Oliver Mueller

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.

Cerebral Cavernous Hemangiomas at 7 Tesla: Initial Experience

RATIONALE AND OBJECTIVES Cavernous malformations (cavernomas) occur in 0.4%-0.9% of the population. The most common symptoms of cavernous malformations are seizures. An improved detection of small cavernomas might possibly help to clarify cryptogenic seizures, which represent 30% of all seizures. The aim of this study was to evaluate the benefit of magnetic resonance imaging at a field strength of 7 T in the detection of cavernomas. MATERIALS AND METHODS Ten consecutive patients with known cavernomas were enrolled in this study. First a T2*-weighted gradient echo sequence was performed at 1.5 T with a slice thickness of 6 mm in axial orientation. Subsequently, the examination was repeated at 7 T. Both examinations were independently read by two blinded senior neuroradiologists. Localization and dimension of the hypointensities were recorded. RESULTS One additional hypointensity was detected in one patient, which was not visible in the 1.5 T examination even retrospectively. In another patient with known cavernomatosis, innumerable new small hypointense lesions were detected at 7 T. CONCLUSION Our small series suggests that ultra-high-field magnetic resonance imaging at 7 T improves the detection of cavernomas.

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.

An Intact Action-Perception Coupling Depends on the Integrity of the Cerebellum

It is widely accepted that action and perception in humans functionally interact on multiple levels. Moreover, areas originally suggested to be predominantly motor-related, as the cerebellum, are also involved in action observation. However, as yet, few studies provided unequivocal evidence that the cerebellum is involved in the action perception coupling (APC), specifically in the integration of motor and multisensory information for perception. We addressed this question studying patients with focal cerebellar lesions in a virtual-reality paradigm measuring the effect of action execution on action perception presenting self-generated movements as point lights. We measured the visual sensitivity to the point light stimuli based on signal detection theory. Compared with healthy controls cerebellar patients showed no beneficial influence of action execution on perception indicating deficits in APC. Applying lesion symptom mapping, we identified distinct areas in the dentate nucleus and the lateral cerebellum of both hemispheres that are causally involved in APC. Lesions of the right ventral dentate, the ipsilateral motor representations (lobules V/VI), and most interestingly the contralateral posterior cerebellum (lobule VII) impede the benefits of motor execution on perception. We conclude that the cerebellum establishes time-dependent multisensory representations on different levels, relevant for motor control as well as supporting action perception. Ipsilateral cerebellar motor representations are thought to support the somatosensory state estimate of ongoing movements, whereas the ventral dentate and the contralateral posterior cerebellum likely support sensorimotor integration in the cerebellar-parietal loops. Both the correct somatosensory as well as the multisensory state representations are vital for an intact APC.

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.

Effects of cerebellar lesions on working memory interacting with motor tasks of different complexities

We examined the influence of focal cerebellar lesions on working memory (n-back task), gait, and the interaction between working memory and different gait tasks in a dual-task paradigm. The analysis included 17 young patients with chronic focal lesions after cerebellar tumor resection and 17 age-matched controls. Patients have shown mild to moderate ataxia. Lesion sites were examined on the basis of structural magnetic resonance imaging. N-back tasks were executed with different levels of difficulty (n = 1-4) during sitting (baseline), treadmill walking, and treadmill tandem walking (dual-task conditions). Patients exhibited decreased n-back performance particularly at difficult n-back levels and in dual-task conditions. Voxel-based lesion-symptom mapping revealed that decreased baseline n-back performance was associated with lesions of the posterolateral cerebellar hemisphere and the dentate nucleus. By contrast, decreased n-back performance in dual-task conditions was more associated with motor-related areas including dorsal portions of the dentate and the interposed nucleus, suggesting a prioritization of the motor task. During baseline walking, increased gait variability was associated with lesions in medial and intermediate regions, whereas for baseline tandem gait, lesions in the posterolateral hemispheres and the dentate nucleus became important. Posterolateral regions overlapped with regions related to baseline n-back performance. Consistently, we observed increased tandem gait variability with growing n-back difficulty in the dual-task condition. These findings suggest that dual-task effects in cerebellar patients are at least partially caused by a common involvement of posterolateral cerebellar regions in working memory and complex motor tasks.

Intracranial aneurysms: optimized diagnostic tools call for thorough interdisciplinary treatment strategies

Objective: Intracranial aneurysms (IAs) require deliberately selected treatment strategies as they are incrementally found prior to rupture and deleterious subarachnoid haemorrhage (SAH). Multiple and recurrent aneurysms necessitate both neurointerventionalists and neurosurgeons to optimize aneurysmal occlusion in an interdisciplinary effort. The present study was conducted to condense essential strategies from a single neurovascular centre with regard to the lessons learned. Method: Medical charts of 321 consecutive patients treated for IAs at our centre from September 2008 until December 2010 were retrospectively analysed for clinical presentation of the aneurysms, multiplicity and treatment pathways. In addition, a selective Medline search was performed. Results: A total of 321 patients with 492 aneurysms underwent occlusion of their symptomatic aneurysm: 132 (41.1%) individuals were treated surgically, 189 (58.2%) interventionally; 138 patients presented with a SAH, of these 44.2% were clipped and 55.8% were coiled. Aneurysms of the middle cerebral artery were primarily occluded surgically (88), whereas most of the aneurysms of the internal carotid artery and anterior communicating artery (114) were treated endovascularly. Multiple aneurysms (range 2–5 aneurysms/individual) were diagnosed in 98 patients (30.2%). During the study period 12 patients with recurrent aneurysms were allocated to another treatment modality (previously clip to coil and vice versa). Conclusions: Our data show that successful interdisciplinary occlusion of IAs is based on both neurosurgical and neurointerventional therapy. In particular, multiple and recurrent aneurysms require tailored individual approaches to aneurysmal occlusion. This is achieved by a consequent interdisciplinary pondering of the optimal strategy to occlude IAs in order to prevent SAH.

Study of angiogenic signaling pathways in hemangioblastoma

Hemangioblastoma (HB) is mainly located in the brain and the spinal cord. The tumor is composed of two major components, namely neoplastic stromal cells and abundant microvessels. Thus, hyper‐vascularization is the hallmark of this tumor. Despite the identification of germline and/or epigenetic mutations of Von Hippel Lindau (VHL) gene as an important pathogenic mechanism of HB, little is known about the molecular signaling involved in this highly vascularized tumor. The present study investigated the key players of multiple angiogenic signaling pathways including VEGF/VEGFR2, EphB4/EphrinB2, SDF1α/CXCR4 and Notch/Dll4 pathways in surgical specimens of 22 HB. The expression of key angiogenic factors was detected by RT2‐PCR and Western blot. Immunofluorescent staining revealed the cellular localization of these proteins. We demonstrated a massive upregulation of mRNA levels of VEGF and VEGFR2, CXCR4 and SDF1α, EphB4 and EphrinB2, as well as the main components of Dll4‐Notch signaling in HB. An increase in the protein expression of VEGF, CXCR4 and the core‐components of Dll4‐Notch signaling was associated with an activation of Akt and Erk1/2 and accompanied by an elevated expression of PCNA. Immuofluorescent staining revealed the expression of VEGF and CXCR4 in endothelial cells as well as in tumor cells. Dll4 protein was predominantly found in tumor cells, whereas EphB4 immunoreactivity was exclusively detected in endothelial cells. We conclude that multiple key angiogenic pathways were activated in HB, which may synergistically contribute to the abundant vascularization in this tumor. Identification of these aberrant pathways provides potential targets for a possible future application of anti‐angiogenic therapy for this tumor, particularly when a total surgical resection becomes difficult due to the localization or multiplicity of the tumor.

Instable cervical spine injury in a toddler: technical note

PurposeInstable upper cervical spine injuries (CSI) in very young children are rare and consecutively only few data on the treatment and operative approaches exist in the literature. Hence, we suggest an operative strategy in the case of a 15-month-old infant treated for an instable CSI at the level of C2/3 at our department. Detailed steps of the operation with special consideration to the challenging anatomy of the immature spine are presented.MethodsA toddler suffered a CSI without neurological deficits after a stair fall. Computer tomography (CT) and magnetic resonance imaging (MRI) of the cervical spine revealed an instable luxation fracture of C2/3. As repositioning in the halo vest immobilization failed, surgical fusion was indicated.ResultsVia a posterior midline approach, the lamina of C2 and C3 was conflated in a modified sublaminar wiring technique using non-resorbable sutures, sparing the ossification zones of the vertebral arches. Postoperative immobilization in a halo vest facilitated bony fusion of the laminae at C2/3 without lordotic displacement of the cervical spine.ConclusionsWe consider the instable CSI of the immature cervical in the very young a challenging situation for every treating physician. The particular features of the growing spine require special attention to avoid damage to the growth centers of the vertebrae. To our knowledge, this is the first technical report giving detailed information of an operative approach to the severely injured immature cervical spine and postoperative management.

Pronounced reduction of acquisition of conditioned eyeblink responses in young adults with focal cerebellar lesions impedes conclusions on the role of the cerebellum in extinction and savings

Human cerebellar lesion studies provide good evidence that the cerebellum contributes to the acquisition of classically conditioned eyeblink responses (CRs). As yet, only one study used more advanced methods of lesion-symptom (or lesion-behavior) mapping to investigate which cerebellar areas are involved in CR acquisition in humans. Likewise, comparatively few studies investigated the contribution of the human cerebellum to CR extinction and savings. In this present study, young adults with focal cerebellar disease were tested. A subset of participants was expected to acquire enough conditioned responses to allow the investigation of extinction and saving effects. 19 participants with chronic surgical lesions of the cerebellum and 19 matched control subjects were tested. In all cerebellar subjects benign tumors of the cerebellum had been surgically removed. Eyeblink conditioning was performed using a standard short delay protocol. An initial unpaired control phase was followed by an acquisition phase, an extinction phase and a subsequent reacquisition phase. Structural 3T magnetic resonance images of the brain were acquired on the day of testing. Cerebellar lesions were normalized using methods optimized for the cerebellum. Subtraction analysis and Liebermeister tests were used to perform lesion-symptom mapping. As expected, CR acquisition was significantly reduced in cerebellar subjects compared to controls. Reduced CR acquisition was significantly more likely in participants with lesions of lobule VI and Crus I extending into Crus II (p<0.05, Liebermeister test). Cerebellar subjects could be subdivided into two groups: a smaller group (n=5) which showed acquisition, extinction and savings within the normal range; and a larger group (n=14) which did not show acquisition. In the latter, no conclusions on extinction or savings could be drawn. Previous findings were confirmed that circumscribed areas in lobule VI and Crus I are of major importance in CR acquisition. In addition, the present data suggest that if the critical regions of the cerebellar cortex are lesioned, the ability to acquire CRs is not only reduced but abolished. Subjects with lesions outside these critical areas, on the other hand show preserved acquisition, extinction and saving effects. As a consequence, studies in human subjects with cerebellar lesions do not allow drawing conclusions on CR extinction and savings. In light of the present findings, previous reports of reduced extinction in humans with circumscribed cerebellar disease need to be critically reevaluated.