Disparities in Neuro-Oncology.

PURPOSEOF REVIEW: Health disparities are preventable differences in the diagnosis, treatment, and outcomes of many diseases, including central nervous system (CNS) tumors. This review will summarize and compile the existing literature on health disparities in neuro-oncology and provide directions for future research and interventions. RECENT FINDINGS: Patients from historically marginalized groups are more likely to receive inadequate treatment, develop complications, and experience a shorter life expectancy. Financial toxicity can be particularly severe for patients with CNS tumors due to the high costs of treatment. Additionally, CNS clinical trials and research lack diverse representation.

The Importance of Therapeutic Time Window in the Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of death and disability. Despite its importance in public health, there are presently no drugs to treat TBI. Many reasons underlie why drugs have failed clinical trials, one reason is that most drugs to treat TBI lose much of their efficacy before patients are first treated. This review discusses the importance of therapeutic time window; the time interval between TBI onset and the initiation of treatment. Therapeutic time window is complex, as brain injury is both acute and chronic, resulting in multiple drug targets that appear and disappear with differing kinetics. The speed and increasing complexity of TBI pathophysiology is a major reason why drugs lose efficacy as time to first dose increases. Recent Phase III clinical trials treated moderate to severe TBI patients within 4-8 h after injury, yet they turned away many potential patients who could not be treated within these time windows. Additionally, most head trauma is mild TBI. Unlike moderate to severe TBI, patients with mild TBI often delay treatment until their symptoms do not abate. Thus, drugs to treat moderate to severe TBI likely will need to retain high efficacy for up to 12 h after injury; drugs for mild TBI, however, will likely need even longer windows. Early pathological events following TBI progress with similar kinetics in humans and animal TBI models suggesting that preclinical testing of time windows assists the design of clinical trials. We reviewed preclinical studies of drugs first dosed later than 4 h after injury. This review showed that therapeutic time window can differ depending upon the animal TBI model and the outcome measure. We identify the few drugs (methamphetamine, melanocortin, minocycline plus N-acetylcysteine, and cycloserine) that demonstrated good therapeutic windows with multiple outcome measures. On the basis of their therapeutic window, these drugs appear to be excellent candidates for clinical trials. In addition to further testing of these drugs, we recommend that the assessment of therapeutic time window with multiple outcome measures becomes a standard component of preclinical drug testing.

Assessment of medication management capacity in a predominantly African American and Caribbean American sample of adults with intractable epilepsy.

INTRODUCTION: Suboptimal or partial adherence to antiepileptic drugs (AEDs) is an avoidable cause of seizures and deleterious outcomes in epilepsy. As self-rated adherence may be unreliable, suboptimal adherence may go undetected. This study assessed generalizability of a performance-based measure of medication management to patients with intractable epilepsy. MATERIALS AND METHODS: Participants were 50 adults (age = 42 ±â€¯14 years, 60% female, 82% Black, 20% Hispanic/Latino) with ≥2 seizures in the preceding 6 months. Antiepileptic drug adherence was electronically monitored for one month via Medication Event Monitoring Systems (MEMS) and self-rated (1 = very poor to 6 = excellent). The Medication Management Ability Assessment (MMAA) was administered at follow-up and scored by raters blind to adherence results. Spearman correlations and Poisson regressions assessed their associations. RESULTS: On average, participants self-reported good-to-very good adherence. According to MEMS, participants took AEDs as prescribed 73% of the time; most participants (58%) missed ≥3 doses. The MMAA demonstrated strong internal consistency (Kuder-Richardson 20 = 0.81) and was associated with MEMS: percentage of days doses were taken correctly (rs = 0.29, p = 0.04) and frequency of missed doses (rs = -0.31, p = 0.03). The MMAA was not associated with self-rated adherence. Poisson regressions showed that self-ratings and MMAA performance accounted for unique variance in frequency of missed AED doses. CONCLUSIONS: These findings provide evidence of the MMAA's criterion validity as a measure of capacity to manage AEDs. It may prove useful in cases where suboptimal adherence is suspected but unreported by patients. Its lack of significant association with self-rated adherence is consistent with prior reports; however, future studies should replicate these findings with larger samples.

Focal Electroencephalographic Changes Index Post-Traumatic Confusion and Outcome.

While the duration and severity of post-traumatic confusional state (PTCS) after traumatic brain injury have well-established implications for long-term outcomes, little is known about the underlying pathophysiology and their role in functional outcomes. Here, we analyzed the delta-to-alpha frequency band power ratios (DAR) from localized scalp areas derived from standard resting electroencephalographic (EEG) data recorded during eyes closed state in 49 patients diagnosed with PTCS. Higher global, occipital, parietal, and temporal DARs were significantly associated with the severity of PTCS, as assessed by the Confusion Assessment Protocol (CAP) observed on the same day, after controlling for injury severity. Also, occipital DARs were positively associated with both the CAP disorientation score 2, and the CAP symptom fluctuation score 4, after controlling for injury severity (n = 35). Posterior DARs were significantly associated with Functional Independence Measure-cognitive subscale average score at 1 (n = 45), 2 (n = 42), and 5 (n = 34) year(s) post-injury. The associations at 1 (temporal left) and 2 (parietal left) years survive after controlling for an injury severity index. Our finding that posterior DAR is a marker of PTCS and functional recovery post-injury, likely reflects functional de-afferentation of the posterior medial complex (PMC) in PTCS. Altered function of the PMC is proposed as a unifying physiological mechanism underlying both acute and chronic confusional states. We discuss the relationship of these findings to electrophysiological markers associated with disorders of consciousness.

Executive attention deficits after traumatic brain injury reflect impaired recruitment of resources.

Deficits in attention are a common and devastating consequence of traumatic brain injury (TBI), leading to functional impairments, rehabilitation barriers, and long-term disability. While such deficits are well documented, little is known about their underlying pathophysiology hindering development of effective and targeted interventions. Here we evaluate the integrity of brain systems specific to attentional functions using quantitative assessments of electroencephalography recorded during performance of the Attention Network Test (ANT), a behavioral paradigm that separates alerting, orienting, and executive components of attention. We studied 13 patients, at least 6 months post-TBI with cognitive impairments, and 24 control subjects. Based on performance on the ANT, TBI subjects showed selective impairment in executive attention. In TBI subjects, principal component analysis combined with spectral analysis of the EEG after target appearance extracted a pattern of increased frontal midline theta power (2.5-7.5 Hz) and suppression of frontal beta power (12.5-22.5 Hz). Individual expression of this pattern correlated (r = - 0.67, p < 0.001) with executive attention impairment. The grading of this pattern of spatiotemporal dynamics with executive attention deficits reflects impaired recruitment of anterior forebrain resources following TBI; specifically, deafferentation and variable disfacilitation of medial frontal neuronal populations is proposed as the basis of our findings.

A Native Haitian Woman with Unverricht-Lundborg Disease.

Unverricht-Lundborg disease (ULD) is an autosomal recessive progressive myoclonic epilepsy. The prevalence is highest in specific European countries and North Africa. Affected individuals have myoclonic and tonic-clonic seizures and a variable degree of ataxia and cognitive impairment. We report a native Haitian woman with ULD who was wheelchair bound due to nearly continuous myoclonic seizures exacerbated by activity and emotional distress. The seizures and their dramatic increase with volitional activity were recorded during video electroencephalography monitoring. Rational antiepileptic drug therapy controlled the seizures well enough for the patient to achieve a level of independence she had not experienced in over 25 years.

EEG asymmetry and BIS/BAS among healthy adolescents.

Asymmetry in frontal alpha activation (FAA) has been associated with specific behavior patterns. Greater activation in the left frontal cortex is related to "approach" motivation, while greater activation in the right cortex is associated with "withdrawal" motivation. Moreover, resting FAA is stable over time among adults. This stability has not been demonstrated among adolescents, and the correspondence between resting FAA and personality has been inconsistently observed. The present study examined stability of FAA and the association between resting FAA and behavioral activation among adolescents. At baseline and 4 months, 99 adolescents completed a resting electroencephalogram (EEG) and a pencil-and-paper measure of personality (BIS/BAS). FAA showed good stability over time (Intra-class correlation coefficient=0.65, p<0.001), but there was no correlation between FAA and personality. Results are interpreted in light of a capability model of FAA; namely, that asymmetry may emerge under conditions of stimulation and recede during resting.

Diminution of the NMDA receptor NR2B subunit in cortical and subcortical areas of WAG/Rij rats.

Modulation of glutamatergic NMDA receptors affects the synchronization of spike discharges in in WAG/Rij rats, a valid genetic animal model of absence epilepsy. In this study, we describe the alteration of NR2B subunit of NMDA receptors expression in WAG/Rij rats in different somatosensory cortical layers and in hippocampal CA1 area. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The distribution of NR2B receptors was assessed by immunohistochemical staining in WAG/Rij and compared with age-matched Wistar rats. The expression of NR2B subunit was significantly decreased in different somatosensory cortical layers in 2- and 6-month-old WAG/Rij rats. In addition, the distribution of NR2B in hippocampal CA1 area was lower in 6-month-old WAG/Rij compared with age-matched Wistar rats. The reduction of NR2B receptors in different brain areas points to disturbance of glutamate receptors expression in cortical and subcortical areas in WAG/Rij rats. An altered subunit assembly of NMDA receptors may underlie cortical hyperexcitability in absence epilepsy.