Robust postmortem survival of murine vestibular and cochlear stem cells

Potential treatment strategies of neurodegenerative and other diseases with stem cells derived from nonembryonic tissues are much less subjected to ethical criticism than embryonic stem cell-based approaches. Here we report the isolation of inner ear stem cells, which may be useful in cell replacement therapies for hearing loss, after protracted postmortem intervals. We found that neonatal murine inner ear tissues, including vestibular and cochlear sensory epithelia, display remarkably robust cellular survival, even 10 days postmortem. Similarly, isolation of sphere-forming stem cells was possible up to 10 days postmortem. We detected no difference in the proliferation and differentiation potential between stem cells isolated directly after death and up to 5 days postmortem. At longer postmortem intervals, we observed that the potency of sphere-derived cells to spontaneously differentiate into mature cell types diminishes prior to the cells losing their potential for self-renewal. Three-week-old mice also displayed sphere-forming stem cells in all inner ear tissues investigated up to 5 days postmortem. In summary, our results demonstrate that postmortem murine inner ear tissue is suited for isolation of stem cells.

Fat implant is superior to muscle implant in vestibular schwannoma surgery for the prevention of cerebrospinal fluid fistulae

OBJECTIVE: Meticulous sealing of opened air cells in the petrous bone is necessary for the prevention of cerebrospinal fluid (CSF) fistulae after vestibular schwannoma surgery. We performed a retrospective analysis to determine whether muscle or fat tissue is superior for this purpose. METHODS: Between January 2001 and December 2006, 420 patients underwent retrosigmoidal microsurgical removal by a standardized procedure. The opened air cells at the inner auditory canal and the mastoid bone were sealed with muscle in 283 patients and with fat tissue in 137 patients. Analysis was performed regarding the incidence of postoperative CSF fistulae and correlation with the patient's sex and tumor grade. RESULTS: The rate of postoperative CSF leak after application of fat tissue was lower (2.2%) than after use of muscle (5.7%). Women had less postoperative CSF leakage (3.4%) than men (5.6%). There was an inverse correlation with tumor grade. Patients with smaller tumors seemed to have a higher rate of CSF leakage than those with large tumors without hydrocephalus. Only large tumors with severe dislocation of the brainstem causing hydrocephalus showed a higher incidence of CSF leaks. CONCLUSION: Fat implantation is superior to muscle implantation for the prevention of CSF leakage after vestibular schwannoma surgery and should, therefore, be used for the sealing of opened air cells in cranial base surgery.

Structural analysis of B-Box 2 from MuRF1: identification of a novel self-association pattern in a RING-like fold

The B-box motif is the defining feature of the TRIM family of proteins, characterized by a RING finger-B-box-coiled coil tripartite fold. We have elucidated the crystal structure of B-box 2 (B2) from MuRF1, a TRIM protein that supports a wide variety of protein interactions in the sarcomere and regulates the trophic state of striated muscle tissue. MuRF1 B2 coordinates two zinc ions through a cross-brace alpha/beta-topology typical of members of the RING finger superfamily. However, it self-associates into dimers with high affinity. The dimerization pattern is mediated by the helical component of this fold and is unique among RING-like folds. This B2 reveals a long shallow groove that encircles the C-terminal metal binding site ZnII and appears as the defining protein-protein interaction feature of this domain. A cluster of conserved hydrophobic residues in this groove and, in particular, a highly conserved aromatic residue (Y133 in MuRF1 B2) is likely to be central to this role. We expect these findings to aid the future exploration of the cellular function and therapeutic potential of MuRF1.

Radiological factors related to pre-operative hearing levels in patients with vestibular schwannomas

The pathogenetic mechanism of hearing loss in patients with vestibular schwannomas (VS) remains unclear. Our aim was to determine the radiological and clinical parameters that might be related to hearing. The radiological images and charts of 99 patients were reviewed. Image processing software was used to analyse the maximal tumor diameter in three planes; its volume; its extension cranially, caudally, anteriorly and posteriorly; the width and length of the intrameatal tumor portion, its shape and consistency; and the tumor-fundus distance. These parameters were correlated with the patient's pre-operative hearing range. The degree of hearing correlated significantly with the tumor size, volume and coronal diameter, the degree of intrameatal tumor growth, and the distance between the lateral tumor end and the fundus (p < 0.05). No correlation was found regarding tumor extension, shape and consistency, the presence of hydrocephalus, or the extent of erosion of the internal auditory canal. Loss of hearing in the VS appears to be multifactorial. Determining the radiological parameters related to the hearing level can help to clarify the pathophysiological mechanisms involved.

Prognostic clinical and radiological parameters for immediate facial nerve function following vestibular schwannoma surgery

OBJECTIVE: The paper aims to define the parameters available before surgery which could predict immediate facial nerve function after excision of a vestibular schwannoma (VS). METHODS: Ninety-nine patients with VS operated consecutively by a single surgeon using an identical surgical technique have been evaluated retrospectively. Data were collected regarding patients' sex, age at onset of symptoms and at surgery, initial symptoms, neurological status at presentation, early post-operative neurological status and complications. The main radiological parameters included in the study were tumour extension pattern, diameters, shape, and volume, as well as extent of bony changes of the internal auditory canal. RESULTS: As the tumour stage and volume increase, facial nerve function is worse after surgery (p < 0.001 and p < 0.05, respectively). Concomitantly, larger extra-meatal tumour diameters in three dimensions (sagittal, coronal and axial) led to worse function (p < 0.01). Anterior and/or caudal tumour extension (p = 0.001 and p = 0.004, respectively) had more significant correlation than posterior and/or cranial extension (p = 0.022 and p = 0.353, respectively). Polycyclic VS had the worst prognosis, followed by the tumours with oval shape. The extent of intra-meatal tumour growth does not correlate with immediate facial nerve outcome. The different angles, lengths and diameters of the internal auditory channel showed no significant correlation with facial nerve outcome. Patients with headache as an initial symptom and those with gait instability and/or pre-operative poor facial nerve function had significantly worse immediate facial nerve outcome. CONCLUSION: Our data suggests that the analysis of the radiological and neurological patient data prior to surgery could give reliable clues regarding the immediate post-operative facial nerve function.

Factors affecting postoperative cerebrospinal fluid leaks after retrosigmoidal craniotomy for vestibular schwannomas

OBJECT: The aim of this study was to identify patients likely to develop CSF leaks after vestibular schwannoma surgery using a retrospective analysis for the identification of risk factors. METHODS: Between January 2001 and December 2006, 420 patients underwent retrosigmoidal microsurgical tumor removal in a standardized procedure. Of these 420 patients, 363 underwent treatment for the first time, and 27 suffered from recurrent tumors. Twenty-six patients had bilateral tumors due to neurofibromatosis Type 2, and 4 patients had previously undergone radiosurgical treatment. An analysis was performed to examine the incidence of postoperative CSF fistulas in all 4 groups. RESULTS: The incidence of CSF leakage was higher in the tumor recurrence group (11.1%) than in patients undergoing surgery for the first time (4.4%). There were no CSF fistulas in the neurofibromatosis Type 2 group or in patients with preoperative radiosurgical treatment. Tumor size was identified as a possible risk factor in a previous study. CONCLUSIONS: Surgery for recurrent tumors is a significant risk factor for the development of CSF leaks.

[Vestibular disorders in Parkinson patients]

Patients suffering from Parkinson's disease frequently complain of dizziness, postural instability and falls. Vestibular tests have been performed in 30 parkinsonian patients and in 28 controls. The results suggest a central vestibular disturbance in Parkinson's disease which correlates with the clinical disability. This vestibular disturbance is assumed to be due to dysfunction of the nigro-striato-collicular tracts.

Caloric vestibular stimulation modulates affective control and mood

BACKGROUND: Clinical evidence suggests a link between vestibular dysfunctions and mood disorders. No study has yet investigated mood and affective control during vestibular stimulation in healthy participants. OBJECTIVE: We predicted a modulating effect of caloric vestibular stimulation (CVS) on affective control measured in an affective Go/NoGo task (AGN). METHODS: Thirty-two participants performed an AGN task while they were exposed to cold left or right ear CVS (20 °C) and sham stimulation (37 °C). In each block, either positive or negative pictures (taken from the International Affective Picture System) were defined as targets. Participants had to respond to targets (Go), and withhold responses to distractors (NoGo). RESULTS: The sensitivity index d' (hits - false alarms) was used to measure affective control. Affective control improved during right ear CVS when viewing positive stimuli (P = .005), but decreased during left ear CVS when compared to sham stimulation (P = .009). CVS had a similar effect on positive mood ratings (Positive and Negative Affect Schedule). Positive mood ratings decreased during left ear CVS when compared to sham stimulation, but there was no effect after right ear CVS. DISCUSSION: The results suggest that CVS, depending on side of stimulation, has a modulating effect on mood and affective control. The results complement previous findings in manic patients and provide new evidence for the clinical potential of CVS.

Purchase decision-making is modulated by vestibular stimulation

Purchases are driven by consumers’ product preferences and price considerations. Using caloric vestibular stimulation (CVS), we investigated the role of vestibular-affective circuits in purchase decision-making. CVS is an effective noninvasive brain stimulation method, which activates vestibular and overlapping emotional circuits (e.g., the insular cortex and the anterior cingulate cortex (ACC)). Subjects were exposed to CVS and sham stimulation while they performed two purchase decision-making tasks. In Experiment 1 subjects had to decide whether to purchase or not. CVS significantly reduced probability of buying a product. In Experiment 2 subjects had to rate desirability of the products and willingness to pay (WTP) while they were exposed to CVS and sham stimulation. CVS modulated desirability of the products but not WTP. The results suggest that CVS interfered with emotional circuits and thus attenuated the pleasant and rewarding effect of acquisition, which in turn reduced purchase probability. The present findings contribute to the rapidly growing literature on the neural basis of purchase decision-making.

Frameless linac-based (Novalis TX) stereotactic treatment for vestibular schwannoma that extend distally into the iac (Internal Acoustic Canal): an analysis of the dose to the cochlea

Objectives: We compare the dose parameters between 3 different radiosurgery delivery techniques which may have an impact on cochlea function. Methods: Five patients with unilateral vestibular schwannoma (VS) were selected for this study. Planning procedure was carried out using the BrainLAB® iPlan planning system v. 4.5. For each patient three different planning techniques were used: dynamic arc (DA) with 5 arcs per plan, hybrid arc (HA) with 5 arcs per plan and IMRT with 8 fields per plan. For each technique, two plans were generated with different methods: with the first method (PTV coverage) it was the goal to fully cover the PTV with at least 12 Gy (normalization: 12 Gy covered 99% of the PTV) and with the second method (cochlea sparing) it was the goal to spare the cochlea (normalization: 12 Gy covers 50% of the PTV/V4Gy of cochlea lower than 1%). Plan evaluation was done considering target volume and coverage (conformity and homogeneity) and OAR constraints (mean (Dmean) and maximum dose (Dmax) to cochlea, Dmax to brainstem and cochlea). The total number of monitor units (MU) was analyzed. Results: The median tumor volume was 0.95 cm³ (range, 0.86-3 cm³). The median PTV was 1.44 cm³ (range, 1-3.5 cm³). The median distance between the tumor and the cochlea's modiulus was 2.7 mm (range, 1.8-6.3 mm). For the PTV coverage method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.872) and in Dmean (p= 0.860). We found a significant correlation (p< 0.05) between the target volume and the cochlear Dmean for all plans with Pearson's coefficient correlation of 0.90, 0.92 and 0.94 for the DA, HA and IMRT techniques, respectively. For the cochlea sparing method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.310) and in Dmean (p= 0.275). However, in this group the V4Gy of the ipsilateral cochlea represents less than 1%. When using the HA or IMRT technique, the homogeneity and conformity in the PTV, but also the number of MUs were increased in comparison to the DA technique. Conclusion: VS tumors that extend distally into the IAC had an equivalent sparing of cochlea with DA approach compared with the HA and IMRT techniques. Disclosure: No significant relationships.