The Cerebellar Nodulus/Uvula Integrates Otolith Signals for the Translational Vestibulo-Ocular Reflex

Background: The otolith-driven translational vestibulo-ocular reflex (tVOR) generates compensatory eye movements to linear head accelerations. Studies in humans indicate that the cerebellum plays a critical role in the neural control of the tVOR, but little is known about mechanisms of this control or the functions of specific cerebellar structures. Here, we chose to investigate the contribution of the nodulus and uvula, which have been shown by prior studies to be involved in the processing of otolith signals in other contexts. Methodology/Principal Findings: We recorded eye movements in two rhesus monkeys during steps of linear motion along the interaural axis before and after surgical lesions of the cerebellar uvula and nodulus. The lesions strikingly reduced eye velocity during constant-velocity motion but had only a small effect on the response to initial head acceleration. We fit eye velocity to a linear combination of head acceleration and velocity and to a dynamic mathematical model of the tVOR that incorporated a specific integrator of head acceleration. Based on parameter optimization, the lesion decreased the gain of the pathway containing this new integrator by 62%. The component of eye velocity that depended directly on head acceleration changed little (gain decrease of 13%). In a final set of simulations, we compared our data to the predictions o

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors reduce the risk of perioperative stroke and mortality after carotid endarterectomy

ObjectiveThere is increasing evidence that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce cardiovascular and cerebrovascular events through anti-inflammatory, plaque stabilization, and neuroprotective effects independent of lipid lowering. This study was designed to investigate whether statin use reduces the incidence of perioperative stroke and mortality among patients undergoing carotid endarterectomy (CEA).MethodsAll patients undergoing CEA from 1994 to 2004 at a large academic medical center were retrospectively reviewed. The independent association of statin use and perioperative morbidity was assessed via multivariate logistic regression analysis.ResultsCEA was performed by 13 surgeons on 1566 patients (987 men and 579 women; mean age, 72 ± 10 years), including 1440 (92%) isolated and 126 (8%) combined CEA/coronary artery bypass grafting procedures. The indication for CEA was symptomatic disease in 660 (42%) cases. Six hundred fifty-seven (42%) patients received a statin medication for at least 1 week before surgery. Statin use was associated with a reduction in perioperative strokes (1.2% vs 4.5%; P < .01), transient ischemic attacks (1.5% vs 3.6%; P < .01), all-cause mortality (0.3% vs 2.1%; P < .01), and median (interquartile range) length of hospitalization (2 days [2-5 days] vs 3 days [2-7 days]; P < .05). Adjusting for all demographics and comorbidities in multivariate analysis, statin use independently reduced the odds of stroke threefold (odds ratio [95% confidence interval], 0.35 [0.15-0.85]; P < .05) and death fivefold (odds ratio [95% confidence interval], 0.20 [0.04-0.99]; P < .05).ConclusionsThese data suggest that perioperative statin use may reduce the incidence of cerebrovascular events and mortality among patients undergoing CEA

A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease

Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1. Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1. To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba(-/-) mice and the control littermate (gba(+/+)) by infecting differentiated primary cortical neurons in culture with an EF1 alpha-SV40T lentivirus. Immortalized gba(-/-) neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba(+/+) neurons. This null allele gba(-/-) mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies

The History of Surgery of the Vestibular Schwannoma (Acoustic Neuroma) and Current Management Strategies

Presentation: 46:5

Microsurgical fenestration of the lamina terminalis reduces the incidence of shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage

Hydrocephalus requiring shunt placement is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). Previous investigations suggest that fenestration of the lamina terminalis during microsurgery for aSAH may be associated with a reduced rate of shunt-dependent hydrocephalus. We report a retrospective analysis correlating fenestration of the lamina terminalis with decreased shunt-dependent hydrocephalus after aSAH. During the past decade, 582 patients were admitted to our institution with aSAH. We compared the rate of shunting in patients operated on by a neurosurgeon ("index neurosurgeon") who routinely fenestrated the lamina terminalis (>98% of his patients) with that in patients managed by 14 other neurosurgeons who rarely fenestrated the lamina terminalis (<5% of their patients) and by 6 interventional neuroradiologists. The total cohort was subdivided into two groups on the basis of surgical approach and microsurgical access to the lamina terminalis. Group A included frontosphenotemporal craniotomies, an approach in which the lamina terminalis is accessible, and Group B included other approaches in which the lamina terminalis is not accessible. Shunting rates of the index neurosurgeon and those of the other practitioners were compared within Groups A and B. Shunting rates were compared by logistic regression and multivariable analysis. This study design isolates the effect of fenestrating the lamina terminalis on the incidence of shunt-dependent hydrocephalus. In Group A, the index neurosurgeon had a significantly lower rate of shunting, 2.3%, versus 12.6% for other practitioners (P = 0.011; odds ratio, 0.15). In Group B, in which the approach did not allow microsurgical fenestration of the lamina terminalis, there was no difference (P = 0.789) in the rate of shunting between the index neurosurgeon (10.0%) and other practitioners (13.2%). Fenestration of the lamina terminalis appears to be associated with a decreased incidence of shunt-dependent hydrocephalus of more than 80% after aSAH. This straightforward microsurgical maneuver should be performed whenever possible during aneurysm surgery