Sports Concussion and Chronic Traumatic Encephalopathy: Finding a Path Forward.

Sports concussion has recently assumed special importance because of the widely publicized entity of chronic traumatic encephalopathy (CTE). Identified primarily in former contact sports athletes with repeated mild traumatic brain injury (mTBI), CTE is a distinct tauopathy that can only be diagnosed postmortem and for which no specific treatment is available. Although the hazards of repeated mTBI are generally acknowledged, a spirited controversy has developed because a firm link between sports concussion and CTE has been questioned. We briefly review the history of CTE, discuss areas of uncertainty, and offer suggestions to assist neurologists confronting these issues and advance understanding of this vexing problem. ANN NEUROL 2023;93:222-225.

Crystallization, Phase Stability, Microstructure, and Chemical Bonding in Ga2O3 Nanofibers Made by Electrospinning.

We report on the crystal structure, phase stability, surface morphology, microstructure, chemical bonding, and electronic properties of gallium oxide (Ga2O3) nanofibers made by a simple and economically viable electrospinning process. The effect of processing parameters on the properties of Ga2O3 nanofibers were evaluated by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Thermal treatments in the range of 700-900 °C induce crystallization of amorphous fibers and lead to phase stabilization of α-GaOOH, ß-Ga2O3, or mixtures of these phases. The electron diffraction analyses coupled with XPS indicate that the transformation sequence progresses by forming amorphous fibers, which then transform to crystalline fibers with a mixture of α-GaOOH and ß-Ga2O3 at intermediate temperatures and fully transforms to the ß-Ga2O3 phase at higher temperatures (800-900 °C). Raman spectroscopic analyses corroborate the structural evolution and confirm the high chemical quality of the ß-Ga2O3 nanofibers. The surface analysis by XPS studies indicates that the hydroxyl groups are present for the as-synthesized samples, while thermal treatment at higher temperatures fully removes those hydroxyl groups, resulting in the formation of ß-Ga2O3 nanofibers.

Cannabis Use in a Cohort of Healthcare-Seeking United States Military Veterans With Persisting Symptoms After Mild Traumatic Brain Injury: Preliminary Observations.

INTRODUCTION: Cannabis products, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are increasingly easy to procure and use across the United States. The 2018 National Survey on Drug Use and Health (NSDUH) reported a past-month cannabis use rate of 8.6% among adults 26 years of age or older in the U.S. general population. Cannabis use is commonly reported by U.S. Military Veterans with histories of mild traumatic brain injury (mTBI) receiving services at the Marcus Institute for Brain Health (MIBH), a specialty interdisciplinary clinic serving this population. The aims of this study are to describe the frequency and characteristics of cannabis product use among Veterans evaluated at MIBH and to compare the rate of cannabis use in this group to that in the general and Veteran populations reported in the 2018 NSDUH. MATERIALS AND METHODS: Study data were collected as part of MIBH clinical assessments between January 2018 and December 2019, which included the evaluation of the current use of cannabis products. Affirmative cannabis use responses were clarified with inquiries about the frequency of use, method of administration, product ingredients (i.e., THC and/or CBD), and reason(s) for use. RESULTS: Among 163 MIBH patients (92.6% male), 72 (44.2%) endorsed cannabis product use during the month preceding the clinical assessment. Cannabis users were significantly younger than nonusers. The frequency of past-month cannabis use was significantly greater than that reported in the comparably aged NSDUH survey general and Veteran populations (44.2% vs. 8.6% and 44.2% vs. 7.7%, respectively, both P < .00001). Among the 72 MIBH patients reporting cannabis use, 62 (86.1%) reported THC or combination product use, and 10 (13.9%) reported CBD product use. Concurrent medication use, including psychotropic medications use, did not differ significantly between cannabis users and nonusers. CONCLUSIONS: Self-reported cannabis use is significantly higher in the MIBH population than in similarly aged individuals in the general population and significantly more frequent among younger than older members of this cohort. Self-reported reasons for cannabis use in this cohort included mTBI-associated neuropsychiatric symptoms, sleep disturbances, and pain for which standard treatments (both pharmacologic and nonpharmacologic) provided insufficient relief and/or produced treatment-limiting adverse events. However, cannabis use did not provide sufficient improvement in those symptoms to obviate the need for further evaluation and treatment of those problems at MIBH or to replace, in part or in whole, standard medications and other treatments for those problems. Further study of cannabis use, including standardized individual cannabinoid (i.e., THC and CBD) and whole-plant cannabis preparations, in this and similar cohorts is needed to more fully understand the drivers, benefits, risks, and safety of cannabis use in this and in similar Veteran populations, as well as the potential pharmacological and/or nonpharmacological therapeutic alternatives to cannabis use.

The Marcus Institute for Brain Health: an integrated practice unit for the care of traumatic brain injury in military veterans.

PRIMARY OBJECTIVE: Traumatic brain injury (TBI) is a signature wound of recent Unites States military conflicts. The National Intrepid Center of Excellence (NICoE) has demonstrated that interdisciplinary care is effective for active-duty military personnel with TBI and related psychological health conditions. This paper details how the Marcus Institute for Brain Health (MIBH), established in 2017 as an Integrated Practice Unit (IPU), is founded on the NICoE model and is dedicated to interdisciplinary care for Veterans with persistent symptoms due to TBI and psychological comorbidities. RESEARCH DESIGN: A highly integrated group of clinicians from diverse disciplines combine their expertise to offer comprehensive evaluation, intensive outpatient treatment, and program outcomes evaluation. METHODS AND PROCEDURES: The role of each discipline in the provision of care, and the regular interaction of all clinicians, are delineated. A strong connection to academic medicine is maintained so that clinical research and education complement patient care. MAIN OUTCOMES AND RESULTS: Over three hundred veterans and family members have received treatment at the MIBH. Program evaluation is underway. CONCLUSIONS: As the understanding of TBI and related psychological conditions continues its rapid evolution, the expert interdisciplinary care at the MIBH has great promise as a Veteran counterpart of the NICoE.

Predicting the size of salt-containing aqueous Na-AOT reverse micellar water-in-oil microemulsions with consideration for specific ion effects.

HYPOTHESIS: Reverse micellar solutions are thermodynamically stable systems in which surfactant molecules surround water droplets within a continuous organic phase. Among their many applications, they can be used for the synthesis of nanoparticles of controlled agglomeration. Here, we consider the role specific ion effects play in reverse micelle size reduction. EXPERIMENTS: Dynamic light scattering measurements and the Gouy-Chapman electrical double layer model were combined to study water/AOT/isooctane reverse micellar systems (wo = 10). Linear relationships between the solvodynamic diameter (D) of reverse micelles containing various concentrations of FeSO4, Mg(NO3)2, CuCl2, Al(NO3)3, Fe(NO3)3, Y(NO3)3, NaBH4, ZrOCl2, and NH4OH, and their calculated Debye screening lengths, κ-1, were observed with decreasing D and increasing salt concentration (c). FINDINGS: By comparing the linear fits for reverse micelle size as a function of c-1/2, we determined the size can be described as a function of the Debye screening length, cation valency (z), and specific anion hydrated radius (ran), where D = 3.1z κ-1 + bi, and bi is linearly related to ran. Our model accurately predicts reverse micelle sizes with the addition of monovalent, divalent, and trivalent salts for which the primary hydrolyzed cation species has a charge that is equal to the cation valency.

Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers.

Concussion or mild traumatic brain injury (mTBI) in athletes can cause persistent symptoms, known as post-concussion syndrome (PCS), and repeated injuries may increase the long-term risk for an athlete to develop neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), and Alzheimer's disease (AD). The Center for Disease Control estimates that up to 3.8 million sport-related mTBI are reported each year in the United States. Despite the magnitude of the phenomenon, there is a current lack of comprehensive prognostic indicators and research has shown that available monitoring tools are moderately sensitive to short-term concussion effects but less sensitive to long-term consequences. The overall aim of this review is to discuss novel, quantitative, and objective measurements that can predict long-term outcomes following repeated sports-related mTBIs. The specific objectives were (1) to provide an overview of the current clinical and biomechanical tools available to health practitioners to ensure recovery after mTBIs, (2) to synthesize potential biological mechanisms in animal models underlying the long-term adverse consequences of mTBIs, (3) to discuss the possible link between repeated mTBI and neurodegenerative diseases, and (4) to discuss the current knowledge about fluid biomarkers for mTBIs with a focus on novel exosomal biomarkers. The conclusions from this review are that current post-concussion clinical tests are not sufficiently sensitive to injury and do not accurately quantify post-concussion alterations associated with repeated mTBIs. In the current review, it is proposed that current practices should be amended to include a repeated symptom inventory, a cognitive assessment of executive function and impulse control, an instrumented assessment of balance, vestibulo-ocular assessments, and an improved panel of blood or exosome biomarkers.

Efficacy of an Interdisciplinary Intensive Outpatient Program in Treating Combat-Related Traumatic Brain Injury and Psychological Health Conditions.

Background: Since 2000, over 413,000 US service members (SM) experienced at least one traumatic brain injury (TBI), and 40% of those with in-theater TBIs later screened positive for comorbid psychological health (PH) conditions, including post-traumatic stress disorder (PTSD), depression, and anxiety. Many SMs with these persistent symptoms fail to achieve a recovery that results in a desirable quality of life or return to full duty. Limited information exists though to guide treatment for SMs with a history of mild TBI (mTBI) and comorbid PH conditions. This report presents the methods and outcomes of an interdisciplinary intensive outpatient program (IOP) in the treatment of SMs with combat-related mTBI and PH comorbidities. The IOP combines conventional rehabilitation therapies and integrative medicine techniques with the goal of reducing morbidity in multiple neurological and behavioral health domains and enhancing military readiness. Methods: SMs (n = 1,456) with residual symptoms from mTBI and comorbid PH conditions were treated in a 4-week IOP at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center (WRNMMC). The IOP uses an interdisciplinary, holistic, and patient-centric rehabilitative care model. Interdisciplinary teams provide a diagnostic workup of neurological, psychiatric, and existential injuries, and from these assessments, individualized care plans are developed. Treatment response was assessed using the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Military Version (PCL-M), Satisfaction With Life Scale (SWLS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Epworth Sleepiness Scale (ESS), and Headache Impact Test-6 (HIT-6) and administered at admission, discharge, and at 1, 3, and 6 months post-discharge. Findings: Following treatment in the IOP, the symptomatic patients had statistically significant and clinically meaningful improvements across all outcome measures. The largest effect size was seen with GAD-7 (r = 0.59), followed by PHQ-8 (r = 0.56), NSI (r = 0.55), PCL-M (r = 0.52), ESS (r = 0.50), SWLS (r = 0.49), and HIT-6 (r = 0.42). In cross-sectional follow ups, the significant improvements were sustained at 1, 3, and 6 months post-discharge. Interpretation: This report demonstrates that an interdisciplinary IOP achieves significant and sustainable symptom recovery in SMs with combat-related mTBI and comorbid PH conditions and supports the further study of this model of care in complex medical conditions.

The Role of Speech-Language Pathology in an Interdisciplinary Care Model for Persistent Symptomatology of Mild Traumatic Brain Injury.

The Marcus Institute for Brain Health (MIBH) provides interdisciplinary care for adults struggling with persistent effects of mild traumatic brain injury and accompanying changes in behavioral health, with specific emphases on Veterans and retired elite athletes. The cognitive, physical, and behavioral symptoms associated with mild traumatic brain injury are interrelated, with neurobiopsychosocial modeling encompassing the factors related to recovery from a traumatic brain injury. The diffuse impacts of chronic concussive injuries require multiple clinical providers to address the breadth of symptoms, facilitating both interdisciplinary and transdisciplinary care models. By implementing integrated practice units, patients receive advanced medical care, imaging, speech-language pathology, physical therapy, behavioral health, neuropsychology, and clinical pharmacy for a cohesive diagnostic and intervention plan. Nationally, speech-language pathologists report challenges with best-practice options for concussion, particularly in the domain of assessment practices. At the MIBH, speech-language pathologists begin their assessment with a structured clinical interview that focuses on patients' needs and concerns. Evaluation modalities focus on hearing, communication, and functional cognition to guide therapeutic treatment planning. The intensive outpatient care program at MIBH incorporates both individual sessions targeting patient-centered goals and group care, where speech-language pathologists work transdisciplinarily to generalize care from all disciplines out into the community. Care practices for concussive injuries continue to evolve rapidly; speech-language pathology at the MIBH offers one such vision for excellence in clinical care.

White Matter and Cognition in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of disability and produces a wide range of cognitive, emotional, and physical consequences. The impact of TBI on cognition is among the most important questions in this field but remains incompletely understood. The immediate cognitive effects of concussion, while usually short-lived, may be profound and lasting in some individuals, and long-term sequelae of TBI may include dementia of several varieties including post-traumatic leukoencephalopathy, chronic traumatic encephalopathy, and Alzheimer's disease. Whereas the etiopathogenesis of cognitive dysfunction after TBI remains uncertain, a reasonable point to begin is a focus on the white matter of the brain, where the neuropathological lesion known as diffuse axonal injury (DAI) is routinely identified. White matter is not typically accorded the significance granted to cortical gray matter in discussions of cognitive dysfunction and dementia, but increasing evidence is accumulating to suggest that cognitive decline after TBI is a direct result of white matter injury, and that lesions in this brain component are crucial in the sequence of events leading ultimately to dementia of several types. In this review, we consider the topic of white matter and cognition in TBI, beginning with DAI and proceeding to the role of inflammation in the pathogenesis of cognitive dysfunction and dementia that can follow. A brief review of possible therapeutic options will also be offered, including the use of anti-inflammatory agents and the exploitation of white matter plasticity, to treat acute and post-acute injuries, and lower the incidence of dementia resulting from TBI.

The Content Validity of a Chemotherapy-Induced Peripheral Neuropathy Patient-Reported Outcome Measure.

PURPOSE/OBJECTIVES: To test the content validity of a 16-item version of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20). 
. RESEARCH APPROACH: Cross-sectional, prospective, qualitative design. 
. SETTING: Six outpatient oncology clinics within the University of Michigan Health System's comprehensive cancer center in Ann Arbor. 
. PARTICIPANTS: 25 adults with multiple myeloma or breast, gynecologic, gastrointestinal, or head and neck malignancies experiencing peripheral neuropathy caused by neurotoxic chemotherapy. 
. METHODOLOGIC APPROACH: Cognitive interviewing methodology was used to evaluate the content validity of a 16-item version of the QLQ-CIPN20 instrument.
. FINDINGS: Minor changes were made to three questions to enhance readability. Twelve questions were revised to define unfamiliar terminology, clarify the location of neuropathy, and emphasize important aspects. One question was deleted because of clinical and conceptual redundancy with other items, as well as concerns regarding generalizability and social desirability. 
. INTERPRETATION: Cognitive interviewing methodology revealed inconsistencies between patients' understanding and researchers' intent, along with points that required clarification to avoid misunderstanding. 
. IMPLICATIONS FOR NURSING: Patients' interpretations of the instrument's items were inconsistent with the intended meanings of the questions. One item was dropped and others were revised, resulting in greater consistency in how patients, clinicians, and researchers interpreted the items' meanings and improving the instrument's content validity. Following additional revision and psychometric testing, the QLQ-CIPN20 could evolve into a gold-standard CIPN patient-reported outcome measure.

Characterisation of interface astroglial scarring in the human brain after blast exposure: a post-mortem case series.

BACKGROUND: No evidence-based guidelines are available for the definitive diagnosis or directed treatment of most blast-associated traumatic brain injuries, partly because the underlying pathology is unknown. Moreover, few neuropathological studies have addressed whether blast exposure produces unique lesions in the human brain, and if those lesions are comparable with impact-induced traumatic brain injury. We aimed to test the hypothesis that blast exposure produces unique patterns of damage, differing from that associated with impact-induced, non-blast traumatic brain injuries. METHODS: In this post-mortem case series, we investigated several features of traumatic brain injuries, using clinical histopathology techniques and markers, in brain specimens from male military service members with chronic blast exposures and from those who had died shortly after severe blast exposures. We then compared these results with those from brain specimens from male civilian (ie, non-military) cases with no history of blast exposure, including cases with and without chronic impact traumatic brain injuries and cases with chronic exposure to opiates, and analysed the limited associated clinical histories of all cases. Brain specimens had been archived in tissue banks in the USA. FINDINGS: We analysed brain specimens from five cases with chronic blast exposure, three cases with acute blast exposure, five cases with chronic impact traumatic brain injury, five cases with exposure to opiates, and three control cases with no known neurological disorders. All five cases with chronic blast exposure showed prominent astroglial scarring that involved the subpial glial plate, penetrating cortical blood vessels, grey-white matter junctions, and structures lining the ventricles; all cases of acute blast exposure showed early astroglial scarring in the same brain regions. All cases of chronic blast exposure had an antemortem diagnosis of post traumatic stress disorder. The civilian cases, with or without history of impact traumatic brain injury or a history of opiate use, did not have any astroglial scarring in the brain regions analysed. INTERPRETATION: The blast exposure cases showed a distinct and previously undescribed pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and at junctions between grey and white matter. This distinctive pattern of scarring may indicate specific areas of damage from blast exposure consistent with the general principles of blast biophysics, and further, could account for aspects of the neuropsychiatric clinical sequelae reported. The generalisability of these findings needs to be explored in future studies, as the number of cases, clinical data, and tissue availability were limited. FUNDING: Defense Health Program of the United States Department of Defense.

Shock Wave Response of Iron-based In Situ Metallic Glass Matrix Composites.

The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of partial devitrification on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4. The samples, designated SAM2X5-600 and SAM2X5-630, are X-ray amorphous and partially crystalline, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements using interferometry techniques at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile launched from a powder gun. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be 8.58 ± 0.53 GPa for SAM2X5-600 and 11.76 ± 1.26 GPa for SAM2X5-630. The latter HEL result is higher than elastic limits for any BMG reported in the literature thus far. SAM2X5-600 catastrophically loses post-yield strength whereas SAM2X5-630, while showing some strain-softening, retains strength beyond the HEL. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding.

Cancer treatment-related neuropathic pain syndromes--epidemiology and treatment: an update.

Cancer treatment-related chronic neuropathic pain (NP) is a pervasive and distressing problem that negatively influences function and quality of life for countless cancer survivors. It occurs because of cancer treatment-induced damage to peripheral and central nervous system structures. NP becomes chronic when pain signal transmission persists, eventually sensitizing neurons in the dorsal horn and other pain-processing regions in the central nervous system. Frequently overlooked, NP due to cancer treatment has been understudied. Consequently, only a few pharmacologic interventions have been shown to be effective based on the results of randomized controlled trials. Future research designed to explore pathophysiologic mechanisms and effective mechanism-targeted interventions is sorely needed.

3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration.

Low temperature 3D printing of calcium phosphate scaffolds holds great promise for fabricating synthetic bone graft substitutes with enhanced performance over traditional techniques. Many design parameters, such as the binder solution properties, have yet to be optimized to ensure maximal biocompatibility and osteoconductivity with sufficient mechanical properties. This study tailored the phosphoric acid-based binder solution concentration to 8.75 wt% to maximize cytocompatibility and mechanical strength, with a supplementation of Tween 80 to improve printing. To further enhance the formulation, collagen was dissolved into the binder solution to fabricate collagen-calcium phosphate composites. Reducing the viscosity and surface tension through a physiologic heat treatment and Tween 80, respectively, enabled reliable thermal inkjet printing of the collagen solutions. Supplementing the binder solution with 1-2 wt% collagen significantly improved maximum flexural strength and cell viability. To assess the bone healing performance, we implanted 3D printed scaffolds into a critically sized murine femoral defect for 9 weeks. The implants were confirmed to be osteoconductive, with new bone growth incorporating the degrading scaffold materials. In conclusion, this study demonstrates optimization of material parameters for 3D printed calcium phosphate scaffolds and enhancement of material properties by volumetric collagen incorporation via inkjet printing.

Reverse micelle synthesis of oxide nanopowders: mechanisms of precipitate formation and agglomeration effects.

We present an analysis of reverse micelle stability in four model systems. The first two systems, composed of unstable microemulsions of isooctane, water, and Na-AOT with additions of either iron sulfate or yttrium nitrate, were used for the synthesis of iron oxide or yttrium oxide powders. These oxide powders were of nanocrystalline character, but with some level of agglomeration that was dependent on calcination temperature and cleaning procedures. Results show that even though the reverse micellar solutions were unstable, nanocrystalline powders with very low levels of agglomeration could be obtained. This effect can be attributed to the protective action of the surfactant on the surfaces of the powders that prevents neck formation until after all the surfactant has volatilized. A striking feature of the IR spectra collected on the iron oxide powders is the absence of peaks in the ~1715 cm(-1) to 1750 cm(-1) region, where absorption due to the symmetric C=O (carbonyl) stretching occurs. The lack of such peaks strongly suggests the carbonyl group is no longer free, but is actively participating in the surfactant-precipitate interaction. The final two microemulsion systems, containing CTAB as the surfactant, showed that loss of control of the reverse micelle synthesis process can easily occur when the amount of salt in the water domains exceeds a critical concentration. Both model systems eventually resulted in agglomerated powders of broad size distributions or particles that were large compared to the sizes of the reverse micelles, consistent with the notion that the microemulsions were not stable and the powders were precipitated in an uncontrolled fashion. This has implications for the synthesis of nanopowders by reverse micelle synthesis and provides a benchmark for process control if powders of the highest quality are desired.

Incidence, clinical course, and predictors of prolonged recovery time following sport-related concussion in high school and college athletes.

Sport-related concussion (SRC) is typically followed by clinical recovery within days, but reports of prolonged symptoms are common. We investigated the incidence of prolonged recovery in a large cohort (n = 18,531) of athlete seasons over a 10-year period. A total of 570 athletes with concussion (3.1%) and 166 controls who underwent pre-injury baseline assessments of symptoms, neurocognitive functioning and balance were re-assessed immediately, 3 hr, and 1, 2, 3, 5, 7, and 45 or 90 days after concussion. Concussed athletes were stratified into typical (within 7 days) or prolonged (> 7 days) recovery groups based on symptom recovery time. Ten percent of athletes (n = 57) had a prolonged symptom recovery, which was also associated with lengthier recovery on neurocognitive testing (p < .001). At 45-90 days post-injury, the prolonged recovery group reported elevated symptoms, without deficits on cognitive or balance testing. Prolonged recovery was associated with unconsciousness [odds ratio (OR), 4.15; 95% confidence interval (CI) 2.12-8.15], posttraumatic amnesia (OR, 1.81; 95% CI, 1.00-3.28), and more severe acute symptoms (p < .0001). These results suggest that a small percentage of athletes may experience symptoms and functional impairments beyond the typical window of recovery after SRC, and that prolonged recovery is associated with acute indicators of more severe injury.

Ionic concentration effects on reverse micelle size and stability: implications for the synthesis of nanoparticles.

We present a systematic investigation and analysis of the structure and stability of reverse micelle systems with the addition of NH(4)OH, ZrOCl(2), and Al(NO(3))(3) salts. We demonstrate that the reverse micelle size decreases with increasing salt additions until one reaches a critical concentration, which characterizes the onset of system destabilization. The concept of an electrical double layer, as it applies to reverse micelles, is considered for explaining features of destabilization, including the initial decrease in reverse micelle size, the destabilization concentration, and the effect of cation valence. We propose that the reduction in size prior to instability is caused by compression of the reverse micelle electrical double layers, as higher concentrations of salts are present. The reduced thickness of the electrical double layers allows the decaying potentials to move into closer proximity to each other before generating enough repulsion to balance the forces for reverse micelle formation and form a new equilibrium average reverse micelle size. The point of reverse micelle instability has been related to the formation of a two-phase system as a result of the inability to further compress the salt co-ions in the core of the reverse micelles, which would cause an excessive repulsive force between the overlapping potentials. We have extracted a critical potential of -89 nV between the two overlapping potentials for the AOT/water/isooctane (ω(0) = 10) systems studied. All these effects have important implications for the preparation of nanopowders by reverse micelle synthesis. If the reverse micelles are unstable before the precipitates are formed, then the advantage of reverse micelle synthesis is immediately lost.