Corpus callosum size in adults with high-functioning autism and the relevance of gender.

The goal of the study was to investigate the size of the corpus callosum (CC) and its subsegments in relation to total brain volume (TBV) as an empirical indicator of impaired connectivity in autism with special respect to gender. In MRI data sets of 29 adults with high-functioning autism (HFA) and 29 age-, gender- and IQ-matched control subjects, the TBV was measured and the CC was analyzed as a whole and in subsegments employing two different manual segmentation procedures. With respect to diagnosis, there were no significant differences in the dependent variables (CC, CC subsegments, and TBV). With respect to gender, only TBV was significantly increased in males compared with females, resulting in a significantly decreased CC/TBV ratio in males. This finding, however, was independent from gender and can be fully attributed to brain size. Our findings do not support the following hypotheses: (1) a hypothesis of impaired CC in HFA adults as a subgroup of patients with autism spectrum disorders, and (2) the sexual dimorphism hypothesis of the CC.

Correlation of passivity symptoms and dysfunctional visuomotor action monitoring in psychosis.

Passivity experiences are hallmark symptoms of schizophrenia that can be characterized by the belief that one's thoughts or actions are controlled by an external agent. It has recently been suggested that these psychotic experiences result from defective monitoring of one's own actions, i.e. disturbed comparison of actions and perceived outcomes. In this study, we examined the function of the previously characterized action monitoring network of the inferior parietal lobule (IPL), medial (mPFC) and lateral prefrontal cortices in patients with different levels of passivity symptoms with an fMRI task. The visuomotor fMRI task demanded control of visually perceived object movements by alternating button presses with the left and the right index finger. In the monitoring condition of this task subjects stopped their actions whenever they detected visuomotor incongruence. fMRI and behavioural data from 15 patients were tested for correlation with passivity symptoms using standardized Scale for Assessment of Positive Symptoms (SAPS)- and AMDP- passivity symptom ratings. Both types of data were tested for differences between the patients group and 15 healthy controls. In the patient group we found the expected correlation of passivity symptoms and visuomotor monitoring performance. There was a significant positive correlation of passivity symptoms with increased latency of incongruence detection and a negative correlation of SAPS-passivity with the number of detected events. fMRI data revealed correlations of passivity symptoms with activation in bilateral IPL, primary motor and sensory cortices in the action monitoring condition. A correlation of passivity symptoms with the main experimental effect (actions with -- actions without monitoring) was found in the posterior cingulate cortex (PCC) and in the left IPL. No group differences or group by task interactions were found within the visuomotor-action-monitoring network. Our results demonstrate the association between passivity symptoms and the dysfunction of visuomotor action monitoring and support the idea that psychotic passivity experiences result from dysfunctions of central action monitoring mechanisms: According to pre-existing concepts of parietal cortex function, IPL-hyperactivation may represent an increase in false detections of visuomotor incongruence while the correlation between passivity and the differential effect of monitoring on PCC-activation assumedly represents greater self-monitoring effort in passivity experiences.

Altered cerebral glucose metabolism in a family with clinical features resembling mitochondrial neurogastrointestinal encephalomyopathy syndrome in association with multiple mitochondrial DNA deletions.

OBJECTIVE: To determine the involvement of cerebral metabolism in 2 siblings with mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE)-like disease with multiple mitochondrial DNA (mtDNA) deletions. DESIGN: Case report. SETTING: Department of Neurology at a university medical center. PATIENTS: Two siblings with MNGIE-like disease with multiple mtDNA deletions. MAIN OUTCOME MEASURES: Clinical, biochemical, genetic, and imaging findings, including cerebral magnetic resonance imaging, proton magnetic resonance spectroscopy, and positron emission tomography with fluorine 18-labeled deoxyglucose (FDG-PET). RESULTS: Genetic analysis of muscle DNA revealed multiple mtDNA deletions, while no mutations were detected in ECGF1, POLG1, ANT1, or Twinkle. Cerebral magnetic resonance imaging and proton magnetic resonance spectroscopy findings were unremarkable. Reduced regional glucose metabolism was found in a patchy and asymmetrical pattern predominantly in the frontotemporal region in both siblings by means of FDG-PET. CONCLUSIONS: The discrepancy between absence of clinical signs of cerebral involvement and the substantial impairment of glucose metabolism reflects a chronic subclinical encephalopathy. To our knowledge, the predominantly frontotemporal distribution has not been described previously in mitochondrial disorders.

Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis.

RATIONALE: Attentional deficits are common symptoms in schizophrenia. Recent evidence suggests that schizophrenic patients show abnormalities in spatial orienting of attention, particularly a deficit of inhibition of return (IOR). IOR is mostly thought to reflect an automatic, inhibitory mechanism protecting the organism from redirecting attention to previously scanned, insignificant locations. Pharmacologic challenges with hallucinogens have been used as models for psychosis. OBJECTIVES: The aim of this study was to investigate the neural correlates underlying orienting of attention in the human N-methyl-D-aspartic acid antagonist and 5-HT2A agonist models of psychosis. MATERIALS AND METHODS: Fourteen healthy volunteers participated in a randomized, double-blind, cross-over event-related functional magnetic resonance imaging (fMRI) study with dimethyltryptamine (DMT) and S-ketamine. We administered a covert orienting of attention task with nonpredictive peripheral cues, and we scanned the subjects on two separate days at least 14 days apart with a placebo and a verum condition on each day. RESULTS: DMT, but not S-ketamine, slowed down reaction times significantly. IOR was blunted after DMT, but not after S-ketamine. Relative to placebo, S-ketamine increased activation in the IOR condition in the right superior frontal gyrus, left superior temporal gyrus, and right midfrontal frontal gyrus. CONCLUSIONS: The discrepancy between the behavioral and functional imaging outcome indicates that pharmacological fMRI might be a sensitive tool to detect drug-modulated blood oxygenation level-dependent signal changes in the absence of behavioral abnormalities. Our findings might help to further clarify the contradictory findings of IOR in schizophrenic patients and might, thus, shed more light on possible differential pathomechanisms of schizophrenic symptoms.

Sonographic detection and follow up of an atypical pineal cyst: a comparison with magnetic resonance imaging. Case report.

The incidental ultrasonographic detection of an asymptomatic cystic pineal lesion in a young woman is described and compared with findings on magnetic resonance (MR) images. Follow-up studies obtained using both imaging modalities are presented. The results indicate that transcranial ultrasonography may represent an easy and cost-effective imaging technique for follow up of cystic lesions of the pineal gland, especially in patients unable to undergo MR imaging.

Time-of-flight-, phase contrast and contrast enhanced magnetic resonance angiography for pre-interventional determination of aneurysm size, configuration, and neck morphology in an aneurysm model in rabbits.

We describe three different magnetic resonance (MR)-angiography techniques to evaluate aneurysm size, configuration, and neck morphology of experimentally created aneurysms in a rabbit model. In five New Zealand White rabbits an aneurysm was created by endovascular occlusion of the right common carotid artery (CCA) using a pliable balloon and subsequent endoluminal incubation of elastase within the proximal CCA above the balloon and distal ligation of the vessel. In all animals, time-of-flight (TOF), phase contrast and contrast enhanced (CE) MR angiographies (MRA) were performed and compared to conventional digital subtraction angiography results. We found, that aneurysms are best visualized employing CE MRA, however, neck morphology was also found to demonstrate interpretable results when evaluating the axial source data of the TOF MRA. The animal model we used can be employed for testing endovascular devices such as new coil material, or covered stents. The described MRA techniques might then be helpful for pre-interventional planning and maybe even for the follow-up of the thus treated aneurysms.

CT findings and clinical features as markers for patient outcome in primary pontine hemorrhage.

BACKGROUND AND PURPOSE: The overall mortality rate of primary pontine hemorrhage (PPH) in recent studies is 40-50%. The aim of the present study was to analyze the predictive value of clinical and neuroradiologic parameters concerning the outcome of patients with PPH. METHODS: We reviewed the clinical data of 29 consecutive patients (mean age, 59 +/- 13.5 years; 12 women, 17 men) with PPH. National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were assessed on admission, and NIHSS, GCS, and Glasgow Outcome Scale (GOS) scores were assessed on discharge. The hemorrhage volume was calculated by using a previously published formula. Clinical manifestations, outcome, and volume and location of the bleeding were correlated. RESULTS: The mean GCS score on admission was 6.8 +/- 3.9 and increased to 9.0 +/- 3.9 on discharge. The NIHSS score improved from 29.1 +/- 12.5 to 12.1 +/- 7.3. Nine patients (31%) died as a result of PPH after 5 +/- 3 days. The mean GOS score was 3.0 +/- 1.5 (3.9 +/- 0.8 for patients who survived). Arterial hypertension was the most common risk factor (90%); other causes were anticoagulation therapy (7%) and amyloid angiopathy (3%). A high correlation was observed between a poor outcome (GOS score < 4) and hematoma volume greater than 4 mL (P =.006), ventral hemorrhage (P <.001), and necessity for mechanical ventilation (P <.001). Patients with dorsally located hematomas less than 4 mL in volume had a significantly better outcome. CONCLUSION: The prognosis of PPH is better than commonly expected. Most patients with moderate neurologic deficits on admission and dorsally located small hematomas are able to survive PPH with minor neurologic deficits.

Perfusion imaging of high-grade gliomas: a comparison between contrast harmonic and magnetic resonance imaging. Technical note.

Transcranial contrast harmonic (CH) imaging is emerging as a promising tool for the evaluation of brain perfusion. The authors report on two cases of histologically proven high-grade gliomas evaluated using CH imaging in comparison to perfusion magnetic resonance (pMR) imaging. In both cases, pMR imaging results demonstrated a massive decrease in signal intensity and an elevated regional cerebral blood volume (rCBV) in the tumor region; however, signal decrease was less prominent and rCBV was lower in healthy brain tissue. In one patient, the rCBV ratio of tumor/brain was 5.0 and the maximal signal decay occurred 3.1 times deeper in the tumor than in the healthy brain tissue. Results of an ultrasonography examination using CH imaging revealed similar data: the tumor/brain ratio for the area under the curve, a parameter corresponding to rCBV, was 4.1. The maximal signal intensity in the tumor was 3.3 times greater than in adjacent healthy brain. Comparable data were obtained in a second patient. Taken together, these findings indicate that CH imaging may be a valuable alternative to pMR imaging. This new, cost-effective bedside ultrasonic technique could be helpful not only as a means of noninvasive staging of gliomas but also as a follow-up imaging modality to evaluate postoperative tumor recurrence or response to antiangiogenic therapy.

Determination of histopathological tumor grade in neuroepithelial brain tumors by using spectral pattern analysis of in vivo spectroscopic data.

OBJECT: In this study, 1H magnetic resonance (MR) spectroscopy was prospectively tested as a reliable method for presurgical grading of neuroepithelial brain tumors. METHODS: Using a database of tumor spectra obtained in patients with histologically confirmed diagnoses, 94 consecutive untreated patients were studied using single-voxel 1H spectroscopy (point-resolved spectroscopy; TE 135 msec, TE 135 msec, TR 1500 msec). A total of 90 tumor spectra obtained in patients with diagnostic 1H MR spectroscopy examinations were analyzed using commercially available software (MRUI/VARPRO) and classified using linear discriminant analysis as World Health Organization (WHO) Grade I/II, WHO Grade III, or WHO Grade IV lesions. In all cases, the classification results were matched with histopathological diagnoses that were made according to the WHO classification criteria after serial stereotactic biopsy procedures or open surgery. Histopathological studies revealed 30 Grade I/II tumors, 29 Grade III tumors, and 31 Grade IV tumors. The reliability of the histological diagnoses was validated considering a minimum postsurgical follow-up period of 12 months (range 12-37 months). Classifications based on spectroscopic data yielded 31 tumors in Grade I/II, 32 in Grade III, and 27 in Grade IV. Incorrect classifications included two Grade II tumors, one of which was identified as Grade III and one as Grade IV; two Grade III tumors identified as Grade II; two Grade III lesions identified as Grade IV; and six Grade IV tumors identified as Grade III. Furthermore, one glioblastoma (WHO Grade IV) was classified as WHO Grade I/II. This represents an overall success rate of 86%, and a 95% success rate in differentiating low-grade from high-grade tumors. CONCLUSIONS: The authors conclude that in vivo 1H MR spectroscopy is a reliable technique for grading neuroepithelial brain tumors.

Preoperative assessment of motor cortex and pyramidal tracts in central cavernoma employing functional and diffusion-weighted magnetic resonance imaging.

BACKGROUND: Functional MRI (fMRI) combines anatomic with functional information and has therefore been widely used for preoperative planning of patients with mass lesions affecting functionally important brain regions. However, the courses of functionally important fiber tracts are not visualized. We therefore propose to combine fMRI with diffusion-weighted MRI (DWI) that allows visualization of large fiber tracts and to implement this data in a neuronavigation system. METHODS: DWI was successfully performed at a field strength of 1.5 Tesla, employing a spin-echo sequence with gradient sensitivity in six noncollinear directions to visualize the course of the pyramidal tracts, and was combined with echo-planar T2* fMRI during a hand motor task in a patient with central cavernoma. RESULTS: Fusion of both data sets allowed visualization of the displacement of both the primary sensorimotor area (M1) and its large descending fiber tracts. Intraoperatively, these data were used to aid in neuronavigation. Confirmation was obtained by intraoperative electrical stimulation. Postoperative MRI revealed an undisrupted pyramidal tract in the neurologically intact patient. CONCLUSION: The combination of fMRI with DWI allows for assessment of functionally important cortical areas and additional visualization of large fiber tracts. Information about the orientation of fiber tracts in normal appearing white matter in patients with tumors within the cortical motor system cannot be obtained by other functional or conventional imaging methods and is vital for reducing operative morbidity as the information about functional cortex. This technique might, therefore, have the prospect of guiding neurosurgical interventions, especially when linked to a neuronavigation system.

An fMRI approach to particularize the frontoparietal network for visuomotor action monitoring: Detection of incongruence between test subjects' actions and resulting perceptions.

Contemporary theories of motor control assume that motor actions underlie a supervisory control system which utilizes reafferent sensory feedbacks of actions for comparison with the original motor programs. The functional network of visuomotor action monitoring is considered to include inferior parietal, lateral and medial prefrontal cortices. To study both sustained monitoring for visuomotor incongruence and the actual detection of incongruence, we used a hybrid fMRI epoch-/event-related design. The basic experimental task was a continuous motor task, comprising a simple racing game. Within certain blocks of this task, incongruence was artificially generated by intermittent takeover of control over the car by the computer. Fifteen male subjects were instructed to monitor for incongruence between their own and the observed actions in order to abstain from their own action whenever the computer took over control. As a result of both sustained monitoring and actual detection of visuomotor incongruence, the rostral inferior parietal lobule displayed a BOLD signal increase. In contrast, the prefrontal cortex (PFC) exhibited two different activation patterns. Dorsolateral (BA 9/46) and medial/cingulate (BA 8, BA 32) areas of the PFC displayed a greater increase of activation in sustained monitoring, while ventrolateral PFC showed greater event-related activation for the actual detection of visuomotor incongruence. Our results suggest that the rostral inferior parietal lobule is specifically involved in the reafferent comparison of the test subjects' own actions and visually perceived actions. Different activation patterns of the PFC may reflect different frontoparietal networks for sustained action monitoring and actual detection of reafferent incongruence.

The Cologne stroke experience: safety and outcome in 450 patients treated with intravenous thrombolysis.

BACKGROUND: Predictors of outcome and safety in intravenous thrombolysis within 3 h in clinical routine is a matter of ongoing debate. Available reports contain small patient numbers or summarize heterogeneous multicenter data. METHODS: Four hundred and fifty patients received intravenous thrombolysis within 3 h after stroke. Pretreatment NIHSS score and detailed medical history were analyzed. Noncontrast CT was performed before thrombolysis, 24-36 h later and in case of clinical deterioration. Symptomatic intracranial hemorrhage (SICH; any bleeding with an NIHSS increase of > or =4 points) and clinical outcome (modified Rankin Scale, mRS) after 3 months were recorded. Logistic regression identified parameters predictive of independence (mRS 0-2) and SICH. RESULTS: Median onset to admission, door to needle and onset to treatment time was 75, 50 and 135 min, respectively. Direct presentation by emergency service (64%) was the fastest way of referral. Median pretreatment NIHSS was 11 points. Independence (mRS 0-2) was reached by 53%. Mortality was 11% (7% intracerebral, 4% extracerebral complications). Logistic regression identified low NIHSS, low age and absent diabetes as predictors of independence. Overall hemorrhagic complications and SICH were found in 18 and 4% of the patients, respectively. Extracerebral bleeding complications and allergic reactions were found in 3 and 1%, respectively. CONCLUSION: This largest single center report presents a sample in the range of the 3 h rt-PA cohort of all randomized controlled trials. Outcome was comparable to randomized studies with a higher rate of independence and a lower rate of mortality and SICH.

Early ischemic edema on cerebral computed tomography: its relation to diffusion changes and hypoperfusion within 6 h after human ischemic stroke. A comparison of CT, MRI and PET.

BACKGROUND: Brain tissue hypoattenuation on early computed tomography is frequently included in decision making in acute stroke management. However, its pathophysiological counterpart needs further evaluation. METHODS: By comparative imaging with diffusion-weighted imaging and 15O-water positron emission tomography we aimed to interpret early (<6 h) hypoattenuation. RESULTS: In 11 patients, the hypoattenuation corresponded to a decreased proton diffusion (median 115.9% relative DWI value) measured by magnetic resonance imaging and to a severe hypoperfusion (below 12 ml/100 g/ min) assessed by positron emission tomography. The volume of parenchymal hypoattenuation correlated to the tissue with disturbed diffusion (Spearman's rho=0.73), but largely underestimated the hypoperfusion below 20 ml/100 g/min. CONCLUSIONS: Early hypoattenuation reflects the coupling of the severity of ischemia and resulting diffusion changes. It allows an estimate of the infarct core but underestimates the penumbral hypoperfusion.

Treatment of experimentally induced aneurysms with stents.

OBJECTIVE: Although Guglielmi detachable coil systems have been widely accepted for treatment of intracranial aneurysms, primary stenting of aneurysms using porous stents, stent grafts, or implantation of coils after stent placement constitute emerging techniques in endovascular treatment. The aim of the present study was to use an animal model to investigate these different approaches to treat cerebral aneurysms with regard to the rate of closure and the histopathological changes within the aneurysm cavity and the parent vessel after stent placement. METHODS: We created aneurysms in 30 rabbits by distal ligation and intraluminal incubation of the right common carotid artery with elastase. Ten animals were treated with porous stents alone, 10 animals with stent grafts (covered stents), and 10 animals with stents and additional coiling via the interstices of the stent, which enabled dense packing of the coils. Five animals in each group were observed for 1 month and the other animals for 3 months. Histological analyses were performed, including immunohistochemical investigations for estimating the proliferation of the intima and possible inflammatory infiltration. RESULTS: Covered stents led to a complete and stable aneurysm occlusion with only minimal proliferative carrier vessel wall changes. One covered stent was completely occluded with old thrombus, and the other 9 remained patent. Porous stents occluded two of five aneurysms in the 1-month follow-up group and four of five after 3 months. However, progressive sprouting of neointima inside the carrier vessel that resulted in a stenosis of up to 40% was present. In the Stent + Coil group, one aneurysm showed recanalization after 1 month, and three of five aneurysms were recanalized after 3 months after coil compaction. Moreover, in-stent stenosis of up to 30% was present. CONCLUSION: This study demonstrates the possible shortcomings and problems of emerging stent techniques to treat intracerebral aneurysms, shows where technical advances have to be made, and describes in which cases of aneurysm morphology caution has to be exercised when considering an endovascular approach using stents.

Three-dimensional color-coded duplex sonography for assessment of the vertebral artery origin and vertebral artery stenoses.

OBJECTIVE: The aim of the study was to assess the potential of 3-dimensional (3D) color-coded duplex sonography (CDS) for evaluation of the vertebral artery origin and stenoses in this location. METHODS: To compare 2-dimensional (2D) and 3D CDS, both techniques were performed in 25 healthy volunteers and in 18 patients with 21 stenoses of the vertebral artery origin. Stenoses were graded in line with hemodynamic criteria on 2D CDS and according to North American Symptomatic Carotid Endarterectomy Trial criteria on 3D CDS. In 6 patients, digital subtraction angiography (DSA) was performed additionally. Stenoses were graded according to North American Symptomatic Carotid Endarterectomy Trial criteria and compared with 2D and 3D sonographic data. RESULTS: Overall correlation of both sonographic techniques concerning the grading of the stenoses was good (r = 0.69; P < .01). The interobserver correlation for assessment of stenoses by means of 3D CDS was high (r = 0.94; P < .01). Three-dimensional CDS correlated excellently with DSA in 3 of 6 patients but showed only intermediate or no correlation in the remaining 3 patients. In contrast, spatial information on the stenotic morphologic characteristics was always very comparable with the results obtained by DSA. CONCLUSIONS: Three-dimensional CDS represents a valuable tool for assessment of the origin of the vertebral artery, allowing important morphologic information on stenoses in this location. For grading of stenoses of the vertebral artery origin, 3D information should be combined with hemodynamic criteria obtained by spectral Doppler imaging in 2D CDS. Three-dimensional CDS could be a valuable tool before interventional procedures of the proximal vertebral artery, saving time and avoiding iodinated contrast agents.

Increased choline levels coincide with enhanced proliferative activity of human neuroepithelial brain tumors.

Proton MR spectroscopy ((1)H MRS)-visible total choline-containing compounds (tCho-compounds) are derivatives of membrane phospholipids and, in part, may act as a long-term second-messenger system for cellular proliferation. Experimental evidence suggests increasing concentrations of tCho-compounds during cellular proliferation. The present study was conducted in order to test the hypothesis that in vivo measurements of tCho-concentrations using (1)H MRS allow assessment of the proliferative activity of neuroepithelial brain tumors presurgically. Single-voxel (1)H MRS (PRESS, TR 1500 ms, TE 135 ms) was performed in 101 patients with neuroepithelial brain tumors prior to surgery and 19 healthy volunteers. Histological diagnoses were confirmed postsurgically according to the WHO classification. Measured tCho-compound signal intensities were corrected for coil loading, numbers of acquisitions and voxel size, and tCho concentrations calculated as institutional arbitrary units. They were matched with the mean immunohistochemical marker of cell proliferation, the Ki-67 (MIB.1) labeling index, using correlation analysis according to Spearman. Compared with low-grade tumors (i.e. WHO grade I/II) and normal white brain matter, high-grade tumors (i.e. WHO grade III/IV) revealed significantly (p < 0.05) elevated labeling indices paralleled by increasingly elevated tCho-concentrations. In contrast tCho-concentrations in low-grade tumor did not differ significantly from physiological values. A highly significant positive correlation (p < 0.0001, r(2) = 0.81) was found between the tCho-concentration and the labeling index. It was concluded that the determination of tCho-concentrations using in vivo (1)H MRS could provide a novel and noninvasive assessment of the proliferative activity of neuroepithelial brain tumors, pointing at (1)H MRS as a useful method for differentiating proliferating from non-proliferating tissues. Hence, potential indications for the clinical application of (1)H MRS are grading tumors presurgically, early detection of anaplastic transformation, and monitoring treatment.

A refined method for creating saccular aneurysms in the rabbit.

We describe a refined animal model of human intracerebral aneurysms for testing endovascular devices for interventional neuroradiological procedures. Saccular aneurysms resulting from a stump of the right common carotid artery (CCA) were created in 15 New Zealand White rabbits by intraluminal incubation of elastase that was applied to the CCA after distal ligation of the CCA and proximal occlusion of the vessel using a pliable balloon. Subsequently a microcatheter was advanced to a position cranial to the balloon and the elastase was infused under fluoroscopic guidance to avoid retrograde flow to the trachea via aberrant vessels. Contrast-enhanced (CE) MRA at 1.5 T and conventional digital subtraction angiography was performed to test for aneurysm size, morphology and neck anatomy. In all 15 animals aneurysms resulted from the stump of the right CCA, ranging in size from 2.0 to 9.9 mm (mean 6.3 mm) in craniocaudal direction, 1.0 to 5.5 mm (mean 3.8 mm) in mediolateral direction and 1.0 to 3.8 mm (mean 2.4 mm) in neck diameter. Aneurysm morphology could be adequately demonstrated using CE MRA. On histological evaluation a loss of the internal elastic lamina was noted. The described method represents an easy, reliable, and reproducible method of aneurysm creation in the rabbit in an area of high shear stress. These aneurysms can be used for testing new endovascular devices for embolization of intracranial aneurysms.