Citations

Objective: The study sought to evaluate whether topiramate prevents development of chronic daily headache (CDH, ≥15 headache days per month) in adult subjects with high-frequency episodic migraine (HFEM, 9–14 migraine headache days/month). A secondary objective was to assess the efficacy of topiramate as preventive migraine treatment in this population. Methods: This was a multicenter, randomized, double-blind, placebo-controlled study comparing topiramate 100 mg/day and placebo for 26 weeks. The primary efficacy variable was new-onset CDH at month 6. Secondary efficacy measures included migraine and headache days. Adverse events (AEs) were evaluated. Results: A total of 159 topiramate subjects and 171 placebo subjects were efficacy-evaluable. At month 6, 1.4% of topiramate subjects versus 2.3% of placebo subjects had CDH ( p = .589). Compared with placebo, topiramate treatment was associated with statistically significant reductions in mean number of migraine days (6.6 vs. 5.3/28 days; p = .001) and headache days (6.6 vs 5.3/28 days; p = .001). Most commonly reported AEs in the topiramate versus placebo group included paresthesia (32.4% vs. 7.0%), fatigue (14.8% vs. 8.6%), dizziness (11.4% vs. 7.6%) and nausea (10.8% vs. 9.2%). Conclusion: Topiramate 100 mg/day did not prevent the development of CDH at six months in subjects with HFEM. Topiramate was effective in reducing headache days and migraine headache days and generally well tolerated.

The role of the Alzheimer's Disease Neuroimaging Initiative Genetics Core is to facilitate the investigation of genetic influences on disease onset and trajectory as reflected in structural, functional, and molecular imaging changes; fluid biomarkers; and cognitive status. Major goals include (1) blood sample processing, genotyping, and dissemination, (2) genome‐wide association studies (GWAS) of longitudinal phenotypic data, and (3) providing a central resource, point of contact and planning group for genetics within the Alzheimer's Disease Neuroimaging Initiative. Genome‐wide array data have been publicly released and updated, and several neuroimaging GWAS have recently been reported examining baseline magnetic resonance imaging measures as quantitative phenotypes. Other preliminary investigations include copy number variation in mild cognitive impairment and Alzheimer's disease and GWAS of baseline cerebrospinal fluid biomarkers and longitudinal changes on magnetic resonance imaging. Blood collection for RNA studies is a new direction. Genetic studies of longitudinal phenotypes hold promise for elucidating disease mechanisms and risk, development of therapeutic strategies, and refining selection criteria for clinical trials.

Purpose. Review the safety and long-term success with portosystemic shunts in children at a single institution. Methods. An IRB-approved, retrospective chart review of all children ages 19 and undergoing surgical portosystemic shunt from January 1990–September 2008. Results. Ten patients were identified, 8 females and 2 males, with a mean age of 15 years (range 5–19 years). Primary diagnoses were congenital hepatic fibrosis (5), hepatic vein thrombosis (2), portal vein thrombosis (2), and cystic fibrosis (1). Primary indications were repeated variceal bleeding (6), symptomatic hypersplenism (2), and significant liver dysfunction (2). Procedures performed were distal splenorenal bypass (4), side-to-side portocaval shunt (3), proximal splenorenal shunt (2), and an interposition H-graft portocaval shunt (1). There was no perioperative mortality and only minor morbidity. Seventy percent of patients had improvement of their symptoms. Eighty percent of shunts remained patent. Two were occluded at a median follow-up of 50 months (range 0.5–13.16 years). Two patients underwent subsequent liver transplantation. Two patients died at 0.5 and 12.8 years postoperatively, one from multisystem failure with cystic fibrosis and one from post-operative transplant complications. Conclusions. The need for portosystemic shunts in children is rare. However, in the era of liver transplantation, portosystemic shunts in selected patients with well-preserved liver function remains important. We conclude that portosystemic shunts are safe and efficacious in the control of variceal hemorrhage and symptoms related to hypersplenism.

Evidence has emerged that the clinical benefit of tamoxifen is related to the functional status of the hepatic metabolizing enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6 is the key enzyme responsible for the generation of the potent tamoxifen metabolite, endoxifen. Multiple studies have examined the relationship of CYP2D6 status to breast cancer outcomes in tamoxifen-treated women; the majority of studies demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a greater risk of breast cancer recurrence. As a result, practitioners must be aware that some of the most commonly prescribed medications coadministered with tamoxifen interfere with CYP2D6 function, thereby reducing endoxifen concentrations and potentially increasing the risk of breast cancer recurrence. After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen.

Object The aim of this study was to evaluate the outcomes of Gamma Knife surgery (GKS) when used for patients with intractable cluster headache (CH). Methods Four participating centers of the North American Gamma Knife Consortium identified 17 patients who underwent GKS for intractable CH between 1996 and 2008. The median patient age was 47 years (range 26–83 years). The median duration of pain before GKS was 10 years (range 1.3–40 years). Seven patients underwent unsuccessful prior surgical procedures, including microvascular decompression (2 patients), microvascular decompression with glycerol rhizotomy (2 patients), deep brain stimulation (1 patient), trigeminal ganglion stimulation (1 patient), and prior GKS (1 patient). Fourteen patients had associated autonomic symptoms. The radiosurgical target was the trigeminal nerve (TN) root and the sphenopalatine ganglion (SPG) in 8 patients, only the TN in 8 patients, and only the SPG in 1 patient. The median maximum TN and SPG dose was 80 Gy. Results Favorable pain relief (Barrow Neurological Institute Grades I–IIIb) was achieved and maintained in 10 (59%) of 17 patients at a median follow-up of 34 months. Three patients required additional procedures (repeat GKS in 2 patients, hypothalamic deep brain stimulation in 1 patient). Eight (50%) of 16 patients who had their TN irradiated developed facial sensory dysfunction after GKS. Conclusions Gamma Knife surgery for intractable, medically refractory CH provided lasting pain reduction in approximately 60% of patients, but was associated with a significantly greater chance of facial sensory disturbances than GKS used for trigeminal neuralgia.

Background and Purpose— Telemedicine techniques can be used to address the rural–metropolitan disparity in acute stroke care. The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use, improved data collection, low risk of complications, low technical complications, and favorable assessment times. The main objective of the STRokE DOC Arizona TIME (The Initial Mayo Clinic Experience) trial was to determine the feasibility of establishing, de novo, a single-hub, multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol. Methods— Methods included prospective, single-hub, 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine system designed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. The primary outcome measure was whether the decision to give thrombolysis was correct. Secondary outcomes were rate of thrombolytic use, 90-day functional outcomes, incidence of intracerebral hemorrhages, and technical observations. Results— From December 2007 to October 2008, 54 patients were assessed, 27 of whom were randomized to each arm. Mean National Institutes of Health Stroke Scale score at presentation was 7.3 (SD 6.2) points. No consultations were aborted; however, technical problems (74%) were prevalent in the telemedicine arm. Overall, the correct treatment decision was established in 87% of the consultations. Both modalities, telephone (89% correct) and telemedicine (85% correct), performed well. Intravenous thrombolytic treatment was used in 30% of the telemedicine and telephone consultations. Good functional outcomes at 90 days were not significantly different. There were no statistically significant differences in mortality (4% in telemedicine and 11% in telephone) or rates of intracerebral hemorrhage (4% in telemedicine and 0% in telephone). Conclusions— It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub, multispoke rural hospital telestroke research network in Arizona. The trial was not designed to have sufficient power to detect a difference between the 2 consultative modes: telemedicine and telephone-only. Whether by telemedicine or telephone consultative modalities, there were appropriate treatment decisions, high rates of thrombolysis use, improved data collection, low rates of intracerebral hemorrhage, and equally favorable time requirements. The learning curve was steep for the hub and spoke personnel of the new telestroke network, as reflected by frequent technical problems. Overall, the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise.

Computational fluid dynamics (CFD) studies provide a valuable tool for evaluating the role of hemodynamics in vascular diseases such as cerebral aneurysms and atherosclerosis. However, such models necessarily only include isolated segments of the vasculature. In this work, we evaluate the influence of geometric approximations in vascular anatomy on hemodynamics in elastase induced saccular aneurysms in rabbits. One representative high aspect ratio (AR—height/neck width) aneurysm and one low AR aneurysm were created at the origin of the right common carotid artery in two New Zealand white rabbits. Three-dimensional (3D) reconstructions of the aneurysm and surrounding arteries were created using 3D rotational angiographic data. Five models with varying extents of neighboring vasculature were created for both the high and low AR cases. A reference model included the aneurysm sac, left common carotid artery (LCCA), aortic arch, and downstream trifurcation/quadrification. Three-dimensional, pulsatile CFD studies were performed and streamlines, wall shear stress (WSS), oscillatory shear index, and cross sectional velocity were compared between the models. The influence of the vascular domain on intra-aneurysmal hemodynamics varied between the low and high AR cases. For the high AR case, even a simple model including only the aneurysm, a small section of neighboring vasculature, and simple extensions captured the main features of the steamline and WSS distribution predicted by the reference model. However, the WSS distribution in the low AR case was more strongly influenced by the extent of vasculature. In particular, it was necessary to include the downstream quadrification and upstream LCCA to obtain good predictions of WSS. The findings in this work demonstrate the accuracy of CFD results can be compromised if insufficient neighboring vessels are included in studies of hemodynamics in elastase induced rabbit aneurysms. Consideration of aspect ratio, hemodynamic parameters of interest, and acceptable magnitude of error when selecting the vascular domain will increase reliability of the results while decreasing computational time.

OBJECTIVE:No study has evaluated the association between state endorsement of American Academy of Pediatrics (AAP) and American Public Health Association (APHA) national guidelines and unnecessary exclusion decisions. We sought to determine the rate of unnecessary exclusion decisions by child care directors in a state that endorses AAP/APHA guidelines and to identify factors that are associated with higher unnecessary exclusion decisions.METHODS:A telephone survey was administered to directors in metropolitan Milwaukee, Wisconsin. Directors were randomly sampled from a list of 971 registered centers. Director, center, and neighborhood characteristics were obtained. Directors reported whether immediate exclusion was indicated for 5 vignettes that featured children with mild illness that do not require exclusion by AAP/APHA guidelines. Weighted data were summarized by using descriptive statistics. Regression analysis was used to identify factors that were associated with directors' exclusion decisions.RESULTS:A total of 305 directors completed the survey. Overall, directors would unnecessarily exclude 57% of children. More than 62% had never heard of the AAP/APHA guidelines. Regression analysis showed fewer exclusions among more experienced compared with less experienced directors, among larger centers compared with smaller centers, and among centers that were located in areas with a higher percentage of female heads of household. Centers with ≤10% children on state-assisted tuition excluded more.CONCLUSIONS:High rates of inappropriate exclusion persist despite state endorsement of AAP/APHA guidelines. Focused initial and ongoing training of directors regarding AAP/APHA guidelines may help to reduce high rates of unnecessary exclusions.