European Multicenter Study for the Evaluation of a Dual-Layer Flow-Diverting Stent for Treatment of Wide-Neck Intracranial Aneurysms: The European Flow-Redirection Intraluminal Device Study.

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow-diverting stents represents a widely accepted technique for the treatment of complex intracranial aneurysms. This European registry study analyzed the initial experience of 15 neurovascular centers with the Flow-Redirection Intraluminal Device (FRED) system. MATERIALS AND METHODS: Consecutive patients with intracranial aneurysms treated with the FRED between February 2012 and March 2015 were retrospectively reviewed. Complications and adverse events, transient and permanent morbidity, mortality, and occlusion rates were evaluated. RESULTS: During the defined study period, 579 aneurysms in 531 patients (median age, 54 years; range, 13-86 years) were treated with the FRED. Seven percent of patients were treated in the acute phase (≤3 days) of aneurysm rupture. The median aneurysm size was 7.6 mm (range, 1-36.6 mm), and the median neck size 4.5 mm (range, 1-30 mm). Angiographic follow-up of >3 months was available for 516 (89.1%) aneurysms. There was progressive occlusion witnessed with time, with complete occlusion in 18 (20%) aneurysms followed for up to 90 ± 14 days, 141 (82.5%) for 180 ± 20 days, 116 (91.3%) for 1 year ± 24 days, and 122 (95.3%) aneurysms followed for >1 year. Transient and permanent morbidity occurred in 3.2% and 0.8% of procedures, respectively. The overall mortality rate was 1.5%. CONCLUSIONS: This retrospective study in real-world patients demonstrated the safety and efficacy of the FRED for the treatment of intracranial aneurysms. In most cases, treatment with a single FRED resulted in complete angiographic occlusion at 1 year.

Assessment and treatment planning of lateral intracranial dural arteriovenous fistulas in 3 T MRI and DSA: A detailed analysis under consideration of time-resolved imaging of contrast kinetics (TRICKS) and ce-MRA sequences.

OBJECTIVES: The current gold standard in the assessment of lateral intracranial dural arteriovenous fistulas (LDAVF) is digital subtraction angiography (DSA). However, magnetic resonance imaging (MRI) is a non-invasive emerging tool for the evaluation of such lesions. The aim of our study was to compare the DSA to our 3 T MR-imaging protocol including a highly spatial resolved (ce-MRA) and a temporal resolved ("time-resolved imaging of contrast kinetics", TRICKS) contrast-enhanced MR angiography to evaluate if solely DSA can remain the gold-standard imaging modality for the treatment planning of LDAVF. METHODS: We retrospectively reviewed matched pairs of DSA and 3 T MRI examinations of 24 patients with LDAVF (03/2008-04/2014) by the same list of relevant criteria for an endovascular LDAVF treatment planning. In particular, we determined intermodality agreement for the Cognard classification, the identifeication of arterial feeders, and the detailed assessment of each venous drainage pattern. RESULTS: Intermodality agreement for the Cognard classification was excellent (ĸ = 1.0). Whereas MRI failed in identifying small arterial feeders, it was superior to the DSA in the assessment of the sinus and the venous drainage pattern. CONCLUSIONS: The combination of MRI and DSA is the new gold standard in LDAVF treatment planning. KEY POINTS: • DSA is superior to the MRI in detecting LDAVF arterial feeders. • MRI excellently evaluates the venous side of an LDAVF. • MRI can replace DSA in initial diagnosis and monitoring of LDAVF. • MRI and DSA combined are the new gold standard in LDAVF treatment planning.

Stent Retriever Thrombectomy in Patients Who Are Ineligible for Intravenous Thrombolysis: A Multicenter Retrospective Observational Study.

BACKGROUND AND PURPOSE: Intravenous thrombolysis with rtPA is the standard of care for patients with acute ischemic stroke within 4.5 hours after symptom onset. However, a considerable number of patients are ineligible for IV thrombolysis due to various contraindications. Recent studies have proved the superiority of mechanical thrombectomy for patients with large-vessel occlusions in combination with IV rtPA compared with IV rtPA alone. We aimed to demonstrate the efficacy of mechanical thrombectomy for patients who are ineligible for IV rtPA. MATERIALS AND METHODS: Patients from the stroke registries of 4 dedicated centers who were treated with mechanical thrombectomy from January 2010 to October 2014 were retrospectively evaluated. Inclusion criteria were the following: acute stroke due to proved large-artery occlusion, ineligibility for IV thrombolysis, and a timeframe of ≤4.5 hours between stroke and the start of mechanical thrombectomy. Recanalization success, periprocedural complications, clinical outcome, and hemorrhages were evaluated. RESULTS: One hundred thirty endovascular recanalization procedures were identified. The locations were the following: proximal ICA in 17 (13.1%), terminus ICA in 25 (19.2%), M1 segment in 77 (59.2%), and M2 segment in 11 (8.5%). TICI 2b/3 results were achieved in 101 (77.7%), and an mRS score of 0-2 in 47 patients (37.9%). There was a significant correlation between TICI 2b/3 results and good clinical outcomes (87.2% versus 6.8%; P = .048). A good clinical result was most frequent when recanalization was achieved within 4.5 hours (37/74 = 50% versus 10/50 = 20.0%; P = .001). Symptomatic hemorrhage occurred in 13.1% of patients; mortality was 24.2%. Periprocedural complications were recorded in 10 patients (7.7%). CONCLUSIONS: Mechanical thrombectomy can achieve good clinical outcomes in patients with acute large-artery occlusion ineligible for IV thrombolysis, in particular when recanalization is reached early.

Use of flow-diverting devices in fusiform vertebrobasilar giant aneurysms: a report on periprocedural course and long-term follow-up.

BACKGROUND AND PURPOSE: Fusiform vertebrobasilar giant aneurysms are a rare (<1% of all intracranial aneurysms) but challenging aneurysm subtype. Little data are available on the natural history of this aneurysm subtype and the impact of the use of flow-diverting stents on the long-term clinical and imaging follow-up. In this article, we present our experience with the treatment of fusiform vertebrobasilar giant aneurysms by flow diverting stents. We aim to stimulate a discussion of the best management paradigm for this challenging aneurysm subtype. MATERIALS AND METHODS: We retrospectively identified 6 patients with fusiform vertebrobasilar giant aneurysms who had been treated with flow-diverting stents between October 2009 and March 2012 in our center. The available data were re-evaluated. The modified Rankin Scale score was assessed before intervention, during the stay in hospital, and at discharge. RESULTS: Six patients were identified (all male; age range, 49-71 years; median age, 60 years). Handling of material was successful in all cases. No primary periprocedural complications occurred. The mean follow-up was 13 months (15 days to 29 months). During follow-up, 3 of 6 patients had recurrent cerebral infarctions, but no patient experienced SAH. Two patients presented with acute thrombotic stent occlusion. The modified Rankin Scale score was not higher than 3 in any of the cases before intervention, whereas the best mRS score at the last follow-up was 5. Four of 6 patients died during follow-up. CONCLUSIONS: Endovascular treatment of fusiform vertebrobasilar giant aneurysms with flow-diverting devices is feasible from a technical point of view; however, changes in hemodynamics with secondary thrombosis are not predictable. We currently do not intend to treat fusiform vertebrobasilar giant aneurysms with flow-diverting devices until we have further understanding of the pathophysiology, natural history, and hemodynamic effects of flow diversion.

Comparison of 3D cube FLAIR with 2D FLAIR for multiple sclerosis imaging at 3 Tesla.

PURPOSE: Three-dimensional (3 D) MRI sequences allow improved spatial resolution with good signal and contrast properties as well as multiplanar reconstruction. We sought to compare Cube, a 3 D FLAIR sequence, to a standard 2 D FLAIR sequence in multiple sclerosis (MS) imaging. MATERIALS AND METHODS: Examinations were performed in the clinical routine on a 3.0 Tesla scanner. 12 patients with definite MS were included. Lesions with MS-typical properties on the images of Cube FLAIR and 2 D FLAIR sequences were counted and allocated to different brain regions. Signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were calculated. RESULTS: With 384 the overall number of lesions found with Cube FLAIR was significantly higher than with 2 D FLAIR (N = 221). The difference was mostly accounted for by supratentorial lesions (N = 372 vs. N = 216) while the infratentorial lesion counts were low in both sequences. SNRs and CNRs were significantly higher in CUBE FLAIR with the exception of the CNR of lesion to gray matter, which was not significantly different. CONCLUSION: Cube FLAIR showed a higher sensitivity for MS lesions compared to a 2 D FLAIR sequence. 3 D FLAIR might replace 2 D FLAIR sequences in MS imaging in the future.

Validation of functional motor and language MRI with direct cortical stimulation.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a widely available method and is therefore progressively utilized in neurosurgical practice. This study was carried out to determine fMRI sensitivity and specificity and to emphasize the threshold dependence of fMRI data. METHODS: A total of 17 consecutive patients, scheduled for surgery on intracerebral lesions near eloquent brain areas, underwent preoperative motor (N = 12) and language (N = 5) fMRI. Functional data were analyzed with SPM software and displayed on a neuronavigation system for intraoperative guidance. High-risk maps for motor and language deficits obtained from direct electric cortical stimulation (DECS) were used for validation of functional activated areas. In a first analysis step, sensitivity and specificity were calculated in terms of a side-by-side correlation. The next step, the threshold dependence of fMRI data sensitivity and specificity, was estimated according to four statistical thresholds (p1 < 0.05, p2 < 0.0005, p3 < 0.00001, p4 < 0.0000001). RESULTS: Both functional imaging and DECS revealed definite results for the investigated areas in all patients. Calculation of sensitivity and specificity resulted in 100 % and 68 % for the motor group and a sensitivity of 75 % and specificity of 68 % for the language group at the fixed threshold analysis. Threshold-dependent analysis of the obtained data revealed a sensitivity/specificity relationship from 100 %/0 % at threshold (p1), 100 %/5 % at (p2), 74 %/9 % at (p3), and 37 %/36 % at (p4) for the motor group. Evaluation of threshold-dependent sensitivity and specificity for the language group resulted in 78 %/51 % at threshold (p1), 67 %/75 % at (p2), 50 %/78 % at (p3), and 33 %/89 % at (p4). CONCLUSIONS: The present findings on the threshold dependence of fMRI data demonstrate why individualized thresholds should be obtained in case of fMRI evaluation. Although the results are satisfying in most cases, fMRI is apparently not sufficient for critical intraoperative decision-making.

Intra-arterial application of nimodipine in reversible cerebral vasoconstriction syndrome: a diagnostic tool in select cases?

INTRODUCTION: Differential diagnoses of the reversible cerebral vasoconstriction syndrome (RCVS) include all forms of intracranial stenotic disease, such as primary or secondary vasculitis of the central nervous system. Here, we tested the hypothesis that angiographic response to intra-arterial nimodipine application may be helpful in differentiating between RCVS and other entities. METHODS: A digital subtraction angiographic (DSA) series of nine consecutive patients with suspected RCVS that were treated by intra-arterial nimodipine due to clinical worsening were retrospectively analyzed. Pre- and post-therapeutic DSA findings of patients with later-confirmed RCVS were compared to those in which another diagnosis was finally made. RESULTS: Intra-arterial nimodipine resulted in a normalization of both the diameter of the main trunks of the cerebral vessels and the caliber of the peripheral vessels in all RCVS patients. This was not the case in the non-RCVS patients, in whom only a slight general vasodilatation was observed. DISCUSSION: Our preliminary results indicate that angiographic response to intra-arterial application might be a helpful differential diagnostic tool in select patients with suspected RCVS.

Comparison of two different odorants in an olfactory detection threshold test of the Sniffin’ Sticks.

The olfactory test battery Sniffin' Sticks is a test of nasal chemosensory function that is based on pen-like devices for odour presentation. It consists of three olfactory subtests: threshold, discrimination, and identification. The detection threshold can be measured using two different odorants--n-butanol or PEA (phenylethyl alcohol). Both tasks are commonly applied in published studies, but little is known about the formal comparison of values obtained using them. Unlike the Sniffin' Sticks with n-butanol as odorant, there is poor validation for the threshold subtest with the odorant PEA. The purpose of this study was to compare these two different odorants. Both odorants were applied to 100 normosmic, healthy subjects (50 females). The experiment was divided into two sessions performed on two different days. After each threshold test the discrimination and identification subtests were conducted. We obtained significant differences in detection thresholds of PEA and n-butanol. The mean score of PEA threshold and PEA TDI (sum of threshold, discrimination, identification) was significantly higher compared to n-butanol. No significant correlation between individual PEA and n-butanol thresholds was observed. The differences between both odorants indicate that a formal validation of the Sniffin' Sticks with PEA as odorant for probing olfactory thresholds may be required.

Bad mood--bad activation? : The influence of emotions on the BOLD signal during finger tapping.

PURPOSE: The aim of this study was to investigate the influence of the subject's emotional state on the BOLD signal during simple finger tapping. MATERIAL AND METHODS: Twenty-nine healthy subjects participated in three functional magnetic resonance imaging (fMRI) sessions each. The sessions differed regarding emotional states, which were induced by standardized pleasant (positive condition, POS), unpleasant (negative condition, NEG), or neutral (neutral condition, NEU) pictures taken from the International Affective Picture System (IAPS) while the subjects performed a finger-tapping task (right index-to-thumb opposition). After each session, the subjects had to rate their actual mood and the pleasantness of the presented pictures. Furthermore, their state anxiety was assessed. Behavioral data were evaluated with SPSS. Functional imaging data were processed using statistical parametric mapping (SPM2) and were analyzed for main effects of emotional stimulation using an analysis of variance (ANOVA). The local maximum of interest was analyzed by a signal change analysis. RESULTS: Compared to the neutral emotional state, the positive and the negative emotional states caused a reduction of signal intensity changes within the primary sensorimotor hand area during simple finger tapping. The behavioral data indicated that the unpleasant pictures had a stronger effect on the emotional state than the pleasant images. According to these data the decrease in signal intensity change was more pronounced (significant; p < 0.001) in the negative condition than in the positive condition. CONCLUSION: This study showed that the emotional state of a test person is indeed influencing fMRI results and that well-balanced subjects in a neutral mood achieve the best fMRI results.

[Angiographic moyamoya in a female with glycogenosis type IA - a case report focusing therapeutic management: bilateral encephalo-duro-arterio-myo-synangiosis (EDAMS)]. / Angiografisches Moyamoya bei Glykogenose Typ IA - Management bei einer erwachsenen Patientin: Fallbericht mit Schwerpunkt auf der Behandlung: beidseitige Encephalo-Duro-Arterio-Myo-Synangiose (EDAMS).

Angiographic Moyamoya is a rare cerebrovascular disease most frequent in asia. Its characateristics are recurrent ischemic attacks due to progressive occlusion of ICA branches. Angiography reveals fine arterial collateralisation reminding of ascending smoke ("moyamoya" in japanese). Neurosurgical treatment strategies include direct and indirect reanastomosation procedures. Randomised trials for comparison of clinical outcome and long term survival remain missing. A 23 years old female with glycogenosis type IA was first diagnosed bilateral angiographic moyamoya with bilateral proximal stenosis of ICA after transient ischemic attack (TIA). Coincidence of both rare diseases moyamoya and glycogenosis has previously been reported in three cases, so that this metabolic dysfunction presumably is a true risk factor for moyamoya. In our case, excellent angiographic and functional results were achieved by bilateral, consecutive Enzephalo-Duro-Arterio-Myo-Synangiosis (EDAMS).

Differential effects of eyes open or closed in darkness on brain activation patterns in blind subjects.

In functional brain imaging, specific task conditions can be compared to a reference condition which is often eyes-open or eyes-closed in darkness without the execution of a specific task. Previous fMRI studies in sighted subjects have shown that eyes-open in darkness, without visual stimulation, increases the relative activity in cortical ocular motor and attentional areas ("exteroceptive" state; contrast OPEN>CLOSED). By contrast, eyes-closed causes a relative signal increase in sensory systems ("interoceptive" state; contrast CLOSED>OPEN). In the present study we used fMRI to determine whether these differential brain activity states can also be found in congenitally blind subjects: there were intragroup differences between the OPEN and CLOSED conditions. These differences were, however, less pronounced and occurred in other areas than in sighted controls. The contrast OPEN>CLOSED revealed a relative signal increase in the left frontal eye field, the middle occipital gyrus bilaterally and in the anterior cingulum. Relative signal increases in occipital cortex areas and the anterior cingulum were also apparent for this contrast in the intergroup comparison (congenitally totally blind subjects vs. sighted controls). They reflect the increased attentional load or arousal during the eyes-open condition and could be indicative of a functional reorganization of the occipital cortex in the blind. The contrast CLOSED>OPEN in the congenitally totally blind subjects lead to relative activations in the somatosensory cortex bilaterally, the middle temporal gyrus on the left and the frontal gyri on the right. These activations are residues of the "interoceptive" state found in sighted controls.

Trigeminal perception is necessary to localize odors.

The human ability to localize odorants has been examined in a number of studies, but the findings are contradictory. In the present study we investigated the human sensitivity and ability to localize hydrogen sulphide (H(2)S), which in low concentrations stimulates the olfactory system selectively, the olfactory-trigeminal substance isoamyl acetate (IAA), and the trigeminal substance carbon dioxide (CO(2)). A general requirement for testing of localization was the conscious perception of the applied stimuli by the participants. Using Signal Detection Theory, we determined the human sensitivity in response to stimulation with these substances. Then the subjects' ability to localize the three different substances was tested. We found that humans can detect H(2)S in low concentration (2 ppm) with moderate sensitivity, and possess a high sensitivity in response to stimulation with 8 ppm H(2)S, 17.5% IAA, 50% v/v CO(2). In the localization experiment, subjects could localize neither the low nor the high concentration of H(2)S. In contrast, subjects possessed the ability to localize IAA and CO(2) stimuli. These results clearly demonstrate that humans, in spite of the aware perception, are not able to localize substances which only activate the olfactory system independent of their concentration, but they possess an ability to localize odorants that additionally excite the trigeminal system.

Unilateral INO is associated with ocular tilt reaction in pontomesencephalic lesions: INO plus.

OBJECTIVE: Correlation of internuclear ophthalmoplegia (INO) with components of the ocular tilt reaction (OTR) in order to localize graviceptive (specifically otolithic) pathways in the brainstem. METHODS: We retrospectively analyzed data of 120 patients with INO (87 unilateral [9 of whom had one-and-a-half syndrome], 33 bilateral) for OTR (subjective visual vertical [SVV], ocular torsion, skew deviation) to localize causative brainstem lesions in MRI. RESULTS: Unilateral INO was accompanied by at least one component of OTR: SVV tilt in 96%, ocular torsion in 79%, and skew deviation in 50%. All components were directed to the contralesional side. Contralateral OTR occurred in 89% of patients with one-and-a-half syndrome. Only 9% of patients with bilateral INO exhibited OTR. MRI showed distinct lesions in 68%, which almost exclusively projected onto the pontomesencephalic medial longitudinal fascicle (96%). Follow-up measurements revealed SVV and ocular torsion normalized faster than the adduction deficit in INO. CONCLUSIONS: First, unilateral internuclear ophthalmoplegia (INO) is regularly associated with contraversive ocular tilt reaction (OTR): INO plus. Thus, graviceptive pathways join the medial longitudinal fascicle after crossing between the vestibular and abducens nuclei. Second, the different time course and degree of recovery of OTR components and INO signs can be explained by the hypothesis that vestibular tone imbalance is compensated by central vestibular adaptation mechanisms (probably driven mainly by cerebellar-vestibular projections), whereas impaired adduction is less susceptible to compensation according to Hering's law and can only be overcome by lesion repair. Third, bilateral INO is seldom associated with OTR, confirming that bilateral impairment of graviceptive pathways does not cause imbalance in roll plane.

Is the center of mass (COM) a reliable parameter for the localization of brain function in fMRI?

The center of mass (COM) in functional MRI studies is defined as the center of a cerebral activation cluster. Although the COM is a well-accepted parameter for exactly localizing brain function, the reliability of COMs has not received much attention until now. Our goal was to investigate COM reliability as a function of the thresholding technique, the threshold level, and the type of COM calculation. Therefore 15 subjects were examined repeatedly using simple hand and tongue movement paradigms. Postprocessing was performed with uncorrected, corrected, and proportional thresholding as well as different threshold levels. Geometric and T-weighted COMs of left-hemispheric primary hand and tongue motor clusters were calculated. The COM variation was evaluated within and between repeated sessions depending on the different postprocessing setups. Mean COM variations over three repeated sessions varied between 1.6 mm and 9.8 mm for the hand paradigm and between 7.0 mm and 14.4 mm for the tongue task. Stringent thresholding techniques and high threshold levels were required to assess reliable results, whereas the kind of COM calculation was of lesser relevance. Thus, COM reliability cannot be presupposed; it depends strongly on the individual postprocessing techniques. This should be considered when using COMs for localizing brain function.

Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is an important cause of intracerebral hemorrhage. Its definite diagnosis still requires histopathologic demonstration of vascular amyloid. Thus, further improvement of noninvasive imaging methods would be desirable. Here we present 3 patients with histologically proved CAA, in which superficial cortical hemosiderosis and subarachnoid hemosiderosis were present in T2*-weighted MR images. Thus, we propose that these 2 findings might be valuable as noninvasive diagnostic markers for CAA.

Reproducibility of activations in Broca area with two language tasks: a functional MR imaging study.

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is rapidly evolving and claims to complement or even substitute intraoperative mapping (IOM) of language functions. However, little is known about the reproducibility of imaging data in the language domain. The aim of our study was to assess the reproducibility of activations for 2 widely used paradigms: naming and word generation. Individual analysis was focused on the Broca area and the left insula. MATERIALS AND METHODS: We examined 13 healthy right-handed subjects in 3 sessions with fMRI. Two conditions were assessed: overt naming and overt naming plus noun generation. The same stimuli were used in all of the sessions. A random-effects analysis was performed to analyze whole-brain activation on a group level. For the regions of interest, the number of voxels classified as active were counted for each subject, and individual reproducibility coefficients were calculated over sessions. RESULTS: For the naming condition, the random-effects analysis did not reveal significant activations in the specified regions; small individual activations were not reproducible. For the combined task, all of the subjects showed activations in the Broca area that were more extensive and reproducible than in the naming task. Activations in the insula were only poorly reproducible. CONCLUSION: Naming is an approved task in IOM but does not identify the Broca area with fMRI in a reproducible way. Priming may have affected our results, but the use of a combined task, in which naming is paired with noun generation, improves the reproducibility of activations and is also suitable for IOM.

Eye closure in darkness animates olfactory and gustatory cortical areas.

In two previous fMRI studies, it was reported that eyes-open and eyes-closed conditions in darkness had differential effects on brain activity, and typical patterns of cortical activity were identified. Without external stimulation, ocular motor and attentional systems were activated when the eyes were open. On the contrary, the visual, somatosensory, vestibular, and auditory systems were activated when the eyes were closed. In this study, we investigated whether cortical areas related to the olfactory and gustatory system are also animated by eye closure without any other external stimulation. In a first fMRI experiment (n = 22), we identified cortical areas including the piriform cortex activated by olfactory stimulation. In a second experiment (n = 12) subjects lying in darkness in the MRI scanner alternately opened and closed their eyes. In accordance to previous studies, we found activation clusters bilaterally in visual, somatosensory, vestibular and auditory cortical areas for the contrast eyes-closed vs. eyes-open. In addition, we were able to show that cortical areas related to the olfactory and gustatory system were also animated by eye closure. These results support the hypothesis that there are two different states of mental activity: with the eyes closed, an "interoceptive" state characterized by imagination and multisensory activity and with the eyes open, an "exteroceptive" state characterized by attention and ocular motor activity. Our study also suggests that the chosen baseline condition may have a considerable impact on activation patterns and on the interpretation of brain activation studies. This needs to be considered for studies of the olfactory and gustatory system.