Radiation exposure in the intra-arterial nimodipine therapy of subarachnoid hemorrhage related cerebral vasospasm.

The selective intra-arterial nimodipine application for the treatment of cerebral vasospasm (CVS) in patients after spontaneous subarachnoid hemorrhage (sSAH) is widely employed. The purpose of this study is to examine the radiation exposure and to determine local diagnostic reference levels (DRLs) of intra-arterial nimodipine therapy. In a retrospective study design, DRLs and achievable dose (AD) were assessed for all patients undergoing (I) selective intra-arterial nimodipine application or (II) additional mechanical angioplasty for CVS treatment. Interventional procedures were differentiated according to the type of procedure and the number of probed vessels. Altogether 494 neurointerventional procedures of 121 patients with CVS due to sSAH could be included. The radiation exposure indices were distributed as follows: (I) DRL 74.3 Gy·cm2, AD 59.8 Gy·cm2; (II) DRL 128.3 Gy·cm2, AD 94.5 Gy·cm2. Kruskal-Wallis test confirmed significant dose difference considering the number of probed vessels (p< 0.001). The mean cumulative dose per patient was 254.9 Gy·cm2(interquartile range 88.6-315.6 Gy·cm2). The DRLs of intra-arterial nimodipine therapy are substantially lower compared with DRLs proposed for other therapeutic interventions, such as thrombectomy or aneurysm coiling. However, repeated therapy sessions are often required, bearing the potential risk of a cumulatively higher radiation exposure.

Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma.

PURPOSE: In the EF-14 trial for newly diagnosed glioblastoma (ndGBM) patients addition of Tumour Treating Fields (TTFields) to temozolomide treatment resulted in a significantly improved overall survival (OS). In the NOA-09/CeTeG trial, combination of lomustine and temozolomide was superior to temozolomide monotherapy in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter methylated (MGMTm) ndGBM. We evaluated combination of these two treatment modalities in patients with MGMTm ndGBM. There have been so far no data on the combination of these two efficient regimens. METHODS: This bicentric retrospective analysis investigated 16 patients. Parameters evaluated included safety outcome as measured by Common Toxicity Criteria for Adverse Events (CTCAE), clinical outcomes, and compliance to treatment. RESULTS: Hematologic adverse events CTCAE ≥ 3 were observed in seven, hepatotoxic adverse events of CTCAE ≥ 3 in four patients. Mild to moderate skin toxicity was detected in six patients. At data cutoff, patients demonstrated a median progression-free survival (PFS) of 20 months. The usage rate of TTFields showed a high median adherence (83%) to the therapy. CONCLUSIONS: This analysis provides first indication that the combination of TTFields/lomustine/temozolomide is safe and feasible. The observed survival outcomes might suggest potential beneficial effects.

Endovascular treatment of cerebral vasospasm after subarachnoid hemorrhage: More is more.

OBJECTIVE: Delayed cerebral ischemia (DCI) is strongly associated with poor outcome after subarachnoid hemorrhage (SAH). Cerebral vasospasm is a major contributor to DCI and requires special attention. To evaluate the effect of vasospasm management on SAH outcome, we performed a pooled analysis of 2 observational SAH cohorts. MATERIALS: Data from 2 institutional databases with consecutive patients with SAH treated between 2005 and 2012 were pooled. The effect of 2 institutional standards of conservative and endovascular vasospasm treatment (EVT) on the rates of DCI (new cerebral infarcts not visible on the post-treatment imaging) and unfavorable outcome (modified Rankin Scale score >2) at 6 months follow-up was analyzed. RESULTS: The final analysis included 1,057 patients with SAH. There was no difference regarding demographic (age and sex), clinical (Hunt & Hess grades, acute hydrocephalus, treatment modality, and infections), and radiographic (Fisher grades and aneurysm location) characteristics of the populations. However, there was a significant difference in the rate (24.4% [121/495] vs 14.4% [81/562], p < 0.0001) and timing (first treatment on day 6 vs 8.9 after SAH, p < 0.0001) of EVT. The rates of DCI (20.8% vs 29%, p = 0.0001) and unfavorable outcome (44% vs 50.6%, p = 0.04) were lower in the cohort with more frequent and early EVT. Multivariate analysis confirmed independent effect of EVT standard on DCI risk and outcome. CONCLUSIONS: A preventive strategy utilizing frequent and early EVT seems to reduce the risk of DCI in patients with SAH and improve their functional outcome. We recommend prospective evaluation of the value of preventive EVT strategy on SAH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with SAH, a frequent and early EVT to treat vasospasm reduces the risk of DCI and improves functional outcome.

Coping strategies have a strong impact on quality of life, depression, and embitterment in patients with Cushing's disease.

PURPOSE: Quality of life (QoL) and psychosocial well-being are substantially impaired in patients with Cushing's disease (CD), not only at the acute illness stage but also after therapy; however, the reason for these impairments remains unclear. METHODS: In this cross-sectional, patient-reported outcome study, we conducted a postal survey on psychosocial impairment and coping strategies in patients after surgical treatment of CD in three large tertiary referral centers. In total, 176 patients with CD completed a compilation of self-assessment inventories pertaining to depression (Hospital Anxiety and Depression Scale, HADS), QoL (Short Form SF-36, Tuebingen CD; Tuebingen CD-25), coping style (Freiburg questionnaire on coping with illness, FKV-LIS), and embitterment (Bern Embitterment Inventory), on average 6.8 ± 6.66 years after surgery. Regression analyses were performed to identify predictors of psychosocial impairment. RESULTS: At the time of the study, 21.8 % of patients suffered from anxiety, 18.7 % experienced an above-average feeling of embitterment, and 13.1 % suffered from depression. Maladaptive coping styles (FKV-LIS subscales depressive coping and minimizing importance) emerged as robust and strong predictors of psychosocial impairment in all inventories; while age, sex, and hydrocortisone intake failed to explain the variance in these measures. CONCLUSION: Similar to several studies in non-pituitary patient cohorts (e.g., patients with multiple sclerosis or lower back pain), our results indicate that psychosocial impairment in CD is significantly influenced by how the patient deals with the illness. Therefore, psychological training of positive coping styles could be a helpful complementary therapy in the overall treatment strategy of CD.

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.

Stimulation of the greater occipital nerve: anatomical considerations and clinical implications.

BACKGROUND: Stimulation of the greater occipital nerve has been employed for various intractable headache conditions for more than a decade. Still, prospective studies that correlate stimulation of the greater occipital nerve with outcome of patients with respect to alleviation of headache are sparsely found in literature. OBJECTIVE: To identify anatomical landmarks for a reproducible stimulation of the greater occipital nerve. For the clinical implication, the individual response to therapy of patients with refractory chronic cluster headache undergoing occipital nerve stimulation was correlated with the postoperative localization of the electrodes and with the distribution of the stimulation field. STUDY DESIGN: Prospective observational study, approved by the local research ethics board (09-4143). SETTING: University hospital, departments of neurosurgery and neurology, institute of anatomy and radiology. METHODS: Ten formaldehyde fixed human cadavers were dissected to identify the passage of the greater occipital nerve through the trapezius muscle. The distance to the external occipital protuberance was triangulated measuring the distance of the nerve from the nuchal midline and the protuberance. Between December 2008 and December 2011, 21 consecutive patients suffering from chronic cluster headache underwent surgery in terms of bilateral occipital nerve stimulation, with electrodes placed horizontally at the level of C1. The postoperative x-rays were compared with the acquired landmarks from the anatomical study. The distribution of the stimulation field was correlated to the individual response of each patient to the therapy and prospectively analyzed with regard to reduction of daily cluster attacks and relief of pain intensity at 3 months and at last follow-up. RESULTS: The greater occipital nerve crosses the trapezius muscle at a mean distance of 31 mm below the occipital external protuberance and 14 mm lateral to the midline as found in the anatomical subjects. The electrodes were targeted at this level in all of our patients and stimulated the greater occipital nerve in all patients. Eighteen of the patients (85.7%) reported a significant reduction of the frequency of their cluster attacks and/or declined intensity of pain during the attacks. Yet, 3 of 21 patients (14.3%) did not benefit from the stimulation despite an adequate spread of the stimulation over the occiput. The spread of the stimulation-induced paraesthesias over the occiput was not correlated to a reduction of cluster attacks, to the intensity of attacks, or to the response to treatment at all. LIMITATIONS: Single center non-randomized non-blinded study. CONCLUSIONS: From our study we conclude that a reproducible stimulation of the greater occipital nerve can be achieved by placing the electrodes parallel to the atlas, at about 30 mm distance to the external occipital protuberance. The response to the stimulation is not correlated to the field width of the paraesthesia. We, therefore, consider stimulation of the main trunk of the greater occipital nerve to be more important than a large field of stimulation on the occiput. Still, an individual response to the occipital nerve stimulation cannot be predicted even by optimal electrode placement.

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.