Faculty Bibliography

BACKGROUND:There is a paucity of data in the literature specific to men with epilepsy on anti-seizure medication (ASM). The current study investigated the time to conception as well as the gestational and the neurodevelopmental outcomes of offspring of men with epilepsy on ASM compared to controls. Additionally, the prevalence of psychiatric comorbidities, and measures of sexual performance in males with and without epilepsy were analyzed. METHODS:A total of 450 male patients with and without epilepsy at one hospital were provided questionnaires to determine demographic characteristics, epilepsy history, type of ASM at the time of conception, comorbidities and sexual health. Time to conception, fertility methods and offspring birth and developmental history born to males with and without epilepsy was recorded. Survey data was evaluated using Student's t-test for continuous variables and Fisher's exact test for categorical variables. Odds ratio (OR) were calculated to determine associations between the measured data. RESULTS:After matching for age, we analyzed a total of 110 males with epilepsy and 110 without epilepsy. In the epilepsy group there was a higher rate of psychiatric comorbidities such as major depressive disorder, general anxiety disorder, bipolar disorder, and suicidal ideation when compared to the control group (N = 110; OR 3.39; 95% IC: 1.87-6.13, p < 0.001). Males with epilepsy also had a higher frequency of low erection scores when compared to males without epilepsy (N = 70 with epilepsy, N = 76 without epilepsy; OR 3.67; 95% IC: 1.44-9.39, p = 0.005). Of the 110 men with a diagnosis of epilepsy, 17 conceived children while using ASMs (38 total children). A total of 18.42% of children born to fathers on ASMs experienced developmental delays compared to 2.63% of controls, however this result was not statistically significant (p = 0.056). In addition, we did not find that offspring had significantly different birth weights or gestational ages in men on ASM compared to controls (p > 0.05). CONCLUSIONS:The present study suggests that men with epilepsy have an increased incidence of psychiatric comorbidities, and altered sexual performance, specifically erectile dysfunction, when compared with men without epilepsy. There was no statistically significant difference in the rates of developmental disorders and birth characteristics among those men with epilepsy on ASM at the time of conception and controls.

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.

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.

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.

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.