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Background Cranial dural arteriovenous fistulas (dAVFs) are rare lesions managed mainly with endovascular treatment (EVT) and/or surgery. We hypothesize that there may be subtypes of dAVFs responding better to a specific treatment modality in terms of successful obliteration and cessation of symptoms and/or risks. Methods All dAVFs treated during 2011–2018 at our hospital were analyzed retrospectively. Presenting symptoms, radiological variables, treatment modality, complications, and residual symptoms were related to dAVF type using the original Djindjian classification. Results We treated 112 dAVFs in 107 patients (71, 66% males). They presented with hemorrhage (n = 23; 21%), non-hemorrhagic symptoms (n = 75; 70%), or were discovered incidentally (n = 9; 8%). There were 25 (22%) type I, 29 (26%) type II, 26 (23%) type III, and 32 (29%) type IV fistulas. EVT was the primary treatment modality in 72/112 (64%) dAVFs whereas 40/112 (36%) underwent primary surgery with angiographic obliteration rates of 60% and 90%, respectively. Using a secondary treatment modality in 23 dAVFs, we obtained a final obliteration rate of 93%, including all type III/IV and 26/27 (96%) type II dAVFs. Except for headache, residual symptoms were rare and minor. Permanent neurological complications consisted of five cranial nerve deficits. Conclusions We recommend EVT as first treatment modality in types I, II, and in non-hemorrhagic type III/IV dAVFs. We recommend surgery as first treatment choice in acute hemorrhagic dAVFs and as secondary choice in type III/IV dAVFs not successfully occluded by EVT. Combining the two modalities provides obliteration in 9/10 dAVF cases at a low procedural risk.

Background Outcome of early, aggressive management of aneurysmal subarachnoid hemorrhage (aSAH) in patients with Hunt and Hess grade V is hitherto limited, and we therefore present our results. Methods Retrospective study analyzing the medical data of 228 aSAH patients in Glasgow Coma Score 3–5 admitted to our hospital during the years 2002–2012. Background and treatment variables were registered. Outcome was evaluated after 3 and 12 months. Results We intended to treat 176 (77.2%) patients, but only 146 went on to aneurysm repair. Of 52 patients managed conservatively, 27 had abolished cerebral circulation around arrival and 25 were deemed unsalvageable. One-year overall mortality was 65.8% and most (84.7%) of the fatalities occurred within 30 days. One-year mortality was higher in patients > 70 years. Without aneurysm repair, mortality was 100%. After 1 year, 21.9% of all patients lived independently and 4.8% lived permanently in an institution. Outcome in the 78 survivors (34.2%) was favorable in 64.1% in terms of modified Rankin Scale score 0–2, and 85.9% of survivors were able to live at home. Return to work was low for all 228 patients with 14.0% of those employed prior to the hemorrhage having returned to paid work, and respectively, 26.3% in the subgroup of survivors. Conclusions Even with aggressive, early treatment, 1-year mortality is high in comatose aSAH patients with 65.8%. A substantial portion of the survivors have a favorable outcome at 1 year (64.1%, corresponding to 21.9% of all patients admitted) and 85.9% of the survivors could live at home alone or aided.

Background While the smoking-related risk of experiencing an aneurysmal subarachnoid hemorrhage (aSAH) is well established, it remains unclear whether smoking has an unexpected “protective effect” in aSAH, or if smokers are more at risk for complications and poor outcomes. Methods Prospective, observational study investigating the course and outcome of aSAH in patients admitted during the years 2011 and 2012. Smoking status at admittance, demographic, medical, and radiological variables were registered along with management, complications, and outcome at 1 year in terms of mortality, modified Rankin score, and Glasgow outcome score extended. We compared current smokers with nonsmokers on group level and by paired analysis matched by aSAH severity, age, and severity of vasospasm. Results We included 237 patients, thereof 138 current smokers (58.2%). Seventy-four smoker/nonsmoker pairs were matched. Smokers presented more often in poor clinical grade, had less subarachnoid blood, and were younger than nonsmokers. Ruptured aneurysms were larger, and multiple aneurysms more common in smokers. Severe multi-vessel vasospasm was less frequent in smokers, whereas all other complications occurred at similar rates. Mortality at 30 days was lower in smokers and functional outcome was similar in smokers and nonsmokers. Poor clinical grade, age, cerebral infarction, and vertebrobasilar aneurysms were independent predictors of 1-year mortality and of poor functional outcome. Serious comorbidity was a predictor of 1-year mortality. Smoking did not predict mortality or poor functional outcome. Conclusions Notwithstanding clinically more severe aSAH, smokers developed less frequently severe vasospasm and had better outcome than expected. The risk for complications after aSAH is not increased in smokers.

Fatigue after aneurysmal subarachnoid hemorrhage (post-aSAH fatigue) is a frequent, often long-lasting, but still poorly studied sequel. The aim of the present study was to characterize the nature of post-aSAH fatigue with an itemized analysis of the Fatigue Severity Scale (FSS) and Mental Fatigue Scale (MFS). We further wanted to assess the association of fatigue with other commonly observed problems after aSAH: mood disorders, cognitive problems, health-related quality of life (HRQoL), weight gain, and return to work (RTW). Ninety-six good outcome aSAH patients with fatigue completed questionnaires measuring fatigue, depression, anxiety, and HRQoL. All patients underwent a physical and neurological examination. Cognitive functioning was assessed with a neuropsychological test battery. We also registered prior history of fatigue and mood disorders as well as occupational status and RTW. The patients experienced fatigue as being among their three most disabling symptoms and when characterizing their fatigue they emphasized the questionnaire items “low motivation,” “mental fatigue,” and “sensitivity to stress.” Fatigue due to exercise was their least bothersome aspect of fatigue and weight gain was associated with depressive symptoms rather than the severity of fatigue. Although there was a strong association between fatigue and mood disorders, especially for depression, the overlap was incomplete. Post-aSAH fatigue related to reduced HRQoL. RTW was remarkably low with only 10.3% of patients returning to their previous workload. Fatigue was not related to cognitive functioning or neurological status. Although there was a strong association between fatigue and depression, the incomplete overlap supports the notion of these two being distinct constructs. Moreover, post-aSAH fatigue can exist without significant neurological or cognitive impairments, but is related to reduced HRQoL and contributes to the low rate of RTW.

BACKGROUND Cerebral dural arteriovenous fistulas (dAVFs) presenting with hemorrhage are so rare that reports on their characteristics and guidelines for their acute management are scarce. OBJECTIVE To identify characteristics of the clinical and radiological presentation of hemorrhaging dAVFs, and establish their frequency of early rebleed so that implications for their acute management can be drawn. METHODS Retrospective analysis of all patients admitted with intracranial hemorrhage from a dAVF during the years 2011 to 2018. RESULTS Twenty patients (14 males) with a median age of 61 yr (27-75 yr) were included. Thunderclap headache was the presenting symptom in 13 (65%) patients. Rebleed prior to treatment occurred in 35% of the patients at median 7.5 h (range 3-96 h) after the ictus. All dAVFs had retrograde venous drainage and a venous aneurysm with a bleb was the source of hemorrhage in 16 (80%) patients, all of them presenting with headache. In contrast, patients bleeding due to diffuse venous hypertension presented with neurological deficits. Endovascular treatment was successful in 2 cases; hence, definite dAVF treatment was surgical in 18 (90%) patients. At median 7 mo (2-29 mo) after the ictus, 13 (65%) patients were in Glasgow Outcome Scale-Extended 7 or 8. CONCLUSION The typical presentation of hemorrhage from a cranial dAVF is thunderclap headache. The origin of hemorrhage is often a ruptured venous aneurysm with a bleb. The high frequency of early rebleeds warrants management strategies equivalent to those established for aneurysmal subarachnoid hemorrhage. Overall outcome is favorable.

Several recently published multicenter studies have reported high treatment feasibility, high safety, and good 6-month to 1-year efficiency when treating smaller intracranial aneurysms (IA) with WEB deployment. The purpose of the study was to evaluate the long-term efficiency and complications related to WEB treatment of larger, complex intracranial aneurysms in a small single-center cohort. Patients with ruptured and unruptured IA were treated with WEB devices; data were collected prospectively and analyzed retrospectively. The study evaluates complications and clinical and radiological findings at immediate and last available follow-up. The study included 16 patients with 16 aneurysms and a median follow-up time of 36 months, range 13–49 months; 9/16 were females. Median age 59 with range 39–71 years. Mean aneurysm size 11.3 ± 1.7 mm, predominant location at the basilar artery bifurcation and anterior communicating artery. Three out of sixteen IAs were ruptured. Even though 75% of the IAs were immediately occluded completely, retreatment was eventually necessary in 7/15 (46.7%). Increasing neck remnants and recurrences were mainly observed past 1-year follow-up. The WEB device showed modifications over time, with six devices showing signs of compression in the long term. There was one fatality due to aneurysm rupture after 4 years. The long-term efficiency of WEB deployment in larger, complex aneurysms is low with about half of the cases needing at least one retreatment. A large fraction of WEB collapse past 1-year follow-up.

Net cerebrospinal fluid (CSF) flow within the cerebral aqueduct is usually considered to be antegrade, i.e., from the third to the fourth ventricle with volumes ranging between 500 and 600 ml over 24 h. Knowledge of individual CSF flow dynamics, however, is hitherto scarcely investigated. In order to explore individual CSF flow rate and direction, we assessed net aqueductal CSF flow in individuals with intracranial aneurysms with or without a previous subarachnoid hemorrhage (SAH). A prospective observational study was performed utilizing phase-contrast magnetic resonance imaging (PC-MRI) to determine the magnitude and direction of aqueductal CSF flow with an in-depth, pixel-by-pixel approach. Estimation of net flow was used to calculate CSF flow volumes over 24 h. PC-MRI provides positive values when flow is retrograde. The study included eight patients with intracranial aneurysms. Four were examined within days after their SAH; three were studied in the chronic stage after SAH while one patient had an unruptured intracranial aneurysm. There was a vast variation in magnitude and direction of aqueductal CSF flow between individuals. Net aqueductal CSF flow was retrograde, i.e., directed towards the third ventricle in 5/8 individuals. For the entire patient cohort, the estimated net aqueductal CSF volumetric flow rate (independent of direction) was median 898 ml/24 h (ranges 69 ml/24 h to 12.9 l/24 h). One of the two individuals who had a very high estimated net aqueductal CSF volumetric flow rate, 8.7 l/24 h retrograde, later needed a permanent CSF shunt. The magnitude and direction of net aqueductal CSF flow vary extensively in patients with intracranial aneurysms. Following SAH, PC-MRI may offer the possibility to perform individualized assessments of the CSF circulation.

Background Dural arteriovenous fistulae are among the most common causes of pulsatile tinnitus. Selective angiography can be necessary for a definitive diagnosis, but in rare cases has been reported to cause sudden cortical blindness. Case presentation We present a woman in her seventies for whom cerebral angiography revealed a dural arteriovenous fistula. Two hours after the angiography she experienced sudden bilateral blindness. A local cause of sudden visual loss was excluded by clinical examination, cerebral bleeding was excluded by CT scan, vascular spasms and occlusions were excluded by CT angiography and acute infarction over the bilateral parieto-occipital cortex was excluded by MRI. The CT scan did, however, show contrast enhancement in the visual cortex from the contrast given during the previously performed cerebral angiography. The patient's vision spontaneously recovered within six days after the angiography, with no residual neurological deficits in her subsequent clinical follow up. Surgery was later performed on her dural arteriovenous fistula, which successfully treated the pulsatile tinnitus. Interpretation Transient cortical blindness is a rare but dramatic complication after cerebral angiography, thought to be caused by the transient neurotoxic effects of iodine-containing contrast agents. When other causes of sudden blindness are excluded, the patient can be reassured about the excellent prognosis for this condition.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Guidelines state that patients with aneurysmal subarachnoid haemorrhage (aSAH) require neurosurgical treatment as early as possible. Little is known about the time frame of transport from the ictus scene to Neurosurgery in large, partially remote catchment areas. We therefore analysed the chronology and transport logistics of aSAH patients in the South-Eastern Norway Health Region and related them to the frequency of aneurysm rebleed and 1-year mortality. Retrospective analysis of aSAH patients bleeding within our region admitted to Neurosurgery during a 5-year period. Date, time and site of ictus and arrival at Neurosurgery, distance and mode of transport and admission were obtained from our institutional quality register and the emergency medical communication centre log. We scored the patients’ clinical condition, rebleeds and 1-year mortality. Five hundred forty-four patients were included. Median time from ictus to arrival Neurosurgery was 4.5 h. Transport by road ambulance was most common at distances between the ictus scene and Neurosurgery below 50 km, whereas airborne transport became increasingly more common at larger distances. Direct admissions, frequency of intubation and airborne transport to Neurosurgery increased with the severity of haemorrhage, leading to shorter transport times. The risk of rebleed was 0.8%/hour of transport. The rebleed rate was independent of distances travelled, but increased with the severity of aSAH, reaching up to 6.54%/hour in poor-grade patients. Distance and time of transport had no impact on 1-year mortality, whereas poor-grade aSAH and rebleed were strong predictors of mortality. Poor-grade aSAH patients have a high risk of rebleed independent of the distance between the ictus scene and Neurosurgery. As rebleeding triples 1-year mortality, patients with Glasgow Coma Score

Background Fatigue is a common and disabling sequel after aneurysmal subarachnoid hemorrhage (aSAH). At present, prevalence estimates of post-aSAH fatigue in the chronic phase are scarce and vary greatly. Factors from the acute phase of aSAH have hitherto barely been associated with post-aSAH fatigue in the chronic phase. Methods Prospective study assessing prevalence of fatigue using the Fatigue Severity Scale (FSS) in patients who were living independently 1 to 7 years after aSAH. We compared demographic, medical, and radiological variables from the acute phase of aSAH between patients with and without fatigue (FSS ≥ 4 versus < 4) and searched for predictors of fatigue among these variables applying univariable and multivariable regression analyses. Results Of 726 patients treated for aSAH in the period between January 2012 and December 2017, 356 patients completed the assessment. The mean FSS score was 4.7 ± 1.7, and fatigue was present in 69.7%. The frequency of patients with fatigue did not decline significantly over time. Univariable analysis identified nicotine use, loss of consciousness at ictus (LOCi), rebleed prior to aneurysm repair, reduced consciousness to Glasgow Coma Scale (GCS) < 14, large amounts of subarachnoid blood, the presence of acute hydrocephalus, and severe vasospasm as factors that were significantly associated with fatigue. In multivariable analysis, nicotine use, reduced GCS, and severe vasospasm were independent predictors that all more than doubled the risk to develop post-aSAH fatigue. Conclusions Fatigue is a frequent sequel persisting several years after aSAH. Nicotine use, reduced consciousness at admission, and severe vasospasm are independent predictors of fatigue from the acute phase of aSAH. We propose inflammatory cytokines causing dopamine imbalance to be a common denominator for post-aSAH fatigue and the presently identified predictors.

Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to shortages in donor organ availability. Organ scarcity also affects the routine supply of human hepatocytes for basic research and the clinic. Therefore, the development of renewable sources of human liver progenitor cells is desirable and is the goal of this study. To be able to effectively generate and deploy human liver progenitors on a large scale, a reproducible hepatic progenitor differentiation system was developed. This protocol aids experimental reproducibility between users in a range of cell cultureware formats and permits differentiations using both, human embryonic and induced pluripotent stem cell lines. These are important advantages over current differentiation systems that will enhance the basic research and may pave the way towards clinical product development.

Background The discovery of an unruptured intracranial aneurysm creates a dilemma between observation and treatment. Neurosurgeons’ routines for risk assessment and treatment decision-making are unknown. The position of evidence-based medicine in European neurosurgery is considered to be weak, high-grade guidelines do not exist and variations between institutions are probable. We aimed to explore European neurosurgeons’ management routines for newly discovered unruptured intracranial aneurysms. Methods In cooperation with the European Association of Neurosurgical Societies (EANS), we conducted an online, cross-sectional survey of 420 European neurosurgeons during Spring/Summer 2016 (1533 non-Norwegians invited through the EANS, and 16 Norwegians invited through heads of departments because of the need for additional information for a separate study). We asked about demographic variables, routines for management and risk assessment of newly discovered unruptured intracranial aneurysms and presented a case. We collected information about gross domestic product (GDP) per capita from the International Monetary Fund. Results The response rate to the invite from the EANS was 26%, with respondents from 47 countries. More than half of the respondents (n = 226 [54%]) reported that their department treated less than 25 unruptured aneurysms yearly. Forty percent said their department used aneurysm size cut-off to guide treatment decisions, with a mean size of 6 mm. Presented with a case, respondents from countries with a lower GDP per capita recommended intervention more often than respondents from higher-income countries. Vascular neurosurgeons more commonly recommended observation. Conclusion The answers to this self-reported survey indicate that many centers have a treatment volume lower than recommended by international guidelines, and that there are socioeconomic differences in care. Better documentation of treatment and outcome, for example with clinical quality registries, is needed to drive improvements of care.

BACKGROUND Maximal size and other morphological parameters of intracranial aneurysms (IAs) are used when deciding if an IA should be treated prophylactically. These parameters are derived from postrupture morphology. As time and rupture may alter the aneurysm geometry, possible morphological predictors of a rupture should be established in prerupture aneurysms. OBJECTIVE To identify morphological parameters of unruptured IAs associated with later rupture. METHODS Nationwide matched case-control study. Twelve IAs that later ruptured were matched 1:2 with 24 control IAs that remained unruptured during a median follow-up time of 4.5 (interquartile range, 3.7-8.2) yr. Morphological parameters were automatically measured on 3-dimensional models constructed from angiograms obtained at time of diagnosis. Cases and controls were matched by aneurysm location and size, patient age and sex, and the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, and site of aneurysm) score did not differ between the 2 groups. RESULTS Only inflow angle was significantly different in cases vs controls in univariate analysis (P = .045), and remained significant in multivariable analysis. Maximal size correlated with size ratio in both cases and controls (P = .015 and

OBJECTIVEAlthough many patients recover to a good functional outcome after aneurysmal subarachnoid hemorrhage (aSAH), residual symptoms are very common and may have a large impact on the patient’s daily life. The particular cluster of residual symptoms after aSAH has not previously been described in detail and there is no validated questionnaire that covers the typical problems reported after aSAH. Many of the symptoms are similar to post-concussion syndrome, which often is evaluated with the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). In the present study, the authors therefore performed an exploratory use of the RPQ as a template to describe post-aSAH syndrome.METHODSThe RPQ was administered to 128 patients in the chronic phase after aSAH along with a battery of quality-of-life questionnaires. The patients also underwent a medical examination besides cognitive and physical testing. Based on their RPQ scores, patients were dichotomized into a “syndrome” group or “recovery” group.RESULTSA post-aSAH syndrome was seen in 33% of the patients and their symptom burden on all RPQ subscales was significantly higher than that of patients who had recovered on all RPQ subscales. The symptom cluster consisted mainly of fatigue, cognitive problems, and emotional problems. Physical problems were less frequently reported. Patients with post-aSAH syndrome scored significantly worse on mobility and pain scores, as well as on quality-of-life questionnaires. They also had significantly poorer scores on neuropsychological tests of verbal learning, verbal short- and long-term memory, psychomotor speed, and executive functions. Whereas 36% of the patients in the recovery group were able to return to their premorbid occupational status, this was true for only 1 patient in the syndrome group.CONCLUSIONSApproximately one-third of aSAH patients develop a post-aSAH syndrome. These patients struggle with fatigue and cognitive and emotional problems. Patients with post-aSAH syndrome report more pain and reduced quality of life compared to patients without this cluster of residual symptoms and have larger cognitive deficits. In this sample, patients with post-aSAH syndrome were almost invariably excluded from return to work. The RPQ is a simple questionnaire covering the specter of residual symptoms after aSAH. Being able to acknowledge these patients’ complaints as a defined syndrome using the RPQ should help patients to accept and cope, thereby alleviating possible secondary distress produced.

The DEFECTIVE KERNEL1 (DEK1) gene encodes the unique plant calpain protein, which is fundamental for cell specification, development, and growth of land plants. The β-glucuronidase (GUS) reporter gene system has been used to characterize and localize gene expression over several decades. When cloning a promoter upstream of the uidA/GUS reporter gene, you visualize when the promoter is activating expression by monitoring enzymatic activity of GUS, by detecting β-glucuronidase cleavage products. Here we describe a protocol for monitoring the DEK1 promoter activity in different tissues in Arabidopsis by GUS staining.

Temporary parent vessel clip occlusion in aneurysm surgery is not always practical or feasible. Adenosine-induced transient cardiac arrest may serve as an alternative. We retrospectively reviewed our clinical database between September 2011 and July 2014. All patients who underwent microsurgical clipping of intracranial aneurysms under adenosine-induced asystole were included. A total of 18 craniotomies were performed, and 18 aneurysms were clipped under adenosine-induced asystole (7 basilar arteries, 8 internal carotid arteries, 1 middle cerebral artery, and 1 anterior communicating artery) in 16 patients (10 females, 6 males). Nine cases were elective and seven after subarachnoid hemorrhage. Mean age was 54 years (range 39-70). The indications for adenosine use were proximal control in narrow surgical corridors in 13 cases and "aneurysm softening" in 4 cases. A single dose was used in 14 patients; 3 patients had multiple boluses. The median (range) total dose was 30 (18-135) mg. Adenosine induced a bradycardia with concomitant arterial hypotension in all patients, and the majority also had asystole for 5-15 sec. Transient cardiac arrhythmias were noted in one patient (AFib in need of electroconversion after two boluses). Nine clinical scenarios where adenosine-induced temporary cardiac arrest and deep hypotension was an effective adjunct to temporary clipping during microsurgical clipping of intracranial aneurysms were identified.

Swollen middle cerebral artery infarction is a life-threatening disease and decompressive craniectomy is improving survival significantly. Despite decompressive surgery, however, many patients are not discharged from the hospital alive. We therefore wanted to search for predictors of early in-hospital death after craniectomy in swollen middle cerebral artery infarction. All patients operated with decompressive craniectomy due to swollen middle cerebral artery infarction at the Department of Neurosurgery, Oslo University Hospital Rikshospitalet, Oslo, Norway, between May 1998 and October 2010, were included. Binary logistic regression analyses were performed and candidate variables were age, sex, time from stroke onset to decompressive craniectomy, NIHSS on admission, infarction territory, pineal gland displacement, reduction of pineal gland displacement after surgery, and craniectomy size. Fourteen out of 45 patients (31%) died during the primary hospitalization (range, 3–44 days). In the multivariate logistic regression model, middle cerebral artery infarction with additional anterior and/or posterior cerebral artery territory involvement was found as the only significant predictor of early in-hospital death (OR, 12.7; 95% CI, 0.01–0.77; p = 0.029). The present study identified additional territory infarction as a significant predictor of early in-hospital death. The relatively small sample size precludes firm conclusions.

Therapeutic parent artery flow reversal is a treatment option for giant, partially thrombosed basilar tip aneurysms. The effectiveness of this treatment has been variable and not yet studied by applying computational fluid dynamics. Computed tomography images and blood flow velocities acquired with transcranial Doppler ultrasonography were obtained prior to and after bilateral endovascular vertebral artery occlusion for a giant basilar tip aneurysm. Patient-specific geometries and velocity waveforms were used in computational fluid dynamics simulations in order to determine the velocity and wall shear stress changes induced by treatment. Therapeutic parent artery flow reversal lead to a dramatic increase in aneurysm inflow and wall shear stress (30 to 170 Pa) resulting in an increase in intra-aneurysmal circulation. The enlargement of the circulated area within the aneurysm led to a re-normalization of the wall shear stress and the aneurysm remained stable for more than 8 years thereafter. Therapeutic parent artery flow reversal can lead to unintended, potentially harmful changes in aneurysm inflow which can be quantified and possibly predicted by applying computational fluid dynamics.

Eukaryotic development and stem cell control depend on the integration of cell positional sensing with cell cycle control and cell wall positioning, yet few factors that directly link these events are known. The DEFECTIVE KERNEL1 (DEK1) gene encoding the unique plant calpain protein is fundamental for development and growth, being essential to confer and maintain epidermal cell identity that allows development beyond the globular embryo stage. We show that DEK1 expression is highest in the actively dividing cells of seeds, meristems and vasculature. We further show that eliminating Arabidopsis DEK1 function leads to changes in developmental cues from the first zygotic division onward, altered microtubule patterns and misshapen cells, resulting in early embryo abortion. Expression of the embryonic marker genes WOX2, ATML1, PIN4, WUS and STM, related to axis organization, cell identity and meristem functions, is also altered in dek1 embryos. By monitoring cell layer-specific DEK1 down-regulation, we show that L1- and 35S-induced down-regulation mainly affects stem cell functions, causing severe shoot apical meristem phenotypes. These results are consistent with a requirement for DEK1 to direct layer-specific cellular activities and set downstream developmental cues. Our data suggest that DEK1 may anchor cell wall positions and control cell division and differentiation, thereby balancing the plant's requirement to maintain totipotent stem cell reservoirs while simultaneously directing growth and organ formation. A role for DEK1 in regulating microtubule-orchestrated cell wall orientation during cell division can explain its effects on embryonic development, and suggests a more general function for calpains in microtubule organization in eukaryotic cells.

OBJECTIVE Early rehabilitation is effective in an array of acute neurological disorders but it is not established as part of treatment guidelines after aneurysmal subarachnoid hemorrhage (aSAH). This may in part be due to the fear of aggravating the development of cerebral vasospasm, which is the most feared complication of aSAH. The aim of this study was to evaluate the effect of early rehabilitation and mobilization on complications during the acute phase and within 90 days after aSAH. METHODS This was a prospective, interventional study that included patients with aSAH at the neuro-intermediate ward after aneurysm repair. The control group received standard treatment, whereas the early rehab group underwent early rehabilitation and mobilization in addition to standard treatment. Clinical and radiological characteristics of patients with aSAH, progression in mobilization, and treatment variables were registered. The frequency and severity of cerebral vasospasm, cerebral infarction acquired in conjunction with the aSAH, and acute and chronic hydrocephalus, as well as pulmonary and thromboembolic complications, were compared between the 2 groups. RESULTS Clinical and radiological characteristics of patients with aSAH were similar between the groups. The early rehab group was mobilized beginning on the first day after aneurysm repair. The significantly quicker and higher degree of mobilization in the early rehab group did not increase complications. Clinical cerebral vasospasm was not as frequent in the early rehab group and it also tended to be less severe. Each step of mobilization achieved during the first 4 days after aneurysm repair reduced the risk of severe vasospasm by 30%. Acute and chronic hydrocephalus were similar in both groups, but there was a tendency toward earlier shunt implantation among patients in the control group. Pulmonary infections, thromboembolic events, and death before discharge or within 90 days after the ictus were similar between the 2 groups. CONCLUSIONS Early rehabilitation of patients after aSAH is safe and feasible. The earlier and higher degree of mobilization does not increase neurosurgical complications. Rather, the frequency and severity of cerebral vasospasm following aSAH are alleviated and are not aggravated by early rehabilitation. Clinical trial registration no.: NCT01656317 (www.clinicaltrials.gov).

Object Indices of cerebrovascular pressure reactivity (CPR) represent surrogate markers of cerebral autoregulation. Given that intracranial pressure (ICP) wave amplitude–guided management, as compared with static ICP-guided management, improves outcome following aneurysmal subarachnoid hemorrhage (SAH), indices of CPR derived from pressure wave amplitudes should be further explored. This study was undertaken to investigate the value of CPR indices derived from static ICP–arterial blood pressure (ABP) values (pressure reactivity index [PRx]) versus ICP-ABP wave amplitudes (ICP-ABP wave amplitude correlation [IAAC]) in relation to the early clinical state and 12-month outcome in patients with aneurysmal SAH. Methods The authors conducted a single-center clinical trial enrolling patients with aneurysmal SAH. The CPR indices of PRx and IAAC of Week 1 after hemorrhage were related to the early clinical state (Glasgow Coma Scale [GCS] score) and 12-month outcome (modified Rankin Scale score). Results Ninety-four patients were included in the study. The IAAC, but not the PRx, increased with decreasing GCS score; that is, the higher the IAAC, the worse the clinical state. The PRx could differentiate between survivors and nonsurvivors only, whereas the IAAC clearly distinguished the groups “independent,” “dependent,” and “dead.” In patients with an average IAAC ≥ 0.2, mortality was approximately 3-fold higher than in those with an IAAC < 0.2. Conclusions The IAAC, which is based on single ICP-ABP wave identification, relates significantly to the early clinical state and 12-month outcome following aneurysmal SAH. Impaired cerebrovascular pressure regulation during the 1st week after a bleed relates to a worse outcome. Clinical trial registration no.: NCT00248690.

Background In patients with aneurysmal subarachnoid hemorrhage (SAH), preliminary results indicate that the amplitude of the single intracranial pressure (ICP) wave is a better predictor of the early clinical state and 6-month outcome than the mean ICP. Objective To perform a randomized and blinded single-center trial comparing the effect of mean ICP vs mean ICP wave amplitude (MWA)-guided intensive care management on early clinical state and outcome in patients with aneurysmal SAH. Methods Patients were randomized to 2 different types of ICP management: maintenance of mean ICP less than 20 mm Hg and MWA less than 5 mm Hg. Early clinical state was assessed daily using the Glasgow Coma Scale. The primary efficacy variable was 12-month outcome in terms of the Rankin Stroke Score. Results Ninety-seven patients were included in the study. There were no significant differences in treatment between the 2 groups apart from a larger volume of cerebrospinal fluid drained during week 1 in the MWA group. There was a tendency toward higher Glasgow Coma Scale scores in the MWA group during weeks 1 (P = .08) and 2 (P = .07). Outcome in terms of Rankin Stroke Score at 12 months was significantly better in the MWA group (P Conclusion This randomized and blinded trial disclosed a significant better primary efficacy variable (Rankin Stroke Score after 12 months) in the MWA patient group. We suggest that proactive intensive care management with MWA-tailored cerebrospinal fluid drainage during the first week improves aneurysmal SAH outcome.

Objective The objective of this study was to determine cognitive functioning and health-related quality of life 1 year after aneurysmal subarachnoid hemorrhage in preoperative comatose patients (Hunt and Hess Grade V patients). Methods Patients who were comatose at hospital arrival and thereafter were investigated for 1 year using a comprehensive neuropsychological test battery and 2 HRQOL questionnaires. Results Thirty-five of 70 patients survived the bleed, and 26 underwent neuropsychological testing. Two distinct patient groups emerged, one (n = 14) with good cognitive function, having mild deficits only, and the other (n = 12) with poor cognitive and poor motor function. Patients performing poorly were older (P = .04), had fewer years of education (P = .005) and larger preoperative ventricular scores, and were more often shunted (P = .02). There were also differences between the 2 groups in the Glasgow Outcome Scale (P = .001), the modified Rankin Scale (P = .001), and employment status. HRQOL was more reduced in patients with poor cognitive function. Conclusion A high fraction of survivors among preoperative comatose aneurysmal SAH patients (Hunt and Hess grade V) recover to good physical and cognitive function, enabling them to live a normal life.

Background and Purpose— Using postrupture morphology to predict rupture risk of an intracranial aneurysm may be inaccurate because of possible morphological changes at or around the time of rupture. The present study aims at comparing morphology from angiograms obtained prior to and just after rupture and to evaluate whether postrupture morphology is an adequate surrogate for rupture risk. Methods— Case series of 29 aneurysms from a nationwide retrospective data collection. Two neuroradiologists who were blinded to pre- versus postrupture images assessed predefined morphological parameters independently and reached consensus regarding all measurements. Prerupture morphology and respective changes after rupture were quantified and linked to risk factors and to the risk of rupture according to the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, site of aneurysm) and unruptured intracranial aneurysm treatment (UIAT) scores. Results— All 1-dimensional parameter medians were significantly larger after rupture, except neck diameter. Number of aneurysms with daughter sacs was 9 (31%) before and 17 (59%) after rupture ( P =0.005). Aneurysm growth from the images prior to and just after rupture increased with the time elapsed between images. Aneurysms in patients with hypertension were significantly larger at diagnosis. Prerupture morphology did not differ in relation to smoke status. Clinical risk factors were not significantly associated with morphological change. Conclusions— The changes in aneurysm morphology observed after rupture reflect the compound effect of time with successive growth and formation of irregularities and the impact of rupture per se. Postrupture morphology should not be considered an adequate surrogate for the prerupture morphology in the evaluation of rupture risk.

Objective To assess the impact of surgical treatment of unruptured and ruptured middle cerebral artery (MCA) aneurysms on cognitive functioning and health-related quality of life (HRQOL). Methods This was a prospective study enrolling 15 patients with unruptured MCA aneurysms and 22 patients with ruptured MCA aneurysms in good clinical condition postictally. Patients with unruptured aneurysms underwent preoperative neuropsychological testing and answered 2 HRQOL questionnaires. All patients were investigated 3 and 12 months postoperatively with a comprehensive neuropsychological test battery, clinical investigation, and interview. The modified Rankin Scale score, Glasgow Outcome Scale score, employment status, and 2 HRQOL questionnaires were also used for assessment. Results Preoperative cognitive deficits were aggravated 3 months after surgery for the unruptured MCA aneurysm group, but after 12 months these patients performed at their preoperative level. Subjects who underwent clipping for ruptured MCA aneurysms had reduced verbal memory; otherwise, they had close to normal cognitive function 12 months postoperatively. There was no difference between the 2 groups in Rankin Scale score or Glasgow Outcome Scale score. High preoperative levels of anxiety and depression markedly decreased after repair of an unruptured aneurysm; however, in both groups, HRQOL was reduced on the same measures even 12 months after surgery. Patients treated for unruptured MCA aneurysms regained their preoperative employment status, whereas only 60% of those who had bled from their aneurysm had returned to full-time work after 12 months. Conclusion Surgical treatment of unruptured MCA aneurysms does not cause new cognitive deficits, but it reduces some aspects of HRQOL in a similar manner as in patients who undergo clipping for ruptured MCA aneurysms.

The neuropsychological outcome and Health Related Quality of Life (HRQOL) after SAH have been largely believed to be unrelated to the location of the ruptured aneurysm. This notion needs verification due to the contemporary availability of more sensitive neuropsychological test batteries and more recent clinical observations of deviant behaviour after SAH. To this end, we compared patients with ruptured aneurysms on respectively the anterior communicating artery (ACoA) (n = 24) or middle cerebral artery (MCA) (n = 22). All patients underwent an extensive neuropsychological examination, clinical interview and answered questionnaires 12 months after SAH. We found mild to moderate discrepancies from population norm in test scores on a number of areas of cognitive functioning in both patient groups, with a consistent, but statistically non-significant trend towards better functioning in MCA patients despite of the fact that patients with ruptured MCA aneurysms were initially in a poorer clinical condition and more often had intracranial haematomas. We observed slight reductions in executive functions, on the first conditions on the Delis-Kaplan Executive Functioning System (D-KEFS) tests, and some measures of memory functions in the ACoA patients. ACoA patients seemed to have problems with initiation of problem solving behaviour. None of the patient groups scored for apathy and depression. Some measures of HRQOL were equally reduced as compared to the population norm in both groups. ACoA patients remained longer on sick-leave compared to MCA patients.

Objective and Importance When treating large unruptured ophthalmic artery (OA) aneurysms causing progressive blindness, surgical clipping is still the preferred method because aneurysm sac decompression may relieve optic nerve compression. However, endovascular treatment of OA aneurysms has made important progress with the introduction of stents. Although this development is welcomed, it also makes the choice of treatment strategy less straightforward than in the past, with the potential of missteps. Clinical Presentation A 56-year-old woman presented with a long history of progressive unilateral visual loss and magnetic resonance imaging showing a 20-mm left-sided OA aneurysm. Intervention Because of her long history of very poor visual acuity, we considered her left eye to be irredeemable and opted for endovascular therapy. The OA aneurysms was treated with stent and coils but continued to grow, threatening the contralateral eye. Because she failed internal carotid artery (ICA) balloon test occlusion, we performed a high-flow extracranial-intracranial bypass with proximal ICA occlusion in the neck. However, aneurysm growth continued due to persistent circulation through reversed blood flow in distal ICA down to the OA and the cavernous portion of the ICA. Due to progressive loss of her right eye vision, we surgically occluded the ICA proximal to the posterior communicating artery and excised the coiled, now giant, OA aneurysm. This improved her right eye vision, but her left eye was permanently blind. Conclusion This case report illustrates complications of the endovascular and surgical treatment of a large unruptured OA aneurysm.

Background Renewed interest has developed in decompressive craniectomy, and improved survival is shown when this treatment is used after malignant middle cerebral artery infarction. The aim of this study was to investigate the frequency and possible risk factors for developing surgical site infection (SSI) after delayed cranioplasty using autologous, cryopreserved bone. Methods This retrospective study included 74 consecutive patients treated with decompressive craniectomy during the time period May 1998 to October 2010 for various non-traumatic conditions causing increased intracranial pressure due to brain swelling. Complications were registered and patient data was analyzed in a search for predictive factors. Results Fifty out of the 74 patients (67.6 %) survived and underwent delayed cranioplasty. Of these, 47 were eligible for analysis. Six patients (12.8 %) developed SSI following the replacement of autologous cryopreserved bone, whereas bone resorption occurred in two patients (4.3 %). No factors predicted a statistically significant rate of SSI, however, prolonged procedural time and cardiovascular comorbidity tended to increase the risk of SSI. Conclusions SSI and bone flap resorption are the most frequent complications associated with the reimplantation of autologous cryopreserved bone after decompressive craniectomy. Prolonged procedural time and cardiovascular comorbidity tend to increase the risk of SSI.

Objective Treatment of certain cerebral aneurysms, caroticocavernous fistulae, and tumors of the neck or cranial base may involve therapeutic arterial sacrifice, which requires preoperative knowledge of the feasibility of permanent occlusion of the internal carotid artery (ICA) or vertebral artery or arteries. Methods Retrospective study of transcranial Doppler ultrasonography-monitored angiographic balloon test occlusion and therapeutic sacrifice of the ICA or vertebral artery. Results We performed transcranial Doppler-guided balloon test occlusion in 136 patients at a procedural risk equivalent to that of conventional neuroangiography, and with correct prediction of the hemodynamic result of therapeutic arterial sacrifice in all instances. Patients with an immediate drop in ipsilateral middle cerebral artery (MCA) velocity to 65% or more of baseline values upon ICA balloon occlusion tolerated ICA sacrifice well, whereas hemodynamic infarction is likely in those with a corresponding drop in MCA velocity to 54% or less. When ICA balloon occlusion caused a drop in MCA velocity to between 55 and 64% of baseline, the pulsatility of the MCA signal had to be analyzed. Patients who tolerated bilateral vertebral artery closure had reversal of flow and an increase in velocity in the P1 section of the posterior cerebral artery. In 212 patient-years of observation after therapeutic arterial sacrifice, no de novo aneurysms formed. Conclusion Angiographic balloon test occlusion with transcranial Doppler monitoring can be performed ultra-swiftly at a risk equal to conventional neuroangiography and with correct prediction of the hemodynamic outcome of arterial sacrifice. Elective therapeutic arterial occlusion is a safe and efficient treatment of large cerebral aneurysms and caroticocavernous fistulae.

An intracranial aneurysm in a child or adolescent is a rare, but potentially devastating condition. As little as approximately 1200 cases are reported between 1939 and 2011, with many of the reports presenting diverting results. There is consensus, though, in that pediatric aneurysms represent a pathophysiological entity different from their adult counterparts. In children, there is a male predominance. About two-thirds of pediatric intracranial aneurysms become symptomatic with hemorrhage and the rate of re-hemorrhage is higher than in adults. The rate of hemorrhage from an intracranial aneurysm peaks in girls around menarche. The most common aneurysm site in children is the internal carotid artery, in particular at its terminal ending. Aneurysms in the posterior circulation are more common in children than adults. Children more often develop giant aneurysms, and may become symptomatic from the mass effect of the aneurysm (tumorlike symptoms). The more complex nature of pediatric aneurysms poses a larger challenge to treatment alongside with higher demands to the durability of treatment. Outcome and mortality are similar in children and adults, but long-term outcome in the pediatric population is influenced by the high rate of aneurysm recurrences and de novo formation of intracranial aneurysms. This urges the need for life-long follow-up and screening protocols.

Hydrocephalus (HC) after aneurysmal subarachnoid hemorrhage (aSAH) is a common sequel. Proper selection of patients in need of permanent cerebrospinal fluid (CSF) diversion is, however, not straightforward. The aim of this study was to identify predictors of CSF shunt dependency following aSAH. We re-analyzed data acquired from aSAH patients previously enrolled in a prospective, controlled single-center clinical trial in which shunt dependency was not one of the end points. In the present study patients were allocated into two groups: those receiving a shunt (here denoted as shunt dependent) and those not receiving a shunt, based on a clinical decision process. Predictors of shunt dependency were identified by applying uni- and multivariable analysis. We tested a set of predefined possible risk factors based on the results of the clinical trial, including the impact of CSF drainage volume exceeding 1,500 ml during the 1st week after ictus. Ninety patients were included in the study. Significant predictors of shunt dependency were poor clinical grade at admission [odds ratio (OR) 4.7, 95 % confidence interval (CI) 1.2–18.4], large amounts of subarachnoid blood (OR 3.8, 95 % CI 1.0–14.0), large ventricular size on preoperative cerebral computer tomographic (CT) scans (OR 1.0, 95 % CI 1.0–1.1), and CSF volume drainage exceeding 1,500 ml during the 1st week after the ictus (OR 16.3, 95 % CI 4.0–67.1). Age ≥70 years, larger amounts of intraventricular blood, vertebrobasilar aneurysm, and endovascular treatment tended to increase the likelihood of receiving a shunt. Outcome was not significantly different between shunted and non-shunted patients. In this cohort of patients with clinical grade aSAH at admission, larger amounts of subarachnoid blood and large ventricular size on preoperative cerebral CT, and CSF drainage in excess of 1,500 ml during the 1st week after the ictus were significant predictors of shunt dependency. Shunt dependency did not hamper outcome.

OBJECTIVE To assess the impact of early mobilization and rehabilitation on global functional outcome one year after aneurysmal subarachnoid haemorrhage. METHODS Prospective, controlled, interventional study comprising patients managed in the neuro-intermediate ward following repair of a ruptured intracranial aneurysm. Patients in the Control group (n = 76) received standard treatment, whereas those in the Early Rehab group (n = 92) in addition underwent early mobilization and rehabilitation. Demographic, clinical and intervention data were registered. Global functional outcome was assessed using the modified Rankin Scale and the Glasgow Outcome Scale Extended. RESULTS The 2 groups were similar in their demographic and clinical characteristics. Early Rehab group patients were mobilized more quickly (p

Object In this study, the authors compare simultaneous measurements of static and pulsatile pressure parameters in the epidural space and brain parenchyma of hydrocephalic patients. Methods Simultaneous intracranial pressure (ICP) signals from the epidural space (ICPEPI) and the brain parenchyma (ICPPAR) were compared in 12 patients undergoing continuous ICP monitoring as part of their diagnostic workup for hydrocephalus. The static ICP was characterized by mean ICP and the frequency of B waves quantified in the time domain, while the pulsatile ICP was determined from the cardiac beat–induced single ICP waves and expressed by the ICP pulse pressure amplitude (dP) and latency (dT; that is, rise time). Results The 12 patients underwent a median of 22.5 hours (range 5.9–24.8 hours) of ICP monitoring. Considering the total recording period of each patient, the mean ICP (static ICP) differed between the 2 compartments by ≥ 5 mm Hg in 8 patients (67%) and by ≥ 10 mm Hg in 4 patients (33%). In contrast, for every patient the ICP pulse pressure readings from the 2 compartments showed near-identical results. Consequently, when sorting patients to shunt/no shunt treatment according to pulsatile ICP values, selection was independent of sensor placement. The frequency of B waves also compared well between the 2 compartments. Conclusions The pulsatile ICP is measured with equal confidence from the ICPEPI and ICPPAR signals. When using the pulsatile ICP for evaluation of hydrocephalic patients, valid measurements may thus be obtained from pressure monitoring in the epidural space. Recorded differences in the mean ICP between the epidural space and the brain parenchyma are best explained by differences in the zero setting of different sensors.

Object The purpose of this study was to determine the frequency of infection and to identify risk factors for infection in connection with the implantation of an intrathecal baclofen (ITB) pump. Methods This retrospective study included all pediatric and adult patients who received ITB at Rikshospitalet during the years 1999–2005. A database was created that included the following variables: patient age, sex, weight, diagnosis, surgical procedure performed, presence of a percutaneous endoscopic gastrostomy (PEG) tube, urinary as well as fecal incontinence, anesthetist's classification of patient status (American Society of Anesthesiologists grade), timing of antibiotics administration, surgeon, assisting nurse, and surgical procedure time. Moreover, the mode of intrathecal screening trial (transcutaneous vs subcutaneous catheter insertion) and any complications were registered. The authors differentiated between deep and superficial infection, and they registered the causative agent. Results A total of 163 patients received ITB; of these, 91 were pediatric patients (median age 10 years), and 72 were adults (median age 44 years). A total of 408 surgical procedures were performed. No infections occurred in direct relation to the screening trials. When a pump was implanted subsequent to a screening trial with transcutaneous catheter insertion, the rate of infection was 9% in the pediatric patients. The corresponding infection rate for pumps implanted after a screening trial with a subcutaneous distal catheter (Albright method) was 12%. This difference was not significant. There was a significantly higher incidence of deep infections following pump implantation in the pediatric group (p = 0.028) than in the adult group. The presence of a PEG tube increased the incidence of infection (p = 0.008) and may be one of the main reasons for a higher frequency of infections in children. When the patient suffered urinary and/or fecal incontinence, there was a higher chance of infection (p = 0.021). The surgical time was significantly longer in the pediatric group than in adults; however, the length of the surgical procedure had no impact on the occurrence of infection. The most common causative agent was Staphylococcus aureus; this microbe was responsible for 69% of deep infections. Also, 69% of deep infections occurred within 1 month after surgery. Conclusions The rate of infection is significantly higher in children undergoing ITB pump implantation than it is in adults. Screening trials applying the Albright method fail to reduce the frequency of infection subsequent to pump implantation. The presence of a PEG tube has the greatest significance as a predictor of infection.

A well documented case of non-secretory myelomatosis with extensive skeletal lesions has been studied by immunohistologic techniques, electron microscopy, various electrophoretic procedures and different studies of serum and urine. In addition, the various lymphocyte populations have been studied by immunofluorescent techniques, rosette formation and stimulation with PHA and PWM mitogens. The ultrastructural studies revealed a well preserved structure of most of the plasma cells, often with a prominent nucleolus. The Golgi apparatus (GOL) was often large and in some cells there appeared to be a striking development of non-granular (smooth) endoplasmic reticulum in association with the GOL. Various non-crystalline inclusions were seen outside the cisternae of the endoplasmic reticulum. The cells contained large amounts of immunoglobulins of the IgG (kappa) class. No paraprotein was present in serum. Normal amounts of serum Immunoglobulins were detected. No abnormalities could be demonstrated in the B or T cell system. It is concluded that the defect must be localized to the plasma cells themselves and not to the precursor cells of the B system.

Background – In Norway, there are approximately 16000 strokes each year and 15% of these are caused by intracerebral hematomas. Intracerebral hemorrhage (ICH) results from the rupture of blood vessels within the brain parenchyma. ICH occurs as a complication of several diseases, the most prevalent of which is chronic hypertension. When hemorrhage develops in the absence of a pre-existing vascular malformation or brain parenchymal lesion, it is denoted primary ICH. Secondary ICH refers to hemorrhage complicating a pre-existing lesion. Primary ICH is the most common type of hemorrhagic stroke, accounting for approximately 10% of all strokes. Despite aggressive management strategies, the 30-day mortality remains high, at almost 50%, with the majority of deaths occurring within the first 2 days. At 6 months, only 20–30% achieve independent status. Material and methods – This article is based on clinical experience, modern therapeutic guidelines for the treatment of intracerebral hematomas and up-to-date medical literature found in Medline. The article discusses the pathophysiology, clinical aspects, treatment, and the prognosis of intracerebral hematomas. Results and discussion – Advances in diagnosis, prognosis, pathophysiology, and treatment over the past few decades have significantly advanced our knowledge of ICH; however, much work still needs to be carried out. Future genetic and epidemiologic studies will help identify at-risk populations and hopefully allow for primary prevention. Randomized controlled studies focusing on novel therapeutics should help to minimize secondary injury and hopefully improve morbidity and mortality.

The purpose of this study was to analyse the cerebral haemodynamic changes brought about by trial occlusion of the internal carotid artery (ICA). Sixteen patients with surgically inaccessible cerebral aneurysms, carotid cavernous fistulas or neck neoplasms were monitored with transcranial Doppler ultrasonography (TCD) during 90-120 s angiographic ICA balloon occlusion or ICA closure with a Selverstone clamp. The blood velocity (V) was registered continuously in both middle cerebral arteries (MCA) while the pulsatility index (PIMCA) and haemodynamic tension (Uhem MCA) were calculated. ICA closure led to an instantaneous drop in the ipsilateral VMCA, PIMCA and Uhem MCA. The VMCA thereafter increased gradually until reaching a stable level. The subjects were grouped into those with initial drops in VMCA toor = 60% of pre-occlusion value (group 1) and those that fell to60% (group 2), respectively. In group 1 autoregulatory mechanisms made the PIMCA decline further, while the Uhem MCA remained unaltered during ICA closure. In group 2, however, the PIMCA did not change further, while the Uhem MCA increased slightly. The cerebral haemodynamic features during ICA test occlusion were thus essentially different in the two groups. On re-opening the ICA, there was an overshoot in VMCA and Uhem MCA. Contralaterally, the VMCA was increased during ICA occlusion. Seven of the patients later had their ICA closed permanently. While none of five group 1 patients developed haemodynamic complications, two group 2 individuals experienced haemodynamic stroke. Assuming ICA sacrifice is feasible when test occlusion results in an ipsilateral initial reduction in VMCA toor = 60% of pre-occlusion value, the corresponding limit for the Uhem MCA isor = 40%. In the pre-operative evaluation of the haemodynamic risk related to ICA loss, TCD emerges as a reliable method. It also seems to allow for the reduction of test occlusion time to 90-120 s.

To explore whether intracranial pulse pressure amplitudes relate to arterial pulse pressure amplitudes and whether correlations between time-related changes in intracranial and arterial pulse pressure amplitudes associate with indices of cerebral autoregulation.A total of 257 continuous and simultaneous intracranial pressure (ICP), arterial blood pressure (ABP) and middle cerebral artery (MCA) blood velocity recordings were obtained 1-14 days after ictus in 76 traumatic head injury patients and analysed retrospectively. Clinical outcome was assessed using the Glasgow outcome scale (GOS). Pulse pressure amplitudes of corresponding single ICP and ABP waves were correlated in consecutive 200 wave pairs. Mean ICP, mean ABP and mean ICP wave amplitudes, and mean and systolic MCA blood flow velocities, were computed in consecutive 6 second time windows. The indices of cerebral autoregulation PRx (moving correlation between mean ICP and mean ABP), and Mx and Sx (moving correlation between mean and systolic MCA blood velocity and cerebral perfusion pressure) were calculated over 4 minute periods and averaged over each recording.Intracranial pulse pressure amplitudes were not related to arterial pulse pressure amplitudes (mean of Pearson's correlations coefficients: 0.04). Outcome was related to mean ICP, PRx and Sx (p/= 0.04, multiple regression analysis). Correlations between intracranial and arterial pulse pressure amplitudes were weakly related to PRx (Pearson's correlation coefficient: 0.16; p=0.01), but were not related to the indices of cerebral autoregulation Mx (Pearson's correlation coefficient: 0.07) and Sx (Pearson's correlation coefficient: 0.04).In this cohort of pressure recordings, we found no evidence of a correlation between intracranial and arterial blood pressure amplitudes. The correlation appeared not to be related to the state of cerebral autoregulation, although a weak correlation was found with pressure reactivity index PRx.

We report on a 65-year-old female with an aneurysmal subarachnoid hemorrhage (SAH) that was followed clinically, radiologically and electrophysiologically before and after converting from intracranial pressure (ICP)-guided to ICP wave-guided intensive care management. Intracranial pressure-guided management is aimed at keeping mean ICP < 15-20 mmHg, while ICP wave-guided management is aimed at keeping mean ICP wave amplitude < 5 mmHg. The aims of management were obtained by adjusting cerebrospinal fluid (CSF) draining volume from her external ventricular drain. No improvement was seen clinically or in cerebral magnetic resonance imaging (MRI) scans during the ICP-guided management. Clinical, MRI and neurophysiologic (electroencephalography and auditory evoked responses) improvements were obvious within 2 days after converting from ICP- to ICP wave-guided management. This case report describes how we used various ICP parameters to guide intensive care management of an aneurysmal SAH patient.

Background Directional intraoperative Doppler (dioDoppler) ultrasonography is well established as a tool in the surgery of intracranial aneurysms and cerebral arteriovenous malformations. The literature provides little information about the possible usefulness of this method during surgery on cranial dural arteriovenous fistulas (dAVFs). Objective To present our experience with the use of dioDoppler during surgery on cranial dAVFs. Methods All patients undergoing craniotomy for cranial dAVF from January 2007 to October 2012 in which dioDoppler was used were included in the study. We reviewed patient records, operating protocols, radiological images, dioDoppler files, and intraoperative videos. Results During the study period, 12 patients with cranial dAVFs underwent surgical treatment facilitated by dioDoppler. Four patients were operated on acutely for cerebral bleeds, and 8 patients were treated for various cerebral symptoms and the assumption of a significant risk for intracranial bleed. Three advantages of dioDoppler were unequivocal identification of veins with cortical/deep venous reflux from the fistula, verification of completeness of occlusion of the fistula, and identification of dural arterial feeders not visualized under the microscope. Conclusion Reviewing our experience, we found that dioDoppler sonography is an easy, safe, effective, reliable, and instantaneous tool during surgery on cranial dAVFs.

Objectives To examine the outcome of surgery for idiopathic normal-pressure hydrocephalus (iNPH) and how outcome relates to the preoperative static and pulsatile intracranial pressure (ICP). Methods An observational cohort study included all patients with iNPH managed at our department during the years 2002−2012 in whom overnight ICP monitoring was part of the preoperative work-up. Clinical data were retrieved from a quality registry and ICP scores from a pressure database. Results The study included 472 patients, 316 in the surgery group and 156 in the nonsurgery group. Among those treated surgically, 278 (90%) showed clinical improvement (Responders) whereas 32 (10%) had no improvement (Nonresponders). Among Responders, only about one third reached the best clinical scores; moreover, the difference in clinical score between Responders and Nonresponders declined with time after surgery, particularly after 3−4 years. The surgery was accompanied by acute intracranial hematomas in 11 patients (3.5%), of whom 4 (1.3%) died. Survival (age at death) was significantly greater among the Responders than in Nonresponders. Although the static ICP was normal in all patients, the pulsatile ICP was significantly greater in Responders than in Non-responders. Conclusions The pulsatile ICP was greater in shunt Responders than Nonresponders. Although the clinical improvement declined over time and the majority did not experience complete relief of symptoms, shunt Responders lived significantly longer than Nonresponders. The present observations suggest that the current surgical treatment regimens for iNPH (primarily shunt surgery) address only some aspects of the disease process, in particular the aspect of brain water disturbance.

Using mathematical model ling , the EFSA GMO Panel ha s previously quantified the risk to non - target (NT) Lepidoptera of conservation concern, potentially occurring within protected habitats, associated with the ingestion of Bt - maize pollen deposited on their host plants. To reduce the estimated larval mortality to a negligible level, an isolation distance of 20 and 30 m was recommended between protected habitats and the nearest fields of maize MON 810/Bt11 and 1507, respectively. Here , the EFSA GMO Panel refines its model predictions , accounting for new ly reported information on maize pollen deposition over long distances . For its calculations , the EFSA GMO Panel considered three exposure scenarios at a range of isolation distances, at two protection levels and for a range of lepidopteran species, including hypothetical ones, with a wide spectrum of sensitivities to Bt toxins . An analysis of various sources of uncertainties affecting the exposure of NT Lepidoptera to Bt - maize pollen was conducted, in order to provide quantitative estimates of realistic exposure levels. The EFSA GMO Panel therefore provides risk managers with a tool to estimate and mitigate the risk for NT Lepidoptera of conservation concern. In contrast to its previous o utcomes obtained for unrealistically large levels of exposure that would not be expected in practice, the EFSA GMO Panel reports here mortality estimates for a more realistic level of exposure. The EFSA GMO Panel concludes that its previous recommendation for a 20 m isolation distance around protected habitats, within which maize MON810/Bt11 should not be cultivated, remains valid. New calculations show that the previously recommended isolation distance of 30 m from the nearest maize 1507 field would still protect NT Lepidoptera with known levels of sensitivity, including the ‘highly - sensitive’ Plutella xylostella . Should hypothetical species with greater sensitivities exist, larger isolation distances would be needed to ensure the desired level of protection.