Hydroxide Ion Mechanism for Long-Range Proton Pumping in the Third Proton Transfer of Bacteriorhodopsin.

In bacteriorhodopsin, representative light-driven proton pump, five proton transfers yield vectorial active proton translocation, resulting in a proton gradient in microbes. Third proton transfer occurs from Asp96 to the Schiff base on the photocycle, which is expected to be a long-range proton transfer via the Grotthuss mechanism through internal water molecules. Here, large-scale quantum molecular dynamics simulations are performed for the third proton transfer, where all the atoms (∼50000 atoms) are treated quantum-mechanically. The simulations demonstrate that two reaction paths exist along the water wire, namely, via hydronium and via hydroxide ions. The free energy analysis confirms that the path via hydroxide ions is considerably favorable and consistent with the observed lifetime of the transient water wire. Therefore, the proposed hydroxide ion mechanism, as in the first proton transfer, is responsible for the third long-range proton transfer.

Multiple protonation states in ligand-free SARS-CoV-2 main protease revealed by large-scale quantum molecular dynamics simulations.

The main protease (Mpro) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) catalyzes the cleavage of polyproteins for viral replication. Here, large-scale quantum molecular dynamics and metadynamics simulations for ligand-free Mpro were performed, where all the atoms were treated quantum-mechanically, focusing on elucidation of the controversial active-site protonation state. The simulations clarified that the interconverting multiple protonation states exist in unliganded Mpro, and the catalytically relevant ion-pair state is more stable than the neutral state, which is consistent with neutron crystallography. The results highlight the importance of the ion-pair state for repurposing or discovering antiviral drugs that target Mpro.

Reversible Sodium Metal Electrodes: Is Fluorine an Essential Interphasial Component?

Alkaline metals are an ideal negative electrode for rechargeable batteries. Forming a fluorine-rich interphase by a fluorinated electrolyte is recognized as key to utilizing lithium metal electrodes, and the same strategy is being applied to sodium metal electrodes. However, their reversible plating/stripping reactions have yet to be achieved. Herein, we report a contrary concept of fluorine-free electrolytes for sodium metal batteries. A sodium tetraphenylborate/monoglyme electrolyte enables reversible sodium plating/stripping at an average Coulombic efficiency of 99.85 % over 300 cycles. Importantly, the interphase is composed mainly of carbon, oxygen, and sodium elements with a negligible presence of fluorine, but it has both high stability and extremely low resistance. This work suggests a new direction for stabilizing sodium metal electrodes via fluorine-free interphases.

Cortical Venous Redness Represents Tissue Circulation Status in Patients With Moyamoya Disease.

BACKGROUND AND PURPOSE: Venous oxygen saturation (SO2) is measured in medical fields to assess tissue circulation insufficiency. This study aimed to elucidate the use of a cortical venous redness measurement to evaluate hemodynamic changes during revascularization surgery for patients with moyamoya disease. METHODS: In this retrospective case-series analysis, we first quantitatively measured and correlated SO2 and R intensity of 24-bit color digital red-green-blue pictures of blood samples from 3 volunteers. Subsequently, based on intraoperative digital pictures of 29 patients with moyamoya disease, we measured the R intensities of a cortical vein near the anastomosis site before and after anastomosis. Cerebral blood flow (CBF) at the site was measured using a single-photon emission computed tomography before and 1 to 3 days after surgery. Venous R intensity and CBF were measured twice by 4 raters, and their correlations were examined using generalized linear mixed effect model and linear regression analysis. RESULTS: A strong linear correlation was found between blood R intensity and its SO2 (coefficients, 0.522; 95% confidence interval, 0.364-0.680, using generalized linear mixed effect model). Venous R intensity before the anastomosis was not correlated with preoperative CBF (coefficients, 0.000352; 95% confidence interval, -0.000369 to 0.00107, by generalized linear mixed effect); however, the increases in venous R intensity after anastomosis were correlated with postoperative increases in CBF (R2, 0.367; 95% confidence interval, 0.116-0.618 to 0.548; 95% confidence interval, 0.331-0.764, by linear regression analysis). CONCLUSIONS: Cortical venous redness represented impaired CBF and could be a useful parameter for assessing hemodynamic changes during revascularization surgery.

Development and validation of a score for evaluating comprehensive stroke care capabilities: J-ASPECT Study.

BACKGROUND: Although the Brain Attack Coalition recommended establishing centers of comprehensive care for stroke and cerebrovascular disease patients, a scoring system for such centers was lacking. We created and validated a comprehensive stroke center (CSC) score, adapted to Japanese circumstances. METHODS: Of the selected 1369 certified training institutions in Japan, 749 completed an acute stroke care capabilities survey. Hospital performance was determined using a 25-item score, evaluating 5 subcategories: personnel, diagnostic techniques, specific expertise, infrastructure, and education. Consistency and validity were examined using correlation coefficients and factorial analysis. RESULTS: The CSC score (median, 14; interquartile range, 11-18) varied according to hospital volume. The five subcategories showed moderate consistency (Cronbach's α = 0.765). A strong correlation existed between types of available personnel and specific expertise. Using the 2011 Japanese Diagnosis Procedure Combination database for patients hospitalized with stroke, four constructs were identified by factorial analysis (neurovascular surgery and intervention, vascular neurology, diagnostic neuroradiology, and neurocritical care and rehabilitation) that affected in-hospital mortality from ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The total CSC score was related to in-hospital mortality from ischemic stroke (odds ratio [OR], 0.973; 95% confidence interval [CI], 0.958-0.989), intracerebral hemorrhage (OR, 0.970; 95% CI, 0.950-0.990), and subarachnoid hemorrhage (OR, 0.951; 95% CI, 0.925-0.977), with varying contributions from the four constructs. CONCLUSIONS: The CSC score is a valid measure for assessing CSC capabilities, based on the availability of neurovascular surgery and intervention, vascular neurology, diagnostic neuroradiology, and critical care and rehabilitation services.

Couplings between hierarchical conformational dynamics from multi-time correlation functions and two-dimensional lifetime spectra: Application to adenylate kinase.

An analytical method based on a three-time correlation function and the corresponding two-dimensional (2D) lifetime spectrum is developed to elucidate the time-dependent couplings between the multi-timescale (i.e., hierarchical) conformational dynamics in heterogeneous systems such as proteins. In analogy with 2D NMR, IR, electronic, and fluorescence spectroscopies, the waiting-time dependence of the off-diagonal peaks in the 2D lifetime spectra can provide a quantitative description of the dynamical correlations between the conformational motions with different lifetimes. The present method is applied to intrinsic conformational changes of substrate-free adenylate kinase (AKE) using long-time coarse-grained molecular dynamics simulations. It is found that the hierarchical conformational dynamics arise from the intra-domain structural transitions among conformational substates of AKE by analyzing the one-time correlation functions and one-dimensional lifetime spectra for the donor-acceptor distances corresponding to single-molecule Förster resonance energy transfer experiments with the use of the principal component analysis. In addition, the complicated waiting-time dependence of the off-diagonal peaks in the 2D lifetime spectra for the donor-acceptor distances is attributed to the fact that the time evolution of the couplings between the conformational dynamics depends upon both the spatial and temporal characters of the system. The present method is expected to shed light on the biological relationship among the structure, dynamics, and function.

The impact of comprehensive stroke care capacity on the hospital volume of stroke interventions: a nationwide study in Japan: J-ASPECT study.

BACKGROUND: The association between comprehensive stroke care capacity and hospital volume of stroke interventions remains uncertain. We performed a nationwide survey in Japan to examine the impact of comprehensive stroke care capacity on the hospital volume of stroke interventions. METHODS: A questionnaire on hospital characteristics, having tissue plasminogen activator (t-PA) protocols, and 25 items regarding personnel, diagnostic, specific expertise, infrastructure, and educational components recommended for comprehensive stroke centers (CSCs) was sent to 1369 professional training institutions. We examined the effect of hospital characteristics, having a t-PA protocol, and the number of fulfilled CSC items (total CSC score) on the hospital volume of t-PA infusion, removal of intracerebral hemorrhage, and coiling and clipping of intracranial aneurysms performed in 2009. RESULTS: Approximately 55% of hospitals responded to the survey. Facilities with t-PA protocols (85%) had a significantly higher likelihood of having 23 CSC items, for example, personnel (eg, neurosurgeons: 97.3% versus 66.1% and neurologists: 51.3% versus 27.7%), diagnostic (eg, digital cerebral angiography: 87.4% versus 43.2%), specific expertise (eg, clipping and coiling: 97.2% and 54% versus 58.9% and 14.3%, respectively), infrastructure (eg, intensive care unit: 63.9% versus 33.9%), and education (eg, professional education: 65.2% versus 20.7%). On multivariate analysis adjusted for hospital characteristics, total CSC score, but not having a t-PA protocol, was associated with the volume of all types of interventions with a clear increasing trend (P for trend < .001). CONCLUSION: We demonstrated a significant association between comprehensive stroke care capacity and the hospital volume of stroke interventions in Japan.

Conformational Dynamics in Proteins: Entangled Slow Fluctuations and Nonequilibrium Reaction Events.

Proteins exhibit conformational fluctuations and changes over various time scales, ranging from rapid picosecond-scale local atomic motions to slower microsecond-scale global conformational transformations. In the presence of these intricate fluctuations, chemical reactions occur and functions emerge. These conformational fluctuations of proteins are not merely stochastic random motions but possess distinct spatiotemporal characteristics. Moreover, chemical reactions do not always proceed along a single reaction coordinate in a quasi-equilibrium manner. Therefore, it is essential to understand spatiotemporal conformational fluctuations of proteins and the conformational change processes associated with reactions. In this Perspective, we shed light on the complex dynamics of proteins and their role in enzyme catalysis by presenting recent results regarding dynamic couplings and disorder in the conformational dynamics of proteins and rare but rapid enzymatic reaction events obtained from molecular dynamics simulations.

Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases.

We tested the validity of two prognostic indices for stereotactic radiosurgically (SRS)-treated patients with brain metastases (BMs) from five major original cancer categories. The two indices are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) and our Modified Recursive Partitioning Analysis (RPA). Forty-six hundred and eight BM patients underwent gamma knife SRS during the 1998-2011 period. Primary cancer categories were non-small cell lung cancer (NSCLC, 2827 patients), small cell lung cancer (SCLC, 460), gastro-intestinal cancer (GIC, 582), breast cancer (BC, 547) and renal cell cancer (RCC, 192). There were statistically significant survival differences among patients stratified into four groups based on the DS-GPA systems (p < 0.001) in all five original cancer categories. In the NSCLC category, there were statistically significant mean survival time (MST) differences (p < 0.001) among the four groups without overlapping of 95 % confidence intervals (CIs) between any two pairs of groups with the DS-GPA system. However, among the SCLC, GIC, BC and RCC categories, MST differences between some pairs of groups failed to reach statistical significance with this system. There were, however, statistically significant MST differences (p < 0.001) among the three groups without overlapping of 95 % CIs between any two pairs of groups with the Modified RPA system in all five categories. The DS-GPA system is applicable to our set of patients with NSCLC only. However, the Modified RPA system was shown to be applicable to patients with five primary cancer categories. This index should be considered when designing future clinical trials involving BM patients.

Semiquantal molecular dynamics simulations of hydrogen-bond dynamics in liquid water using multi-dimensional Gaussian wave packets.

A semiquantal (SQ) molecular dynamics (MD) simulation method based on an extended Hamiltonian formulation has been developed using multi-dimensional thawed gaussian wave packets (WPs), and applied to an analysis of hydrogen-bond (H-bond) dynamics in liquid water. A set of Hamilton's equations of motion in an extended phase space, which includes variance-covariance matrix elements as auxiliary coordinates representing anisotropic delocalization of the WPs, is derived from the time-dependent variational principle. The present theory allows us to perform real-time and real-space SQMD simulations and analyze nuclear quantum effects on dynamics in large molecular systems in terms of anisotropic fluctuations of the WPs. Introducing the Liouville operator formalism in the extended phase space, we have also developed an explicit symplectic algorithm for the numerical integration, which can provide greater stability in the long-time SQMD simulations. The application of the present theory to H-bond dynamics in liquid water is carried out under a single-particle approximation in which the variance-covariance matrix and the corresponding canonically conjugate matrix are reduced to block-diagonal structures by neglecting the interparticle correlations. As a result, it is found that the anisotropy of the WPs is indispensable for reproducing the disordered H-bond network compared to the classical counterpart with the use of the potential model providing competing quantum effects between intra- and intermolecular zero-point fluctuations. In addition, the significant WP delocalization along the out-of-plane direction of the jumping hydrogen atom associated with the concerted breaking and forming of H-bonds has been detected in the H-bond exchange mechanism. The relevance of the dynamical WP broadening to the relaxation of H-bond number fluctuations has also been discussed. The present SQ method provides the novel framework for investigating nuclear quantum dynamics in the many-body molecular systems in which the local anisotropic fluctuations of nuclear WPs play an essential role.

Quantum-Mechanical Molecular Dynamics Simulations on Secondary Proton Transfer in Bacteriorhodopsin Using Realistic Models.

Bacteriorhodopsin (BR) transports a proton from intracellular to extracellular (EC) sites through five proton transfers. The second proton transfer is the release of an excess proton stored in BR into the EC medium, and an atomistic understanding of this whole process has remained unexplored due to its ubiquitous environment. Here, fully quantum mechanical (QM) molecular dynamics (MD) and metadynamics (MTD) simulations for this process were performed at the divide-and-conquer density-functional tight-binding level using realistic models (∼50000 and ∼20000 atoms) based on the time-resolved photointermediate structures from an X-ray free electron laser. Regarding the proton storage process, the QM-MD/MTD simulations confirmed the Glu-shared mechanism, in which an excess proton is stored between Glu194 and Glu204, and clarified that the activation occurs by localizing the proton at Glu204 in the photocycle. Furthermore, the QM-MD/MTD simulations elucidated a release pathway from Glu204 through Ser193 to the EC water molecules and clarified that the proton release starts at ∼250 µs. In the ubiquitous proton diffusion in the EC medium, the transient proton receptors predicted experimentally were assigned to carboxylates in Glu9 and Glu74. Large-scale QM-MD/MTD simulations beyond the conventional sizes, which provided the above findings and confirmations, were possible by adopting our Dcdftbmd program.

Gamma knife surgery for 1-10 brain metastases without prophylactic whole-brain radiation therapy: analysis of cases meeting the Japanese prospective multi-institute study (JLGK0901) inclusion criteria.

We evaluated the results of stereotactic radiosurgery (SRS) alone using gamma knife (GK) for selected patients with 1-10 brain metastases without prophylactic whole-brain radiation therapy (WBRT) among JLGK0901-eligible cases. Seven hundred seventy-eight consecutive cases meeting the following JLGK0901 study inclusion criteria were analyzed: (1) newly diagnosed brain metastases, (2) 1-10 brain lesions, (3) less than 10 cm(3) volume of the largest tumor, (4) less than 15 cm(3) total tumor volume, (5) no magnetic resonance (MR) findings of cerebrospinal fluid (CSF) dissemination, and (6) no impaired activity of daily living [<70 Karnofsky Performance Score (KPS)] due to extracranial disease. At initial treatment, all lesions were irradiated with SRS without upfront WBRT. Thereafter, enhanced magnetic resonance imaging (MRI) was applied every 2-3 months, and new distant lesions were appropriately retreated with SRS or WBRT. We divided patients according to tumor number: single lesion for group A (280 cases), 2 for group B (135), 3-4 for group C (148), 5-6 for group D (93), and 7-10 for group E (122). Differences among groups were compared in terms of overall, neurological, qualitative, and new-lesion-free survival (NLFS). Median age was 65 years (range 26-92 years). There were 505 men and 273 women. The primary organ was lung in 579 patients, gastrointestinal tract in 79, breast in 48, urinary tract in 34, and others/unknown in 38. Mean survival time was 0.72 years (0.83 years for 1, 0.69 years for 2, 0.69 years for 3-4, 0.59 years for 5-6, and 0.62 years for 7-10 metastases). On multivariate analysis, significant poor prognostic factors for overall survival (OS) were active systemic disease, poor (<70) initial KPS, and male gender. Neurological survival and qualitative survival at 1 year were 92.7% and 88.2%, respectively. NLFS at 6 months and 1 year were 69.8% and 43.8%, respectively. There were statistically significant differences in new lesion emergence between groups A and B and between groups B and C. SRS using GK provides excellent results in selected patients with 1-10 brain lesions, without prophylactic WBRT. This study revealed that brain lesion number has no effect on any of the four types of survivals, which is anticipated to be confirmed by the JLGK0901 study.

Hydroxide Ion Carrier for Proton Pumps in Bacteriorhodopsin: Primary Proton Transfer.

Bacteriorhodopsin (BR) is a model protein for light-driven proton pumps, where the vectorial active proton transport results in light-energy conversion. To clarify the microscopic mechanism of primary proton transfer from retinal Schiff base (SB) to Asp85 in BR, herein, we performed quantum-mechanical metadynamics simulations with the isolated BR model (∼3750 atoms). The simulations showed a novel proton transfer mechanism, viz. the hydroxide ion mechanism, in which the deprotonation of specific internal water (Wat452) yields the protonation of Asp85 via Thr89, after which the resulting hydroxide ion accepts the remaining proton from retinal SB. Systematic investigations adopting four sequential snapshots obtained by the time-resolved serial femtosecond crystallography revealed that proton transfer took 2-5.25 µs on the photocycle. The presence of Wat401, which is the main difference between snapshots at 2 and 5.25 µs, is found to be essential in assisting the primary proton transfer. Furthermore, the hydroxide ion mechanism was confirmed by the minimum energy path for the primary proton transfer in BR obtained by the nudged elastic band calculations with the embedded BR model (10,119 atoms), in which BR was embedded within lipid membranes in between water solvents.

Ultrafast energy relaxation and anisotropy decay of the librational motion in liquid water: A molecular dynamics study.

We theoretically investigate intermolecular motions in liquid water in terms of third-order infrared (IR) spectroscopy. We calculate two-dimensional (2D) IR spectra, pump-probe signals, and three-pulse stimulated photon echo signals from the combination of equilibrium and nonequilibrium molecular dynamics simulations. The 2D IR spectra and the three-pulse photon echo peak shift exhibit that the frequency correlation of the librational motion decays with a time scale of 100 fs. The two-color 2D IR spectra and the pump-probe signals reveal that the energy transfer from the librational motion at 700 cm(-1) to the low frequency motion below 300 cm(-1) occurs with a time scale of 60 fs and the subsequent relaxation to the hot ground state takes place on a 500 fs time scale. The time scale of the anisotropy decay of the librational motion is found to be approximately 115 fs. The energy dissipation processes are investigated in detail by using the nonequilibrium molecular dynamics simulation, in which an electric field pulse is applied. We show that the fast energy transfer from the librational motion to the low frequency motion is mainly due to the librational-librational energy transfer. We also show that the fast anisotropy decay mainly arises from the rapid intermolecular energy transfer.

Development of Large-Scale Excited-State Calculations Based on the Divide-and-Conquer Time-Dependent Density Functional Tight-Binding Method.

In this study, the divide-and-conquer (DC) method was extended to time-dependent density functional tight-binding (TDDFTB) theory to enable excited-state calculations of large systems and is denoted by DC-TDDFTB. The efficient diagonalization algorithms of TDDFTB and DC-TDDFTB methods were implemented into our in-house program. Test calculations of polyethylene aldehyde and p-coumaric acid, a pigment in photoactive yellow protein, in water demonstrate the high accuracy and efficiency of the developed DC-TDDFTB method. Furthermore, the (TD)DFTB metadynamics simulations of acridinium in the ground and excited states give reasonable p Ka values compared with the corresponding experimental values.

Age-associated increases in poor outcomes after traumatic brain injury: a report from the Japan Neurotrauma Data Bank.

Age is an important factor influencing outcome after severe traumatic brain injury (TBI). In general, the older the victim, the higher the probability of a poor outcome. To investigate the mechanism underlying the link between age and outcome, the data for 797 patients enrolled in the Japan Neurotrauma Data Bank (JNTDB), aged 6 years or older, with Glasgow Coma Scale (GCS) scores of 8 or less on admission or deterioration to that level within 48 h of impact were analyzed. Thirty-eight percent of the patients were between the ages of 40 and 69 years, and 24% of the patients were older than 69 years. Older patients had higher rates of mortality and lower rates of favorable outcome. The frequency of mass lesions which were associated with poorer outcomes significantly increased with age, but regardless of the intracranial lesion type, older patients had poorer outcomes. The GCS score and the occurrence of systemic complications did not differ significantly according to age. Multiple systemic injury was less frequent in older patients. The varied occurrence of intracranial lesion types according to age is likely caused by the disparity between the young and aged brain in the progression of secondary brain injury. Alteration in the pathophysiological response, which is related to the development of secondary brain injury in the aging brain, probably contributes to more severe and irreversible brain damage in older patients, and is thus associated with poor outcomes.

Comparison of the results of 2 targeting methods in Gamma Knife surgery for trigeminal neuralgia.

OBJECT: Gamma Knife surgery (GKS) is an effective treatment for intractable trigeminal neuralgia (TN). The authors compared results using two major GKS target points, the dorsal root entry zone and the retrogasserian portion, in a series of patients with intractable TN. METHODS: One hundred patients with medically refractory TN underwent GKS between August 1998 and December 2007. Thirty-seven were men, and 63 were women. The median age at GKS was 74 years. With a single isocenter and use of a 4mm collimator, 51 patients received 80 Gy at the proximal trigeminal nerve (posterior group) and 7 patients received 80 Gy, 1 patient received 85 Gy, and 41 patients received 90 Gy at the retrogasserian portion (anterior group). Follow-up was obtained by clinic visits every 3-6 months after GKS. Data on pain control, complications, and pain recurrence were recorded. The relationships between pain control status, complications, recurrence, and the target portions (anterior vs posterior) were analyzed. RESULTS: The median duration of follow-up was 30 months (range 3-88 months). Initially, 87 patients achieved pain-free status and 64 achieved complete remission. At the final follow-up visit, 68 patients were still in pain-free status and 42 were in complete remission. Recurrence of facial pain occurred in 15 patients. Forty-one patients developed some degree of trigeminal dysfunction. The rate of initial complete remission was higher in the posterior group than in the anterior group (p = 0.003). More complications were observed in the anterior group than in the posterior group (p = 0.009). CONCLUSIONS: The posterior targeting group had better pain control and a lower complication rate. The authors recommend the posterior targeting method and use of 80 Gy for treatment of TN with GKS.

Gamma Knife surgery for metastatic brain tumors.

OBJECT: The authors compared results of Gamma Knife surgery (GKS) for brain metastases obtained at 2 institutions in Japan. METHODS: They analyzed a consecutive series of 2390 patients with brain metastases who underwent GKS from 1998 through 2005 in 2 institutes (1,181 patients in Chiba; 1,209 in Mito). In the 2 facilities, 1 neurosurgeon each was responsible for diagnosis, patient selection, GKS procedures, and follow-up (T.S. in Chiba, M.Y. in Mito). Even if tumor numbers exceeded 4, all visible lesions were irradiated with a total skull integral dose (TSID) of

Transient expansion of vestibular schwannoma following stereotactic radiosurgery.

OBJECT: The authors prospectively analyzed volume changes in vestibular schwannomas (VSs) after stereotactic radiosurgery. METHODS: One hundred consecutive patients with unilateral VS treated with Gamma Knife surgery (GKS) at Chiba Cardiovascular Center between 1998 and 2006 were analyzed in this study. For each lesion the Gd-enhanced volume was measured serially every 3 months in the 1st year, then every 6 months thereafter, using volumetric software. The frequency and degree of transient tumor expansion were documented and possible prognostic factors were analyzed. Concurrently, neurological deterioration involving trigeminal, facial, and cochlear nerve functions were also assessed. RESULTS: The mean observation period was 65 months (range 25-100 months). There were 32 men and 68 women, whose mean age was 59.1 years (range 29-80 years). Tumor volumes at GKS averaged 2.7 cm3 (range 0.1-13.2 cm3), and the lesions were irradiated at the mean 52.2% isodose line for the tumor margin (range 50-67%), with a mean dose of 12.2 Gy (range 10.5-13 Gy) at the periphery. The tumor volume was increased by 23% at 3 months and 27% at 6 months. Tumors shrank to their initial size over a mean period of 12 months. The maximum volume increase was < 10% (no significant increase) in 26 patients, 10-30% in 23, 30-50% in 22, 50-100% in 16, and > 100% in 13. The peak tumor expansion averaged 47% (range 0-613%). A high-dose (> or = 3.5 Gy/min) treatment appears to be the greatest risk factor for transient tumor expansion, although the difference did not reach statistical significance. Transient facial palsy and facial dysesthesia correlated strongly with tumor expansion, but only half of the hearing loss was coincident with this phenomenon. CONCLUSIONS: Transient expansion of VSs after GKS was found to be much more frequent than previously reported, strongly suggesting a correlation with deterioration of facial and trigeminal nerve functions.