auscultatory BP readings at an interval of one week apart (American Academy of paediatrics (Updated guidelines 2017) in each student. The R shiny app calculator was used for classifying hypertension in adolescents. The study was funded by AIIMS Bhopal and ethical clearance was obtained from the institute. Results: The overall prevalence of elevated BP/hypertension in adolescents was 1.4% (N=795). There was a positive correlation between BMI and (SBP & DBP). The generalised linear mixed model showed age, BMI and boys to have higher predisposition to elevated BP/HTN. There was a significant difference in the SBP and DBP between the 3 visits stratified by sex. Also, the change in SBP and DBP between the readings were significant by ANOVA. Conclusion: The prevalence of elevated BP/HTN was 1.4% with girls being protective for girls. The study cannot be generalised as it is limited to the Government schools with relatively small sample size.

Patient selection, surgery and perioperative management in lung transplantation in Japan.

Lung transplantation (LT) is the final treatment option for end-stage respiratory diseases. The current prognosis of LT recipients in Japan is good, however, the reason for the good prognosis is unclear. In Japan, the waiting time for cadaveric LT is long, which is approximately 900 days on average. A long waiting time affects several aspects of LT. The diseases progress while they await LT in most patients are waiting for LT. Along with the disease progression of the disease, secondary pulmonary hypertension can newly emerge. Some patients suffer from refractory secondary pneumothorax and may receive pleurodesis. Transplant operations can become more difficult, and postoperative management becomes more complicated owing to the disease progression. Thoracic surgeons in Japan have managed the tough difficult situation of LT patients with LT. Possible explanations for how we to maintain a better prognosis in such a situation include sophisticated surgical techniques and ideas, and vigorous postoperative management by thoracic surgeons. Thoracic surgeons are vigorously involved both in operations and in postoperative management in the intensive care unit with or without intensivists in Japan. On the other hand, the long waiting time in Japan and allocation rules with age restriction without considering the severity of patients may have resulted in the selection of recipients to include relatively young recipients, fewer patients with interstitial lung disease and fewer recipients with extracorporeal membrane oxygenation (ECMO) as a bridge to LT. These recipients' characteristics possibly may have affected the prognosis of LT patients with LT in Japan. There is a chance that a future increase in the number of cadaveric donors in Japan may result in a prognosis close that is similar to the international average if the current waiting time in Japan decreases. We review patient selection, surgery and perioperative management in LT in Japan to address the question of why the current prognosis of LT recipients in Japan is good.

Primary aldosteronism and cardiovascular risk. Review

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, occurs in 5—10% of hypertensive patients, with prevalence dependent on the severity of hypertension. The main etiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone‑producing adenoma (APA), while less common causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I—IV, aldosterone‑producing carcinoma, and ectopic aldosterone synthesis. This condition, characterized by excessive secretion of aldosterone, leads to increased reabsorption of sodium and water along with potassium loss, culminating in the distinct clinical signs of elevated aldosterone, suppressed renin, and hypertension. It should be noted that hypokalemia is present in only 28% of patients with PA and is not the main indicator. The association of PA with an increased risk profile for cardiovascular disease, regardless of blood pressure level, is notable. Patients with PA show an increased rate of cardiovascular events compared to patients with essential hypertension, adjusted for age, sex, and blood pressure level. Despite its prevalence, PA often remains undiagnosed, highlighting the need for enhanced screening protocols. The diagnostic process for PA involves a three‑pronged assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtype tests. A positive ARR requires confirmatory testing to rule out false positives. Examination to detect PA should be carried out in patients with arterial hypertension: moderate (> 160—179/100—109 mm Hg) or severe (> 180/110 mm Hg); resistant to treatment; with idiopathic or diuretic‑induced hypokalemia; with an accidentally diagnosed tumor of the adrenal glands; if first‑generation relatives are diagnosed with PA, or family history indicates early onset of arterial hypertension, or cerebrovascular disorders at a young age (< 40 years); with accompanying obstructive sleep apnea.

Bronchopulmonary Dysplasia in a Tertiary Level Neonatal Unit of North India: Risk Factors and Outcome: A Case-control Study

Background: Bronchopulmonary dysplasia (BPD) in preterm neonates is a dreadful complication that increases the length of neonatal intensive care unit (NICU) stay, increases the cost of treatment, and poses long-term respiratory morbidity. Methods: This was a case-control study to determine risk factors for BPD among preterm neonates (gestational age <32 weeks). Also, the proportion of BPD neonates developing secondary pulmonary arterial hypertension (PAH), vitamin D levels, and their outcomes were studied. Results: Of 70 neonates with a mean birth weight of 1392 ± 544.28 grams and a mean gestational age of 30.14 ± 1.12 weeks, 35 cases of BPD (mild 42%, moderate 27%, severe 31%) and 35 controls were enrolled. After multivariate analysis, SGA (adjusted odds ratio [AOR] 12.6 with 95% CI 1.5-109.3; 0.022), lack of antenatal steroids (AOR 9.4 with 95% CI 1.8-50.7; 0.009), mechanical ventilation [MV] within the first 48 hours of life (AOR 8.7 with 95% CI 1.4-54.1; 0.021), and lack of surfactant administration (AOR 16.5% CI 3-89.1; 0.005) were independent risk factors. No significant difference was reported in vitamin D levels between BPD and non-BPD neonates (33.89 ± 22.50 ng/mL vs. 27.00 ± 8.17 ng/mL; 0.356). 14.3 % of BPD neonates expired, and 23% developed PAH. Neonates had a longer NICU stay than controls (46.66 ± 7.96 vs. 21 ± 8.82 days; <0.001) Conclusion: We found SGA, lack of antenatal steroids, MV, and lack of surfactant administration to be independent risk factors for BPD. BPD neonates had dismal outcomes (one-fourth expired and left against medical advice), and one-fifth had PAH among survivors, increasing the length of their NICU stay.

Practical consensus for the treatment and follow-up of primary aldosteronism: a multidisciplinary consensus document.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC).

Onco-Hypertension: A Continuously Developing Field between Cancer and Hypertension.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension (HT), which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary HT related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, HT per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, particularly thiazide diuretics, which may increase the risk of skin cancer. As a result, in light of the similar risk factors and overlapping pathophysiological mechanisms between HT and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

Laboratory Testing for Endocrine Hypertension: Current and Future Perspectives.

Secondary hypertension (SH) is a form of high blood pressure caused by an identifiable underlying condition. Although, it accounts for a small fraction of the overall hypertensive population, detection and management of SH is of utmost importance, because SH phenotypes carry a high cardiovascular risk and can possibly be cured by timely treatment. This review focuses on the endocrine causes of SH, such as primary aldosteronism, Cushing syndrome, thyroid disease, pheochromocytoma and paraganglioma, acromegaly, and rare monogenic forms. It discusses current biomarkers, analytical methods, and diagnostic strategies, highlighting advantages and limitations of each approach. It also explores the emerging -omics technologies that can provide a comprehensive and multidimensional assessment of SH and its underlying mechanisms. Endocrine SH is a heterogeneous and complex condition that requires proper screening and confirmatory tests to avoid diagnostic delays and improve patient outcomes. Careful biomarker interpretation is essential due to potential interferences, variability, and method-dependent differences. Liquid chromatography-tandem mass spectrometry is a superior method for measuring low-concentration hormones and metabolites involved in SH, but it requires expertise. Omics approaches have great potential to identify novel biomarkers, pathways, and targets for SH diagnosis and treatment, especially considering its multifactorial nature.

Teaching NeuroImage: Transcalvarial Lymphoma: A Rare Cause of Secondary Intracranial Hypertension.

Teaching NeuroImage: Transcalvarial Lymphoma: A Rare Cause of Secondary Intracranial Hypertension.

Development and Implementation of a Dynamically Updated Big Data Intelligence Platform Using Electronic Medical Records for Secondary Hypertension

Development and Implementation of a Dynamically Updated Big Data Intelligence Platform Using Electronic Medical Records for Secondary Hypertension

Clinical diagnosis of pheochromocytoma and paraganglioma-induced secondary hypertension through UPLC-MS/MS analysis of plasma catecholamines and their metabolites.

This study aimed to elucidate the clinical diagnostic value of plasma catecholamines and their metabolites for pheochromocytoma and paraganglioma (PPGL)-induced secondary hypertension using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). The study population included 155 patients with PPGL that were divided into the PPGL with hypertension (n=79) and a PPGL without hypertension (n=76) groups, and 90 healthy volunteers and 90 patients with primary hypertension as the control groups. UPLC-MS/MS was performed to detect plasma levels of catecholamines and their metabolites, including dopamine, vanillylmandelic acid (VMA), norepinephrine, metanephrine, and normetanephrine. Receiver operating characteristic curves were generated to analyze the diagnostic value of the plasma levels of catecholamines and their metabolites in PPGL-induced secondary hypertension. Patients in the primary hypertension and PPGL without hypertension groups had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal group (all p<.05). On the other hand, patients in the PPGL with hypertension group had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal, primary hypertension, and PPGL without hypertension groups (all p<.05). Collectively, our findings showed that dopamine, VMA, norepinephrine, metanephrine, and normetanephrine are all effective biomarkers for the diagnosis of PPGL and PPGL-induced secondary hypertension.

Prevalence of primary aldosteronism in acute stroke or transient ischemic attack: a systematic review and meta-analysis.

Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension with a prevalence of 14% in patients with newly diagnosed hypertension. Patients with PA experience a higher rate of cardiovascular events including stroke when compared to those with blood pressure matched essential hypertension. This systematic review and meta-analysis summarize current evidence on the prevalence of PA in patients with acute stroke or transient ischemic attack (TIA). Two reviewers independently reviewed the literature for observational studies on the prevalence of PA in patients with acute stroke or TIA. MEDLINE and Embase were searched for studies up to December 13, 2023. Three single center studies conducted in Japan, Singapore and China were found to meet the inclusion criteria. The reported prevalence of PA in two cohort studies of adults with stroke or TIA were 3.1% and 4.0% and a third cross-sectional study in adults under 45 years old revealed a prevalence rate of 12.9%. Following a meta-analysis, the pooled prevalence of PA in adults with stroke or TIA is 5.8% [95% CI 1.6%-12.3%]. A considerable proportion of patients with stroke or TIA may have PA as the underlying cause of their hypertension. Given the increased risk of stroke associated with PA, clinicians should consider screening for PA in hypertensive patients with stroke or TIA. Further research is needed to evaluate the effect of timing and interfering medications on test results, which will inform an evidence-based approach to testing for PA following TIA or stroke. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022328644.

Study of the possibilities of non-invasive assessment of increased intracranial pressure according to MRI data on the example of patients with secondary intracranial hypertension

Modern methods of neuroimaging make it possible to develop approaches for assessing intracranial pressure as a replacement for the “gold standard” of invasive monitoring. Aim of the study was to investigate the possibility of using magnetic resonance (MR) characteristics to assess the increase in intracranial pressure in patients with secondary intracranial hypertension. Material and methods. Group 1 – 40 patients with brain tumors, group 2 – 15 patients with communicating hydrocephalus, control group – 36 individuals. The patients underwent MRI with measurement and evaluation of the optic nerve sheath diameter (ONSD), the optochiasmal cistern and the pituitary gland vertical sizes, and tortuosity of the ON. Patients of the 2nd group underwent a phase-contrast MRI with an assessment of the velocity and volumetric characteristics of blood and cerebrospinal fluid flows with the calculation of the intracranial compliance index (ICC). Using the FreeSurfer program, the brain volumes were estimated. Results and discussion. A statistically significant increase in ONSD was found in the groups of patients compared with the control group (by 24 %, p &lt; 0.05), decrease in the vertical size of the pituitary gland and an increase in the vertical size of the optochiasmal cistern (p &lt; 0.05), as well as ICC lowering in group 2 (by 1.7 times, p &lt; 0.05). Tortuosity of ON in group 1 was observed more often than in other groups. A statistically significant positive correlation between ONSD and brain volumes in group 1 (r = 0.55, p &lt; 0.05) and a negative correlation between brain volumes and ICC in group 2 (r = –0.86, p &lt; 0.05) has been found. Conclusions. Based on the presented results, we believe that the combined use of qualitative and quantitative MRI criteria can expand the diagnostic capabilities of non-invasive assessment of increased intracranial pressure.