The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. METHODS: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient. RESULTS: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79-0.99), DCI 0.68 (95% CI 0.50-0.87) and functional outcome 0.74 (95% CI 0.57-0.91). Cohen's kappa between the two raters was moderate to substantial (0.57-0.63). CONCLUSIONS: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome.

The Unruptured Intracranial Aneurysm Treatment Score as a predictor of aneurysm growth or rupture.

BACKGROUND AND PURPOSE: The Unruptured Intracranial Aneurysm Treatment Score (UIATS) was built to harmonize the treatment decision making on unruptured intracranial aneurysms. Therefore, it may also function as a predictor of aneurysm progression. In this study, we aimed to assess the validity of the UIATS model to identify aneurysms at risk of growth or rupture during follow-up. METHODS: We calculated the UIATS for a consecutive series of conservatively treated unruptured intracranial aneurysms, included in our prospectively kept neurovascular database. Computed tomography angiography and/or magnetic resonance angiography imaging at baseline and during follow-up was analyzed to detect aneurysm growth. We defined rupture as a cerebrospinal fluid or computed tomography-proven subarachnoid hemorrhage. We calculated the area under the receiver operator curve, sensitivity, and specificity, to determine the performance of the UIATS model. RESULTS: We included 214 consecutive patients with 277 unruptured intracranial aneurysms. Aneurysms were followed for a median period of 1.3 years (range 0.3-11.7 years). During follow-up, 17 aneurysms enlarged (6.1%), and two aneurysms ruptured (0.7%). The UIATS model showed a sensitivity of 80% and a specificity of 44%. The area under the receiver operator curve was 0.62 (95% confidence interval 0.46-0.79). CONCLUSIONS: Our observational study involving consecutive patients with an unruptured intracranial aneurysm showed poor performance of the UIATS model to predict aneurysm growth or rupture during follow-up.

Prediction of Outcome After Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- Early prediction of clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH) is still lacking accuracy. In this observational cohort study, we aimed to develop and validate an accurate bedside prediction model for clinical outcome after aSAH, to aid decision-making at an early stage. Methods- For the development of the prediction model, a prospectively kept single-center cohort of 1215 aSAH patients, admitted between 1998 and 2014, was used. For temporal validation, a prospective cohort of 224 consecutive aSAH patients from the same center, admitted between 2015 and 2017, was used. External validation was performed using the ISAT (International Subarachnoid Aneurysm Trial) database (2143 patients). Primary outcome measure was poor functional outcome 2 months after aSAH, defined as modified Rankin Scale score 4-6. The model was constructed using multivariate regression analyses. Performance of the model was examined in terms of discrimination and calibration. Results- The final model included 4 predictors independently associated with poor outcome after 2 months: age, World Federation of Neurosurgical Societies grade after resuscitation, aneurysm size, and Fisher grade. Temporal validation showed high discrimination (area under the receiver operating characteristic curve, 0.90; 95% CI, 0.85-0.94), external validation showed fair to good discrimination (area under the receiver operating characteristic curve, 0.73; 95% CI, 0.70-0.76). The model showed satisfactory calibration in both validation cohorts. The SAFIRE grading scale was derived from the final model: size of the aneurysm, age, Fisher grade, world federation of neurosurgical societies after resuscitation. Conclusions- The SAFIRE grading scale is an accurate, generalizable, and easily applicable model for early prediction of clinical outcome after aSAH.

Clinical relevance of short-term follow-up of unruptured intracranial aneurysms.

OBJECTIVE: Unruptured intracranial aneurysms are common incidental findings on brain imaging. Short-term follow-up for conservatively treated aneurysms is routinely performed in most cerebrovascular centers, although its clinical relevance remains unclear. In this study, the authors assessed the extent of growth as well as the rupture risk during short-term follow-up of conservatively treated unruptured intracranial aneurysms. In addition, the influence of patient-specific and aneurysm-specific factors on growth and rupture risk was investigated. METHODS: The authors queried their prospective institutional neurovascular registry to identify patients with unruptured intracranial aneurysms and short-term follow-up imaging, defined as follow-up MRA and/or CTA within 3 months to 2 years after initial diagnosis. Medical records and questionnaires were used to acquire baseline information. The authors measured aneurysm size at baseline and at follow-up to detect growth. Rupture was defined as a CT scan-proven and/or CSF-proven subarachnoid hemorrhage (SAH). RESULTS: A total of 206 consecutive patients with 267 conservatively managed unruptured aneurysms underwent short-term follow-up at the authors' center. Seven aneurysms (2.6%) enlarged during a median follow-up duration of 1 year (range 0.3-2.0 years). One aneurysm (0.4%) ruptured 10 months after initial discovery. Statistically significant risk factors for growth or rupture were autosomal-dominant polycystic kidney disease (RR 8.3, 95% CI 2.0-34.7), aspect ratio > 1.6 or size ratio > 3 (RR 10.8, 95% CI 2.2-52.2), and initial size ≥ 7 mm (RR 10.7, 95% CI 2.7-42.8). CONCLUSIONS: Significant growth of unruptured intracranial aneurysms may occur in a small proportion of patients during short-term follow-up. As aneurysm growth is associated with an increased risk of rupture, the authors advocate that short-term follow-up is clinically relevant and has an important role in reducing the risk of a potential SAH.

A Case Report About Cluster-Tic Syndrome Due to Venous Compression of the Trigeminal Nerve.

BACKGROUND: The term "cluster-tic syndrome" is used for the rare ipsilateral co-occurrence of attacks of cluster headache and trigeminal neuralgia. Medical treatment should combine treatment for cluster headache and trigeminal neuralgia, but is very often unsatisfactory. CASE: Here, we describe a 41-year-old woman diagnosed with cluster-tic syndrome who underwent microvascular decompression of the trigeminal nerve, primarily aimed at the "trigeminal neuralgia" part of her pain syndrome. After venous decompression of the trigeminal nerve both a decrease in trigeminal neuralgia and cluster headache attacks was seen. However, the headache did not disappear completely. Furthermore, she reported a decrease in pain intensity of the remaining cluster headache attacks. DISCUSSION: This case description suggests that venous vascular decompression in cluster-tic syndrome can be remarkably effective, both for trigeminal neuralgia and cluster headache.

Predictive Factors for Rebleeding After Aneurysmal Subarachnoid Hemorrhage: Rebleeding Aneurysmal Subarachnoid Hemorrhage Study.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating type of stroke associated with high morbidity and mortality. One of the most feared complications is an early rebleeding before aneurysm repair. Predictors for such an often fatal rebleeding are largely unknown. We therefore aimed to determine predictors for an early rebleeding after aSAH in relation with time after ictus. METHODS: This observational prospective cohort study included all consecutive patients admitted with aSAH between January 1998 and December 2014 (n=1337) at our University Neurovascular Center. Clinical predictors for rebleeding ≤24 hours were identified using multivariable Cox regression analyses. Kaplan-Meier analyses were applied to evaluate the time of rebleeding ≤72 hours after aSAH. RESULTS: A modified Fisher grade of 3 to 4 was a predictor for an in-hospital rebleeding ≤24 hours after ictus (adjusted hazard ratio, 4.4; 95% confidence interval, 2.1-10.6; P<0.001). The numbers needed to treat to prevent 1 rebleeding ≤24 hours was calculated 15 (95% confidence interval, 10-25). Also, the initiation of external cerebrospinal fluid-drainage (adjusted hazard ratio, 1.9; 95% confidence interval, 1.4-2.5; P<0.001) was independently associated with a rebleeding ≤24 hours. Cumulative in-hospital rebleeding rates were 5.8% ≤24 hours, and 1.2% in the time frame 24-72 hours after ictus. CONCLUSIONS: In our opinion, timing of treatment of aSAH patients, especially those with an modified Fisher grade of 3 or 4 in a good clinical condition, should be reconsidered. These aSAH patients might be regarded a medical emergency, requiring aneurysm repair as soon as possible. In this respect, our findings should provoke the debate on timing of aneurysm repair, especially in patients considered to be at high risk for rebleeding.

The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas-a critical review.

Meningiomas are the second most common primary tumors affecting the central nervous system. Surgical treatment can be curative in case of complete resection. 5-aminolevulinic acid (5-ALA) has been established as an intraoperative tool in malignant glioma surgery. A number of studies have tried to outline the merits of 5-ALA for the resection of intracranial meningiomas. In the present paper, we review the existing literature about the application of 5-ALA as an intraoperative tool for the resection of intracranial meningiomas. PubMed was used as the database for search tasks. We included articles published in English without limitations regarding publication date. Tumor fluorescence can occur in benign meningiomas (WHO grade I) as well as in WHO grade II and WHO grade III meningiomas. Most of the reviewed studies report fluorescence of the main tumor mass with high sensitivity and specificity. However, different parts of the same tumor can present with a different fluorescent pattern (heterogenic fluorescence). Quantitative probe fluorescence can be superior, especially in meningiomas with difficult anatomical accessibility. However, only one study was able to consistently correlate resected tissue with histopathological results and nonspecific fluorescence of healthy brain tissue remains a confounder. The use of 5-ALA as a tool to guide resection of intracranial meningiomas remains experimental, especially in cases with tumor recurrence. The principle of intraoperative fluorescence as a real-time method to achieve complete resection is appealing, but the usefulness of 5-ALA is questionable. 5-ALA in intracranial meningioma surgery should only be used in a protocolled prospective and long-term study.

Appreciation of CT-negative, lumbar puncture-positive subarachnoid haemorrhage: risk factors for presence of aneurysms and diagnostic yield of imaging.

OBJECTIVE: Patients without a subarachnoid haemorrhage (SAH) on brain CT scan (CT-negative), but a lumbar puncture (LP)-proven SAH, are a challenging patient category. The optimal diagnostic approach is still a matter of debate. Also, there is little knowledge on the probability of finding an underlying vascular lesion. DESIGN: In this observational study, a consecutive cohort of 94 patients with CT-negative, LP-positive SAH was prospectively collected between 1998 and 2013. The yield of diagnostic modalities as well as patient outcome was studied. In addition, risk factors for the presence of a vascular lesion were analysed. RESULTS: In 40 patients (43%), an intracranial vascular abnormality was detected: 37 aneurysms and three arterial dissections. Female gender was significantly associated with detection of a vascular lesion. Time between ictus and diagnosis of SAH was not associated with the presence of vascular pathology. Overall, 99% of patients had a modified Rankin Score of 0-2 after a median follow-up of 72 months. The yield of additional digital subtraction angiography in patients with a negative CT angiography was zero. CONCLUSIONS: In this study, the chance of finding a vascular lesion in a patient with CT-negative, LP-positive SAH was 43%, underlining the need for an adequate diagnostic workup. In general, the patient outcome was favourable. Female gender was found to be predictive for detecting a vascular lesion. In contrast with previous reports, the interval between ictus and LP was not associated with the presence of an aneurysm.

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data are available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in patients with nontraumatic SAH with the occurrence of DCI and functional outcome at 2 months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, World Federation of Neurosurgical Societies after REsuscitation). METHODS: In this study, the rSO2 distribution of patients with and without DCI after SAH was compared. The optimal cutoff points to predict DCI and outcome were assessed, and its predictive value was compared with the SAFIRE grade. RESULTS: Of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve of 0.77 (95% confidence interval 0.62-0.92; P = 0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an area under the curve of 0.86 (95% confidence interval 0.74-0.98; P = 0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade. CONCLUSIONS: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.

Posterior transdural discectomy: a new approach for the removal of a central thoracic disc herniation.

BACKGROUND: The optimal surgical approach for thoracic disc herniation remains a matter of debate, especially for central disc herniation. In this paper, we present a new technique to remove central thoracic disc herniation, the posterior transdural approach, and report a series of 13 cases operated on in this way at our institute. METHODS: Between September 2004 and October 2010, 13 patients with symptomatic central thoracic disc herniation were operated on, utilising this posterior transdural approach. All patients underwent magnetic resonance imaging (MRI) of the thoracic spine before surgery. All patients were followed at our outpatient department for at least 3 months. In addition, all patients were interviewed in April 2009 and February 2011 to evaluate the final results. A seven-point Likert scale was applied and the Frankel score was determined preoperatively and postoperatively. Additionally, a postoperative MRI was obtained for all but two patients. RESULTS: The most frequently involved levels were T10-11 and T12-L1. Median operative time was 210 min (range 140-360). Three patients experienced reversible complications. No patient required spinal fixation. The median duration of hospitalisation was 6 days (range 4-20 days). With a median follow-up of 18 months, symptoms improved in 12 patients (92%), including the three patients with complications. One patient was unchanged (8%), while none of the patients experienced worsening of symptoms. CONCLUSIONS: The posterior transdural approach is well tolerated by the patient and has a relatively high success rate. It is a relatively simple and safe procedure, suitable for the operative treatment of almost all types of thoracic disc herniation, but especially the centrally located disc herniation.

Emotion Recognition in Patients with Low-Grade Glioma before and after Surgery.

Research on patients with low-grade gliomas (LGGs) showed neurocognitive impairments in various domains. However, social cognition has barely been investigated. Facial emotion recognition is a vital aspect of social cognition, but whether emotion recognition is affected in LGG patients is unclear. Therefore, we aimed to investigate the effect of LGG and resection by examining emotion recognition pre- and postoperatively. Additionally, the relationships among emotion recognition and general cognition and tumor location were investigated. Thirty patients with LGG who underwent resective surgery were included and matched with 63 healthy control participants (HCs). Emotion recognition was measured with the Facial Expressions of Emotion-Stimuli and Tests (FEEST) and general cognition with neuropsychological tests. Correlations and within-group and between-group comparisons were calculated. Before surgery, patients performed significantly worse than the HCs on FEEST-Total and FEEST-Anger. Paired comparisons showed no significant differences between FEEST scores before and post-surgery. No significant correlations with general cognition and tumor location were found. To conclude, the results of this study indicate that the tumor itself contributes significantly to social cognitive dysfunction and that surgery causes no additional deficit. Impairments were not related to general cognitive deficits or tumor location. Consequently, incorporating tests for emotion recognition into the neuropsychological assessment of patients with LGG is important.

Surgical clipping as the preferred treatment for aneurysms of the middle cerebral artery.

OBJECTIVE: In recent years the endovascular treatment of intracranial aneurysms (coiling) has progressively gained recognition, particularly after the publication of the International Subarachnoid Aneurysm Trial (ISAT) in 2002. Despite the fact that in ISAT middle cerebral artery (MCA) aneurysms were clearly underrepresented, the study is often used as an argument to favor coiling above surgery in MCA aneurysms. Taken into account that MCA aneurysms are very well accessible for surgery, a contemporary assessment of the benefits of a preferred surgical strategy for MCA aneurysms was performed in a tertiary neurovascular referral center. METHODS: A prospectively kept single-center database of 151 consecutive patients with an MCA aneurysm was reviewed over a 6-year period (2001-2006). Long-term follow-up after surgical treatment of a ruptured MCA aneurysm was obtained in 74 out of 77 (96%) patients. The outcome was compared with relevant series in the literature. RESULTS: After a mean follow-up of 4.7 years, 59 out of 74 surgically treated patients (80%) with a ruptured MCA aneurysm had a good outcome (mRankin 0-2). All patients with an unruptured MCA aneurysm also had a good outcome after clipping. This is well-matched with the findings of the literature search, and competitive with the endovascular results. CONCLUSION: Surgical clipping is recommended as the principal treatment strategy for MCA aneurysms. This is not only ethically defendable in view of the surgical results but also in line with a strategy to maintain surgical experience within centralized neurovascular centers.

Feasibility of magnetic resonance angiography (MRA) follow-up as the primary imaging modality after coiling of intracranial aneurysms.

BACKGROUND: Digital subtraction angiography (DSA) is still regarded as the gold standard for detecting residual flow in treated aneurysms. Recent reports have also shown excellent results from magnetic resonance angiography (MRA) imaging. This is an important observation, since DSA is associated with a risk of medical complications, is time consuming, and is more expensive. PURPOSE: To determine whether MRA could replace conventional DSA and serve as the primary postinterventional imaging modality in patients with coiled intracranial aneurysms. MATERIAL AND METHODS: We studied a prospectively enrolled cohort of 190 patients treated endovascularly for a first-ruptured and/or unruptured intracranial aneurysm between January 2004 and December 2008. The imaging protocol included a 1.5T time-of-flight (TOF) MRA and a DSA at 3 months (on the same day) and, depending on comparability, a 1.5T TOF-MRA or DSA 1 year after treatment. All images were evaluated by a multidisciplinary panel. RESULTS: In 141/190 patients, both an MRA and DSA were performed after 3-month follow-up. In 2/141 patients (1.4%), (small) neck remnants gave false-negative MRA results. In one patient (0.7%), this led to additional neurosurgical clipping of the aneurysm. In 25/141 patients, future follow-up (>3 months) consisted of DSA because of various reasons. In 24/25 of these patients, primary MRA images alone would invariably have led to additional DSA imaging. CONCLUSION: The present study shows that 1.5T TOF-MRA is a feasible primary follow-up modality after coiling of intracranial aneurysms. Given our data, we now suggest that, in every patient with a coiled intracranial aneurysm, the first follow-up, 3 months after coiling, should be an MRA study. Only when this MRA is inconclusive (e.g., because of coil artifacts), or in the case of suspicion of recanalization, should DSA be performed additionally.

Concordant symptomatic intracranial aneurysm in a monozygotic twin: a case report and review of the literature.

The development of an intracranial aneurysm (IA) is a multifactorial process, involving genetic and environmental factors. The presence of IA or aneurysmal subarachnoid hemorrhage (aSAH) in twins is particularly interesting, since both genetic and environmental factors can be studied. It also raises the question of whether, when one twin is affected, the other asymptomatic twin should be examined for an IA. We report on a monozygotic (MZ) twin-pair with aSAH in both twins and we review all reported cases of IA in MZ twins. Including our case, we found only 14 MZ twin-pairs in which both twins harbored an IA, suggesting a heavy underreporting in the medical literature. In this small group, a high concordance was noted in the sites of IAs. In MZ twins, the preferred sites for IAs are the branching arteries, while aneurysms arising from fusion arteries are rare. These sites differ from the preferential sites seen in series of familial IAs and series of sporadic IAs. We therefore hypothesize that the twinning process might play a significant role in the development of IAs in MZ twins. To further explore and substantiate this, the large twin registries should be studied. Although IAs in MZ twins with a negative family history for IAs should not be regarded as familial IAs, screening of the asymptomatic twin should be seriously considered if one MZ twin presents with an aSAH or an IA, because of the high fatality rates reported in asymptomatic (and not screened) MZ twin-halves.

Return to work after subarachnoid hemorrhage: The influence of cognitive deficits.

INTRODUCTION: Cognitive deficits are frequently found after subarachnoid hemorrhage (SAH), but their influence on return to work is largely unknown. To improve identification of those patients at-risk for long-term return to work problems, we aimed to examine the value of cognitive deficits in the prediction of long-term return to work after subarachnoid hemorrhage. METHODS: SAH patients (N = 71) who were employed before SAH and were able to undergo neuropsychological assessment, were included. Demographic characteristics and acute SAH-related variables (SAH-type and external cerebrospinal fluid drainage) were taken into account. Neuropsychological tests for memory, speed, attention, executive function, and emotion recognition and a questionnaire for executive functions were used. Return to work was assessed using the Role Resumption List. RESULTS: Results showed that patients with incomplete return to work had significantly lower scores on neuropsychological measures for complex attention and executive functions (p < 0.05) compared to patients with complete return to work. Return to work could not be significantly predicted using only demographic characteristics and acute SAH-related variables, but adding measures of complex attention and executive functions resulted in a prognostic model that could reliably distinguish between complete and incomplete return to work. Statistically significant predictors in the final model were cerebrospinal fluid drainage and scores on a questionnaire for executive functions: patients with cerebrospinal fluid drainage and higher scores on the a questionnaire for executive functions were less likely to return to work. DISCUSSION: Together, these findings show that neuropsychological measures, especially for complex attention and executive functions, have added value to acute SAH-related and demographic variables in the prediction of long-term return to work after SAH.

An auditory brainstem implant for treatment of unilateral tinnitus: protocol for an interventional pilot study.

INTRODUCTION: Tinnitus may have a very severe impact on the quality of life. Unfortunately, for many patients, a satisfactory treatment modality is lacking. The auditory brainstem implant (ABI) was originally indicated for hearing restoration in patients with non-functional cochlear nerves, for example, in neurofibromatosis type II. In analogy to a cochlear implant (CI), it has been demonstrated that an ABI may reduce tinnitus as a beneficial side effect. For tinnitus treatment, an ABI may have an advantage over a CI, as cochlear implantation can harm inner ear structures due to its invasiveness, while an ABI is presumed to not damage anatomical structures. This is the first study to implant an ABI to investigate its effect on intractable tinnitus. METHODS AND ANALYSIS: In this pilot study, 10 adults having incapacitating unilateral intractable tinnitus and ipsilateral severe hearing loss will have an ABI implanted. The ABI is switched on 6 weeks after implantation, followed by several fitting sessions aimed at finding an optimal stimulation strategy. The primary outcome will be the change in Tinnitus Functioning Index. Secondary outcomes will be tinnitus burden and quality of life (using Tinnitus Handicap Inventory and Hospital Anxiety and Depression Scale questionnaires), tinnitus characteristics (using Visual Analogue Scale, a tinnitus analysis), safety, audiometric and vestibular function. The end point is set at 1 year after implantation. Follow-up will continue until 5 years after implantation. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Institutional Review Board of the University Medical Centre Groningen, The Netherlands (METc 2015/479). The trial is registered at www.clinicialtrials.gov and will be updated if amendments are made. Results of this study will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT02630589. TRIAL STATUS: Inclusion of first patient in November 2017. Data collection is in progress. Trial is open for further inclusion. The trial ends at 5 years after inclusion of the last patient.

Transcranial Doppler Versus CT-Angiography for Detection of Cerebral Vasospasm in Relation to Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Prospective Single-Center Cohort Study: The Transcranial doppler and CT-angiography for Investigating Cerebral vasospasm in Subarachnoid hemorrhage (TACTICS) study.

Cerebral vasospasm in the first 2 weeks after aneurysmal subarachnoid hemorrhage is recognized as a major predictor of delayed cerebral ischemia. The routine screening for cerebral vasospasm with either transcranial Doppler or CT angiography has been advocated, although its diagnostic value has not yet been determined. Our study investigated the diagnostic accuracy of detecting vasospasm by transcranial Doppler and CT angiography for the prediction of delayed cerebral ischemia and functional outcome. Additionally, agreement between transcranial Doppler and CT angiography was determined. DESIGN: Prospective diagnostic accuracy study. SETTINGS: Neurocritical care unit and neurosurgical ward at a tertiary academic medical center. PATIENTS: Between 2013 and 2016, 59 consenting patients were included. INTERVENTION: Patients undergo both transcranial Doppler and CT angiography for detection of cerebral vasospasm on days 5 and 10 after aneurysmal subarachnoid hemorrhage. Delayed cerebral ischemia was defined as secondary neurologic deterioration, not explained otherwise. Unfavorable outcome was defined modified Rankin Scale > 2 at 6 months. MEASUREMENTS AND MAIN RESULTS: On transcranial Doppler, cerebral vasospasm was observed in 26 patients (45%). On CT angiography, vasospasm was observed in 54 patients (95%). The agreement between transcranial Doppler and CT angiography was 0.47. Delayed cerebral ischemia occurred in 16 patients (27%); unfavorable outcome in 12 patients (20%). Transcranial Doppler predicted delayed cerebral ischemia with a sensitivity of 0.44 (day 5) and 0.50 (day 10), with a specificity of 0.67 (day 5) and 0.57 (day 10). CT angiography predicted delayed cerebral ischemia with a sensitivity of 0.81 (day 5 and 10) and with a specificity of 0.070 (day 5) and 0.00 (day 10). The highest accuracy for predicting unfavorable outcome was on day 5 (0.61 for transcranial Doppler vs 0.27 for CT angiography). CONCLUSION: The diagnostic accuracy of both CT angiography and transcranial Doppler for detection of cerebral vasospasm as well as prediction of delayed cerebral ischemia and functional outcome is limited. The agreement between CT angiography and transcranial Doppler is low.

The relation between flocculus volume and tinnitus after cerebellopontine angle tumor surgery.

PURPOSE: Chronic tinnitus is a common symptom after cerebellopontine angle (CPA) tumor removal. Sometimes, the tinnitus is gaze-modulated. In that case, patients can change the loudness or pitch of their tinnitus by ocular movements. During tumor removal by a retrosigmoid craniotomy, the cerebellar flocculus is manipulated by the surgical approach to access the tumor. The flocculus has been associated with tinnitus in rats, and is involved in eye-gaze control. This suggests that the flocculus may have a role in gaze-modulated tinnitus after CPA tumor removal. In order to investigate this hypothesis, the relation between the flocculus volume and the characteristics of postoperative tinnitus was studied. RESULTS: A single-center cohort of 51 patients completed a questionnaire after CPA tumor removal. The questionnaire asked for the effect of eye movements on tinnitus and included the Tinnitus Functional Index (TFI). Tinnitus was present in 36 patients (71% of 51), of which 29 (81% of 36) described gaze-modulation. The median TFI was 22 (range 0-85). A postoperative MRI-scan of sufficient quality was available in 34 cases. The volumes of the (para)flocculi ipsilateral and contralateral to the surgery, and the ratio of these volumes were similar between patients with and without tinnitus. The TFI correlated with the volume of both ipsi- and contralateral (para)flocculus (rs(23) = .516, p = .008 and rs(23) = .430, p = .032). The ipsilateral-to-contralateral volume ratio of the (para)flocculi volumes was significantly lower in patients that could modulate the loudness of their tinnitus by eye gaze, compared to patients that could not (t(23) = 3.337, p = .003). CONCLUSIONS: The lack of a relation between flocculus volumes and the presence of tinnitus, combined with the significant correlation between tinnitus severity and flocculus volumes, suggests that the flocculus may not be the primary source of tinnitus, but is likely to mediate tinnitus severity. The reduced ipsi-to-contralateral volume ratio in patients with gaze-modulated tinnitus suggests that atrophy of the flocculus on the surgery side triggers cross-modal interactions leading to modulation of tinnitus.

Social cognition impairments after aneurysmal subarachnoid haemorrhage: Associations with deficits in interpersonal behaviour, apathy, and impaired self-awareness.

Behavioural disturbances are frequently found after aneurysmal subarachnoid haemorrhage (aSAH). Social cognition impairments have been suggested as a possible underlying mechanism for behavioural problems. Also, aSAH is likely to result in damage affecting frontal-subcortical circuits underlying social cognition. Therefore, we aimed to investigate social cognition after aSAH and its associations with behavioural problems (deficits in interpersonal behaviour, apathy, and impaired self-awareness) and focal as well as diffuse brain damage. 88 aSAH patients (in the subacute phase post-aSAH) and 60 age-, sex- and education-matched healthy controls participated. Tasks for emotion recognition, Theory of Mind (ToM), and empathy as well as questionnaires were used. Cortical infarctions in frontal and non-frontal areas on MRI, aneurysm circulation and aSAH-related events were taken into account. Compared to healthy controls, aSAH patients performed significantly worse on tasks for emotion recognition, ToM and empathy. Poor performance on ToM and emotion recognition was associated with proxy-ratings indicating impaired interpersonal behaviour and apathy and with indications of impaired self-awareness. No associations were found between deficits in social cognition and frontal or non-frontal cortical lesions on MRI. Also, aneurysm circulation and aSAH-related events such as hydrocephalus, vasospasm, and treatment method did not explain why and how social cognitive deficits did occur after aSAH. In conclusion, emotion recognition, ToM and empathy were clearly impaired in aSAH patients and these deficits were related to apathy and deficits in interpersonal behaviour as reported by proxies and to impaired self-awareness. This association strengthens the assumption of impaired social cognition as an underlying construct of behavioural problems after aSAH. Consequently, social cognition tests and proxy-ratings should be used in clinical practice, irrespective of lesion location on MRI or aneurysm circulation, to improve the detection and treatment of apathy and deficits in interpersonal behaviour after aSAH.

Prediction of outcome after subarachnoid hemorrhage: timing of clinical assessment.

OBJECTIVE Currently, early prediction of outcome after spontaneous subarachnoid hemorrhage (SAH) lacks accuracy despite multiple studies addressing this issue. The clinical condition of the patient on admission as assessed using the World Federation of Neurosurgical Societies (WFNS) grading scale is currently considered the gold standard. However, the timing of the clinical assessment is subject to debate, as is the contribution of additional predictors. The aim of this study was to identify either the conventional WFNS grade on admission or the WFNS grade after neurological resuscitation (rWFNS) as the most accurate predictor of outcome after SAH. METHODS This prospective observational cohort study included 1620 consecutive patients with SAH admitted between January 1998 and December 2014 at our university neurovascular center. The primary outcome measure was a poor modified Rankin Scale score at the 2-month follow-up. Clinical predictors were identified using multivariate logistic regression analyses. Area under the receiver operating characteristic curve (AUC) analysis was used to test discriminative performance of the final model. An AUC of > 0.8 was regarded as indicative of a model with good prognostic value. RESULTS Poor outcome (modified Rankin Scale Score 4-6) was observed in 25% of the patients. The rWFNS grade was a significantly stronger predictor of outcome than the admission WFNS grade. The rWFNS grade was significantly associated with poor outcome (p < 0.001) as well as increasing age (p < 0.001), higher modified Fisher grade (p < 0.001), larger aneurysm size (p < 0.001), and the presence of an intracerebral hematoma (OR 1.8, 95% CI 1.2-2.8; p = 0.002). The final model had an AUC of 0.87 (95% CI 0.85-0.89), which indicates excellent prognostic value regarding the discrimination between poor and good outcome after SAH. CONCLUSIONS In clinical practice and future research, neurological assessment and grading of patients should be performed using the rWFNS to obtain the best representation of their clinical condition.