Moyamoya syndrome and PHACE syndrome: clinical and radiographic characterization of the intracranial arteriopathy and response to surgical revascularization.

OBJECTIVE: PHACE syndrome (PHACES) has been linked to cervical and cerebral vascular anomalies, including persistent embryonic anastomoses and progressive steno-occlusive disease. However, no prior studies have documented the long-term response of PHACES patients with moyamoya disease to surgical revascularization with pial or myosynangiosis. The authors present their experience with 8 consecutive patients with PHACES and moyamoya disease. METHODS: Retrospective review of patients who underwent pial synangiosis revascularization for moyamoya disease with concurrent diagnosis of PHACES. RESULTS: A total of 8 patients out of 456 surgically treated moyamoya patients had a diagnosis of PHACES. All patients were female, and their average age at the time of surgical treatment was 9.3 years (range 1.8-25.8 years). Five patients had associated basilar artery anomalies or stenosis. All patients had symptomatic narrowing of the petrous segment of the internal carotid artery with tortuous collateralization. Three patients underwent unilateral pial or myo-synangiosis and 5 underwent bilateral procedures. The average hospital length of stay was 5.0 days (range 3-7 days). There were no postoperative complications. Follow-up ranged from 8 to 160 months (average 56 months). Seven of 8 patients have had follow-up angiograms and all had Matsushima grade A or B collateralization without progression of stenosis in other locations. All patients had reduced cortical FLAIR signal on 6-month follow-up MRI and no evidence of new radiographic or clinical strokes. CONCLUSIONS: Patients with moyamoya disease and PHACES had an intracranial arteriopathy characterized by ectactic anterior vasculature with concomitant basilar artery stenosis, and were all female. The patients had both radiographic and clinical responses to pial synangiosis. The surgical treatment of these patients can be challenging given facial hemangiomas located near the surgical field. Patients with unilateral disease did not have evidence of progression in other cerebral circulation during the given follow-up period.

Prediction of depression and anxiety via patient-assessed tremor severity, not physician-reported motor symptom severity, in patients with Parkinson's disease or essential tremor who have undergone deep brain stimulation.

OBJECTIVEDeep brain stimulation (DBS) is an effective therapy for movement disorders such as idiopathic Parkinson's disease (PD) and essential tremor (ET). However, some patients who demonstrate benefit on objective motor function tests do not experience postoperative improvement in depression or anxiety, 2 important components of quality of life (QOL). Thus, to examine other possible explanations for the lack of a post-DBS correlation between improved objective motor function and decreased depression or anxiety, the authors investigated whether patient perceptions of motor symptom severity might contribute to disease-associated depression and anxiety.METHODSThe authors performed a retrospective chart review of PD and ET patients who had undergone DBS at the Cleveland Clinic in the period from 2009 to 2013. Patient demographics, diagnosis (PD, ET), motor symptom severity, and QOL measures (Primary Care Evaluation of Mental Disorders 9-item Patient Health Questionnaire [PHQ-9] for depression, Generalized Anxiety Disorder 7-item Scale [GAD-7], and patient-assessed tremor scores) were collected at 4 time points: preoperatively, postoperatively, 1-year follow-up, and 2-year follow-up. Multivariable prediction models with solutions for fixed effects were constructed to assess the correlation of predictor variables with PHQ-9 and GAD-7 scores. Predictor variables included age, sex, visit time, diagnosis (PD vs ET), patient-assessed tremor, physician-reported tremor, Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score, and patient-assessed tremor over time.RESULTSSeventy PD patients and 17 ET patients were included in this analysis. Mean postoperative and 1-year follow-up UPDRS-III and physician-reported tremor scores were significantly decreased compared with preoperative scores (p < 0.0001). Two-year follow-up physician-reported tremor was also significantly decreased from preoperative scores (p < 0.0001). Only a diagnosis of PD (p = 0.0047) and the patient-assessed tremor rating (p < 0.0001) were significantly predictive of depression. A greater time since surgery, in general, significantly decreased anxiety scores (p < 0.0001) except when a worsening of patient-assessed tremor was reported over the same time period (p < 0.0013).CONCLUSIONSPatient-assessed tremor severity alone was predictive of depression in PD and ET following DBS. This finding suggests that a patient's perception of illness plays a greater role in depression than objective physical disability regardless of the time since surgical intervention. In addition, while anxiety may be attenuated by DBS, patient-assessed return of tremor over time can increase anxiety, highlighting the importance of long-term follow-up for behavioral health features in chronic neurological disorders. Together, these data suggest that the patient experience of motor symptoms plays a role in depression and anxiety-a finding that warrants consideration when evaluating, treating, and following movement disorder patients who are candidates for DBS.

Towards understanding the dose and timing effect of hydrocortisone treatment on the scleral ossicle system within the chicken eye.

Previous work, almost four decades ago, showed that hydrocortisone (HC) treatment reduces the number of skeletogenic condensations that give rise to the scleral ossicles in the chicken eye. The scleral ossicles are a ring of overlapping intramembranous bones, the sclerotic ring, and are present in most reptiles, including birds. The scleral condensations that give rise to the scleral ossicles are induced by a series of overlying thickenings (or papillae) of the conjunctival epithelium. Here, we further explore the effects of altering the dosage and timing of HC treatment on the morphology and number of skeletogenic condensations and conjunctival papillae. We show that high doses can completely obliterate the entire sclerotic ring. Significantly, the reduction in papillae number we observed was less extreme than that of the scleral condensations, indicating that additional factors contribute to the observed skeletogenic condensation loss. Via immunohistochemical analyses, we show that HC treatment alters the spatial expression pattern of several extracellular matrix components (tenascin-C, decorin and procollagen I) and also alters the vasculature network within the sclera. This research provides important insights into understanding the role of the scleral tissue components in ossicle development within the vertebrate eye.

Anticoagulation vs Antiplatelet Treatment in Patients with Carotid and Vertebral Artery Dissection: A Study of 370 Patients and Literature Review.

Background: Dissection of the carotid and vertebral arteries is an important cause of stroke in young patients. Objective: The objective of this study is to compare antithrombotic treatments in patients with carotid and vertebral dissections. Methods: Three hundred seventy patients with carotid and vertebral artery dissections were included. Univariate and multivariate analyses were conducted to analyze the association between treatment and new or recurrent events and clinical outcome. Results: Mean follow-up was 24.3 months. In patients with spontaneous dissection, 55% received antiplatelets, 29.4% anticoagulation, and 12.6% combined treatment. New or recurrent ischemic and hemorrhagic events occurred in 9.6% of patients on antiplatelets, 10.4% on anticoagulation, and 13.3% on combined treatment. For traumatic dissection, 58.3% received antiplatelets, 26.9% anticoagulation, and 10.2% combined treatment. New or recurrent ischemic and hemorrhagic events occurred in 6.9% on antiplatelets, 11.1% on anticoagulation, and 20% on combined treatment. In patients with intracranial dissection, 63.1% were started on antiplatelets, 19.7% on anticoagulation, and 14.5% on combined treatment. Ischemic and hemorrhagic events occurred in 8.5% on antiplatelet treatment, 15.4% on anticoagulation, and 18.2% on combined treatment. In patients with extracranial dissection, 54.4% were on antiplatelets, 28.9% on anticoagulation, and 11.2% on combined treatment. Ischemic and hemorrhagic events occurred in 10.1% on antiplatelet treatment, 9.3% on anticoagulation, and 13.8% on combined treatment. The association between antithrombotic treatment and ischemic/hemorrhagic events and clinical outcome was not significant for all subtypes of dissection. Conclusion: The rate of new or recurrent events is similar with antiplatelet and anticoagulation treatment in treating intracranial and extracranial carotid and vertebral artery dissection.

Power of Peers: Students' Perceptions of Pairing in Clinical Dental Education.

Prior studies have identified many benefits of peer mentoring in higher education, but the subject has not been widely examined in dental clinical education. Students at Midwestern University College of Dental Medicine-Arizona are paired with a partner for the duration of the clinical phase of education. The initial vision behind pairing was to train students in a realistic four-handed, efficient general practice model. The aim of this study was to assess the students' perceptions of the peer mentoring component of pairing third- and fourth-year dental students in the clinical phase of their education. A survey was developed to seek answers to three questions: 1) Did the students perceive that the peer mentoring supported principles of adult learning? 2) Did the students feel they were prepared to enter into the peer learning relationship? 3) What were the students' perceptions of peer mentoring in their clinical education? Data were collected through an online survey delivered to third- (n=114) and fourth-year (n=104) students at the completion of the 2014-15 school year. The 19-question survey had a 61% response rate. The benefits of pairing were found to go far beyond the initial vision of promoting a general practice model. The majority (70.1%) of responding students perceived that it added to the educational experience, and 68.5% frequently/always agreed that the mentor-mentee relationship motivated them to learn. Although the students expressed many benefits of pairing, 29.3% identified a need for more focused training prior to entering into the mentor-mentee relationship.

What shapes the oral jaws? Accommodation of complex dentition correlates with premaxillary but not mandibular shape.

BACKGROUND: Teeth are integrated into the vertebrate oral jaws to provide a functional unit for feeding, however little is known about how this integration occurs during growth and development. The purpose of this study is to identify the ontogenetic changes in oral jaw shape that are associated with the transition of the oral dentition from unicuspid teeth to multicuspid teeth. Here, we compare the shape of the occluding upper (premaxilla) and lower (mandible) jaws of the toothed Mexican tetra (Astyanax mexicanus) and the toothless (oral teeth present, pharyngeal teeth absent) zebrafish (Danio rerio) over development. Gross morphology combined with morphometric analyses were used to analyse shape changes of the occluding oral jaws in each species. Histological analyses were also used to examine the development of the mandibular symphysis. RESULTS: The occluding edge of the premaxilla is the first region to ossify in the Mexican tetra, but the last to ossify in zebrafish. Morphometric analyses revealed that the early shape of the premaxillae (in fish younger than 8mm SL) is the same in each species but that the premaxilla shape changes significantly at larger sizes. These changes are apparent in the tooth bearing region of the Mexican tetra. The rostral region of the mandible also houses teeth, however ossification and shape in this region were surprisingly similar between species despite differences in the presence of oral dentition. Furthermore, we found that the mandibular symphysis of the Mexican tetra is composed of interdigitating bone, while the symphyseal region of the zebrafish is composed of fibrous connective tissue. CONCLUSIONS: These differences in the jaw skeleton have likely evolved due to different feeding strategies utilised by each species. Our results show that premaxillae shape correlates strongly with the development of complex dentitions unlike in the mandible. This study provides important insights into the relationship between jaw and tooth development in bony fishes and suggests that these mechanisms may be similar amongst vertebrates.

Decreased CSF output as a clinical indicator of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Vasospasm is a significant cause of morbidity and mortality among those with aneurysmal subarachnoid hemorrhage (aSAH). Treating increased intracranial pressure by drainage of cerebral spinal fluid through an external ventriculostomy is routine practice. The objective of this study is to evaluate the trends of CSF output in patients who experience vasospasm. METHODS: Electronic medical charts were reviewed to identify two groups of patients with aSAH, 75 consecutive patients who developed vasospasm and 75 matched patients who did not develop vasospasm. CSF output was recorded within 3 days before and 3 days after the occurrence of vasospasm. CSF output was recorded for the same days after SAH in matched patients with no vasospasm. RESULTS: Total CSF output was lower in patients with vasospasm as compared to patients without vasospasm matched for the same day (p<0.001). In patients with vasospasm, CSF output recordings were significantly higher prior to the occurrence of vasospasm (438ml/day) than the period following vasospasm (325.7ml/day), with a consistent decrease in CSF drainage from day 3 before vasospasm to day 3 after vasospasm (p=0.012). Decreasing CSF output was significantly associated with the occurrence of vasospasm (p=0.017). Youden indices demonstrated that daily CSF drainage <160ml was significantly associated with the occurrence of vasospasm. The sensitivity of this test was 64.79% and the specificity was 55.38%. CONCLUSIONS: In addition to clinical exam findings, observation of a CSF output decline to less than 160ml/day may be used as additional support for the diagnosis of vasospasm.

Dissecting pseudoaneurysms: predictors of symptom occurrence, enlargement, clinical outcome, and treatment.

OBJECTIVE Dissection of the carotid and vertebral arteries can result in the development of aneurysmal dilations. These dissecting pseudoaneurysms can enlarge and cause symptoms. The objective of this study is to provide insight into the progression of dissecting pseudoaneurysms and the treatments required to manage them. METHODS A review of the electronic medical records was conducted to detect patients with carotid and vertebral artery dissection. An imaging review was conducted to identify patients with dissecting pseudoaneurysms. One hundred twelve patients with 120 dissecting pseudoaneurysms were identified. Univariate and multivariate analyses were conducted to assess the factors associated with undergoing further interventions other than medical treatment, pseudoaneurysm enlargement, pseudoaneurysms resulting in ischemic and nonischemic symptoms, and clinical outcome. RESULTS Overall, 18.3% of pseudoaneurysms were intracranial and 81.7% were extracranial, and the average size was 7.3 mm. The mean follow-up time was 29.3 months; 3.3% of patients had a recurrent transient ischemic attack, no patients had a recurrent stroke, and 14.2% of patients had recurrence of nonischemic symptoms (headache, neck pain, Horner syndrome, or cranial nerve palsy). Follow-up imaging demonstrated that 13.8% of pseudoaneurysms had enlarged, 30.2% had healed, and 56% had remained stable. In total, 20.8% of patients had an intervention other than medical treatment. Interventions included stenting, coiling, flow diversion, and clipping. Predictors of intervention included increasing size, size > 10 mm, location in the C2 (petrous) segment of the internal carotid artery (ICA), younger age, hyperlipidemia, pseudoaneurysm enlargement, and any symptom development. Significant predictors of enlargement included smoking, history of trauma, C2 location, hyperlipidemia, and larger initial pseudoaneurysm size. Predictors of pseudoaneurysm resulting in recurrent ischemic and nonischemic symptoms included increasing size and location in the petrous segment of the ICA. Smoking was a predictor of unfavorable outcome. CONCLUSIONS Dissecting pseudoaneurysms have a benign course and most will not cause symptoms or enlarge on follow-up. Medical treatment can be a sufficient, initial treatment for dissecting pseudoaneurysms.

A comparative analysis of chick culturing methods on skeletogenesis.

Chick embryos are desirable models for the study of developmental biology. Despite this, there are very few studies that examine the effect of different culturing methods on skeletogenesis, specifically, intramembranous and endochondral bones. This study presents a detailed description of these effects by comparing two different culturing methods: windowed (in the shell) eggs and ex-ovo or shell-less culturing to normal development. Using whole mount bone staining, we determined that there is no significant difference in the length of the ossified region of intramembranous and endochondral bones in control versus window cultured embryos. However, these bones are significantly underossified in shell-less embryos. Shell-less embryos also exhibit abnormalities in endochondral bones. Intramembranous bones, interestingly, are morphologically normal in shell-less embryos. This study provides the first detailed description of ossification in window (in-ovo) and shell-less (ex-ovo) cultured embryos compared with controls (in-ovo). Patterning of the skeleton is unaffected regardless of culturing method. We conclude that studies involving endochondral bones should not utilise shell-less culturing methods. This data has been lacking in the literature and will serve as an important resource for those using cultured chick embryos in the study of skeletogenesis.

Safety and efficacy of the Pipeline Embolization Device in 100 small intracranial aneurysms.

OBJECT Flow diverters are increasingly used for treatment of intracranial aneurysms. In most series, the Pipeline Embolization Device (PED) was used for the treatment of large, giant, complex, and fusiform aneurysms. Little is known about the use of the PED in small aneurysms. The purpose of this study was to assess the safety and efficacy of the PED in small aneurysms (≤ 7 mm). METHODS A total of 100 consecutive patients were treated with the PED at the authors' institution between May 2011 and September 2013. Data on procedural safety and efficacy were retrospectively collected. RESULTS The mean aneurysm size was 5.2 ± 1.5 mm. Seven patients (7%) had sustained a subarachnoid hemorrhage. All except 5 aneurysms (95%) arose from the anterior circulation. The number of PEDs used was 1.2 per aneurysm. Symptomatic procedure-related complications occurred in 3 patients (3%): 1 distal parenchymal hemorrhage that was managed conservatively and 2 ischemic events. At the latest follow-up (mean 6.3 months), 54 (72%) aneurysms were completely occluded (100%), 10 (13%) were nearly completely occluded (≥ 90%), and 11 (15%) were incompletely occluded (< 90%). Six aneurysms (8%) required further treatment. Increasing aneurysm size (OR 3.8, 95% CI 0.99-14; p = 0.05) predicted retreatment. All patients achieved a favorable outcome (modified Rankin Scale Score 0-2) at follow-up. CONCLUSIONS In this study, treatment of small aneurysms with the PED was associated with low complication rates and high aneurysm occlusion rates. These findings suggest that the PED is a safe and effective alternative to conventional endovascular techniques for small aneurysms. Randomized trials with long-term follow-up are necessary to determine the optimal treatment that leads to the highest rate of obliteration and the best clinical outcomes.

Endovascular management of cerebral vasospasm following aneurysm rupture: outcomes and predictors in 116 patients.

OBJECTIVE: To retrospectively assess the safety and efficacy of endovascular treatment of cerebral vasospasm with different modalities and assess predictors of outcome. METHODS: Endovascular treatment was indicated in the event of neurological deterioration refractory to medical therapy. Data were collected for 116 patients treated at our institution. RESULTS: Vasospasm was treated with balloon angioplasty in 52.6%, intra-arterial nicardipine infusion in 19.8%, or both in 27.6%. Angiographic vasospasm was reversed in all but 4 (96.6%) patients. The complication rate was 0.9%. Twenty patients (17.2%) had incipient pre-procedure hypodensities; 3 (15%) hypodensities were reversed and neurological improvement occurred in 60% of these patients. Retreatment was required in 22 (19%) patients. Higher Hunt and Hess grades and treatment with nicardipine alone predicted retreatment. Neurological improvement was noted in 82%. Male gender, pre-procedure hypodensities, and posterior communicating artery aneurysm location negatively predicted neurological recovery. Favorable outcomes were noted in 73%. Higher Hunt and Hess grades, pre-procedure hypodensities, posterior circulation aneurysms, and no neurological recovery predicted poor outcome. CONCLUSION: Endovascular therapy for vasospasm has an excellent safety-efficacy profile. Balloon angioplasty and nicardipine are equally effective but effects of nicardipine are less durable. Patients with incipient pre-procedure hypodensities benefit from endovascular intervention and should probably not be excluded from treatment.

Adaptive evolution of the lower jaw dentition in Mexican tetra (Astyanax mexicanus).

BACKGROUND: The Mexican tetra (Astyanax mexicanus) has emerged as a good animal model to study the constructive and regressive changes associated with living in cave environments, as both the ancestral sighted morph and the cave dwelling morph are extant. The cave dwelling morphs lack eyes and body pigmentation, but have well developed oral and sensory systems that are essential for survival in dark environments. The cave forms and surface forms are interfertile and give rise to F1 hybrids progeny known as intermediates. In cavefish, degeneration of the lens is one of the key events leading to eye regression. We have previously shown that surgical lens removal in surface fish embryos has an effect on the craniofacial skeleton. Surprisingly, lens removal was also found to have an effect on the caudal teeth in the lower jaw. In order to understand this result, we analyzed the lower jaw and upper jaw dentitions of surface, cavefish and F1 hybrids of surface and cavefish and compared our findings with surface fish that underwent lens removal. We also investigated the upper jaw (premaxillae and maxillae) dentition in these fish. RESULTS: Our tooth analyses shows that cavefish have the highest numbers of teeth in the mandible and maxillae, surface forms have the lowest numbers and F1 hybrids are between these groups. These differences are not observed in the premaxillae. A wide diversity of cuspal morphology can also be found in these fish. Jaw size also differs amongst the groups, with the mandible exhibiting the greatest differences. Interestingly, tooth number in surgery fish is different only in the caudal region of the mandible; this is the region that is constrained in size in all morphs. CONCLUSION: Our data provides the first detailed description of the jaw dentitions of two morphs of Astyanax mexicanus, as well as in F1 hybrids. Tooth number, patterning and cuspal morphology are enhanced in cavefish in all jaws. This is in contrast to the increase in tooth number previously observed on the lens ablated side of the surgery fish. These findings indicate that the mechanisms which govern the constructive traits in cavefish are different to the mechanisms causing an increase tooth number in surgery fish.