Stephan G. Wetzel

The Pipeline Embolization Device for the Intracranial Treatment of Aneurysms Trial

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow diverting devices represents a novel constructive technique for the treatment of cerebral aneurysms. We present the results of the first prospective multicenter trial of a flow-diverting construct for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with unruptured aneurysms that were wide-necked (>4 mm), had unfavorable dome/neck ratios (<1.5), or had failed previous therapy were enrolled in the PITA trial between January and May 2007 at 4 (3 European and 1 South American) centers. Aneurysms were treated with the PED with or without adjunctive coil embolization. All patients underwent clinical evaluation at 30 and 180 days and conventional angiography 180 days after treatment. Angiographic results were adjudicated by an experienced neuroradiologist at a nonparticipating site. RESULTS: Thirty-one patients with 31 intracranial aneurysms (6 men; 42–76 years of age; average age, 54.6 years) were treated during the study period. Twenty-eight aneurysms arose from the ICA (5 cavernous, 15 parophthalmic, 4 superior hypophyseal, and 4 posterior communicating segments), 1 from the MCA, 1 from the vertebral artery, and 1 from the vertebrobasilar junction. Mean aneurysm size was 11.5 mm, and mean neck size was 5.8 mm. Twelve (38.7%) aneurysms had failed (or recurred after) a previous endovascular treatment. PED placement was technically successful in 30 of 31 patients (96.8%). Most aneurysms were treated with either 1 (n = 18) or 2 (n = 11) PEDs. Fifteen aneurysms (48.4%) were treated with a PED alone, while 16 were treated with both PED and embolization coils. Two patients experienced major periprocedural stroke. Follow-up angiography demonstrated complete aneurysm occlusion in 28 (93.3%) of the 30 patients who underwent angiographic follow-up. No significant in-construct stenosis (≥50%) was identified at follow-up angiography. CONCLUSIONS: Intracranial aneurysm treatment with the PED is technically feasible and can be achieved with a safety profile analogous to that reported for stent-supported coil embolization. PED treatment elicited a very high rate (93%) of complete angiographic occlusion at 6 months in a population of the most challenging anatomic subtypes of cerebral aneurysms.

High-Profile Flow Diverter (Silk) Implantation in the Basilar Artery: Efficacy in the Treatment of Aneurysms and the Role of the Perforators

Background and Purpose— The introduction of flow diverters (FDs) has expanded the possibilities for reconstructive treatment of difficult intracranial aneurysms. Concern remains as to the long-term patency of the perforating arteries and side branches covered during stent placement. Our purpose was to evaluate the performance of and early effect on covered branches after implantation of the Silk FD in the treatment of basilar artery aneurysms. Methods— Twelve patients with an aneurysm of the basilar artery that was treated by implantation of the Silk FD were included in our retrospective study. Both unruptured and previously ruptured, formerly untreated, and recurrent aneurysms were treated. During follow-up, patients were monitored for clinical evolution, patency of the covered vessels, and aneurysmal obliteration. Results— Of the 2 ruptured aneurysms, 1 was initially treated by FD implantation. The FD covered the basilar bifurcation and the origin of a P1 segment of the posterior cerebral artery in 9 cases, the origin of the superior cerebellar artery in 9, and of the anterior inferior cerebellar artery in 3. There was 1 acute basilar artery occlusion a few hours after FD implantation. During a mean follow-up of 16 weeks, 3 patients experienced a symptomatic neurologic event. Conclusions— Implantation of the Silk FD in the basilar artery was feasible and well tolerated in most cases to date. However, late ischemic events affecting perforating arteries may occur after FD implantation, suggesting that the indication should be restricted to otherwise untreatable aneurysms in this location.

Measuring blood volume and vascular transfer constant from dynamic, T*2-Weighted contrast-enhanced MRI

Dynamic, contrast‐enhanced MRI (deMRI) is increasingly being used to evaluate cerebral microcirculation. There are two different approaches for analyzing deMRI data. Intravascular indicator dilution theory has been used to estimate blood volume (and perfusion), usually from T2‐ or T  2* ‐weighted images of the first pass of the bolus. However, the theory assumes that the tracer (i.e., contrast agent) remains intravascular, which is often not the case when the blood–brain barrier (BBB) is damaged. Furthermore, the method provides no information on the vascular transfer constant. Pharmacokinetic modeling analyses of T1‐weighted images after first pass do give values of the vascular transfer constant and the volume of the extravascular, extracellular space (EES), but they generally are unable to give estimates of blood volume. In this study we apply pharmacokinetic modeling to dynamic T  2* ‐weighted imaging of the first pass of a tracer bolus. This method, which we call first‐pass pharmacokinetic modeling (FPPM), gives an estimate of the blood volume, vascular transfer constant, and EES volume. The method was applied to a group of 26 patients with surgically proven tumors (10 glioblastomas multiforme (GBMs), six lymphomas, and 10 meningiomas). The measurements of the blood volume and transfer constant were consistent with the known physiology of these tumors. Magn Reson Med 51:961–968, 2004.

Thrombolysis in Stroke Mimics: Frequency, Clinical Characteristics, and Outcome

Background and Purpose— Intravenous thrombolysis for acute ischemic stroke is usually based on clinical assessment, blood test results, and CT findings. Intravenous thrombolysis of stroke mimics may occur but has not been studied in detail. Methods— We determined frequency, clinical characteristics, and outcome of mimic patients versus patients with stroke treated with intravenous thrombolysis using data of a prospective, single-center thrombolysis data bank. Results— Among 250 patients, 243 (97.2%) had strokes and 7 (2.8%) were mimics. Seizure was the most frequent diagnosis among mimics. There was a trend toward lower National Institutes of Health Stroke Scale scores in mimics (9.9±4.2) compared with strokes (13.7±5.4; P=0.06). Global aphasia without hemiparesis was the presenting symptom in 3 (42.9%) mimics versus 8 (3.3%) strokes (P=0.002). Orolingual angioedema, symptomatic intracranial hemorrhage, and asymptomatic intracranial hemorrhage occurred in 3 (1.2%), 13 (5.3%), and 30 (12.3%) patients with stroke, but were absent in mimics. After 3 months, 6 (85.7%) mimics and 86 (35.4%) strokes had a modified Rankin Scale score of 0 to 1 (P=0.01). Conclusions— Only few patients receiving intravenous thrombolysis did eventually have a final diagnosis other than stroke, ie, mostly seizures. Their outcome was favorable. Although clinical features differed between the stroke and the mimic groups, the differences were not distinctive enough to allow assigning individual patients to either of the groups. Multimodal neuroimaging or electroencephalographic recordings may be helpful for this assignment. However, their potential benefit has to be weighed against the potential harm of delayed thrombolysis.

Cortical reorganization after acute unilateral hearing loss traced by fMRI

Article abstract Unilateral acoustic stimulation produces a functional MRI (fMRI)–blood-oxygenation-level-dependent (BOLD) response mainly in the contralateral auditory cortex. In unilateral deaf patients, the BOLD response is bilateral. We studied a subject with sudden hearing loss after cochlear nerve resection before and repeatedly after surgery. During normal bilateral hearing, contralateral cortical BOLD responses were found. Progressing compensatory reorganization with bilateral representation of unilateral stimulation was detected over a period of approximately 1 year.

Effect of combined mouth closure and chin lift on upper airway dimensions during routine magnetic resonance imaging in pediatric patients sedated with propofol.

BACKGROUND In pediatric patients, obstruction of the upper airway is a common problem during general anesthesia. Chin lift is a commonly used technique to improve upper airway patency. However, little is known about the mechanism underlying this technique. METHODS The authors studied the effect of the chin lift maneuver on airway dimensions in 10 spontaneously breathing children (aged 2-11 yr) sedated with propofol during routine magnetic resonance imaging. The minimal anteroposterior and corresponding transverse diameters of the pharynx were determined at the levels of the soft palate, dorsum of the tongue, and tip of the epiglottis before and during the chin lift maneuver. Additionally, cross-sectional areas were calculated at these sites, including tracheal areas 2 cm below the glottic level. RESULTS Minimal anteroposterior diameter of the pharynx increased significantly during chin lift at all three levels in all patients. The diameters of the soft palate, tongue, and epiglottis increased from 6.7+/-2.8 mm (SD) to 9.9+/-3.6 mm, from 9.6+/-3.6 mm to 16.5+/-3.1 mm, and from 4.6+/-2.5 mm to 13.1+/-2.8 mm, respectively. The corresponding transverse diameter of the pharynx also increased significantly at all three levels in all patients but without significant predominance. The diameters at the levels of the soft palate, tongue, and epiglottis increased from 15.8+/-5.1 mm to 22.8+/-4.5 mm, from 13.5+/-4.9 mm to 18.7+/-5.3 mm, and from 17.2+/-3.9 mm to 21.2+/-3.7 mm, respectively. Cross-sectional pharyngeal areas increased significantly at all levels (soft palate, from 0.88+/-0.58 cm2 to 1.79+/-0.82 cm2; tongue, from 1.15+/-0.45 cm2 to 2.99+/-1.30 cm2; epiglottis, from 1.17+/-0.70 cm2 to 3.04+/-0.99 cm2), including the subglottic level (from 0.44+/-0.15 cm2 to 0.50+/-0.14 cm2). CONCLUSIONS This study shows that all children had a preserved upper airway at all measured sites during propofol sedation. Chin lift caused a widening of the entire pharyngeal airway that was most pronounced between the tip of the epiglottis and the posterior pharyngeal wall. In pediatric patients, chin lift may be used as a standard procedure during propofol sedation.

The clinical significance of diffusion-weighted MR imaging in infratentorial strokes

Objective: To study the association between diffusion-weighted imaging (DWI) characteristics and stroke etiology, stroke severity, and functional outcome in patients with infratentorial strokes. Methods: The authors prospectively studied 22 consecutive patients with acute infratentorial strokes. They used a blinded comparison of DWI features (number, distribution, and volume of lesions) with clinical characteristics, namely, stroke etiology (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] classification), severity (NIH Stroke Scale [NIHSS]), length of stay (LOS), and functional 3-month outcome using modified Rankin Scale, Barthel Index, and a dichotomized outcome status (living at home vs institutionalization or death). Results: Acute infratentorial DWI lesions were detected in 95% (21/22) of the patients. The number (p = 0.01) and the distribution (p < 0.001) of DWI lesions were correlated with stroke etiology. Patients with cardioembolic strokes (n = 5) had more DWI lesions (8.0 ± 6.0) than those with other stroke etiologies (n = 17; 1.3 ± 0.9; p < 0.001). Their lesion distribution differed from that of patients with noncardioembolic strokes (p < 0.001). Clinically silent, acute DWI lesions in the anterior circulation in addition to their infratentorial lesions were visualized in 3 of 5 patients with cardioembolic stroke and in none of 17 patients without sources of cardioembolism (p < 0.001). Pure infratentorial lesions were present in 15 of 17 patients with noncardioembolic strokes and in none of 5 cardioembolic stroke patients (p < 0.001). DWI lesion volume was not correlated with NIHSS score, LOS, outcome scores, or outcome status. Conclusion: In infratentorial strokes, multiple DWI lesions and a distribution of subsidiary, clinically silent DWI lesions in the anterior circulation suggest a cardioembolic stroke etiology. However, DWI lesion volume did not correlate with the NIHSS score and was no predictor of outcome.

Diffusion-Weighted Imaging in Stroke Attributable to Patent Foramen Ovale Significance of Concomitant Atrial Septum Aneurysm

Background and Purpose— Patent foramen ovale (PFO) is an established cause of stroke in young patients without other determined etiologies (ie, cryptogenic stroke). The additional presence of atrial septum aneurysm (ASA) possibly increases stroke risk, but it remains undetermined which factors best predict thromboembolism in patients with PFO. Diffusion-weighted imaging (DWI) may help to distinguish the characteristics of cerebral embolism associated with different features of the interatrial septum in PFO stroke. Methods— In a stroke databank–based cohort study, DWI and transthoracic/transesophageal echocardiography findings were assessed in 48 consecutive patients with cryptogenic ischemic stroke associated with PFO. The number, size, and distribution of acute ischemic lesions on DWI were correlated with PFO size, degree of interatrial right-to-left shunt (RLS), and the presence of ASA. Results— Patients with PFO plus ASA combined more often had multiple acute DWI lesions (16 of 30, 53%) than those with PFO alone (3 of 18, 17%; P=0.01). This association remained significant after correction for PFO size, degree of RLS, and vascular risk factors in a logistic-regression analysis (P=0.04). No significant associations between DWI lesion characteristics and PFO size or degree of RLS were found. Conclusions— The presence of concomitant ASA is independently associated with multiple cerebral ischemic lesions in PFO stroke, which may indicate an increased embolic risk.

Functional MRI, DTI and neurophysiology in horizontal gaze palsy with progressive scoliosis

IntroductionHorizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disease due to a mutation in the ROBO3 gene. This rare disease is of particular interest because the absence, or at least reduction, of crossing of the ascending lemniscal and descending corticospinal tracts in the medulla predicts abnormal ipsilateral sensory and motor systems.MethodsWe evaluated the use of functional magnetic resonance imaging (fMRI) for the first time in this disease and compared it to diffusion tensor imaging (DTI) tractography and neurophysiological findings in the same patient with genetically confirmed ROBO3 mutation.ResultsAs expected, motor fMRI, somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP) were dominantly ipsilateral to the stimulation side. DTI tractography revealed ipsilateral ascending and descending connectivity in the brainstem yet normal interhemispheric connections in the corpus callosum. Auditory fMRI revealed bilateral auditory activation to monaural left-sided auditory stimulation. No significant cortical activation was observed after monaural right-sided stimulation, a hearing defect having been excluded. Prosaccades fMRI showed no activations in the eye-movement network.ConclusionMotor fMRI confirmed the established findings of DTI and neurophysiology in the same patient. In suspected HGPPS, any technique appears appropriate for further investigation. Auditory fMRI suggests that a monaural auditory system with bilateral auditory activations might be a physiological advantage as compared to a binaural yet only unilateral auditory system, in analogy to anisometropic amblyopia. Moving-head fMRI studies in the future might show whether the compensatory head movements instead of normal eye movements activate the eye-movement network.

Cerebral Venous Thrombosis: Diagnostic Accuracy of Combined, Dynamic and Static, Contrast-Enhanced 4D MR Venography

BACKGROUND AND PURPOSE: MR including MRV is an established method to diagnose CVT. However, it remains unsettled which MR imaging modalities offer the highest diagnostic accuracy. We evaluated the accuracy of a combined, dynamic (1.5 seconds per dataset) and static (voxel size, 1.1 × 0.9 × 1.5 mm), contrast-enhanced MRV method (combo-4D MRV) relative to other established MR/MRV modalities. MATERIALS AND METHODS: A total of 39 patients with CVT (n = 20) and control subjects (n = 19) underwent combo-4D MRV, 2D TOF MRV, GRE imaging, and T2W imaging. For these modalities, diagnostic accuracy (ROCs) for CVT affecting 53 out of 234 predefined venous segments was determined. Sensitivity and specificity were separately calculated for different stages of CVT (acute/subacute/chronic). RESULTS: Combo-4D MRV showed the highest accuracy (AUC, 0.99 [95% CI, 0.97–1.0]; sensitivity, 97% [84%–100%]) for thrombosed dural sinuses. For all thrombosed segments including cortical veins, its sensitivity was best (76% [64%–84%]; AUC, 0.92 [0.88–0.96]), followed by TOF MRV (72% [59%–81%]; AUC, 0.93 [0.88–0.97]). Even for chronic CVT, it showed a relatively high sensitivity of 67% (30%–90%). For thrombosed cortical veins alone, GRE images achieved the highest sensitivity (66% [46%–81%]; AUC, 0.88 [0.78–0.97]). Specificities of all modalities ranged from 96% to 99%. CONCLUSIONS: Combo-4D MRV showed an excellent accuracy for the diagnosis of dural sinus thrombosis. The analysis of dynamic patterns of contrast enhancement in dural sinuses appeared useful to identify chronic thrombosis. To diagnose thrombosed cortical veins, GRE images should primarily be analyzed.