John Sladky

White Matter Hyperintensities and Hypobaric Exposure

Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid‐attenuated inversion recovery magnetic resonance imaging (MRI).

Lower neurocognitive function in U-2 pilots: Relationship to white matter hyperintensities

Objective: Determine whether United States Air Force (USAF) U-2 pilots (U2Ps) with occupational exposure to repeated hypobaria had lower neurocognitive performance compared to pilots without repeated hypobaric exposure and whether U2P neurocognitive performance correlated with white matter hyperintensity (WMH) burden. Methods: We collected Multidimensional Aptitude Battery–II (MAB-II) and MicroCog: Assessment of Cognitive Functioning (MicroCog) neurocognitive data on USAF U2Ps with a history of repeated occupational exposure to hypobaria and compared these with control data collected from USAF pilots (AFPs) without repeated hypobaric exposure (U2Ps/AFPs MAB-II 87/83; MicroCog 93/80). Additional comparisons were performed between U2Ps with high vs low WMH burden. Results: U2Ps with repeated hypobaric exposure had significantly lower scores than control pilots on reasoning/calculation (U2Ps/AFPs 99.4/106.5), memory (105.5/110.9), information processing accuracy (102.1/105.8), and general cognitive functioning (103.5/108.5). In addition, U2Ps with high whole-brain WMH count showed significantly lower scores on reasoning/calculation (high/low 96.8/104.1), memory (102.9/110.2), general cognitive functioning (101.5/107.2), and general cognitive proficiency (103.6/108.8) than U2Ps with low WMH burden (high/low WMH mean volume 0.213/0.003 cm3 and mean count 14.2/0.4). Conclusion: In these otherwise healthy, highly functioning individuals, pilots with occupational exposure to repeated hypobaria demonstrated lower neurocognitive performance, albeit demonstrable on only some tests, than pilots without repeated exposure. Furthermore, within the U2P population, higher WMH burden was associated with lower neurocognitive test performance. Hypobaric exposure may be a risk factor for subtle changes in neurocognition.

Lambert-eaton myasthenic syndrome and merkel cell carcinoma

Lambert-Eaton myasthenic syndrome (LEMS) is an antibody-mediated disorder of the neuromuscular junction that is most commonly diagnosed in association with small cell lung carcinoma (SCLC). Small cell lung carcinoma is histologically similar to the aggressive cutaneous neuroendocrine malignancy Merkel cell carcinoma (MCC). We provide a full report and longitudinal clinical follow-up of a case of LEMS occurring with MCC. We also review the literature on paraneoplastic syndromes associated with MCC and other nonpulmonary small cell carcinomas.

White matter integrity in high-altitude pilots exposed to hypobaria

INTRODUCTION Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability. METHODS There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values. RESULTS Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots. DISCUSSION Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes.McGuire SA, Boone GRE, Sherman PM, Tate DF, Wood JD, Patel B, Eskandar G, Wijtenburg SA, Rowland LM, Clarke GD, Grogan PM, Sladky JH, Kochunov PV. White matter integrity in high-altitude pilots exposed to hypobaria. Aerosp Med Hum Perform. 2016; 87(12):983-988.

Reproducibility of quantitative structural and physiological MRI measurements

Quantitative longitudinal magnetic resonance imaging and spectroscopy (MRI/S) is used to assess progress of brain disorders and treatment effects. Understanding the significance of MRI/S changes requires knowledge of the inherent technical and physiological consistency of these measurements. This longitudinal study examined the variance and reproducibility of commonly used quantitative MRI/S measurements in healthy subjects while controlling physiological and technical parameters.

Clinical Reasoning: Persistent respiratory failure following cardiac arrest

A 49-year-old woman was found unresponsive in bed, with ventricular fibrillation ultimately diagnosed. She was intubated and cardiac life support administered. Amiodarone was loaded and maintenance initiated. Left heart catheterization/ventriculography demonstrated no coronary artery disease, with reduced ejection fraction (EF)/global hypokinesis and dilated left ventricle. Intermittent ventricular tachycardia continued, causing recurrent arrests and metabolic acidosis. She was transitioned to extracorporeal membrane oxygenation (ECMO) with improved arrhythmias and acidosis but continued cardiogenic shock. She was transferred to an outside hospital for potential left ventricular assist device (LVAD) or cardiac transplant.