Faculty Bibliography

We typically misestimate the dimensions of our body e.g., we perceive our fingers as shorter, and our torso as more elongated, than they actually are. It stands to reason that those metric biases may also extend to objects that we interact with, to facilitate attunement with the environment. To explore this hypothesis, we compared the metric representations of seven objects and the subjects' own hand using the Line Length Judgment task, in six experiments involving 152 healthy subjects. We evaluated the size estimation errors made for each target (hand or previously observed objects) by asking subjects to compare the vertical or horizontal dimension of a specific target against the length of a vertical or horizontal line. As expected, we showed that the hand is misperceived in its dimensions. Interestingly, we found that metric biases are also present for daily-life objects, such as a mobile phone and a coffee mug, and are not affected by familiarity with the objects. In contrast, objects that are less likely to be manipulated, either because they are potentially harmful or disgusting, were differently represented. Furthermore, the propensity to interact with an object, rated by an independent sample of subjects, best predicted the pattern of metric biases associated with that object. Taken together, these findings support the hypothesis that biases affecting the hand representation extend to objects that elicit action-oriented behavior, highlighting the importance of studying the body as integrated and active in the environment.

Ethmoidal dural arteriovenous fistulas are vascular malformations with arterial supply from the anterior ethmoidal artery and ultimate drainage into the sagittal sinus.1-3 They are characterized by a high risk of hemorrhage. Microsurgical disconnection of the fistula represents a safe and robust treatment option. Endovascular treatment requires catheterization of the ophthalmic artery and carries a risk of visual deficits. The supraorbital craniotomy provides an excellent corridor to the anterior skull base and is well suited for the treatment of ethmoidal dural arteriovenous fistulas. The supraorbital craniotomy may be performed through a transpalpebral "eyelid" incision. The transpalpebral incision allows for a well-hidden scar and does not have any associated hair loss, as can be seen with the eyebrow incision. The patient consented to the procedure and being videotaped.

BACKGROUND:Eye-hand coordination (EHC) is a sophisticated act that requires interconnected processes governing synchronization of ocular and manual motor systems. Precise, timely and skillful movements such as reaching for and grasping small objects depend on the acquisition of high-quality visual information about the environment and simultaneous eye and hand control. Multiple areas in the brainstem and cerebellum, as well as some frontal and parietal structures, have critical roles in the control of eye movements and their coordination with the head. Although both cortex and cerebellum contribute critical elements to normal eye-hand function, differences in these contributions suggest that there may be separable deficits following injury. METHOD/METHODS:As a preliminary assessment for this perspective, we compared eye and hand-movement control in a patient with cortical stroke relative to a patient with cerebellar stroke. RESULT/RESULTS:We found the onset of eye and hand movements to be temporally decoupled, with significant decoupling variance in the patient with cerebellar stroke. In contrast, the patient with cortical stroke displayed increased hand spatial errors and less significant temporal decoupling variance. Increased decoupling variance in the patient with cerebellar stroke was primarily due to unstable timing of rapid eye movements, saccades. CONCLUSION/CONCLUSIONS:These findings highlight a perspective in which facets of eye-hand dyscoordination are dependent on lesion location and may or may not cooperate to varying degrees. Broadly speaking, the results corroborate the general notion that the cerebellum is instrumental to the process of temporal prediction for eye and hand movements, while the cortex is instrumental to the process of spatial prediction, both of which are critical aspects of functional movement control.

Enhancing repair of myelin is an important therapeutic goal in many neurological disorders characterized by demyelination. In the healthy adult brain, ventral neural stem cells (vNSCs) in the subventricular zone, marked by GLI1 expression, do not generate oligodendrocytes. However, in response to demyelination, their progeny are recruited to lesions where they differentiate into oligodendrocytes and ablation of GLI1 further enhances remyelination. GLI1 and GLI2 are closely related transcriptional activators but the role of GLI2 in remyelination by vNSCs is not clear. Here, we show that genetic ablation of Gli1 in vNSCs increases GLI2 expression and combined loss of both transcription factors decreases the recruitment and differentiation of their progeny in demyelinated lesions. These results indicate that GLI1 and GLI2 have distinct, non-redundant functions in vNSCs and their relative levels play an essential role in the response to demyelination.

Seizures are a common presentation in both emergency departments and general pediatric practices. Epilepsy affects more than 3.4 million people nationwide, of which approximately 500,000 are children, with greater than 200,000 first-time seizures each year.¹ Of the affected individuals, as many as 100,000 are estimated to experience status epilepticus (SE). Both general practitioners and neurologists alike must be able to define, recognize and treat seizure emergencies. This review article defines and describes SE, discusses the emergency evaluation and management of SE that is both new-onset and breakthrough in people with epilepsy, reviews the current treatment recommendations for SE in both the home and hospital settings, and introduces special populations that may be at high risk for SE or other seizure emergencies.

A subset of glioblastomas (GBMs) harbors potentially druggable oncogenic FGFR3-TACC3 (F3T3) fusions. However, their associated molecular and clinical features are poorly understood. Here we analyze the frequency of F3T3-fusion positivity, its associated genetic and methylation profiles, and its impact on survival in 906 IDH-wildtype GBM patients. We establish an F3T3 prevalence of 4.1% and delineate its associations with cancer signaling pathway alterations. F3T3-positive GBMs had lower tumor mutational and copy-number alteration burdens than F3T3-wildtype GBMs. Although F3T3 fusions were predominantly mutually exclusive with other oncogenic RTK pathway alterations, they did rarely co-occur with EGFR amplification. They were less likely to harbor TP53 alterations. By methylation profiling, they were more likely to be assigned the mesenchymal or RTK II subclass. Despite being older at diagnosis and having similar frequencies of MGMT promoter hypermethylation, patients with F3T3-positive GBMs lived about 8 months longer than those with F3T3-wildtype tumors. While consistent with IDH-wildtype GBM, F3T3-positive GBMs exhibit distinct biological features, underscoring the importance of pursuing molecular studies prior to clinical trial enrollment and targeted treatment.

Objective: To investigate the intra-observer reproducibility of Ki-67　　　assessment in breast cancers using three methods based on digital slide. Methods: Thirty cases of invasive breast cancer tissues were immunostained for Ki-67 by automatic stainer, and then scanned into digital pathological slides. Ki-67 positive index was measured individually by three pathologists using size-set visual assessment of hot spot (SSVAHS), size-set semi-automatic counting of hot spot(SSSACHS), and size-set automatic counting of hot spot (SSACHS), respectively, and repeated for 10 times. Intraclass correlation coefficient (ICC) of each assessment method was calculated, and the intraobserver reliability was classified as excellent, good, fair and poor according to ICC. Results: The ICC by 3 pathologists using SSVAHS was 0.832, 0.843 and 0.826, respectively, The ICC using SSSACHS was 0.926,0.938,0.929, and the ICC using SSACHS was 0.964, 0.971 and 0.968.The intraobserver reliability level of all three methods was excellent. Conclusion: The three methods of Ki-67 assessment achieve satisfactory intraobserver reproducibility, and the order of reproducibility from high to low is SSACHS, SSSACHS, and SSVAHS.

Impaired clearance in the Alzheimer's Disease (AD) brain is key in the formation of Aβ parenchymal plaques and cerebrovascular deposits known as cerebral amyloid angiopathy (CAA), present in >80% of AD patients and ~50% of non-AD elderly subjects. Aβ deposits are highly heterogeneous, containing multiple fragments mostly derived from catabolism of Aβ40/Aβ42, which exhibit dissimilar aggregation properties. Remarkably, the role of these physiologically relevant Aβ species in cerebrovascular injury and their impact in vascular pathology is unknown. We sought to understand how heterogeneous Aβ species affect cerebral endothelial health and assess whether their diverse effects are associated with the peptides aggregation propensities. We analyzed cerebral microvascular endothelial cell (CMEC) viability, blood-brain barrier (BBB) permeability, and angiogenesis, all relevant aspects of brain microvascular dysfunction. We found that Aβ peptides and fragments exerted differential effects on cerebrovascular pathology. Peptides forming mostly oligomeric structures induced CMEC apoptosis, whereas fibrillar aggregates increased BBB permeability without apoptotic effects. Interestingly, all Aβ species tested inhibited angiogenesis in vitro. These data link the biological effects of the heterogeneous Aβ peptides to their primary structure and aggregation, strongly suggesting that the composition of amyloid deposits influences clinical aspects of the AD vascular pathology. As the presence of predominant oligomeric structures in proximity of the vessel walls may lead to CMEC death and induction of microhemorrhages, fibrillar amyloid is likely responsible for increased BBB permeability and associated neurovascular dysfunction. These results have the potential to unveil more specific therapeutic targets and clarify the multifactorial nature of AD.

BACKGROUND AND PURPOSE/OBJECTIVE:Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied. MATERIALS AND METHODS/METHODS:This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core. RESULTS:We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03). CONCLUSION/CONCLUSIONS:In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.