Phoenix, AZ, United States
Phoenix, AZ, United States

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Research Triangle Institute, Virginia Commonwealth University and Barrow Neurological Institute | Date: 2012-11-19

The invention provides hydroxybupropion analogues capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.


The transciliary supraorbital approach (TCSO) provides an anterior view for visualizing sellar, parasellar, and suprasellar structures. Whether an orbital osteotomy adds to this exposure has not been quantified. We quantitatively evaluated the TCSO and benefits of an additional orbital osteotomy for exposing common sites of anterior circulation aneurysms. Under image guidance, TCSO and orbital osteotomy were performed on 10 sides of 5 cadaver heads to quantify exposures of 4 surgical targets: (1) the junction of the anterior cerebral and anterior communicating arteries (ACoA); (2) the internal carotid artery (ICA) at the level of the posterior communicating artery (PCoA); (3) the bifurcation of the ICA; and (4) the middle cerebral artery (MCA) bifurcation. Horizontal and vertical angles of attack and surgical freedom for instrument manipulation were measured before and after the orbital rim and roof were removed. An orbital osteotomy significantly increased surgical freedom to the ACoA (from 471.15 +/- 182.14 mm2 to 683.35 +/- 283.78 mm2, P = .021); PCoA (from 746.58 +/- 242.78 mm2 to 966.23 +/- 360.22 mm2, P = .007); ICA bifurcation (from 616.08 +/- 310.95 mm2 to 922.38 +/- 374.88 mm2, P = .002); and MCA bifurcation (from 1160.77 +/- 412.03 mm2 to 1597.71 +/- 733.18 mm2, P = .004). There were no significant differences in horizontal angles of attack. The vertical angles of attack were significantly greater after orbital osteotomy, principally with the ACoA and ICA bifurcation as targets. TCSO combined with orbital osteotomy improves exposure. Removing the orbital rim and roof increases the area for instrument use and improves the vertical angle of attack to common sites in the anterior circulation involving aneurysms.


Otero-Millan J.,Barrow Neurological Institute
Journal of vision | Year: 2014

Microsaccades, small involuntary eye movements that occur once or twice per second during attempted visual fixation, are relevant to perception, cognition, and oculomotor control and present distinctive characteristics in visual and oculomotor pathologies. Thus, the development of robust and accurate microsaccade-detection techniques is important for basic and clinical neuroscience research. Due to the diminutive size of microsaccades, however, automatic and reliable detection can be difficult. Current challenges in microsaccade detection include reliance on set, arbitrary thresholds and lack of objective validation. Here we describe a novel microsaccade-detecting method, based on unsupervised clustering techniques, that does not require an arbitrary threshold and provides a detection reliability index. We validated the new clustering method using real and simulated eye-movement data. The clustering method reduced detection errors by 62% for binocular data and 78% for monocular data, when compared to standard contemporary microsaccade-detection techniques. Further, the clustering method's reliability index was correlated with the microsaccade-detection error rate, suggesting that the reliability index may be used to determine the comparative precision of eye-tracking devices.


Chung S.S.,Barrow Neurological Institute
Therapeutic Advances in Neurological Disorders | Year: 2015

Topiramate has been widely utilized worldwide as an effective medication against partial- and generalized-onset seizures. Extended-release topiramate was developed to provide patients with the convenience of once-daily dosing and potentially improved tolerability by reducing serum concentration fluctuation. USL255 is a once-daily, extended-release formulation of topiramate, which was recently approved in the USA. Compared with immediate-release topiramate taken twice daily, once-daily USL255 provides equivalent topiramate exposure with a 26% reduction in plasma fluctuations. A multinational, phase III, randomized, double-blind, placebo-controlled clinical trial in patients with refractory partial-onset seizures demonstrated that USL255 (200 mg/day) significantly improved seizure control and was well tolerated with low overall neuropsychiatric and neurocognitive adverse events. © The Author(s), 2015.


Craig A.D.,Barrow Neurological Institute
Brain structure & function | Year: 2010

This article addresses the neuroanatomical evidence for a progression of integrative representations of affective feelings from the body that lead to an ultimate representation of all feelings in the bilateral anterior insulae, or "the sentient self." Evidence for somatotopy in the primary interoceptive sensory cortex is presented, and the organization of the mid-insula and the anterior insula is discussed. Issues that need to be addressed are highlighted. A possible basis for subjectivity in a cinemascopic model of awareness is presented.


Craig A.D.(B.),Barrow Neurological Institute
Brain Structure and Function | Year: 2010

This article addresses the neuroanatomical evidence for a progression of integrative representations of affective feelings from the body that lead to an ultimate representation of all feelings in the bilateral anterior insulae, or "the sentient self." Evidence for somatotopy in the primary interoceptive sensory cortex is presented, and the organization of the mid-insula and the anterior insula is discussed. Issues that need to be addressed are highlighted. A possible basis for subjectivity in a cinemascopic model of awareness is presented. © 2010 Springer-Verlag.


Craig A.D.B.,Barrow Neurological Institute
Annals of the New York Academy of Sciences | Year: 2011

An ascending sensory pathway that underlies feelings from the body, such as cooling or toothache, terminates in the posterior insula. Considerable evidence suggests that this activity is rerepresented and integrated first in the mid-insula and then in the anterior insula. Activation in the anterior insula correlates directly with subjective feelings from the body and, strikingly, with all emotional feelings. These findings appear to signify a posterior-to-anterior sequence of increasingly homeostatically efficient representations that integrate all salient neural activity, culminating in network nodes in the right and left anterior insulae that may be organized asymmetrically in an opponent fashion. The anterior insula has appropriate characteristics to support the proposal that it engenders a cinemascopic model of human awareness and subjectivity. This review presents the author's views regarding the principles of organization of this system and discusses a possible sequence for its evolution, as well as particular issues of historical interest. © 2011 New York Academy of Sciences.


Sanai N.,Barrow Neurological Institute
Current Opinion in Neurology | Year: 2012

PURPOSE OF REVIEW: In recent years, the safety and efficacy of neurosurgical intervention has rapidly improved for brain tumor patients. Technological advances, combined with refined intraoperative techniques, now enable well tolerated surgical access to any region of the human brain. For patients with gliomas, these improvements have redefined the clinical possibilities, and here we review several emerging operative strategies that are essential for next-generation neurosurgical oncologists and major brain tumor centers. RECENT FINDINGS: The value of glioma extent of resection remains controversial, but review of the modern literature reveals important opportunities for early neurosurgical intervention. Although microsurgical resection must be balanced by the risk of neurological compromise, improvements in intraoperative stimulation techniques now enable resection of highly eloquent tumors with minimal morbidity. Additionally, the emergence of fluorescence-guided surgery as a new operative paradigm provides a unique opportunity to resect tumors to the margins of microscopic infiltration. SUMMARY: Neurosurgical intervention remains the first step in effective glioma management. With intraoperative mapping techniques, aggressive microsurgical resection can be safely pursued even when tumors occupy essential functional pathways. With the development of tumor-specific fluorophores, such as 5-aminolevulinic acid, real-time microscopic visualization of tumor infiltration can be surgically targeted prior to adjuvant therapy. © 2012 Wolters Kluwer Health / Lippincott Williams & Wilkins.


Prigatano G.P.,Barrow Neurological Institute
Cortex | Year: 2014

Disturbances of self-awareness are observed in a wide variety of patients. While group studies can provide useful information concerning potential mechanisms underlying these complex disturbances, experienced clinicians, such as Babinski, recognized the potential value of repeated observations on individual patients to insure the reliability of findings and to aid in diagnosis. This paper describes patterns of impaired self-awareness (ISA) that are observed in clinical practice that suggest a model for clinical classification. Repeated observations are reported on four patients ranging from anosognosia for hemiplegia (AHP), ISAassociated with bilateral cerebral dysfunction with frontal lobe involvement, and apparent denial of disability (DD). A patient who presents with denial of ability (DA) is also studied for comparison purposes. When coupled with brain imaging findings, the nature of the patients' subjective responses to feedback regarding their functional capacities, speed of finger tapping in the left, nondominant hand, and their capacity to express and perceive affect suggests different clinical correlates in these four conditions. © 2014 Elsevier Ltd.


The rationale for choosing between the condylar fossa and transcondylar variations of the far-lateral approach requires understanding of the relationships between the occipital condyle, jugular tubercle, and hypoglossal canal. We examined the anatomic relationship of these 3 structures and analyzed the effect that changes in these relationships have on the surgical exposure and angle of attack for these 2 approaches. Anatomic measurements of 5 cadaveric heads from 3-dimensional computed tomographic scans were compared with direct measurements of the same specimens. The condylar fossa and transcondylar approach were performed sequentially in 8 of 10 sides. Surgical exposure and angle of attack were measured after each exposure. The jugular tubercle (JT) angle (JTA) measures the angle formed by reference points on the condyle, hypoglossal canal, and JT. When the JT and occipital condyle are not prominent (JTA > 180 degrees ), the transcondylar approach does not significantly increase petroclival or brainstem exposure compared with the condylar fossa approach; however, it does significantly increase the angle of attack to the junction of the posterior inferior cerebellar and vertebral arteries and the surgical angle for the medial part of the JT (P < .05). The condylar fossa and transcondylar approaches provide similar exposures of the petroclivus and brainstem when the JT and occipital condyle are not prominent (JTA > 180 degrees on 3-dimensional computed tomographic). However, for lesions below the hypoglossal canal, the transcondylar approach is preferred because it significantly increases the angle of attack.

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