Philipp Dammann

Occipital nerve stimulation for intractable chronic cluster headache or migraine: A critical analysis of direct treatment costs and complications

Background Occipital nerve stimulation (ONS) has been shown to be effective for selected patients with intractable headache disorders. We performed a prospective critical evaluation of complications and direct treatment costs. Methods Twenty-seven patients with chronic cluster headache (CCH, n = 24) or chronic migraine (CM, n = 3) underwent a trial phase with bilateral ONS and subsequent implantation of a permanent generator (IPG), if responsive to treatment according to predefined criteria. Procedural and long-term complications as well as direct treatment costs of neuromodulation therapy of ONS were recorded over a mean follow-up period of 20 months (range 5–47 months). Results Twenty-five of 27 patients (93%) responded to treatment. Twenty-one complications in 14 patients were identified, necessitating reoperation in 13 cases. Overall treatment costs were €761,043, including hardware-related costs of €506,019, costs for primary hospital care of €210,496, and complications related to hospitalization costs of €44,528. This results in a per case-based cost of €9445 for hospitalization and €18,741 for hardware costs, totaling €28,186. Conclusion ONS for treatment of refractory CCH and CM is a cost-intensive treatment option with a significant complication rate. Nevertheless, patients with refractory primary headache disorders may experience substantial relief of pain attacks, and headache days, respectively.

Loss of CCM3 impairs DLL4-Notch signalling: implication in endothelial angiogenesis and in inherited cerebral cavernous malformations

CCM3, a product of the cerebral cavernous malformation 3 or programmed cell death 10 gene (CCM3/PDCD10), is broadly expressed throughout development in both vertebrates and invertebrates. Increasing evidence indicates a crucial role of CCM3 in vascular development and in regulation of angiogenesis and apoptosis. Furthermore, loss of CCM3 causes inherited (familial) cerebral cavernous malformation (CCM), a common brain vascular anomaly involving aberrant angiogenesis. This study focused on signalling pathways underlying the angiogenic functions of CCM3. Silencing CCM3 by siRNA stimulated endothelial proliferation, migration and sprouting accompanied by significant downregulation of the core components of Notch signalling including DLL4, Notch4, HEY2 and HES1 and by activation of VEGF and Erk pathways. Treatment with recombinant DLL4 (rhDLL4) restored DLL4 expression and reversed CCM3‐silence‐mediated impairment of Notch signalling and reduced the ratio of VEGF‐R2 to VEGF‐R1 expression. Importantly, restoration of DLL4‐Notch signalling entirely rescued the hyper‐angiogenic phenotype induced by CCM3 silence. A concomitant loss of CCM3 and the core components of DLL4‐Notch signalling were also demonstrated in CCM3‐deficient endothelial cells derived from human CCM lesions (CCMEC) and in a CCM3 germline mutation carrier. This study defined DLL4 as a key downstream target of CCM3 in endothelial cells. CCM3/DLL4‐Notch pathway serves as an important signalling for endothelial angiogenesis and is potentially implicated in the pathomechanism of human CCMs.

Susceptibility weighted magnetic resonance imaging of cerebral cavernous malformations: prospects, drawbacks, and first experience at ultra–high field strength (7-Tesla) magnetic resonance imaging

High-resolution susceptibility weighted MR imaging at high field strength provides excellent depiction of venous structures, blood products, and iron deposits, making it a promising complementary imaging modality for cerebral cavernous malformations (CCMs). Although already introduced in 1997 and being constantly improved, susceptibility weighted imaging is not yet routine in clinical neuroimaging protocols for CCMs. In this article, the authors review the recent literature dealing with clinical and scientific susceptibility weighted imaging of CCMs to summarize its prospects and drawbacks and provide their first experience with its use in ultra-high field (7-T) MR imaging.

Caudal Image Contrast Inversion in MPRAGE at 7 Tesla: Problem and Solution

RATIONALE AND OBJECTIVES The magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) sequence regularly shows caudal image contrast inversion at 7 T and therefore reduced clinical applicability. The investigators report the technical source of this problem and present a practical solution. MATERIALS AND METHODS A total of 71 subjects were scanned using a 7-T whole-body magnetic resonance imaging system using a 32-channel transmit/receive head coil. In 39 subjects, 45 high-resolution T1 contrast image data sets were acquired with the standard MPRAGE sequence. A modified sequence with an adiabatic wideband uniform rate smooth truncation pulse for magnetization preparation was used for 45 further scans in 39 subjects. In total, seven subjects underwent scans with both sequences. The homogeneity of T1 contrast and the occurrence of caudal image contrast inversion were evaluated in consensus reading by two neuroradiologists. RESULTS Caudal image contrast inversion was depicted in 19 acquisitions (42.2%) using the standard MPRAGE sequence. Using the adiabatic wideband uniform rate smooth truncation pulse for magnetization preparation, caudal image contrast inversion was depicted in only three acquisitions (6.7%). A χ(2) test showed a significant difference between the two preparation pulses (P < .001). CONCLUSIONS Magnetization preparation with an adiabatic wideband uniform rate smooth truncation pulse in the MPRAGE sequence at 7 T can significantly reduce the occurrence of caudal image contrast inversion and improves signal homogeneity.

The venous angioarchitecture of sporadic cerebral cavernous malformations: a susceptibility weighted imaging study at 7 T MRI

Background and purpose To test the hypothesis that sporadic cerebral cavernous malformations (CCMs) are systematically associated with venous malformations (VMs) using susceptibility weighted imaging (SWI) at 7 Tesla (T) field MRI. Methods A prospective unselected series of 20 patients with symptomatic or asymptomatic sporadic CCM diagnosed using 1.5 T MRI was additionally scanned using high resolution (250 µm2 in-plane) SWI at 7 T MRI. Imaging data were analysed to examine the presence and formation of CCM associated venous vessel structures. Interobserver agreement was assessed using kappa statistics. Results In the 20 patients harbouring 23 CCMs, a solitary or multiple venous drainage was found in all lesions. A ‘typical’ VM was found in seven lesions. In the other cases, associated abnormal venous structures were also depicted although they appeared structurally different. Excellent interobserver agreement was achieved (95% confidence interval 0.92 to 0.99). Conclusions Our data support previous assumptions that sporadic CCMs are systematically associated with local venous abnormalities involving larger outflow vessels. However, the typical appearance of a VM was not confirmed in all cases. The role of the venous environment in the pathomechanism of CCMs remains unclear.

Spontaneous cerebellar hemorrhage—experience with 57 surgically treated patients and review of the literature

The treatment of spontaneous cerebellar hemorrhage is still discussed controversially. We analyzed a series of 57 patients who underwent surgical evacuation of a cerebellar hematoma at our department. Preoperative clinical and radiological parameters were assessed and correlated with the clinical outcome in order to identify factors with impact on outcome. The overall clinical outcome according to the Glasgow Outcome Scale at the last follow-up was good (GOS 4–5) in 27 patients (47%) and poor (GOS 2–3) in 16 patients (28%). Fourteen patients (25%) died. The initial neurological condition and the level of consciousness proved to be significant factors determining clinical outcome (p = 0.0032 and p = 0.0001, respectively). Among radiological parameters, brain stem compression and a tight posterior fossa solely showed to be predictive for clinical outcome (p = 0.0113 and p = 0.0167, respectively). Overall, our results emphasize the predictive impact of the initial neurological condition on clinical outcome confirming the grave outcome of patients in initially poor state as reported in previous studies. The hematoma size solely, in contrast to previous observations, showed not to be predictive for clinical outcome. Especially for the still disputed treatment of patients in good initial neurological condition, a suggestion can be derived from the present study. Based on the excellent outcome of patients with good initial clinical condition undergoing surgery due to secondary deterioration, we do not recommend preventive evacuation of a cerebellar hematoma in these patients.

Evaluation of Hardware-related Geometrical Distortion in Structural MRI at 7 Tesla for Image-guided Applications in Neurosurgery

RATIONALE AND OBJECTIVES Geometrical distortion is a well-known problem in structural magnetic resonance imaging (MRI), leading to pixel shifts with variations up to several millimeters. Because the main factors of geometrical distortion are proportional to B(0), MRI spatial encoding distortions tend to increase with higher magnetic field strength. With the increasing prospects of utilizing ultra-high-field MRI (B(0) ≥ 7 Tesla) for neuroimaging and subsequently for image-guided neurosurgical therapy, the evaluation and correction of geometrical distortions occurring in ultra-high-field MRI are essential preconditions for the integration of these data. Hence, we conducted a phantom study to determine hardware-related geometrical distortion in clinically relevant sequences for structural imaging at 7 T MRI and compared the findings to 1.5 T MRI. MATERIAL AND METHODS Hardware-related geometrical distortion was evaluated using a MRI phantom (Elekta, Sweden). Both applied scanner systems (Magnetom Avanto 1.5 T and Magnetom 7 T, Siemens Healthcare, Erlangen, Germany) were equipped with similar gradient coils capable of delivering 45 mT/m of maximum amplitude and a slew rate of 220 mT/m/ms. Distortion analysis was performed for various clinically relevant gradient echo and spin echo sequences. RESULTS Overall, we found very low mean geometrical distortions at both 7 T and 1.5 T, although single values of up to 1.6 mm were detected. No major differences in mean distortion between the sequences could be found, except significantly higher distortions in turbo spin-echo sequences at 7 T, mainly caused by B(1) inhomogeneities. CONCLUSION Hardware-related geometrical distortions at 7 T MRI are relatively small, which may be acceptable for image coregistration or for direct tissue-targeting procedures. Using a subject-specific correction of object-related distortions, an integration of 7 T MRI data into image-guided applications may be feasible.

Non-enhanced MR imaging of cerebral aneurysms: 7 Tesla versus 1.5 Tesla.

Purpose To prospectively evaluate 7 Tesla time-of-flight (TOF) magnetic resonance angiography (MRA) in comparison to 1.5 Tesla TOF MRA and 7 Tesla non-contrast enhanced magnetization-prepared rapid acquisition gradient-echo (MPRAGE) for delineation of unruptured intracranial aneurysms (UIA). Material and Methods Sixteen neurosurgical patients (male n = 5, female n = 11) with single or multiple UIA were enrolled in this trial. All patients were accordingly examined at 7 Tesla and 1.5 Tesla MRI utilizing dedicated head coils. The following sequences were obtained: 7 Tesla TOF MRA, 1.5 Tesla TOF MRA and 7 Tesla non-contrast enhanced MPRAGE. Image analysis was performed by two radiologists with regard to delineation of aneurysm features (dome, neck, parent vessel), presence of artifacts, vessel-tissue-contrast and overall image quality. Interobserver accordance and intermethod comparisons were calculated by kappa coefficient and Lins concordance correlation coefficient. Results A total of 20 intracranial aneurysms were detected in 16 patients, with two patients showing multiple aneurysms (n = 2, n = 4). Out of 20 intracranial aneurysms, 14 aneurysms were located in the anterior circulation and 6 aneurysms in the posterior circulation. 7 Tesla MPRAGE imaging was superior over 1.5 and 7 Tesla TOF MRA in the assessment of all considered aneurysm and image quality features (e.g. image quality: mean MPRAGE7T: 5.0; mean TOF7T: 4.3; mean TOF1.5T: 4.3). Ratings for 7 Tesla TOF MRA were equal or higher over 1.5 Tesla TOF MRA for all assessed features except for artifact delineation (mean TOF7T: 4.3; mean TOF1.5T 4.4). Interobserver accordance was good to excellent for most ratings. Conclusion 7 Tesla MPRAGE imaging demonstrated its superiority in the detection and assessment of UIA as well as overall imaging features, offering excellent interobserver accordance and highest scores for all ratings. Hence, it may bear the potential to serve as a high-quality diagnostic tool for pretherapeutic assessment and follow-up of untreated UIA.

7 Tesla MPRAGE imaging of the intracranial arterial vasculature: nonenhanced versus contrast-enhanced.

PURPOSE To intraindividually compare the delineation of intracranial arterial vasculature in nonenhanced versus contrast-enhanced magnetization prepared rapid gradient echo (MPRAGE) imaging at 7 Tesla (T). MATERIALS AND METHODS Sixteen subjects were examined on a 7 T whole-body magnetic resonance system (Magnetom 7T) equipped with a 32-channel transmit/receive head coil. MPRAGE imaging was performed pre- and postcontrast after the application of 0.1 mmol/kg bodyweight gadobutrol. For qualitative analysis, the delineation of the intracranial arteries, overall image quality, and image impairment were assessed in the nonenhanced and contrast-enhanced datasets using a 5-point scale (5 = excellent to 1 = nondiagnostic). Additionally, contrast ratios (CR) of the middle cerebral artery in correlation to surrounding gray matter in nonenhanced and postcontrast images were obtained. For statistical analysis a Wilcoxon signed-rank test was applied. RESULTS Nonenhanced MPRAGE imaging offered an excellent delineation of the central vessel segments of the anterior circulation (mean anterior circulation 4.6) and a moderate- to high-quality assessment of the vessels of the posterior circulation (mean posterior circulation 3.9). Vessel delineation was improved in all assessed segments in the contrast-enhanced datasets, except for the cavernous segment of the internal carotid artery. Quantitative analysis revealed a mild, nonsignificant increase in CR mean values of the M1 segment (CRnonenhanced 0.67; CRcontrast-enhanced 0.69). CONCLUSION Our results demonstrate the high diagnostic value of nonenhanced 7 T MPRAGE imaging for the assessment of the intracranial arterial vasculature, with improved assessment of the peripheral segments because of the application of a contrast agent.

Improved cerebral time-of-flight magnetic resonance angiography at 7 Tesla--feasibility study and preliminary results using optimized venous saturation pulses.

Purpose Conventional saturation pulses cannot be used for 7 Tesla ultra-high-resolution time-of-flight magnetic resonance angiography (TOF MRA) due to specific absorption rate (SAR) limitations. We overcome these limitations by utilizing low flip angle, variable rate selective excitation (VERSE) algorithm saturation pulses. Material and Methods Twenty-five neurosurgical patients (male n = 8, female n = 17; average age 49.64 years; range 26–70 years) with different intracranial vascular pathologies were enrolled in this trial. All patients were examined with a 7 Tesla (Magnetom 7 T, Siemens) whole body scanner system utilizing a dedicated 32-channel head coil. For venous saturation pulses a 35° flip angle was applied. Two neuroradiologists evaluated the delineation of arterial vessels in the Circle of Willis, delineation of vascular pathologies, presence of artifacts, vessel-tissue contrast and overall image quality of TOF MRA scans in consensus on a five-point scale. Normalized signal intensities in the confluence of venous sinuses, M1 segment of left middle cerebral artery and adjacent gray matter were measured and vessel-tissue contrasts were calculated. Results Ratings for the majority of patients ranged between good and excellent for most of the evaluated features. Venous saturation was sufficient for all cases with minor artifacts in arteriovenous malformations and arteriovenous fistulas. Quantitative signal intensity measurements showed high vessel-tissue contrast for confluence of venous sinuses, M1 segment of left middle cerebral artery and adjacent gray matter. Conclusion The use of novel low flip angle VERSE algorithm pulses for saturation of venous vessels can overcome SAR limitations in 7 Tesla ultra-high-resolution TOF MRA. Our protocol is suitable for clinical application with excellent image quality for delineation of various intracranial vascular pathologies.