Aaron Plitt

Objective Dizziness is one of the most prevalent and debilitating symptoms associated with vestibular schwannoma (VS), and there are little data on contributing or alleviating factors in the perioperative setting. In this study, we aimed to evaluate whether vestibular nerve sectioning or labyrinthectomy concomitant with surgical resection would improve dizziness in the postoperative period. Methods This is a retrospective study of a consecutive series of VS patients who underwent resection at a large tertiary care center between 2009 and 2023. Dizziness at 6 months was the primary endpoint, whereas facial nerve and hearing outcomes were secondary endpoints. Fisher's exact test was used to identify significant differences between categorical variables, and multivariate logistic regression analysis was performed to identify predictors of dizziness as well as facial nerve and hearing outcomes. Results A total of 333 patients underwent resection of VS at our institution. There was no significant difference in binary reported dizziness based on surgical approach (p = 0.14). However, patients reported significantly less dizziness at discharge (p < 0.01) as well as 6-month (p = 0.02) and 1-year (p < 0.01) follow-up in the translabyrinthine group. On the other hand, patients who underwent labyrinth-sparing approaches reported a significant increase in dizziness that remained up to 1 year from the time of surgery. Conclusion Our data suggest that labyrinthectomy may improve dizziness symptoms in patients with VS. Selective VN sectioning does not appear to affect dizziness or hearing outcomes. Finally, surgical approach does not affect facial nerve outcomes.

OBJECTIVE: Meningioma prognostication and treatment continues to evolve with an increasing understanding of tumor biology. In this study, the authors aimed to test conventional predictors of meningioma recurrence, histopathology variables for which there exists some controversy (brain invasion), as well as a novel molecular-based location paradigm. METHODS: This is a retrospective study of a consecutive series of patients with WHO grade I–III meningioma resected at The University of Texas Southwestern Medical Center between 1994 and 2015. Time to meningioma recurrence (i.e., recurrence-free survival [RFS]) was the primary endpoint measured. Kaplan-Meier curves were constructed and compared using log-rank tests. Cox univariate and multivariate analyses were performed to identify predictors of RFS. RESULTS: A total of 703 consecutive patients with meningioma underwent resection at The University of Texas Southwestern Medical Center between the years 1994 and 2015. A total of 158 patients were excluded for insufficient follow-up (< 3 months). The median age of the cohort was 55 years (range 16–88 years) and 69.5% (n = 379) were female. The median follow-up was 48 months (range 3–289 months). There was not a significantly increased risk of recurrence in patients with evidence of brain invasion, in patients with otherwise WHO grade I meningioma (Cox univariate HR 0.92, 95% CI 0.44–1.91, p = 0.82, power 4.4%). Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence (n = 52, Cox univariate HR 0.21, 95% CI 0.03–1.61, p = 0.13, power 71.6%). Location (midline skull base, lateral skull base, and paravenous) was significantly associated with RFS (p < 0.01, log-rank test). In patients with high-grade meningiomas (WHO grade II or III), location was predictive of RFS (p = 0.03, log-rank test), with paravenous meningiomas exhibiting the highest rates of recurrence. Location was not significant on multivariate analysis. CONCLUSIONS: The data suggest that brain invasion does not increase the risk of recurrence in otherwise WHO grade I meningioma. Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence. Location categorized by distinct molecular signatures did not predict RFS in a multivariate model. Larger studies are needed to confirm these findings.

Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as ways to prevent and treat these disturbances. An illustrative case vignette is presented describing a patient's experience of cycles of manic-like behavior and depression while on high-dosage prednisone, with long-term cognitive disorganization, vulnerability to stress, and personality changes. Severe neuropsychiatric consequences (including suicide, suicide attempt, psychosis, mania, depression, panic disorder, and delirium, confusion, or disorientation) have been reported to occur in 15.7 per 100 person-years at risk for all glucocorticoid courses, and 22.2 per 100 person-years at risk for first courses. The majority of patients experience less severe but distressing and possibly persistent changes in mood, cognition, memory, or behavior during glucocorticoid treatment or withdrawal. Although prediction of such effects is difficult, risks vary with age, gender, dosage, prior psychiatric history, and several biological markers. Key mechanisms thought to underlie these risk factors are briefly described. Recommendations are given for identifying individual risk factors and for monitoring and managing adverse neuropsychiatric effects of glucocorticoids.

Background: Stimulating the glycine_B binding site on the N‐methyl‐d‐aspartate ionotropic glutamate receptor (NMDAR) has been proposed as a novel mechanism for modulating behavioral effects of ethanol (EtOH) that are mediated via the NMDAR, including acute intoxication. Here, we pharmacologically interrogated this hypothesis in mice.Methods: Effects of systemic injection of the glycine_B agonist, d‐serine, the GlyT‐1 glycine transporter inhibitor, ALX‐5407, and the glycine_B antagonist, L‐701,324, were tested for the effects on EtOH‐induced ataxia, hypothermia, and loss of righting reflex (LORR) duration in C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mice. Effects of the glycine_B partial agonist, d‐cycloserine (DCS), the GlyT‐1 inhibitor, N‐[3‐(4′‐fluorophenyl)‐3‐(4′‐phenylphenoxy)propyl]sarcosine (NFPS), and the glycine_B antagonist, 5,7‐dichlorokynurenic (DCKA), on EtOH‐induced LORR duration were also tested. Interaction effects on EtOH‐induced LORR duration were examined via combined treatment with d‐serine and ALX‐5407, d‐serine and MK‐801, d‐serine and L‐701,324, as well as L‐701,324 and ALX‐5407, in B6 mice, and d‐serine in GluN2A and PSD‐95 knockout mice. The effect of dietary depletion of magnesium ( Mg ), an element that interacts with the glycine_B site, was also tested.Results: Neither d‐serine, DCS, ALX‐5407, nor NFPS significantly affected EtOH intoxication on any of the measures or strains studied. L‐701,324, but not DCKA, dose‐dependently potentiated the ataxia‐inducing effects of EtOH and increased EtOH‐induced (but not pentobarbital‐induced) LORR duration. d‐serine did not have interactive effects on EtOH‐induced LORR duration when combined with ALX‐5407. The EtOH‐potentiating effects of L‐701,324, but not MK‐801, on LORR duration were prevented by d‐serine, but not ALX‐5407. Mg depletion potentiated LORR duration in B6 mice and was lethal in a large proportion of S1 mice.Conclusions: Glycine_B site activation failed to produce the hypothesized reduction in EtOH intoxication across a range of measures and genetic strains, but blockade of the glycine_B site potentiated EtOH intoxication. These data suggest endogenous activity at the glycine_B opposes EtOH intoxication, but it may be difficult to pharmacologically augment this action, at least in nondependent subjects, perhaps because of physiological saturation of the glycine_B site.

Individual variation in sensitivity to acute ethanol (EtOH) challenge is associated with alcohol drinking and is a predictor of alcohol abuse. Previous studies have shown that the C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mouse strains differ in responses on certain measures of acute EtOH intoxication. To gain insight into genetic factors contributing to these differences, we performed quantitative trait locus (QTL) analysis of measures of EtOH-induced ataxia (accelerating rotarod), hypothermia, and loss of righting reflex (LORR) duration in a B6 × S1 F2 population. We confirmed that S1 showed greater EtOH-induced hypothermia (specifically at a high dose) and longer LORR compared to B6. QTL analysis revealed several additive and interacting loci for various phenotypes, as well as examples of genotype interactions with sex. QTLs for different EtOH phenotypes were largely non-overlapping, suggesting separable genetic influences on these behaviors. The most compelling main-effect QTLs were for hypothermia on chromosome 16 and for LORR on chromosomes 4 and 6. Several QTLs overlapped with loci repeatedly linked to EtOH drinking in previous mouse studies. The architecture of the traits we examined was complex but clearly amenable to dissection in future studies. Using integrative genomics strategies, plausible functional and positional candidates may be found. Uncovering candidate genes associated with variation in these phenotypes in this population could ultimately shed light on genetic factors underlying sensitivity to EtOH intoxication and risk for alcoholism in humans.