René-Ludwig Bernays

Hydrocephalus in 389 patients with aneurysm-associated subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) often leads to hydrocephalus, which is commonly treated by placement of a ventriculoperitoneal (VP) shunt. There is controversy over which factors affect the need for such treatment. In this study, data were prospectively collected from 389 consecutive patients who presented with an aneurysm-associated SAH at a single center. External ventricular drainage placement was performed as part of the treatment for acute hydrocephalus, and VP shunts were placed in patients with chronic hydrocephalus. The data were retrospectively analyzed using two-sample t-tests, Fishers exact test and logistic regression analysis. Overall, shunt dependency occurred in 91 of the 389 patients (23.4%). Using logistic regression analysis, two factors were found to be significantly associated with VP shunt placement: an initial Glasgow Coma Scale (GCS) score of 8-14 (8-14 versus 3-7, p = 0.016; 15 versus 3-7, p = 0.55); and aneurysm coiling (p = 0.017). Patients with an initial GCS score of 8-14 after aneurysm-associated SAH had a 2.5-fold higher risk of receiving a VP shunt than those with a GCS score of 3-7. Those with a GCS of 15 had a 50% lower risk of becoming shunt dependent than did the subgroup with a GCS score of 8-14. To clarify and strengthen these observations, prospective, randomized trials are needed.

Excessively high soluble Klotho in patients with acromegaly

Abstract.  Sze L, Bernays RL, Zwimpfer C, Wiesli P, Brändle M, Schmid C (Division of Endocrinology and Diabetes, University Hospital, Zurich; Division of Endocrinology and Diabetes, Kantonsspital, Gallen; Department of Neurosurgery, University Hospital, Zurich; and Department of Internal Medicine, Kantonsspital Frauenfeld, Frauenfeld, Switzerland). Excessively high soluble Klotho in patients with acromegaly. J Intern Med 2012; 272: 93–97.

Soluble α-klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas.

OBJECTIVE Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study, we present baseline αKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery. DESIGN Prospective controlled study. METHODS We measured soluble αKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples. RESULTS Soluble αKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812-6623 pg/ml) and declined after surgery during early follow-up (2-6 days; median 645 pg/ml, IQR 550-1303 pg/ml) (P<0.001) and during late follow-up (2-3 months post-operatively; median 902 pg/ml, IQR 497-1340 pg/ml; P<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400-677 pg/ml; P<0.001). Following surgery, soluble αKL remained low during early and late follow-up - changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls. CONCLUSION High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).

Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery: A Histology-Based Evaluation.

BACKGROUND Glioblastoma resection guided by 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative magnetic resonance imaging (iMRI) may improve surgical results and prolong survival. OBJECTIVE To evaluate 5-ALA fluorescence combined with subsequent low-field iMRI for resection control in glioblastoma surgery. METHODS Fourteen patients with suspected glioblastoma suitable for complete resection of contrast-enhancing portions were enrolled. The surgery was carried out using 5-ALA-induced fluorescence and frameless navigation. Areas suspicious for tumor underwent biopsy. After complete resection of fluorescent tissue, low-field iMRI was performed. Areas suspicious for tumor remnant underwent biopsy under navigation guidance and were resected. The histological analysis was blinded. RESULTS In 13 of 14 cases, the diagnosis was glioblastoma multiforme. One lymphoma and 1 case without fluorescence were excluded. In 11 of 12 operations, residual contrast enhancement on iMRI was found after complete resection of 5-ALA fluorescent tissue. In 1 case, the iMRI enhancement was in an eloquent area and did not undergo a biopsy. The 28 biopsies of areas suspicious for tumor on iMRI in the remaining 10 cases showed tumor in 39.3%, infiltration zone in 25%, reactive central nervous system tissue in 32.1%, and normal brain in 3.6%. Ninety-three fluorescent and 24 non-fluorescent tissue samples collected before iMRI contained tumor in 95.7% and 87.5%, respectively. CONCLUSION 5-ALA fluorescence-guided resection may leave some glioblastoma tissue undetected. MRI might detect areas suspicious for tumor even after complete resection of all fluorescent tissue; however, due to the limited accuracy of iMRI in predicting tumor remnant (64.3%), resection of this tissue has to be considered with caution in eloquent regions.

You can't stop the music: reduced auditory alpha power and coupling between auditory and memory regions facilitate the illusory perception of music during noise.

Our brain has the capacity of providing an experience of hearing even in the absence of auditory stimulation. This can be seen as illusory conscious perception. While increasing evidence postulates that conscious perception requires specific brain states that systematically relate to specific patterns of oscillatory activity, the relationship between auditory illusions and oscillatory activity remains mostly unexplained. To investigate this we recorded brain activity with magnetoencephalography and collected intracranial data from epilepsy patients while participants listened to familiar as well as unknown music that was partly replaced by sections of pink noise. We hypothesized that participants have a stronger experience of hearing music throughout noise when the noise sections are embedded in familiar compared to unfamiliar music. This was supported by the behavioral results showing that participants rated the perception of music during noise as stronger when noise was presented in a familiar context. Time-frequency data show that the illusory perception of music is associated with a decrease in auditory alpha power pointing to increased auditory cortex excitability. Furthermore, the right auditory cortex is concurrently synchronized with the medial temporal lobe, putatively mediating memory aspects associated with the music illusion. We thus assume that neuronal activity in the highly excitable auditory cortex is shaped through extensive communication between the auditory cortex and the medial temporal lobe, thereby generating the illusion of hearing music during noise.

Advantages and Limitations of Intraoperative 3D Ultrasound in Neurosurgery. Technical note

Three-dimensional ultrasound (US) technology is supposed to help combat some of the orientation difficulties inherent to two-dimensional US. Contemporary navigation solutions combine reconstructed 3D US images with common navigation images and support orientation. New real-time 3D US (without neuronavigation) is more time effective, but whether it further assists in orientation remains to be determined. An integrated US system (IGSonic, VectorVision, BrainLAB, Munich Germany) and a non-integrated system with real-time 3D US (iU22, Philips, Bothell, USA) were recently compared in neurosurgical procedures in our group. The reconstructed navigation view was time-consuming, but images were displayed in familiar planes (e.g., axial, sagittal, coronal). Further potential applications of US angiography and pure US navigation are possible. Real-time 3D images were displayed without the need for an additional acquisition and reconstruction process, but spatial orientation remained challenging in this preliminary testing phase. Reconstructed 3D US navigation appears to be superior with respect to spatial orientation, and the technique can be combined with other imaging data. However, the potential of real-time 3D US imaging is promising.

Extensive spherical amyloid deposition presenting as a pituitary tumor.

A 71-yr-old man was admitted for further evaluation and trans-sphenoidal surgery of a pituitary tumor. He complained of impotence and decreased libido over a period of about 40 yr. Thirty-eight yr ago he was treated for bilateral gynecomastia with galactorrhea. Endocrinological investigation at presentation revealed only mild hyperprolactinemia and hypogonadotropic hypogonadism. Pituitary magnetic resonance imaging (MRI) showed a tumor up to 2.5 cm in diameter with infiltration of the sphenoid sinus and right cavernous sinus. The tumor exhibited a heterogeneous hyperintense signal on T1-weighted images and hypointense signal on T2-weighted images. Standard trans-sphenoidal surgery was performed and a brownish mass was found inside the sella, which was removed. Histological examination of the mass revealed extensive spherical amyloid deposits with strongly positive immunohistochemical staining for prolactin. Therefore, a prolactinoma with extensive spherical amyloid deposition was diagnosed. Extensive spherical amyloid deposition is a rare finding in prolactin-secreting pituitary adenomas. So far, characteristic radiological findings by MRI have been described only twice. Due to characteristic MRI findings, the diagnosis of extensive intrasellar amyloid deposition can be entertained pre-operatively. Trans-sphenoidal surgical resection is essential to confirm the diagnosis histologically and because of the potential lack of tumor shrinkage under dopaminagonist therapy in this type of prolactinoma.

Intrasellar malignant peripheral nerve sheath tumor (MPNST).

SummaryIntracranial malignant peripheral nerve sheath tumors (MPNST) and intrasellar schwannomas are rare tumors. We describe a case of an intrasellar schwannoma with progression to a MPNST, a finding that, although very rare, extends the differential diagnosis of intrasellar lesions.

Rapid and Accurate Anatomical Localization of Implanted Subdural Electrodes in a Virtual Reality Environment

BACKGROUND An accurate and rapid anatomical localization of implanted subdural electrodes is essential in the invasive diagnostic process for epilepsy surgery. OBJECTIVE To demonstrate our experience with a three-dimensional (3D) virtual reality simulation software (Dextroscope®, Bracco Imaging, Milano, Italy) in the postoperative localization of subdural electrodes. METHODS Postoperative thin-slice computed tomography (CT) scans were coregistered to preoperative 3D magnetic resonance (MR) images in the Dextroscope environment in 10 patients. Single-electrode contacts were segmented and their positions in relation to specific brain anatomic structures were obtained by 3D reconstruction within the Dextroscope environment. The spatial accuracy was tested by comparing the positions of the electrode contacts as visible in the 3D reconstruction with intraoperative photographs. Image processing time was also recorded. RESULTS The 3D stereoscopic reconstruction provided an accurate representation of the implanted electrodes with highly detailed visualization of the underlying anatomy. The mean absolute difference between 3D reconstruction and intraoperative photographs was 2.4 mm ± 2.2 mm. The processing time to obtain the 3D reconstructions did not exceed 15 minutes. CONCLUSIONS The results indicate that the 3D virtual reality simulation software used in our series is a useful tool for rapid and precise localization of subdural electrodes implanted for invasive electroencephalography (EEG) recordings.

Growth hormone secreting pituitary microadenomas and empty sella – An under-recognized association?

OBJECTIVE To describe an association of growth hormone (GH) secreting pituitary microadenomas and empty sella (ES), which has been described in case reports - the underlying mechanisms are unclear. METHODS We retrospectively analyzed patients operated for GH-producing pituitary adenomas between February 2004 and February 2009. Magnetic resonance imaging (MRI), computed tomography (CT) imaging, and pituitary function testing were performed. All cases underwent transsphenoidal surgery (TSS). Mean follow up was 38 months (range 12-80 months). RESULTS Out of 152 patients with acromegaly due to GH-producing pituitary adenomas (female:male=73:79; age range 17-63 years), 69 patients had microadenomas (45.4%; 38 females, 31 males). We found 14 cases (14/69, 20.3%), all microadenomas, with presurgical evidence of ES - 10 females (71%) and 4 males (29%) (female:male=2.5:1). When compared with 103 patients with GH-negative microadenomas treated in the same time period (ES in 4 of 103; 3.9%), ES was highly significantly associated with GH production by the microadenoma (p=0.001). In acromegalics with empty sella, no cases of ectopic adenoma were found. Postoperatively, GH and IGF-1 levels fell in all patients, and 7 cases had random GH and IGF-1 levels consistent with cure. CONCLUSION The combination of GH-producing microadenomas and empty, enlarged sella is not rare. In this setting, preoperative CT scans are very useful and the transsphenoidal approach is efficient and safe. The mechanism underlying the association of GH-producing microadenomas and empty sella remains unclear and requires further studies.