Lateral Skull Base Chordoma Mimicking a Paraganglioma.

We present an unusual case of chordoma arising entirely from the lateral skull base with imaging features suggestive of a paraganglioma. Clinical history, management, histopathology, and imaging characteristics are described, including a review of gallium-dotate PET scanning somatostatinreceptor-positive tumors. We further provide a review of management options, including a summary of our approach with surgical biopsy via retrosigmoid and resection via transtemporal approaches. Based on radiologic characteristics and location, lateral skull base chordoma may arise with isolated lateral skull base involvement and has the potential to be misidentified as a glomus jugulare on initial workup.

Multifocal neutrophilic meningoencephalitis: a novel disorder responsive to anakinra.

We report a 57-year-old man with recurrent meningoencephalitis resulting in bouts of altered consciousness, encephalopathy, tremors, focal seizures, and paraparesis. The neurological manifestations were accompanied by fever and leukocytosis in the absence of other systemic manifestations. MRI abnormalities of the brain, brainstem, spinal cord and meninges and CSF pleocytosis and elevated protein were observed. Exhaustive studies failed to reveal an etiology. Brain biopsy revealed nodules of neutrophils and macrophages, but no vasculitis. The lesions were not vasocentric as would be expected with neuro-Behcet's disease and neuro-Sweet's disease. The disorder was responsive to high-dose corticosteroid therapy and, ultimately, to anakinra, an IL-1α and IL-1ß receptor antagonist.

Navigated Ultrasonic Osteotomy to Aid in En Bloc Chordoma Resection via Spondylectomy.

BACKGROUND: Chordomas are rare, locally malignant tumors derived from remnants of the notochord that can manifest anywhere in the spine or base of the skull. Surgical treatment for chordomas of the lumbar spine often fails to achieve successful en bloc resection, which is critical to minimizing recurrence risk. CASE DESCRIPTION: In this case report, the authors describe total en bloc resection of a lumbar vertebral body chordoma via the first documented approach of navigated ultrasonic osteotomy for spondylectomy. The patient is a 43-year-old man with end-stage renal disease, requiring dialysis, secondary to diabetes mellitus. The lesion in question was incidentally discovered in the L5 vertebral body during full body scanning for evaluation for a renal transplant. The lesion was diagnosed as a chordoma via percutaneous coaxial needle biopsy. Allogeneic renal transplant was canceled pending treatment of this newly discovered lesion. A combined, staged approach of L3-pelvis posterior instrumented fusion, L5 laminectomy and spondylectomy, and anterior L5 cage reconstruction with L4-S1 fusion was planned. Intraoperative computed tomography scan was performed and stereotactic osteotomies were planned. Ultrasonic osteotome (SONOPET Ultrasonic Aspirator) was registered as a navigation tool and employed, after verification, to complete the posterior stereotactic osteotomies, with postoperative computed tomography, magnetic resonance imaging, and pathology demonstrating successful en bloc resection. The navigated osteotome provided a critical combination of surgical precision and efficiency intraoperatively. CONCLUSIONS: This approach offers a promising technological adjunct for the treatment of complex spine tumors requiring precise resection and reconstruction.

Microsurgical Trapping and Excision of Ruptured Mycotic Aneurysms in a Patient with Mitral Valve Endocarditis: A Surgical Technique.

This case Video 1 demonstrates a microsurgical technique for trapping and excision of 2 ruptured mycotic aneurysms. The patient was a 64-year-old man with severe mitral regurgitation and valvular vegetations suggestive of endocarditis. On examination, the patient presented with speech difficulty. Preoperative imaging showed a large left temporoparietal intracerebral hemorrhage and associated sulcal subarachnoid hemorrhage from 2 distal aneurysms of the left middle cerebral artery. In the presence of ruptured aneurysms in a patient who requires anticoagulation for valve replacement, endovascular options are limited. For aneurysms located in an eloquent area in the left hemisphere, microsurgical treatment with small corridors can facilitate excision and minimize damage to the surrounding tissue. As such, the patient was treated with microsurgical trapping and excision of the aneurysms followed by evacuation of intraparenchymal hemorrhage using stereotactic navigation. Intraoperative neurophysiologic monitoring was used to prepare for a potential bypass in the event of inadequate collaterals or changes in neurophysiologic potentials. Postoperatively, the patient remained symmetric in his motor strength and had improved speech deficits, indicative of an uneventful recovery. The patient was cleared for full anticoagulation and valve replacement on postoperative day 10. The patient underwent intravenous antibiotic therapy with ceftriaxone before undergoing mitral valve replacement by cardiac surgery.

A partially-open inward-facing intermediate conformation of LeuT is associated with Na+ release and substrate transport.

Neurotransmitter:sodium symporters (NSS), targets of antidepressants and psychostimulants, clear neurotransmitters from the synaptic cleft through sodium (Na+)-coupled transport. Substrate and Na+ are thought to be transported from the extracellular to intracellular space through an alternating access mechanism by coordinated conformational rearrangements in the symporter that alternately expose the binding sites to each side of the membrane. However, the mechanism by which the binding of ligands coordinates conformational changes occurring on opposite sides of the membrane is not well understood. Here, we report the use of single-molecule fluorescence resonance energy transfer (smFRET) techniques to image transitions between distinct conformational states on both the extracellular and intracellular sides of the prokaryotic NSS LeuT, including partially open intermediates associated with transport activity. The nature and functional context of these hitherto unidentified intermediate states shed new light on the allosteric mechanism that couples substrate and Na+ symport by the NSS family through conformational dynamics.

Cyanine fluorophore derivatives with enhanced photostability.

Fluorescence applications requiring high photostability often depend on the use of solution additives to enhance fluorophore performance. Here we demonstrate that the direct or proximal conjugation of cyclooctatetraene (COT), 4-nitrobenzyl alcohol (NBA) or Trolox to the cyanine fluorophore Cy5 dramatically enhanced fluorophore photostability without otherwise affecting its native spectral characteristics. Such conjugation is a powerful means of improving the robustness of fluorescence-based applications demanding long-lived, nonblinking fluorescence emission.

CODA-RET reveals functional selectivity as a result of GPCR heteromerization.

Here we present a new method that combines protein complementation with resonance energy transfer to study conformational changes in response to activation of a defined G protein-coupled receptor heteromer, and we apply the approach to the putative dopamine D1-D2 receptor heteromer. Remarkably, the potency of the D2 dopamine receptor (D2R) agonist R-(-)-10,11-dihydroxy-N-n-propylnoraporphine (NPA) to change the Gα(i) conformation via the D2R protomer in the D1-D2 heteromer was enhanced ten-fold relative to its potency in the D2R homomer. In contrast, the potencies of the D2R agonists dopamine and quinpirole were the same in the homomer and heteromer. Thus, we have uncovered a molecular mechanism for functional selectivity in which a drug acts differently at a G protein-coupled receptor (GPCR) protomer depending on the identity of the second protomer participating in the formation of the signaling unit--opening the door to enhancing pharmacological specificity by targeting differences between homomeric and heteromeric signaling.

Structural dissociation of attentional control and memory in adults with and without mild traumatic brain injury.

Memory and attentional control impairments are the two most common forms of dysfunction following mild traumatic brain injury (TBI) and lead to significant morbidity in patients, yet these functions are thought to be supported by different brain networks. This 3 T magnetic resonance diffusion tensor imaging (DTI) study investigates whether microstructural integrity of white matter, as measured by fractional anisotropy (FA) within a small set of individually localized regions of interest (ROIs), is associated with these cognitive domains in normal adults and adults with mild TBI. Results in a sample of 23 normal controls reveal a significant correlation between attentional control and FA within a ROI in the left hemisphere anterior corona radiata. Furthermore, the controls demonstrate a correlation between memory performance and FA in a ROI placed in the uncinate fasciculus. Next, to examine whether these relationships are found in the pathological ranges of attention, memory and microstructural white matter integrity associated with mild TBI, these analyses were applied to a group of 43 mild TBI patients. Results, which generally demonstrated a wider range of attention, memory and FA scores, replicated the correlation between attentional control and FA in left hemisphere anterior corona radiata, as well as the correlation between memory performance and FA in the uncinate fasciculus. These two sets of brain-behaviour relationships were highly specific, as shown by a lack of correlation between attention and uncinate fasciculus FA and the lack of correlation between memory performance and anterior corona radiata FA. Furthermore, a 'correlational double dissociation' was demonstrated to exist between two distinct frontal structures independently associated with attention and memory, respectively, via a series of multiple regression analyses in both normal controls and adults with mild TBI. The results of the multiple regression analyses provide direct evidence that tract-specific variation in microstructural white matter integrity among normal controls and among mild TBI patients can account for much of the variation in performance in specific cognitive domains. More generally, such findings suggest that diffusion anisotropy measurement can be used as a quantitative biomarker for neurocognitive function and dysfunction.

Response anticipation and response conflict: an event-related potential and functional magnetic resonance imaging study.

Response anticipation and response conflict processes are supported by executive control. However, few neuroimaging studies have attempted to study the relationship between these two processes in the same experimental session. In this study, we isolated brain activity associated with response anticipation (after a cue to prepare vs relax) and with response conflict (responding to a target with incongruent vs congruent flankers) and examined the independence and interaction of brain networks supporting these processes using event-related potentials (ERPs) and functional magnetic resonance imaging. Response anticipation generated a contingent negative variation ERP that correlated with shorter reaction times, and was associated with activation of a thalamo-cortico-striatal network, as well as increased gamma band power in frontal and parietal regions, and decreased spectral power in theta, alpha, and beta bands in most regions. Response conflict was associated with increased activation in the anterior cingulate cortex (ACC) and prefrontal cortex of the executive control network, with an overlap in activation with response anticipation in regions including the middle frontal gyrus, ACC, and superior parietal lobule. Although the executive control network showed increased activation in response to unanticipated versus anticipated targets, the response conflict effect was not altered by response anticipation. These results suggest that common regions of a dorsal frontoparietal network and the ACC are engaged in the flexible control of a wide range of executive processes, and that response anticipation modulates overall activity in the executive control network but does not interact with response conflict processing.

Increased oculomotor deficits during target blanking as an indicator of mild traumatic brain injury.

Given the susceptibility of cerebellar-cortical tracts to shearing injury from traumatic brain injury (TBI), we investigated impairment in the generation of predictive eye movements and its relationship to cognitive deficits in mild TBI patients using a smooth pursuit target-blanking paradigm. Compared to a target-tracking paradigm without blanking, this paradigm more greatly necessitates the generation of predictive eye movements, which are subserved by brain regions involved in cognitive processing. Mild TBI patients showed impaired prediction of target trajectories during target blanking, demonstrated by generation of saccades at earlier and more variable time points, as well as greater and more variable oculomotor error compared to controls. In addition, California Verbal Learning Test (CVLT-II) scores related to working memory, learning, and executive function were more highly correlated with oculomotor variability during target blanking than during target tracking. Our results suggest that a disruption of cerebellar-cortical connections in TBI may account for both oculomotor and cognitive impairment, and that measures of predictive eye movements during target blanking may be a sensitive metric of cognitive deficits after mild TBI.

Deficits in predictive smooth pursuit after mild traumatic brain injury.

Given that even mild traumatic brain injury (TBI) may produce extensive diffuse axonal injury (DAI), we hypothesized that mild TBI patients would show deficits in predictive smooth pursuit eye movements (SPEM), associated with impaired cognitive functions, as these processes are dependent on common white matter connectivity between multiple cerebral and cerebellar regions. The ability to predict target trajectories during SPEM was investigated in 21 mild TBI patients using a periodic sinusoidal paradigm. Compared to 26 control subjects, TBI patients demonstrated decreased target prediction. TBI patients also showed increased eye position error and variability of eye position, which correlated with decreased target prediction. In all subjects, average target prediction, eye position error and eye position variability correlated with scores related to attention and executive function on the California Verbal Learning Test (CVLT-II). However, there were no differences between TBI and control groups in average eye gain or intra-individual eye gain variability, or in performance on the Wechsler Abbreviated Scale of Intelligence (WASI), suggesting that the observed deficits did not result from general oculomotor impairment or reduced IQ. The correlation between SPEM performance and CVLT-II scores suggests that predictive SPEM may be a sensitive assay of cognitive functioning, including attention and executive function. This is the first report to our knowledge that TBI patients show impaired predictive SPEM and eye position variability, and that these impairments correlate with cognitive deficits.