Early Treatment Decisions in Poor-Grade Patients with Subarachnoid Hemorrhage

Background: Patients with World Federation of Neurosurgical Societies (WFNS) grade V subarachnoid hemorrhage (SAH) mostly have a poor outcome. Correct identification of patients who might benefit from treatment remains challenging. We investigated which disease-related characteristics, present at admission, could identify patients with chance of good outcome. Methods: In total, 146 consecutive patients with WFNS grade V SAH (2002–2013) were included. Demographic and disease-related characteristics were compared between patients with a good outcome (Glasgow Outcome Scale 4 and 5) and a poor outcome (Glasgow Outcome Scale 1-3). Subgroups were made of patients with aneurysm treatment according to outcome; 1) good outcome; 2) poor outcome, with optimal general treatment; and 3) poor outcome, general treatment discontinued. Results: In total, 34 of the 146 patients had a good outcome (36% of all treated patients); 16 (47%) of these presented with a Glasgow Coma Scale score of 3, versus 65 (58%) of patients with a poor outcome (P = 0.33). Eleven (33%) patients in the good outcome group presented with pupillary abnormalities; 4 (12%) even had bilaterally fixed and dilated pupils, versus 49 (46%) in patients with a poor outcome (P < 0.01). In 51 patients, the aneurysm was not treated; all died. Conclusions: More than one third of all treated patients with WFNS grade V SAH had a good outcome. All patients in whom the aneurysm was not treated died. Reliable identification of patients who will reach good outcome, on the basis of symptoms on admission, seems impossible, as these symptoms are not discriminating enough

Why Do Patients with Poor-Grade Subarachnoid Hemorrhage Die?

Background: Poor-grade subarachnoid hemorrhage (SAH) has been associated with a high case fatality, either in the acute phase or in the later stages. The exact causes of death in these patients are unknown. Methods: We performed a retrospective study of all consecutive patients with SAH with World Federation of Neurosurgical Societies grade IV or V on admission from 2009 to 2013 at 2 tertiary referral centers in Amsterdam, the Netherlands, and Toronto, Ontario, Canada, who had died during their hospital stay. Results: Of 357 patients, 152 (43%) had died. Of these 152 patients, 87 (24%) had not undergone aneurysm treatment. The median interval to death was 3 days (interquartile range, 1–12 days) after initial hemorrhage. The major cause of death in both centers was withdrawal of life support (107 patients [71%]; 74 of 94 [79%] in Amsterdam and 33 of 58 [58%] in Toronto; P < 0.01), followed by brain death in 23 (15%; 16 of 58 [28%] in Amsterdam vs. 7 of 94 [7%] in Toronto; P < 0.01). The remaining causes of death represented <15%. Conclusions: The decision to withdraw life support was the major reason for death of patients with poor-grade SAH for an overwhelming majority of the patients. The exact reasons for withdrawal of life support, other than cultural and referral differences, were undetermined. Insight into the reasons of death should be prospectively studied to improve the care and clinical outcomes of patients with poor-grade SAH

The added value of cerebrospinal fluid analysis in patients with subarachnoid hemorrhage after negative noncontrast CT

OBJECTIVE In patients presenting within 6 hours after signs and symptoms of suspected subarachnoid hemorrhage (SAH), CSF examination is judged to be no longer necessary if a noncontrast CT (NCCT) scan rules out SAH. In this study, the authors evaluated the performance of NCCT to rule out SAH in patients with positive CSF findings. METHODS Between January 2006 and April 2018, 1657 patients were admitted with a nontraumatic SAH. Of these patients, 1546 had positive SAH findings on the initial NCCT and 111 patients had an NCCT scan that was reported as negative in the acute setting, but with positive CSF examination for subarachnoid blood. Demographic data, World Federation of Neurosurgical Societies grade, and SAH time points (ictus, time of NCCT, and time of lumbar puncture) were collected. All 111 NCCT scans were reevaluated by an experienced neuroradiologist. RESULTS Of the 111 patients with positive CSF findings, SAH was initially missed on NCCT in 25 patients (23%). Reevaluation of 21 patients presenting within 6 hours of symptom onset confirmed NCCT negative findings in 12 (5 aneurysms), an aneurysmal SAH (aSAH) pattern in 8 (7 aneurysms), and a perimesencephalic pattern in 1 patient. Reevaluation of 90 patients presenting after 6 hours confirmed negative NCCT findings in 74 patients (37 aneurysms), aSAH pattern in 10 (4 aneurysms), and a perimesencephalic pattern in 6 (2 aneurysms). CONCLUSIONS CSF examination is still mandatory to rule out SAH as NCCT can fail to show blood, even within 6 hours after symptom onset. In addition, the diagnosis SAH was frequently missed during initial reporting

The added value of cerebrospinal fluid analysis in patients with subarachnoid hemorrhage after negative noncontrast CT

OBJECTIVE In patients presenting within 6 hours after signs and symptoms of suspected subarachnoid hemorrhage (SAH), CSF examination is judged to be no longer necessary if a noncontrast CT (NCCT) scan rules out SAH. In this study, the authors evaluated the performance of NCCT to rule out SAH in patients with positive CSF findings. METHODS Between January 2006 and April 2018, 1657 patients were admitted with a nontraumatic SAH. Of these patients, 1546 had positive SAH findings on the initial NCCT and 111 patients had an NCCT scan that was reported as negative in the acute setting, but with positive CSF examination for subarachnoid blood. Demographic data, World Federation of Neurosurgical Societies grade, and SAH time points (ictus, time of NCCT, and time of lumbar puncture) were collected. All 111 NCCT scans were reevaluated by an experienced neuroradiologist. RESULTS Of the 111 patients with positive CSF findings, SAH was initially missed on NCCT in 25 patients (23%). Reevaluation of 21 patients presenting within 6 hours of symptom onset confirmed NCCT negative findings in 12 (5 aneurysms), an aneurysmal SAH (aSAH) pattern in 8 (7 aneurysms), and a perimesencephalic pattern in 1 patient. Reevaluation of 90 patients presenting after 6 hours confirmed negative NCCT findings in 74 patients (37 aneurysms), aSAH pattern in 10 (4 aneurysms), and a perimesencephalic pattern in 6 (2 aneurysms). CONCLUSIONS CSF examination is still mandatory to rule out SAH as NCCT can fail to show blood, even within 6 hours after symptom onset. In addition, the diagnosis SAH was frequently missed during initial reporting

Complications in cranioplasty after decompressive craniectomy: timing of the intervention

Objective: To prevent complications following decompressive craniectomy (DC), such as sinking skin flap syndrome, studies suggested early cranioplasty (CP). However, several groups reported higher complication rates in early CP. We studied the clinical characteristics associated with complications in patients undergoing CP, with special emphasis on timing. Methods: A single-center observational cohort study was performed, including all patients undergoing CP from 2006 to 2018, to identify predictors of complications. Results: 145 patients underwent CP: complications occurred in 33 (23%): 18 (12%) epi/subdural hemorrhage, 10 (7%) bone flap infection, 4 (3%) hygroma requiring drainage, and 1 (1%) post-CP hydrocephalus. On univariate analysis, acute subdural hematoma as etiology of DC, symptomatic cerebrospinal fluid (CSF) flow disturbance (hydrocephalus) prior to CP, and CP within three months after DC were associated with higher complication rates. On multivariate analysis, only acute subdural hematoma as etiology of DC (OR 7.5; 95% CI 1.9–29.5) and symptomatic CSF flow disturbance prior to CP (OR 2.9; 95% CI 1.1–7.9) were associated with higher complication rates. CP performed within three months after DC was not (OR 1.4; 95% CI 0.5–3.9). Pre-CP symptomatic CSF flow disturbance was the only variable associated with the occurrence of epi/subdural hemorrhage. (OR 3.8; 95% CI 1.6–9.0) Conclusion: Cranioplasty has high complication rates, 23% in our cohort. Contrary to recent systematic reviews, early CP was associated with more complications (41%), explained by the higher incidence of pre-CP CSF flow disturbance and acute subdural hematoma as etiology of DC. CP in such patients should therefore be performed with highest caution

The GALANT trial:Study protocol of a randomised placebo-controlled trial in patients with a ⁶⁸Ga-DOTATATE PET-positive, clinically non-functioning pituitary macroadenoma on the effect of lan reotide on t umour size

INTRODUCTION: At present, there is no approved medical treatment option for patients with non-functioning pituitary adenoma. A number of open-label studies suggest that treatment with somatostatin analogues may prevent tumour progression. In vivo somatostatin receptor imaging using 68Ga-DOTATATE PET (PET, positron emission tomography) could help in preselecting patients potentially responsive to treatment. Our aim is to investigate the effect of the somatostatin analogue lanreotide as compared with placebo on tumour size in patients with a 68Ga-DOTATATE PET-positive non-functioning pituitary macroadenoma (NFMA). METHODS AND ANALYSIS: The GALANT study is a multicentre, randomised, double-blind, placebo-controlled trial in adult patients with a suprasellar extending NFMA. Included patients undergo a 68Ga-DOTATATE PET/CT of the head and tracer uptake is assessed after coregistration with pituitary MRI. Forty-four patients with a 68Ga-DOTATATE PET-positive NFMA are randomised in a 1:1 ratio between lanreotide 120 mg or placebo, both administered as subcutaneous injections every 28 days for 72 weeks. The primary outcome is the change in cranio-caudal tumour diameter on pituitary MRI after treatment. Secondary outcomes are change in tumour volume, time to tumour progression, change in quality of life and number of adverse events. Final results are expected in the second half of 2021. ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Research Ethics Committee of the Academic Medical Centre (AMC) of the Amsterdam University Medical Centres and by the Dutch competent authority. It is an investigator-initiated study with financial support by Ipsen Farmaceutica BV. The AMC, as sponsor, remains owner of all data. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NL5136 (Netherlands Trial Register); pre-recruitment

Continuing Challenges in the Definitive Diagnosis of Cushing’s Disease: A Structured Review Focusing on Molecular Imaging and a Proposal for Diagnostic Work-Up

The definitive diagnosis of Cushing’s disease (CD) in the presence of pituitary microadenoma remains a continuous challenge. Novel available pituitary imaging techniques are emerging. This study aimed to provide a structured analysis of the diagnostic accuracy as well as the clinical use of molecular imaging in patients with ACTH-dependent Cushing’s syndrome (CS). We also discuss the role of multidisciplinary counseling in decision making. Additionally, we propose a complementary diagnostic algorithm for both de novo and recurrent or persistent CD. A structured literature search was conducted and two illustrative CD cases discussed at our Pituitary Center are presented. A total of 14 CD (n = 201) and 30 ectopic CS (n = 301) articles were included. MRI was negative or inconclusive in a quarter of CD patients. 11C-Met showed higher pituitary adenoma detection than 18F-FDG PET–CT (87% versus 49%). Up to 100% detection rates were found for 18F-FET, 68Ga-DOTA-TATE, and 68Ga-DOTA-CRH, but were based on single studies. The use of molecular imaging modalities in the detection of pituitary microadenoma in ACTH-dependent CS is of added and complementary value, serving as one of the available tools in the diagnostic work-up. In selected CD cases, it seems justified to even refrain from IPSS